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Bone OMo001 B o h u s l a v i z k i K.H., Brenner W., Krrner T., Brinkmann G., KiShnlein

S., Kreusch T., Wolf H., Clausen M., Henze E. Clinics of Nuclear Medicine, Diagnostic Radiology and Oral Surgery, Universitiy of Kiel, Germany VALUE OF BONE SCAN AND M R ] IN INITIAL DIAGNOSIS AND FOLLOW-UP OF MANDIBULAR OSTEOMYELITIS Treatment strategy in patients suspected of mandibular osteomyelitis depends mainly on both clinical aspect and 3-phase bone scan (3-PBS). In recent time, MRI has replaced nuclear medicine procedures in many fields. However, in patients with osteomyelitis MRI is rendered difficult by metal artefacts generated from antibiotic chains inserted in the mandible. Therefore, this study was designed to compare the value of 3-PBS and MRI in mandibular osteomyelitis. In 12 patients with histologically verified mandibular osteomyelitis conventional 3-PBS was performed. In addition, all patients received standard MRI consisting of STIR-, T2- and Tl-weighted sequences including contrast enhancement with gadolinium. Surgical treatment was made dependend from clinical aspect and 3-PBS. 7/12 patients were re-examined 6 months after insertion of antibiotic chains. Activity of osteorayelitis was divided semiquantitatively in a 3 grade score by either investigation. In initial diagnosis MRI and 3-PBS yielded comparable results in 7/12 patients. In 3 patients activity of osteomyelitis was overestimated by MRI by 1 grade, and in 2 patients for 2 grades. There was no underestimation of osteomyelitis activity by MRI. In follow-up investigations metal artefacts due to inserted antibiotic chains were detectable by MRI in all 7 patients. However, interpration of MRI images was feasable in these patients. While MRI overestimated acitivity of osteomyelitis in 1/7 patients only, in 6/7 patients MRI and 3-PBS yielded comparable results. In conclusion, in this study with limited number of patients MRI and 3phase bone scan yielded comparable results in estimation of osteomyelitis acitivity in the mandible.

OMo002

G. Berdina1, H. Schliephake2, G. Neumann2, R. Schmelzeisen 2, F.W. Neukam2, J.E. Hausamen2, G.J. Meyer1, K.F. Gratzl, H. Hundeshagen 1, ~Abteilung for Nuklearmedizin und spezielle Biophysik, 2Klinik und Poliklinik for Mund-, Kiefer- und Gesichtschirurgie, Medizinische Hochschule Hannover, Germany. EVALUATION OF BONE HEALING IN THE JAW USING SEQUENTIAL BONE-SPECT Bone-SPECT was applied for early differentiation between uncomplicated and complicated processes of healing in the jaw alter fracture or bone transplantation. 25 patients who sustained 40 mandibular fractures and 24 patients with severe alveolar ridge atrophy who received onlay osteoplasties were investigated. B o n e - S P E C T was

performed within 1-2 months and after approximately 4-5 months. SPECT studies were clone with single-camera systems (Siemens Diacom, Picker Dyna Camera) starting 2-3 h after i.v. injection of 8 MBq 99mTc MDP per kg body weight. 64 frames of 35 sec duration each were acquired and reconstructed in a 64*64 matrix without attenuation correction. Traceruptake in the jaw was assessed semiquantitatively in coronal tomograms based on region of interest analysis and using the calvarium as reference region. In fractures with uncomplicated healing a decline of jaw to calvarium ratios was observed, whereas an increase occurred in fractures that exhibited infections in the later course. Ratios were significantly higher at the follow-up investigation in cases with complications (6.11 vs 3.75, t-test: p<0.05). After onlay osteoplasty ratios obtained within 1-2 months were significantly lower in cases that showed sequestrum formation in the later course compared to those with uncomplicated healing (4.51 vs 5.50, t-test: p<0.05). The observed significant differences of uptake in the jaw between cases with and without complications in the later course lead to the conclusion, that bone-SPECT can give prognostic information regarding bone healing.

OMo003 z. BURAK, A. DIRLIK, A. MEMi~, Z. (SZCAN, R. ARKUN, E. TEBER, H. 6ZKILIQ. Ege University Depts. of Nuclear Medicine and Radiology, izmlr, Turkey EVALUATION OF MUSCULOSKELETAL (MS) TUMORS WITH DYNAMIC Tc-99m SESTAMIBI IMAGING : COMPARISON WITH DYNAMIC MAGNETIC RESONANCE STUDY Dynamic magnetic resonance study (DMRS) has been introduced as a noninvasive procedure to distinguish malignant and benign MS tumors and to assess response to preoperative chemotherapy. The purpose of this study was to investigate the role of Tc-99m MIBI imaging in differential diagnosis of bone and soft tissue lesions by comparing its uptake and clearance patteme with DMRS. Twenty two patients (10ts) including 9 oateoasrcomas (OS), 4 chondrnsarcomas (CS), 4 Ewing'e sarcomas (ES), 1 fibr0sarcoma (FS), 1 metastasis (met) and 3 non-malignant lesions were studied. All pte were evaluated by DMRS, Tc-ggm MDP three phase bone sclrttigraphy and Tcggm MIBI imaging. DMRS was performed with SE Tl-weighted sequences. Bolus injection of Gd-DTPA was administered and images were acquired at 45 set:. intervals for a total bedofl of 6 minutes. Scintigraphic imaging was perfomed after bolus injection of 740 MBq Tc99m MIBI and identical acquisition protocol as DMRS was applied. CuP#as were generated from ROia drawn over sum frames. Initial MIBI uptake and clearance pattern of MS lesions were determined and compared with DMRS. In dynamic MIBI study, curve characteristics of 8 0 S , 4ES, 1FS, 3CS, and 1 met demonstrated early peak and plateau Indicating delayed tracer clearance. DMRS was comparable showing early and persistent enhancement of contrast matedal. Posttherapy MIBI uptake patterns of 2 OS and 2 ES demonstrated early peak and rapid wash-out in regard to plateau pattern in pretherapy curves. DMRS findings were consistent with regression of the tumoral lesions. In benign lesions early peak and clearance of MIBI was observed in respect to late peak and delayed clearance in DMRS. In conclusion, assessment of early uptake and clearance characteristics of Tc-99m MIBI in MS lesions demonstrated excellent correlation with DMRS. While DMRS offers better anatomic delineation of tumoral infiltration, combined evaluation of these modalities may provide valuable data especially in assessment of therapy response.

OMo004 G. Matiani, C. Motta, G. Calcagno, O. Taddei, G. Villa, R. Costa, C. Maragliano, N. Molea, P. Tom,t, R. Gatti. Nuclear Medicine Service, DIMI, University of Genoa, "G. Gaslini" Children's Hospital; Genoa; Nuclear Medicine Center, University of Pisa; Pisa (Italy).

99mTc-SESTAMIBI FOR THE SCINTIGRAPHIC EVALUATION OF LIPID DEPOSITS IN THE BONE MARROW 1N PATIENTS WITH GAUCHER'S DISEASE The aim of this study was to evaluate the feasibility of directly imagin_q . . . . . 99m bone marrow involvement by Gaucher hpld infiltrates, employing TcSestamibi (99mTc-MIBI) instead of the previously reported procedure based on inhalation of the lipid-soluble gas xenon-133, Eight patients with histologically proven bone marrow involvement from Gaucher's disease were studied (5 males and 3 females, 3-67 yrold); some of them were followed at various times after initiating substitutive therapy with the defective enzyme, ceredase. Upon i.v. injection of 99mTc-MIB1(10 MBq/kg), dynamic gamma-camera imaging over the affected areas (knees) was acquired from 0-30 min, followed by static acquisitions at both 30 rain and 2 hr. 99mTc-MIBIuptake at the affected sites was detectable few rain after i.v. injection of the radiopharmaceutical, and led to clear scintigraphic imaging of bone marrow involvement by the lipid Gaucher infiltrates. Comparison with the lipid-soluble 99"Tc-HMPAO indicated that 99"~Cc-MIBl uptake reflects both the extent of lipid infiltration and the degree of metabolic activation at the involved sites. Target-to-nontarget ratios ranging between 1 with a 1.7-2.8 were estimated on the static 99mTc-MIBI im a,~ ~,esat 3 0 re'n, very slow wash-out from the affected sites at 2 hr (about 10-15% reduction in radioactive uptake). The extent of involvement visualized by 99mTc-MIBIwas positively correlated with the lipid deposits visualized by Mill, and with the changes in lipid infiltration induced by substitutive therapy. The results obtained in this study indicate that 99mTc-MIB1 can be employed for the direct scintigraphic visualization of lipid deposits in the bone marrow of patients with Gaueher's disease, as also to monitor the effect of substitutive therapy with the enzyme ceredase, thus providing a more practicable alternative in these patients than the scintigraphic procedure based on xenon-133. 1033

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OMoO05

OMoO07

H-J Bair1. E Palluch2, G Platsch1, FG Wolf 1, 1Departments of Nuclear

O.Yenici,M.Manisall, T.Canda, I.G~rkem, B.~ekero~lu, D.0zaksoy, S.Saydam, H.Alanyalz. Depts. of Nuclear Medicine, Radiology, Pathology, Radiation Oncology, General Surgery and Medical Oncology, Medical Faculty, Dokuz Eyl~l University, ~zmir, TURKEY

Medicine and 2Maxillofacial Surgery, University of Erlangen-Nuremberg. Erlangen, FRG. DYNAMIC BONE SCINTIGRAPHY AND SPECT IN OSTEORADIONECROSIS OF THE MANDIBLE Osteonecrosis of the mandible is an unevitably risk in the curative therapy of oropharynx and mouth-cavity cancer. The aim of the study was to evaluate if osteoradionecrosis can be localized and differentated from osteomyelitis and infected osteoradionecrosiswith dynamic bone sciutigraphyand SPECT. In total 30 patients with osteoradionecrosis (n=lS) and osteomyelitis (n=12) were examined. After injection of 740-800 MBq Tc-99m DPD (Teceos; CIS bio international) a dynamic study with flow phase and blood pool (5-6 min. pi.) was performed. For SPECT-acquisiton (2 hrs. postinjection) we used a single-head gamma camera (HIRE collimator, 180°, 45 sec./step, 64x64 matrix) linked to an Icon computer system. Data were evaluated by region of interest technique. We calculated target-to-background ratios 5-6 rain. and 2 hrs. postinjection (counts osteoradionecrosis/countscontralateral mandible). 3 different entities could be classified: I. Photone deficient areas in the blood pool and mineralization phase (n=5): classically sign of osteoradionecrosis. 2. Area of osteoradionecrosis with reactive bone formation (n=9): increased tracer accumulation in the delayed views (1.3+/-0.2) (intact osteoblasts are present) and a normal blood p o o l (target/background ratio 0.9+/-0.1). 3. Infected osteoradionecrosis (n=4): area of hypervascularity in the bloodpool (I.1+/-0.0) and increased Tc-99m uptake in the mineralization phase (1.4+/-0.2) comparable with osteomyelitis (n=12) (blood pool: 1.2+/-0.1; mineralization phase 1.5+/0.2). Beside radiologically techniques (orthopantomogram; CT with ultrahigh algorithm) the combined dynamic study and Tc-99m DPD SPECT of the mandible is an important examination in the preoperative diagnostic procedure.

RELATION OF BONE AND VISCERAL METASTASES WITH ESTROGEN RECEPTOR IN PATIENTS WITH BREA~T CARCINOMA

Purpose: To predict the role of estrogen receptor(ER) activity in patients(pts) with breast carcinoma(Ca) for the site of first metastasis. Method: i01 breast Ca pts with ER activity but without metastasis at their first appearance were retrospectively analyzed. All pts had serial bone scintigraphies (Tc-99m MDP) and radiologic follow-up. ER activities were studied in primary tissue following surgery/biopsy. ER activities in primary tissue of pts were compared with the site of first metastasis, bone or distant visceral involvement. Mean follow-up of the pts were 24 months. Results: The ratio of ERand ER+ tumors were 35.6% and 64.4% respectively. 20 pts had bone (ER+ 14, ER- 6) and ii pts had visceral metastases (ER+ 4, ER- 7). While the relation between ER and visceral metastasis was significant,p:0.04, the relation between ER activity and bone metastases was not strong,p:0.55. Conclusion: Pts with ER- tumors have higher frequency of visceral metastasis than ER+ tumors, however, ER activity does not influence the frequency of bone metastasis.

OMoO06

OMoO08

JC Roos1, CM de Ridder 2, M van Loon1, A van Lingen 1, E Schoute3, JC Netelenbos 4, HA Delemarre-van de Waal 2. Free University Hosp, Departments of Nuclear Medicine ~, Pediatrics 2, Epidemiology and Binstatistics ~, and Internal Medicine 4, Amsterdam, The Netherlands.

W. BrenneL K.H. Bohuslavizki, H. Wolf, N. Sieweke, U. Teichert, M. Clausen, E. Henze Clinic of Nuclear Medicine, University of Kiei, Germany

BONE MINERAL DENSITY IN 153 HEALTHY GIRLS IN PUBERTY Bone growth is accelerated during puberty. A longitudinal study is started in 153 girls (8-13 years) to analyze the effects of several factors (e.g. diet, hormonal status) on this process and on the height of the peak bone mass. The results of the baseline studies are now available. In adults, bone mineral density (BMD) values often are corrected for age. However, correction for differences in age-dependent variables as pubertal stage (according to Tanner), weight or height may be more appropriate in puberty. A proper correction of BMD values is not only important for the studied bone growth but also for the interpretation of BMD values in pubertal patients suspected to have a low BMD. The BMD was measured in the lumbar spine, femoral trochanter and neck, in 2 regions in the forearm and in the total body (Hologic 2000). The values were related to age, weight, height and pubertal stage. The latter four variables are mutually related and the purpose of analysis was to determine the quantitative influence of each variable on BMD. The BMD at 1/3 distance of the distal end of the radius showed the highest correlation (least squares method) with all four factors: with age R2 was 0.39, with pubertal stage 0.48, with weight 0.43, and with height 0.51, and this location, therefore, was used for further analysis. It appears that 51% of the variance in a BMD measurement is explained by height. With a stepwise multiple regression analysis it appeared that addition of pubertal stage augmented this figure to 57% (R= 0.75, p < 0.0001). Age and weight did not further increase this percentage. We conclude that BMD values around puberty should be corrected for height and preferrably also for pubertal stage to facilitate analysis of studies in this period of life and to increase the discriminating power of a BMD measurement in pubertal patients. Age and weight do not add to the explanation of the variance in a BMD measurement and are, therefore, of minor importance.

1034

Q U A N T I F I C A T I O N OF BONE UPTAKE BY CONVENTIONAL BONE SCANNING The reference method for quantification of bone uptake is the measurement of 24 h whole body retention of Tc-99m-labelled diphosphonate. In this study a new method for bone uptake measurement based upon routine bone scanning has been evaluated. Studies were performed in 13 patients with normal bone scans and normal kidney function. Eight whole body scans were obtained in each patient at 3 min, and at 1, 2, 3, 4, 5, 6, and 24 b after injection of 600 MBq Tc-99m-HMDP using a double head gamma camera system. For each image the activities of the whole body, the urinary bladder and the adductorial muscles of the thighs representative for soft tissue were measured by conventional ROI-technique. Urinary excretion was determined as difference of whole body activities between the image at 3 rain and the image of interest plus urinary bladder activity. From these data timeactivity curves of soft tissue and urinary excretion were established by least squares fit. Bone uptake was then calculated as initial total whole body activity at 3 rain minus both urinary excretion and remainder soft tissue activity. Data are given as percentage of initial total whole body activity at 3 rnin (= 100 %) and represent mean _+one standard deviation. Soft tissue activity decreased exponentially reaching a plateau after 6 h according to a remaining activity of 14.7 _+6.1%. After 24 h soft tissue activity was almost the same revealing values of 13.5 _+6.2 %. In contrast to soft tissue activity bone uptake already reached a stable plateau of 27.3 -+ 5.1% after 3 h p.i. with no significant changes up to 24 h. The corresponding urinary excretion increased from 49.3 _+8.6 % to 57.4 + 10.1 % and 59.0 +_ 10.4 % at 3 h, 6 h, and 24 h p.i., respectively. Thus, after 6 h a constant bone-to-soft tissue ratio of about 2:1 was reached and urinary excretion was less than 2 % during the time period from 6 to 24 h p.i.. The results of this easy-to-perform method are in good agreement with findings of 24 h whole body retention measurement. Furthermore, this method allows assessment of pure bone uptake instead of whole body retention of diphosphonate simply by acquiring two whole body scans and - because of correction for urinary excretion - bone uptake can be calculated at any acquisition time.

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OMo009

OTu011

i. Gtzttkara~C. Yurdo~lu, M. Bumk, M. Mglazim@,lu,E. Uyan~ T. O z p a ~

A. Fume, °A. Sudanese, °L. Busanelli, °A. Toni,*C. Basile Nucl Meal, *Immunohematology Depts Azienda USL Citta di Bologna °University Orthopaedics Clinic, Rizzoli Institute, Bologna

Okmeydam Hospital, lstanbul, Turkey

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SCINTIGRAPHIC DETEC~FIONOF PATELLAR AVASCULAR NECROSIS IN TOTAL KNEE ARTHROPLASTY Because of its supportive role to the joint mechanics, the idea of the preservation of patella in total knee arthroplasty (TKA) is growing. The deterioration of patellar perfi~ien, seen not infrequently during this operation, may cause avascular necrosis and subsequently fracture in patella .The determination of patellar avascular necrosis during the early post-operative period is very important to change advises and rehabilitation program to the patient. To understand weather this important compticaO.onof TKA could be determined scinligraphically,this study was planned Nineteen patients with 26 TKA s, aged 50 - 65, were included to the study. Prosthesis were placed to the knee, cutting slightly the femoral and tibial surfaces of the knee joint. Polyetilen patelIer part of the prosthesis was placed to the hole made on the posterior surface of the patella. Tc-99rn MDP bone piruhotc scinf.graphy were done on anterior and lateral projection on the both knees. Seven TKA s were studied twice ,a week before and 15 days after the operation. Ten TKA s were studied once, I5 days after the operation. On the other 9 TKA s the studies were performed in 2 - 24 months after the operation. The scintigrams were analyzed companng lateral position patellar activity to the activity on the joint surfaces cut, on post - op images and ! or to the same patellar area activity on the pro - op images; Equal or higher activities of patella accepted as normal, patella aO'ivitieslower but seen clearly accepted as partial damage and patella with no aetivity seen accepted as avascular necrosis. Sixteen out of 27 (59.2 %) TKA showed normal patella[ findings. Six TKA s (22.2 %) showed par/iN damage. Four out of 27 ( 14.8 %)TKAs showed avascula[ necrosis. This last group has been following up. Two avascular necrosis cases appeared on two patients with the most traumatic TKA operations Findings showed that TKA operation may cause patellar avascula[ necrosis and this could be detected and followed up by Tc-99m MDP. pinhole bone scintigraphy

99mTc HMPAO GRANULOCYTE SCINTIGRAPHY IN HIP ARTHROPLASTY LOOSENING: A PROSPECTIVE STUDY

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Aim of the study: to evaluate the diagnostic value of 99mTc HMPAO granulocyte scintigraphy (GS) in the pre-operative phase of patients with hip arthroplasty loosening for clinical decision making. Methods: 111 consecutive patients were enrolled in this prospective study. 93 subjects completed the follow-up program after surgery and were considered for result analysis. All patients, with a proved prosthetic loosening needing surgery, underwent GS in the immediate pro-operative phase (7-20 days). A sulphur colloid scintigraphy was performed in case of equivocal positivity at GS. Patients with macroscopic evidence of infection were excluded from the study. GS was considered positive if clear uptake of labeled cells was seen in the head zone of prosthesis with surrounding sot~ tissue involvement; any other positivity was considered as indeterminate and a further study with radiocolloid was performed 48h later. During surgery all patients were evaluated by intraoperative smears and subsequent culture for bacterial growth. Arthroplasties were considered infeedted (n=18) if: a) intraoperative cultures grew-out organisms (n=16) or b) gross purulence was evident at surgery (n=2). Aseptic loosening was diagnosed (n=75) when: a) operative smears revealed no teukocytes and intra-operative cultures were reported as no-growth (n=70) and b) no signs of infection developed during a 6 months follow-up period (n=75) despite a positive culture result (n=5). Results: there were 17 TP scintigraphic results, 69 TN, 1 FN and 6 FP. Sensitivity was 94%, specificity 92%, the NPV=99% and the PPV=74% Culture results and intraoperatory evaluation resulted respectively in: sensitivity=89 and 83%, specificity=93 and 97%, NPV=97 and 96%, PPV=76 and 88%. Conclusions: a negative GS excludes with high probability infection in patients with hip arthroplasty loosening and a reimplant may be programmed. A positive GS result, even if completed by a bone-marrow scan, must be regarded only as suspected for infection and a careful evaluation of the patient is needed before and during surgery.

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OTu010

OTu012

R . S Liu~ L . S Chu, CP. Chang, H.Y. Hsiau, K L Chou, C W . Chang and S H . Yeh. National PET/Cyclotron Center, Taipei Veterans General Hospital, National Yang-Ming University School &Medicine, and National Defense Medical Center, Taipei, Taiwan.

T. Baso~lu, P. Olivier, D.Hestin, N. Quid, N. David, T. Arsena, E.Renoult, P.Y.Marie, G.Karcher, MKesster, A.Bertrand CHU-Nancy ,Depts. of Nuclear Medicine and Nephrology, FRANCE

ASSESSMENT OF THE OUTCOME OF DIABETIC FOOT LESIONS B Y [F- 18]FLUOROMISONIDAZOLE PET SCAN.

EVALUATION OF RENAL OSTEODYSTROPHY IN KIDNEY TRANSPLANTED PATIENTS USING BONE SClNTIGRAPHY

The diabetic foot may lead to skin ulceration, wound infection, gangrene, and amputation. The net result of the pathologic conditions of diabetic foot is a focal hypoxia. This study aimed to assess the outcome of diabetic foot lesions by a hypoxic imaging agent [F-18]fluoromisonidazole (FMISO) using PET scan.

The regression of renal osteodystrophy (ROD) after kidney transplantation (TX) is often difficult to assess because of the limited value of biological and radiotogical findings. The objective of this study was to evaluate the bone-scintigraphic findings in renal-transplanted patients with functioning grafts. Bone scintigraphy with Tc-99m MDP was performed in 344 kidney transplanted patients with functioning grafts at different times following TX varying between one month and 22 years. Three hundred patients without any surgical intervention for hyperparathyroidism constituted the main study group. Plasma values of intact parathormone were obtained the day of bone scanning or within a time interval of + 30 days in all 300 patients. Fourty-four of 344 patients with previously performed subtotal parathyroidectomy (PTX) because of severe hyperparathyroidism and clinically manifest osteodystrophy were studied separately. A semi-quantitative metabolic index (MI), known as Score of Fogelman with a maximum value of 14, was determined in all patients and in 60 sex and age matched control subjects. The MI values of the main study group were significantly different then those of the normal group ( p < 0.05 ). Eighty-one percent of the main study population presented moderately increased MI scores. The mean MI values obtained in 300 transplant recipients and the control group were 5.18 + 2.07 and 0.74 + 0.92 respectively . In 45.5% of the main study group moderately elevated i-PTH values (mean=12.51 + 7.21 pmol/L) were found. There was no significant correlation between MI and i-PTH values ( r=0.12, p=0.07 ). Slightly elevated MI scores were found in 70% of the parathyroidectomized group with a mean M1 of 4.52 _+ 1.3 but the decrease of osteodystrophic signs on the bone scans following PTX could be statistically demonstrated. PTX-Age ( time elapsed between parathyroidectomy and the day of bone scintigraphy ) and MI in the parathyroidectomized group was negatively correlated ( r = - 0.70 p < 0.0001 ). To conclude, the semi quantitative analysis shows the persistence of moderate bone scan findings of ROD in the majority of the studied population.

We evaluated t6 patients (pts) with diabetic foot (11 male, 1 female; Age: 33-82 yrs, median: 68 yrs). The severity of the diabetic foot of the pts evaluated by Meggitt-Wagner diabetic foot lesion grading system were: 2 superficial ulcer (grade 1), 5 deep ulcer (grade 2), 3 abscess osteitis (grade 3), and 6 gangrene forefoot (grade 4). PET imaging of feet was started at 2 hr after intravenous injection of 10 mCi (370 MBq) of FMISO. Focal accumulation of FMISO in the feet was assessed visually. All pts had careful history taking, physical examination, blood sugar measurement and Doppler ultra-sound before the PET Study. Periodically, re-examinations were done at 6 men to 1 year thereafter. All patients received local wound care and antibiotics treatment. Four pts (2 gr. 1, 2 gr. 2) showed negative FMISO uptake in the feet (normoxic) with eventual wound healing. Ton pts (2 gr. 2, 2 gr. 3, 6 gr. 4) showed positive FMISO uptake (hypoxic) with eventual failure to heal. Amputation was done in two of t h e m One pt with osteomyelitis showed normoxic scan pattern but the wound did not heal. One hypoxic wound healed at 6 men after treatment. The scan sensitivity, specificity and accuracy for predicting non-healing and/or amputation are 91%, 80% and 94%, respectively. In summary, FMISO-PET is feasible to evaluate the focal hypoxia of diabetic foot and may provide a reliable way to predict the outcome of the diabetic foot lesions.

1035

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OTu013

OTu015

M Mitjavila* , A Morales**, A G=.Parra, L Diez, A Crespo. Nucler Medicine and ** Rheumatology department, H Ram6n y Cajal. * Nuclear Medicine department, H.U. Getafe. Madrid, Spain.

8.Gratz. H:G.Bratm, J.Meller, M.Conmd, A.Herrmann, D.Rathruann, R.Bertagnoli, H-G.Willert, W.B~ker Deparlrnents of Nuclear Medicine and Orthopaedics,Georg-AugustUniversityof GOttingen,Germany

BONE ORAL

PHOTOPENIA IN CHRONIC VERTEBRAL OSTEOMYELITIS WITH 99 M TC ANTIGRANULOCYTEANTIBODY {BW 250/183)

SCINTIGRAPBY AND ALKALINE PHOSPHATASE TILUDRONATE THERAPY IN PAGET'S DISEASE

AFTER

Tiludronate is a powerful third generation bisphosphonate which is not associated with impaired bone mineralization. This study examined the changes in bone scan (BS) appearences following tiludronate therapy and its relationship with alkaline phosphatase (AP) in patients with Paget's disease (PD). Twenty five patients (16M, gF) were studied. BS and AP was performed at baseline, 3, 6, and 12 months after tiludronate administration~ BS was scored using a validated semiquantitative scale in 4 points. Summated score was taken to reflect the overall scan picture. Average lesion intensity was calculated by dividing summated score by the number of lesions. The scintigraphic extent of PD has been evaluated by using the index proposed by Coutris. In addition to being scored each lesion was also considered as either predominately uniform or dishomogeneous. Decrease in the above score or in lesion intensity was deemed as an improvement in BS appearance. The BS score improved in 23 patients (92%) and remained unchanged in i. The average score fell with treatment from 2.86 to 2 (29.5%). Completely resolved lesions were found in 1 patient (4%).In II cases (44%) scan appearances changed from uniform to predominantly dishomogeneous. All patients showed decrease in AP after therapy (averge decrease 76.1%). In 18 cases (69%) AP reached the normal range. Only 1 patient showed biochemical relapse. Minor side effects during administration therapy were noted in 5 patients (19%) Tiludronate produces a marked effect on AP and BS in patients with PD. We have failed to demonstrate an association between BS score and AP changes.

Rationale: Photon-deficientareas in 99 m Te / 111 In white Blood cell images (wbe) for the diagnosisof vertebralosteomyelitiswere often published.The aim of this retrospaofivestudy was to evaluate, if the use of 99 m Te labelled moncelonal antigranulceyteantibodies (BW 250/183) is superior to wbe and offers higher spceifieity. Patients and methods: 81 patients ( m=46, f=35, mean age 55 + 2 years, 19891995) with clinical supeeted vertebral osteomyelitisunderwent seintigraphie imaging after intravenousinjectionof 555 MBq 99 m To labelledmoncelenal antigranulceyte antibodies. 40 patients suffered from osteomyelitis (m=20,f=20;mean age 56i-9 years), 6 patients had metastases, 28 patients spondylosisand disc herniation, 5 patients vertebralcompressionfractures. No diagnosis was histologically verified in 2 patients. Planar images were performed 4 and 24-hours postinjeetion.Histolo~¢was available in 30 patients, clinical follow - up in 10 patients. Visuell uptake scores and a quantitative uptake scoresof the suspectedareas were oaloulated.The results were compared with a semiquantitativehistologicalscore( high, medium,low grade) and with the scinfigraphiesuares. Results: Seintigraphyshowed photopenia in all patients with histologioally proven vertebral osteomyalitis i n , d e n t of the grade of infection. The quantitative evaluation 4 and 24 hours ~ injection demonstrated a 58% inercese of the uptake score in eases of histollogieallyhigh grade infections. This increasewas seen predominantlyin thoracicspine, but not in lumbal spine. All non-osseous paravertebral abscesses showed positive images and an increasedquantitativeuptakeover 24 h. Coneh~lom: paravertebral soft tissue infeofions can be excellently differentiated, whereas no differentiation between vertebral cateomyellfis, vertebral turnoutsor fracturesis possible,

OTu014

OTu016

D. Yang, P. Mittal, K. Tai, J. Giovanniello, New York Methodist Hospital, Division of Nuclear Medicine, Department of Radiology

E.Sayit, A.S.Dogan, M.Ozkan, O.Ulker, T.Kabaklioglu, H.Durak

"SUPER- S U P E R SCAN"- D E M O N S T R A T E D IN T H R E E PHASE TOTAL BODY BONE IMAGING(TPTBBI)

"Super Scan" has been described as diffusely increased uptake in skeletal structures and absence of renal activities in 3 hours ddityed static bone scans. We are presenting the new findings of markedly increased bone perfusion and uptake within 3 to 5 minutes after injection ofTc-99m MDP seen in TPTBBI in the first- arterial and second blood- pool phases as well as in the Third- phase 3 hours delayed static bone images. Renal activities are seen in the first and second phases, not in the third phase. We name them a s " SuperSuper Scan". We have found seven in 3,000 cases of TPTBBI (a technique introduced by Yang et ale) performed during the period from January 1993 to February 1996. All seven male patients, age ranging 75 to 85, have primary malignancy in the prostate with extensive metastasis in the bones. They all have very high serum alkaline phosphatase ranges from 537 to 1975 (N: 30-115), PSA 748 to 3684 (N: 0 to 4.0), PAP 35515 (N: 0 to 2.7). This is the first time the unusual findings of rapid perfusion and high early as well as delayed uptake o f the radio- tracer by the skeletal structures, and absence of renal activities in the delayed images in the metastatic disease ever presented. W e recommend them to be called as " Super-Super Scan".

1036

S.Arac,

T.Ertay,

Dept.s of Nuclear Medicine and Orthopaedics, Dokuz Eylul Univ.,School of Medicine, Izmir/TURKEY COMBINED BONE, LABELED WHITE BLOOD CELL BONE MARROW IMAGING IN DIAGNOSING PROSTHETIC INFECTION

AND

This study is designed to evaluate the accuracy of combined bone, labeled white blood cell (WBC) and bone marrow imaging in diagnosing prosthetic infection. Twelve patients (one male, ii female) with painful prostheses (six hips, five knees, one shoulder) were studied. Radionuclide imaging was performed if clinical, radiographic and bacteriologic data w e r e not diagnostic. Final diagnoses were based on surgical macroscopic and culture findings. WBC imaging was performed 4 and 24 hours after iv i n j e c t i o n of autologous WBCs labeled with 185-200 MBq of Tc-99m HMPAO. After the WBC study, patients were injected with 740 MBq (20mCi) of Tc-99m MDP. If there was a suspicion of m a r r o w expansion, T c - 9 9 m sulfur colloid bone marrow images were obtained. Combined radionuclide study showed infection in five of the six infected prostheses, confirmed operatively. The only falsenegative case had a shoulder prosthesis and was under antibiotic therapy. The sensitivity of this p r o c e d u r e was 83%, the s p e c i f i c i t y 100% and accuracy 91%. The infection sites were correctly identified in all cases. Combined WBC and bone scintigraphy improves the specificity of the test by providing better definition of bone and soft tissue compartments where abnormal accumulation of labeled WBCs are noted. TC-HMPAO appears to be a valid alternative to In-lll as a label for WBCs, and yields good results w h e n combined with bone and bone marrow studies, in diagnosing prosthetic infection.

•

Bone/Cardiovascular

Cardiovascular

OTu017 A Devillers, A Moi~an, F Hennion, J Y Poirier, CRLCC Eugene Marquis, Department of Nuclear Medicine, CHU Pontchaillou Department of endocrinology, Rennes DIABETIC FOOT INFECTIONS : A PROSPECTIVE EVALUATION WITH TC99M HMPAO LEUCOCYTES SCINTIGRAPHY. The aim of this study was to evaluate the utility of HMPAO leucocytes scintigraphy (HMPAO-LS) in diabetic patients suspected of osteomyelitis (OM) of the foot. Methods : Thirty consecutive diabetic patients clinically suspected to have foot osteomyelitis were studied. Thirty five foot lesions were found on the basis of physical examination. All patients underwent three phase bone scintigraphy (BS) with 740 MBq 99mTc MDP. HMPAO-LS was performed 4 hours after intravenous injection of 99mTc HMPAO labelled leucocytes. The injected dose was 200 MBq. Both scintigraphic studies were obtained within 4 days of each others and were reviewed by two nuclear medicine physicians. The final diagnosis of osteomyelitis was based on clinical, radiological follow up and/or bacteriological and histological criteria after surgical biopsies. Soft tissue infection was differentied from OM by the combined interpretation of HMPAO LS and BS in all patients. The congruence of abnorma[ focal uptake in HMPAOLS and BS was considered as OM, while no congruence was considered as soft tissue infection. Results : OM was diagnosed in 20 lesions. In these 20 lesions, 16 true positive of HMPAO-LS were proved (7 sites with radiological and biopsy criteria of OM, 6 with radiological follow up, 3 with biopsy criteria alone) and 4 false negative were observed (radiological follow up and biopsy). Ten sites with initial OM were controled after antibiotic treatment, all sites were neg~itive with HMPAO LS. Fifteen lesions were not considered to be OM, theirs signs responded to topical therapy with no relapse and no radiological evolution. All these sites were true negative of HMPAO-LS. Conclusion : HMPAO-LS with a sensitivity (80%) and a highly specificity (100%) seems to be a good diagnostic method of OM involving diabetic foot and useful in follow up after antibiotic treatment.

OTu018 K. Balali~ f;. Kouvidi~ S. Koukouraki, A. Xilouris, E. Velivasakis, P. Kamnis, N. Karkavitsas. University Hospital of Iraklion, 71110 Stavrakia - Crete - Greece. BONE SCINTIGRAPHY IN RECURRENT IRRITABLE HIP.

During a period of 4 years (1992-1995), a 3-phase Tc-99m-MDP scintigraphy was performed in 25 patients with recurrent irritable hip. There were 16 buys and 9 girls with average 6 years (3-10). The mean time between recurrences v~as 26 days 02-43). All but one had negative plain radiograph~ while Ultrasonography revealed hip effusion in all cases. From 25 patients, diffuse increased uptake was presented in 6 (two bilaterally). Five patients were presented with decrease uptake in lateral upper part of femoral head, and 14 patients were presented with in normal limits. The patients were followed up for a period of 2 years. Four of them with evidence of scintigraphic ischemia developed typical radiographic features of Perthes desease. Four of the 6 patients with diffuse iucrease uptake were diagnosed for septic arthritis, one for multiple epiphyseal dysplasia and one for Juvenille reumatoid arthritis. We concider that the nuclide bone scan is at valuable and a necessary investigation in all cases of recurrent irritable hips.

OSu019 D. Agostini, A. Belin*, P. Scanu**, E. L~cluse**, A. Manrique, F. [~uennelle, G. Grollier**, JC Potier**, G. Bunvard. Departments of ~luclear Medicine, Cardiac Rehabilitation Center*, Cardiology**, ~HU Cfte de Nacre, Caen, France.

INFLUENCE OF REHABILITATION ON CARDIAC NEURONAL FUNCTION OF MIBG IN PATIENTS WITH CONGESTIVE HEART FAILURE.

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Patients with congestive heart failure (CI-IF) often have cardiac sympathetic dysfunction. Recent reports showed rehabilitation (R) improves the exercice capacity of these patients. Although this improvement is primarily due to peripheral adaptations, the cardiac neuronal function has not been well defined. The purpose of this study was to determine whether R could induced changes in cardiac neuronal uptake by using 1123 metaiodobenzylguanidine (MIBG) seintigraphy. We prospectively studied twice 14 patients (11 M, 3 F, 47+_8.5 yrs o/d) with ischemic (12) and idiopathic dilated (2) cardiomyopathy who underwent radionuclide ventriculography, planar MIBG scintigraphy and exercice testing (Bruce protocol) before and after R. Rehabilitation consisted of muscle exercice and endurancy training (3 times per week, 60 sessions). Therapy consisted of an association of diuretics, angiotensin converting enzyme-inhibitors and vasodilators. After an intravenous injection of 185 MBq of 1123 MIBG, a chest anterior view was acquired 4 hours later on an ELSCINT APEX-415 camera. Thus, heartmediastinum (H/M) ratio activity was measured, as previously described. Rehabilitation improved NYHA functional class from III to II. R improved exercice time (504+190 vs 649+125 s, p<0.05), peak exercice workload (777+415 vs 1300+283 Kpm/min, p<0.001). LV EF did not change (23+-9% vs 21+1%, NS). H/M ratio improved from 135+-19% to 156_+_25%,p<0.02). We conclude that 1/rehabilitation induces significant improvement in cardiac neuronal uptake and 2/1-123 MIBG scintigraphy may be a valuable tool in the following assessment of sympathetic adrenergic function in patients with CHF

OSu020 D. Agostini, F. Quennege, A. Be/in*, P. Scanu**, A. Manrique, G. Grollier**, JC Potier**, G. Bouvard. Departments of Nuclear Medicine, Rehabilitation center-Trunville*, Cardiology**, CHU CSte de Nacre, Caen, France. MYOCARDIAL NEURONAL DYSFUNCTION MYOCARDITIS. A 123I-MIBG STUDY.

IN

ACUTE

Right ventricular endomyocardial biopsy currently remains the procedure of choice for identifying patients with symptomatic heart failure due to myocarditis from the larger population with idiopathic dilated cardiomyopathy. The aim of this study was to explore the cardiac neuronal function by using 123I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with confirmed myocarditis on biopsy. We studied 11 patients (age: 39+9 years) with chest pain or congestive heart failure (mean radionuclide left ventficular ejection fraction 40+8%) and 8 normal volunteers (age : 38+7° mean radionuclide LVEF 67+8%, p=0.0003). All patients underwent planar cardiac unaging after intravenous injection of 185 MBq of 123I-MIBG and fight venlzieular biopsy within 7 days. A chest anterior view was acquired 4 hours later on an ELSCINT APEX-415 camera. Thus, heart-mediastinum (H/M) ratio activity was measured, as previously described. All patients had positive histologic findings of myocarditis. Significant impairment of cardiac neuronal uptake of MIBG was observed and based upon a reduction of heart to mediastiunm ratio 148_+19%vs 224+27%, p=0.0004). We conclude that acute myoearditis is associated with an injury of the cardiac neuronal function. In addition to the inflammatory injury of the myocytes, the impairment of adrenergic function may be involved in the cardiac pump failure induced by myocarditis.

1037

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Cardiovascular

OSu021

0Su023

S Nishimura T. Ohta, K. Katoh, K. Sano, T. Tamaki, H. Konagai, K. Yumoto, M. Tanaka, Y o k o h a m a Rosai H o s p i t a l Yokohama, Japan

D. Le Guludec', S. Dinanian**, N. Delahaye*, P. Merlet °, H. Mzabi, D. Samuel, C. Adams, M. Slama**. *Medecine Nucl6aire, hopital Bichat, °SHFJ, DSV-CEA, Orsay, and **Cardiology, hopital A. B~cl~re, Paris, France.

L I M I T E D P R O G N O S T I C V A L U E OF Q U A N T I T A T I V E 123-I M I B G M Y O C A R D I A L I M A G I N G IN P A T I E N T S W I T H HEART FAILURE cardiac 123 -I -met a i o d o b e n z y l g u a n i d i n e (MIBG) scintigraphy has been proposed as a potent p r o g n o s t i c m a r k e r in p a t i e n t s (pts) w i t h severe heart failure. To e x a m i n e w h e t h e r q u a n t i t a t i v e M I B G m y o c a r d i a l image can p r e d i c t the p r o g n o s i s in pts w i t h heart failure, We p r o s p e c t i v e l y s t u d i e d 105 pts (age65y.,M/F=71/34). The s t u d y p t s c o n s i s t e d of four groupl coronary artery disease (CAD) (n=35), idiopathic dilated cardiomyopathy (DCM) (n=22), v a l v u l a r heart d i s e a s e (VD) (n=23) and h y p e r t e n s i v e heart d i s e a s e (HHD) (n=25). C a r d i a c M I B G u p t a k e was a s s e s s e d as the h e a r t - t o - m e d i a s t i n u m activity ratio on the p l a n a r a n t e r i o r v i e w image o b t a i n e d 4 hour after i n t r a v e n o u s injection. LV f u n c t i o n was e v a l u a t e d by UCG. The pts had f o l l o w - u p for 1-30 months (mean 15 months), at w h i c h t i m e 16 pts had d i e d c a r d i a c c a u s e s (6 = s u d d e n d e a t h and i0 = progressive heart failure) , 2 patients from n o n - c a r d i a c causes. The 15 m o n t h s s u r v i v a l rate was 81% in CAD, 70% in DCM, 90% i n V D and 96% i n H H D (p<0.05, DCM Vs HHD) . There was s i g n i f i c a n t d i f f e r e n c e in L V E F (28--+9% vs 42_+15%, p<0.02)but not H/M ratio (0.93--+0.25 vs 0.98-+0.20, p=ns) b e t w e e n d e a d pts due to cardiac causes and survivors. In conclusion, these results s u g g e s t a l i m i t e d v a l u e for q u a n t i t a t i v e M I B G m y o c a r d i a l imaging in p r e d i c t i n g p r o g n o s i s in p a t i e n t s w i t h m i l d to severe heart failure due to various etiologies.

ABNORMAL MYOCARDIAL SYMPATHETIC INNERVATION ASSESSED BY MIBG IMAGING IN FAMILIAL AMYLOIDOSIS

Defective autonomic regulation of the heart has been reported in patients (pts) with familial amyloid polyneuropathy (FAP), but considered to be due to conduction system infiltration rather than to defective innervation. Seven pts with FAP, sensory polyneuropathy and/or peripheral autonomic disorders (5 males, age 40+10) were studied before liver transplantation. Echocardiography, coronary-angiography, ECG ambulatory monitoring and Thallium SPECT were performed. Cardiac MIBG uptake was assessed as the heart to mediastinum activity ratio (H/M) measured on the chest anterior view image obtained 4 hours after intravenous injection. All pts had normal coronary arteries and systolic left ventricular function (mean LVEF= 69 _+ 6 %, cardiac index 3.1 + 0.7 I/mn/mZ), as well as Thallium SPECT images. Echographic studies showed a mild septal hypertrophy (13.1 _+ 1.3 mm) and increased echogeni-city, and normal posterior wall thickness (9.7 + 1.8 mm). Two pts had no patent peripheral neuropathy, while 5 had a severe one with autonomic disorders. MIBG uptake was low in all pts, from 1 to 1.45 (mean 1.19 _+0.18), significantly decreased compared to 6 age-matched controls (1.96 + 0.22, p<0.01), even when peripheral disorders were not apparent. Conclusion. In pts with FAP, a sympathetic myocardial denervation seems a frequent and early feature, before alteration of the LV function and even in the absence of peripheral neuropathy.

OSu022

OSu024

PZanco.GFBuja*,F.Chierichetti,M Miorelli*,N.Borsato,S.Cargnel and G.Ferlin. Nuclear Medicine-Castelfranco V.,*Cardiology Dept-Padua Univ.,Italy.

A. Giordano,G.Lanza*,M.L.Calcagni,G.Meduri,A.F@,C. Pristipino*,C.Trani*,A.Maseri*,R.Franceschini**, L.Troncone. Departments of Nuclear Medicine and *Cardiology, Catholic University, Rome ; **Sorin Biomedica, Saluggia (Vercelli)- Italy.

SYMPATHETIC INNERVATION, PERFUSION AND METABOLISM IN HYPERTROPHIC CARDIOMYOPATHY. To evaluate myocardial adrenergic activity, blood flow and metabolism in hypertrophic cardiomiopathy(HCM),l 7 pts were studied(l 4m,3f, aged 18-63yrs,mean 37).Three pts showed a progression to ventricular dilatation(LVD).All the pts underwent:l)I-123 MIBG-SPECT (MS) and planar LAO 45 ° (MPI) at 30' and 5 h;2) rest N13-NH3 perfusion PET(PP); 3)glucose-load 18F-FDG-PET(MP);4)echocardiography.As controls, 5 normal subjects (4m, 1 f, aged 33-62yrs, mean 43) were submitted to MIBG study.With regard to MPI, a wash-out index (WI=30'/Sh myocardial uptake ratio) and a heart/lung ratio at 5 h (t-ILR) were calculated. Regarding the SPECT and PET studies a severity index (SI), concerning the extension and the severity of the uptake defects, was calculated.All the HCM pts presented a lower HLR respect to the normals (1.19+_0. I 1 vs 1.61_+0.18,p<0.0001), while the 3 pts with LVD presented a significant rise in WI in comparison to both normals and non-dilated pts (respectivelyl.96+0.12, 1.63_+0.08, 1.68+0.09, p=0.007 and 0.002). The SI of MS resulted significantly higher in HCM with respect to the normals (8.88+4.99 vs 2.25_+2.21, p=0.019), with highest values in LVD (10.66+_7.02, p=0.003). The SI of PP and MP distinguished LVD from non-dilated pts well(respectively 7.0_+5.29 vs 2.0_+1 94, 9.33+3.51 vs 24+2 17, p 0.05 and 0.005). The defects were not correlated to the site of hypertrophy at the echocardiography. The uptake defects at PP and MP are weakly correlated in site (k=0.421), but not with MIBG defects In conclusion our experience could suggest that 1) all HCM pts presented severe damage in sympathetic innervation, identified as low HLR; 2) defects in perfusion and metabolism of the myocardium are present too, greater in dilated pts; 3) a faster washout of MIBG from the heart could be a marker of evolution toward venticular dilatation.

1038

ASSESSMENT OF HEART FUNCTION IN S Y N D R O M E - X AND SPET SCINTIGRAPHY.

AND (SX)

LUNGS SYMPATHETIC BY 123I-MIBG PLANAR

A i m of the study was to quantify 123I-MIBG (MIBG) uptake of heart and lungs in i0 pts with SX (4M/6F, mean age 53±5 yrs, with anginal pain, exercise induced ST depression and normal coronary angiography) as compared to i0 control (C) subjects (3M/7F, mean age 53±10 yrs) and to assess the reproducibility of the scintigraphic findings by repeated studies. SX patients and C subjects underwent MIBG scintigraphy (185 MBq of high specific activity MIBG, 3.1 MBq/~g) by planar scans at 30,60,120,180 min and 18 hrs and SPET at 180 min. Seven SX pts repeated the procedure after ~ 3 months for reproducibility assessment. SX pts also underwent 20IT1 stress/redistribution SPET. Results: 5/10 SX pts showed reduced or absent global cardiac uptake of MIBG (<1.56 H/M ratio at 180 min); Lung/Mediastinum ratio was normal in I0/i0 SX pts (>1.005 at 180 min). 7/10 SX pts showed regional MIBG and 201TI defects at SPET (MIBG regional score was 35±3 in SX pts and 4.0±2.5 in C subjects; p=0.008). Reproducibility of H/M ratio and MIBG regional score was high (r=0.96,p=0.001 and r=0.99,p<0.001 respectively). In conclusion: for the first time it is demonstrated that global and regional MIBG abnormalities are frequent in the heart of SX pts while the lungs (also richly innervated by the sympathetic system) are unaffected.

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A.Bnmo, G.M DeFerran, M.Castellani,G.Marotta, R.Casan, S.G,Pnon, Gasparini M, CNapolitano, PJ.Schwartz,P.Gerundini. . * . ^ Nuc[ Med. Dept.Osp Maggiore, IRCCS, Mdano, Chn Phisiol, Milano Univ.. - Cardioi Dept..PaviaUniv.,Italy MYOCARDIAL UPTAKE AND PATIENTS WITH LQTS S Y N D R O M E

DISTRIBUTION

OF

123I-MIBG

IN

The Long QT Syndrome (LQTS) is an idiopathic congenital cardiac disease characterized by a QT prolongation on the ECG and, clinically, by a high incidence of cardiac sudden death. Nowadays the "s~rnpathetic imbalance" based on a prevalence of left side simpathetic innervation is the most accreditate pattrogenetic mechanism. The myocardial distribution of 123I-MIBG in 17 LQTS pts (5 mate and 20 female; mean age 20 yrs) and 10 volunteers subjects (4 male and 6 female; mean age 41 yrs) ~as investigated. A myocardial SPET (180°; 35"/6°angular step) was performed 4 hours after i.v. injection of 222 MBq of 123I-MIBG The global myocardial uptake ~sas calculated positioning regions of interest (ROIs) on the whole left ventricle, right lung, and mediastinum on the LAO 40 image. The mean values of H/M (hearV'mediastinumratio) and H/L (heart/lung ratio) in LQTS pts were found statistically higher than the mean values of controls (respectively 2.51+_0.38 vs 2.06_+0.32 and 1.67_+0.24vs 141+0.31). A segmental visual analysis and a semiquantitative evaluation of the regional uptake of 123I-MIBG on the short axis midventricular slices demonstrated a significative increase in the relative uptake of MIBG on the inferolateral region (78__+12.57 vs 56.2_+14.09) and a relative decrease on the anteroseptal region (74.8%_+11.04 vs 84.5%+_5.34) in LQTS pts. Furthermore, the anterior/mferobasal ratio (A/I) obtained drawing two ROIs on the vertical long axis images shov,ed a significant relative decrease in LQTS pts (1.00_+0.16vs 1.52_+0A7) and confirmed the visual and the semiquantitativc data analysis. In conclusion, our data suggest that an increased catecholamines containt could exist in LQTS. Moreover the different regional pattern of MIBG myocardial distribution between normal and LQTS is consistent with "sympathetic imbaiancc hypothesis".

Cardiovascular

OSu027 S. Severi*, R. Bettini, L. Visona', E. Lorenzi*, M. Camerani* Nuclcar Medicine*- Cardiology. S.Chiara Hospital Trento Italy FUNCTIONAL DYSINNERVATION OF THE LEFT VENTRICLE DEMONSTRED BY 123I-MIBG SCAN IN ARRHYTHMOGENIC VENTRICULAR CARDIOMYOPATHYDYSPLASIA (AVC).

The 123I Metaiodobenzylguanidine tomographic scan (MIBG SPET) maps the post-ganglionic presynaptic function of the left ventricle using the same uptake and storage norepinephrine systems. With this modality we studied the AVC of the right ventricle caracterized from presence of Hyperkinetic Ventricular Arrbythmias (HVA) frequently manifested with a life treathening aspect. We tried to document the presence of left ventricle involvement especially in an early stage of the disease when all the traditional imaging diagnostic tools were negative. Matherials a n d M e t h o d s : we studied 17 patients with HVA without evaluable cardiomyopathy (NC), 22 with AVC and 5 healthy subjects as controls. In all of them a complete cardiological study with baseline ecg, holter, angiographic study (15/39), ecocardiography M and 2D mode, magnetic resonance (31/39) and programmed ventricular stimulation were performed. The Nuclear Medicine protocol was comprehensive of a perfusional tomographic rest scan with 99mTe-sestamibi or tetrofosmin (99mTc SPET) and of a MIBG SPET with double blind qualitative and quantitative evaluation. Results: Sympathetic Nervous System (SNS) functional defects, with prevalence in the apex and in the inferior wall, were demonstred in 26/39 (5/17 NC. 21/22 AVC). All the controls were normal. Versus AVC the MIBG SPET sensitivity was 95%, the specificity 70% and the accuracy 84%. The extension and the severity of the MIBG SPET defects were greater and perfusion defects in the same area was present only in patients with life treathening arrhythmias (sustained VT and aborted SD). We had 13/22 defects in the left ventricles without evidence of disease at morpho-functional studies (MR, Echo and Angiography). Conclusions: Our data shown: a) the MIBG SPET is a sensitive tool to diagnose the left ventricular functional dysinttervation in the AVC, b) among the imaging moralities the MIBG positive scan was the only sign of left ventricular involvement in 59% of AVC patients, c) the SNS involvement of the left ventricle is more frequent and greater in the severe disease d) we look forward to see if the 5 patients with HVA but without evaluable cardiomvopathy, demostrated as positive with the MIBG SPET, will develop an AVC,

OSu026

OSu028

S. Dresel, M.Weiss, O.Schnell #, K.Tatsch, K.Hahn Department of Nuclear Medicine and #Diabetes Research Institute, University of Munich, Germany

Garcfa-Burillo A Cinca J, Castell J, Carrefio A, Porta F, Candell J, Ortega D. Hospitals Vail d'Hebron. Barcelona. UPTAKE OF 99mTc~TETROFOSMIN IN HEALED TRANSMURAL MYOCARDIAL INFARCTION IN PIGS.

EVIDENCE FOR CARDIAC DYSINNERVATION IN PATIENTS WITH NEWLY DIAGNOSED IDIOPATHIC DIABETES MELLITUS 1-123 MIBG scintigraphy is an established non-invasive method for the assessment of cardiac sympathetic dysinnervation in patients with longstanding diabetes mellitus. In newly diagnosed idiopathic diabetes mellitus (IDDM) ECG signs indicating cardiac autonomic neuropathy are usually absent. Therefore, early detection of the latter is a diagnostic challenge. The current MIBG-SPECT study was undertaken to evaluate whether global and regional sympathetic cardiac dysinnervation of the leftventricular myocardmm occurs in this patient group and to further characterize its degree and patterns. In 33 patients (<35 yrs) suffering from newly diagnosed, metabolically stabilized IDDM SPECT scans were performed 5 hrs p.i. of 185 MBq 1-123-MIBG (Siemens MULTISPECT 3, LEHRcollimators). Global and regional uptake patterns were evaluated by two independend observers using polar maps and a relative score ranging from l=normal uptake to 6= severe defect. Data of 9 patients suffering from carcinoid without clinical cardiac findings were used as controls. To exclude that possible defects may be due to perfusion abnormalities, MIBt-scans (250 MBq Tc-99m-MIBI) were additionally acquired. 20/33 patients showed reduced global MIBG uptake (gMU) compared to the controls. In 15 patients a slightly reduced (gMU 2/3), _ global anterior lateral posterior septal apex MW 2,77 2,87 2,43 2,33 2,73 2,93 SD 0,82 1,01 0,94 0,92 1,08 1,t6 in 5 patients a markedly reduced uptake (gMU > 4) was found. Perfusion scans were normal in all cases. A predominant involvement of particular myocardial regions was not observed. Only 2 patients presented with typical ECG-based cardiac autonomic neuropathy. Newly diagnosed, metabolically stabilized IDDM patients show evidence for cardiac sympathetic dysinnervation detectable by 1-123MIBG-SPECT. The significant higher rate of positive MIBG compared to ECG findings suggest a higher sensitivity of MIBG-SPECT for the early detection of cardiac autonomic neuropathy in those patients.

99mTc-labeled radiotracers can distribute across the cell membrane of cultured mouse fibroblasts. Hypothetically, connective cells within the infarct scar may take up imaging agents and this would be relevant for the assessment of myocardial viability, Methods: 23 chloralose anesthetized open chest pigs (25-30 kg) with a 1month old transmural myocardial infarction elicited by ligature of the left anterior descending (LAD) coronary artery underwent a second coronary occlusion at the LAD (n= 13) or at the circumflex (Cx) coronary artery (n=10). One hour after coronary occlusion 5 mCi of 99mTc-tetrofosmin were injected into the left atrium and specific activity (well counting, cpm/g) during 20 s was measured in transmural samples obtained at the infarct scar, acute ischemic area, and normal myocardium. Fluorescein and triphenyl-tetrazolium were use to identify acute ischemic and infarct scar regions. Results: The Table depicts mean _+ SD of % activity (cpm/g) respective to normal tissue: 2nd ligadure

Infarct Scar

Acute Ischemia

LAD Cx

18.1 _+11.4 2 6 . 0 -+ 8.9

5.2+5.7* 6.3_+3.8"

(') p<0.O01 compared with infarct scar. A thin band of about 0.25 mm of subendocardial cells survived in both the necrotic scar and acute ischemic area, In conclusion: The infarct scar takes up 99mTc tetrofosmin despite the tissue is virtually lacking of viable myocardial cells. Radiotracer uptake at the necrotic scar is approximately three times greater than that in acute ischemic myocardium.

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Cardiovascular

OSu029

OSu031

J.Ku~mierek, A.Plachci~ska, A.Ko~mider, E.Trzos, M . K o ~ m i d e r , M e d i c . U n i v . o f Lodz, D e p t . N u c l . M e d . I n s t . C a r d i o l . , l - s t Cl. Int. D i s e a s e s ; Poland.

ZdBURAK, H. AKIN, S. BUKET, A. SAG,CAN, M. ARGON, Y. ATAY, I. DURMAZ, Y. DUMAN. Ege University, Depts. of Nuclear Medicine, Cardiology, Cardiovascular Surgery, izmir, Turkey.

PLANAR 9~Tc-MIBI CARDIAC PERFUSION SCINTIGRAPHY IN S Y N D R O M E X; A S S E S S M E N T OF F R E Q U E N C Y A N D T Y P E OF PERFUSION DEFEECTS.

THE ROLE OF Tc-99m TETROFOSMIN MYOCARDIAL PERFUSlON IMAGING IN DIAGNOSIS OF SIGNIFICANT CORONARY ARTERY DISEASE: A COMPARATIVE STUDY WITH TI-201

Anginal chest pain in patients with coronarographically normal arteries is a basis of diagnosis of syndrome X. The aim of work is assessment of perfusion defects frequency and type in syndrome X. The study included 109 patients: group 1 - 61 patients with syndrome X; group 2 - 48 patients, with perfusion defects resulting from critical stenosis of at least one main coronary artery (without a history of myocardial infarction). Perfusion impairment, based on quantitative analysis of scintigrams, was detected in 18 of 61 patients with syndrome X, that amounted to 30 per cent. A comparison of perfusion defect type in group 1 and group 2 was based on a reversibility index (RI) of stress perfusion defects. The RI was defined as a ratio of a difference between quantitative measurements of stress (S) and rest (R) SgmTc-MIBI uptake deficit to its uptake deficit in stress scintigram [RI=(S-R)/S] (RI may be positive as well as negative). Mean values of RI in group of patients with syndrome X amounted to 0.04 (s=0.76) and was signifficantly lower than in group of patients with criticaly stenosed coronary arteries: RI = 0.48 (s=0.47), (p<0.05). Conclusions: l.In about 1/3 of patients with syndrome X a quantitative scintigraphy revealed perfusin defects. 2.In the group of patients with syndrome X a degree of reversibility of stress perfusion defects was signifficantly lower than in the group of patients with critical stenosis of coronary arteries (perfusion defects were rather fixed - they were present both in stress and rest scintigrams).

The aim of this study was to determine the utility of Tc-9gm Tetrofosmir (TFM) cardiac imaging in diagnosis of significant coronary artery disease (CAD) in patients (Lots)with chronic left ventricutar dysfunction in comparison to TI-201 cardiac imaging. Until now, 18 pts (15 men, 3 women) with angiographica~ly proven significant CAD were studied by one day exemise-rest TFM and exercise rest-reinjoction (RI) TI-201 cardiac imaging. For each study, semiguantitative visual analysis was performed by dividing 3 short axis (more apical, mid-ventricuiar, more basal) and 1 vertical long axis slices covering the whole ventricle into 20 segments and each segment was analyzed by a 4 point scale (0-= normal - 3= no uptake). Uptakes ~ 2 were accepted as perfusicn defects and reversibility was defined as a shift towards <1 grade on subsequent images. The degree of uptakes were correlated with the significanceof coronary artery stenosis. Fifteen Lotshad muitiveasel disease, of these 8 t0ts had one and 4 pts had 2 totally occluded coronary artedas (TOCA). Of 360 myocardial segments, 128 were supplied by TOCA (35.5%), Group I, 191 were supplied by significantly stenotic arteriee (53%), Group II and 41 (11.5%) were normal. In Group I, TFM imaging demonstrated 14 reversible (11%) and 76 fixed (59%) defects while 15 segments were reversible (12%) and 69 were (54%) fixed in TI-201 imaging. After RI, 15 additional segments were reversible. In Group II, both TFM and TI-201 demonstrated 25 reversible defects, no fixed defect was observed. In TFM myocardial perfualon imaging, more fixed defects corresponding tc myocardial segments supplied by totally occluded arteries were observed when compared with TI-201 scintigraphyindicatingdiscrepancy between twc tracers. Therefore, we suggest that, fixed TFM defects has to be interpreted with caution in pta wl~ significantCAD. The role of TFM over TI201 in this respect needs to be further investigated.

OSu030

0Su032

J. vom Dah!, E. Kleinhans, K.-C. Koch, T. Reffelmann, G. Schulz, H.G. Klues, M. Sigmund, U. Buell, P. Hanrath Departments of Cardiology and Nuclear Medicine, University of Aachen, Germany

F.Branly, P.Y.Marie, P.Olivier, N.David, S.Denet, N.Quiri, T.Arsena, N . H a s s a n , M.Angioi, N.Danchin, G . K a r c h e r a n d A . B e r t r a n d . D e p a r t m e n t s of C a r d i o l o g y a n d of N u c l e a r M e d i c i n e , Nancy, FRANCE.

HIGH FREQUENCY ROTATIONAL CORONARY ATHERECTOMY INDUCES A TRANSIENT MYOCARDIAL ISCHEMIA AS DETECTED QUANTITATIVELY BY Tc-99m SESTAMIBI SPECT

I M P A C T OF T H E S U B S E Q U E N T C H A N G E S IN A N T I - A N G I N A L T H E R A P Y O N THE P R O G N O S T I C V A L U E OF E X E R C I S E TI201SPECT PARAMETERS Exercise TI201-SPECT provides important prognostic i n f o r m a t i o n in p t s w i t h c o r o n a r y a r t e r y disease (CAD). However, a n t i - a n g i n a l treatments, w h i c h a r e l i k e l y to m o d i f y the results, are f r e q u e n t l y w i t h d r a w n b e f o r e o r f u r t h e r a d a p t e d a f t e r the test. T h i s s t u d y w a s a i m e d to d e t e r m i n e w h e t h e r e x e r c i s e T I 2 0 1 - S P E C T gave b e t t e r p r o g n o s t i c inform a t i o n w h e n p e r f o r m e d u n d e r the same a n t i - a n g i n a l t r e a t m e n t t h a n t h a t g i v e n for follow-up. W e s t u d i e d 421 pts, w i t h k n o w n or s u s p e c t e d CAD, who had exercise TI201-SPECT and coronary angiography and who were subsequently treated medically. A n t i - a n g i n a l t r e a t m e n t at exercise T I 2 0 1 - S P E C T w a s the s a m e as that g i v e n for f o l l o w - u p in 168 p t s (GI) a n d d i f f e r e n t i n 256 (GII). D u r i n g 5±2 y r s of follow-up, 45 p t s (11%) h a d c a r d i a c d e a t h or m y o c a r d i a l i n f a r c t i o n (GI: 12% vs GII: 10%, NS). O n a C o x model, p r o g n o s t i c i n f o r m a t i o n s p r o v i d e d by each catheterization variable ( n u m b e r of d i s e a s e d vessels, L V e j e c t i o n fraction, ..) a n d b y e x t e n t of i r r e v e r s i b l e T 1 2 0 1 defect, w e r e h i g h l y s i g n i f i c a n t in b o t h GI a n d GII ; t h o s e v a r i a b l e s provided equivalent relative r i s k s in t h e 2 groups. B y contrast, b o t h p r e s e n c e a n d e x t e n t of reversible T1201 defect gave a highly significant p r o g n o s t i c i n f o r m a t i o n in G I (p =.007 and p =.001) b u t n o t in G I I (p=.9 and p =.08). In p t s w i t h k n o w n o r s u s p e c t e d CAD, e x e r c i s e ischemia, assessed by TI201-SPECT (reversible, d e f e c t ) , l o s e s its p r o g n o s t i c s i g n i f i c a n c e w h e n the t e s t is n o t p e r f o r m e d u n d e r the s a m e a n t i a n g i n a l t r e a t m e n t t h a n t h a t g i v e n for follow-up.

High frequency rotational atherectomy is a valuable interventional tool for revascularisation of long calcified, ostial, or moderately angulated coronary lesions. Myocardial hypoperfusion during the procedure has been reported to result from coronary spasm and peripheral capillary obstruction due to distal embolisation of debris or washout of vasoactive substances. This hypoperfusion is often associated with anginal symptoms, ischemic ECG changes or atriovenlricular block. To evaluate quantitatively the extension and severity of this phenomenon, 23 consecutive patients (14 men; 58+7 years; 17 type C, 6 type B2 lesions; 12 LAD, 10 RCA and 1 circumflex stenoses) were studied using resting SPECT with Tc-99m sestamibi before rotablation, during the procedure with SPECT imaging after 90 minutes, and two days after the procedure. Visual analysis revealed reversible perfusion defects in regions corresponding to the revascularised vessel in 18/23 patients, while 5 patients had no defect. For quantitative analysis, the left ventricular myocardium was divided into 25 regions. Perfusion was expressed as % of sestamibi uptake of the region with maximal uptake. Baseline perfusion in the territory supplied by the target vessel was 79+8%, decreased to 58+12% (p<0.01 vs. baseline) during the rotablation, and normalised again two days later to 79+12% (p<0.01 vs. during rotablation). Transient perfusion reduction below normal minus 2.5SD, normalised for the region location, was observed in 3+2 regions/patient. During 48 hour monitoring, there were no persistant ECG changes or a significant increase of creatine kinaseMB or cardiac troponin T indicating myocardial necrosis. None of the following factors correlated with size or severity of induced perfusion defects: vessel, type of stenosis, degree of calcification, lesion length, collaterals, burring time, bur size, and gender. Thus, coronary rotablation induces a significant transient regional ischemia as detected and quantified by sestamibi-SPECT during the intervention. Procedural and periprocedural factors correlating with the extent of hypoperfusion could not be identified.

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Cardiovascular

OSu033 P.Zanco, A.Zampiero*, A.Favero°, F.Chierichetti, D.Rubello, B.Saitta and G.Ferlin. Nuclear Med.-Castelfranco V, *Cardiology-Camposampiero, °C.R.O.Aviano - Italy.

OSu035 H. Htffkert L. Rybinsky, P. Ahlhom, H.W. Fritsch, J. Seelinger, F. Horbach, R. Moosdorf, K. Joseph Klinikum der Philipps-Universitiit Marburg, Abteilung for Klinische Nuldearmedizin

INCREMENTAL VALUE OF MIBI-SPECT IN LONG-TERM PROGNOSTIC EVALUATION OF CAD PATIENTS.

FOLLOW-UP OF TRANSMYOCARDIAL LASER RE,VASCULAR/SATION (TMR) WITH TC-99M-TETROFOSMIN Transmyocardial laser revascularisation may be an additive method for myocardial revascularisation in patients after successless CABG. We studied 50 patients with CABG and severe unstable angina pectoris to evaluate improved myocardial perfusion after TMR. Patients: In 19 patients revascularisation was performed by combination of CABG and TMR (group 1). As CABG was not possible, the other 31 patients were treated by TMR only (group 2). Methods: Due to the severeness of CAD the investigation before and 10 days after TMR could only be performed at rest. Three months after TMR myocardial perfusion was evaluated using a one-day exercise-restprotocol. During exercise 185 MBq Tc-99m-Tetrofosmin were injected intravenously and at rest 555 MBq, respectively. SPET-studies were acquired one hour after injection with a 3-head gamma-camera with high resolution collimators. Projection-data were acquired in 120 image matrices with 40s acquisition time each. The matrix size was 128x128 pixels. After prefiltefing of the projection-data (Butterworth, 0.35 Nyquist, order 4) short axis and radial long axis slices were reconstructed. For visual and semiquanfitative assessment polarplots were derived from radial longaxis slices. Results: In 7 patients of group 1 and 16 patients of group 2 Perfusion defects had decreased 3 months after TMR. No changes of the scintigraphic findings were detected in 10 patients of group 1 and in 12 patients of group 2. In crease of perfusion defects were found only in 3 patients of group 1 and in 2 patients of group 2. Conclusion: TMR may be a successful new method for revascularisation of those myocardial areas which cannot be treated by CABG. Myocardial scintigraphy with tetrofosmin is able to show improved myocardial perfusion and is leasable in the follow up after TMR.

The aim of the study was to compare the role of different clinical findings and instrumental techniques in the risk stratification of CAD patients. To this end, a follow up program was started in 1988: during the ensuing 3 years, 300 pts submitted to rest-stress sestamibi SPECT for CAD were enrolled. So far 269 pts (206m, 63f, aged 27-68 yrs) have completed a follow up of at least 4 yrs (range 48-72 mo, mean 55). At enrolment 92 patients were affected by a previous myocardial infarction (MI), occuring at least 3 mo before, and 72 pts suffered from typical angina. Rest echocardiography, calculating the wall motion index (WMI) and the ejection fraction (EF), was also performed on 121 pts. Beside SPECT and echo findings, age, gender, risk factors for CAD, previous MI, angina, stress double product and heart rate, as well ST depression during stress were also included in the analysis. During the follow up, 46 pts (17%) presented cardiac events (CE): 5 cardiac death, 8 MI and 33 unstable angina. Multivariate analysis, using logistic regression method, indicated that an abnormal MIBI scan (p=0.0004), the presence of a reversible defect on MIBI-SPECT (p=0.01), the extension of the defect (p=0.007), and the presence of typical angina (p=0.001) were the only significant and independent prognostic factors of ensuing CE. The relative risks, calculated as oddsratio, were respectively 36.49, 6.58, 1.23 and 4.85. Only 1 pt in a total of 46 with CE presented a normal scintigraphy. Thus, in our experience, MIBI SPECT proved to be a fundamental tool in long-term risk stratification of CAD patients.

OSu034 Marcel L Geleijnse, Abdou Elhendy, Ron T van Domburg, Jan H Cornel, Eric P Krenning, Paolo M Fioretti. Thoraxcenter and Department of Nuclear Medicine, University Hospital Dijkzigt and Erasmus University, Rotterdam, The Netherlands.

OSu036 T. Gr~nin.q*, J. Kropp*, S. Wiener*, B. W~tzig**, S. Sch~ler**, W.-G. Franke*, *Department of Nuclear Medicine and **Heart Center, University Hospital, Dresden, Germany

PROGNOSTIC VALUE OF DOBUTAMINE SESTAMIBI SCANS

ASSESSMENT OF TRANSMYOCARDIAL LASER REVASCULARIZATION BY GATED SESTAMIBI SCINTIGRAPHY PRELIMINARY RESULTS

Rationale: There are no published data on the prognostic value of dobutamine-atropine sestamibi SPECT (DASS). Methods: 392 patients with chest pain underwent DASS. Mean age was 60 years, 220 were men and 190 had a previous myocardial infarction. SPECT patterns were divided into normal or equivocal (n=130), fixed defects alone (n=102), reversible defects alone (n=60) and fixed plus reversible (or partially reversible) defects (n= 100). A reversible defect score was calculated by summating the reversible defects according to a 6 (extent) x 4 (severity) model (range 0-18), and was subsequently corrected for peak rate-pressure product. The value of clinical and imaging variables was analyzed using stepwise logistic regression. Results: During an average follow-up of 22 + 13 months, 44 patients had hard cardiac events (27 cardiac death, 17 nonfatal myocardial infarction). Annual event rates for the imaging patterns were: 0.8% for normal, 6.8% for fixed defects alone, 8.1% for reversible defects alone, and 11.6% for fixed plus reversible defects. Patients with a corrected reversible defect score of 0 and high stress, 0 and low stress, 1-2, 3-4, > 4 (n=100, 100, 109, 62, 21) had a 2.1%, 5.0%, 5.5 %, 13.0 % and 14.6 % annual event rate, respectively. Multivariate analysis demonstrated that age (OR=2.1; 95% C1, 1.0-4.4), history of heart failure (OR=2.6; 95% CI, 1.3-5.2), an abnormal scan (OR= 10.0; 95 % CI, 2.3-43.0), and reversible defects (OR=3.2; 95 % CI, 1.6-6.4) had independent predictive value. Conclusions: In a heterogeneous population referred for chest pain, DASS provides useful, independent prognostic information, according to the imaging pattern and extent and severity of perfusion abnormalities.

-I-ransmyocardial laser revascularisation (TMLR) is a relatively novel treatment for coronary artery disease in patients (pts) unsuitable for conventional myocardial revascularization by CABG or PTCA. In order to determine whether TMLR led to an increased myocardial perfusion in lased segments gated sestamibi scintigraphy was carried out after combined dipyridamol/ergometric stress and at rest (standard one-day protocol) at baseline and 1, 3, 6, and 12 months after surgery. Seventeen pts (7 women, 10 men, mean age 67 yrs) underwent TMLR, which was combined with single or multiple CABG to nonlased segments in 16 cases. Five pts were excluded from the study because a baseline scan could not be obtained in 2 pts, 2 pts died before the first follow-up and 1 patient did not attend for her follow-up investigations. A thallium scan was required in 3 pts for verification of myocardial viability which is mandatory before TMLR. Before TMLR myocardial perfusion at stress in the segments to be lased was decreased in 4 pts. After a total follow-up of 3 months (n=3), and 6 months (n=l), respectively, this was improved in 2 pts and remained unaffected in 2 pts. A decreased peffusion at rest in 8 pts improved in 2 pts and did not change in 6 pts after a follow-up of 1 month (n=2), 3 months (n=5), and 6 months (n=l), respectively. Mean left ventricular ejection fraction (LVEF) was 62% before treatment and 58% at the end of the follow-up period. Our preliminary findings show that perfusion of previously ischaemic myocardium was improved by TMLR in 2/4 pts, whereas perfusion of scar tissue improved in 2/8 pts. Myocardial contractility as measured by LVEF did not change significantly. Changes in myocardial perfusion after TMLR can be assessed by gated sestamibi scintigraphy. 1041

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Cardiovascular

0Mo037

0Mo039

A.Flotats. [.Carri6, M.Estorch, Ll.Bern/t, A.M.Catafau, M.Ballester. Hospital de Sant Pau, Barcelona, Spain.

R. Valkema, D. Poldermans, A.E.M. Reijs, J. van Peski, R. Rambaldi, P.M. Fioretti, E.P. Krenning. Depts. of Nuclear Medicine, Internal Medicine III, and Thoraxcenter, University Hospital Dijkzigt, Rotterdam, The Netherlands.

N I T R A T E ADMINISTRATION T O E N H A N C E D E T E C T I O N O F M Y O C A R D I A L VIABILITY BY Tc-99m-TETROFOSMIN SPECT.

99mTc-tetrofosmin myocardial perfusion tomography on baseline and after nitrate administration, with a 2-day protocol, was compared to restreinjection 201-T1 SPECT studies to assess whether nitrates enhance the detection of viable myocardium with 99mTc-tetrofosmin. 12 patients with severe coronary artery disease, previous myocardial infarction and EF < 40 % underwent baseline and post-nitroglycerin (0.4 mg sublingual) 99mTc-tetrofosmin imaging, and 201-T1 studies within the same week. Tomograms were divided into 15 segments based on 3 short-axis slices, 1 vertical-axis slice and 1 horizontal-axis slice.

On baseline studies, quantitative regional distribution (% of peak activity) of 99mTc-tetrofosmin correlated with that of 201-TI (r=0.807, p < 0.001). Viability was defined as presence of tracer uptake -> 50 % of peak activity at baseline or after reversibility. On baseline 99mTctetrofosmin images, 37 (20%) myocardial segments had normal tracer uptake ( _. 85 % of peak), 88 (49 %) mild-moderate (50-84 % of peak) and 55 (31%) severe reduction of uptake ( < 5 0 % of peak). 22 (12%) segments, 14 with mild-moderate and 5 with severe reduction of uptake, showed reversibility after nitrates. All these segments had either reversibility on 201-TI scans (6 segments) or had uptake _>50% of peak activity on the resting 201-T1 scan (16 segments). 14 segments which remained unchanged after nitrate administration showed 20I-T1 reversibility; 11 (79%) of these segments had 99mTc-tetrofosmin uptake _>50 % of peak activity on the baseline scan. Overall agreement between 99mTc-tetrofosmin with nitrates and thallium-reinjection was 90%. Administration of nitrates enhances the detection of viable myocardium on 99mTc-tetrofosmin perfusion studies. Nitrate-induced changes correlate with viability criteria on thallium-reinjection studies.

DETECTION OF MYOCARDIAL VIABILITY BY SIMULTANEOUS ACQUISITION OF Tc-99m-TETROFOSMIN AND 18-FDG USING A 3-HEAD SPECT CAMERA. Aim: To study the ability of the Picker Prism 3000 3-head camera, with ultra high energy (UHE) collimators, for assessment of myocardial viability using dualisotope simultaneous acquisition (DISA) SPECT with Tc-99m-tetrofosmin and 18-FDG, in comparison with low dose dobutamine echocardiography (LDDE). Methods: Thirteen non-diabetic patients with coronary artery disease, all with ejection fraction -<40%, were studied with DISA-SPECT and LDDE prior to coronary revascularization. LDDE was performed using dobutamine (5 and 10 ,ug/kg/min. for 5 min. each). Standard views were obtained. Sixty rain. after 600 MBq Tc-99m-tetrofosmin i.v. at rest, SPECT (low energy high resolution (LEHR) collimators, 360 °, 3 ° steps of 30 see.) was obtained. Acipimox (250 mg p.o.).in combination with a light carbohydrate-rich meal was given to stimulate myocardial 18-FDG uptake. Ninety rain. later 185 MBq 18FDG was injected; DISA-SPECT (UHE, 360 °, 3 ° steps of 30 sec.) was started 45 min. post injection. For comparative analysis vascular territories (LAD, LCX, RCA) were visually scored for LDDE and DISA-SPECT, independently of each other. Territories with areas of severe hypokinesis, akinesis, or dyskinesis at rest were scored for viability (improved wall motion during dobutamine infusion or FDG/tetrofosmin mismatch with LDDE and DISA-SPECT respectively) and scar. Territories without severe dyssynergies at rest were scored as "normal". Results: The image quality of the tetrofosmin perfusion images from DISASPECT was slightly inferior to the initial rest images with the LHER collimators, but the diagnostic value of both sets was the same. The myocardial 18-FDG uptake was good in all patients, yielding images of good quality. Of the 39 vascular territories, 31 showed areas of severe dyssynergy at rest. Of these 31, 13 contained viable and 7 no viable dyssynergic areas with both techniques; 7 territories with improvement with LDDE showed no mismatch with DISASPECT, and 4 without LDDE improvement showed mismatch with D[SASPECT (agreement 65%). Conclusion: Tc-99m-tetrofosmin and 18-FDG DISA-SPECT with e 3-head camera after stimulated myocardial glucose uptake by acipimox is a promising technique for assessment of myocardial viability. Further clinical follow-up in a larger group after revasculadzation is needed.

0Mo038

OMo040

L Mortelmans A Maes, J Nuyts, M Borgers, P Sergeant, G Bormans, W Flameng, D e p a r t m e n t of N u c l e a r Medicine, U.Z. K.U. Leuven, B e l g i u m

A.Baszko, K. Btaszyk, A.Cieglifiski, L.Paluszkiewicz, A.Szyszka, Z.Sarnowska, P.Kwinecki, LSowifiski, A.Poni~tyfiski Institute of Cardiology & Department of Endocrinology, University of Medical Sciences. Poznah, Poland - PL

A S S E S S M E N T OF M Y O C A R D I A L V I A B I L I T Y U S I N G T C 9 9 M - S E S T A M I B Z SPECT: C O M P A R I S O N W I T H M Y O C A R D I A L U L T R A S T R U C T U R E , PET A N D FUNCTION V i a b i l i t y a s s e s s m e n t w i t h T c 9 9 m - s e s t a m i b i was s t u d i e d in the s e t t i n g of c h r o n i c c o r o n a r y a r t e r y d i s e a s e (CAD). Thirty patients with CAD and anterior wall motion abnormalities were prospectively included. A Tc99ms e s t a m i b i r e s t i n g S P E C T study, a PET f l o w (13NH3) and m e t a b o l i s m (18FDG) study, and a n u c l e a r a n g i o g r a p h y w e r e performed preoperatively. During bypass surgery, a b i o p s y was t a k e n f r o m the left v e n t r i c u l a r a n t e r i o r w a l l for a s s e s s m e n t of % f i b r o s i s . Three months after surgery, a n u c l e a r a n g i o g r a p h y was repeated. S i g n i f i c a n t l y h i g h e r M I B I v a l u e s w e r e f o u n d in the PET v i a b l e g r o u p (85±14% vs 58_+19%, p<0.0l) and in the group with enhanced contractility at 3 m o n t h s (76_+13% vs 53-+22%, p<0.01). A l i n e a r r e l a t i o n s h i p was found b e t w e e n MIBI u p t a k e a n d % f i b r o s i s in the b i o p s y (y=-0.86x+93; y = % f i b r o s i s ; x = M I B I uptake, r:0.78, p < 0 . 0 0 0 0 1 ) . Using a c u t o f f v a l u e of 60% of p e a k for M I B I a n d f u n c t i o n a l i m p r o v e m e n t as g o l d s t a n d a r d for viability, p o s i t i v e a n d n e g a t i v e p r e d i c t i v e v a l u e s w e r e 73% and 75% r e s p e c t i v e l y . W h e n m a x i m i z i n g the threshold, a c u t o f f v a l u e of 50% was found w i t h p o s i t i v e a n d n e g a t i v e p r e d i c t i v e v a l u e s of 82% and 78%. It can be c o n c l u d e d t h a t the level of T c 9 9 m - s e s t a m i b i u p t a k e is l i n e a r l y r e l a t e d to the a m o u n t of i n t e r s t i t i a l fibrosis. When using left ventricular functional i m p r o v e m e n t as g o l d s t a n d a r d for viability, p o s i t i v e and negative predictive values around 75% w e r e found, i n d i c a t i n g that a s e s t a m i b i d e f e c t r e f l e c t s n o t o n l y d e c r e a s e d flow, but also, at least in part, m y o c a r d i a l viability.

1042

,MIBI SPECT AND DOBU-ECHOCARDIOGRAPHY IN EVALUATION OF PERFUSION AND FUNCTION RECOVERY AFTER CABG To investigate whether the reduction of myocardial perfusion defects is parallel with improved left ventricular function after revascularization. 28 patients (age_+sd: 54.0+7.9years, 27 males, 1 female, 21 post-Ml) referred to CABG after angiography were studied before, and 3-6 months after surgery. All patients (pts) underwent dobutamine echocardiography (DE) and dipyridamolerest Tc-99m-MIBI SPECT. The perfltsion and contractility were assessed semiquantitatively in 16 segments. Perfusion (PI) aed wall motion indices (WMI) were calculated for each coronary artery territory. Angiography revealed I-vessel disease in 1 pt, 2-vessel in [4, and 3-vessel disease in 13 pts. Of 68 regions supplied by stenosed arteries, 58 (85%) were revascularised and submitted for further analysis. Before surgery all patients presented perfusion defects at SPECT, and 19 had abnormal resting LV wall motion. The area of abnormal perfusion at dipyridamole (dip) and rest SPECT was significantly more extensive than area with abnormal contractility at rest and high-dose DE. RevascLllarization improved perfusion, resting and stress induced LV asynergy. Perfusion recovery was more pronounced in comparison to LV wall motion improvelnent (25% for SPECT and 16% for DE). The number of regions with impaired both perfusion and function decreased from 22 before to I I after revascularisation. Perfusion and contractile recovery was highly significant for regions with initially abnormal motion, ~erfusion and both, abnormal perfusion and function. Before CABG After CABG Study

abnormal

PI

abnormal

WMI

p value

segm. segm. dip-SPECT 183 2.78_+1.11 99 2.07-+0.97 <0.0001 rest-SPECT 101 2.04-+1.01 56 1.71+0.83 <0.0001 Rest ECHO 72 1.36_+0.55 42 1.24+0.44 0.005 High-dose DE 105 1.60+0.71 54 1.34+0.58 <0.0001 We conclude that revascularization improves perfusion and function of tile left ventricle, regardless the initial regional perfusion and function status. The perfusion improvement is more significant than contractile recovery.

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Cardiovascular

0Mo041

0Mo043

S. Maurea A. Cuocolo, A. Soricelli, L. Castelli, N. De Luca, A. Nappi, B. Trimarco, M. Salvatore. Nuclear Medicine and Internal Medicine, Universitg degli Studi "Federico II", CNR, Istituto Nazionale dei Tumori, Napoli, Italy

G. Marcucci, M. Leoncini*, M. Silvestri, M. Magni*, A. Arena, M. Paoletti*, A. Petrella*, A. Mennuti. Nuclear Medicine and *Division of Cardiology -Prato Hospital.

DETECTION OF VIABLE MYOCARDIUM IN CHRONIC CORONARY ARTERY DISEASE BY RESTING MIBI CARDIAC TOMOGRAPHY USING NITRATES ADMINISTRATION OR DELAYED IMAGING: RELATION TO CORONARY ANATOMY. Nitrates administration or delayed imaging have been proposed to detect viable myocardium in chronic coronary artery disease (CAD) by resting Tc-99m MIBI cardiac imaging. We evaluated 31 patients (29 M, 2 F, mean age 55+10 yrs) with chronic CAD and severe left ventricular (LV) dysfunction (ejection fraction=39L-_9%). All patients underwent resting Tc-99m MIBI SPET with initial and delayed images as well as MIBI SPET after nitroglycerine (NTG), echocardiography and coronary angiograpby. MIBI uptake was quantitatively analyzed. Regional LV function was assessed by echocardiography using a 4-point scale (l=normal, 2=hypokinetic, 3=akinetic and 4=dyskinetic). Coronary abnormalities were evaluated as showing significant stenosis (>50%) or total occlusion; furthermore, totally occluded vessels were subgrouped on the basis of the presence or absence of collaterals. A total of 682 myocardial segments was analyzed, of which 154 (23%) were adyskinetic and showed a severe reduction (<50% of peak) of MIBI uptake on initial images; in particular, these segments were observed in 26 (84%) patients. Of these 154 segments, 55 (36%) were reversible on delayed and/or NTG MIBI images, while 99 (64%) were irreversible. No significant difference in the percent of coronary stenosis was observed between reversible (86+17%) and irreversible (90+13%) defects. However, when only segments with totally occluded coronary vessels were considered, a significant (<0.01) difference regarding the presence of collaterals was observed between reversible (95%) and irreversible (63%) defects. Thus, since the presence of collateral vessels has been demonstrated in viable myocardium, these results show that resting Tc-99m M1BI cardiac tomography, using nitrates administration or delayed imaging, is able to detect the presence of myocardial viability in patients with chronic CAD and LV dysfunction particularly in regions with a severe reduction of coronary blood flow.

PERFUSIONAL (99m-Tc-MIBI SPET) AND FUNCTIONAL (2DECHO) CHANGES DURING LOW-DOSE DOBUTAMINE AND POST-REVASCULARIZATION IN VIABLE MYOCARDIUM Recent studies suggest that low dose dobutamine (DOB) improves myocardial thickening in dyssinergic areas with residual viability also by an improvement of regional bood flow. The aim of this study was to evaluate the effect of DOB on myocardial perfusion (99mTc-MIBI SPET) and contractility (2D-ECHO) in viable myocardium. 19 patients with coronary artery disease (16 with previous IMA) were studied at rest (PRE), during DOB (10mcg/Kg/min) and after revascularization (POST). MIBI uptake was graded from 0 to 4; regional function was analyzed using a score index ranging from 1 to 4. Left ventricle was divided into 16 segments and two vascular territories were considered. RESULTS: DOB improved myocardial function in 12 of 24 asynergic vascular territories at rest (DOB+). SPET showed perfusion recovery in 10/12 DOB+ and in 3/12 DOB- asynergic territories in respect to PRE scintigraphy (p=0.006). Mean uptake score decreases significantly (SPET PRE 21_+7 vs SPET DOB 17,6_+7; p=0.0005) in DOB+, but not in DOB- (SPET PRE 19+5 vs SPET DOB 19,5_+6). 12 patients underwent successfull revascularization. Of the 14 asynergic territories demonstrated before revascularization, 9 showed functional recovery after intervention (viable myocardium) whereas 5 showed no changes (fibrotic myocardium). After revascularization mean perfusion defect score decreases significantly in viable territories (SPET PRE 22,1_+7 vs SPECT POSTI3,3_+7; p=0.0001), while remained unchanged in fibrotic regions (SPECT PRE 17,8_+6 vs SPECT POST 15,6_+4). CONCLUSIONS. These preliminary data suggest that improvement of myocardial perfusion and contractility in asynergic territories during infusion of DOB is probably related to increased blood flow in viable myocardium identificated by MIBI SPECT.

0Mo042 E.Milan. O.Aified*, R.Ferrad**, M.Nardi°°, A. Terzi, G.La Canna°, R.Giubbini°, Nuclear Medicine Service, Cardiac Surgery Opt°, Chair of Cardiology**. Civic Hospital and Universityof Brescia. Brescia, Italy

A. Cuocolo. E. Nicolai, C. Morisco, L. Pace, N. De Luca, B. Trimarco, M. Salvatore. Centro per la Medicina Nucleare del CNR and I Clinica Medica, Universit~ Federico II, Napoii, Italy.

%201 REST-REDISTRIBUTION SPECT AND LOW DOSE DOBUTAMINE ECHO FOR PREDICTING EARLY RECOVERY OF CHRONICALLY DYSFUNCTIONING MYOCARDIUM IN CAD PATIENTS.

LONG-TERM EFFECTS OF CORONARY REVASCULARIZATION 'ON R E G I O N A L T H A L L I U M - 2 0 1 U P T A K E AND LEFT VENTRICULAR FUNCTION IN PATIENTS WITH CHRONIC CORONARY ARTERY DISEASE.

Impaired left vantdcular (LV) dysfunotion may improve in pts with hibernating myocardiumafter CABG. The operative risk is high and predictionof early postoperative recovery is essentialfor defining indMdual risk. We studied28 pts severe global LV dysfunction by "11-201rest-redistributionSPECT (El R-R) and low dose Dobutamineechecardiographywithin 1 monthbefore surgery. Baseline LV functionwas evaluated before surgery, 15 days and 3 monthsalter CABG by tran-lhoracic ECHO and intraoperativelyby epicardial ECHO. A 16 segments model was used to compare TI R-R and ECHO. 263/448 segmentswere akinetic before surgery. Of these, 175 were identifiedas viable by TI R-R and 135 by LDDE. Upon reperfuslon 138/263 improved and 125 did not. 114/175 with preserved TI uptake and 112/135 with positive LDDE recovered alter surgery. Therefore the positive predictivevalue of TI R-R and LDDE was 65.1% and 83%, respectively. 64/88 segments with scar pattern by TI R-R and t01/128 with no contractile reserve by LDDE did not improve after CABG. Therefore the negative predictive value was 73 and 80% for Tt R-R and LDDE, respectively. The combination of the two tests improvedthe negativepredictivevalue to 98%. in conclusion, as far as early recovery of contraction is concerned, LDDE compares favourably to TI R-R. However if should be noted that these results reflect only a segmental analysis and do not take into account late recovery and long term prognosis. The combination of the two tests improvesthe negative predictive value for early recovery of regional function and seems to be mandatory to exclude pts from surgery.

0Mo044

Several studies, performed after short-term follow-up, suggest that coronary revascularization improve regional myocardial peffusion and left ventricular (LV) function in patients with coronary artery disease (CAD). However, it is still unclear whether these improvements persist in the long-run. To evaluate the long-term effects of revascularization procedures on myocardial perfusion and LV function, 38 patients with chronic CAD underwent, while off drugs, thallium-201 cardiac tomography, 2D-echocardiography and radionuclide angiography before and 13+__2months after revascularization. Regional thallium-201 activity was quantitatively measured in 13 segments/patient. Systolic function was scored in corresponding segments from 1 (normal) to 3 (akinesiadyskinesia). At baseline, on the basis of regional LV function and thallium-201 uptake, myocardial segments were classified as normal (n=276), dysfunctional-viable (n=169) and nonviable (n=49). After revascularization, LV ejection fraction (EF) increased (from 39+9% to 43+8%, p<.01) and LV wall motion score index (WMSI) was reduced (from 1.68+0.4 to 1.42+0.3, p<.001) compared to baseline. In patients with a basal EF between 36% and 49% (n=25) the changes in WMSI and EF were lower as compared to those with a basal EF below 35% (n=13) (both p<.01). In the entire group of patients, a significant relationship between the number of dysfunctional-viable segments at baseline and the magnitude of the EF change after revascularization was observed (r=-.61, p<.001). The majority (88%) of the dysfunctional-viable segments at baseline showed functional recovery at fditow-up. On the contrary, the majority (81%) of the nonviable segments at baseline did not show functional improvement. Thus, in patients with chronic CAD the beneficial effects of revascularization on myocardial perfusion and LV function are detectable at long-term follow-up and are greater in patients with more severe LV dysfunction at baseline. Furthermore, preserved thallium-201 uptake in dysfunctional regions is highly predictive of improvement in LV function at long-term follow-up after revascularization.

1043

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t~ tO

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Cardiovascular

0Mo045

0Mo047

A. Cuocolo, E. Nicolai, F. Squame, P. Sullo, A. Nappi, M.R. Grivet Fojaja, A. Discepolo, L. Spinelli, M. Salvatore. Centro per la Medicina Nucleate del CNR and I Clinica Medica, Universit~ Federico II, Napoli, Italy.

G. K a r a n i k a s , M a r g a r i d a R o d r i g u e s , S u s a n n e G r a n e g g e r , B.A. Peskar, H. S i n z i n g e r , D e p a r t m e n t of N u c l e a r M e d i c i n e , U n i v e r s i t y of V i e n n a , A u s t r i a

PREDICTION OF SPONTANEOUS DELAYED RECOVERY OF CONTRACTION AFTER MYOCARDIAL INFARCTION. COMPARISON BETWEEN Tc-99m SESTAMIBI TOMOGRAPHY AND DOBUTAMINE ECHOCARDIOGRAPHY.

PLATELET PGI^-RECEPTOR DESENSITIZATION INCREASES ARTERIAL DEP6SITION OF 111IN-OXINE LABELED PLATELETS C o n t i n u o u s e x p o s u r e of p l a t e l e t s to the a n t i a g g r e g a t o r y p r o s t a g l a n d i n (PG) 12 c a u s e s r e c e p t o r desensitizationand decreased an£iaggregatory a c t i o n s . W h i l e this p h e n o m e n o n has b e e n d e s c r i b e d i n - v i t r o as w e l l as in-vivo, the r o l e of PGI 2desensitized platelets on vascular thrombogenicity has not b e e n a s s e s s e d yet. H u m a n b l o o d p l a t e l e t s (healthy donors, 26 - 48 a, w i t h o u t a n y r i s k f a c t o r for the d e v e l o p m e n t of a t h e r o s c l e r o s i s ) w e r e d e s e n s i t i z e d by i n c u b a t i o n w i t h a s t a b l e P G I 2 - a n a l o g u e (iloprost) a n d the p a r e n t c o m p o u n d at I, 10 a n d 100 nM. P l a t e l e t s w e r e l a b e l e d with 111In-oxine. Perfusion over everted arteries a n d v e i n s m o u n t e d on a rod in a B a u m g a r t n e r perfusion chamber was done under controlled c o n d i t i o n s at 120/60 m m H g , 60 Hz and 37°C.

The aim of this study was to compare the results of low-dose dobutamine (5 ~tg/kg/min i.v.) 2D-echocardiography (echo) with those of Tc-99m sestamibi tomography in the identification of viable myocardium in patients with recent myocardial infarction (MI). Twenty-four consecutive patients with recent MI and angiographically proven coronary artery stenosis (13 patients with one-vessel disease and 11 patients with multivessel disease) were studied 14 days of MI (study 1) and after 9!-_3 months (study 2). At study 1, all patients underwent Tc-99m sestamibi tomography (370 MBq i.v. during dobutamine infusion and 1110 MBq i.v. at res0 and echo (at rest and during dobutamine infusion). Regional Tc-99m sestamibi activity was quantitatively measured in 16 segments/patient Systolic function was scored in corresponding segments from 1 (normal) to 3 (a-dyskinesia). Segments with normal Tc99m sestamibi uptake, reversible defects and moderate irreversible defects (uptake >50% of peak) were considered Viable, while those with severe irreversible defects (uptake <50% of peak) were considered nonviable. Of the 112 infarct-related segments with severe dysfunction at rest at study 1, 42 (38%) showed contractile reserve and 70 (62%) did not show contractile reserve at dobutamine echo. The majority (85%) of the 42 dysfunctional segments at rest showing contractile reserve at dobutamine echo were identified as viable at Tc-99m sestamibi imaging. However, a substantial number (54%) of infarct-related segments with severe dysfunction at rest and without contractile reserve at dobutamine echo were identified as viable at Tc-99m sestamibi. Of these latter segments, 53% showed functional recovery at study 2. In conclusion, these results suggest that in patients with coronary artery disease and recent MI the evaluation of contractile reserve alone may underestimate the identification of dysfunctional but viable myocardium compared to Tc-99m sestamibi tomography.

A d h e s i o n a n d p l a t e l e t t h r o m b u s f o r m a t i o n (morphometry) as w e l l as d e p o s i t i o n of (111In-oxine) radiolabeled platelets was significantly higher u s i n g d e s e n s i t i z e d p l a t e l e t s in a d o s e - d e p e n d e n t manner. Both techniques revealed comparable results. No difference between arteries and v e i n s was s e e n if e x a m i n e d u n d e r i d e n t i c a l c o n ditions. These findings indicate that PGI.desensitized human platelets show a significantly enhanced tendency towards thrombus formation, a f i n d i n g w h i c h s u p p o r t s the r o l e of PGI 2 in h a e m o s t a t i c b a l a n c i n g a n d the v a l u e of i n t e r m i t t e n t i n f u s i o n s c h e m e s p r o p o s e d e a r l i e r b y us.

0Mo046

0Mo048

H. S i n z i n g e r , A. O g u o g h o , M a r g a r i d a R o d r i g u e s , B.A. Peskar, D e p a r t m e n t of N u c l e a r M e d i c i n e , U n i v e r s i t y of V i e n n a , A u s t r i a

F.L. Weiland, G.T. Obranovieh, P.R. Vande Streek, R.F. Carretta, D. Aliberti. Sutter Roseville Medical Center.

OXIDIZED LIPOPROTEIN(a) TIC LESIONS?

FOR IMAGING ATHEROSCLERO-

V a r i o u s l i p o p r o t e i n s and in p a r t i c u l a r l o w - d e n s i t y l i p o p r o t e i n (LDL) a c c u m u l a t i n g u n d e r p a t h o l o g i c a l c o n d i t i o n s in the v a s c u l a r w a l l h a v e b e e n u s e d for r a d i o i s o t o p i c imaging. N a t i v e (n) l i p o p r o t e i n Lp(a) e n t e r s the a r t e r i a l w a l l to a m u c h h i g h e r e x t e n t as c o m p a r e d to n-LDL. AS o x i d i z e d (ox)-LDL m o r e r e a d i l y is t a k e n up as n-LDL, w e w o n d e r e d , w h e t h e r ox-Lp(a) m i g h t be an e v e n b e t t e r i m a g i n g a g e n t for an i n c r e a s e d e n t r y at v a s c u l a r l e s i o n sites. In an e x p e r i m e n t a l r a b b i t m o d e l (male N e w Zealand white rabbits, after feeding a 1%-choles t e r o l s u p p l e m e n t e d d i e t for 4 w e e k s , d e n u d a t i o n of e n d o t h e l i u m u s i n g a F o g a r t h y catheter) 125ILp(a) w a s a d m i n i s t e r e d . Lp(a) w a s d e r i v e d f r o m p a t i e n t s w i t h e l e v a t e d (> 50 mg/dl) Lp(a), isol a t e d a n d o x i d i z e d as d e s c r i b e d . T h e r e a f t e r , r a d i o l a b e l i n g w a s p e r f o r m e d u s i n g the m o n o c h l o r i d e technique. Arterial cholesterol content, ox-Lp(a)a c c u m u l a t i o n and s u r f a c e m o r p h o l o g y w e r e m o n i t o r e d in the a o r t a and in the i l i a c a r t e r i e s . 1 2 5 I - o x Lp(a) s h o w s s i m i l a r a c c u m u l a t i o n at l e s i o n s i t e s as c o m p a r e d to 1 2 5 I - n - L p ( a ) , h o w e v e r , the e x t e n t b e i n g 15 - 81% h i g h e r . P l a s m a t i c d e c a y of 1 2 5 I ox-Lp(a) is f a s t e r t h a n t h a t o f 125 I - n - L p ( a ) . T h e s e f i n d i n g s i n d i c a t e t h a t ox-Lp(a) m i g h t b e the l i p o p r o t e i n m o s t r e a d i l y a c c u m u l a t i n g in the a r t e r i a l wall. T h i s c o u l d b e of p a r t i c u l a r p a t h o p h y s i o l o g i c a l i m p o r t a n c e in p a t i e n t s w i t h e l e v a t e d Lp(a) (> 30 mg/dl) a n d m i g h t b e u s e d for b e t t e r i m a g i n g of a t h e r o s c l e r o t i c l e s i o n s in the future.

1044

A NEW TECHNETIUM-99m LABELED PEPTIDE, P280 IN THE

EVALUATION OF ACTIVE THROMBUS FORMATION: STUDY IN 32 PATIENTS.

A PROSPECTIVE

Teahnetium-99m P280 is a synthetic cyclic peptide which binds to the GPllb/llla receptors expressed on activated platelets. The purpose of this prospective study was to evaluate the safety and efficacy of Technetium-99m P-280 labeled peptide in the detection of actively forming clots in patients with suspected deep vein thrombosis. Thirtytwo studies were accomplished in thirty patients who had undergone doppler ultrasound for suspected thrombosis. Patients were injected with 20 mCi (740 Mbq)/70 kg of body weight with Technetium-99mlabeled P280. Appropriate images were performed at I0 minutes and at 60 minutes. Results were compared using ultrasonography as the criterion standard in a blinded fashion. Out of 32 studies there were 23 true positives, 6 true negatives, 2 false positives and one false negative. The sensitivity was 96%, specificity 75%, accuracy 91%, positive predictive value 92%, and negative predictive value was 75%. We conclude that the use of Tc-99m P280 may be an effective agent for the detection of venous thrombosis in patients with active clot formation.

•

Cardiovascular

0Mo049

0Mo051

J.Soares Jr., E.Azeka, D.Albertotti, M.C.P.Giorgi, M.Jatene, A.Fiorelli, M.Izaki, V.Aiello, P.R.Camargo, M.B.Marcial, E.Atik, LHMassonetto, MEbaid,G.G.Cerri, J.C.Meneghetti. Heart Institute University of SaD Paulo Medical School, Department of Nuclear Medicine, Brazil. GALLIUl~-67 SCINTIGRAPHY IN THE FOLLOW-UP OF HEART TRANSPLANTED CHILDREN.

G. Mariani, G. Villa, P.F. Rossettin, C. Motta, P. Spallarossa, G. Calcagno, G.P. Bezante, C. Brunelli, S. Capormetto, K.Y. Pak, J. Narula, B.A. Khaw, and H.W. Strauss. Nuclear Medicine Service and Cardiology Unit, DIMI, University of Genoa; Genoa (Italy); Molecular Targeting Technology Inc.; Frazer, PA; Stanford University Medical Center; Stanford, CA (USA).

Endomyocardial biopsy is a precise method for diagnosis and follow-up after heart transplantation. Previous studies have shown that gallium-67 cardiac scintigraphy (Ga) is a sensitive and specific method for diagnosis of rejection in adult heart transplanted patients. The purpose of this study was to evaluate the importance of Ga in the follow-up of heart transplanted children through correlation with endomyocardial biopsy and/or clinical evolution. Eleven children, between 4 months and 6 years of age, underwent heart transplantation from November 1992 to November 1995. Ninety Ga were performed within a postoperative period of up to thirty-six months. Seven biopsies have been performed in six patients with an interval between biopsy and Ga of 4 to 14 days. Ga was classified as negative or classified in absence or presence of acute rejection (mild, moderate or severe). In patients who had biopsy: two patients with moderate acute rejection presented moderate positive Ga; two biopsies with mild acute rejection also corresponded to mild positive Ga and in two patients'with negative biopsies the scintigraphies were negative. Ga suggested pericarditis in one patient which was confirmed by pathology Sequential studies with gallium-67 in this group of patients were negative and corresponded to a favorable clinical outcome. Despite the small patient population studied, data suggest that gallium-67 cardiac scintigraphy, a uoninvasive and risk free method, can be used in the follow-up of heart transplanted children for the evaluation of rejection

OMo050 L. Sarda, M. Faraggi, R. Lebtahi, D. Daou, E. Palazzo, M.F. Kahn, 0. Le Guludec. Bichat Hospital. Nuclear medicine deparlment. Pads. France.

SPECIFIC MYOCARDIAL INVOLVEMENT IN SYSTEMIC DISEASES ASSESSED BY INDIUM111-ANTIMYOSIN-ANTIBODY(AMA) AND REST THALLIUM SPECT. The diagnosis of myocardial involvement related to systemic diseases is often difficult, but clinically relevant since the occurrence of a specific left ventricular (LV) dysfunction is of poor prognosis. 12 patients (1 systemic lupus, 4 pedartedtis nodosa, 2 polymyositis, 1 sarcoidosis, 4 systemic sclerosis) were investigated and classified in 2 groups according to the presence (G1, n=7) or the absence (G2, n=5) of LV dysfunction, on the basis of clinical and echocardiographic data. Planar images (anterior, LAD 40 and 70°) were obtained 48h after IV injection of Inlll-AMA (92 MBq). Then, 111MBq of thallium (TI) were injected, and dual isotope rest SPECT acquisition was performed. Results: 6f7 G1 patients demonstrated a significant AMA uptake, assessed on planar images, with myocardial to lung ratio • 1.8 (mean value: 2.04+0.16). Simultaneous TI and AMA SPECT showed in 3 cases homogeneousTI scintigraphywith diffuse AMA uptake on the left (n=2) or both (n=l) ventricles. In the 3 other patients, dual isotope SPECT demonstrated a significant diffuse AMA uptake (on both ventricles in 2 cases), despite small segmental thallium defects. Those two types of TI and AMA mismatch patterns cannot be explained by recent myocardial infarction consecutive to coronary artery occlusion. They argue for myecytes' necrosis probably related to injury of the microvessels. Only one G1 patient did not demonstrate significant AMA myocardial uptake. All G2 patients had no significant AMA uptake, with homogeneous TI scintigraphy. Conclusion: The combination of Inlll-planar imaging and dual isotope TI / In111 myocardial SPECT is useful for the detection of specific myocardial involvement in patients with systemic diseases, and may be helpful for the differential diagnosis of myocardial infarction due to coronary artery occlusion.

~0 C 0

= m

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DIRECT SCINTIGRAPHIC IMAGING OF ACUTE MYOCARDIAL INFARCTION WITH 99mTc-D-GLUCARIC ACID IN HUMANS. 99mTc-D-Glucaric acid (99mTc-GLA)localizes in areas of experimental myocardial infarction within one hour of vessel occlusion. We now report the initial clinical and imaging experience in patients with acute myocardialinfarction (AMI) using this agent. Thirteen patients (11 men and 2 women, average age 56.6 years) presenting with chest pain suggestive of AMI who agreed to participate were injectedwith 99mTc-GLAi.v. (900-1000 MBq) within 2 to 41 hours of onset of chest pain. Planar images (anterior, LAD 45 ° and left lateral views) were recorded in a dedicated computer system for 2-3 M-counts each (5-10 rain/view) about 3 hours after injection. Peffusion images with 201 T1 or 99mTc-MIBI were recorded within 2 days of the 99taTc-GLA study, and 11/13 patients bad coronary angiography within 10 days; echocardioglaphic monitoring was also performed. All patients except one (who had heparin therapy at the time of AM]) were treated with thrombolytic therapy within 4 hours, and all had abnormal perfusion studies. Cl~ar and persistent 99mTc-GLA uptake at the site of myocardial infarction was observed in 10/13 patients. When compared to the 2°tTl or 99~Tc-MIBI perfusion images as well as to echocardiographic evaluation ot' wall motion, the area of 99mTe-GLAuptake slightly overestimated the size of the actually infarcted myocardium. In the 3 patients with negative 99mTc-GLA scan, the tracer had been injected at times greater than 9 hours after the onset of chest pain, after the peak serum CPK levels had been reached. There was no correlation between the intensity of 99raTc-GLAuptake and either the size of myocardial infarction and/or the peak serum CPK levels. Five patients with positive scans acutely, who were reinjected with 99r~Tc-GLA4-8 weeks later, had negative scans on the repeated study. r These data sU togest that 99m Tc-GLA can identify zones of acute ischemic injury of the myocardium leading to myocardial necrosis, when injected within 9 hours after onset of chest pain (or before the peak in serum CPK leveh is reached) in patients with AM].

0Mo052 GW Sloof, FC Visser, JJ Bax, J Eersels, A v Lingen, *FF Knapp, GJJ Teule. Free University Hospital, Amsterdam, The Netherlands. *Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA. COMPARISON OF 1-123-p-IODOPHENYL-3-METHYLPENTADECANOIC ACID 01MIPP) AND F-18-FLUORODEOXYGLUCOSE (FDG) UPTAKE IN ISCIIEMIC HEART DISEASE. To evaluate the potential role of BMIPP for the detection of myocardial viability, BMIPP uptake was compared with FDG/thallium-201 (I'1) rest SPECT. Twenty patients (M/F: 17/3) with previous (4 wks - 12 yrs) myocardial infarction (9 anterior, t 1 inferolateral) underwent FDG SPECT (185 MBq), to assess viability, and TI rest SPECT, to define regional perfusion, on the same day. BMIPP SPECT at rest occurred on a separate day (interval 5 days), 30 minutes after 111 MBq iv. SPECT images were displayed as polar maps (13 segments), analyzed visually and scored by a 4-point grading scale. A total of 260 segments were analyzed. Results: In 60% (156/260) of all segments, perfusion was normal. One normally perfused segment showed a decresed BM1PP uptake. BMIPP uptake was decreased in 93% (97/104) of the hypoperfused segments. Forty-nine FDG/TI matches and 55 mismatches were observed. FDG/TI: match mismatch (n=49) (n=55) T1= BMIPP 47 22 TI < BMIPP 2 26 TI > BMIPP 0 7 The distribution of TI/BMIPPA patterns was significantly different (p < 0.1301) between both groups. Conclusions: 1) Three different TlfBMIPP patterns exist in hypoperfused myocardium in wich BMIPP-uptake is not complementary to FDG-uptake. 2) Concordant TLEIMIPP uptake does not distinguish viable from nonviable myocardium. In contrast, not only a relatively decreased (to perfusion) BMIPP uptake, but unexpectately also an increased uptake is observed in chronically hypoperfused but viable myoeardium.

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Cardiovascular

OMo053 GW Sloof, A van Lingen, FC Visser, J Eersels, JJ Bax, MJA van Loon, *FF Knapp, GJJ Teule. Free University Hospital, Amsterdam, The Netherlands. *Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA. DIFFERENCES IN BIODISTRIBUTION OF MONO- AND DIMETHYLSUBSTITUTED RADIOIODINATED FATFY ACIDS IN HUMANS, Radioiodinated fatty acid analogues, modified by methyl-substitution are used for SPECT imaging of the heart. The effect of mono- and dimethylsubstitution on biodistribution was investigated in humans to evaluate their relative merits for SPECT image quality. Methods: Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, one hour after administration of 111 MBq 1-123-p-iodophenyl-3-methylpentadecanoic acid (BMIPP, n=7) or 111 MBq 1-123-p-iodophenyl-3,3-dimethylpentadecanoic acid (DMIPP, n=4). Because these branched fatty acids are used for cardiac imaging, we focussed on heart/organ ratios, by comparing small roi-counts in heart, liver, lung, muscle (thigh) and bladder. Results: Both tracers showed good visualization of the heart. While DMIPP showed a relatively high liver uptake, increased background, ie lung, activity was found for BMIPP. In contrast to DMIPP, BMIPP also showed elevated activity in the bladder. Heart/Organ Ratios

BMIPP

DMIPP

significance*

Heart/Liver

1.00_0.12

0.394-0.5

p<0.0001

Heart/Lung

1.63_+0.17

2.324-0.28

p<0.001

Heart/Muscle

3.174-0.58

3.904-0.37

p<0.05

*t-test for unpaired data. Conclusions: BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake effect cardiac SPECT image quality and therefore BMIPP may provide superior cardiac SPECT image quality in humans.

OMo054

OMo055 W.Yu.Ussoy, A.A.Garganeeva, A.Y.Fedorov, V.A.Dmitrichenko, R.S.Karpov. Tomsk Medical Research Center, Siberia, RUSSIA. QUANTIFICATION OF MYOCARDIAL BLOOD FLOW IN ABSOLUTE UNITS FROM LOCAL UPTAKE OF 99mTc-MIBI DECONVOLVED 'WITH ARTERIAL INPUT 99mTc-MIBI has been widely used for diagnosis of coronary heart disease, yet quantitification of myocardial blood flow (MBF) is complicated by extraction fraction below 1. We aproached to design of a technique for quantification of MBF using 99mTc-MIBI from single and dual-isotope first-pass study and quantitative SPET. We assumed regional MBF can be obtained as: MBF = A(T) / [E* J" Ca(t)dt], where A(t) is the local radioactivity in myocardium (as cpm/100 cm3), E extraction fraction of 99mTc-MIBI by heart, Ca(t) - blood input concentration of the tracer (cpm/100 cm3). We acquired dynamic frames of myocardial accumulation of 99mTc-MIBI after bolus injection and thereafter commenced SPET of 99mTc-MIBI uptake in heart Extraction fraction was determined from myocardial time-activity curve deconvolved with input obtained from artedalised blood samples. 99mTc-MIBI extraction fraction was corrected for tissue background using intravascular reference tracer assumed to have heart extraction fraction equal to zero. In 5 patients the study was validated using 99mTc labelled macroaggragates of albumin (MAA). Extraction fractions observed in control group (n=9) and in patients with coronary disease (n=34) were respectively 0.62 (sd 0.06) and 0,65 (sd 0.07).Rest MBF was 79 (sd 10) ml/min/100 cm 3 in controls and 75 (sd 9) in coronary stenosis, In nonviable scar regions the MBF was < 35 . By dipyddamole test MBF increased for more than 2.3-fold in normal regions, not more than x 1.53 in stenosis-dependent areas and not more than x 1.44 in scar regions. MBF calculated from 99mTc-MIBI kinetics correlated well with regional 99mTc-MAA uptake (r > 0.9, p<0.01). Thus myocardial 99mTc-MIBI SPET study combined with deconvolution of heart uptake with blood input provides absolute quantification of myocardial blood flow.

OMo056

Heiko Sch6de~, Richard J. Knight, Klaus F. Kofoed, H e i n r i c h R. Schelbert, Denis B. Buxton. Pharmacology, UCLA School of Medicine, LOS Angeles, CA 90095

G.Cannizzaro, G.Calsamiglia, R.Saponaro, O.Zoccarato, C.Aprile Dept. of Nuclear Medicine - S.Maugeri Foundation - IRCCS Montescano (Pv) - Italy -

EFFECTS OF DICHLORACETATE (DCA) ON GLUCOSE M E T A B O L I S M IN POSTISCHEMIC M Y O C A R D I U M IN VIVO. PET F-18 fluorodeoxyglucose (FDG) studies in dogs demonstrated that myocardial glucose utilization (GU) is d e c r e a s e d during early reperfusion. In isolated hearts DCA, an activator of p y r u v a t e dehydrogenase (PDH), stimulates glycolysis and glucose oxidation, improving recovery of cardiac work. We therefore determined if DCA (150mg/kg) increased glucose utilization in postischemic myocardium in viyQ. 35 open-chest dogs were studied: A (n= 17): 20 min LAD occlusion followed by 3h reperfusion; B (n= 18) same as A with iv. injection of DCA over 5 min at the end of occlusion. GU was quantified with FDG-PET. After 3h reperfusion, biopsies of the beating heart were taken and analyzed for PDH activity. R e s u l t s Myocardial b l o o d f l o w (microspheres) during LAD occlusion was reduced to 44 ± 10% and recovered to 89 ± 25% of baseline after 3h reperfusion. Without DCA, GU in postischemic was lower than in remote myocardium (0.28 ± 0.II vs. 0.42 ± 0.15 ~mol/min.g, p<0.001). DCA increased GU in both territories (p=0.001 vs non-DCA), but regional differences between postischemic and remote myocardium persisted. Glucose extraction ratio and oxidation increased significantly after DCA. PDH activity did not differ between postischemic and remote territory and was 70% higher with DCA in both postischemic and remote tissue (p<0.05). A d m i n i s t r a t i o n of DCA lowered plasma l a c t a t e levels to 30% of baseline and also n o r m a l i z e d lactate extraction in p o s t i s c h e m i c tissue. We conclude that glucose u t i l i z a t i o n in vivo is decreased even after short-term ischemia, but it can be increased by DCA-mediated activation of PDH, suggesting DCA may be beneficial for recovery of cardiac function in vivo.

'SCINTIGRAPHY WITH 99m-Tc-MIBI INFUSION: A NEW PROCEDURE FOR THE IDENTIFICATION OF MYOCARDIAL VIABILITY Conventional Sestamibi rest tomoscintigraphy (Tc-bol) underestimates myocardial viability. On the other hand Thallium-201 (T1) shows a suboptimal specificity. Furthermore, in patients (pts) with advanced CAD and left ventricular disfunction the quality ofT] imaging is often poor. The aim of the present study was to verify if the adnmistration of 99m-Tc Sestamibi by infusion (Te-in0 may" increase the uptake of the tracer in regions with Tc-bol defects, but still viable. Twenty three pts (median age 60 y, range 3674) with previous M.I., EF echo -< 40% (median 30%, range 15-40%) underwent T1 stress (Tl-st)-reinjection (Tl-rest) and, after 72-96 hours, Tc-bol and Tc-inf (one hour infusion). RESULTS Quality of images: Tc-bol: good in 15 pts, sufficient in 8; Tc-inf: good in 17 pts, sufficient in 6; Tl-rest: good in 8, sufficient in 9, poor in 6 (low target/non target ratio; high subdiaphragmatic activity). Comparison between Tc-bol and Tc-inf: 208/322 (64.6%) segments (sgts) were abnormal in Tc-bol. Among them 29 sgts (13.9%) improved their scores in Tc-inf, while only 3 ( 1.5%) worsened. Comparison between Tl-rest and Tc-inf: 197/322 (61.2%) sgts were abnormal in Tl-rest Among them 50 (25.4%) had a better Tl-rest score; 20 (t0.2%) had a better Tc-inf score. Evaluation of viability: 71 sgts were judged scarred in Tc-bol; 13/71 (18%) were viable in Tc-inf Of the 62 sgts judged scarred in Tc-inf, 10 (16%) resulted viable in Tl-rest. Clinical impact: in 3/23 (13%) patients the clinical impact of infusion was considered strong (when at least two "scarred" segments in Tc-bol were judged "viable" in Tc-inf). CONCLUSIONS Tc-inf seems to localize in a small but not negligible number of sgts with perfusion defects with Tc-bol. The number of sgts judged viable with Tc-inf is higher than with Tc-bol, but lower when compared with TI. This partial disagreement can be attributed to a residual underestimation of viability by Tc-inf, but also to an overestimation by T1, due in some cases to lower image quality. The clinical impact of Tc-inf procedure may be important in some patients.

1046

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Cardiovascular ~0

OMo057

OMo059

M. Unlu, B.Turgut, S. Gtinaydm, S. Atavcl, (3. Kapucu, T. Atasever, A.~engel, L.G6kg6z. Gazi University Medical Faculty, Departments of Nuclear Medicine, Cardiology, Cardiovascular Surgery, Ankara -TURKEY.

CestelI-Conesa J, Santana-Boado C, CandelI-Riera J, Garcta-Burillo A, Aguad6 S, Ortega D, Soler-Soler J. Hospital General Universitari Vail d'Hebron. Barcelona

Tc-99m TETROFOSMIN SPECT I M A G I N G IN A SAME DAY REST - DOBUTAMINE STRESS PROTOCOL: COMPARISON WITH Tc-99m MIBI. The aim of the study was to determine the diagnostic value of Tetrofosrnin SPECT in the detection of coronary artery disease (CAD) using a short one day rest- dobutamine stress protocol on an intraindividual comparison basis with MIBI. Nineteen patients ( mean age: 54.3, range: 41-65 ) with suspected CAD who had limitations to perform treadmill exercise were included in the study. All patients had coronary angiography (CA) within 2 weeks. SPECT studies were performed 30 min. after Tetrofosmin and 60 min. after MIBI administration, using identical acquisition protocol either at rest or following dobutamine infusion ( 5lxg/kg / min. up to 40 gg ). Heart to adjacent activity ratios were calculated on anterior planar images acquired just before SPECT imaging. Myocardial perfusion SPECT data were evaluated visually using a 20 segments 5 point scoring system ( 0: normal to 4: absent uptake ). Dobutamine stress parameters were similar for both studies (Tetrofosmin; PDP: 163.4+26.5, duration: 8.33+1.75 rain. MIBI; PDP: 159.8 +_29.1, duration: 8.52+1.79 rain.) and no serious side effects were observed. Although,time interval between tracer injection and acquisition was short in Tetrofosmin protocol, there was no significant difference in heart to liver (Tetrofosmin; rest: 1.2+.4, stress: 1.0!-_.2 MIBI; rest: 1.1+.4, stress: .9+.3) and heart to lung (Tetrofosmin; rest: 2.3+.4, stress: 2.1+.3 MIBI; rest: 2.3+.4, stress: 2.2+.3) ratios for both tracers. According to CA results overall diagnostic accuracy was similar for Tetrofosmin and MIBI; Sens.: 82%, 82%, Spec.: 84%, 88%, Acc.: 82%, 84%, respectively. A good correlation was found in segmental evaluation ( normal; r:.92, fixed defects; r:.97, reversible defects; r:.89, p_<.001 ). However, the degree of reversibility was better for Tetrofosmin ( 38.0 % ) in segments showing severely reduced or absent uptake when compared to MIBI ( 16.5 % ), p=.05. In conclusion, although the diagnostic accuracy was similar for both tracers the degree of defect reversibility seems to be better with Tetrofosmin. Tetrofosmin offers same quality of images with almost same biodistrubution characteristics in a shorter period of time when compared to MIBI in the same day rest dobutamine pharmacological stress protocol in the detection of CAD.

CULPRIT LESION AND JEOPARDIZED MYOCARDIUM: CORRELATION BETWEEN CORONARY ANGIOGRAPHY AND egmTc-MIBI-SPECT One hundred and fifty-nine patients with coronary artery disease without previous myocardial infarction were investigated to assess a) the agreement between coronary angiography and myocardial single photon emission computed tomography (SPECT) for the identification of the culprit lesion, and b) the correlation of the two studies in the quantification of jeopardized myocardium. A score for myocardial SPECT was correlated with the angiographic scores by Califf and Gensini and with a personal score which includes adjustment for collateral circulation. The agreement between coronary angiography and SPECT for the diagnosis of the culprit lesion was 84%. It was higher for the right coronary artery (92%) and the left anterior descending (85%) than for the circumflex coronary artery (54%). The correlations between the scores of angiography and SPECT to assess jeopardized myocardium when all coronary stenoses were taken into account were significant (p<0.0001). However, their coefficients were suboptimal for any score, either Califf's (r=0.48), Gensini's (r=O.5g) or our own's (r=0.55). When only the jeopardized myocardium depending from the culprit lesion was considered, the correlation clearly improved (r=0.85). In 18% of patients with multivessel disease a disagreement between coronary angiography and myocardial SPECT for the diagnosis of the culprit lesion was observed. The correlation between these techniques for the identification of jeopardized myocardium was suboptimal when all stenotic arteries were considered, but it was satisfactory when only the jeopardized myocardium from the culprit lesion was considered.

OMo058

OMo060

R. Zimmermann, Ph. Wende, R, Mura, T.J. Dengler, C.P. Tiefenbacher, J. Hoffend, J. Zehelein, W. KSbler. Departments of Cardiology and Nuclear Medicine, University of Heidelberg, Germany.

J Knuuti, O-P. Pitk~lnen. O.T. Raitakari. H. Niinikoski. P. NuutUa. H. lida, L-M. Voipio-Pulkki, J. Viikari, T. R0nnemaa. DepL of Nuclear Medicine and Turku

PERSISTENT TRACER DEFECTS AT DIPYRIDAMOLE TL-201 IMAGING AS PREDICTORS OF RESTENOSIS AFTER CORONARY STENTING In 63 patients, SPECT dipyridamole thallium-201 imaging was performed at a mean of 1 0 + 4 days following successful emergency coronary stenting (Palmaz-Schatz stent, Johnson & Johnson). In all patients, indication for coronary stenting was an unstable dissection in the course of elective transluminal coronary angioplasty. The target vessel was the right coronary artery in 1 8 (28%), the left anterior descending coronary artery in 32 (51%), and the left circumflex coronary artery in 13 patients (21%). All patients underwent quantitative angiographic follow-up (CASS II system, Pie Medical Equipment). This was routinely performed 6 months after coronary stenting in 51 patients and, prematurely, at a mean of 103 days (range 8 to 1 94 days) in 1 2 symptomatic patients. Thallium scintigraphy revealed normal tracer uptake or reversible defects in 43 patients (Group I), and persistent defects in 20 patients (Group II). Angiographic data were comparable in the t w o groups both before (diameter stenosis in Group I vs Group Ih median, 83% vs 83%) and immediately after coronary stenting (median, 21% vs 19%). At the time of angiographic follow-up, however, luminal diameter narrowing was significantly lower in Group I compared with Group II (median, 29% vs 4 8 % ; P=O.O04), and restenosis > 5 0 % occurred in only 6/43 patients of Group I but in 10/20 patients of Group II (14% vs 50%, P
PET Center, Turku University, Turku, Finland.

Coronary Flow Reserve Is Impaired in Young Men with Familial Hypercholesterolemia Precursors of morphological coronary artery disease are known to be present in adolescents and young adults with high risk factor profile. To investigate whether functional abnormalities in coronary vasomotion exist in young adults we studied 15 non-smoking otherwise healthy men (age 31+7.5 y) with familial hypercholesterolemia and a matched group of 20 healthy subjects. Methods: The myocardial blood flow was measured at the basal state and during dipyridamole induced hyperemia using positron emission tomography and 1SO-labeled water. The serum total and LDL- cholesterol concentrations were higher in the patients than in controls (7.7+1.9 vs. 5.3+1.5 mmol/I, 6.1+1.8 vs. 3.5+1.4 mmol/I, respectively, p<0.001 in both). The HDLcholesterol concentrations were 1.0+0.2 and 1.2+0.3 mmoVI, respectively (p<0.01). No difference were found in plasma glucose, serum insulin and tdglyceride concentrations, heart rate and blood pressure between the subject groups. Results: The baseline myocardial blood flow was similar in the patients and controls (0.92+0.24 vs. 0.83+0.13 mL.g-l.min-~, respectively, ns.). A significant increase in the flow was obtained in both subject groups by dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients (3.2+1.6 vs. 4.5+_1.6 mL.g-~.min-~, p=0.011). Consequently, coronary flow reserve (the ratio of flow during hyperemia to flow at baseline) was 35% lower in patients than in controls (3.5+_1.6vs. 5.4+_1.5,p=0.0008). Respectively, total coronary resistance during hyperemia was higher in the patients (36_+25 vs. 21+10 mmHg.min.g.mL-1, p=0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration (r=-0.47, p=0.004). Conclusions: Coronary flow reserve is reduced already in young men with familial hypercholesterolemia and, consequently, coronary resistance during hyperemia increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

1047

C 0

,,l=a ,l=a

C

(b

Q..

6

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Cardiovascular

0Mo061

OTu063

M.J. Garcia Velloso, A. Huelmos*, J.M. Mart1, A. Villas, A. Cabrera, D. Martinez-Caro*, J.A. Richter. Departments of Nuclear Medicine and Cardiology*. University Hospital of Navarra School of Medicine. Pamplona. Spain.

M.DONDI; P.L.GUIDALOTTI; IL CASANOVA; A.L. PATRONCINI; S.FANTI; P.F.CAPACCI; A. MARESTA. Nuclear Medicine Service and Division of Cardiology; Ospedale per gli Inferan, Faenza (RA), Italy

RELATIVE MYOCARDIAL PERFUSION RISK LIPID PROFILE PATIENTS.

RESERVE

IN

HIGH

The purpose of this study was to evaluate the myocardial perfusion reserve (MPR) in patients with high risk lipid profile ( H L ) defined as LDL/HDL>3.5 and/or total serum cholesterol >240mg/dl. Thallium-201 SPECT at rest and after pharmacological stress with a 6 min adenosinetriphosphate infusion (140 mcg/Kg/min) was performed in 40 patients with high risk lipid profile and in 12 control subjects. ATP-rest values subtraction was applied in order to obtain the stress data. Relative MPR indexes were calculated as the ratio between stress and rest values. The coronary angiography performed in 8 patients was normal. Lipid profiles and regional MPR of the vascular territories were:

Age ICholesterol

]LDL/HDL [MPR-LAD [MPR-LCX IMPR-RCA **P<0.01

control subjects

HL patients

50.33 ± 10.96 215.33 ± 15.31 2.88 ± 1.82 1.85 ± 0.0,9 1.79 ± 0.11 1.79 ± 0.09

55.17 ± 10.52 270.4 ± 42.6** 4.8 ± 1.81.* 1.51 ± 0.21.* 1.44 ± 0.19.* 1.46 ± 0.19"*

Conclusion: The reduction of the MPR indexes evaluated by means of ATP and Thallium-201 SPECT was highly significant in patients with high risk lipid profile. Primary alterations on the level of the microcirculation could be responsible for the reduction of MPR indexes in the patients evaluated in this study.

MYOCARDIAL SPET WITH TRANSMISSION/EM/SSION ATrENUATION CORRECTION: EFFECTS ON DIAGNOSTIC ACCURACY. Attenuation of the photon flax through the thorax is the known source of artifacts which affect specificity of myocardial SPET perfusion studies. Attenuation correction using simultaneously acquired transmission maps have been made recently available. This study aimed at assessing ff transmission/emissien attenuation correction can improve diagnostic capabilities of SPET. To this purpose, all patients referred for myocardial parfusion imaging underwent myocardial SPET performed with a tltreeheaded camera (Picker Prism 3000XP) equipped with a transmission line source specially designed for simultaneous transmission/emission acquisition. All studies were reconstructed with an iterative algorithm involving 20 iterations. A double series of tomographic studies, attenuation corrected (AC-studies) and non-attenuation corrected (NAC-studies) were produced for each patient. A set of representative slices (3 short-, 1 vertical long- and 1 horizontal long-axis) was subdivided into 29 segments and analysed adopting a qualitative 5-point score (0=nurmal; 4=no uptake). Segments were then assigned to the main epicatdial coronary vessels (septum and anterior wall to the LAD, inferior wall to the RCA, lateral wall to CX'). Out of the population studied, 60 patients (48 males; 12 females) were submitted to coronary angiography and are the subjects of the present study. Significant CAD (steansis >70%) was found in 51 pts. LAD was involved in 27 cases, RCA in 24 and CX in 30. Single-vessel disease (1VD) was detected in 28 pts, two-vessel disease (2VD) in 16 and three-vessel (3VD) in 7. Results: Out of the 9 pts with all patent vessels, CAD was correctly ruled out in 8/9 (spec 89%) by AC-studies and in 5/9 (spec 56%) by NAC-studies. As regards single or phirivessel disease (munber and specific arteries involved), ACstudies identified 1VD in 24/28 cases (86%); 2VD in 9/16 (56%) and 3VD in 6/7 (86%). NAC-studies identified 1VD in 15/28 (54%); 2VD in 8/16 (50%) and 3VD in 2/7 (29%) of eases. Stenutic arteries were identified as follows: AC-sluflles SENS SPEC

SENS

NAC-studies SPEC

92% (25/27) 97% (32/33) 67% (18/27) 100%(33/33) 87% (21/24) 92% (35/38) 91% (22/24) 53% (20/38) CX 87% (26/30) 96% (27/28) 73% (22/30) 96% (27/28) Coadusions: simultaneous transmission/emissiun acquisition permits an effective correction for attenuation, improving both sensitivity and specificity of SPETand diagnostic accuracy. The technique seems to be a definite iarprnvearent of myocardial SPETand deserves serious clinical consideration. LAD RCA

0Mo062

OTu064

C. Meyer ~, K. Kofoed 2, J. Hove 2, R.B. Schambye ~, S. Carstensen 2, H. Kelbmk2 and B. Hessek Department of Clinical Physiology and Nuclear

R. Kluge, A. Seese, W.H. Knapp, Department of Nuclear Medicine, University of Leipzig, Germany

Medicine I and Department of Cardiology2, National University Hospital, Rigshospitalet, Copenhagen, Denmark. IS M Y O C A R D I A L B L O O D F L O W C H A N G E D IN A T H L E T E S ? Whereas it is wellknown that pathological left ventricular hypertrophy (LVH) is a risk factor for caronary artery disease and leads to impaired flow reserve and endothelial dysfunction, little is known about the influence of LVH from heavy physical training on myocardial blood flow (MBF) regulation. It was the purpose of the present study to examine in elite athletes and age matched controls, MBF by PET at baseline (MBFr~t), during a cold pressor test (MBF:pt)and after dipyridamole (MBFdipy). Methods: 10 elite, male oarsemen (age 27±5 years) and 11 sedentary males (age 30±5 years), all non-smoking, non-hypertensive, with normal levels of blood glucose and cholesterol, in whom cardiac disease was excluded by history and exercise ECG, were investigated with PET and N13-NH3 with a 2- compartment model. Individual recovery correction was applied,based on echocardiographic determination of LV free wall thickness.Results: Maximal oxygen uptake during an upright bicycle test, LV mass index and free wall thickness were all significantly higher (p<.01), and resting heart rate lower (p<.01) in the athletes. ~/[BFr¢st (.55 vs .66 ml/g/min,p=NS), MBFopt(.71 vs .83 ml/min/g,p=NS) and MBFalp (2.02 vs 1.96 ml/mirdg, p=NS) were similar in athletes and controls. Also, there was no significant difference in myocardial flow reserve(3.80 vs 3.12 ml/mirdg,p=NS).As expected MBF=~t was closely related to the rate-pressure product, but only in the controls (r=.86,p<.001). Interestingly this relationship was absent in the athletes (r=.55, p=NS).Conclusion: Myocardial flow reserve and the response to endothelial stimulation by the cold pressor test are unchanged in physiological hypertrophy. But resting MBF appears to be regulated by factors other than heart rate and systolic pressure, maybe wall thickness or LV volume?

1048!

NON-UNIFORM ATTENUATION CORRECTION IMPROVES THE QUANTITATIVE EVALUATION OF MYOCARDIAL SPET STUDIES Intrathoracic photon attenuation may limit the accuracy of myocardial SPET. Frequently, there are significantly less counts from the inferior wall, even in patients with normal coronary arteries. Non-uniform attenuation correction (AC) can be performed by' simultaneous emission and transmission tomography. The aim of the study was to assess the benefit of AC for defining a normal pattern of activity distribution and for differentiation between presence or absence of CAD. 35 patients with a likelihood for CAD < 5 % and 20 patients with myocardial infarction (MI) were investigated with and without AC (400 MBq Tc-99m-tetrofosmin, ADAC Vertex camera, two scanning Gd-153 line sources) using a 90° rotation. Thus, an orbit of 180° (64 views) was covered. After reconstruction using filtered back projection and/or an iterative algorithm the resulting myocardial representation was analysed using circumferential count rate profiles. In normal subjects the maximal segmental count differences were significantly decreased by AC (range 35.8 -+10.8 % without correction (NC), 20.9 _+ 3.3 % with AC). Significant effects of AC were verified for the inferolateral, inferior, inferoseptal and septal wall segments. AC resulted in a significant reduction of the interindividual variability and, therefore, in a narrowing of the width of normal range far the count rate distribution. In 10 patients with inferior wall infarctions, extent and severity of defects were more clearly represented. The maximal distance of the individual count profiles from the normal range averaged 25.9 -+ 11.8 % in AC studies but only 16.4 + 12.3 % in NC studies (p < 0.005). In 10 patients with MI of different locations (7 of them anterior MI) there was no significant difference in profile abnormality between AC and NC studies.Thus, AC improves the quantitative evaluation of myocardial SPET studies, the definition of the normal range of count rate distribution, and the detection of inferior wall perfusion deficits.

•

Cardiovascular

OTu065

OTu067

O. Sehulz, J. Kupferschlager,H.J. Kaiser, J. vom Dahl, G. Wagenknecht, R. Schwarz, R. Marggraf, U. Buell. Departments of Nuclear and Intomal Medicine I (Cardiology), Aachen University of Technology, Aachen, Germany

R. Walser, A. Tausig, P. Knesewitsch, A. Knez*, D. Slotty, N. Win**, K. Hahn Depts. of Nuclear Medicine and Internal Medicine Klinikum Grosshadern and Khmkum Innenstadt , Umverslty of Mumch, Germany

NON-TRANSMISSIVE ATTENUATION AND SCATTER CORRECTION OF Tc-99m CARDIAC SPECT IN PATIENTS WITH AND WITHOUT PERFUSION DEFECTS.

EFFECTS OF PATIENT SPECIFIC ATTENUATION CORRECTION ON MYOCARDIAL SPECT FINDINGS IN CONTROLS

Both attenuation and scatter impair the acearaey of left; ventricular inferior wall (1W) perfusion imaging by SPECT. We developed an attenuation and scatter correction (ASC) method without transmission for SPECT using triple-energy window acquisition for primary, scatter and backscatter photons (400 MBq Tc-99m-MIBI, double-head camera, 360* rotation, matrix 128z). Two groups of pts were examined at rest: (A) 17 pts with angiographieally proved advanced CAD and perfusion defects oflW and (B) 10 patients with normal myocardial perfusion. Following filtered backprojektion (Butterworth 5~ order, cutoff 0.3) with and without ASC, count-equivalents (cts) of 33 let'¢ ventrieular ROIs (8 out of these IW) were normalised to the ROI with best perfusion (MIBI 100%). We compared relative MIBI uptake (%), ets and ets ratios with/withoutASC. meanvalues± SD *F, ~flsignificantforp<.05 */* forp<.001 in all groups MIBI % without ASC withASC cts withoutASC* with ASC* cts with / without ASC

group A (IW-defect) group B (no CAD) lW" remainder 1W remainder 136 ROIs 425 ROls 80 ROIs 250 ROIs 43.6 _+-20.0 64.9 +93.5 70.8 +15.7+ 77.1 +18.6 40.1+91.0 61.7+95.4 74.5 +13.7+ 77.0 +18.0 765 _-t372 820 .+.387 396 +939 582 .+337 606 z~373 929 .+.524 1133 +495 1174.+.549 1.62 i-0.70 1.68 :~0.63 1.66 +1.07" 1.46 5_'0.32"

A$C increased cts significantly in all myocardial areas of both A and B. Normal IW (B) mean relative uptake was elevated to 74.5%, i.e. homogeneity of myocardial distribution was improved in B. In A, ASC did not change the contrast between IW-defects and remaining myocardium. The latter results suggest that in IW with severely decreased MIBI uptake, scatter correction may predominate attenuation correction. We conclude that triple-window based, non-transmissiveASC for Te-99m improves discrimination between normal and reduced perfusion in IW.

OTu066 C. Rossetti. A. Savi, M. Ippolito, G. Rizzo, C. Landoni, G. Garraffa G; Lucignani M.C: Gilamdi and F. t-azio INB-CNR, H S. Rarraeie, untversita' ai Mimno EFFECT OF ATTENUATION CORRECTION ON SPET TI201 MYOCARDIAL PERFUSION IMAGES: COMPARISON WITH PET N-13NH3 With the aim of measuring the effect of attenuation correction on SPET myocardial perfusion images seventeen patients were studied: seven with mild thoracalgia and normal coronary arteries and ten with stabilized AM]. SPET studies were carried out four hr after administration of TI-201 at stress. Transmissive and emissive images were simultaneously acquired using a triple head gamma camera equippeo with fan oeam commator ano a line source riheo with 20 mCi of Tc-99m. Data were corrected for attenuation by using a maximum-likelihood expectation-maximisation algorithm. In all patients also a N-13NH3 PET scan corrected for attenuation was also obtained. The three sets of images (SPET non corr, SPET corr, PET) were coregis(ered by surface matching of SPET and PET transmissive images. Left ventricle was divided into 11 segments for a total of 187 segments. Segmental activity for each study was normalized and expressed as a percent of maximum. Following SPET attenuation correction, a relative decrease of activity in the anterior wall was observed, while it was recovered =n the septum, inferior and lateral wall. Using regression analysis, SPET-non corr vs PET was significantly different (coefficient= l p = <0.001, intercept= 0 p= <0.005), whereas no significant difference was found for SPET-corr vs PET (coeffictent= 1 p= >0.10, intercept= 0 p = 0.42). In both comparisons, data were rather scattered around the identity line, although better correlation with PET was found for SPET-corr (r= 0.87) than for SPET-non corr (r= 0,76). The TI-201 SPET data affected by attenuation artefacts are recovered by the measured attenuation correction. Although less evident, discrepancies are still present between SPET-corr and PET data and these may be due to different tracers' behaviour and/or residual physical limitations of SPET technology.

Recently simultaneous transmission-emission protocols for non-tmiform patient specific attenuation correction (AC) have been introduced in myocardial seintigraphy (MS). Theoretically AC is expected to improve myocardial findings particularly in the posterior wail. To evaluate this aspect we analyzed myocardial SPECT scans of controls focusing on the findings in the posterior and anterior wall as well as on the effects of different postfilters. SPECT scans were performed in 14 controls .(9 males, 5 females) without cardiac disease as indicated by negative cardiac catheter and conventional diagnostic methods. Examinations were done according to a oneday-protocol (stress: 250 MBq Tc-99m-Sestamibi, 3hrs later rest: 650 MBq) using a triple head camera (Prism 3000, PICKER, Cardio Fan). A Gd-i-53 line source was used to establish the transmission ,projections. The raw data were processed with and without AC, iteratlvely reconstructed and postfiltered with Low Pass (LOP) and Wiener (Wnr) filters. Semiquantitative analysis was performed with a bull's eye program dividing the left ventricle into 16 segments. The results for the segments representing no AC with AC the anterior (a) and pos- n=14 Wall Mean SD Mean SD terior (p) wall are ex- LoP a 89% -+ 5,6 88% 4" 5,5 pressed as counts per p 78% + 8~0 88% _+4~3 voxel normalized to the Wnr a 85% _+7,8 86% -+ 5,5 maximum of the study, p 71% + 9,5 87% + 7,8 Mean values and standard deviation (SD) for the 14 controls are summarized in the table. Since in rest and stress studies similar results were observed only the first ones are shown. The findings indicate that AC equalizes the count rates between the anterior and posterior wall. Particularly in the posterior wall AC data showed only minor variations as demonstrated by low values for the SD. AC data assessed with LoP postfiltering showed lower SD values compared to the ones obtained vclth the Wnr filter. This observation suggests that the use of LoP instead of Wiener postfittering may be superior for the correct classification of normal as well as pathologic findings.

OTu068

~

, R. Walser, P. Knesewitsch, D. Slotty, N. Win*, K. Theisen*,

Departments of Nuclear Medicine and *Internal Medicine, Klinikum Inneustadt, University of Munich, Germany "INFLUENCE OF POSTFILTERING ON THE ACCURACY OF MYOCARDIAL SCINTIGRAPHY USING NONHOMOGENEOUS ATTENUATION CORRECTION Recently simultaneous transmission-emission(T/E) protocols have been established in myocardial scintigraphy (MS) for non-uniform patient related attenuation correction. For further processing users can choose smoothing (e.g Low pass, LoP) or restorative(e.g. Wiener, Wnr) filters. Aim of our study was to analyze the differences of both choices concerning sensitivity (SN), specificity (SP) and accuracy of T/E-MS. So far the data from 14 pts with myocardial infarction (MI), 8 pts with coronary artery stenosis >75% (S) and 34 controls are included in our study. T/E MS was done according to a one-day-protocol using a triple head camera (PRISM 3000, Cardio Fan, PICKER). A Gd-153-line-source was used to establish the transmission projections. Raw data were iteratively reconstructed and postfiltered withWnr and LoP filters. Semiqnantitative analysis was performed with a bull's eye program, summarizing the results in 16 myocardial segments. Due to the wide range of mean counts/voxel among the different segments within one study (60%-96% of the maximum) we used a segment-specific (SSP) lower threshold instead of a general one to discriminate MI and S from normal findings. The optimized SSPthreshold values were obtained by ROC-analysis and came out as SSPmean minus the (2,2 to 3,2)-fold of the standard deviation (dependent on study type (rest, stress, stress/rest-ratio) and filter selection). This approach results in a subtraction from the SSP-mean ranging from 11%-22% for the LoP and 13%-26% for the Wnr filter. The values obtained for SN, SP and accuracy are listed below. W T ~ Conclusion: Semiquantitatively analyzed nr Lot" T/E-MS using both Wnr or LoP postfflterSP 94% 91% ing is highly accurate to discriminate MI SN(S) 75% 88% and S from normal findings. At a comparaSN(MI) 86% 86% ble specificity level LoP seems to be snpei Accuracy 89% 89% rior to Wnr postfiltering for detection of hemodynamieally relevant coronary stenosis even though the number of patients especially in this subgroup is currently still small. Subjects of ongoing analyses are to increase the member ofpts for determinat]on of SN and to compare intraindividually the data of MS evaluated with and without T/E.

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M.Conrad I, A.J. Morguet-', J. Meller/, H.-A. Sctunitt2, A. HerrmarmI, S.Gratz I, H. Lui~/, W, Becker I Departments of Nuclear Medicine I and Internal Medicine2 of the University of G6ttingen in Germany

PR Franken P Dendale, P Flamen, H Everaert, A M o m e n , A Bossuyt. Nuclear Medicine and Cardiology. Free University Brussels (AZ V U B ) Brussels, Belgium.

CLINICAL RELEVANCE OF ITERATIVE RECONSTRUCTION IN TL-201 -MYOCARDIAL SCINTIGRAPHY

RELATIONSHIP BETWEEN MYOCARDIAL PERFUSION, WALL THICKENING AND FREE FATTY ACID UPTAKE EARLY AFTER ACUTE MYOCARDIAL INFARCTION.

The aim of this retrospective study was the intraindividual comparison of iterative (ISA) and filtered back (FBP) reconstruction in thallium myocardial scintigraphy Methods: 36 patients (age 44-78 years) were examined with a three-headed gamma camera (Picker : ,,PRISM 3000", 360 ° acquisition, 2o increments, 45 sec/frame, 128x128 matrix) under stress and rest conditions. Results of coronary angiography: 13 one vessel, 10 two vessel and 12 three vessel diseases. One patient had no coronary artery disease. The reconstruction was performed with a FBP-algorithm ( Ramp/Metz filter) and with ISA (7 iterations, absorption correction). Nine volume segments of the myocardium were evaluated using vertical, and horizontal long axis slices (anterelateral, anterobasal, apex, posterobasal, diaphragmal, posterolateraI near to the apex, posterolateral near to the base, septal near to the apex and septal near to the apex). In total we examined 324 segments of 36 patients. Three independant readers evaluated the images with a three grade score (normal, decreased or missing uptake). Finally the concordance with the findings of coronaryangiography, laevocardiography and the clincial situation was evaluated. Results: ISA reconstruction proved to be superior to FBP reconstruction in the diagnosis of reversible and irreversible defects of the septum (26 segments correctly positive versus 20 segments) and the posterolateral wall (19 correctly positive segments versus 13). FBP reconstruction and ISA demonstrated similar sensitivity both in the anterior and the posterior wall. ISA decreased highly significant the number of false positive results (specificity) in the posterior wall (10 versus 20 false positive segments). Myocardial viability after stent or PTCA was more often correctly diagnosed in 27 segments using ISA versus FBP (21 versus 13 segments). Conclusion: 1.) The sensitivity of ISA is significantly higher in the identification of iscbemie myocardium in the septum and posterolateral wall in comparison to FBP. 2.) The specificity of ISA is higher in the posterior wall. 3.) ISA is advantageous over FBP in the follow-up of patients after stant or PTCA

OTu070 D. Daou, M. Faraggi, R. Lebtahi, Y. Petegnief, L. Sarda, C. Peker, D. Le Guludec. Nuclear Medicine department, Bichat Hospital, Paris, France.

A COMPARATIVE STUDY OF THE VALUE OF LUNG TO HEART RATIO (L/H) WITH DIPYRIDAMOLE COMBINED TO EXERCISE VERSUS EXERCISE IN PATIENTS WITH THREEVESSEL DISEASE In patients (pts) with coronary artery disease, increased lung TI201 uptake with exercise (E) SPECT evaluated by L/H ratio, is considered as reflecting multi-vessel disease (VD). In pts unable to perform maximal E, the addition of dipyridamole (D) improves the test performance but the value of L/H ratio is not well assessed. We compared the value of L/H ratio according to the stress test in 100 control normal pts (61 pts with E, and 39 with combined E+D) and 108 consecutive 3VD pts (64 pts with E and 44 with E+D). L/H ratio was computed with ROIs drawn on SPECT projection corresponding to the anterior view. L/H ratio was linearly correlated with the percentage of target heart rate in controls (p<0.03). Thus, it was normalized for this percentage (L/Hc). Then, the thresholds for abnormal L/Hc (mean+2SD) were defined in each of the 2 control groups. The % of pts with 3VD and abnormal L/Hc were calculated.

E E+D L/Hc in controls 0.34 + 0.09 * 0.41 + 0.10 * L/Hc in 3VD pts 0.64 + 0.35 * 0.71 + 0.27 * Abnormal L/Hc in 3/61 = 5% 1/39 = 3% controls Abnormal LIHc in 3VD pts 42164 = 67% * 22144 = 50% * • : p
Discrepancies between wall thickening and myocardial blood flow m a y be observed soon after thrombolysis for acute myocardial infarction (stunning). To characterize such myocardium metabolically we c o m p a r e d wall motion kinetics and myocardial perfusion (using sestamibi gated SPECT) with the uptake o f BMIPP, a free fatty acid analog. B M I P P uptake mainly reflects the energy dependent activation process of long chain free fatty acids prior to beta oxidation and triglyceride synthesis, Sestamibi SPECT gated in 8 time bins and BMIPP S P E C T were obtained 4-12 days after coronary thrombolysis for acute myocardial infarction in 24 patients (pts). Both tracers were injected at rest, on t w o separate days. Wail thickening was measured by the Stanford method, Functional, perfusion and metabolic parameters were quantified on polar maps divided into 9 regions. Results were expressed as percent of mean normal values obtained in 20 pts with low probability of C A D . Wall thickening was abnormal in 73 segments (segs). Stunned segs, defined by a wall thickening/perfusion ratio <0.71 (normal ratio = 0.99 + 0.14) had a lower metabolic/perfusion ratio than other dysfunctional segs (0.75 + 0.39 vs 0.95 +- 0.14, p< 0.001) indicating d e c r e a s e d fatty acid uptake. Fatty acid uptake was more closely related to the amplitude o f wail thickening than perfusion. The metabolic/perfusion ratio w a s 0.95 + 0.12 in segs with normal wall thickening, 0.79 + 0.26 (p< 0.001) in segs with mild to moderately reduced wall thickening a n d 0.27 + 0.60 (p< 0.001) in segs with severe dysfunction. W e conclude that soon after thrombolysis for acute m y o c a r d i a l infarction, wall thickening is more closely related to fatty acid uptake than to myocardial perfusion. This may indicate a relationship between decreased fatty acid metabolism and stunning.

OTu072 R.S. Liu. Y.H. Chen, L.S Chu, S.M Yu, T.C. Yen, S.P. Wang, MS. Chang and S.H. Yeh. National PET/Cyclotron Center, Taipei Veterans General Hospital. National Yang-Ming University School of Medicine and National Defense Medical Center. Taipei, Taiwan. 'ASSESSMENT OF GLUCOSE METABOLISM. OXYDATIVE METABOLISM AND TISSUE HYPOXIC STATUS 1N STUNNED MYOCARDIUM WITH POSITRON EMISSION TOMOGRAPHY. Myocardial stunning is the mechanical dysfunction that persists after repeffusinn despite the absence of irreversible damage and despite restoration of normal or nearnormal coronary flow. The purpose of this study is to assess the oxydative metabolism and tissue hypoxia in the regional stunned myocardium (SM) with [C-I l]acetate (ACE) and [F-18]fiuoromisonidazole (FMISO). Nine patients (pts) with postischemic ventricular dysfunction were studied with [N13]NH3, [F-18]fiuorodeoxyglucose (FDG), ACE and FMISO. FDG myocardial PET was done with ghicose-loading ACE PET imaging of heart was perfornmd from 3 min to 16 rain after intravenous injection of a dose of 0.125 mCi (4.6 MBq) per kg of body weight. Serial emission scanning of 2 min duration was obtained for 16 min. FMISO PET imaging was done at 2 hr after intravenous injection of 10 mCi (370 MI3q) of tracer. Images were displayed in tomographic transverse, sagittal and coronal views. They are read in a segmental fashion over 13 myocardial regions (septal, anteroseptal, anterior, lateral, inferolateral, and inferior at the basal and midventricular level and apical segment). Fourteen segments of regional stunned myocardium were diagnosed by the criteria of paradox of normal perfusion with impaired contractile function. 11 out of 14 SM showed decreased FDG uptake and the remaining SM showed normal FDG uptake. All 14 segments of SM showed normal uptake of ACE as the same distribution pattern of myocardial blood flow. None of the SM segments had avid uptake of FMISO. In addition, l0 segments with scar formation showed absent myocardial perfusion, glucose metabolism, ACE uptake and FMISO uptake. In summary, regional SM has a characteristic picture of normal myocardial peffusion. normal or decreased glucose metabolism, and normal oxydative metabolism ACE is better than FDG in assessing the myocardial viability. FMISO is not useful in detecting SM.

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OTu075

J Knuuti, M. M~ki, M. Luotolahti, P. Nuutila, M. Haaparanta, J. Bergman, U. Wegelius Dept. of Nuclear Medicine and Turku PET Center, University of Turku, Finland.

J.J. Bax, J.H. Cornel, F.C. Visser, P.M. Fioretti, A. van Lingen, C.A. Visser. Free University Amsterdam, Academic Hospital Rotterdam, Netherlands.

Myocardial fatty acid metabolism in the chronically dysfunctional but viable myocardium as studied with [18F]FTHA and positron emission tomography

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PREDICTION OF FUNCTIONAL RECOVERY AFTER REVASCULARIZATION USING THALLIUM REST-REDISTRIBUTION AND FDG SPECT.

ID L-

We have previously found a preserved hormonal control of glucose uptake in the chronically dysfunctioning but viable myocardium. Fatty acid metabolism in a such condition has not been previously studied. 14(R,S)-[18F]fiuoro-6-thia-heptadecanoicacid ([18F]FTHA) is a new fatty acid analog tracing beta-oxidation of long-chain fatty acids. Methods: Seven patients with an occluded major coronary artery but no previous infarction were studied twice with positron emission tomography and [18F]FTHA, once in the fasting state and, once during hyperinsulinemic euglycemic clamp. The myocardial region beyond an occluded artery that showed stable wall motion abnormality represented chronically dysfunctioning but viable tissue. Results: In the fasting state the beta-oxidation index (calculated by multiplying fractional [18F]FTHA uptake and serum FFA concentrations) were similar in the dysfunctioning and in the normal myocardial regions (5.8+_1.7 vs. 5.8+2.1 ~Jmolll00glmin, ns.) In both region types insulin infusion reduced beta-oxidation index by 76%. The beta-oxidation index was similar in the dysfunctioning and normal myocardium during insulin clamp (1.4+0.5 and 1.4+0.4 tJmol/100g/min, ns.). Conclusions: In the chronically dysfunctioning but viable myocardium the fatty acid beta-oxidation probed by [~SF]FTHA uptake is preserved. Both in the normal and dysfunctioning regions insulin infusion clearly reduces FFA oxidation. The results are concordant with our earlier findings obtained with [~SF]FDG and PET and suggest the preserved hormonal control on myocardial substrate metabolism in the dysfunctioning but viable tissue.

To compare thallium-201 rest-redistribution (TL-RR) and F18-fluorodeoxyglucose (FDG) SPECT in the prediction of improvement of regional wall motion (RWM) after revascularization, 24 patients with regional left ventricular dysfunction were studied. RWM was evaluated by transthoracic echo (13-segment model) before and 3 months after revascularization. The TL-RR and FDG SPECT were performed on the same day. The early TL image obtained in the TL-RR protocol was also used as a perfusion study for comparison with FDG SPECT. All SPECT data were analyzed semiquantitatively, using circumferential profiles and a polar map display. The polar maps were divided into 13 segments for alignment to the echo data. On FDG SPECT, the segments were classified as viable in the presence of normal perfusion or by increased FDG uptake in perfusion defects (mismatch). For TL-RR SPECT, criteria for viability were both the level of TL uptake and reversibility of defects. 106 segments showed RWM abnormalities. Improvement of function was observed in 36 segments; 70 segments showed no improvement. The sensitivities to detect improvement of RWM were 86% for FDG SPECT and 78% for TL-RR SPECT, whereas the specificities were 77% and 59% respectively. These data suggest that FDG SPECT is superior over TL-RR SPECT in the prediction of functional recovery after revascularization.

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OTu076

M.Angioi, P.Y.Marie P.Olivier, N.David, S.Denet, N.Quiri, T.Arsena, N.Hassan, N.Danchin, G.Karcher and A.Bertrand. D e p a r t m e n t s of C a r d i o l o g y a n d of N u c l e a r Medicine, Nancy, FRANCE.

J.J. Bax, F.C. Visser, M.A. Veening, A. van Lingen, C.A. Visser. Free University Amsterdam, Netherlands.

IMPACT OF ISCHEMIC M Y O C A R D I U M O N LEFT VENTRICULAR R E M O D E L L I N G A N D F U N C T I O N A F T E R A N G I O P L A S T Y OF A N INFARCT RELATED CORONARY ARTERY C o r o n a r y angioplasty (PTCA) of an infarct related artery m a y improve left ventricular (LV) remodell i n g a n d function. E x e r c i s e T I 2 0 1 - S P E C T w i t h r e s t - r e i n j e c t i o n was u s e d to a n a l y s e the impact of the amount of ischemic m y o c a r d i u m (reversible defect) on the f u r t h e r e v o l u t i o n of LV v o l u m e s a n d e j e c t i o n f r a c t i o n (LVEF) a f t e r P T C A of an infarct r e l a t e d artery. L V volumes and LVEF were c a l c u l a t e d on X - r a y v e n t r i c u l o g r a m s b e f o r e PTCA and > 4 months later (area-length method). S i x t y four c o n s e c u t i v e p a t i e n t s w e r e s t u d i e d ; 61% h a d h a d thrombolytic therapy, 84% h a d Q w a v e and 92% h a d one vessel disease. At follow-up, 38 pts h a d no restenosis (Grl) and 26 h a d restenosis (Gr2). E v o l u t i o n of end d i a s t o l i c v o l u m e s w e r e not s t a t i s t i c a l l y d i f f e r e n t b e t w e e n Grl a n d 2 (+1±18 vs +10±30 ml). However, in Grl, e n d systolic v o l u m e s w e r e s i g n i f i c a n t l y d e c r e a s e d (-6±19 vs +8+_24 ml, p<.01) a n d L V E F w a s s i g n i f i c a n t l y i m p r o v e d (+5±9 vs -13±I0%, p<.02). O n a s t e p w i s e r e g r e s s i o n analysis, i n d e p e n d e n t p r e d i c t o r s of i m p r o v e m e n t o f L V E F w e r e [i] e x t e n t of r e v e r s i b i l i t y of e x e c i s e T I 2 0 1 d e f e c t (p<.002) [2] a b s e n c e of r e s t e n o s i s (p<.002) and o f e v o l u t i o n of e n d d i a s t o l i c v o l u m e was [i] d e l a y t i m e b e t w e e n infarction and PTCA (p<.02) [2] extent of r e v e r s i b i l i t y of exercise TI201 defect (p<.02). A m o u n t of i s c h e m i c myocardium, as a s s e s s e d b y e x e r c i s e T I 2 0 1 - S P E C T w i t h rest-reinjection, appears to be a d e t e r m i n a n t of the e v o l u t i o n of LV v o l u m e s a n d f u n c t i o n a f t e r P T C A of an i n f a r c t r e l a t e d artery.

tO

FDG SPECT IMAGE QUALITY USING ACIPIMOX; COMPARISON WITH ORAL GLUCOSE LOADING AND HYPERINSULINEMIC GLUCOSE CLAMPING. SPECT imaging using F18-fluorodeoxyglucose (FDG) can detect viable myocardium. To obtain optimal image quality in all patients, FDG SPECT should be performed during hyperinsulinemic glucose clamping. To avoid this time-consuming procedure, FDG imaging following administration of Acipimox (a nicotinic acid derivative) has been proposed. We compared the image quality of cardiac FDG SPECT in 8 patients using Acipimox, hyperinsulinemic glucose clamping and oral glucose loading in random order. Image quality was expressed as the myocardial to blood pool (M/B) activity ratio. The clearance of FDG from plasma was also evaluated. Results: M/B ratios were not different after clamping and Acipimox: 2.8+0.8 vs 2.9-20.7, ns. After oral glucose loading the M/B ratio was lower (2.2+0.3, P<0.05 vs clamp and Acipimox). Similarly, FDG clearance from the blood was comparable after clamping and Acipimox ((T½ clamp=8.1+3.1 min, T½ Acipimox=10.7+4.0 rain, ns) but slower after oral glucose loading (T½ oral loading=16.2_+5.7 rain, P<0.05 vs clamp and Acipimox. Thus, FDG SPECT imaging using Acipimox yields comparable image quality and clearance rates as obtained during clamping. FDG SPECT after Acipimox can be used in the clinical setting to assess myocardial viability.

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A. Cuocolo. A. Nappi, E. Nicolai, C. Mainolfi, A. Discepolo, M.R. Grivet Fojaja, F. Menna, M.R. Panico, B. Trimarco, M. Salvatore. Centro per la Medicina Nucleare del CNR and I Clinica Medica, Universi~ Federico II, Napoli, Italy.

W. Miiller-Sehauenburg1.J. LogemannI, H.M. HoffmeisterZ,U. Helber2, S. Walehl, J. Knpfersehl~iger l, U. FeineI, L. Seipel 2, R. Bares1 Departments of 1Nuclear Medicine and ZCardiology, Eberhard-Karls-University of Tiibingen, Germany

Tc-99m T E T R O F O S M I N UPTAKE AFTER NITRATE ADMINISTRATION IN PATIENTS WITH ISCHEMIC LEFT VENTRICULAR DYSFUNCTION: RELATION TO METABOLIC ACTIVITY BY F-18 FDG PET IMAGING.

CHARACTERIZATION OF NON-CONTRACTING MYOCARDIAL SEGMENTS BY GATED 18-FDG-PET

In patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction myocardial perfusion imaging after nitrate administration may improve the identification of dysfunctional but still viable myocardium. The aim of this study was to assess the relation between Tc-99m tetrofosmin uptake after nitrate administration and metabolic activity by F-18 FDG PET imaging. Twelve consecutive patients (all men, mean age 54+13 years) with angiographically proven CAD and chronic ischemic LV dysfunction (ejection fraction 394--'8%) underwent Tc-99m tetrofosmin tomography (740 MBq iv) at rest and after nitrate administration (nitroglycerine 0.005 mg/kg per os) in two separate days. In all patients metabolic PET imaging with F-18 FDG was performed after glucose loading within one week. Regional Tc-99m tetrofosmin uptake and metabolic activity were quantitatively measured in 22 segments/patient. On Tc-99m tetrofosmin imaging at rest, 40 (15% of the total) dysfunctional segments showed a severe reduction (<50% of peak activity) of tracer uptake. Of these segments, 13 (33%) showed increased tracer uptake (>10% vs resting study) after nitrate administration and the remaining 27 (67%) did not change after nitrate. All segments with severe reduction of Tc-99m tetrofosmin uptake at rest and increased tracer uptake after nitrate showed preserved metabolic activity (F-18 FDG uptake _>50% of peak) on PET imaging. On the other hand, the majority (70%) of the segments with severe reduction of Tc-99m tetrofosmin uptake at rest and unchanged tracer uptake after nitrate did not show metabolic activity (F-18 FDG uptake <50% of peak) on PET imaging. These results demonstrate that enhanced Tc-99m tetrofosmin uptake after nitrate in dysfunctional segments with severe reduction of tracer uptake at rest correlated with metabolic activity by F- 18 FDG PET imaging. Thus, Tc-99m tetrofosmin imaging after nitrate administration may improve the identification of severely ischemic but still viable myocardium in patients with chronic ischemic LV dysfunction.

Segmental wallmotionis regarded as cardiological gold-standardin the assessmentof myocardial viability prior to revascularisation. High quality myocardial PET-movies, processedby a special FOURIERlowpassfiltering, permit a semiquantitativescoring of segmentalwalimotion.In the classificationof motility Dobutaminstimulationplays an increasingrole in expandingthe assessmentof myocardiumviability. We reIatethis approachto Cineventrieulography(CVG)and 201-TICI-SPECTas perfusionmarker. Patients and methods: We investigated totally 434 segmentsin 31 patients with multi-vesseldisease. 40 minutesafter injection of 350 MBq 18-FDG, the basic gated study was acquired for i5 to 20 minutes, and subsequentlyin 9 patients one or two low level gated Dobutamin studies. The whole assessmentwas performed under insulin-glucose-clamp-conditions. 201-TIC1-SPECT was performed as early reinjection-techniqueincludingadditional late secondday imaging. Results: 152 of 434 segmentsshowedconcordantfunctionimpairmentcorrelatingto an uptake defect/severelyreduced uptake in 201-TICIrest SPECT, 9 only in PET, 17 only in CVG and 20 only in 20I-T1CI-rest-SPECT( concordance89.5 % ). 3 patients (13/42 segments)showed a distinct mismatchwith severely reduced uptake in 201TICI-SPECTand normaluptake and wallmotionin 18-FDG-PET. Comparisonof functionand FDG uptake in 434 segments: FDGTpETmotil.!ty FDGreduced'l'FDG. . . . 1 t TICIredu"ced' TICInormaf seyer~ly.hy~o-/akin~ic.. 199 158 41 167 32 n~rmg-/mi~ h~p~kinetie 12~'~1 0 1 235 ''1 13 1 222 .I Dobutamin stimulation revealed functional change in 8/126 segments (8/38 hypokinetic segments = 21%). All those 8 segmentswere discordantto CVG and 4 of themwereconcordant,4 of them discordantto 201-TICI-SPECT. Conclusion: Motionassessmentby especiallyprocessed 18-FDGmyocardialmovies were concordant to CVG in 94% and corresponded to 201-TICI-SPECT in 93% already withoutusing Dobutaminstimulation. IncludingDobutaminan improvement was achieved in 21% of hypokinetic myocardial segments(in 5 of the 9 Dobutamin studies). Thereforewe concludethat rest 18-FDG-PETis superiorto 20 I-TIC1-SPECT and Dobutamin18-FDG-PETis a useful add-onin detection of myocardialviability.

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WS Richter, S Beckmann, M Cordes, T Schuppenhauer, M Schartl, DL Munz, Klinik f'tk Nuklearmedizin, Charitt, Strahlenklinik und Abteilnng Far Kardiologie, Virchow-Klinikum, Humboldt-Universittit zu Berlin, Berlin, Germany

A. Fikrle, D. Ltischer, E.-P. Ritter, M. Fleisch*, A.R. Haldemann, J.A. Kinser, S. Lourens. Dept. of Nuclear Medicine, . Dept. of Cardiology, University of Berne, CH-3010 Berne, Switzerland

D y n a m i c I P P A - S P E C T for Prediction of W a l l Motion R e c o v e r y After Acute M y o c a r d i a l Infarction

Aim of the study was to assess whether myocardial stunning is associated with alterations in fatty acid metabolism which can be assessed with I123-Iodophenylpentadecanoic acid (IPPA). 15 patients were examined after acute myocardial infarction and reperfusion. In all patients a dynamic IPPA SPECT, a T1-201 stress-rest SPECT study, and an echocardiography were performed in the subacute stage 12:55 days after infarction. A follow-up echocardiography was carried out 24:58 days later. The dynamic IPPA SPECT protocol consisted of 15 180°-SPECT rotations with an acquisition time of 120 sec each within the first 90 min after injection. Regional time-activity curves were generated and the terminal IPPA elimination half-life calculated. Wall motion improved between initial and repeat echocardiography in 14 of 75 segments (18.7%). Wall motion recovery was more likely in segments with either a terminal IPPA elimination half-life longer than 140 min (p<0.05) or a mismatch with normal T1-20l and reduced IPPA uptake (p<0.005). 11 ischemic and 7 scarred segments were documented. Ischemic segments were characterized by a longer terminal IPPA elimination half-life (239.9:5220.6 min vs. 119.84-86.1 min in nun-ischemic segments, p<0.05). In myocardial scars, IPPA uptake was lower (73.6:515.5% vs. 90.4:510.9% in non-scarred regions, p<0.005) whereas terminal IPPA elimination half-life was not significantly different. These data suggest that myocardial stunning can be characterized by a reduced fatty acid uptake relative to regional viability as assessed with TI-201, and a reduced fatty acid turnover.

1052

COMPARISON OF THE POST-STRESS AND REST LEFT VENTRICULAR EJECTION FRACTION (EF) ASSESSED BY GATED Tc-99m MIBI SPECT (GSPECT) The aim of this study was to compare the post-stress EF and rest EF assessed by GSPECT. Using a 2-dayprotocol, stress and rest GSPECT was performed with Tc-99m MIBI on a 3-head camera in 362 consecutive pts referred for evaluation of myocardial perfusion. The EF was obtained by GSPECT performed 30 min. after exercise-stress MIBI-injection (S-EF) and, on the following day, 60 rain. after MIBI-injection at rest (R-EF). The EF determination was performed using 3D Perfusion/Motion Map T M Software (with a 3D model derived from an automatic surface detection algorithm) on the Picker Odyssey computer. The pts were divided into 7 groups: those with normal stress and rest scinngrams without clinical history or ECG evidence of myocardial infarction (MI) and either no arterial hypertension (n =125) = Group A, with hypertension (n=46) = Group B or >6 months after revascularisation with PTCA or ACB (n=50)=Group C; pts with scintigraphic evidence of stress-ischemia but without MI (n=28) = Group D; pts >tmonths after MI with a defect in the stress/rest scintigraphy without ischemia (n=57) = Group E or with isehemia (n=56) = Group F. Of the 362 pts, contrast left ventriculography (CVG) was performed in 57 within 2 weeks of the scintigraphic study = Group G. The S-EF and R-EF were (in %) Group A: S-EF = 61+4, R-EF=59+4 (p<0.05); B: S-EF=58+6,R-EF=62+6 (p<0.05); C:S-EF=58_+5, R-EF=59+5 (n.s.); D: S-EF=56+7,R-EF=60L-_5 (p<0.05); E: S-EF=45+_11, R-EF---48_+I0 (n.s.); F:S-EF=47+9,R-EF=5t_+8(p<0.05); G:S-EF=53_+12, R-EF=53+10 (n.s.). The difference CVG-EF (58+14) vs S-EF and R-EF in Group G was significant (p<0.05) and a correlation coefficient CVG-EF vs S-EF of 0.81 and CVG-EFvs R-EF 0.87. The assessment of EF with MIBI-GSPECT revealed good correlation with CVG, although it systematicallyunderestimated the EF in comparison with CVG. The 30 min. post-stress EF was not always the same as the rest EF. In ,,normal" pts without hypertension, S-EF was significantly higher than the R-EF. In those groups with ischemia, but also in pts with hypertension, S-EF was significantly lower than R-EF. In the other groups without ischemia, no significant difference was found between S-EF and R-EF. The estimation of EF with MIBI-GSPECT provides useful information regarding myocardial function after stress and at rest permitting simultaneous assessment of myocardial perfusion and function.

•

Cardiovascular

OTu081

OTu083

G Germano, JD Friedman, PB Kavanagh, H Kiat, DS Berman Division of Nuclear Medicine, Cedars-Sinai Medical Center, Los Angeles 90048, USA

A.Bentrup(1) , G.Claus(2) , R.Coenen (i),H.J.Otto (2) , H.Klein(2) , Departments of Nuclear Medicine (i) and cardiology and Angiology( 2 ), Otto-v.GuerickeUniversity Magdeburg, FRG

QUANTITATIVE LVEF FROM GATED 201-TL SPECT: COMPARISON WITH GATED 99m-Tc-SESTAMIBI SPECT.

S]IVfJLTANGUS ASSESSMENT OF MYOCARDIAL PI~RFUSION AND WALL MOTION USING ECG GATED SINGLE PHOTON EMISSION T(IHOGRAPHY

Left ventricular ejection fraction (LVEF) at rest is an important diagnostic predictor of outcome in coronary artery disease (CAD) patients. We have previously developed and validated automated software to quantitatively measure LVEF from gated 99m-Tc-sestamibi perfusion SPECT (gMIBI) [J Nucl Med 1994;35(5):116P]. We now report on the possibility of measuring LVEF from gated 201-T1 SPECT (gT1), and compare the measured values to those obtained from gMIBI performed on the same patients. Thirty-two patients were studied with a rest gT1 (3 mCi)/stress gMIBI (25 mCi) separate dual isotope approach on a 90 ° dual detector camera (Vertex, ADAC). Acquisition parameters were non-circular rotation, 3 o projections over 180 °, 25 sec/proj (gMIBI) or 35 sec/proj (gT1), 8 gating intervals, no arrythmia.rejection. After prefiltering with a 2-dimensional Butterworth filter of order 5 (gMIBI) or 10 (gT1), and critical frequency 0.25 (gMIBI) or 0.2 (gTl) cycles/ pixel (pixel size = 6.4 mm), the projection data was reconstructed with ramp-filtered backprojection and no attenuation correction, and reoriented into short-axis (SAX) images. Our automated quantitative software operates in the 3-D SAX space. It segments the LV, extracts the mid-myocardial surface and fits count profiles normal to it to derive the epicardial surface, for each gating interval. Epicardial end-diastolic and end-systolic volumes yield LVEF. The software was applied to all the 32 gMIBI/gT1 SAX image sets, and executed successfully in 100% of the cases. The agreement between homologous LVEF value pairs was ascertained by linear regression analysis to be excellent (y=2.06+1.02, r=0.938, S.E.E.=4.58) over a wide range of EF (20%-80%). The slightly higher LVEF values for gTl are likely a consequence of the lower resolution of 201T1 at these statistics and filtering levels, although a small reduction in gMIBI LVEF from post-exercise stunning cannot be excluded. These findings suggest that myocardial viability and LVEF may be assessed from a single injection, substantially augmenting the useful clinical information derived from resting 201-T1 SPECT.

OTuO82 Zeynep Do~ruca, Levent Kabasakal, A. Fuat Yapar, Vural A. Vural, Cavit Ni@i, Zeki Ongen, Nedim Erdo~gan,Cetin 0nsel. Cerrahpa.~a Medical Faculty, Departmentof Nuclear Medicine. THE VALUE OF GATED Tc-99m-MIBI SPECT IN SEPARATION OF INFERIOR WALL ATTENUATION ARTIFACTS FROM MYOCARDIAL INFARCTION Myocardial fixed defects, especially in inferiorwall may result from myocardial infarction or soft. tissue attenuation which decreases the test specificity. With the higher injected doses of Tc-99m-MIBI it is possible to obtain gated SPECT data and evaluate myocardial perfusion and wall motion simultaneously. The dim of the present study was to investigate the value of Gated SPECT MIBI in separation of attenuation defects from infarcts. Study populationwas composedof 30 patients, mean age 56.34-5.3 years (27m, 30. All patients had standard same day dipyridamole stress-rest Gated MIB1 SPECT and dipyridamole stress-4hrs rest reinjection TI-201 SPECT studies. Fixed inferior defect was observed in all patients. In 23 patients prone TI-201 (P-TI) study was also performed. The presence of coronary artery disese was identified by angiography in all patients. Gated study was performed8 cycles per frame. Perfusionstudieswere evaluated by 2 observers blindly and final decision was made by consensus in areas of disagreement. Gated studies were evaluated from 8 slices on VLA, HLA and apical and basal oblique planes (4 slices from each stress and rest study simultaneously). Fixed defects with markedly decreased function (absence of wall motion and thickening) were evaluated as MI and the others as attenuation. Regional wall motion was judged subjectively and scored. Inferior wall was divided apical and basal segments. From 60 fixed segments 34 segments were classified as normal and 26 segmentswere classified as infarct. In 3 segments clissified as normal, angiography documented infarction and in 4 segmentsidentified as fixed defect, angiography showed normal myocardium.With P-TI, 21 of 46 segmentswere identified as infarct and 25 segmentsas normal. In P-TI study angiographyrevealed false (+) and false (-) in 5 and 7 segments respectively. The overall specifity, sensitivity and accuracy for Gated MIB1were 85%, 91% and 88%, respectivelyand for P-T1 were 70%, 78% and 74% respectively. We concluded that Gated Tc99m-M1BI SPECT is a valuable method and in charactherization of artefacts from infarcts and increasesthe test specificity.

AND

tO

| m

t-

ARBUTAMINE

Arbutamine, a new regional myocardial dohutamine. The aim

beta-adrenoreceptor can provoke ischemia in a manner superior to of this study was to enhance the

sensitivity and specifity of ecg gated single photon emission tcmography (gated SPECT) in the diagnosis of coronary artery disease (CAD) by infusion of arbutamine in a close-loop device. Using a two-day protocol, 30 patients with anginal symptoms and STsegment changes were included; all patients were controlled by coronary angiography, a subset of 25 patients underwent arbutamine stress echocardiography testing. Stress gated SPECT was performed 60 min after receiving 14 mCi Tc99m-MIBI by peak bycicle excercise under the administration of 1-5 ~g/kg arbutamine (total dosis).Rest gated SPECT acquisitien was obtained after injection of 7 mCi Tc99m-MIBI. Myocardial count increase rate between end-diastolic and end-systolic frames was calculated and related to wall thickening. Ischemia was defined as diminished stress-related regional perfusion with decreased wall motion by improved perfusion and motion in matching segments at rest. Results: In 24 Patients with CAD in 50 vessels regional ischemia related to 46 vessels was detected (91%). In 6 patients without CAD no evidence of i schemia was found (100%) . Sensitivity and specifity of arbutamine echocardiography were 94% and 75%, respectively. In conclusion, the c mmbined perfusion and function study with gated SPECT and arbutamine may provide significant contribution to the evaluation of CAD and identification of myocardium at risk in doct~nented CAD.

OTuO84 R.Giubbini, E.Milan, O.Zoccarato*, A.Terzi, A.Vaccari, L.Facchetti, A.Vignati°. Nuclear Medicine Services, CMc Hospitals of Brescia, Busto-Arsizio° and Veruno Medical Center*. Italy. GATED BLOOD POOL SPECT (G-SPECT) FOR THE EVALUATION OF GLOBAL AND REGIONAL LEFT VENTRICULAR FUNCTION IN COMPARISON TO PLANAR IMAGING AND ECHOCARDIOGRAPHY (ECHO). Planar equilibrium radionuclide ventricuiography (P-RNV) is considered a standard for the assessment of left ventricular (LV) ejection fraction (EF). However owing to its limited ability to evaluate the regional wall motion (RWM), due to the two-dimensional imaging, its clinical use is progressively declining in favour of ECHO. Aims of this study were the comparisons of: 1) LV EF, peak ejection and filling rate ( ER and FR) values between G-SPECT and P-RNV and 2) RWM between G-SPECT and trans-thorecio ECHO. A 32 frames acquisition was adopted for P-RNV. G-SPECT was acquired over 180 = at 16 frames per cardiac cycle, after Tc-99m-pyrophosphate in vivo labelling of red blood cells.Short, vertical and horizontal long axis slices were extracted from transaxial tomograms. Short axis slices were summed to calculate the global EF. A 16 segment model was adopted for the comparison to ECHO RWM, graded according to a 4 grade score. For each one of the 16 segments the normal range of G-SPECT EF was quantified and a normal data file was defined; the average value -2.5 SD was used as lower threshold to identify abnormal segments. 34 patients with no history of previous cardiac surgery and optimal ECHO window were evaluated. Agreement between P-RNV and G-SPECT EF was high (y=t .14+1.05 x, r=0.961, p
i n

t~

•

Cardiovascular

oru085 E,Milsn, M.L.Muiesan°, P.Franzoni°, E.Agabiti-Resei°, A,Terzi, R.Giubbini. Nuclear Medicine SeMce, Civic Hosprtal of Brescia. Chair of Medical Semeiotics°, Universit'/of Brescia. Brescia. Italy LEFT VENTRICULAR (LV) CAVITY SIZE ENLARGEMENT DETECTED BY STRESS TC-99M-SESTAMIBI (MIBI) SPECT IN HYPERTENSIVE PATIENTS WITH NORMAL EPIOARDIAL CORONARIES: A LIKELY MARKER OF ISOHEMIA LV hypertrophy is a common finding in pts affected by systemic hypertension. Hypertrophy implies combination of increased demand and lessened supply leading to increased likelihood of myocardial iechemia. Post ischemic LV dilstion after exercise, due to transient LV dysfunction, is considered as a marker of severe and extensive CAD at TI-201 scintigraphy : this explanation does not hold true for MIBI-SPECT due to the delayed imaging after tracer injection. Aim of the study was the evaluation of prevalence and characteristics of LV dilation in post stress MIBI SPECT in 12 hypertensive pts (hpts) with normal coronary angiograms in comparison to a control group with less than 5% pre-test probability of CAD. Furthermore, the study group was divided into pts with (group1) and without (group2) LV hypertrophy. An automated program able to identify inner LV border by a thresholding method was used in order to determine LV cavity (VC) size expressed in arbitrary units. SPEOT studies were analyzed for inducible isohemia by a quantitative evaluation of gender matched polar maps. Significant difference in rest VC (160 + 92 vs 229 + 67; p<.05) was found between h-pts and control group. After stress a significant increase in VC in comparison to baseline values was found in h-pts (160 + 92 vs 213 + 88; p<.05), but not in the control group. Group 1 showed a significant increase in VC after stress in comparison to baseline images (201 + 91 vs 129 + 100; p<.05). No significant changes were observed in the rest and stress parameters in group 2. Significant difference in the extension of inducible ischemia was found between group t and 2 (4.8 + 42 vs 0.8 + 1; p<.05) as welt as between group 1 and control group (4.8_+ 42 vs 0.5_+0,6; p<.01), tn group 1 significant correlation was found between reversible defects size and AVC (= stress VC- rest VC) (p<.05), while in group 2 no correlation was found. Thus LV cavity enlargement is a common finding in h-pts with LV hypertrophy and should be taken into account for a correct interpretation of MIBI SPECT studies. LV cavity enlargement alter stress in h-pts might be explained by a diffuse subendocardial ischemia in presence of normal epicardial coronary artedes.

OTu086 N. D e l a h a y e , A. C o h e n - S o l a l t , M- Fara~gL D. C z i t r o m t , D. Le Guludec, D e p a r t m e n t s of N u c l e a r M e d e c i n e a n d t C a r d i o l o g y , Bichat a n d Beaujon hospitals, Paris, France. LEFT VENTRICULAR HEMODYNAMIC RESPONSE TO MAXIMAL AND SUBMAXIMAL EXERCISES IN IDIOPATHIC CARDIOMYOPATHY. Peak o x y g e n c o n s u m p t i o n assessed by gas exchange m e a s u r e m e n t a n d left v e n t r i c u l a r ejection f r a c t i o n (LVEF) a r e s t r o n g p r e d i c t o r s of f a t a l e v e n t s in p a t i e n t s w i t h i d i o p a t h i c d i l a t e d c a r d i o m y o p a t h y (IDCM), d e s p i t e LVEF p o o r l y c o r r e l a t e s with clinical exercise t o l e r a n c e . Daily life c l i n i c a l t o l e r a n c e is often e v a l u a t e d b y s u b m a x i m a l e x e r c i s e s like s t a i r c l i m b i n g (SC) o r w a l k i n g (W). O u r s t u d y a i m to c o m p a r e the hemodynamic r e s p o n s e s of t h e LV m e a s u r e d with an a m b u l a t o r y r a d i o n u c l i d e d e t e c t o r (VEST, C a p i n t e c , Inc., Ramsey, N.J.) d u r i n g t h r e e d i f f e r e n t t y p e s of s t a n d a r d i z e d exercises: u p r i g h t m a x i m a l g r a d e d b i c y c l e e x e r c i s e , c l i m b i n g two stairs a n d six m i n u t e walk test. After in v i t r o T c - 9 9 m r e d cells l a b e l l i n g ( l l l O MBq), LVEF a n d v o l u m e s w e r e c o n t i n u o u s l y m o n i t o r e d in 13 p a t i e n t s w i t h IDCM a n d c o m p a r e d to b a s e l i n e p r e c e d i n g e a c h test. The t h r e e stress tests d i f f e r e n t l y affected the h e m o d y n a m i c r e s p o n s e of the LV. Bicycle Stair climbin~ Six minute walk test Baseline LVEF (%) 22 ± 9 24 ± 11 22 ± 10 I, LVEF -5.1 -+7 1"¥ -3 -+6 1"# 1 _+3 ¥# ~EDV 15±10%t¥ 4 ± 4 % t¥# 10±6%t# AESV 2 3 ± 1 8 % t¥# 8±9%t¥ 8_+8%f# A: changes f r o m baseline (absolute f o r LVEF, r e l a t i v e f o r e n d diastolic a n d end-systolic volumes); "tp_
1054

OTu087 T.B. Lindhardt, N. Gadsball, H. Kelb~ek, K. Saunamgki, J. Kyst Madsen, E. Jorgensen, B. Hesse. The Heart Center, Cardiovascular Laboratory, Rigshospitalet. The National University Hospital, Copenhagen, Denmark. CONTINUOUS MONITORING OF LEFT VENTRICULAR FUNCTION DURING PTCA WITH A MINIATURE NUCLEAR DETECTOR. Purpose: To study the acute impact of transluminal coronary angioplasty (PTCA) on left ventrieular function during and after PTCA. Methods: Continuous monitoring of LV function was performed in 40 patients during PTCA using a non-imaging, miniature nuclear detector (Cardioseint). Red blood cells were labeled in vive with ego MBq 99m-Technetium. Mean duration (4-SD) of balloon inflation: 113 + 45 see. Results: LVEF:

LVEDC%

LVESC%

LAD CX RCA LAD CX RCA LAD CX RCA

n 23 9 8 23 9 8 23 9 8

pre-PTCA .64 4, .11 .61 4- .7 .65 4. .10 100 4- 30 100 4- 17 100 4- l0 1O0 4, 52 lOg 4- 25 lO0 4. 20

during PTCA .47 4- .16 * .55 4- .10 * .60 4- .8 101 4- 30 * 100 4- 17 101 4, l l 145 ~: 69 * 116 4- 34 * 107 4- 17 *

post-PTCA .64 4- .ll .62 4- .7 .67 ± .10 101 4- 32 10l 4. 17 101 4- 12 lOg 4- 48 97 4- 28 87 3:20

* p < 0.05 vs pre-PTCA values. LVEDC%, LVESC%: percentage of LV enddiastolic and end-systolic count rate in relation to pre-PTCA values. 65% of the patients with LAD disease had a decrease in LVEF >10 EF units while the corresponding figures for patients with CX or RCA disease were 33% and 25%, respectively. The fall in LVEF and the return to post-PTCA levels occurred within seconds after balloon inflation and deflation. Conclusion: Balloon dilatation of LAD leads to an abrupt and substantial decrease in LVEF in the majority of patients, while balloon dilatation of the CX and RCA results in less pronounced effects on LVEF. The decrease in LVEF is explained by an increase in end-systolic volume with no detectable change in end-diastolic volume indicating a reduced enntr~tility during PTCA. No patient showed any sign of post-PTCA stunning.

OTu088 Levent Kabasaka!, Zeynep DoOruca, Vural A. Vural, A. Fuat Yapar, Cavit Ni~li, Zeki Origen, ~etin ¢)nsel Cerrahpa§a Medical Faculty, Department of Nuclear Medicine. E N H A N C E D A S S E S S M E N T OF M Y O C A R D I A L VIABILITY WITH T c - 9 9 m - G A T E D S P E C T USING NITRATE INFUSION Nitrates have been shown to increase regional coronary blood flow and increase contractile force in ischemic areas. The aim of the present study was to evaluate the value of gated MIBI SPECT study under the effect of nitrate intervention in assessment of viable myocardium. For this purpose, 23 patients were studied (21m, 2f mean age 56.9+8.9). In all patients CAD was documented by angiography. Eleven patients had history of infarction and 16 patients had severe LV dysfunction. All patients had stress-4 hours rest reinjection TI-201 SPECT (Sd-TI) studies and 16 patients had additional 24 hours delayed redistribution SPECT studies (24-TI). Standard stress-rest same-day Tc-99m-MIBI gated SPECT (Sd-MIBI) studies and also a separate MIBI gated SPECT study under the effect of nitrate (Ng-MIBI) were performed to all patients. Nitroglycerin infusion was given with a rate of 25 pgr/mt/min and incremented 10~g/ml/min in every 5 rain. Patients were monitorised and 20 mCi MtBI was injected according to the change in heart rate or blood pressure. During the acquisition 25 p.g/ml/min of nitrate infusion was also given. No severe side effects were observed. For the gated SPECT study 8 frames per cycle and 30 projections were acquired. Sd-MIBI and rest-Ng-MIBI studies and Sd-TI and stress-24-TI studies were independently evaluated by 2 observers and segmental analysis was performed. Of 96 segments were evaluated as fixed defect in Sd-MIBI. However, 35 of 96 segments (36%) reperfused in Ng-MIBI (p<0.05). In Sd-TI and 24-TI viability was detected in 36 (37%) and 41 (43%) of these segments respectively (p>0.1). Ng-MIBI demonstrated 61 (64%) fixed defects. Of these segments Sd-TI and 24-TI revealed 60 (63%) and 55 (57%) nonviable myocardium respectively (p>0.1). In 14 segments we observed disagreement between Ng-MIBI and both of TI studies (agreement 90% kappa. 0.81). Wall motion analysis was performed on 4 slices (VLA, HLA, apical and basal Oblique axis) and 55% of major vessel segments were improved in Ng-MIBI study as compared to rest-MIBI study. In TI studies, all of these segments have also demonstrated perfusion improvement. Thus, gated SPECT with nitrate administration improves the detection of viable myocardium and gives comparable results with Sd-TI and 24-T1.

•

Endocrinology

Endocrinology

OMo089

OMo091

V. TODINO, C.M. PAOELLA, A. CRESCENZI, Z. ROSSI, C. PANUNZI, E. PAPINI Diagnostic Imaging Dept, Histopathology Service, Gastroenterology Unit, Endocrinology Unit - Regina Apostolorum Hospital, Albano - Rome (Italy)

H. Durak, M. S0ylev, E. 0 z b i l e k , B. De~irmenci, t. Durak, M. Ergin. Departments of N u c l e a r Medicine and O p h t h a l m o l o g y , Dokuz Eylill U n i v e r s i t y School of Medicine, Izmir, Turkey.

E C T O P I C THYROID TISSUE IN T I l E L I V E R : CASE REPORT. Ectopic thyroid tissue is an exceptional finding below the diaphragm and it usually represents an occasional discover during surgical or postmortem evaluation of undefined abnormal masses. We describe a case of ectopic thyroid tissue in the liver, evaluated by 123-I neck and whole body scans. The patient (a 66 years old woman) was referred to the Gastroenterology Unit o f our hospital because o f epigastric pain. Ultrasound (US) and CT scans showed a space-occupying lesion (SOL) of the fourth liver segment (46 x 26 mm), characterized by homogeneous pattern and marked ehancement after administration of contrast agent. US-guided biopsy revealed cytological and histological features consistent with thyroid tissue. The morphological diagnosis was confirmed by histochemical evaluation (positive staining for thyroglobulin). The patient underwent a complete nuclear medicine evaluation to exclude a secondary lesion from an occult differentiated thyroid cancer and to confirm the diagnosis of thyroid ectopia of the liver. The relatively high-energy gamma ray and beta emissions of 131-1 render it a poor agent for imaging with gamma camera, and its use is not suitable for whole-body scan while thyroid gland is still present because of the elevated radiation dose. The combination of a 13.3-hours half-life, the absence of beta emissions and a gamma emission of 159 KeV render 123-I close to ideal for in vivo imaging with gamma camera. 74 MBq of 123-[ have been administred per os after an overnight fast. Neck scan and anterior and posterior whole body scans were performed 6 hours later. A gamma camera with LEAP collimation was used (XR/T-4000, General Electric Medical Systems, Milwaukee, WI). Thyroid scan showed a multinodular goiter (T) with radioiodine uptake values, previously determined with 185 KBq of 131-I, within the normal limits (6thh: 24%, 24thh: 30%). Nevertheless, whole body scan revealed also an elevated radioiodine uptake of the abdominal SOL (SOL / T ratio = 0.67, determined by geometric means between KOIs counts on anterior and posterior views). The estimated uptake of the SOL was 15% at 6thh and 20% at 24thh, confirming the normal function of the ectopic thyroid tissue. This finding and the absence of other abnormal sites of 123-1 uptake were consistent with the results o f fine needle aspiration biopsy performed under US guidance, excluding thyroid malignancy.

Tc 9 9 m POLYCLONAL HUMAN IMMUNGLOBULIN G IMAGING IN GRAVES OPHTHALMOPATHY Presence of active i n f l a m m a t i o n in 36 orbits of 18 p a t i e n t s (13 f e m a l e , 5 m a l e , m e a n a g e 5 1 + 1 0 ) w i t h G r a v e s o p h t h a l m o p a t h y was i n v e s t i g a t e d b y Tc 9 9 m p o l y c l o n a l h u m a n i m m u n g l o b u l i n G (HIG) s c i n t i g r a p h y . P a t i e n t s w e r e i m a g e d 4 h o u r s after 10 mCi Tc 9 9 m HIG i n j e c t i o n . SPECT of the o r b i t s was p e r f o r m e d using a t r i p l e d e t e c t o r g a m m a c a m e r a (Neurocam, GEL Tc 9 9 m ttIG u p t a k e of the o r b i t s w a s g r a d e d a c c o r d i n g to t h e i n t e n s i t y a n d l o c a l i s a t i o n o n two p i x e l t h i c k t r a n s a x i a l slices as: O: No uptake, 1: Mild (diffuse or i focal) 2: Moderate (1 - 2 foci) 3: I n t e n s e (diffuse or m o r e t h a n 2 foci). The clinical s e v e r i t y of o c u l a r disease were categorized as 0: Normal, Class I: Mild i n v o l v e m e n t Class II: M o d e r a t e Class III: Severe, a c c o r d i n g to the c r i t e r i a d e s c r i b e d b y Fetdon a n d UnsOld. Disease was c o n s i d e r e d to be c l i n i c a l l y i n a c t i v e if s y m p t o m s a n d s i g n s w e r e s t a b l e or i m p r o v e d i n t h e l a s t two e x a m i n a t i o n s p e r f o r m e d a t l e a s t 6 m o n t h s a p a r t . T h e r e was n o c o r r e l a t i o n b e t w e e n t h e c l i n i c a l g r a d i n g a n d Tc 9 9 m HIG u p t a k e . Two p a t i e n t s w i t h c l i n i c a l l y a c t i v e d i s e a s e b o t h s h o w e d i n t e n s e Tc 9 9 m HIG u p t a k e . 16 p a t i e n t s w e r e c l i n i c a l l y inactive, b u t HIG u p t a k e was p r e s e n t in 15 of 32 eyes (47%). Tc 9 9 m HIG i m a g i n g s h o w e d that t h e r e m a y be a n o n g o i n g s u b c l i n i c a l i n f l a m m a t i o n in the o r b i t s of the p a t i e n t s w i t h Graves o p h t h a l m o p a t h y i r r e s p e c t i v e of the c l i n i c a l d i s e a s e a c t i v i t y . Tc 9 9 m HIG SPECT s e e m s a p r o m i s i n g p r o c e d u r e for the e v a l u a t i o n of t h e o r b i t a l inflammation.

OMo090 M, Chianelli. S.J. Mather, E. Procaccini, G. Ronga, D. Ellison, A. Fritzberg, A. Grossman, K.E. Britton, A. Signore. II Clinica Medica, University of Rome =La Sapienza", Italy; ICRF and St. Bartholomew's Hospital, London, U.K.; NeoRx corp., Seattle, U.S.A.

0Mo092

IN V1VO DETECTION OF LYMPHOCYTIC INFILTRATION IN THYROID AUTOIMMUNE DISEAES BY 99mTc-lL2

THYROID AUTONOMY RECURRENCE DURING AFTER SURGERY.

We have recently described a new method for labelling IL.2 with 99mTc to high specific activity and retained receptor binding capacity using a bifunctional N3S chelating agent. Aim of this study was to investigate the thyroid uptake of 99mTc-lL2 in patients with thyroid autoimmune diseases to in rive quantify the severity of intrathyroidal lymphocytic infiltration and to correlate this parameter with autoantibody titre. 99mTc-lL2 was labelled with a specific activity of ~6GBq/mg and purified by reversed phase chromatography using a miniaturised tC2 Sep-Pak column to a radiochemical purity >99%. 37MBq of 99mTc-lL2 (~13p.g), were injected into 22 normal human volunteers; 24 patients with Hashimoto's thyroidifis, 10 patients with Graves' disease, 3 patients with Primary Mixoederna, 2 patients with acute thyroiditis and 4 patients with simple goitre were studied by injecting185MBq of 99m Tc-IL2. Dynamic images were acquired for 45 minutes and static gamma-camera images were acquired after 60 mins. Thyroid accumulation was calculated by measuring the thyroid to background ratio. Results showed no accumulation in the thyroid of normal subjects (T/B = 1.1_+0.3) whereas a variable accumulation of 99mTc-lL2 was observed in the thyroid of all patients with different autoimmune thyroid diseases (T/B Hasimoto = 1.6+_0.8 p<0.0001 vs NS; T/B Graves = 1.5_+0.4 p<0.001 vs NS). No correlation was found between antibody titres and thyroid uptake of 99mTc-lL2. In conclusion, our results suggest that in thyroid autoimmunity there is no correlation between humeral-mediated and cell-mediated phenomena as detected by autoantibodies and 99mTc-lL2 respectively. Thus both markers could be useful for therapy follow-up.

K. Hamad, F. GrOnwald, C. Menzel, H. Bender, E. Klemm, P. Willkomm, H. Palmedo and HJ. Biersack. Department of Nuclear Medicine, University of Bonn, Germany AND GRAVES" DISEASE: LONG-TERM FOLLOW-UP

Surgery and radioiodine therapy (PJT) are thought to be alternative strategies for definitive therapy of autonomous adenomas (AA) (Plummets" disease) or Graves" disease (IHT). The results of scintigraphy, thyroid hormones (TH), TSH and autoantibodies (TSAb) were evaluated to determine the recurrence rate after surgery. In AA, criteria for recidivation were Tc-99m-uptake values higher than 1% in the presence of a suppressed basal TSH For diagnosis of IHT, suppressed basal TSH in connection with rising antibody titers for TSAb were measured. Overall, 128 patients (88 AA, 40 IHT) were followed post-OP for a mean of 7.76 (AA) and 7.79 years (IHT). Group characteristics were as follows: AA (m:f = 69:19; mean age 44.6 yrs.) and IHT (re:f= 32:8; mean age 35.6 yrs.). Surgery in AA (unifocal 68, multifocal 20) was carried out as total thyroidectomy in l. bilateral subtotal in 58. euucleation in 7 and hemithyroidectomy in 22 cases respectively. In IHT, total thyroidectomy was done in 2, bilateral subtotal thyroidectomy in 31 and hemithyroidectomy in 7 cases respectivly. During follow-up 24/88 (27.3 %) of initial AA developed recurrence of clinically relevant autonomous adenomas. Those patients who underwent surge~ for IHT lind recurrent disease in 12/40 (30 %). All patients were free of clinical sylnptomcs and presented with normal TH/TSH - values during the initial postsurgical phase. The second therapeutical approach to AA-recidivation was surgery in 1, RaT in 8 and thyreostatic medication in 7 cases. Pts. with recidivation of 1HT uodelnvent RaT in 6 and thyreostatic medication in 3 cases. The rate of recidivation in AA and 1HT was comparable. Due to the natural course of IHT postsurgical recidivation did not occur unexpectedly. The number of postsurgical AA-recidivation, hmvever, was surprisingly high. Therefore - as known in IHT surgical approaches to AA seem to be associated with a high recurrence rate. possibly on the basis of the growth of AA during postsurgical phase, which initially were neither detectable using scintigraphy nor a possible target for surgery. As RaT is a feasable treatment even for smaller autononmus cell nests, our data further uuderline a primery indication for radiioiodine therapy in autononmus adenmnas.

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• Endocrinology 0Mo093 D. Sandrock, S. Gratz, J. Meller, H. Siggelkow, W. Becker, and D.L. Munz. Departments of Nuclear Medicine and Endocrinology, Georg August University, GOttingen, and Clinic for Nuclear Medicine, Charitd, Humboldt University,Berlin, Germany. IS P E R C U T A N E O U S E T H A N O L I N J E C T I O N AN E F F E C T I V E T R E A T M E N T IN P L U M M E R ' S D I S E A S E ?

Aim of this study was to evaluate the efficacy of percutaneous ethanol injection for the treatment in Plummer's disease (autonomous thyroid adenoma). Other groups claim to have remarkable success in normalizing functional status and scintigraphic appearance as well as size decrease (Monzani et al; Clin Endocrinol 1992; 36: 491-497) and, therefore, recommend ethanol instead of radioiodine. In 30 pts (19 women, 11 men, aged 54.5 +/- tt.2 years) with autonomous thyroid adenoma (suppressed TSH, thyroidal uptake under endogenous or exogenous suppression > 1.6 %), a total of 142 injections of 1.5 - 3 ml 96 % ethanol were done under sonographic guidance (mean 5.1 +/- 2.5 injections / patient, time interval between 1 and 4 weeks). Follow-up was done monthly and "success" was measured by normalization of fT3, fT4, TSH, scintigraphic appearance ("uptake") and sonography. Heterogeneous results were found: After 6 months 11 of t8 primarily hyperthyroid patients had normal fT3/fT4 values (and 12 of 12 primarily euthyroid patients remained euthyroid), but only 5 of all 30 patients finally had a normal TSH. After the first 2 injections, fT3/fT4 levels increased in 12 pts. Thyroid uptake decreased to 67 % of the initial value (mean) and sonographically measured volume to 77 % (mean). Patients felt pressure and discomfort following 58 injections, 24 reported pain, and 2 hoarseness of less than 48 hrs duration. In conclusion, although in some patients treatment is successful after 3 to 5 ethanol injections, some patients may need more injections or fail to respond. Therefore, this treatment cannot be recommended yet as a replacement of radioiodine therapy.

OMo094

F. Grtinwald H. Palmedo, R. Fimmers, R. Otte, C. Menzel, P. Zamora, C. Steinecker, E. Klemm, H. Bender, H.J. Biersack, Department of Nuclear Medicine and Institute for Medical Statistics, University of Bonn, Germany

THYROGLOBUL1N - TUMOR MARKER OR THYROID MARKER? Thyroglobulin (Tg) has been proven to be a suitable marker for differentiated thyroid carcinoma after total thyroid ablation by surgery and 1-131 therapy. Since serum Tg can originate also from benign remnant tissue, it is not a reliable "tumor marker" prior to the first 1-I 31 treatment. The aim of the present study was to evaluate the clinical significance of serum Tg prior to the first 1-131 therapy. It was hypothesized that the ratio of serum Tg to 1-131 uptake in the thyroid bed could be used to normalize the data correcting for variations in the amount of post-surgical thyroid tissue. The hypothesis was evaluated prospectively in 111 cases of highly-differentiated thyroid cancer (38 follicular/73 papillary) with a mean follow-up of 56 months. Tg was measured prior to the first 1-131 therapy and 1-131 uptake in the thyroid bed was determined 5 hours after administration of 74 MBq scintigraphically. Subsequently, the ratio of Tg to 1-131 uptake was determined in four groups (A: tumor free; B: lymph node metastases; C: distant metastases; D: later recurrence (during follow-up)). Kruskal-Wallis test was used to test for significant differences between the four groups. Subsequently, a Wilcoxon two-sample test was performed to determine statistical significance between group A on one hand and groups B/C/D on the other hand. Significant differences of the Tg/I-131-uptake ratios (median values are given) between group A (i.0 ng/ml/%) and groups B (3.3 ng/ml/%), C (20.2 ng/ml/%), and D (3.3 ng/ml/%) were observed (p<0.0l). Using a threshold of 2.4 ng/ml/%, sensitivity/specificity/positivepredictive values/negative predictive values are 73%/83%/36%/96% for lymph node metastases, 82%/83%/39%/97% for distant metastases, and 75%/83%/30%/97% for recurrence, respectively. Conclusion: The results suggest that the ratio of Tg/l-13l uptake in the thyroid bed can be used as a prognostic marker for thyroid cancer suitable already prior to ablation with t-I3t. Therefore, Tg can be addressed as a "tumor marker" in these cases. 1056

OMo095

B. O. Helal, D. Le Guillouzic, D. Daou, P. Attal, R. Lebtahi Department of N u c l e a r M e d i c i n e . 94275 Kremlin Bic~tre France. HIGH RESOLUTION PINHOLE SPECT IN THYROID DISEASES : COMPARISON WITH PLANAR PINHOLE IMAGES AND ULTRASONOGRAPHY. To determine if pinhole tomography offers advantages to detect small and deep thyroid nodules compared with pinhole planar images we studied both pinhole planar and SPECT images in some patients with thyroid nodular diseases using ultrasonography as the morphological standard. A group of 18 patients was investigated. All had ultrasound examination and were classified as following : Graves' disease with nodule (2), Hashimoto's thyroiditis (1), single thyroid nodule (10), multinodular goiter (3) and normal thyroid gland (2). The acquisition was performed with a camera equipped with a pinhole collimator and a dedicated Elscint Computer. 4 h after IV injection of 400 gci 123I (n=10) or 15 min after IV injection of 5 mci 99mTc (n=8), planar and SPECT images were obtained.The camera was rotated along an arc of 180 ° from the right to the left lateral position. Each image was acquired in 128x128 matrix and 30 images were coUected, at every 6 ° intervals of 40 s each. Using a SPECT reconstruction algorithm, transaxial, coronal slices and 3 D views were reconstructed. The imaging acquisition and computer processing time were 20 and 5 rain respectively. Results : In normal thyroid glands and in Graves'diseases no difference between planar and SPECT images was observed. In Hashimoto's thyroiditis additional functional information was obtained. In multinodular goiter SPECT showed 2 further small nodules (9, 11 mm) and in single thyroid nodules, SPECT was more performant in 4/10, detecting an evident small cold isthmic nodule (9 mm) in one case and 3 others small cold posterior and lateral nodules in 3 cases (9, 10, 1 lmm). All these results were confirmed by ultrasound examination. In conclusion : according to these results, it seems that pinhole tomography was more performant in thyroid nodular diseases than planar pinhole images, especially when nodules are small, posterior, lateral and isthmic and this method can be used in clinical practice.

OMo096 P. Netzer*, C. AIs*°, M. Listewnik*, H. Rosier*. Departments of *Internal Medicine and *Nuclear Medicine, Institute of °Pathology, University of Berne, Inselspital, CH-30t0 Berne, Switzerland. HYPERTHYROIDISM AND ASSOCIATED THYROID CANCER. Aim: In the literature, the association between thyroid carcinoma (TC) and hyperthyroidism (HT) is found with a 1-21% frequency. In the endemic goiter region of Berne, we looked for the frequency and for a distinct versus identical genesis of this association. Method: All patients (pat.) thyreidectomized for TC between 1971 and 1983, whose latent or open HT was documented by preoperative scintigraphy and laboratory findings, were included. The appearance of radioiodine-retaining heterotopias dudng the follow-up until 1990 or death was considered as metastases and hence, as a second proof of malignancy of the primary tumor. The histologic and cytologic samples were newly reviewed and confronted with the findings of preoperative palpation, scintigraphy and surgery. We classified TC and HT as having an identical genesis when: a) 'hot' nodules were congruent with the TC, b) autoradiography was positive, c) (toxic) metastases retained radioiodine with the thyroid or thyroid remnants still in place. The sensitivity of palpation-guided fine-needle-aspiration biopsy (FNAB) was controlled as well. Results: Of 585 reviewed case documents with TC, 270 pat. had had a preoperative thyroid scintigraphy. 51 pat. (18.9%) had also preoperative HT: 4 Graves' type (GD), 15 multifocal functional autonomies (MFA) and 32 unifocal autonomies (UFA). The histologic types of TC occurred with the same frequency as in the overall local population. A distinct genesis of HT and TC was preoperatively suspected in 24 pat. (47%). In 27 pat. (53%), the identical genesis of both diseases was clinically suspected and could be confirmed after clinical follow-up and histologic reevaluation in 18 pat. (35.2% of the present 51 pat. or 6.6% of the 270 TC pat.). Scintigraphically, 17 of these had an UFA, 1 an MFA (with toxic metastases). In 15/18 pat., 'hot' metastases were demonstrated in the radioiodine scan (7 preoperatively). The histology of the 18 'toxic carcinomas' was well differentiated: 14 follicular and 4 papillary TC. FNAB was found positive or suspicious in 16 of 31 (52%) pat. Conclusions: The association of TC and HT in 18.9% of Bernese patients operated between 1971 and 1983 lies in the upper domain of literature data and was more often found with functional autonomy than with GD. With a contribution of 'toxic carcinomas' of 6.6% within 270 scintigraphied TC or of 35.2% within 51 TC with HT in a 13-year period, a 'hot' nodule cannot he considered as benign a priori. The hypothesis that HT can inhibit initiation and/or growth of TC, is to be revised. As is known from the literature, cytology before the epoch of ultrasound had an insatisfactory sensitivity.

• Endocrinology 0Mo097

OWe099

M.P. Bedigian, J.P. Vansant, J.M. Hoffman, E. Garcia. Emery Center for PET, Emery University School of Medicine, Atlanta, GA

A.Giordano I, G.Meduri ~, P.Marozzi z, U.Ficola 2, M. Cappagli~, A.Montepagani3, G. Rubini3, G. Di Giovine4,G.Petracca Ciavarella 5. Nuclear Medicine Depts of IRome Catholic University, ZPalermo Hospital,3La Spezia Hospital,4Bari University, SSan Giovanni Rotondo Hospital.

DETECTION

OF

PAR/%GANGLIOM-AS

BY

FDG-PET

Paragangliomas are tumors of neural crest origin typically imaged with CT, MRI and MIBG. The role of F-18-FDG-PET in the evaluation of these tumors is currently undefined. Five patients with newly diagnosed or recurrent paragangliomas underwent FDG-PET studies to determine the ability of PET to detect tumor presence. Five patients underwent CT and/or MRI, in addition to PET imaging using the Siemens ECAT 921 scanner. Four out of 5 patients had confirmatory pathology. PET imaging was performed using 10-12 mCi of F-18-FDG with standard delay sequence and subsequent body emission scans. All PET studies were correlated with existing CT and MRI images. In 4 patients with confirmatory pathology, PET identified all positive lesions including adrenal as well as extra-adrenal sites. In one case, a small cervical lymph node metastasis was identified with intense FDG uptake, yet failed to meet size criteria for nodal disease using standard CT evaluation. In 1 patient with biochemical and clinical evidence of recurrent pheochromocytoma, PET identified a spinal abnormality which was subsequently confirmed as a lyric process by CT. In 2 patients, PET identified unsuspected metastatic disease which changed the clinical management and therapeutic approach. Our preliminary study of F-18-FDG-PEt imaging in patients with paragangliomas supports the possi-bility of a high positive predictive accuracy of lesion detection as compared to conventional CT and MRI findings. Also, PET identified in one patient, lesions which were confirmed pathologically yet not detected anatomically by standard imaging procedures resulting in a change in management.

99mTc-TETROFOSMIN

IN

PA/~ATHYROID

4--J

C

SCINTIGRAPHY.

Five italian centers joined to commonly evaluate the diagnostic value of 99mTc-Tetrofosmin (TETR) in parathyroid scintigraphy (PS). STUDY1: TETR vs 201TI (TI); 52 pts; enrolment concluded; TETR 555-740 MBq, T1 74 MBq, 99mTcO 4- (Tc) 74 MBq; imaging 5 min after injection; evaluation of TETR-Tc and TI-Tc subtracted images. Definitive results: concordance between TETR and T1 was 43/52 (83%). Sensitivity, specificity and accuracy of TETR and T1 were, respectively: 92%, 75%, 90% and 78%, 75%, 77%. Adenoma/background ratios of TETR and T1 were, respectively: 2.46 ± 1 and 1.81 ± 0.52 (p<0.05). STUDY2: TETR vs Sestamibi (MIBI); 93 pts; enrolment ongoing; TETR 370-740 MBq, NIBI 370-740 MBq, Tc 37 MBq; imaging 5 min and 2-3 hrs after injection; evaluation of early/delayed images and Tc subtracted images. Preliminary results: no significant differences in image quality and in adenoma/thyroid ratio were obtained between TETR and MIBI. Concordance was 91% for early and 83% for delayed images. Dual phase accuracy was 59% for TETR and 88% for MIBI (p=0.016). After Tc subtraction TETR and MIBI results were identical. Conclusions: l) TETR is superior to T1 in PS; 2) TETR and MIBI have similar but not identical scintigraphic characteristics and appear equally effective in PS provided that the appropriate procedure (dual-phase or Tc subtraction) is used.

OWe098

OWelO0

F. Griinwald H. Bender, C. Menzel, H. Palmedo, E. Klemm, J. Ruhlmalm, P. Willkomm, H.J. Biersack, Department of Nuclear Medicine, University of Bonn, Germany

D. Huglo,V. Beauchat, T. Prangere, P. Ziegeis, M. L e c o m t e - H o u c k e , B. Carnaille, C. Proye, M. Steinling H6pital Huriez - C H U de Lille - 59037 Lille Cedex - F R A N C E

COMPARISON OF SESTAMIBI SCINTIGRAPHY AND FDG-PET IN THYROID CANCER.

99mTc-TETROFOSMIN F O R P A R A T H Y R O I D I M A G I N G The aim of this prospective study was to assess parathyroid scintigraphy using 99~Tc-tetrofosmin (Myoview, Amersham) in the preoperative detection and localization of parathyroid lesions. Methods : 550 MBq 9~Tc-tetrofosmin were injected, and images performed 20 min and 2 h later. 12aI was then injected and thyroid scan obtained 2 h later. Parathyroid scan was evaluate versus surgical finding, parathyroid mass and pathological anatomy. A ROC analysis was performed to study the mass threshold. 55 patients (47 females, 8 males, mean age : 59.4 y) with known primary hyperparathyroidism were cured by surgery 11.7 +_ 27 d after scintigraphy. Among 201 glands, 67 were abnormal : 37 adenomas [60 rag-17 g], 30 hyperplasias [50-6218 rag]. 45 patients had only one lesion, 8 patients 2 lesions and 2 patients 3 lesions. Results : Localization was correct in 45/67 lesions (67 %), 30 adenomas (81%), 15 hyperplasias (50 %), 37/45 (82 %) patients with one lesion and 8/22 (36 %) multiple lesions. There was only onr false positive. At least one lesion was seen for 44/55 (80 %) patients. There was no significant difference between lesions with (22 positive /30) or without (23 positive/37) oxyphil cells. Mass of positive lesions [r : 60 mg-17 g, mean : 1798 rag, median 757 nag] were significantly (p < 0.0001) higher than negative lesions [r : 50-638 rag, mean : 204 rag, median 154 rag] but mass of multiple lesions [r : 50-1395 mg, mean : 296 mg] were also significantly lower than unique lesions [r : 60 mg-17 g, mean : 1753 rag]. ROC analysis demonstrate a visibility threshold between 380 and 210 nag (correct results : 84 %). Conclusions : The results of 99mTc-tetrofosmin in the preoperative localization of parathyroid lesions are similar to our previous results with 99~Tc-MIBI with the same protocole and both tracers could be used in parathyroid scintigraphy.

The aim of the study was to compare the clinical results of sestamibi (MIBI) scintigraphy with FDG-PET in the follow-up of differentiated thyroid carcinoma. FDG-PET (Siemens/CTl ECAT Exact 921/47 PET scanner, wholebody technique with measured attenuation matrix) was performed in 33 patients with differentiated thyroid cancer. MIBI scintigraphy (whole body imaging and SPECT study of head and neck) was done in 20 of these cases. Twentysix patients suffered from papillary carcinoma, 7 patients from follicular tumor. Primary tumor stage (pT) was pT1 in 6 cases, pT2 in 8 cases, pT3 in 3 cases and pT4 in 14 cases, respectively. FDG-PET was normal in 18 patients. In 3 patients, a slightly increased metabolism was observed in the thyroid bed, supposed to be related to remnant tissue. In one case local recurrence, in 10 cases lymph node metastases (one false-positive, caused by sarcoidosis) and in 3 cases distant metastases were found with FDG-PET. In comparison with whole-bodyscintigraphy using I-131 (WBS) there were a lot of discrepancies in imaging results. Whereas 3 patients had distant metastases (proven with 1-131) and a negative FDG-PET, in 4 cases 1-13 l-negative lymph node metastases were detectable with PET. MIBI was positive in 2 of these cases. Even in the patients with concordant "staging", differences between 1-131 and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 1131-positive/FDG-negative, 1-131-negative/FDG-positive and 1-131-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG-PET was observed with MIBI scintigraphy (performed in 20 cases)than with WBS. In highly-differentiated tumors 1-131 scintigraphy had a high sensitivity, whereas in low-differentiated carcinomas MIBI and FDG-PET seemed to be more sensitive. Compared with M1BI seintigraphy, FDG-PET was superior (particularly in small lymph node metastases), probably due to higher spatial resolution. Conclusion: FDG-PET and MIBI scintigraphy can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and are particularly useful in cases with elevated serum Tg levels and negative WBS. MIBI has the advantage of a lower logistic demand and should be performed initially in these cases, whereas FDG-PET has a higher sensitivity.

C O |l

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• Endocrinology OWe101

OWe 103

~Dapartment of Nuclear Medicine and Special Endocrinology, ZDepanment of Surgery Landeskrankenhaus Klagenfurt, Austria

S. Maurea, M. Klain, P. Varrella, R. Rossi, C. Malnolfi, H. Wang, A. Boccanfuso, F. Ruffolo, L. Marzano, M. Salvatore. Nuclear Medicine, Endocrinology and Oncology; Istituto Nazionale dei Tumori, CNR, Universit5 degli Studi "Federico I]", Napoli, Italy CLINICAL SIGNIFICANCE OF RADIOLABELED NORCHOLESTEROL, MIBG AND FDG UPTAKE IN PATIENTS WITH NON-SECRETING ADRENAL MASSES

Preoperative scintigraphic and intraoperative scintimetric localization of parathyroid adenoma with cationic To-99m complexes and a hand-held gamma-probe

Tumor characterization is requested in patients with incidentally discovered non-secreting adrenal masses. In this study, 36 patients with incidentally discovered non-secreting unilateral adrenal lesions (15 adenomas, 4 pheochromocytomas, 3 cysts, 2 mielolipomas, 1 liver hyperplasia, 4 carcinomas, 6 metastases and 1 sarcoma) were evaluated using radionuclide imaging studies, of which selenium-75 or iodine-131 nor-cholesterol (n=20), iodine-131 or iodine-123 MIBG (n=22) and fluorine- 18 FDG PET (n= 10). Laboratory evaluation of adrenal function was normal in all cases. Nor~cholesterol studies were performed in 15 adenomas, 2 cysts, 2 mielolipomas and 1 metastasis showing increased uptake only in adenomas. Nor-cholesterol uptake in non-secreting adenomas was semi-quantitatively compared to that of a separate group of 14 patients with secreting adenomas using the following 4-point scoring: 0=background activity, l=just visible uptake, 2=increased uptake, but inferior to liver activity and 3=uptake equal to liver activity. In this analysis, nor-cholesterol uptake was significantly (p=0.01) higher in secreting (2.8+0.5) compared to non-secreting (2.2+0.6) adenomas. MIBG studies were performed in 9 adenemas, 2 cysts, 4 pheochromocytomas, 3 carcinomas, 2 metastases, 1 liver hyperplasia and 1 sarcoma showing increased uptake only in pheochromocytomas. FDG PET studies were performed in 2 adenomas, 1 mielolipoma, 4 carcinomas and 3 metastases showing increased uptake only in carcinomas as well as in metastases. In conclusion, the results of this study show that radionuclide imaging has a relevant clinical role to characterize incidentally discovered non-secreting adrenal masses. In particular, nor-cholesterol allows to identify non-secreting adenomas; the difference in nor-cholesterol uptake between non-secreting and secreting adenomas may suggest a lower hormone synthesis in nonsecreting lesions. MIBG is able to characterize an adrenal mass as a nonsecreting pheochromocytoma. Finally, FDG PET allows to identify malignant adrenal lesions such as carcinoma and metastasis.

Hans J0rden Gallowitsch 1, Johann Feltinger 2, Ewald Kresnik ~, Peter Mikosch 1, Peter Lind 1 Dystopic adenomas may be problematic in intraoperativelocaitzationdespite preoperative imaging, resulting in a longer operating time and more extensivesurgical preparation.The aim of our study was to evaluate the possibility of intraoperativesc[ntimetttc detectionof parathyroidadenomaswith Tc.99m labelledtracers for its usefulnessin dystopicor ectopic apenomas. Patients and methods: 12 women (mean age: 57, range: 24 - 69 yr.) with hyperparathyroidism (11 primary, 1 secondary); mean PTH levels: 329.3 pg/ml (normal range: 10 - 65), 2 had previous neck surgery, wereincluded in our study. After injectionof 370 MBq Tc-99mTetmfosmin e g. Seetamibi, preoperativescintigraphy(double phase study and SPECT) was performedand T/NT ratioswere evaluatedfor eady, detayedand SPECT images. Surgerywas performedusinga hand-heldgamma probe (C TRAK®,CarawiseInc, Morgan Hill. CA} aRer preoperativeinjection of 555 - 925 MBq Tc,-99m Tetmfosmin e.g. Sestamibi. Countrates(cts/10sac) were measured and used for calculating in situ - and ex situ - T/NT ratios. Results: In 9 out of 12 patients, adenomacould be detected on static images. MeanTiNT ratios for Tc-ggm Tetrofosminwere 129 for earlyand 1.23 for delayed images, respectively1.39and 1.23for earlyand delayedTc-99m Sestamibiscan. Two cases could only be detected with SPECT reconstruction.SPECT showed slightly better TINT ratios (1.57 e.g. 1.41) and influenced surgical approach in two cases with dystopic adenomas.MeanTINT ratiosor in situ and ex situ - measurementsat a meantime of 61 e,g. 76 sin p.l. showedsimilarvalues(1,87e,g. 't.9). Scintimetricallyevaluatedratios showedno significant correlationto preoperativelymeasuredTiNT values (r =25). 10 of 11 parathyroid adenomascould be confirmed intraoperetively.One false negativecasewith oxyphi]cell -poor adan~ma, also preoperativelyshowed t~wer values (TINT: Q.65; 1.05; 1.571. HistoLogicaL examination demonstratedpredominant chief cells in 5 cases with 1 oxyphil cell - poor adenoma, mainlyoxyphilceils in 2, and mixed cellularityin 2 cases. Meansize was 22 mm (range: 16 - 30 mm diameter).Conclusion: SPECTwith Tc-99m Tetrofosminor Sestamibi showed clear advantages in detection, precise localization and contrast over static scintigraphy and shouldthereforebe performed at [east in easeswflh poor or no uptakeon static images to avoid failures in detectionof deeply sited, dislocated glands or adenomas with low uptake. Intraoperativelocalizationand confirmationof parathyroidadenomawith Tc99mTetrofosminlSeetamibiand a gamma probe is possible in cases with dys-or ectopic adenomaand may probablyinfluencesurgicalapproachand operatingtime.

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invisible in MNI 13tZj a n d in p a t i e n t s with tumors inactive after treatment tIOZ. In b o t h p a t i e n t s w h o d i d n o t reveal adenomas in M ~ I s c a n s t h e i n c r e a s e d uptake of 99mTc-M]BI was observed. In conclusion, 99mTc-MIB] pituitary S P E C T s e e m s to b e tool to e s t i m a t i o n hTpophyseal adenomas.

1058

SCINTtGRAPHY

FOR

good

aim

radiological findings. SPECT employing 9@mTc-M]B] was performed in 15 p a t i e n t s 20 m i n a f t e r iv injection

A. SIGNORE, E. PROCACCINI, R. BARONE, M. CHtANELLI, G. VENTRONI, M. CIANCAMERLA, M. MELLOZZI, L. PASTORE, G. ~ and G TAMBURRANO. Servizio Medicina Nucleare and Endocrinologia (I), Clinica Medica (11), University "La Sapienza", R o s a , Italy.

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Endocrinology

sensitive

We present the results in 28 patients operated f o r p a n c r e a t i c insulinoma. Patients were selected on the basis of fasting hyperinsulinemia and inverted plasma g l u c o s e / i n s u l i n ratio. Tumours at surgery were smaller than 2 cm of diameter. Two patients did not show any turnout at surgery. Octreoscan was performed by acquisition of SPET images at 6 and 24 hours a f t e r administration of 3 mCi 1 1 1 - l n - O c t r e o t i d e . SPET images w e r e acquired for 360 ° with 60 steps. A general purpose c o l l i m a t o r was used. The effect of different acquisition times and r e c o n s t r u c t i o n filters was investigated. We also compared the s e n s i t i v i t y of Octreoscan with other 5 diagnostic techniques. Results are summarised in the following table: Exam Ultrasound CT scan NMR Arteriography A S V S (Ca-gluc.) Octreoscan 6H Octreoscan 24H

Total 18 21 18 16 17 22 22

True+ 2 4 10 6 11 15 13

True-

0

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False16 15 7 11 2 3 6

Overall, Octreoscan showed a sensitivity of 80%, NMR of 5 5 % , ASVS of 65%. Both 6h and 24h acquisitions are required. Best d e f i n i t i o n was obtained acquiring SPET images for 40 seconds/step and using an Hanning filter (0.5 cycles) and a pre-attenuation c o r r e c t i o n ( 0 . 1 2 5 cm -t attenuation coefficient). We conclude that Octreoscan does increase the detection rate of pancreatic insulinoma and provides a fundamental indication f o r surgery. Sensitivity of Octreoscan is improved by o p t i m i s a t i o n of acquisition and elaboration protocols.

•

Endocrinology/Gastroenterology

Gastroenterology OWe105 S,lJnal, Y. Menda, H. O~uz, N. D e p a r t m e n t s o f N u c l e a r Medicine i s t a n b u l Medical Faculty, l s t a n b u l

(/)

0Su107 O z b e y , S. Cantez. and E n d o c r i n o l o g y ,

T H E R O L E OF T H A L L I U M - 2 0 1 , T E T R O F O S M I N A N D I O D I N E 131 IN D E T E C T I O N OF D I F F E R E N T I A T E D THYROID CARCINOMA METASTASES T h e aim o f this study is to investigate the role o f 99m Tc T e t r o f o s m i n e (T) w h o l e b o d y s c a n n i n g in detection o f differentiated thyroid c a r c i n o m a m e t a s t a s e s ( D T C M ) and to c o m p a r e the results with thallium-201 (TI) and Iodine131 (I) scans. T w e n t y five patients with D T C (18 papillary, 7 follicular ) were studied. After thyroid h o r m o n e discontinuation for 2 w e e k s all patients u n d e r w e n t TI 201, Tc 9 9 m T and I t31 w h o l e b o d y s c a n s and thyroglobulin (Tg) determination and computerized t o m o g r a p h i c (CT) examinations. T h e results w e r e also c o m p a r e d with the clinical conditions. In 16 patients, T, T1 and I s c a n s w e r e negative; these patients also clinically d i d n ' t s h o w any evidence o f m e t a s t a s e s and their Tg levels w e r e within n o r m a l limits. In 8 patients all three s c a n s s h o w e d m e t a s t a s e s in the s a m e regions. In only l patient although 1 131 scan w a s negative TI and T s c a n s s h o w e d increased uptake in the cranium, thyroid bed, s u p r a c l a v i c u l a r region and in left apical lung. T h e Tg level o f this patient w a s elevated; CT also p r o v e d the m e t a s t a s e s in these regions. The sensitivity and specificity o f T and TI s c a n s w e r e 100 % c o m p a r e d to 88 % sensitivity o f I scanning.

V. Artiko, M.Petrovi~,V.Obradovid,M Stojkovic,N.Kova~evi~,K.Koshc

Institute of Nuclear Medicine, Institute ibr Digestive Diseases, School ot Medicine, Clinical Center,Beograd-YU GALLBLADDERMOTILITYEVALUATIONAVI'ERGASTRIC SURGERY BY INFUSIONCHOLESCINTIGRAPHY

The aim oftlm studyis the estimationof the gallbladder(GB) motilityin the controls (C, It=8), patients after partial gastrectmny(Biilroth t -B [, a=7 and Bilkoth II- 13 II, n=7), gastroplasty ((.3, n=7 ) and in those after total gastrectumy (PG, n=10) in order to assess the influence of the tnmcal vagotomy(GP, PG) and exclusionof the duodenaltransit (B II, PG) of food on the GB motility. The study was performeddtmng (3 h,10 ml:hl infusionof 150 MBq, 0.25 mg/ml 99m-Te-EHIDA,preeeeded by a loading dose. Test meal was given in 120. rain. in the patients withpreservedn wlgnsand duodenal transit (BI), ejection fraction (EF=66,~+/-9.2%), emiW~" lin~e (ET=35.1+/-6.2 rain) and ejection rate (ER=2.1+/-0.5%/min)wereahnost physiological~p > 0.05) IC;EF=76.7+/17.9%; ET=-37.8+/-11.4 rain and ER=2.1+/-0A5%malL In the patients with exclusionof duodenal transit (RV BID,EF v',fluaswere (58.3+/-[1.4%) slightly, but not significantlydecreased(p -- 0.05) in comparisonto C and RV BI while ET and ER were completelytmdisturbed(39.0 mm and 1.61+/-0.46%'raink In those with truncal vagotomy(GP), EF wss slightly decreased (5 ~.,1+/-14.4%}, ER unchanged (1.8~-/-0.84%/min)while F.T (23.3+z75 rain) was sig~fificanfly (p < 00.5) decreased in comparisonto C, RV B] and RV BIL In the PG, udth both trancal vagotmnyand exclusionof the duodemd transit, EF. ET and ER (23.3+/-8.5%; 23.5+/-7.5 rain; 0.92+;-0.40 %;min~were signilScantIy(p < 0.05) decreased in comparisonto C, RV Br, RV EII and GP. We can conclude thal trmlcal vagotom3,especially if accompaIfiedby the exclusionof duodenal transitcause GB mr~filitydisorders So, in the choice ol gastric surgery, advantagemust be given to the melhod~fllat preserven. va~mls and duodenal transit as oflan as it can, m order to avoid forum|ionof GB calculosis.

In c o n c l u s i o n T scan can be used safely to localize the metastatic r e g i o n s in D T C M .

OWe106 I.Adalet, P.Demirkale, H.O~uz, S.IJnal, M.Ko~ak, F.Alagdl, S.Cantez Departments of Nuclear Medicine and Endocrinology, Istanbul Medical Faculty, TOrkiye DETECTION OF MEDULLARY THYROID CARCINOMA METASTASES BY Tc-99m TETROFOSMIN: COMPARISON WITH Tc-99mVDMSA AND TL-201 Tc-99mVDMSA (VDMSA) scintigraphy has become an accepted method for localizing metastases of medullary thyroid carcinoma (MTC). T1-201 has been investigated for the same purpose. Recently, Tc-99m Tetrofosmin (Tetro) has been reported as a tumor imaging agent in lung, breast, brain and thyroid malignancies. In this study, we compared Tetro, as a new agent to localize recurrence and metastases of MTC with VDMSA and TI-201. We studied 9 patients (3M, 6F, mean age 41 yrs, ranging from 23 to 68) treated with total thyroidectomy for MTC with suspect of disease recurrence. Six of these cases were sporadic and 2 were familial. All images were obtained in whole body format in anterior and posterior positions and 300 second static images taken from head and neck region, thorax and pelvis. The scintigraphies were grade as 1+, 2% 3+ activities in the pathologic regions. Scan results were compared to clinical, radiologic, histopathologic findings and calcitonin levels. Five patients had positive scans. The results were as follows: Tetro TI-201 VDMSA TP 3 4 5 TN 4 4 4 FP 0 0 0 FN 2 1 0 (TP:True positive,TN:true negative,FP:false positive,FN:false negative) One of these 5 patients bad multiple lung metastases in which TI-201 scan showed 3+ activity while two other scans showed 1+ activity. The other 4 patients who had metastases in soft tissue demonstrated more intense radionuclide accumulation (3+) with VDMSA than the other two scans (1+) In conclusion, VDMSA should be used as a first choice in detecting MTC metastases. TI-201 may have a eomplemantary role. Tetro yielded poor results and cannot be proposed as routine procedure.

OSu108 G.Heidendal, S.Halders, G.Kemerink, R.Brummer(*), D e p a r t m e n t of Nuclear M e d i c i n e and D e p a r t m e n t of G a s t r o e n t e r o l o g y ( * ) , A c a d e m i s c h Ziekenhuis Maastricht.

STOMACH EMPTYING AND BOWEL TRANSIT STUDIES A c o m b i n a t i o n of stomach emptying with small-bowel and colon transit c a r lead to quick d i a g n o s i s for patients with d y s f u n c t i o n of the gastrointestinal tract. Integrating the three e x a m i n a t i o n s into one r e d u c e s the burden of r a d i a t i o n for the p a t i e n t and saves costs as well. A c o m b i n e d test was d e s c r i b e d in 1992 (Mayo Clin Proc, Vol 67 1169-1179). In this test the p a t i e n t is given a capsule, w h i c h is coated with m e t h a c r y l a t e and contains lllIn, in a r a d i o a c t i v e b r e a k f a s t (99mTch e p a t a t e I I in a fried egg with bread). The 99mTc is used to calculate the s t o m a c h emptying and passage through the small intestine. The lllIn m e t h a c r y l a t e c a p s u l e does not d i s s o l v e until it reaches the ileocecal region due to a change in pH at that point. Thus, the lllIn reaches the colon as a bolus, which gives the o p p o r t u n i t y to d e t e r m i n e the regional and total colon transit time. For this purpose the colon is d i v i d e d into four parts, namely, c. ascendens, c. transversum, c. d e s c e n d e n s and rectum. The foecal e x c r e t i o n is also measured. }Te have m o d i f i e d the M a y o Clinic test and w r i t t e n a c o m p u t e r p r o g r a m to work out the test. We also tested t:he r e p r o d u c i b i l i t y of this procedure. Normal values for the c o m b i n e d test have not yet been described. We now attemp to determine the normal values for this ideal c o m b i n e d test.

1059

C O r(/) s_

0.. s_

0

• Gastroenterology OSu109

OSu111

K K Balan, J. Bennett ~, P Maltby, S Woods, S Vinjamuri, J R Playfer ~ and M Critchley, Departments of Nuclear Medicine, G a s t r o e n t e r o l o g y ~ and Geriatrics ~ , Royal Liverpool University Hospital, Liverpool. L7 8XP U.K.

E. G. E i s i n g I, M.R. v o n d e r O h e 2, J. S c i u k I. ~Clinic for N u c l e a r M e d i c i n e a n d ~Clinic for I n t e r n a l M e d i c i n e , Univ. of Essen, G e r m a n y

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY FEEDING - SCINTIGRAPHIC DETECTION OF GASTROOESOPHAGEAL REFLUX AND ASPIRATION.

IS C O L O N T R A N S I T S C I N T I G R A P H Y A B L E TO D I F F E R E N TIATE SUBTYPES OF PROLONGED COLONIC TRANSIT?

Pereutaneous endoscopic gastrostomy (PEG) is the method of choice for feeding patients who are unable to eat adequately and yet have a functional GI tract. PEG eliminates the need for surgery or nasogastrio tubes, is easily performed with few demands on health service resources. Aspiration pneumonia may complicate PEG insertion but there are few studies on gastrooesophageal reflux (GOR) in PEG patients.

P r o l o n g e d c o l o n i c t r a n s i t c a n be c a u s e d e i t h e r b y slow transit constipation or pelvic outlet obstruction (needing d i f f e r e n t t h e r a p e u t i c regimes). This s t u d y r e f l e c t s o u r p r e l i m i n a r y e x p e r i ences, w h e t h e r s c i n t i g r a p h i c a s s e s s m e n t of c o l o n t r a n s i t u s i n g the m e t h o d p u b l i s h e d b y C A M I L L E R I * is u s e f u l for this d i f f e r e n t i a t i o n .

Methods: 16 patients (i0 M, 6 F, age 65-83 years, mean 73) with PEG underwent radionuelide GOR studies, i0 patients had neurological and 6 had mechanical dysphagia. They received i00 ml of orange juice containing 25 MBq of To99mtin colloid followed by 250 ml of normal saline, through the PEG tube. Patients lay supine under the gamma camera linked to a digital computer system. 4 minute and 4 hour images over stomach, oesophagus and lungs were examined for GOR and lung aspiration.

C o l o n s c i n t i g r a p h y was a p p l i e d in 19 p a t i e n t s with idiopathic constipation at l e a s t at 8, 24 a n d 48 h o u r s a f t e r o r a l a d m i n i s t r a t i o n of a p H sensitive, m e t h a c r y l a t e - c o a t e d c a p s u l e of I n d i u m iii l a b e l e d m i c r o p e l l e t s (3.5 M B q / c a p s u l e ) . The c a l c u l a t i o n of g e o m e t r i c c e n t r e (GC) w a s u s e d to d e t e r m i n e the v e l o c i t y of c o l o n i c t r a n s i t .

Results: 6 patients, 4 of whom with neurological dysphagia and g of whom with mechanical dysphagia, had severe GOR. 2 other patients with neurological dysphagia had mild GOR. One patient with severe GOR also had lung aspiration at A hours. 8 patients had normal studies. Conclusions: i) Radionuelide imaging can assess GOR in PEG patients 2) G0R appears to be a significant problem in patients with PEG and S) PEG patients with neurological dysphagia appear to be at greater risk for GOR than those with mechanical dysphagia. Further studies are in progress.

The 9 5 % - c o n f i d e n c e i n t e r v a l of t h e GCs of 16 p a t i e n t s s h o w e d s i g n i f i c a n t d e c r e a s e a f t e r 24 a n d 48 h o u r s c o m p a r i n g to the l o w e r b o u n d of the n o r mal range ( c a l c u l a t e d f r o m 22 h e a l t h y controls) indicating slow transit constipation. 3 patients h a d n o r m a l t r a n s i t u p to the r e c t u m b u t d e l a y e d rectal emptying revealing pelvic outlet obstruction with normal values of GC a f t e r 24 hours. To conclude, d i f f e r e n t i a t i o n of t h e two s u b t y p e s of c o l o n t r a n s i t p r o l o n g a t i o n was possible l e a d i n g to d i f f e r e n t t h e r a p e u t i c m a n a g e m e n t . *) Camilleri M. 1992,

103:36-42,

Gastroenterology

OSu110

OSu112

B Huszno, J. Bogdat*, T. Mach*, A,Sakran, F, Gotkowski, Z.Szybifiski Unit of Nuclear Medicine. Chair and Department of Endocrinology C M U J, Krak6w *Department of Gastroenterology CM UL Krak6w.

B. Kettner 1, D. Sandrock 1, R. Aurisch 1, B. Hoksch 2, and D.L. Munz 1. ~ r Nuclear Medicine and 2Clinic for Surgery, Charitd, Humboldt University, Berlin, Germany.

Influence of Helicobacter pylori infection on stomach emptying.

The role of Helicobacter pylori (H.p.) in etiopathogenesis of gastric ulcer has been well documented, but patients with this infection are not a homogeneous group. Sometimes Hp. infection is associated only with dyspepsia, without gastric ulcer, or the symptoms are not observed at all. The authors decided to observe stomach emptying in two groups of patients with H.p. infection. Group A represents patients with gastric ulcer, group B only with dyspepsia. Group A consisted of 14 patients (9 males, 5 females) aged 23-56 years. Group B consisted of 12 patients (7 males, 5 females) aged 21-52 years. The control group named group C consisted of 8 volunteers, without H.p. infection and dyspepsia. Stomach emptying was examined after stomach solid meal labelled with 37 Mbq 99mTc-PVP colloid. The study was performed using Digitrac ZLC (Siemens) gammacamera with MiaroDelta computer Half emptying time (T 1/2) was compared with the intake maximum activity over the stomach. Significant difference in stomach emptying between groups A and B was found. In group A T1/2 was 0,7 ± 0.15 h and was comparable with group C. In group B T 1/2 was longer - 1.1 ± 0.2 h. Conclusion: stomach emptying in patients with H.p. infection and dyspepsia is prolonged and could stand for one of the reasons of dyspeptic symptoms. group A

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1060

E V A L U A T I O N OF D I F F E R E N T INTESTINAL T I M E S IN P A T I E N T S A F T E R G A S T R E C T O M Y

HALF E M P T Y I N G

Aim of this study was to evaluate differences in the emptying time of a semisolid meal after gastrectomy and different surgical gastric reconstructions. 25 patients (14 men, 11 women, mean age 61 +/- 11 years) with total gastrectomy due to gastric cancer had a Longmireinterposition (maintaining a physiological duodenal transit, 7 patients), a Roux-Y limb (without duodenal transit, 6 patients), a pouch (jejunal interposition) of 7.5 cm length (7 patients), and of 15 cm lenght (5 patients). After 12 hrs fasting conditions and landmarking of the anastomoses under fluoroscopic guidance, patients were positioned in front of a gamma camera in the same sitting position as for X-ray. The test meal was prepared by mixing 45 MBq Tc-99m sulfur colloid with 30 ml rice pudding. After meal ingestion dynamic and static images were acquired in anterior view until emptying half time of the interposed jejunum / pouch was reached (region of interest technique). Scintigraphy was repeated 2 weeks, 3, 6, and 12 months after the surgical reconstruction. 61 studies have been performed thus far. Normal values of emptying half time were obtained from 13 normal volunteers (mean 15 +/- 4 rain). The mean emptying half time in patients without pouch reconstruction (32 studies) but with Longmire-interposition and with Roux-Y limb was 16 +/- 13 min and 1t +/- 10 rain, respectively (n.s.), Patients with pouch reconstruction of 7.5 cm and 15 cm length had significantly longer (p < 0.01) emptying half times 32 +/- 18 and 36 +/- 32 min, respectively (n.s.). In conclusion, emptying time of pouches is longer than that of Longmire-interpositions or Roux-Y limbs.

•

Gastroenterology

0Su113

0Su115

F. Scopinaro, O. Schillaci, E. Corazziari*, A. Vignoni, M. Cicala*, F.I. Habib*, V. Picardi, N. Pallotta*, R. Massa, A. Centi Colella, Nucl. Med. and *Gastroent., Univ. "La Sapienza", Rome

R. Linke, K. Tatsch, J. Schwarz*, T.N. Witt*, K. Hahn. Departments of Nuclear Medicine and Neurology*, University of Munich, Germany

HILUM-DUODENUM TRANSIT TIME CHOLESCINTIGRAPHIC PARAMETER SPHINCTER OF ODDI,S DISFUNCTION.

(HDTT): A TO DIAGNOSE

Manometry of Oddis sphincter (MOS) as well as choledoch-pancreatic retrograde endoscopy are accurate but invasive and potentially harmful methods to diagnose sphincter of Oddi's dysfunction (SOD). We have studied the clinical reliability of the cholescintigraphic parameter HDTT. Cholescintigraphy (Diethyl-IDA, 3 mCi, 4 frames min x 40 min) was performed in 140 cholecystectomized patients, 20 of them with normal manometric findings. The scintigraphy was repeated within 6 months. ROIs were selected on heart, liver parenchima, biliary tree and duodenum. Hepatic and biliary time-activity curves were normalized and the hepatic curve was subtracted from the biliary one, to get a "net" biliary curve. HDTT was defined as difference between the onset of biliary curve and the first appareance of bile into duodenum. The normal value of HDTT ranged from 3 to 9 min. All the patients with HDTT longer than 9 min had pathological MOS. Linear regression showed very significant agreement between the HDTT measured in ist and 2nd study (R= 0.7, P < 0.01) and between HDTT and MOS (R=0.78, P <0.01). HDTT is an accurate and reliable method to diagnose SOD. It can be considered as a non invasive MOS.

M Frier, Spiller

AC

Perkins,

RM

Vincent,

JM

Hebden,

RC

D e p a r t m e n t s of Medical Physics and Therapeutics, U n i v e r s i t y Hospital, N o t t i n g h a m UK COLONIC TRANSIT CAPSULES

M E A S ~ S

USING

ENTERIC-COATED

Colonic transit measurements provide useful data in the management of a variety of g a s t r o i n t e s t i n a l disorders, e s p e c i a l l y c h r o n i c constipation. The technique involves administration of an e n t e r i c - c o a t e d capsule c o n t a i n i n g an i o n - e x c h a n g e resin r a d i o l a b e l l e d w i t h 5 M B q indium-lll. In a series of 120 p a t i e n t studies, capsules apparently failed to disintegrate on 5 occasions. Possible reasons include a) variations in thickness of the enteric coat, b) rapid smallbowel transit together with stasis in the colon, leading to p o o r dispersion of the c a p s u l e contents, or c) a c o m b i n a t i o n of r a p i d smallbowel transit and low caecal pH. The former is unlikely, since the p h e n o m e n o n was o b s e r v e d in i n d i v i d u a l s dosed with capsules p r e p a r e d as p a r t of a larger batch, and some d i s p e r s i o n of capsule contents is to be expected even in a r e l a t i v e l y q u i e s c e n t colon. It is possible, however, that p r o l o n g e d r e t e n t i o n of contents of the colon can lead to a lowering of pH as the result of products of fermentation. In a c r o s s o v e r study, involving 18 n o r m a l subjects, we h a v e c o m p a r e d the t r a n s i t of dispersing and non-dispersing capsules. In 25 of the 30 instances for which comparable data were obtained, the intact, non-dispersed capsule d e m o n s t r a t e d significantly faster transit. In c l i n i c a l studies, therefore, f a i l u r e of a capsule to disperse may not invalidate the test, but results should be interpreted with care.

t~ e-

ASSESSMENT OF ESOPHAGEAL FUNCTION IN PATIENTS WITH UNTREATED AND TREATED MYASTHENIA GRAVIS Myasthenia gravis pseudoparalytica (MG) is an autoimmune disease in which impairment of neuromusculartransmission results in a pathologic

fatigability of striated muscles. Dysphagia is a common symptom in this disorder. It is caused by weakness of the striated muscles in the pharynx and upper esophagus. Purpose of our study was to evaluate whether esophageal dysfunction in pts with MG may be detected by esophageal scintigraphy and whether this method could be used to document the effects of therapy. In 7 pts with MG complaining of dysphagia and 26 controls esophageal transit was investigated with a multiple swallow test protocol (semisolid testmeal, 6 swallows at 30 see. intervals, dynamic acquisition, 240 images ~i 0,8 see, 64x64 matrix). Pts were studied twice, under baseline conditions and immediately atter pharmacological stimulation with 10 mg tensilon (edrophoniumchlorid). E h ~ -,z-, Under baseline conditions all pts sop .-lzmpty.tz,) showed reduced esophageal transit Controls 95,4 +_ 5,1 I compared to controls After injecMG-pts: tion of tensilon esophageal emptying baseline 65,9+ 25,2* increased significantly. In 6/7 pts after tensilon 73,0 + 20,4 *0 esophageal transit improved, reach*D ing the normal range in 3/6 cases , < 0,01 cornoared to contro1s I° o < 0 05 comparedto baseline I One pt showed no effect niter ad" ' ministration oftensilon. Our findings indicate that bolus transit is compromised in patients with untreated MG. Pharmacological inhibition of cholinesterase positively affects striated muscles in the pharynx and upper esophagus, which resuits in a significant improvement of esophageal transit as objectively demonstrated by our scintigraphic data. Thus, esophageal scintigraphy may be considered as a simple, non invasive method for diagnosing impairment of esophageal function in patients with untreated MG and to monitor the changes under specific therapy.

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L.I.Vinnitsky, M.V.Poroykova. Research Centre of Surgery RAMS, Moscow, Russia. RADIO-IMMUNOLOGICAL EVALUATION OF PEPTIDE REGULATION IN PATIENTS WITH ESOPHAGUS AND D U O D E N U M DISEASES. We examined 72 patients: 19 - with cardiospasm (1 group), 18 - with reflux-esophagitis (2 group), 16 - with duodenal ulcer complicated by reflux-esophagitis (3 group) and 19 were practically healthy persons (4 group). We investigated blood levels of glucagon, gastrin, somatostatin, insulin and c-peptide; investigations were performed with the use of radioimmunological method before and after surgical treatment and also before and after functional toadings (food and sugar). The following treatment were performed: cardiodilatation - in 1 group, selective proximal vagotomy - in 2 group, fundoplication and selective proximal vagotomy - in 3 group. We revealed a statistically significant increase of glucagon before operation in patients of 2 group (105,55_+13,88 ng/ml) in comparison with healthy persons (77,24_+13,23 ng/ml). In 1 and 3 groups we didn't reveal any difference in comparison with 4 group. After operation glucagon concentrations in all groups didn't practically differ from normal concentrations. Gastrin concentrations before operations in patients of all groups was increased significantly. In patients of 2 and 3 groups gastrin concentrations increased after operations. Somatostatin contents were significantly increased defore operation in patients of 2 and 3 groups. After operation somatostatin contents decreased in 2 group and didn't change in 3 group. The dynamics of hormones concentrations after functional Ioadings both before and after surgical treatment corresponded to indices in 4 group, but quantitative changes were different. After an effective surgical treatment there were changes in the regulatory function of gastro-intestinal peptides which in 2 years approached to levels in practically healthy persons.

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• Gastroenterology OWe 117

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J. Mortensen, K. Roelsgaard, J. Marqversen, L. Bass, S. Keiding, N. Olsen. Departments of Clinical Physiology and Nuclear Medicine, Surgery L, Medicine V and PET Centre, Aarhus University Hospital, Aarhus, Denmark, and Dept. of Mathematics, University of Queensland, Brisbane, Australia.

L. M a d ~ c s y , B. V e 1 6 s y , T. Tak~cs, A. Szepes, M. L a z a r * , L. C s e r n a y * , J. L o n o v i c s , F i r s t Dept. of Medicine a n d Dept. of N u c l e a r M e d i c i n e * , Albert S z e n t - G y S r g y i M e d i c a l U n i v e r s i t y , Szeged, H u n g a r y

THE HEPATIC EXTRACTION FRACTIONS OF Tc-99m MEBROFENIN IN THE PIG: A COMPARATIVE METHODOLOGICAL STUDY The following two measures of the hepatic extraction fraction of Tc-99m mebrofenin were determined and compared in the present study: E(t) calculated by blood sampling measurements, and HEF estimated by deconvolutional analysis of the hepatic scintigram. An intravenous bolus injection of 200 MBq Tc-99m mebrofenin was given to nine anesthetized pigs. Successive blood samples were drawn from the abdominal aorta and a hepatic vein during the next 120 min. Simultaneously, the radioactivity of the liver and the left ventricle of the heart was detected by a gamma camera. The radioactivity of the samples was measured by a well-counter and analysed by HPLC. The experiments were performed under controlled physiological steady state conditions (hepatic blood flow rate, arterial pressure, heart rate, arterial and hepatic vein oxygen saturations, rectal temperature). E(t) was calculated from the arterial and venous concentrations of the agent as [C(a) - C(vl]/C(a) at a given time t. HEF was calculated as the ratio of the y-intercept of the exponential fit to the liver impulse response curve divided by the maximum data value of the response curve. Values are given as mean ~ SD. Statistical evaluation was performed by non-parametric statistics using a significance level of 0.05. E(t) was initially 78% ~ 9.4 and gradually decreased to 15% 11.6 during the next 60 min (p
C O M P A R I S O N O F T H E R E S U L T S OF E N D O S C O P I C S P H I N C T E R OF O D D I M A N O M E T R Y A N D Q U A N T I T A T I V E HEPATOBILIARY SCINTIGRAPHY IN P A T I E N T S W I T H A C A L C U L O U S BILIARY PAIN AND INTACT GALLBLADDER Introduction: Acalculous biliary pain (ABP) in patients with an intact gallbladder (GB) m a y b e c a u s e d b y s p h i n c t e r of O d d i d y s f u n c t i o n (SOD). T h e aim of the study was to determine whether obstructive signs on the quantitative hepatobiliary scintigraphy (QHBS) could identify patients with SOD diagnosed by endoscoplc s p h i n c t e r of O d d i m a n o m e t r y (SOM). Patients and methods: QHBS was performed in 16 patients w i t h A B P . 60 m i n f o l l o w i n g 4 mCi 99mTcEHIDA administration, 1 ng/kg/min caerulein (Takus) was infused over a i0 m i n period. The h a l f - t i m e of c o m m o n b i l e d u c t (CBD) e m p t y i n g (CBDTI/2) before caerulein administration, DAT and the GB ejection fraction (GBEF) were determined. Endoscopic SOM was performed in e a c h p a t i e n t in the same week after QHBS. Basal pressure (BP), phasic wave contraction amplitude (PCA), and phasic wave frequency (PWP) w e r e d e t e r m i n e d with the Synectic perfusion manometric system. R e s u l t s : P a t i e n t s w e r e d i v i d e d i n t o t w o g r o u p s on t h e b a s i s of SOM. 6 o f 16 p a t i e n t s w i t h B P o v e r 40 mmHg were diagnosed a s h a v i n g S O D ( g r o u p I). T h e remaining i0 p a t i e n t s had completely normal SOM ( g r o u p II). T h e m e a n BP, P C A a n d P W P in g r o u p s I a n d II w e r e : 48.9+6.1 mmHg, 186.3+41.6 mmHg and 8~4/min vs. 26.2+I-0.2 m m H g , 142.1~19.1 mmHg and 4.2+0.8/min, respectively. The~e were no significant differences in G B E F b e t w e e n g r o u p s I a n d II: 3 8 . 5 + 3 7 . 8 % vs. 4 4 . 6 + 2 1 . 6 % . However, both CBD-TI/2 and--DAT were significantly increased in g r o u p I as c o m p a r e d t o g r o u p II: 4 5 . 8 + 9 . 8 m i n a n d 6 2 . 8 + 9 . 8 m i n , vs. 2 3 . 8 + 3 . 8 m i n a n d 2 5 . 2 + 6 . 8 m i n . Com¢lusions: Although-a low GBEF prove~ to be an insensitive parameter, application of Q H B S m a y b e useful for the non-invasive diagnosis in p a t i e n t s w i t h S O D a n d i n t a c t GB. ( S u p p o r t e d b y E T T : 6 0 9 / 9 3 ) .

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OWe 120

B o h u s l a v i z k i K,H,, Brenner W., Lassmann S., Tinnemeyer S., Sippel C., T6nshoff G., Wolf H., Clausen M., Henze E.

V~J.G. Oven, O.C. Boerman, E,T.M. Dams, G. Storm, L. van Bloois, E~B. Koenders, D.J. Crommelin, J. W.M. van der Meer, F.H.M. Corstens. University Hospital Nijmegen and University of Utrecht, The Netherlands.

Clinic of Nuclear Medicine, Universitiy of Kiel, Germany QUANTITATIVE SALIVARY GLAND SCINTIGRAPHY IN THE DIAGNOSIS OF PARENCHYMAL DAMAGE AFTER RADIOIODINE In most patients treated for thyroid cancer with high cumulative doses of radioiodine salivary gland damage could be shown by qualitative salivary gland scintigraphy, while mild parenchymal impairment could not be detected so far. Therefore, this study was undertaken to evaluate parenchymal damage of salivary glands after low dose radioiodine treatment using standardized quantitative salivary gland scintigraphy. A total of 106 patients underwent standardized quantitative salivary gland scintigraphy with 40-100 MBq Tc-99m-pertechnetate prior to and 3 months after radioiodine therapy with 1-131 ranging from 400 MBq to (cumulative) 24 GBq. Parenchymal function was quantified by calculating pertechnetate uptake at 13 min post injection. Uptake was compared to a normal data base consisting of 267 normals without evidence for salivary gland disease. There was no difference of pretherapeutic parenchymal function in all patients as compared to normals (p>0.05)i In patients who received more than 10 GBq 1-131 severe parenchymal function loss could be documented by quantitative evaluation as well as by visual analysis. In contrast, after low dose radioiodine treatment with less than 10 GBq mild but significant parenchymal impairment (p<0.05) could be demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigrapby is essential for reliable detection of mild parenchymal malfunction, which was missed by visual analysis only. Thus, a standardized evaluation of parenchymal function might be suggested in all patients receiving radioiodine. This is feasable without additional application of radioactivity since it can be performed in the context of thyroid scintigraphy performed for clinical reasons.

EVALUATION OF EXPERIMENTAL COLITIS WITH I n - l l l LABELED LIPOSOMES, LEUKOCYTES, AND IgG. Evaluation of inflammatory bowel disease is an important indication for scintigraphic techniques. The radiopharmaceutical of choice is labeled white blood cells (WBC). In this study, two new agents (In-Ill labeled polyethyleneglycol (PEG) coated liposomes (lips) and I n - l l l labeled human nonspecific immunoglobulin G (IgG) were compared to In-111-WBC in a rabbit model of colitis. In rabbits, acute colitis was induced by colonic installation of 1 ml of 30 mg trinitrobenzene sulfonic acid in 30% ethanol, followed by 1 ml 50% ethanol flush, at 25 crn from the anal sphincter, After 24 hours, 10 MBq of the radiopharmaceuticals was i.v. injected in groups of 4 rabbits. 24 hours after injection, the animals were killed and macroscopic abnormalities were scored in 7 consecutive affected colonic segments of 5 cm each [0 = (near) normal, 1 = inflammation, 2 = ulcers]. The uptake (%ID/g) was measured in normal ascending colon and the affected colonic segments. A colitis index (CI, affected-to-normal-colon-ratio) was calculated and expressed as mean+SEM. Histologically, an acute, patchy, transmural colitis was observed at the site of installation and the distal colon. The CI of all agents in colitis lesions correlated with the severity of the abnormalities (lips > WBC > IgG: lips r2=0.68, p<0.001; WBC r2 = 0.31, p<0.01; IgG r2=0.29, p<0.02). seore

llps

WBC

IgG

0

1.86 _+ 0.24

1.77 + 0.32

1.60 4- 0.29

1

4.88 + 0.42

3.10 + 0.58

2.81 _+_0.21

2

7.42 _+ 0.54

5.54 + 0.83

2.65 _.%0.21

In conclusion, In-I 1l labeled WBC, IgG and lips all show increased uptake in inflamed colon. In-11 l-lips show the highest CI, which correlates best with the morphological abnormalities. In-ll 1-WBC are superior to In-ll 1-1gG for this indication.

•

Gastroenterology

OWe121 R. Lebtahi, G..Cadiot, L. Sarda, D. Daou, M. Faraggi, J.P. Marmuse, N. Delahaye, M. Mignon, D. Le Guludec. Nucl. Med. and Gastroenterology Dept. Bichat Hospital, Paris, France.

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CLINICAL IMPACT OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN THE THERAPEUTIC MANAGEMENT OF PATIENTS WITH GASTROENTEROPANCREATIC (GEP) TUMORS,

ABDOMINAL SCINTIGRAPHY IN PATIENTS WITH SERONEGATIVE SPONDYLARTHROPATHIES AND R H E U M T O I D A R T H R I T I S : R E L A T I O N S H I P W I T H USE O F NON- S T E R O I D A L ANTI- I N F L A M M A T O R Y DRUGS

This study evaluates the impact of somatostatin receptor scintigraphy (SRS) on patient's management. Three groups of patients were referred for SRS (n=160 pts): GI corresponded to 90 pts with potential indication of curative surgery or explorative laparotomy for isolated known (n=44) or unknown (n=46) primary tumors; GII corresponded to 59 pts with potential indication of liver surgery for liver metastases; Gill corresponded to 11 pts excluded from surgery due to known extra-hepatic metastases and referred to SRS for evaluation before octreotide therapy. In the 90 pts of GI, 18 pts were excluded from curative surgery because extra-hepatic tumors discovered by SRS; liver metastases were discovered by SRS in 7 pts with potential liver surgery. For the other 65 GI pts, SRS ~ocNzed the primary tumor in 33 pts: only SRS was positive in 17 of them helping the potential surgical cure. In the 59 GII pts, 13 pts were excluded from liver surgery because extra-hepatic metastases discovered by SRS. Additional controlateral liver sites were found in 2 pts and hepatectomy was therefore excluded. SRS confirmed known liver metastases in 95% of pts and discovered in 23 pts, 25 new sites (primary tumors or lymph nodes: 22, liver: 3). The group Ill increased from 11 to 42 pts; all had an uptake at SRS but 28% of them had an intense uptake suggesting a possible response to octreotide therapy. We conclude that somatostatin receptor scintigraphy has a major impact on patient's management and must be indicated before therapeutic decision in patients with GEP tumors.

OWe122 Y. Petegnief, R. Lebtahi, G. Cadiot, J.P. Marmuse, C. Vissuzaine, L Sarda, D. Daou, M. Mignon, D. Le Guludec. Nucl. Med., Gastroenterology and Surgery Dept. Bichat Hospital, Paris, France. A PROSPECTIVE STUDY OF THE VALUE OF INTRAOPERATIVE DETECTION OF GASTRO-ENTERO-PANCREATIC (GEP) TUMOURS WITH IN-111 PENTETREOTIDE.

ALONSO JC, SORIANO A, RUBIO C, ROLLAN B, ZARCA MA, SANCHEZ A. Umdad de Medicina Nuclear, Servicio de Reumatologia Complejo Hospitalario de Ciudad Real

We have found an increased uptake in some patients with seronegative spondylarthropathies (SSp) without previous diagnosis of inflammatory bowel disease (IBD) , and without past or present symptoms and signs of IBD. Purpose To evaluate if these lesions are related to the use of non-steroidal anti-inflammatory drugs (NSAIDs) Methods We have studied 27 consecutive patients with defined SSp or undifferentiated SSp without clinical symptoms and signs of IBD. (15 primary ankylosing spondylitis, 5 oligoarthritis, 3 psoriatic arthritis, 3 reactive arthritis, 1 polyarthritis and 1 plantar fasciitis ) and 10 control patients with rheumtoid arthritis ( R A ) . All patients received established mean dose of NSAIDs. Abdominal scintigraphy was performed using 99m- Technetium Hexamethyl Propylene Amine Oxine-labeled leukocytes (99m-Tc-HMPAO-wBC) and scored from 1 ( low uptake) to 4 ( high uptake ) . Results The 99m-Tc-HMPAOwBC scan were positive in 15 patients (55.5%): 11 primary ankylosingspondylitis, 2 oligoarthritis, 2 psoriatic arthritis, 2 reactive arthritis, 1 polyarthritis. Eleven patients had scores from 2 to 4. Colon and terminal ileum were predominanty involved, In control group with R A , only one patient had uptake ovei" colon and his score was 1. We found significative difference uptake between SSp and RA (55.5 % vs 10%; x: 0.04 ) Conclusions These lesions are not related to the use of NSAIDs, because the control patients were also on these medications on same dose . The increase uptake is really due to implication the gut in the development of SSp.

O W e 124 Z. Kopafisld. LMicherdzhiski,J.Niziol,H.Wasilewska-Radwafiska,A.Cieneiala, J.Lassa ClinicalMilitary Hospital, Faculty of Physics and Nuclear Techniques AGH, lnstitiul of Nuclear Physic

The C-14 urea breath test and location infected by Helicobaeter pylori in the alimentary canal Purpose of the study

We report our preliminary study of the feasibility of the intraoperative isotopic detection in 8 patients with 11 neuroendocrine GEP turnouts: 6 duodenal tumours (3, 3, 3,.6, 8, 12 mm), 2 pancreatic (10mm), 2 lymph nodes (18mm) and 1 liver metastasis (80mm}. th~aoperative detection using cesium iodine gamma probe (Gammed 2, Cis-Bio) was performed 48 hr. after injection of 111 MBq of 1111n-Penteti'eotide.Counting rates were recorded in vivo in tumours and surrounding tissues and ex vivo in the removed tumours. Quantitative autoradiography (AR) was performed with a multiwires proportional counter on sections of the tumoral tissues. Ten tumours were directly found by palpation by the surgeon. The other one was only found after duodenotomy: The tumour to normal tissue ratio (TNR) was 1.4. Four tumours (2 duodenal, 2 pancreatic) were not detected by intraoperative detection (-INR: 1); in two cases, AR was positive. For the 7 other tumours, intraoperative detection was positive with TNR varying from 1.4 to 12 in vivo. For the liver tumour, TNR was 3 in vivo and 8 ex vivo; AR showed heterogeneous activity within tumour and a maximum TNR of 10. For a duodenal tumour, a TNR of 2 was found in vivo despite a negative preoperative somatostatin receptor scintigraphy. TNR varied from 1 to 30 ex vivo with larger heterogeneities of activity within the same turnout. AR gave activity concentrations varying from 5 to 29 Bq per g of tumour. No additional tumour was found by intraoperative detection in this preliminary series. Small sizes and great variability of uptake within tumours appear to be the major limiting factors of intraoperative detection. Thus, the role of intraoperative detection in neuroendocrine GEP tumours is closely related to the level of tumoral uptake.

The purpore of the present research was to determine the usefulnes of the breath test (with C-14 urea) in detectingthe H. pylori infection in the mouth and in the stomach of patients with chronic gastritis and gastriticulcer. Material and methods

The analysis incIudet 152 selected patients with chronic gastritis and gastric ulcer 92 men and 60 women aged 20 to 67, in whom a bacteriological (cultures) tesl comfirmedthe presenceof H. pyloriinfi~ctien.In 92 patients the bacterium occurred only in the stomach (group I), whereas in 60 it simultaneouslyeolonisadthe mouth (gingival pockets) and the gastric mucosa (group II). All the patients were subjected to the C-14 area breath test to detect the H. pylori infection. The difference in the distribution oJ activity(cpm/mmol CO2) of the samples of e,'daaledin both groups of patients. Results

The data show characteristicdifferences between the pattern of the average values of epm/mmol CO2 for the both groups of patients Thus, for everypatientof group I the values of cpm/mmol CO2 obtained from successive samplesof exhaledair alwaysled to a curvewith one maximum occurring between 15 and 25 min (mostly 15 min) from the beginning of the test. For every patient of group It the activityof the specimens of exJaaledair always led to a curve with two maxima, the ftrsl afterca 5 rain, the second,usuallythe stanger, at between 15 and 25 min (most conu'nonly 15 rain) fi'omthe start of the test It was evident that both maximum values of cprrdmmol CO2 for each patients examined ass'amendan individualdifferentation. Conclusion

The C-I4 urea breath test not only allows to detectionof a patient infected by Helieobacterpylori but also enables to establish the place of occurrence ( mouth andYot stomach) of the infectionin the alimentary,canal to be established.

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• Haematology, Metabolism Haematology, Metabolism OSu 125

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1. Szilv~isi,J. Kocsis', G. Tarkov~ics', Zs. Nebentfihrer', Sz. Benedek' Dept of Nuclear Medicine, Haynal University, Budapest, 3rd Dept. of Medicine, S emmelweis Medical University, Budapest'

C.Mainolfi, A.Petrillo, A. Brunetti, H.Wang, P.Varrella, S. Maurea, M.R. Panico, A. Boccanfuso, LBazzicalupo. CNR - Medicina Nucleare-Radiologia -Universit~t "Fedefico II" and Istituto Tumori "Pascale" - Napoli - Italy

COMBINED USE OF Tc-99m-MIBI AND Ga-67 SCINTIGRAPHY IN PATIENTS WITH MALIGNANT LYMPHOMA The aim of our study was to evaluate clinical usefulness of two scintigraphic methods in patients with malignant lymphoma. Tc-99m-sestamib (at 30 minutes and 3 hours after injection) and Ga-67 scintigraphy were performed within one week in 22 patients with malignant lymphoma, lc patients had Hodgkin's disease (HL) and 12 had non-Hodgkin's lymphoma (NHL). Scintigraphic results were compared to clinical, histological and radiotogical findings. Results: in paUents with untreated IlL, and high- or intermediate-grade NHL all the involved peripheral and mediastinal malignant lesions were clearly visualized on Tc-99m-sestamibi scintigraphy. In patients with low-grade NHL (n=7) Tc-99m-sestamibi scintigraphy.was positive only in 2 cases, however Ga-67 scintigraphy was positive in 4 patients. No false-positive finding was observed on Tc-99msestamibi scintigraphy. Two therapy-resistant NHL had also discrepancy: negative by sestamibi and positive by gallium scintigraphy. In conclusion Tc-99m-setamibi has high specificity in patients with malignant lymph. oma. Sensitivity is high in patients with untreated IlL and with high- and intermediate-grade NItL. Ga-67 scintigraphy is indicated in patients with low-grade NHL and. in patients with therapy-resistant malignant lymph oma to detect residual malignant tissue.

DETECTION AND FOLLOW-UP OF EXTRANODAL DISEASE IN NON-HODGKIN LYMPHOMAS WITH PET-FDG PET studies with [F-18]fluorodeoxyglucose (FDG) have been suggested as a valuable tool for detection of disease sites in patients with lymphoma. Selection of treatment in lymphomas is critically dependent upon correct staging. Presently staging of lymphomas is mainly based on morphologic imaging techniques (CT, MRI, Ultrasound, radiography and lymphography). A critical issue in the staging in Non-Hodgkin lymphomas (NHL) is the detection of extranodal disease. We tested the potential value of whole body imaging with FDG as a staging procedure in NHL, with a prospective assessement of 38 patients with non-Hodgkin lymphomas (NHL) (age range 8-75). Clinical examination, abdominal ultrasound, CT of the chest, abdomen and pelvis were obtained in all cases; CT scans of the brain and MRI studies for bone marrow assessement were performed in selected cases. Whole body PET studies were performed 30-40 rain following iv administration of 370 MBq FDG. Transmission/emission tomographic scans were also performed on selected areas. Three experienced observers assessed the presence of areas of abnormal uptake in PET-FDG images. Sixteen of the 38 patients had subsequently proven involvement of extranodal areas. Of these, 1 patient with a cutaneous lymphoma had a negative PET scane, while in the remaining 15 eases PET showed areas of extranodal uptake respectively in stomach (n=3), intestine/ abdomen (n=5) thyroid (n=l), bone (n=3), skin (n=2), retro-orbital fat (n=l). Post-treatment PET scans obtained in 7/15 cases at 6 months showed no evidence of extranodal uptake (n=2), decreased number/intensity of extranodal uptake sites (n=3), unchanged pattern (n=l), increased number of extranodal abnormalities (n= 1). Our results indicate that whole-body PET-FDG studies, in addition to detection of nodal disease, can reliably identify extranodat involvement in NHL, providing crucial information for selection of appropriate treatment. PET-FDG studies can also assist in monitoring effects of treatment and disease progression over time.

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J.Th.Locher, P.Lind*, K.Seybold, G.A.Janoki** Inst. Nucl. Med. Kantonsspital Aarau (Switzerland), *Inst. Nucl. Med. Allg. Offentl. Krankenanstalten Klagenfurt (Austria) **Nat. FJC Res. Inst. for Radiobiology Budapest (Hungary)

F. S c o p i n a r o , R. T a v o l a r o , M. Ciavolella, O. S c h i l l a c i , R. Danieli. M. Ierardi, M. Di Loreto, F. La Torte*, G. De V i n c e n t i s , Nucl. Med. and *III Surg., Univ. "La S a p i e n z a " , Rome, Italy.

AMELIORATED BONE MARROW (BM) SCANNING FOR TUMORS AND INFECTIONS BY SMALLER SIZED ANTIGRANULOCYTE MONOCLONAL ANTIBODY MAB47. The BM uptake of labeled leucocytes is prominent very early after injection. But, in tumors and chronic infections the blood supply is not unit'ormely high, the number of BM cells is decreased and the turnover may be low. Because metastases are most common in bones with high proportion of vascular red marrow, BM scintigraphy is increasingly used for both tumor staging and control of therapy. But, the sensitivity and accuracy of the method depend on pathophysiological barriers and the biokinetic properties of the agent used. Methodical improvements (increased targetto-background ratio, earlier and shorter scanning times) are available by reducing the molecular size of the mab without loss of immunoreactivity. We studied a smaller sized variant of the antigranulocyte mab47. Kit formulation: Portion of mab47 were mixed with 2-mercaptoethanol, incubated and purified by gel filtration. Protein fractions were pooled, stabilized with additives and lyophilized. The labeling with Tc99m is an easy one step procedure. The labeling yield obtained was over 95% and, therefore, no further purification was required. Pharmakological and clinical dam: Blood samples showed elimination in two distinct phases with half lives of 0.7 and 4.5 hrs. respectively. Ufin excretion was about 10% of injected dose per day. Effective cell bound activity was 20+8%. In healthy BM the local activity, as measured by the ROI technique, was highest at about 10 min. post inj. It rapidly declined according to the blood activity during the short first phase and remained constant thereafter. Diagnostically relevant irregularities of BM uptake are seen after 20-30 rain. aheady in cases of metastatic BM destruction (cold lesions) and after 2-5 hrs. in acute infections (hot lesions). Dynamic SPET was used to demonstrate abscess formations in tumor cases and after BM suppressive chemotherapy. The values for sensitivity and specificity ranged between 90-99% and were slightly higher in tumor cases compared to infections. After injection of <200 p.g protein only HAMA response was very faint.

1064

99mTc ANTI IN MAN.

D

DIMER

MoAb

DETECTS

VENOUS

THROMBI

D d i m e r is a s p e c i f i c e p i t o p e c r e a t e d d u r i n g the c r o s s - l i n k i n g p r o c e s s of f i b r i n strains. Thus antibodies against D dimer specifically b i n d to c r o s s l i n k e d f i b r i n n e t w o r k of thrombi. 5 normal v o l u n t e e r s and i0 p a t i e n t s w i t h leg v a r i c e s w e r e g i v e n i0 mCi of 9 9 m T c F(ab)" of anti D dimer MoAb (research a p p r o v e d by the Rome University Ethical Committee. Each patient gave his informed consent). Images were performed at 5, 60, 180 min. No adverse reaction was observed. 6 patients underwent s a p h e n o u s s t r i p p i n g 3 h a f t e r injection, in the other 4 patients scintigraphic images were a c q u i r e d at 6 and 8 h. 28 hot s p o t s w e r e imaged. Of t h e s e 20 w e r e localized during operation with a pencil-like probe and exserted. Specific activity of exserted thrombi, saphenal walls and a blood samples was measured in a w e l l counter. A t h r o m b u s to v e i n w a l l r a t i o of 2.2 ± 0.6 and a t h r o m b u s to b l o o d of 3.1 ± 0.8 w a s m e a s u r e d . In non o p e r a t e d p a t i e n t s the b e s t s c i n t i g r a p h i c i m a g e s w e r e o b t a i n e d b e t w e e n 60 a n d 180 min. Our results show that 99mTc anti D dimer MoAb is a safe a n d e f f e c t i v e a g e n t for l o c a l i z a t i o n of v e n o u s t h r o m b i .

•

Haematology, Metabolism

0Su129

OSu131

M. Ierardi, F. Scopinaro, w. Gianni*, G. De Vincentis, N.S. Tiberio, M. Cacciafesta*, V. Marigliano*, I Silvestri, G. Naso, A.M. Agliano, Exper. Med. Dpt., *I Med., Univ. "La Sapienza", Roma, Italy.

G. Mariani, M. Bagnasco, C. Motta, G. Passalacqua, M. Bartolomei, and G.W. Canonica. Nuclear Medicine Service and Allergy and Clinical Immunology Service, DIMI, University of Genoa; Genoa (Italy).

ABILITY OF 99mTc BW 250/183 MoAb TO BIND G R A N U L O C Y T E S : T H E M O D E L O F 3 2 D C I 3 ( G ) C E L L LINE.

32D C 13 (G) is an interleukine 3 (IL-3) dependent non-tumorigenic murine hematopoietic cell line, which undergoes terminal differentiation into granulocytes when exposed to granulocytic-colony stimulating factor (GCSF). We used the monoclonal antibody (MoAb) BW 250/183 and the above cell line, with the aim of verifying if young, newly formed granulocytes and possibly less differentiated cells in bone marrow expose NCA in plasma membrane. We brought cells to terminal differentiation using G-CSF in the medium and analyzed aliquots of 2,500,000 cells at days 5-7-9-14. These cells were washed, linked to the antibody and rewashed. The ~adioactivity was measured in a well counter and e x p r e s s e d as % of the entire dose. The results have been summarized in the table. Days %Myelo- %Pro-i%Myelo- %Meta- %Granul. % of bl. myel. cyt. myel. radio act. 5 0 i0 60 25 0 5 7 0 2 40 40 18 72 9 0 0 i0 30 60 85,7 14 0 0 0 20 80 79,3 Binding of BW 250/183 to metamyelocytes was confirmed with 2nd antibody immunofluorescence technique. These results show that BW 250/183 is bound by Granulocytes , Metamyelocytes and perhaps myelocytes. Our results explain the high uptake of BW 250/183 in bone marrow and allow to speculate on a possible use of BW 250/183 in the scintigraphic imaging of bone marrow diseases.

OSu130 Sabahat inanir, Sevil Atavci, Berna Okudan, Mustafa UnlU, Rauf Haznedar, Gazi University Medical Faculty, Departments of Nuclear Medicine and Hematology,Ankara, Turkey. THE EVALUATION OF ARTERIOVENOUS SHUNTING IN PATIENTS WITH MULTIPLE MYELOMA In this study, we aimed to evaluate the presence and effect of arteriovenous shunting in bone lesions of multiple mydoma, as a responsible factor for the development of high output cardiac failure. After the exclusion of other causes of high output failure and getting their informed consents, eleven patients who had stage 2-3 disease, heart failure and femoral bone lesions were studied (7 female, 4 male, age range: 45-71) Arteriovenous shunting was determined using Tc-99m MAA particles. In the first step of this acquisition, these particles were injected into the femoral artery at the lesion site. And then, antecubital intravenous injection was performed. 37 MBq Tc-99m MAA (particle size:10-60 Ixm and approximately 5x104 particles) was administered and thoracoabdominal images were acquired for each step. Mean counts per pixel were obtained from ROFs drawn over the mid zone of the right lung and left upper abdomen in the arterial and venous phase images (Al~g, Abody, Vlung, Vbody. respectively). Arteriovenous shunting ratio was calculated using the following formula: Alung*Vbody / AJoody*Vlung. Cardiac output was determined in all patients with indicator dilution method. AV shunting ratio (mean_+sd) was 19.10_+16.99(4.80-47.70) in study group. There was moderate correlation (r = 0.65, p = 0.01) between AV shunting ratios and cardiac outputs of patients. These results suggest that AV shunts may have an important role in the development of high output cardiac failure in patients with multiple myeloma and extensive bone lesions. This method can also be used to determine therapeutic efficiency in patients underwent embolization procedures.

AN EXPERIMENTAL STUDY ON THE ABSORPTION AND DISTRIBUTION KINETICS IN HUMANS OF THE MAJOR PARIETARIA ALLERGEN ADMINISTERED BY ALTERNATIVE ROUTES. No data are available on the kinetics in humans of allergens administered by alternative routes for specific immunotherapy, despite the fact that this type of treatment is being clinically employed since at least 80 years. We studied therefore the fate of the radioiodinated major Pcqetaria allergen (Par& purified by HPLC as a single species with a molecular weight of about 12 kD), after sublingual, oral and nasal administration. After tracer administration to 12 healthy volunteers (50 ,ug of Par J labetedwith 185 MBq of ~-'3I), early dynamic scans (1 frame/rain for 30 min, matrix 64x64) and delayed static scans (1-48 hr) were recorded by gamma-camera imaging. Blood and urine samples were also taken at serial intervals, to evaluate the kinetics of absorption and excretion, and to identify radioactive species present in the samples (by Sephadex G-25 column chromatography). Sublingual route: No circulating radioactivity is detected until the tracer is kept sublingually without swallowing. Afterwards, the labeled allergen is rapidly degraded and absorbed in the GI tract; plasma activity peaks at about 1.5 hr and is mostly free radioiodide, with minor radiolabeled peptides (<1 kD) present only in the early samples. Some activity not due to free [231 remains associated with the sublingual mucosa until 6-10 hr. Free radioiodide is the sole radioactive species detected in the urine. Oral mute: The results are similar to those observed after sublingual administration, without however any specific imaging of the mouth other than due to free radioiodirte. Nasa{ route: The pattern of ~tasma activity mimics the sublinguat route, absorption of activity from ~-3I-PcwJbeing mostly linked to swallowing after transport to the pharynx by mucociliary clearance. A relevant fraction of radioactivity remains steadily associated with the nasal mucosa, until at least 48 hr after administration through this route. The results obtained in this study provide, for the first time in humans, some experimental basis for exploring the pathophysiologic mechanisms taking place after administration of allergens for specific immunotherapy through alternative routes.

OSu132

V. Ivancevic A. Alavi, E. Souder, P.D. Mozley, R.E. Gur, A.H. Sadek. Division of Nuclear Medicine, University of Pennsylvania, Philadelphia, USA, and Clinic for Nuclear Medicine, Charite, Humboldt University, Berlin, Germany S I G N I F I C A N C E OF T R A N S A X l A L , C O R O N A L , AND SAGITTAL PLANES IN THE EVALUATION OF FDG PET STUDIES OF THE BRAIN

Regional cerebral glucose metabolism (RGM) as measured by FDG PET has generally been determined using transaxial planes. However, not all the brain structures can be properly visualized on transaxial slices alone. In order to evaluate different brain regions in all three planes (transaxial, coronal, and sagittal) we q~Jalitatively analyzed the PET scans of 96 right-handed healthy volunteers (19-51 years) injected with 4.2 MBq/kg of F-18-FDG and imaged in a PENN PET H 240 scanner. Transverse, coronal, and sagittal slices of the reconstructed and scatter, random coincidences and attenuation corrected images were read independently by adopting a relative scale with 1=equal to, 2=mildly, 3=moderately, and 4=markedly less than the area with the highest RGM in the respective plane. The areas with the highest RGM were the posterior cingulate gyri with mean scores of 1.03 to 1.15, thalami (1.19 to 1.33), basal ganglia (1.37 to 1.94), and visual cortex (1.47 to 1.64). The lowest values were found in the occipital cortex (2.66 to 2.77) and the cerebellum (2.30 to 2.41). Whereas reliable analysis of the mesial temporal aspects was not possible in the sagittal plane, the anterior poles of the temporal and frontal lobes could not be evaluated on the coronal, and the inferior temporal areas on the transaxial slices. In all three planes RGM was lower in the lateral temporal areas on the left than on the right (p<0.001). Inconsistency of readings as measured in terms of s.d. was highest in the transaxial plane for the anterior temporal poles, the caudates, and the posterior cingulate gyri (lowest in the sagittal, coronal, and coronal planes, respectively). In conclusion, the integrated analysis of the transaxial, coronal, and sagittal planes enhances the comprehensive evaluation of the RGM in FDG PET studies of the brain. Analyzing transaxial slices alone is insufficient especially in the inferior and anterior temporal areas. 1065

co |mm 4,,,I

t~ e11) o~ s._

O. m

t~

8

• Haematology, Metabolism/Hypertension OSu133 Frusciante V., Rinaldi M., Polito G., Modoni S., Barbano F., Dicembdno F., Schiavanello S.,* Modola G., * Giacobbe A., * Facciorusso D. Nuclear Medicine and * Gastroenterology, "CASA SOLLIEVO della SOFFERENZA", Scientific Institute, S. Giovanni Rotondo (FG), Italy. LIVER CIRROSIS (LC) OSTEODYSTROPHY: A QUANTITATIVE SKELETAL SCINTIGRAPHIC STUDY. Osteodystrophy in liver cirrosis is due to disturbed Vitamin D and calcium metabolism and it has been often ovedooked because the bone disorder itself is not life threatening and difficult to diagnose. We evaluated whether QSS improves the diagnosis of cirrhotic osteodystrophy in companson to qualitative bone scan. 20 pts and 20 controls (free of liver and renal diseases) matched for age, sex and menopausal state were studied. Global skeletal uptake (GSU) and whole body retention (WBR) of 99m-Tc have been determined by measurement of counts in whole body ROIs drawn on 5 minutes and 4 hour total body digital scan images; GSU ROIs have been drawn excluding bladder and soft tissues; geometric mean from counts in anterior and posterior views was calculated; WBR and GSU figures, expressed as percentage of the administered dose, were compared by t test for unpaired data. WBR: (pts.) 56.9_+14.5 (contr.) 47.0_+8.12 p<0.0116 GSU: (pts.) 47.1_+12.3 (contr.) 38.9_+6.41 p<0.0114 In 7 pts. the bone scan showed focal areas of increased uptake (the number of sites vaded from 1 to 3 in different pts.), almost exclusively localized in dbs and vertebrae; only in 1 patient two areas of increased uptake were evident in the long bones of the left leg. In 8 pts GSU figures were 1 sd above the mean of our controls and the range of GSU in these 8 pts is from 47 to 8 1 . 1 % . In 1 patient showing a db area of increased uptake GSU figure was within normal limit (mean_+lsd). In 6 pts. the result was concordant, in 1 pt only the GSU figure was abnormal. We conclude that QSS is a powerful clinical tool to investigate cyrrotic osteodtstrophy because it gives a quantitative estimate of bone turnover rate and so allows to follow-up the complication and to monitor the effect of different therapeutic approaches on this bone disorder.

OTu 135 M. Fraile. M.T. Luque, J. Riba, R. Romero, J. Bonet, and J. Bonal.

NuclearMedicine andNephrology Departments. Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona. Spain. 99~Tc-MAG3 RENOGRAPHY AFTER PROSTAGLANDIN INHIBITION WITH INDOMETHACIN IN THE EVALUATION OF PATIENTS WITH SUSPECTED RENOVASCULAR HYPERTENSION. BACKGROUND : In RVH, prostaglandin (PG) synthesis in the stenotic kidney is increased to maintain renal blood flow and to stimulate the renin system. Preliminary experience suggests that renography alter PG inhibition may detect RVH (Imanishi, Kidneylnt. 1994). We conducted a prospective investigation to assess the diagnostic value of MAG3 combined with indomethacin ( -IND- being a strong PG inlfibitor) in a clinical setting. PATIENT POPULATION AND METHOD: Pts with high climcal suspicion of RVH were selected.To establish a diagnosis, renal angaograms were obtained w~hin two menttm. There were 23 pts (15 men), with a mean age of 51 (25 to 75 y)...A~.'ography disclosed significant (>50%) renal artery stenosis in 18 (3 with bilateral disease) (prevalence 78%). There were 3 pts w ~ one kidney (43 renal units), and 8 pts had a smaIi hypofunetional kidney. Nine pts were on single-drug therapy, and 14 were on double or triple therapy. Renogmms were done both at baseline and 90 minutes after an oral dose of 50 mg of RID, in separate days, using about 110 MBq of 99mTc-MAG3 each tmae. RESULTS: IND was well tolerated. Only 6/23 pts complained of mild[ PxzzEm-s ~ z cr~rs drowsiness. No renal function [ TP 7 9 derangement was seen. IND did not [ TN 5 22 change blood pressure (152/83 vs[ FP 3 3 155/82 mmHg) or heart rate (71 vs 71 [ FN 8 9 bin-n). Compared with baseline, INDI reno gmrrmhad better sensitivity at the cost of lower specificity. Diagnostic power increased when renographic changes after IND were Corlsid~red, then our overall results were as shown No differences were seen when several clinical variables were accounted for, including baseline global renal function, and medication. IND reno~aphy performed better in pts older than 35 and also when small hypofunetaonal kidneys were excluded from the analysis. CONCLUSION: Based on our results, its seems that MAG3 renography before and at~er PG inhibition with IND does not reach enough diagnostae accuracy to be recommended for routine use in the clinical setting. If young (fibrodysplastie)pts and small hypofunetional kidneys were excluded, RID renography couldbe beneficial in suspected RVH.

Hypertension OTu 134

OTu 136

E.B. Pedersen, M. Egeblad, J. Jcrgensen, S.S. Nielsen, E.S. Spencer, M.Rehling. Aarhns University Hospital, Section Skejby Hospital, Dept. of Clinical Physiology and Nuclear Medicine, and Radiology, Aarhns, Denmark.

A.Palermo, A.Romeo, S.Zoboli, N.Monetti. Dpts of Nuclear Medicine

SCREENING FOR RENOVASCULAR HYPERTENSION A COMPARISON BETWEEN CONVENTIONAL RENOGRAPHY, CAPTOPRIL RENOGRAPHY AND ULTRASOUND DOPPLER IN A LARGE CONSECUTIVE SERIES OF PATIENTS WITH ARTERIAL HYPERTENSION. The purpose of the study was to compare the positive and negative predictive values of conventional renography (RenD-A), captopril renography (RenD-B) and ultrasound Doppler (UD) with regard to the diagnosis renal artery stenosis. In consecutively admitted patients with severe arterial hypertension these three tests were performed, and in addition a renal angiography. Patients with occlusion of a renal artery or a serum creatinine higher than 300 p.mol/1were excluded from the analysis. Of 131 patients included, 28 had a renal artery stenosis (RAS) exceeding 50% and 19 exceeding 70%. The predictive values of a negative test for a RAS more than 50% were 0.88 for RenD-A, 0.90 for RenD-B, 0.86 for changes from Reno-A to RenD-B, 0.92 for abnormalities either in RenD-A, Reno-B or changes from Reno-A to B, and 0.91 for UD. The correspouding values for a RAS more than 70% were 0.94, 0.97, 0.93, 0.98 and 0.96, respectively. The predictive values of a positive test were clearly lower ranging from 0.20 to 0.75, but best when changes from Reno-A to Reno-B were used, 0.69 to 0.75. It is concluded that conventional renography, captopril renography and ultrasound Doppler all are very good screening tests for renal artery stenosis. Is is suggested that captopril renography always should be performed when conventional renography is abnormal and vice versa to obtain the highest positive predictive value.

1066

S.Fanti, M.Dondi, M.Mirelli, S.Tarantini, C.Corbelli, R.Galassi,

and Vascular Surgery, S.Orsola-Malpighi Hospital, Bologna; Dpt of Nuclear Medicine, Ospedaleper gli Infermi, Faenza. DIAGNOSIS

OF

RENOVASCULAR

HYPERTENSION

BY

C A P T O P R I L R E N A L S C I N T I G R A P H Y IN PATIENTS W I T H A

SINGLE KIDNEY. In recent years many studies have reported on the effectiveness of Captopril Renal Seintigraphy (CRS) in diagnosing renovaseular hypertension (RVH) The present study sought to evaluate the reliability of CRS in patients with a single kidney. Experimental investigations have suggested that the one-kidney one-clip (1K, 1C) model may be a volume-dependent rather than a renin-dependent form of hypertension. CRS feasibility in patients with a single kidney may therefore be questionable. Renal function impairment after Captopril administration has been reported occasionally in single-kidney patients and CRS may thus be a problem in these patients. To investigate these issues we reviewed CRS carried out in single kidney hypertensives. Renal scans were performed 1 hour after oral administration of 50rag Captopril using 100 MBq of 99mTc-MAG3 and repeated in baseline condition. To determine the renovaseular origin of hypertension we considered eligible only patients affected by renal artery stenosis that were subsequently submitted to revnseularization: RVH was diagnosed on the basis of blood pressure response to intervention. Seintigraphie findings (CRS positive in presence of Captopril-induced abnormalities) were compared with elinieal outcome after revaseularization. Overall 18 patients with a single kidney were studied from 1990 to 1995, and 6 met inclusion criteria for CRS assessment (12/18 pts were not revaseularized: 9 had no renal artery stenosis and 3 were not operated on for different reasons). No significant side effect due to Captopril administration was recorded. CRS results are re ~orted in table 1. PTAGE SEX CAUSEOFSINCq_EKIDNEY CR8 RESPONSE TO FINAL INTERVENTION ASSESSMENT 65 F NEPHRECTOMY PYELONEPHRfflS + IMPROVED TRUEPOS 47 M NEPHRECTOMY HYDRONEPHROStS IMPROVED TRUEPOS 21 M CONGENITAL AGENESIS CURED TRUEPOS 54 F NEPHRECTOMY HYDRONER-IRO~IS + IMPROVED TRUEPOS 6t M NEPHRECTOMY NEOPL~SIA IMPROVED FALSENEG 63 M NEPHRECTOMY NEOPLASIA FAILED TRUENEG Our data demonstrate the feasibility and reliability of CRS in patients with a single kidney. The findings also support the hypothesis of renln-dependeney of hypertension in these patients.

• Hypertension/Infection OTu137 E.N.Khodareva, l.V.Sergienko, Institute of Clinical Cardiology, Cardiology Research Center, Moscow, Russia. I/V N A T R I U M NITROPRUSSIDE I N F U S I O N VERSUS CAPTOPRIL SC1NTIGRAPHY IN PATIENTS W I T H RVH. The aim of our study was to evaluate & compare scintigraphic (SC) renal functional changes after blood pressure lowering by ACEI & nitroprusside (NTP) in order to determine their diagnostic & prognostic value in pts with RVH. Captopril (ACEI) SC is based on the A2- dependent mechanism of maintenance of glomerular filtration (GFR) on the side of renal artery stenosis (RAS). There are some reports about reversible renal failure after BP lowering by nitroprusside; some of the authors note a possibility of deterioration renal function after ACEI as a result of the fall of systemic BP below the critical threshold in pts with severe hypertension. We studied 24 pts with severe arterial hypertension & unilateral RAS (URAS) documented by angiography. 20 pts underwent surgical treatment, normalization & improvement of BP control were obvious in 12 of them, poor BP outcome (failure) occured in 8 pts. In all cases renal SC with 99m-Te-DTPA was performed at baseline conditions & during the acute hypotensive probe (ACEI n=14, NTP n=10). The total & sprit G F R was measured with a single compartement radiotracer infusion clearance. The SC criteria for a positive test were a decreased split renal function, a delayed peak uptake & a prolonged pMTT. I/v NTP infusion significantly decreased mean arterial pressure [MAP](108 rmn.Hg vs 155 mm.Hg, P<0.001), total G F R didn't change (80 ml/min/1.73m vs 90 ml/min, P>0.05), GFR on the side of RAS decreased from 39 ml/min to 30 ml/min (,p<0.01), there was correlation between changes in MAP & split G F R (r=0.8, P<0.001). ACEI decreased MAP level (I25mm.Hg vs 155 mm.Hg. (P<0.001), total G F R didn't change, on the side of RAS decreased from 32 ml/min to 24 ml/min (P<0.001), r=0.43 (p<0.01)~ Sensitivity of SC increased after ACEI from 71% to 93%, positive test results were obvious in 71% of pts. NTP also increased sensitivity of SC in detecting RAS, but positive probe results were observed only in 50'% of pts. In pts with successfull surgical treatment acording BP outcome positive ACEI-test were in 90% of cases, during NTP in 60% pts. In any case deterioration of renal function on the side of RAS or contralateral kidney during NTP-SC couldn't predict BP outcome of surgical treatment or preserved renal function. The results of our investigation showed pressuredependent relationship detween BP lowering by NTP & deterioration of renal function on the side of RAS. Howerever this fact hadn't significant diagnostic or prognostic value in RVH pts. ACEI test is highly predictive in identifying pts with URAS & RVH.

OSu 139 D. Brecht-Krauss, C.A. Guhlmann, G. Suger, G. Glatting, L. Kinzl, S.N. Reske. Departments of Nuclear Medicine and Surgery III, University of U/m, Germany [F-18]FDG-PET IN OSTEITIS: COMPARISON WITH IMMUNOSClNTIGRAPHY WiTH T¢-99m-LABELED MONOCLONAL Purpose: To evaluate use of FDG-PET in comparison to immunoscintigraphy (IS) with Tc-99m-labeled monoclonal antigranulocyte antibodies (MAb) in the detection of osteitis. Methods: Fifty-five patients (pts) with suspected bone infection (47 were localized in the peripherat skeleton, 8 in the trunc) were evaluated by FDG-PET and IS. IS was performed 5h and 24h after i.v.-injection of 300-400 MBq Tc-99m-MAb. Static FDG-PET imaging was performed l h after i.v.-injection of 250-350 MBq [F-18]FDG within 1 week after IS. Both studies were evaluated by visual interpretation, which was graded on a five-point scale of two observers" confidence of osteitis. Receiver-operating characteristic (ROC) curve areas were generated for both methods. The final diagnosis was established in 33 pts by means of histopathologic examination. In 22 pts diagnosis was verified by follow-up over 2 years. Results: Out of 55 pts 32 (58%) had infection of bone and 23 pts (42%) had no osteitis. ROC curve areas were 0.95 for FDG-PET and 0.87 for IS. Sensitivity, specificity, and accuracy of FDG-PET for detecting osteitis were 99%, 90%, and 95%, respectively. Sensitivity, specificity, and accuracy of IS were 86%, 79%, and 83%. All of the 8 pts with suspected osteitis of the trunc were correctly classified by FDG-PET, while IS failed. Conclusions: FDG-PET enables with a high degree of accuracy non-invasively the detection and the definition of extent of osteitis. In particular, it is highly accurate and superior to IS in detecting bone infection of the trunc and should be helpful in further treatment selection.

0Su138

0Su140

S,Gratz,T.Behr,J.Meller, C.Langer,L.Tarditi,R.Franceschini,B.Rahodes, KM.Starmer, W.Bocker Department of Trauma, Plastic and Reconstructive Surgery and Department of Nuclear Medicine of the University of GOttingen, FRG, SORIN Biomedical Saluggia, Italia and RHOMED, Albuquerque, New Mexiko, USA

C.J. van der Laken O.C. Boerman, W.J.G. Oyen, M.T.P. van de Ven, R . A . M J . Claessens, J.W.M. van der Meer, and F.H.M. Corstens. Dpts. of Nuclear Medicine and Internal Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.

Ratlonale:99mTc-antigranulocyte antibodies are ready to use, sensitive and specific in the diagnosis of infections diseases. The affinity constant of different monoclonal antibodies to granniocytes is different. Low affinity constants offer a high amount of circulating free antibody, which may lead to an unspecific uptake in infections. 99m Tc - SSEA antigranulocyte antibodies have a very high affinity constant (1.6 x 1fin) and are used in this study to detect infectious feel. Patients and methods: 10 patients with suspected infections were examined with 555 MBq 99mTc - SSEA-1 routine monoclunal antibody (RHOMED, USA, SORIN, ITALIA) and with 370 MBq 99mTc-HMPAO labelled autologons leukocytes within of 7 days. All the infections were proven by culture, biopsy, surgery and follow-up. Whole body images with the antibody were performed lh , 4h and 24h p.i. and the biodistribution of the antibody was documented. Planar images of the focus were performed l h , 4h and 24h p.i. and the results were compared with the 99mTc white blood cell images. Results: The mean uptake of the antibody l h , 4h and 24h p.i. in the liver was 37.4%, 36% and 27,9%, in the spleen 22%, 21,9% and 11%, in one kidney 2.5%, 2.7% and 3.9% and in a clear defined bone marrow area 8.4%, 9.9% and 12.5%. In the lesion we found also an increasing uptake of 0.3°/o, 0 2 % and 2.2% of the injected activity. All the lesions could be seen in the 99mTc white blood cell scans and the 99mTc antigrunniocyte scans. All the antibody images were positive lh p.i.. The specific binding of the antibody and the high affinity is supported by an increasing uptake from lh to 24h p.i. in the infectious loci and the bone marrow. Conclusions : 99mTc-anti-SSEA-1 antigranniocyte antibodies demonstrate promising results comparable to the results of 99mTclabelled autologous white blood ceils. The antibody is ready to use, has excellent image qualities due to a high target/background ratio and showed no adverse reactions.

e19

ANTIGRANULOCYTE ANTIBODIES

Infection

99mTC-LABELLED ANTI-SSEA-1 MURINE IGM M O N O C L O N A L ANTIBODIES F O R I M A G I N G I N F E C T I O N

eO iim

THE BEHAVIOUR OF RADIOLABELED HUMAN RECOMBINANT I N T E R L E U K I N - 1 IN VARIOUS MOUSE I N F L A M M A T I O N M O D E L S Recently, we demonstrated that radiolabeled human recombinant interleukin-1 (IL-I) specifically accumulated in Staphylococcus aureus induced infections in mice. Radiolabeled IL-1 localized at the site of inflammatory cells in the infectious focus as shown by autoradiography, tn this study, the potential of IL-1 to image infection and inflammation was examined in several other inflammation models in mice and compared to the results obtained in the S. aureus model. IL-1 was radiolabeled with 1-125 via the iodogen method, resulting in a specific activity of 2.5-4 MBq/,ag. The receptor binding fraction in vitro, determined on EL-4 thymoma cells, was 70-95%. Infections or sterile inflammations were induced in groups of 25 Swiss mice by injection of S. aureus, Escherichia cell, Candida albicans, zymosan or turpentine in the left calf muscle. Furthermore, before induction of i.m. zymosan induced inflammations, 25 mice were made granulocytopenic ( < 1 0 ~ WBC/L) by s.c. injections of cyclophosphamide. After 24 hr, all mice were i.v. injected with 0.2 ml 0.4 MBq 1-125-IL-1. Groups of 5 mice were dissected at 2, 6, 12, 24 and 48 hr p.i. In all models, 1-125-IL-1 rapidly cleared in a similar pattern from blood and most other organs. After 6 hr p A , the abscess uptake was the organ with the highest activity uptake in all models. However, the level of abscess uptake was different for each model. At 48 hr p.i., the abscess uptakes were : zymosan (0.65_+0.06 %ID/g), S. aureus (0.56_+0.06 %ID/g), E. cell (0.42_+0.08 %ID/g), C.albicans (0.38_+0.06 %ID/g), turpentine (0.22_+0.04 %ID/g). The abscess-tocontralateral muscle ratios (48 hr p.i.) varied from 16.0 _+ 1.6 (turpentine) to 47.9 _+ 4.2 (S. aureus). Histological evaluation demonstrated that the retention in the abscess correlated with the extent of the inflammatory cell infiltration. The inflammatory cell infiltration in the zymosan induced abscess, and hence the number of IL-1 receptors, was reduced in granulocytopenic mice. These mice showed significantly lower abscess uptake compared to immunocompetent mice (0.05+_0.004 vs 0.65+_0.06 %ID/g at 48 hr p . i , p<0.0001). In conclusion, our results indicate that radiolabeled IL-1 can be applied for imaging of a wide variety of inflammatory or infectious loci provided that there is sufficient inflammatory cell infiltration in the focus. These results confirm our previous data showing specific binding of IL-I to its receptors on inflammatory cells in S. aureus induced infections.

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Infection

OSu141

0Su143

WJG Oven, M W Nijhof A van Kampen, RAMJ Claessens, JWM van der Meer, FHM Corstens. University Hospital Nijmegen, Depts. of Nuclear Medicine, Orthopedics, and Internal Medicine, Nijmegen, The Netherlands.

O.C. Boerman. W.J.G. Oyen, G. Storm*, L. van Bloois*, E.B. Koenders, J.W.M. van der Meet, F.H.M. Corstens. Department of Nuclear Medicine, University Hospital Nijmegen and Department of Clinical Pharmacy*, University of Utrecht, The Netherlands.

I n - l l l LABELED HUMAN IgG SCINTIGRAPHY F O R DETECTION OF INFECTIOUS BONE AND JOINT DISEASE. Adequate delineation of infection in bone and joints is an important, clinically relevant issue. One of the newer agents suggested for scintigraphic evaluation is In-111 labeled human nonspecific IgG (In-111-IgG). In this study, the utiIity of this agent was studied in routine clinical practice. A dose of 75 MBq In-lll labeled to 2 mg lgG (MacroScint, RW Johnson PRI, Spring House, PA) was i.v. injected in 226 patients (108 5', 118 9; mean age 54.3 yr, range 5-90 yr) with 232 possible foci of infection/inflammation. Imaging was performed 4, 24, and 48 hr postinjection. The results were verified by culture, obtained either surgically (42%) or via puncture (19%), and longterm clinical and r6ntgenological follow-up (39%). Follow-up data were used in patients of whom the vast majority had a negative work-up, including negative In-I iI-IgG scintigraphy. AII infected total hip (THP) and total knee (TKP) prostheses, focal osteomyelitis, diabetic foot infections, arthritis, and soft-tissue infections were detected (61 foci). Only one patient with early, low-grade spondylodiscitis was false-negative with In-lll-IgG. Since In-lll-IgG scintigraphy does not discriminate between infectious and sterile inflammation, careful interpretation is necessary in cementless THP up to one yr after insertion, uptake around the neck of the femoral component of a THP, recent fractures, and pseudarthrosis. When uptake is seen in these instances, this may be caused by sterile inflammation and not by infection (specificity for inflammation 100%). TKP often showed mild soft-tissue uptake without apparent osseous involvement, which is caused by continuous irritation by the TKP and not by infection. Infectious and auto-immune arthritis could in most cases be differentiated by the intensity or pattern of uptake, such as symmetrical joint involvement. This results in an overall specificity for infection of - 75%. In conclusion, In-111-IgG scintigraphy is a very sensitive tool for detection of infections bone and joint disease. Moreover, when possible causes for sterile inflammation is taken into account, infection can be ruled out with a high degree of certainty.

Tc-99m LABELED PEG-LIPOSOMES TO IMAGE INFECTION: EFFECT OF PARTICLE SIZE AND COMPARISON WITH Tc-99m LABELED LEUKOCYTES. In previous studies, we have shown that liposomes - sterically stabilized with polyethylene glycol (PEG) - preferentially localize in infectious and inflammatory loci. In the present study we optimized the formulation of these PEG-liposomes for infection imaging in a rat model with regard to particle size. Furthermore, the potential of these small PEG-liposomes to image focal infection was compared with Tc-99m-labeled white blood cells (WBC) in a rabbit model. Biodistributions and imaging characteristics of 4 liposomal formulations of increasing size 0nean diameter varying from 90 nm to 220 rim) labeled with Tc-99m were determined in rats with S.aureus infection in the left calf muscle (5 rats/group). The smallest liposomes displayed optimal characteristics for infection imaging: 90 nm liposomes revealed highest abscess uptake (1.6 _+ 0.3 %ID/g, 24 hr p.i.) in combination with lowest splenic accumulation (6.9 _+ 0.7 %ID/g, 24 hr p.i.)_ Splenic uptake with 120 nm, 160 pan and 220 nm liposomes was 9.0 %ID/g, 24.6 %ID/g and 39.7 %ID/g, respectively. Abscess-tocontralateral muscle ratios with the 90-nm liposomes (24 hr p.i.) were as high as 35. These results indicate that the formulation of PEG-liposomes can be optimized to allow optimal imaging of infection by using small-sized particles. Rabbits with S.aureus infection in the left calf muscle (4 rabbits/group) were imaged after i.v. injection with either small PEG-liposomes or with white blood cells from a donor rabbit labeled with Tc-99m-HMPAO. Clearance from the heart region was much faster for the WBC (tVz = 1 hr) than for the liposomes (0A > 20 hr). Splenic uptake of the PEG-liposomes was significantly lower than splenic uptake of the Tc-99m-WBC (0.3 %ID/g vs. 0.7 %ID/g, p < 0.05). At 20 hr p.i. abscess uptake with Tc-99m-liposomes was significantly higher (4.0 %lD vs. 9.0 %ID, p <0.05). In addition, abscess-to-contralateral muscle ratios 20 b p.i. v~ere higher with lipsomes (38 _+ 7) than with WBC (24 _+ 3). These studies indicate that relatively small (100 nm) Tc-99m-labeled PEG-liposomes may have clinical potential to image infection.

OSu 142

OSu144 R.A.M.J. Claessens, W. Calame and F.H.M. Corstens, Departments of Nuclear Medicine, University Hospital, University of Nijmegen, Nijmegen and University Hospital, University of Leiden, Leiden, The Netherlands.

E. Th.M. Dams W.J.G. Oyen, O.C. Boerman, R.A.M.J. Claessens, E.B. Koenders, A.B. Wymenga, P.W. Pavlov, J.W.M. van der Meer, F.H.M. Corstens. University Hospital Nijmege~ and St. Maartenskliniek, Nijmegen, The Netherlands. TECHNETIUM-99m LABELED TO HUMAN IMMUNOGLOBULIN G VIA THE NICOTINYL HYDRAZINE DERIVATIVE (HYNIC): FIRST CLINICAL RESULTS. A novel method to label polyclonal human immunoglobulin G with Tc-99m via a nicotinyl hydrazine derivative has shown a similar in vivo behaviour as indium-111-lgG in animals with focal infection. In this study, Tc-99m-HYNIC-IgG was compared to In-111-DTPA-IgG in patients suspected of acute or chronic infection. After administration of 740 MBq Tc-99m-IgG, imaging was performed at 4 and 24 hrs. To avoid cross-over activity, 75 MBq In-111-IgG was injected 24 hrs after Tc-99m-IgG and imaged at 4, 24 and 48 hrs postinjection. Thirteen patients were studied (9 M, 4 F, mean age 44 yr, range 17-70 yr). Verification was obtained by (intraoperative) cultures, radiological evaluation or clinical follow-up. The results of Tc-99m-IgG and In-lll-IgG scintigraphy were 100% concordant. Six patients were true positive: three patients had an infected joint prosthesis, one soft tissue infection and arthritis of the ankle, one spondylodiscitis and one acute femoral vein thrombosis. Five patients were true negative: one patient had osteoarthritis, two non-infected pseudarthrosis, and one aseptical loosening of a hip prosthesis. The fifth patient had persisting fever after central venous catheter infection. No focus could be detected, and eventually the fever subsided without specific intervention. In two patients, the concordantly positive I n - l l l - l g G and Tc-99m-IgG scintigraphy in the lungs remained unexplained. One of those patients was suspected of having pulmonary sarcnidosis. However, high resolution CT scan and bronchial lavage were negative. The other patient had subfebrile temperature without pulmonary complaints. Both chest X-ray and CT scan were normal. Our first clinical results suggest that distribution and performance of Tc-99m-HYNIC-IgG is highly similar to In-lll-DTPA-IgG in detecting infection and inflammation. The use of Tc-99m over I n - l l l has apparent advantages with regard to availability, cost, image quality, and radiation burden.

1068

INTRAPERffONEAL (I.P.) RETENTION OF In-lll-lgG IN TWO MODELS OF PERITONITIS WITH DIFFERENT FIBRIN CONTENTS In-111-lgG is well suited for detection of inflammatory loci, because of the locally increased plasma volume and, to some extent, because of a trapping mechanism of unknown nature. The question of a possible retention of In-111 in inflammation cells has not been settled yet. Some suspicion was raised against fibrin as a possible factor in the retention of In-111-lgG. We compared the i.p. uptake of In111-lgG in two models of peritonitis in rats with different extent of fibrin formation. At 24 hr after i.p. injection of either a suspension of S.aureus bacteria or thioglycolate broth rats were iv iniected with 4 MBq of In-111-lgG. For each model up to 48 hr p.l. in groups of five anesthetized rats the peritoneal cavity was washed once with heparin containing Hank's buffer. Inflammation cell containing pellets were separated from the collected washing fluids after centrifugation. Four other rats with an i . p . S , aureus infection were iv injected with 200 MBq In-111-lgG. At 24 hr p.i. the peritoneal cavity was washed with heparin containing Hank's buffer and autoradiography was performed on smears of the combined cell pellets. In both models the i.p. In-111 activity was <2% I,D. and >85% of it was found in the supernatants. At similar countings of i.p. white cells in both models (1E8), the percentage of i.p. In-Ill-activity in the cell pellets was significantly higher in the infection model (7.8 vs. 3.4% at 24 hr p.i.). In the infection model many fibrin fibers and clots were observed in the washing fluids; in the sterile inflammation model however, almost none. Autoradiography showed almost no cellassociated Ira111 activity. However, increased concentrations of In-111 were observed in fibrin fibers and clots. Fibrin, formed in inflammatory foci, might be a trapping agent contributing to the local retention of In-111 -IgG.

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Infection/Lung

Lung 0We147

OSu145 K a s h y a p R, Hall AV, Solanki KK, Vinjamuri S, Das SS, B r i t t e n KE. St Bartholomew's Hospital D e p a r t m e n t s of Nuclear Medicine and Microbiology London ECIA 7BE. Imaging Bacterial Infeoton

Infection with Tc-99m

P.Lass, E.Jassem, .&.Badzio, G.Romanowicz, J.M.Slomifiskl Depts. of Nuc]ear Medicine~ Radiotherapy and Pneumonology; University Medical School, Gdafisk, Poland

Aim: early consequences of radiopneumonitis are fairly well described, also by means of radionuclide studies, but we know little about longterm consequences of post-radiotherapy damage of lung tissue. We decided to perform perfusion, ventilation aerosol and Tc-99mDTPA lung clearance radionuclide studies in patients 1 - 3 years after radiotherapy due to breast cancer, together with CT scanning and spirometric studies. PatientS: We studied 18 women 1 - 2 years (mean 16 months after mastectomy and scar irradiation with a beam of electrons. In all of them respiratory insufficiency II-III grade was seen. Results: We found the regional perfusion defects in all 18 patients varying from 25 - 65 % of expected value (mean 55 %), corresponding with the thorax region subjected to irradiation. The regional Tc-99mDTPA radioclearances T 112 was slowed down by mean 32_1%. CT depicted the regional fibrosis in 3 patients. No significant ventilation and spirometrie alterations were detected. Conclusions: Those results indicate for a long-term lung perfusion impairment after radiation therapy. The split between perfusion and ventilation may be the explanation for the states of respiratory insufficiencies seen in this group of patients. The lung perfusinn/ventilation seintigraphy seems to be the test of choice in long-term screening of patients with radiopneumonitis.

OSu146

OWe148

Gi.insel Vural A~:lkq6z, Sabahat inamr, Nahide G6k~:ora, Tamer Atasever, GUld0ren KaragLizel and Mustafa 0nlii, Gazi University Medical Faculty, Departments of Nuclear Medicine and Lung Disease, Ankara, Turkey

J. Kotzerke, A. Guhlmann, J. Weber, S.N. Reske, University of Ulm, Germany

STUDY WITH Ga-67 The aim of the study was to evaluate the diagnostic value of Tc-99m polyclonal human immunoglobulin (HIG) scintigraphy in the detection and determination of disease activation in sarooidosis patients who had suspicious clinical signs of active alveolitis. Cardiac involvement was also investigated using mulfigated acquisition with same 'agent in pooling phase. Nineteen patients who had histopathologically proven diagnosis of sarcoidosis were included to the study, According to the clinical and laboratory findings, 14 of them had high suspicion of active pulmonary disease. After the injection of 555 MBq Tc-99m HIG, multigated acquisition was started at best septal LAg position. Whole-body and anterior thoracal images were obtained at 4 hr and 24 hr post-injection. Following HIG scintigrephy, 148 MBq Ga-67 citrate was injected and planar images were acquired in a classical manner. A quantitative method was used to evaluate HIG scintigraphy. Pulmonary to liver activity ratios were calculated using liver activity as a reference. Gallium-67 scintigraphy was assessed visually considering soft tissue and liver uptake as reference. Cardiac function was evaluated with systolic and diastolic parameters using semi-automated processing method.Gallium-67 scintigraphy was positive in 10 (71%) of 14 patients who had active alveolitis and was negative in 5 cases with inactive sarcoidosis. However, quantitative results of Tc-99m HIG scintigrephy at 4 and 24 hr revealed statistically significant difference between 14 cases (clinically active disease) and the remaining 5 cases (inactive disease). Pulmonary to liver ratios were significantly higher in active disease (0.68+0.09 at 4 hr and 0.55±0.05 at 24 hr) compared to inactive disease (0.45±0.04 at 4 hr and 0.39±0.04 at 24 hr). In ±1.5 SD limits, pulmonary to liver activity ratios reached a cut off value of 0.55 (4 hr) and 0.47 ( 24 hr) between two groups. Out of 19 patients, 5 had decreased peak filling rate (26%), and 2 showed abnormal peak emptying rate. Low ejection fraction rate was found in one patient.Our data suggest that Tc-99m HIG scintigraphy is a sensitive quantitative method in the determination of disease activation in sarcoidosis, especially in Ga-67 suspicious cases. Multigated acquisition with Tc-99m HIG allow to determine cardiac dysfunction without additional dose. Furthermore, this method offers advantages of easy preparation, continuous availability, fast response time and low radiation dose.

0

REMOTE REGIONAL LUNG PERFUSION DEFECTS IN PATIENTS AFTER BREAST CANCER RADIOTHERAPY; TIlE RESULTS OF LUNG PERFUSION, AEROSOL AND LUNG CLEARANCE RADIONUCLIDE STUDIES

The aim of the study was to evaluate Tc-99m Infecton, a derivative of the antibiotic ciprofloxacin, as an aid to localising bacterial infection. Patients were referred in w h o m focal infection was suspected. In 56 patients comparison with radiolabelled white cell imaging was made. In 64 further patients m i c r o b i o l o g i c a l and clinical criteria were used to determine efficacy. Each patient had 400 MBq Tc-99m Infecton given i.v. with planar images, 500K, over the body and limbs taken at 1 and 4 hours. Results to date show that T c - 9 9 m Infecton is more sensitive (84% to 81%) and specific (96% to 77%) than radiolabelled white cells in localising bacterial infection. Provided that successful antibiotic therapy was taken into account in determining true negatives and failed therapy for true positives, then the overall sensitivity and specificity were 83% and 91%. In conclusion Tc-99m Infecton is so far a safe (no side effects in ii0 patients) and a useful adjunct to the management of patients with suspected but unlocalised bacterial infection. It avoids the taking of blood and is effective in the immunocompromised patient.

DETERMINATION OF DISEASE ACTIVATION IN PULMONARY SARCOIDOStS USING Tc-99m HIG SCINTIGRAPHY: COMPARATIVE

C Imm

REPRODUCIBILITY OF PERTECHNEGAS-LUNGCLEARANCE Groth et al. demonstrated that the clearance rate from the lungs is influenced by the number of particles as well as the content of water of the aerosol using Tc-99m-DTPA for the estimation of the alveolar permeability. Pertechnegas is a dry aerosol with a mean particle size of 0.2 lim causing a definite alveolar deposition. The amount of acitivity and number of panicles deposited in the lungs can easily be regulated by the amount of tracer simmered in the boot. We investigated the lung clearance using two different amounts of activity differing by the factor of 8 to 10. The intraindividual reproducibility of alveolar clearance was investigated in 15 patients. Initial and afterwards sinunered activity was 805:16 and 705+88 MBq Pertechnetate. Pertechnegas was inhaled with a single breath directly after the bum followed by dynamic acquisition in supine position (60 frames in 15 minutes). The clearance rates were derived by monoexponential fitting of the first five minutes of the right lung acitivity curve without any background correction. The deposited activity amounted to 9.4+4.3% of the sinunered acitivity. There was no statistically significant difference in the clearance rates using less or more activity. Activity [MBq] lstnm

80-2_16

Counts [10e3 cpm] 21+10

k mono [1/mini

T1/2 [mini

0.070-+0,019 10.55:2.7

2ndrun 7055:88 206-+94 0,070-+0.017 10.4-+2.4 Using Pertechnegas for the estimation of the alveolar integrity no standardisation is necessary for the number of particles. However, the influence of the breathing pattern needs to be evaluated. Groth S: J Appl Physiol 66:2750-2755, 1989.

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• Lung OWe 149

OWe151

J. Lear, N. Trujillo, J. Pratt, S. Talusani, R. Quaife, D. Kumpe. University of Colorado Health Sciences Center, Denver, CO, USA

D.S. Lee, S.N. Yoon, C Kwark, J - K Chung, MC Lee, C - S Koh. Seoul National University Hospital, Department of Nuclear Medicine, Seoul, Korea

V E N T I L A T I O N / PERFUSION S C I N T I G R A P H Y IN DIAGNOSIS OF P U L M O N A R Y EMBOLISM: TC-99m DTPA AEROSOL IS SUPERIOR TO XE-133 Ventilation / perfusion (V/Q) scintigraphy has generally been performed using xenon-133 for ventilation. However, PIOPED (the largest trial using Xe-133,755 scans / angiograms) and other studies that have employed this technique have raised questions about accuracy in the diagnosis of pulmonary embolism (PE). Tc-99m diethylenetriamine pentacetic acid (DTPA) is increasingly being used as a ventilation agent. The use of DTPA offers potential advantages: greater resolution and the ability to perform ventilation imaging in the same eight views as those of the perfusion study. We studied the accuracy of V/Q scintigraphy using DTPA aerosol in the evaluation of suspected PE. Diagnostic criteria developed specifically for DTPA aerosol were prospectively applied to 3655 patients being evaluated for suspected PE over a seven year period. Of these patients, 16% had normal scans, 54% had low probability scans, 11% had indeterminate probability scans, 10% had medium probability scans and 9% had high probability scans. Pulmonary angiography was performed on 336 patients. Pulmonary embolic disease was identified in 0/2 normal scans, 4/80 (5%) low probability scans, 19/72 (26%) indeterminate scans, 49/121 (40%) medium probability scans, and 61/65 (94%) high probability scans. These results indicate that V/Q scintigraphy using Tc-99m DTPA aerosol is accurate in the diagnosis of PE. Compared to PIOPED results using Xe-133, there were fewer intermediate probability scans (21% vs. 39%, p<.01) and fewer false negative, low probability scans (5% vs.16%, p<.01). We believe that Tc-99m DTPA aerosol can replace Xe-133 in V/Q scintigraphy for the diagnosis of suspected pulmonary embolism.

I N F L A M M A T O R Y LUNG LESIONS COULD N O T BE DIFFERENTIATED FROM MALIGNANCY WITH F-18-FDG PET Benign lesions could be sometimes so hypermetabolic s o m e t i m e s that they could not be differentiated from malignant tumors in lungs with F-18-FDG PET. Semiquantitative m e t h o d s (standardized uptake value: SUV) were reported to improve the differentiation. W e questioned how much benign hypermetabolic lesions mimic maliganancy. W e m e a s u r e d S U V in lung lesions with whole-body and regional P E T in 19 patients. Eleven patients were confirmed to h a v e malignant lesions by pathology, three of t h e m were metastatic. T r i m m e d m e a n S U V in malignant lesions(7.6_+2.5) w a s higher than that of benign lesions(3.7_+l.5)(p<0.05). T h r e e of 8 benign lesions were not even visible both in regional and whole-body studies. A m o n g the five w h o had visible uptake at the region of interest~ one w a s active cavitary tuberculosis(SUV 9.5) and the other was aspergiUosis with old tubersulosis(SUV 8.2). T h r e e of four tuberculous lesion showed S U V over 4.9. T w o aspergillosis lesions had higher SUV. W e conclude that active inflammatory lesion s u c h as tuberculosis could mimic malignancy in l u n g s and that F - 1 8 - F D G P E T h a s a limited value as for positive predictive value especially in countries who h a d high prevalence of tuberculosis.

OWe150

0We152

K.M&re, T.Nilsson, F. Christiansen, Dept of Diag Radiology, Huddinge University Hospital and Orebro Medical Center Hospital, Sweden.

R. Moncayo, W. Lang, M. Freund*, A. St6ger*, G. Riccabona. University of Innsbmck, Departments of Nuclear Medicine and *Radiology, Innsbruck, Austria.

CLINICAL RELIABILITY OF THE LUNG SCAN REPORT

LUNG PERFUSION SCANS AND HELICAL CT IN THE DIAGNOSIS OF PULMONARY EMBOLISM

Lack of clinical confidence in the lung scan report does exist. This may influence the establishment of diagnosis and treatment for patients with suspicion of pulmonary embolism. The following study was undertaken in order to evaluate variations in the interpretation of lung scans. Materials and methods. 170 V/Q scans were read together with chest radiographs by three experienced independent readers on two occasions 6 months apart, followed by consensus reading. Modified PIOPED criteria were used. The patients were consecutive from a prospective study, without evidence of DVT and all had undergone pulmonary angiography regardless of lung scan findings. Results. 51 patients had pulmonary embolism by angiography. Consensus reading resulted in the following % distribution in probability categories: Normal/very low (N):35, low (L):16, intermediate (I):22, high (H) :27. The % distribution at the six independent readings varied as follows. N:II-35, L:24-30, I:17-24, H:17-31. By kappa values calculations the inter observer agreement varied from fair to moderate, and the intra observer agreement ranged from moderate to good. Conclusions. The limited accuracy of the clinical lung scan report should be recognised and encouraged more integrated diagnostic workup.

1070

The recent introduction of improved techniques for fast CT scans has promoted the use of this method for routine diagnosis of pulmonary embolism (PE). The aim of this study was to compare the results of lung perfusion (LuP) scans and of helical CT of the chest. A total of 36 pmients, who were referred because of suspected PE, were studied prospectively using a standard protocol. The LuP study was done • 99m . . . . using 111 MBq of Tc-MAA, images were done m 6 projections. The LuP results were evaluated on the basis of PIOPED-criteria. Helical CT (High Speed Advantage, GE) was done within I to 2 days after LuP. Pathological changes in any segment of the lung were individually scored for each examination type. Finally the matches of the defects in both investigations were analyzed. Results: Altogether LuP showed a higher number of defects in correlation with the clinical picture (LuP:84 vs. CT:4I). Low probability defects showed abnormal CT findings only rarely (LuP:40% vs. CT:7.3%), whereas intermediate defects were commonly seen in CT (LuP:36% vs. CT:70%). High probability defects were found in similar percentages (LuP 22% vs. CT. 23%). Perfusion defects in the apical segments (LuP:23 vs. CT 2) and in peripheral locations were missed frequently in CT. An identical localization of the defects was seen only in 15 cases. In 3 cases (8%) with clear PE according to LuP the CT study was negative. Conclusions: The inherent differences of both methods lead to different rates of positive findings in PE. CT-imaging alone can lead to an. understimation of the extent of the disease.

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Lung/Miscellaneous

OWe153

OWe155

E. Sayit*, H. Durak*, S. Akto~u**, G. Erkmen**, T. Ertay*, M. BOyfik~;idn**, E. Ozbilek*, S. G0910** Dokuz Eyl01 University School of Medicine, Department .of Nuclear Medicine* and Yeni~}ehir Hospital of Chest Diseases**, Izmir, TURKEY

AC Santos, MJ Ribeiro, ME Maehado, N Ferreira, JJP de Lima Biophysics Dept, Medical School, University of Coimbra, Azinhaga de Sta Comba 3000 COIMBRA, PORTUGAL

EFFECT OF CANCER CHEMOTHERAPY ON PULMONARY EPITHELIAL PERMEABILITY IN LUNG CANCER Measurement of lung epithelial permeability with Tc-99m DTPA radioaerosol is a sensitive method for the detection of pulmonary epithelial leakage. The aim of this study is to investigate the effect of one course cancer chemotherapy (CRx) on the clearancerate of Tc-99m DTPA. 18 patients (t 8 male; mean age: 59_+ 10 years) with lung cancer (11 nonsmall cell, 7 small cell) were included in the study. The patients inhaled 40 mCi Tc-99m DTPA from a nebulizer (Venti-Scan III, Biodex) for 3 minutes. Thirty images of one minute duration were acquired from posterior projection. Regions of interest were drawn around the periphery of the lungs and on the major airways. Decay corrected time activity curveswere generated without background correction. The first 7 minutes of the curves were used to calculate lung clearance half time (T1/2). Penetration index (PI) was given as peripheral/central counts ratio on the first mfnute image. T 1/2 values are as follows : Peripheral (min) Central (min) PI (%)

Before CRx

After CRx

39±17 131 -t-113 38_.+13

59+_.38 205-1-140 39+__12

P value .005
Our results showed slowing of peripheral and central clearance of the radioaerosol after CRx as shown above. In addition to a~veolarclearance, mucociliary clearance of the radioaerosol may also be a determining factor of the peripheral clearance rate. Our study shows that Tc-99m DTPA radioaerosol study may be used to monitor the toxic effects of CRx on the pulmonary epithelium and possibly on mucociliary function as well.

E V A L U A T I O N OF T H E E X C H A N G E A B L E W A T E R S P A C E - PRELIMINARY RESULTS

The aim of the present work is to study the potential use of liposomes in the evaluation of the exchangeable pulmonary water space, an important parameter in some pulmonary oedema situations. The idea behind this study is based upon the delivery or release of a diffusible radiotracer into the lung cappillaries which equilibrates with the hmg interstitial water space and returns to the blood circulation, with a time constant that depends on the magnitude of this space. The delivery of the diffusable radiotracer in the lung capillaries is achieved by means of giant liposomes which are instable at 37°C, incorporating the tracer and injected i.v. at a lower temperature. The liposomes used in this study are biocompatible, biodegradable, with low toxicity and showed no immunogenicity A drug labelled with 99mTc encapsulated in the aqueous phase of giant liposnmes (20-30 lain O) (Needham and Evans 1988) has been used. Liposomes were prepared in a sterile environment and with pyrogenie materials. The lipid films comprised DSPC/EPG/CHOL 1 (60%/10%/30% mass ratio). After i.v. injection in the femoral vein of Wistar rats 2(300-600 g), the liposomes entrapped in the pulmonary circulation released the radiodrug locally. When the radiotracer is diffusible we will be able to evaluate the volume of the exchangeable pulmonary water through disappearance time curves, which will probably be slower for greater water spaces. When a non-diffusible tracer is used, the disappearance curves will not be influenced by an increase in the water space.

DSPC = distearoylphosphatidylcholine;EPG = phosphatidylglycerol;CHOL = cholesterol. This compositionhas been approved for clinical purposes. 2 Accordingto National and International legislations

Miscellaneous

0Mo156

M. U n l u , S. I n a n l r .

N,MoIe&C.R.BeUina,G.Boni,L Bodei,E.Lazzeri,F.Matteucci,P.B enincasa,F.Borsetd, A.Calderazzi,M.Gabdele,R.Bianchi.

PROLONGED LUNG R E T E N T I O N AND REDUCED CARDIAC UPTAKE OF IODINE-123 MIBG IN DIABETIC PATIENTS W I T H CORONARY ARTERY DISEASE

1-123 M I B G has been introduced as a biochemical marker in the assessment of pulmonary endothelial cell integrity and myocardial g-adrenergic sympathetic innervation. The aim of the study was to evaluate 1-123 MIBG lung extraction and myocardial innervation in diabetic patients with or without coronary artery disease (CAD). 44 nonsmoking cases with normal respiratory function tests were included to the study. Simultaneous injection of 110 MBq of 1-123 MIBG and T1-201 was performed in 12 diabetics, 11 diabetics with CAD (DCAD) and 14 CAD patients without diabetes (mean age:52_+5.4, range:45-61). Seven age matched controls were also studied. Lung uptake ratios (LU), washout rates (Wr) and tl/zWr (using monoexponential curve fitting method) were calculated for the mid zone of the right lung on early and delayed planar images. To evaluate cardiac sympathetic innervation, heart to upper mediastinum ratio (HMR) was used. In all cases T1-201 lung to heart ratio (T1-L/H) were also calculated. In DCAD group, significantly decreased cardiac 1-123 MIBG uptake and prolonged lung retention were found. LU of 1-123-MIBG was inversely correlated with HMR in this group (r= -.76, p < .01). Lung to heart ratios of T1-201 were significantly increased in CAD patients, but there was no significant difference between diabetic and non diabetic CAD patients. LU Wr t l/zWr HMR T1-L/H controls 70.7+1.8 29.5+1.7 445.2+57.7 2.5_+.24 .34_+.06 diabetics 74.6_+9.7 30.3-+8~6 477.6+120.2 2.04-.27 .42-+.07 CAD 74.0-2-_8.7 26.2_+8.7 535.4_+108.3 2.1_+.34 .63-+.23 DCAD 80.I_+4.I 20.I-+4.8 678.3_+106.9 1.7_+.15 .64+.14 In conclusion, prolonged lung retention of 1-123 MIBG was associated with decreased cardiac sympathetic innervation in diabetic CAD patients. Pulmonary congestion or cardiac dysfunction itself did not affect I-123 MIBG lung uptake. T1-L/H ratios showed no increase in DCAD when compared to CAD patients. Increased lung retention of 1-123 MIBG is highly suggestive of ongoing pulmonary endothelial dysfunction together with ischaemic events in patients with diabetes.

Nuclear Medicine Center,Radiology Pisa,Italy.

and Odontostomatology

Institute,University

of

SALIVARY SCINTIGRAPHY WITH 99roTe: A QUICK EVALUATIONMETHOD OF SJOGREN DISEASE Dynamic salivary scintigraphy is a safe,noninvasive test which can outline major salivary glands.Salivary gland disfunction is the most common cause of xerostomia. the scintiscan is a particularly valuable tool because it produces a visible dynamic measure of glands function,allowing differentiation between abnormalities in uptake and excretion. The aim of this study was to evaluate salivary gland uptake curves in order to calculate a simple,accurate grading scale.We tested the possibility to show salivary gland diseases even in the first 10 or 15 minutes after 3 mCi of a 99mTc-pertechnetate injection,without waiting an hour nor using stimulation tests. A group of 45 patients with salivary glands disfunction and complaints of xerostomia was age-matched with a healthy control group. Fourteen patients affected by Sjogren syndrome (all female,age-ranged 25-53),twentyone patients (17 female,4 male age-ranged 26-88) affected by Sjogren-like syndromes and ten normal controls (7 female,3 male,ageranged 26-71) were enrolled in this study. Our results (see table below) show the activity ratios of parotid and submandibular glands at 10 and 15 minutes after injection in Sjogren, Sjiogren-like and normal patients. Table 1 (S=Sjogren;SL=Sjogren-like;N=normal)

S SL N

Parotid glands 10 min 15 rain 2.86_+1.02 3.9_+1.26 4.2_+1.3 4.89+1.31 4.5_+1;06 5.37_+1;4

t~ c-

PULMONARY

OWe 154 Gazi University Medical Faculty, Department of Nuclear Medicine, Ankara - TURKEY.

co ll

Submandibular glands 10 rain 15 rain 3.37+_0.95 3.41+0;76 5.94+1;26 6.76-+1.68 5.17+1;03 5.54+1;33

Differences in data fiom Sjogren patients and the group of Sjogren-like and normal ones were statistically significant (p<0.05).So the calculation of salivary uptake curves at early times from injection opens a new perspective of an early and quick diagnosis of Sjogren syndrome,and of a simple differentiation from other salivary disfunctinns.

1071

O. B

t~

x_

O

•

Miscellaneous

0Mo157

0Mo160

AC P e r k i n s , P Y e o m a n , A J H i n d l e , R M V i n c e n t , M F r i e r , KR B l a c k b a n d , R W i n t e r Depts. of Medical Physics and Adult Intensive Care Unit, University Hospital, Nottingham, UK. BEDSIDE N U C L E A R M E D I C I N E IN THE INTENSIVE CARE UNIT (ICU) Many p a t i e n t s in ICU can not be t r a n s f e r r e d to diagnostic i m a g i n g d e p a r t m e n t s . We have i n v e s t i g a t e d t h e role of bedside radionuclide procedures for monitoring organ function of ICU p a t i e n t s . A M e d i s c i n t S y s t e m w i t h four dual radionuclide probes linked to a PC with curve processing software (Oakfield I n s t r u m e n t s , Oxford, UK) was used. A range of procedures h a s been u n d e r t a k e n . Vascular lung permeability has been m e a s u r e d in 16 patients with clinical s y m p t o m s of Adult Respiratory Distress Syndrome. Due to t h e poor availability of I n - l 1 3 m we have e s t a b l i s h e d a technique for the invivo labelhng of serum transferrin with In11 I-chloride together with Te-99m-RBC for calculation of the p l a s m a p r o t e i n accumulation index. Hepatobilliary function h a s been a s s e s s e d using Te-99m-disofenin in 7 n e r m a l s and 11 p a t i e n t s including 8 with systemic sepsis. Other studies i n c l u d e t h e m e a s u r e m e n t of g a s t r i c outflow following p a r e n t e r a l feeding and Tc-99m-DTPA probe renograms. The provision of a n I C U service h a s r a i s e d i m p o r t a n t questions regarding radiopharmaceutieal administration, i n s t r u m e n t a t i o n , data analysis and radiation protection. The h i g h s e n s i t i v i t y of t h e e q u i p m e n t r e q u i r e s only low a d m i n i s t e r e d a m o u n t s of activity. We r e c o m m e n d t h a t p a r e n t e r a l injections should not be a d m i n i s t e r e d to ICU p a t i e n t s t h r o u g h giving sets or via Teflon c a n n u l a e and radiopharmaeeuticals should not be diluted excessively. We conclude t h a t a bedside service is a valuable aid to the m a n a g e m e n t of patients undergoing intensive care.

N i e l s Vinberq* a n d K l a u s Ennow* The Isotope-Pharmacy* and The State Institute for Radiation Hygiene ~, Frederikssundsvej 378, DK 2700 Br~nsh~j, D e n m a r k

DANISH NUCLEAR M E D I C I N E PROCEDURES 1984-1994

On average, 200 a d m i n i s t r a t i o n s of radiopharmaceuticals take place in D e n m a r k each day. This correspcnds to ca 14 administrations annually per I000 inhabitants. These figures have been fairly constant during the last i0 years but cover large variations in choice of radiopharmaceuticals and choice of procedures. One of the p r o v i s i o n s for p r a c t i s i n g diagnostic and therapeutic nuclear m e d i c i n e in Denmark is that the p r a c t i s e must be reported annually to The D a n i s h Institute for Radiation Hygiene. The reporting specify number of administrations, type of radiopharmaceutical, type of investigation~treatment, m e a n activity administered, and m a x i m u m activity administered. Based on this reporting, an overview of Danish nuclear m e d i c i n e procedures in 1984 1994 is presented. The overview includes va= riations in the choice of radiopharmaceutieals for d e f i n e d n u c l e a r m e d i c i n e procedures.

0Mo159

0Mo161

O. Yenici, H. Berk, M. Yllmaz Depts. of Nuclear Medicine and Traumatology, Medical Faculty, University, Izmir, TURKEY

R.D. Gunasekera W.H. Thomson, L K Harding, City Hospital NHS Trust, Birmingham

OrthopaedicsDokuz EylOl

THE E V A L U A T I O N O F S K E L E T A L M U S C L E I S C H E M I A R E P E R F U S I O N BY THALLIUM-201 SCINTIGRAPHY

SITTING ON A BUS SEAT NEXT TO A PATIENT WHO HAS HAD RADIO1ODINE TREATMENT AND

Purpose : Reperfusion following long lasting ischemia causes ~no-reflow" and its occurrence can be prevented by antioxidants like allopurinol. We studied no-reflow p h e n o m e n o n following 6 hours limb ischemia. M a t e r i a l a n d M e t h o d : 50 rats were used in 5 groups ( Control (C), Ischemia (I), IReperfusion (IR), IR and Allopurinol (IRA), IR and Vit C+E (IRCE) ). Perfusions were evaluated by scintigraphy using 300 ~Ci and 200 ~[Ci of TI-201 during first and last ten mins of 60 mins reperfusion period. Right to left side ratios were calculated. R e s u l t s : Difference was significant between C and I groups (p<0.001). Reperfusion revealed nonsignificant differences hetween groups, however revealed significant difference between

C and other groups (p<0.001 and p<0.05 respectively). Conclusion : Our results show that TI-201 scintigraphy is valuable in the evaluation of skeletal muscle ischemia, reperfusion cannot restore muscle perfusion after 6 hours of ischemia.

1072

Restrictions on public transport by outpatients receiving radioiodine therapy are mainly based on administered activity. While dose rate models have been applied, no direct measurements have been made of the dose to other passengers. Within half an hour of having a 1-131 capsule (188-450 MBq) we asked 52 patients to sit on a standard bus seat for 20 - 30 minutes. A water filled phantom of a human torso with digital dosemeters on either side of chest wall was placed next to the patient. A further dosemeter in a waterproof case was immersed in the middle of the phantom. The body weight and height was recorded. At the end of the study their dose rate was measured at distances of 0.1, 0.5 and 1.0 m from anterior, right and let~ lateral, and posterior mid trunk with the patient standing. The phantom measurements normalized to one hour and 200 MBq gave mean (± 2SD) adjacent 122 pSv (~: 84), middle (in water) 20 gSv (+ 13) and opposite 4 p.Sv (:t: 2.6 ). Measurement from the anterior mid trunk yielded dose rates 1.3 - 1.8 times the corresponding right and left lateral and posterior measurements at 01, 0.5 and 1.0 m Guidelines based on anterior dose rates are therefore over-restrictive, tn addition, published tables show the effective dose from lateral irradiation is approximately half the entrance skin dose. Using the above 95th percentile figure for the lateral dose showed that even with 1000 MBq activity, the dose to a passenger should net exceed 0.5 mSv in a one hour journey.

• Miscellaneous/Nephrology OMo162

OMo164

j. T Nielsen' J.'Marqvarsen 1, E. 1. Christensen ~. 1Dept. of Nuclear Medicine, University Hospital of Aarhus, DK-8000 Aarhus C Denmark; 2Dept. of Cell Biology, University Of Aarhus, DK-8000 Aarhus C Denmark.

J. Verdt%, Caballero.

NORMAL BIOLOGICAL T U R N O V E R OF IN-I I1-LABELED MONOCLONAL ANTIBODY IN WISTAR RATS. Introduction: ln-111 Oncoscint CR 103 is a mouse-derived monoclonal antibody used for detection of colorectal cancer by immunosciutigraphy. Unfortunately, hetarologous monoclonal antibodies, are also sequestered in several non-target organs which may lessen their diagnostic value. Materials and methods: Forty-eight male Wistar rats weighing 300 g were injected with 20 pg of In- 111 Oncoscim CR 103 labeled to a specific activity of 185 MBq/mg. Twenty-four animals received labeled antibody alone (group A) while the remaining 24 (group B) in addition received 80 gg of unlabeled antibody. Six animals from each group were anesthetized by sodium pentothal at 24, 48, 72 and 96 hours. Whole-body activity was measured immediately after injection of isotope and at each sampling time. One ml of blood was sampled and the liver, spleen and kidneys were quickly removed and placed on ice. The radioactivity in each of the organs was measured and samples of the organs were pooled and homogenized. Membrane-bound and soluble activity in homogenate were separated by uitracentrifugation at 100,000 G for 1 hour. The molecular weight of soluble activity was determined by size exclusion HPLC-analysis. Results: The whole body-activity in groups A and B decreased with a half-life of 105 and 157 hours, respectively (NS). The activity in blood at 24 hours was in group A: 35.2 + 3.6 % ID with a half-life of 45.5 hours and in group B 34.4 + 3.4 % ID with a half-life of 44.2 hours (NS). The results for max. activity in organs and changes in soluble activity are shown in the table: Kid neys Spleen Liver Max. Max. % sol. Max. Max % sol Max. Max % sol. hp.i. % ID 24-96h h . p . i . . % ID 24-96h h.p.i %ID 124-96h A: 724.3+0.451173721.0+0.1774142, ,20+171,31,~ B: 96 52~_0.743 69 72 1.0_~02 71 44 24 14.0+~1.165 37 The radioactivity in blood corresponded to labeled antibody. The soluble activity in all organs eluted in 2 peaks representing compounds with molecular weights of <23.000 and < h000, respectively. Conclusions: Unlabeled antibody in amounts of four times labeled antibody did not significantly effect sequestration of the labeled antibody. The fall in soluble activity from 24 through 96 h.p.i, in liver and spleen, may reflect decreased offer of intact antibody, whereas the increased soluble activity in kidney may reflect accumulation of the metabolized low molecular weight products and free ln-I ] 1.

J. Rosas, J. Serrano, A. Martlnez, O. Servicio de M e d i c i n a Nuclear, Hosp. Sat: Servicio Reumatologia, Hosp. Villajoyosa.

Juan. Alicante.

SPAIN

SCINTI~RAPHIC ASSESMENT OF SALIVARY FUNCTION XEROSTOMIA. COMPARISON WITH PILOCARPINE STIMULATION

I. G 6 ~ ; ~. Karsho~lu, T. Ozpa~acl Hospital tstanbul Turkey

The aims of the study were to assess the clinical value of the 15 min. salivary gland uptake (GUI5) of 9 9 m T c - p e r t e c h n e t a t e in patients with xerostomia, and to compare its results with those o b t a i n e d from the salivary gland scintigraphy (SGS) and pilocarpine stimulation test (PS). We studied 27 patients (22 p r i m a r y Sj6gren syndrome, and 5 r h e u m a t o i d arthritis), age 58.8±14 years, with complaints of xerostomia and u n s t i m u l a t e d whole saliva collection less than 1.5 ml in 15". SGS, GUI5, and PS were p e r f o r m e d in all of them. 15 patients (age 52.8±12.6 years) served as control group for GUI5. SGS studies l a s t e d 45" and results were classified according to salivary involvement: I (normal,n=2), II (mild/moderate, n=ll), III (severe, n=7), and IV (very severe, n=7).GUI5 was d e f i n e d as: (sum of 15" b a c k g r o u n d c o r r e c t e d counts of all salivary g l a n d s / i n j e c t e d dose cpm) X 100; from the results of the control group a t h r e s h o l d of n o r m a l i t y of 0.4% was considered. PS was i n t e r p r e t e d as positive when whole saliva collection exceeded 1.6 ml in 15".SGS was abnormal (groups II,III,IV) in 25/27 patients. GUl5 was p a t h o l o g i c in 100% patients of group III,IV, in 9~ of II, and in 0% of I. PS was p o s i t i v e in 13/27 (48%). C o m p a r i s o n with sointigraphy was as follows: SGS Group GUI5 I,II Ill,IV Norm. Pathol. PS + 12 1 ii 2 PS 1 13 I 13 P<0.0001 C o n c l u s i o n s : i) GUI5 is a useful alternative technique in d e t e c t i n g severe or very sever salivary gland i n v o l v e m e n t in patients with xerostomia. 2) GUI5 can p r e d i c t the response to p i l o c a r p i n e treatment in this patients.

OSu165 Hipokrat Laboratories and ~i~h Effal

SCINTIGRAPHIC ASSESSMENT OF TIlE YASCULARIZATION OF HYDROXYAPAT1TE OCTJLAR IMPLANTS Hydroxyapatite ocolar implants are preferred, became they are reaction flee and similar to bone structure. The holes of the implant are failed in by the patient's fibrovascular tissue and implant turns to an alive tissue in about six months a~er the implantation, normally. Eye prosthesis is placed in front of the implant aider being sure about the completion of implant vascttlarizatinn.This study was planned to evaluate of the effeetivaness ofTe-99m MDP scinfigraphy in assessing the vaseularization levd of the implant. Fifteen patients (10 males, aged 16-43) with comlliue hydroxyapafita ocular implant were included to the study. Six months after the implantalion, Tc-99m MDP three phased anterior planar stratigraphy of the orbital area were performed to all the patients. After the completion of LEGP collimator images pinhole anterior and both lateral images were obt=ned. The activity of the implant area were compared to the symmetrical area on perthsinn and blood pool images,, aad;.it was compared to the nasal bone activity and contralateral orbital activity on anterior metabolic phase pinhole images The activity patterns of implants were classified in two groups as homogenous cimular and nonhomogenous.. The activity levels of the implants were classified in three groups as equal or higher than nasal activity, lower than nasal activity and very lower than nasal activity but equal or higher than eontralateral orbital aehvily. The implant metabolic phase activities were explained as follows: homogenous and equal or higher than nasal activity is normal vescularmation, nonhomoganous bat equal or higher than nasal activity is uncompleted normal vasculanzafion, lower than nasal activity is iusufficiant vaseularization. Fourteen implants showed normal or uncompleted normal vascularization,; All these implants showed equal or higher than nasal (6 equal) metabolic phase activity Only one implant showed insufficient vaseulafzation. Five out of 15 implants showed homogenous circular and the other 10 implants showed nonhomogertous metabolic phase activity.. Eye prosthesis were placed to the 14 implants and they have been following up for 1-23 months without any problem and functional damage. The other implant, accepted hypovusctflar, has bean waiting for the sufficiency of its vaseulanzation. Findings showed that the evaluation of the vaseularization level of implant can be assessed easily by scinfigraphy...The placement of the eye prosthesis in the implants insufl]ciantly vascular, should be postponed.

co

IN

Nephrology

OMo163

co ii

L.J. Petersen 12, J.R. Petersen 1, U. Talleruphuus 1, M.L. Moiler 1, J. Mehlsen 1, S.D. Ladefoged2, H./E. Jensen2. ~Dept. of Clinical Physiology & Nuclear Medicine, Frederiksberg Hospital, and 2Dept. of Nephrology, Hvidovre Hospital, Denmark. GFR ESTIMATED BY Tc-DTPA RENOGRAPHY IN PATIENTS WITH CHRONIC RENAL FAILURE The purpose of this paper was to evaluate GFR estimated from a Tc-DTPA renography as comparred to GFR estimated from renal clearance of Cr-EDTA in patients with chronic renal failure. Fifty patients with chronic renal failure (serum creatinin between 150 and 600 micromol/I) were included in the study. GFR was estimated from the uptake phase (1-3 minutes after injection). Renal clearance during constant infusion of Cr-EDTA was used as standard method for estimating GFR. Furthermore, GFR was estimated from 24 hour urine clearance of creatinine, the mean of urea and creatinine clearance, and from serum creatinine by the Cockcroft-Gault formulae. The mean GFR was 30 ml/min (range: 9-83) estimated from clearance of Cr-EDTA. A regression analysis between the two GFR estimates did not differ from the line of identity (r=0.97). The limits of agreement (LA) was 1.5 + 17.0 ml/min. The mean difference of 1.5 ml/min did not differ significantly from zero. LA between renal clearance of Cr-EDTA and creatinine clearance was -3.8 -+ 20,0 ml/min, the mean of urea and creatinine clearance 6.4 -+ 17.6 ml/min, and the estimate from the Cockcroft-Gault formulae -2.1 _+ 20.2 ml/min. The mean difference between the standard method and creatinine clearance (p=0.02) and the mean of urea and creatinine clearance (p<0.001) was significantly differend from zero, wich was in disconcordance to the estimate from the Cockcroft-Gault formulae (p=0.2). The GFR estimation from a Tc-DTPA renography had acceptable LA at the same level or even smaller than the other tested methods. GFR estimated from Tc-DTPA renography was acceptable for clinical use in patients with chronic renal failure.

1073

(n

,= ¢X l

L-

O

• Nephrology 0Su166

0Su168

V. Rufini, C. Vellante, G. D'Errico, R. Piraccini, G. Galli. Department of Nuclear Medicine, Catholic University of the Sacred Heart, Rome - Italy

J. Kotzerke, F. Moog, K. Kleinschinidt, S.N. Reske, University of Ulm, Germany NEW DATA ON THE REPRODUCIBILITY OF TC-99M-MAG3CLEARANCE

THE VALUE OF SOME SIMPLIFIED METHODS WITH Tc-99m DTPA FOR GFR DETERMINATION In 25 patients we compared three Tc-99m DTPA simplified methods (SM) with a reference method performed with Cr-51 EDTA. Namely: 1) a method proposed by Galli et al. (no dose calibration) (Nucl Meal Commun 15: 831, I994) 2) the well-known Gates' method (no sampling); 3) the Caflsen's method (neither sampling nor dose calibration) (Nut1 Med Commun 16: 405, 1995). An estimation of GFR derived from the plasma creatinine by the Cokcroft-Gault formula (Nephron 16: 31, 1976) was also taken into account for comparison. Reference methods (Cr-51 EDTA): in 13 pts. the Sapirstein's n% with 11 blood samples during 4 hrs; in 12 pts. (who refused Sapirstein's n~) the two samples Russel's m. As already quoted by others, Russel's (two samples) m. is practically equivalent to Sapirstein's no. In our cases: 1{2 = 0,946; linear regression: intercept no significantly different from 0, slope not significantly different from 1. SM (Tc-99m DTPA) vs Reference Methods S.E.% Impr C.L.(ml/min) LR (SM=a+b Ref.m) % Infer Super a b Sy.x R2 Galli -1.35 11.1 -16.1 22.0 2.16 0.94 6.0 0.916 Carlsen -7.07 2 7 . 5 -21.8 45.3 16.6 0.69 8.4 0.705 Gates - 2 8 . 4 23.53 -16.1 64.5 -3.6 0 . 6 8 5 12.35 0.623 Cokcroft -8.02 2 3 . 4 -29.9 3 7 . 6 -16.9 1.21 12.5 0.804 S.E. systematicerror; C.L. concordancelimits; L.R. linear regression Conclusion: The results of Galli's method are similar to those previously published. In comparison with Cr-51 EDTA a small systematic error is present but the precision seems sufficient for practical use. Cadsen's method, although imprecise, performs better than Gates' method. The results of the latter, as implemented in a commercial software, are affected by remarkable systematic error and do not seem more reliable than a simple GFR estimate from plasma creatinine.

The intraindividual reproducibility of clearance measurements using 99mTc-MAG3 was investigated using three different groups: in 30 patients the clearance (C1) was done using two different amounts of activity (10 / 100 MBq) (Gr. 1). In another 30 pts. the estimation was repeated within 10 days (Gr. 2). In a third group the clearance values from yearly controls were compared if the split function and the kinetics were unchanged (Gr. 3). Blood samples were taken after 20 and 25minutes. Clearance values were averaged from two blood samples ( m e ~ D for the first and second estimation [ml/min/1,73 qm]). For the clearance estimation on the same day, time depending background correction for residual activity was done. Clearance algorithm proposed by Bubeck was used. For each pair of clearance data, the difference between the first and the second measurement was expressed as percentage of the mean value of the two calculations. CI_+.SD(1)

CI+SD (2) 10%

50%

90%

Gr. 1

199-2:66

205+66

-2.8%

4.2%

Gr. 2

179-Z'_78

169-&-_78 -12%

-6%

37%

Gr. 3

191+62

192.+.63

-0.2%

13%

-12% -18%

The reproducibility was highest for the estina_ationon the same day (precision: 7.3%). Repeated measurements within 10 days or within one year, however, revealed standard deviations of the mean differences of 24% and 12.5%, respectively. Therefore, in clinical routine identical, conditions for clearance measurements cannot be guarantied resulting in serious differences. For evaluation of changing kidney function (i.e. surgery or chemotherapy) the MAG3-clearance is not precise enough and other radiotracers should be used. Bubeck B: Semin Nucl IVied23:73-86, 1993.

OSu167

08u169

M. Rehling and L.E. Nielsen. Aarhus University Hospital, Section Skejby Hospital. Department of Clinical Physiology and Nuclear Medicine, Aarhus, Denmark.

B. Erbas, J. Kanski, G. Young, N. Tamarapalli, CD. Russell, E.V. Dubovsky. UAB, Division of Nuclear Medicine and V.A. Medical Center. Birmingham, Alabama. APPLICATION OF A NEW SINGLE-INJECTION SINGLE-SAMPLE FORMULA FOR MEASURING Tc-99m MAG3 CLEARANCE.

SINGLE-SAMPLE PLASMA CLEARANCE OF ACCURACY OF FOUR METHODS.

99mTc-MAG3.

99mTc-MAG3 is widely used for renography and measurement of renal function with the single-injection plasma clearance technique. We studied the accuracy of four single-injection single-sample methods in 51 adult patients with GFR fzom 4 to 132 ml/min. Reference plasma clearance was determined tiom 16 blood samples taken 2-300 rain post injection (p.i.). In patients with GFR < 15 ml/min and additional blood sample was taken 24 h.p.i. RESULTS: Method 1) MiiUer-Suur

Correlation equation y = 1.12x + 9.51

SEE(ml/min) 19.4

r 0.981

Age

19-29 60/51 30-39 62/97 40-49 58/74 50-59 23/49 60-69 7/8 Total 210/279 P value (ANOVA)

2) Bubeck

y = 1.08x - 2.96

16.9

0.984

3) Russell A

y = 1.12x - 4.67

20.8

0.978

4) Russell B

V = 1.117¢ - 7.$8

20.0

0.979

x = Reference plasma clearance; y = Single-sample plasma clearance Method 2 and 4 incorporates scaling for body size and should be valid for both children and adults. Method 1 requires blood sampling at an exact point in time which is inconvenient. We therefore recommend method 2 (or 4).

1) Miiller-Suur et al. Eur J Nucl Med 18:28-31 (1991) 2) Bubeck. Sere Nucl Med 23:73-86 (1993) 3) Russell ct al. J Nucl Med 30:1955-1959 (1989) 4) Russell et al. (To be published. Personal communication)

1074

Several algorithms have been proposed to determine the 99mTcMAG3 renal clearance. Formulas based on single plasma sample are reproducible and can be easily used in routine applications. Recently, a new single-injection single plasma sample formula has been described (Russell et a]. JNM 1996). This formula incorporates scaling for patient size and is valid for both children and adults. The aim of this study was to describe the normal values of 99mTc-MAG 3 clearance using the new formula. Renal clearance of 99mTc-MAG3 was determined in 489 healthy candidates of renal donation (210 males, 279 females, age range=19-67 years). Plasma samples were obtained from 40 to 50 rain post injection. Subjects were divided into 5 age groups. Parameters for age and sex groups were expressed as mean_+S.D. Results were compared with the values determined using Bubeck's formula. m/f

99mTc-MAG3 clea~nce(ml/min/1.73 m2) Russell's method Bubeck's method male* female male female 312±63 333±76 273±38 284±43 309±74 299±66 270±40 266±41 272±79 281±88 247±44 253±50 255±57 236±65 231±41 225±46 218±65 272±187 192±36 243±63 290±74 289±80 257±44 256±47 0.001 0.001 0.001 0.001

In both groups, 99mTc-MAG3 clearance values were negatively correlated with age ( p=0.0001 r=-0.34 and r=-0.36, respectively). The Russell's formula yields higher values for high normals, accounting for the higher mean and s.d., however both methods showed a significant correlation (p=0.0001 r=0.98). There were no gender differences in either method. This new formula is recommended as a replacement for the formula described before (JNM 1969).

• Nephrology 0Su170

0Su172

L. Kabasakal, K. Ozker, Y. Liu, R.S. Hellman, A,Z. Krasnow, A.T. lsitman, B.D. Collier, Medical College of Wisconsin, U.S.A.

C.Sawas-Dimopoulou, M+Neves, A.Vlahoyannis, Inst Radioisotopes and Radiodiagnestics N,C S R Democritos 15310 Aghia Paraskevi, Attikis,Greece and Inst. Nuclear e Tecnolegico,Estrada Nacional 10,2686 Sacavem,Portugal,

COMPARISON OF Tc-99m-BICISTATE (ECD) WITH Tc-99m ETHYLENEDICYSTEINE (EC), Tc-99m-MAG3 AND 1-131 OIH AS RENAL SCANNING AGENTS ECD, a widely used brain perfusion agent, is rapidly converted to monoacid (ECM) and diacid (EC) polar metabolites. Tc-99m-EC has previously been shown to be a useful renal scanning agent with little or no substantial hepatic uptake. We incubated ECD in rabbit plasma (ECD-P) for 10 minutes and compared ECD-P and ECD with EC, MAG3 and OIH as renal scanning agents. ECD ECD-P EC MAG3 Plasma 51+8 39±7 37±6 43±9 Clearance (ml/min) Urinary 35+5 3 2 _ + 9 34+6 39_+5 Clearance (ml/min) lh Urinary 64_+2 72:1:1 7 9 _ + 3 8 1 _ + 3 Excretion

OIH 48+7 42±7 81+1

(%)

Extrarenal Extraction

28+2

17_+1 4±6

4_+4

6±3

These results are best explained by the hepatobiliary uptake of the parent compound ECD but not the EC metabolite. Rapid de-esterification of ECD by a 10-minute in vitro incubation in plasma results in less extrarenai extraction for ECD-P than for ECD, The renogram curves and other pharmacokinetic parameters of ECD-P and ECD are similar, but less favorable than those seen using the other three agents for renal scanning. However, the quality of images obtained with ECD and ECDP are comparable to MAG3 images. We conclude that ECD and its polar metabolites are promising for renal imaging especially when a multi-dose ECD is prepared each working day for both brain and renal imaging.

THE BIOKINETICS OF 99mTc-Big AND ITS IMAGING ABILITY FOR THE KIDNEYS. 99mTc-Big is a renal agent obtained by 99mTe-labeling of a biguanide sulphate l i g a n d We studied its'in vitro stability, radiopharmakokinetics and imaging ability by radiochromatography,biodistribution studies in mice,whole-body autoradiograph¥ (WBA)and y-camera study,Protein binding and the mechanism of 99mTc-Big renal handling were investigated using biogel P6,ultrafiltration+TCA precipitation and experiments of biochemical intervention,The results show that the product is stable in vitro:4h after labelling,free 99mTcO4 is less than 5%,After injection,99mTc-Big is cleared from blood and excreted in urine, The proteinbound activity in human plasma,15min after in vitro incubation is equal to 60,5±0+7%,Dog y-camera study displays the kidneys in a few min after injection,WBA show maximum radioactivity in medulla and pelvis 1 min after injection.Activity accumulates into renal cortex versus time,99mTc-Big is to its largest extent excreted in a non-metabolised form,Probenecid and uric acid decrease the 30 min urinary excretion from 47.42±4,97% of inj, dose in control mice to respectively 27,14± 3,45% and 28,83±3,24% of injected dose, Acidosis reduces the excreted activity to 19,73±1,67% of inj, dose, Disodium Maleate decreases the excreted activity to 5,38±1,81% of injected d o s e The above results suggest that 99mTc-Big is submitted both to glomerular filtration and tubular transport, In conclusion 99mTc-Big is a labelled compound with interesting biological properties as a kidney a g e n t

0Su171

OSu 173

S.S Nielsen, E.U Poulsen, J Marqversen, L.E Nielsen, T Bacher, M Rehling. Aarhus University Hospital, Section Skejby Hospital, Dept. of Clinical Physiology and Nuclear Medicine. Aarhus, Denmark.

E. N i t z s c h e , H. Middlekauff, G. Simon, A. Otte, C. Hoh, H. Schelbert, E. Moser. Div. of Nuclear Medicine and Cardiology, U C L A and University of Freiburg, Germany

THE KINETICS OF 99m-TC-L,L-ETHYLENE-DICYSTEINE, 131I-OIH AND 125I-IOTHALAMATE IN PIGS. 99m-Tc-l,l-ethylene-dicysteine (EC) is a recently developed radiopharrnaceutical, proposed as an alternative to 131-I-OIH and 99m-Tc-MAG3 for measurement of renal function. To examine the biokinetics ofEC, 7 Halothane anaesthetized pigs were injected with 99mTc-EC (EC-acid, formulation 3, Mallinckrodt, Holland), 131-I-OIH and 125-I-iothalamate. Blood samples were taken until 240 minutes post injection from the aorta, the right renal vein and a hepatic vein. Urine and bile were collected. The following results were obtained (mean plasma clearance ±SEM).

EVIDENCE ADENOSINE

Clearance (ml/min)

99mTc-EC

131I-OIH

125I-iothalamate

Renal clearance

173 (±8)

178 (±8)

65 (+2)

Hepatic clearance

82 (±10)

0.9 (± 0.12)

1(±0.21 )

Plasma clearance

265 (±17)

185 (±9)

73 (±2)

Renal clearance of EC was equal to that of OIH and 2.7 times the renal clearance ofiothalamate (GFR) but the plasma clearance was greater than that of OIH due to a substantial hepatic clearance, Renal plasma extraction of both EC and OIH decreased significantly, EC from 085 to 0.45 and OIH from 0.93 to 0.57 2-240 rain post injection. Erythroeyte binding of EC and OIH was 5.8% and 21% respectively. The protein binding of EC and OIH was 32% and 33% respectively. We conclude that in pigs under Halothane-anaesthesia the tested formulation of 99mTc-EC is not a suitable tracer for measuring renal function by single injection plasma clearance technic. This is due to a significant hepatic clearance and a decreasing renal extraction.

FOR A N E U R O E X C I T A T O R Y IN HUMANS

ROLE

FOR

Background: Although adenosine has been considered an inhibitory neuromodulator, there is g r o w i n g evidence for a n e u r o e x c i t a t o r y effect. Adenosine is an ischemic metabolite which activates muscle metaboreceptors to cause a reflex increase in muscle sympathetic nerve activity (SNA). Since ischemic handgrip exercise causes reflex renal vasoconstriction, we hypothesized that adenosine activation of muscle m e t a b o r e c e p t o r s would also m o d u l a t e renal cortical blood flow (RCBF). M e t h o d s : Eight h e a l t h y humans (age 37±6 yrs.) were studied. RCBF was m e a s u r e d by PET, during single-blinded boluses of adenosine (2 and 4mg) and placebo, into the brachial artery. To confirm that adenosine increases muscle SNA reflexly, muscle SNA was recorded (microneurography) during an identical protocol at a separate session in the eight subjects. Results: RCBF d e c r e a s e d by 10% (p=0.02) and renal cortical vascular resistance (RCVR) increased by 20% (p=O.02) for 2 m g . For 4mg, RCBF d e c r e a s e d by 16% (p=0.O08) and RCVR increased by 30% (p=0.002~ ~. Muscle SNA increased by 30% (p=0.01) for 2mg and by 60% (p=0.004) for 4mg. C o n c l u s i o n s : Adenosine activates muscle metaboreceptors, producing decreased RCBF and increased RCVR and m u s c l e SNA. We speculate that during exercise adenosine engages the metaboreflex to redirect blood flow from areas of low demand, e.g. the kidney, to regions of high demand.

1075

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• Nephrology OSu 174 NV Budihna, M Mil~inski. University Medical Centre, Nuclear Medicine, Ljubljana, Slovenia. FREQUENCY OF REFLUX PULSES: INCREASED DIAGNOSTIC VALUE OF CYCLIC DIRECT RADIONUCLIDE CYSTOGRAPHY (c-DRC) IN CHILDREN

C-DRC is commonly accepted screening method for detection of vesicoureteric reflux (VUR). As confirmation of VUR has further diagnostic and therapeutic consequences, the method has to be reliable. Aim of our study was to evaluate diagnostic impact of frequency of reflux pulses reaching pelvis in different grades of VUR diagnosed using standard c-DRC reading criteria. Methods: c-DRC was performed in 236 consecutive children, 472 kidneys (K), of which in 173 K for follow-up in known VUR, average age 5.9 (+4.5) years. The bladder was filled twice through the urinary catheter with Tc 99m-O4, 40 MBq/500 ml of saline. The bladder and renal area were scanned for average 955 (+465) seconds (s) with gamma camera, connected to the computer, one frame/5 s. Studies were first analysed for the grade of VUR using standard evaluation. In addition, frequency of reflux pulses reaching pelvic area was observed for reevaluation and compared with resuls of the first reading. Results: First reading Number of Second reading- pulse kidneys frequency/100 frames noVUR 139 VUR 1 111 ns VUR 2 201 10 ( + 1 2 ) @ p<0.001 VUR 3 21 45 (+29) ~ p<0.001

~((:~),~.~

VUR was more frequent in the first cycle of DRC (NS). It was more often seen during the filling than during the voiding phase (p<0.005). Conclusions. The frequency of reflux pulses increases significantly with increasing grade of VUR. Clinical relevance of low frequency reflux pulses remains to be proven.

OMo175 ,l~tk~id E_ Beatovid S, Zagar [. Paunko~id N. Stelimovi6 A, ,\jdino~id FJ, [tan R.: Institute of Nuclear Medicine, Clinical Centre of Serbia, Belgrade, Yugoslavia

MULTICENTRIC STUDY OF INTEROBSERVER VARIABILITY ON 99mTc-DMSA SCINTIGRAPHY REPORTS 99mTc-DMSA renal scintigraphy is a "gold standard for detection of global and regional reduction of functional cortical mass. Data on standardisation and objectivity of the interpretations are insufficient. The aim of the study was to evaluate the interobserver variability and reproducibility of the scintigraphy reports. The study was performed in 30 DMSA scintiglaphies (60 kidneys), done in one centre, displayed on X ray films as analogue 300 KC images in 4 standard positions (posterior, anterior, right and left oblique). Six observers from 4 different centres were included in interpretation of original scans. Seven parameters of scintigraphy protocol were analysed with at least two responses: kidney size(l), uptake(2), outlines(3), scars(4), SOL(5), differential function(6) and conclusions(7). In the conclusion, 3 responses for each kidney were possible: normal, abnormal and equivocal. The type of abnormality had to be precisely Iocalised in the drawing. Among 60 kidneys, concordant results in interpretation of seven points of report, from 1 to 7, were found in 69%, 38%, 52%, 9%, 46%, 51% and 400/0, respectively. Absence of instructions given to the observers as well as lack of standardisation of criteria and terminology for reporting, seems to be responsible for high interobserver discordance, particularly in evaluation of scars, renal uptake and conclusion report.

1076

OMo176 O. Carlsen, Dept. of Clinical Physiology and Medicine, V e j l e Hospital, DK-7100 Vejle, Denmark.

A

Nuclear

EVALUATION OF THE Tc-99m DTPR DIURESIS IN THE D I A G N O S I S OF RENAL O U T F L O W OBSTRUCTION.

QUANTITATIVE

RENOGRAPHY

The r e n o g r a m s (after b a c k g r o u n d subtraction) in the d i u r e s i s r e n o g r a p h y were e x p o s e d to m o n o e x p o n e n t i a l fits d u r i n g two 5 m i n u t e s long time intervals prior to and shortly after the injection of the loop diuretic, furosemide. Let RC a and RC b denote, respectively, the rate constants of the m o n o e x p o n e n t i a l fits (min "~) after and before furosemide was administered. If the d i f f e r e n c e RCa-RC b was significantly below zero, the diuretic r e s p o n s e was taken to be positive. A negative response suggests total renal o u t f l o w obstruction. The renal p e l v i c v o l u m e PV (ml) was e s t i m a t e d using a count based ratio m e t h o d applied to the renal pelvic image before the furosemide injection (hut after correction for renal b a c k g r o u n d and renal p a r e n c h y m a l activity). The diuretic response, DR (ml/min), was c a l c u l a t e d as: DR = PV*(RCb-RCa). Let SKGFR denote the single kidney glomerular filtration rate (ml/min) e s t i m a t e d in the p r e c e d i n g renography. Based on data in the l i t e r a t u r e the mean normal diuretic response, MNoR (ml/min), was a p p r o x i m a t e d as MNDR = 0 . 2 5 * S K G F R + 0.7 with a standard error of estimate, SEEoR (ml/min), c a l c u l a t e d as SEEDR = 0.073*SKGFR. A d i u r e t i c response b e l o w the n o r m a l range suggests a p a r t i a l renal o u t f l o w obstruction. The m e t h o d p r e s e n t e d takes into account two important f a c t o r s w h i c h are often o v e r l o o k e d in the i n t e r p r e t a t i o n of d i u r e s i s renography: i) The actual size of the renal p e l v i c volume, and 2) That the expected diuretic r e s p o n s e of the k i d n e y is related to its glomerular filtration rate. This provides a more fair basis of c o m p a r i s o n of the d i u r e t i c response of a k i d n e y w i t h a d i l a t e d renal pelvis and impaired renal function than does a visual i n s p e c t i o n of the decline of the r e n o g r a m following the furosemide injection.

OMo177 PF Kao 1, KY Tzen 1, CB Shieh 2, DLYou l 1 Department of Nuclear Medicine, Chang Gung Memorial Hospital and 2 Department of Pediatric, Taipei Municipal Hospital, Taipei, Taiwan, Republic of China. DIURETIC RENOGRAM IN THE CASES OF HORSE-SHOE KIDNEY Horse-shoe kidney was supposed to interfere the passage of urine through the fusion portion of the bilateral kidneys. Twenty-one pediatric cases (9 females and 12 males) of Tc-99m DMSA proved horse-shoe kidney were studied with Tc-99m DTPA diuretic renogram to rule out the possibility of obstructive hydronephrosis. The diuretic renogram was performed with 1 mg/kg of furosemide hV. injection. No urinary bladder catheterization was done. All patients were advised to empty bladder before furosemide injection. In 21 cases, only 1 case showed obstructive hydronephrosis. Among the 20 nonobstructive cases, 7 cases showed stasis of radioactive urine in the pelvic region of the kidneys prior to furosemide injection. All of the 7 cases but one showed clearance of the radioactive urine from the renal pelvis immediately after standing up for voiding. Supine position in this study may enhance the interference of the urine passage through the fusion part of the horse-shoe kidney and cause transient stasis of urine in the renal pelvis and proximal ureter. After standing up, the interference of the urine passage relieved immediately. The only case of the obstructive hydronephrosis was a horse-shoe kidney with duplication of the left upper pole kidney. The obstruction was the upper pole of the urinary tract. In conclusion, there was not any case of obstructive hydronephrosis in our series of 20 horse-shoe kidneys. The only one case of obstructive hydronephrosis was accompanied with duplication of kidney.

• 0Mo178 F. Maranetto P. Antonacci, M. Bellb, G. Bertuccio, A. Cistaro, G. Bisi Cattedra di Medicina Nucleare - Universita di Torino (I)

Renal Scintigraphy in Prediction of Recovery Time after Kidney Transplantation An ischemic injurywith a variable degreeof acute tubular necrosis (ATN) initially occurs in cadaver renal allografls; therefore early stratification of patients to predict functional evolutionis a major issue. Dynamicrenal'scintigraphycould be a powerful tool to this purpose.We evaluatedretrospectively200 first renograms obtained with 99rnTc-MAG3in recipients within sevendays (4.0+1.3)of a cadaver renal transplant. Recovery of renal function after surgery was defined as the fall in serum creatinine below 3 mg/dl; we divided our population into three groups, according to the time of function recovery after transplantation: group A (n = 70) with recoverytime _<10 days, group B (n = 46) with recoverytime > 10 days and < 20 days, and group C (n = 84) with recoverytime > 20 days. The percent renal uptake of MAG3 occurring at 30" to 90" following administration (uptake at 90") was evaluated in group A (2.5+_0.9), group B (1.4+_0.6)and group C (1.0_+0.5);p<0,001 for all comparisons. Assuming a cut-off uptake valueof 1,5%, 116 pts had a low uptake, while 84 had a high value; amongthe 116 pts with low uptake, 105 (91%) belong to groups B or C; among the 84 pts with high uptake, 59 (70%) are included in group A; overall accuracy is 82% (164/200). A relation betweenuptakeand recoverytime was observed:out of the 105 low-uptakepts with recoverytime>10 days (groups B + C), 77 (73%) belong to group C; out of the 25 high-uptakepts with recovery time>10 days (groups B + C), only 7 (28%) are included in group C. Early detection of MAG3 uptake at 90" reflects actual renal function and thus provides important prognosticinformation aboutallograft recovery.

Nephrology

OMo180 C.Aprile, G.Villa,GMerlini,* R.Saponaro, V.Piazz.a, G Cannizzaro, P.Garini*, A S a l v a d e o Fond."S.Maugeri" and *S.Matteo Hospital- Pavia - Italy

SCINTIGRAPHIC DETECTION OF DIALYSIS RELATED AMYLOIDOSlS (DRA) WITH 99rn Tc APROTININ

t|O m

e,, ~D

The anti-serine protease inhibitor Aprotinin labelled with 99m Tc (TcA) has been recently reported to localize in amyloid deposits. The aim of this work was to assess the possibility to image D R A deposits in 25 pts on chronic hemodialysis (HD)(median HD age 87 months, range 1-288 mo.), 90 min after i.v. injection of 400 Mbq of TcA. Significant accumulation in medium and large size joints was observed in 19 pts, faint uptake in 4, while no uptake could be seen in the remaining two as well as in 9 control pts with osteoarthritic changes. A positive relationship was observed between articular uptake (number of visualized joints and scintigraphic score) and functional impairment, HD age and subjective pain score. X-ray findings were less frequent and present only in TcA positive joints. Prominent wrist uptake was observed in 13 pts and it was inversely related to median nerve sensory conduction velocity. Visceral accumulation)was observed in four pts (3 thyroid and 1 lung), while diffuse gut accumulation of the tracer was a common finding in all anephric pts. TcA binding to amyloid deposits was stable, as shown by late scan taken several hours, up to 24 after injection and after HD. Neither clearance of the tracer during dialytic treatment nor absorption onto cuprophane filters was o b s e r v e d Congo red positive amyloid fibrils were detected in synovial fluids of 3/3 positive joints as well as in 2/2 thyroid fine needle biopsies. These results indicate that the scintigraphy with 99mTcA is able to depict amyloid deposits also in DRA pts; in addition the non invasive method and the easily available low-cost tracer allow a routine use even on an outpatient basis.

OMo179

OMo181

J.E. Greenland, J.J. Hvistendahl, H. Andersen, T.M. Jcrgensen, C.E. Constantinou, G. McMurray, A.F. Brading, J. Fr~ki~r, Institute of Experimental Clinical Research, Aarhus University, Denmark, and Department of Pharmacology, Oxford University, UK.

F. Montraver~, C. Rousseau 1, J.D. Doublet2, B. Gattegno2, N. Younsi 1, J.N. Talbotl.Services de Mrdecine Nucl~aire 1 et d'Urologie2, hrpital Tenon, F75020 Paris, France

DECREASED BLOOD FLOW IN BLADDER AND KIDNEYS IN RESPONSE TO EARLY BLADDER OUTLET OBSTRUCTION IN PIGS. Bladder outlet obstruction is associated with marked changes of both bladder and kidney function. We studied the effects of mild partial outlet obstruction on regional blood flow in bladder and kidneys together with measurements of tissue oxygen tension in the detrusor muscle. Five female pigs had a partial urethral obstruction created at 8 weeks of age, and 5 were sham operated controls. At 26 weeks the animals were anaesthetised and cystometry performed. Regional vesical blood flow (VBF) and renal blood flow (RBF) were measured using radioactive labelled micropheres (141Cerium and 1°3Ruthenium) w i t h bladders empty and at cystometric capacity. Simultaneously, vesical wall oxygen tension (PbO 2) was measured w i t h an oxygen sensitive electrode, and cholinergic nerve density of the detrusor was determined histochemically. ~/BF and PbO 2 differed significantly at low and maximal capacity of the bladder in both groups w i t h marked regional differences. In addition, mean VBF and PbO 2 at 200 ml w e r e 75.8 ml/min/100g and 3.95 kPa respectively in controls and 41.6 ml/min/100g and 2.99 kPa in obstructed bladders (p<0.05, t-test).At cystometric capacity the respective values were 54.7 ml/min/100g and 3.26 kPa in controls and 26.0 ml/min/100g and 2.03 kPa in obstructed bladders (p<0.05). Similar, total RBF and regional RBF were significantly lower in obstructed animals at both low and maximal bladder capacity compared with sham operated. Finally, cholinergic counts in sham operated animals were 252 m m -2 compared w i t h 199 mm -2 in obstructed animals (p<0.05). In conclusion, VBF and PbO~ were lower and fell to a greater degree in obstructed bladders suggesting that an impaired VBF and P b Q may result in partial denervation of bladders with mild outlet obstruction. Furthermore the study indicates, that detrimental RBF reductions appear at an early stage of infravesical obstruction.

IN VIVO VISUALISATION OF SOMATOSTATIN RECEPTORS IN PRIMITIVE RENAL CELL CARCINOMA By In- 11 IPENTETREOTIDE - LACK OF ACCESSIBILITY OF THE LIGAND IN LARGE TUMORS. The presence of somatostatin receptors (SSR) on human renal cell carcinomas has been demonstrated by autoradiographic techniques on surgically removed kidneys. In-.lll-pentetreotide is a radioligand designed for in vivo imaging from octreotide, a somatostatin analog. The aim of our study was to evaluate in vivo the SSR content of primitive renal tumours and their possible metastases before surgery. TI-201 was used as a sensitive tumour seeking agent with a blood flow dependant uptake. 13 patients (10 male, 3 female, mean age 59+-13.6 years) were imaged before the surgical removal of the renal tumour using sequentially T1201 (1 MBq/kg)and In-111-pentetreotide (120 MBq injection, imaging at 4 and 24 h p. i.). At surgery, 11 tumours were large (> 4.5 cm in diameter) and 2 tumours were small measuring 1.5 and 2,5 cm. The l I large tumours did not accumulate either In-111-pentetreotide or TI-201 and appeared photopenic in comparison with the normal kidney. The 2 small tumours accumulated both markers. In a patient with a large primitive tumour appearing photopenic with the two markers, a cranial focus taking up the two markers was discovered, corresponding to a skin metastasis of renal cell carcinoma histologically proven and unknown before scintigraphy. These data seem to indicate that, in large primitive renal cell carcinomas, In-I 11-pentetreotide could be unable to reach the receptors whereas in one of these patients a metastasis of a smaller size was positive, showing the presence of SSR. This hypothesis is supported by the reduced blood supply in large tumours objectivated by their photopenic aspect on the vascular images obtained after TI injection. In one case of photopenic lesion, this hypothesis has been confirmed by positive labeling of the surgically removed tumour by in vitro autoradiographic technique with incubation of the turnout slice with i 1]In-pentetreotide.

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• Nephrology/Neurology 0Mo182 J.A.C.Prenen. Department of Nuclear Medicine, Franciscus Hospital, Roosendaal, The Netherlands. VARICOCELE SCINTIGRAPHY : A SIMPLIFIED SCREENING METHOD FOR THE DETECTION OF SPERMATIC VEIN REFLUX For the detection of spermatic vein reflux we applied Te-99m varicocele scintigraphy as a simplified routine method in 43 men who visited the infertility clinic, to exclude

underlying varicoeele as a possible cause of decreased semen quality. Total acquisition time amounted to as little as 200 seconds for each study : 100 seconds for dynamic phase imaging, followed by another 100 seconds for static phase imaging. Data analysis included calculation of the left-to-right hemiscrotum ratio and generation of time-activity curves. Three groups could be distinguished: 1. (n=3:~) normal bloodflow pattern, 2. (n=7) locally increased activity in the left hemiscrotum in the static phase only, 3. (n=4) both spermatic vein reflux in the dynamic phase and increased plexus pampiniformis activity in the static phase. The differences concerning the left-to-right hemiscrotum ratio's between these groups were significant according Dunn's all pairwise multiple comparison test (post hoc test). group no n median 20% percentile 80% percentile p vs group 1

2

1 32 1.03 0.90 1.14

7 1.22 1.18 1.41 < 0.05

p vs group 2

3 4 3.76 2.39 5.43 < 0.05

< 0.05

......................................................................................................................................

The dynamic phase appeared to be an essential part of the study for the detection of clinical significant spermatic vein reflux and subsequent proper patient selection for therapeutical treatment. Three out four (75 %) of the group 3 patients ensued pregnancy within 6 months after ligation of the left internal spermatic vein. In conclusion, this simplified scintigraphic procedure may be useful far the detection of spermatic vein reflux in patients with suspicion of varicocele and proved to be suitable as a screening method.

0Su184 E. Donnemiller~ G. Ransmayr, L Heilmann, W. Berger, W. Poewe, G. Riccabona, Depts. of Nuclear Medicine and Neurology, University of Innsbruck, Austria

DISTINCTION BETWEEN DEMENTIA OF ALZHEIMER TYPE (DAT) AND OF DIFFUSE LEWY-BODY DISEASE (DBLD) BY SPECT WITH 99~Tc-HMPAO AND 123I-fb-CIT

Besides the classical symptoms of DAT such as loss of higher cortical function and memory without focal neurological signs parkinsonlan symptoms and ,,Gegenhaiten" occur in up to 50 % of patients. The second most common cause of degenerative dementia -DLBD - shows also progressive cognitive deterioration and a Parkinson syndrome but also psychiatric symptoms and orthostatic syncope. The distinction between the 2 syndromes may therefore be difficult in some cases. We tried to provide a solution by studying cerebral perfusion with 99=TcHMPAO-SPECT and striatal dopamine transporter function with 123IB-CIT-SPECT in 6 patients with DAT and 6 patients with DLBD. SPECT-studies were performed with a single head rotating camera (Siemens OrbiterZLC 3000), data acquisition and analysis was done using methods described previously. As expected we found symmetrical temporo-parietal perfusion defects in DAT, with hypoperfusion also in frontal and occipital regions in advanced stages. The perfusion pattern in DLBD, however, showed constantly a severe hypoperfusion in the occipital association cortex producing ,,horseshoe-like" cold areas in this region, while other perfusion defects were similar to the DAT-group. In '~I-B-CIT-studies the alteration of the dopamine transporter system was more severe in DLBD (striatum/ cerebellum-count-ratio after 3 hrs 1,8 _+ 0,3, after 18 hrs. 2,1 + 0,4) than in DAT (striatum/cerebellum-count-ratio after 3 hrs. 2,6 _+ 0,8, after 18 hrs. 5,4 _+ 1,7). Overall therefore the different patterns of brain-SPECT-studies ofrCBT and dopamine-transporter-functionseem to provide a possibtity to distinguish DAT from DLBD clearly.

Neurology

OSu183 JL LAMPREAVE P DOMINGU~Z, MP MADARIAGA, C TRAMPAL, A BITTINI, JL CARRERAS, I ALMOGUERA, JM PEREZ-VAZQUEZ. Servicio de Medicina Nuclear. Hospital General U n i v e r s i E a r i o Gregorio MaraNon. U n i v e r s i d a d Complutense de Madrid. Spain. TECHNETIUM-

NON-TREATED

9 9 m - E/4PA0

TOURETTE

SPECT PATTEP/~ PATIENTS

IN

Objective: To define the cerebral b l o o d flow pattern in drug-free and neuroleptic-naive patients diagnosed with Tourette's Syndrome (TS) (DSM-IV), and to test the hypothesis of a possible frontal/basal ganglia disfunction. Method: Thirteen normal controls and 14 u n m e d i c a t e d TS patients (13 males, 1 female), right h a n d e d and b e t w e e n 6 to 16 years old were submitted to a 99"Te-HMPAO brain SPECT. Imaging was p e r f o r m e d u s i n g a r o t a t i n g gamma camera w i t h a h i g h - r e s o l u t i o n collimator. A total of 64 projections of 20 sec each were a c q u i r e d in a 64*64 m a t r i x and a 360 ° continuous circular orbit. A t t e n u a t i o n correction (0.12) was applied. S e m i q u a n t i t a t i o n was p e r f o r m e d by c i r c u m s c r i b i n g 3 ROIs on each paramedial sagital cortex (orbitofrontal, anterior and p o s t e r i o r frontal regions) and 2 on each temporal lobe (mesial and lateral cortex on coronal slices), c a l c u l a t i n g the ROI average counts-to-cerebellum ratios. Statistical a n a l y s i s was p e r f o r m e d by means of the Mann-Whitney test, and Bonferroni's correction was applied. Results: Statistical significant h y p o p e r f u s i o n in both frontal and temporal lobes was found (p<0.001) . Visual assimetries in the p e r f u s i o n subcortical p a t t e r n were also detected. Conclusions: The presence of frontal h y p o p e r f u s i e n agrees with previous r e p o r t e d data which suggest a p o s s i b l e d i s f u n c t i o n in some of the n e u r o a n a t o m i c a l circuits connecting frontal areas w i t h basal ganglia.

1078

0Su185 E. Dor~nem~ller=G. K. Worming, B. Kreczy-Kleedoffer, G. Sixt, r. Heilmanr, W. Poewe, G. Riccabona, Departments of Nuclear Medicine and Neurology, University of Innsbruck, Austria

STRIATAL DOPAMINE TRANSPORTER FUNCTION AND RECEPTOR BINDING IN ,,DE NOVO PARKINSONISM" (DNP) STUDIED BY SPECT WITH n3I-BCIT and n3I-IBZM Several reports on pts. with DNP have shown impaired presynaptic nigrostriatai transmission, while function of postsynaptic D2-receptors in the striatum remains a controversial issue in such pts.. Only few data exist regarding both pro- and postsynaptic dopaminergic function in such patients. We therefore studied 11 pts. with DNP (disease duration 1,7 +- 1,2 yrs.) with SPECT using 148 MBq 1231-13CITand 185 Mbq 123I-IBZM as tracers. Data were compared with a normal control group for 1231-13CIT/Z3I-IBZM of 4/6 persons. SPECT was perfomed with a single head Siemens orbiter ZLC 3700 camera using a standardized protocol. For evaluation of data count ratios striatum/cerebellum were calculated for n3I-IBZM 2 hrs. at%er tracer application as well as 3 hrs. and 18 hrs. after ~23I-/3CIT. The data were compared with the motor response to a Levodopa challenge. In comparison with normal subjects all pts. showed normal 123I-IBZMuptake in the striatum (2,16+_0,78) while 123I-BCIT-uptake and kinetics were depressed in 9/11 pts. (1,99+_ 0,574 after 3 hrs., 3,89_+1,352 after 18 hrs.). Asymmetrical uptake occured in 6/11 pts., usually showing lower 123I-/3CIT binding in the clinically affected side while 123I-£BZM activity was lower on the tess parkinsonian side. The DOPA-test was positive in all pts. These results confirm a significant reduction of dopamine transporter function in DNP, probably due to nigral cell loss and terminal degeneration. These findings indicate that this loss of dopamine transporter induces an up-regulation of D2-receptors which could explain the crossed asymmetrics of tracer uptake in basal ganglia. Moreover it seems likely that this type of study can help to distinguish Idiopathic Parkinson's Disease from Multiple System Atrophy.

•

OSu186 C. D~cker',W. Burehcrt#, K. Rogmanrt, H. Hundeslmgen', T. M~ndc' Dcpts. of Nudczr Mcdicinc - Mcdicat School Hannm,c~ and MarlinLuther-Univ=zi~ I-/allc-W~berg', D ~ t of N~'dogy - Medical School Hannover, Gemam~ CEREBRAL GLUCOSE METABOLIC RATES IN G'~.r.~8 DE LA TOURETTE-b'YNDROME

C-,31=sd= la T~zc'a=-Syndromc(G'rs) is a complexnc='opr~hianic disorder~ by mldliple motor and vocal ti~ =ad a s ~ bdmvioc=ldi=m-b~c=. Aim of the ln~em mm'y w'~ m evalmtioaof c=-¢bral~ =¢talmli=mb limbk-tda=d ~ o = of the cmmx, of the basal *-~,~, end cortical rcgiom invetvcd in the initiation o f movement. Thc~ sa'ucttu¢~ may play a role in the pathogenesisof GTS. 18 p a ~ m (17 men, I woman; mean:~SD ~ = 27,4±13 years)with TomCat= In/n&om¢and I0 age,- and scx-matchcd control ~t~ojcetswere examin~l by d3man~ PET..~,~s (Sicmca~ ECAT-951/31) after inmav'enom ~aie~don of 370 MBq x*F-FDG. 5 of 18 patients had a t h e r ~ with the ~ l e p l i c drug #mozide. The comtm'ison of global c.crcbral glucose un~dz~ion showed no .~6cmt d~R'~ bctwccn p~icnts m d con~Is. Dcercascd regionalglucosemetabolicra~ wea~ caleulat=din the c~_-,l-~enucleus

Ltr~0,0~; the tee (p--o,o4) and ~

Lt~0,os)lea~orm

nuclm~s;the tight infmior latmal pr=fi'ontal cortex (I~0,06);the right (p--o,02) and lctt (p---0,06) iusda and the ~ight hipp~_-~.~., us (p---0,02). In neuroleptic-treated pmi~nts compared with drug-fz=e patients we observed a hypometabolism of thc midbrain Qt~:0,01) and k:fl 1 ~ (p<0,05). The gincusc mctabelic rates of ~,~=*~ nucleus, lcntiform nucleus, thalamus, midbrain and hippocampus correlatedpo~ with the severityof complex motor tics. The data suggestthat basal ganglia eir~uim projcclingto fi'ontalmd temporal coV.cxare neuroana~mic~ involved in the pathogenesis of GTS.

OSu187 C. Dupel-Pottierl, C. Loc'h 1, P. Hantraye 1, P. Cesaro2, M. Vidailhet3,y. Samson 1, C. Halldin 4, L. Farde4, B. Mazi~re 1, P. Remyl, 2. 1- SI-IFJ, DRM/CEA, Orsay; 2- CHU Henri-Mondor, Crdteil; 3- CHU Snip&fibre, Pals; 4- Karolisnska Institute, Stockholm. A PRELIMINARY PET STUDY OF THE DOPAMINE TRANSPORTER TRACER Br-76 13-CBT-FE IN PAKKINSON'S DISEASE. The use of a tracer of the dopaminergic transporter might be more sensitive than F-18 Fluorodopa to reveal early dopnmlnergic neuronal loss in the stfiattma of Parkinsonian patients. We present the preliminary results of a PET study using Br-76 I3-CBT-FE, a cocaine analogue, in patients with Parkinsoffs disease (PD). Three severe and one de novo PD patients (56.0 ± 8,3 year-old) and one age-matched control were studied. PET studies were performed using a high-resolution tomograph (ECAT 953B/31). A~er a measured attenuation correction, a 90-rain emission scan was acquired aRer intravenous injection of 37 to 44 MBq of Br-76 13-CBT-FE. Circular regions-of-interest were placed by visual inspection on candate, putamen and occipital cortex, and striatal/occipital radioactivity concentration ratios were calculated versus time. These ratios reach a peak at 40 and 70 rain after tracer injection in the PD patients and control subject respectively. The peak caudate ratios were 8.1 in the control, 4.6 in the de n o v o patient and 2.0 ± 0.3 in the severe patients (n=3). The peak putamen ratios were 6.8, 2.9 and 1.6 ± 0.2, respectively. The candate/putamen ratios were 1.2 in the control, and 1.6, and 1.25 ± 0.03 i~ the de n o v o and severe PD patients, respectively. Br-76 13-CBT-FE seems to be a sensitive tracer to measure dopaminergic neuronal loss, and might be useful to follow-up gaited PD patients. The comparison of caudate/putamen ratios suggests a late involvement of nigro-caudate dopaminergic fibers in the pathological process of the disease.

Neurology

OSu188 C.Messa. G.Lucignani, A.Carpinelli, MA.Volocat~, F.Zito, A.d'Amico, G.Rizzo, RM. Moresco, M.Franceschi, E.Paulesu, F.Fazio. INB-CNR, H San Raffaele Institute, University of Milan, Italy. PRESYNAPTIC DOPAMINERGIC ACTIVITY IN PD AND PSP PATIENTS EVALUATED WITH [123-1]13-Cl'rAim of the study was the evaluation of the dlopaminergic reuptake tracer ([123-1]B-CIT) to differentiate patients with Parkinson's uisease [PD) and Progressive .Supr.anuclear Palsy (PSP). The distribution of [123-rJ13-CITin oesal ganglia (BG) was assessed by SPET in 6 age matelhed normal subjects (N), 16 PD and 5 PSP patients (mean duration of disease 2 yrs for PD and 3.5 yrs for PSP). M e t h o d s : Transaxiai images were obtained 24+_2 hrs p.i. A 6.5 mm thick slice including BG was cnosen ano circumr ROis (10 mm diameter) were drawn over BG (4/side) and occipital cortex. On SPECT images coregistered to MRI in 4 N subjects these ROIs corresponded to: head of caudate (HC), an area between caudate and putamen, .an.terior and posterior putamen (aP and pP). Specilic to non displaceable BG uptake ratio (V3") was calculate(] according to previous studies (van Dyck et al, JNM 95, 1175) for all regions ipsi (i) and contralaterally (c) to the clinically most affected sEde or to the dominant hand. Regional differences between N vs PD and PSP were analyzed with one-way ANOVA's. Post-hoc ar~aly.ses were carried-out with Sheff~ F-tests (P<0.05). Results: V3"+ s.d. for HC and pP were: V3"HC i V3"HC c ~ " N 6.4+1.5 6.2+1.7 4.4i~).9 4.2:!:0.9 PD 4.0L-_1.7* 3.7_+1.5* 1.6_+0.6* 1. t_--K).5* PSP 1.~+0.4"$ 2.1_+0.9" 0.8_+0.4* 0.6~-0.3" *= statistically different from N; $= statistically different from PD Conclusion: Regional quantification of [123-1]B-CIT uptake in BG areas allow to evaluate the relative caudate-putamen damage, that differentiates PD from PSP. Further studies are needed in "de novo" parkinsonian patients to evaluate the diagnostic varue of the methoo.

OSu189 J. Booij, G. Tissingh, G.J. Boer, A.G.M. Janssen, J.D. Speelman, E.Ch. Wolters, J.C. Stool E.A. van Royen, Depts. Nuclear Medicine and Neurology, Academic Medical Centre, Amsterdam; Dept. Neurology, Free University, Amsterdam; Cygne BV, Technical University, Eindhoven, The Netherlands. DIAGNOSIS OF PARKINSON'S DISEASE IN A ONE-DAY PROTOCOL EMPLOYING [I-123]FP-CIT SPECT. The main neuropathological feature in Parkinson's disease (PD) is a degeneration of dopaminergic (DAergic) neurons in the substantia nigra resulting in a loss of DAergic terminals in the striatum. Recently, FPCIT, a N-fluoropropyl analogue of {2g-carbomethoxy-3g-(4-iodophenyl)tropane}, became available as SPECT ligand with fast brain kinetics, allowing in vivo imaging of the DA transporter on these terminals in a one-day protocol. We have studied the striatal uptake of [I-123]FP-CIT (71-126 MBq intravenously) with SPECT in 18 patients with PD (mean age 60.8 y; range 40-77) and varying degrees of severity (Hoehn and Yahr), as well as 6 healthy age-matched controls (mean age 57.5 y; range 44-83). SPECT was always carried out 3 hours post-injection with a brain-dedicated tomograph (SME 810) using manufacturer's developed protocols for acquisition and data processing. Specific binding was calculated as follows: (region of interest minus occipital cortex)/occipital cortex and expressed as average (SEM). Statistical analysis (Mann-Whitney U test) demonstrated significantly lower uptake in the caudate and particularly in the putamen of PD patients than of controls (p<0.01): PD: controls:

caudate = 1.47 (0.15) caudate = 2.94 (0.41)

putamen = 0.83 (0.08) putamen = 2.56 (0.37)

Striatal uptake was correlated with clinical severity (r=-0.64, Spearman Rank correlation). A subgroup of early PD patients (Hoehn and Yahr rating < 2.0) also showed significantly lower striatal uptake. In conclusion, at 3 hours post-injection striatal binding of [I-123]FP-CIT is dramatically decreased in PD patients compared to controls,

1079

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= m

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[] Neurology OSu 190

0Su192

W. Pirker, S. Asenbaum,S. Wonder, J Kornhuber*, P. Angelberger**, L. Deceke, I. Podreka & T. Briicke Neurological University Clinic, Vienna, Austria, (*)Psychiatric Univ. Clinic Wt~rzburg, Germany, (**)Forschungszentrum Seibersdorf, Austria

R. Larischt, A. Klhnke2, VosbergHl, JartzA2, W. Gaebel2, H.-W Miiller-Giirtnert'3 UniversityClinic of Nuclear Medicine1, Universityof Diisseldorf;UniversityClinic of Psychiatry2, Universityof Diisseldoff;Institute of Medicine3, Research Center Jialich.

1123-I]-EPIDEPRIDE-SPECT: STUDIES IN PARKINSON'S DISEASE, MULTIPLE SYSTEM ATROPHY AND HUNTINGTON'S DISEASE

EVIDENCE FOR THE INVOLVEMENT OF DOPAMINE D~ RECEPTORS IN STRIATUM AND CINGULATE GYRUS IN MAJOR DEPRESSION: A STUDY USING 123I-IODOBENZAMIDE AND SPECT

Epidepride is a benzamidc with very high affinity for dopamine D2 receptors, which in its [123I]-labeled form can be used for SPECT. The aim of the present study was to evaluate the usefulness and accuracy of[123I] epidepride-SPECT for the differential diagnosis of different basal ganglia disorders Imaging with a triple headed scintillation camera (Siemens Multispeet 3) was performed in 5 patients with Parkinson's disease, 5 patients with probable multiple system atrophy, 16 patients with Huntington's disease and 12 controls 3hrs after i.v. injection of ~4mCi of [123I] epidepride. The ratio target/cerebellum minus 1, reflecting specific/nonspecific binding was used as a semiquantitative measure of D2 receptor binding. Epidepride showed highest binding in striatum, but clearly visible activity was as well evident in several extrastriatal regions (thalamus > temporal cortex > frontal cortex > occipital cortex). Kinetic studies showed peak striatal uptake about 3 hrs pi. and a slow decline thereafter. A high interindividual variation of specific striatal binding (striatum - cerebellum; cpm/mCi x kg) was found in controls and in all patient groups. The interindividual variation of striatum/cerebellum ratios was lower, but still considerable. The ratio striatum/cerebellum was significantly reduced in MSA (10.74-2.9, controls: 18.14-5.7; p<0.005), but in 2 MSA patients of OPCA-type the ratio fell within the range of controls. The use of various cortical reference regions did not improve discrimination of MSA and PD patients, who showed values within the range of controls (PD: 15.74-4.2; n.s.) The ratio striatum/cerebellum was significantly reduced in HD (HD: 8.84-3.3; p<0.001). In one HD patient calculation of the striaturrdcerebellum ratio was impossible due to extremely low nonspecific binding. Epidepride appears to be a useful ligand for studying striatal and extrastriatal dopamine receptors in basal ganglia disorders. However, the markedly higher striatum/cercbellum ratio in comparison to IBZM did not result in a better discrimination between different extrapyramidal disorders. Calculation of plasma input curves and volumes of distribution might improve the accuracy of [ 123I] epidepride-SPECT.

Purpose of the study The cerebral dopaminergic pathway is a candidate neurotransmitter system thought to be involved in depression. The aim of this study was to evaluate the potential effect of selective serotonin re-uptake inhibition (SSRI), effective in alleviating depressive symptoms, onto striatal dopamine-D2receptors. Methods Striatum and neocortex of eIeven patients (eight females, three males) fulfilling DSM-IV criteria for major depression were prospectively investigated with the specific dopamine-D2-receptor antagonist iodobenzamide (IBZIvl),using single photon emission computed tomography before and under treatment with SSRI. Results Under SSRI treatment, the Hamilton Depression Scale total score (HAMD) decreased from 27.6 4- 4.9 to 13.5 4- 9.1 (mean 4- SD; p < 0.00t). The dopamine-D2-reeeptor binding of IBZM averaged across subjects remained tmchanged in striatum as well as in other regions of the frontal, temporal and parietal lobe Improvement of HAMD and increases of IBZM dopamine-D~-receptor binding were positively correlated in striatum (r = 0.63, p = 0.04) and anterior cingulate gyms (r = 082, p = 0.02). Conclusion tn conclusion, the results prove an interaction between the serotanergic and dapaminergic system in striatum and anterior cingulate gyms in major depression. The results further strengthen the hypothesis that the dopaminergic system is involved in disturbances of emotions. In addition, data confirm the role of striatum in major depression. Finally, data lend further support to the concept that the anterior cingulate gyms is involved in mood regulation, a central role of which might be attributable to cingalate dopamine-D2-receptors.

0Su191

0Su193

K. Tatsch, P.D. Mozley, J. Schwarz, R. Linke, O. Pogarell, R.S. Fieber, ~ . F . Kung. Depts. of Nuclear Medicine and Neurology, Univ. of Munich, Germany, andDept, of Radiology, Univ. of Permsy[vania, Philadelphia0 USA

F.Lauriero, F.Federico, G.Rubini, D.Rubini, V . I n e h i n g o l o , V.Lucivero, IL.Simone, A . D ' A d d a b b o Dept. of N u c l e a r M e d i c i n e and Dept. of M e n t a l a n d N e u r o l o g i c a l Diseases, Bari U n i v e r s i t y

R E L A T I O N S H I P BETWEEN CLINICAL FEATURES OF PARK[NSON'S DISEASE AND PRESYNAPTIC DOPAMINE TRANSPORTER FUNCTION ASSESSED WITH [I-123] IPT AND SPECT

ALZHEIMER'S DISEASE: SPET and IH-MRS D A T A

IPT (N-(3-iodo-propen-2-yl)-21Lcarbomethoxy-3g-(4-chlorophenyl) tropane) is a new coeain analogue which allows to image the presynapttc dopamme transporter with SPECT as early as 1 to 2 hrs p.i. In the present study IPT-SPECT was performed in pts with Parkinson's disease (PD) to analyze the relationship between specific dopamine transporter binding and several clinical features like duration and clinical stage of disease. SPECT scans of the brain were performed in 25 PD-pts (Hoehn & Yahr stage I-V[ age range 40-79 yrs) and 8 age matched controls. Imaging was done 90-i'20 rain following i.v. injection of 160-185 MBq 1-123-IPT using a triple head camera (Picker PRISM 3000) equipped with HR-fan beam colhmators. Transverse slices corrected for attenuation (Chang) were used for semiquantitative evaluation of specific IPT binding calculating ratios between caudate (C), putamen (P) and a reference region (R). Specific uptake of IPT was significantly reduced in PD-pts compared to controls. Most pts had a marked asymmetry with more pronounced decrease of IPT binding on the side contralateral to the predominant clinical findings. The putamen was more affected than the caudate. IPT binding showed a significant exponential relationship with disease duration (r=0.83, p<0.001) but not with the age of PD-pts. Striatal IPT-binding ratios (C/R, P/R, and P/C) decreased markedly from H&Y stage I to IV. N C/R contra C/Ripsi P/R eontra P/Ripsi P/C Controls 8 8.4+ 1.3 8.4+ 1.3 6.4_+ 1.3 6.4_+ 1.3 0.75 PD-pts 25 5.8_+3.2 6.9_+2.9 1.9_+2.3 2.8+2.5 0.34 H&Y I 5 8.6+4.3 9.3_+3.7 3.9_+4.8 5.0_+4.7 0.42 H&Y II 1 l 6.3-+2.4 7.l-+2.2 2.0_+0.5 2.9_+1.0 0.39 H&Y III 4 5.4+1.8 7.5+_1.9 1.0+_0.3 1.7+_0.8 0.22 H&YIV 5 2.5_+l.0 3.7_+1.1 0.6_+0.6 1.0_+0.4 0.25 Our findings indicate that IPT SPECT may be a useful technique to estimate the extent of nigrostriatal degeneration in PD-pts. Close relations between IPT SPECT findings and several clinical features suggest that this method can be used to objectively follow the course and progression of PD. Reduced putamen/candate ratios observed even in pts with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis already in the early course of PD.

1080

COMPARISON

OF

99mTc-HMPAO

The r e d u c t i o n of rCBF in t e m p o r o - p a r i e t a l cortex is the t y p i c a l p a t t e r n in A l z h e i m e r ' s disease (AD). C o r r e l a t i o n s w e r e sought b e t w e e n t e m p o r o parietal cortex hypo perfusion, evaluated by 99mTc-HMPAO SPET, and neuron metabolite (NAA a s p a r t a t e : NAA, c r e a t i n e : Cr+PCr, c h o l i n e : Che, lactate: LAC) c o n c e n t r a t i o n s , e v a l u a t e d by p r o t o n magnetic resonance spectroscopy (1H-MRS), in 18 men a n d i0 w o m e n a g e d 60-79 w i t h AD. r C B F was evaluated semiquantitatively by r e l a t i n g ROI in the temporo-parietal area with major blood d e f i c i e n c i e s w i t h those in e q u a l - s i z e ROI in the primary visual cortex. Metabolite values were d e t e r m i n e d s e m i q u a n t i t a v e l y by r e l a t i n g the a r e a of t h e i r p e a k s on the I H - M R S s p e c t r u m o b t a i n e d f r o m 8 cm3 VOI l o c a t e d on the s a m e t e m p o r o parietal and visual cortex areas. LAC was d e t e r m i n e d q u a l i t a t i v e l y (presence or a b s e n c e ) . A p o s i t i v e l i n e a r c o r r e l a t i o n was f o u n d b e t w e e n reduced rCBF and the reduced NAA (marker of n e u r o n a l viability) a n d C r + P C r (marker of e n e r g y reserve) levels in the p o s t e r i o r t e m p o r o - p a r i e t a l areas a t t r i b u t a b l e to local n e u r o n d e g e n e r a t i o n . Lac, m a r k e r of a n a e r o b i c m e t a b o l i s m , a p p e a r e d in same areas. The hypoxia could be caused by reduced permeability to n e u r o t r o p h i c factors, s u c h as o x y g e n , following the extra cellular a c c u m u l a t i o n of b e t a a m y l o i d or p r i m a r y r e d u c t i o n of n e u r o n a l a e r o b i c metabolism.

• Neurology t~

OSu 194

0Su196

A.Soricelli, A.Postfglione*, A.Varrone, P.P.Mainenti, A.Discepolo, M.R. Grivet Fojaja, M.Salvatore, N.A.Lassen**. Nuclear Medicine CNR, *Int. Med., Univ. of Naples Federico II, Italy, **Nuclear Medicine/Clinical Physiology, Bispebjerg Hosp., Copenhagen, Denmark

S. Bettin, C. Dannenberg, D. Zedlick, J. Dietrich, K. Jobst, W.H. Knapp. Departments of Nuclear Medicine, Psychiatry and Radiology, University of Leipzig, Germany, and OPTIMA, University of Oxford, United Kingdom.

COMPARISON BETWEEN 99mTcHM AO AND 123I-IOMAZENIL (123IMZ) SPECT SCANS IN ALZHEIMER'S DISEASE (AD).

COMPARISON OF CEREBRAL PER.FUSION SPET AND LINEAR PARAMETERS OF AXIAL CT 1N PATIENTS WITH PROBABLE DEMENTIA OF ALZHEIMER TYPE (DAT)

The clinical role of 99mTc HMPAO SPECT scans in AD is well established although atypical and non diagnostic patterns can be found, specially in the early stages of the disease. 1231MZ is a specific ligand for GABA receptors, that are present virtually on all cortical neurones. The reduced distribution of 1231MZ can be considered an index of the neuronal loss • typical of neurodegenerative diseases as AD. In 5 patients (4 m, mean age 63.2 + 8 yr) with a clinical diagnosis of probable AD both 99mTc HMPAO and 1231MZ were performed within an interval of three weeks, using a dedicated high resolution system (Ceraspect, DSI) SPECT scans were performed 20 min from the i.v. injection of 740 MBq of 99mTc HMPAO, while two studies were acquired 20 and 180 min after the injection of 250 MBq of 1231MZ. In all studies the tracer injection was performed in the same environmental conditions. Scans were reconstructed using the filtered back projection method and corrected for attenuation. SPECT repositioning errors were corrected by moving the scan matrix, using a semiatomatic algorithm. Multiple regions of interest were positioned over all the cortical areas, and ratios were obtained using as reference the occipital area, well preserved in AD. The regions of reduced uptake with 123IMZ were better defined compared to 99mTc HMPAO and a significant reduction of the receptor uptake was observed in the upper parietal (p<0.03) and temporoparietal areas (p<0.01) bilaterally. Moreover with 1231MZ, using a blood sample and the table look up method (Onishi JNM 95), absolute values as ml of receptors/ml of tissue can be obtained. In conclusion despite different physiopathological information 1231MZ can be successfully used in AD. The neuronal loss assessed by 1231MZ can probably be evident in the early stages of the disease and differentiate AD from other neuropsychiatric disorders.

Cortical atrophy and temporo-parietal perfusion deficits are common findings in patients with DAT. It has been suggested that the degree of perfusion deficits exceeds that of atrophy. This study deals with the questions whether there are morphologic parameters that correlate with the degree of perfusion deficits and which parameters separate best DAT patients and control subjeets. Patients: n = 72, 40 10t. with probable DAT (NINCDS-ADRDA, 23 m, 17 f, age: 72 _+8.5 a), control group: n = 32 (15 m, 17 f). CT: Scan orientation parallel to the orbitomeatal line, slice thickness: 5 mm, 12 linear parameters. SPET: dual-head camera, 500 MBq Tc-99m-HMPAO, visual scoring by 3 observers (7 scores, 0 = normal, 3 = severe perfusion defect). Comparison of the scores of the SPET studies between the group with probable DAT and the control group resulted in significance levels with p < 0.0001 for frontal and temporo-parietal areas. Out of 12 linear parameters only minimal thickness of left medial temporal lobe (MTL) equaled the SPET parameters regarding group separation. ROC analysis substantiated the differential information content of the parameters investigated. 3 CT parameters (Huckman number (HN), frontal-horn-index (FHI), posterior-hornindex (PHI)) showed a significant positive or inverse correlation, respectively, with the scores of SPET studies (HN r = 0.44, PHI r = -0.42, FHI = 0.42 (all parameters p < 0.001 )). Conclusion: Cortical perfusion deficits are significantly correlated with the degree of cortical atrophy. Perfusion imaging discriminates DAT and controls more effectively than morphologic parameters except MTL This substantiates the assumption of additional mechanisms responsible for diminished perfusion of cortical regions in DAT.

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0Su197

C. Dannenberg, B. Marschall, D. Zedlick, S. Bettin, A. Seese, W.H. Knapp. Departments of Nuclear Medicine and Psychiatry, University of Leipzig, Germany.

JA Arias 1, E Gomez-Tortosa 2, C Pardo 1, A Del Barrio z, and JA Sanehez-Martin I. Departments of Nuclear Medicine~ and Neurology 2, Fundaci6n Jim~nez Diaz, Madrid, SPAIN.

COGNITIVE ACTIVATION AND VASOACTIVATION IN PATIENTS WITH PROBABLE DEMENTIA OF ALZHEIMER TYPE (DAT) OR MILD COGNITIVE DYSFUNCTION USING Te-99m-HMPAO-SPET

RATE OF DETERIORATION IN ALZHEIMER'S DISEASE: A L O N G I T U D I N A L SPECT STUDY

Characteristic perfusion deficits are only found in a limited percentage of patients with DAT. Therefore, attempts have been made to increase local contrasts in cerebral blood flow (CBF). This study deals with responses of local CBF patterns on vfisodilation or cognitive activation in patients with subjective or objective cognitive dysfunction. Patients: n = 80, 30 with probable DAT according to NINCDS-ADRDA, 50 with mild cognitive dysfunction (MMS 24-28 or memory complainers, respectively), CT without focal lesions, Hachinski score < 4. SPECT: dualhead camera, 500 MBq Tc-99m-HMPAO under baseline conditions and after vasoactivation (0.5 g aeetazolamide) or during cognitive activation (labyrinth task). 24 ROIs for activity quantitation, reference area: cerebellum (c/c ratios). In addition tomograms were visually classified by 3 experts (scores from 0 to 3, 0 = normal, 3 = severe defect). Vasoactivation: significant bilateral increase in temporal c/c ratios (82.5 + 3.5 to 87.7 +_3.8%, p < 0.01 ) and unilateral increase in frontal and prefrontal ROIs. Cognitive activation: significant bilateral decrease in temporal c/c ratios (83.8 _+3.8 to 79.0 + 3.6, p < 0.01) and unilateral decrease in parietal, frontal and prefrontal ROls. Visual scoring: decrease in temporal and parietal scores from 1.5 + 0.8 to 0.8 _+ 0.7 by vasoactivation and increase from 13 -+ 0.9 to 1.8 _+0.9 by cognitive activation in probable DAT. The respective values for mild cognitive dysfunction changed from 0.9 _+0.8 to 0.7 -+0.6, and from 1.0 -+ 0.8 to 1.5 +_0.8. Conclusion: ]CBF deficits in patients with cognitive dysfunction may be elicited or enhanced by cognitive activation but may be masked by vasomotor activation.

PURPOSE: Reliable and objective pathophysiological markers to trace functional progression in Alzheimer's disease (AD) are needed. Clinical and neuropsychological examinations are only of limited value in this context. The purpose of the present work was to examine the sensitivity of SPECT for monitoring the longitudinal progression of AD. METHODS: We studied 21 patients (mean age: 69.4 -+ 7.9 years) meeting criteria for probable AD. Regional cerebral blood flow (rCBF) was measured longitudinally (mean interval 11.2 months, ranging from 6 to 24 months) with 99mTeHMPAO-SPECT. RESULTS: When all patients were considered, rCBF decreased significantly (paired t test) in the left temporal (p<0.01), right temporal ( p < 0 . 0 5 ) and left parietal (p<0.05) regions of interest (ROt), and in the brain as a whole (p<0.05). There were no significant correlations between cognitive and rCBF progression indices, rCBF in the left temporal ROI showed a mean decrease of 0.58 % per month. If a linear decline is assumed, differences in mean perfusion indices in that area could have reached significancy, at 7 months. However, 5 patients showed no change or even a mild increase in left temporal rCBF. CONCLUSIONS: Our findings support a moderate usefulness of longitudinal rCBF measurements to assess individual decline profiles along a short interval of time ( = 1 year). However, they strongly suggest a potential role in the design of clinical trials; i.e., the rate of rCBF decline could be used to evaluate the efficacy of therapeuthic agents.

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• Neurology OSu198

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P. Bartenstein [, A. Kurz2, C. Hirsch l, K. Buch 2, F. Willoch t, S. Minoshima3, M. Schwaiger 1 Dept. of Nuclear Medicine 1 and Psychiatry 2, Tech. Univ. M~inchen, Dept. of Nuclear Medicine 3, Univ. of Michigan, Ann Arbor

C. Vanhove, G. Demonceau. J. De Vuyst, G. De Rick, V. Lieko, H. Colaert, C. Monte. St Elisabeth Hospital, Zottegem, Belgium.

A N T A G O N I S T I C E F F E C T S OF E D U C A T I O N AND R C B F ON C O G N I T I V E P E R F O R M A N C E IN A L Z H E I M E R ' S DISEASE

VARIATIONS WITH AGING OF THE NORMAL CEREBRAL PERFUSION DISTRIBUTION, DEMONSTRATED BY DATABASE COMPARISON. A normal cerebral database including 120 patients was previously achieved with Tc-HM-PAO. We now compare the normal perfusion distribution of its subgroups, classifying the patients according to age in 5 categories: between 3 and 10 years (group A), between 10 and 30 years (B), between 30 and 50 years (C), between 50 and 70 years (D) and more than 70 years (E). The creation of database included activity normalisation based on the healthy cortex, warping and elastic transformation to correct for the different cerebral sizes and shapes and transfert into an anatomical atlas. The comparison within the different subgroups was based, slice by slice, on the ratio of the voxels and its level of significancy was based on the intensity as well as the area of the variation, Finally, we take into account, in the final interpretation, the physiological perfusion decrease with aging of the global CBF. Visualisable as soon as in the comparison between A and B, there is a bilateral decrease of the middle frontal gyms, no longer observed in the further comparisons. From the comparison between B and C and the following ones, there is a progressive slow and diffuse dilatation of the lateral ventricles as well as the sulci, specially the central ones. Finally, the comparison between C and D shows a significant decrease of the activity of the medial aspect of the frontal lobe, bilaterally. At all times, there is also a relative increase & t h e activity of the cerebellum, the occipital lobe and the basal nuclei, maybe related to the known decrease of the cortical blood flow with aging. At all times also, the left temporal activity is higher than the right one. The presence of these significant variations & t h e cerebral perfusion distribution with aging seems to reinforce the need of comparison with normal database in the interpretation of brain imaging.

Aim: Epidemiological and clinical studies have suggested that high educational and occupational attainment may increase brain reserve and thus counterbalance neuronal and synaptic Ioss in dementing disorders. Aim of the study was to investigate the protective effect of education in patients with probable Alzheimer's disease (AD) using rCBF-SPECT as a marker of progression of disease and an observer independent analytical approach. Methods: The study refers to 81 patients (mean age 69.9y, f=52, m=29) with probable AD (NINCDS-ADRDA criteria) and a mean Mini Mental Status Examination score of 20 + 4.6. Cognitive performance was measured using the appropriate section (CAMCOG) of the Cambrigde mental disorders of the elderly examination. The SPECT studies were performed on a three headed system with Tc-99m ECD under standard resting conditions. FoIlowing realignment of the SPECT dataset to the intercommissural line, stereotactic normalization was performed. ECD uptake was normalized to thalamic activity and compared to the reference values of 10 controls of comparable age. Regional rCBF deviations were expressed as Z-scores. Results: Multiple linear regression analysis revealed a significant negative correlation of temporoparietal rCBF and a significant positive correlation of vocational training on cognitive performance. In addition the total reduction of cortical rCBF was correlated to the cognitive performance. Region specific associations were found between speech and left temporal reduction of rCBF and between visuo-spatial skills and right temporal reduction (p < 0.01 for all correlations). C o n c l u s i o n : The antagonistic effects of brain perfusion and vocational training lend support to the hypothesis that early and enduring mental stimulation can partly compensate brain pathology in AD.

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H. Barthel, M. Wiener, S. Bettin, C. Dannenberg, W.H. Knapp Departments of Nuclear Medicine and Pediatrics, University of Leipzig, Germany

RJ Meiier, D Hasan, J van Peski, R Valkema, PJ Koudstaal, EP Krenning Dept. of Neurology and Dept. of Nuclear Medicine University Hospital Rotterdam Dijkz_igt, The Netherlands

AGE-DEPENDENCE OF CEREBRAL PERFUSION INVESTIGATIONS OF 4 TO 15 YEARS OLD CHILDREN AND ADULTS WITH Tc-99m-ECD Previous studies demonstrated that the local cerebral blood flow (ICBF) pattems in infants differed from those of adults. No data, however, are available regarding the normal pattern of 1CBF in the age from 4 years until adolescence. This present study deals with the question whether normal distribution of 1CBF-agents in adults can be transferred to the above age group. Patients: 22 children (13 f, 9 m), age: 4-15 years (mean 10 ± 4 y) underwent SPET (Ceraspect, ADAC Lab.) for exclusion of epileptic episodes after injection of 150-600 MBq Tc-99m-ECD. Follow-up and CT/MRI did not confirm neurological disease. Control group: 10 adults (7 f, 3 m), age: 27-56 years (mean 45 ± 10 y). Quantitation: 69 ROIs in 4 transversal and 2 coronal slices, ROI counts related to those of cerebellar ROIs (= 100%). Results: In children, frontal, temporal and parietal activity exceeded that of adults, whereas no differences were found in the visual cortex. Relative count density (% cerebellum) in children and adults: frontal 96.9 ± 8.1 and 79.4 + 8.9% (p < 0.001), temporal 99.6 ± 8.9 and 84.9 ± 10.1% (p = 0.001), parietal 110.2 ± 9.4 and 84.1 ± 12.4% (p < 0.001), basal ganglia 110.6 ± 8.2 and 99.8 ± 10.9% (p < 0.01). Cerebral activity uptake/injected dose 13.3 ± 5.3 and 9.2 ± 1.7 kcts/MBq (p < 0.05). Correlation of relative local count density with age: r = -0.67 to -0.82 in 13 parietal ROI, r = -0.56 to -0.82 in 14 frontal ROI, r = -0.43 to -0.82 in 16 temporal ROI and r = -0.66 in cingular cortex (p < O.OOl). In 5 conical regions there was a significant difference in relative counts when subgroups of children aged 4-10 and 11-15 y were analysed. Conclusion: There are systematic differences between 4 to 15 years old children and adults regarding the normal distribution of ICBF. Diagnostic use of perfusion agents has to consider the respective normal flow maps for age groups of 4-1O and 11-15 years.

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CEREBRAL UPTAKE OF 18FDG AND 9SmTc HMPAO BY SPECT IN ISCHEMIC STROKE Background: Both thrombolitic treatment and low molecular weight heparin given in the acute phase of ischemic stroke has recently been shown to improve clinical outcome. However, reperfusion of infarcted brain tissue still harbors the risk of cerebral edema and hemorrhage. It is therefore of interest to identify patients with viable brain tissue in the ischemic area by detecting the presence of increased glucose exlraction in that region. Until recently, this was possible only with positron emission tomography. Special collimators are now available for single photon emission computed tomography (SPECT) to detect 511 keV photon emitting radionuclides, such as 18F-fluoro-2-deoxyglucose (18 FDG), a compound for the assessment of glucose metabolism. We investigated the uptake of ISFDG in cerebral ischemia in relation to 99mTc HMPAO uptake (cerebral perfusion, rCBF) by SPECT. Methods and Results: Seven patients with an acute ischemic stroke were entered in this study. The resolution of the laFDG images allowed detection of more than 2 cm FWHM, which was present in four of seven patients. To prevent scatter from 18F photons in the low energy channel, 99mTc HMPAO uptake was scanned shortly before 18FDG administration. The cerebral uptake of both tracers was detected by a three headed SPECT camera (Picker, Cleveland, Ohio). Images of each patient obtained from the ~8FDG and 99mTc HMPAO studies were matched (registered), voxel by voxet, using reorientation software (Nuclear Diagnostics, Stockholm, Sweden). Tracer uptake was normalized to the highest uptake in the cerebellum. Decreased uptake of 18FDG was compared to the uptake of 99mTc HMPAO in corresponding regions. In four patients, a regional decreased uptake of "~8FDG and of 99mTc HMPAO was seen. One patient had a lower normalized regional uptake of 18FDG when compared to 99mTc HMPAO (0.52 vs.0.62), and did not improve within 3 months. In the three remaining patients, the normalized regional uptake of ~SFDG was higher than that of 99mTc HMPAO (0.38 vs. 0.29, 0.59 vs. 0.57, and 0.51 vs. 0.39, respectively). They improved after 11 days, 1 month, and 2 months respectively. Conclusion: This study shows that a relative increased cerebral ~8FDG uptake can be detected with SPECT in regions of decreased perfusion following an ischemic stroke. This method may therefore be of value in the detection of viable brain tissue.

• Neurology OSu202 H. Herzog, L.Tellmann, R.J. Seitz*, H.W. M011er-G~rtner. Institute of Medicine, Reseamh Centre J~lich and Department of Neurology*, Heinrich-Heine University Hospital D~sseldorf, Germany A COMPARISON OF NORMALIZED AND QUANTITATIVE RCBF IMAGES USING O15-BUTANOL AND O15-WATER The purpose of this study was to compare rCBF images which have been obtained by normalization and quantitation using the rCBF-tracers O15-water and O15-butanol in activation studies ,~erformed in individual patients. ix patients with cerebral infarction or glioma were investigated with both tracers each at rest and during different motor stimulation tasks of either limb. PET and arterial blood data was acquired in listmode over 3 rain after intravenous bolus injection. From this data normalized activity images as well as quantitative rCBF images were derived. The maxima in the activated motor cortex were examined with respect to the standard deviation in rest images. This measure was regarded as noise against which the activation has to be detected. Furthermore, an individual analysis approach was applied to subtraction images comprising the motor cortex. The percentage data given below are averaged over the six patients and the examined planes. The level of significance of the paired t-tests was Bonferroni corrected. Normalized rest images of both tracers showed practically the same mean values of the image maxima, whereas the standard deviation within the whole brain region was 17% lower (p
OSu204 J.-P. PAPAZYAN 1, A. NAIMI 1, M. ALLAOUA 1, J. DELAVELLE2, F. V I N G E R H O E T S 3, A. REVERDIN 4, G.P. PIZZOLATO 5, D.O. SLOSMAN t . Division of Nuclear Medicine s, Department of Radiology2, Clinics of Neurology 3 and Neurosurgery 4, Neuro-pathology Unit 5, Geneva University Hospital, 1211 Geneva 14, SWITZERLAND. BRAIN SPECT I M A G I N G : D I S C R E P A N C I E S BETWEEN 99mTc-HMPAO AND 99mTc-ECD. Aim : Among several brain radiopharmaceuticals for SPECT imaging, 99mTc complexes of HMPAO and ECD are the most widely used. They are considered equivalent for mapping cerebral blood flow. Discrepancies between HMPAO and ECD brain uptake have been recorded in stroke patients, namely when luxury perfusion occurs. In this work, we report our experience of such discrepancies in patients with suspected brain tumours or presumed cerebral metabolic abnormalities. Material & Methods: Among all patients who were investigated with brain SPECT, 22 presented either a focal hyperactivity with 99mTc-HMPAO or a presumed cerebral metabolic disease. In these cases, a brain SPECT with 99mTc-ECD was then performed. All these examinations were acquired using a 3-head GCA-9300 Toshiba gamma-camera with fan beam collimation, 30 minutes after intravenous injection of 925 MBq (25 mCi) of 99mTc-HMPAO and 740 MBq (20 mCi) of 99mTc-ECD. Results: 14 of 22 patients (63.6%) showed discrepancies between HMPAO and ECD, namely an intense focal hyperactivity with HMPAO, while only minimal or no change was detected on ECD-SPECT. 8 of these 14 patients went to surgery. The histopathological diagnoses were: 6 high grade gliomas, 1 low grade glioma, 1 cerebral lymphoma. Based on clinical and radiological evolution, the other diagnoses were: 2 suspected dysembryoplasic tumours, 1 non specific inflammatory lesion, 1 presumed cerebral abcess, 1 recurrent fibrillary astrocytoma and 1 postisehemic luxury perfusion. Conclusions: On the basis of these clinical observations and the recent in vitro findings regarding cellular mechanisms of HMPAO and ECD, we suggest that increased HMPAO retention in brain tumours could be related not only to regional perfusion abnormalities but also to focal metabolic disorders, namely focal increase of oxygen free radicals and alteration of tissular redox equilibrium.

OSu203 D.O. SLOSMAN A. NAIMI, J-P. PAPAZYAN, L. BIDAUT ÷, F. BUCHEGGER, M. AUFFRET*, C. MOREL, A. DONATH. Division of Nuclear Medicine, +CIH, Department of Radiology, Geneva University Hospital, CH-1211 Geneva 14; *Focus Medical, F-38240 Meylan.

0Su205 W. Burchert, T. Koch, *B. Haubitz, **H. Riickoldt, J. van den Hoff, G.-J. Meyer, H. Hundeshagen. Abt. f. Nuklearmedizin u. spez. Biophysik, *Abt. Neuroradiologie, **Abt. An~isthesiologie I I Medizinische Hochschule Hannover, Germany

THE USE OF PET / SPECT / CT / MRI BRAIN IMAGING

ASSESSMENT OF CEREBRAL BLOOD FLOW: A COMPARISON BETWEEN STABLE XE-CT AND 15-O-WATER PET

FUSION IN CLINICAL SETTING. The purpose of this study is to report our experience in the clinical use of multimodality imaging in neuroscintigraphy. MuItimodality imaging describes the processes of realignement and volumetric imaging fusion of SPECT, PET, CT or MRI. Its goal is either to improve structure recognition of functional abnormalities, either to perform parametric analysis (among them activation task or stress test). A commercial software that does not require external markers (ImageMatch, Focus Medical) was used and we retrospectively evaluated the clinical impact of its use in 12 patients with a presurgical imaging program of partial epilepsy (interietal and ictal ECD-SPECT / 3 heads Toshiba GCA 9300HG, interictal FDG-PET / Siemens ECAT ART and gradient echo 3D MRI / Picker PQ-2000 1.5 Tesla), 6 patients with brain tumors (T1-20I SPECT, HMPAO SPECT and FDG PET) and 2 patients with acetazolamide challenge (ECD SPECT). SPECT or PET and MRI realignements and image fusions were succefull in all patients with partial epilepsy or tumors. In 2 out of 12 patients with partial epilepsy, image fusion enable to correct the precise localization of focal hyperperfusion (insuIa). In case of tumor imaging, multimodality process enables to evaluate precisely the structural limits and heterogeneity of the tumor. In case of parametric analysis (pixel differences display of interictal / ictal SPECT, n=4, base-line / acetazolamide challenge SPECT, n=2), the correct alignement requires pixel-normalization by cerebellar activity prior processing. Multimodality greatly improves the evaluation of the regional differences between the 2 states (base-line, activation). Our clinical experience suggests that multimodality imaging analysis improves the qualitative analysis of brain SPECT/PET in identyfiing more precisely anatomical location of focal abnormalities and in interpreting activation or functional SPECT.

Regional cerebral blood flow can be assessed quantitatively either by x-ray computed tomography after inhalation of stable xenon (XeCT) or by 15-O-water PET. The aim of the study was a comparison of both procedures with respect to clinical application. Methods; 18 patients with cerebrovascular disease (CVD) (5f, 13m; 58+_13 years) at rest and after Diamox®, and 17 patients after head injury (HI) (3f, 14m; 40_+20 years) were investigated by XeCT and by 15-O-water PET. Parametric flow images of both imaging modalities were generated. After coregistration ROIs were placed covering the vascular territories of the anterior, the middle, and the posterior cerebral artery as well as the hemispheres. Results: Absolute flow values did not differ significantly in CVD patients at rest, after Diamox®, and in HI patients. The correlation of hemispheric flow data between PET and XeCT was high (y=0,97x; r=0,95). The analysis of normalized blood flow values showed significant differences in CVD patients in the posterior cerebral artery ROI at rest, after Diamox@, and in the right middle cerebral artery ROI after Diamox®. The analysis of s y m m e t r y showed a larger scattering of values in XeCT. In PET measurements the functional correlation between the ROIs are higher than in XeCT. In CVD patients the dependence between angiographic grade of stenosis and blood flow values measured by PET were higher than measured by XeCT. C o n c l u s i o n : Although mean flow values do not differ significantly between PET and XeCT, individual cerebral blood flow seems to be assessed more accurately by PET.

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• Neurology 0Su206

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SP Mfiller 1, M Krams 2, M Rijntjes 2, L Geworski 1, C Kappeler z, D Bier 1, HH Coenen 1, C Weiller 2, J Sciuk 1. Nuclear Medicine I and Neurology~, University Essen, FR Germany.

B. De~irmenci, H. Durak, E. Hazan, M. Y,Imaz, O. Karabay, E. (3zbilek,E. Derebek, S. Do,an, C). Oto.Depts of Nuclear Medicine and Cardiovasculer Surgery,Dokuz Eyl(Jl University, Izmir, Turkey

TIlE F U N C T I O N A L O R G A N I Z A T I O N OF T H E L A N G U A G E PROCESSING CENTERS IN THE BRAIN OF LEFT-HANDED SUBJECTS. The recovery from aphasia after persistent destruction of Wernicke's area in the dominant hemisphere is associated with a recruitment of homotopic areas in the non-dominant hemisphere. These findings indicate that the recovery involves a functional reorganization of a preexisting bilateral network of language processing centers. We extended our studies to investigate the localization of language function in 6 lefthanded subjects during a primarily phonological pseudoword repetition task and a primarily semantic verb generation task. An integral [O-15]CO2 inhalation technique was used to assess changes in rCBF due to neuronal activation in 6 left-handed subjects. The activation tasks were the silent generation of verbs matching presented substantives and the silent repetition of pseudowords. We performed 6 scans (rest, verb generation, pseudowords, pseudowords, verb generation, rest). After coregistration and transformation of the brain into the coordinates of the atlas of Talairach & Tournoux, the images were normalized for global flow differences by analysis of covariance, and areas of significant rCBF changes (p<0.05) were displayed as statistical paramelric maps. During both tasks, the left-handed subjects activated Wernicke's and Broca's area, however, as in the right-handed subjects, the left lateral prefrontal cortex (LPFC) was only activated during the verb generation task. The right-hemispheric activations, homotopic to Wernicke's and Broca's area, were significantly more intense than in right handed subjects; in addition, the right LPFC was activated as well. The activation pattern in left-handed subjects shows a striking similarity with the activations in right-handed patients who have recovered from Wernicke's aphasia. The functional reorganization of the language processing centers in recovered Wernicke aphasics attains the same configuration as in left-handed subjects where it may be genetically determined.

THE EFFECT OF CORONARY ARTERY BYPASS SURGERY ON BRAIN PERFUSION The purpose of the study was to evaluate brain perfusion patterns before and after coronary artery bypass surgery (CABG) and to locate brain perfusion changes in patients w,th neurologic and neurophysiologic complications after CABG. 25 patients with open heart surgery (22 CABG, 3 valve replacement) and 5 patients (4 cholecystectomy, 1 periferic vasculer surgery) as a control group were included in the study.925 MBq Tc99m HMPAO was injected. 20-60 minutes after injection brain perfusion SPECT images were obtained with a triple headed brain dedicated SPECT camera. Imaging was made one week before and four to six weeks after surgery.Tc 99m HMPAO Brain SPECT slices were evaluated visually and semiquantitatively. None of patients had severe neurologic complications. Cognitive deterioration and depressive mood occured in five patients with CABG.Frontal hypoperfusion was found in these patients by visual and semiquantitative evaluations (.01
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SP Mfiller t, C Weiller 2, A May 2, C Kappeler 1, L Geworski 1, HH Coenen 1, EJ Knust 1, M Jtipmerz, J Sciuk 1, HC Diener 2. Nuclear Medicine 1 and Neurology2, University Essen, FR Germany.

A.M. Catafau, E. Parellada, F. Lomefia, M. Bernardo, F J . Setoain, S. Catarineu, J. Pavfa, J. Setoain. Hospital Clfnic. University of Barcelona, Spain.

PET r C B F - S T U D I E S E L U C I D A T E T H E SPONTANEOUS MIGRAINE.

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Today the etiology of migraine attacks is no longer seen in hemodynamic changes but rather in changes of the interactions between nuclei in the midbrain. Therefore, we investigated 9 patients with spontaneous migraine attacks with PET activation studies. An integral [O-15]CO2 inhalation technique was used to assess changes in rCBF due to neuronal activation. A baseline study was performed within 6 hours of the onset of the first symptoms of a migraine. After the s.c. injection of 6 mg Sumatriptan, repeated studies were performed until the pain subsided. Within one week, all patients underwent an additional control study without migraine on a different day. After coregistration and transformation of the brain into the coordinates of the atlas of Talairach & Tournoux, the images were normalized for global flow differences by analysis of covariance, and areas of significant rCBF changes (p<0.05) were displayed as statistical parametric maps. Compared to the control study without migraine, there were bilateral activations in the cingulare gyms, the auditive and visual association cortices and an intense activation in the midbrain (Talairach coordinates +4, -26, -16 ram). While the cortical activations disappeared after the pain subsided, the midbrain activation persisted. The activations in the cingulate gyrus are in agreement with similar observations during pain from other etiologies and may be related to the emotional response to pain. Their disappearance as well as the decline of the activations in the anditive and visual cortices with pain relief and the termination of the photo- and phonophobia favor a symptomatic etiology. The persistence of the midbrain activation after the cessation of all symptoms, however, indicates a direct involvement of the midbrain nuclei in the etiology of migraine attacks and may explain the frequent recurrence of the migraine after the effect of Sumatriptan has worn off.

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ASSESSMENT OF FRONTAL AND CINGULATE BLOOD FLOW CHANGES DURING WISCONSIN CARD SORTING TEST BY A RANDOMIZED 99mTc-HMPAO SPECT STUDY IN NORM AL SUBJECTS To investigate frontal and cingulate rCBF changes during Wisconsin Card Sorting Test (WCST), two 99mTc-HMPAO SPECTs were performed on 13 right-handed normal volunteers (mean age 19.8_+0.8 yrs.), randomizing the order of the resting and activated SPECT to avoid "order effects". SPECTs were performed on an Elscint-Helix HR cammera fitted with HR fanbeam collimators. Semiquantitative analysis was performed after 3-D software realignment, obtaining region/cerebellar ratios for the anterior (prefrontal) and posterior (including the motor area) regions of the frontal lobe and the anterior and posterior cingulate. An activation score (activated-resting ratios) was also obtained for each region. A significant rCBF increase during the WCST was found in the left hemisphere for the anterior cingulate and the posterior frontal region (Wilcoxon signed-rank p<0.033). Although the relative rCBF values of the right and left prefrontal regions and the right anterior cingulate were higher during the WCST in 9/13 subjects, no statistical difference was achieved in these areas. No differences in the activation score were found between subjects undergoing the resting SPECT in the first study and subjects undergoing the resting SPECT in the last (Mann-Whitney Utest). No correlation was found between the activation scores and the WCST performance. No order effect was found in this study. The rCBF increase in the left posterior frontal region during the WCST could be explained by the motor task implied in the WCST. The left anterior cingulate cortex, a region that has been implicated in attentional mechanisms, is the region predominantly activated during the WCST.

• Neurology 0Mo210

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M.Sygitowicz~ P Lvczak, P.Lass~ MTaraszewska, E.Stcpiefi. MStempniewicz, P.Zielifiski, EMierzeiewska, M.Dubaniewicz, R.Hebel, M.Bilinska, K.Mizan, G.Romanowicz, JM.Slominski Medical University, Gdaflsk, Poland

F. Chierichetti~ *G. Pizzolato, *M. Dam, P. Zanco, S. Cargnel, B. Saitta, A. Fini, "P. Burra, *A. Cagnin, AC. Ori, "C. Mantovan, P. Trento, G. Ferlin Nuclear Medicine D p t , Castelfranco Veneto and *Neurology, "Gastroenterology, "AnesthesiologyDpt, Padua University - Italy

TC-99M-MIBI AND TC-99M-HMPAO ACCUMULATION IN AND METASTATIC BRAIN TUMOURS PRIMARY ASSESSED BY BRAIN SPECT The aim of the study: the imaging of intracranial lesions is frequently met with difficulties in CT/MRI diagnostics. The promising alternative seemed the introduction of the oncophilic tracer MIBI. We aimed to compare the accumulation of Tc-99m-MIBI and HMPAO as a potential diagnostic tool in CT/MRI interpretionally difficult intraeranial lesions, turnout suspected. Patients and methods: we performed brain SPECT scanning with the single-head DIACAM camera after i.v. administration of mean 20 mCi of Te-99m-HMPAO/MIBI. We performed HMPAO scanning in 34 patients, MIBI scanning in 41 pts. CT and /vlRl scanning was performed simultaneously. Histological diagnosis was done intraand/or postoperatively. Results: an increased accumulation of Tc-99m-MIBI was seen in 7/7 meningiomas (100 %), 7/9 gliomas (77 %), 10/15 brain metastases (66 %), 2/4 unverified. In 5 cases with finally non-neoplastic diagnosis (stroke, a-v malformation) no MIBI accumulation was seen. An increased accumulation of HMPAO was seen in 3/11 gliomas, 2/7 meningiomas, 2/8 metastases and 2/4 unverified. In 4 eases nonneoplastic diagnosis was established. Comments: our results seem to be less promising, than reported so far, particulady of heterogenous accumulation of MIBI in metastatic tumours. The couple Te-99m-MIBI/HMPAO scanning may be useful in primary tumours diagnostics, particularly in meningiomas.

ALTERATIONS OF BRAIN GLUCOSE METABOLISM IN CIRRHOTIC PATIENTS WITH SUBCLINICAL ENCEPHALOPATHY Subtle impairments of cognitive function may be detected in cirrhotic patients (pts) without an overt hepatic encephalopathy. These abnormalities can be evidentiated on neu~'opsychological tests even if neurological examination and morphological brain imaging are normal. The aim of this study was to identify changes in the brain metabolism in cirrhosis without or with minimal clinical symptoms of encephalopathy. Methods: 14 cirrhotic pts (mean age 50 ± 11 yrs) who were under evaluation for liver transplantation and 6 age-matched healthy controls underwent a complete neuropsychological evaluation and PET scan (ECAT EXACT 47, Siemens) with 18F-FDG (230-340 MBq i.v.). Cardiac input function was used for calculating rCMRgl in cortical and subcortical regions of interest using Sokoloff equation with standard values for the rate constants and LC (Phelps). Radial artery was catheterized to obtain the arterial input function as a validation. Results: neurologic and EEG examinations were normal in all pts. MR1 showed mild atrophy in 3 pts with alcohol-related cirrhosis. Neuropsychological evaluations evidentiated deficits in frontal functions, short-term and spatial memory, visuo-spatial abilities. rCMRgl was significantly reduced in all cortical and subcortical examined regions The greatest reductions from control mean values were found in cortical regions (25-30%), followed by cerebellum. Thalamus and basal ganglia were less affected. Conclusions: PET shows diffuse derangements of brain metabolism in subclinical and hepatic encephalopathy. Cortical regions resulted to be the most involved, so that, qualitatively there was an apparent redistribution of 18F-FDG toward subcortical regions. Metabolic abnormalities in cirrhotic pts seems to be more wide than suggested by neuropsychological evaluation.

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T.Okuda, H.Fu)ii, T.Okae, M.Tadokoro, T.lshigaki Department of Radiology, NagoyaUniversity School of Medicine, Japan. Anjou Kousei Hospital, Japan

A. Nai'mi, M. Allaoua, J-P. Papazyan, J. Delavelle, F. Lazeyras, *M. Seeck, *Z. Qayoom, #J-G. Villemure, D.O. Slosman. Department of Radiology, *Clinic of Neurology, #Clinic of Neurosurgery, Geneva University Hospital, 1211 Geneva 14, Switzerland.

Improved quantification of regional cerebral blood flow of 1231-IMp-autoradiographical method by the correction of lipophilic fraction in each subject. Autoradiographical quantification (ARG) of regional cerebral blood flow (rCBF) with 123I-IMP has been proposed by lida et al., as a simple and non-invasive method using a standardized input function. ARG requires an arterial blood sampling at 10 min to create the input function of each subject from a standardized input function. Although ARG become accepted as a convenient method of rCBF quantification in clinical practice in Japan, we found a group of subjects with unreasonably low rCBF values. To find the cause of wrong computation and improve the quantification, we performed a comparative assesgment of ARG and microsphere model method (MSM) which is considered to be one of the most reliable method of rCBF estimation with 123I-IMP SPECT. Fifteen patients with suspected cerebral ischemia were studied. After intravenous infusion of 123I-IMP, arterial blood was sampled continuously for 7 rain for MSM and at 10 rain for ARG. SPECT scan was acquired 25 min after injection for 20 min with a dual-head gamma camera system. We s u p p l e d it is one of causes that input function is obtained by calibrating a standard input function by one point arterial blood sampling.Tbe standard input function has been already generated by combining the input functions from 12 independent studies before.However, the standard input function dose not r~tch each input functions in any cases. Therefore, we treated the blood with cctanol to obtain the fraction of true tracer activity in one point arterial blood sample in 10 min after intravenous infusion of 1231IMP. By our method, a good correlation was observed between the two methods. However, an underestimation of this modified iMP-ARG method CBF as compared with microsphere motel method CBF still remained. IMP-ARG method is useful,but it has some room for improvement. The present study is reported as one of the improvement of IMP-ARG method,

GENEVA'S EXPERIENCE IN PRESURGICAL EVALUATION OF PARTIAL EPILEPSY Aim: The purpose of this study is to report our experience in the presurgical evaluation of partial epilepsy in the past year. Material and methods: From February 1995 to February 1996, we evaluated 30 patients in our presurgical program of partial epilepsy. This evaluation included: EEG monitoring, neuropsychological testing, cerebral MRI, MRI hippocampal volumetry, iuterictal FDG PET and interictal/postictal/ictal ECD SPECTs. During the hospitalisation, the patient was placed under constant EEG monitoring, which enabled a perfect electro-clinical correlation of the crisis and allowed a precise timing of the Nuclear Medicine procedures. The neuropsychological testing included interictal and postictal performance testing. The cerebral MRI was made of T1 and T2 gated coronal images, inluding a gradient echo 3D volumic acquisition, from which the bilateral amygdalohippocampal volumetry was performed. The FDG interictal PET (at least 4 hours without crisis before the examination) was performed on a Siemens ECAT ART and the ECD SPECTs (ictat, postictal, interictal) were performed on a 3 heads Toshiba GCA 9300HG. Both exams were displayed in axial and coronal slicing relative to the temporal lobe plane. For both procedures, statistical analysis was performed on bilateral whole temporal and internal temporal ROIs, drawned on 12 jointive 3.375 nma coronal cuts. Results: 9 of 30 patients have been operated. The histological findings of the 9 patients operated were 5 mesial sclerosis and 4 internal temporal cortical dysplasias. The correlation of all the investigations was able to determine the lateralisation of in the epileptic focus with a good confidence level. In respect of lateralisation, MRI amygdalohippocampal volumetry and ictal/postictat SPECTs correlated best with the electro-clinical findings, followed by the interictal PET and at last by the interietal SPECT. Conclusions: Our experience confirms the need for a multidisciplinary approach in the presurgical evaluation of partial epilepsy including clinical, neuropsychological, electrical, morphometric and functionning parameters. In respect of lateralisation, ictal SPECT correlates best with the electro-clinical findings.

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E. Ambrus, L. P~ivics, A. Kuncz*, E. VOrds**, L. Balkay***, M. Emri***, L. Trdn***, M. Bodosi*, L. Csernay Departments of Nuclear Medicine, Neurosurgery* and Radiology**, Albert Szent-Gydrgyi Medical University, Szeged, University of Debrecen, PET Centre***, Debrecen, HUNGARY

J.Pinkert1, W.-G.Franke 1, H. Broeker2 and J. Miiller~ Technical University Dresden, Depts. of Nuclear Medicine1 and Neurology2, Practice of Neurology and Psychiatry Dresden3

COMPARATIVE STUDY IN B R A I N T U M O U R S

OF FDG-PET

AND M I B I - S P E C T

EVALUATION OF DUAL TIME EPILEPSY

1-123 IOMAZENIL SPECT

IN

FDG-PET investigation is an established method for determination of the malignancy or recurrence of brain tumours. The clinical value of MIBI-SPECT in this field has been investigated by only a few groups. The aim of this work was to compare the diagnostic value of MIBI-SPECT with that of FDGPET in the identification of primary or recurrent brain tumours. SPECT and PET examinations were carried out within a week in 16 patients (13 males, 3 females, mean age: 35 years, range: 961 years) with brain tumours. Seven patients had a primary tumour and 9 a suspicion of tumour recurrence based on MRI or clinical signs and symptoms. All tumours were verified by histology as gliomas of grade I-IV. The SPECT and PET images were analysed visually and semiquantitatively. Seven tumours proved a glioma of grade III-IV on histology. An increased MIBI uptake was found in all of 7 cases, but FDG accumulation was detected in only 5 of them. Neither MIBI nor FDG uptake was found in tumours of grade [-IL The intensity of radiopharmaceutical uptake at the site of the tumours was visually and semiquantitatively higher with MIBI than with FDG (tumour/non-tumour ratio: 9.48 (5.1-13) vs. 1.94 (1.06-3.9). W e conclude that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours.

1-123 Iomazenil (IMZ) is bound selectively on central type benzodiazepin receptors which are reduced in epileptic loci. Recently full quantitative estimation with dynamic SPECT was reported. However this method is not practicable for routine examinations, therefore a single SPECT study after 2 hours or later was widely used tO estimate Iomazenil receptor binding. In this study we evaluated the clinical value of regional wash-out in the epileptic foci as an additional parameter of receptor density. 29 patients with clinical suspicion of focal epilepsy in the temporal lobe were studied. All underwent clinical, EEG and MR/(3 pts. only CT) examinations. An additional interictal perfusion (IP) SPECT with 750 MBq Tc-99m HMPAO or ECD was performed in 25 pts. Two SPECT scans were performed in each patients at 10 minutes (early scan, 30 s / frame) and 2 hours (late scan, 60 s / frame) after intravenous injection of 150 MBq IMZ using a dual head camera equipped with low energy high resolution collimators (64 frames at a 64x64 Matrix). After reconstruction with filtered backprojection (Butterworth filter 8/0.34) or iterative maximum likeIihood (ML) method an attenuation correction using the CHANG-algorithm was performed. Coronal, transversal and temporal slices were reconstructed. The site of a uptake defect representing an epileptic focus was visually assessed and the regional washout for this region estimated in contralateral comparison. 21/29 showed an unilateral uptake defect in late IMZ- SPECT and 18/29 pts. had additional increased local washout. Only i3/25 pts. demonstrated abnormal findings on IP-SPECT and 17/29 pts. localised EEG findings which correspond well with IMZ-SPECT results. Our results indicate a higher sensitivity of 1MZ- SPECT with deeper uptake defects compared with interictal perfusion SPECT. The elevated local washout of IMZ in the epileptogenic area seems to be a useful tool and may support the correct lateralizatlon in small findings.

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F.M.Fdnguel!i,R.Campini,L.Mazzini*,C.Camana*,F.RognoneO,R.Giubbini, O.Zoccarato "SalvatoreMaugeri"FoundationIRCCS RehabilitationInstituteof Veruno and Pavia(Italy) NuclearmedicineService,*RehabilitationDivision,°RadiologyService

C. Menzel F. GrOnwald, S Steidele*, L. Pavics, A. Hufnagel*, E. Klemm, H. Bender, H. Palmedo, CE. Elger* and H.J. Biersack. Dept. of Nuclear Medicine and Epileptology*, University of Bonn, Germany

PROGNOStiCASSESSMENTAFTERSEVEREHEADINJURY(SHI)BYHMPAO.SPETandMRI Different cerebral patologies may occur after SHI,The aim of the study was the

CAN SECONDARY ACTIVATION / INHIBITION OF TRACER UPTAKE IN PARTIAL EPILEPSY AS SEEN WITH ICTAL R C B F - S P E C T BE USED TO SUGGEST THE POSSIBLE AREA OF SEIZURE ONSET 9

prospective evaluation of a group of pts.after SHI to determine the relationship between clinical outcome and 99mTc HMPAO-SPET and MRI patterns. 32 pts. (23 M, 9 F, mean age 29+11(17-58) were evaluated by SPET and MRI within 90 days after SHI; t2 of them had a follow up study at 6 and 12 months(M).The following clinical parameters were considered: age,Glasgow coma scale (GCS) within 6 h.after the HSI, GCS at the time of the besaline SPET, coma duration, Glasgow Outcome Scale (GOS), Neurobehavioural Rating Scale (NRS), memory and attention disorders graded according to a severity score( 0= normal, 1= mild, 2= severe). The mean duration of coma was (30.2+_15days). 3 pts were in persistent vegetative state (PVS).A panel of 4 experts evaluated presence, extent and severity of SPEr perfusion defects (PD) and MRI abnormalities in corresponding cerebral territories (temporal, frontal, basalganglia, parietal, occipital, extracerebral) using a severity score (0= normal; 1 =mild; 2=moderate; 3=severe);in MRI reports the grade of hydrocefalus, the presence of diffuse atrophy and axonal damage were also considered.There was significative correlation between PD and: hydrocefalus grade (p<.001), diffuse atrophy (p<.03). No correlation was found between MRI location of lesions and clinical variables; MRt hydrocefalus grade and diffuse atrophy correlated with age(p<.02), 6 M GOS (p<.02), 12 M GOS (p<.001), coma duration (p<.003) and attention disorders (p<.01); no correlation was found with memory and behaviour disorders. The presence of frontal lobes PD in early studies was significantly correlated with 12 M NRS (p<.001), memory disorders (p<.002), attention disorders(p<.008); significant correlation was also found betweeen the presence of temporal PD and attention disorders (p<.005). There was no correlation between SPET patterns and the other clinical variables. The MRI pattern did not change during the follow-up.The SPET pattern showed worsening in PVS and in pts. with unfavourable outcome. In conclusion both SPET and MRI provide useful information for early charactedzation of the clinical outcome of SHI pts.Eady SPET pattern in comparison to MRI shows higher predictive value for cognitive and behavioural outcome. 1086

The rationale for the application of ictal rCBF-SPECT in partial epilepsy may be primarily to (A.) lateralize the disease and if so to further detect the lobe of seizure origin (B.) and if this is possible to find the generator focus itself (C.). Studies have shown that it does so (A.) almost always, (B.) most.ly, (C.) sometimes. The wide interindividual variability of partial epilepsy and the limited information of ictal rCBF-SPECT concerning its function of time while providing only a "snapshot" of the seizure often complicate proper evaluation of the results. The ictal rCBF-SPECT results of 20 pts. (m:f = 11:9; mean age: 28 yrs.) with temporomesial and those of 16 pts. (m:f= 9:7; mean age: 24 yrs.) with frontal partial seizures were evaluated, lctal injections were done irmnediately after EEG- or clinical onset of the seizure using 555-740 MBq 99mTc-ECD and a Ceraspect-system with a dt interval of at least 45 minutes, lctal uptake patterns in temporomesial epilepsies were (i.) temporal (complete lobe) in 55 %, (2.) temporemesial only in 9 % and (3.) temporolateral only in 36 %. In 65 % of cases an ipsilateral frontal, mainly frontobasal, hypofixation was seen and in no case ipsilateraI frontally increased tracer-uptake was noticed. In coutrast, in frontal lobe epilepsies hyperfixation of the tracer was seen (4.) bifrontally in 25 %, (5.) frentomesial 44 %, (6.) frontolateral 25 %, (7.) frontopolar 6 %. Ipsilateral temporal hyper- and hypofixation was seen in 3 1 % each. Limitations of these data are seen in the smafl number of patients, missing postsurgical information of some pts., uncertain injection latency and in the lack of online EEG-information during the tracer application in some patients. Prelimina~ conclusions in terms of rCBF-SPECT are: A. Ictal temporomesial discharges rapidly involve temporobasal and -lateral areas, B. temporomesial depression of tracer uptake might already occur in the early ictal phase. C. temporomesiat foci often lead to a depression of tracer uptake in the ipsilateral frontal lobe but do not activate frontal structures, D. frontal seizures can activate temporal structures. These findings might cautiously be used for interpretation of SPECT results but require confirmation using well designed data acquisition protocols.

•

Neurology

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J.-P. PAPAZYAN l , A. NAIMI l , M. ALLAOUA 1, J. DELAVELLE 2, F. V I N G E R H O E T S 3, A. REVERDIN 4, G.P. PIZZOLATO 5, D.O. SLOSMANL Division of Nuclear Medicine 1, Department of Radiology2, Clinics of Neurology 3 and Neurosurgery a, Neuro-pathology Unit 5, Geneva University Hospital, 1211 Geneva 14, SWITZERLAND. B R A I N T U M O U R S D I A G N O S I S : I M P O R T A N C E OF A MULTI-MODALITY RADIO-ISOTOPE IMAGING SEQUENCE.

F. Chierichetti, *G.L. Bianchin, *A. Vallerini, N. Borsato, P. Zanco, D. Rubello, * G Pigato, G. Ferlin, Nuclear Medicine Dpt, Castelfranco Veneto and *Psychiatry Dpt ULSS 8 - Italy

Aim : Suspected brain tumours are first investigated with radiological examinations providing morphological data. CT and MRI reveal oedema and integrity of the blood-brain barrier. Nuclear medicine techniques add complementary functional information. In this work, we evaluate the importance of a functional multi-modality radio-isotope imaging sequence with 99mTc-HMPAO / 2mThallium SPECT (dual isotope acquisition mode) and 18F-FDG PET in patients with suspected brain tumours. Material & Methods: 95 patients were investigated for suspected brain tumour. 87 2mThallium SPECT were performed, 84 of which were acquired in dual isotope acquisition mode with 99mTc-HMPAO. 63 patients were investigated with a IaF-FDG PET exam. These examinations were considered as positive for a turnout with a high grade of maiignancy in the presence of focal hyperactivity with 99mTc-HMPAO and 2mThallium and focal high uptake of 18F-FDG on PET-scan. The final diagnosis was based on histopathologicai analysis available in 68 patients and on the association of clinical and radiological evolution in the other 27 patients. Results: SENSITIVITY

201-T1 20I-T1 & HMPAO FDG 201-TI & HMPAO & FDG

93,3 % 53,6 % 78,3 % 50%

SPECIFICITY

66,6 % 87,5 % 80,8 % 95,1%

Conclusions: 201Thallium SPECT is the most sensitive examination for brain tumour detection, remaining more sensitive than 18F-FDG PETscan. The multi-modality radio-isotope sequence improves the specificity of the diagnosis of a brain tumour of high grade of malignancy.

CONTRIBUTION OF 99mTc-ECD SPET TO A COMPREHENSION OF NEUROBIOLOGY IN OBSESSIVECOMPULSIVE (OCD), DEPRESSIVE AND SCHIZOPHRENIC DISORDERS Many Authors have reported high prevalence of comorhidity between OCD and depression (31.7%, Robins et al. 1984), between OCD and schizophrenia (13%, Fenton and Mc Glashan 1986) and between depressive disorder and chronic schizophrenia (25-50%, Van Putten and May 1978; Johnson et al. 1981). Aim of our study was to investigate, by perfusion SPET, if there is a focal brain alteration which is shared by these pathologies. Methods: we performed 99mTc-ECD SPET in 12 schizophrenic subjects, 10 OCD pts, 8 pts affected by major depression and l0 healthy controls. SPET data were evaluated by semi-quantitative method (each cortical and subcortical area/MBA, mean brain activity) and then statistical analysis was performed. Results: schizophrenic pts presented statistically significant increase of blood flow in orbito-ffontal regions (p = 0.003) and hypoperfusion of the left upper frontal cortex (p = 0.001). OCD subjects showed increase of blood flow in the orbito-frontal regions (p = 0.001), too and a non relevant hypopeffusion of the upper frontal cortex while basal ganglia tended to be hyperperfused. In depression, frontal hypoperfusion was evident especially in the upper regions (p = 0.003). Conclusions: frontal cortex seems to be the more affected brain area in every of the examined disease even if in presence of different features and other cortical and subcortical impairments. This finding suggests that, in these entities, contiguous brain regions may be affected, thus explaining the high prevalence of comorbidity. As an hypothesis, there is probably the involvement ofkindling's processes.

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VW Pike1, JA McCarronl, S OsmanL AA LammertsmaL SP Hume, SK Luthra1, P Sargent1, CJ Bench1, PM Grasbyl, IA Clifle2 and AC Fletcher2 1PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, RPMS, Hammersmith Hospital, Ducane Road, London W12 ONN, U.K. 2Cerebrus Ltd, Silwood Park, Ascot, Berkshire, SL5 7PN, U.K.

F. Chierichetti, *G.L. Bianchin, *A. Vallerini, P. Zanco, A. Fini, L. Vettorato, *O.M Galvano, P. Trento, G. Ferlin, Nuclear Medicine Dpt, Castelfranco Veneto and *Psychiatry Dpt ULSS 8 - Italy

STRATEGIC SELECTION OF LABELLING POSITION RESULTS IN A GREATLY IMPROVED RADIOLIGAND FOR PET STUDIES OF BRAIN 5-HT1A RECEPTORS IN HUMANS - - [CARBONYL-C-11]WAY-100635 We have previously shown that WAY-100635 [ N - ( 2 - ( 4 - ( 2 methoxy p heny I)-1 -pip eraziny I)ethy I)-N-( 2-py ridyl)-c y c l o h e x a n e carboxamide] labelled in the methoxy position with C-11 (tl/2 = 20.4 min) can be used with PET to delineate 5-HTIA receptors in human brain. However, our further studies have shown that the descyclohexanecarbonyl analogue ([C-11]WAY-100634) is a metabolite in humans, with high affinity for 5-HT1A receptors and high ability to enter brain, so hampering quantitation of radioligand uptake in vivo. As a strategy for avoiding Iipophilic metabolites, including [C-11]WAY-100634, we chose instead to label WAY-100635 with C-11 in the carbonyl position. Here we report the first PET studies of [carbonyI-C-11]-WAY-100635in humans, including analysis of radioactive metabolites in plasma. [Carbonyt.C-11]WAY-100635(-7.3 mCi; -2 Ci/i.tmol)was injected intravenously into each of 5 healthy male volunteers who were then scanned parallel to the orbito-meatal line with PET. The acquired data, summed from 20 to 90 min after radioligand injection, provided excellent delineation of 5-HT1A receptors in brain, with high uptake in receptor-rich regions, including medial temporal lobe, insula, cinguiate cortex and the raphe nuclei. The cerebellum, which is virtually devoid of 5-HT1A receptors, had very low uptake of radioactivity such that the ratio of radioactivity in receptor-rich medial temporal cortex to that in cerebellum reached 20 by 60 min after injection. This value is - 9 times greater than that previously obtained by using [methoxy-C-11]WAY-100635. Analysis of plasma revealed only very polar radioactive metabolites; no radioactive WAY100634 or desmethyl-WAY-100635 was detected. Unchanged radioligand on average represented 99% of the radioactivity in plasma at 1.5 min after injection and 7.5% at 40 min. Application of a standard reference tissue tracer-kinetic model to the acquired PET data gave binding potentials that average 7.8 in medial temporal lobe. Thus, strategic selection of the position for labelling WAY-100635 with C-11 has resulted in a greatly improved radioligand for clinical and pharmacological PET studies of brain 5-HT1A receptors in humans.

18F-FDG PET IN CHRONIC DRUG-FREE AND ACUTE DRUGNAIVE SCHIZOPHRENIC PATIENTS Many Authors (Wolkin 1985; Buchshaum 1987, 1990; De Lisi 1989; Cleghorn 1989) performed 18F-FDG PET in groups of schizophrenic patients (pts) considering various clinical states such as the presence of positive and negative symptoms, the duration of the disease and the effects of therapy. Aim of our study was to evaluate schizophrenia in different clinical states and duration of disease. Methods: we performed 18F-FDG PET in 19 schizophrenic pts (diagnosis according to DSM IV) and 6 age-matched healthy subjects. The pts were divided into: 1) group A (10) with negative symptoms, duration of disease > 5 yrs, drug-free for at least 8 weeks; 2) group B (9) with positive symptoms, at the onset of disease, drug-naive. PET data were evaluated by semi-quantitative method (each cortical and subcortical area/MBA, mean brain activity) and statistical analysis. Results: in group A we found hypometabolism of the whole frontal cortex (p = 0.000) and of the upper temporal regions (p - 0.006), while basal ganglia were hypermetabolic (p = 0.001). Group B presented hypometabolism of the upper frontal (p = 0.01) and upper temporal regions (p - 0.005); hypermetabolism was statistically significant for the head of caudate nucleus bilaterally (p - 0.002). Conclusions: acute pts (B) with positive symptoms showed lesser extension of involved brain areas than chronic pts with negative symptoms. Group A had an overall alteration of basal ganglia possibly correlated with the presence of avolition and asociaiity. But the more interesting result seems to us the constant report of hypometabolism of the upper temporal cortex in both groups, suggesting that it may be unrelated to the duration of illness, previuos therapies and clinical features of schizophrenia.

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• Neurology 0Mo222 H.Feistel, D.Ebert*, A.Pimer, G.Platsch, F.Wolf Dept. of Nuclear Medicine and *Dept. of Psychiatry Friedrich- Alexander- University Erlangen- Nuremberg, Erlangen, FRG DOPAMINE AND DEPRESSION - IBZM-SPECT BEFORE AND AFTER ANTIDEPRESSANT THERAPY Aim of an IBZM- SPECT study was to demonstrate effects of different antidepressant therapies an the D2- receptor availability in human brain. 30 male patients (pts.) with major depression (DSM-III-R) were investigated§. All patients were right handed and drug naive for neuroleptic medication. Severety of depressiun was rated with the CGI and Hamilton Depression Scale (HDS). (a) 10 pts. underwent two investigations before and after one night of therapeutic sleep deprivation (TSD). (b) 10 pts had received 150 mg amitriptylline(AMT) /day for two weeks, (c) 10 pts. were free of psychoactive drugs for at least 6 months. The latters received 150 mg AMT/day after the first brain scan and were reinvestigated three weeks later. "Responders" were considered to have a 50% decrease on the HDS. We found 5 responders in TSD and 5 respunders in medical treatment. (d) 10 male controls were investigated suffering from other diseases. IBZM- SPECT was performed 120 minutes p.i.. Its. were instructed to keep sitting until atier the scans to restrict motoric activity. Brain scans were evaluated semi-quantitatively (regional activity index, RAI) by means of KOI placed in anatomical relevant areas. Basal ganglia (BG) uptake was calculated as one ratio "BG/whole brain" and "BG/ cerebellum" respectively. In patients with TSD there was a significant difference ( p < 0 . 0 i Wilcoxou) in responders in receptor occupancy, which was decreased in the second scan, demonstrating enhanced therapeutic dopamine release. Also in five responders of pharmacotherapy a decrease in receptor availability could be found (p<0.05). Four of them had psychomotoric retardation before but not after medication. In these pts. the RAI before therapy were elevated on the right side° indicating a decreased dopamine turnover. There was no significant difference in RAI of the medicated, unmedicated and the controls. In conclusion an in-voivement of the dopaminergic system into the effect of TSD could be shown as well as in pts. with psychomotorie retardation. ($Appr. of the Ethical Commitee)

0Mo224 SP Miiller 1, D Timmann 2, M Rijntjes 2, FP Kolb 3, L Geworski 1, C Kappeler 1, D Bier 1, HH Coenen 1, C Weiller 2, J Sciuk 1. Nuclear Medicine 1 and Neurology 2, University Essen; Physiology 3, University Munich, FR Germany. PET ACTIVATION STUDIES REVEAL TIlE BRAIN STRUCTURES INVOLVED IN THE CLASSIC CONDITIONING OF TIlE FLEXOR REFLEX. Current concepts postulate a central role of the cerebellum in the learning of new complex movements. A fundamental simple example of the learning of a motor task is the classic conditioning (Pavlov's dog) of the flexor reflex. The flexor reflex is a spinal pain reflex which can be evoked by electrical stimulation of the sole of the foot. The stimulus for conditioning was a sound which was presented via earphones 350 ms before the electric pulse. The decrease of the response time was used as a measure for the degree of conditioning. Throughout the duration of conditioning, which lasted about two hours, 12 integral PET images were acquired every 8 - 12 min during a 60 s infusion of [O-15]H20. The interval between the electrical stimuli was 45 - 65 s and 8 - 12 s during the PET scans. Five patients were studied~ After coregistration of the PET and MRI images and after stereotactic normalization into the coordinates of the arias of Talairach & Toumoux, the images were normalized for global flow differences by analysis of covariance. Pixels in which the CBF was correlated significantly (p<0.05) with the degree of the conditioning were displayed as statistical parametric maps. There were increases of the rCBF, which correlated with the reduction of the response time, in the left amygdaia extending along the left hippocampus into the left cerebellum. Our results in humans are in agreement with animal studies of classic conditioning, which also demonstrated an involvement of the same brain structures. Our study also confirms the role of the cerebellum in the learning of motor tasks. At most five stimuli fell within the time frame of each 60 s data acquisition; this underlines the high sensitivity of correlation analysis for PET activation studies.

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D.F. Smith I'=, A.D. Gee a, E. Danielsen 2, S.B. Nansen =, F. Andersen a, A. Gjedde 2 Zlnstitute for Basic Research in Psychiatry, Aarhus University Psychiatric Hospital, 8240 Risskov and aPET Center, Aarhus University General Hospital, 8000 Aarhus C, Denmark

A Ahonen I, T P J Laine 2, 0 Niemel~ 3, P P/is~nen2, P Torniainen I, J Heikkil~ I, J Pyhtinen 4, J Hiltunen s, M Hilllxx~6, iDivision of Nuclear Medici_he, Departr~nts of ~eurology, 2Psychiatry and 4Radiology, University Hospital of Oulu; ~ P Central Hospital Laboratory, Sein~joki; ~ Technologies, Tikkakoski, Finland. STRLa~AL D O P A M I N E A N D SEROTONIN TRANSPORTER LEVELS IN ALCOHOLICS

BINDING OF [O-METHYL-zzC]VENLAFAXINE IN LIVING PIG BRAIN: WEAK DISPLACEMENT BY SEROTONIN REUPTAKE INHIBITORS

D U R I N G E T H A N O L WITHDRAWAl.

Venlafaxine is a relatively new, fast-acting antidepressant drug which inhibits pres~nuaptie monoamine reuptake but does not interact with other neuroreceptors, z'C-labelled venlafaxine was synthesized and injected intravenously into anesthetized pigs for determining whether the radioligand would be suitable for studying neuronal reuptake sites using PET neuroimaging. Arterial blood samples were drawn for kinetic analysis of the brain images. [nc]-Venlafaxinederived radioactivity entered the brain readily and showed higher apparent partition volumes in cerebral (ca. 12.0 15.9) than in cerebellar (ca. 8.0 - 9.0) brain regions. Compartmental analysis indicated that a single tissue compartment model accounted adequately for the findings so Logan analysis was used for estimating kinetic parameters. [~C]-Venlafaxine was found to bind preferentially in dlencephalie (e.g. thalamus) and telecephalic (e.g. frontal cortex) regions, although it had relatively low binding potentials (i.e. ca. 0.5 - 0.8). Scatchard plots indicated that nonspecific binding was marked for venlafaxine in most brain regions. Displacement studies carried out with intravenous injection of a selective serotonin reuptake inhibitor (SSRI), either paroxetine or citalopram, showed that [xiC]venlafaxine competed weakly at 5-NT reuptake sites in dieneephalic and telecephalic regions in living pig brain. Taken together, the findings show that [O-methyliXC]venlafaxine may be of use for studying certain monoamine uptake mechanisms by PET, hut that the radioligand fails to fulfill traditional criteria for routine use for quantifying the serotonin reuptake sites in the living brain.

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The effect of acute ethanol withdrawal on htwnan dopanline (DA) transporters was investigated with SPECT using [123-I] 2~carbometoxy-3~-(4-iodophenyl)tropane ([123-I]~-CIT) ligand (F~{P Medical Technologies Inc. ). [123-I]~-CIT binding to striatmm was examined in 12 alcoholics (n~_an age 42 yrs, range 32-53) during withdrawal symptoms after a period of at least 2 weeks of heavy ethanol intake (>140 g/day). Controls were 15 healthy volunteers (mean age 36 yrs, range 21-51). Transporter levels were examined 1-4 days after cessation of ethanol intake and after four weeks of abstinence monitored b y interviews and biochemical markers (sertwn desialotransferrin, CUr) and by urinary screening for narcotics. The first scan was taken one hour (serotonin transporter density) and the second scan one day after injection of the tracer (dopamine transporter density). Transaxial slices oriented in orbito-meatal (GM) line were reconstructed and the following regions were drawn: i) medial prefrontal cortex (MEC), 2) striattrn (STK) and 3) frontal white matter (F~4). ROIs were drawn using MBI. The following ratios were calculated: i) MEC/F~4 at one hour (serotonin transporter density) and 2) STR/F~IM at one day (dopanine transporter density). Dopamine transporter density was significantly higher after four weeks of abstinence (8.0) ccrqoared with withdrawal situation (7.3), (p<0.01). After four weeks of abstinence the levels were similar to those of healthy controls (STR/F~4=8.0; n=lS). Both I-type (n=6) and II-type (n=3) alcoholics showed decreased density of striatal dopanine transporters. In contrast, no significant difference could be found in serotonin transporter density in medial prefrontal cortex (MZC/F~4) during withdrawal (1.18) and after four weeks of abstinence (1.12). The present data indicates that decreased striatal dopamine activity may be an important mechanism of ethanol-induced withdrawal symptoms.

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J.T.Kuikka, U. Lepola, J. Hiltunen, K.A. BergstrOm, K. Akerman, J. Tiihonen, E.L~nsimies, Kuopio University Hospital, Kuopio, MAP Medical Technologies Inc., Tikkakoski, Finland, Karolinska Institute, Stockholm, Sweden

C. Boy 1, A. Klimkes, M. Holschbach2, H. Herzog 1, H. Miahlensiepenl, E. Rota-Kops 1, R. Markstein4, W. Gaebel3, G. StOcklin2, H.W. MiillerGartner 1, 'Inst. Med., :Inst. Nucl. Chem., Res. Center Jillich, Germany; adept. Psychiatry,Diisseldorf,Germany;4SandozPharm.,Preclin.Res., Basel, Switzerland

ABNORMAL BENZODIAZEPINE RECEPTOR UPTAKE IN THE PREFRONTAL CORTEX IN PATIENTS WITH PANIC DISORDER: AN INITIAL EXPERIENCE WITH [I-123]NNC 13-

PET-IMAGING OF DOPAMINE-D4-LIKE BINDING SITES IN PRIMATE BRAIN USING [I1C]-SDZ GLC 756

Panic disorder is a chronic psychiatric disorder and is characterized by episodic panic attacks, severe anxiety, phobic fears, and several autonomic and endocrine symptoms. We have previously evaluated 1123 labelled 3-(5-cyclopropyl-l,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro5-methyl-6-oxo-4H-imidazo[1,5-a] [ 1,4]-benzodiazepine ([I-123]NNC 13-8241) as a probe for imaging benzodiazepine receptor sites in the human brain. In the present study we report our initial experiences with this new tracer in patients with panic disorder. [I-123]NNC 13-8241 was prepared by iododestannylation method with > 100 GBq/gmol specific radioactivity. A dose of 120-160 MBq was given intravenously and two SPET scans were acquired; 5-25 minutes ("perfusion" image) and 5-6 hours ("receptor" image) after injection of tracer. Siemens MultiSPECT 3 gamma camera with fanbeam collimators was used. Transaxial, sagittal and coronal slices were reconstructed and visually surveyed. Regions of interest were drawn from various brain areas. Receptor images revealed an increased uptake in the right middle/inferior frontal gyms in patients with panic disorder. This "hot spot" was surrounded by neighborhood regions with reduced radioactivity. Image quality of [I-123]NNC 13-8241 SPET scans was superior to that of [I-123]iomazenil. [I-123]NNC 13-8241 is a promising SPET ligand for imaging benzodiazepine receptor sites in patients with panic disorder.

A significant increase of dopamine-D4 receptors has been demonstrated in postmortem striatal tissue of patients with schizophrenia. This study describes the first attempt to quantify D4-1ike binding sites in the normal primate brain. Dynamic PET-scans were performed in baboons (n=3) using [11C]-SDZ GLC 756 (GLC) which has a nanomolar affinity to human D4-receptor clones and lower affinities to D2- or Dl-receptors. The maximal difference of regional uptake in neostriatum (neocortex) and the cerebellar activity was used as indicator of specific receptorbinding (SB) given as % of the injected dose per volume [%ID/IJ. In neostriatum, blockage of D1 and D5 receptors by 1.7 gmol/kg SCH 23390 (SCH) caused a marked decrease of striatal SB from 17.84-3.3 %lD/l to 10.2±3.1%ID/l (mean±SD, p<0.05). Following the blockage of D1, D2, D3 and D5 receptors by SCH + 5,7 gmol/kg raclopride, (RAC), specific binding to D4-1ike binding sites was indicated by a further decrease of striatal SB to 4.0±1.9 %ID/I (p<0.05). In neocortex, binding of GLC to D4-1ike binding sites was found to be 2.7±0.6 %ID/I. In both regions SB was reduced significantly to a non-specific level after blocking all known dopamine receptor subtypes by SCH + RAC + 2.5 gmol/kg spiperone. The regional densities of D4-1ike binding sites were estimated to be below 4.9±2.7 (striatum) and 3.6±1.4 pmol/g (neocortex). The data suggest a low and homogeneous concentration of D4-1ike binding sites in striatum and neocortex of primate brain. The results correspond to the density of D4-1ike binding sites reported for the human striatum in vitro (2.1 pmol/g, Seeman P. et al., Nature 365:441). This new mapping-approach should be useful to test the hypothesis of an increased D4-receptor density in the brain of schizophrenic patients in vivo.

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Otte A, Ettlin TM, Wachter K, Htgerle S, Fierz L, Nitzsche EU, Mueller-Brand J, Moser E. University Hospitals Freiburg and Basel, Rehabilitation Clinic RJaeinfelden, Switzerland

v w Pike 1, S.P Humel, JA McCarronl, S AshworthL DJ Nutt2 and RD Clark3 ~PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, RPMS, Hammersmith Hospital, Ducane Road, London, W12 0NN, U.K. 2PsychopharmcoIogy Unit, University of Bristol, Bristol, BS8 1TD, U.K. 3Roche Bioscience, Pharma Division, Paolo Alto, California, USA

8241 SPET

PET AND HIGH RESOLUTION SPECT IN WHIPLASH BRAIN: A NEW APPROACH TO A FORGOTIEN SYNDROME Introduction: Whiplash-associated disorders of the brain as a result

of distorsion of the cervical spine are a medicolegally controversial condition becom-ing increasingly worrisome in the Western world. This study was designed to evaluate perfusion and glucose metabolism in whiplash brain. Patients/Methods: Using Tc-99m-bicisate (ECD) SPECT and F-18fluorodeoxyglucose (FDG) PET, 6 clinically and neuropsychologically controlled patients (PAT; aged 41+16) with late whiplash syndrome and 12 normal controls (CON; aged 44+19) were investigated. All subjects additionally underwent magnetic resonance imaging (MRI). Region of interest (ROI) analysis: Standardized cortical and subcortical elliptical ROIs were determined in three adjacent transaxial slices in the frontal, parietal, temporal, parieto-occipital (p-o) cortex, in the cerebellum, brain stem, basal ganglia and thalamus. Then, for PET, the glucose metabolic index (GMI; GMI=ROI uptake/global uptake at the level of basal ganglia) and, for SPECT, the perfusion index (PI; PI=ROI/global) was calculated. Results: In 5/6 PAT there was significant hypometabolism and hypoperfusion in the p-o regions (on the right (R) and left (L) side) compared to CON: PET data: GMI p-o R: CON 1.066+0.081, PAT 0.924_+0.044; p=0.0022, Mann Whitney. GMI p-o L: CON 1.034_+0.051, PAT 0,901_+0.059; p=0.0033. SPECT data: PI p-o R: CON t.256+-0.057, PAT 1.075+_0.019; p=0.0002. PI p-o L: CON 1.224+_0.090, PAT 1.070-2_0.048; p=0.0011. In addition, in whiplash with head impact (n=2) there was hypometabolism (> 2 SD of CON) in regions not p-o, too. Conclusions: The group's working hypothesis is that p-o hypometabolism may be caused by activation of nociceptive afferences from the upper cervical spine, since all patients complained about cervicovertebral pain.

EVALUATION AND C-11 LABELLING OF RS-79948-197 AS A POTENTIAL RADIOLIGAND FOR PET STUDIES OF BRAIN a2-ADRENOCEPTORS IN VlVO PET may be used to investigate receptor populations in humans, provided that effective positron-emitting radioligands are available. At present there is no effective radioligand for PET studies of brain a2-adrenoceptors in relation to neuropsychiatric disease or human psychopharmacology. RS-79948-197 {(8aR, 12aS, 13aS)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy12-(ethylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridine} is a highly potent and selective antagonist at ~2-adrenoceptors. We now report an evaluation of radiolabelled RS-79948-197 as a prospective PET radioligand by biodistribution studies ex vivo. After Lv. administration into rats [ethyl3H]RS-79948-197 (8 p.Ci; 50-100 Ci/gmol) clears rapidly from plasma but is retained in brain. At 90 rain after injection the regional distribution of radioactivity matches the distribution of c~2-adrenoceptors seen in vitro, with high radioactivity uptake in entorhinal cortex, amygdala and septum. The ratio of radioactivity in receptor-rich entorhinal cortex to that in receptor-devoid cerebellum reaches 7 at 90 min after injection. The radioactivity uptake in entorhinal cortex and other receptor-rich regions was blocked by predosing the rats with high doses (2 mg/kg i.v.) of RS-79948-197 or other ~2adrenoceptor antagonists (idazoxan or RX 821002). Predosing with the aladrenoceptor antagonist, prazosin, or the 5-HT1A receptor antagonist, WAY100635, was without effect on receptor-specific radioactivity uptake in entorhinal cortex. These data warrant the further development of R,S-79948197 as a radioligand for PET studies of brain a2-adrenoceptors in vivo, especially since the receptor-specific signal develops over a time span commensurate with the short half-life of positron-emitting C-11 (t112= 20.4 min). We have now labelled RS-79948-197 efficiently with C-11 at high specific radioactivity by treating the desmethyl analogue with [C-11]iodomethane in acetone with sodium hydroxide as base. RS-15385197, is the methylsulfonyl analogue of RS-79948-197, and possess very similar pharmacology. We have similarly labelled this compound with C-11. Thus, both C-11 labelled compounds are now available for further evaluation as potential radioligands for PET studies of ct2-adrenoceptors in vivo.

1089

•

Neurology

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ATTENUATION COMPENSATION : AN IMPROVEMENT IN BRAIN SPECT IMAGE QUALITY The purpose of this study was to compare brain SPECT image quality between standard scans and attenuation corrected scans (transmission CT: TCT Tr~Toshiba). Pairs of SPECT were acquired sequentially in 9 patients (3 normals, 1 mesial temporal epilepsia, 1 hydrocephalus, 1 recurrent anaplastic astrocytoma, 3 encephalopathies). Standard brain Tc99m-ECD SPECT (3 heads fan-beam collimator Toshiba GCA 9300HG; 120 ° rotation & 6°/1 min step) was followed by SPECT-TCT (simultaneous transmission and emission scan : 360 ° rotation & 4°/20 sec steps with a 5 mCi Tc99m transmission rod). Both acquisition were compensated for Compton scatter using the dual energy window and the scans were displayed in the same axes. Comparison between SPECT and SPECTTCT was performed blindly by two independant observers for 1) image quality and 2) ability to determine impact of underlying pathology. Transversal and coronal planes were displayed blindly (as A and B) and graded : 0- plane A better than B, 1- plane A equal to B and 2- plane B better than A. Repeated analysis was performed after knowing the clinical diagnosis. Both observers independantly noticed that TCT-SPECT improved image quality particularly at the level of the basal ganglia and the mesial temporal area. For the observer 1 and 2, TCT-SPECT was better than SPECT : 67% (12/18 planes) and 89% (16/18 planes), TCT-SPECT and SPECT were equal for 2/i8 planes and 0/18 while SPECT was better than TCT-SPECT for 4/18 and 2/18 planes respectively (TCT-SPECT was significantly better for the 2 observers, Chi-square: p<0.05 and p<0.001; differences between observers were not significant). The knowledge of the clinical diagnosis tended to improve image quality: TCT-SPECT was better : 67% (12/18) and 78% (14/18), it was equal to SPECT for 4/18 and 3/18 planes and SPECT was better for 2/18 and 1/18 planes. Discrepancies between observers were exclusively related to normal brain SPECT and 1 hydrocephalus. In all cases of focal abnormalities, TCT-SPECT was superior to SPECT. Attenuation compensation improves image quality, particularly for deep structures analysis and in presence of focal pathology.

K.K. Akerman l, J.T. Kuikka t, K.A. Bergstrtm 1'2, C. Halldin2, J. Hiltunen3, J. Tiihonen4, E. Lansimies1, L. FardJ. 1Kuopio University Hospital, Finland; 2Karolinska Institutet, Sweden; 3MAP Medical Technologies Oy, Finland; 4 Niuvanniemi Hospital, Finland. IODINE-123 LABELLED NOR-13-CIT AS A POTENTIAL TRACER FOR THE SEROTONIN TRANSPORTER IMAGING IN THE HUMAN BRAIN Iodine-123 labelled 2-13-carbomcthoxy-3-13-(4-iodophenyt)nortropane (nor-[3-CIT) is an analog of [3-CIT and has a high affinity for the serotonin transporter. In the present study initial SPET studies with [l123]nor-13-CIT were performed in 2 healthy male subjects. [I-123]nor-13CIT metabolism in plasma was also investigated. [I-123]nor-[3-CIT was prepared by a destannylation method which gave a specific radioactivity of higer than 180 GBq/~tmol. The SPET imaging was performed using a Siemens MultiSPECT 3 gamma camera with fan-beam collimators. The pattern of [I-123]nor-13-CIT metabolism in plasma was determined with a gradient HPLC method. The dynamic SPET studies demonstrated a high and rapid uptake of radioactivity in the brain (6%/tD at 30 min). Highest accumulation was observed in the striatum, the midbrain, and in the thalamus. Midbrainto-cerebellum (MB/CBL) ratio was 4.0 at 10 hours after injection of tracer, which is higher than that of [I-123113-CIT. Unchanged [I-123]nor13-CIT in plasma was 37% and 19% of total radioactivity after 1 and 3 hours, respectively. The high radioactivity in the midbraln is assumed to represent the accumulation of [I-123]nor-13-CIT in the serotonin transporter rich regions which indicates that [I-123 ]nor-13-CIT might be a potential tracer for visualization of serotonin transporter sites in the human brain with SPET.

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W.-G.Franke~ R.Freyer, H.-D.Gebaner, L.Oehme, T.Schmitt, Department of Nuclear Medicine and Institute of Biomedical Engineering, Dresden, University of Technology, Dresden, Germany

K.A. Bergstrtm ~'2, C. HalldinI, H. Hall l, C. Lundkvist~, N. Ginovart ~, C-G. Swahnl, L Farde ~. 1Karolinska Instituter, Department of Clinical Neuroscience, Stockholm, Sweden; 2Kuopio University Hospital, Kuopio, Finland.

IMPROVEMENT OF THE CLINICAL EVALUATION OF BRAIN PERFUSION STUDIES BY RESTORATION FILTERING This research work was aimed at the improvement of the clinical evaluation of brain SPECT studies with HMPAO using a restoration filter. Therefore an adaptive two-dimensional Kalman filter with an image quality and image structure dependent control was designed . Applied as a prereconstmction filter it delivers visually improved images by noise suppression and resolution recovery. In tests with scintigrams from the Jasczcak phantom and the 3D Hoffman brain phantom it was proved that small structures of about 10 mm become much better visible than without filtering. Thus the Kalman filter seems to be especially suitable to improve the detection and delineation of small scintigraphic defects localized within distinctly structured organs. Twelve brain SPECT studies froml l patients who were suspected of having not only diffuse but also circumscribed perfusion deficits (TIA, vascular abnormalities, inflammatory brain diseases, migraine) were selected for a previous study of restoration filtering. Image reconstruction was performed both from the original SPECT projections and from Kalman filtered projections. The results were visually compared and correlated with clinical and paraclinical findings. In 8/11 cases lesions were suspected but could not be surely proved in the unrestored images. However, these doubtful regions could be clearly identified as lesions in the filtered images. Furthermore the restored images appeared more distinctly structured. Cortex and white matter were better differentiated from each other. The preliminary results indicate that the Kalman filter is useful for a better delineation and identification of small intracerebrally localized scintigraphic defects. Supported by Deutsche Forschungsgemeinschaft

1090

I N VITRO AND IN VIVO CHARACTERIZATION OF NOR-~CIT:

A NEW RADIOLIGAND FOR VISUALIZATION SEROTONIN TRANSPORTER IN BRAIN

OF

THE

RadiolabeUed [3-CIT has been used in clinical studies for the imaging of monoamine transporters with SPET. 2~-carbomethoxy-313-(4-iodophenyl)nortropane (nor-~-CIT) is a metabolite of ~-CIT, which in vitro has a tenfold higher affinity (IC50=0.36 riM) to the serotonin transporter than 13-CIT. In the present study 1-125 and C-11 labelled nor-~-CIT were prepared for autoradiographic studies in vitro on the human brain and for PET studies in vivo on a Cynomolgus monkey. [I-125]nor-l~-CIT was prepared from the trimethyltin precursor by the chloramine-T method and [C-11]nor-13-CIT by O-methylation of the free acid with [C-I 1]methyl iodide. The specific radioactivities were 37 and > 80 GBq/gmol, respectively. Whole hemisphere autoradiography with [I-125]nor-I]-CIT demonstrated a high binding of radioactivity in the striatum, the thalamus and in cortical regions of the human brain. Addition of a high concentration (10 IxM) of citalopram inhibited the binding in thalamus and neocortex, but not in the striatum. In PET monkey studies there was a rapid uptake of radioactivity in brain (6% oflD at 15 min) and a high accumulation of radioactivity in the striatum, the thalamus and in neocortical regions. Thalamus-to-cerebellum (TI-I/CB) and eortex-to-cerebeUum (CX/CB) ratios were 2.5 and 1.8 at 60 min, respectively. The TH/CB and CX/CB were 20% and 40% higher, respectively, than those obtained with [C-11]I3-CIT. The radioactivity in the TH and CX was decreased by 20% after injection of citalopram (5 mg/kg). In conclusion, high accumulation of radioactivity, which was displaceable by citalopram, in thalamic and cortical regions in vitro and in vivo indicates that nor-13-CIT has potential for imaging the serotonin transporter in brain with PET and SPET.

[] Neurology/Oncology OTu234

OTu236

H. Hall 1, C. Lundkvist 1, C. Halldin 1, L. Farde 1, V.W. Pike 2, J.A. McCarron 2, I.A. Cliffe 3, A. Fletcher 3, T. Barf4, H. Wikstr6m4, and G. Sedvall 1. 1Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden, 2MRC CSC, Hammersmith Hospital, London, 3Cerebms Ltd, Ascot, U.K. and 4Department of Medicinal Chemistry, University of Groningen, Groningen, The Netherlands.

L. Farde, C. Halldin, C. Lundkvist, N. Ginovart, S. Nyberg, H. Hall, H. Itoh, C.-G. Swahn, A.A. Cart*, F. Jaquet** and F. Brunner**. Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden and Hoechst Marion Roussel, *Cincinatti, USA and **Fehraitorf, Switzerland.

AUTORADIOGRAPHIC LOCALISATION OF 5-HT]A RECEPTORS IN THE POST-MORTEM HUMAN BRAIN USING [H-3]WAY100635 AND [C-11]WAY-100635. The distribution of 5-HT1A receptors was studied in the normal postmortem human brain using whole hemisphere autoradiography "and the 5-HT1A receptor antagonist [H-3]WAY-100635 ([O-methyl-H-3]-N-(2(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclobexanecarboxamide trihydrochloride). The autoradiograms showed very dense binding to hippocampus, raphe nuclei and neocortex. The labelling in neocortex was slightly lower than in the hippocampus and was mainly at superficial layers. Other regions, such as the amygdaia, septum and claustmm, showed low densities of 5-HTIA receptors. There was no labelling in basal ganglia, in cerebellum or in other structures of the brain stem. The labelling of human 5-HT1A receptors with [H-3]WAY-100635 was inhibited by the addition of the 5-HT1A receptor agonists 5-HT, buspirone, pindolol or 8-OH-DPAT (10 gM). WAY-100635 was also radiolabelled with carbon-11 (T1/2 = 20 rain) in two different positions ([methyl-C-11] and [carbonyl-C-11]) and used for in vitro autoradiography on human whole hemisphere sections. [C-11]WAY-100635 labelled in any position gave images qualitatively similar to each other and to those of [H-3]WAY-100635, although with a lower resolution. Thus, the hippocampal formation was densely labelled, with lower receptor density in the neocortex. The in vitro autoradiography of the distribution of 5-HT1A receptors obtained with radiolabelled WAY-100635 provide detailed qualitative and quantitative information on the distribution of 5-HT]A-receptors in the human brain. Moreover, the autoradiograms obtained give complementary information for the interpretation of results obtained at lower resolution in humans with PET and [C-11]WAY-100635. These data provide a strong basis for expecting [C-11]WAY-100635 to behave as a highly selective radioligand in vivo.

[C-11]MDL 100907, A NEW PET RADIOLIGAND FOR SELECTIVE IMAGING OF 5-IlT2A RECEPTORS IN TIlE H U M A N BRAIN.

t~ eID

ID i.__

MDL 100907 ((R)-(+)-4-(1-hydroxy-l-(2,3-dimethoxyphenyl)methyl)N-2-(4-flurophenylethyl)piperidine) has high affinity (Ki = 0.36 nM) and selectivity for 5-HT2A receptors. The compound is currently in clinical trials. We report on the preparation of [C-11]MDL 100907, the autoradiographic localization of 5-HT2A receptors in the human brain using either [C-11]- or [H-3]MDL 100907, metabolite studies in monkey and human plasma with HPLC, a pharmacological characterization of [Cll]MDL 100907 binding by PET in Cynomolgus monkeys and human PET studies in three healthy subjects. The detailed distribution of 5-HT2A receptors was examined in the post-mortem human brain using whole hemisphere autoradiography. There was dense binding in the 5-HT2A receptor rich neocortlcal regions. After i.v. injection of [C-11]MDL 100907 in Cynomolgus monkeys there was a marked accumulation of radioactivity in neocortical regions. The neocortex to cerebellum ratio was about 4 after 60-80 minutes. Transient equilibrium occurred within 60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [C-11]MDL 1130907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. Three human subjects recieved [C-11]MDL 100907 and were examined by PET for 54-87 minutes. The neocortex to cerebellum ratio was 2.5 after 87 minutes. The fraction of radioactivity in monkey and human plasma representing [C-11]MDL 100907 was 15-25 (n=7) and 20-40% (n=3) at 60 minutes, respectively. [C-11]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.

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Oncology 0Su237

L. Farde 1 C, Halldin 1, V.W. Pike 2, C. LundkvistJ, N. Ginovart l, J.A McCarron 2, C.-G. Swahn 1, S. Osmana, I.A. Cliffe 3 and A. Fletcher3 ]Karolinska Institutet, Department of Clinical Neuroscience, Stockholm Sweden, 2Cyclotron Unit, MRC CSC, RPMS, Hammersmith Hospital London, U.K. and 3Cerebrus Ltd, Silwood Park, Ascot, Berkshire, U.K.

F. Scopinaro, O. Schillaci, W. Ussov*, G. De Vincentis, K. Nordling**, R. Danieli, M. Ierardi, R. Tavolaro, A. Centi Colella, Univ. "La Sapienza", Rome, I, **Gjevik Hosp. Norway, *Tomsk M.C., Siberia.

COMPARISON OF [METIIOXY-C-11]- AND [ C A R B O N Y L C-11]WAY-100635 BINDING TO 5 - H T I A RECEPTORS IN THE MONKEY BRAIN.

ACCURACY PRONE SCINTIMAMMOGRAPHY C E N T E R S T U D Y O N 305 P A T I E N T S

WAY-100635, (N- (2-(4-(2-methoxyphenyl)-1-pi~perazinyl)eth~l)-N-(2 p yridyl)cyclohexanecarboxamide) is a potent 5-HT1A receptor antagorest. Previously, labelfing in the methoxy position with C-11 provided the first radioligand for the delineation of 5-HT1A receptors in the human brain. Also the descyclohexanecarbonyl analogue ([C- 11 ]WAY- 100634) was shown to be a labelled metabulite in primates with high affinity to 5-HT1A receptors and high ability to enter the brain, so hampering the quantitation of the uptake of the radioligand in vivo. WAY-100635 has recently been labelled with C-11 in the carbonyl position. We now report a comparison of the binding of [methoxy-C-11]- and [carbonyl-C11]WAY-100635 to 5-HTIA receptors.in monkey brain by PET. PET studies were performed on Cynomolgus monkeys injected i.v. with either no-carrier-added [methoxy-C-11]- and [carbonyl-C-11 ]WAY100635. Each radioligand accumulated rapidly in brain (5% after 4 rain). There was a high accumulation of radioactavity in neocortical regions with frontal cortex tO cerebellum ratios reaching about 6 and 15, respectively, at 60 min. Transient equilibrium of specific binding was obtained at about 40 min. Pretreatment of the monkey with buspirone, pindolol or 8-OH-DPAT blocked 50-60% of [methoxy-C-11]WAY100635 specific bindifig whereas 8-OH-DPAT or WAY-635 blocked 80100% of [carbonyl-C-11]WAY-100635 spe.cific binding. There was a conspicuous accumulation of radioactivity in raphe nuclei and parahippocampus using [carbonyl-C-11]WAY-100635- giving ratios to cerebellum of 2-3 and 7-8, respectively. 5-HT1A receptor density was determined in a Scatchard analysis with high and low specific radioactivity of [carbonyl-C-11]WAY~100635. The Bmax and Kd in the frontal cortex was 16.7 pmol/ml and 1.6 nM, which is consistent with results reported from animal studies in vitro. Analysis of plasma showed that [carbonyl-C-11]WAY-t00635 gave only polar radioactive metabolites. Thus, the labelling of WAY-100635 m a position that avoided all lipophilic radioactive metabolites, including [C-11]WAY100634, provided a radioligand which is suitable for quantitative determination of 5-HT1A receptors in the primate brain in vivo.

t/l c=O m

(SM):

A

THREE-

We have performed a m u l t i c e n t e r study in Rome, Italy, Tomsk, siberia and Gjovik, Norway,in order to assess the accuracy of SM in detecting breast cancer. All the centers used the technique proposed by Khalkhali. Data were c o l l e c t e d and r e v i e w e d in Rome. 305 patients (247 cancers) were studied. SM was performed w i t h i n 1 w e e k after X-ray m a m m e g r a p h y (XM) and 1-2 days before surgery. The results are summarized in the table. Sizing of the tumors was always pathological. BENIGN CANCERS -~stol. T2 Tlc Tlb Tla Scint.~ MIBI+ 3 I00 83 22 ii MIBI55 3 4 12 12 The specificity was 96.7. When stratified a c c o r d i n g with the tumor size the sensitivity of SM was 97.1% for T2 cancers, 95.4% for Tlc, 64.7% for Tlb, 47.8% for Tla. Noteworthy no significant d i f f e r e n c e in a c c u r a c y was noted among the three centers. Our data suggest that SM should always be used when XM shows lesion larger than i cm: in these patients the diagnosis of m a l i g n a n c y is a c h i e v e d with an a c c u r a c y of 96%. If the size of the lesion is smaller, SM p r o v i d e s the diagnosis in more than 50% of cases. The biopsy is still necessary when SM is negative. SM is an easy and reliable method that can be performed with similar results by different N.M. centers and accepted in various countries despite very different organization of public health services.

Q. m

t~

8

• Oncology 0Su238

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J.Soares Jr, AP.Costa Filho, R.TLima, M.A.Oliveira~ A.CSDBarros, AZSouza, J.APinotti, MCPGiorgi, M.Izaki, G.G.Cerri, J C.Meneghetti. Heart Institute University of S~o Paulo Medical School, Department of Nuclear Medicine, Brazil

R.G6mez-Barqu~n, R.Quirce, I.Blanco,I.Uriarte, A.Vega, I.Banzo, J.M.Carril. SERVICIO DE MEDICINA NUCLEAR. HOSPITAL UNIVERSITARIO M°VALDECILLA. SANTANDER. ESPA~A.

99mTc-SESTAM1BI IN THE EVALUATION OF LYMPHATIC DRAINAGE IN BREAST CANCER Scintimammography with lymphatic drainage study was performed in 19 females and 1 male with histologycal diagnosis of breast cancer, followed by axillary lymph node emptying. The goal of this study was to compare histologycal findings with scintimammographic data. Anterior, lateral and posterior oblique images were acquired ] h after intravenous injection of 740 MBq 99m Tc-Sestamibi, using a conventional gamma-camera with 128x128 pixels matrix. Axillary, mediastinal and clavicular lymphatic drainage were analysed by two nuclear physicians without previous knowledge of histologycal findings.Eighty percent (16 patients) showed axillary lymph node metastasis in histologycal examination Seventy-five percent of them (12 patients) had positive scintigraphies. From the total, 20% of the patients (4) had negative scan and histopathologycal data. The following values were found: sensitivity 75%, specificity 100%, positive predictive value 100%, negative predictive value 50% and accuracy 80%.These results suggest that the method has high specificity and positive predictive value in the detection of axillary lymph node involvement in breast cancer. It could be a useful tool in pre-operative staging and in the follow-up after therapeutic approach.

0Su239 ~ , H.Sommer, R.Moser, M.Pechmann, G.Meyer, Th.Pfluger, K.Tatsch, K.Hahn Departments of Nuclear Medicine, Radiology and Gynecology Ludwig-Maximilians-University of Munich, Germany THE ROLE OF SESTAMIBI SCINTIMAMMOGRAPHY AND GADOLINIUM ENHANCED MRI IN THE EVALUATION OF MICROCALCIFICATIONS DETECTED BY MAMMOGRAPHY.

Purpose of this study was to define the preferable diagnostic strategy in patients with unclear microcalcifications detected in routinely performed mammography. In this prospective study 44 patients with mammographically detected indeterminate microcalcifications underwent both scintimammography (SM) using Tc-99m sestamibi and Gd-enhanced MRI. Prone scintimammography was done 5 and 60 min after injection of sestamibi. Dynamic MtLI was performed with a surface coil using gradient echo sequences before and after the administration of GdDTPA. In scintigrams focal sestamibi uptake was scored visually and compared with the contrast behaviour in MRI as the major criterion for malignancy. All patients subsequently underwent surgery. The results are listed in the table below: Malignant (carcinoma) Benign ductal ductal lobular masto- fibroscar invasive in situ invasive pathy adenoma SM pos/neg 7/1 4/1 1/1 3/21 0/1 1/3 MRI pos/neg 8 / 0 4/1 1/1 12/12 0/1 1/3 Sensitivity and specificity of scintimammography was 80% and 86%, respectively. MILl provided a higher sensitivity (87%), but a considerable lower specificity (55%). In conclusion our findings suggest, that in patients with mammographically detected unclear microcalcifications the high number of biopsies yielding benign results can be reduced, if scintimammography is preferred as the additional diagnostic method. However, for the planning of the adequate therapeutic management the occurrence of false negative sestamibi findings may not be neglected. Due to the lower specificity of MRI resulting from Gd-uptake in different benign lesions MRI should not be used in this particular situation.

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99mTc-MIBI SCINTI/4M~OGRAPHY AND MAk~4OGRAPHICAL P R O B A B I L I T Y OF M A L I G N A N C Y IN THE D I A G N O S I S OF NONPALPABLE B R E A S T LESIONS. Mar~nography(MG) is the accepted technique to detect non-palpable lesions and to select patients for histological evaluation. However, its low specificity and positive predictive value, involves a high number of false positives and therefore the addition of scintiman~ography (SMM) has been suggested to reduce the number of unnecessary biopsies. We present an evaluation of SMM contribution in a group of 36 non-selected patients with non-palpable lesions which required histological confirmation. According to the man~ographical signs the probability of malignancy was: high(14)(HP), intermediate(15)(MP) and low(7)(LP). S M M w a s done whithin 3 days after MG. AP and prone lateral views were taken i0 minutes after injection of 740 MBq of 99mTc-MIBI. Definitive diagnosis was 17 malignant and 19 benign lesions. Of the 17 malignant, in 14 SMM was positive(S=82%), and of the 19 benign l2 were negative. On the other hand, 13 of the 14 with HP on MG were malignant and 2 of them were MIBI-negative. Of the 15 with MP on MG, 12 were benign and 3 malignant and SFIM correctly detected 8 of the 12 benign and 2 of the 3 malignant. Of the 7 with LP, SMMcorrectly identified 4 of the 6 benign and the one malignant. Therefore, altogether of the 22 with MP and LP there was only one false negative for SMM, and 12 out of 19 benign(63%) were correctly identified as true negative. According to these results, the addition of MIBI-SMM to MG is of limited value when MG shows a HP of malignancy. However, MIBI-SMM is of great value in the evaluation of lesions with MP and LP of malignancy on MG and may allow the reduction of 63% of unnecessary biopsies indicated b y M G .

0Su241 V. Ivancevic, S. Marnitz, E. Wandke, I. Reisinger, and D.L. Munz. Clinic for Nuclear Medicine, Charite, Humboldt University, Berlin, Germany PHANTOM STUDY ON THE VALIDITY OF THE TUMOUR/BACKGROUND RATIO IN PLANAR PRONE SCINTIMAMMOGRAPHY The t u m o u r / b a c k g r o u n d ratio (TB) in planar scintimammography (SM) is often used in order to separate malignant from benign tumours. We investigated the validity of the TB for SM by phantom measurements. Three spherical tumour phantoms (6.4, 9.2, and 24.4 ml) and 3 breast phantoms in pairs (250, 500, and 750 ml) filled with 80 and 12 MBq/I Tc-99m solution, respectively, were used. Imitating lateral views in prone scintimammography, each of the tumour phantoms was imaged in each of the breast phantoms in 3 different positions (lateral, central, medial). In addition, all the tumour phantoms were imaged in the largest breast phantom in 7 different positions increasing the tumourto-detector distance by 1 cm per measurement. TB calculated as count densities ranged from 1.29 to 2.72 and increased with tumour volume (KruskalI-Wallis, p
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J.L. Moretti, M. Duran Cordobes, V. De Beco, B. Boissier, J.C. Kouyoumdjian, S. Chevillard, A. Starzec. Biophysique et Biosignaux EA449. Institut d'Oncologie Cellulaire et Mol6culaire Humaine, Bobigny-Paris 13 ; Henri Mondor Cr6teil, Institut Curie France.

E. Bombardieri, F. Crippa, R. Agresti, M. Greco, C. Pascali, A. Bogni, C. Chiesa, V. De Sanctis, D. Decise. lstituto Nazionale per lo Studio e la Cura dei Tumori, Milan (Italy).

o

MRP 190 AND MDR Pgp 170 IN H U M A N C A N C E R CELL LINES : T H E I R I N F L U E N C E ON Tc-99m S E S T A M I B I

UPTAKE Acquisition of multidrug resistance to chemotherapy has been associated with increased levels of the mdrl gene product (P-glycoprotein:Pgpl70) and recently with overexpression of 190 kD multidrug resistance associated protein (MRP), a putative transporter glycoprotein. Pgp induces an increase cellular efflux of drugs. Tc99mSestamibi (MIBI) is known to be a substrate for Pgp. To explore wether MIBt was also bound by the 190 kD protein,we studied its uptake at 4°C and 37°C by human cancer cell lines: MRP+/MDR- (A 549 Lung adenoca; KB 3.1 mouth ca.; and MCF7breast ca) and MRP+/IVIDR+ (MCF7 MDR+breast ca; and KB A.1 epidermoid mouth ca).MRP and mdrl genes expression we are determined by reverse transcriptase-polymerase chain reaction. Tc-99mMIBI radioactivity incorporation into the cells was determined after different times of incubation at 37°C. Results presented here are the percentage of radioactivity added after 90rain of incubation. Type of MRP+/MDRMRP+ MRPresistance MDR+ MDR+ Cell lines MCF7 I A549 ] KB3.1 KBA1 MCF7 MIBI uptake at 37°C 13.9-2_ ] 7.9-&-_ I 12.1+ 0.6+ 0.7+ n=6 X_+.sd% 1.9 0.8. 0.6 0.05 0.6 At 4°C MIBI uptake was 0.84+0.44%for MRP+/MDR- cell lines. In conclusion, these preliminary results demonstrated that MIBI efflux was not mediated through the MRP 190 kD as it was for Pgp 170 kD, conferring to MIBI a specificity for multidrug resistance mediated by Pgp 170.

The aim of the study was to evaluate the diagnostic accuracy of PET imaging in the pre-operative detection of locoregional lymph node metastases (M+) in patients (10ts) with breast tumors. To date, 40 pts, scheduled for surgery, have been pre-operatively studied using a PET scanner (General Electric 4096 Plus) 30 minutes after i.v. injection of 18 400 MBq of [ F]Fluorodeoxyglucose (FDG). The PET images were visually evaluated for the presence of increased FDG uptake i n t h e primary mrnors and the locoregional lymph nodes. Moreover, parametric SUV images were generated to obtain semi-quantitative evaluation of the FDG tumor uptake. The PET results were compared to the post-operative histological timings. Twenty-eight of the 40 examined pts are currently evaluable: 4 pts with already operated primary tanrors scheduled for axillary dissection, 22 pts with newly detected primary tumors (3 with bifocal cancer and 2 with bilateral cancer, total number of breast cancers 27) and 2 pts with supraclavicular metastases. All 27 primary tumors but 2 (non-invasive ductal carcinomas; size 5 ram) were detected with PET; SUV was 5.1 41.7 (mean ± S.D.) in 9 tumors with M+ and 3.4 ± 1.9 in 16 tumors without M+. PET detected all the M+ (9 axillary M+ and 2 supraclavicular M+); PET was negative in 18/19 patients without M+. In conclusion, FDG-PET seems to have a very high diagnostic accuracy in M+ detection of breast cancer.

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S. Del Vecchio, A. Ciarmiello, M.I. Potena, M.V. Carriero, G. D'Aiuto, T. Tsuruo, M. Salvatore. Centro Medicina Nucleate CNR, Istituto di Scienze Radiologiche Universita' "Federico II" and Istituto Nazionale Tumori, Napoli, Italy.University of Tokyo, Tokyo, Japan.

H. Bender, J. Kirst, A.S. Schomburg, H. Palmedo, K. Hamad, C. Menzel, E. Klemm, F. Gmenwald, J. Ruhlmann, and H.-J. Biersack. Dept. Nuclear Medicine and PET-Center of the University of Bonn, Germany.

Since 99mTc-SESTAMIBI is a transport substrate recognized by the multidrug-resistant P-glycoprotein (Pgp), we tested whether tumors with initial accumulation of 99mTc-SESTAMIBI show different rates of tracer efflux depending on the relative concentration of Pgp within the tumor. We determined the effiux rates of 99mTc-Sestamibi and Pgp levels in tumors of 30 patients with untreated breast carcinoma. Patients were i.v. injected with 740 MBq of 99mTc-SESTAMIBI and underwent a fifteen-minute dynamic study followed by static planar images at 0.5, 1, 2 and 4 hours. All breast carcinomas showed high uptake of 99mTcSESTAMIBI and region of interest analysis was performed on serial images. Decay corrected time-activity curves were generated and the efflux rates were calculated using a monoexponential fitting. Surgically excised tumors were obtained from each patient and Pgp levels were determined using 125i_labele d MRK16 monoclonal antibody and in vitro quantitative autoradiography. For comparison 6 benign breast lesions were also tested. The efflux rates of 99mTc-SESTAMIBI ranged between 0.00121 and 0.01690 rain -1 and were directly correlated with Pgp levels measured in the same tumors ( r = 0.62 ; p < 0.001). Ten out of 30 breast carcinomas (33 %) contained 5 times more Pgp than benign breast lesions and showed a mean concentration of 5.73 + 1.63 pmol/g of tumor (group A ). The remaining 20 breast carcinomas had a mean Pgp concentration of 1.29 + 0.64 pmol/g (group B ) equivalent to that found in benign breast lesions. 99mTc-SESTAMIBI efflux from tumors of group A was 2.7 times higher than that observed in tumors of group B (0.00686 -+ 0.00390 min -1 vs 0.00250 -+ 0.00090 rain -1, p
= m

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L O C O R E G I O N A L STAGING OF PRIMARY BREAST C A N C E R W I T H FDG-PET: PRELIMINARY RESULTS.

Acknowledgement_ This work was partially supported by an AIRC grant (N ° 420.198.542)

9 9 m T c - S E S T A M I B I SCAN FOR FUNCTIONAL IMAGING OF MULTIDRUG-RESISTANT PHENOTYPE IN UNTREATED BREAST CANCER PATIENTS.

r.

RESTAGING OF RECURRENT BREAST CARCINOMA: ROLE OF WHOLE-BODY FDG-PET

Whole-body positron-emission tomography (PET) employing fluoro18-deoxyglucose (FDG) is increasingly used in cancer patients (pts). We studied a total of 86 pts.suffering from breast carcinoma (BC) that were refered for restaging. We employed a routine multiple (3-6) bed position protocol, with 10-min emission and 10-min transmission acquisitions per bed position, starting 45-60 min after i.v. injection of 266 MBq FDG (range, 181-363); mean blood sugar levels were 4.83 (2.87-9.9) mmol/L. At this time, 56 pts have been completely evaluated. Primarily, lesions were visually graded depending on the intensity of uptake (intense = malignant; moderate = suspicious; minimal = unspecific/inflammation; normal uptake = normal). In addition, semiquantitation using body-surface corrected standardized uptake values was performed but not yet included in the diagnostic evaluation. PET findings were compared with histology and CT/MRI results. The majority (n=48) of pts had known BC and were refered for restaging; 7 pts. were studied for suspicious clinical or mammographic findings, in 1 10t., BC was histologically proven (PET false negative), while 6 pts had histologically benign disease (PET 4 true negative, 2 false positive). In 48 pts., PET correctly confirmed the absence of distant disease in 15 pts and yielded false positive findings in 7 pts. In 26 pts with advanced BC, PET showed 23 true positive findings (axillary lymph nodes, 15 pts; bone, 9 pts; lung, 4 pts; liver, 2 pts; soft tissue, 10 pts) and missed distant metastases (local recurrence, soft tissue) in 3 pts.: overall diagnostic accuracy 79% (sensitivity, 77%; specificity, 83%). Comparing PET vs. CT/MRI findings, major differences were found in the detection rate of lymph-node-, liver- and bone metastases (PET>>CT/MRI), and soft-tissue tumors (PET
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0Su248 A.Chiti, R.Agresti, G.Savelti, R.Giovanazzi, L.Maffioli, M.Greco, E.B0mhardieri.

Division of Nuclear Medicine and Surgical Oncology "B '" Istituto Nazionale Tumori, Milano, Italy BREAST CANCER STAGING WITH In- 111-PENTETREOTIDE (OCT) AND Te-99m-SESTAMIBI (MIBI) Aim of the study was to assess the role of OCT and MIBI in evaluating axillary node involvement in breast cancer. 15 female patients (mean age 53.9 years) with clinical and radiological findings of T1-2N0-1 breast cancer were studied. Patients were i.v. injected with 925 MBq of MIBI and 4 hours later with 225 MBq of OCT. SPET images were acquired 20 min after MIBI injection, 4 and 24 hours after OCT injection, using a dual-head gamma camera. The day atter the 24 hour OCT acquisition quadrantectomy or mastectomy with axillary dissection was performed. Pathological examination revealed 16 tumors in 15 patients, with 1 bilateral neoplasm. The mean tumor diameter was 18.7 nun and metastatic lymph nodes were found in 6/16 tumors, with a mean of 5 metastatic nodes per axilla. Both radiopharmaceutieals correctly identified 15/16 primary tumors and 5/6 metastatic axillae. We found no significant difference between the 2 tracers in tumor and metastases visualization. MIBI seems to be superior in terms of physical characteristics, execution time and cost/effectiveness. This study suggests preoperative scintigraphic evaluation may avoid axillary dissection in patients with T1 breast cancer. Moreover, the tumor/background ratio of MIBI was significantly higher in tumors lacking estrogen receptors and in those with a high Mib-1 value, suggesting this tracer may also give information on tumor biology.

Bohuslavizki K.H., Brenner W., Bolling C., Lehmann-Willenbrock E.,

Brinkmann G., Wolf H., Sippel C., Clausen M., Henze E. Clinics of Nuclear Medicine, GynecoIogy and Obstetrics and Diagnostic Radiology, Universitiy of Kiel, Germany SCINTIMAMMOGRAPHY USING TC-99M-TETROFOSMIN IN PREOPERATIVE WORK-UP OF BREAST CANCER Technetium-99m labelled perfusion tracers as MIBI and tetrofosmin are commonly used in myocardial imaging. Moreover, both tracers are used successfully in diagnostic work-up of patients with various malignancies. Therefore, we designed this study to evaluate the usefulness of Tc-99m-tetrofosmin in pre-operative work-up of patients suffering from breast cancer. 30 patients with suspicious nodules of the breast diagnozed by sonography, mammography, MRI and fine needle aspiration biopsy were surgically treated. Final histological diagnosis revealed breast cancer in 26 patients and fibroadenoma in 4 patients. In addition, mammoscintigraphy was performed preoperatively 1 hour after injection of 600 MBq Tc-99m-tetrofosmin. Whole body scans and lateral views of both breasts were obtained in prone position with elevated arms. For quantification T/B-ratios were calculated by conventional ROI technique from lateral views. In primary tmnours mammoscintigraphy was true positive in 16126 patients corresponding to a sensitivity of 61%. The smallest true positive (TP) tumour was 0.6 cm in diameter, the largest false negative (FN) was 2.0 cm in diameter. In 3/4 patients with fibroadenoma mammoscintigrapyh was true negative corrsponding to a specificity of 75 %. T/B was 1.42-+0.13 and 1.11+0.07 in TP and TN patients, respectively. Mammoscintigraphy was true positive in 2/9 histologically verified axillary lymph node metastases. In conclusion, in this study with limited number of patients mammoscintigraphy using terofosmin provides no additional information to the diagnostic methods routinely applied.

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S.Taucher. A.Kurtaran, M.Leimer, P.Angelberger, Th.Pangerl, M.Beck, M.Gnant, R.Jakesz, I.Virgolini Departments of Nuclear Medicine and Surgery, University o f Vienna

H. Ya~clo~lu, S. ibi~ * S. NaldOken Ankara Numane Hospital, Department of Nuclear Medicine and Radiodiagnostic* Samanpazan- Ankara - TURKEY.

VASOACTIVE INTESTINAL P E P T I D E ( V I P ) AND SOMATOSTATIN (SST) R E C E P T O R S C A N N I N G IN PRIMARY BREAST CANCER

DIFFERENTIATION OF MALIGNANT AND BENIGN BREAST MASS USING Tc99M-TETROFOSMIN: COMPARISON WITH MAMMOGRAPHY, ULTRASONOGRAPHY AND BIOPSY.

R e c e n t i n - v i t r o s t u d i e s s u g g e s t that a s i g n i f i c a n t proportion o f human breast tumors express VIP and/or SST receptors. The aim o f this study was to investigate and c o m p a r e the p o t e n t i a l value o f VIP and SST r e c e p t o r s c a n n i n g in patients with breast cancer. 24 patients with histologically confirmed diagnosis of p r i m a r y b r e a s t c a n c e r w e r e a d m i n i s t e r e d 123I-VIP (150 MBq, 1 ug) and/or 1111n-DTPA-D-Phe-1octreotide (OCT, 150 MBq, 10 ug) allowing a 6-hour time interval b e t w e e n both scintigraphies. Planar and SPECT acquisitions were performed up to 48 hours p.i. In vivo results were c o m p a r e d with in vitro b i n d i n g data in tumor s a m p l e s obtained after removal o f the primary. In 4 o f 19 patients (21%) 1231-VIP receptor scanning indicated the primary breast tumor, whereas l l l l n - O C T identified the tumor in 20 o f 22 patients (91%). Positive VIP s c a n s c o r r e l a t e d w i t h n e g a t i v e e s t r o g e n and p r o g e s t e r o n receptor status, whereas no correlation was found for OCT scans. Positive OCT scans were based on the e x p r e s s i o n o f SSTR2 s u b t y p e as i n d i c a t e d by Northern blotting in primary tumors (n=5). We conclude that the c o m b i n e d use o f 123I-VIP and l l l l n - O C T in patients with primary breast cancer may be an indicator for the patient's prognosis prior to surgery.

The aim of this study was to assess the value of Tc99m-tetrofosmin in the detection of breast carcinoma and the differentiation of malignant from benign lesions. In this respect we studied in 50 pts presenting with a palpable breast mass. Within a week period; scintigraphy, USG and mammography were performed in all patients. Twenty mCi Tc99m-tetrofosmin was injected in the arm contralateral to the breast with abnormality Planar views at 10 and 60 min postinjection using anterior and lateral views of the chest were obtained. Definite diagnosis were made base on the histopathologic results. Radioactivity accumulations were detected in 41 pts. False positive images was obtained in 2 patient. One of them was reported as fibroadenoma and other on was chronic inflammation. Mammographic evaluation showed high suspicion for malignancy in 33 pts. Histopathologic results demonstrated malignant breast lesion in 39 pts and benign pathologies in 11 pts. For detection malignancy sensitivity and specificity values for scintigraphy and mammography were found as 100 %, 82 % and 85 % and 73 % respectivly. Also we demonstrated no differrences tetrofosmin uptake between early and late images. Tetrofosmin showed superior results in regard to radiology. We concluded that this agent is a useful tumuor imaging agent to diffrentiate malignant from benign lesions.

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L Mansi, PF Rambaldi, V Cuccurullo, B Pecori, A Laprovitera, F Di Gregorio, E Procaccini. Inst of Radiology, Inst of E x p e r i m e n t a l Surgery; II Univ. Naples.

S. Piccolo, S. Lastoria, P. Muto, C. Carac~, G. D'Aiuto, R. Thomas, M R Rubulotta, G. Botti, M. Salvatore. N a t i o n a l C a n c e r I n s t i t u t e a n d N u c l e a r Medicine Center C.N.R., Napoli.

Tc-99m TETROFOSMIN COMPLEMENTARY ROLE CANCER.

SMM WITH MAMMOGRAPHIC

IN

SCINTIMAMMOGRAPHY: THE DIAGNOSIS OF BREAST

co |m 4-a

Tc-99m MDP IN THE MICROCALCIFICATIONS

STUDY OF WITHOUT

A i m of our s t u d y has b e e n to individuate the possible role of Tc99m Tetrofosmin mammoscintigraphy in diagnosis of patients a f f e c t e d w i t h b r e a s t cancer. MATERIALS ~ METHODS: F o r t y - s e v e n p a t i e n t s (2374 years, m e a n age 51) p r e s e n t i n g 55 breast lesions and ten normal controls were included into the study. At m a m m o g r a p h y (Mx), 22 lesions were diagnostic for cancer (ca), 9 were s u s p e c t e d for ca and ii h a d a b e n i g n pattern. M x was not diagnostic in 13 cases because of m a s t e c t o m y or dense breasts. All w o m e n were injected with 555 740 MBq of 99mTc-TF (Myoview, Amersham International, UK). Five m i n u t e s scans or at least 1.5 m i l l i o n counts were o b t a i n e d u s i n g a large field of v i e w gamma camera (Orbiter 75, Siemens, Erlangen-Germany) w i t h a l o w - e n e r g y h i g h - r e s o l u t i o n collimator. P l a n a r images were a c q u i r e d in supine anterior, p r o n e lateral and in lateral in recumbence. RESULTS: A c l e a r u p t a k e of T c - 9 9 m t e t r o f o s m i n was evident in 35 out of 37 m a l i g n a n t lesions individuated (sensitivity 94.5%, specificity 100%). No false p o s i t i v e r e s u l t s were observed. L y m p h node u p t a k e was o b s e r v e d in 15 out of 16 patients presenting lymph node metastases (sensitivity 93.7%), including five cases without clinical signs. The internal m a m m a r y c h a i n i n v o l v e m e n t was a l s o s e e n in one case. DISCUSSION: Our s t u d y s u g g e s t s that TF can be utilized in diagnosis of breast carcinoma, recurrence and in lymph node involvement detection, e v e n in those cases that can not be evaluated with mammography.

M A S S . T h e m a m m o g r a p h i c (MMx) e v i d e n c e of i s o l a t e d or c l u s t e r e d m i c r o c a l c i f i c a t i o n s w i t h o u t p a l p a b l e mass is not highly specific for breast cancer (BC) r e q u i r i n g an e x c e s s of d i r e c t b i o p s i e s for the final diagnosis. This is a c h a l l a n g i n g s i t u a t i o n to test the potential benefits of scintimammography (SMM) w i t h T c - 9 9 m M D P for c l i n i c a l practice. We h a v e p e r f o r m e d S M M in 67 women presenting a MMx pattern of m i c r o c a l c i f i c a t i o n s w i t h o u t p a l p a b l e mass. The p a t i e n t s w e r e i m a g e d i0 m i n a f t e r i n t r a v e n o u s i n j e c t i o n of 740 M B q of T c - 9 9 m NDP u s i n g lateral views of b o t h glands in prone position. B y MM_x the m i c r o c a l c i f i c a t i o n s w e r e c l a s s i f i e d as follows: granular 35, p u n c t a t e 16, b r a n c h i n g 9, anulaz 2, and linear 5. By histology BC was d i a g n o s e d in 41 (21 DCIS, 8 i n f i l t r a t i n g ductal ca., 7 m i x e d ca., 4 LCIS, 1 i n f i l t r a t i n g l o b u l a r ca.) and b e n i g n d i s e a s e s in 26 l e s i o n s (20 f i b r o c y s t i c changes, 3 w i t h severe atypia, 2 p a p y l l o m a t o s i s and 1 chronic inflammation). All different m i c r o c a l c i f i c a t i o n types w e r e a s s o c i a t e d e i t h e r w i t h m a l i g n a n t or b e n i g n lesions. SMM w a s truly p o s i t i v e in 38 out of 41 BC (Sens. 93%) a n d truly n e g a t i v e in 23 out of 26 b e n i g n l e s i o n s (Spec. 8 8 % ) . T h e a c c u r a c y w a s 91%, the p o s i t i v e and n e g a t i v e p r e d i c t i v e values (PV) were r e s p e c t i v e l y 92 a n d 88%. The P P V of S M M w a s s i g n i f i c a n t l y h i g h e r than that c o m m o n l y r e p o r t e d for MI~, w h i c h ranges b e t w e e n 20 and 40%. Thus, SMM m a y be very h e l p f u l in b e t t e r c h a r a c t e r i z i n g s u s p i c i o u s N]Vix c a l c i f i c a t i o n s w i t h o u t m a s s a n d in r e d u c i n g the excess of unnecessary biopsies.

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V Bong~r~, AJ van Dongen, R Pijnappel*, DMDS Sie-Go#, IHM Borel Rinkes@, PP van Rijk. Departments of Nuclear Medicine, Radiology', Pathology# and Surgery@, Utrecht University Hospital, The Netherlands. 99mTc-Myoview® Scintigraphy in the Diagnosis of Suspected Breast Cancer: Preliminary Results. Introduction: The routine mammogram remains the procedure of choice for screening women for breast cancer. However, in many cases intraoperative biopsies are required to differentiate benign from malignant lesions. Therefore, new radiopharmaceuticals, including 99mTc-tetrofosmin (Myoview~), are under investigation to enhance the pretest probability before fine needle aspiration. Patients and methods: In an ongoing study eight palpable breast lesions with mammographic or ultrasonographic suspicion of malignancy were evaluated in eight patients with a mean age of 42 + 16 yrs. An amount of 700 MBq 99mTc-Myoview® (Amersham International plc) was injected in the antecubital vein opposite to the side of the breast lesion. 30 minutes after injection planar breast images were successively performed in supine position (anterior view), and in lateral position (right and left lateral views), in addition, 75 minutes after injection a SPECT of the thorax was obtained in supine position. Images were acquired with the ADAC Vertex dual head gamma camera using high resolution collimators. Excision biopsy or mastectomy with axillary dissection was done in all patients. Resu/ts: Three of the 3 primary breast turnouts, ranging between 16 and 29 mm, were detected (all invasive ductal carcinomas). In addition, in one patient an axillary lymph node metastasis with a diameter of t 1 mm was detected during scintigraphy, which was later shown to be the only malignant node out of 17 nodes obtained with an axillary dissection. The other 2 patients did not have positive lymph nodes scintigraphically and in the axillary dissection preparation. None of the five patients with histopathological[y proven benign lesions demonstrated 99mTc-Myoview® accumulation in the turnout (5 fibroadenomas) or axilla. The SPECT images of the thorax did not give any additional information to the planar images. Conclusion: The initial results with 99mTc-Myoview® in patients with otherwise equivocal breast lesions are very promising. Thusfar a correct diagnosis was made for all eight benign and malignant turnouts. Moreover, 99mTc-Myoview® seems to have potential for the detection of small positive axillary lymph nodes.

H. Wolf, B. Frieling, C. Nacke, K. Kaiser, K. H. Bohuslavizki, W. Brenner, S. Tinnemeyer, U. Teichert, M. Clausen, E. Henze Clinic of Nuclear Medicine, Christian-Albrechts-University of Kiel, Germany TC-99M TETROFOSMIN ACCUMULATION IN SENSITIVE AND MULTIDRUG RESISTANT TUMOUR CELLS WITH AND WITHOUT VERAPAMIL A major problem in cytostatic treatment of many turnouts is the development of multidrug resistance (MDR). It is the purpose of this study to prove whether Tc-99m tetrofosmin is also recognized by human p-glycoprotein like sestamibi. Measurements were performed in human drug-sensitive breast and gastric carcinoma cells and in MDR-resistant cells of breast, gastric (2 different cell lines) and pancreatic carcinoma. 10 kBq of Tc-99m tetrofosmin were given with an incubation time of 1 h. Further experiments were done by addition of verapamil, a classical MDR modulator. The cellular uptake was expressed as % of activity added, normalized to 1 million cells. All results are given as mean + 1 s.d. (n = 10 each). In breast carcinoma ceils the 1 h-uptake of 1,76 _+0,10 % is significantly decreased to 0,97 _+ 0,03 % in the resistant variant. In gastric carcinoma cells similar results are seen: the uptake of 1,58 _+0,05 % is reduced to 0,71 _+0,08 % resp. 0,45 + 0,06 % in the resistant cells. Addition of verapamil did not affect the uptake in the sensitive cells, but greatly increased accumulation in the resistant cells. We found an 1,53 fold higher uptake in the resistant breast resp. 1,38 fold in the resistant pancreatic carcinoma cells after addition of verapamil. These results are qualitatively similar to our results with sestamibi in these cells. In conclusion, Tc-99m tetrofosmin is recognized by p-glycoprotein like sestamibi and it seems to be a potential tracer for functional imaging of multidrug resistance in various tumours in-vivo. 1095

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L J . M . Riiks, G. van Tienhoven, L.A. Noorduyn, K. de Bruin, G.L Boer, A.G.M. Janssen, E.A. van Royen, Depts. of Nuclear Medicine, Radiation Oncoiogy, and Pathology, Academic Medical Centre, Amsterdam, The Netherlands; Cygne BV, Technical University, Eindhoven, The Netherlands.

M.H.G.C. Kranenborg, E. Oosterwijk, O.C. Boerman, M.G. Steffens, M.C.A. de Weijert, I.C. Oosterwijk, F.H.M. Corstens Departments of Nuclear Medicine, and Urology, University Hospital Nijmegen, The Netherlands

In previous studies the Z-isomer of l lg-methoxy-17o~-[I-123]iodovinylestradiol (Z-[I-123]MIVE) showed high estrogen receptor binding in both rat and human mammary turnout tissue in vitro as well as high estrogen target tissue uptake selectivity in rat in vivo. This study investigated the potential of Z-[I-123]MIVE as diagnostic imaging agent of primary breast cancer. In healthy human volunteers Z-[I-123]MIVE showed low lung retention, rapid hepato-hiliary excretion and diffuse uptake in normal breast tissue. For l I women with primary breast lesions (age 47 - 79 years) anterior and posterior whole body scans were made at 1, 2, 4 and 6 h after i.v. injection of 150 MBq Z-[I-123]MIVE (SA 200 MBq/nmol). Also spot planar and SPECT images of the thorax were performed at various time points. Regions of interest were drawn to calculate the lesion-to-nonspecific uptake ratios. Low lung uptake and rapid hepato-biliary excretion resulted in favourable imaging conditions for the thoracic region. Focal accumulation of Z-[I123]MIVE was detected in the primary breast lesions. The lesion-tononspecific uptake ratios at 2 - 3 h after injection were in the range of 1.3 to 2.9. All lesions were already visible on the whole body images. Interestingly, in two patients no Z-[I-123]MIVE accumulation could be detected in scintigraphically suspected bone lesions. Further radiological examination (CT) revealed indeed no metastatic disease. On the contrary, a radiologically confirmed bone metastasis was recorded correctly by the Z-[I123]MIVE scan. Receptor specificity of tumour uptake of Z-[I-123]MIVE was established in 3 patients who were studied a second time 2 to 3 weeks after initiation of anti-estrogen (tamoxifen) treatment. Uptake of Z-[I123]MIVE in the primary breast lesions was completely blocked by the antiestrogen, which indicates that the tumour uptake of Z-[I-123]MIVE is indeed estrogen receptor-mediated. In conclusion, Z-[I-123]MIVE accumulates specifically in primary breast carcinomas.

T U M O R ANTIGEN SATURATION W I T H ANTI-RCC M O N O C L O N A L ANTIBODIES IN NUDE MICE W I T H RCC TUMORS The choice of an adequate antibody dose is essential for optimal radioimmunotherapy. Therefore, the effects of anti-renal cell carcinoma (RCC) antibody protein dose on tumor uptake were investigated in nude mice with human RCC xenografts. The biodistribution of radioiodinated anti-RCC MAbs G250 and RC38 (directed against different RCC-associated antigens) was determined 3 days p.i. in nude mice bearing NU12 or SK-RC-52 xenografts. Protein doses varying from 0.3 to 100 #g were studied. In NU12 tumors the % ID/g G250 was similar at protein doses of 0.3 and l #g (131 + 15 % ID/g), but decreased at higher doses. Saturation of G250 antigen in the tumor occurred at the 3 ~g dose level, with approximately 2.2 ~tg G250 specifically bound per gram tumor. Assuming 109 cells/g tumor this would mean that 10,000 accessible G250 epitopes were targeted per cell. In contrast, G250 antigen saturation was not observed in the SK-RC-52 model. Tumor uptake increased with increasing protein dose from 3.6 _+ 2 . 1 % ID/g at 1 ~g to I0.8 _+ 1.7 at 100 /zg G250. Concomitantly, very low G250 blood levels were observed in the SK-RC-52 model at the lowest protein dose levels (0.4 _+ 0.2 % ID/g at 1 ,ag), indicating rapid metabolization of G250 antibody in the tumor. To determine whether the G250 saturation in NU12 tumors was antigen/MAb specific, the biodistribution of the anti-RCC MAb RC38 was determined in the NU12 model. Tumor uptake of RC38 remained constant up to the i0 jzg dose level (34 _+ 7 % ID/g) and decreased at higher doses, indicating saturation of RC38 antigen in the tumor. Approximately 7/zg RC38/g NU12 could be bound, indicating that 30,000 accessible RC38 epitopes/cell were targeted. These data indicated that the observed antigen saturation was antigen independant. The biodistribution data of G250 in the NU12 model are strikingly in line with our observations in RCC patients that were injected i.v. with '3~I-G250: optimal uptake in primary RCC tumors was observed at relatively low protein dose levels (0.52 % ID/g at 5 mg protein dose vs 0.012 % ID/g at 50 mg protein dose). Our studies indicate that some RCC tumors are saturated with anti-RCC MAbs at relatively low protein doses. At non-saturable doses relatively high tumor uptake can be achieved.

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M.G. Ste[['ens, E. Oosterwijk, O.C. Boerman, G.O.N. Oosterhof, E. Koenders, J.C. Oosterwijk-Wakka, J.A Witjes, F.M.J. Debruyne, F.H.M Corstens. Departments of Nuclear Medicine and Urology, University Hospital Nijmegen, The Netherlands.

V.U. Chengazi. M.R. Feneley, S.J. Mother. D. Ellison. M. Stalteri. C.C. Nimmon. M. Granmvska, A. Granowski, R.S. Kirby. and K.E. Britton. Departments of Nuclear Medicine and Urology, and the I('RF .V~cle.ar.lledicme Group, ,";t. Bartholomew's Hospital, London E('t.~ 7BF, UK.

RADIOIMMUNOTARGETING WITH ~3q-LABELED CHIMERIC G250 MONOCLONAL ANTIBODY IN RENAL CELL CARCINOMA PATIENTS. In previous studies excellent tumor targeting of the nmrine monoclenal antibody (mAb) G250 (m-G250) in Renal Ceil Carcinoma (RCC) patients was shown (Oosterwijk et ak l Clin Oncol 11, 738, 1993). However, although m-G250 seemed a suitable vehicle for radioimmunotherapy, the occurrence of human anti-mouse antibodies (HAMA) in all patients studied, hampered the development of m-G250 for radioimmunotherapy. To circumvent the occurence of HAMA, a chimeric version (c-G250) with identical antigen recognition and affinity (K,> 109/M) has been developed. A phase 1 protein dose escalation study was performed to investigate the radioirranunotherapeutic potential of c-G250 in RCC patients. Sixteen patients have been studied at 5 protein dose levels (2-5-i0-25 and 50 rag). Patients received a single intravenous infusion of 6 mCi t 131 labeled c G250. The intmunoreactive fraction following iodination was > 92 %. Planar images were acquired on day 1,2,3,5 and 7 Normal tissue samples and tumor biopsies were obtained at surgery (7 days p.i.). In t3 patients the rumors were clearly visualized as early as 24 hours p.i. Primary tumors as well as ntctastases were imaged, including tumorous lymph nodes (histopathologically confirmed), hnage quality improved with time. Three patients had an immunohistochemically confirmed antigen-negative minor. These tumors were not visualized. The tumorous kidneys showed remarkably high overall tumor uptake (range: 2.4 - 9.0 %ID). Focally, t3q-c-G250 uptake as high as 0.52% ID/g was observed. However, mtratumoral uptake was highly heterogeneous with uptake values varying within two orders of magnitude. I~q-e-G250 uptake in non-tumorous tissues remained low, with the exception of liver uptake at the lowest protein dose level. These observations are similar to findings with m-G250. Plasma clearance of t~q-c G250 was protein dose dependent with increasing tit.@t at higher protein doses (32 to 80 hours at 2 mg and 50 mg dose levels, respectively). Dosimetric analysis revealed that 48 rad/mCi can be guided to the primary tumor. More importantly, metastatic lesions received 23 rad/mCi (bone metastasis) and 20 rad/mCi (regional lymph_node metastases). A sandwich-ELISA to detect human anti-chimeric antibodies (HACA) in patient sera (detection level 20 ng HACA/ml), revealed minimal HACA responses in 3 patients 3 months p.i., irrespective of the administered protein dose. This contrasts strongly with the high titers of HAMA observed with m-G250. In conclusion, the in vivo behavior of ~3q-c-G250in RCC patients is very similar to ~3q-mG250. The uptake of c-G250 compares favourably to most other mAbs investigated in solid tumors and dosimetric analysis indicates that tumor sterilizing levels may be guided to the minor when therapeutic doses are administered (> 100 mCi) In addition c-G250 appears to be immunosiletu and thus is a profffisnig vehicle for radiointmunotherapy.

PROSTATE CANCER IMAGING W I T H THE MONOCLONAL ANTIBODY Tc-99m-CY"r-351

I M A G I N G OF PRIMARY BREAST CANCER W I T H THE ESTROGEN RECEPTOR SPECIFIC RADIOLIGAND Z-[I-123]MIVE.

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The performance of the Tc-99m labelled monoclonal antibody CYT351 (Cytogen Corporation, USA) in visualising prostate cancer was assessed by performing radioimmano-scinfigraphy (RIg) in 35 patients. 0 5 mg of antibody labelled with 600 MBq Tc-gqm was injected intravenously after obtaining informed consent. Planar and SPET imaging was performed at 10 minutes and 6-8 and 22-24 hours post-injection. The scans were evaluated for visualisation of the primary focus or local recurrence, extra-prostatic invasion, lymph node involvement and uptake in bone and soft tissue metastases. 36 studies in 35 patients were c a m e d out. In 13/14 evaluable studies with clinically localised prostate cancer, RIS detected 92% true positives (TP) (12/13). In eight studies with previous incidental carcinoma identified at trans-urethral resection undertaken for clinically benign disease, there were 86% TP (6/7) and one true negative (TN), confirmed at reoperation. In six studies with evidence of local recurrence after a previous radical prostatectomy, there were 100% TP (6/6) confirmed by raised or rising prostate specific antigen (PSA) levels and/or by biopsy. There were 4/4 TP and 3/4 TN in the eight studies with known metastatic disease. The overall accuracy was 92%. These results suggest that Tc-99m-CYT-351 can provide good quality images and clinically useful information safely. It may therefore have a potentially important role in patients with rising PSA levels and yet negative imaging by conventional modalities.

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K. Schc{a~cker, T. Fischer, A. Scharl I B. Gabruk*Szostak, J.

G.Ronga, M.Filesi, C.Barbarossa, R.Barone, E.Ferranti, E.Procaccini, G. Ventruni, A. Signore S.S.Nuclear Medicine/Clinica Medica II - University "La Sapienza" of Kome LONG-TERM SURVIVAL IN 73 YOUNG PATIENTS TREATED WITH 13lI FOK THYROID CANCER Aim of this work was to evaluate the importance of only age in survival of patients with differentiated thyroid carcinoma (DTC). On 1293 patients with DTC, we considered 104 cases with age lower or equal to 18 yrs (23 follicular, 78 papillary, 3 undefined; 25 males and 79 females; mean age 14.1 ± 3.8 yrs; follow-up 3-32 yrs). Then, excluding any other variable, we calculated survival curve at 5, I0, 15 and 20 yrs. Results were 100% at 5th and 10th yr, and 98.1% at 15th and 20th yr. According to same paramethers, survival rates of all the casistics were 94.8, 90.8, 86.2 and 79.4%. Comparing both series, we obtained a signiticative difference (p<0.00l). In younger group, only two patients deceased, both after 11 yrs: one for cerebral metastases, unique for non 13~I uptaking metastases, and another for lung 1311 uptaking metastases. Out of all younger patients, 73 were treated with ~3~I: 46 for thyroid remnant ablation (mean dose 100.6 mCi - 3722 Mbq), and 27 for metastases (11 lymphonodal: mean dose 200.6 mCi - 7422 Mbq; 13 lungs: mean dose 313.9 mCi - 11614 Mbq; 3 other sites: mean dose 520.6 mCi 19262 Mbq). Also after long time, no considerable secundary radiation effect occurred; so, later, no problems during and after 21 pregnancies post radioiodine therapy. In conclusion, probably due to absence of bone metastases and rare non uptaking metastases, we observed a good survival in all younger patients, with effective response to 13=I therapy, better in lymphonodal localizations, that need lower dose. We confirm the age as condictioning factor in survival of DTC.

K6rnyei 2, K. Scheidhauer, S.K. Shukla 3 , H. Schicha, Departments of N~clear Medicine and lobster & Gyn, University of Cologne, Germany, 2Institute of Isotopes, Budapest, Hungary, 3CNR Rc~e, Italy3. TUMOR-AFFINE RADIONUCLIDE-MERCAPTOACETYLTRIGLYCINE (MAG-3)-COMPLEXES T h e a i m of this s t u d y w a s to test the b i o d i s t r i b u t i o n of M A G - 3 l a b e l l e d w i t h T c - 9 9 m , Yb-169, Sm-153, Y-90, a n d I n - I l l in t u m o u r - b e a r i n g mice, a n d to d e t e r m i n e t h e i r s u b c e l l u l a r d i s t r i b u t i o n w i t h i n the t u m o n r cells.

A n i m a l e x p e r i m e n t s w e r e c a r r i e d out on t u m o r b e a r i n g m i c e (DBA/2N mice, male, 25 g, m a m m a c a r c i n o m a in the h i n d u p p e r limb) d e m o n s t r a t e d h i g h t u m o r u p t a k e for the l a b e l l e d M A G - 3 (24 h p.i.: appr. 5 - 8 % of the radioactivity applied per g tissue ). The t u m o r / b a c k g r o u n d r a t i o s w e r e s u f f i c i e n t (>50, T c - 9 9 m - M A G - 3 : I 0 ) . The s u b c e l l u l a r d i s t r i b u t i o n of the d i f f e r e n t M A G - 3 c o m p l e x e s was i n v e s t i g a t e d a f t e r h o m o g e n i s a t l o n of a t u m o u r m a s s c o r r e s p o n d i n g to 5x10 ~ cells in 0.25 M Sacc h a r o s e b y c e n t r i f u g a t i o n at 1 , 0 0 0 x g (I0 min), 3 3 , 0 0 0 x g (7.5 min) a n d 7 8 , 0 0 0 x g (i00 min). The c e n t r i f u g a t i o n s r e s u l t in 4 cell f r a c t i o n s (cell n u c l e i / m i t o c h o n d r i a e , lysosomae, p e r o x y s o m a e / m i c r o s o m s e / c y t o s o l as was p r o v e n b y m a r k e r enzymes. The m a i n p a r t of the r a d i o a c t i v i t i e s was f o u n d in the c y t o s o l fraction.

T h e s e r e s u l t s i n d i c a t e that MAG-3 l a b e l l e d w i t h m e t a l lic r a d i o n u c l i d e s y i e l d s a c l e a r t u m o r affinity. The r a d i o a c t i v i t y is c o n c e n t r a t e d w i t h i n the t u m o u r cells in the cytosol.

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Y.Duman, 0,Bilkay, E.Teber, D.YOksel, S.Erdem, M.Argon, R.Y11maz, O.Ozbal Ege University, Dept. of Nuclear Medicine 12}~tR-TURKEY

C.Messa, C Landoni L.Fridrich* G.Lucignani G.Striano G.Riccabona F.Fazlo. INB-CNR, Umvermty of Mr an S c e n t f i c Institute H San Raffaele, Milan, Ita y and * University of Innsbruck, Austria.

VISUALIZATION OF BREAST CANCERSWITH Te-gYmGLUTATHIONE

-18]FDG UPTAKE IN METASTASTATIC THYROID RCINOMA PRIOR AND AFTER 1-131 THERAPY. Seven patients (3M 4F, age range 46-77 yrs) with metastatic lesions (rots) of thyroid carcinoma (ThC) were evaluated with PET-[18F]FDG before and 50-70 days after 1-131 therapy. ThC (2 papillary - 5 follicular) was diagnosed 5-25 yrs before PET. All patients had total (2) or partial (5) removal of the thyroid gland and had several 1-131 treatments more than 6 mo. prior to PET. Methods Transaxial images over the thorax (5) or pe v s (2) were acquired dynamically for 1 h. after i.v. Jnj. of 370 MBq of [18F]FDG with a Siemens 931/04-12 tomograph and corrected for measured attenuation. In 4 pts F-18 plasma concentration was measured through arterial sampl ng Parametric images (PI) of FDG upta~.e were obta ned by applying Patlak Graphical analysis (Kpat) and uptake index body weighted (SUV) to the transaxial images p xe by p xe Activityin mts was calculated by ROIs drawn over P-I. Kpat and SUV values were compared between each other and with Thyreogloouline (TG) levels measured at 1st, 2nd scans and 6 mo later. The % changes of metabolism measured at 2nd PET were compared to clinical outcome at 1 year. Results: 1) there was a good correlation between Kpat and SUV (r=0.82); 2) Kpat and SUV values best correlated with TG levels at 6 mo.(R=0.9 for Kpat and R=0.6 for SUV), 3) as measured with SUV pts who progressed showed either increase or no more than 20% reduction of metabolism while pts in regression or stable showed a metabolic reduction of more than 25%. C o n c l u s i o n : Our data show that PET-FDG is a valuable technique to measure metabolic changes duringtherapy of ThC pat ents which correlate withprognosis. In this type of study a simple analysis such as S U V gives similar resu ts to a more complex kinetic analysis, such as Kpat

The purpose of this investigu~onwas to evaluate the value of

Tc-Ygm Glutathzone (Tc-PgmGSH) For v i s u a l i z a t i o n of breast cancers. The charecterization of Tc-YYm GSH as a radiopharmaceutical was evaluated previously, and parameters such as electrophoretic m o b i l i t y , ' i t s e x t r a c t i o n in n-butanol, i t s s t a b i l i t i y in plasma, binding to serum proteins and erytrocytes and HPLC analysis were determined. 2&patients (pts) were included in the study group (25 primary palpable breast tumor and I metastatic breast cancer).6 h a f t e r I.V i n j e c t i o n of 20 mCi Tc-Y?m GSH planar images were obtained at sophy DSX camera. Images were evaluated q u a l i t a t i vely and q u a n t i t a t i v e l y using ROIs over i n v o l v e d a r e a and the opposite side. Tc-YYm GSH uptake values and oestrogen/progesterone receptor (ER/PR) status demonstrated a relationship (Table) Patient N T/C ER(+) PR (-) : 10 2.31 + 0.08 ER(+) PR (+) : 5 - (No uptake)

ER(-) PR (-)

:

8

- ( ....

)

ER(-) PR(+)

:

3 (Pi)

- ( ....

)

Glutathione S-transferase Pi (GST-Pi)represents isoenzymes that conjugate glutathxone with various tumors and play on important role in d e t o x i f i c a t i o n . A strang inverse c o r r e l a t i on between GST-Pi expression and ER and PR status has been reported previously (Gilbert L, et a l ) . Our results indicate that that Tc-99m GSH may be used for the v i s u a l i z a t i o n and follow-up of ER(+), PR(-) breast cancers.

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H. Wolf, A. Ditmag, B. Frieling, W. Brenner, S. Tinnemeyer, K. H. Bohuslavizki, M. Clausen, E. ttenze Clinic of Nuclear Medicine, Christian-Albrechts-University of Kiel, Germany

Bohuslavizki K.H., Brenner W., Behnke A., Tinnemeyer S., Hugo H.H., Wolf H., Clausen M., Mehdom HM., Heuze E. Clinics of Nuclear Medicine and Neurosurgery, Universitiy of Kiel, Germany

IN-VITRO U P T A K E OF TC-99M-FURIFOSMIN IN T U M O U R CELLS - FIRST RESULTS Tc-99m-furifosmin is a mono-cationic complex for myocardial perfusion imaging, but little is known about uptake in tumours. It was the aim of this study to determine the cellular uptake in different tumour cell lines. Tc-furifosmin was prepared with a one-step kit formulation reaching a radiochemical purity higher than 98 %. Uptake kinetics were performed in 60 culture tubes of h u m a n melanoma cells (MML-1) with incubation intervals ranging from 10 to 180 min. Additional measurements ~ 1,2 melanomacells were performed in 2 gastric and 2 pancreatic carcinoma ~ 1,0 [ cell lines (one sensitive and 37° C ! one multidrug resistant ~ 0,8 each) after l h of incubation time. The uptake was = o,6 calculated as the percentage 0,4 (mean +_ 1 ~) of the added activity and standardized to 0,26 time [mini 100 one million tumour cells.

, ~ \6oc

I M P A C T OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN PATIENTS WITH SUSPECTED MENINGEOMA Neurosurgical treatment of brain tumors depends on their biological behaviour. Therefore, prior to treatment characterization of tumors is desired by the neurosurgeon. However, even MRI is not able to discriminate meningeoma and neurinoma in all patients. This study was designed to evaluate the usefulness of somatostatin receptor scintigraphy (SRS) in patients with suspected meningeoma. 68 patients suspected of meningeoma were investigated prior to surgery. All patients received standard MRI including T2-, T1-, and TI weighted SE sequences plus gadolinium. Whole body images were obtained up to 24 hours following i.v. injection of 200 MBq In-111octreotide, and SPECT images were acquired at 4 and 24 hours p.i.. Final diagnosis was established by histology. True positive SRS was obtained in 50 out of 61 meningeoma showing increasing target-to-background ratios over time. SRS was tree negative in 7 neurinoma. However, SRS was false negative in 11 patients with histologically proven meningeoma. Tumor volume was < 10 ml in all of them. On the other hand, in 18 out of 50 true positive SRS tumor volume was also < 10 ml.

In m e l a n o m a cells increasing accumulation over time was seen at 37 ° C. By an incubation temperature of 6 ° C the 1 h-uptake is 1,3 fold lower. Significant differences resulted between the sensitive and the resistant gastric cell line resp. pancreatic cell line. In the resistant cells the uptake is 4,1 fold decreased in gastric resp. 2,1 fold lower in pancreatic carcinoma cells. In conclusion Tc-99m-furifosmin is a potential tumour tracer and seems to be suitable to indicate specific turnout resistance.

MRI was decisive for meningeoma in 41 of 68 patients. In the remaining 17 patients, corresponding to 28 %, MRI could not differentiate between meningeoma and neurinoma. Of these 17, positive SRS confirmed meningeoma in i0 patients, and negative SRS excluded meningeoma in the remaining 7.

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M.Hosono, M.N.Hosono, F.Kraeber-Bodtrt, A.Devys, P.Thedrez, J.Barbet, E.Gautherot, K.Machida, J.F.Chatal. Saitama Medical Center-Saitama Medical School, Japan, Osaka City Univ, Japan, INSERM U.211, France, Immunotech SA, France RADIOIMMUNODETECTION OF MEDULLARY THYROID C A N C E R BY B I V A L E N T H A P T E N A N D B I S P E C I F I C ANTIBODY IN MICE.

Two-step radioimmunodetection using 1-125-labeled bivalent DTPAindium (1-125-DTPA-In) hapten and bispecific antibody was evaluated for human medullary thyroid cancer in athymic mice. I-125-DTPA-In and anti-carcinoembrionic antigen(CEA)/anti-DTPA-In hapten bispecific antibody (BsAb) F6-734 were prepared as described previously (Cancer Res, 1990; 50: 1358-66). BsAbs F6-679 (anti-CEA/anti-histamine hapten), G7A5-734 (anti-melanoma/anti-DTPA hapten) were used as irrelevant BsAbs. F(ab')2 fragment of F6 anti-CEA Ab was labeled with I-125. Athymic mice inoculated with T r medullary thyroid cancer cells expressing CEA were administered with 500 pmol (50 gg) of BsAbs F6-734, F6-679 or G7A5-734, and then 48 hr later, 50 pmol (65 ng) of I-125-DTPA-In hapten. I-125-labeled/=6 F(ab')2 fragment was injected into other groups of mice. Biodistributions were examined at 30 min, 5, 24, 48, and 96 hr after injection of 1-125-DTPA-In hapten or 1-125labeled F6 F(ab')2 (4 mice per time point). In mice injected with BsAb F6-734 and 1-125-DTPA-In, tumor uptake was 9.1+2.1, 8.7+3.5, 8.0+2.3, 5.1_+0.9, 3.5+1.5 %ID/g at 30 min, 5, 24, 48, and 96 hr and tumor-to-blood, -to-liver, -to-kidney ratios were 37.0-+12.5, 32.3-+10.9 and 10.4+2.7 at 24 hr, whereas 1-125 F6 F(ab')2 fragment showed a tumor uptake of 7.39 %ID/g and tumor-to-blood, -to-liver, -to-kidney ratios of 1.8_+0.6, 7.3_+2.9 and 3.6+1.6 at 24 hr. In mice injected with F6-679 or G7A5-734, tumor uptake and tumor-to-normal tissue ratios for I- 125-DTPA-In were much lower than in the mice injected with t:6734. These results were confirmed by autoradiographic studies which demonstrated clear tumor-to-normal tissue contrast. In conclusion, this 2-step targeting method seems very efficient for the diagnosis and therapy of human medullary thyroid cancer since it combines high tumor uptake and low normal tissue background.

1098

In conclusion, SRS has significant clinical impact in differential diagnosis of meningeoma versus neurinoma yielding information not provided by MRI in a considerable amount of patients.

Zissimopoulos A I, Baziotis N I, Geronikola-Trapali X I, Yakoumakis E l, Karaitianos 13 , Georganda H 2 , Economou G ~ . l)Nuclear Medicine Dept. 2)First Oncologic clinic 3)Third Surgical clinic Greek Anticancer Inst. "St. Savas" Hospital Athens, Greece. THE USE OF INDIUM-III-PENTETREOTIDE IN THE DETECTION AND THE FOLLOW UP OF PATIENTS WITH MELANOMA. It is known that melanoma is a malignant tumor of melanocytes. These cells are considered to be derived from the neural crest. As the prognosis of the melanoma is very poor, the early detection of metastases is very important. AI___MM: The aim of this study ~as the evaluation of the use of In-lll-Pentetreotide in the detection of metastases during the follow up of patients with melanoma. PATIENTS AND METHOD : We studied 27 patients with melanoma (16 males -ii females) aged from 19 to 63 years (mean age 38 years). 18 of them (group A) had metastases to lymph nodes, bone and liver and the others 9 (group B) were in follow up. The images were performed 24 hours after IV administration of ii0 MBq In-lll-Pentetreotide (Octreoscan-Mallinckrodt). RESULTS : From the 18 patients (group A) with metastatic disease 15 had positive scintigraphy (83,3%). The 62% of the known lesions was imaged. From the group B (9 pts) with no evidence of metastatic disease 3 had positive scintigraphy (lymph nodes), indication of reccurence of the disease. Subcutaneous and lympatic metastases were detected with greater accuracy. CONCLUSIONS : In-lll-Pentetreotide is a very promising procedure in the management of patients with melanoma. The sensitivity was high (83,3%) . It can be used in the staging of melanoma - detecting the metastatic lesions (62%) and in the follow up of these patients.

•

0Mo268

0Mo266

P.J. van den Anker-Lugtenbur~, R. Valkema and E.P. Krenning. Rotterdam; Dr. Daniel den Hoed Departments of Haematology and

Oncology

B. Lfwenberg, S.W.J. Lamberts, H.Y. Oei, Erasmus University and University Hospital Cancer Center, Rotterdam; The Netherlands, Nuclear Medicine.

L Mansi, PF Rambaldi, B Pecori, F Fallanca, P Puntieri, E Di Lieto, V Pastore. Inst of Radiological Sciences and Inst of Chest Surgery; II U n i v e r s i t y of Naples.

THE ROLE OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN THE STAGING OF NON-HODGKIN'S LYMPHOMAS.

RADIOGUIDED In-OCT.

We performed a prospective blinded study comparing somatostatin receptor (SSR) scintigraphy with conventional staging methods (CSM) for initial staging of patients with histologically confirmed non-Hodgkin's lymphomas (NHL). CSM included a physical examination, computed tomography of chest, abdomen and pelvis and bone marrow biopsy. 90 consecutive previously untreated NHL patients (26 low grade, 40 intermediate grade, 21 high grade and 3 unclassifiable) underwent scintigraphy after i.v. injection of [lll-ln-DTPA-D-Phe-1]-octreotide (220 MBq). Planar images were recorded 24 and 48 h post-injection and in all patients 24 h SPECT of the upper abdomen was performed. SS-R scintigraphy and conventional diagnostic tests were interpreted independently and the results compared. The patient-based analysis yielded an overall sensitivity of 80% (72/90)• In 18/90 patients the scan was completely negative• SS-R scintigraphy was superior to CSM in t7 patients (19%). In I0 patients (I 1%) the clinical stage was altered because of the results of SS-R scintigraphy. As a result the treatment plan was changed in 3 patients (3%). In 14 patients (16%) some lesions were not detected by SS-R scimigraphy. Total agreement between SS-R scintigraphy and CSM was seen in 38 patients (42%). In 3 patients (3%) a false positive result was observed. The lesion-based analysis showed an overall sensitivity of 66% (175/264). The sensitivity in the supradiaphragmatic region was 72% (122/169). The sensitivity in the infradiaphragmatic region was 52% (44/85). SS-R scintigraphy visualized 22 previously unknown lesions. Bone marrow infiltration was apparent on SS-R scintigraphy in 1/18 patients only. In conclusion it appears that the highest sensitivity for SS-R scintigraphy is above the diaphragm. This new imaging modality may affect the management of patients with NHL. The majority of patients have SS-R positive lesions and this may be important for treatment with a (radionuclide labeled) SS analog.

Aim of this study was to evaluate the role of radio-guided surgery (RGS) with In-lll pentreotide (OCT) of primary lung tumors. MATERIAL AND METHODS: 13 patients (average age 62) with primary lung tumor (12 NSCLC and one bronchial carcinoid) without metastases at conventional preoperative staging were included in our study. 37-111MBq of OCT were i.v. injected 1-6 days before surgery. Patients underwent multiple scans in a period ranging from 4 to 72 hours~ RGS was performed with an hand-held gamma probe(Modelo 2-ORIS, France). RESULTS: In all patients the scintigraphy confirmed OCT uptake in lung cancer. RGS detected the primary tumor in all patients and correctly defined surgical boundaries. Moreover an unsuspected parietal involvement, histopathologically confirmed, was found in two cases. Lymph node analysis demonstrated a true positive, a false negative and a true negative in a patient with false positive results at CT. Tumor/non-Tumor ratio ranged from 1.5 to 6 invivo and 2.7-40 ex-vivo. CONCLUSION: Our data suggest that RGS could be a reliable method in the definition of surgical boundaries in operable lung cancer. Further studies are necessary to evaluate its role in guiding lymphadenotomy.

0Mo267 • .

0Mo269

[, Retslnger i , K.H. Bohuslavizki 2, S. Braune 3, A. Geide t, B. Kettner 1, H.-J. Otto 3, S. Schmidt 4 Clinic of Nuclearmedicine of the HumboldtI 2 Universit~t- Berlin (Charit6) , Christian-Albrechts-Universit~it- Kiel , Ottovon-Guericke-Universit~t - Magdeburg 3 and Universit~it des Saarlandes, Homburg/Saar 4 S O M A T O S T A T I N R E C E P T O R S C I N T I G R A P H Y (SRS) IN S M A L L C E L L L U N G C A N C E R (SCLC) - R E S U L T S O F A STUDY OF FOUR CENTERS The purpose of the study was to evaluate the role of SRS in detection and staging of SCLC and its value in the continuation of this disease. We investigated together 100 patients (23 women, 77 men) with the same protocol. Planar whole body scans and SPECT of the thoracic region and other areas suspicious of metastases were performed 4 and 24 hours after i.v. administration of approximately 200 MBq 111-InOctreoScan (Mallinckrodt). A tumor-to-background ratio (t/b) was calculated for quantification of the octreotide uptake of the primary tumor (pt). 27 patients were examined two times - before and after chemotherapy. The visualisation rate for primary tumors was 96 %. Only 54 % of the metastases could be shown by SRS. The sensitivity of SPECT was higher than of planar imaging, especially for the detection of metastases. We found a decreasing of the octreotide uptake of pt in patients who were at the second investigation in remission (t/b 2,40 vs. 1,63; p<0,001) . The uptake value was different in patients prior to chemotherapy compared with patients after therapy (t/b 2,35 vs. 1,63; p<0.001). Conclusion: Compared with conventional imaging modalities SRS provides no additional information in staging of SCLC. The intensity of the octreotide uptake of the primary tumor may be a prognostic factor.

SURGERY

OF

LUNG

CANCER

USING

Ill-

P.P.M. Kooij, W.H. Bakker, M.E. vd Plu!jm~ W.A.P. Breeman and E.P. Krenning. University Hospital Dijkzlgt, Department of Nuclear Medicine, Rotterdam, The Netherlands. COMPARISON OF [TB-161-DTPA-D-PHE~]OCTREOTIDE AND [IN-111-DTPA-D-PHE~}OCTREOTIDE: A STUDY IN HUMANS• I n - l l l emits gammaradiation (174 and 247 keV), conversion electrons (144-245 keV) and auger electrons (0•5-25 keV). Because of the high energy of the ~ammaradiation and the physiological tissue accumulation of [In 1 ll-DTPA-D-Phe~loctreotide (In-O) tt is not the radionuclide of choice to perform radioguided surgery (RGS), especially in the abdomen. At the moment In-O is also used for radiotherapy (RT). Although promising results are reported a beta emitting radionuclide seems to be more appropiate. Tb-161 emits gamma- (25-74 keV) and beta-radiation (134-180 keV). Because of these properties ITb-161-DTPA-D-Pheqoctreotide (Tb-O) is expected to be more suited for both RGS and RT. In this study the biological characteristics of Tb-O are compared to those of In-O in 2 patients• The injected dose was 50 MBq Tb161 labeled to 20 #g IDTPA-D-PhCI6ctreotide. Urine, p l a s m a and faeces were collected during 72 h. In both patients Tb-O and l n - u are comparable with regard to the amount ol~ radioactivity in urine, plasma and faeces. Both radiopharmaceuticals are cleared mainly by the kidneys. Fecal excrelion was limited to a few percent• Patients were scanned 0.5, 4 24 48 and 72 h p.i. Uptake of Tb-O in kidneys, liver and tumors 'was'calculated and compared to uptake of 5550 MBq (40#g) ln-O. Uptake of ln-O was used as the "golden" standard. Patient 1 : In this patient uptake in kidneys was the same for both radiopharmaceuticals while uptake in liver and tumor was 2 and 4 times lower respectiv'ily. Uptake in these organs decreased in time. Patient 2: Uptake m kidneys was twice as high. Uptal~e in river and tumor was 3 and 10 times lower respectivilv. Uptake in liver increased in time, indicating instability of Tb-O. This was confirmed by HPLC analysis of the urine. In both patients all tumors were visible, although in some cases, because of the low uptake of Tb-O, it was necessary to have prior knowledge of the distribution of In-O• In contusion: In contrast to what may be expected, the biological characteristics of Tb-O, in its present form, differ from those of Inn . Because of the low uptake in tumors it is unsuited for RT but it may be useful for RGS.

1099

(/) tO

C: (I) u) Q.

8

• Oncology 0Mo270

0Mo272

O. Schillaci, F. Scopinaro, R. Danieli, S. Angeletti*, R. Tavolaro, E. Polettini**, P. Cannas, B. Annibale*, G.F.Gualdi**, G.F. Delle Fave*, Nucl. Med., *Gastroent., **I Med., Univ. "La Sapienza", Rome, Italy.

H. Kolesnikov, D. Huglo, M. Nocaudie, C. Proye, M. Steinling, X. Marchandise, Department of Nuclear Medicine, C H R U of Lille, 59037 Lille cedex - F R A N C E

COMPARISON AMONG In-lll PENTETREOTIDE (P) S P E C T A N D O T H E R I M A G I N G T E C H N I Q U E S IN T H E D E T E C T I O N O F T U M O R S (T) IN Z O L L I N G E R - E L L I S O N S Y N D R O M E (ZES).

The localization of all the T, wheter primary or metastatic, has important therapeutic implications in patients (pts) with ZES. Despite the combined use of several imaging modalities, some T remain undetected, and an accurate assessment of the extent of the disease is difficult. Whereas In-lll P scintigraphy has shown to be useful in the visualization of gastrinomas (ga), SPECT has so far been performed but occasionally, and its additive value has not yet been completely established. To this purpose 19 pts with biochemical evidence of ZES and secretin test positive were evaluated. All underwent total body planar (pl) images (at 4, 24 and 48 hours) and abdominal (ab) SPECT (at 4 hours) after the injection of In-lll P. Scintigraphic data were compared to ab CT and ab MRI performed within one month. SPECT detected 27 lesions (le) in 19 pts, pl images 17 (3 extra-ab) le in ii pts, CT i0 le in 7 pts and MRI 18 le in I0 pts. SPECT visualized hepatic (hep) le in 9 pts, pl images in 3 pts, CT in 2 pts and MRI in 5 pts. Nine pts were operated after scintigraphy; gastrinemia was reduced from 740 ± 385 pg/ml before to 131 ± 82 after surgery (p<0.05). These data suggest that In-lll P SPECT is the most sensitive noninvasive modality for detecting ab ga: it is superior to pl scan, CT and MRI in the detection of both hep and ab extrahep le, and may therefore have a major role in the accurate stage of tumor extension and in therapeutic decisions.

FACTOR ANALYSIS OF DYNAMIC STUDIES (FADS) IN SOMATOSTATIN RECEPTOR SCINTIGRAPHY The aim of this work was to study physiopathology of tumoral uptake of 111In pentetreotide (OctreoScan, Matlinckrodt) using FADS and assess the usefulness of FADS in somatostatin receptor scintigraphy. Methods : 42 patients were included, 23 females, 19 males After intravenous injection of 111 MBq of rain pentetreotide, a dynamic acquisition (68 images of 30 sec or 200 images of 3 sec) started in front of the suspected tumoral site : cervicothoracic in 11 cases of medullary carcinoma of the thyroid (MCT), thoracic in 2 cases of bronchogenic carcinoid (BC), or abdominal in 12 cases of carcinoid of small intestine (CSI) and 18 cases of other GEP tumors FADS was performed with FAMIS (Sophs Medical) using 4 factors. Static acquisitions (SA) and if necessary SPECT were perfomed 4 and 24 h later. For every patient, surgery and/or clinical follow up (4 years) were used to classify results in true (T) or false (F) positive (P) or negative (N) and to evaluate the sensitivity of SA and the usefulness of FADS. Results :

pathology i MCT BC CSI GEP

n 11 2 12 17

OctreoScan (SA) 4 TP, 2 TN, 5 FN 2TP 6TP, 6 T N 9TP, 3TN, 2FP, 3 F N

FADS 7 TP, 2 TN, 2 FN 2FN 6TP, 6 T N 4TP, 5TN, SFN

Conclusions : - FADS demonstrates that tumoral kinetics are similar to splenic one.

- In MCT, FADS can show a diffuse tumoral uptake corresponding to tumoral infiltrate while SA were normal or doubtful. - In carcinoid tumors, the kinetics are different according to the localization : vascular without initial uptake in BC and slow uptake in CSI. - Small abnormalities (2 FP included) on SA may be normal with FADS.

0Mo271

0Mo273

A,Sundin, B.Eriksson, H.Ahlstr~m, M.Bergstr~m, A. Lilja, P.Bjurling, B.Lgngstr~m, K.Oberg. Uppsala University PET-centre

C Bischof, D. Ghidovacz, Q. Yang, M. Leimer, T. Pangerl, M. Beck, P. Angelberger, K Kaserer, N. Neuhold, I. Virgolini, Department of Nuclear Medicine, University of Vienna, Austria.

POSITRON EMISSION TOMOGRAPHY WITH (I%C)-5HYDROXYTRYPTOPHAN IN CARCINOID TUMOURS

VALIDATION OF VASOACTIVE INTESTINAL PEPTIDE (VIP) AND SOMATOSTATIN (SST) RECEPTOR EXPRESSION IN HUMAN TUMORS BY DIFFERENT TECHNIQUES

PET with (llC)-5-Hydroxytryptophan (5-RTP) was evaluated as a marker for imaging and therapy monitoring in patients with carcinoid metastases and compared with computed tomography (CT). Positron emission tomography (PET) was performed in 16 patients, following i.v. administration of the serotonin precursor 5-HTP. The ensuing emission scan w a s corrected for attenuation and scatter. The reconstruction produced a set of dynamic images of radioactivity d'istribution. Data from 14 to 45 minutes were summated and recalculated to provide images of standardized uptake values (SUV). Plasma llC-radioactivity in samples collected during scanning provided the input function for recalculation of images of transport rate. 5-HTP accumulated to a high degree in liver metastases and lymph node metastases whereas the uptake in normal liver was low. This resulted in better visualisatlon by PET than with CT in 7 patients with liver metastases and in 3 patients with lymph node metastases. In one patient PET detected skeletal and pleural metastases which were not visualized by CT. In l0 patients PET was used for treatment monitoring and a correlation was seen between changes in U-HIAA and the transport rate constant. It is concluded that [[C-5-HTP-PET provides novel possibilities in the management of patients with earcinoid tumours.

1100

Various human tumors co-express receptors for V1P and SST. In this study, we used different methods (various radioligand binding assays, autoradiography and Northern blotting) for the determination of VIP/SST receptors in human tumors (adenocarcinomas, breast cancer, endocine tumors, lymphomas, n = 30) and respective cell lines (HT29, A431, PANCI). By use of radioligand binding assays VIP/SST receptors were demonstrable in almost all human tumors with variable binding capacities and affinities for ~23I-VIP as well as rain-OCT. The highest receptor numbers were identified when the unlabeled ligand was separated from the cell surface-bound ligand by filtration > centrifugation > celt harvesting, however, with Kd-values in the same range (0.5-10 nM). Competition studies as well as functional studies enabled the determination of agonist behaviour. Expression of receptor binding sites was also confirmed in 24 of 30 tumors by autoradiography using 1251-VIP and ~25I-Tyr-3-OCT. Autoradiography enabled the localization of binding sites on 10 gm tissue sections and demonstrated a high quantitity of VIP/SST receptors which is in line with the high numbers of binding sites estimated from the Scatchard plots (radioligand binding studies). Further confirmation of receptor existence was obtained by the demonstration of mRNA for SST-R and VIP-R subtypes using respective eDNA probes (hSSTRI-5, pHVIPR, pHIVR-8c). VIP/SST subtype receptor expression was variable from tumor to tumor. We conclude, that the combined use of different methods is essential for a precise evaluation of V1P/SST receptor and subtype receptor expression in human tumors

•

Oncology

OMo274

OMo276

I.Virgolini, T.Pangerl, C.Bischof, M.Leimer, A.Kurtaran, Q.Yang, M~Peck-Radosavjlevic, K.Kaserer, B.Niederle, P.Angelberger, A.Gangl and P.Valent. Depts. of Nuclear Medicine, Gastroenterology, Surgery and Pathology, University of Vienna.

M de Jon B, I-IF Bernard, EJ Rolleman, WAP Breeman, WH Bakker, ME vd Pluijm, TJ Visser, JC Reubi, EP Krenning. Dept of Nuclear Medicine,

S O M A T O S T A T I N (BST) A N D V A S O A O T I V E I N T E S T I N A L T I D E (VIP) R E C E P T O R (R) S U B T Y P E E X P R E S S I O N

PEP-

In recent years at least 5 distinct human SSTR (SSTRI-5) and 2 VIPR subtypes have been identified and characterised by molecular cloning. We investigated the expression of subtype R in a variety of human tumors following hybridization with cDNA probes (hSSTR1-5; pHVIPR (VIPRI);pHIVR-Sc (VIPR2)). Patients underwent SSTR/VIPR scanning prior to surgery using 123I-VIP (150 MBq; 1 ug) and 1111noctreotide (OCT). After histopathologieal diagnosis, in vitro receptor evaluation by Northern blotting, autoradiography as well as radioligand binding studies was performed. Surprisingly, intestinal adenocarcinomas (colorectal, n=5; pancreatic, n=5) imaged by 123I-VIP, but not by 111In-OCT, expressed SSTR3>>>SSTRS, SSTR4, SSTR2, and did not express SSTRI, and only moderately VIPRI and VIPR2. By large interindividual variation, a similar SSTR/ VIPR expression pattern was found for neuroendocrine tumors (n=4) imaged by 123I-VIP, but not by 1111n-OCT, with predominant expression of SSTR3. In contrast, carcinoid tumors (n=5) imaged with both 1111n-OCT and 123I-VIP expressed SSTR2 as well as SSTR3, whereas pheochromocytomas (n=4) imaged with 11fin-OCT expressed >>>SSTR2 and only moderately SSTR3. Breast cancers (n=6) expressed mainly SSTR2 and SSTR5. Radioligand binding studies and autoradiography confirmed the binding of 11fin-OCT and 123I-VIP to all human tumors. Our results allow the conclusion that SSTR2 is the main R involved in focal accumulation of 11fin-OCT, whereas positive VIP scans are related to the expression of subtype SSTR3.

Erasmus University, Rotterdam, The Netherlands; Dept of Pathology, University of Berne, Berne, Switzerland. RECEPTOR BINDING IN VITRO, AND BIODISTRIBUTION OF NEW VIP AND PACAP ANALOGS IN RATS. Many human tumors have Vasoaetive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) receptors, enabling receptor imaging in vivo using radiolabelled analogs. We studied 1) the binding affinity of new VIP and PACAP analogs for their homologous receptors in vitro (by displacement of 1-125-VIP or -PACAP) and 2) bitdistribution of 1-3 pmol 1-125- or In-Ill-labelled VIP and PACAP analogs (Table) in rats by counting radioactivity in isolated organs 2,8,15 min, 3h and 24h post injection (pi). Analogs were designed in such a way that radioiodination resulted in only one radioactive compound (only 1 Tyrosihe). Results in vitro: All VIP and PACAP analogs had high receptor binding affinity (low nM range), except for DTPA-VIP (FM range). Results in vivo: For all analogs, except DTPA-VIP, lung was the primary site of uptake: 2 rain pi over 45% of the injected dose (ID) was found, but due to degradation in the lungs radioactivity rapidly declined: for 1-125VIP to 14%ID/g 15 min pi and to 0.4%ID/g 3h pi. Radioactivity peaked at 2 rain pi in lungs and liver; for other organs, uptake increased in time with peaks at 15 min-3h and then parallelled that of iodide, pointing to uptake of degraded material. Uptake of DTPA-VIP in the lungs was 1o*, but in kidneys it remained very high (Table). More results, given as % uptake of radioligand relative to that of 1-125-VIP at 15 min, are given in the Table. Analogs were radiolabelled at Tyr-10 with I-125, DTPA-VIP with In-111. Tablei n~3~ mean (sd) I ) VIP

blood 100

lun~ 10D

2} Nle17r Phe22-VIP

99.8(10.4)

3) DI~A-Hisl-VIP

72.22(5.5)

181.7(31.3) 3,1(10,3} 241.2~t0.6) 2.0(0.09)

4) Phe13vNle17,Phe22-PACAP 101.7(12.3) 5) 1-125-iodide 164.9(20.7)

liver 100

kid,'~e~ 100

183.5~31,2) 94.1(8.3) 1756(165) 319,4(26,3) 44.2(3.9) 76.5(12.2) 69.1(8.4) 87.1(6.4)

Injection of 1-125-VIP with 100 Fg compound#2 resulted in decreased uptake in lung (5% of control), and to a lesser extent in liver, kidney, pituitary, cortex, ileum, aorta, colon and pancreas, pointing to specific uptake. PACAP-uptake exceeded VIP-uptake (in %ID/g) in liver,lung, pituitary and aorta. Conclusion: Compared to native VIP, the new VIP and PACAP analogs tested, except for DTPA-VIP, have suitable receptor binding and (less rapid) metabolism properties, therefore they are promising for tumor imaging.

OMo275

OMo277

M. Raderer A. Kurtaran, S. Li, 3. Pidlich, M. Hejna, S. Meghdadi, P. Angelberger, G. Kornek, and I. VirgolinL Depts of Nuclear Medicine, Internal Med I and Radiology, University of Vienna.

W,H. Bakker, M.E. van der Pluijm, W.A.P. Breeman, M. de Jong, T.J. Visser, E.P. Krenning, Departments of Nuclear Medicine and Internal Medicine, University Hospital and Erasmus University Medical School, Rotterdam, The Netherlands.

123I-VIP-RECEPTOR-SCANN1NG FOR PANCREATIC CANCER: A NOVEL TOOL IN THE DIAGNOSTIC ARMAMENTARIUM. Recent data have demonstrated a high sensitivity (>90%) in the visualization of pancreatic cancers as well as metastases by means of 123IVIP. This prospective study investigated the diagnostic value of radioiodinated VIP in 60 consecutive patients (26 females/34 males) suffering from adenoearcinoma of the exocrine pancreas. Nineteen patients presented with organ-confined malignancy, while 25 patients also had distant metastases along with local malignancy, and 6 patients had liver metastases after resection of the primary lesion. In 4 of these patients, documented abdominal lymph node metastases were present at the time of scanning. Ten patients had undergone potentially curative surgery for their cancer. During follow-up over 6 months, 3 of theses patients developed recurrent disease (2 cases of Ideal recurrence and 1 of liver metastases). All patients were administered ]~I-labeled VIP (150200 MBq; 1 lag V1P). Scanning results were compared with conventional radiologieal results. The overall VIP-scan sensitivity for primary pancreatic adenocarcinomas was 56% (27/46 cases). In patients with disease confined to the pancreas, tumors were visualized in 18/21 patients (90%), while the primary tumor was imaged in only 9/25 eases (36%) in patients suffering both from loeoregional and disease metastatic to the liver indieating gradient loss of VIP receptor affinity. Liver metastases, however, were imaged in 29/31 patients, resulting in a scan sensitivity of 93%, and 3/4 patients with lymph node metastases had positive scans. All 7 patients without evidence of disease at the end of the follow-up period had negative scans. In total, 5 patients had a positive VIP-scan suggestive of recurrent/metastatic disease at least 6 weeks before radiologie evidence was obtained. We conclude that radioimaging of pancreatic adenoeareinoma by means of 123I-VIP is highly sensitive method and could beneficially influence the decision making process.

RADIOIOD1NATED VIP FOR PEPTIDE RECEPTOR SCINTIGRAPHY (PRS) AND PEPTIDE RECEPTOR RADIOTHERAPY (PRRT) Many human tumors have receptors for 28-amino acid-containing VIP, therefore radioiodinated VIP can be used for PRS and PRRT. Radioiodination is a first choice to label tyrosine-containing VIP; this was investigated with respect to 1-123 (PRS) and 1-131 (PRRT). During the labelling of V1P two tyrosines (#10 and #22) can be labelled and methionine (#17) can be oxidixed. This results in 4 radiolabelled analogues: A) I-Tyr(10)-VIP, B) I-Tyr(22)-V1P, C) l-Tyr(10)Metox(17)-VIP and D) l-Tyr(22)-Metox(17)-VIP, each with different receptor binding characteristics. Under mild oxidative circumstances (chloramine-T : peptide = 0.2) more A and C (with better receptor binding properties than B and D) are formed. However, the labelling yield was relatively low (13 %) and the other two compounds were still present (..~ 25 %). Therefore, a well-defined VIP receptor binding analogue NIe(17)-Phe(22)-VIP was synthesized in which only Tyr(10) can be labelled. In our experience at least a 25-fold excess of tyrosine groups over radioiodide has to be used to get a labelling yield > 60 %. Suppose that a 555 MBq 1-123 SPECT-dose is required, that routine labelling will yield > 6 0 % and that 15 % is lost during the procedures, the labelling needs 1088 MBq 1-123. Using "carrier-free" (about 0.8 pmol/MBq) or carrier-added (5 pmol/MBq) iodide, this will result in patient doses of 18 nmol (53 #g) VIP or 120 nmol (361 #g) VIP. After subsequent HPLC-separation this will become 43 pmol (1.3 /xg) and 290 pmol (8.7 /zg). So, as the maximal well tolerated human dose of VIP is probably in the tzg-range, HPLC will always be required to isolate the desired compound. As requirements for 1-131 are exactly similar, for a 3700 MBq (standard therapeutic) patient dose (1-131:10 pmol/MBq) the peptide dose will be 1.6 #mol (5 mg) and 37 nmol (0.1 mg) before and after HPLC respectively, indicating that also here HPLC will be required. However, with regard to PRRT, for octreotide we showed rapid degradation by irradiating 30 #g peptide by 370 MBq 1-131 under small geometrical HPLC-circumstances (317 #L), resulting i n a t% of intact peptide = 1 h. This will hamper PRRT using 1-131VIP. 1101

l0 |m C 0 0 Q. m

t~

• Oncology 0Mo278

0Mo280

A. Kurtaran, M. Mentes, M. Raderer, Ch. Mf]ller, G. Novacek, P. A~]gelberger, and I. Virgolini. Departments of Nuclear Medicine, Oncology, Radiology and Gastroenterology, University of Vienna, Austria.

S.R. Li, C. Bischof, S. Kapiotis, Q. Yang, M. Radosavljevic, H.A. Welch, P. Angelberger and I. Virgolini, Depts of Nuclear Medicine, Medical Laboratory Diagnostics, University of Vienna and Research Center Seibersdsrf, Austria. GBF, Dept. Gene Expression, Brannschweig, Germany

RECEPTOR SCINTIGRAPHY WITH 99mTc-NEOGALACTOALBUMIN (NGA) A N D 123I-TYR- (14) - I N S U L I N I N T H E D I F F E R E N T I A L DIAGNOSIS OF HEPATIC MASS LESIONS

EXPRESSION OF VEGF RECEPTORS ON HUMAN ENDOTHELIAL CELLS

ANDVARIOUS HUMAN TVMOR TISSUES*

In an approach to describe the imaging p a t t e r n of hepatocellular carcinoma (}{CC), metastatic liver lesions, hepatic adenoma and focal nodular h y p e r p l a s i a we investigated the combined use of 2 hepatocytespecific receptor tracers, 99mTc-NGA and 123I-Tyr (AI4)insulin. We examined 32 patients with HCC, i0 patients with metastatic liver lesions, 6 p a t i e n t s w i t h focal nodular hyperplasia and 2 patients with hepatic adenom.l~. After i .v-adminstration of 150 MBq/50 nmol 99"~c'-NG;<. ~l] Z C C - ] e s i o n s as well as m e t a s t a t i c liver ]e~ns w~Le [dentlfied as cold spots. In contrast, in ~ i patieil! s with focal n o d u l a r h y p e r p l a s i a and hepatic adenomas a normal or increased a c c u m u l a t i o n of 99mTc-NGA was observed. A f t e r i.v-injection of 150 MBq ~23I Tyr(AI4) -insulin all HCC lesions showed an accumulation, however, no a c c u m u l a t i o n of z23I-Tyr- (AI4) -insulin was present in patients with liver metastases. In v i t r o studies demonstrated a hack of surface receptors specific for NGA, whereas lesions of focal n o d u l a r hyperplasia and benign hepatic adenomas expressed normal or even higher numbers of NGA receptors. In contrast to this finding, I{CC demonstrated a significantly higher number of specific receptors for 123I-Tyr (AI4) -insulin as compared to normal liver tissue, whereas metastatic lesions expressed no receptor for 1231 Tyr- {AI4 ) -insulin. We conclude that ti: ,_s dual tracer m e t h o d is c l i n i c a l l y useful for the ];fi~re~itial diagnosis of focal liver lesions.

Angiogenesis may play an important role in tumor growth and metastasis formation. Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has recently been identified. VEGF is expressed and secreted by several tumor cells of animal and human origins. In this study we have characterized the VEGF receptors expressed on human umbilical vein endothelial cells (HUVEC), various human tumor cells and primary human tumor tissues using a direct binding assay. VEGFt65 was iodinated with 123-I in view of in vivo studies in patients with vascularized tumors. The binding of 123-I labeled VEGF16~ as well as the functional properties of radiolabeled and unlabeled VEGFI~ were investigated. Scatchard analysis of equilibrium binding experiments revealed two classes of binding sites on the cell surface of HUVEC with dissociation constants (Kd) of 2.7 and 90 pM, respectively, displaying about 1200 and 14100 binding sites, respectively. Two classes of binding sites were also found on most primary tumors (such as breast cancer, glioblastomas, hepatoeellular cancer). Furthermore, labeled and unlabeled VEGF dose-dependently stimulate DNA synthesis of HUVEC and tumor cells as determined by 3-H-thymidine incorporation. Our data indicate the existence of specific binding sites for VEGF on HUVEC and various human tumor tissues. We conclude that 123-Ilabeled VEGF may be used for the in vivo localization of vascularized tumors expressing VEGF receptors.

0Mo279

0Mo281

U. Haberkorn, A. Attmann, I. Morr, G. van Kaick. Dept. of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany.

F. Brnard, S. Kudrevich, J. Rousseau and J.E. van Lier. Department of Nuclear Medicine and Radiation Biology, Universite de Sherbrooke, Sherbrooke, Quebec, Canada.

UPTAKE OF SPECIFIC SUBSTRATES IN HEPATOMA CELLS DURING GENE THERAPY WITH HSV THYMIDINE KINASE. This in vitro study investigates the possible application of positron emission tomography (PET) for monitoring of gene therapy with the HSV-tk suicide gene. After transfection of a rat hepatoma cell line with a retroviral vector and the HSV-tk gene different TK-expressing clones were established by G418 selection. Thereafter uptake measurements were done in a TK-expressing cell line and a control cell line bearing the empty vector using thymidine (the uptake was measured under therapy conditions), fluorodeoxycytidine (FdCyt) and ganciclovir. These experiments were done up to 48 hours. The uptake was further differentiated as acid-soluble and acid insoluble fraction. Furthermore bystander experiments and competition studies were done. During therapy a decrease of the uptake/well for thymidine was seen in the TK-expressing cell lines. Normalisation to the viable ceil number revealed an increased (up to 250% of the control) thymidine uptake in the acid-soluble fraction and a decrease (to 5.5% of the control) in the acid-insoluble fraction. The FdCyt uptake was higher in the TK-expressing cell line with a maximum after 4 hours (12fold and 3-fold higher in the acid-insoluble and acid-soluble fraction respectively). The difference in ganciclovir uptake was higher: up to 180-fold in the acid-insoluble and 26-fold in the acid-soluble fraction. The competition experiments showed a decrease of ganciclovir uptake by inhibitors of the equlibrative nucleoside transport systems, by nucleosides as thymidine, uridine and chloro-adenosine and by the purine nucleobase adenine. Bystander experiments revealed a relation of the growth inhibition and the ganciclovir uptake to the amount of TK-expressing cells. Ganciclovir uptake and growth inhibition were correlated with r=0.97. These data show that PET with ganciclovir may be used for the measurement of the enzyme activity and therefore may be used for the monitoring of gone therapy with the suicide system HSV-tk.

PHTHALOCYANINES AS TUMOR-IMAGING AGENTS: EVALUATION OF INDIUM- 111-DTPA DERIVATIVES IN TUMORBEARING RATS.

1102

* This study was supported in part by the Jubil~iumsfonds of the Austrian National Bank (Project No. 5529)

Phthalocyanines are potent photosensitizers proposed as second generation drugs for photodynamic therapy of tumors (PDT). High tumor uptake of negatively charged, sulfonated derivatives in areas of neovascularisation suggest their potential for tumor imaging by either fluorescence or gamma emission imaging. Such compounds could be useful for planning PDT treatments and predicting tumor response. METHODS: We have radiolabeled derivatives of zinc phtalocyanines (ZnPc) with indium- 111 by the bifunctional chelator (DTPA) method. We have evaluated the biodistribution and pharmacokinetics of In-111-monoDTPA-tbutyl-ZnPc, In-111-di-DTPA-tbutyl-ZnPc and In-111-tetraDTPA-ZnPe in mammary adenocarcinoma-bearing Fisher rats and compared the results to the biodistribution of gallium-67-citrate, indium111-chloride, Tc-99m sestamibi and Tc-99m HSA assessed in the same animal model. Pinhole scintigraphy was also performed to assess the whole-body distribution of the phthalocyanine compounds. RESULTS: The highest tumor uptake (1.73 + 0.25 %i.d./g.) was observed with the most polar tetra-substituted (In-111-tetra-DTPA-ZnPc) compound, which is higher than that observed with gallium-67 (1.47 + 0.37 %i.d./g), indium-chloride (1.23 _+0.21%i.d./g) and Tc99m-sestamibi (0.36 + 0.11 %i.d./g). The mono-substituted derivative also showed excellent tumor uptake (1.43 + 0.29 %i.d./g) with a good target-background ratio. The biodistribution of these radiolabelled phthalocyanines is similar to that of their non radiolabelled sulfonated analogues. CONCLUSION: Indium labelled Pcs present high tumor affinity and may be suitable tumor imaging agent for planning PDT protocols and predicting the tumor response to therapy.

• Oncology OTu282

OTu284

M Laci6*, GJR Cook, P Marsden, MN Maisey *Department of Nuclear Medicine and Oncology, University Hospital "Sestre Milosrdnice" Zagreb, Croatia. The Clinical PET Center,Guys and St Thomas' Hospital Trust,London, UK

L. Maffioli i, M. GasparinP, A. ChitP, A. Gramaglia =, A. PozzP, E. BombardierP. ~Nuclear Medicine Dept., 2Radiotherapy Dept. - Ist. Naz. Tumori; Weuro-oncology Dept. - Ist. Naz. Neurologico "C.Besta"- Milano.

11C METHIONINE AND 18FDG PET SCAN IN THE EVALUATION OF MALIGNANT BRAIN TUMOURS

ASSOCIATION OF Tc-99m-SestaMIBI SPET (MIBI) AND COMPUTED TOMOGRAPHY (CT) IN PRE-TREATED G L I O M A PATIENTS: C L I N I C A L I M P L I C A T I O N S .

Both t i c methionine ( l l c MET) and 18FDG have been used to evaluate brain tumors but the number of comparative studies is limited. Five patients (pts) with new presentations and 15 pts with a suspected recurrence of primary brain tumours were included in this study. All pts underwent a l l c MET and 1 8 F D G PET scan and at least one radiological scan (CT or MRI). Five pts also had a dynamic 11C MET and t8FDG PET acquisition performed. Scans were carried out on a Siemens/CTI ECAT 951R PET scanner. Calculated attenuation correction was applied. Standardised uptake values (SUVs) and tumour to cortex ratios (TCRs) were calculated and correlated with the turnout grade. 18 ]1C MET scans were interpreted as positive for the presence of tumour (5/5 new presentations and 13/15 recurrent) compared to 16 with 18FDG(4/5 new presentations and 12/15 recurrent). No significant, consistent difference in tracer uptake was found between-low grade and high grade tumours for 1 8 F O G o r 11C MET whether measured by TCRs or SUVs (p>0.05). This result was the same when only the 15 pts with suspected recurrence were included in the analysis. When tumour extent was assessed with each radiopharmaceutical a better correlation was found with morphological techniques using 11C MET (r=+0.78) than with 18FDG (r=+0.59). Six (33%) patients showed qualitative and quantitative evidence of crossed cerebellar diaschisis on 18FDG examinations but this phenomenon was not seen with 11C MET. Dynamic studies showed that 1 1 C MET uptake reaches a plateau within 10 minutes in tumour and normal cortex whereas 18FDG may take 60 minutes or more. Five (25%) patients showed a different distribution of 11C MET and 18FDG within tumours. We concluded that a combined l l c MET and 18FDG scanning protocol is a practical investigation from which complementary informations can be gained especially for the assessment of recurrent brain turnouts.

The treatment of human glioma produces in many cases radiological alterations which represent a clinical dilemma. In fact, CT or MRI are not always able to discriminate between brain recurrences and radiation injury in pre-treated patients. Preliminary experiences indicate that MIBI can play a role in imaging brain tumours. Aim of the study was to evaluate the clinical usefulness of the association of MIBI and CT in the detection of brain tumour relapses. We enrolled 61 patients previously treated for glioma and presenting a worsening of the neurological situation and with a radiological suspicion of neoplastic relapse (or persistence) during follow-up. CT scan and M]BI were performed within 15 days. The results were compared with follow-up data and, when possible, histology. In these 61 patients we performed 72 CT and 72 MIBI studies. Main results are showed in the following table: MIBI CT MIBI+CT 100 % Sensitivity 88 % 98 % Specificity 91% 67 % 75 % Accuracy 88 % 92 % 96 % Positive predictive value 98 % 93 % 96 % N e g a t i v e predictive value 63 % 86 % 100 % Our study suggests that the association of MIBI to CT is useful in the follow-up of patients pre-treated for gliomas, when a differential diagnosis between the presence of neoplastic tissue and radiation necrosis is needed.

OTu283

OTu285

~ ~ , K.Csaplftr1, H. M0hlensiepena, K. Ziemonsl, M. Holsehbach2, J.C.W. Kiwit, K. Zllles4, H.-W. MiJller-G/irtoer aa. Inst. of MedJ and Nucl. Chem. 2, Research Center Jiilich, Dept. of Neuroanatomy3 and Neurosurgery4, Univ. of Diisseldorf, Germany.

E. Book1), M. Gliese2), J. Marienhagen 1), J. Rtischoff3), O.W. Ullrich2), V. Spies4), A. Brawanski2), St. Feuerbacb 41, Chr. Eilles]). • • i) 2) • 3) Depts. of Nuclear Methclne , Neurosurgery , Institute of Pathology and Dept. of Radiology4), University of Regensburg, Germany.

COMPARISON OF 1-123-c~-METHYLTYROSlNE (IMT) AND 1-125O-METHL-c~-METHYLTYROSINE (OMIMT) UPTAKE IN A RAT GLIOMA MODEL BY DUAL TRACER AUTORADIOGRAHPY

PREDICTING MALIGNANCY IN BRAIN TUMOURS EXCELLENT RESULTS OF SEQUENTIAL 2°1THALLIUM SPECT

IMT has proven to be a promising SPECT tracer of amino acid uptake in cerebral gllomas. An analogue of the molecule, OMIMT, showed 5 times higher brain uptake in mice than IMT. The aim of this study was to compare tumor/brain accumulation of IMT and OMIMT. Cell suspensions of the anaplastic rat glioma clone F98 were inoculated stereotactically into the brain of six adult Fischer-CDF rats. After 8 days of tumor growth animals were anesthetized and 1-123-IMT and 1-125-OMIMT injected simultaneously into a tail vein. Animals were killed after 15 min, brains removed and frozen in liquid isopentane. Serial 20 pm sections of the tumor bearing brain area were produced and exposed to photo imager plates immediately and after decay of 1-123 radioactivity. IMT and OMIMT distribution images were generated by image subtraction. An example is shown in Fig.1.

We have recently demonstrated the diagnostic value of sequential 2°]TISPECT in patients with supratentorial brain lesions. Aim of the current investigation was to validate our preliminary results in a greater number of patients. We performed 132 2°ITI-SPECT studies in 112 patients. 90 patients underwent surgery/stereotactic biopsy and MRT/CT. SPECT studies were acquired 15 min. and 3 hrs. p.i. using a 3-headed camera (MS3, Siemens). Geometric means for T/NT regions in early and delayed images (grading indices R~ and R2) were calculated for 2 subsequent oblique slices, as well as the gradient angle c~ of a straight line between R~ and Rz. c~<0 indicated thallium washout, c~>_0thallium retention. Using R] - 1.5 as a cut-off value concerning malignancy, results were as follows: RI>I.5 Astrocytoma Astrocytoma Astrocytoma Glioblastoma

I II III IV

cz>0

0/1 1/I 1 9/13 29/30

0/1 1/11 3/13 9/30

10/11

2/11

!

Metastasis 1-123-IMT

IMT

OMIMT

1 2,42 2,11

2 3,0 2,8

(x > 0

1/0

0/1

Meningioma I Meningioma II Meningioma IV

I5/16 2/2 1/1

1/16 0/2 0/1

No tumour

0/4

0/4

1-125-OMIMT

Tumor/brain ratios are given in Table 1. Rat

RI>I.5 Lymphoma

3 3,43 3,16

4 2,24 2,13

S 2,60 2,45

6 2,23 2,22

mesa + SD 2T65± 0~48 2,48 + 0.42 (not significant)

Extent of tumor labelling with IMT and OMIMT was identical in all cases.Tumor/brain ratios for OMIMT were only slightly lower than for IMT in this glioma model. Thus, OMIMT, due to its higher brain uptake, may offer significant reduction of cost and radiation exposure compared to IMT.

Sensitivity of R~ concerning malignancy is excellent for all brain lesions (88.4-89.3 %), whereas specificity drops significantly when including meningiomas (93.8-47.1%). Gradient angle c~ shows low sensitivity, but superior specificity for all lesions (91.7-94.1%). Hence, the diagnostic value value of sequential 2°IT1-SPECT including calculation of grading indices e 1 as well as gradient angles c~ consists in a markedly improved specificity especially in an unselected group of patients.

1103

tO =m t~ e-

(D L

1:1. m

t~

• Oncology OTu286 *F.G~nq~r,H.Bezircio~lu,G.G~venc,*B.Karayalcin E.Ulu¢,$.GOney,A.I$isa~,M.Ongun *Akdeniz University Fac.of Med. ANTALYA,TURKEY izmir AtatOrk State Hospital IZMIR,TURKEY TEE CORRELATION OF TI-2Ol UPTAKE WITH PROLIFEB~TING CELL NUCLEAR ANTIGEN LABELING INDEX IN BRAIN TUMOURS

The aim of this study was to assess if TI-201 uptake index(UI) can be r e p r e s a n t a t i v e of p r o l i f e rative activity(PA) of the brain tumours. For this p u r p o s e , T i - 2 0 1 SPECT imaging(15 min after the injection of 100MBq of TI-201) was p e r f o r m e d on 26 p r e o p e r a t i v e p a t i e n t s ( 2 1 M / S F , m e a n age:43±12) and p r o l i f e r a t i n g cell n u c l e a r antigen labeling index (PCNA-LI) was c a l c u l a t e d in p o s t o p e r a t i v e l y for all tumours. H i s t o l o g i c a l diagnosis were as follows:7 high grade g l i o m a s ( H G G ) , 9 low grade gliom a s ( L G G ) , 8 m e n i n g i o m a s ( M G ) , a n d 2 h e m o r r h a g i c infarcts(HI).While none of the LGG and HI showed TI-201 uptake,all of the HGG and MG showed TI201 u p t a k e . U I , e x p r e s s e d as the ratio of the total count of the tumour to the total count of the contralateral n o r m a l region was 2.98±0.85 and 3.95±1.13 in HGG and MG,respectively. PCNA-LI values revealed as 1 8 . 2 4 ± 6 . 8 8 , 1 . 0 8 ± 0 . 6 5 , 2 . 7 5 ± 1 . 3 2 in H G G , L G , a n d MG,respectively. PCNA-LI value was significantly higher in HGG than that in LGG and MG.While a significant correlation was o b s e r v e d b e t w e e n the UI and PCNA-LI values in e x c i s e d tumour specimens in H G G ( r = 0 . 8 6 , p < 0 . 0 5 } , t h e r e was not a correlation in M G . T h e s e findings suggest that while TI-201 u p t a k e can be due to the PA of the tumour in HGG,the increased b l o o d flow and the disruption of the b l o o d - b r a i n b a r r i e r are m o r e responsible in MG rather than PA. We concluded that TI-201 uptake can be a r e p r e s a n t a t i v e index of PA of the HGG.

OTu288 D. Brecht-Krauss, C.A. Guhlmann, M. Schulte, G. Glatting, L. Kinzl, S.N. Reske. Departments of Nuclear Medicine and

Surgery III, University of U/m, Germany MONITORING CHEMOTHERAPY RESPONSE IN OSTEOSARCOMA BY [F-18]FDG-PET Purpose: To evaluate use of FDG-PET in the assessment of chemotherapy response in patients with osteosarcomas. Methods: Ten patients (pts) with high malignant osteosarcomas were studied by FDG-PET within 3 days before and after chemotherapy according to COSS 86c protocol. Nine tumours were initially classified as stage liB by open biopsy, one patient had stage III disease with pulmonary metastases. Tumour response to chemotherapy was determined histologically by analysis of resected specimen and classified in grade of regression according to Salzer-Kuntschik on a scale from 1-6. FDG-PET was performed with a Siemens ECAT-931-08-12 scanner. After transmission scanning 200-300 MBq [F-18]FDG were administered and emission scans were started 45 rain later. Quantitative image analysis was performed using standardized uptake values (SUV) and turnout background ratios (TBR) 60rain p.i. Results: Six responders, defined as histological regression _< 3, demonstrated a reduction of FDG uptake after chemotherapy of (72_+16)% of initial FDG uptake, whereas 4 non-responders showed a reduction of (16_+7)% (x _+ SD, p<0.05). Change of pre- to posttherapy SUV and TBR of FDG showed a significant correlation (rsuv=0.81, rTSR=0.87, p<0.05) to histoIogic grade of regression (threshold values for SUV and TBR ratios are 0.59 and 065, respectively). Conclusions: These preliminary data indicate that FDG-PET is a promising tool for monitoring chemotherapy response in osteosarcomas, possibly implicating different surgical strategies.

OTu287

OTu289

G. Mariani, A. Lasku, G. Villa, C. Motta, G. Calcagno, G. Taddei, A. Dorcaratto, A. Pau, A. Epenetos, L. Zardi, and G. Viale. Nuclear Medicine Service, DIMI, and Institute of Neurosurgery, University of Genoa; National Cancer Institute (IST); Genoa (Italy); Imperial Cancer Research Fund; London (United Kingdom).

H. Sumiya, J. Taki, T. Miyauchi, N. Tonami, H. Tsuchiya, K. Tomita, I~partments of Nuclear Medicine and Orthopedics, Kanazawa University, Kanazawa, Japan

A PILOT PHARMACOKINETIC AND IMMUNOSCINTIGRAPHIC STUDY OF BRAIN TUMORS WITH THE 99~"Tc-LABELED MONOCLONAL ANTIBODY BC-1 DIRECTED AGAINST ONCOFETAL FIB RONECTt N Preliminary experiments in the animal model (nude mice beating human tumor implants) have shown the favourable tumor targeting potential of radiolabeled BC-1, an IgG, monoclonal antibody (MoAb) that recognizes the fibronectin isoform containing the ED-B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues and high expression in fetal and tumor tissues, particularly in high-grade astrocytomas and gliomas. The study was carried out in 5 patients with brain tumors (3 women and 2 men, age range 32-58 years): 4 patients had brain glioma and 1 had a malignant angioblastic meningioma. The BC-1 MoAb was labeled with 99mTcby MDP-transchelation (1110 MBq/0.5 rag), and purified by gel Sephadex G-25 column chromatography. Planar and SPECT imaging was acquired at 4-6 and 20 hr after i.v. injection, and compared to the nonspecific indicator of blood-brain barrier disruption, 9~Tc-DTPA. Pharmacokinetic analysis was based on serial whole-body scans, plasma and urine samples. All patients underwent surgery at the end of the immunoscintigraphicstudy. The plasma clearance curves were biexponential, with average T ~ values of 2-4 hours and 28-33 hours, respectively; 99mTc-BC-1 showed very low nonspecific uj~take in bone marrow, liver and spleen. Planar and SPECT imaging with ~mTc-BC-1 visualized brain tumors in all patients, with a pattern of intratumor distribution that specifically identified areas of ~eripheral tumor growth more accurately than the nonspecific indicator, rn Tc-DTPA. Tumor uptake of 9 9 m Tc-BC-I reflected high expression of the specific oncofetal fibronectin, as shown by immunohistochemistryon surgical samples. These results indicate the potential usefulness of immunoscintigraphy with the MoAb 99mTc-BC-1 in cancer patients, at least in those clinical conditions characterized by important angiogenesis induced by cancer.

1104

TECHNETIUM-99m-MIBI SCINTIGRAPHY IN EVALUATION OF BONE AND SOFT TISSUE LESIONS ThaUium-201 (T1) has been widely used for the evaluation of bone and soft tissue tumors. The purpose of this study was to compare the ability of T1 and Technetium-99m-methoxyisobutylisonitrile (MIBI) to detect and assess the tumor response to chemotherapy in malignant and benign bone and soft tissue lesions. Forty-two patients with various bone and soft tissue pathologies were studied with TI and MIBI. There were 21 men and 21 women (age range, 8 to 87 years; average age, 47+_21 years). Twenty-eight had malignant tumors and 14 had benign lesions. Planar T1 scintigraphy was performed at 15 rain after injection of 111 MBq of T1. Within one week of the TI study, radionuclide angiography with 600-740 MBq of MIBI was performed and planar imaging was also performed 15 rain later. In visual analysis, 31 of 42 patients showed similar uptake of both tracers, 8 (5 malignant and 3 benign lesions) showed more intense uptake of MIBI than TI, and 3 (all malignant lesions) showed more intense uptake of T1 than MIBI. In quantitative analysis, similar T1 and MIBI uptake ratios were obtained (1.96_+1.25 vs 1.96+1.02 respectively, p=ns). Perfusion index derived from MIBI radionuclide angiography was higher than MIBI uptake ratio (2.33+-1.23 vs 1.96_+1.02 respectively, p<0.005), but correlated well with MIBI uptake ratio (r=0.75). In 11 cases with malignant tumors, T1 and MIBI scintigraphies were repeated after chemotherapy and the uptake of both tracers was significantly suppressed in patients with complete response confirmed by histological evaluation. In patients with complete response (n=3) uptake ratio of both tracers was reduced by more than 50 %, whereas, less than 20 % reduction of uptake ratio was observed in patients with non-response (n=6). The ability of MIBI to detect malignant and benign bone and soft tissue lesions and assess the tumor response to chemotherapy was comparable to that of T1. In addition, blood flow could be assessed by radionuclide angiography with MIBI. Thus, it is concluded that MIBI is a promising radiopharmaceutical for the evaluation of bone and soft tissue lesions.

• Oncology OTu290

OTu292

S.Klra~ K.Kumanllo~lu, E.Teber, S.KUr~at, Y.Tokat Ege University, Medical Faculty, iZMiR-TORKiYE

S. Stroobants P. Dupont, G. Verhoef, J. Thomas, S. Vleugels, G. Bormans, M. De Roo, L. Mortelmans. Nuclear Medicine, Haematology and Oncology, University Hospital Gasthuisberg, Leuven, Belgium.

co

i m

THE ASSESSMENT OF RENAL FUNCTIONS IN KIDNEY TRANSPLANT CASES Radionuclide imaging studies have become routine assessing renal function after transplantation procedure. Differentiation among of many complications is possible with radionuclide studies. In this study, renal perfusion time, renal perfusion peak count-to-aort peak count ratio, and bladder visualization time were used for evaluating of transplanted kidney functions. Study group consisted of 59 subjects who were operated on renal transplantation. 23 of donors were live, and the others were kadaveric allografts. Of transplanted patients, 22 had normal (NL) graft function, 25 were diagnosed as acute rejection (AR) and 14 cases with chronic allograft nephropatia (CAN). The mean age was 34~9yr, 29~9yr, 29~7 yr, respectively. Cyclosporine-A level was measured as normal in all patients (pts). Percutanous renal biopsy was performed to 32 pts. All pts underwent Tc-99m DTPA study. 740 MBq was injected intravenously to the patient with supine position. Renal dynamic and static images were immediately obtained after injection. Renal perfusion was delayed in CAN group (8.8~i second) than the ones of NL group (2±1 s) and AR group (3.5±3 s), piO.05. Renal perfusion peak count-to-aort peak count ratio was similar in each group. The bladder activity arrival time was prolonged for CAN group (10±7 min) than the values of other groups (NL:6±4 min and AR: 6~3 min), pi0.05. Consequently, we suggest that renal transplant perfusion time and bladder activity arrival time are significant in the differential diagnosis and management of the patients with chronic allograft nephropatia.

COMPARISON OF WHOLE-BODY FDG-PET AND GALLIUM-67 CITRATE IMAGING FOR STAGING OF LYMPHOMA. Accurate staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is important for treatment managment. The aim of this study is to compare the sensitivity of whole-body FDG-PET and Gallium-67 citrate scanning (Ga) in the initial staging of untreated lymphoma patients in relation to CT. Until now 15 patients with biopsy-proven lymphoma (6 I-ID, 2 high grade NHL, 5 intermediate grade NHL and 2 low grade NHL) underwent PET, Ga and CT within one week prior to the start of chemotherapy. The PET study (6 min/bedposition) was performed with an ECAT 931/8/12 scanner and started 60 min post injection (p.i.) (dose: 6.5 Mbq/kg). The Gallium scan was started 72 h p.i. (dose: 180-230 Mbq). Three anterior and posterior planar images (10 min/image) were acquired with a double headed gamma camera. In each patient 14 different lymph node regions were defined (Waldeyer, cervical L/R, clavicular L/R, axillary L/R, mediastinal, upper abdominal, spleen, iliacal L/R, inguinal L/R). CT was positive in 84, PET in 90 and Ga in 46 regions out of 210. PET and CT were concordant in 195 regions, eight regions were positive exclusively on PET and consisted of small lesions of less than 1.5cm. The seven regions positive on CT but not on PET were all in patients with low grade malignancy. Gallium scintigraphy detected only half of the lesions compared to PET or CT and all positive regions on Ga were also positive on PET. With Ga especially small regions and lesions located in the abdominal or axillary region were missed. Anatomical localisation of lesions is improved with PET compared to Ga due to a better resolution and image quality. We conclude that FDG PET is more sensitive as compared to Gailium scintigraphy in the staging of lymphoma patients. Smaller lesions and abdominal lymphnodes are more easily detected.

OTu291

OTu294

F. Mooq, J. Kotzerke, A. Guhlmann, M. Bangerte~, SN Reske. Departments of Nuclear Medicine and Internal Medicine*, University of UIm, Germany

D.M. Goldenberm R.P. Baum, M.J. Blend, and C.M. Pinsky, Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Newark, NJ; University Clinic, Frankfurt, Germany; University of Illinois, Chicago, IL; Immunomedics, Inc., Morris Plains, NJ, USA

ROLE OF FDG-PET IN DETECTING WHOLE BODY EXTEND OF MALIGNANT LYMPHOMA Purpose: To prospectivly evaluate the use of FDG-PET versus CT and bone marrow biopsy in primary staging of malignant lymphoma. Methods: 60 consecutive and untreated patients with proven malignant lymphoma (33x NHL, 27x Hodgkin disease) underwent whole body imaging with CT. After a 12 hrs fasting period and injection of 270-370 MBq 2-(fluodne-18)-fluoro-2-deoxy-D-glucose (FDG) PET scans of the trunc were acquired with a ECAT-Siemens 931/08-12 scanner. Transversal slices were calculated by iterative reconstruction and attenuation correction. A bone marrow biopsy was performed in each patient. CT and PET scans were read independently and blinded to all clinical or imaging data by 2 experienced observers respectively. Increased focal uptake of FDG was considered a sign of malignancy. Concordant CT/PET findings were regarded as true positive. Discordant results were vedfied by biopsy, MR or clinical follow up > 6 month (22/50). Results:

Total True positive False positive Unconfirmed

CT+/PET+ Nodal Extra 160 22 160 22

CT+/PETNodal Extra 6 8 1 3 4 3 3

PET+/CTNodal Extra 25 11 7 4 2 1 16 6

Discrepant findingswere correctly judged by CT (CT+/PET-) in 12.5% (1/8) and by PET (PET+/CT-) in 78.6% (11/14) of confirmed lesions. Out of 7 cases with histologically confirmed focal bone marrow infiltration imaged by PET, only 2 could be detected by a biopsy of lilac crest. On the other hand, 5 cases with diffuse bone marrow infiltration could not be imaged by PET. Conclusion: FDG-PET has excellent sensitivity and specificity for detecting malignant lymphoma. CT provides little additional information but adds significant false positive results. PET and bone marrow histology give complementary information about bone marrow infiltration.

t~ e-

CLINICAL RESULTS WITH A NEW IMAGING AGENT FOR NON-HODGKIN'S LYMPHOMAS (NHL), LYMPHOSCANTM

Purpose: LymphoScanTM is a monoclonal antibody Fab' fragment that reacts with the CD22 of lymphomas, and when labeled with Tc99m functions as an imaging agent for NHL. A Phase I/II study involving 58 patients with NHL has been undertaken with 0.25-5.0 mg of LymphoScanTM labeled with 30 mCi of 99'*Tc, with imaging occurring at 3-5 and 18-24h post-injection. Results: For 43 evaluable patients, the overall imaging statistics showed a sensitivity of 86% and a positive predictive value of 100%. Since all patients had known disease, specificity and negative predictive value could not be estimated. The imaging results showed that tumors could be targeted at protein doses as low as 0.25 mg, that normal spleen was hot, but not normal lymph nodes, that all grades and histological types of NHL were imaged, that tumors in all sites of the body (bone, bone marrow, lymph nodes, and visceral organs) were disclosed, and that same-day imaging is accurate and convenient. HAMA responses at this low protein dose were negligible, and no adverse reactions have been reported. Conclusion: LymphoScanTM appears to be a useful new imaging agent for staging NHL and for determining the presence of viable disease in normal-sized lymph nodes, permitting a whole-body scan and regional views to demonstrate sites of disease in all body regions and for all histological types and stages. Phase III trials are being prepared.

1105

Q. m

t~

O

• Oncology OTu295

OTu297

Y. Cottin, C. Touzery, B. Coudert, M. Toubeau A Berriolo, M. Cohen, S. Roy, F. Brardy, JE. Wolf, F. Brunotte. Centre Georges Franqois Leclerc, rue du Pr Marion, 21000 Dijon, France.

K. S c h e i d h a u e r W. Groth*, U. P i e t r z y k #, W. Eschner, Th. Schaefer*, B. Dederichs, P. T h e i s s e n and H. Schicha. D e p a r t m e n t s of N u c l e a r Medicine, Dermatology*, and M a x - P l a n c k - I n s t i t u t e # , U n i v e r s i t y of Cologne, G e r m a n y D I A G N O S I S OF M E T A S T A T I C M A L I G N A N T MELANOMA: IN C O M P A R I S O N TO IMNLrNOSCINTIGRAPHY

FDG-PET

COMPARISON OF EPIRUBICIN AND DOXORUBICIN CARDIOTOXICITY INDUCED BY LOW DOSES: EVOLUTIONOF THE DIASTOLICAND SYSTOLIC PARAMETERS STUDIEDBY RADIONUCLtDEANGIOGRAPHY. Previous studies demonstrated that epirubicin (EPI) had a lower propensity to produce cardiotoxicity effects than Doxorubicin (DXR) for high doses. In a prospective study, seventy seven patients without cardiac disease with a mean age of 51 +_ 13 years were studied before and one month after the end of chemotherapy. The group I included thirty-three patients receiving 241 _+ 100 mg/m2 of DXR and the group II included fourty-four patients receiving EPI with an equivalent dose of 220 + 96 mg/m2 of DXR. The purpose of this work is to study the differences of cardiac toxicity of these two anthracyclines by assessment of both diastolic and sytolic changes in ventricular function. By gated radionuclide angiography, we determined the ejection fraction (EF), the peak ejection rate (PER), the peak filling rate (PFR) (expressed in end diastolic volume per second, EDV/sec). Comparison of intra-group means was performed by the paired t-test : EF (%) PER(EDV/SEC) PFR(EDV/sec) GROUP I : 58 ± 6 3.08 + 0.44 2.75 :I:0.58 Before After 55 ± 6 2.84 + 0.51 2.44 :h 0.58 < 0.001 <0.05 < 0.02 t test EF (%) PER(EDV/SEC) PFR(EDV/sec) GROUP II : 58 5:6 2.95 + 0.49 2.78 + 0.46 Before 55 ~ 6 2.75 ± 0.36 2.68 + 0.46 After < 0.00l <0.001 NS t test Our results show moderate and similar alterations of left ventricular ejection fraction for low doses of anthracyclines. In contrast, none diastolic alteration appeared in the epirubicin group for the same equivalent dose of anthracycline. A possible mechanism for explanation of specific alteration after DXR could be the increased production of semiquinone free radicals which are know to induce membrane damage and consequently myocardial edema and diastolic alteration.

The p u r p o s e of the study was to c o m p a r e the a c c u r a c y of F D G - P E T imaging w i t h that of immunos c i n t i g r a p h y (IS) u s i n g c o m m e r c i a l l y a v a i l a b l e a n t i - m e l a n o m a m o n o c l o n a l a n t i b o d i e s (Mab 225.28S, Sorin Comp.) in 20 p a t i e n t s s u f f e r i n g from m a l i g n a n t melanoma. F i n d i n g s w e r e e v a l u a t e d a g a i n s t r o u t i n e e x a m i n a t i o n s (clinical check, sonography, X-ray, CT, and histology). Planar IS images as well as SPECT w e r e o b t a i n e d 4 - 6 and 20 hours after ivi n j e c t i o n of 900 M B q 99m-Tc l a b e l l e d Mab. PET images were a c q u i r e d o n a CTI ECAT Exact s c a n n e r s t a r t i n g 30 m i n after i v - i n j e c t i o n of 370 M B q FDG in fasting state. E v a l u a t i o n was b a s e d on the c l a s s i f i c a t i o n of i n v o l v e m e n t of a) soft tissue, b) lymph nodes, c) skeleton, and d) p a r e n c h y m a l organs. B e f o r e IS and PET, 11/20 p a t i e n t s w e r e c l i n i c a l l y disease-free. 9 p a t i e n t s s h o w e d e v i d e n c e of m e t a s t a t i c disease. IS found M a b - p e s i t i v e foci in 14 patients, but two t u r n e d out as false positive. In contrast, PET d e m o n s t r a t e d F D G - u p t a k e in 16 patients, all later c o n f i r m e d as true p o s i t i v e lesions. B a s e d on the i n v o l v e m e n t of o r g a n s y s t e m s (a - d), 14 lesions w e r e k n o w n before, 19 w e r e s h o w n by IS (including 2 false p o s i t i v e ) . PET y i e l d e d 32 i n v o l v e d l e s i o n areas. In 5 p a t i e n t s PET p r o v e d m e t a s t a t i c p r o g r e s s not k n o w n before. PET r e v e a l e d a m o r e e x t e n d e d stage of d i s e a s e in a d d i t i o n a l 6 patients, c l a i m i n g i m m e d i a t e c l i n i c a l effect. IS c o n f i r m e d m o s t l y initial c l i n i c a l l y s u s p i c i o u s lesions (16/17}, a n d s h o w e d p r o g r e s s i o n in i case. In conclusion, PET i m a g i n g was c o n s i d e r a b l y m o r e a c c u r a t e than IS. F D G - P E T m a y p r o v i d e a r e l i a b l e and c o s t - e f f e c t i v e tool in the c l i n i c a l m a n a g e m e n t of p a t i e n t s w i t h m e t a s t a t i c melanoma.

OTu296

0Tu298

H.Bender, K.Hamad, J.P.Frohmann*, M.Grapow, A.SSchomburg, U. Reinhold*, H.Palmedo, E.Klemm, F.Gruenwald, C.Menzel, J.Ruhlmann, and H.-J.Biersack Depts. of Nuclear Medicine and *Dermatology; University of Bonn, Germany.

R. Lietzenmayer l, U. Feine j, J. Held ~, ]. Kreissig 2, A. Smnowsky 2, M. Mfiller-Berg ~, W. Mfiller-Schauenburg =, R. Bares 1 Departments of Nucle~ Medicine ~ and Ophthalmology 2 Eberhard-Karls-University, Tfibingen, Germany.

STAGING OF MALIGNANT MELANOMA: VALUE OF WHOLE-BODY FDG-PET AND RADIOIMMUNOSCINTIGRAPHY Whole-body positron-emission tomography (PET) employing fluoro18-deoxyglucose (FDG) is increasingly used in oncologic patients (pts). We studied a total of 92 pts.diagnosed with malignant melanoma (MM). We employed a routine multiple (4-6) bed position protocol, with 10-min emission and 10-min transmission acquisitions per bed position, starting 45-60 min after i.v. injection of 287 MBq FDG (range, 185-314); mean blood sugar levels were 4.92 (2.87-6.9) mmol/L At this time, 5810ts have been evaluated in detail. Pts were refered for staging following removal of the primary tumor; Lesions were visually graded depending on the intensity of uptake (intense = malignant; moderate = suspicious; minima1 = unspecific/inflammation; normal uptake = normal). All pathological PET findings were controlled by CT, MRI and/or resection. In 25 pts. no pathological glucose-uptake was observered (23 true negative; 2 false negative); In 33 patients a total of 132 lesions were detected; 51 lesions were graded as normal (51 true negative, 1 false negative, 1 undetermined); 47 lesions were suspected to be malignant (4 right positive; 12 false positive, 31 undetermined); 33 lesions were graded malignant (22 true positive; 5 false positive; 6 undetermined). Additionally, in 48 pts. radioimmunoscintigraphy (RIS) was performed and compared with the PET results. RIS was normal in 35 pts (12 false negative) and positive in 13 pts. showing metastases in lymph nodes (N=ll; PET N > 40 true positive) and in bone (N=3; PET N=22), but was unable to detect metastases in liver (PET 11), lung (PET 6), and brain (PET N=2). A more detailed analyses as well as semiquantitation of all lesions is currently being performed.

1106

DETECTION

OF OCULAR

MELANOMA

BY

18-FDG-PET

D i a g n o s i s of ocular m e l a n o m a is u s u a l l y e s t a b l i s h e d by use of ophthalmoscopy, ultrasound, or fluoroscopy, c o m p l e t e d by x - r a y CT or MRI. A l t h o u g h these methods are known to be sensitive in tumor detection, differe n t i a t i o n b e t w e e n m a l i g n a n t m e l a n o m a and b e n i g n tumors is still d i f f i c u l t and needs further refinement. The aim of this study was t o analyze the use of [18F] F D G - P E T for d e t e c t i o n or d i f f e r e n t i a l d i a g n o s i s of ocular melanoma. Fourteen patients w i t h s u s p e c t e d ocular m e l a n o m a were examined p r o s p e c t i v e l y by static PET scans o b t a i n e d 45 min. after i.v. i n j e c t i o n of 370 MBq FDG. In addition whole b o d y PET scans were acq u i r e d without a t t e n u a t i o n correction. Image analysis was p e r f o r m e d v i s u a l l y as well as q u a n t i t a t i v e l y by c a l c u l a t i n g r e c o v e r y - c o r r e c t e d SUVvalues of tumor and contralateral eye. Results were v a l i d a t e d by surgery (n=13) or clinical course (n-l). Ten out of 13 ocular m e l a n o m a s r e v e a l e d intensive F D G - u p t a k e {tumor prominence: 5-12.5mm), 3 patients showed normal findings (3 patients with tumor promi nonces of 2.3, 3.7 o r 4.5 mm; one patient after laser therapy). I n one patient without i n c r e a s e d FDG-uptake a focal h e m a t o m a was c o n f i r m e d laten. Whole B o d y PET d e t e c t e d p r e v i o u s l y u n k n o w n distant m e t a s t a s e s in two patients. We conclude that FDG-PET is suitable for d e t e c t i o n of small ocular m e l a n o m a s and allows d e t e c t i o n of dis rant m e t a s t a s e s d u r i n g the same examination. Sensit i v i t y a p p e a r s t o be m a i n l y limited by tumor size (prominence) w h i c h should exceed 5 mm to obtain posi tire results.

•

Oncology

OTu299

OTu301

W. Brenner, *H.-J. Klomp, K.H. Bohuslavizki, B. Szonn, H. Wolf, U. Teichert, C. Stauch, M. Clausen, E. Henze Clinics of Nuclear Medicine and *Surgery, Christian-Albrechts-University of Kiel, Germany

R.A. Vald6s Olmos, R.T. Gregor, A.J.M. Balm, F.J.M. Hilgers, W. Koops, B.M. Loftus-Coll, I.H. Liem, S.H. Muller, C.A. Hoefnagel. The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, NL.

WHOLE BODY IMAGING WITH THALLIUM-201 T I E N T S W I T H MALIGNANT MELANOMA.

IN PA-

TI-201 SPECT TO ASSESS THE PRIMARY TUMOUR, LYMPH NODE INVOLVEMENT AND RECURRENCES OF HEAD AND NECK CANCER,

Thallium-201 has proven valuable in various malignant tumours for imaging of lesions not too close to heart, liver, and intestine. Up to date however, there has been only few reports of imaging melanomas by T1-201. The aim of this study, therefore, was to investigate the diagnostic value of TI-201 whole body imaging for detecting metastases in patients with malignant melanoma. In ,total 25 melanoma patients with known or suspected metastases have been investigated prior to surgical therapy. Whole body imaging was performed simultaneously from anterior and posterior views at 5 and 30 min after administration of 150 MBq T1-201 using a dual head gamma camera with high resolution collimators. For quantification, target-to-background ratios were calculated by conventional ROI-technique using contralateral normal tissue for comparison. Imaging results were correlated with histopathological findings of each patient on a lesion-by-lesion basis. A total of 39 metastases was proven histologically. 30 out of 39 lesions were true positive by scintigraphic imaging including 4 in-transit metastases in 2 patients which were not known at the time of investigation. This corresponds to a sensitivity of 77 %. On the other hand, T1-201 imaging was false negative in 9 lesions, 5 of them lymph node metastases and 4 skin metastases. Furthermore, TI-201 imaging was true negative in one patient with an inguinal hematoma, and there were 2 false positive thallium scans with tracer accumulation in inflammatory lesions located in the lung and in the colon, respectively. The mean target-to-background ratio in tree positive scans was 1.67 _+0.48 and 1.55 + 0.43 (p > 0.05) at 5 rain and at 30 rain p.i., respectively. In conclusion, TI-201 whole body imaging is a sensitive tool for detecting both lymph node and in transit metastases of malignant melanoma. Since imaging is easy to perform yielding results within one hour, this method might be employed in follow-up examinations of patients with malignant melanoma.

The purpose of this study was to evaluate the accuracy of TI-20I SPECT for diagnosis of primary lesions, lymph node metastases and recurrences in head and neck cancer. SPECT imaging was obtained 60 min after administration of 150 MBq of T1-201 chloride and findings were compared with clinical results and CT (or MR/when CT not available). In 70 patients studied for primary lesions (larynx, hypopharynx, oropharynx, nasopharynx and oral cavity), TI-201 SPECT was able to correctly identify 59 of 63 (94% vs 87% for CT/MRI) histologically confirmed malignancies including 56 squamous-cell carcinomas; the method was particularly useful in localizing 4 occult naso-and oropharynx carcinomas not seen on CT/MRI. T1-201 SPECT was correctly negative in 2 patients without tumour and in 4/5 cases with no confirmed primary tumour in head and neck. With respect to regional lymph node metastases only patients who underwent neck dissection were evaluated and findings were recorded per neck side: TI-201 SPECT correctly identified metastases in 26 of 30 neck sides with proven lymph node involvement (87%), was correctly negative in 9 and false positive in 2; although sensitivity of CT/MRI was higher (96%), considerably more false positive cases (7) affected its accuracy (78% vs 85% for SPECT). Finally, in 26 patients investigated for recurrences, TI-201 SPECT correctly identified 23 of 25 histo-or cytologically confirmed tumour sites (92%) and was correctly negative in 7; although CT/MRI was able to identify 19 tumour sites, a higher number of false positives (7 vs 3 for SPECT) did decrease its accuracy (63% vs 86% for SPECT). It is concluded that TI-201 SPECT appears to be an accurate method for diagnosis of head and neck cancer. The method is particularly indicated for detection of occult head and neck tumours, and for assessing recurrences. It may also be of complementary value in the staging of primary lesions and in the differentiation of metastatic from reactive lymph nodes in the neck.

OTu300

OTu302 C.A. Guhlmann, M. Storck, J. Kotzerke, F. Moog, L. SunderPlassmann, S.N. Reske. Department of Nuclear Medicine and

S. Leskinen, P. Lindholm, H. Minn, M. Lapela, M. Haaparanta, K. Nggren, P. Lehikoinen, U. Ruotsalainen, U. Wegelius, E. Nordman. Dept. of Oncology and R a d i o t h e r a p y and Turku Medical Cyclotron/PET-Center, Univ. of Turku, Finland HEAD AND NECK CANCER: DOES THE UPTAKE OF FDG AND [IIC]METHIONINE PREDICT SURVIVAL? Both FDG and [llC]methionine can be used for imaging of head and neck cancer by PET. However, the applicability of PET for assessment of biological aggressiveness of cancer has not been proven. Seventy-two PET studies were performed on patients with squamous cell carcinoma of the head and neck with FDG (n=37) or [11C]methionine (n=35) prior to therapy. In FDG-PET, the overall survival of patients with a SUVlean<9.0 (median) was clearly better in univariate analysis (p=0.02) than that of patients with SUVlean>9.0. By contrast, no significant difference was found between the survival of patients with a SUVlean<9.0 (median uptake of [llC]methionine in tumor) and patients with a SUVlean higher than the median. Metabolic imaging of head and neck cancer with FDG-PET is helpful in the assessment of the biological aggressiveness of the disease, while uptake of [llC]methionine in squamous cell carcinoma does not seem to predict the outcome of the patients.

Department of Thoracic and Vascular Surgery, University of UIm, Germany NON-SMALL CELL LUNG CARCINOMA: PREOPERATIVE NODAL STAGING AND DETECTION OF RECURRENCE WITH FDG-PET We investigated the accuracy of [F-18]FDG-PET in the detection and lymph node staging of non-small cell lung cancer (NSCLC). Forty-six patients (pts) with pulmonary tumors (32 pts with NSCLC, 14 pts with a benign process) as well as 9 pts with biopsy-proved recurrent NSCLC underwent preoperative CT and FDG-PET scanning. The final diagnosis in pts with lung cancer was established by means of histopathologic examination, and the N classification was performed by complete mediastinal lymphadenectomy. Sensitivity, specificity, and accuracy of FDGPET for characterizing the primary lung lesion as malignant or benign were 93.8%, 85.7%, and 91.3%, respectively. All of the 9 recurrent tumors showed intense FDG uptake. Overall accuracy of FDG-PET for thoracic lymph node staging in NSCLC was 87.5% (28132), whereas CT was 59.4% (19132) accurate (p<0.02). FDG-PET identified absence of lymph node tumor involvement in No disease at 100% (12/12). Lymph node metastases in N1 disease were correctly detected at 80% (3/5), in N2 at 83% (9/11), and in N3 at 100% (4/4). With regard to resectability, accuracy of FDG-PET for differentiating pts with NI/N2 disease from those with unresectable N3 disease was 100%. We conclude that FDG-PET is most promising in detecting recurrent lung cancer and provides a new and effective method for thoracic lymph node staging in NSCLC. In particular, it is highly accurate and superior to CT in identifying patients with N3 disease which are considered unsuitable for definitive surgical treatment. 1107

C O =I~ =I~

C a.)

t~ L_

O

• Oncology OTu303 P. E. Valk, D. M. Hopkins, R. D. Tesar, T. R. Pounds, E. Abella-Columna, M. K. Haseman and R. W. Myers. Northern California PET Imaging Center, Sacramento, California, USA

OTu305

UTILITY PET-FDG NODULES

TECHNETIUM-99m SESTAMIBI UPTAKE IN LUNG CANCER: RELATIONSHIP W I T H HISTOLOGICAL PATTERN AND CLINICAL RESPONSE TO CHEMOTHERAPY.

AND COST-EFFECTIVENESS OF WHOLE-BODY IMAGING IN MANAGEMENT OF PULMONARY A N D N O N - S M A L L C E L L L U N G C A N C E R (NSCLC).

The treatment records of 72 patients who had undergone PET imaging for diagnosis of lung nodules or staging of NSCLC were reviewed, to determine the impact of PET findings on patient management. Thirty-four patients were referred for staging and 20 of 38 patients with lung nodules also proved to have NSCLC. Diagnostic lung resection was avoided in 8 patients with benign lung nodules that were negative by PET. Resection of NSCLC was avoided in 6 patients by demonstration of unsuspected non-resectable disease. Mediastinoscopy was avoided in ii patients. The cost impact of these management changes was calculated from average PET reimbursement and from Medicare reimbursement rates for other diagnostic and surgical procedures. The ratio of cost savings to PET cost was more than 2:1 when PET was considered as an additional procedure and more than 3:1 when the cost of abdominal CT and bone scan was subtracted from the PET cost. In this patient sample, the improved management that resulted from the use of PET imaging for diagnosis of lung nodules and staging NSCLC was accompanied by decrease in management cost.

OTu304

H. Wang, S. Maurea, C. Mainolfi, V. De Rosa, M. Panico, A. Green, F. Scognamiglio, L. Bazzicalupo, M. Salvatore. Nuclear Medicine, Radiology and Oncology, Istituto Nazionale dei Tumori, Universit~ degli Studi "Federico II", CNR, Napoli, Italy

L. Ceriani, L. Giovanella, M. Bandera*, B. Beghe' *, M. Orteili * and G. Roncari

Department of Nuclear Medicine and Division of Pneumology * Regional Hospital - Varese - Italy

Aim.

The purpose of this study was to measure semiquantitatively Sestamibi uptake of tumoral tissue in pts with lung cancer (LC) and to investigate its relationship with histological type and clinical response to polichemoterapy (CHT). Methods.

740-950 MBq of 99mTc Sestamibi were injected intravenously and SPET study was performed at the time of diagnosis in 28 patients with histologically proven LC ( 16 SCLC and 12 NSCLC ) undergoing CHT. 15 pts were also investigated after one and three months during CHT. In order to quantify Sestamibi uptake a Tumor/Lung ratio (T/Lr) was calculated on tomographic slices for 39 localizations. The results were expressed as median and interquartile range. Results.

The median T/Lr in the studied population was 1.88 (range 1.7 - 2.2). Pts with SCLC showed higher Sestamibi uptake than subjects with NSCLC (T/Lr median 2.1 ( range 1.85 - 2.4) vs 1.75 ( range 1.67 - 1.76); Mann Whitney U-test p = 0.02 ). Out of 15 pts 10 showed complete or partial response to the CHT and parallel reduction of T/Lr. In the pts with no response to CHT no reduction or increase of T/Lr were found. A T/Lr =/> 1.8 estimated before the initiation of CHT predicted chemosensitivity of LC with sensitivity, specificity and accuracy of 86%, 89% and 87%, respectively. Conclusions.

Histological pattem affects Sestamibi uptake in LC. Semiquantitative assessment of Sestamibi uptake in LC provides a good tool to predict and follow up clinical response to CHT.

OTu306 W.Yu.Ussov V.NKorsunski, S.A.Kolomietz, S.L.Stukanov, I.G.Frolova, S.A.Velichko, B.N.Zyrianov. Tomsk Institute of Oncology, Siberia and Institute of Biophysics, Moscow. RUSSIA EARLIEST DIAGNOSIS OF LUNG CANCER USING 99mTc-MIBI SPET

Tc-99m TETROFOSMIN IMAGING IN PATIENTS WITH LUNG CANCER: COMPARISON WITH CT AND FLUOR/NE-18 FDG PET STUDIES Tc-99m tetrofosmin (TF) imaging has been recently proposed in nuclear oncology. In this preliminary report, we studied 16 patients (13 M, 3 F, mean age=59+3 yrs) with proven lung tumors (9 epidermoid, 4 adenocarcinoma, 2 metastasis and 1 small cell cancer) using Tc-99m TF imaging (740 MBq iv, planar and SPET imaging). All patients also underwent chest computed tomography (CT) and fluorine-18 deoxyglucose (FDG) PET studies. TF and FDG radionuclide images were qualitatively and quantitatively analyzed using region of interest analysis; in particular, quantitative evaluation of TF and FDG activities was performed calculating tumor/non-tumor ratios. On CT, 14 lung tumors were detected, while 2 lesions were not localized since these were obscured by the presence of extensive pleural effusion; furthermore, 21 lymph node mediastinum tumor sites (>1.5 cm) were observed in 8 patients. For lung lesions, the diagnostic sensitivities of planar and SPET TF imaging were respectively 88% (14/16) and 94% (15/16); in particular, the 2 undetected lesions measured less than 2 cm. FDG increased uptake was found in all lung tumors; however, the quantitative analysis of lung tumor FDG and TF activities showed that FDG uptake was significantly (p<0.001) higher compared to TF uptake (4.52+1.5 vs 1.55+0.3); furthermore, concordant FDG and TF images were observed in 2 lung lesion in terms of central activity defect showing central necrotic tumor tissue on CT. For lymph node abnormalities, TF planar scan detected only 4 lesions in 3 patients, while TF SPET identified 17 lesions in 8 pts. Increased FDG uptake was found in all lymph node abnormalities detected on CT scan. These preliminary data suggest that Tc-99m TF imaging is a useful radionuclide technique to evaluate patients with lung cancer. In particular, similar results of TF SPET and FDG PET images were observed; however, FDG lung tumor uptake was significantly higher compared to TF activity suggesting a high glucose tumor metabolism. 1108

99mTc-MIBI SPET is widely used in diagnosis of lung cancer, also in detection of central necrosis of tumour or prediction of its chemoresistancy. Nevertheless it remains unclear at which clinical extent of cancer process it becomes visible using 99mTc-MIBI. Hence we have retrospectively analysed records of 49 patients referred for 99mTc-MIBI SPET because of atypical chest pain, recidives of bronchopneumonia and/or minimal X-ray pathology, with particular attention to early appearance of cancer on SPET. 99mTc-MIBI SPET was performed using 740 - 950 MBq of the agent and 1 cm slices were reconstructed using 64 planar projections recorded over 360°of rotation. Local accumulation of 99mTc-MIBI in lung was reported as pathologic if separated visually from lung background and was > 1.39 when quantified as [Lung~Background]ratio of 99mTcMIBI uptake per voxel. Among the patients recruited for the study diagnosis of lung cancer was verified in seven. In four pathologic uptake of 99mTc-MIBI was revealed on SPET simultaneously with earliest verification of diagnosis using complex of techniques including X-ray, CT, bronchoscopy, CT-guided biopsy and thoracoscopy, in three patients nodular 99mTc-MIBI uptake in lung was the earliest sign of cancer, was then followed-up for 3-5 months and verified during the time later using other techniques. Surgery revealed in all cancer cases tumours smaller than 2.5 cm in diameter. No false-positive or falsenegative cases were observed. Therefore we conclude nodular lung uptake of 99mTc-MIBI is early sign of cancer, should be followed-up and referred to thoracic surgeon even if revealed as isolated pathology.

•

Oncology

OTu307

OWe309

1]. Bilkay, Y. Duman, A. Dirlik, S. Ktra~, D. YOksel, T.!]nsal, G. Kayalar, T. Aysan

P.E. Valk, E. Abella-Columna, R. D. Tesar, T. R. Pounds, M. K. Haseman and R. W. Myers. Northern California PET Imaging Center, Sacramento, California, USA

Departments of Nuclear Medicine and Chest Diseases Ege University Medical Sch hmir / Turkey A COMPARATIVE STUDY WITH TL-201 AND TC-99m GLUTATHIONE (GSH) IN THE EVALUATION OF LUNG MASS LESIONS

DIAGNOSTIC WHOLE-BODY COLORECTAL

In this study, it was aimed to investigate the value of Tc-99m GSH comparative with T1-201 as an imaging agent of lung masses. The study group included 38 pts. with lung lesion proven histologically (The. mean age was 51 yrs. old). All pts. were examined with Tc-99m GSH and T1201 within the same week. Planar and SPECT images were recorded 6 hr after inj. of 555 MBq Tc-99m GSH. T1-201 planar views were acquired at 10 min. (early) and 3 hr. (delayed) after I.V. inj. of 148 MBq TI-201. GSH uptake (A) and early 03) and delayed (C) TI-201 uptakes of the lesion (T) and contralateral normal tissue (N) were calculated using ROI's drawn over these areas. The degre of T1-201 retention (retention index=RI) in lung lesions was calculated as follows :

Whole-body PET-FDG imaging was compared prospectively to CT in 73 patients with recurrent colorectal cancer. A final diagnosis was established at 102 sites of imaging abnormality, histologically at 81 sites and by follow-up imaging at 21 sites. PET imaging detected 77/82 tumor sites (94%) in 62/62 patients (100%), whereas CT detected 42/68 tumor sites (62%) in 37/53 patients (70%). The treatment records of 88 patients were reviewed to evaluate the management impact of PET findings. PET findings had directed change in surgical management in 30/88 patients (34%). In 17 patients undergoing evaluation for resection of metastatic tumor, PET demonstrated non-resectable disease and in 4 other patients, PET findings avoided exploratory laparotomy. In 7 patients, findings initiated surgery by demonstrating potentially-resectable tumor, and in a further 2 patients, surgical plans were altered on the basis of PET results. When the cost impact of PET was calculated, a net savings-to-cost ratio of approximately 3:1 was determined. Whole-body PET FDG imaging may prove to be more accurate and cost-effective in the evaluation of recurrent colorectal cancer than conventional anatomic imaging.

RI= C - B / B. T / N ratios in malignant and bening lesions were presented in this table. Malignant (24 pts.) A : 1.73 4- 0.25 B: 1.444-0.23 C: 1.574-0.24 RI : positive

Beni~a (14 pts.) No uptake 1.364-0.19 1.264-0.14 negative

A x B = P<0.05 B x C =P>0.05 A x C = P > 0.05

One benign lesion (osteofit) and 3 malignant lesions (heart superposition) were not visualized by both modalities. No 5 small cell carcinamas were detected by Tc-99m GSH scan. As a conclusion, easy in-house preparation, inexpensiveness and superior physical characteristics including high-image quality and low-radiation dose to the pts. support Tc-99m GSH to be promising alternative to the other tumor imaging agents Tc-99m GSH can be especially used in the differential diagnosis of malignant and benign lung lesions.

ACCURACY PET-FDG CANCER.

AND COST-EFFECTIVENESS OF IMAGING IN RECURRENT

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M.N.Hosono, M.Hosono, A.K.Mishra, A.Faivre-Chauvet, J.Barbet, E.Gautherot, F.F.Knapp, R.Yamada, K.Machida, J.F.Chatal. Osaka City Univ, Japan, Saitama Medical Center, Japan, INSERM U.211, France, Immunotech SA, France, ORNL, Oak Ridge, USA.

C.M. Pirlsk¥, K.S. Hughes, F.L Moffat, L.D. Hammershaimb and D.M. Goldenberg. Immunomedics, Inc., Morris Plains, N J, Lahey Clinic, Boston, MA, University of Miami, FL, and Garden State Cancer Center, Newark, NJ, USA. USE OF CEA-SCANT M IN THE MANAGEMENT OF PATIENTS (PTS) WITH CARCINOMA OF THE COLON OR RECTUM CEA-ScanT M is the Fab' fragment of the anti-CEA monoclonal antibody, IMMU-4, formulated for direct labeling with Tc-99m. In a study of 382 pts with known or suspected eolorectal carcinoma, 210 pts, who underwent surgical procedures, could be evaluated for the relative ability of CEAScanT M and CT to predict the presence, location and extent of metastatic or recurrent disease, at surgery. Clinical correlation permitted evaluation of the relative capability of each diagnostic method to identify the presence of resectable disease, as opposed to absence of disease, or the presence of disease which was non-resectable. CEA-ScanTM had significantly higher sensitivity than CT (71% vs. 58%, p=0.006, McNemar's Test). The higher sensitivity was seen in extrahepatic abdomen (55% vs. 32%, p=0.007, McNemar's Test) and the pelvis (69% vs. 48%, p=0.005, McNemar's Test). In the liver, CT and CEA-ScanT M were complementary (only CEAScanT M detected proven liver metastases in 14% ofpts). In the evaluation of resectability, CEA-ScanT M was significantly better able to identify pts with resectable and non-resectable disease (p=0.014 and p=0.004, respectively, McNemar's Test.) When both tests were positive for a lesion, surgery confirmed cancer in 154/157 lesions (98%). Similarly, when both tests were concordant for non-resectable disease, the surgical result was confirmatory in 14/14 (100%). This indicates that further work-up is probably not necessary when CEA-ScanT M and CT are concordant for the presence of disease. In the 71 cases where CT and CEA-ScanT M were discordant, and one test was correct, CEA-ScanT M was correct in 46 (65%) vs. CT 25 (35%). The only potentially serious side-effect was an unwitnessed seizure in a severely hypertensive pt, with no sequelae. Induction of HAMA occurred in < than 1% ofpts. We conclude that CEAScanT M is a useful, diagnostic method for pts with carcinoma of colon and rectum, especially when used in conjunction with CT.

LOCALIZATION OF S M A L L - C E L L LUNG CANCER XENOGRAFTS BY R E - 1 8 8 - L A B E L E D M O N O C L O N A L ANTIBODIES. The purpose of this study was to evaluate the potential of Re- 188-labeled monoclonal antibodies (Mabs) for targeting small-cell lung cancer (SCLC) tumors. Re-188, which has beta energy of 2.1 MeV and gamma particle of 155 kev, was obtained as carrier-free perrhenate from a W188/Re-188 generator. Mabs C218 and NK1NBL1, murine IgGls reactive with NCAM, and nonspecific Mab OC125 were pretreated with 2-iminothiolane(2IT) to provide thiol-reactive sites for the attachment of rhenium without splitting the disulfide bonds of Mabs. The modified Mabs were labeled with Re-188 using stannous chloride as a reduction agent. The immunoreactivity and integrity of Mabs were well-preserved. The Mabs were also labeled with 1-125 by the chloramine T method. Re188 and 1-125 Mabs were injected i.v. into groups of athymic mice inoculated with NCI-H69 (SCLC cell line). Biodistributions of Re-188 and 1-125 Mabs were determined at 1, 5, 24, 48, and 96 hr after injection. At 48 hr, uptake of Re-188 NK1NBLI in the blood, liver, kidney and tumor was 0.9+0.3, 3.1+0.8, 2.9+0.5, 3.3+0.6 %ID/g, respectively, and for 1-125 NK1NBL1, 11.3+3.3, 2.7+0.9, 3.1+0.9, 18.1+2.0 %ID/g. Tumor-to-blood ratios of Re-188 NK1NBL1 were 4.0!-_0.9 and 6.8+2.1 at 48 and 96 hr vs 1.7_+0.3 and 2.5+0.7 for 1-125 NK1NBL1. Re-188 C218 and OC125 showed tumor uptake of 1.7_+0.9 and 0.9+0.2 %ID/g, and tumor-to-blood ratios of 2.0+0.6 and 0.6+0.1 at 48 hr. Re-188 NK1NBL1 localized in NCI-H69 tumors better than Re188 C218, probably due to the difference of affinity between the two Mabs. Re-188 NK1NBL1 and C218 cleared from normal tissues faster than 1-125 counterparts, resulting in higher tumor-to-normal tissue ratios. In conclusion, anti-NCAM Mabs labeled with Re-188 using pretreatment by 2IT, especially Re-188 NK1NBL1, seemed to be useful for imaging and therapy of SCLC tumors.

1109

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• Oncology OWe311

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R. Hustinx, P. Paulus, T, Benoit, G. Jerusalem, N. Jacquet, P. Rigo, University Hospital, Sart Tilman, Liege, Belgium.

H. Breitz, B. Ratliff, P. Beaumier, S. Kunz and A. Fritzberg, Virginia M a s o n M e d i c a l C e n t e r and NeoRx Corporation, Seattle, WA, USA.

CLINICAL VALUE OF WHOLE-BODY FDG-PET IN THE DETECTION OF LIVER METASTASES : PRELIMINARY RESULTS. We have performed a retrospective study to evaluate the clinical usefulness of whole-body FDG-PET in the assessment of malignant liver involvement. 64 patients with a history of malignant tumor (38 digestive tract, 9 breast, 9 lung, 3 ovary and 5 other sites) were investigated by FDG-PET and conventional imaging. Liver metastases were present in 31 patients, confirmed by histopathological analysis in 15 cases (3 hepatectomies, 7 laparotomies with biopsy, 5 transpafietal biopsies) or by clinical follow-up in 16 cases. Absence of liver involvement was asserted by pathology (4 cases), perioperative US (12 cases) or clinical follow-up (17 cases). The mean follow-up was 9 months (4-15). FDGPET results were compared to CT and US when available. Metabolic and structural imaging demonstrated concordant results in 44/64 patients (69%; 19 true positives and 25 true negatives). FDG-PET correctly modified the conventional imaging diagnosis in 15/64 patients (23%). PET was true positive in 11 patients where conventional imaging was false negative (5 patients) or doubtful (6 patients). PET was true negative in 4 patients where conventional imaging was equivocal. FDGPET was erroneous in 5/64 patients (8%) : 4 false positive exams from which 1 was described as positive and 3 as equivocal. There was only 1 false negative. Whole-body FDG-PET therefore has a 97% sensitivity, 88% specificity, 88% positive predictive value, 97% negative predictive value and 92% accuracy in the detection of liver metastases. In conclusion, our retrospective study suggests that whole-body FDG imaging is a powerful complementary tool for the detection of liver metastases.

INTRAPATIENT COMPARISON OF A N T I B O D Y NR-LU-10 P R E T A R G E T E D In-lll WITH Tc-99m FAB F R A G M E N T FOR A S S E S S I N G T A R G E T E D RADIOTHERAPY DELIVERY.

Tumor imaging and radiotherapy using whole antibodies is limited by slow tumor uptake and blood disappearance. Pretargeting is a multi-step targeted delivery system that delivers a high affinity "receptor", streptavidin (SA), to tumor via antibody conjugate, NR-LU-10-SA, t h e n clears circulating conjugate at 48 hr (biotin-HSA-galactose), and finally delivers radioactivity via In-lll/Y-90 DOTA-biotin at 72 hr. Patients (>45) h a v e b e e n qualified for entry to a pretargeting tumor radiotherapy trial u s i n g Tc-99m NR-LU-10 Fab imaging product,Verluma TM. Since these two targeting s y s t e m s a r e b a s e d on t h e same antibody, NR-LU-10, an intrapatient comparison w a s m a d e t o r e l a t e t u m o r u p t a k e seen with pretargeted In-lll to the Tc-99m Verluma TM diagnostic standard. The T c - 9 9 m Fab images at 20 hr post injection were compared with In-lll images at 0.2, 3 and 20 hr post In-lll DOTA-biotin injection. Of 44 known lesions in s e v e r a l o r g a n s a n d t i s s u e s in 7 patients analyzed, 35 (81%) were seen with Tc-99m a n d 37 (86%) with In-Ill. Another 7 occult and subsequently confirlned lesions were seen with both agents. In several pretargeting patients, tumors were seen within i0 min. Also, with pretargeting, tumor retention of r a d i o a c t i v i t y was seen to over 5 days. Both agents effectively imaged c a n c e r lesions. T h e rapid uptake and long tumor retention for DOTA-biotin is promising for Y-90 radiotherapy.

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OWe314

A. Dimitrakoooulou-Strauss ~, L.G, Strauss ~, B. Krems', P. Bachert', P. Hohenberger 2, P. Schlag 2, W. Semmler ~, F. Oberdorfer ~, U. Haberkorn ~, G. van Kaick '. 1German Cancer Research Center, Heidelberg, =Robert-R6ssle-Klinik, 3Institute for Diagnostics and Research, Berlin, Germany

A. Dimitrakoooulou-Strauss 1, LG. Strauss ~, F. Gutzler 2, F. Oberdorfer ~, G. Irngartinger 1, J. Doll ~, G. van Kaick ~. 'German Cancer Research Center, Heidelberg, 2Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany

STUDIES OF FLUOROURACIL (FU) PHARMACOKINETICS USING POSITRON EMISSION TOMOGRAPHY (PET) AND MAGNETIC RESONANCE SPECTROSCOPY (MRS). Double examinations with PET and MRS were performed in patients with liver metastases from colorectal carcinomas and surgically implanted catheters (a. gastroduodenalis). All patients were scheduled for regional chemotherapy. The aim of the study was to investigate the FU-pharmacokinetics after regional application to optimize and individualize the therapeutic protocol. The advantage of PET is the accurate, quantitative measurement of regional drug concentrations, while F-19-MRS provides a differentiation of the FU metabolites. Dynamic PET data were acquired beginning with a 12-minute regional F-18-FU infusion together with nonlabeled FU. F-19-MRS was performed with a 1.5 Tesla System and a 15 cm surface coil positioned over the metastasis. The data acquisition was comparable to PET. The preliminary evaluation of the ongoing study includes 5 patients. The time-activity curves for F-18-FU in the liver demonstrated an rapid increase followed by a slow elimination up to 120 min. In contrast, the metastases demonstrated only in some lesions an initial increase of the F-18-FU concentrations, followed by a rapid elimination. The F-18-FU uptake in the metastases 120 min p.i. was less than one third as compared to the normal liver parenchyma. The F-19-MRS data showed initially a high FU-signal, followed by an increase of the main catabolite, Fluor-beta-alanine (FRAL). The downslope of the 1=-18time-activity curve for the metastases was comparable to the time-signal curve for FU obtained by MRS. The data show, that the F-18-FU accumulation in the metastases reflects primarily non-metabolized, trapped FU. Therefore, the transport and retention of FU is from major importance for the chemotherapy outcome. The combined use of PET and MRS allows an estimation of the therapeutically active FU in metastatic lesions.

POSITRON EMISSION TOMOGRAPHY (PET) WITH C-11-ETHANOL AND F18-DEOXYGLUCOSE (FDG) IN HEPATOCELLULAR CARCINOMAS FOR THERAPY MANAGEMENT. PET studies were performed in patients with nonresectable hepatocellular carcinomas scheduled for intratumoral ethanol therapy. One aim of the study was the evaluation of the regional ethanol distribution. Furthermore, FDG follow-up studies were performed to assess the tumor viability and to monitor the response to therapy. The preliminary evaluation of the ongoing study includes 7 patients. Dynamic PET studies (60 min) with FDG were performed prior to therapy {day 0), immediately after treatment (day 1), one day (day2), and one week after therapy (day8). C-11-Ethanoi (37-80 MBq) was applied together with the nonlabeled therapeutic dose of the drug, at day 1 via a biopsy needle positioned by ultrasound guidance. All tumors demonstrated a high C-11-uptake shortly after the end of the ethanol injection without any major changes during the 30 minutes acquisition time (5/7 pat.). PET data demonstrated no significant elimination of the C-11-ethanol out of the tumors during the acquisition time. The normal liver parenchyma had a very low C-1t-uptake in 5/7 patients, and in only one patient a significant C-11-uptake was noted in the early phase. The time activity curves of the liver gave evidence of a slow but steady increase of the tracer uptake with time in two patients. A possible explanation of that is a low ethanol elimination out of the tumor cells. The evaluation of the FDG data demonstrated a low uptake in all primary tumors, with uptake values equivalent to the liver. The tumors were hypometabolic in the center with a rimJike FDG-accumulation at day 2 and day 8. The quantitative evaluation of the FDG uptake in the peripheral parts of the tumor, using Standardized Uptake Values (SUV), showed an increase of FDG at day 8. CT-follow-up studies four weeks after the first ethanol therapy showed no significant change in the tumor volume. The increased FDG-uptake in the tumor periphery may reflect viable tumor tissue or may be caused by repair mechanisms.

1110

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Oncology/Paediatrics

0We315

OWe317

B.M. Dohmen, R. Bares, M. Teusch, U. Buell. Department of Nuclear Medicine, University of Technology, Aachen, Germany.

A. Vattimo, P. Bertelli, M. Cintofino*, L. Burroni, D. Volterrani, A. Vella, Nuclear Medicine Unit and Institute of Pathology* University of Siena, Italy

QUANTITATIVE PARAMETERS VS VISUAL IMAGE INTERPRETATION FOR FDG-PET CLASSIFICATION OF PANCREATIC TUMORS: COMPARISON BY ROC-ANALYSIS

PREOPERATIVE DETECTION OF HORTHLE CELL TUMOR BY MEANS OF TECHNETIUM-99m-SESTAMIBI SCINTIGRAPHY (SINGLE INJECTION DOUBLE-PHASE STUDY) Hiirthle cells tumor accounts for 7-10% of all thyroid carcinomas and is one of the most invasive tumors. Usually it does not concentrate radioiodine so that its preoperative detection is of paramount importance. Single injection dual-phase (15'-30', 3-4 hrs p.i.) thyroid scintigraphy with Tc99m-Sestamibi (MIBI) was performed on 41 patients displaying a cold nodule on a previous Tc99m scintigraphy. A visual score of the nodule uptake has been done in comparison with thyroidal and background uptake of the tracer. Nodular-to-thyroid (N/T) uptake ratio in the early and late images, and washout rate from the nodule (WON) and the thyroidal tissue (WOT) were also measured. Cytology was obtained for all patients, histopathology for 20 operated patients. In 8 patients (group A) the nodule displayed intense and persistent uptake of MIBI; in all 5 operated patients histopathology revealed a Hiirthle cell tumor (2 carcinoma, 3 adenoma). In 15 patients (group B) the nodule displayed intense uptake in the early image with fading activity in the late image; in I0 operated patients histopathology revealed a colloid nodule (n=l), papillary carcinoma (n=4) and follicular carcinoma (n=5). In the remaining 18 patients (group C) the nodule was cold: in these patients the late image was not acquired; in 5 operated patients histopathology revealed a colloid nodule (n=2) and follicular adenoma (n=3). Cytology showed an abundant quantity of oncocytarian cells in all but one patient (inadequate specimen) of group A only. Table shows scintigraphic values of N/T, WON and WOT.

FDG-PET, evaluated by visual image analysis of static scans, has recently been shown to be accurate in differentiating cancer from chronic pancreatitis. While quantitative image analysis and dynamic acquisition protocols give additional information about tissue metabolism, it is not clear whether diagnostic sensitivity and specificity could be further improved by these techniques. A total of 46 patients, all investigated by dynamic FDGPET, was included into the study. Metabolic quantitation was achieved by calculating FDG uptake (SUV), tumor to liver ratio (TLR), FDG transport (TR), and glucose metabolic rate (MR). Results were compared by ROCanalysis using histology or clinical outcome as "gold standard". The calculated results for the quantitative parameters were as follows: area under the ROC-curve ~sensitivity (if specificity>90%) specificity (if sensitivity>90%) maximum accuracy

SUV 0.78 54% 50% 76%

TLR 0.79 54% 50% 76%

TR 0.77 45% 46% 75%

MR 0.88 60% 55% 80%

MR revealed the largest area under the ROC-curve, indicating that this parameter was the most reliable one for differential diagnosis. More detailed analysis, however, demonstrates that this was only true for a mean range of 60-80% sensitivity or specificity. If high specificity or high sensitivity is required, corresponding sensitivities resp. specificities were quite similar for SUV, TLR, and MR. Furthermore none of the quantitative parameters was definitely superior to visual image interpretation (75% accuracy). We conclude, that the benefit of quantitative PET-parameters for classification of pancreatic tumors is limited. Apparently it depends on the pre-test probability of malignant disease and the required, values for sensitivity or specificity. This should be considered before establishing acquisition and quantification protocols for routine use of FDG-PET.

0We316

group A ~roup B

early N/T late N/T 1.77_+0.46 3.20+1.37 1.45_+0.54 0.84-+0.30

WON (%/h) 17.2+_6.3 30.0_+7.3

WOT (%/h) 24.6_+7.5 24.5-+6.8

Single injection dual-phase MIBI scintigraphy is capable of identifying Hlirth.le cell tumors due to their intense and persistent uptake of the tracer in contrast to other thyroid tumors. The characteristic abundant granular acidophilic cytoplasm of Htirthle cells, represented by crowded mitochondria, is probably responsible for MIBI uptake.

Paediatrics 0Su318

R. Lietzenmayer, U. Feine, W. M~iller-Schauenburg, R. Bares. Department of Nuclear Medicine Eberhard-Karls-University, T~ibingen, Germany.

P.Olivier, P.Chastagner, N.David, P.Y.Marie, G . D e Miscault, S.Denet, C.Schmitt, D.Sommelet and A.Bertrand. Departments of N u c l e a r Medicine, Paediatric Oncology and Surgery. CHU Nancy. France

DETECTON OF RECURRENT THYROID CANCER BY [ 1 8 - F ] - F D G - W H O L E - B O D Y - P E T

IS 99mTc-MDP B O N E S C A N A S E F F E C T I V E AS 1 2 3 I - M I B G S C A N IN T H E A S S E S S M E N T OF S K E L E T A L I N V O L V E M E N T A T I N I T I A L S T A G I N G A N D F O L L O W - U P OF N E U R O B L A S T O M A ?

Follow up of differentiated thyroid cancer comprises physical examination, cervical ultrasound, whole body scintigraphy with radioiodine (RI) and measurement of serum thyroglobuline (hTg). This approach is known to be effective, although limited since false negative or positive findings are possible due to the presence of RI-negative metastases or inflammatory lymphnode enlargement. Purpose of the present study was to evaluate [18-F]-FDG-Whole-Body-PET for the detection of recurrent thyroid cancer. Thirty-six patients (follicular ca=26; papillary c a = 10) with suspected (group 1; n = 17: elevated hTg or enlarged lymphnodes with normal RI-scans) or known (group 2; n = 19: positive RI-scans) metastatic disease were included in the study. All examinations were performed 30 rain. after i.v. injection of 370 MBq FDG using a WholeBody-PET-Scanner (axial FOV: 15 cm). Image analysis was visual with regard to presence of unphysiological FDG accumulations as sign of malignancy. Validation was established by histology (n = 13) or clinical course ( n : 2 3 ) . To evaluate the clinical impact, we analyzed whether curative or palliative treatment could be achieved due to the PET findings. Positive PET scans were obtained in 26 pts. (gr. h 11/17, group 2: 15/19). Curative surgical treatment was induced in 9 pts. of group 1, additional palliative treatment (radiotherapy or surgery) was initiated in 5 further pts. (group I: 1/11, group 2: 4/15) with originally unknown generalized disease. Compared to the final diagnoses, the true positive rate was 26/31 (group h 11/13, group 2: 15/18), no false positive results were obtained in these pts. We conclude that PET modified the management in 10/17 pts. (59 %) of group 1, and in 4/19 pts. (21%) of group 2. It allows for detection of iodine-negative recurrencies as well as metastases and should therefore be employed in patients with suspected recurrent thyroid cancer, in particular in case of elevated thyroglobulin levels and inconclusive outcome of routine diagnostic procedures.

T h e r e s p e c t i v e d i a g n o s t i c accuracies of b o n e a n d M I B G s c a n s in n e u r o b l a s t o m a remain debated. We retrospectively studied investigations, including 123I-MIBG a n d 99mTc-MDP b o n e scans, p e r f o r m e d in i0 p a t i e n t s (6 girls, m e d i a n a g e 30 m o n t h s at diagnosis) who had a stage IV neuroblastoma. The scans w e r e c o m p l e t e d w i t h i n a m e a n of 7 d a y s (127 days) of each other. Eight of these i n v e s t i g a t i o n s w e r e p e r f o r m e d at d i a g n o s i s a n d 6 at f o l l o w - u p (4 to 27 m o n t h s a f t e r d i a g n o s i s ) . M I B G a n d M D P s c a n s w e r e r e v i e w e d simultaneously and uptake abnormalities were determined using a 8 s i t e s d i v i s i o n of the body. At diagnosis, 48 s i t e s w e r e j u g g e d p o s i t i v e o n e i t h e r M I B G or b o n e scans. T h i s p o s i t i v i t y was o b s e r v e d on b o t h M I B G a n d b o n e scans for 39 sites (81%), o n M I B G b u t n o t on b o n e s c a n for 5 s i t e s (10%), a n d t h e c o n v e r s e ( p o s i t i v i t y on M D P s c a n b u t n o t o n M I B G scan) for 4 s i t e s (8%). At follow-up, a f t e r c o m p l e t i o n of c o n v e n t i o n a l chemotherapy, 25 s i t e s w e r e j u g g e d p o s i t i v e o n e i t h e r M I B G o r b o n e scans. T h i s p o s i t i v i t y was o b s e r v e d on b o t h M I B G a n d b o n e scans for ii sites (44%), on M I B G b u t n o t on b o n e s c a n for 12 s i t e s (48%), a n d the c o n v e r s e (positivity on MDP scan b u t not on M I B G scan) for 2 sites (8%). Therefore, in p a t i e n t s w i t h n e u r o b l a s t o m a , bone s c a n a p p e a r s to b e as s e n s i t i v e as M I B G s c a n for the detection of skeletal involvement at d i a g n o s i s (90% vs 92%;NS) b u t not for the followup (52% v s 9 2 % ) ; p = 0 . 0 0 2 ) . 1111

co |l=lm ,@a

e,(9 t__ m

t~

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Paediatrics

0Su319

OSu321

B.Brans, G.Laureys, C. Van De Wiele, M.Simons, R.Dierckx, University Hospitals of Ghent and Antwerp, Belgium

MMC Tiei-van Buul. M Petjak, JC Greve, CR Staalman. Academic Medical Center, University of Amsterdam, Departments of Nuclear Medicine and Radiology, The Netherlands.

UPTAKE OF 1-123 MIBG IN NEUROBLASTOMA:RELATION TO DIFFERENTIATION AND CATECHOLAMINESECRETION The uptake of MIBG in neuroblastoma (NB) has been attributed to a specific (type I) uptake system, but its relationship with cellular differentiation remains unspecified. Hence, in 29 t u m o u r of 26 children, we compared MIBG u p t a k e w i t h catecholamine (CA) secretion and with histology obtained after primary resection at diagnosis (n=13, left in table) or after secondary resection following chemotherapy (n=16, right in table). Table 1 shows the histological diagnosis: undifferentiated NB (N1), differentiating NB (N2), ganglioneuroblastoma (N3) and ganglioneuroma (N4), versus their intensity scores on preoperative f-123 MIBG scintigraphy: 0=no-;l=slight-;2=moderate- and 3=intense uptake and n u m b e r of patients with a b n o r m a l values of neuron specific enolase (NSE) and CA (vanillyl mandelic acid, homovanillic acid a n d / o r dopamine).

MIBG SCINTGRAPHY AND ULTRASONOGRAPHY SUSPECTED ABDOMINAL NEUROBLASTOMA

o CA--> 80 33 25 0 Yo)N S E . . > ~ ] 8 0 33 25 0

number of .~ patients

0 NI N2

33 100 38 25

[]

MIBG0

67 100 !

[]

MIBGI

i~ ~1 ]~4 N1 N2

2i

~'~ MIBG2 []

MIBG3

Of the 6 tumours with no MIBG uptake, CA and NSE were elevated in 2 (two primary resected N1 and N2 NB's). In conclusion, these results point to the heterogeneity of MIBG uptake in NB patients, not related to the levels of neuron secretory amines or to the degree of differentiation.

IN

In this study, the role of MIBG scintigraphy and abdominal ultrasonography(US) was evaluated in both initialdiagnosis and follow-up of abdorninals lesions of neuroblastoma (NBL). Data of 28 consecutive pediatric patients with NBL or suspected NBL were included, 16 M and 12 F, mean age 2.8 y, range 3 w-13.4 y. In 22 patients, NBL was histologically proven, ganglioneuroblastoma in 5, and ganglioneuroma in one patient. The intrinsic results of 61 MIBG-scans (123-1 and 131-1, including 26 SPECTS) and US, performed within a period of 14 days, could be evaluated. Full agreement between the two modalities concerning the localisation of abdominal lesions was reached in 37 comparisons (61%), of which all of the 7 histopathological proven cases were diagnosed correctly by both methods. In approximately50% of the MIBG scans in which SPECT was available, SPECT provided significant additional information. Partial agreement was found in 17 cases (28%): 3 out of 7 histopathological proven cases were confirmed by the MIBG scan, while the other 4 cases were confirmed by US. No agreement was seen in 7 cases (11%), of which 3 were histopathological proven (2 correctly diagnosed with the MIBG scan, the other one correctly diagnosed with US). Problems in the interpretationof the adrenal region were seen in both methods, especially in children under one year of age. Lymph node involvement was missed with MIBG in 3 histologically and ultrasonographically proven cases, while US was false positive in 7 other cases. We conclude that in patients with suspected neuroblastoma, MIBG scintigraphy and ultrasonography are of complementary value in the detection of abdominallesions. Congruent results of both methods, found in 61% of cases, indicate a high reliability in diagnosing and localising abdominal NBL. Because of the favourable results of additional SPECT, it is advicable to perform SPECT routinely in this diagnosis.

OSu320

OSu322

B. Brans, K. Casier, C. Van De Wiele, G. Laureys, M.Simons, R.A. Dierckx, University Hospitals of Ghent and Antwerp, Belgium

A. Herte[, J. Herwig*, R.P.Baum, A.C. Sewell*, S. Adams, M. Ostedoh, H.J. B6hles*, G. H0r Department Nuclear Medicine, Pediatrics*, Goethe-University Medical School, Frankfurt/Main, Germany

UPTAKEOF Tc-99mMDPIN PRIMARYNEUROBLASTOMATUMOURS IS ASSOCIATEDWITH THE PRESENCEOF CALCIFICATIONS Bone seeking radiopharmaceuticals have been reported to a c c u m u l a t e in p r i m a r y n e u r o b l a s t o m a , b u t without discussion of histological and radiological correlations. To assess the hypothesis that uptake of Tc-99m MDP is related to the presence of calcifications, we performed a retrospective study on 26 children, in whom the bone scan was part of the initial staging. The uptake of Tc-99m MDP was c o m p a r e d w i t h the presence of calcifications o n pathological examination of the primary resected specimens a n d / o r CT. Concordance was found in 23/26 patients (88%). Thirteen tumours with calcifications took up Tc-99m MDP. In 9/13 (69%), the intensity of Tc-99m MDP uptake correlated well with the extent of calcifications. Absence of tracer uptake and of calcifications was found in 10 tumours. Two patients with calcifications showed no MDP uptake (in the presence of 1-123 MIBG uptake): one with widespread necrosis, the other with a cystic lesion. While these morphological changes may have influenced uptake, hypothetically this pattern may also be attributed to an extinct calcification process. One p a t i e n t s h o w e d slight u p t a k e without calcifications, possibly indicating an early calcification process. FinatIy, we found no relationship between the intensity of MDP uptake and 1-123 MIBG uptake or histological grade of the tumour. In conclusion, in the patient group presented the positive or negative uptake of Tc-99m MDP generally concurred with the presence or absence of calcifications in primary NB tumours.

BRAIN FDG-IMAGING IN PEDIATRIC METABOLIC DISEASES

1112

Pediatric metabolic diseases due to inherited enzyme defects can lead to varying expressions of functional brain deficits, either caused immediately after birth or in the course of the inherited disease. If the lifelong medication/dietary therapy is not strictly adhered to, further neurological deterioration is possible. Purpose of the PET FDG brain imaging was to evaluate brain functional deficits in inherited metabolic diseases. After parental informed consent FDG imaging was performed in 6 children (3 female, 3 male, 3 months-15 years age, mean 7.2) suffering from argininemia, propionic acidemia, glutaraciduria, arginino-succinate-lyase-deficit, phenylketonuria and citrullinemia. PET imaging was performed on a Siemens ECAT 47 PET scanner, scans were obtained 30 rain post injection of a mean 135 MBq F-18 FDG (85-210 MBq). In one patient (PKU) a follow-up control scan after initiation of PKU diet was performed. Results: Only one patient (citrullinemia) had a normal FDG brain scan. The other 5 demonstrated varying pathological glucose metabolic defective patterns. Defects in the basal ganglia were most pronounced in patients with argininemia, propionic acidemia and glutaraciduria. The cerebellum was affected in argininemia and arginino-succinate-lyase deficit. The girl with phenytketonuria (untreated for 15 years) had globally reduced brain metabolism and improved mildly after 3 months of PKU diet. PET brain imaging demonstrated in 5/6 patients with metabolic disease reduced glucose metabolism especially in the basal ganglia and cerebellum. The findings can be used for further therapy/diet control.

• OSu323

(n

OSu325

K Mastrangelo~ A. Tomesello, V. Rufini~ A. Festa, S. Mastrangelo, L. Troncone. Depts. of Pediatric Ontology and Nuclear Medicine. Catholic University of the Sacred Heart, Rome - Italy

FREATMENT OF STAGE W NEUROBLASTOMA USING A COMBINATION OF 1-131 MIBG AND CHEMOTHERAPY Advanced neuroblastoma (NB) has a dismal prognosis. Encouraging results have been reported with 1-131 MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempts to explore the integration of this new treatment modality with chemotherapy. Cisplatin (CDDP) was initially chosen. Seven patients, 5 with relapsed heavily pre-treated, progressive stage IV NB, and 2 with stage IV NB at diagnosis, all with a good MIBG uptake, were investigated. Treatment consisted of CDDP (50 mg/m2) i.v. administered in 6 h on day 1 and 8 and 1-131 MIBG (100 mCi) i.v. given in 6 h, on day 2 and 9. Two CK and 3 PR were observed in relapsed patients 4-6 weeks following only one single course of both CDDP and 1-131 MIBG at "standard" dosage; 1 mixed response (MR) and 1 VGPR was observed in the 2 patients at diagnosis. The only toxicity was hematologic, which was significant and relatively long-lasting. In order to reduce toxicity, we have treated 6 additional patients with a modified chemotherapeutic approach, which includes cyclophosphamide (Cy). Both CDDP and Cy were administered a week before 1-131 MIBG, with the aim of reducing radiation toxicity through a "priming" effect. In 4 relapsed patients 3 PR and one MR was obtained. In 2 out of 2 patients treated at diagnosis VGPR and PR were observed respectively. Hematological toxicity was acceptable, except for in one case with massively infiltrated bone marrow. The general condition of all patients was excellent. The results of the present study compare very favourably with similar results ~om the literature obtained with multiple courses of 1-131 MIBG, over a period of several months. The second approach should be further investigated, particularly at diagnosis. Supported by C.N.R., A.C.R.O. GRANT no. 94.01196.PF39 and by A.I.R.C.

OSu324

~

C A kyiiz, G. Vural, A. Oauz, T Atasever, M 9u, M0nlfi. Gazi and Hacettepe University, Ankara-

IN

CHILDREN.

Nowadays, it is known that gastroesophageal reflux (GER) may be part of a complex disease, where other disturbances of the digestive tube may exist. Our purpose was not only to compare pHmetry with the scintigraphic detection of RGE, but also to study if there was any gastric emptying abnormality that correlated with the presence of gastroesophageal reflux. We have performed 21 studies in 18 children, all of them with symptoms that required pHmetry. Four of these children had negative pHmetry and no other known disease, 2 had only gastroesophageal reflux and 12 were neurologically impaired children. The pHmetry was performed with a DIGITRAPPER MKIII and, for purposes of comparison with the scintigraphic studies the following parameters were considered: Reflux Index (refl/hour) and Esophageal Clearance (min/refl). The scintigraphic study was performed with a milky meal, adapted to the age and habits of the child, with a lipid content > 20% and labelled with Tc-99m-stannous colloid. Immediately after the ingestion, a dynamic study was started with 186 frames of 20 seg each, in a 64x64 matrix. Planar images of 60 seg each were also acquired at 90 min, 2, 3 and 4 hours. The following parameters were calculated: Gastroesophageal Reflux Index (%) and Gastric Retentions of the meal at 15, 30, 45, 60 and 90 rain and 2, 3 and 4 hours (%). To statistically compare the values obtained we used linear regression. We found a positive strong correlation between scintigraphic gastroesophageal reflux index and esophageal clearance @--0,91; p<0,001). This same scintigraphic parameter and gastric retention at 4 hours also correlated @=0,64; p<0,05), as well as the latter and esophageal clearance @=0,61; p<0,05). Although the true pathological meaning of these correlations is still to be elucidated, it does seems that the gammagraphic detection of GER is associated with esophageal disturbances and eventually with slow gastric emptying.

co

| m

TECHNETIUM-99m-SESTAMIBI SCINTIGRAPHY AND RESPONSE TO THERAPY IN CHILDREN WITH MALIGNANT LYMPHOMA. Previous studies have shown that a membrane glicoprotein, P glycoprotein, which is implicated in multidrug resistance in some tumour cells by outward transportation of several chemotherapeutics, also recogmzes Tc-99m-MIBI and avoids radionuclide concentration. The aim of this study was to investigate the relation between 99mTcsestamibi accumulation in tumours and response to chemotherapy in children with malignant lymphomas. 24 children (13M, 11 F) aged between 1 to 17 years (mean: 9.5±4.4) with malignant lymphoma (16 with Hodgkin's disease and 8 with non-Hodgkin lymphoma) were studied with TI-201 and then with 9~rnTc-sestamibi scintigraphy prior to any therapeutic intervention. The regions of interest in 99mTc-sestamibi scmtigraphy were drawn corresponding to the lesions visualized in thallium sointigraphy. 99mTc-sestamibi scintigraphy was considered negative if tumor/background ratio was below 1.15. The remission rates were evaluated at the end of induction therapy and patients were then followed clinically for one to two years. Partial or no response to chemotherapy leading to early relapse or death, was observed in 2 patients with Hodgkin's disease, and in 5 patients with non-Hedgkin lymphoma, three of them died during followup and 2 had early relapse with bone marrow involvement. All patients who had positive 9°JriTc-sestamibi scintigraphy, subsequently had complete response to chemotherapy, and aJl patients who had negative 99mTc-sestamibi scintigraphy, subsequently had partial or no response to chemotherapy, irrespective of the lymphoma type. The mean tumor/background ratios of patients with complete response and with partial or no response were 1.395:L'0.2 and 1.031±0.05 (P=0.0002) respectively. 201"i"1 scintigraphy results were not related to the response to chemotherapy. The results of this study show that 9~mTc-sestamibi sointigraphy can provide information regarding the response to chemotherapy in patients with malignant lymphoma.

OSu326

A. i Santos, A. I. Lopes, T. Martins, C. Rodrigues, P. Magalh~es Ramalho, F. Godinho. Institute de Medicina Nuclear . FML, Unidade de Gastrenterologia do Service de Pediatria - HSM. Lisbon. Portugal GASTROESOPHAGEAL REFLUX DISEASE USEFULNESS OF SCINTIGRAPHIC STUDIES.

Paediatrics

M Mitiavila*, G 0cete**, C Nieto, A Mufioz&, JM Cordero, L Diez, A Crespo. Nuclear Medicine, **Orthopaedic Paediatric and &Paediatric departments, H Ram6n y Cajal, Madrid. * Nuclear Medicine, H.U. Getafe, Madrid. Spain. THALLIUM-201 (Ti-2oi) SCINTIGRAPHY AS INDICATOR OF C H E M O T H E R A P Y EFFECTS IN BONE SARCOMA. The p u r p o s e of this study was to characterize TI201 uptake in patientss with bone neoplasms and n o n - s p e c i f i c entities resembling skeletal neoplasms and to evaluate the ability of TI-201 scintigraphy to reflect the histological response of sarcomas to c h e m o t h e r a p y (cht) . 39 patients (23F, 16M), age range 6/31 years with suspected malignant bone tumors were studied using TI-201. 56 studies were performed; 32 were done at diagnosis and 24 during the follow-up. I0 minutes following intravenous inyection of TI-201 multiplanar images were obtained. The uptake ratio of the lesion (L) to contralateral normal bone (BKG) was c a l c u l a t e d in all cases. In 18 patients (group B) the response to preoperative cht was determined by g r a d i n g of the p e r c e n t a g e (%) of tumor necrosis present on slides of the resected specimens. This (%) was correlated with TI-201 ratio before and after cht. TI-201 L/BKG ratio before onset on treatment was b e t w e e n 1.3-4.0 (X= 2.15) in 36 high grade sarcomas (21 osteosarcoma, 14 Ewing sarcoma, 1 fibrosarcoma). 1 aneurismal bone cyst and 1 osteomyelitis showed TI-201 uptake. In group B there was no c o r r e l a t i o n b e t w e e n TI-201 ratio before and after cht. (r=0.29 ns. Spearman correlation coefficients). Patients with TI-201 ratio of
1113

e-

{n a)

O. m

L_

O

•

Paediatrics

0Mo327

0Mo329

L. Burroni, P. Bertelli, D. Volterrani, A. Vella and A. Vattimo Department of Nuclear Medicine, University of Siena, Policlinico "Le Scotte", Siena, Italy.

J.SoaresJr. I K.Miura, M.C.P.Giorgi, G.Porta, C.C.JMedeiros, M.Izaki, MA.Oliveira, R.Abe, GGCerri, JCMeneghetti Heart Institute University of Sg.o Paulo Medical School, Department of Nuclear Medicine, Brazil

INTERICI'AL BRAIN SPET IN CHILDREN WITH THERAPYRESISTANT EPILEPSY: COMPARISON BETWEEN Tc99m-HMPAO AND Tc99m-ECD. Tc99m-HMPAO and Tc99m-ECD are two agents for cerebral blood flow imaging with SPET and probably effective tracers for diagnostic assessment in epilepsy. The aim of this study was to evaluate the accuracy of both tracers in studying the cerebral perfusion abnormalities in two groups of children with therapy-resistant epilepsy and to compare these findings with those obtained using MRI, clinical examination and EEG monitoring. We performed Tc99m-HMPAO SPET in 37 patients (Group A: 20 boys and 17 girls aged 18 months to 14 years) and Tc99mECD SPET in 33 children (Group B: 19 boys and 14 girls aged 17 months to 16 years) with severe therapy-resistant epilepsy. In 49/70 noncooperative patients a mild sedation was carried out. All children underwent detailed clinical examination, EEG investigation and brain MRI. Positive results of the various techniques are summarized in the tbllowing table:

INTRAPULMONARY SHUNTING (IPS) IN CHILDREN WITH CRHONIC LIVER DISEASE (CLD): COMPARISON BETWEEN RADIONUCLIDE SCAN AND CONTRAST ECHOCARDIOGRAPHY

These data confirm that brain SPET is considerably sensitive in detecting perfusion abnormalities and localizing epileptic foci in these groups of patients, even when the MRI pattern is normal. SPET, EEG data and clinical examination agree reasonably well. Tc99rn-HMPAO appears to be more sensitive than Tc99m-ECD in revealing brain blood flow abnormalities but the patients of group A were more seriously ill than those of group B, since 14 of them presented anatomical lesions revealed by MRI. However no statistical differences (Fisher Exact test) were tbund between the two groups. On the other hand, in comparison with HMPAO, ECD has the great advantages of long radiochemical stability, rapid wash-out from extracerebraf tissues and favourable radiation dosimetry and for this reason is recommended in children.

Recent data show that the prevalence of hypoxemia in children with liver disease range from 0.5% to 20%. Intrapulmonary shunting, the main mechanism of hypoxemia, has been attributed to pulmonary vascular dilatations. It can be diagnosed by radionuclide scan and twodimensional contrast-enhanced echocardiography (CE). The aim of this study was to evaluate the presence of IPS using radionuclide scan and CE and to analyse the concordance between these methods. Patients: nineteen patients(pts) with CLD and portal hypertension, candidates for orthotopic liver transplantation were evaluated. Ten pts were female and 9 male. The mean age was 1 ly4m. Dyspnea, cyanosis and /or digital clubbing were observed in all pts. Hypoxemia(PaO2 < 70 mmHg) was seen in 3 cases. The pulmonary function tests were done in order to rule out pulmonary diseases.Methods: radionuclide scan was performed in 17 pts using 99mTc-macroaggregated albumin (MAA). A shunt index (S1) was calculated as brain/lung activity x 100. CE was done with saline solution in 19 pts. SI >1.0 and the presence of microbubbles in the left cardiac chambers within 3 and 6 beats after leaving the right ventricle were considered positive for the presence of IPS. Results: SI>I.0 was found in I0/17 pts(52.63%) and the CE was positive in 6/19pts(31.57%). The concordance between the two methods was 13/17(76.47%). In the 4 discordant cases both exams were repeated one year later: the CE became positive in all pts and in 3 of them the SI increased. Conclusion: this study suggests that IPS can be diagnosed by MAA scan earlier and more preciselly than CE. In doubtful cases, the sequential study of IPS could allow a more reliable diagnosis. Further investigations are needed in order to clarify the role of MAA scan in this setting.

0Mo328

0Mo330

SPET 35/37 (94.6%) 28/33 (84.8%)

Group A Group B

i

2

MRI 14/37 (37.8%) 8/33 (24.2%)

,

.

EEG ] 35/37 (94.6%) 32/33 (96.9%)

I

I

,

.

M Valkama P Tornlalnen L Valnlon.... 2 .... " . 2 1 . '. , ' . , paa M Kolvlsto , D Z V l S l O n of N u c l e a r M e d l c l n e and 2Department of Pediatrics, U n i v e r s i t y Hospital of Oulu, Finland PROSPECTIVE STUDY IN HIGH RISK P R E T E R M NEONATES TC-99m ECD BRAIN SPET. Asphyxiated and v e r y low birth weight neonates are at enormous risk to d e v e l o p cerebral palsy. The purpose of this study was to e v a l u a t e the prognostic value of TCD b r a i n perfusion SPET in the assessment of cerebral palsy diagnosis. Until now 19 premature neonates have been studied. Imaging studies were carried out b e t w e e n 36 and 44 gestational weeks (some weeks after birth). A dose of ii0 MBq of 99m-To ECD was given after feeding. Imaging was carried out using a single head (Siemens/Orbiter) or a double head (Adac/Vertex) rotating g a m m a camera equipped with a fan beam or a slant collimator. Results of visual interpretation and semiquantitative m e a s u r e m e n t s were following: Cranio-caudal abnormalities w e r e found in 7 (4 mild, 3 substantial) and hemispheric asymmetry in i0 (7 mild, 3 substantial) out of the 19 neonates. All five proved CP cases (at least o n e year follow-up time) had abnormal brain perfusion SPET findings w h e r e a s US o r MRI s h o w e d abnormal findings suggesting CP in 3 of them. Pathological changes in sensorimotoric area could be found in all proved CP cases. In neonates w i t h normal brain SPET no b r a i n d a m a g e related to CP could be found. These preliminary results encourage the selective clinical use of ECD b r a i n p e r f u s i o n SPET in high risk p r e m a t u r e neonates. USING

1114

L. Wallin, I. Herin, M. Bajc Departments of Clinical Physiology and Paediatrics, University Hospital Lurid, Sweden QUALITATIVE AND QUANTITATIVE F O L L O W UP OF ACUTE PYELONEPHRITIS The aim: A prospective study was designed to follow up children with acute pyelonephritis and to identify those who are at risk of developing progressive renal lesions. Patients and methods: Twenty-four children, aged 2 weeks to 2 years (median 5 months), with clinically and biochemically verified first time pyelonephritis, were examined with DMSA renal scintigraphy within a week atter onset of symptoms. All were followed up clinically and by DMSA scintigraphy 6 months and one year atter first infection. Scintigraphie images were analysed qualitatively for activity distribution changes and quantitatively by measurement of renal uptake and renal size. The results were related to clinical and laboratory data. Results: All children showed uptake defects on scintigraphic images in the acute stage. Bilateral lesions were found in 22/24 children. Single kidney uptake during the acute stage was in average 10 % of injected dose. ARer 6 months about 75% of kidneys showed improved or normalised DMSA uptake pattern and uptake in percent of injected dose had increased in average to 12 % in single kidney. Kidney growth was within expected limits according to age in most children. DMSA uptake pattern remaining six months after the infection did not show any improvement after one year. In some infants renal growth and absolute uptake of DMSA deteriorated during follow up Conclusion: Pyelonephritis causes bilateral lesions in a majority of children (92%). Quantitative measurements as a complement to visual evaluation o f D M S A scimigraphic images improved the diagnostic ability at follow up and may be valuable in identifying children at risk to develop progressive renal lesions and who need follow up for an extended period.

• 0Mo331 PF Rambaldi, Argenziano, Radiological Paediatrics,

Paediatrics

0Mo333 G M a r i n o , L V a l e n t i n o , F Masone, G G Lama, L Mansi. Inst of S c i e n c e s - N u c l e a r M e d i c i n e , D e p t of II U n i v e r s i t y of Naples.

URINARY TRACT OBSTRUCTION: MAG3 SCAN FOLLOW-UP.

THE VALUE OF DIURETIC

We have retrospectively evaluated TI/2 washout and Spit Function (SF) in 35 newborn with hydronephrosis, that had equivocal d i u r e t i c r e n o g r a m at f i r s t M A G 3 scan. In all c a s e s a s e c o n d s c a n w a s p e r f o r m e d to s e l e c t the patient that need surgical intervention. Patients: 35 i n f a n t s (25 boys, i0 girls, age r a n g e 1-3 months) s t u d i e d o v e r a p e r i o d of 4 y e a r s (1992-1996), w e r e i n c l u d e d i n t o the study. Methods: Diuretic renograms were performed uslng standard procedures. A l l p t s i n c l u d e d i n the s t u d y h a d at f i r s t M A G 3 f u r o s e m i d e s c a n a T I \ 2 washout >i0' All data obtained from the b a s e l i n e s t u d y w e r e c o m p a r e d w i t h t h o s e of the M A G 3 f o l l o w - up. H y d r o n e p h r o s i s was u n i l a t e r a l 30 infants, b i l a t e r a l in five. RESULTS: 32 kidney had good split function (>45%), 5 h a d s l i g h t r e d u c t i o n (40-44%), 3 h a d significant reduction (20-39%) a s s o c i a t e d w i t h d e c r e a s e in r e n a l size. A l l k i d n e y s h a d a T I \ 2 >I0' at f i r s t scan: 15 w i t h T I \ 2 <20', 25 w i t h TI\2 >20' Of the 40 kidney, 28 s h o w e d T I \ 2 improvement at second MAG3 scan; they were considered as d i l a t e d but not obstructed. A t h i r d M A G 3 s c a n w a s p l a n n e d in five k i d n e y w i t h TI\2 >20' w i t h o n s e t of w a s h o u t at 15' (<20%) that c o n t i n u e d b r i s k w a s h o u t at 30' (25-40%). Four infants marked nephromegaly and three i n f a n t s w i t h h y p o p l a s t i c ~idney, h a d T I \ 2 >20' w i t h a n i n s i g n i f i c a n t 15' a n d 30' w a s h o u t (<20%) were considered obstructed and underwent pyeloplasty. Split renal function was unchanged in a l l c h i l d r e n o v e r time. C o n c l u s i o n : O u r d a t a c o n f i r m that a n T I \ 2 <20' has to b e c o n s i d e r e d as a n o n o b s t r u c t e d p a t t e r n e s p e c i a l l y w h e n s p l i t f u n c t i o n is good. A n y w a y a follow-up is r e c o m m e n d e d . When the follow-up c o n f i r m TI\2 >20' a n d the s p l i t function is d e r a n g e d e s p e c i a l l y w h e n a d y s p l a s i a is p r e s e n t , s u r g e r y has to be c o n s i d e r e d . INTRODUCTION:

F.ARCHAMBAUD*, B.BADER-MEUNIER**, V.BAUDET**, A RAMADAN*, C HIGNETTE*,J-P DOMMERGUES** * S e r v i c e de M 6 d e c i n e N u c l 6 a i r e , H 6 p i t a l de Bic6tre, 9 4 2 7 5 B I C E T R E Cedex, F r a n c e * * S e r v i c e de P 6 d i a t r i e G 6 n 6 r a l e , H 6 p i t a l de B i c 6 t r e . DMSA RENAL SCAN IN ACUTE PYELONEPHRITIS IN CHILDREN (PNA):AGED-RELATED SENSITIVITY D M S A r e n a l s c a n is h i g h l y s e n s i t i v e to d e t e c t P N A in animal model(>85%), the a i m of this study is to e v a l u a t e its s e n s i t i v i t y in a c h i l d r e n p o p u l a t i o n w i t h in 80%, a first s u p e c t e d PNA. M A T E R I A L A N D METHOD: 49 c h i l d r e n w e r e i n c l u d e d (23 m a l e a n d 26 female); 24 w e r e less t h a n 1 y e a r a n d 25 m o r e than i. P N A d i a g n o s i s was based on c l i n i c a l (fever) a n d b i o l o g i c a l d a t a (white b l o o d c e l l count, C R P level, u r i n e c u l t u r e ) . A r e n a l s c a n was p e r f o r m e d at the t i m e of i n f e c t i o n (mean 5 days) w i t h e a r l y (lh p o s t iv; p o s t e r i o r view, p i n h o l e ) a n d late i m a g e s (6h p o s t iv; p o s t e r i o r , o b l i q u e posterior, and lateral views). Renal scan w a s c o n s i d e r e d as p o s i t i v e in c a s e of a focal o r g l o b a l a r e a s of d i m i n i s h e d u p t a k e of D M S A w i t h p r e s e r v a t i o n of the r e n a l c o n t o u r . RESULTS: According to t h e p r o b a b i l i t y of P N A d i a g n o s i s , p a t i e n t s w e r e c l a s s i f i e d in 2 groups: g r o u p I c (high risk) a n d IIc (intermediate risk) on c l i n i c a l findings; a n d in g r o u p I r (high risk) a n d IIr (low risk) o n r e n a l s c a n r e s u l t s . < 1 year > i year Ir IIr Ir IIr Ic ii(61%) 7(39%) 18(82%) 4 (128%) IIc 0 6 1
0Mo332

0Mo334

G. Meyer ~, A. Piepsz 2, FJ. Rink ~, J. Kolinska 2, j. Lepej 2, R. Sixt 2, K. Hahn ~, Department of Nuclear Medicine, Ludwig-MaximiliansUniversity, Munich, Germany ~, Paediatric Task Group od EANM 2

J. Verd~, M. Juste,O. Caballero, J. Serrano, A. Martinez, and M. Moya. Departamentos de Medicina Nuclear y Pediatria. Hosp. San Juan. Alicante. SPAIN

Tc-99m-MAG3-CLEARANCE ,,NORMAL" VALUES IN CHILDREN: A MULTICENTER STUDY

ESOPHAGEAL TRANSIT SCINTIGRAPHY CHILDREN WITH GASTROESOPHAGEAL REFLUX

P u r p o s e : Tc-99m labelled mercaptoacetyltriglycine (Tc-99m-MAG3) simplifies and improves the clearance quantification in children by its permanent availability, good imaging properties and low radiation exposure. Due to the deficiency of ,,normal" values of Tc-99m-MAG3 clearances in children the Paediatric Task Group of EANM initiated a multicenter study to evaluate Tc-99m-MAG3-clearance ,,normal" values in children. Patients and methods: 125 children aged between 12 months and 17 years - who were classified as ,,normal" using defined diagnostic criteria - were included to the study. Tc-99m-MAG3-clearance was calculated using an algorithm by means of a single blood sample at any time between 30 and 40 rain after tracer injection. In addition, the absolute Tc99m-MAG3-clearances were normalized to body surface area. For further evaluation the investigation age was classified in several different groups. Results: There was a continuous increase of Tc-99m-MAG3-clearance for the non-corrected values from the age of 1 year up to the age of 17 years. (mean value < 2 years: 98 + 57 ml/min; mean value > 8 years: 208 +- 66 ml/min). Normal clearance values of adults were achieved up to the age of 8 years. The correlation between non-corrected clearance and age was r = 0.7. When these absolute clearances were normalized to body surface area we found nearly constant clearance values for all age groups with a mean clearance value of 315 + 114 ml/min*l.73 mk The correlation of normalized clearances to age was r = 0.28.

In c o n c l u s i o n , the clearance of Tc-99m-MAG3 increases continuously througout childhood into adolescense due to the maturation and growth of the kidney. After normalization of the absolute clearance to body surface area no correlation between clearance and age could be proved.

(ETS) (GER)

IN

The aim of the study was to assess the utility of ETS in demonstrating esophageal motility abnormalities in children with GER, and its capability in discerning the relationship between GER and respiratory symptoms secondary to aspiration. We have studied 33 patients age 3.4±2.3 years.GroupI:digestive symptoms(n=lS); Group II: recurrent respiratory symptoms (n=5); Group III:digestive and respiratory symptoms (n=13);Control group: patients with neither GER nor esophageal disease(n=ll).29 ETS with liquid and 22 with semisolid bolus were suitable for quantification. Late thoracic views(3 and/or 24 hours) were obtained in 31 cases. Parameters of esophageal motility were obtained from the first swallow, calculating global transit time GTT, and 90% clearance time (90CL). Thresholds of pathology were obtained from the control group. GTT (seg) 90CL (seg) liq. semisol, liq. semisol. (path/norm) Gr I I/ii 2/5 i/ll 3/4 Gr II 0/4 1/4 0/4 1/4 Or III 5/8 6/4 7/6 7/3 Late thoracic views were all normal. Conclusions: I)ETS can detect esophageal motility abnormalities in GER.2)ETS solid shows a higher percentage of abnormal results than does liquid, in all groups.3) Motility abnormalities are more frequent in group III patients.4) Late thoracic views have a poor sensitivity in detecting pulmonary aspiration.

1115

U) C O C u) e~

0

•

Paediatrics/Radionuclide Therapy

0Mo335 ~xtstafa, H.*; ~in, A.~; E I - ~ , Sh.*; Fis~, K.**, Soling, N. **~ and W a g , Sh. * Nuclear M~dicine*, UrDlc~/y*** an/ Pediatric*** DepartnP~ts, Ca/_ro University, Egypt. DIAGNOSIS

OF V E S I C O U R E T E R I C

REFLUX

A N D ITS ROLE TO R E F L U X N E P H ~ O P A T H Y

BY

DIFFERENT

0Mo337 GS Limourts1, M Manetou 2, N Toubanalds 1, V Giannakopoulos1, M Margaritaki1, V Voliotopoulos1, A Stavraka 1, L Vlahos I 1RadiologyDept, Nucl Med Sec,Areteion UnivHow, Athens 2NuclMed Dept, NIMTS Hosp, Athens,

METHODS

IN PEDIATRICS •

Seventy nine patients with urinary tract infection (158 renal units) ~ evaluated using ~ ([~S), indirect radicnuclide cystcgr~y (I~C) and radiologic ascending cystcurethrm~ra~hy (AUJ). Positive- ve~ico-ureteric reflux (VOR) was evident in 38 patients (59 kidneys). 50% of patients with positive VUR had history of r~current urinary tract infection, whereas there was no oorre/atien of age and sex in relatien to positive VUR. The frequency of positive VUR using I~C, D~C and ACU were 28.4%, 22.4% and 16.7% respectively. Early grade I, II of VUR was evident using []9C in 20% versus 6.6% in IBC and 4.2% in BSU. Sensitivity and specificity of D~C ~ 81.8% and 87.5% versus 66.7% and 81.7% for IBS. The addition of both methods showed higher sensitivity (100%) and specificity of 76.3%. %q]e total studied renal units (158) were divided ir~to 2 ~ : group A with nozmal gl~nerular function and no evidence of scars (74 renal units), however, 16 renal units in this group have high grade 3 - 4 VtR (21.6%)*. Group B with different grades of functional impairnent and scarr/ng {84 renal units with 36 renal units have high grade 3 - 4 (42.9%)* which is significantly different if ccrqoared with group A (P<0.05)*. T O 00'~11t"~: C_.~rbinEd glcn~rular and tubular function with V~R assessment are essential for detection of high grade 3, 4 VUR in padiatrics which may contribute to renal

mp~=~nt.

ABSORBED DOSE AND ANALGETIC DURATION AFTER l.V. DISODIUM PAMIDRONATE/Sr-89 CHLORIDE/Re.186 HEDP APPLICATION IN BREAST AND PROSTATE OSSEOUS METASTASES Sr-89 Chloride and Re-186 HEDP have been proposed as two very promising radiophamaceuticals for the palliative treatment of bone metastatic pain. Besides the world wide efforts to achieve optimal doses for a longest possible analgetic duration, the therapeutic response remains still moderate for both radio-pharmaceuticals. In an attempt to improve the traditional therapeutic schemes in a total of 17 patients with bone metastases due to breast and prostate cancer, 180 mg of Disodium Pamidronate (Aredia, Ciba- Geigy Ltd, Basel), 148±15 MBq of Sr-89 Chloride (Amersham lnt pie, Bacldnghamshire) and 1400±100 MBq of Re-186 HEDP (Mallinckrodt Medical BV, Petten) were i.v. applied at onset, in weekly intervals between each other. The efficacy of the treatment was assessed by a pain and performance questionnaire that patients were asked to complete daily and by comparison of bone scans and MRI images before, 3 and 9 months after Sr-89/Re-186/Disodium Pamidronate administration. The absorbed dose was correlated with the therapeutic effect achieved, using a quantitative conjugateview counting technique with a gamma camera (ELSCINT SP4, ECT) to calculate the retention curves. It was assumed that both Sr-89 and Re-186 are volume seeking radiopharmaceuticals. This radio,udide coctall resulted in a marked longer duration of osseous analgesia (x: 4.2-+0.8 months) compared to that achieved with Sr-89 Chloride (x: 1.6±0.2 months, 9 cases) or Re-186 HEDP (x: 2.1±0.3 months, 11 cases) alone. The accumulative radiation deposition on the osseous metastases from both radionudides was calculated to be approx 1800 cGy, pretty below the 4OX)cGy, absorbed from external radiation therapy, considered necessary for healing. In contusion the sum of the combined radiation delivered has to be considered as still palliative rather than curative, albeit MRI scans 9 months post treatment show recalcification of the lytic component, interpreted as response to therapy. A more advanced therapeutic scheme would be to individualizethe radionuclidic administration dose in relation to Bone Scan Index before treatment. Only then we could hope rather for curative then for palliative results.

Radionuclide Therapy 0Mo336 C Pirich, E Sohwameis, A W a n i v e n h a u s , E H a v l i k J Flores,P Angelberger,H Kvaternik, H Sinzinger Departments of N u c l e a r Medicine, Orthopedics, Physics & B i o m e d i c a l E n g i n e e r i n g , U n i v e r s i t y of Vienna, A u s t r i a RADIATION SYNOVECTOMY WITH DYSPROSIUM 165FERRIC H Y D R O X I D E - I N F L U E N C E OF R A D I O G R A P H I C STAGE ON C L I N I C A L A N D D O S I M E T R I C O U T C O M E 165Dysprosium (165Dy) o f f e r s p r o m i s i n g p h y s i c a l properties for r a d i a t i o n synovectomy and the carrier ferric hydroxide minimizes the c u m u l a t i v e r a d i a t i o n dose to n o n - t a r g e t organs b y c a u s i n g less l e a k a g e . W e are r e p o r t i n g about p r o p e c t i v e c l i n i c a l and d o s i m e t r i c studies in 24 p a t i e n t s (pts); m e a n o b s e r v a t i o n period: 22 months. 14 females (i0 males), m e a n age 49 (42) years. 17 pts h a d rheumatoid, 5 pts p s o r i a s i s arthritis, w h i l e 2 pts h a d r e c u r r e n t e f f u s i o n s due to o s t e o a r t h r i t i s . R e s p o n s e to t r e a t m e n t was c l a s s i f i e d as e x c e l l e n t to good b y clinical and r a d i o l o g i c a l evaluation in 70% (n = 17) while 30% (n=7) showed little or no improvement. Pannus f o r m a t i o n was r e d u c e d in 17 pts w i t h L a r s e n stages I (n=9) or II (n=9), and in 5 pts with L a r s e n stages III (n=7) or IV (n=2).The range of m o t i o n was i m p r o v e d in p a t i e n t s w i t h L a r s e n stages I and II b y 28°and 21 o, in joints w i t h L a r s e n stages III and IV by 20 ° and 7 ° , r e s p e c t i v e l y . Biokinetics and biodistribution were e v a l u a t e d in 12 p a t i e n t s using the clinical whole-body counter. In 7 patients activity profiles did not reveal any leakage. Leakage was detected in 5 p a t i e n t s (<0.1%) b e i n g not r e l a t e d to the r a d i o g r a p h i c stage. These clinical and d o s i m e t r i c results confirm the safety and efficacy of r a d i o s y n o v e c t o m y w i t h 165Dy.

1116

OMo338 A. Hoekstra, J.M.H. de Klerk, B.A. Zonnenberg and P.P. van Rijk. Department of Nuclear Medicine. University Hospital Utrecht, The Netherlands. RADIATION SAFETY STUDY OF Sr-89-ClAND Re-186-HEDP IN PATIENTS WITH PAINFUL BONE METASTASES The radiopharmaceuticals Sr-89-CI and Re-186-HEDP are often used for treatment of metastatic bone pain in patients with prostatic cancer. An important aspect of this treatment option is the radiation safety to the immediate caregivers of the patient, including the nursing staff. Previously we reported (Brussels, 1995) a significant doserate detectable from patients treated with Sr-89-CI, although this nuclide emits only ~-radiation. At an early stage we verified the "f-exposure from patients treated with Re-186-HEDP. As a result of both studies the measured exposure data will be analyzed in detail. In addition to the treatment with Sr-89 we investigated the radiation safety for Re-186. The questions addressed were: 1. Is ~,-radiation detectable outside the patient? 2. What is the radiation dose to non-patients due to this therapy? Material and method: A portable dose ratemeter (PDM1, Nuclear Enterprise) was calibrated suited for the detection of 9" and low energy y-radiation. Specifications: detection area 100 cm 2, window thickness 8 mg/cm2. Simulation of the patient measurement is done by using a point source of sufficient activity attenuated by different thicknesses of soft tissue equivalent material. The patients were hospitalized for three days in case of Sr-89 treatment (150MBq) and one day in case of Re-186 treatment (1295 MBq). The exposure originating from the patients was measured at various points in time during the hospitalization. Results: 1. Analysis of the plotted exposure rate against the thickness of the equivalent material indicates the detection of ~-radiation. 2. The mean patient 13-doserate of Sr-89 is 10+9 ~Sv/hr at 1 m distance and 1.5 hour after injection. 3. The mean patient (~,+7) doserate of Re-186 is 16_+3 p.Bv/hr and the mean patient 13-doserate equals 13__.3 i~Sv/hr at 1 m and 1 hour after injection. Conclusion; Contrary to the common opinion of complete ~ absorption we detected p-radiation outside the body. So non-patients get an effective radiation dose in response to this exposure, depending on the situation.

•

Radionuelide Therapy

0Mo339

0Mo341

M~ Aas,_ A. Skretting and ~. Bruland, Departments of Nuclear Medicine, Medical Physics and Technology, and Oncology, The Norwegian Radium Hospital, Montebello, N-0310 OSLO, Norway

J.Pinkertt, W.-G.Franke t, K.Schomiicker2, B.Friebel L and T.Woschick~ Technical University Dresden 1, University of Cologne2, Depamnents of Nuclear Medicine

IS3Sm-EDTMP TREATMENT

IN OSTEOSARCOMA

PATIENTS

= m

=I~

TREATMENT OF SOFT TISSUE TUMORS WITH YTTRIUM-90 CITRATE: BIODISTRIBUTION, SIDE EFFECTS AND EFFICIENCY

The purpose of this study was to evaluate the use of a bone seeking radiopharmaceutical, 153Sm-EDTMP, as a new treatment modality in recurrent osteosarcoma (OS). Ten patients with OS, presenting either with local recurrence or metastatic disease after all conventional treatment modalities had failed, were given i.v. infusions of 153Sm-EDTMP, 35-60 MBq/kg body weight on one or two occasions, usually 6 weeks apart. All patients showed transient fall in platelets and white and red cells, the values were restored after 6 to 8 weeks. In all three patients where p a i n was present before treatment, the pain was significantly relieved. In five patients significant growth delays, lasting up to 18 months, were observed. One patient showed progressive tumor growth despite good uptake of the pharmaceutical in numerous metastatic lesions. Three others had relatively low tumor uptake and p r o g r e s s e d rapidly. The absorbed radiation doses were estimated using attenuation corrected c o n j u g a t e d view whole body scans and CT images. Calculations indicate that the average tumor doses could exceed 30 Gy, and in areas with intens u p t a k e considerably higher, following a single treatment course. Pretreatment dosimetry may be based o n 99mTc-MDP scintigraphy. Conclusion:Targeted radionuclide therapy using 153Sm-EDTMP may give considerable palliative effect in patients with osteoblastic OS and possibly be u s e d already in the primary treatment of OS as a boost technique to conventional radiotherapy and as an adjunct to chemotherapy.

Recently several papers described the enrichment of radiometal ligand complexes like Yttrium-90 citrate in soft tissue tumors. Therefore the usefulness of its use in tumor therapy is discussed too. As an important prerequisite to study the therapeutic use of Yttrium-90 citrate we examined the time course of of Yttrium-87 citrate in liver, muscle, blood, bone, spleen, gastroqntestinal tract, lung and tumor until 48 h alter intraperitoneal (i.p.) injeclion in melanoma and mamma carcinoma bearing mice. Side effects in the bone marrow and liver as well as changes of blood count and glutamic-pyruvic transaminase (GPT) were examined at 2, 5, 9, 15, 21 and 36 days after (i.p.) injection of Yttrium-90 citrate. The inhibition of tumor growth was studied as well as by melanoma, mamma carcinoma and fibrosarcoma bearing mice (9-16 mice for each verum and control group) with measurement of the tumor diameter (implanted in the right hind leg). The LD-50 was determined by i.p. injection of 435, 516,705 and 860 MBq / kilogram body weight (kgbw). 24 h after i.p. injection Yttrium enrichment ratios expressed as tunror/muscle, tumor/liver and tumor/bone of 20, 0.4 and 0.1 were found. The LD-50 within 14 days p.i. was estimated with 460 MBq/kgbw. No significant changes of GPT after application of Yttrium-90 citrate from 18.5 to 370 MBq/kgbw could be observed. However a clear, dose dependend drop in blood count could be seen. The minimum of the leucocytes (especially the granulocytes) was found at 9 days p_i.. No complete normalization until 36 days pi. could be reached with 185 and 370 MBq / kgbw. A significant inhibition of tumor growth was seen in mamma carcinoma, melanoma and fibrosarcoma but a clear regression of tumor was not provable. The amount of radioactivity necessarily for treatment was sublethal in this

0Mo340

0Mo342

DA Podoloff. ES Delpassand, S. Tu, T Jones, R Amato, J Ellerhorst, R Kilborne, WF Broussard and C. Logothetis, U.T. M.D. Anderson Cancer Center and University of Texas, Houston, Texas.

F. Pens., R. Herranz, A. Garcfa, C. Conill1, E. Verger ~, A. Alcovera, S. Vidal-Sicart, F. Lomefia, J. Setoain.

STRONTIUM-89 (SR-89) DOES NOT ADD TO THE TOXICITY OF ADRIAMYCIN IN THE TREATMENT OF PATIENTS WITH ANDROGEN INDEPENDENT (AI) PROSTATE CARCINOMA. Patients (pts.) w i t h AI carcinoma of the prostate are c o m m o n l y treated w i t h adriamycin to control their disease. It w a s the purpose of this work to determine whether the addition of Sr-89 increased toxicity in pts. treated w i t h adriamycin alone. Sr-89 (4 mCi q 3 months) was combined with adriamycin (15-20 m g / m 2, i.v. CI over 24 hrs q weekly). All pts. had progressive AIPC w i t h bone metastases. Adequate cardiac function (LVEF > 50%) and adequate hematologic reserve (platelet >100,000/ml, neutrophils > 1500/ml) was required. All pts. had failed h o r m o n a l ablative treatment. Serial assays of pain scores, serum PSA a n d alkaline phosphatase was accomplished. 17 of 23 pts. (74%) were evaluable. Median age 65, m e a n performance data 0.65, m e a n pain score 1.42 (Robinson et al). Median PSA 28.7, (range 25 to 2000). Toxicity was limited to hematologic and GI. Thrombocytopenia > Grade 2, 5 of 17 (29%); neutropenia > Grade 3, 6 of 17 (35%); mucositis > Grade 2, 4 of 17 (24%); Sr-89 pain flare 6 of 17 (35%). Results: 14 of 17 (82%) had reduction of pain score (8 of 17 pts. (47%) had complete resolution of pain). 16 of 17 pts. (94%) h a d serial reduction of alkaline phosphatase and 6 of 17 pts. showed evidence of a response w i t h > 50% decrease in PSA. Onset of PSA decline and clinical response occurred at a m e a n of 2.5 weeks post-therapy and the duration of response was 12 to 25 weeks. Two pts. whose PSA stabilized h a d gradual and late decline in their PSA's (11 and 15 wks.). Conclusion: Combination Sr-89 chloride (4 rnCi) q 3 months and w e e k l y adriamycin can be administered to pts. safely. Toxicity is not increased by this combination.

tO

case.

Therefore the therapy with Yttrium-90 applied as citrate seems not to be promising for effective therapy of the studied tumor types. The radiogenic affection of the haemopoietic bone marrow is the major side effect. Studies of new kinds of Ytttium-90 complexes are on the way.

Nuclear Medicine, Radiation Oncology (1) and Urology (2) Departments. Hospital Cl[nic. University of Barcelona. Barcelona, Spain. RESULTS OF TREATMENT OF PAINFUL BONE METASTASES WITH STRONTIUM-89. To evaluate the efficacy of Strontium-89 in the palliation of pain from bone metastases, 66 patients (43 males with prostatic carcinoma, 23 females with breast cancer) were treated with 148 MBq of Sr-89 chloride, nine patients receiving a second injection. Inclusion criteria were: scintigraphic evidence of multiple bone metastases, bone pain localized in the areas of higher uptake and resistance to usual pain-releasing treatments, adequate hematologic and renal function and life expectation of at least three months. A scoring system was used for pain and analgesia. The pain (P) was calculated as the product of severity and frequency and analgesia (A) as the product of analgesic potency and frequency of dosage, with a more specific scoring for opiates. The performance status was assessed by the Karnofsky Index (KI). The efficacy of Sr-89 was evaluated after three months of treament. Three levels of response were considered, taking into account the variation in P and/or A and/or KI: a variation with a score higher than 4 was considered a good response, a score of 3-4 a partial response and a score of 0-2 no response. In prostate cancer patients, a good response was obtained in 30 (73%), partial in 7 (17%) and no improvement in 4 (10%). Two patients could not be evaluated. In breast cancer patients, the responses were good in 15 (65%), partial in 6 (26%) and no improvement in 2 (9%). We conclude that the high number of good responses in respect to partial and bad responSes, indicates that Sr-89 chloride can be used safely as an effective agent in palliative therapy of metastatic bone pain.

1117

C (b

r./) (I) s._ m

s._

0

•

Radionuclide Therapy

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OTu345

G. M6dder Spezialpraxis for Radiosynoviorthese, D-50858 Cologne/Germany

T.M. Behr 1'3, R.M. Sharkey ~, R.D. Blumenthai ~, G. Sgouros 2, R.M. Durra ~, R. Alisauskus I, M.E Juweid ~, G. Griffiths ~, W.S. Becker3, D.M. Goldenberg'. Garden State Cancer Center at the Center for Molecular Medicine and ImmunologyI, Newark, N J, USA, Memorial Sloan-Kenering Cancer Center 2, New York, NY, and Department of Nuclear Medicine 3, Georg-August-Uni versity of G6ttingen, Germany. IiV~ROVEMENT OF THE THERAPEUTIC EFFICACY OF RADIOMETALCONJUGATED ANTIBODY FRAGMENTS AND PEPT1DES BY OVERCOMING THEIR NEPHROTOXIC POTENTIAL

RADIOSYNOVIORTHESIS OF THE SHOULDER IN RHEUMATOID ARTHRITIS Treatment of the rheumatoid shoulder consists of systemic and local therapy. Besides of surgical intervention radiosynoviorthesis has been well established for two decades, but is performed very rarely in Europe. In the own specialized practice for radiosynoviorthesis glenohumeral joints of 273 patients were treated with rhenium-186 from 1992 til 1994. 154 patients of them suffered of rheumatoid arthritis. Obligatory apparative diagnostics are ultrasound for detection of rotator cuff rupture and morphological condition of synovialis, also soft tissue scintigraphy of the joints (Tc-99m-MDP) to look for the inflammatory activity of synovialis. The mandatory strict intraarticular injection of the radiopharmaceutical is performed under fluoroscopic control and arthrography. The mean posttherapeutical observation period is 20 months. Very good improvement (pain, mobility) is found in 87 % of all patients. Own earlier experience (since 1982) suggest, that therapeutical success will stay over a period of about ten years. Two years after radiosynoviorthesis treated joints will mostly not react in rheumatoid attacs any more. Repetion of radiosynoviorthesis (reradiosynoviorthesis) is useful in especially thickened synovium or involvement of bursa subdeltoidea (in 15 %). The good results are the reason for the recommendation of the german, swiss and austrian surgeons of rheumatoid shoulders (Salzburg, 1995) to perform radiosynoviorthesis before surgical treatment.

Renal uptake of radiolabeled antibody (MAb) fragments and peptides is a problem in their therapeutic application. We have shown earlier that administration of cationic amino acids is able to reduce this renal accretion. The aim of this present study was to evaluate whether this methodolgy will benefit therapy with °°Y-labeled antibody fragruents. The maximum tolerated dose (MTD), as well as the duse-limiting toxicities of 9°Y-labeled anti-CEA MN-14 Fab, F(ab)2, and IgG, were determined in GW-39 human colon cancerbearing nude mice. The mice were treated with or without kidney protection by D-lysine (Behr et at., Cancer Res. 55 (1995): 3825-3834), bone marrow transplantation (BMT), or combinations of each. Tumor growth, blood counts, kidney and liver function parameters were monitored at weekly intervals. Histology was obtained #ore tissues and minors. Dosimetry was calctdated from biodiswibutiun studies using 8sY-labeled antibody. The kidney was the first dose-limiting organ with the use of Fab fragments. Acute radiation nephritis occurred at injected activities > 325 gCi (renal dose > 100 Gy), and chronic nephrosis at doses > 250 gCi (renal dose >70 Gy). Application of lysine decreased the renal dose by approximately five-fold, enabling an increase in the MTD by 25%, because myelotoxicity became dnse-limiting, despite red marrow doses of less than 5 Gy. By using BMT and lysine, the MTD was doubled from 200 to 400/aCi, where no biochemical or histological evidence of renal damage was observed (kidney dose < 40 Gy). The MTD of F(ab)z fragments could be elevated ot~ly by the combination of BMT and lysine by 30% (from 200 to 260 ~tCi). With IgG the bone marrow alone was dose-limiting (100 gCi without, 130 ~tCi with BMT). Tumor dnsimetry correlated well with the observed antitumor effects (> 10 Gy led to growth inhibitinn for 5 weeks, and > 20 Gy for > 13 weeks). Fab fragments showed a higher initial dose rate and more homogenous dose distribution than IgG or F(ab)> At their respective MTDs (with lysine and/or BMT), Fab was mere effective than F(ab)2 and IgG in controlling tumor growth. These dala show that radiation nephrotoxicity is an important issue in cancer therapy with radiometal-eonjugated antibody fragments or peptides. Chronic nephrosis may develop without previously occurring acute nephritis. Radiation nephrotoxicity can be overcome succesfuUy with the application of cationic amino acids, thereby substantially increasing the anti-tumor efficacy of antibody fragments. Initial clinical results on the application of thJ; methodology in patients are promising (Behr et al., J. ,Vucl. Med 37 (1996): in press). (Supported by DFG grant Be1689/1-1/2 and by USPHS grants CA39841 and CA62444.)

OMo344

OTu346

EP Krennin~ t'2, R V a l k e m a t, P P M Kooij t W A P B r e e m a n t. W H B a k k e r 1, P T E P o s t e m a i, W W d e H e r d e r ~, C H J v a n E i j c k , D J K w e k k e b o o m 1 and S P a u w e l s 4. D e p a r t m e n t s o f N u c l e a r 14 , and Internal Medicine 2 and Surgery 3, University Hospital Rotterdam, T h e Netherlands and Catholic University o f Louvain, Brussels, Belgium.

T.M. Behr. R.M. Sharkey, M.E. Juweid. R.M. Dunn, R.C. Vagg, L.C. Swayne. Z. Ying, J.A, Siegel, D.M. Goldenberg. Garden State Cancer Center at the Center for Molecular Medicine and Immunology. Newark, N J, USA.

RADIONUCLIDE TltERAPY WITH mln-I)TPA-OCTREOTIDE Side- and antiproliferative effects o f the A u g e r - and conversion electrons from high doses o f [ n t l n - D T P A - D - P h e r ] o c t r e o t i d e w e r e studied in patients with end-stage disease. The table illustrates the main characteristics o f applied doses and results

TABLE: Preliminary information of phase I treatment-study with [mIn-DTPA-D-Phel]-octreotide. Pat

Age Yrs

1H 2H 3R 4S 5S 6B 7W 8W 9B 10D 11H

74 56 66 32 57 55 58 62 65 57 62

Diagnosis

" q n dose . . . . . . . . . . . . F O L L O W U P . . . . . . . . . . . . . GBq CT/MR/scan Horm/Tumorm

Carcinoid' MTC 2 Carcinoid s Leiomyosarc. t Papill. Thyroid 2 Glomustumors s MTC 2 Carcinoid s Carcinoid 3 Glucagonomas Insulinoma 3

5 6 6 11M 17M 24M 25M 30M 35M 37M 53M

Incr Incr Un 9. ? Decr ?* Decr Deer Deer Deer

Un Incr Incr NA ? NA Incr Un Deer Deer Deer

D A D D A A D A A A D

Legend: Follow up is evaluation e v e r y 2-3 months after administration(s) o f radioligand. C T / M l l l - s c a n and H o r m / T u m o r m = c h a n g e s in tumorsizes on C T / M R I - s c a n s and in production o f h o r m o n e s and t u m o r m a r k e r s by the neuroendocrine tumors. U n = unchanged; N A = not applicable; Incr = increase and D e e r = decrease. A = alive and D = deceased. ill In doses are cumulative doses if indicated by M Radioligand accumulation is based on visual scoring o f tracer uptake, 3 is highest and 0 the lowest score, s h o w n in superscript with the diagnosis. *= clinical progression. C o n c l u s i o n s : 1. N o major side-effects w e r e observed. 2. High a m o u n t s o f [ 111I n - D T P A - D - P h e 1]-oetreotide administered in divided doses m a y h a v e an antiproliferative effect.

1118

PHASE I[11 RAD1OIMMUNOTHERAPY TRIAL OF CEA-EXPRESSING CANCERS WITH AN ~31I_LABELEDANTI-CEA MONOCLONAL IgG, The aim of this study was to determine, in a phase l/II clinical trial, the pharmacokinetics, dosimetry, toxicity, as well as anti-tumor activity of the ~'l-labeled marine anti-CEA monoclonal antibody, NP-4 (IgG~ subtype). A total of 57 patients with CEA-expressing tumors, mostly in very advanced stages, were treated (e.g, 29 colorectal, 9 lung, 7 pancreas, 6 breast, and 4 medullary thyroid cancer patients). The patients underwent a diagnostic study (8mCi ~ i ) to assess tumor targeting and to estimate dosimetry, followed within two weeks by the therapeutic dose (44268mCi), based upon the radiation dose to the red marrow. Blood and whole-body clearance were determined from blood sampling and whole-body scanning; radiation doses were calculated from imaging (planar and SPECT) according to the MIRD scheme. Red marrow doses ranged from 45 to 706 cGy, and whole-body doses from 31 to 344 cGy. Differences in pharmacokinetics were found between different types of CEA-producing tumors, which is probably due to complexation with the circulating antigen: at comparable plasma CEA levels, blood TV's were significantly lower in colorectal cancer when compared to all other tumor types (21.4 :t: 11.1 h vs. 35.8 • 13.2 h; p<0.01), as were also tile whole-body t,/=s. Consequently, red marrow doses were lower hi colorectal cancer patients than in other rumor types (219 = 1.09 vs. 3.54 • 0.73 cGy/mCi; p<0.001). Myelotoxicity was dose-limiting, and its severity was related to the types of prior therapy and extent of bone marrow involvement. In patients without prior radiation or chemotherapy, marrow doses as high as 600 cGy were tolerated without evidence of doselimiting toxicity. No major toxicity to other organs was observed. Tumor doses were inversely related to the tumor mass and ranged between 2 and 218 eGy/mCi. Anti-tumor effects were seen in 12 of 35 assessable patients (one partial remission, four minor/mixed responses, seven with stabilization of previously rapidly-progressing disease). These results suggest that prior rnyelotoxic therapy is an important risk factor for the development of hematological toxicity in radioimmunotherapy, and that nigher radiation doses may be delivered to tumors of patients without prior therapy compromising the bone marrow reserve. These different and, in the individual case, unpredictable clearance rates suggest the necessity of dosimetry-based treatment planning rather than mCi/m-' dosing. Small tumors seem to be more suitable for radioimmunotherapy because of their favorable dusimetry, but in order to achieve better therapeutic results in patients with bulky disease, the application of higher, potentially myeloablative doses is indicated. (Supported by DFG grant Be1689/1-1/2 and by USPHS grants CA39841 and CA54425.)

• 0Tu347 A. Merle ~, E. Jermann 2, O. Hausmann t, A. Probst 3, O. Gratzl ~, H.R. M~icke2, J. MOiler-Brand 2, University Hospital, Neurosurgery t, Nuclear Medicine 2, Neuropathology 3, 4031 Basel, Switzerland

Radionuclide Therapy

0Tu349 T.M. Behr 1'2, R.M. Sharkey I, M.E. Juweid I, R.M. Dann I, J.A. Siegel I, W.S. Becker 2, D.M. Goldenherg 1. Garden State Cancer Center at the Center for Molecular Medicine and Immunology j, Newark, NJ, USA, and Department of Nuclear Medicine 2, GeorgAugust-University of G6ttingen, Germany. T H Y R O I D R A D I A T I O N DOSES A N D THEIR BIOLOGICAL EFFECTS IN THE

INTRALESIONAL BOLUS-INJECTION OF IN-111/Y-90 LABELLED ISOTHIOCYANATO-BENZYL-DTPA MODIFIED ANTI-TENASCIN MAB BC-2 IN GLIOBLASTOMA PATIENTS

TI-[ERAPY WITH I~II-LABELED IMMUNOCONJUGATES

Radioimmunotherapy holds promise to become a novel therapeutic option for glioblastomas complementing the conventional armamentarium of surgery and radiochemotherapy. We analyzed biodistribution of the murine monoclonal antibody (MAB) BC-2 and F(ab')2 fragments of BC-2 that recognize tenascin, a compartmentally specific tumor-associated antigen that is expressed in virtually all gliobtastomas. The activated ligand isothiocyanatobenzyl-diethylenetriaminepentaacetic acid was conjugated onto MAB and fragments, and these conjugates were labelled with In111 or Y-90, displaying immune reactivity of > 90 % and labelling efficiency of 99 +_ 1 % . Following intravenous administration of whole MAB or fragments in 5 glioblastoma patients, almost the entire injected dose was found to be trapped in liver, spleen and bone marrow while tumor uptake was marginal. Uptake into the tumors, however, could be substantially improved by direct intralesional injection of radiolabelled MAB into a catheter-reservoir device. By assessing biodistribution of In-Ill-labelled MAB in another 14 glicblastoma patients, 80 - 90 % of the total injected dose was found to remain stably bound within the confines of the tumor for several days, effectively reducing potential systemic toxicity. In conclusion, labelling DTPA modified MAB BC-2 with the radiochemically matched pair In-111/Y-90 yields stable radioimmunoccnjugates suitable for intralesional bolus-injection and internal radiotherapy in glioblastoma patients.

High variability of thyroid doses is a frequently observed feature in therapy with '~llabeled antibodies or other iodinated radiopharmaceuticals. The aim of this study was to evaluate which factors may influence these doses in radioimmunotherapy (RAIT), as well as to determine whether they cause any biological effects, e.g., hypothyroidism. Data from 36 patients with CEA-expressing tumors who underwent RAIT with the 131Ilabeled anti-CEA antibody MN-14 (45.8-220.0 mCi) were analyzed. The thyroid was blocked with 120 mg iodine (Lugol's or SSKIn~) and 400 mg perchiorate per day. Blood clearance and molecular composition of labeled plasma compounds were determined by blood sampling and HPLC analysis. The cumulated activities and residence times of tissues were calculated from imaging data (up to 240 h p.i.). Doses were derived fi'om the MIRD scheme. Thyroid doses varied between 1.2 and 37.7 cGy/mCi (11.1 ± 8.3 cGy/mCi), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was, at 2.4 ~- 1.9 gCi / injected mCi (range 0.2-10.0/.tCi/mCi), less than 1% of the injected activity, indicating more than 99% blocking of the thyroid in all eases. No correlation was found between thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the MAb preparation, rapid metabolic breakdown of the labeled MAb due to human anti-mouse antibodies (HAMA), or complexation with circulating antigen. However, a correlation between the thyroid doses and the patients' compliance to take their blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (median 220.8 h; range from 31.1 h to virtually infinity), is indicated. No rising TSH titers or other signs of (latent) hypothyroidism were seen in these patients during a two-year follow-up period; longer follow-up was not possible because of the terminal condition of most patients. These data suggest that patient compliance in taking their blocking medication may be the most crucial factor for reducing thyroid doses in therapy with 131I-labeled antibodies. Premedication with Lugol's and perchlorate is sufficient for an over 99% blocking in all cases. Doses reached in such standard-dose RAIT are lower than those generally assumed to be required to cause late hypothyroidism. Even when higher activities will be used, potential hypothyroidism may be overcome easily by hormone substitution. (Supported by DFG grant Be1689/1-1/2 and by USPHS grants CA39841 and CA54425.)

0Tu348

OTu350

P.Riva*, C.Sturiale °, G.Franceschi*, A.Arista °, N.Riva*, M.Casi*. *Nuclear Med. Dept. And Istituto Oncologico Romagnolo, ° Neurosurgery Dept. M.Bufalini Hospital-Cesena (Italy).

P.Galofr~ °, S. Guti~rres'w E. Carbonell =, A.Garc~a-Burillo', M. Soler =, T. C a n e l ~ , R. M a r c o s =' • Medicina Nuclear, Hospitals Vall d'Hebron, = Grup de Mutag#nesi, Universitat Autrnoma, Barcelona, Spain.

LOCO-REGIONAL RADIOIMMUNOTHERAPY OF MALIGNANT GLIOMAS: PROBLEMS AND PERSPECTIVES. Since 1990 n 53 patients were enrolled in a phase II study. All were affected by high grade malignant glioma (50Glioblastoma and 3 anaplastic astrocytoma), with a very bad prognosis. 26 pat. presented newly diagnosed tumour and subsequently were treated with debulking surgery, external radiotherapy ( 55-60 Gy) and intralesional radioimmunotherapy (IL-RIT) (BC-4 Mab 4 mg ,and 1-t3t 49.5 mCi). IL-RIT was given repeatedly, up to 6 times, by means of an indwelling catether. A second group of cases (27) presented a lesion which recurred after previous surgery and radiotherapy. So they underwent second operation and then received IL-RIT. The infusion of radiopharmaceutical, directly in the site of lesions, resulted in a fast and homogeneous distribution when the patient had a postoperative cavity. When a solid remnant was present, the Mabs spread more slowly through the neoplastic tissue but completely permeated the tumour mass, as assessed by means of istoautoradiography. In some cases with a communication between the cavity and CSF, a diffusion of radioactivity in ventricles, cisterns, and spine was recorded. But most of radiolabelled Mabs remained in the site of disease. Locoregional RIT resulted clinically effective. The median survival was prolonged: 25 months ( 27 small diseases, and 16 bulky lesions). 10 SD (4 Bulky 6 small), 7 PR (2 Bulky, 5 small), 3 CR (1 Bulky, 2 Small) and 15 NED (Not Evidence of Disease) were obtained. The response rate was 47% (15% Bulky and 66% small). IL-RIT is a Nuclear Medicine effective treatment which could be favourably inserted in a mulfimodality approach to control malignant gliomas. Best results can be obtained in cases with minimal lesion after surgery and external radiotherapy or after a second operation in patients with recurrent tumour. (Work supported by National Research Council program (ITALY): Clinical Applications of Oncology Research, subproject n.8,and by AIRC: Italian Association on Cancer Research).

MICRONUCLEI INDUCTION: AN EFFECT HYPERTHYROIDISM PATIENTS.

OF 131 IODINE TREATMENT

IN

To evaluate the genetic damage induced by 131-I exposure, we have studied the frequency of micronuclei (MN) in peripheral blood lymphocytes from a group of 24 hyperthyroidism patients t h e r a p e u t i c a l l y exposed to 131-I. Blood samples were obtained before treatment and 1 week, 1 month and 3 months after treatment. Lymphocyte cultures were done according Fenech and M o r l e y method, n i n u c l e a t e d cells with micronuclei (BNMN) frequency was stablished scoring i000 binucleated cells, t-test for dependent s a m p l e s w a s used to compare BNMN frequencies. BNMN frequencies observed were: pretreat.

1 week

1 month

3 months

28.0±3.7

32.7±3.2

33.9±4.2

30.8±2.7

They showed a raising trend after treatment, although not statistically significant. When two groups of patients were created according to the doses received, significant increases in the group receiving more than 500 MBq can be seen when compared with those receiving ~500 MBq. pretreat.

1 week

i month

3 months

> 500 MBq

32.4±7.8

40.9±5.1

43.7±6.8*

37.6-+4.5

S 500 MBq

24.9±3.2 p < 0.01

26.9-+3.5

26.9±4.8

25.9-+2.8

These results indicated both the 131-I exposure genotoxicity and the e f f e c t i v e n e s s of the micronuclei a s s a y in the evaluation of risks g e n e r a t e d by exposure to radiactive sources.

1119

¢) eO |l t~ eID

O. m

•

Radionuclide Therapy/Physics and Instrumentation

OTu351

0Tu353

W. Brenner, K.H. Bohuslavizki, C. Waldherr, H. Wolf, G. T6nshoff, U. Teichert, S. Tinnemeyer, M. Clausen, E. Henze Clinic of Nuclear Medicine, University of Kiel, Germany

H.Nguyen, M.Roelandts, M.Lemort, G.Andry, A.Badr-El-Din, A.Verbist, C.Desfosses, S.Simon, P.Van Houtte and J.FrUhlin9, Departements of Radio-Oncology, of Surgery and of Medical Imaging, I n s t i t u t J. Bordet, Brussels, Belgium.

[NTRATHERAPEUT1C MEASUREMENT OF THE T R E A T M E N T DOSAGE IN RADIOIOD1NE THERAPY

The gold standard for the pretherapeutic calculation of the activity for radioiodine treatment is the measurement of both thyroid uptake and clearance half-life by a scintillation probe counter after application of minute amounts of I- 131. Intratherapentic measurement of the dose achieved can be performed with a lead shielded scintillation probe counter by the same procedure. The aim of this study was to compare the proposed organ dose with the dose actually achieved in the thyroid. 22 patients with toxic nodular goiter (TNG) and 8 patients with Graves' disease (GD) underwent radioiodine therapy with administered activities ranging from 400-1500 MBq. The proposed thyroid dose was 400 Gy in TNG and 150 Gy in GD. For both pretherapeutic calculation of treatment activity and for intratherapeutic dose assessment the activities of the administered capsules as well as thyroid uptake after 24 and 168 h were measured by the same probe counter. For therapeutic measurements a designed attenuation lead shield was used. The system with shielding was validated for linearity from 0.1 to 2 GBq 1-131 (r2 = 0.9865; n = 30). In TNG patients the achieved thyroid dose was 263.0!148.6 Gy. Thus, the intratherapeutic dose in the thyroid was 47 % lower than the proposed dose of 400 Gy corresponding to a difference of 189.7_+41.0 Gy. In GD patients intratherapeutic dose was 103.0+45.4 Gy. Thus, mean dose reduction was 43 % in GD as compared to the proposed dose of 150 Gy corresponding to a difference of 64.7+42.0 Gy. While activity measurements up to 2 GBq I-I31 proved reliable by the lead shielded probe counter, pretherapeutic measurements using 1-2 MBq showed up with poor count statistics at 24 h and especially at 168 h. This may lead to an overestimation of both thyroid uptake and half-life due to high background activity. This yields both a significant underestimation of the radioiodine activity administered and consequently a reduction of the dose delivered to the thyroid. In conclusion, these results suggest a higher amount of activity for the pretherapeutic dose estimation, e.g. 20-40 MBq I-131. Furthermore, intratherapeutic dose measurements are necessary to document the thyroid dose achieved and to more accurately predict therapeutic efficacy.

INFUSIONAL BRACHYTHERAPYBY DIRECT INTRATUMORAL INJECTION OF COLLOIDAL 32-P IN THE TREATMENT OF ADVANCED HEAD AND NECK CANCER. The aim of the present communication is to present a new technique of d i r e c t infusional brachytherapy using chromic phosphate 32-P preceeded by intratumoral i n j e c t i o n of MAA, in order to d e l i v e r s e l e c t i v e l y a continous r a d i a t i o n dose in addition to conventional f r a c t i o n a t e d external radiotherapy (RT) improving thus the treatment of l o c a l l y advanced unresectable or reccurent head and neck cancer. Eleven pat i e n t s were included into the study : seven of them were treated f o r an unresectable squamous cell carcinoma o f the head and neck and the other four patients f o r an recurrent disease a f t e r conventional RT and surgery. The 2,5 m i l l i o n p a r t i c l e s of MAA, resuspended in 0,25 ml of i sot oni c s t e r i l i z e d saline were injected followed by the administration of 185-407 MBq o f 32-P chromic phosphate c o l l o i d a l suspension (standardized s p e c i f i c a c t i v i t y : 555 MBq/5ml) in general anesthesia underCT-scan c o n t r o l . Planar and SPECT Bremsstrahlung imaging was performed by a y'-camera f o r d i rect tumor-volume q u a n t i f i c a t i o n and dosi~etry. (Estimated tumor doses were between 500 and 1500 Gy).The s c i n t i g r a p h i c findings allowed to i d e n t i f y the 32-P a c t i v i t y at the i n j e c t i o n s i t e s up to 70 days post-deposite without s i g n i f i c a n t migration out of the tumor-site. Minimal a c t i v i t y (<0,001%) was found in the blood as well as in the s a l i v a . No acute treatment-related hematological or mucosal t o x i c i t y was observed. S i g n i f i c a n t tumor regression was noted f o r 5 out o f 6 evaluable p a t i e n t s , treated by combined intratumoral c o l l o i d a l 32-P-infusion and external i r r a d i a t i o n . The proposed technique may be a valuable adjunct to conventional RT to boost-under by nuclear medicine v i s u a l i z a t i o n - t e c h n i q u e controled dosimetric conditions - the delivered r a d i a t i o n dose in l o c a l l y advanced head and neck cancers.

OTu352

Physics and Instrumentation 0Su354

J Sisson B Shapiro, B Shulkin, S Spaulding, Zempel. U n i v of Michigan, A n n A r b o r MI.

V . R a p p o p o r t , B.Kline, C . B . L i m R e s e a r c h L a b o r a t o r y , Inc.

P R E D I C T I N G T H E R A P E U T I C 131-I M I B G IN W H O L E BODY, BLOOD AND MALIGNANT PHEOCHROMOCYTOMAS. W e t e s t e d the p o s s i b i l i t y that t h e r a p e u t i c doses of 131-I MIBG were handled differently than d i a g n o s t i c doses. T h e r a t i o n a l e was: treatments of m a l i g n a n t pheochromocytoma with 131-I MIBG r e d u c e d t u m o r s b u t b e n e f i t s h a v e b e e n less t h a n expected; in c u l t u r e d cells and xenografts of adrenergic tumors, increasing doses of MIBG saturated uptake-retention mechanisms; in u s i n g 1 3 1 - i o d i d e for t h y r o i d cancer, tumor u p t a k e s a f t e r t h e r a p y w e r e o f t e n <50% of those a f t e r diagnosis. 4 patients w e r e t r e a t e d w i t h 1 3 1 - I M I B G 12 times. D x doses c o n t a i n e d 37-41 M B q a n d 0 . 2 7 - 0 . 5 2 mg. From values obtained at 3 or 4 days, we c o m p a r e d r e s p e c t i v e % of doses in the body, b l o o d a n d tumor; % R x d o s e / % Dx d o s e = Rx/Dx. D x teff 1/2 h e l p e d r e c o n c i l e the few h o u r s d i f f e r e n c e in D x a n d Rx i n t e r v a l s b e f o r e measurements. P t . R x m g R x G B q B o d y Rx/Dx B l o o d R x / D x T u m o r R x / D x 1 8.9 12.5 1.13 1.06 1 9.3 13.2 1.01 1.60 0.89 1 9.0 14.0 0.98 1.41 0.80 2 5.1 8.5 1.15 1.61 0.91 2 5.0 8.6 0.84 0.86 0.69 2 6.5 9.7 1.19 1.29 0.77 3 7.5 11.2 0.91 0.74 0.78 3 7.0 11.5 0.75 1.18 0.81 3 5.6 8.9 0.83 0.86 1.06 4 7.5 12.4 0.60 0.94 0.80 4 6.4 9.8 0.84 1.61 1.03 4 5.9 8.9 0.84 0.93 0.98 m e a n +/- SD 0.92+/-.18 1.18+/-.34 0.88+/-.13 Conclusion. Pretherapy diagnostic dosimetry reliably predicts absorbed radiation doses from t h e r a p e u t i c 131-I MIBG.

FDG/MIBI DUAL ACQUISITION

1120

ISOTOPE

, Trionix

SIMULTANEOUS

S i m u l t a n e o u s s t u d y of F D G - F I 8 a n d T c - 9 9 m M I B I allows comparison of c a r d i a c m e t a b o l i s m and perfusion. We have studied TRIAD XLT perform a n c e w i t h 511 k e V c o l l i m a t o r s in r e s p o n s e to b o t h 140 a n d 511 k e V p h o t o n s f r o m T c - 9 9 m a n d F-18. T w o e n e r g y w i n d o w s w e r e u s e d to a c q u i r e two images. Linearity and uniformity correct i o n s s p e c i f i c to e a c h e n e r g y w e r e a p p l i e d . Detector intrinsic uniformity, and spatial resolution with the bar phantom are essentially the same for Tc-99m and F-18. Collimated detector spatial resolution at i0 c m d e p t h w a s 6.6 nun (FWHN) f o r T c - 9 9 m , a n d 8.2 ram for F-18. P l a n a r s e n s i t i v i t y p e r d e t e c t o r w a s 65 a n d 52 c p m / m C i for Tc-99m and F-18, respectively. Reconstructed spatial resolut i o n w i t h r a m p f i l t e r at N y q u i s t frequency w a s 9 . 3 m m ( F W H M ) , a n d 1 8 . 0 m m (FWTM) f o r Tc-99m; 10.7 and 21.5 mm for F-18. The Data S p e c t r u m C a r d i a c P h a n t o m f i l l e d w i t h lmCi of T c - 9 9 m a n d 0.3 m C i of F - 1 8 w a s i m a g e d . T w o defects of 1 5 x 1 0 a n d 2 0 x 5 m m w e r e i n s e r t e d and phantom was placed inside a water-filled 22 c m c y l i n d e r . D e f e c t s a r e c l e a r l y v i s i b l e for both isotopes, and circumferential prof i l e s of r e c o n s t r u c t e d slices closely follow e a c h o t h e r f o r t h e two i s o t o p e s . T h e s y s t e m provides excellent Tc-99m/F-18 simultaneous studies with similar resolutions.

•

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OSu357

OSu355 J. Jianq, C. Lim, T r i o n i x Research ~aboratory, Twinsburg, Ohio 44087, USA ADVANCED TECHNIQUE SPECT IMAGING

Physics and Instrumentation

M. Ivanovic, D.A. Weber, S. Loncaric* University of California Davis Medical Center, Sacramento, CA,USA *University of Zagreb, Clinical Hospital Rebro, Zagreb, HRV

Inc.,

FOR WHOLE

BODY

SCAN AND

C O

i m

d~ ,b,a

MONTE CARLO SIMULATIONS OF MULTI-PINHOLE ROTATING SPECT TO OPTIMIZE HIGH RESOLUTION BREAST IMAGING.

¢..

W h o l e - b o d y i m a g i n g p l a y s an i m p o r t a n t r o l e in d e t e r m i n i n g the p r e s e n c e a n d e x t e n t of m e t a s t a t i c d i s e a s e s . Due to the d i f f i c u l t y of a p p l y i n g l i m i t e d d e t e c t o r f i e l d of v i e w (FOV) of S P E C T system to e n t i r e body, whole-body imaging usually only entails anterior and posterior two p l a n a r v i e w s , w h i c h g r e a t l y l i m i t s c l i n i c a l u t i l i t y . We i m p r o v e the t e c h n i q u e of w h o l e - b o d y i m a g i n g by a c o m b i n a t i o n of e n l a r g e d 20 inches axial F 0 V a n d o p t i m i z e d e l e c t r o n i c s and s o f t w a r e system. T r i p l e - h e a d camera TXLT20 whole b o d y scan introduce a gantry rotation during imaging and end by creating six-view whole-body images at 60 d e g r e e angular intervals. A n t e r i o r and p o s t e r i o r views plus four a d d i t i o n a l o b l i q u e v i e w s p r o v i d e m u c h more diagnostic information while only increasing imaging time by i0-15%. Whole-body SPECT studies using our unique a u t o m a t i c t r a n s l a t i o n of the p a t i e n t t a b l e acquire multiple F0V data within a single s t u d y . B e c a u s e of the a c c u r a t e m e c h a n i c a l supporting system and cutting-edge techn i q u e s u s e d in d a t a a c q u i s i t i o n and a n a l y sis, the image a c q u i r e d is the same as from a s i n g l e FOV. The r e l a t i v e u p t a k e t h e r e f o r e can been more accurately evaluated. The c l i n i c t r i a l s on b o n e scan, G a 6 7 a n d o c t r e o t i d e s t u d i e s d e m o n s t r a t e that a d v a n c e d t e c h n i q u e is a c o s t - e f f e c t i v e and p o w e r f u l tool for whole-body imaging.

A Monte Carlo simulation study was conducted to optimize a multipinhole collimator and image reconstruction algorithm to provide a new approach to high spatial resolution SPECT imaging of the breast. The modification in conventional SPECT imaging provides the means to detect tumor at an earlier stage of development than is feasible with current imaging techniques. Several recent studies have shown T]-201 and Tc99m MIBI provide highly sensitive tests for detecting and differentiating tumor from benign lesions in the breast. We investigated rotating SPECT with a specially designed multi-pinhole collimator to significantly improve sensitivity of this procedure to detect tumors as small as 0.5 cm by 0.5 cm. The high sensitivity is achieved by using multiple pinholes, and rotating the camera 90-180 degrees around the breast with the patient in the prone position. Monte Carlo simulation studies and analytical methods are applied to determine the number of holes, hole position, hole aperture size, conical field of view, and focal length of the collimator to optimize spatial resolution and sensitivity for breast imaging. Shielding is optimized to accommodate radiopharmaceutical imaging over the energy range of 50-511 keV. An image reconstruction algorithm for cone beam imaging geometry for rotating single pinhole SPECT is modified to accommodate simultaneous imaging from multiple pinholes with limited angular sampling. Special emphasis is placed on evaluation of imaging with small pinhole apertures (1-2 mm), that are required to achieve the resolution of 3-7 mm at the distance of 10-15 cm with radionuclides having energies < 140 keV. Complete 360 ° acquisition of the breast tumor model was simulated to study the artifacts in reconstructed images due to incomplete sampling (limited angle acquisition) and to select an optimal reconstruction algorithm. The breast tumor model was treated as a conically shaped object with lesions of different size and shape at various depths in the breast. Incomplete projection sets are derived by deleting images at angles considered inaccessible in patient studies. Reconstruction of the full 360 ° projection set served as a comparison template for limited angle reconstructions.

u~

OSu356

OSu358

A . M . J . Paans lj, W. Koo121, A . T . M . Willemsen 1), D.A. Piers 2), W. Vaalburg 1), PET-Center 1~ and Department of Nuclear Medicine2~,Groningen University Hospital, Groningen, the Netherlands.

S. Holm. Dept. of Nucl. Medicine, Rigshospitalet (National University Hospital) K. Ennow, National Institute of Radiation Hygiene, Copenhagen Denmark.

MEASUREMENT OF leFDG IN SINGLE PHOTON AND C O I N C I DENCE MODE: SENSITIVITY, SPATIAL RESOLUTION AND SIGNAL TO NOISE RATIO. For over 15 years the glucose analogue ~SFDG is used for the measurement of the glucose consumption. Recently special collimators and uncollimated dual headed camera coincidence

systems became commercially available resulting in a spectrum for 18FDG imaging: 1 )planar arid SPECT scintigraphy using a 511 keV collimator, 2)PET-systems using an uncollimated dual headed camera coincidence system, 3)PET ring systems, in 2D and 3D mode. The system parameters as spatial resolution, sensitivity and c o u n t rate capability have been assessed, both theoretically and experimentally, using a Siemens MultiSpect2 with 511 keV collimators, a dual headed uncollimated Searle LFOV scintillation camera coincidence system and a Siemens 951/31 PET ring system. Large differences in spatial and time resolution, count rate capability and in sensitivity were found while the possibility of dynamic studies and exact quantification w a s limited to PET ring systems. From the measurements it is evident that the sensitivity of single p h o t o n systems is significantly lower than a 2D PET ring system (factor of 50) while the spatial resolution is roughly 12-15 mm FWHM compared to 4-6 mm for PET systems. For dual headed coincidence systems the maximum coincident count rate, and so the signal to noise ratio, is the crucial factor in the comparison w i t h 2D PET ring systems (factOr of > 5 0 ) . Although the sensitivity is high for the dual headed systems, the n e w 3D PET generation has an even higher sensitivity while the discrepancy in c o u n t rate capability has increased again.

EFFECTIVE DOSE FROM TRANSMISSION SCAN PROCEDURES IN PET The use of attenuation information is mandatory for quantitative PET. Most often this is obtained by transmission scanning using line or ring sources of Ge-68 or other 511 keV emitters. The procedure adds to the total effective dose to subjects and should - in principle -be included in dosimetry, particularly when examining normal controls. Measurements were performed on the General Electric Advance PET scanner

(aperture 59 cm, FOV = 55 cm, and axial extension 15 cm). For transmission scans it uses 2 pin sources with a maximum activity of about 400 MBq each. With a rotation diameter of 63 cm the pins are only partially covered by front or back shields and exposure extends to the whole body. Using a Rando-

Alderson wholebody (head +torso) phantom we placed 30 TLD-IO0 dosimeters corresponding to the positions of (most of) the organs involved in the calculation of effective dose (ICRP 60, 1990). Some larger organs like lungs and liver) had several dosimeters. We did measurements over 15 hours in positions corresponding to a brain scan and a heart scan. From the measured organ doses (in pGy) we have calculated the effective dose in the two important situations and express the result as pSv per MBq*hour. The measured dose rate in the empty scanner was 1.5 pGy/(MBq*h) in the center and 6.0 pGy/(MBq*h) at the edge of the field of view.

Effective dose pSv/(MBq* h) Tytoical values of in MBq*h of {pin source strength) * (scan time) Effective dose per scan in pSv

Brain study

Heart study

O,18

0.4

100 18

200 80

Due to the cylindrical geometry, results are equally valid for ring sources at the same diameter. Monte Carlo simulations are currently being performed that will be validated against the measured values, with the intention of extrapolating the results to other machines, imaging positions and 'non-standard' man, e.g,, children.

1121

(D O. m

•

Physics and Instrumentation

0Su359

0Su361

M. Ivanovic, D.A. Weber, S. Loncaric*, D.K. Sbelton, C.W. Sutter. University of California Davis Medical Center, Sacramento, CA, *University of Zagreb, Clinical Hospital Rebro, Zagreb, HRV COMPARISON OF THREE PATIENT MOTION CORRECTION METHODS FOR MULTIHEAD SPECT CAMERAS. We de,)eloped and compared three methods for patient motion correction for multihcad SPECT cameras. The artifacts introduced by patient motion significantly affect qualitative and quantitative accuracy of the SPECT images, particularly in cardiac imaging. The motion detection and correction methods investigated were based on using multiple fast scans (3-10 scans per study), or employing projection data from all heads rotating 360 ° instead of conventional partial orbit ( 90 °,120 ° or 180° depending on number of camera heads). Total acquisition time was kept constant. The evaluation was done using simulations and experimental measurements of point sources placed in a cylinder and a cardiac phantom. The degree of deformation of an object caused by motion was expressed as the ratio of the moments of inertia corresponding to the principal axes. Cross-correlation of images from different heads at the same angular position or from the same head from consecutive scans are used to detect and correct for motion. The following methods for motion correction were investigated: 1) summation of 3 projection sets or multiple scans without correction, 2) multiple fast scan without motion are determined and summed to be used for correction of the scans with motion. All multiple scans (without motion and motion corrected) were summed prior to reconstruction. 3) Frames in 360 ° rotation studies with motion were detected and deleted; projections without motion were summed and counts normalized to corresponding total time per projection to replace bad frames. 4) Frames without motion at each angular position were used to correct the frame with motion, and all three sets are summed. Method 1 (no correction) minimizes blurring from motion and is qualitatively satisfactory for small movements (translations < 0.5 cm and rotations < 5 °). Artifacts are eliminated or significantly reduced using all three methods where at least two uncorrupted data sets (66% of counts) at each angular position are available and used for correction. The proposed methods successfully correct for arbitrary motion (translation and rotation).

0Su360 #CCN Saint-Denis,

France.

HEART M O T I O N CORRECTION IN M Y O C A R D I A L A 90 ° DUAL-HEAD CAMERA.

SPECT WITH

Our e x p e r i e n c e with 3 d i f f e r e n t 90 ° d u a l - h e a d cameras (90DHC) s u g g e s t e d that v e r t i c a l h e a r t m o t i o n (VHM) is critical, p r o b a b l y b e c a u s e the last p r o j e c t i o n from head#1 and t h e first one from head#2 are acquired several m i n u t e s apart sometimes creating an abrupt discontinuity around the LAO azimuth.We investigated a/ the ability of a new p r o g r a m dedicated to 90DHC to c o r r e c t for V H M ; b / the subjective results on r e c o n s t r u c t e d data (RD). 120 a c q u i s i t i o n s were s t u d i e d : 30 stress TI, 30 re-inj TI, 30 rest TI, 30 stress MIBI. The p r o g r a m c o n s i s t e d in: * s u m m a t i o n of c o r r e s p o n d i n g projections from both h e a d s ; * b e s t shift search by 2D cross-correlation and parabolic interpolation;*vertical registration of raw projections by linear interpolation (lateral shift ignored). V H M was scored b l i n d l y for r a w and corrected series on projections cine d i s p l a y from 0 = n o n e to 3 = v e r y important. D i f f e r e n c e s between randomly ordered pairs of RD were blindly s c o r e d by 2 i n d e p e n d e n t r e a d e r s : ± 2 = c l i n i c a l l y significant,±l=mild, 0=none. V H M s c o r e i m p r o v e d from 0.91 to 0.12 (p<0.0001) (from 1.33 to 0.00 for the MIBI group).For RD, readers'agreement was good (mean difference=0.08; p=0.31 vs m=0) t h u s the summed score [-4..+4] was used: in 12% it was <-I or >1 and was not c o r r e l a t e d w i t h V H M score improvement.We c o n c l u d e t h a t a/ o u r p r o g r a m d e d i c a t e d to 90DHC e f f i c i e n t l y c o r r e c t e d f o r V H M ; b / c o r r e c t i o n had a c l i n i c a l l y s i g n i f i c a n t impact in 12% of our series by u n f o r e s e e a b l e filling in or out of defects.

1122

Nucleaire Geneeskunde, De Bijloke Ziekenhuis, Gent, Belgium

DUAL PINHOLE SPECT : PHYSICAL EVALUATION. High resolution Pinhole-SPECT (P-SPECT) is used in routine in our department for examining the thyroid. The sensitivity of a single pinhole is too low for performing investigations of other organs in a clinical acceptable time. We have build a dual pinhole collimator to improve the sensitivity and reduce the acquisition time. The 2 holes are separated by a distance of 8 cm and are located 17 cm above the crystal. This collimator is used on a single head camera. The system gives two pictures of an object without overlapping of the two images. The acquisitions are performed over 180° or 360 ° , in 128 by 128 square matrix, zoom 1. The camera can also be slightly tilted to reduce the distance between the collimator and the object to be investigated. The tilt angle and the distance between camera and centre of rotation must be known with a great accuracy to avoid distortion and artefacts. The acquisition frames are corrected for inhomogeneity and displacement of centre of rotation. This last correction is particularly important for very small pinhole diameters (< 3 mm). The 3D-reconstruction algorithm uses the filtered backprojection. It takes into account the two pictures and gives a set of transaxial frames. A series of 20 transaxial slices is reconstructed in 1 min. Coronal slices and 3-D images are derived from these transaxial pictures. The major advantage of dual P-SPECT is the improvement in sensitivity. For a rotation diameter of 20 cm, 2 pinholes of 3ram give a resolution of 5 mm with the same sensitivity as a LEHR parallel collimator. The reconstruction program has been tested with several types of phantoms to verify the performance of the method. This collimator can be used for investigating small organs or small animals. We have used it until now for thyroid studies but cervical bonePSPECT could be possible due to the improvement in sensitivity. In conclusion, Dual Pinhole SPECT is a interesting tool to improve sensitivity when this factor is critical.

0Su362

E.Gremill~*,A.Champailler*,M.Wartski°,A.Blasco#, S.Guillot*. *C.I.N. S a i n t - E t i e n n e , °CCML Le Plessis-Robinson,

P. Wanet, A. Sand, J. AbramovicL

R, ~, Smith. F. Benard, A. Alavi, J. S. Karp, Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia AN OPTIMIZED PROTOCOL FOR ATTENUATION CORRECTED, WHOLE BODY FDG-PET IMAGES OF CANCER PATIENTS. Whole body FDG PET imaging is a valuable method for detecting and monitoring cancer. Frequently, semi-quantitative uptakes (SUVs) are used to reliably assess tumor response to therapy. This requires accurate and precise attenuation correction as well as high quality activity distribution images. Methods: In the PENN-PET 240H volume imaging scanner, whole body FDG surveys over 60 cm of the body's length consist of 10x4 minute scans of the emission distribution, each displaced by 6.4 cm axially, followed by 10x2 minute transmission scans using a 6 mCi Cs137 source, a single photon emitter. Thus, the whole body survey is completed in 60 minutes. Accurate attenuation coefficients are applied by segmenting these transmission images. Delayed imaging has also been studied to assess improvements in tumor detectability. Image quality may then be further improved by utilizing an iterative maximum likelihood algorithm (OS-EM) for reconstruction of the data. These methods are compared to conventional procedures for both quantltation and image quality.Results: Singles transmission scans combined with segmentation and transmission image reprojection provide reliable attenuation correction with noise levels in corrected images comparable to pre-injection coincidence transmission values (<5% S.D). Attenuation corrected count densities by this method are within 6% of coincidence transmission values for patient (n=12 subjects) and phantom studies. Delayed imaging provides higher contrast with tumor SUVs increasing by 36+10%/hour for up to 2 hours post-injection (n=6). Finally, OS-EM reconstruction, with 2 iterations and 8 ordered subsets, provides improved signal/noise compared to filtered backprojection (FBP) images with comparable reconstruction times on a SUN computer. Both image contrast (ML/FBP=0.98+0.12) and quantitation (0.94_+0.10) are consistent across 8 patients with more than 200 regions of interest. Conclusions: We describe a successful whole-body protocol that combines delayed imaging, singles transmission with segmentation, and OS-EM reconstruction to generate quantitative images of high quality, while the total scan duration is 1 hour. This has significant implications for patient throughput and the ability to quantitate tumor response to treatment.

• 0Su363 P. Maniawski, S. Miller, Picker International, Nuclear Medicine Division, Cleveland, Ohio, USA.

COMBINED ATTENUATION AND SCATTER CORRECTION WITH TRANSMISSION EMISSION SPECT SYSTEM (STEP) PRACTICAL IMPLEMENTATION AND PHANTOM EVALUATION. A triple detector gamma camera (Prism 3000XP, Picker Int) equipped with fan beam collimators and a transmission line source (Gd-153 to be used with TI-201 or Co-57 with Tc-99m) was designed to measure and correct for both attenuation and scatter concurrently. Transmission, emission" and scatter data are collected simultaneously with scatter measured using split window criteria ( two 4 keV energy windows one full width half m a x i m u m (FWHM) b e l o w and above the emission photopeak centerline). Transmission data are reconstructed using either filtered backprojection algorithm (brain SPECT) or m a x i m u m likelihood i t e r a t i v e algorithm (cardiac SPECT). Emission data are reconstructed using ordered subsets implementation of expectation maximization m a x i m u m likelihood algorithm (OS-EMML). Both attenuation and scatter correction are performed internally within OSEMML. Total processing time (64x64 cardiac study or 128x128 brain study) was less than 3 minutes using a standard workstation (Odyssey VP, Picker Int.). Initial validation of the system performance was done using TI-201 filled heartlung phantom with liver insert. Both visually and quantitatively a significant improvement in defect size and count uniformity were observed. No image artifacts were created. Attenuation correction alone improved uniformity outside the defect area. Combined attenuation and scatter correction further improved defect size estimate and contrast resolution. Preliminary results demonstrate that STEP system offers clinically practical technique of combined attenuation and scatter correction.

Physics and Instrumentation

0Su365 P.L.GUIDALOTTI;M.DONDI: S.FANTI; 1L CASANOVA; A.L. PATRONCINI; A. MARESTA Nuclear Medicine Service and Division of Cardiology; Ospedale per gti Infermi, Faenza iRA); Italy ATTENUATION CORRECTION WITH SIMULTANEOUSLY ACQUIRED TRANSMISSION MAPS DURING MYOCARDIAL SPET: EFFECTS ON SEGMENTAL UPTAKE OF TC-99M COMPOUNDS. Multihead SPET systems allow for simultaneous acquisition of transmission maps

during collection of emission projection profiles. Transmission maps may be subsequently used to correct for nonuniform attenuation due to different tissue densities within the thorax. We aimed at assessing how attenuation correction modifies myocardial SPET images. A commercially available simultaneous transmission/emissinn protocol (STEP) was applied to the studies of all patients referred for myocardial SPET from September 95 through November 95. All patients underwent exercise or pharmacological stress testing and were injected at peak stress. Afterwards, SPET was acquired with a three-headed camera (Picker Prism 3000XP) equipped with cardiac fan-beam collimators. In 151 cases, teehnetium-labelled compounds were used and for these studies transmission maps were acquired with a Gadolinium-153 (Gd-153) line source mounted on a motur-driven source holder. A reconstruction iterative algorithm involving 20 iterations was used to reconstruct a double series of tomographic studies, attenuatlun corrected (AC) and non-attenuation corrected (NAC), for both the stress and the rest studies. A set of representative slices (3 short-, 1 long- and 1 horizontal-lung axis) for each patient was subdivided into 29 segments and analysed adopting a qualitative 5-point score (0=normal; 4=11ouptake). After scoring, all segments were regrouped into the anterior, inferior, lateral and septal walls, and the apex. A total score (TS) and a mean segmental score (MSS) for each myocardial wall were calculated, both for AC and for NAC images. To assess whether attenuation correction did introduce some kind of artifact, stress-rest uptake ratio (SRUR) between the scoring of stress and rest studies was also calculated for both sets of images (AC and NAC). Statistical analysis was carried out by means of non parametric analysis of variance and Wilcoxon test. After attenuation correction, segments belonging to the inferior and septal walls showed a significant decrease of their score (p<0,05 and p<0,02, respectively). The anterior wall showed an opposite behaviour with an increase of both TS and MSS, though the change did not reach statistical significance (p=ns). Apex and lateral wail did not significantly modify their scores. No geoder-related differandes were observed. Conclusions: attenuation correction with a Gd-153 line source modifies tracer uptake mainly on the inferior and septal walls which are heavily affected by non-uuiform attenuation within the thorax. This approach may potentially decrease false positive SPET studies. Its introduction in the clinical setting might greatly impact on diagnostic accuracy of myocardial SPET.

0Su364

0Su366

C h i - H u a Tuna, J o s e p h J. Riznar, and Chun B. Lim, T r i o n i x R e s e a r c h Laboratory, Inc.

E. Rota Koos. M. Schmand, H.Herzog, K. Wienhard*, H.-W. Miiller-G~tner Intitute of/qledicine, Forschungszentrum Jtilich GmbH, J/ilich, Germany *Max-Planck-Institut fiir Neurologische Forschung, K(iln

A M E T H O D TO S I M U L T A N E O U S L Y C O R R E C T FOR NONUNIFORM ATTENUATION AND DETECTOR BLURRING

PHANTOM MEASUREMENTS FOR VALIDATION OF A SCATTER CORRECTION ALGORITHM~IN3D PET SCANNERS

An iterative f i l t e r e d b a c k p r o j e c t i o n a l g o r i t h m is d e s i g n e d to s i m u l t a n e o u s l y correct for the p h o t o n a t t e n u a t i o n and d e p t h - d e p e n d e n t d e t e c t o r blurring, w h i c h g r e a t l y reduce the quantitative a c c u r a c y of SPECT imaging. A patient-specific t r a n s m i s s i o n m a p and d e p t h - d e p e n d e n t d e t e c t o r spread function are u s e d b y a p r o j e c t i o n routine to model the p h o t o n a t t e n u a t i o n and d e t e c t o r blurring. A c o l l i m a t e d scanning line source a t t a c h e d to a triple-detector, parallelb e a m SPECT system is u s e d to acquire the t r a n s m i s s i o n p r o j e c t i o n data w h i c h generates truncation-free, n a r r o w - b e a m a t t e n u a t i o n map. The d e t e c t o r spread function is assumed to be a c o n e - s h a p e d distribution. The results of the cardiac p h a n t o m study after 3 iterations of this m e t h o d show contrast improvement from 39.4% to 79.2% in the left ventricle of the short-axis slice. The F W H M m e a s u r e m e n t of the left ventricle is 31.5 nun w i t h o u t compensation for a t t e n u a t i o n and d e t e c t o r blurring. After 3 iterations, the FWHM is 19.4 mm. Results of a normal v o l u n t e e r TC-99m-MIBI myocardial p e r f u s i o n study show s i g n i f i c a n t l y improved contrast and resolution. The d e c r e a s e d uptake in the septal/posterior wall of the left v e n t r i c l e due to a t t e n u a t i o n is adequately compensated. The brain p h a n t o m study also shows significant improvement of contrast and resolution over the conventional filtered b a c k p r o j e c t i o n algorithm.

The evolution from 2D to 3D PET requires new developments regarding data correction. This work presents a validation study of a 3D scatter correction algorithm developed by Watson (to be published in IEEE Trans Nucl Sci, 1996). Using the Klein-Nishina formula the method simulates the scatter distribution taking into account measured transmission and emission data. These first measurements were performed with the ECAT HR installed at the MPI in Cologne using the Utah phantom and the whole body EEC phantom, with which extreme and real scatter conditions were simulated. The bottom chamber (B) and the main chamber (M) of the Utah phantom were filled with F18-water (110 Bq/cc). The long cylinder (A) inside the main chamber contained air, while the short one (C) contained a water-CaC12 solution. All chambers of the EEC phantom except the air-filled lung contained water. The thorax wall and the myocardium were activated with F18 with a ratio of 1:5. Transmission measurements were performed for both phantoms. The data reconstruction was done without (WOC) and with (WC) scatter correction. ROIs were evaluated. The results were compared with the corresponding well counter values. For the Utah phantom with B inside the field of view (FOV) the scatter fraction in C, A, and M decreased from about 40% (WOC) to about 6% (WC). With B outside FOV a small increase of the scatter fraction in the whole phantom was observed. Wrong correction was performed in the transition between mediums of strong different densities (water and air). In the EEC phantom the activity concentrations were corrected satisfactorily with an error of 3.5% in the myocardium and 2.5% in the thorax wall. In the cold inner part of the heart the scatter fraction was overestimated leading to a small negative activity concentration. The results show that the newly developed scatter correction algodthm is able to estimate and correct the scatter distribution in objects with different densities and activity concentrations. Similar measurements with the ECAT EXACT HR+ are planned.

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Physics and Instrumentation

OSu367

0Su369

V.RappoDort, B.Kline, C.B.Lim, T r i o n i x R e s e a r c h Laboratory, Inc.

S. Walrand, L. van Elmbt and S. Panwels. Department of Nuclear Medicine, University of Louvaln Medical School, Brussels, Belgium.

N E W SCATTER E L I M I N A T I O N TECHNIQUE B A S E D ON LOCAL E N E R G Y SPECTRA A N A L Y S I S

FAST POSITIVE ALGORITHM FOK SPECT KECONSTKUCTION.

Detection of Compton scattered photons degrades image c o n t r a s t and q u a n t i t a t i v e accuracy. A new scatter elimination technique, S E S A M E , is b a s e d on a p i x e l - b y - p i x e l e n e r g y s p e c t r u m a n a l y s i s a n d m e a s u r e d s c a t t e r function. The images are a c q u i r e d in m u l t i c h a n n e l a c q u i s i t i o n m e m o r y that s t o r e s a 128 c h a n n e l e n e r g y s p e c t r u m in e a c h of 1 2 8 x 1 2 8 p i x e l s . A c e n t r o i d of the e n e r g y s p e c t r u m is c a l c u l a t e d for each pixel, and the c e n t r o i d shift towards lower e n e r g y is u s e d as the c r i t e r i u m to indicate a s c a t t e r c o n t r i b u t i o n . The s p e c t r a w i t h c e n t r o i d s b e l o w a p r e s e t t h r e s h o l d are a v e r a g e d to o b t a i n a " s c a t t e r c u r v e " , w h i c h is t h e n n o r m a l i z e d to e a c h l o c a l s p e c t r u m . T h e n u m b e r of counts u n d e r the n o r m a l i z e d s c a t t e r c u r v e is s u b t r a c t e d f r o m the a c q u i r e d c o u n t s in e a c h p i x e l to o b t a i n the s c a t t e r c o r r e c t e d i m a g e . T h e t e c h n i q u e w a s t e s t e d for p l a n a r , SPECT and t r a n s m i s s i o n studies. A p l a n a r study with a water-filled cylinder containing 3 smaller cylinders with different activity c o n c e n t r a t i o n s r e p r o d u c e d the m e a s u r e d activi t y r a t i o s w i t h i n to 5%. I n a d d i t i o n , t h e scatter-eliminated energy spectrum approaches Gaussian. The m e a s u r e d a t t e n u a t i o n coefficient for 140 keV photons in water with SESAME r e s u l t s in a n a r r o w - b e a m v a l u e of 0.15 c m -I. S E S A M E was t e s t e d w i t h a D a t a S p e c t r u m T h o r a x phantom, and a Hoffman Brain phantom with T c - 9 9 m and F-18, and v o l u n t e e r studies. SESAME improves image contrast, edge sharpness, resolution, and q u a n t i t a t i v e accuracy.

OSu368 G. Glatting, M. Rentschler, J. Ruckgaber, R. Weller, C. R6hm, S.N. Reske, Universit~t UIm, Nuklearmedizin, Germany. FILTERED BACKPROJECTION (ITE) RECONSTRUCTION in LESIONS

(FBP) VERSUS ITERATIVE PET: DETECTABILITY OF

Purpose of the study was to quantitatively compare FBP and ITE [1] of positron emission tomography (PET) images in the detection of small liver lesions. The sinogram file (Siemens ECAT 931-08/12) of a patient with normal liver findings was artificially modified to contain 15 lesions of 5 and 7 pixel diameter (1 pixel = 3.1 mm). The contrast of the lesions was varied. These manipulated sinograms were reconstructed by FBP (Hanning filter, cutoff 0.5) and ITE [1] (8 steps). The relative number of correctly identified lesions t was determined without prior knowledge about number and localization. A fit to a quantity similar to a t-Test yields the dependence of n on lesion contrast x, i.e. t = (x-P1)IP2. Both parameters P1 and P2 were determined and tested on significance of difference. In the FBP-images only 81% of the lesions detected by ITE were seen. Iterative reconstruction allows detection of lesions having a smaller contrast, as consequence of a lower P1 value. The differences are si~nifican: (5% / for the 7 pixel diameter lesions. Parameters 5 Pixel 5 Pixel 7 Pixel 7 Pixel P1 P2 P1 P2 FBP 3.43+0.72 7.78+1.17 2.94-+0.41 7.34_+0.69 ITE 1.78_+0.78 9.03_+1.11 0.17+1.18 9.38+1.58 In conclusion, ITE detects small defects with low ontrast in liver parenchyma of a patient more sensitively than FBP. [1] Schmidlin, P. (1972): Iterative Separation of Sections in Tomographic Scintigrams, Nuclear-Medizin 11:1-16 1124

Reduction of Poisson noise may be achieved by the Expectation Maximization of the Maximum Likelihood (EM-ML) reconstruction algorithm. However, routine application of the conventional EM-ML is limited by its very slow convergence speed. We propose a new positive algorithm based on a multiplicative scheme, preserving 2 important EM-ML properties, i.e. pixel positivity inside the patient body and null activity outside. The convergence is mathematically proved and the weighted ehi-square decreases at each iteration step towards the minimum. Therefore, in contrast with EM-ML based on a Poisson distribution modal, the algorithm can take into account additional non Poisson errors due to energylinearity-uniformity corrections, attenuation map, scatter subtraction by spectral analysis, ... By optimizing the choice of the approximate inverse, we obtain a fast positive algorithm (FPA) usable in clinical routine applications even when the 7-path in the matter is taken into account (scatter). The method was validated on a phantom simniating lesions near a more active organ: bottles of 2-2.5 em diameter, filled with increasing specific activities, were placed near a large active bottle immersed in water. The contrast coefficient, for 2 small bottles fLlled with 100% (bottle a) and 25% (bottle b) of the specific activity of the large bottle, are: Contrast

> 0.6 > 0.9

Number of iterations Bottle a Bottle b EM-ML FPA EM-ML FPA 12 1 68 3 42 2 162 9

The use of FPA results in an acceleration of the convergence speed by a factor of 20 that can reach 100 in high spatial frequency or low count region. Reconstruction of whole chest or abdomen (32 slices, matrix 64)<64, SUN SPAKC 10-41), is achieved within 2 hours. FPA applied on I n - i l l pentetreotide studies shows a significant improvement of the contrast of small low-count lesions located near more active organs.

OSu370 J.A.K. BloklandI., R. Winn2, E.K.J. PanwelsI, 1Leiden University Hospital, Department of Diagnostic Radiology and Nuclear Medicine, ZFaculty of Medicine, University of Sydney, Australia

TRIPLE ENERGY WINDOW SCATTER CORRECTION: OPTIMISING THE FILTERS SPECT data acquisition is disturbed by several factors, including scatter of photons. These scattered photons prevent an accurate quantification of the radionuelide distribution. The triple energy window scarer correction method (TEW) may solve this problem. But, by subtraction of the scattered photons, the signalto-noise ratio (SNR) will decrease, which in turn may hamper the reading of the images. Therefore filters are applied to remove noise before scatter correction. However, low pass filters will also reduce the resolution of the imaging system. In this study we have determined the cut-off frequencies (COO of the Butterworth filters applied to the scatter energy window (SEW) data and to the main energy window data (MEW), which result in highest SNR. SNR's were measured as follows. A Jaszezak phantom was filled with a T1201 solution. Data was acquired with count densities eomparable with normal patient data. After reconstruction a circular profile was drawn through the bails section. The maximum density differences between in- and outside the bails were measured for each visible ball. The noise was measured as the standard deviation of the densities in the uniform section of the phantom. First the MEW filter was optimised without any scarer correction. Next the COl of this filter was fixed to this setting and the SEW filter was optimised by adapting the COf. Finally the MEW filter was optimised again, but now scarer correction was included and the filter settings for the SEW data as determined in the previous step were used. From the results it turned out that the COf of the SEW data filter should be set as low as possible in our system (0.07 eyeles/pixel). The COf for the best MEW filter ranged from 0.12 to 0.15 eycles/pixel depending on the size of the ball being analysed. Even though the SNR decreased by scatter correction from a maximum of 28.6 to 25.6 for the biggest balls, the (visually assessed) contrast increased, resulting in a more readable image. Therefore we conclude that for the given imaging situation the filters for the TEW scatter correction method can be optimised in terms of the SNR.

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Physics and Instrumentation

0Mo371

0Mo373

D. Scellier~ J. Maublant, J.Y. Boire, A. Veyre, Department 0t" Nuclear Medicine, Centre Jean Perrin, Clermont-Ferrand, FRANCE.

D. Lindahl, J. Palmer, M. Ohlsson, C. Peterson, L. Edenbrandt, Departments of Clinical Physiology, Radiophysics and Theoretical Physics, L u n d University, Sweden

APPLICATIONOF MATHEMATICALMORPHOLOGYAND FUZZYLOGICFOR. MYOCARDIALSPECTQUANTIFICATION. We propose a new approach for the automatic quantification of the relative tracer distribution in myocardial SPECT, based on the application of mathematical morphology (MM) and fnzzy logic (FL). Starting from a set of 64 transverse sections, the left ventricle'(LV) is automatically reoriented and isolated inside an ellipsoidal ROI. Then MM operators allow to extract the "skeleton" of the myocardium, a 3D shape that follows the center of the LV wall. A linear transtbm~ation and interpolation allows to fill the defect areas in the skeleton. FI. calcttIates for each pixel its probability of belonging to the myocardium, using us input data local activity levels, discrete distances and the in~[bln'lations contained in the skeleton. This generates a functional image in whtch the gray level represents the probability of belonging to the myocardmm. The contrast is highly enhanced and the defects are suppressed in this representation of the myocardium. A thresholding can be used much more easily than on the original activity image. The image is finalIy partitioned into I8 sectors. This program was applied to a series of 43 patients studied with T1-201, sestamibi, or tetrofosmin at stress and rest. The level of agreement between the program and a visual analysis by two observers was graded between 0 (total discordance), and 3 (Iotal agreement). Results were the following (in patients) : 0 1 2 3 stress/rest 0/0 2/1 8/6 33/3fi Agreement was good or excellent in 96,5% of the stodi,'~ f'bc discordances were concerning apical abnormalities that were minored t~y the quantification. In conclusion, MM and FL appear to be very helpful for the objective analysis of tracer distribution in myocardial SPI!(?T

a m

A U T O M A T E D INTERPRETATION OF M Y O C A R D I A L PERFUSION S C I N T I G R A M S USING ARTIFICIAL NEURAL NETWORKS The p u r p o s e was to develop artificial neural networks for automated interpretation of myocardial scintigrams. The ability of the networks to detect and localize coronary artery disease (CAD) v e r i f i e d by coronary angiography was studied. M e t h o d s A population of 142 patients who had u n d e r g o n e both myocardial 99m-Tc-Sestamibi SPET s c i n t i g r a p h y and coronary angiography within 3 months was studied. CAD was defined as >=70% d i a m e t e r stenosis. The LAD and the RCA/LCX v a s c u l a r segments were studied separately. The neural networks were trained to detect CAD in each of the two segments separately. Bull's eye images were used as inputs. After the training process, separate test sets were used for evaluation. The performance of the networks were compared to that of a human expert who blindly interpreted the Bull's eye images. Results The sensitivity for detecting CAD in the LAD segment was 67% for the neural network and 69% for the human expert at a specificity of 83%. The sensitivities in the RCA/LCX segment were 72% for the network and 75% for the human expert at a s p e c i f i c i t y of 73%. Summary Artificial neural networks can be trained to interpret myocardial perfusion images almost as proficiently as a human expert. In the future one can expect neural networks to be used as decision support tools for image interpretation.

0Mo372

0Mo374

H Everaert, PR Franken, P Flamen, A Momen, A Bossuyt, ML Gods* Free University of Brussels (AZ VUB), Brussels, Belgium and (*) Stanford University School of Medicine, Stanford, CA, USA.

M.C. Lee, C. Kwark, D.S. Lee, J.S. Lee, J.M. Jeong, J-K. Chung, C-S. Koh, Seoul National University Hospital, Department of Nuclear Medicine, Seoul, Korea.

LEFT VENTRICULAR EJECTION FRACTION ASSESSED FROM GATED PERFUSION SPECT STUDIES.

A QUANTITATIVE APPROACH FOR THE ASSESSMENT AND LOCALIZATION OF CEREBRAL PERFUSION RESERVE IN C E R E B R O V A S C U L A R D I S E A S E S USING BASAL/DIAMOX TC-99m HMPAO BRAIN SPECT AND IMAGE COREGISTRATION TECHNIQUE. The quantitative assessment of cerebral perfusion reserve(CPR) by the simple subtraction of basal images from post Diamox(subtracted Diamox) could be inappropriate due to the count difference in both images, which depends on the varying biodistribution of Tc-99m HMPAO. We have implemented an image coregistrative technique for the normalized and correlative calculation of CPR from sequential basal/Diamox brain SPECT. Post Diamox scan(30mCi) was performed following the basal scan(15mCi) with the same protocol(120projections, Metz filter with x=2.0). Total counts were normalized, and cerebral regions were segmented and coregistered using the optimal threshold by discriminant criteria and the maximization of cross correlation. Refined forward /backward subtraction images and the normalized ratio images of Diamox to basal were generated with the windowed discrete color scale. The results showed that i) basal/Diamox brain SPECT could reflect the CPR more distinctively than simple subtraction method using the normalized coregistration images, and 2) CPR ranged to 50% of basal perfusion in our selected patient studies. We conclude that the quantitative estimation of CPR using the correlated image coregistration technique could be useful for the diagnosis and assessment of pre- and postoperative comparison in cerebrovascular diseases.

The basis of this method is the assumption that in a gated tomographic perfusion image the average position of the ventricular wall can be localized by the first moment of the distribution of count rate density along the radius originating in the center of the left ventricle. Perfusion SPECT images gated in 8 time bins were recorded in 50 patients with coronary artery disease 60 rain after the injection of 740 MBq 99mTc-Tetrofosmin. Preprocessing was performed in parallel for aII time bins. Tomographic images were reconstructed, normalized for tail drop correction, centered and reoriented. Non-myocardial structures were masked and images were thresholded at 20% of the maximum activity measured in the myocardial wall. The average position of the wall relative to the center of the cavity was then calculated radially as the first moment of the count rate distribution, and not by edge detection. Left ventricular volume at a given time bin was then estimated as the cube of all distances in that time bin. Subsequently the LVEF was calculated. The method was successful in 50/50 studies (100%), including those studies with severe perfusion defects. For 30 patients the measurements were validated against planar gated 99mTc blood pool studies that were obtained within a mean time interval of 6.1 days. LVEF determined by planar gated 99mTc blood pool studies ranged from 12 to 88%. Agreement between the two methods was excellent (y = 3.03 + 0.90 x, r = 0.92, p< 0.001, s.e.e.= 4.52). The reproducibility in determinating the LVEF from gated tomographic perfusion images was high with a mean (+sd) absolute difference of 3.2 + 3.1. We conclude that LVEF can be determined accurately from gated myocardial perfusion SPECT images, thus providing clinically useful additional information to myocardial perfusion studies.

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0Mo375

0Mo377

JBA Habraken, JC de Munck, M van Herk, J Booij, EA Dubois, J Claus, B Verbeeten Jr., EA van Royen, Academic Medical Centre, Antoni van Leeuwenhoek Hospital, The Netherlands.

A. Buck, C. Burger, Division of Nuclear Medicine, University Hospital, Switzerland INCREASED BLOOD VOLUME MAY ADVERSELY AFFECT P A R A M E T E R ESTIMATES F R O M KINETIC M O D E L I N G

R O L E OF CEREBRAL ATROPHY IN THE MEASUREMENT OF MUSCARINIC RECEPTOR DENSITY IN PATIENTS W I T H ALZHEIMER'S DISEASE Cerebral atrophy as well as a diminished density of the cortical muscarinic receptor have been described in patients with Alzheimefs disease (AD). [I-123]dexetimide (IDEX) has been shown to be useful for brain Spect IDEX imaging. However it remains to be investigated whether a decreased uptake of IDEX represents a true dowaregulation of the muscarinic receptor or whether this is related to cerebral atrophy. Therefore, we performed [I-123]IDEX SPECT and measured the cerebral atrophy using MRI in 5 AD patients and 5 age-matched controls. SPECT was performed 8 hours post-injection of 185 MBq[I123]IDEX (SMES10, 64x64 matrix, center to center slice-distance 5 mm). MRI was performed using a Magneton 63 SP]4000 (256x256 matrix, center to center slice distance 6.5 nun). MRI and SPECT images were co-registrated using the chamfer matching technique. Chamfer matching uses an automatic pre-processing step which makes a drawing from both modallties. Therefore, in the present matching (SPECT-MRI) a 3D-drawing is automatically made of the edge of the brain-volume. An optimal matching is reached by minimalization of the distance between the two 3D drawings. ROIs for the frontal, parietal, and temporoparietal cortex, and for the basal ganglia were drawn on the MR images, and automatically copied to the co-registrated SPECT image. Subsequently ratios over basal ganglia were calculated. Thus we assessed the functional mnscarinic receptor density (SPECT) based on anatomical (MR/) information. Within each ROI the percentage of cerebral atrophy was calculated. A distinction between fluid and braintissue was made by using histogram analysis. Statistical analysis showed a significant lower mnscarinic receptor density in the tempoparietal cortex of AD patients compared to controls. Using multiple linear regression analysis, the observed density differences proved to be independent of cerebral atrophy. These results indicate that a decreased uptake of IDEX in AD represents a true decrease of mnscarinic receptor density which was independent from cerebral atrophy.

Conclusion: Standard compartmental modeling may be compromised in situations with increased vascular space. This is due to 2 effects: a) increased vascular space affects K1 and b) the basic assumption of a constant value for K1 may no longer be valid.

0Mo376

0Mo378

AA Lammertsma, CJ Bench, SP Hume, S Osman, P Sargent, JA McCarron, VW Pike and PM Grasby, PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Harnmersmith Hospital, London, U.K.

C. Kwark, Y.W. Park, D.S. Lee, J.M. Jeong, J-K. Chung, M.C. Lee, C-S. Koh, and M. Xu, Seoul National University Hospital, Department of Nuclear Medicine, Seoul, Korea; Mallinckrodt Institute of Radiology, St. Louis, MO. WHOLE BODY PARAMETRIC IMAGES OF STANDARDIZED UPTAKE VALUE(SUV) IN F-18 FDG PET Standardized u p t a k e value(SUV) has been used as a quantitative index in differentiating benign and malignant tumors. We have produced whole body parametric images of SUV(WBPIS), and evaluated the usefulness of WBPIS when tumor localization and quantitation of F-18 FDG uptake are not always possible by regional scans. Also the quantitative values of measured and segmented/smoothed attenuation correction methods were compared. Whole body and regional F-18 FDG PET scans were performed sequentially, and projections were acquired 7min for each bed position in whole body scan(WBS), and 30min for regional scan(RS). Measured and local threshold segmented/smoothed attenuation correction(Xu et al, JNM(abstr), 1995) were applied using the 2min transmission scan for each bed position in WBS and 30min transmission scan in RS. The SUVs f r o m W B P I S were compared with those of the consecutive regional scans for validation. The effects of attenuation correction methods on SUVs were evaluated quantitatively using the F-18 filled cylindrical phantom studies. The results showed that SUVs from WBPIS were exactly consistent with those from regional scan, and attenuation correction by directly measured transmission showed relatively higher SUVs(by a factor of 1.4). We conclude that WBPIS could be useful in the diagnosis of tumors, which are often outside the field of view in RS, by the appropriate segmented/smoothed attenuation correction with much shorter transmission scan.

K I N E T I C ANALYSIS OF [C-11]WAY-100635

STUDIES

WAY-100635 has been labelled with carbon-ll in both the methoxy and carbonyl positions, As both these radioligands have the same chemical structure, they have the same selectivity for the 5HT IA receptor. The main difference is in the profile of labelled metabolites. The purpose of the present study was to assess the .impact of this difference on the kinetic analysis of human PET data. [Methoxy-C-11] and [CarbonyI-C-11]WAY-100635 studies were performed in normal subjects (4 and 5 scans, respectively). Dynamic 3D PET scans (20 frames; 90 minutes; ECAT-953B) were performed. Frames were corrected for scatter using the dual energy window technique and time-radioactivity curves were derived for medial temporal cortex and cerebellum. Arterial blood was withdrawn continuously and monitored on-line. Discrete samples were collected for plasma/whole blood partitioning and metabolite measurement. The ratio of medial temporal cortex over cerebellum for [methoxy-C11]WAY-100635 was 2.3_+0.6 (mean+SD), 60 minutes after injection. There was significant variation in the degree of non-specific binding, which correlated with plasma levels of the labelled metabolite WAY100634. Rat studies established that this metabolite is accumulated nonspecifically in brain. Quantitative analysis of these studies will, therefore, require a model which includes the tissue kinetics of the metabolite. Tissue activity in both medial temporal cortex and cerebellum was lower following [carbonyl-C-11]WAY-lO0635 injection. The labelled metabolites of this ligand do not cross the blood brain barrier. This had a major impact on the medial temporal cortex to cerebellum ratio at 60 minutes which was now 19.8+5.9. The variability was due to the very low uptake in cerebellum. Analysis using the metabolite corrected plasma curve as input function was hampered by the rapid clearance from plasma, together with associated difficulties in measuring metabofites at late times. Therefore, a three parameter reference tissue model was applied. This provided excellent fits in all subjects, with a binding potential of 7.8+1.2. In conclusion, [carbonyl-C-11] but not [methoxy-C-11]WAY-lO0635 studies in man can be quantified using a reference tissue model.

1126

In tracer kinetic modeling it is assumed that K1 and k2 adequately describe exchange of ligand between vascular and tissue space. The aim of this study was to analyse this assumption especially in the presence of increased vascular space. For this purpose ligand exchange between vascular space and tissue was modeled with a simplified capillary exchange model with assumed instantaneous, homogeneous mixing of ligand in vascular space. The model included additionally intravascalar protein binding. Tissue time-activity curves (TACs) were generated using this model and an input curve from a human C- 11 iomazenil experiment. The vascular fraction 13was varied from 0-0.5, all other parameters (blood flow=0.5 ml/min/g, permeability-surface product=1 ml/min/g and parameters describing protein binding) were kept constant. These TACs were then refitted with a standard 1-tissue compartment model (K1, k2). Results: The graph on the left demonstrates an increase of K1 with the vascular fraction 13due to an increased first pass extraction fraction EF (K1 = flow x EF). The graph on the right shows that the standard compartment model does not adequately describe the tissue kinetics when vascular space is increased. At vascular fractions <10%, the TACs were adequately fitted by the K1, k2 model. lit with Kl,k2 model 0.0

75;0

5130 250

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lissus lime-activity capillary exchange model

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Physics and Instrumentation

0Mo379 A.R. Formiconi, A. Passeri, R. Guelfi, M. Masoni, A. Pupi, U. Meldolesi, A. Guidazzoli*, A. Sarti*. U n i v e r s i t ~ di Firenze, CINECA*, Bologna, Italy.

OTu381 H. Pohjonen I, S. Savolainen 2, P. N i k k inenl, V.-P. Poutanen ~, T. K o r p p i - T o m m o l a ~, K. Liewendahl ~, IHelsinki Univ. Central Hospital, 2University of Helsinki, F i n l a n d

A D V A N C E D R E C O N S T R U C T I O N OF SPECT DATA W I T H M A S S I V E L Y PARALLEL COMPUTERS A C C E S S E D T H R O U G H N E T W O R K C O N N E C T I O N S FROM A C L I N I C A L ENVIRONMENT.

ABDOMINAL

The p o s s i b i l i t y of p e r f o r m i n g a d v a n c e d r e c o n s t r u c t i o n s of SPECT data in a clinical environment by means of H i g h Performance C o m p u t i n g and N e t w o r k i n g (HPCN) t e c h n o l o g y was investigated. The a i m of the project is to a l l o w the use of very a d v a n c e d and computing intensive SPECT r e c o n s t r u c t i o n algorithms for the e x p e r i m e n t a t i o n in clinical environments. The 20 GFLOPS 128 nodes Cray computer at CINECA was chosen for p o r t i n g high r e s o l u t i o n 2D and 3D iterative r e c o n s t r u c t i o n algorithms. A s t a n d a r d 6 M b i t / s e c n e t w o r k c o n n e c t i o n was used. A speedup factor over 240 was o b t a i n e d in c o m p a r i s o n w i t h a 30 MFLOPS floating point processor. The p r o j e c t is conceived for setting up a coo p e r a t i o n w i t h clinical groups w i l l i n g to experiment the algorithms implemented at CINECA from their clinical laboratories. The m a i n o b j e c t i v e is to experiment the algorithms w i t h data a c q u i r e d from a b r o a d range of cameras and collimators. This work shows the p o s s i b i l i t y of e x p e r i m e n t i n g very computing intensive algorithms for accurate SPECT in a clinical environment today and it can drive the e x p l o i t a t i o n of parallel a r c h i t e c t u r e s for a d v a n c e d imaging processing; m o r e o v e r it gives an o p p o r t u n i t y of comparing data from different laboratories using the same p r o c e s s i n g software.

SPET/MRI

e"

FUSION

To test the usefulness of abdominal fusion of MRI and SPBT for development of 3 D - d o s i m e t r y for systemic radionuclide therapy a p p l i c a t i o n s we s e l e c t e d three volunteers for h e p a t i c and splenic uptake studies using thrombocytes and colloids labelled w i t h ill-In and 99m-Tc, respectively. The a i m was also to investigate if the u p t a k e of thrombocytes in the spleen and liver can be m e a s u r e d more a c c u r a t e l y using r e g i s t e r e d data. SPET imaging was p e r f o r m e d w i t h a Picker SX300 single h e a d gamma camera starting one hour after intravenous injection of l l l - I n - l a b e l l e d p l a t e l e t s (3.7-7.4 MBq) . 9 9 m - T c - l a b e l l e d tin colloids (37 MBq) were injected two days later. M R images w e r e a c q u i r e d w i t h a Siemens M a g n e t o m V i s i o n 1.5 T MRI scanner. Four to six skin markers, i d e n t i f i a b l e with both imaging modalities, were used for retrospective image registration following a noniterative least squares method. For q u a n t i f i c a t i o n regions of interest were drawn on the registered MR images and transferred a u t o m a t i c a l l y to the c o r r e s p o n d i n g positions in SPET images for calculation of counts in ROIs. S e g m e n t a t i o n m e t h o d s in SPET are inadequate for a c c u r a t e m e a s u r e m e n t of the a c t i v i t y d i s t r i b u t i o n and r e g i s t r a t i o n is therefore needed. A good c o r r e l a t i o n was found b e t w e e n s p l e e n / l i v e r activity ratios derived from registered data using v o l u m e t r i c average activity per pixel values and total activities, but not p r o j e c t i o n d a t a - b a s e d ratios. R e g i s t r a t i o n a c c u r a c y was a p p r o x i m a t e l y 1-2 cm, w h i c h is clinically sufficient and can be further improved using larger m a t r i x sizes in SPET.

OTu380 M Pagani, C Jonsson,M Ingvar, L Thurfjell, S Kimiaei, M Serrander, H Jacobsson and SA Larsson. Departments of Hospital Physics and Clinical Neurophysiology, Karolinska Hospital, STOCKHOLM;Center for Image Analysis,UppsalaUniversity, UPPSALA; Sweden.

OTu382

IMPLEMENTATION OF THE COMPUTERIZED BRAIN ATLAS FOR PET/SPECT : COMPARATIVE STUDIES.

MEASUREMENTS OF BRAIN GLUCOSE CONCENTRATION - A COMPARISON OF NMR SPECTROSCOPY AND PET With PET the cerebral metabolic rate (CMR) of glucose and other compounds can be accurately determined. Usually a compartment model is applied, and CMR is obtained from a combination of the rate constants (multiplied by the plasma substrate concentration). Estimates of other parameters are also obtained, but such estimates are often more model dependent than the CMR estimate. We have validated the PET estimate of brain glucose concentration by comparison between our PET results and results of 13C NMR spectroscopy (1). Using 13C labeled glucose as tracer the average brain glucose concentration can be measured directly with the latter method without any compartment model. As tracer [1-11C]-D-glucose was used. After correction for the loss of [11C]CO2 the rate of uptake of this tracer reflects the rate of glucose

Receptor and pharmacokinetic studies often require repeated examinations in the same patient, as well as examination using PET and SPECT may be desirable. In order to better identify the target cerebral strucmres, several coregistration methods have been developed. We propose the use of a Computerized Brain Atlas (CBA) in order to investigate the reliability of PET/SPECT interstudy analysis. PET 1502-butanol and SPECT 99mTcHMPAO examinations, both representing blood flow, were performed at rest in 8 healthy volunteers. The CBA was modified in order to fit the brain shape and PET and SPECT image data were reformatted. In both studies normalisation was performed with the brain count average set to 50. Cerebral structures were automatically defined by CBA in the brain volume and 2D ROIs were manually drawn fitting the structure's contour. ROI size and counts were separately calculated and each ROI averaged between the subjects. Small structures (i.e. Caudate, Putamen), intermediate (i.e. Brodmann 6 and 19) as well as large structures (temporal and parietal lobes) were considered. Comparison between PET and SPECT images was expressed as percentage count difference using the formula (PET counts-SPECT counts)/PET counts. Our results (Fig.) demonstrate that ROI value in structures as large as 500 mm 2 or more exhibit a very low intermethod variability while smaller structures show a greater variability. F~Gt.IRE

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This may be due to the predominant action of partial volume effect on small structures in the SPECT study. We conclude that the CBA is a valuable tool in studies were different functional imaging modalities are used.

C O |m

G Blomqvist, V Grill, M Ingvar, S Stone-Elander, L Wid@n

Departments of Clinical Neuroscience and Endocrinology, Karolinska Hospital, and Karolinska Pharmacy, Stockholm, Sweden

oxidation. From the usual two tissue compartment model the brain glucose concentration was estimated as the product of the plasma glucose concentration and the expression kl/(k2+k3), where kl, k2, and k3 are the rate constants in the model. In a double study the time course of the tracer in the brain was measured in five healthy males at normoand hyperglycemia (5.3-+0.7 and 13.8+_1.6 ~mol/ml, respectively). The average brain glucose concentration was estimated to be 1.3_+0.2 and 2.5_+0.3 ~tmol/ml at normo- and hyperglycemia, respectively. In comparison, using MRI (1) the average brain glucose concentration was found to be 1.0_+0.1 l-tmol/ml at normoglycemia (plasma glucose concentration 4.7-+0.3 ~tmol/ml) and 1.8 - 2.7 #mol/ml at hyperglycemia (plasma glucose concentration 7.3 - 12.1 p.mol/ml). In conclusion, the estimate of the brain glucose concentration using PET and [1-11C]-D-glucose was found to be close to the concentration determined by 13C MRI. The result shows that other parameters besides the rate of uptake can be reliably estimated using compmartment models. (1) R Gruetter et al. Direct measurement of brain glucose concentration in humans by 13C NMR spectroscopy. Proc Natl Acad Sci USA, 89:1109-1112, 1992

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0Tu383

0Tu385

E. Miot-Noirault. L. Barantin, S. Akoka, A. Le Pape. Laboratoire de Biophysique Cellulaire et RMN-INSERM U316/CNRS-2 bis, bd Tormellt-37032 Tours CEdex - FRANCE.

A. Karonen*,S. Savolalnent, M. Tagesson$, K. Kairemo§, and S.E. StrandS *Accelerator Laboratory, Universityof Helsinld, tDepamnent of Physics, University of Helsinki, *Radiation Physics Department, Lund University Hospital, §Department of Oncology,Helsinki UniversityCentral Hospital

MR INVESTIGATIONS OF CEREBRAL DEVELOPMENT IN T H E B E A G L E PUPPY: T 2 - W E I G H T E D I M A G I N G A N D PROTON LOCALIZED SPECTROSCOPY.

MONTE CARLO SIMULATION OF RADIATION DOSES IN RADIOIMMUNOTHERAPY

There are major biochemical changes accompanying myelination which contribute to neurological and motor development in satisfactory conditions. Despite the unique ability of MRI to differentiate between myelinated and non-myelirrated brain tissues, the biochemical changes at the origin of maturation are not available from MR images and can only be approached by quantitative analysis of MR data and spectroscopy. Three young beagles were followed from 8 days of age to 4 months of age. T2-weighted imaging and proton localized spectroscopy were performed once a week for each of the animals. Spin-echo scans were performed to acquire T2 weighted images, using a 2.35 Tesla imaging system and a 500 gm pixel resolution. T2 value was obtained from three regions of interest in both grey and white matter (frontal, parietal and occipital), and from one region in the cerebellum grey matter. 1H spectra were acquired from 8 ml voxels in the central grey nuclei region. Relative concentrations of N-acetylaspartate (NAA)/Choline(Cho), Cho/Creatine(Cre), Lactate (Lac)/NAA, and NAA/Cre have been studied. T2 values and relative concentrations of metabolites were followed as a function of age. T2 values were observed to decrease from 45% from 15 days of age to 60 days of age. During the first two months of life, we observed a rapid decline of brain T2 values,followed by a more gradual decrease over the next months. This decrease was correlated with an increase in the grey/white matter contrast. This T2 kinetics evolution was observed to be secondary to the metabolites changes: The NAA/Cho ratio rapidly increased from a value 9f 0.2 to a value of 1.2~ whereas the Cho/Cre ratio decreased from a value of 5 to a value of 1.7 (from 8 days of age to 16 days of age). The observed metabolites changes could be attributed to an initiation of the myelination process (NAA is accepted to be a neuronal marker in adults, and choline is known to be associated with myeline, as maturation oecured). Combining T2 relaxation time and metabolites concentrations measurements provide a powerful/tool to investigate normal and pathologic brain development.

Many specific intraeellular target molecules have been characterized by cancer biologists; these include molecules in cellular signaling and they bind specifically to cellular DNA. Labeling of these substancesby Auger-electronsmakes cell killing precise, whereas e.g. in radioimmunotherapy(RIT) with [~-emJttersalso surroundingcells will be killed depending on the range of the radiation emitted by the radionuclide. The ability to quantifythe dose delivered to tumor and norreal tissues when using radiolabeled monoclonaiantibodieshas been a problem. This is true, especially, for cellular level dosimetry. The aim of this study was to compare two potentially usable In isotopes in PIT both on cellular and macroscopic levels. The physical dose distributionswere calculated using the EGS4 MonteCarlo (MC) code and the MC codedeveloped at Lurid UniversityHospital. In macroscopicregime some results were also calculated with MIRD formalism using the MIRDOSE3program. In modeling,cells were assumedto be homogeneous spheresof water. S-valuecurves calculated for 113minand 11lin isotopeshomogeneouslydistributed in water spheresof different diameters using the EGS4 code cross at about diameter 0.05 cm. Comparisonof the results calculated with the two MC codes show agreement in S-values at larger sphere diameters. For smaller spheres there are differences that can be attributed mainly due to differences in radiation spectra used as input for calculations. The results of the MIRDOSE3 program are in agreement with the simulated S-values at macroscopic sphere diameters. Dose calculations were also performed using the EGS4 code by modelingthe tumor by a cluster of water spheres. The activity was distributed in different cell compamnents. The results show that the therapeutic effect of radionuclides used in RIT depends stronglyon the cellular level geometryand the microscopic distribution of activity. Moreover, in calculating the absorbed dose, care should be taken in using as complete spectrum of the source radiation as possible.

0Tu384

0Tu386

A. Skrettin~, ~. Bruland, N. Aas, The N o r w e g i a n R a d i u m Hospital, Departments of Medical Physics and Technology, O n c l o l g y and N u c l e a r M e d i c i n e

J. Lampinen. C. Aschan, A. Kuronen, K. Kairemo*, T. Korppi-Tommola* and S. Savolainen, Dept. of Physics, University of Helsinki (POB 9, FIN-00014 Helsinki University), *Helsinki University Central Hospital

C O M B I N E D USE OF SPECT, CONJUGATED V I E W W H O L E BODY SCANNING AND CT-SCANNING FOR ESTIMATION OF ABSORBED R A D I A T I O N DOSE IN THE T R E A T M E N T OF O S T E O S A R C O M A W I T H iS3Sm - EHDNP. The p u r p o s e of this project was to develop tools to e s t i m a t e the a b s o r b e d radiation dose due to an a c c u m u l a t i o n of ~53Sm-EHDMP in a metastatic lesion o r i g i n a t i n g from an osteosarcoma. A m e t h o d has been developed whereby the anterior/posterior counts obtained from whole body scans are c o r r e c t e d for a t t e n u a t i o n by means of a t t e n u a t i o n c o e f f i c i e n t s d e r i v e d from the CT scans. In order to g e o m e t r i c a l l y m a t c h the CT-data to the whole b o d y images, the b o n y structures (H.U. above 150) were s e g m e n t e d and, using a parallel p r o j e c t i o n geometry, p r o j e c t e d into an image p l a n e p a r a l l e l to the e x a m i n a t i o n table. By proper interpolation b e t w e e n the CT slices, an image was formed that c o u l d (by scaling and translation) be m a d e to c o i n c i d e w i t h the I~3Sm-EHDMP bone scintigram. The tumour contours w e r e drawn in the CT-images, and the tumour v o l u m e and the attenuation corrected s c i n t i g r a p h i c counts were d e t e r m i n e d automatically. SPECT images, a l i g n e d w i t h the whole b o d y scans, w e r e u s e d to determine the c o n t r i b u t i o n from o v e r l a p p i n g normal bone to counts w i t h i n a region of interest, and b a c k g r o u n d regions were used to assess scatter contributions. Transmission scans o b t a i n e d during whole b o d y scanning a g r e e d v e r y well w i t h the calculated attenuation, and p h a n t o m experiments showed that the a c t i v i t y c o u l d be d e t e r m i n e d to w i t h i n 5 percent.

1128

ESTIMATING INTERNAL PATIENT DOSE USING A FLEXIBLE ANATOMICAL PHANTOM BASED COMPUTER PROGRAM A new computer program for estimating internal patient dose was developed. Both the radionuclide distribution and the anatomical layout of the patient are described to the program using case specific bitmaps. The radionuclide distribution (source) and the anatomical topology (target) bitmaps are constructed from SPET- and CT-pictures respectively. The organs in which the absorbed doses are of interest are marked with organ specific cotours to the anatomic bitmaps. The program developed reads both the target and source bitmaps and creates an array to be used as a 3dimensional phantom. Different values in phantom array cells are used to describe different organs or the proportional amount of radionuclide in the cell in question. The amount of radiation energy transferred from one source cell to one target cell is proportional to the total emitted radiation from the source cell and the distance. The absorbed doses are calculated to the center of every target cell by integrating over all of the source cells. The average absorbed dose to each target organ is then calculated. The program was used to calculate absorbed doses of patients treated with radioimmunotherapy. Three patients received intraperitoneal infusions with a cumulative injected approx. 3700 MBq 131-I-labeled monoclonal anti-TAG 72 antibody. The patients had widely spread intraperitoneal cystadenocarcinomas. The' calculated absorbed doses to the most critcal organs, i.e. kidneys, were under 5 Gy in all the cases. The doses were verified with Monte Carlo simulations. The results of TLD dose measurements correlated with the results of these two calculation methods. The developed computer program for estimating internal patient dose in systemic radionuclide therapy was found accurate and flexible in clinical use.

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Physics and Instrumentation

0Tu387

0Tu389

C Aschan, M Toivonen*, J Lampinen, K Kairemo% A Jekunen% M Tenhunent and S Savolainen,,Dept of Physics, Helsinki University (POB 9, FIN-00014 Helsinki University), *Finnish Centre for Radiation and Nuclear Safety, tHelsinki University Central Hospital

Jari Heikkinen I, Jyrki T. Kuikka l, Aapo Ahonen 2, Pentti Rautio 3 and Kauko Hartikainen 4 IKuopio University Hospital, 2Oulu University Hospital, 3North Karelia Central Hospital, 4The Association of Finnish Local Authorities, Finland

TL DOSIMETERS FOR DOSE ESTIMATIONS IN RADIOIMMUNOTHERAPY

A multicenter evaluation p h a n t o m SPET images

The aim of the study was to clarify the usefulness of the TL dosimeters for dose estimation in radioimmunotherapy. Three cancer patients (35-40 years; two male, one female) had a widely spread intraperitoneal cystadenocarcinoma originating from appendices (males) or from ovary with disease course varying from three to five years. The patients 'received intraperitoneal infusions with a cumulative injected activity of approx. 3700 MBq 131-I-labeled monoclonal anti-TAG 72 antibody. TL dosimeters were highly sensitive CaSO4:Dy powdered samples in paper packages. Six reference points were selected on the skin of patients for dose estimations. Four first points corresponded fight kidney, left kidney, heart and sacrum, and two remaining points were selected above the abdomen. Dosimeters were placed on the reference points for one hour, measurements were repeated daily for a week, and dose rate versus time curves were derived for each reference point. An exponential decay function was fitted into the each set of points and the cumulative dose was integrated. The dose delivered to critical organs, kidneys, can be concluded to be less than 5 Gy for the first patient, whose right kidney was in immediate contact with a very large tumor, and less than 1 Gy for the second and the third patients. The main purpose of the measurements in the reference points is to give rapid information on the dose of the organs which are most seriously exposed beside the tumor. Doses measured with TL dosimeters conelated well to the calculated doses. It is concluded that doses in radioimmunotherapy can be verified in vivo by using TL dosimeters.

A three dimensional high resolution brain phantom {JB003) was filled in 12 laboratory with a solution of Tc-99m (110 MBq), water and detergent. P h a n t o m was imaged as a brain perfusion patient. Reconstruction and printing was also p e r f o r m e d according to clinical routine. All image sets were evaluated a n o n y m o u s l y by three nuclear medicine specialist. Results were ranked from one to five (worst - best). Also a performance phantom (Jaszczak) was filled with a solution of Tc-99m (925 MBq) and water. Acquisition, reconstruction and printing parameters were exactly the same as in the brain phantom scan hut only transaxial slices were printed. Three experts evaluated the anonymous image series of the performance phantom. Resolution and contrast were visually ranked according to how m a n y s e p a r a t e d hot lesions (from 0 to 8) and cold lesions (from 0 to 7) could be discerned. Also count densities from hot and cold lesions were calculated and compared to reference counts. Average rank for brain phantom images was 2.68 ± 0.76 (range from 1.5 to 4.5). From performance phantom images experts saw 2.80 ± 1.04 (1.33 - 5.00) hot and 4.92 ± 0.94 (3.00 7.00) cold lesions. This means that mean resolution was about 16 m m (from 9.2 to 20.0 mm) and average size of the smallest cold lesions detected was II ram (5.9 - 14.3). Calculated values of the p e r f o r m a n c e phantom did not correlate with those visually ranked. Only correlation was found between brain rank and hot lesion rank, r = 0.87. Only four laboratories received good results. Image quality was suprisingly poor with the others. We think that printers with poor resolution of the cameras are the weakest part in most eases. Also wrong colour tables and filtering might be the reason. There is a need for better brain SPET.

0Tu388

OTu390

J.A.K. Blokland ~, R.J. Lopulalan2, JA.J. Camps 1, R. Merbis 1, S.AT. Pompstra 2, aDep. Of Diagnostic Radiology and Nuclear Medicine, Leiden University Hospital, 2Faculty of Technical Mathematics and Informatics, Delft University of Technology

A.Skrettinq, V.Volodin, P.Kopp, J.Mester, K.de

A COMPUTER ASSISTED PLANNING SYSTEM FOR NUCLEAR MEDICINE EXAMINATIONS. Planning nuclear medicine examinations requires knowledge about the procedure itself, the gamma cameras and computers which may be used, the pharmaceuticals needed and their availability, etc. Also the actual number of technicians present at any time of the day, the presence of physicians, and the agenda with already planned examinations and with maintenance appointments for the gamma cameras must be included when planning an examination. Even a skilled planner often does not possess all this knowledge and for inexperienced newcomer it will take a lot of time achieve it. It will result in sub-optimal plans with a peaking workload and it may maintain long patient waiting lists. To support the planning of examinations we have developed a computer assisted planning system. This system incorporates all the above-mentioned knowledge required for planning an examination. Other information used by the system includes the time required for each step of a procedure, and intervals between the steps, priorities, and the acquisition system settings of preceding and following investigations on the same system. It preserves time for at least two emergency examinations. Each possibility is assigned a score depending on how far it fulfils the constraints. After searching the agenda the computer presents all the alternatives, starting with the one with the highest score. The user has to make its choice from the presented alternatives, or he may overrule the system by planning the investigation on any day or time he likes. Next, the user only has to enter the patient ID, all other patient data is obtained from the hospital information system which is connected to the planning system. The system is running since June 1995 and it has helped to balance the daily workload of the department. It also can be used to print lists for the preparation ofradiopharmaceuticals, and it eases the administrative procedures after performing an examination.

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Y.Xie, H.Bergmann,G.Hart, Metz, H.J.Serdijn

A WHO/IAEA-COORDINATED INTERLABORATORY COMPARISON OF BONE SCINTIGRAPHY IN SIX EUROPEAN COUNTRIES CARRIED OUT BY THE USE OF A TRANSMISSION PHANTOM

Identical transmission phantoms were distributed to country coordinators in Austria, Belgium, Great Britain, Hungary, the Netherlands and Norway. The phantom contained structures that would simulate accumulation, with different contrast ratios, in the ribs and the spine as seen in a posterior v i e w of t h e t h o r a x . Simulated bone studies were performed on a total of 165 gamma camera systems/ rectilinear scanners. Both spot images and whole body scans were performed. The country coordinators and their coworkers travelled to the individual laboratories who performed the examination according to t h e i r o w n protocols. The laboratories w e r e a s k e d to f i l l i n a reporting scheme concerning instrumentation, quality control routines and the actual image acquisition technique. With reference to an anatomical sketch, the physicians were asked to report a score, for each bone segment, reflecting their findings and their confidence in t h e s e . A total of 196 such reports were collected. From the rib segment scores, an ROC-curve was constructed for each report. There were significant variations between the laboratories, depending on total count content and age of the equipment. The ROC areas mean was 0.84, the median 0.84 and the standard deviation 0.17. The detection rates ranged f r o m i0 p e r c e n t f o r a r i b accumulation with a contrast ratio equal to 1 . 1 8 to i 0 0 p e r c e n t f o r a c o n t r a s t r a t i o e q u a l to 2 . 3

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Physics and Instrumentation

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B.Hesse (DK), MH.Bour,quiqnon (F), E.Busemann Sokole (NL), PR.Franken (B), A.AI-Saadi (UK), MT.Benoit (B), R. Campini (I), M. Clausen (D), D Fagret (F), BE.Jones (UK), J.Kuikka (SF), M.P.Larrock (B), E. Milan (I), MTh.Pakbiers (NL), &Palmer (S), Y. Ricard (E), G. Schultz (D), J.Verdenet (F).

PR.Franken (B), MH.Bourguignon (F), E.Busemann Sokole (NL), 8.Hesse (DK), JC.Cardot (F), R.Campini (I), D.Fagret (F), R.Giubbini (I), A.Hertel (D), BE.Jones (UK), J.Kuikka (SF), A.Lagerwaard (NL), r).Le Guludec (F), H.Kart (UK), MP.Larock (B), PY.Marie (F), J.Martin Comin (E), J.Mester (H), MTh.Pakbiers (NL), CL.Petersen (DK), H.Valette (F).

EUROPEAN NUCLEAR CARDIOLOGY DATA BASE TRIAL 1: MYOCARDIAL PERFUSION STUDIES WITH ggmTc - MIBI Quality assurance of nuclear medicine software and the assessment of variability between operators and centres are two of the goals of the European Nuclear Cardiology (ENCD) data base project. In the ENCD trial 1, myocardial perfusion of the 3 main vessels was assessed with ~mTc- MIBI. SPECT studies of 30 patients were collected with a General Electric 400T camera linked to a Starcam 3000 RT computer (courtesy of B. Hesse Righospitalet Copenhagen - DK) according to the ENCD protocol (Eur. J. Nucl. Med. 1993, 20:59-65). Reconstructed transverse slices were distributed on 3.5" diskettes in Interfile V3.3. format to ENCD trial 1 participants recruited on a voluntary basis from a list of known ENCD contributors. Participants were asked to further analyze the data (i.e., reorientation, analysis) with the software they use routinely and 1o provide an interpretation of myocardial pertusion with a 5 point score (normal, probably normal, equivocal, probably abnormal, abnormal). Data could be read by only 7 of the 18 participants from 10 countries. Six different software packages from 5 manufacturers were used. 61% of the 90 territories were diagnosed with full agreement of all observers (scores 1&2, and 4&5); 82 % of these territories accurately predicted the absence and presence of significant stenosis on coronary angiegrams. Five out of the 11 normal patients included in the trial were correctly scored by all observers. This trial was too small 1o draw any conclusion concerning the interpretation of myocardial SPECT studies throughout Europe. The ENCD trial 1 will be extended to more centers with more studies in the near future. Although SPECT projections were not distributed because of a lack of standardization concerning COR and uniformity corrections, only 39 % of participants could finally complete the whole process with reconstructed SPECT data. To achieve the goals of ENCD, efforts need to be made by all parties to allow the routine exchange of tomographic data throughout Europe.

EUROPEAN NUCLEAR CARDIOLOGY DATA BASE TRIAL 2: GLOBAL LVEF ASSESSED FROM GBP STUDIES Quality assurance of nuclear medicine software and the assessment of variability between operators and centres are two of the goals of the European nuclear cardiology data base (ENCD) project. In the ENCD trial 2, global left ventricular ejection fraction (LVEF) was the investigated parameter. Gated blood pool (GBP) data of 30 consecutive patients were collected with a Siemens Orbiter camera linked to a Sophy AP computer (courtesy of PR.Franken - VUB Brussels) according to the ENCD protocol (Eur J Nucl Med 1993, 20:59-65). Data were distributed on 3.5" diskettes in Interfile V3.3. format to ENCD 2 trial participants recruited on a voluntary basis from a list of known ENCD contributors. Data could be read by the19 participants from 10 countries, although the Interfile headers required manual editing in 3 centres. Participants were asked to analyze the GBP data with the software they use routinely and to provide the global LVEF. The Amsterdam Medical Centre (AMC) volunteered to provide the results of 10 different observers who used the same software, to assess an intracentre variability. Ten different software from 7 manufacturers were used. LVEF values ranged from 14 % to 88 %. For each study the mean and standard deviation of LVEF were calculated. These standard deviations of LVEF ranged from 2.4 % to 11.4 % with an average value of 6.8 %. In comparison, the corresponding values [Tom the AMC ranged from 0.8 % to 5.3 % (average value 2.4 %). Results were further analyzed b y variance analysis for repeated measures with StatView 512+ TM software for Macintosh. Global ANOVA showed a significant centre effect with the mean LVEF values per centre ranging from 33.5 % to 53.4 % (p=.0001). This trial was too small to further test any specific effect. In conclusion the ENCD trial 2 shows a large variability of LVEF results throughout Europe. It is our belief that efforts should be made to reduce the intercen~e variability. In order to better understand the causes of the variability of calculation of global LVEF and to ensure quality assurance of software, the ENCD tdal 2 will be enlarged to include a greater number of centres, software, and studies.

0Tu392

0Tu394

M.H.Bourquignon(1), E. Busemann Sokole(2), R. Giubbini(3), P.R.Franken(4), B. Hesse(5), J. Mester(6) , R. Bidet(7) and H. Sochor(8).(1) CEA Orsay France, (2) AMC Amsterdam, The Netherlands, (3) SC Brescia, Italy, (4) VU Brussels, Belgium, (5) RH Copenhagen, Denmark, (6) ASG Szeged, Hungary, (7) CHU Besan~on, France (8) AKH Vienna, Austria.

M. Eckholt, H. Bergmann Department of Biomedical Engineering & Physics, University Hospital AKH, and Ludwig Boltzmann lnst. of Nuclear Medicine, Vienna, Austria

EUROPEAN NUCLEAR CARDIOLOGY DATA BASE TRIAL 3 TO DEFINE NORMALCY AND DECISION THRESHOLDS IN NUCLEAR CARDIOLOGY. A diagnostictest reported as normal is generally used to rule out certain diseases and/or to carry a good prognosis. Therefore, to establish normalcy, i.e. to establish the range of normal values and normal patterns, is critical. Indeed nuclear cardiology is no exception and factors that affect the definition of normalcy are: - acquisition parameters, reconstruction software, processing and data analysis. A minimum of standardization and rigorous quality assurance are needed to ensure that all results have the same significance for a nuclear cardiologist wherever he is located and wherever the test is performed. One expects that nuclear cardiology is able to produce the same and reproducible results within a defined margin of error. The distribution of the normal population may or may not be a Gaussian. It must be established in order to measure its actual overlap with the distribution of patients with respect to the test and to set up threshold values as decision criteria. Furthermore, the strategies used for a population and for an individual patient may be quite different and depend on the respective distributions of test results. A normal bank of nuclear cardiology data is being built in Europe under the auspices of EANM, ESC and COST B2 and the participation of national working groups of nuclear cardiology. Normal subjects are selected and radionuclide data sets acquired in accordance with a common protocol (Eur J Nucl Med 1993, 20:59-65). So far, the collection of normal data includes planar gated blood pool studies and SPECT myocardial studies using Tc99m MIBI. Over 150 set of normal data have been collected for distribution. However other ENCD trials have revealed problems with Interfile V3.3, especially for SPECT data. Consequently, the large scale distribution of data, necessary to build the statistical distributions of the parameters of interest to help define normalcy and decision thresholds, is not really possible at this moment. An optimization of Interfile is necessary and a clear limit between acquisition and processing must be defined, both tasks to be achieved in agreement with all equipment manufacturers. [

1130

C O M P U T E R - C O N T R O L L E D ROUTINE QUALITY C O N T R O L P R O C E D U R E F O R M E A S U R E M E N T OF ANGULATION OF PARALLEL HOLE SPECT-COLL1MATORS Purpose: To assess angulation of parallel hole collimators used for SPECT in order to develop a routine procedure for both quality control and acceptance testing, M e t h o d s and materials: Placing a radioactive point source (99~Tc) at a small and a large distance (2 and 118 mm respectively) from the collimator's surface on one perpendicular line, we have measured the respective image positions by calculation of the centroids [E. Busemann Sokole et al.: J. Nucl. Med 28: 1592-1598, 1987]. An angulation of nominally parallel holes causes a relative shift between these two image positions. Using the MATLAB rM software package, we have developed an analysis program for automatic peak identification, calculation of the angulation and visualization of the results. We have also designed an easyto-use computer-controlled x-y positioning table to facilitate accurate positioning and coverage of the whole collimator surface. Results: The figure shows the results for twelve points on the surface of a LEGP collimator. Grid spacing is 10 cm Direction and relative magnitude of the angulation are ..............' "i ..~ given by the arrow's direction and , ~ . . . . ~ length respectively. The largest angulation amounts to -0.76 °, the ~,~ -"~ "~ • ),~ measurement accuracy is 0.4 °, as " .......... .... " indicated by the circles. Conclusion: The method is well( ..-g'; ............` 7 ' suited for accurate and comprehensive measurement of collimator angulation.

•

Physics and Instrumentation/Dosimetry and Radiation Biology

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OTu397

M. Marengo, D. Pancaldi, S. Civolla*ff, S. Milanesi, C. Bergamim. Department of Medical Pbysics, S.Orsola - Malpigtfi Puliclinic Hospital, Bologna (Italy)

SP Miiller 1,2,3, F Rybicld 1,2, SC M o o r e 2, M F Kijewski 1,2. B r i g h a m and W o m e n ' s H o s p i t a l 1 a n d H a r v a r d M e d i c a l S c h o o l 2, Boston, U S A , University Essen 3, FRG.

AN EFFICIENT ALTERNATIVE METHOD TO MEASURE DIFFERENTIAL UNIFORMITY Differential mfffomffty was introduced as a measurement of die rate of change of the flood field over a linffted distance. The processing of subsets of 5 pixels both in X and in Y direction to identify maxmmm local count variations is time consuuffng and not always easy to program with typical nuclear medicine macro languages. Moreover, such sort of "pixel driven" approach to the calculation, does not makes an efficient use of tile built in frame processing capabilities of nuclear medicine computers. We tested an alternative method of calculation, ill which a "differential unifomffty image" is obtained by convolution in the space donmin with a 5x5 ken*el wbere negative cross elements are balanced by a cantraI positive wllue; tiffs mask enlmnces local variations in counts. Applying the mask is sinfflar to 0 0 -1/8 0 0 scalming tile nmtrix in tile row and 0 0 -1/8 11 D colunm directions, but is very easily done for the whole frame; regions of -1/8 -1/8 I -1/8 -1/8 interest defined for UFOV and 0 0 -1/8 D D CFOV can then be applied to resulting image and the pixel in wich 0 0 -l/8 [/ [) the maxinmm local variation is centered can be ilmnediatley found. Kalowing flue coordinates of the pixel of inaximum variation, differential unifonnily is then obtained by applying a 5x5 pixels RO1, centered around tiffs point, in the original image and calculating tile index as usual by tile ratio of tile difference and the sum of maximum and minimum count values ill the ROI. Tbe metbod described has bean compared to the classical NEMA procedure witb simulated and real flood inmges; results are substantially the same, with a few points to note: 1) in our method the measure is sinmltaneous in both X and Y direction and the application of the 5x5 ROI in the orginal inmge can produce a differential uniformity index relative to pixels that are diagonal, i.e. not ill tile same row or column; 2) applying the 5x5 sq*mre ROI to the flood image can lead to pixels that are actually outside the UFOV or CFOV being considered in tile calculation. These observations notwithstanding, tile method described is straightforward and reliable; its use can be suggested in routine unffonnily checks and for systems where NEMA software or off line data analysis are not available.

INTERVAL ESTIMATION - A NEW APPROACH FOR PREDICTING QUANTITATION PERFORMANCE AT LOW SNR. M a x i m u m likelihood (ML) estimation has been e s t a b l i s h e d as a p a r a d i g m for assessment o f i m a g i n g system p e r f o r m a n c e in nonlinear quantitation tasks but it also has relevance, e.g., for p a r a m e t e r estimation in tracer kinetic modeling. T h e C r a m e r - R a o b o u n d (CRB) o n the p a r a m e t e r variance provides an absolute theoretical limit f o r quantitation performance. At l o w SNR, however, the best achievable parameter variance m a y be substantially larger than the theoretical limit. Instead o f u s i n g v a r i a n c e b o u n d s for point estimation, we are n o w p r o p o s i n g interval estimation to describe directly the expected dispersion o f the e s t i m a t e s a r o u n d the true p a r a m e t e r values. W e i n v e s t i g a t e d the p r o p e r t i e s o f z 2 - b a s e d c o n f i d e n c e intervals o n the p a r a m e t e r s as predictors o f quantitation performance at low SNR. W e modeled spherical objects (radius 4 pixels) i m a g e d with a system with a G a n s s i a n P S F (4-pixel F W H M ) . Various levels o f stationary G a u s s i a n white noise were added. The parameters, activity concentration a n d size, were estimated b y ML, and v a r i a n c e s and c o v a r i a n c e s calculated b y simulation over 1000 replications per condition; the CRB w a s calculated for the same parameters. W h e n the parameters are perturbed f r o m their true values, the c h a n g e in Z 2 reflects the decrease o f the likelihood o f these p a r a m e t e r values. W e generated univariate confidence intervals, w h i c h were c o m p a r e d to the distribution o f the estimates, b y projecting appropriate 2D iso-z2-confidence regions onto the parameter axes. At high SNR, the x2-based confidence intervals a n d those calculated f r o m the CRB coincide, and both agree with the distribution o f the M L estimates. W i t h decreasing SNR, the distribution o f the estimates o f the activity concentration no longer followed the confidence intervals calculated f r o m the CRB but w a s well described b y the x2-based confidence intervals which are asymmetric about the true parameter value. Interval estimates, such as z2-based confidence intervals, are robust predictors o f quantitation p e r f o r m a n c e at l o w SNR, a n d m a y h a v e broader applicabilitiy to other nonlinear parameter estimation problems in nuclear medicine, such as, e.g, tracer kinetic modeling.

Dosimetry

and Radiation

Biology

OTu396

OM0398

J. Sijbers I, J.P. Straatman 2 P. Scheunders z, D. Van Dyck ~ ; 2Department of N u c l e a r Medicine, H . - F a m i l y Hospital, Reet and iVision Lab, Department of Physics, R U C A U n i v e r s i t y of Antwerp; B e l g i u m

v. Cavelier& A. Goodbody, L.Tran, A. Bossuyt, J. Thornback, Department of Nuclear Medicine, AZVUB, Brussels, Belgium and Resolution Pharmaceuticals, Mississauga, Canada.

SNR Q U A N T I F I C A T I O N AND IMPROVEMENT OF M U L T I P L E SPECT IMAGES BY MEANS OF C R O S S - C O R R E L A T I O N

HUMAN DOSIMETRY OF TC99m-RP128, A POTENTIAL INFLAMMATION IMAGING AGENT.

We d e v e l o p e d a p r o c e d u r e to q u a n t i f y and improve the s i g n a l - t o - n o i s e ratio (SNR) of S P E C T images. Images were aquired on a t h r e e - h e a d e d SPECT system ( TRIAD 88, Trionix) u s i n g a standard J a s z c z a k Deluxe p h a n t o m at count densities similar to patient studies. The image SNR is q u a n t i f i e d u s i n g the c r o s s - c o r r e l a t i o n function of three independent acquisitions of an image [i] . To test the performance of the quantification, SNR m e a s u r e m e n t data are fitted to t h e o r e t i c a l l y e x p e c t e d curves. The p r o p o s e d c o r r e l a t i o n technique is also u s e d to improve the SNR. A f t e r geometrical r e g i s t r a t i o n and noise d i s t r i b u t i o n c o r r e c t i o n the amplitude of the signal s p e c t r u m is e s t i m a t e d by means of cross-correlation. The technique is a p p l i e d to a set of three SPECT images and its performance, in terms of gain in SNR and resolution loss, is compared to that of classical noise filters: Averaging, Butterworth and Wiener filtering. The SNR is found to be i m p r o v e d w i t h a factor of 3 w i t h m i n o r loss of r e s o l u t i o n compared to the factor of 1.7 g a i n e d b y a v e r a g i n g 3 acquisitions. A l t h o u g h we used a t h r e e - h e a d e d system for the aquisition, the m e t h o d can be i m p l e m e n t e d on dualh e a d e d and s i n g l e - h e a d e d systems as well.

Tc99m-RP128 is a small bifunctional peptidic chelate consisting of a tripeptide Tc-99m chelator, dimethylgiy-ser-cys(acm), attached through a glycine residue to a pentapeptide, thr-lys-pro-pro-arg, with a high affinity for the tuftsin receptor. Studies in animal models of both infectious and non-infectious inflammation have shown that there is a positive correlation between accumulation of Tc99m-RP128 and quantitative measures of inflammation.

i. Bonnet, N.; Lebonvallet, Colliot, G.; B e o r c h i a ; J. i:p.1349-1358; 1991.

S.; E1 Hila, H.; Phys. III France

After approval of the institutional ethical committee a Phase 1 trial was conducted with the objective to determine the safety, biodistribution and human dosimetry of Tc99m RP128 in 8 healthy volunteers. After i.v injection of 280 MBq Tc99m-RP128 anterior and posterior whole body scans were performed at 10, 30, 60 min and 3, 6, 8, and 24 hr. Blood samples were taken at 2,5,10,20,30 60 min and 2, 4,8 and 24hr. Urine samples were collected ad libitum over the 24 hr period and 3 subjects collected all faeces up to 24 hr post-injection. The net weight ct the peptide administered was either 150 or 200 ~g. Injection of the radiopharmaceutical was found to be safe and we~l tolerated and no effects on vital signs or blood chemistry was observed. Tc99m-RP128 was cleared rapidly from the blood by renal excretion and there was no significant accumulation in any of the major organs. In all subjects a clear visualisation of the synovia of the major joints was observed. The disappearance rate of the tracer in brain, thyroid, lung, head, liver, spleen and abdomen parallelled the plasma disappearance curve. At 24 hours 81.4 % i.d. had been excreted into the urine. Cumulated faecal activity was 1.57% i.d. Dosimetry calculations were based on standard MIRD methodology, using the ICRP 30 GI tract model and a voiding bladder model with an interval of 4.8 hrs. The effective dose equivalent and the effective dose were calculated to be 0.012 and 0.01 mSv/MBq, respectively. The highest dose was to the bladder wall which received 0.08 mGy/MBq A proposed radioactive dose of 370MBq for clinical studies will produce an effective dose which is well within the range of effective doses for commonly used radiopharmaceuticals.

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• Dosimetry and Radiation Biology 0Mo399

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T.M. Behr 1'3, G. Sgouros ~, R.M. Sharkey ~, R.M. Durra L. R.D. Blumenthal 1, K. Kolbert-', J.A. Siegel', W.S. Becker ~, D.M. Goldenberg'. Garden State Cancer Center at the Center for Molecular Medicine and Immunology ~, Newark, N J, USA, Memorial SloanKettering Cancer Center 2, New York, NY, and Department of Nuclear Medicine 3, Georg-August-University of GOttingen, Germany.

T.M. Behr, R.M. Dural*, S. Gratz~ W.S. Becker. Department of Nuclear Medicine of the University of G6ttingan, Germany; and Garden State Cancer Center at the Center for Molecular Medicine and Immunology*, Newark, NJ, USA.

9°Y-DOSIMETRY IN NUDE MICE REQUIRES ACCOUNTING FOR CROSSORGAN RADIATION: EVALUATION OF THREE DOSIMETRIC MODEL ASSUMPTIONS IN RELATION TO OBSERVED BIOLOGICAL EFFECTS

AN AUTOMATED SCHEME FOR INTERNAL DOSIMETRY IN NUCLEAR THERAPY: GAMMA- OR BREMSSTRAHLUNG-BASED DOSE CALCULATION IN THE THERAPY OF DIFFERENTIATED THYROID CANCER, RADIOSYNOVIORTHESIS, BONE PAIN PALLIATION AND RADIOIMMUNOTHERAPY

Due to the long path length of high-energy 13--emitters, cross-organ radiation may become an important issue in smaller animal models. The aim of this study was to evaluate three different dosimetry models in relation to observed biological effects in radinimmunotherapy with 9°Y-labeled immunoconjugates in nude mice. The '~°Y-doses were calculated, based on the biodistributiun of the respective SSy. labeled conjugate (anti-CEA MN-14 Fab, F(ab)z, and lgG) in GW-39 human colon cancer xenografled nude mice, using three different model assumptions: (1) accounting only for self-to-self doses, using S factors for ~,Oyin small spheroids [J Nuel Med 1988; 29: 803]; (2) correcting for cross-organ radiation according to Hui et al. [Cancer 1994; 73: 951], which does not correct for crossfire to the red marrow: and (3) using actual mouse anatomy as represented by mouse MRI with a three-dimensional internal dosimetry package (3D-ID). developed by Sgouros et al. [J Nucl Med 1990; 31: 18841. Doses were correlated to biological toxicity data obtained with the respective 90y. labeled conjugates. For this purpose, the maximum tolerated dose (MTD), blood counts kidney and iiver function parameters, and their histology were determined. Self-m-self doses of Model I were not sufficient to describe observed biological effects, especially close to organs with high activity accretion. With Fab, in addition to nephromxicity, rising liver enzymes (GOT) were observed at injected activities > 325 pCi, not explained by a self-to-self dose of 4.3 Gy. Model 2 shows crossfire from the kidneys, resulting in a mean liver dose of 90.5 Gy/mCi. With F(ab)a fragments, only the combination of bone marrow transplantation and inhibition of renal uptake by lysine increased the MTD, explained by cross organ radiation from the kidneys to the red marrow of the lumbar spine, described only by Model 3 (marrow self-dose < 5 Gy, crossfire up to 30 Gy/mCi). Additionally, substantial crossfire from the left kidney to the spleen (34 Gy/mCi) may contribute to the radiation-induced leukopenia. These data show that for understanding biological effects of 9Oy in a mouse model, accounting for cross-organ radiation is mandatory. The best correlation between biological effects and the dosimetry was obtained by the third, MRI-anatomy based model, which also accounts for crossfire from abdominal organs to the red marrow. (Supported by DFO grant Be1689/1-1/2 and by USPHS grants CA39841 and CA62444.)

Reliable, quantitative internal radiation dosimetry is not only mandatory for any dosimetry-based treatment planning, e.g., radioimmanotherapy, but also allows for more adequate dosing in the therapy of metastatic differentiated thyroid cancer with NaT3tI; furthermore, it enables estimation of organ and whole-body doses in the radiosynoviorthesis with 9Oy or ISSRe, as well as lesion and whole-body dosimetry in palliation of metastatic bone disease. The aim of this study was to establish a simple, automated methodology for dosimetry in nuclear therapy, using gamma (131I, 186/~8~Re etc.) or bremsstrahlung emissions (pure if-emitters, such as 9Oy) for quantification. Conjugate view who~e-body scans of patients are acquired at multiple time points. For gamraa-emitting nuclides, the respective photo peak is used, whereas for ymium dosimetry, bremsstrahlang is recorded in a 120-300 keV window. An activity standard is measured under the same conditions as the patient; for 90y, an 0,5-mei point source is placed in a body-like water phantom. Regions are drawn over the whole-body, organs and tumors, and appropriate background correction is carried out (Dunn et al., Med Phys. 22 (1995): 1549-1550). All calculations are performed by a PC software developed for this purpose: the whole-body, organ, and tumor activities are calculated by using the build-up factor methodology (Wu & Siegel, Med Phys. 11 (1984): 189-192), which was shown to be more accurate than the geomeWie-mean method. Time-activity curves are generated, integrated, and cumuiated activities as well as residence times are derived; two integration methods are applied: a trapezoidal, as well as an analytical, using a least squares fitting to exponential functions. The cumulated activities of the red marrow are calulated from blood samples and imaging data. These data are entered into the MIRDOSE3 program (Stabin et al., Oak Ridge National Laboratory, Oak Ridge, TN, USA) which yields the organ, red marrow, tumor, and whole-body dosimetry according to the MIRD scheme, based on derived residence times. The automated dosimetry scheme developed by us is reliable, simple to use and allows for dosimetry-based treatment in the therapy of benign and malignant conditions with gamma emitting nuclides and pure beta emitters as well. Further studies on its application in dosimetry-based treatment planning and therapeutic dosimetry in clinical radinimmtmotherapy are in progress. (Supported in part by grant Be1689/1-1/2 from the Deutsche Forschangsgemeinschafl.)

OMo400

OMo402

G.J.Beyer (1), R.E.Offord (2), RWeden (2), G.K~nzi (2), YuAleksandrova (2), H.M~cke (3) and the ISOLDE Collaboration (4) 1. Division Nuclear Medicine, HCU Geneva 2. Department of Medical 8ieahemist~, University of Geneva, 3. Department of Nuclear Medicine, Cantonsspital Basel 4. CERN, Geneva, (Switzedand)

COMPARISON OF THE BIOKINETICS OF OCTREOTIDE LABELLED WITH RADIO-LANTHANIDES AND 111In IN TUMOR BEARING RATS INTRODUCTION: Radio-labelled Octreotides are promising for both diagnosis and therapy of tumors. When substituted with appropriate chelators, O~eotide can be labelled with 1111nand other radio-metals. We compare in this paper the biokineticsof Octreotide labelled with radio-lanthanideswith that of the 1111n-labelledform, injected simultaneously. RADIOISOTOPES: The radioisotopes (141Ce, 143Pm, 153Gd and 159Dy) were produced using the on-line isotope separator ISOLDE at CERN in carrier free form and high concentration. 1111nwas purchased from Amersham. LABELLING: The O~eotide was linked to aminobenzyI-DTPA (derivatizatJon on the backbone for highest metal-ion affinity). Labelling was in acetate at pH 5-6 for 30-60 rain. Labelled Octreotide was separated from the major, unlabelled fraction by HPLC, labelling yield 70-80 %. Only unlabelled O~eo'dde gave an UV signal in the separation, indicating the high quality of the radio-lanthanides used. RESULTS: Insulinoma-bearingrats (INS-1 cells) were used. All lanthanide labelled Octreotides showed satisfactory in viva stability, which increased from Ce (lowest value) to Pro, Gd and Dy (highest, indistinguishable values). The lanthanide- and In-labelled tracers showed a very similar, rapid clearance, and similar Ussue uptake. Tumor uptake of the lanthanide-labeUedforms was even higher than that of the In-labelled mNecu~e. The fast clearance led to clinically useful tumor to-liver-ratios for all lanthanides (3 for Ce and greater than 20 for in and the other lanthanides). Lanthanide labelled Octreotides are clearly receptor bound in tumor, pancreas, suprarenal gland and partly in bone. The kidney is now the "new" critical organ. CONCLUSION: The whole variety of lanthanide radioisotopes is open to be used for O~eotide labelling. Of special interest may be the o~-emitter 149Tb (4.15 h) with respect to radionuclidetherapy. 1132

K. Schom&cker

A. ScharlI, K. Scheidhauer, B. Gabruk-Szostak. B.

B6ttcher, S. Abu-Mraheel, S.K. Shukla2, H. Schicha, Departments of Nuclear Medicine and Iobstet & Gyn, University of Cologne, Germany, , and 2CNRRome, Italy 3 . TIME FROM

DEPENDENCE

OF

RECEPTOR-MEDIATED

RADIOCYTOT0XICITY

1 6 A L P H A - [ 1 2 5 I ] - I 7 B E T A - E S T R A D I O L ([125I]E)

T h e a i m of this s t u d y was to i n v e s t i g a t e the radioc y t o t o x i c e f f e c t s in e s t r o g e n r e c e p t o r (ER) c o n t a i n i n g MCF-7 cells of a mamma adenocarcinoma following i n c u b a t i o n w i t h [125I]E r a n g i n g from 1 h to 24 h. T h e r e c e p t o r status of the cells was c o n f i r m e d by i m m u n o h i s t o c h e m i c a l s t a i n i n g and a p e r o x i d a s e - a n t i p e r o x i d a s e s t a i n i n g (ER-ICA, Abbott). The a c c u m u l a t i o n of [125I]E in M C F - 7 c e l l s w a s t e s t e d in the p r e s e n c e and a b s e n c e of r a d i o i n e r t E and in E R - n e g a t i v e cells in c o m p a r i s o n to E R - p o s i t i v e cells. The s u b c e l l u l a r dist r i b u t i o n was i n v e s t i g a t e d in 0.25 M S a c c h a r o s e b y ultra c e n t r i f u g a t i o n . The r a d i o c y t o t o x i c i t y w a s a s s e s s e d in E R - p o s i t i v e and n e g a t i v e c e l l s b y a s t a n d a r d c o l o n y f o r m i n g a s s a y after i n c u b a t i n g w i t h [1251]E (1.85 k B q / m l - 55.5 kBq/ml) and [127I]E (0.005 rum - 0.002 pmol) at i n c r e a s i n g c o n c e n t r a t i o n s for i, 2, 4, 8, 12, and 24 hr. The c h r o m o s o m e d e f e c t s w e r e testes b y light microscopy. A s i g n i f i c a n t c y t o t o x i c i t y was o b s e r v e d o n l y w h e n E R - r i c h M C F - 7 - c e l l s w e r e i n c u b a t e d w i t h [125IlE alone. T h e m a x i m a l c y t o t o x i c effect was a r e d u c t i o n of survival f r a c t i o n to 20-25%. This was a c h i e v e d at radioact i v i t y c o n c e n t r a t i o n s > 37 kBq/ml. M a x i m a l effect was s e e n a f t e r 8 hr incubation, e x t e n s i o n of i n c u b a t i o n t i m e d i d not f u r t h e r i n c r e a s e toxicity. T h e r e s u l t s suggest that the r a d i o a c t i v i t y was b o u n d to E R . T h r o u g h t h e i r n u c l e a r l o c a l i z a t i o n r a d l o e s t r o gens t a g g e d w i t h r a d i o n u c l i d e s e m i t t i n g v e r y low e n e r g y electrons (Auger electrons) b e a r p o t e n t i a l for t h e r a p y b y E R - m e d i a t e d d e p o s i t i o n of lethal doses of i o n i z i n g r a d i a t i o n to single cells w i t h o u t a f f e c t i n g n e i g h b o u r ing cells.

•

Dosimetry and Radiation Biology

0Mo403

0Mo405

N.A. Maznik, V.A. Vinnikov, Institute of Medical Radiology, Laboratory of Radiation Cytogenetics

J.G. Hengstler*, A. Bockisch÷, W. Grimm~, K. Lade*, A.O.-Zapf*, F. Oesch*

CHROMOSOME ABERRATIONS IN SUBJECTS RADIATIONALLY EXPOSED DUE TO THE CHERNOBYL ACCIDENT: EARLY AND LATE EFFECTS Chromosome aberrations in blood lymphocytes are widely used as the t e s t - s y s t e m for d e t e c t i n g of mutagenic affection-to the human genome. The cytogenetic investigations in evacuees from the town of Pripjat' and in liquidators were carried out during i0 years after the accident, and the sufficient increasing of aberration levels in subjects investigated have been shown. It was found no significant difference between chromosome aberration levels in cohorts of evacuees and liquidators. The moderate positive correlation between the radiation-induced aberration yields with physical m e a s u r e d external irradiation doses in liquidators have been determined during the first year after exposure. The approach of lymphocytes analysing for stable chromosomal aberrations, which level in the cells is constant with time, have been employed for obtaining the information about the real degree of genome damage in Chernobyl victims in the late time after the accident. The stable translocation frequency, detecting by fluorescence in situ hybridization (FISH) method, in liquidators was foun~ to be significantly higher than control level. It was concluded that FISH-technics may readily be applied retrospectively to verify early biological dosimetry performed on cohorts of persons irradiated due to the Chernobyl accident.

0Mo404 M. Monsienrs C. Van tic Wiele, H. Thierens, B. Brans, M. Simons, RA Dierckx. University Hospital Gent, Belgium.

IMPACT OF ICRP-60 ON TIlE ROUTINE GUIDELINES GIVEN AIZ'I'ER 131-1TIqERAPY : PRELIMINARY RESULTS. 1n the light of l C RP-60 limitations, a prospective study was performed to wdidate the present guidelines given to the nursing staff and family mcmbers of patients treated with 131-1 for both hyperthyroidism (hyp) and thyroid carcinoma (lea) at our depmlment : 1) for both groups, Io lninimizc cc)ntact and to maximi:,.e distance to Ihe patient ; 2) for couples, to sleep separalely for 7 days, At present, 9 pls have been included, mean (It) age 49.2 yrs, range 27 - 71 yrs. Seven pts were hospitalized for 2 to 3 days: 5 lea pts (receiving a it of 4.64 Gbq for ablation) and 2 hyp pts ( it mtexitnal thyroid retcnlion = 488.2 Mbq). The 2 remaining hyp pts were trealed on an outpatient basi~ ( p. nla_ximal thyroid retention = 181.1 Mbq). For the 7 hospitalized pts II~eEquivalent Dose Rate was measured m the cnlrunce Ic~Ihc lock during the period of hospitalization and the Air Kernaa Rate (AKR) was measured at Im l'rotn the patient's neck before discharge. Eleven family members of 6 pls, 4 hospitalized and 2 ambtdatory pts, were asked to wear a wrist-TLI) d~semetcr Ibr 7 days afler the patients left the hospital. On the basis of a tt total of 44 hospitalized treated pts per year the last 5 years, 6 tea pts and 38 hyp pts, and a it dose rcccived by nurses during hospilaliz~ulion of tea pls of 9.4 i~Sv and4.0 ItSV for hyp pls, a cnmuhuive dose of 208.4 ~.~Sv/yrfor one nurse may be expected. The it AKR before discharge was 10.1 ,ttSv/h. The it dose receivcd by fmnily members was: 14.7 ItSv lbr tea pts, 208.8 ttSv lbr hyp pls who had been hospitalized and 80.4 l.tSv lor outpatients. These preliminary results suggcst tlmt 1CRP-60 rcgulati~ms according to the guidelines given at our dcpartmcnt, will not bc violated for th~ nursing staff and family members of outpatients and tea pts. Contrarywise, following discharge, guidelines for family members of hospitali~'.cd hyperthyroidism pts should be more strict. Furthermore, we suggest a mean hospital slay of 2 days lot tea pls and 3 days for hyp pts (pts arc allowed to go home when their AKR at 1 m from the neck Ires tlroppcd below 2 itSv/h).

(*) Inst. for Toxicology and (#) Clinic for Nucl. Med., Univ. of Mainz, (+) Clinic for Nucl. Med., Univ. of Essen, Germany CONTINUOUS INCUBATION OF HUMAN MONO-NUCLEAR BLOOD CELLS WITH 1-131 CAUSES SYNTHESIS OF DNAPROTECTIVE PROTEINS. In an earlier study we showed that incubation of human mononuclear cells (MNC) witch 22 MBq 131I/ml at 4°C caused a linear time dependent induction of 1140 DNA single strand breaks (DNA-SSB)/cell/100 min in vitro. At 4°C all DNA-SSB induced by ionizing radiation can be detected (total DNA-SSB induction) since DNA repair enzymes are almost inactive. In this study we investigated the ability of MNC to compensate DNA-SSB induced by ~31Iat 37°C using a modified alkaline elution assay. Incubation of M N C with 44 MBq 13]I/ml at 37°C caused 850 DNASSB/cell after 100 rain but only 1240 DNA-SSB after 300 rain and 1420 DNA-SSB cell after 500 min. A further decrease in the time-effect curve was observed after longer incubation periods. As the total induction of DNA-SSB at 4°C was constant with time, the decrease in DNA-SSB induction with time at 37°C could be interpreted as an increase in DNA repair activity, e.g. caused by an increased synthesis of DNA-repair enzymes. To test this hypothesis a time dependent incubation of MNC with 44 MBq ~a~I/mlwas performed with and without inhibitors of RNAsynthesis (anisomycin/actinomycin D) or protein-synthesis (cycloheximide) respectively. None of the inhibitors induces DNA-SSB alone. Already after 100 min of incubation a small but statistically significant increase in DNA-SSB was observed in the presence of inhibitors of RNAor protein-synthesis compared to the incubation without inhibitors. After 500 rain of incubation with ~3~I cycloheximide increased the number of DNA-SSB induced by 131I by 1155 DNA-SSB/cell (81%) and anisomycin/actinomycinD by 1340 DNA-SSB/cell (94%). In conclusion, continuous exposure of MNC to t3tI results in an increased synthesis of proteins repairing DNA-SSB or protecting DNA from SSB induction.

0Mo406 M. Faraq.qi', I. Gardin", JL. Stievenart", B. Bok" and D. Le Guludec. Nucl. Med. Dept. "Bichat and "'Beaujon Hospital, Paris, France. RESPECTIVE CONTRIBUTION OF THE SELF AND CROSS ELECTRON RADIATION DOSE DELIVEREDTO THE NUCLEUS OF A TARGET CELL. APPLICATION TO Tc-99m, 1-123, In.111, Ga-67 AND TI-201 RADIOPHARMACEUTICALS. The electron radiation self-dose (self) emanating from the target cell itself and the cross-dose (cross) emanating from the surrounding cells were computed using an analytical model. A close-packed hexagonal cells arrangement was assumed with a cell radius (R=,) and a nuclear radius (R,,) respectively ranging from 4 to 10 pm and 2 to 6 pro, and a constant tracer uptake. Results were expressed in mean energy (E, keV) deposited within the cell nucleus per disintegration and per cell. Various uniform subcellular distributions of the tracer were studied: cell nucleus, entire cell and cell membrane. For a fixed set of Rce, and R,u, E,e, was strongly dependent on the ~'acer distribution while E,,o~ variations were less than 5%. For a cell membrane distribution only, Ese,/Ecro~swas always less than 0.1 and E,e, may be neglected compared to Ec,o,s. For Rce,= 5Urn and Rnu=4pm:

Tc99m 1-123 1n-111 Ga-67 TI-201

Nucleus Eself Ecross Eself / E=-,~s 2.65 5.12 0.52 5.04 8.32 0.61 4.77 11.31 0.42 6.04 10.36 0.58 13.8 11.02 'L25

Eself

Cell Ecross

1.43 2.83 2.74 3.54 8.10

5.2 8.45 11.5 10.4 11.1

Eself / E=o,, 0.27 0.34 0.24 0.34 0.72

Membrane Ese~" E=-os, E.~, / E.... .084 5.2 0.016 .337 8.5 0.040 .426 11.56 0.037 .263 10.46 0.025 .977 11.45 0.085

Thus, the knowledge of the radiotracer cellular distribution is crucial for an accurate computation of the self electron dose to the cell nucleus but not for computation of the cross-dose. When a membrane distribution is assumed, the self electron radiation dose may be neglected.

1133

tO

i n

,4-.I

t-

t__

O. m

t~ L.

O

• Radiochemistry and Radioassays Radiochemistry

and Radioassays

OSu407

0Su409

AC P e r k i n s , M F r i e r , MV P i m m , F Hudecz, R D u n c a n Dcpts of Medical Physics, University Hospital, Nottingham, UK, L E6tv6s University, Budapest, Hungary London School of Pharmacy, London, UK

T. GYR, H. R. MAECKE, Institute of Nuclear Medicine, University Hospital, 4031 Basel, Switzerland P. SCHOENHOLZER, Hoffmann-La Roche, Basel, Switzerland

SYNTHETIC POLYMERS AS POTENTIAL DESIGNER RADIOPHARMACEUTICALS The conjugation of synthetic polymers to drugs results in both increased drug bioavailability and reduced toxicity. We have examined the radiolabelling, biodistribution, turnout targeting and imaging characteristics of two different groups of synthetic polymers and copolymer drug conjugates in normal and turnout bearing models. The first was A N - ( 2 - h y d r o x y p r o p y l ) m e t h a e r y l a m i d e (HPMA) copolymer-doxorubicin conjugate. Imaging studies using 1-131 and 1-123 demonstrated the biodistribufion of these conjugates in transplanted melanoma and mammary carcinoma. Specific t a r g e t i n g of hepatocytes was also achieved by the addition of galactosamine to the conjugate. The second type of polymer was a group of Branched Chain Polypeptides (BCP). These were composed of a poly(L-lysine) backbone with side chains containing DL-alanine amino acid and a t e r m i n a l glutamie acid residue. I n - l l l - D T P A - B C P showed poor tumour uptake but, by modification of the side chain structure the change in molecular charge resulted in different invivo biodistribution and kinetics. This led to the examination of Tc-99m-BCP as a possible blood pool agent. Imaging for up to 4 hours demonstrated good circulatory survival of Te-99m-BCP and the chance finding of increased accumulation in a site of infection. We conclude t h a t radiolabelled synthetic polymers offer valuable alternatives to radiopharmaceutieals produced from h u m a n or animal related material.

SILVER (I)COMPLEXES OF NEW N4S4 AND N3S3 MACROCYCLIC LIGANDS FOR BIOMOLECULE LABELLING Metal ion recognition is of importance in different fields of chemistry and medicine. As an example metal complexes are used in diagnostic and therapeutic medical applications. High kinetic and/or thermodynamic stability is necessary for this type of application, A special challenge is the design of bifunctional ligands for the targeting of the metallic radionuclide Ag-111 (Tv2 = 179 h, E~(max) = 1.04 MeV, mean range in tissue = 1.1 mm, Ey = 342 keV) to tumors by use of specific biomolecules. To date there are no reports of Ag*complexes which have sufficient stability for an in vivo application. Therefore we initiated a program to develop stable Ag*-111 complexes using tri- and tetraazamacrocycles with pendant (2-Me-thio)ethyl arms (L1 (n=0), L2= (n=l)). Results: L1 and L2 react readily with Ag* and were isolated as ~ c ~ S ~ ~ /~/s~cH, PF6-salts as crystals with x-ray N N quality. The structure of AgL2 showed hexaco-ordination about Ag* which is bound to 4 nitrogens (250 + 5 pm) and 2 sulfur atoms (272 ± 2 pm). The 4 N form an almost perfect plane (±0.8 pm) with Ag* sitting 134 pm above this plane. The solution structure was studied by C-13 NMR at variable temperature. Surprisingly only one C13 methyl resonance was detected indicating that all S donor atoms are equivalent in solution or that the interchange between different environments is too rapid above 213K. L1 and L2 dissolve Agl indicating very high affinity. The stability constant was determined to log K • 19 and a competition experiment with the known highly stable silver complex of 18-aneS6 revealed that L2 affords complete transmetalation within 10 min if mixed 1:1 with Ag(18-aneS6)*. The kinetic data of transfer of Ag*-110m to serum proteins is somewhat equivocal. About 40% of radio[abel is transferred to proteins within 2-3 h. The remaining complex is stable over 24 h. Conclusion: The presented ligands form the most stable Ag* complexes known to date and may be able to immobilize Ag'-I 11 in vivo.

OSu408

OSu410

D. Bier*, H.H. Coenen, K. Dutschka, W. Wutz AG Nuklearchemie und Radiopharmazie, Universit~it Essen, *Klinik for Nuklearmedizin, Universittit WiJrzburg, FRG

S. R u b o w * , D.A. R6hlen, E. Rota Kops, T. Fixmann, M. H o l s c h b a c h , H.Herzog, H.,W. Meller-G&rtner. Institutes of Medicine and Nuclear Chemistry, Research Center JOlich *-I'yger Hospital and University of Sfellenbosch, Cape Town, South Afr ca CEREBRAL UPTAKE OF C11-CHOLINE IN RABBITS STUDIED WITH DYNAMIC PET

EFFECT OF SPECIFICACTIVITY ON THE BIODISTRIBUTIONOF 1231-LABELLEDIMT, J%CIT,MIBG AND IODOLISURIDE Although the specific activity is an important quality parameter of radiopharmaceuticals, its influence on the pharmacokinetics is most often not systematically examined. Since 1231-labelling is possible with a high specific activity (s.a.) the biodistribution of four iodine compounds was studied in bulb-c mice, in each case with six different specific activities ranging from 37 MBq/pmol to 3 7 TBq/pmol. While IMT and iodolisuride were labelled by direct electrophilic substitution, 13-CIT was prepared via iododestannylation and MIBG via Cu-assisted non-isotopic exchange with high radiochemical purity (> 99%) according to published methods. For L-[1231]iodo-~-methyltyrosine (IMT), an indicator of amino acid transport, constant uptake values, e.g. in brain, liver and kidneys, were observed over the whole range of specific activity at 15 rain pJ. An increasing carrier amount of the D2-receptor ligand [1231]iodolisuride leads 1 h p.i. to a decrease in accumulation in striatum and cerebellum at s.a. < 10 GBq/IJmol. Nevertheless, the striatum/cerebellum ratio indicated an optimal range between 1 and 100 GBq/pmot In contrast, the dopamine reuptake inhibitor [1231]J3-CIT exhibited a steady decrease of uptake from n.c.a conditions to 370 MBq/pmol in the striatum and cerebellum 1 h p.i., resulting in a constant striatum-to-cerebellum ratio of about four over this range. Saturation effects occurred beyond this level. A very strong effect on the uptake of [1231]MIBG was found in the heart, with about 40% ID/g (n.c.a,) continuously decreasing to about 12% ID/g at 37 MBq/pmol. A smaller decrease was observed in the adrenals (from 10 to 6% ID/g) while levels remained constant in kidneys (4% ID/g) and blood (1% ID/g) over the whole range. The present results indicate that the effect of specific activity on biodistribution of radiopharmaceuticals can hardly be predicted and that it may strongly influence organ uptake and thus diagnosis. Further studies on all radiotracers appear mandatory in pathological tissues and man.

1134

To characterize the biochemical processes in the pathogenesis of early Alzheimer's disease we evaluated C11-choline as a potential tracer of the in vivo quantitation of the synthesis of acetylcholine. Cerebral uptake of C11-choline was studied in 11 measurements performed on six rabbits with dynamic PET over 40 min. Acquisition protocols with wobble and interleaved mode provided the optimum scanner transaxial resolution of 5 mm and 30 image planes with 3.2 mm interplane distance. The input function was derived by arterial blood sampling. High resolution MRI images done on the same animals allowed the anatomical orientation of the ROIs defined in the PET images. C11-choline was rapidly taken up into brain and showed no washout. The mean hippocampus/cerebellum uptake ratio at 10 min p.i. was about 2.5. Patlak analysis yielded linear plots showing a significantly higher uptake rate in the hippocampus compared to the cortex (p< 0.01) and cerebellum (p<0.001). There was no significant difference between cortex and cere-

bellum. Our data suggest that C11-choline uptake in rodent hippocampus reflects the activity of the high affinity choline uptake system and therefore of acetylcholine synthesis.

•

R a d i o c h e m i s t r y and R a d i o a s s a y s

OSu411

OSu413

R.A.M.J. Claessens, J.G.M. van der Linden and Z. Kolar. University Hospital and Department of Inorganic Chemistry, University of Nijmbgen, Nijmegen and Interfaculty Reactor Institute, Delft, The Netherlands.

J. Ouivy, A. Delcorde, G. Leciercq and J. Friihling. Laboratoire J.-C. H e u s o n de Canc6rologie M a m m a i r e , D6partement de Radio-Oncologie, Institut J. Bordet, Brussels, Belgium.

THE MECHANISM OF ADSORPTION OF TIN(II) COMPLEXES TO HYDROXYAPATITE (HA). To optimize the formulation of Sn-117m-labelled agents for treatment of pain in malignant bone disease, we studied the mechanism of binding of tin complexes to HA. Complex formation with tin is necessary to prevent hydrolysis of tin under physiological conditions. However, the presence of the tin binding ligands will hamper the interpretation of results of tin binding studies. Therefore, a computer model was developed to fit with the experimental tin adsorption data and to assist in the interpretation of binding of tin to HA.. We measured the adsorption to 100 mg aliquots of HA (Ca/P ratio: 1.76; spec. surface area: 65 m2/g) of Sn-119m-stannous tin in 3 ml portions of solutions of either P-32-MDP or C-14HEDP under nitrogen. Tin concentration: 0-10 mM; tin : diphosphonate (DP) ratio: 0-0.9; pH: 6.4-7.5 (0.1 M tris buffer); incubation at 25 ° or 37 ° for 72 hr. The compositions of the stannous MDP and HEDP solutions were estimated using published stability and acid dissociation constants. With these data the adsorption to HA for each of the tin containing components of the experimental solutions was calculated, assuming a Langmuir adsorption model and separate binding sites for DP and tin. Then, varying the affinities for HA of each of the tin species in solution, each calculated tin adsorption curve was fitted to the experimental data. Maximum adsorption capacity for MDP and HEDP resp. 0.16 and 0.18 mM/g; affinity constants for MDP and HEDP resp. 0.7 and 3 I/mM. The adsorption isotherms clearly indicated the dissociation of the tin DP complexes in the adsorption process. The maximum tin adsorption with MDP was twice as high as with HEDP. The computer model was in excellent agreement with the experimental data and suggested that the adsorption of tin DP to HA may be considered as a transconjugation process. The model predicted a much higher affinity of tin to HA than that of either MDP or HEDP. Similar experiments with tin and C-14-DTPA are under way.

B L O C K I N G T H E 3-0 P O S I T I O N C O U L D I N C R E A S E T H E TUMOR UPTAKE LEVEL OF THE BREAST CANCER RADIOPHARMACEUTICAL STEROID AGENT, Z-CMIV W e demonstrated the breast cancer targeting properties of the selective ligand of the estrogen receptor, Z-17a-iodovinyl-1 ll~-chloromethyl estradiol (Z-CMIV) in preclinical and clinical studies where an important liver uptake o f the product was noted in humans. It is k n o w n that this estradiol derivative is partially metabolized in 3-0 conjugates after its hepatic capture during the first pass. In order to evaluate the effect of blockage the 3-0 metabolism, we prepared and labeled b y 125I the 3 - ( h y d r o x y p r o p y l o x y ) - Z - C M I V derivative and studied its biodistribution in an animal model, grafted with E R + M C F - 7 tumors, in comparison to Z-CMIV. Hence, the new molecule exhibited a high affinity (0.4 nM) in direct binding in M C F - 7 whole cell assay. Biodistribution studies (from m i n up to 24 h p.i.) showed that target tissues uptake was significantly increased in c o m p a r i s o n to Z-CMIV, even if the activity level in non specific tissues was also higher. Nevertheless, t u m o r / b l o o d ratios and uterus/blood ratios were improved up to 24 h except for the uterus/blood ratio at 24 h. It seems that the positive effect o f the 3-0 blocking was m o r e p r o n o u n c e d for the tumoral tissue than in uterus. Activity levels in urine a n d intestine were greatly reduced. In conclusion, the linkage of a chemical g r o u p in 3-0 position has a significative effect of the targeting properties o f Z - C M I V and could be used to obtain higher levels of radioisotopes in tumoral tissues.

0Su412

OSu414

S. VaUabhaiosula, I. Machac, K. Knesaurek, I. Telsey, H. Lipszyc, D.A. Bastidas, Q.H. Zhao, Mount Sinai Medical Center, New York, NY

F.-O. Denzler F. R6sch, S. M. Qaim, Institut f~r Nuklearchemie, Forschungszentrum Jfilich GmbH, D-52425 J~lich, Germany

NON-INVASIVE IMAGING OF ATHEROSCLEROTIC MACROPHAGE DENSITY BY POSITRON EMISSION TOMOGRAPHY USING F-18FLUORODEOXY-GLUCOSE (FDG): PRECLINICAL STUDIES IN RABBITS

PRODUCTION OF 147Gd FOR APPLICATION AS A RADIONUCLIDIC MARKER IN MAGNETOPHARMACEUTICALS Several gadolinium compounds are used in macroscopic amounts as MRI contrast agents (magnetopharmaceuticals). Their biodistribution is usually measured in animals using lSaGd (Tv2= 241.6 d) labelled analogues. However they cannot be used in humans because of the long half-life of the radioactive marker. The shorter lived radioisotope 1 4 7 Gd (T~2= 38.1 h), which has main y-rays at 229 keY (64%) and 396 keY (34%), on the other hand, may be able to bridge MRI and SPET imaging techniques. Excitation function measurements showed that it is possible to use both the 147Sm(ZHe,3n)- and the ~44Sm(o~,n)-process for the production of 147Gd. The optimum energy ranges were found to be EaHe = 36 ~ 13 MeV and E~ _>27 ~ 13 MeV. A high current Sm203 target capable of withstanding 15 pA beam currents was constructed. A two step method was developed to separate large amounts of the target material ~47Smor 144Smfrom n.ca. isotopes of Eu and Gd In a first step consisting of an amalgam extraction the bulk target material was separated from the n.c.a. Gd-isotopes. The second step entailed the well known cation-exchange technique either on a small glass column or in combination with HPLC, using c~-H[B (0.25 M, pH = 4.7) as an eluent. Finally a purification with either 7 M HNO3 or direct chelate synthesis with DTPA was carried out. The separation could be completed within 5 h with an overall ~47Gdyield of 60-70% without any detectable contamination from Sm or Eu. The batch yield of 147Gdamounted to 370-555 MBq (10-15 mCi), which, combined with the high radionuclidic purity should allow the in vivo evaluation of the pharmacokinetics of Gd-magnetopharmaceuticals in patients and a better estimate of the diagnostic potential of chemically different Gd-MRI agents. Experiments with Gd-DTPA and other magnetopharmaceuticals (e.g. (Gd-DTPA).PL), involving first phantom SPET measurements, are in progress in collaboration with the Institut for Medizin, KFA J(Jlich.

Recent studies have indicated that the maerophage density in atherusclerotic lesions (AL) is an important determinant of plaque vulnerability and risk of rupture. Antoradiographic studies have recently shown that FDG is taken up by macrophages in a tumor tissue. Since active AL are rich in macrophages, we have evaluated the diagnostic utility of FDG to detect AL in two animal models of atherosclerosis; rabbits fed on high cholesterol (HCR) diet and HCR with AL in the abdominal aorta induced by balloon angioplasty (BA). Ten HCR and g normal rabbits (NR) were injected iv with 20-30MBq of FDG. At 5 and 30 rain, PET imaging was performed using a GE brain PET camera. The animals were sacrificed at 40 rain and the aortas were isolated. The percentage injected dose (% I.D.) in different tissues is shown below: Both in-vivo and ex-vivo PET images showed intense focal uptake of FDG in the aortic arch of HCR compared to NR. % I.D./gram % I.D. in aorta Heart Liver Marrow Ascending HCR 0.057~-0.029 0.090-t4).008 0.029-/'0.010 0.055i-0.018 NR 0.059i-0.023 0.060~0.008 0.008.~-0.003 0.008:L-0.002 In a second group of HCR (n=4), 6 weeks after BA and HC diet, dual tracer studies were performed with FDG and Tc--oxidized-LDL (Tc-oxLDL), a radiotracer known to accumulate in ATL macrophages. In rabbits with BA, FDG-PET images showed intense uptake in the abdominal AL compared to the uptake in aortic arch. The FDG uptake in the abdominal aortic lesion was significantly higher (90% more) than in the aortic arch with only fatty streaks. The % II) of FDG (0.018:i: 0.011) in AL was, however, similar to that of Tc-oxLDL (0.013~0.004). Since FDG cleared from circulation i'aster than Tc-oxLDL, AL/blood ratio with FDG, however, was 6-10 times higher compared to Tc--oxLDL. Immanohistopathology clearly documented macrophages in fatty streaks and also enhancement of macrophage density in AL of rabbits with BA. There was a significant accumulation of FDG by liver and marrow in HC rabbits compared to that in normals (RES in HC rabbits was known to be rich in macrophages). These results suggest that maerophages in AL sequester FDG and that PET imaging is potentially useful to detect active AL in high risk patients.

1135

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• Radiochemistry and Radioassays OSu415

0Su417

F. B~nard, A. Alavi, J.B. Alavi, E. Stadtmauer, R.J. Smith, Division of Nuclear Medicine, Department of Radiology and Division of HematologyOncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA.

RJ Davenport, VW Pike, DR Turton, K. Dowsett and KG Poole PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, RPMS, Hammersmith Hospital, Ducane Road, London, W12 0NN, U.K.

WHOLE-BODY FDG-PET IMAGING IN METASTATIC BREAST CANCER PATIENTS BEFORE HIGH DOSE CHEMOTHERAPY WITH STEM CELL SUPPORT.

CHEMOENZYMATIC RADIOSYNTHESIS OF NO-CARRIER-ADDED [CARBONYL-C-11]PROPIONYL-L-CARNITINE FOR PHARMACOKINETIC STUDIES WITH PET

High dose chemotherapy with autologous stem cell support is an expensive treatment that can offer long term survival in carefully selected patients with metastatic breast cancer. Whole-body PET FDG imaging could assess the extent and activity of metastatic disease before and after treatment more accurately than anatomical imaging techniques. We report preliminary results on the utility of PET FDG imaging in this group of patients. METHODS: The whole body PET studies were obtained on 17 patients who demonstrated partial or complete response to conventional chemotherapy, before they underwent high dose chemotherapy. Each study was acquired on the PENN-PET 240H volume imaging scanner with 8 - 10 overlapping 12.8 cm frames covering the thorax and abdomen. Attenuation correction was measured with transmission scans over the chest, and calculated in the abdomen utilizing elliptical body contours. The results of the PET studies were compared with the clinical and other imaging data. RESULTS: 6/17 patients had no evidence of active disease on PET prior to high dose chemotherapy, confirming the effectiveness of previous conventional chemotherapy in reducing tumor burden. 11/17 still had metabolically active metastatic disease, with active disease in 3 patients shown only by PET imaging. Some lesions demonstrated by anatomical imaging studies were metabolically inactive as a result of prior treatment. Thus, PET agreed with other imaging modalities in 13/17 cases, confirmed the clinical impression of responding liver metastases in one patient, and demonstrated unsuspected active disease in the 3 remaining patients. CONCLUSION: FDG-PET imaging contributes additional independent information about disease activity in candidates for high dose chemotherapy with stem cell support. We believe such findings may have significant prognostic impact and may help select optimal candidates for high dose chemotherapy with stem cell support. Further clinical and PET follow-up are planned to establish the appropriate role of FDG-PET imaging in this setting.

PropionyI-L-camiti n e (L-4-t ~nethylammoniu m-3-hydroxybutyrate propionyl ester; PLC) is under investigation as a therapeutic for peripheral artery disease, coronary artery disease and heart failure. The beneficial effects of PLC are assumed to result from the intramitochonddal release of L-carnitine and propionate, with the latter promoting energy production through the tricarboxylic acid cycle. Previously we have labelled PLC with C-11 (tl/2 = 20.4 rain) in its N-methyl group and have studied the pharmacokinetics and fate of the carnitinyl moiety in humans in vivo with PET. We now wish to complement these findings by similar studies of the fate of the propionyl moiety of PLC. For this purpose we set out to label PLC in its carbonyl group with O-11 at high specific radioactivity. Attempts to label PLC by acylating L-camitine with [oarbonyI-C11]propionyl chloride were only successful in the presence of added carrier and suffered from low radiochemical yield (12%, decay-corrected). Hence, we considered alternative chemoenzymatic approaches to labelling from no-carrier-added (NCA) [carbonyl-C-11]propionate. The latter was prepared efficiently and conveniently by a newly devised procedure based on C-11 carboxylation of immobilised ethylmagnesium bromide. Treatment of labelled propionate with acetate kinase and phosphotransacetylase together and then with camitine acetyltransferase gave [carbonyl-C-11]PLC in 14% radiochemical yield (decay-corrected) after HPLC purification at 68 min form the end of radionuclide production (EOB). However, this procedure required tedious HPLC purification of the intermediate, [C-11]propionylCoA. A simple single-pot method was established for converting labelled propionate into [carbonyl-C-11]PLC by using two enzymes, S-acetyl coenzyme A synthetase and carnitine acetyltransferase, in tandem. Purification by HPLC on a strong cation exchange column gave radiochemically and chemically pure NCA [carbonyl-C-11]PLC in 48% overall radioehemical yield at 30 min from EOB, in a form ready for Lv. administration and pharmacokinetic studies. This radiosynthesis is amenable to straightforward automation for the regular production of high radioactivities of [carbonyl-C-11]PLC.

0Su416

OSu418

K. N~ren*, C. Halldin, L. Lundkvist, P. Mtiller, C.-G. Swahn, C. Lehikoinen*. *Radiopharmaceutical Chemistry Laboratory, National PET Center, Turku, Finland and Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden

JA McCarron VW Pike, DR Turton and KG Peele PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, RPMS, Hammersmith Hospital, Ducane Road, London, W12 0NN, U.K. PRODUCTION

GENERAL UTILITY OF [C-11 ]METHYL TRIFLATE IN ROUTINE PRODUCTION OF [C- 11]RADIOPHARMACEUTICALS FOR HUMAN PET STUDIES. The most extensively used labelled precursor for the synthesis of C-11radiopharmaceuticals is [C-It]methyl iodide (MI). Recently, [C-ll]methyl triflate (MT) was proposed by Jewett as a highly reactive alternative to MI. This new precursor has several advantages when compared with MI in the preparation of [C-11]radiopharrnaceuticals by amine methylation (NSgren et al., 1995). We have evaluated MT also for general use in C-11 methylation of amide, thiol and phenol anions and found that MT is compatible with small amounts ofNaOH. MT can thus be used for labelling of [C-11]radiopharmaceuticals by these reactions. The only limitation that we have observed so far concerns the ehoise of unlabelled precursors. Hydrobromide salts are not suitable, as MT reacts with bromide ion to form [C-11]methyl bromide. In these cases, the precursors have to be either liberated into the free amine form or converted to another, less reactive salt. The high reactivity of MT enables C-11 radiolabelling to be performed rapidly at RT or 60°C which simplifies automation of the labelling procudure. We have during the last 18 months routinely used MT for the remote controlled preparation of C-11 labelled ]3-CFT, NNC-756, Deprenyl, MHED, NMSP, Flumazenil and Methinnine for human PET studies. Our experience is that MT gives better results than MI with regard to yield, specific radioactivity and, in the case of [C-11]methinnine, a lower degree of racemization. K. N&gren el aL, (1995) Nucl. Med Biol. 22:235-239.

1136

OF THE 5-HT1A

RECEPTOR

RADIOLIGAND,

[CARBONYL-C-11]WAY-100635, VIA NOVEL C-11 CARBOXYLATION OF AN IMMOBILISED GRIGNARD REAGENT WAY-100635, N-(2-(4-(2-Methoxyphenyl)-l-piperazinyl)ethyl)-N-(2pyridyl)-cyclohexanecarboxamide, tabelled in the carbonyl position with C-11 (tl]2 = 20.4 min) is a highly effective radioligand for the delineation of 5-HT1A receptors in human brain in vivo with PET. In order to pursue PET studies with this radioligand a simple, efficient and reliable method for production is required. Here we report a novel and effective procedure based on C-11 carboxylation of an immobilised Grignard reagent. Commercial cyclohexylmagnesium chloride is coated onto the inner surface of a narrow polypropylene tube. Cyclotron-produced [C-11]carbon dioxide is passed into the cooled tube (0 to - 5°C). The radioactivity traps efficiently (> 95%). A dilute solution of thionyl chloride (5 ~L) in tetrahydrofuran is then passed through the tube to release radioactive acid chloride into a vial containing descyclohexanecarbonylWAY-100635 (3.5 mg) and triethylamine. The vial is sealed and heated to 70°C for 5 min. [CarbonyI-C-11]WAY-100635 is separated by sample enrichment and reverse phase HPLC and formulated for intravenous injection by removal of solvent and dissolution in saline. The simplicity of this method has enabled easy remote control based on the use of a Peltier cooling device, solenoid operated valves, a single syringe drive and a microrotary evaporator, controlled by a rotary switch and programmable logic controller. The radiosynthesis takes 45 min and gives [carbonyl-C-11]WAY-100635,ready for intravenous injection, in high radioactivities (typically, 80-120 mCi) with 99% radiochemical purity and with a specific radioactivity of - 6.5Ci/ptmol at the end of synthesis. The immobilised Grignard reagent has several advantages for the preparation of the involatile [C-11]acid chloride. Since only small amounts of reagents are used, no separation of the [C-11]acid chloride is required. Moreover, only a small amount of precursor is required for efficient reaction (acylation radiochemical yield, 70% decay-corrected). The technique is also applicable to the preparation of other involatile [carbonyl-C-11]acid chlorides as labelling agents, such as [carbonyl-llC]benzoyl chloride.

• Radiochemistry and Radioassays OSu419 C. Gilissen, G. Bormans, T. de Greet, A. Verbruggen Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U.Leuvert, UZ Gasthuisberg, B-3000 Leuven, Belgium IDENTIFICATION OF LONG-LIVED RADIONUCLIDIC IMPURITIES IN CYCLOTRON PRODUCED 18F AND 13N The purpose of this study was to detect and identify long-lived radionuclidic impurities in 18F and 13N productions, which could be produced by 10-MeV proton irradiation of target materials in our IBA 10/5 cyclotron. After a waiting period of 5 days to allow sufficient decay of respectively 18F and 13N, gamma spectra from the irradiated liquids (resp. 180-H20 and 160-H20) were acquired during 3 hours on a coaxial germanium detector coupled to a Canberra multi-channel analyser. Analysis of the obtained spectra allowed to identify 52Mn, 56Co and 96Tc as radionuclidic impurities in 18F and 13N productions (Table). These contaminating radionuclides are generated by proton activation of some of the stable isotopes present in the Havar® target window foil with subsequent dissolution in the target liquid. Impur reaction

t1/2

52Mn

52Cr(p,n) 52Mn

56d

56Co

59Ni (p,tx) 56Co

78.76 d

96Tc

96Mo (p,n) 96Tc

4d

T-energy in keV (ori* 180-H20; el-i* 160-H20) 511 (10;20),744(2;21), 935 (2;16) 1434 (1;9) 511 (10;20), 846 (17;16), 1038 (2;2), 1238 (10;7), 1360 (0.5;0.6) 312 (2;2), 771 (20;2), 806 (13;1.5), 842 (17;1), 1119 (2;0.5)

*observed relative intensity (%) We were unable to identify any long lived radionuclide originating from activation of the target metal (resp. Ag (18F) and A1 (13N)). Investigations are ongoing to determine the relative amounts of these radionuclidic impurities in the 18F and 13N productions.

0Su420 M. Holschbach*, T. rein ~, W. Wutz*, M.Sch011er*,K.Hamacher*, R. Lewis*, U. Schwabe'~, G.St6cklin*, R.A. Olsson~* *lnstitut f0r Nuklearchemie, Forschungszentrum J01ich GmbH, 52425 J01ich; #Pharmakologisches Institut der Ruprecht-Kads-Universit~it Heidelberg, 69120 Heidelberg; *Present address: Department of Internal Medicine, University of South Florida, Tampa, FL, 33612 N.C.A. RADIOLABELLED ADENOSINE At RECEPTOR ANTAGONISTS AS LIGANDS FOR PET AND SPET

The clinical impedance of the A1 adenosine receptor (A1AR) makes it an attractive target for radJonuclide imaging. The A1AR is neuromodulatory, inhibiting neuronal firing and synaptic transmission; in the brain those tonic inhibitory influences may prevent seizures. Even brief periods of hypoxia can reduce receptor density greatly. Recent work indicates that the AIAR plays an essential role in cerebral protection by ischemic preconditioning. Four derivatives of the highly selective and high affinity A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, I~ 0.17nM), modified in the 3-position of the purine system, have been synthesized, namely 1-propyl-3-methyl-, 1, 1-propyl-3-(3-fluoropropyl)-, 2, 1-propyl-3(2-fluoro-propyl)-, 3, and 1-propyl-3-(E-3-iodoprop-2-en-l-yl)-8-cyclopentylxanthine, 4. In vitro binding studies using calf codex membranes indicated high affinities and good selectivity for the A1AR (K~ values were 0.31, 0.18, 0.09 and 0.23 nM for compounds 1-4, respectively). Radiolabelling on the no carrier added (N.C.A.) level with either carbon11, fluorine-18 or iodine-123 gave the ligands 1"-4" in excellent radiochemical yields (80-95%) and high radiochemical purities (>98%). The specific radioactivities were in all cases higher than 103 GBq/IJmol (2.8 Ci/pmol). Preliminary in vivo evaluation using NMRI mice revealed good stability of the radiolabels and high brain uptake for all ligands (2.5% id/g 5 min p.i., decreasing to 1.5% id/g 60 min p.i.). Preloading and displacement experiments using cold DPCPX (1 mg/kg mouse 20 min before tracer application) in all cases led to a significant decrease in brain uptake (70-90%), indicating high specific binding of these reversible receptor ligands.

OSu421 I,, Besmt. M.C. Petit-Tabour, S. Guillouet, L. Barrr, B. Landeau, A.R. Young, X. Blaizot, E Dauphin and J.C. Baron. CEA/DSV/DRM, INSERMU320, CNRS URA 1829, CYCERON, CENTRE E BACLESSE, UNIVERSITEDE CAEN, Caen, France.

co

= m

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IN VlVO EVALUATION OF 11C-S21007, A PUTATIVE PET RADIOLIGAND FOR CENTRAL 5HT3 RECEPTORS (5HT3-R), IN THE BABOON. PET imaging of the semtonergic 5HT3-R would be of great interest in both neumloglcand psychiatricdimmers.$21007, a novelhigh-aflrmitypartial agonist at 5HT3-R was mdiolabeled with llC-benzyl iodide. Pilot studies in the rat showed that 11C-$21007 readily crosses the blnod-brain barrier since only the parent ligand was detected in brain up to 40 rain after i.v. injection. As the density and discrete localization of the 5HT3-R in the rat brain, would make it difficult to characterize binding in vivo to these sites in the rodent, we evaluated the potentialof 11C-$21007 as a 5HT3-R radioligand in the anesthetized baboon. Four high-resolutiondynamic (0-90 min) coronal PET studies were performed in the baboon after i.v. bolus injection of trace amountsof 11C-$21007 (SRA= 200-300 Ci/mmol).Anatomicallyprecise regionsof interest were obtained from co-registered MRI scans, llC-kinetics were determined in whole blood and plasma; the plasma time-activity curve ffAC) was corrected for llC-labeled metabolites determined by thin layer radiochromatography. High l 1C-uptake (~lO % ID/L at t=2O rain) was seen in the hippocampus (Hp) and area postrema (AP); both richly endowed with 5HT3-R. However, this increased uptake was not meaningfully different from that observed in the cerebellum (C'b,a regionknown to be virtually devoid of 5H'I3-R) at any time. Data (0-90rain TACs) werefurtheranalyzed by modellingprocedures according to beth non-linearleast square (NLSQ) and Logan-Patlak analyses, with the Cb taken as referencestructure and the vascularfractionfilled. NLSQ on Cb showed that a 3-ClXmodel [i.e., differentiatingfreeligand and non-specific(NS)binding] was more appropriatethan a 2-Cpt model. The k5/k6 ratio was higher than that generally found with successfulligands, consistent with a high NS binding of 11C-$21007. Both the Hp and AP TACs could be fitted according to a 3-Cpt NLSQ model, but not with a 4-Cpt model, suggestinglack of detectable specific binding. Accordingly,Logan-Patlak slopeswere essentiallyideantical among the Co, AP and Hp. Neitherpresaturationnor displacementwith cold $21007 (lmg/ kg injected i.v. 10 min before or 10 min after l 1C-$21007, respectively, n=l baboon each) provided evidence for specific binding in Hp or AP. ThesePET findingsobtainedfromdiscretebrainregionsin the non-humanpinnate suggest 11C-$21007 is not a suitable ligand for imaging of the 5HT3-R.

0Su422 R. S e n e k o w i t s c h - S c h m i d t k e , R. T r u c k e n b r o d t , M. Herz, K. H a m a c h e r * , G. St6cklin, M. Schwaiger, Nuklearmedizinische Klinik der TU M~nchen,

* I n s t i t u t f~r N u k l e a r c h e m i e ,

KFA J~lich

E V A L U A T I O N OF 4- [F-18] F L U O R O P R O L I N E AS A T R A C E R F O R C O L L A G E N S Y N T H E S I S IN 3 D I F F E R E N T T U M O R M O D E L S

Aim: Collagen is the main component of structural proteins and is also synthesized to a high degree in tumors. We therefore used 3 tumor models known to have different collagen content to evaluate F-18-fluoroproline as a tracer for collagen synthesis. Methods: (2S,4R)-4-[F-18Ifluoroproline was prepared by no-carrier-added nucleophilic fluorination starting from the corresponding N-Boc -4 -O-tosyl -hydroxyproline-methylester with radiochemical yields of 30-40%. Mice bearing 2 carcinoma with different collagen content as indicated by histology and inrma~ohistochemistry or an osteosarcoma were injected i.v. with 1.5 MBq F-18fluoroproline or H-3 -proline and distribution was determined at 1,2 and 4 hrs p.i.. R e s u l t s : The biodistribution data showed that the highest activity concentration was always found in tumor tissue. Osteosarcoma with the highest collagen content also exhibited the highest proline uptake of 9 %/g both for F-18 and H-3 labelled proline 2 hrs p.i.. Both mamTmry carcinoma showed an uptake of 5.6 and 4.7 %/g, respectively at 2 hrs p.i. depending on the collagen content. In blood and all other tissue even those with high collagen content uptake values between 2.4 and 4.5 %/g were found. The tumor/blood ratio reached 2.2 at 2 hrs. C o n c l u s i o n : [F-18]fluoroproline is a promising tracer for the detection of newly synthesized collagen and may also be useful for the evaluation of other diseases with a high collagen synthesis rate such as Lung fibrosis or liver cirrhosis.

1137

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t~

6

• Radiochemistry and Radioassays OSu423

OSu425

A.van Waarde, T.J.Visser, P.H.Elsinga, B.M~Oe Jong, J.Kraan, T.W. van der Mark, K.Ensing, J.Pruim, A.M.J.Paans, W.Vaalburg, PET Center, Groningen University Hospital, The Netherlands

M. Eisenhut, A. Mohammed, C. Nicholl, U. Titsch. Deptartment of Nuclear Med., University of Heidelberg, Germany

POSITRON EMISSION TOMOGRAPHY OF B-ADRENOCEPTORS IN THE HUMAN BRAIN USING S-1 '-PSFIFLUOROCARAZOLOL S-l'-[~SF]fluorocarazolol (1), a non-subtype-selective f~-adrenoceptor antagonist, is lipophiiic and therefore potentially suitable for f~-adrenoceptor imaging in the human brain, where l$-adrenoeeptors have not yet been visualized. Moreover, in vitro binding assays showed that I is rather selective for the I~ (pK~ 9.4) and B2 (pK, 10.0) subtypes as compared to 5HT1A (pK~ 7.4) and 5HT~B (pK~ 8.1) receptors. Animal studies were carried out to examine the suitability of I for in vivo r&adrenoceptor imaging. Blocking experiments in rats using nonselective (propranolol, CGP12177, isoprenaline), 13~-selective (ICI 89,406, CGP 20712A) and r&2-selective (ICI 118,551, procatarol) drugs indicated that uptake of radioactivity by brain, heart and lungs reflects binding of I to g-adrenoceptors. Stereoselectivity of the in vivo binding was demonstrated by treatment of rats with S- and R propranolol before injection of the radioligand. Saturation experiments in which I was coinjected with various amounts of unlabeled S-1' fluorocarazolol indicated receptor densities of 6.0 (heart), 21 (lung), 9.8 (cerebral cortex) and 7.6 pmol/g (cerebellum). Dynamic PET studies of the brain were performed in 5 healthy volunteers. Uptake of radioactivity delineated grey matter and was particularly high in cingulate cortex and striatum. Low uptake occurred in thalamus and the lowest uptake was observed in white matter (corpus callosum). After oral administration of pindolol (3 x 5 mg during 12 h) uptake was strongly (> 2 fold) reduced and it became homogeneous throughout the brain. PET scans of the thorax in 5 other volunteers clearly showed both heart and lungs; uptake in these tissues was blocked after oral administration of pindolol. Thus, I seems a promising radioligand for in vivo studies of f~-adrenergic receptors, It is the only ligand available for imaging of cerebral B-adrenoceptors which are altered in depressed patients and respond to treatment with antidepressants.

RADIOIODINATED N-SUBSTITUTED METHOXY-, HYDROXYAND AMINO-BENZAMIDES FOR MELANOMA IMAGING: COMPARISON WITH 1-123-BZA and 1-123-IBZM. Syraheses of 28 radiolabeled new 4-methoxy-,4-hydroxy-and 4-amino-N-(alkylaminoalkyl)benzamides were performed. The compounds were tested in order to find out whether polar phenyl groups affect melanomauptake and melanoma to non-target tissue ratios. As animal model we used C57B16 mice with B 16 melanoma. Structural variations investigated so far were restricted to a numberof amide substituents and the position of radioiodine at the phenyl group. As comparedto 123I-BZAseveral of the new compoundsshowedimprovedmelanomato non-target tissue ratios indicating promissingscintigraphiccontrast. Due to unfavourable biological characteristics u3I-IBZMprovedto be less suited for melanoma imaging. In this study the followingthree compoundsranked amongthe best: z ~ , ~ ~

NR'-(CI{~) -R

#

X~

X~

CZNR'

n

R

1

H2N MeO 5J~l 1311 MeO H 1311 MeO H

CONH

2

Et2N

2 3

#

%lD/g Melanoma 1h/6h

Blood 1h/6h

1 2 3 ~z~I-BZA I=°I-IBZM

5.5/4.0 5.5•4.2 6.7•3.5 2.7•6.7 3.1/2.0

26/165 271109 32/88 10/84 4/2

X2

CONH 2 CONH

Melanoma/Non-Target Tissue Lung Liver Muscle 1h/6h 1h/6h I h/6h 5/71 3/24 10/43 <1/11 1/1

1/10 2/6 2/13 <1/2 2/3

l-Piperidyl

2

24•297 171144 37/123 4/75 9/10

EI2N

Brain 1h/6h 43•478 19/321 67•350 3•42 3/20

With penyl substituentsX2 = OH, NH2 and several mixed disubstituted benzamides the above shown results were not attained. For this ainmal model radioiodinated 4-methoxybenzamidesproved, therefore, to be optimal. First clinical resuits using benzamide 3 in patients with melanomametastasesconfirmedexcellent melanoma to non-target tissue ratios in humans.

OSu424

OSu426

F. Koumanov, C. Henry, C. G h e z z i , C. Morin, J.P. Mathieu, M. Vidal, J. de L e i r i s a n d M. Comet. LER, UPRES A CNRS 5077 Grenoble University, France.

D. W, M~Pherson, H. Luo*, A. L. Beets, and F. F. Knapp, Jr.. Nuclear Medicine, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN, USA.

123I-6-DEOXY-6-IODO-D-GLUCOSE (6DIG), A P O T E N T I A L T R A C E R OF G L U C O S E TRANSPORT. A s s e s s m e n t of in vivo g l u c o s e t r a n s p o r t is of major c l i n i c a l importance since a l t e r a t i o n s in glucose transport are a s s o c i a t e d with various p a t h o l o g i e s . An analogue of g l u c o s e l a b e l e d w i t h 123 Iodine in position 6 has been s y n t h e s i z e d : 123I-6-deoxy-6-iodo-D-glucose (6-DIG) . Its b i o l o g i c a l b e h a v i o u r was c o m p a r e d to that of 3O-methyl-D-glucose (30MG), a r e f e r e n c e t r a c e r of g l u c o s e transport, on two b i o l o g i c a l models : human e r y t h r o c y t e s in s u s p e n s i o n and n e o n a t a l rat c a r d i o m y o c y t e s in culture. In e r y t h r o c y t e s in suspension, the k i n e t i c s of u p t a k e of 6DIG a n d 3 O M G are similar, the u p t a k e is m a x i m a l from the first minute a n d the a c t i v i t y remain stable for up to 60 minutes. The a d d i t i o n of cytochalasine B (an inhibitor of glucose transport) in the suspension medium caused a constant i n h i b i t i o n of the two t r a c e r s u p t a k e of approximately 95%. A d d i t i o n of D - g l u c o s e (5-40 mM) d e c r e a s e the uptake of 6DIG a n d 3OMG in a dose-dependant manner (p<0,001) . The m o l e c u l e s have been subjected to a washout from the erythrocytes : 6DIG and 3OMG are r e l e a s e d v e r y q u i c k l y : after 5 minutes, the a c t i v i t y p r e s e n t in the cells was r e s p e c t i v e l y 7.18 ± 0.21% a n d 5.54±0.26% of the initial activity. The a d d i t i o n of c y t o c h a l a s i n e B slowed down this release (p<0.001) b e t w e e n 1 and 60 minutes. In n e o n a t a l rat c a r d i o m y o c y t e s in culture, insuline (I00 IU/I) i n c r e a s e d the uptake of 6DIG a n d 3OMG in the cells up to 15 minutes. The biological behaviour of 6DIG is t h e r e f o r e v e r y close to that of 3OMG, and it could be u s e d as a t r a c e r of g l u c o s e t r a n s p o r t w i t h SPECT. 1138

EVALUATION OF IODINE-125 E-(R)-I-METHYL-PIPERIDIN-4-YL o~-HYDROXY-o~-(1-IODO- 1-PROPEN-3-YL)-ct-PHENYLACETATE. A NEW LIGAND FOR SPECT IMAGING OF mAChR.

The benzilic ester of N-methylpiperidine has long been established as a potent antagonist of muscafinic acetylcholinergic receptor complex (mAChR). Labeled with carbon-11 on the piperidinyl nitrogen, 1 has been investigated for the evaluation of mAChR by PET. We have shown the replacement of a phenyl ring of QNB with an iodoallyl moiety allows the ligand to retain a high affinity for mAChR. We prepared (R)-E-3 and investigated its potential for use in SPECT. R-E-2 was prepared by transesteridfication of the ethyl ester with 4-hydroxy- 1-methylpiperidine followed by l~eatmentwith tributyltin hydride. (R)-E-2 was reacted with iodine in chloroform afforded (R)-E-3. Treatment of (R)-E-2 with sodium iodide-125 in an acidic 3% hydrogen peroxide solution followed by C- 18 Sep-Pak and HPLC purification afforded [I-125]-(R)-E-3 in 72 % radiochemieal yield. A study in rats (n=3) showed substantial uptake of activity in the cortex (0.76 % ]D/g) and striatum (0.72 % ID/g) and a cortex and striatum to cerebellum ratio of 2.3:1 and 2.2:1, respectively, at 60 min. These initial results suggest that (R)-E-3 is a potential ligand for the study of mAChR by SPECT.

{Bu)~Sn 1

I~ R-E-2

R-E-3

Research supported at ORNL by OHER, U.S. DOE under contract DE-AC0596OR22464 with Lockheed Martin Energy Research Corp. *DOE Hollander Postdoctoral Fellow.

• 0Su427 J.-E. Ryser, P. Bl~uenstein. I. Novak-Hofer, U. Roetcke, B. Kaser-Hotz, N. Crompton, N. R~my, R. Weinreich and P.-A. Schubiger. Paul Scherrer Institute, Villigen and University of Zfirich, Switzerland. Br-76-BROMODEOXYURIDINE: COMPARISON WITH 1-131-1ODODEOXYURIDINE IN MICE AND FIRST PET MEASUREMENT IN DOGS The advantages of 76Br-BrdU are the half life and positron emission rate of 76Br and biological parameters which suggest that 7SBr-BrdU could be the best candidate tracer for the imaging of cell proliferation by PET. Two labelling protocols were tested and the superior one optimised, namely the Iodogen ® method (yield up to 40%) and copper assisted iodine bromine exchange (yield less than 5%). The reason .of this difference was an increasing pyrolysis at higher temperatures. The utilisation of *BrdU (76Br- or 77Br-BrdU) as DNA precursor by tumour cells growing in vitro was higher than that of 131 I-IdU. The distribution of the same tracers showed a higher recovery (%lD/g) of *Br in all organs except the thyroid, 18 hours after their injection into mice with a tumeur xenograft: tumour blood lung kidney liver muscle car- skin cass *BrdU 4.37 4.49 4.31 3.50 1.25 0.77 1.34 2.30 *ldU 0.48 0.29 0.36 0.25 0.15 0.06 0.20 0.36

intest, spleen wall 6.73 12.5 1.89 2.74

Preliminary experiments were done to analyse the incorporation of *BrBrdU into DNA. The liver did not contain significant amounts of DNA bound activity, while the DNA of the spleen contained about 30% of the total activity of this organ. This shows that the higher uptake of *BrdU compared to 1311-IdU shown in the table is due to a higher incorporation into the DNA as welt as more non-specific retention. The activity in the blood was analysed at different time points after injection. Already 15 min p.i. it was present in the form of bromide (90%) with small amounts of BrdU (8%) and bromo-uracil (1%). The results of the first PET studies in dogs with spontaneous tumours and a comparison with the tumours T-pot will be presented. The obtained images demonstrate that the tumour is well visible despite the rather high background of bromide in the blood. This work is suDDorted by the ,,Krebsforschung Schweiz".

0Su428 K. and (i) (2)

Chavatte(1), M. Gysemans(2), J. Mertens(2) A. Bossuyt(1). AZ-VUB,Dept. Nucl. Medicine,Brussels,Belgium VUB-Cyclotron,Brussels,Belgium.

IMPROVED SYNTHESIS AND II23-~-METHYLTHYROSINE.

RADIOSYNTHESIS

OF

L-3-

L-3-II23-~-methylthyrosine is an interesting radiopharmaceutical for the visualisation of brain tumors with SPECT. Clinical application requires the non-radioactive reference product. The rather time consuming s y n t h e s i s earlier described (i) yielded high amounts of diiodothyrosine and the crystalisation from an HCI solution failed due to the high solubility in acidic conditions. Here an improved fast synthesis is proposed: the amount of diiodothyrosine is limited to <15% by using a iodine/substrate ratio of 1.25 in ammonia/ethanol 50/50 v/v at 0°C. Evaporation under vacuum of the solvent is also achieved at 0°C. This avoides demethylation. Washing of the residue with ice cold water results in an overall yield of 70% of pure I-~-methyl-thyrosine within 2 hours. The diiodothyrosine is found in the eluate. Radioiodination is performed by electrophilic substitution using Iodogen as oxidant. iml of PBS buffer containing respectively 0.5mg of substrate, l~g of NaI(to obtain the required specific activity) and the radioiodide solution is transferred to a flat bottom vial coated with Iodogen and cooled to 0°C in a closed lead container filled with water/ice and vibramixed for 3 min.. A labelling yield of > 98% is obtained. Purification on and recovery from a SepPak yields 80% of L-3-Ii23-~-methyltyrosine with a r a d i o p h a r m a c e u t i c a l p u r i t y > 99%. l . K r u m m e i c h et al, P e r g a m o n V o 1 4 5 N ° 9 , 1 9 9 4 .

Radiochemistry and Radioassays

0Su429 K.A. Ber=strtm t,2, C. Halldln*, H. Hall*, J. Hiltunen 3, H. Ro t, N. Ginovart*, C-G Swahn*, D. McPherson4, F.F. Knapp Jr. 4, S. Larsson*, P.O. Schnell*, L. Farde ]. IKarolinska Institutet, Sweden; 2Kuopio Univ. Hospital, SMAP Medical Teeh., Finland; 4Oak Ridge Nail. Lab., USA.

C 0 |m =l=a

C

I N VITRO CHARACTERIZATION AND I N V/VO METABOLIC

STUDIES OF 1-125 AND 1-123 LABELLED E-(-,-)-IQNP: A NEW RADIOLIGAND FOR VISUALIZATION OF M1 MUSCARINIC ACETYLCHOLINE RECEPTOR IN BRAIN

E-(-,-)*1-Azabicyclo[2.2.2]oct-3 -yl (x-hydroxy-ct-( 1-iodo-1-propen-3-yl)~x-phenylacetate, (E-(-,-)-IQNP) has a high alfmity and selectivity to M1 muscarinic acetylcholine receptor (mAchR) subtype according to in vitro and in v i m studies in rats. In the present study 1-125 end 1-123 labelled E-(-,-)-IQNP were prepared for in vitro autoradiographic studies in human and for in vivo SPET and metabolic studies in Cynomolgus monkey. The tributylstannyl derivative of E-(-,-)-IQNP was labelled with either no-carrier-added 1-125 or 1-123 by the chloramine-T method with a radiochemical purity higher than 99%. The SPET imaging was performed with Trionix gamma camera with low-energy collimators. The metabolite pattern of E-(-,-)-[I-123]IQNP in monkey plasma was determined with a gradient HPLC method. In vitro autoradiography with E-(-,-)-[I-125]IQNP demonstrated a binding in MI mAchR rich regions such as the neocortex and the striatum in human brain which was displaceable by biperiden (1 IxM) (a selective ligand for MI subtype). In vivo SPET studies with E-(-,-)-[I-I23]IQNP demonstrated highest accumulation in the monkey neocortex. A major more lipophilic radioactive metabolite appeared in plasma rapidly at~er injection. The percentage of unchanged E-(-,-)-[I-123]IQNP was less than 2% at 10 min aRer injection. The lipophilic metabolite has the same retention time using HPLC as the free acid of E-(-,-)-IQNP. In conclusion, E-(-,-)-[I-123]IQNP binds in vitro in human brain M1 mAchR subtype rich regions. The rapid hydrolysis in vivo may hamper its use in SPET imaging.

0Su430 F. Mokler ! '2 * * , Q. Lint's~ H. Luo 1~, D. W. McPhersonI, K. R. Ambrosel, A. Bockisch2'4, J. Kropp5 and E E Knapp, Jr. I. !Nuclear Medicine, Oak Ridge National Laboratory (ORNL), USA, 2Univ. Mainz, FRG, 3Xavier Univ., New Orleans, LA, USA, 4Univ. Essen and 5Univ. Dresden, FRG.

DUAL-LABEL STUDY WITH [I-125]-3R AND [I-131]-3S-BMIPP DEMONSTRATES SIMILAR METABOLISM OF THE TWO ISOMERS IN RAT TISSUES. Clinical SPECT by comparison of regional uptake of racemic [1-123]-3R,S-BMIPP and flow tracers (Sestamibi, TI-201) can identify post-ischemic viable myocardium. Since 3R-BMIPP has higher heart uptake in rats than 3S-BMIPP, a [I-125]-3R/[I-131]*3S-BMIPP mixture was administered to rats to evaluate the relative metabolism of the two isomers. Groups (n = 3/ group) were sacrificed after 15, 60 and 180 min, and urine and feces collected from group 4. Blood, heart, liver, lungs, kidney and urine were Folchextracted. I- 125/I- 131 distribution in lipid, aqueous and pellet samples were similar. Distribution of 1-125/I-131 by TLC of lipid extracts (hexane:ether:HOAc, 70:30:1 ) was similar, with incorporation into FFA and TG. HPLC of FFA (C18) also showed similar 1-125/1-131 profiles, corresponding to BMIPP, (x-methyl-C14 (AMIPT), and the C12 and C6 linear catabolites. By TLC, urine I- 125/1-131 chromatographed with hippuric acid. HPLC of acid-hydrolyzed urine gave a single I-125/1-131 component with the same RT as 2-(p-iodophenyl)acetic acid (PIPA), the final BMIPP catabolite. HPLC of lipids from base-hydrolyzed TG from heart, showed 1-125/1131 short- and intermediate chain acids, with only low levels in BMIPP. These results show that 3R- and 3S-BMIPP are metabolized similarly in rat tissues. Higher myocardial uptake of 3R-BMIPP (20-30 % > 3S) may reflect differences in membrane transport of the 3R- and 3S-isomers. "Operated by OHER, the U.S. DOE under contract DE-AC05-96OR22464 with Lockheed Martin Energy Research Corp.; *'Heinrich J. Klein Foerderstiftung in Mainz, FRG; 1DOE/HBCU Program at ORNL; ~DOE Hollander Postdoctoral Fellow at ORNL.

1139

m

L-

0

• Radiochemistry and Radioassays 0Su431

0Su433

F. Moati (1), C. Loc'h (2), G. Vassal (3), M.H. Bourguignon (2), C. Ghezzi (4), C. Morin (5), M. Ottaviani (2), C. Coulomb (2), C. Fuseau (2), D. Fagret (4), M. Vidal (5), A. Desgrez (1), B. Maziere (2). 1 Mddecine Nucldaire Le Kremlin Bic&re, 2 SHFJ-CEA Orsay, 3 IGR-URA 147 Villejuif, 4 CNRS 1287 Grenoble, 5 CNRS 332 Grenoble - France.

V. de Beco, A. Starzec, M. Duran Cordobes, J.C. Kouyoumdjian, J.L. Moretti. Laboratoire de Biophysique et des Biosignaux, Institut d'Oncologie Cellulaire et Mol6culaire H u m a n e , Bobigny-Paris 13, Henri Mender Cr6teil, France.

123I 6-1ODO-6-DEOXY-D-GLUCOSE (6IDG) AS A POTENTIAL TRACER OF GLUCOSE TRANSPORT.

SESTAMIBI BINDING 170 G L Y C O P R O T E I N .

6IDG is a glucose analog which is carried into the cells by glucose transporters. Since the substitution of the 6 hydroxy group with an iodine atom blocks the phosphorylation by hexokinase, 61DG could be used to assay glucose transport. 61DG labelling was performed by 123-127 iodine isotopic exchange, free iodine removed by anionic resin and the radiochemical purity assessed by RP-radio-TLC (ACN/H20, 33/66) was 90%. Biodistributions of 61DG were obtained in Wistar rats (n = 28) from 5 to 90 min after the injcction of 1- 3 MBq (0.2 to 0.6 ~mol) 1231-61DG into the tail vein. The fraction of injected dose per gram (% ID/g) and organ/blood radioactivity concentration ratios were calculated. The brain was dissected in eight specific regions. In one rat administrated with 35 MBq of 6IDG, an autoradiographic study was performed lh postinjection. Human tumor xcnografts in nude mice (n=10) were used as a model of increased glucose transport (Glut-l). The following subcutaneous tumors were tested: glioma (XN88, 6 weeks growing), medulloblastoma (XN33 and XNll respectively 10 and 14 weeks) and PNET (XN34, 4 weeks). 12316IDG biodistributions (150 to 250 nmol injected) were studied in glioma from 5 to 120 rain (n=5), at one and two hours for the other tumors. Tumor/brain ratios were calculated. Kinetics of all the organs, except muscle and brain, follow blood kinetic (mean of organ/blood ratios = 1.01 + 0.14). In brain and muscle, the 6IDG uptake increased up to 20 rain, and remained in plateau for one hour. Biodistribution and autoradiography studies showed that 123I6IDG radioactive regional brain concentrations were homogeneous; at any time of observations, coefficients of variation were less than 9 %. In mice, a higher radioactive concentration was found in xenograft tumors than in brain. All tumor/brain ratios were positive (mean = 1.5 -+ 0.15), and the maximum (1.7) was obtained at 20 min. As the 6IDG uptake in muscle, brain and brain tumors is Iikely due to the expression of Glut-1 and Glut-5 transporters, 123I-6IDG appears to be a potential radiotracer for glucose transport measurement.

Previous studies realized in our laboratory have shown that the Tc99m Sestamibi (M1BI) uptake in human carcinoma cell lines is correlated to the presence of the multidrug resistant gene related protein (Pgp 170). For the human breast cancer MCF7 wild-type cell, we observed 13,9+1,9% uptake, while for the resistant type (Doxorubicine maintened) MCF7/Dox, the MIBI uptake was 0,7+0,6%. Concerning the human leukemic lymphoblastic cell lines K562, we observed that the wild-type cells concentrated 30,6+2,8% of MIBI, whereas the Doxorubicine treated cell lines exhibited only 0,7+0,1% MIBI uptake. As we have observed that Tc-99 MIBI is toxic for cell culture, we have analyzed in the present study the MIBI binding on cell membrane preparation. The total binding was determined at 37°C for 1 hour in the presence of lnM MIBI. Non specific binding was determined by addition of I00 nM Tc-99 MIBI. Specific binding was calculated by substraction (total minus nonspecific). Our data indicate that the specific binding of MIBI is three times higher with membrane preparation isolated from Doxorubicine treated ceils compared to wild type cells. This data suggest that Tc-99m MIBI is a possible substrate of Pgp170 protein.

0Su432

0Mo434

C. Botti, D.R.M. Negri, S. Canevari, V. Ramakrishna, S. Nerini-Molteni, L. Maffioli, A. Bogni, C. Pascali, F. Crippa, C. Lombardo, F. Remonti, E. Seregni, E. Bombardiefi NationalCancer Institute of Milan

B.Johannsen, H.-J.Pietzsch, M.Scheunemann, R.Berger, H.Spies, R.Syhre, Ch. Schenker, P.Brust. Inst. Bioanorg. u. Radiopharm. Chemie, FZR Rossendorf, Germany

LABELLING OF ACTIVATED LYMPHOCYTES FOR ADOPTIVE IMMUNOTHERAPY W I T H DIFFERENT RADIOTRACERS Aim of the study: adoptive immunothempy is a promising strat~y for antincoplastie treatment. Few data are available regarding the biodistributiun of autologous lymphocytes injected in cancer patients. Radiolabelled lymphocytes could provide this information. In this study we evaluated different methods for in vitro radiolabellingof autologous lymphocytes. Methods: autologous T-lymphocytes coated with a bispecifie monoclonal antibody (Movl8/antiCD3) were labelled with 99mTc-cxametazime, l l l I n oxinate and 18F-FDG. 1150 MBq of 99mTe-HMPAO (Ceretec, Amersham Int., Italy), 55MBq of 111In-oxine (DRN4908, Byk Gulden, Italy) and 55 MBq of 18F-FDG were added to 2,5x10 s cells. Cells were radiolabelled in proper media at 37°C for 25..45 rain. Unbound activity was removed by washing with autologons plasma. Results and discussion: the mean labe!ling efficiencies obtained using 99mTcHMPAO, lllIn-oxine and 18F-FDG wore 31% (range: 30.5-31.5%), 68% (range: 59-75%) and 64% (range: 53-70.5%), respectively. As regards the stability of the radiocomplexes inside the cells, our results indicate that the stability of 99mTe-HMPAO and 18F-FDG are inferior to that of 11 lIn-oxine, as demonstrated by the increasing mean release of the radioisotopes with time (44% of initial cell-bound 99mT¢-HMPAO activity vs. 12% for lllIn-oxine after 240 rain. and 55% of the initial cell-bound 18F-FDG is released after rain.). The radiolabelling procedures no alteration in lymphoeytes viability (9095% using 99mTe-HMPAO and 11 lIn-oxine after 240 rain4 80-85% afetr 150 rain. using 18F-FDG). However a marked reduction of eytotoxie activity against the target cells (ovarian IGRO cell line) was observed when 18F-FDG and 11 lln-oxine were used as label agents, respectively. Only in the case of 99mTcHMPAO labelling the eytotoxie activity was not altered. In addition a strogn reduction (70% on average) of the proliferation rate occurred after the radiolabellingusing all the 3 radioisotopes. So in conclusion, our resufls indicate that the best radiolabelling method for biodistibution studies is 1 l lIn.-oxine, even though the activity used in this study caused a loss of lymphocyte functions and proliferation capability. For this reason we now evaluating the lymphocytes radiolabellingusing a lower activity and a greater number of cells.

1140

STUDIES

BY MEMBRANE

Pgp

STRUCTURE-AFFINITY CONSIDERATIONS FOR SEROTONIN RECEPTOR BINDING TECHNETIUM AND RHENIUM COMPLEXES In order to find Tc coordination compounds that imitate organic serotonin receptor ligands we have synthesized complexes with structural similarities to ketanserin, a prototypic serotonin antagonist. The key compounds in our design concept are small-sized neutral mixedligand (so-called 3+1) complexes of technetium and rhenium (Re as surrogate for radioactive Tc), having the potential for convenient derivatization in order to provide series of candidates for structure-affinity and selectivity studies. Substantial 5-HT 2 serotonin receptor binding could be achieved, as determined in in vitro [H-3]ketanserin displacement assays. Minor alterations of spacer lengths within the molecule and/or F substitution in a simple aryl portion of the monodentate thiol co-ligand hardly attenuate 5-HT 2 affinity, but remarkably change selectivity (ICso ratio 5-HT2/D 2 ~ 0.020.09, 5-HT2/5-HTIA ~ 0.03-0.13, 5-HT2/5-HT transporter ~ 0.04-0.38). Alteration of the chelate unit drastically reduces 5-HT 2 affinity. A crucial structural feature is a protonable N atom in the complex, which is necessary for 5-HT 2 affinity and interferes with blood-brain transfer in dependence of the nature and pK of the amine functionality.

• Radiochemistry and Radioassays 0Mo435

0Mo437

M. Santimaria, L. Uccelll, A. Duatti, U. Mazzi, M. Giganti, A. Piffanelli, University of Padua, University of Ferrara, University of Bologna, Italy.

G. Patsis, M. Papadopoulos, I. Pirmettis, Ch. Tsoukalas, E. Chiotellis Institute of Radioisotopes and Radiodiagnostic Products, NCSR "Demokritos", 253 10, Ag. Paraskevi, Athens, GREECE.

A NEW CHELATING SYSTEM FOR LABELING SMALL PEPTIDES WITH TECHNETIUM-99m AND RHENIUM-188

NOVEL Tc(V)-LABELLED FATTY ACID ANALOGUE THE MIXED LIGAND APPROACH.

Tetradentate ligands are very useful chelating agents for technetium and rhenium, and could provide suitable substrates for attaching a small peptide chain to a Tc-99m or Re-188 complex. We report here the preparation of the first technetium and rhenium nitride complexes with the tetradentate ligand showed below. This ligand possesses a 'pendant carboxylic functional group which might be used for linking to the resulting complex a short peptide chain through the usual reaction with a terminal amino group.

Our efforts to synthesize new chelating systems for technetium(V) for in vivo diagnostic imaging led us to the development of a novel class of mixed ligand comlplexes, TcO(SNS) (S) (3+1 combination). These complexes were stable, neutral and lipophilic showing a significant heart uptake. We have synthesized and report here such a mixed ligand complex, TcOLIL2, where LIH2=HOOC(CH2)IoN(CH2C(CH3)2SH) 2 and L2H=p-HSC6H4CH3, containing a fatty acid substituent on the tridentate ligand (LI). In this way the complex formed preserves the fatty acid integrity and may thus prove a useful agent for studying myocardial cell viability. We realized the synthesis of the tridentate ligand in three steps. The complex was prepared in macrosopic amounts (yield 68%) by ligand exchange reaction using 99Tc-gluconate as precursor and equimolar quantities of L1 and L2. Brown crystals were isolated and characterized b y IR, UV-vis, NMR and elemental analysis. At tracer level, the complex formed also in high yield (over 85%) using 99mTc-glucoheptonate as precursor. The identity of 99mTc-complex was determined by comparative HPLC studies of authentic reference samples at carrier level. Biodistribution studies of HPLC purified 99mTccomplex were carried out in mice. The new agent showed significant initial myocardial uptake (4.53 %ID/g at 5min p.i.), which decreased rapidly with time(0.92 %ID/g at 30min p.i.). It seems that, development of longer alkyl-chain analogues is required to provide agents with better biological properties.

0

The ligand gives rise to both square-pyramidal and octahedral complexes in reacting with the Tc-N and Re-=N cores. Generally, it has been observed that the stability of the final products was higher for rhenium complexes than for technetium complexes. The new ligand, therefore, appears to show a good coordinating ability toward the Re-~-N core and might be used for the preparation of a new class of therapeutic agents with the radionuclide Re-188.

BASED ON

0Mo436

0Mo438

I. Pirmettis, M. Papadopoulos, C. Sawas-Dimopoulou, E. Chiotellis. Institute of Radioisotopes and Radiodiagnostic Products, NCSR "Demokritos", 153 i0, Ag. Paraskevi, Athens, GREECE.

H. Vanbilloen, B. Cleynhens, L. Michiels, C. Boonen, M. De Roo, A. Verbruggen Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U.Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuven, Belgium

,TECHNETIUM-99m-SMI-86. A POTENTIAL BRAIN AGENT: SYNTHESIS AND BIOLOGICAL STUDY.

IMAGING

In developing new brain imaging agents we have studied a series of mixed ligand complexes of the general formula TcOLIL2. The compound SMI-86, LIH2=(C2Hs)2NCH2CH2N(CH2CH2SH) 2 and L2H=HSCH2C6H~OCH 3 showed the best biological characteristics and is reported here. Synthesis at carrier, level, Tc-99, proceeded via Tc(V)-gluconate precursor. The complex was characterized by IR, UV-vis, NMR and elemental analysis. The X-ray crystallography demonstrated that the coordination geometry is trigonal bipyramidal. The basal plane is formed by two S atoms of L1 and the oxo group, while the N atom of L1 and the S of L2 occupy the two apical positions. The synthesis at tracer level was completed in high yield (>95%) by exchange reaction using Tc-99mglucoheptonate as precursor. The complex was characterized by HPLC using the Tc-99 complex as reference. Biodistribution studies of the 99mTc-complex in mice and rats showed high initial uptake and significant retention in the brain; the fast blood clearance resulted in a high brain to blood ratio. The whole body and coronal brain !Tn % ID/organ in mice ]sections autoradiographies confirm - ~ - ~ - ~ - - ~ - ] t h e ability of this complex to I cross the blood brain barrier. rain 4.2 4.2 3.6]Brain distribution is inhomogeneo~s lood 2.4 1.7 1.51with high activity into the cortex r/Bl 5.7 7.7 7.21up to 30 min p.i.. The novel Tc99m iver 12.3 17.8 30.0Jagent, SMI-86, presents promising fine 0.I I.I 2.21biological characteristics for further evaluation as a brain imaging agent.

SYNTHESIS AND BIOLOGICAL EVALUATION IN MICE OF CONJUGATES OF 99mTe-CYSTEINYLTRIGLYCINE Cysteinyltriglycine 1(!) can be o considered as an analogue of I ' - c ° ~ ' ' - ~--~NM/---~"~ MAG3 in which the mercap- V - - - q toacetyl group is replaced by a N~S H cysteinyl moiety. This implies the ~ ~c~ presence of a primary NH2group on the ligand that can be conjugated with compounds having interesting biological characteristics. It can be expected that such molecules will be cleared efficiently by the renal system as the ligand's carboxyl group is not involved in the conjugation. Technetium-99m labelled bioconjugates can be prepared either by coupling the bioactive molecule to 1 and subsequent labelling with technetium-99m, or by coupling the bioactive molecule to 99mTc-1. In a first approach we have symhesized a series of R-acyl derivatives o f l , starting from R-acyl-S-benzyl-L-cysteine (R= ethyl, benzyl, ethylidene,..). Direct labelling with Tc-99m (RT, pH 12) resulted each time in the formation of two, probably diastereomeric, complexes. After isolation, all complexes were stable up to 8 h post labelling. Biodistribution in mice of the different HPLC-purified isomers showed that all complexes are cleared from the blood by both the kidneys and the liver. Compared to 99mTc-I they accumulate to a substantially higher degree in the hepatobiliary system despite the presence of a free carboxylic acid group, probably due to the added lipophilic aliphatic or aromatic substituent. These results indicate that it is possible to design and prepare a new bifunctional chelate for the facile and efficient incorporation oftechnetium99m into small molecules under mild conditions. The possibility to conjugate bioactive molecules with Tc-I is now being studied.

• Radiochemistry and Radioassays 0Mo439

0Mo441

K.Nakamura*, l.Sugawara**, S.Satake***, A.Kubo*, and H. Takami*** *Keie Univ. Schsol of Med., **Saitama Medical Center, and ***Teikyu Univ. Sehs.I sfMed., JAPAN

J. Sartor I A. S c h a f f l a n d z, J. B o g a t z k y I, S. Guhlke z'2, FT.F~ (--~-uss) Knapp2r H. J. B i e r s a c k I aKlinik fir Nuklearmedizin, U n i v e r s i t y of Bonn, Bonn, Germany, 2Oak Ridge Nat. Lab., Oak Ridge, TN, U S A

COMPARISON OF Tc-99m-MIBI AND Tc-99m-TETROFOSMIN UPTAKES IN ANAPLAST1C THYROID CARCINOMA The aim of this study is to compare Tc-99m-MIBI(M1BI) and Tc99m-Tetrofosmin(Tetrofosmin) with regarding to the potential to enable characteristic of the multidmg resistance in anaplastic thyroid carcinoma which is very poor prognostic, regardless of various therapeutic trials. We studied uptakes of MIB1 or Tetrofosmin in human anaplastic thyroid carcinoma (KB3-1), and two human recombinant cell lines: MDRl-transferred (KB-G2) and multidrug resistance-associated protein:MRP-transferred (C-A500). Experiments were carried out by incubating cell in the culture medium containing MIBI or Tetrofosmin in the presence or absence of verapami[ at 37°C for 60 rain. Net accumulation values were quantified as radioactivity of Tc-99m associated with the cells per milligram of cell prutein normalized to constant extraccllular conccntratinn of Tc-99m. The verapamil index (VI) represents the ratio of net uptake in the presence of verapamil over control. Athymic mice implanted with each of cell lines received MIBI or Tetrofosmin and biodistribatiun was examined 60 rain after injection. Verapamil significantly enhanced cellular accumulation of MIBI as well as Tetrofosmin in KB-G2 and C-A500; indicating that MDR cytotoxic agents inhibited P-gp-mediated MIBI or Tetrofosmin efflux~ thereby enhancing MIBI or Tetrofosmin accumulation. M1BI had higheT VI than Tetrofosmin. Cells associated net uptake values in vitro were related with Iocalizatian in tumors in vivo. MIBI showed higher tumorto-blood ratio than Tetrofosmin. Wc conclude that MIBI is a more scnsitivc rcportcr of the functional cxprcssion of transporter mediated by P-gp as well as by MRP, although Tetrofosmin may also provide the function of multidmg resistance in anaplastic thyroid carcinoma.

TC-99mANALOGUE

AND Re-188 LABELING OF A USING MAG3-p-NITROPHENYLESTERS

D-Lys~-LHRH

Therapeutic use of LHRK-analogues for hormone dependent m e t a s t a t i c breast cancer supresses ovarian oestrogen production (chemical castration). However, also direct antiproliverative effects on various cancers expressing LHRH-receptors have been d e m o n s t r a t e d in-vitro. Thus r a d i o l a b e l e d analogues of LHRH are i n t e r e s t i n g as p o t e n t i a l r a d i o p h a r m a c e u t i c a l s for imaging or r a d i o t h e r a p y of L H R H - r e c e p t o r positive tumors. We have extended our r e c e n t l y d e v e l o p e d [Tc-99m or Re-188]-MAG3-nitrophenylester method for labeling LHRH-analogues. The synthesis is carried out by prelabeling MAG~ w i t h Re-188 or T c - 9 9 m followed by active ester f o r m a t i o n u s i n g b i s n i t r o p h e n y l c a r b o n a t e A D-Lys ~ analogue of LHRH was labeled under aqueous, pH c o n t r o l l e d conditions in order to obtain a regiospecific labeling at the lysine residue avoiding labeling of the arginine group w h i c h is part of the pharmacophoric sequence of the peptide. However, even higher yields of these L y s - l a b e l e d products can be o b t a i n e d u s i n g the organic solvent DMF. The Tc- as well as R e - l a b e l e d compounds were tested for binding to an anti-LHRH antibody. These experiments revealed high total b i n d i n g (up to 4050%), w h i c h could be d i s p l a c e d almost q u a n t i t a t i v e l y by u n l a b e l e d peptide at n a n o m o l a r concentrations (high specific binding). E x p e r i m e n t s w i t h v a r i o u s cell lines have been initiated and also revealed reversible b i n d i n g to the cells. *Operated by OHER, the U.S. DOE under contract DEAC05-960R22464 with Lockheed Martin Energy Research Corp.

0Mo440

0Mo442

D.S. Edwards, J. A. B a r r e t t , S. Liu, M. Z i e g l e r , T. M a z a i k a , M. V i n i n g , G. B r i d g e r , J. H i g g i n s , I I I M.J. A b r a m s , DU P o n t M e r c k P h a r m a c e u t i c a l Co. s N. Billerica, MA, a n d J o h n s o n - M a t t h e y Biomedical Research, West Chester, PA

M. Rusckowski, T. Qu, F. Chang, D.J. Hnatowich. Department of Nuclear Medicine. University of Massachusetts Medical Center, Worcester, MA, USA.

A STABILIZED Tc-99m COMPLEX OF A C H E M O T A C T I C PEPTIDE-HYNIC CONJUGATE FOR IMAGING INFECTION Te-99m labeled forMet-Leu-Phe-Lys (hydrazinonicotinamide) (FMLFKHynic), a potent agonist, has been previously reported as a p o t e n t i a l imaging agent for focal infection. However, the binary Tc-99m complexes e x i s t in a n u m b e r of i s o m e t i c f o r m s a n d a r e n o t s t a b l e in t h e a b s e n c e of e x c e s s coligand. We h a v e f o u n d t h a t t h e c o m b i n a t i o n of two c o l i g a n d s , tris (3-sulfonatophenyl) phosphine (TPPTS) a n d t r i e i n e r e s u l t s in a s t a b l e t e r n a r y ligand complex, Tc-99m (FMLFKHynic) (tricine) (TPPTS) in 9 0 % y i e l d a n d h i g h s p e c i f i c activity (20,000Ci/mmol). The H P L C - p u r i f i e d complex was compared to t h e b i n a r y c o m p l e x e s formed using t r i c i n e or g l u c o h e p t o n a t e in t w o a n i m a l m o d e l s of focal infection. U p t a k e a t t h e s i t e of i n f e c t i o n in the g u i n e a p i g m o d e l w a s 0 . 6 - 0 . 7 % I D / g at 1 h in all 3 g r o u p s a n d d e c r e a s e d to 0 . 2 % I D / g at 4h in b o t h the T P P T S / t r i c i n e and tricine groups w h i l e the g l u c o h e p t o n a t e group remained constant. These results reflect the more rapid clearance f r o m the b l o o d . In the r a b b i t m o d e l a s i m i l a r up take was observed at t h e f o c a l s i t e w i t h the target-to-background ratio (T/B: i n f e c t e d muscle/ normal muscle) of 3 - 4 : 1 a t 3-4 b p o s t - i n j e c t i o n . The s t a b i l i z e d complex was superior w i t h a T / B of 5 - 7 : 1 a t 3-4 h p o s t i n j e c t i o n reflecting an increased clearance from the normal muscle. In t h e r a b b i t m o d e l in a l l c a s e s a t r a n s i e n t decrease in w h i t e b l o o d c e l l c o u n t of 3 5 % w a s o b s e r v e d during the f i r s t 30 m i n p o s t i n j e c t i o n . It is c o n c l u d e d that HPLC-purified FMLFK-Hynic ternary ligand complex produces superior images in t h e r a b b i t f o c a l i n f e c t i o n model.

VIA AN NHS-MAG3: A NEW TUMOR PROBE. The membrane bound epidermal growth factor receptor (EGFr), over expressed in a number of cancers, has been investigated by others as a target for tumor imaging. Considered in this report is its ligand, the epidermal growth factor (EGF), a 6kD molecular weight (raw) peptide, radiolabeled with Tc-ggm using an easily synthesized acetyl protected NHS-MAG3. We describe the first /21 vitro and tumor mouse model evaluation of this agent. Human recombinant EGF was conjugated to NHS-MAG3 using chelate to peptide molar ratios of 1-20:1 and radiolabeled with Tc-99m by transchelation from tartrate. Labeling efficiencies of up to 50% were observed and specific activity of 150 ~ci/pg easily obtained. The unconjugated EGF radiolabeled in an identical fashion showed only 2% of radiolabeled bound. HPLC size exclusion analysis showed one peak containing more than 80% of the recovered activity, and a minor higher and low mw component. Incubation in human serum at 3 7 ~ showed about 90% stability through i hr, with gradual appearance of two high mw peaks by 24 hr. No appreciable catabolic products were apparent at low mw. The Tc-99m-labeled EGF demonstrated a saturation binding curve using two EGFr positive tumor cell lines, which was completely inhibited at all doses by presaturation of cells with unlabeled EGF. A competition binding assay with tumor cells using TC-99m-EGF as tracer showed the unlabeled MAG3-EGF to be indistinguishable from uncoupled EGF, thus demonstrating full retention of biological activity. Biodistribution in normal mice was evaluated at 0.5 and 3 hr following administration through a tail vein. Rapid clearance was evident with no appreciable retention in any organ sampled. HPLC of urine showed the label co-eluting with EGF, as well as a prominent lower mw peak. EGFr positive tumors grown as xenografts in the left thigh of nude mice showed positive accumulation relative to a control peptide of similar mw, BPTI. Mice receiving TO-99m-EGF demonstrated a tumor thigh to normal thigh ratio of 2.6 ratio (n=3), whereas the control peptide showed a ratio of 1.4 (n=3). This positive localization in vivo of TC99m-MAG3-EGF peptide offers a potential new Tc-99mpeptide tumor imaging agent.

1142

EPIDERMAL

GROWTH

FACTOR

RADIOLABELED

WITH

TECHNETIUM-99M

•

Radiochemistry and Radioassays

0We443

0We445

B. Gri~nert, H. Amthauer, H. Xu, T. Schumacher, R. Jochens, H Eichst~idt Strahlenklink und Poliklinik, Virchow-Klinikum, Humboldt Universi~t zu Berlin

E. Seregni, A. Martinetti, L. Maffaoli, F. Belli, A. Mazzoeehi, L. Maseheroni, S. Massaron, G. Parmiani, N. Cascinelli, E. Bombardieri. National Cancer Institute of Milan

CHANGES OF BIOCHEMICAL BONE TURNOVER MARKERS tN PATIENTS AFTER LIVER TRANSPLANTATION

SERUM 2'-5' OLIGOADENYLATE (AS) AND B2-MICROGLOBULIN (B2M) IN PATIENTS W I T H NODAL METASTASES FROM CUTANEOUS MELANOMA TREATED WITH rIFN-~t2A

Purpose: Bone mineral density loss after organ transplantation is a well known entity in follow-up of patients after orthotopic liver transplantation (OLT) Aim of this study was the evaluation of bone metabolism after transplantation with radioimmunassays. Metbo..ds: 68 patients (24 female, 44 male) with a mean age of 46 years and a descreased bone mineral density of 2SD in dual energy X-ray absorptiometry (DPX-L-Expert, Lunar) after OLT and a control group with 38 patients without bone mineral density loss were evaluated. Follow-up examinations with radioimmunassays for osteocalcin (OSC), bone alkaline phosphatase (BAP). carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal cross-linked telopeptide of type I collagen (ICTP), parathyroid hormone (PTH) and 25-hydroxy-vitamin D(25 OH D) were simultaneously performed every 6 months for 6 years after OLT. Results: OSC (p<0,001), BAP(p<0,01) and PICP (p<0,001) as marker of bone formation and ICTP (p<0,001) as a marker of collagen resorption were significantly increased in patients after OLT in comparism to control subjects. In follow up normalization of bone turnover after OLT was first detected by ICTP and OSC in comparison to bone density measurements. PTH and 25 OH D parameters showed no signifcant difference in patient and control group as well as in follow-up. Conclusion: OSC, BAP, PICP and ICTP are sensitive parameters for the evaluation of bone turnover and metabolism status in patients after OLT. Especially ICTP reflects sensitively bone density loss and correlates with bone density measurements. Determined in combination, these parameters give an early and precise diagnosis of bone mineral changes in patient follow up after OLT.

Introduction and aim of the study: rIFN~2A is a promising adjuvant agent in patients with regional melanomatous metastases (stage IIIB). Both AS and B2M are molecules induced by IFN.' The aim of this study is to verify whether evaluation of these proteins can predict the clinical response to rlFN~2A. Material and Methods: AS activity was measured in serum with a radioimmunoassay (Eiken Immunocbemieal Lab., Tokyo). The lower detection limit of the method is 15 pmol/dl and the imprecision, evaluated as intra and interassay enefficients of variation, is less than 15%. B2M was determined by means of RIA (Diagnostie System Lab. Inc., Webster, Texas, USA). lntra and interassay precision ranged from 5.9% to 9.3%. Forty-two patients who had undergone radical dissection of nodal metastases were evaluated. All patients received adjuvant rlFN..a2A (3 million units s.c. three limes weekly) for 3 years or until progression. The patients were followed for a median period of 43 months (range 19-50 months). During follow-up 22 patients had disease progression. AS activity and B2M were determined at diagnosis and after 3 and 6 months of IFN treatment Results and discussion: the results of AS and B2M evaluation are as follows: Baseline 1st month 6th month 20,2 226,2 ** 56,4 * 1.13 1.86 ** 1.5 * Mann-Whitney test **p<0.005; *p<0.05 As is shown we found an 11 fold increase in AS serum activity after 1 month and this trend was maintained in the following 6 months. Similar results were obtained also for B2M. However, we failed to find any significant difference in AS and B2M serum levels between responders and non-responders. So, our results indicate that AS and B2M are markers of the biological activity of administered IFN but they have little efficacy in predicting the clinical outcome of the treatment.

0We444

0We446

K Liepe I M. Darrehnann l P. Knuschke 2, G. Wanderlich I, U. Neumat-m3, ~,V.-G. Franke 1, J. t(ropp 1, G. Wozel 2 Depts. of 1Nuclear Medicine, 2Dermatology, 3Radiology, Dresden University of Technology Germany

Pasqualini, A. Starzec. Biophysique et Biosignaux, Institut d'Oncologie Cellulaire et Mol6culaire Humaine, Bobigny-Paris 13, Cis Bio International, Saclay, France.

EVALUATION OF MARKERS OF BONE RESORPTION AND

TECHNETIUM-99m

FORMATION FOR THE FOLLOW-UP OF OSTEOPOROSIS

We were interested in the evaluation of specific markers of bone metabolism for the diagnosis and follow-up of osteoporosis. Markers of bone resorption are fractions of the bone collagen and the markers of bone formation consists of procollagenes and the bone specific alkaline phosphatase. We investigated 26 patients (pts) 71-97 years of age which were followed-up for a period of one year. As diagnostic procedures a CT was performed three times and two times a OD of the radius (pq CT) which were compared to the results of hnmunoassays of three markers of bone resorption: a) CrossLaps (CL), b) ELltest Ntx and c) deoxypyridinolin-erosslinks-EIA (DPD) and of two markers of bone formation: d) RIA for procollagen type I-propeptide (PICP), e) bone specific alkaline phosphatase (BAP). As control parameters we measured the serum levels of calcium, PTH, osteocalcin, vitamine D und the general alkaline phosphatase. With the "classical" procedures (CT and OD) an osteoporosis was diagnosed in 15 pts and the two methods corresponded in four 10ts. The correlation of CT/OD and the markers of bone metabolism revealed the followmg results: Osteoporosis a) CL b) NTx c) DPD e) BAP positive Sens Spec Sens Spec Sens Spec Sens Spec CT 80% 69% 70% 69% 80% 62% 80% 62% Osted.. 67% 59% 67% 65% 78% 59% 67% 53% CT and OD 100% 36% 100% 40% 100% 45% 75% 45% CT or OD 66% 82% 60% 72% 73% 66% 66% 64% Sens.=sensitivity; Spec=specificity PICP showed no correlation to osteoporosis. Conclusion: The specific markers of bone metabolism seem to be of value in the diagnosis and follow-up of osteoporosis and might therefore be helpful to diminish the frequency of CT/OD. Because of the complex genesis of this diseasethese markers provide additional information e.g. to discriminate between the low or high turnover osteoporosis.

v. de Beco, J.L. Moretti, M. Duran Cordobes, F. Benazzouz, R.

TECItNETIUM-99m LINES

SENSITIVE

NOET UPTAKE VERSUS S E S T A M I B I IN C A N C E R C E L L (se) AND R E S I S T A N T (rt) TO

CHEMOTHERAPY

We have previously reported uptake of cationic Tc-99m Sestamibi (MIBI) by cancer cells sensitive to chemotherapy (se-MCF7). Development of multidrug resistance (MDR) related to a membrane glycoprotein (Pgp 170) overexpression blocks this process in resistant cells (rt-MCF7/Dox). We have evaluated the cellular uptake of the neutral lipophilic imaging tracer Tc-99m bis(N-ethoxy Nethyl)dithiocarbamato nitrido (NOET) by chemotherapy sensitive and resistant cancer cells lines. Time-course incorporation of lnM of MIBI and NOET by human breast carcinoma cells (se-MCF7, rt-MCF7/Dox) and human leukemic lymphoblastic cells (se-K562, rt-K562/Dox) were studied at 4°C and 37°C. 50gM verapamil, a MDR-reversing agent was added 10 minutes before tracers. Results are expressed in percent of the total activity taken up by cells after 90 minutes of incubation : 1/MIBI uptake was less than 1% at 4°C for all cell lines. It was lower in resitant cells than in the sensitive ones at 37°C. Verapamil increased MIBI uptake in resistant cells (4,4_+0,2% vs 0,7_+0,1% for rt-K562/Dox ; 3,7% vs 0,7+0,6% for rtMCF7/Dox). 2 / N O E T uptake of sensitive cells was : 3,3_+0,7% (seMCP7) ; 4,9_+0,4% (se-K562). Uptake of resistant cells was 6,4+0,6% for rt-K562/Dox, and surprisingly high 47,7+6,4% for rtMCF7/Dox. NOET uptake was affected neither by temperature nor by verapamil. The mechanism of NOET uptake is known to be different from that of cationic Sestamibi. The uptake of the neutral lipophilic NOET in resistant breast cancer cells may probably involve its interaction with membrane bearing the Pgp-170. This characteristic may be different for resistant epithelial and lymphoblastic cells.

1143

m c 0 C

t~

6

• Radiochemistry and Radioassays 0We447

OWe449

Modoni S., Polite G., Nardella G., Dicembrino F., * Di Fazio P., Bruno A., Frusciante V. Nuclear Medicine,"C.S.S.",Scientific Institute,S.Giovanni Rotondo (FG); • Dpt. of Nuclear Medicine, City Hospital, Barletta (BA), Italy.

M.~arkavij, J.Tennvall, S-E.Strand*, H-O.Sjogren**, Chen Janging*, Rune Nilsson**. Departments of Oncology, Radiation Physics* and Immunology**, Lund University, Lund, Sweden.

CLINICAL USEFULNESS OF BONE SCINTIGRAPHY AND PSA LEVELS IN RADICAL PROSTATECTOMY-TREATED PATIENTS FOLLOW-UP.

EXTRACORPOREAL WHOLE BLOOD IMMUNOADSORPTION (WBIA) E N H A N C E S RADIOISI~UNOTARGETING O F 12SI-LABELED B R 9 6 - B I O T I N M O N O C L O N A L A N T I B O D Y IN S Y N G E N E I C R A T T U M O R MODEL.

PSA is probably the best tumor marker available at present. Aim of this work is to evaluate whether PSA can replace bone scintigraphy (BS) in follow up of patients undergone radical prostatectomy and radiotherapy. Hormonally treated pts., because of influence of this therapy on PSA levels, were excluded from the study. 200 patients (age range: 43-90 yrs.) fulfilled the criteda and were included in the study. The range of follow-up since therapy was 3-90 mths. PSA samples and bone scintigraphy were obtained at the same time. Whole body scan was performes 3 hrs. after administration of 740 Mbq of 99mTcMDP. PSA was assayed by a commercial kit; its cut-off value was 3 ng/ml. By scintigraphic results we distinguished three group of patients: A) 149 pts. without bone metastases; B) 43 pts.with bone metastases only, subdivided, on the base of number of metastatic sites, in eig~lt subgroups; C) 8 pts. with bone and soft tissues metastases (5 local, 2 liver and 1 lung). 125/200 pts. with negative BS had PSA<3; in all pts.with positive BS and in 32•200 pts. with negative BS, PSA was >3; no patient with positive BS had PSA lower than 3. Correlation between PSA and metastases extension was good (r=-0.85). By ROC analysis we obtained, with a PSA level at 8 ng/ml, an interesting sensitivity (97.6), specificity (94.6), NPV (99.2) and PPV (89.1). In conclusion, a PSA level less than 8 ng/ml in radically prostatectomized pts. without hormone therapies, makes unnecessary the BS; a positive BS, even if uncertain for metastases, can be interpreted by PSA assay. In all hormone-treated pts., indipendently of PSA levels, BS must be always performed.

OWe448

OWe450

EM.R.Fern~ndez C.Plancha, D.Fuster, *J.Filella, *A.Ballesta and J.Setoain. S e r v i c e s of N u c l e a r M e d i c i n e a n d * B i o c h e m i s t r y . C l f n i c H o s p i t a l , U n i v e r s i t y of B a r c e l o n a . Spain. EFFECTS

O F HAM_AS I N C L I N I C A L

DIAGNOSIS

W e s t u d i e d a n t i - i s o t y p i c a n d a n t i - i d i o t y p i c HAM_As i n t e r f e r e n c e s in c l i n i c a l d i a g n o s i s , in v i t r o a n d in vivo. MATERIAL AND METHOD:I)-HAMAs were measured by a n e w R I A a s s a y ( B i o m i r a Inc.) c a p a b l e of d e t e c t i n g both ~ s separately. We used sera from 10 p a t i e n t s w h o r e c e i v e d a s i n g l e M Ab i n j e c t i o n , for pre-surgery inununoscintigraphyc localization of colon cancer. II)-HAMAs effects were studied using a n " i n - v i t r o " p a t t e r n , t r e a t i n g the ( + ) H A M A s e r a f r o m a p a t i e n t w i t h 1 to 400 ~ g / m l c o n c e n t r a t i o n s of i n j e c t e d MAb, to f i n d the b e s t b l o c k i n g one. III)-The interferences were studied in two clinical d i a g n o s t i c parameters, CEA and TSH. RESULTS: I ) - I n 4 of the p a t i e n t s an a n t i - i s o t y p i c HAPLA r e s p o n s e w a s f o u n d (40%). A l s o a n a n t i - i d i o t y p l c r e s p o n s e w a s s h o w n in 3 of t h e m (75%). I I ) - I n h i b i t i o n e f f e c t (94-98%), w a s g i v e n w h e n I00 ~ g / m l of M A b w a s a d d e d to the s e r a s a m p l e s . III)-Falsely elevated concentrations of C E A a n d T S H w e r e f o u n d in the (+)HAM_As s a m p l e s . CONCLUSIONS: - H A M A s i n t e r f e r e in T S H a n d C E A determinations, r a i s i n g its c o n c e n t r a t i o n s a n d occasionally giving pathological results. This can happen in o t h e r tests. -The i n t e r f e r e n c e s c a n b e a v o i d e d , p r e - t r e a t i n g the s a m p l e s w i t h the i n j e c t e d MAb. - R e s u l t s e x t r a p o l a t i o n to " i n - v i v o " M A b b e h a v i o r , in ( + ) H A M A p a t i e n t s s u b m i t t e d to a s e c o n d study, c o u l d e x p l a i n the p h a r m a c o k i n e t i c s m o d i f i c a t i o n s o b s e r v e d in s o m e i m m u n o s c i n t i g r a p h i e s

1144

Aim. TO investigate the efficacy of tumor radioimmunotargeting with 125I-labeled BR96-biotin monoclonal antibody(MAb) using a new method, (WBIA), based on direct adsorption of unbound MAb from blood without preceding separation of plasma. Method. Chimeric BR96 is a MA~ of isotype IgGl with high tumor selectivity and rapid internalization. Forty-six Brown Norwegian male rats inoculated intramuscularly and beneath the liver or kidney capsule with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, were investi-gated. The rats were injected i.v. with 3.5-4.5 MBq 12SI-BR96-biotin. Twenty of the rats underwent WBIA starting 5h or 12h after injection. About 6 blood volumes were passed through an avidin-gel adsorption column during 2h. Results. By using WBIA, whole body radioactivity was reduced by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33 h later, the activity uptake in tumors manifested only a nonsignificant decrease as compared with corresponding controls (p>@.05), and had approximately similar time-activity curves. Uptake ratios for T(umor):bone marrow, T:liver, T:kidney and T:lung were enhanced 2.3-3.5-fold in all 3 tu-mor models as compared with controls. The ratio of liver tumor:bone marrow was improved from I0:I to 30:1. Conclusion. The present study showed that a new method of extracorporeal immunoadsorption from whole blood yields a significantly improved radioimmunotargeting, and that this method also is applicable on the internalizing and highly tumor-selective MAb BR96.

M B~h.._...~6, A. Heppeler, H.R. Mticke, Institute of Nuclear Medicine, University Hospital, Basel, Switzerland

NEW SOMATOSTATIN ANALOGS FOR SPECT AND PET Somatostatin (SRIF) receptors are highly expressed on a wide range of human tumors which are routinely visualized in vivo with a metabolically stabilized DTPA modified analogue In-ll 1-OctreoScan. Because of a fast blood clearance short lived radionuclides like Tc-99m for SPECT and Ga68 for PET appear to be more suitable for labelling of these analogs. We investigated 2 new conjugates of SRIF analogs which can be labelled with Tc-99m. HYNIC (6-nicotinyl hydrazide) was coupled directly to octrotide (L1) and its tyr3-analogon (L2). Both conjugates showed specific in vitro binding to the SRIF receptor with KD values of 0,2 nM. The labelling with Tc-99m and tricine as coligand gave labelling yields of >97% at specific activities >220 GBq/~mol. Receptor binding of Tc-99m-L1 (L2) showed a relativley high unspecific binding but K:) values are in the nM range. In a tumor bearing mouse model (AR4-2J) a fast and specific tumor uptake was demonstrated. Results (4 h p.i.) expressed as % ID/g tissue and compared with In-111-OctreoScan are shown in the table. Tumor (blocked) L1 3,5 (1,9) L2 2,5 (0,8) In-Ill-Oct 2,4 (0,6)

Blood Liver Spleen Muscle 0,73 1,02 0,30

1,33 0,65 2,57 0,55 0,7 0,35

0,43 0,47 0,25

Pancreas (blocked) 1,7 (0,6) 1,2 (0,5) 0,5 (0,15)

Moreover a new derivative was sythesized by coupling of 1,4,7,10tetraazacyclododecane-N,N', N"-t ris(tert-butoxyca rbonyl) methyI-N'"-acetic acid to (BOC-lysS)-tyr3-octrotide and deprotection (DOTA-octreotide). The conjugate was labelled with Ga-67 with >99% yield (40 GBq/pmol). The in vitro assay showed a high affinity to the SRIF receptor (Ko=0,47+0,05 riM). The tracer was stable in human serum with only 3 % loss of Gs-67 to serum proteins within 24 h. Conclusion: 2 new Tc-ggm Somatostatin analogs were synthesized and proved to be specific radiotracers for SRIF receptor positive tumors in vitro and in vivo. Surprisingly the tyr~ derivative proved to be superior to octreetide. A new conjugate was developed for Ga-67,68 which is being tested in an animal model.

•

Radiochemistry and Radioassays/Risk/Benefit/Costs ffl e-

0We451

OSu453

B. St____~',R. Albert', P. Smith-Jones', H. Knecht', H, M~-..ke=and C. Bruns'

H.Bender, M.Grapow, A.Schomburg, U. Reinhold*, H.-J. Biersack DeNs.Nuclear Medicine and *Dermatology of the University Bonn, Germany

| lO

DOES REPEATED INJECTION OF Tc-99m-LABELED MONOCLONAL ANTIBODIES EFFECT THE SURVIVAL OF MELANOMA PATIENTS ?

e'tD ID

Despite the rapid in-vitro cleavage of some of the conjugates, in-vivo all DTPNoctreotide analogues containing metabolizable linkers resulted in higher kidney/tumor ratios when compared to the stable conjugates. Thus, no kidneyspecific reduction of activity accumulation was observed when a cleavable inking moiety was introduced into the DTPNoctreotide conjugate. In this series o4 expedments the lowest Iddney/tumo¢ ratio was obtai~d with the conjugates containing (amtde) linkers that are stable against ef~'ymatic degradation.

Induction of an immune response against monoclonal antibodies (MAb) specific to tumor-associated antigens as a result of immunoscintigraphy has been shown to be associated with an overall prolongation of survival in patients (pts). Especially in ovarian carcinoma, the diagnostic application of MAb has been linked with this effect, suggesting an activation of the anti-idiotypic network. The aim of our retrospective study was to investigate, the effect of repeated application of commercially available Tc-99m-labeled F(ab)2-fragment of MAb 225.28s (Technemab-K-1 [MAb-K-1], Sorin; isotype IgG2; specific to highmolecular-weight melanoma-associated-antigen [HMW-MAA]) on the overall survival of melanoma pts. In total, 212 pts were evaluated, which had received 1 or multiple injections of MAb-K-1 (lmg, 20mCi) between 1984 and 1994. Pts. had been refered for routine staging or restaging of histologically confirmed melanoma, usually after resection of the primary tumor site. Pts were divided in two groups: (1) 1 injection vs. (2) 2 and more injections. In order to compare the survival data, pts of group 2 were matched with patients of group 1 including the following significant prognostic factors: (1) age, (2) sex, (3) grading according to Clark, (4) tumor depth according to Breslow, (5) location of primary, and (6) number and location of metastases. By this way, 27 pts could be matched No statistically significant difference was observed in the two groups comparing the above mentioned relevant prognostic factors. Additionally, no significant difference was found com-paring either the interval between first diagnosis of disease or first injection of Technemab-K-1. Surprisingly, overall survival time was significantly prolonged in group 2 (multiple injections) as compared to group 1 (single injection). Our preliminary data suggest, that repeated application of Tc-99m225.28s-F(ab)2 has a positive effect on survival. A matching of all antibody treated patients with untreated patients is currently under way. Further studies are needed, to evaluete the type of immune response following antibody-fragments in these patients (HAMA, anti-idiotypic antibodies).

Risk/BenefigCosts 0Su452

0Su454

1Sandoz Pharma Ltd., Praclinical Research, CH-4OO2-Basel, Switzerland =Kantoesspital Basel, Inst. Nuclear Medicine, CH 4002-Basel, Switzerland OCTREOTIDE ANALOGUES WITH METABOLIZABLE LINKING GROUPS: BIODISTRIBUTION AND RENAL HANDLING A significant amount of a given dose of labelled DTPA/octmotide conjugates accttmulates in the kidneys. Various strategies aim at lowering the uptake of radiolabelled octreotide analogues into the kidney tissue, comprising the administration of various types of diuretics, o! inhibitors of renal enzyme activity and the evaluation of competitors for renal peptide uptake by using unrelated proteins or peptides. One strategy that we followed was the introduction of cleavable linkers into the DTP/Voctreotide conjugates that are amenable to kidney specific enzyme degradation. These linking units were designed to enable lysosomal or brush border membrane degradation of the labelled conjugates and thus a rapid excretion of the activity. A series of [DTPA-Tyr']octreotide as wells as [DTPA]-octreotide conjugates were synthesized co.taining potentially kidney specific cleavable linking units, such as di-ester-, mono-ester-, Ala-Pro-Phe-, Ala-Leu-Ala-Leu-, C-11, glutamic acid-, and amide moieties, All octreotide analogues exhibited nanomolar affinities for the sst~ receptor both unlabelled or labelled with In-111. The majority of the new octreotide analogues was rapidly degraded in rat kidney homogenate in-vitro. In-vive the following activity accumulations in different tissues were obtained 24 h p.i. in rodents: TISSUE Kidaey Liver Pancreas Tumor KIONEY/TUMOR R,4"rio

CLEAVABLE LINKER - % OF INJECTED DOSE, 24 h p.f Di-Ester Ala-Leu-Ala-LeuGlutamicacid Am/de 0.49 7.65 6.22 2.96 0,06 0.60 0.04 0.03 O.18 1.55 1.03 I. 18 0.06 0.41 O.18 0.63

8.20

19.15

34.60

4.73

I . M a l m b e r g , Z e n e c a Ltd Gothenburg, U. Persson, H e a l t h Economics Institute, A.Ask, J.Tennvall, D e p a r t m e n t o f Oncology, U n i v e r s i t y Hospital, Lund, P-A. A b r a h a m s s o n , D e p a r t m e n t of U r o l o g y , U n i v e r s i t y Hospital, Malmoe,Sweden. E C O N O M I C COSTS OF S T R O N T I U M ( S r ) - 8 9 A N D / O R E X T E R N A L RADIOTHERAPY(ER) FOR P A L L I A T I O N IN HORMONE REFRACTORY METASTATIC PROSTATE CANCER(HRMPC). P u r p o s e of the study: In a p r o s p e c t i v e r a n d o m i z e d trial ,addition of Sr-89 to ER was found to p r o l o n g the time to further ER by 15 w e e k s ( 3 5 vs 20,p=0,006) c o m p a r e d to ER a l o n e , i n p a t i e n t s w i t h H R M P C . T h e total d i r e c t life-time costs for the two t r e a t m e n t strategies a) ER i n i t i a l l y and in the event of r e l a p s e and b) ER+Sr-89 initially and ER in the event of r e l a p s e was e s t i m a t e d in p r e s e n t s t u d y . M e t h o d s : C a l c u l a t i o n of l i f e - t i m e costs was b a s e d on the initial total t r e a t m e n t cost and the p r o b a b i l i t y of future t r e a t m e n t costs. In a r e t r o s p e c t i v e analysis, the a v e r a g e cost of a relapse t r e a t e d w i t h ER alone was c a l c u l a t e d from the actual care c o n s u m p t i o n of 79 c o n s e c u t i v e p a t i e n t s from south of S w e d e n w h o r e c e i v e d ER o w i n g to s k e l e t a l p a i n due to HRMPC. The c o s t s included skeletal scintigraphy, ER, outp a t i e n t visits, in-patient days and travels. W h e n Sr-89 was added, the cost also included the i s o t o p e and its administration. R e s u l t s : T h e t a b l e shows a v e r a g e total d i r e c t costs per patient. (1993,SEK) Patient residence Initial cost Life-time cost ER ER+Sr-89 ER ER+Sr-89 within county 31,011 43,426 100,250 97,530 o u t s i d e c o u n t g 48,585 61,000 157,060 145,770 C o n c l u s i o n : S t - 8 9 as initial supplement to ER for p a l l i a t i o n of p a i n in HRMPC is superior to ER alone, b o t h in b e n e f i t to the p a t i e n t and in lifetime h e a l t h service costs.

Ralph McCreadV and Roger P A'Hern The Royal M a r s d e n N.H.S. Trust, Sutton, U.K. A M O R E R A T I O N A L A P P R O A C H TO N U C L E A R IMAGING IN ONCOLOGY

Surrey,

MEDICINE

Current activities u s e d to image p a t i e n t s w i t h cancer take no account of the relative risks of the r a d i a t i o n d o s e to the c o n s e q u e n c e s of a misdiagnosis of the disease being investigated. The present recommended activities are b a s e d on t r a d i t i o n and cost r a t h e r than logic. The images are often difficult to interpret b e c a u s e of the low i n f o r m a t i o n densities and lack the q u a l i t y of X-rays, u l t r a s o u n d and p e r h a p s C T scans. The reason for k e e p i n g d i a g n o s t i c a c t i v i t i e s low are to p r e v e n t i n d u c t i o n of cancer and reduce the genetic load. In g e n e r a l these l i m i t a t i o n s are not r e l e v a n t to m o s t patients with cancer since the induction p e r i o d for c a n c e r is up to 20 years and m o s t do not have further children. The d o s e f r o m the d i a g n o s t i c i n v e s t i g a t i o n should be r e l a t e d to the risks of the disease. For example in the case of lung c a n c e r we h a v e c a l c u l a t e d that an a c c e p t a b l e r a d i a t i o n r i s k would permit the administration of 15400 M B q of T c 9 9 m M D P g i v i n g a d o s e of 170 m S v . This activity could increase the information density by up to about 28 times from the p r e s e n t levels increasing the counts per pixel over n o r m a l rib f r o m i0 to 280 d r a s t i c a l l y r e d u c i n g i m a g e noise, making diagnosis more certain, s e n s i t i v e and accurate. This p a p e r will relate the risks of r a d i a t i o n from a diagnostic activity to the m o r t a l i t y and morbidity in cancers with different prognosis.

1145

Q. m

•

Risk/Benefit/Costs/Bone

0Su455

PMo457

Margarida Rodri~ues O. Karanikas, Susanne Granegger and H. Sinzinger, Department of Nuclear Medicine, University of Vienna, Austria.

M. Kafi, B. Caner, R. Klral, G. ~zkoq, C. Bekdik. Hacettepe University Medical Faculty, Ankara, Turkey.

DEXTRAN USED FOR PROCESSING DURING CELLULAR LABELING MAY CAUSE SEVERE SIDE EFFECTS DUE TO BRADYK1NIN.

IMAGING of MUSCULO-SKELETAL Tc-99m-MIBI :Its role in d i a g n o s i s of m a l i g n a n c y f r o m

The annual report on adverse reactions upon radiopharmaceuticals (EJNM 1995; 22: 29-33) listed 2 (out from a total of 146) on exametazime labeled white blood cells. The clinical symptoms were similar to those reported after dextran or after extracorporal circulation in hemodialysis and LDL-apheresis. We assessed the influence of dextran and various anticoagulants (heparin (H), 3.8% sodium citrate (C), acid citrate dextrose (ACD) and nafamostat mesilate (NM) on bradykinin (BK)-formation during processing for white blood cell labeling (n=l 0 each group). H significantly (p<0.01) increased BK (63.4 ± 15.7 vs. 5.7±2.3 fMYmi) in presence of dextran, but not in absence (89±3.2 fM/ml). The same was found for C and ACD, but to a much lesser extent. NM, in contrast, inhibited this increase due to contact activation. These findings indicate that in patients on ACE-inhibitors, where BKdegradation is inhibited by kinases I and II, subsequent liberation of prostaglandin 12 and nitric oxide and potential functional synergism may cause severe side effects. As a consequence, the use of dextran should be a v o i d e t If dextran is used, patients on ACE-inhibition should not be examined or the drug should be withdrawn at least for 4 half-lives. Further possibilities include the use of a BK antagonist or NM, which has been shown to inhibit the contact system These findings explain the pathomechanism of a rare, but potentially lifethreatening side effect.

Bone PMo456

LESIONS with differential infection.

Although its role in the field of cardiology and o n o o l o g y has been well e s t a b l i s h e d , T c - 9 9 m - M I B I (MIBI) accumulation in inflammatory lesions has not been evaluated. Twenty patients with infection and I0 patients with malignant lesions of lower or upper e x t r e m i t i e s u n d e r w e n t MIBI scintigraphy. Planar scintigrams were taken at 5, 15, 30 and 60 min following the injection of 740 MBq MIBI. The ratios of lesion/normal (L/N) were calculated by d r a w i n g ROI over the lesion and contralateral normal area for each patient and at each time interval. The final diagnosis of all patients was based on hystopathological evaluation. The results were as follows LIN~ 5 min 15 min 30 min 60 min INFECTION 2.90+1.7 * 2.88+1.9 2.62±1.69.21+1.1 * (n=20) Malignant 4.84±3.1 4.6±2.8 4.2-+2.6 3.6±2.3 (n=10) The mean L/N of malignant lesions at 5, 15, 30 and 30 min. was found to be slightly but not s i g n i f i c a n t l y higher than those of infectious lesions (*p>0. 005) . In conclusion, MIBI can a c c u m u l a t e in b o t h infectious and m a l i g n a n t l e s i o n s a l l o w i n g no differentiation between these two entity

PMo458

M. Kafi, B. Caner, G. Ozkog, R. Kral, C.Bekdik. H a c e t t e p e U n i v e r s i t y M e d i c a l School, Ankara, Turkey

M. Laci~ T. Bokuli6, J. Luka~, K. Kova~id, R.P. Baum*, Z Kusid. Department of Nuclear Medicine and Oncology, University Hospital "Sestre Milosrdnice" Zagreb, Croatia. *Department of Nuclear Medicine, Goethe University Hospital, Frankfurt / Main, Germany

IMAGING (MIEI):

BONE MARROW IMMUNOSCINTIGRAPHY AND BONE SCAN IN DETECTION OF SKELETAL METASTASIS IN PATIENTS WITH BREAST CANCER

OF Its

OSTEOMYELITIS WITH role in c o m p l i c a t e d

Tc-99m-MIBI bone.

The diagnosis of osteomyelitis (OM) particularly in complicated bone (previously affected by other pathologic conditions such as operation, trauma) is a challenge. In order to evaluate the role of MIBI in diagnosis of i n f e c t i o n in c o m p l i c a t e d b o n e , 1 8 p a t i e n t s w i t h OM in c o m p l i c a t e d . bone (Group A) and ii with traumatic bone fracture (not infectious, Group B) u n d e r w e n t MIBI scintigraphy. Scintigrams were taken 30 min after the i n j e c t i o n of 740 M B q MIBI. Region of interests w e r e d r a w n over the lesion (L) and contralateral normal area (N) a n d L / N w a s c a l c u l a t e d for each patient. The diagnosis of infection was confirmed by the hystopathological evaluation in all patients of Group A. The final diagnosis in Group B was based on radiological methods and/or at least 4 months clinical follow up. Group

A

(n=18) L/N(mean±sd)

2.39 ±0.85*

Group

E

(n=ll) i.ii±0.14

*p<0.005 versus Group B In conclusion, MIBI w i t h a s e l e c t i v e l y higher uptake in infection that healing but not infectious bone has a potential in diagnosis of infection in complicated bone.

1146

The aim of this study was to evaluate the role of bone marrow immunoscintigraphy (BMIS) in the assessment of skeletal metastases in patients (pts) with breast cancer. 23 pts with histologically confirmed breast cancer were included in this study. Whole body MBIS was carried out 3-6 h after i.v. infusion of 0.200.33 mg MAb BW 250/183 labeled with 259-555 MBq Tc-99m In 4 pts additionally a SPET scan of the lumbar spine was acquired. Alkaline phosphatase (AF) was determined in all pts and HAMA response in 16 ones. Tc-99m MDP bone scan (BS) was performed within a period of I week in 19 pts, 2 weeks in 2 pts, 3 weeks in 1 patient (pt) and 4 weeks in I pt. The final diagnosis was confirmed by radiology and/or a 2 years follow up. On a per pt bases we calculated sensitivity (S) of 86%, specificity (Sp) of 88%, accuracy (A) of 86%, positive predictive value (PPV) of 92% and negative predictive value (NPV) of 78% for BMIS and S=100%, Sp=75%, A=89%, PPV=85%, NPV=78% for BS. When we excluded a p t with previous irradiation of the area with metastatic lesion and another one with metastatic lesion in peripheral skeleton BMIS reached S of 100%, A of 95% and NPV of 100%. There were no significant differences between BMIS and BS on a per pt bases (p>0.05) although BS detected significantly more lesions than BMIS (p<0.01). In one pt with normal planar BMIS of lumbar spine SPET scan detected a BM metastatic lesion. Correlation coefficient between BMIS and BS, between BMIS and AF and between BS and AF was: r=+0.688, r=+0.483 and r=+0.374 respectively. One of 16 (6%) pts developed HAMA after BMIS. We concluded that BMIS is a powerful nuclear medicine technic, complementary to BS, for detection of metastatic BM involvement with relatively low HAMA response and without correlation with AF. SPET scan of the lumbar spine may contribute to better sensitivity of the technic.

• PMo459 P.Predi6, *D.Dodig, **E.Gregori6, D.Hrastnik, B.Pustovrh, G. Veningek Hospital Celje, Slovema, * University Hospital "Rebro", Zagreb, Croatia ** Hospital Izola, Slovenia

QUANTITATIVE ANALYSIS OF RELATIVE PERFUSION IN THE ARTERY PHASE (3T) IN DIFFERENTIAL DIAGNOSIS OF ASEPTIC HIP NECROSIS AND ARTHRITIC CHANGES Static scintigram and SPECT of the hips in different hip pathologies very precisely evidence the pathological processes in these regions, however, not allowing the differential diagnosis between such different processes. Therefore, we tried to find out in our study whether a differential diagnosis between different processes would be possible by a quantitative analysis of relative perfusion in the artery phase (3T) of the first phase (dynamic scintigram) of a three-phase scintigraphy of hip skeleton. Our study included 112 patients out of which 73 pts with aseptic hip necrosis and 39 pts with one-side manifested arthritic changes of a hip. 550-740 MBq of Tc-99m-DPD were bolus injected. All patients were subjected to three-phase scintigraphy of hips, SPECT, and calculation of 3T. SPECT and late static scintigram detected in all patients an increased accumulation in the affected hip. 3T in 73 pts with aseptic hip necrosis evidences reduced values, from 0,99 to 0,29, indicating hypoperfusion of the affected hip. In 39 pts with one-side manifested hip arthritis, 3T, however, detected slightly increased values, from 0,98 to 1,35, thus indicating isoperfusion up to slightly increased perfusion. Conclusion: Quantitative analysis of perfusion 3T atows differential diagnosis of the aseptic hip necrosis sothat we can distinguish with great reliability between the aseptic hip necrosis and other pathological changes in the hips.

Bone

PMo461 H. Amthauer, B. Gr0nert, E. HeiBler, T. Schumacher, R. Jochens, W. Stock, J. Ricks, C. Stroszczynski, B. Hell, J. Bier, H. Eichst~dt Strahlenklinik und Potiklinik, Klinik for Mund-, Kiefer- und Gesichtschirurgie, Virchow-Klinikum, Medizinische Fakult~.tder Humboldt-Universit~.t zu Berlin FOLLOW-UP WITH 3-PHASE-BONE-SCINTIGRAPHY IN SPECTTECHNIQUE AFTER MANDIBULAR RECONSTRUCTION WITH FIBULA AND ILIAC BONE GRAFTS Purpose: After free tissue transler and microvascular reanastomoses of bone transplants the monitoring of perfusion and osteoNastic activity is of paramount importance. Aim of our study was to evaluate perfusion and osseointegration of bone grafts with bone scintigraphy in planar and SPECT-technique. Methods: In 45 patients a 3-phase-bone scintigraphy in planar and SPECT-technique was performed after injection of 550 MBq 99m-TeDPD. Scintigraphy was obtained 7-30 days, 6 and 12 months after bone transplantation using a three head. (Multispect, Siemens) or two head gamma camera (Helix, Elscint). Semiquantitative measurements of bone graft uptake was obtained using ROI (region of interest) technique. Regional averages of the uptake in bone grafts were compared with the contrary part of mandible and frontal bone. Results: ScintJgraphy showed a typical hyperperfusion and highly increased osteoblastic activity in osteotomy regions and bone grafts in early phase (7 days to 1 months) with an average uptake value of 2.9+/-0.4. After 6 months osteotomy regions showed a decreased uptake, whereas the bone graft still had an increased uptake with 1.9 +/-0.3. In the further follow-up after 12 months the osteoblastic activity was slightly increased with an uptake of 1.2 +/-0.3. Conclusions: These data indicate that 3-phase-bone-scintigraphy in SPECT-technique is a valuable method for analysis of different levels and periods o! perfusion and osseointegration in the bone graft and osteotomy region. Therefore the method seemsto be promising for the assessment of viability of fibula and lilac bone grafts in mandibular reconstructions.

C O

| m

,1=,1

G)

,= PMo460 z, .~)z.p_an, z. Burak, K. Kumanhoglu, D. Sabah, G. Ba@demir, H. 0zkfl=9.

Ege University Medical Faculty, Nuclear Medicine, Orthopedic Surgery and Pathology Departments, JzmirTurkey. THREE PHASE DYNAMIC BONE IMAGING VERSUS STATIC BONE SCINTIGRAPHY IN THE ASSESSMENT OF THERAPEUTIC EFFECTS Static bone scintigraphy is known to offer insufficient data in the evaluation of chemotherapeutic effects in muskuloskeletal tumors. In this study it was aimed to correlate changes in serial dynamic bone imaging with histopathological response to preoperative chemotherapy. 20 patients (pts) (13 osteosamoma, 7 Ewing's sarcoma) underwent Tc ggm MDP three phase dynamic bone ssintigraphy before and after chemotherapy. Data was interpreted by two nuclear medicine specialists 1) using only 3 hr delayed static images without the knowledge of first two phases and, 2) by the combined evaluation of first-pass, blood pool and delayed images. Lesion/contralateral normal tissue blood flow ratio was also obtained by ROI technique. Seintigraphic findings were categorized as improvement, no change and worsening according to the change in tumor vascularity, tumor extension and lesion intensity. Histologically 13 pts showed complete response to therapy. The correlation of combined evaluation of blood flow/blood pool and delayed images and final histology was excellent (13/13). When only 3hr static images were taken into account, 4 out of 13 were misinterpreted as no change and worsening. Quantitative data demonstrated mean 53±14 % decrease and -5.4±16 % change in tumor vascularity in the responder and non-responder pts respectively.

¢)..

PMo462

U.Bilkay, UoBilkay, M.Ar~on, T.GUrler, K.KumanlzoOlu Departments of Nuclear Medicine and P l a s t i c - R e c o n s t r u c t i v e Surgery, Ege U n i v e r s i t y , Izmlr Turkey. THE VALUE OF BONE SCAN IN k~NDIBULAR FRACTURE TREATMENT The e f f e c t s of r i g i d and F l e x i b l e F i x a t i o n ( I n t e r m a x i l l e r f l x a t l o n - l M F ) methods in the treatment of long bone f r a c t u r e s were studied by many authors. The aim o f our study was to compar pare these two treatment modalities of mandible f r a c t u r e s by bone scan. Two study groups were selected From 23 pts. who have had mandibular f r a c t u r e s . None o f the p~s. suffered from systemic or metabolic disease which can i n t e r f e r e with bone healing. The 1st. group underwent only IMF and 2nd group underwent r i g i d f i x a t i o n (RF) and then IMF. The c a l l u s Formation was evaluated by bone scan in the postop. 1st, lOth, 20th,30th days. 2 hr. a f t e r the IV i n j . of 10 mCi Tc?gm MDP, s t a t i c i a n t e r i o r c r a n i a l images were obtained. ROIs drawn over the Fracture s i t e (F) and the i n t a c t p a r i e t a l bone (C). The mean p i x e l counts For ROIs were calculated and F/C r a t i o s were obtained. Peak a c t i v i t y was Found using F/C r a t i o s . Of a l l I~F. pts 2/12 reached peak a c t i v i t y a t 1st day, Y/12 at 10th day, 1/12 at 20th postop, day. OF a l l RF+IMF 1/11 pts. reached peak a c t i v i t y at 10th day, 7/11 a t 20th day and 3/11 30th postop, day. In conclusion, e a r l i e r peak F/C r a t i o s were obtained with IMF which i s known to be a more p h y s i o l o g i c a l method that allows minimal motion a t the f r a c t u r e s i t e .

As a conclusion it is suggested that three phase dynamic bone imaging more accurately predicts therapy response than static bone scintigraphy. Alteration ratio in tumor vascularity may also be complementary in the assesment of therapeutic effects.

1147

O

n

•

Bone

PMo463

PMo465

JR Garcia, M Ysamat, M Balsells, J Ma~osa, F Tarroc, M Cuchi. CTD - Hospital Mutua de Terrassa.

H HOftken R. Stiletto, H.W. Fritsch, F. Horbach, S. Hoffmann, L. Gotzen, K. Joseph Klinikum der Philipps-Unlversitat Marburg, Abteilung fur Klinische Nuklearmedizin

NON-HEALING DIABETIC FOOT ULCERS: CLINICAL USEFULNESS OF LEUKOCITE SCINTIGRAPHY COMBINED WITH BONE SCAN.

ASSESSMENT OF BONE GRAFT INGROWTH BY SPET The ingrowth characteristics of homologous or allogenic bone transplants cannot be assessed by radiological methods such as CT or standard Xray, because they only visualize indirect phenomena. Due to the artefacts caused by the implanted anterior plates or posterior spinal fixateurs MILI cannot be applied, too. Therefore the goal of our study was to evaluate transplant viability by in vivo imaging of the bone metabolism with Tc99m-MDP using SPET. Patients: We examined 12 patients with spinal fractures. In 6 patients a wedge compression fracture was treated by an interpedicular bone graft and associated posterior bone grafting by chips of cancellous bone. The fractures of the other six patients were stabilized by anterior allogenlc bone block transplants. Methods: Two hours after injection of 555 MBq Tc-99m-MDP the SPET-studies of the spine were performed using a 3-head gamma-camera with high resolution collimators. The projection data were acquired in 192 image matrices with a size of 128x128 pixels. The acquisition time was 30s per view. After prefiltering of the projection data (Butterworth, 0.5 Nyquist, order 4) transversal, frontal and sagittal slices were reconstructed by backprojection. Radionuclide uptake in the bone transplants was evaluated visually. Results: In all six patients treated by posterior transpedicular bone grafts, as well as in four patients with anterior stabilisation by allogenic block transplants ingrowth was shown by a significant radionuclide uptake in the transplant region. Two bone blocks were mechanically stable but did not show Tc-99m-MDP utake, wich was interpreted as a nonconsolidation of these transplants. Conclusion: According to the results of this study bone SPET may be usefull for the long-term follow-up monitoring of bone graft ingrowth in spinal surgery.

PURPOSE: In diabetic foot ulcers, the presence of an underlying osteomyelitis often leads to an unfavourable evolution. The aim of this study was to assess the utility of leukocyte scaning in non-healing diabetic foot ulcers (NHFU) . MATERIAL AND METHODS: Out of 150 episodes of ulceration managed in an outpatient basis, 33 required admission for NHFU evaluation in 28 patients (12 men/16 women mean age 65+/-12 years). We performed plain radiograph, ~mTc-MDP two phase bone scan and 9~mTc-HMPAO autologous leukocite scan, within a week. Both isotopic studies were adquired in a 512 matrix, in order to have better resolution between soft-tissues and bone structures. We performed biopsy in 16 cases with bad outcome after severals weeks of antibiotic therapy. The others 17 lesions were evaluated by scintigraphic-clinical control during 4=7 months.

RESULTS: Osteomyelitis was diagnosed in 19 of 21 cases. The 2 False negative were found in patients with severe vasculopathy. The only 1 False positive was localizated in the last phalange of the fifth finger, probably for the proximity of the ulcer. CONCLUSIONS: Combined bone and leukoeite scanning is a non-invasive useful test for diagnosing bone infection in NHFU. The simple technical innovation of 512 matrix allows delimitation of the leukocite uptake, in relation of localization of bony structures.

PMo464

PTu466

E. G r e m i l l e t * , A. C h a m p a i l l e r * , D. A v e t °, R. B a r d o n n e t °. * C e n t r e d'Imagerie Nucl~aire and °D~partement d'Orthop~die, Polyclinique de Beaulieu, Saint-Etienne, France

S.Erdem, IoKorabekir, O.ArpaczoOlu, M.Azgon, E.Kzzzikaya, F.Karsh. Departments of Nuclear Medicine, Traumatology and Radiodiagnostics, Ege University and GATAHaydarpa~a, Turkey.

A S S E S S M E N T OF A L L O G R A F T I N C O R P O R A T I O N PHASE BONE SCAN AND SPECT

WITH

THREE

Radiosterilized freeze-dried allografts are used to fill in bone defects of various origins: revision arthroplasty, trauma, tumour. We investigated the ability of bone scan (three phases and SPECT) to assess if allograft was incorporated and if incorporation was homogenous o r n o t . 11 p a t i e n t s w e r e s t u d i e d a f t e r a m i n i m u m follow-up o f o n e year. I n t e r p r e t a t i o n criteria were: (i) p h a s e s 1 a n d 2: l o c a l d e c r e a s e = n o n incorporation; normal or increase = unconclusive; (ii) p h a s e 3 ( p l a n a r ) : n o r m a l o r i n c r e a s e d u p t a k e (with respect to adjacent and/or controlateral bones) = good incorporation unless (iii) S P E C T : heterogeneity = partial non-incorporation. Overall results: 8 homogenous incorporation, 3 partial non-incorporation. In 2 of the 3 last cases heterogeneity was not obvious on planar images but well shown by SPECT. These findings were consistent with clinico-radiological findings and surgery ( p e r f o r m e d in 2 c a s e s f o r material removal). Moreover three phase bone scan showed Sudeck's disease in 2 c a s e s (1 g o o d incorporation, 1 partial non-incorporation) confirmed by clinical and therapeutic follow-up. In conclusion: as in most focal bone diseases, three phase bone scan combined with SPECT appears t o b e u s e f u l in a s s e s s i n g a l l o g r a f t i n c o r p o r a t i o n and especially incorporation homogeneity (an i m p o r t a n t i s s u e in t h i s c a s e ) .

1148

SCINTIGRAPHIC PATTERNS OF THE REFLEX SYMPATHETICDYSTROPHY SYNDROMEOF THE HANDAND THE FOOT The Reflex Sympathetic Dystrophy Syndrome (RSDS) is a clinical syndrome of poorly understood aetiology with well defined clinical features. The aim of the study was to provide additional information about the scintigraphic pattern of patients with RSDS. Three phase bone scanning was performed in 38 pts. suffering

from RSDS of the hand or the f o o t . The affected regions were in 22 cases w rist and hand in 16 cases foot and ankle. Pts. were c l a s s i f i e d according to c l i n i c a l stage of RSOS at the time of r e f e r r a l and the t i m e - i n t e r v a l a f t e r trauma . Regional tracer accumulation was quatitated f o r the a r t e r i a l (0-30 sec), blood pool (0,5-5 min) and delayed bone f i x a t i o n (2-3hr).There main stages of RSDS were demonstrated s c i n t i graphically. The rate of positive scintigraphy in a r t e r i a l and blood pool phases was determined to be %66 , ~o57 and ~53 f o r stage I , I I and I I I respectively. The s e n s i t i v i t y of delayed bone f i x a t i o n phase was found to be ~78, %71 and %73 f o r stage I , I I , I I I respectively. In conclusion bone scintigraphy is more l i k e l y to be positive in the l a t e r c l i n i c a l stages of RSOS and the most consistent uptake pattern was a homolateral p e r i a r t i c u l a r uptake in the bone phase. The recognition of specific patterns of tracer uptake in the bone phase increases the diagnostic u t i l i t y of bone scintigraphy in RSDS.

•

Bone

PTu467

PTu469

M. Rajt~ir, S. Sonkodi*, L. Csernay A. Szent-GySrgyi Medical University, Department of Nuclear Medicine, International Medical Center, International Dialysis Center*, Szeged, Hungary

A. Bockisch\ A. Eckardt*, M.Thom~*, R. GOrges~, J. Heine* (+)Clinic for Nucl. Med., Univ. of Essen and (*)Clinic for Orthopedics and (#)Clinic for Nucl. Med., Univ. of Malnz, Germany

Dual energy X-ray absorptlometry in patients with end-stage renal failure

SPACIAL RESOLVED ANALYSIS OF TIME-COURSE OF BONE MINERAL TURN OVER AND BONE MINERAL CONTENT IN THE NEIGHBOURHOOD OF THE ABG-ARTHROPLASTY OF THE HIP.

Bone mineral measurements were performed on the lumbar spine (LS) and femoral neck (FN) of 74 patients (40 males, 34 females, mean age 56.2 yr +/-13.3) with end-stage renal failure (ESRF), using dual energy X-ray absorptiometry. Twenty-nine of the female patients had been in menopause for an average of 16.3 yr (+/-10.6). In the overall group, the mean duration of haemodialysis was 20 months (+/-26.3). Significant negative correlations were found between the LS bone mineral density (BMD) and the age, the duration of dialysis and the serum PTH level (r= -0.36, -0.31, 0.33, p<0.05), respectively. The FN BMD correlated only with the age (r = -0.45, p<0.05). A significant bone loss (>25%) relative to the peak bone mass was shown in 30 pts (40.5%; 12 males, and 18 females). The bone loss was more pronounced in the FN (26.1% +/5.6) than in the LS (22.8% +/-4.8). The rate of bone loss was significantly higher in postmenopausal (PM) females than in males in both evaluated regions (LS PM females: 30.5% +/-6.1, LS males: 20.4% +/-5.7; FN PM females: 34.6% +/-6.8, FN males 24.7% +/-6.2). The results suggest that an early decrease of the ovarial function (oligo-raromenorrhoea, menopause) in females aggravates the alterations in bone metabolism associated with ESRF. This study emphasizes the need to pay more attention to the regular monitoring of BMD and to the prevention of bone loss in female patients (otherwise having a lower peak bone mass than that for males) with ESRF.

In a prospective study, the bone mineral turn over (BMTO) and the absolute bone mineral content (BMC) in the bone next to the cementless anatomical shaped press fit fixating ABG-hotal hip prosthesis were analyzed. The proximal part of the stem and the hemispherical cup are coated with a thin layer of hydroxyapatite providing an early bony ingrowth of the prosthesis, the biomechanical stress-transfer is attained only in the proximal femur, the distal part of the prosthesis should remain without bony contact and load transfer to avoid proximal bone loss and stress-shielding. So far 30 patients were monitored 10 days, 3, 6 and 12 months after surgery by a 3-phase bone scan together with BMC measurements of both hips and the lumbar spine. Additionally long term data of 5 patients could be evaluated who underwent total hip replacement 2 to 3 years before. Results: The blood pool and BMTO were found to be increased in the early postoperative phase. In the - load beating - intertrochanteric region the BMTO showed persisting elevated values. The surrounding bone of the distal part of the prosthesis shows activity at any time. A bony ingrowth of the prothesis is therefore unlikely corresponding to the design of the prosthesis with a proximal fixation of the stem. In patients, who developed heterotopic ossifications this could already be detected 10 days after surgery. Any predictive parameter for its later relevance could not be isolated, however.

co

= B

t~ e-

t/} Ill x.__ PTu468

PTu470

CCo~kun,i Bernay,L.tncesu,CVan,F.Cant(irk,T Ba~oglu,M. Sahin Ondokuz Mayls University Hospital, Departments of Nuclear Medicine, Physical Therapy and Rehabilitation and Radiology, Samsun, Turkey.

A. Serra. P. Solinas, M.D. Azzena, P. Sulas, S. Nuvoli, I.Vannucchi, A.Spanu and G.Madeddu. Dept. of Nuclear Medicine. University of Sassari, Italy

CONTRIBUTION OF PINHOLE BONE SCINTIGRAPHY TO THE DIAGNOSTIC EVALUATION OF PAINFUL S H O U L D E R

MOC AND NEW BIOCHEMICAL MARKERS IN DETECTING BONE MASS CHANGES DURING L- THYROXINE TREATMENT.

Although there are numerous studies on the evaluation of painful shoulder by arthrography, CT, magnetic resonance imaging (MRI) and ultrasound, there is only a few data on the diagnostic value of bone scintigraphy We evaluated 24 chronically painful shoulders in 23 patients with planar bone scintigraphy using a pinhole collimator. Bone scintigraphy was positive in all of the shoulders which took the diagnosis of painful shoulder by clinical examination and radiography. Bone and soft tissue structures in twelve shoulders were also evaluated by MR[. Scintigraphies were visually interpreted independently by two investigators defining the increased tracer accumulation in articular and periarticular regions, particularly in muscle insertion points .The results were compared to IvlRI findings. There were 37 pathological sites in 12 shoulders examined by MRI. The distribution of the MR1 and scintigraphy findings in all examined shoulders are given below.

The aim of this study is to clarity whether L=Tiroxine (T4) treatment accelerates skeleton turnover, causing bone loss. To this purpose we investigated 152 female pts, 57 in pre (P) and 95 in post-menopause (M); 36 pts (17P,19M) were on replacement (R) T4 therapy tot primary hypothyroidism after goiter excision or due to chronic thyroiditis and 116 on suppressive (S) T4 for thyroid carcinoma (SC) in 54 cases (19P, 35M) and for nodular goiters (SG) in 62 cases (21P, 41M). Mean T4 dose, treatment time interval and TSH levels were: 87.15 _+33 Ilg/die, 37.053_+28 mths and 0.89_+0.86 IJU/ml in R pts, 148.15_+25.47 Ilg/die, 68.52_+52.30 mths, 0.046-+0.032 llU/ml in SC, 94.15+_26.94 fig/die, 30.45_+39.64 mths, 0.086_+0.06 IJU/ml in SG, respectively. In all pts, none ever affected by hyperthyroidism and continously monitored with serial FT3, FT4 and TSH assays, BD was measured in spine by multidetector (DPA); 76 osteoporotic(OP) pts (33P, 43M) without thyroid disease and 132 sex- age matched controls (C), 33P and 99M, were also investigated. Both R and SC as well as SG pts had significantly low BD values in respect of C but only in M cases; all 3 thyroid pt groups showed lower BD in M than in P pts when mutually compared. However, the significantly lower BD in OP pts compared to R, SC, SG and C was independent of menopause. In 69 suppressive T4 treated pts, 37 SC (14P, 23M) and 32 SG (15P,17M), and in 41 C (18P, 23M), bone alcaline phosphatase (BAP) and osteocalcin (O) were also assayed in serum by IRMA and pyridinoline (PYRI in urine by ELISA. None of the 3 markers were significantly different in the 2 groups of pts in respect of C; moreover, there was no difference between SC and SG pts. However, in both these groups the markers were higher in M than P pts, but not significantly. Negative significant correlation was accerlained between BAP, O, PYR and BD while none of these parameters correlated with T4 dose, treatment time interval, TSH, FT3 or FT4. Our data seem to indicate an apparently low turnover bone loss may be present in L-Tiroxine treated pts, but only in menopause and independently of T4 dose, treatment time and TSH suppression. Both BD and biochemical markers may be useful for a better selection of pts to treat with T4, to submit to bone disorder preventive therapy and for a more accurate~ prolonged follow-up.

MRI SC1NT Acromioclavicular joint degeneration n=9 + 8 of 9 + Supraspinatus tendinitis n=8 + 6 of 8 + Biceps tendinitis n=9 + 9 of 9 + Supscapularis tendinitis n=8 + 6 of 8 + Teres minor tendinitis n=3 + 0 of 3 + TOTAL n=37 37/37 29/37 In one patient with increased tracer accumulation in the insertio of biceps ,MRI was normal .Considering that MRI is a primarily sensitive tool in the evaluation of soft tissue pathologies, here muscle tendons, we can conclude that, pinhole bone scintigraphy can contribute to the assesment of painful shoulder by giving more information about bony involvement

1149

O IX

•

Bone

PTu471

PTu473

A.OZDEM~R,M.ERKILIC, H.~ZDEM~R,B.KAKAYAL¢IN, F.GUNGOR Departments of Nuclear Medicine and Orthopaedic Surgery, Akdeniz University School of Medicine,Antalya,TURKEY

F. Pons 1, L. del Rio 2, FJ. Setoain1, D. Fuster 1, J. Setoain la

THE VALUE TEARS

OF

HIGH-RESOLUTION

BONE

SPECT

(1) Nuclear Medicine Department, Hospital Clinic, University of Barcelona (2) CETIR, Centre Mddic. Barcelona, Spain. ARE LUMBAR SPINE MEASUREMENTS OF BONE MASS ENOUGH IN ASSESSING OSTEOPOROSIS RISK AT THE MENOPAUSE?

IN MENISCAL

The aim of this study was to identify the most accurate diagnostic criteria in meniscal tears by high-resolution(H.R)bone SPECT.For this,three phase bone scan and H.R SPECT were performed after 740 MBq Tc-99m MDP injection in 14 patients(9M/5F mean age 37).Arthroscopy was accepted as gold standart and was applied to all patients in the study.The effect of the presence or absence of tibial,femoral and blood pool activity on sensitivity, specificity, positive predictive value(pPV),negative predictive value(nPV) for H.R spect imaging were evaluated.Using a halfcrescent or more of tibial plateau activity for diagnosis,sensitivity was f o u n d 100%,specificity 33%,pPV 66%,nPV 100%.Using a half-crescent or more of tibial plateau activity and adjacent femoral activity as diagnostic criteria,sensitivity was found 100%,specificity 50%,pPV 72%,nPV 100%.Using a half-crescent or more of tibial plateau activity, adjacent femoral activity and blood pool activity as diagnostic criteria ,sensitivity was found 87%,specificity 100%,pPV 100%,nPV 85%.We found that the most accurate diagnostic criteria in diagnosis of meniscal tears was the half crescent or more of tibial plateau activity with femoral and blood pool activity. In conclusion,H.R SPECT is highly sensitive and specific imaging method for the diagnosis of meniscal tears.

The main goal of this study was to evaluate whether measurements of bone mass performed only in the lumbar spine are sufficient in assessing individual risk for osteoporosis in menopausal women. A wide group of 7425 women who were in the early period of menopause (the first 5 years) were studied by bone densitometry at least twice (mean interval of 20.5 months). Bone mineral density (BMD) was measured in the lumbar spine and proximal femur with a DXA technique (Lunar DPX-L). The risk of osteoporosis was defined either as a low BMD (1 SD or more below the mean BMD for healthy premenopausal women) or a rapid rate of bone loss. When only lumbar BMD was assessed, 25.7% of the women were considered at risk of osteoporosis while when only the proximal femur was evaluated, the percentages of women detected at risk were 16.2% for femoral neck, 17.2% for Ward's triangle and 13.2% for trochanteric region. From those women considered at risk just taking into account one spine BMD measurement, 14.2% had a normal femoral BMD. However, when we only evaluated femur BMD, from 6.6% to 18% (depending on the femoral region) of patients at risk of osteoporosis showed normal BMD spine values. The annual rate of bone loss was greater in spine (-1.19%) and Ward's triangle (-1.27 %) than in the femoral neck (-0.94%) or trochanter (-0.28%). The ratio between bone mass loss and precision was higher for lumbar spine than for femur. These findings confirm that BMD measurements performed in different skeletal sites in a very large population group are discordant and, obviously, it is advisable to scan both regions to assess more acurately the individual risk of osteoporosis in postmenopausal women.

PTu472

PTu474

*G.Ka~ar, C.Ka~ar, *B.Karayal~m, T.Tuncer

S-O. Yang, Y-¥. Choi, J-S. Ryu, Y-T. Kim, S-B. Ha, K-Y. Kim and H-K. Lee.

Akdeniz University Fat.of Med, *Depamnent of Nuclear Medicine and Department of Physical Medicine and Rehab. ANTALYA.TURKIYE

Asan Medical Center, Ulsan University, Seoul 138-040, KOREA Tc-99m MDP BONE SCAN FINDINGS IN BERTOLOTTI'S SYNDROME.

QUANTITATIVE SACROILIAC JOINT SCINIIGRAPHY Contrary to radiographic methods (X-ray and CT), early stage sacroiliitis (SI) can be diagnosed by bone scinfigraphy. The sensitivity o f this method can be increased by quantitative assessment and in this way it may be possible to diagnose bilateral SI more objectively. The aim o f this study : 1. To find the sacroiliac indexes (SII) of the normal control group and, 2. To compare these values with patients having SI. 47 normal {36 (13M, 23F) age between 20-60 years; 11 (5M,6F) age > 60 years} and 10 patients {(SM, 2F) age between 20-50 years} were included to the study. 3 hours after IV injection of 740 MBq Tc99mHMDP, anterior and posterior images were obtained from pelvis. Focal and whole sacroiliac joint ROIs were taken for calculation of SII. 20x20 pixel ROI was taken from the most active part of sacrum which was the reference bone The results are given as mean +- 1SD: FEMALE

A retrospective study was done to evaluate bone scan findings in the diagnosis of symptomatic transitional vertebrae (Bertnloni's syndrome). The relationship of lumbar back pain to transitional vertebrae at lumbosacral junction is not clear, but transitional vertebrae that articulate with only one side of the sacrum are more likely to be associated with symptoms. During the last six years, we experienced seven patients (male: female = 2:5) with symptomatic transitional vertebrae who were performed bone scan. We analyzed the findings of bone scan (n=7), bone SPECT (n=2), CT and MRI (n=l) in these patients. All patients showed lumbosacral transitional vertebrae unilaterally (right:left = 4:3) on simple radiography. Six patients had definite local pain in the lumbosacml junction and one patient had moderate back pain. Five patients with definite backache showed increased activities at the corresponding site of transitional

MALE

vertebra on Tc-99m MDP bone scan. Four patients with asymptomatic transitional

20-60 y

) 60y

20-60y

> 60y

Left $1I

0.98+_0.12

0.87_+0.09

t.09+_0.12

1.02+_0,1

noted. Two patients with mininal increase at the lesion performed bone SPECT

Rigth Sll

0.99_+0.14

0.87+_0.09

1.08+_0.11

1.02_+0.08

which resulted in clear demonstration of increased activity along the articular

SII was higher in men than women (p(0.05). Although SII did not change significantly in aging men, it decreased signiftcantly in aging women (p(0.05). In all patients with sacroiliitis SII was higher than normal controls. Our results suggest that quantitative sacroiliac joint scintigraphy is a sensitive method in the diagnosis of early stage SI.

1150

vertebrae who performed bone scan were evaluated, but no abnormalities were

surface of the transitional articulation. Each one case of CT and MRI also showed sclerosis and narrowing of the transitional articulation. We conclude that bone scan and bone SPECT can be useful to know the symptomatic correlation in tlle patients with transitional vertebrae at the lumbosacral junction.

•

Bone/Cardiovascular

PTu475

PMo477

L. Carp (1), B. Krug (1), M. Driessens (2), P. Blockx ~1). Departments of Nuclear (1) and Physical Medicine (2), Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium.

V.B.SOrensen, It.Wroblewski, S. Galatius-Jensen, S. Hauns¢ and J. Kastrup, Rigshospitalet, National University Hospital, The Heart Center B 2142, 9 Blegdamsvej, DK-2100 Copenhagen O, Denmark.

BONE SPECT OF THE CERVICAL SPINE IN THE EVALUATION OF W H I P L A S H INJURY WITH NEGATIVE RADIOLOGICAL FINDINGS.

C O N T I N U O U S C A L F SKELETAL M U S C L E BLOOD F L O W D U R I N G G R A D E D B I C Y C L E E X E R C I S E USING T H E LOCAL W A S H O U T T E C H N I Q U E : M E T H O D O L O G I C A L CONSIDERATIONS

Whiplash injury is described as an hyperextension- hyperflexion injury of the cervical spine, usually caused by a motor vehicle accident. A significant proportion of patients without radiographic evidence of acute trauma experience neck pain or associated symptoms for months, or even years after trauma. Our purpose was to study if there is a role for bone SPECT of the cervical spine in the evaluation of whiplash injuries in patients with negative radiological findings concerning bone injury. In 11 patients (1 male, 10 females; mean age 35 yrs, range 21 - 57 yrs), bone SPECT of the cervical spine was performed. Median elapsed time betweeninjuryand imagingwas 13 months (range2 - 42 months). At the time of imagingall patients were still symptomatic. ConventionalX-R and/or CT-MRI were performed in all patients prior to bone SPECT. On X-R/CT/MR1 no patient was found to have major bone injury. With bone SPECT positive sites were found in 10/11 patients: vertebral body (n=3, number of positive sites 2, 6 and 2), intervertebral joint (n=8, numberof positive sites 2, 4, 2, 1, 2, 2, 2 and t). Hot spots at the intervertebral joints were most suggestive for active osteoarthropathy and one of these patients (with a single hot spot) responded well to an intra-articular injection with a local anesthetic agent. Although our number of patients is still too small to permit definitive conclusions, it is clear that bone SPECT of the cervical spine in whiplash injury can reveal bone abnormalities not shown by radiologic imaging modalities. The fact that bone SPECT imagingshowed positive sites in 10/11 patients encourages further prospective study. In view of the medico-legal and socio-economic impact of malingering and litigation it is important to state that absence of active bone remodeling within the cervical spine virtually eliminates occult fractures, traumatic periostitis or active osteoarthritis and allows appropriate conservative treatment.

Cardiovascular PMo476 C. M a u n o u r y , C.C. Chen, K. B. Chua, C. J. Thompson, G. Burns, and L.E. Holder. University of Maryland Medical System, Baltimore, MD, U S A A S S E S S M E N T OF L E F T V E N T R I C U L A R F U N C T I O N W I T H G A T E D SPET: A R E L I A B L E A L T E R N A T I V E TO F I R S T PASS R A D I O N U C L I D E A N G I O G R A P H Y . T h e p u r p o s e of the s t u d y w a s to c o m p a r e t e c h n e t i u m - 9 9 m s e s t a m i b i m y o c a r d i a l g a t e d SPET to standard first pass radionuclide angiography for the evaluation of left v e n t r i c u l a r function. Sixty-seven consecutive patients were studied. F i r s t p a s s a c q u i s i t i o n w a s p e r f o r m e d i m m e d i a t e l y a f t e r the i n t r a v e n o u s i n j e c t i o n of 925 M B q (25 mCi) of T c - 9 9 m s e s t a m i b i . Rest myocardial gated SPET acquisition was p e r f o r m e d at 1 h o u r p o s t i n j e c t i o n of T c - 9 9 m sestamibi. A c o m m e r c i a l l y a v a i l a b l e a u t o m a t e d gated SPET processing software was used. Parameters evaluated were left ventricular ejection fractions (LVEF), end diastolic v o l u m e s (EDV), e n d - s y s t o l i c v o l u m e s (ESV) a n d stroke v o l u m e s (SV). There was excellent correlation between myocardial gated SPET with Tc-99m sestamibi a n d first p a s s r a d i o n u c l i d e a n g i o g r a p h y : r : 0.86 for LVEF, 0.88 for EDV, 0.93 for E S V a n d 0.70 for SV. In c o n c l u s i o n , myocardial gated SPET q u a n t i f i c a t i o n of left v e n t r i c u l a r f u n c t i o n is a r e l i a b l e t e c h n i q u e a n d is a g o o d a l t e r n a t i v e to first p a s s r a d i o n u c l i d e a n g i o g r a p h y .

Purpose: Measurement of skeletal muscle blood flow during exercise is of

great interest, but hard to perform due to technical difficulties. The aim of the present study was to apply the non-invasive local washout method for skeletal muscle blood flow measurements duriug graded bicycle exercise comparing the isotopes 13SXenon and 9SmTc-pertechnetate. M e t h o d : Calf skeletal muscle blood flow of 15 healthy subjects was measured continuously during bicycle exercise in supine position with 133Xenon and 99mTc-pertechnetate in the left and right leg, respectively. Counts were accumulated in two seconds intervals. Results: Satisfactory continuous blood flow registrations were obtained for both isotopes during exercise. With 133Xenon, blood flow increased continuously with increasing working load. In contrast, using 99mTc-pertechnetate the blood flow levelled out at the second load and no further increase was seen. Whert exercise stopped, blood flow decreased immediately to pre-exercise levels for both isotopes. The absolute blood flow levels at rest and during exercise from 3-2t rain were higher with sSmTc-pertechnetate compared to 13ZXenon. At maximum working load for each subject, the increase in blood flow for 133Xenon and 99mTc-pertechnetate was 10 and 2 fold, respectively. Mean arterial pressure and heart rate increased gradually during the exercise. Conclusion: Our observations indicate that 133Xenon can be applied sueessfuUy for measurements of continuously skeletal muscle blood flow during graded bicycle exercise. 99mTc-perteehnetate is not useful for the high blood flow measurements obtained during exercise. We attribute this t o diffusion limitation.

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PMo478 J. Kotzerk¢, S. Glatz, M. H6her, S.N. Reske, University of Ulm, Germany TC-99M-SESTAMIBI WHOLE-BODY DISTRIBUTION AFTER STRESS TESTING WlTH ARBUTAMINE AND DIPYRIDAMOLE We investigated the uptake of Tc-99m sestamibi in various tissues after myocardial blood flow stimulation with the chronotrope/inotrope, arbutamine (Arb), and the vasodilator dipyridamole (Dip), in 9 patients with suspected coronary artery disease. Arb produced a mean maximum heart rate (HR) of 91+11% of the age predicted maximum HR before injection of 415+10 MBq Tc-99m sestamibi. After 24 hours 0.56 mg/kg Dip was administered over 4 minutes and the isotope injection repeated. The rest study was performed on a subsequent day within one week. Activity in the whole body, lungs, heart, and lower limbs was calculated from planar anterior whole body imaging which was acquired 30 min after injection.

Dipyridmnole

Tc-99m Sestamibi Uptake Heart/Whole Lower Limbs/ Heart/Lung body (%) Whole body (%) (Ratio) 2.4_+0.4 26.1+5.0 2.8+0.5

Arbutamin

2.1-+0.5

Rest

Ins 1# }# 2.1+0.4 17.7-+2.6 2.2+0.3 # p<0.05, ## p<0.001, ns Non significant

}#

}##

13.7_+1.7

}#

2.5_+0.4

Reversible perfusion defects were identified in 3/9 patients with Arb and Dip. Only minor adverse effects were noted with both agents. While Arb produced significantly less isotope uptake in the peripheral skeletal muscle than Dip, the latter agent produced a greater heart/lung ratio although there was no difference in diagnostic outcome. A.rb could be used as an alternative to Dip especially when the latter is contraindicated.

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Cardiovascular

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PMo481

N.David P.Y.Marie, P . O l i v i e r , S.Denet, N . Q u i r i , T.Arsena, N.Hassan, M.Angio[, N.Danchin, G . K a r c h e r a n d A . B e r t r a n d . D e p a r t m e n t s of C a r d i o l o g y a n d of N u c l e a r Medicine, Nancy, FRANCE.

B.L.F.van Eck-Smit, S, Poots, A.H.Zwinderman, E.K.J.Pauwels, E.E.van der Wall. Department of Nuclear Medicine, Leiden University Hospital. Netherlands.

COMPARED EXTENTS OF UNDERPERFUSED MYOCARDIUM B E T W E E N E X E R C I S E A N D D I P Y R I D A M O L E T I 2 0 1 - S P E C T IN PATIENTS WITH EXERCISE MYOCARDIAL ISCHEMIA D i p y r i d a m o l e - S P E C T h a s b e e n s h o w n to f r e q u e n t l y u n m a s k m y o c a r d i a l i s c h e m i a in pts h a v i n g a n o r m a l s u b - m a x i m a l e x e r c i s e - S P E C T . However, no s t u d y h a d systematically compared exercise and dipyridamole T I 2 0 1 - S P E C T in pts u n a b l e as w e l l as in those able to p e r f o r m a m a x i m a l e x e r c i s e test. T h i s was the a i m of this s t u d y w h e r e 23 c o n s e c u t i v e pts, h a v i n g a n g i n a or ~ 2 m m ST d e p r e s s i o n d u r i n g an e x e r c i s e T I 2 0 1 - S P E C T (EX), w e r e r e f e r r e d to a T I 2 0 1 - S P E C T p e r f o r m e d a f t e r 4 0 W b i c y c l e e x e r c i s e a n d 0.56 m g / k g d i p y r i d a m o l e i n f u s i o n (DIP). B a s e l i n e exerc i s e T I 2 0 1 - S P E C T was m a x i m a l (~85% of max. predicted heart rate) in 9 p t s (GI) a n d not in 14 (GII). ST s e g m e n t d e p r e s s i o n w a s l o w e r a f t e r D I P t h a n a f t e r EX (1.3 ± 1.3 mm vs 2.1 ± 1.3 ram, p :.001) but e x t e n t of S P E C T d e f e c t w a s e q u i v a l e n t w i t h the 2 t e s t s (21 f 15 % of LV vs 18 ± 9 % of LV, NS). T h e r e were, however, m a r k e d i n d i v i d u a l variations: in GI (n=9), the d e f e c t s w e r e l a r g e r a f t e r D I P t h a n a f t e r EX in 2 pts (22 %), a n d larger a f t e r EX than a f t e r DIP in 4 (44 %) ; in GII (n=14), the defects w e r e l a r g e r a f t e r D I P in 6 p t s (43 %), and l a r g e r a f t e r E X in 5 (35 %). S u r p r i s i n g l y , the d e f e c t s extents w e r e e q u i v a l e n t w i t h the 2 tests in o n l y 6 p t s (23 %) a n d f r e q u e n t l y u n d e r e s t i m a t e d b y DIP c o m p a r e d w i t h EX, i r r e s p e c t i v e of the p e r f o r m a n c e of a m a x i m a l test (max.:44 % vs sub-max.: 35 %, NS). In p t s w i t h e x e r c i s e m y o c a r d i a l ischemia, d i p y r i d a m o l e and e x e r c i s e T I 2 0 1 - S P E C T p r o v i d e d i f f e r e n t e s t i m a t i o n s of the i s c h e m i c area. T h o s e d i f f e rences m a y not be s i m p l y e x p l a i n e d b y the a b i l i t y or not to p e r f o r m a m a x i m a l e x e r c i s e test.

DIAGNOSTIC VALUE OF MYOCARDIAL SPECT IMAGING WITH TECHNETIUM-99M TETROFOSMIN: COMPARISON OF REST-STRESS SAME-DAY AND SEPARATE-DAY IMAGING, To assess the difference in diagnostic value of SPECT imaging using technetiom-99m(Tc)-tetrofosmin, between rest-stress same-day and separate-day protocols, we compared the scintigraphic findings with coronary arteriography(CAG) in 60 patients(pts) with anginal pain. AIethods 26 pts(Group I) were investigated using a same-day protocol and in 34 pts(Group II) a separate-day imaging protocol was performed. In Group I SPECT images were acquired 60 rain after injection of 250 MBq(7 mCi) of Tc-tetrofosmin at rest. Four hours after the rest injection 750 MBq(20 mCi) was administered at peak exercise and imaging was repeated 30 rain later. In Group II 500 MBq(14 mCi) was injected at rest and at peak exercise on two separate days. SPECT images were acquired 30 rain after rest inject/on and 60 rain after the exercise inject/on. Scintigraphic data were analysed by experts blinded for CAG data. Results.Sensitivity and specificip/values for CAD detections in 60 pts. Group I Group II p-value Sensitivity 83% (19/23) 90% (27/30) NS Specificity 100% (3/3) 75% (3/4) NS Vessel related sensitivity and specificity in 180 vessel regions Sensitivity Group I Group II p-value LAD 75%(12/16) 92%(12/13) NS RCA 80%(t2/15) 73%(16/22) NS LCX 40%(2/5) 43%(3/7) NS Overall 72% (26/36) 74% (31/42) NS Specificity LAD 100%(10/10) 90%(19/21) NS RCA 82%(9/11) 75%(9/12) NS LCX 100%(21/21) 100%(27/27) NS Overall 95% (40/42) 92% (55/60) NS Coaclusiozz Tc-tetrofosmin SPECT imaging is an adequate modality for the detection and localisation of CAD. Imaging with the same-day rest-stress and separate-day rest-stress protocols provides similar diagnostic sensitivities and specificities in patients with suspected and ke~own CAD,

PMo480

PMo482

A. Hubalewska-Hota,*J.£3rodecki, *B.Bacior, *T.Kr61ikowski,*K.Kawecka]aszcz, Z.gzybifiski, B. Huszno Jagiellonian University,Collegium Medicum, Chair and Departmentof Endocrinology, *1 Cardiac Department

T. Leitha H. Bailer, M. Gwechenberger, M. Pruckmayer, A. Staudenherz, G. Kronik. University Clinic Nuclear Medicine Vienna, A. 6. Krankenhaus der Stadt Krems an der Donau, AUSTRIA

LOW DOSE OF DOBUTAMINE RADIONUCLIDE VENTRICULOGRAPHY USEFULNESS TO IDENTIFY PATIENTS FOR REVASCULARISATION. RELATIONSHIP WITH REGIONAL Tc99m-MIBI UPTAKE IN REST SPECT.

DIAGNOSTIC UTILITY OF THREE DIMENSIONAL P E R F U S I O N M A P P I N G OF E C G - G A T E D 99~Tc S E S T A M I B I MYOCARDIAL SPECT Background: The simultaneous computation and display of wall motion

The aim of the study was to assess myocardial viability and effects of revascutarisationon left ventricalar function in patients after MI. 37 patients aged 42-63 years/x=52,8/ were examined. Equilibrium radionuclide ventriculography before and after dobutamine infusion / 10ug/min/kg / and TC99m-MIBI SPECT were performed in all patients. Left wenlricular ejection fraction /EF/, 1/3EF, maximal empting rate /MER/, maximal filling rate /MFR/ and regional contractility with respect to myocardial scintigraphy and coronary angiography results were analysed. In 15 patients the studies were repeated at 8 weeks after revascularisation/studyin progress/. Results: In 23 patients segmental ejection fractions increased in the areas supplied by narrowed arteries with visible accumulation of Tc99m-MIBI in these areas. .................................................................................................... EF % I/3EF % MER MFR EDV/s ..................................................................................................... Initially 47,1+12,1 17,0+6,1 2.1+0,6 1,6+0,5 p <0,01 <0,01 <0,01 <0,05 Dobutamine 51,6+12,0 22,0+0,9 2,5+0,9 1,8+0,7 p <0,05 >0,05 >0,05 >0,05 Revascularisation 53,0+14,6 21,5+7,9 2,7+I,2 2,3+I,4 ..................................................................................................... Conclusion: Improvedregional contractility after dobutamine in radionuclide ventriculography correspondsto accumulation of Tc99m-M1Bl in SPECT. In all these patients systolic and diastolic function improved after revascularisation.

1152

and perfusion patterns in a single 3D ventricular model would considerably ease the assessment of ECG-gated 99~Tc sestamihi SPECT, yet the effect on the accuracy of the allocation of regional perfusion has not to been validated. Methods and results: 3D perfusion mapping (3D Perfusion/Motinn Map Software) was compared to the visual assessment ofungated tomographic slices and polar perfusion mapping (Cedars-Sinai PTQ) by correlation analysis and receiver operating characteristics (ROC) analysis at different cut-off levels for coronary stenoses in 50 patients (11 Single-, 22 two-, 16 three-vessel disease). Ungated SPECT data were obtained by adding the intervals prior reconstruction and displaying conventional tomographic slices. All display options were visually assessed in 8 ventricular segments according to a 4-point scoring system and compared to the graded results of coronary angiography. Results: All three display options showed a comparable diagnostic gain for the detection of severe stenoses, however 3D mapping provided the highest diagnostic gain. The diagnostic gain for the detection of stenoses above 59% was highest for ungated tomographic slices, followed by gated 3D mapping and ungated polar mapping. Regional assessment revealed a limited performance of 3D mapping in the pro~dmal anterior in the distal lateral wall. Polar mapping provided a balanced but inferior regional performance. Conclusion: 3D Perfusinn mapping provides comparable information to conventional display options with the highest diagnostic strength in severe stenoses. Further improvement of the algorism is suggested in the definition of the valve plane.

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Cardiovascular

PMo483

PMo485

A Hubalewska-Hota, J. Path, B. Huszno, D. Pach, S. Kroch, Z. Szybiflski Jagiellonian University, Collegium Medicum, Chair and Department of Endocrinology, Department of Toxicology, Cracov, Poland.

B. Krug, L. Carp, I. Huyghe, P. Blockx D e p a r t m e n t of N u c l e a r Medicine, A n t w e r p U n i v e r s i t y H o s p i t a l , Wilrijkstraat 10, B-2650 Edegem, Belgium.

MYOCARDIALISCHEMIA DETECTED BY Tc99mMIBI SPECT IN PATIENTS WITH ACUTE CARBON MONOXIDE POISONING. Carbon monoxide /CO/ is not metabolised within the bedy, bul through the impairing of oxygen delivery and atilisation lead to cellular and-organ hypoxia, thas organs with the higest oxygen requirements/heart and brain/are the most susceptible to carbon monoxide poisoning Clinical diagnostic and prognostic usefulness of MIBI SPECT imaging was investigated in patients with myocardial ischemia using uni- and multivariate analisis to assess the incremental value of the MIBI scan in comparison to the other tests. This study was aimed to assess myocardial ischemia in patients after acute CO poisoning using rest Te99m-MIBI SPECT. 15 patients /8women and 7men/aged 18-46 ~ears /x=26+9/after CO poisoning in their permanent residence were studied. COHb concentrations, lactate levels, duration of exposures, and ECG on admission and during the following 24h, the level of ALAT, AspAT, CPK, tropenin were evaluated. 2-5 days after CO poisoning rest Tc99m-MIBI SPECT was performed in all patients. COHb level was 24-51% /x=34+8/, lactate 1,23-6,53mmol/1 /x=3,23+1.4/ and exposures time 20-6Jmin /x=27+13,7/. The changes in myocardial scan were graded: I- decreased accumulation of Tc99m-MIBI in myocardium; II- decreased accumulation of marker and small focus defects; III- decreased accumulation of Tc99m-MIB1 and one larger area abnormal marked; IV- extensive "cold" loci /Table/. Myocardial scan was abnornal in all patients. 80% of changes were observed in the anterior or anterior and inferior walls of heart. Grade of change I 11 lII IV Total in the myocardium ................................................................................................ Number of patients 3 4 7 1 15 Abnormal ECG curve /various changes/ was observed in 80% of patients. The correlation between myocardial scintygraphy and levels of myocardial enzymes were not found CONCLUSION: The myocardial scintygraphy, ECG curve and myocardium darnage indicatory enzymes evaluated simultaneously allow to assess properly injury of the heart in patients with acute CO poisoning.

INFLUENCE OF SEX, AGE, TYPE OF STRESS STUDIES O N THE INTERFERENCE OF TRACER ACTIVITY I N THE LIVER WITH THE INTERPRETATION OF SESTAMIBI MYOCARDIAL SPECT Previous studies reported that the presence of the tracer activity in the liver can vary with the different types of stress studies. The aim of this s t u d y was to evaluate the influence of age, gender and different types of exercise studies on the interference of the liver activity of Tc-99m sestamibi with the interpretation of heart images. Two groups of 53 subjects (32 males, 21 females), matched for both sex and age, underwent myocardial SPECT after exercise test on ergometric bicycle (ERG) or low dose d i p y r i d a m o l e infusion (DIP) as well as after their related rest studies (ERG-rest, DIP-rest). The subjects were divided in three g r o u p s : < 60 years, 60 - 69 years and > 70 years. Visual assessment of the interference of the liver activity with the heart images was performed independently by two observers. The global interference of liver activity was 30 % for DIP versus 2 % for ERG. In the related rest studies the global interference was 27 % for DIPrest and 14 % for ERG-rest Both age and gender had no influence on the proportion of interference. Quantitative analysis was performed to compare the interference in ERG, DIP and their related rest studies. Therefore, quantification was done on a group of 24 (14 males,10 females) of the former 53 subjects, according to the method of Primeau et al (EJNM 1991, 18: 247-251). Statistical analysis (Wilcoxon Signed Rank Sum Test) showed a significantly higher h e a r t / l i v e r ratio in ERG (median 1.42, range 0.61-2.65) as compared to DIP (median 1.12, range 0.46-1.75). This was also the case between ERG and ERG-rest (median 1.16, range 0.65-1.87). No statistical diffgrence could be observed in DIP and DIP-rest (median 1.13, range 0.45-1.63), nor between both groups of rest studies. These results suggest there is no parallellism between the heart/liver ratios and % interference. Indeed, while similar heart/liver ratios were found for DIP, DIP-rest and ERG-rest, the latter group showed about only half as much % interference as DIP and DIP-rest. As expected, ERG yielded the lowest interference of the liver activity and a significant higher heart/liver ratio.

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PMo484

PMo486

B. Krug, L. Carp, I. Huygbe, P. Blockx Department of Nuclear M ~ w e r p University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium.

I Krupp*, D. Werner**, S. Wiener*, T. Grtining*, W.G. Daniel ** Depts. of *Nucl. Med., **Cardiology, Univ. of Dresden; Germany

E V A L U A T I O N OF THE INTERFERENCE OF S E S T A M I B I A N D TETROFOSMIN LIVER UPTAKE WITH M Y O C A R D I A L SPECT Sestamibi and tetrofosmin are myocardial perfusion imaging agents that have s h o w n similar results in clinical trials. In comparison to sestamibi, tetrofosmin w a s reported to clear out of the liver more rapidly after injection, yielding less interference w i t h the interpretation of the heart image. This could allow to shorten the delay before imaging a n d / o r could obviate the need of a fatty meal to accelerate the liver clearance. The purpose of this study was to determine the degree of interference of liver activity w i t h the interpretation of the heart i m a g e in routine conditions. Two g r o u p s of twenty-four subjects, matched for both sex a n d age, u n d e r w e n t myocardial SPECT after rest (n=13) and after exercise test (n=11) on ergometric bicycle (ERG, n=6) or with low dose d i p y r i d a m o l e infusion (DIP, n=5). One group received Tc-99m sestamibi, the other Tc99m tetrofosmin. Both tracers were compared using the same acquisition protocol and delay between injection and acquisition (30-45 rain for studies w i t h ergometric exercise and 45-60 rain for both d i p y r i d a m o l e tests and the rest studies). MIBI-images were performed after ingestion of a fatty meal (15 g milk hazelnut chocolate and 2 dl whole milk), 30 min before imaging. Tetrofosmin-images were acquired without fatty meal, according to the recommendation of the manufacturer. Visual a s s e s s m e n t of the interference of liver a c t i v i t y w i t h the interpretation of the heart image was performed for all scintigraphic studies. Taken as a whole, or even s u b d i v i d e d into rest, ERG and DIP, the tetrofosmin group showed a much higher incidence of interfere~ace of liver activity compared to MIBI :

MIBI Tetrofosmin

Rest 1 ERG 15.4 %1 0 % 38.5 % 16.7 %

DIP ERG + DIP [ Total 20 % 9 %1 12.5 % 40 % 27.3 %1 33.3 %

These results cast doubt upon the a s s u m p t i o n that Te-99m tetrofosmin can be used without fatty meal.

EVALUATION OF THE BENEFITS OF ENHANCED EXTERNAL C O U N T E R P U L S A T I O N (EECP) IN P A T I E N T S W I T H C H R O N I C A N G I N A L PAIN. Intraaortic balloon counterpulsation (IABC) is a well established procedure to reduce afterload and enhance myocardial perfusion. The drawback of this strategy is a high rate of complications. A new method, the noninvasive pneumatic enhanced external counterpulsation (EECP, Crdiomedics, USA) which works by diastolic compression of the lower limbs, avoids the risks of IABC, allows an longer use and repeated therapies. We investigated patients (pts) before and after chronic treatment (group I, 3 pts, 30 hours of therapy, 1 h/day) and four pts with an old myocardial infarction before and after a single one hour treatment (group II). In group I Tc-99m-MIBI and 1-123-IPPA scans were performed at each time point whereas in group II only Tc-99m-MIBI scans were acquired. An especially developed software enabeled us to compare pre- and post-therapeutic slices to evaluate the effect of EECP readed by increased or decreased radioactivty concentrations (RC) in rest (MIBIR) and stress (MIBIS) MIBI-slices and changes of the turnover rates of IPPA (IPPATR). In addition, the bull ~s-eye was divided into 33 segments (sgs) and the RC evaluated. In group I semiquantification revealed an global increase of MIBIR of 9,4% _%2.3% and of MIBIS of 14.5% _+ 4.2%. The difference was statistically significant (p < 0 . 0 5 ) and paralleled clinical improvement of the pts. I P P A T R improved globally by 15.1% ___ 3.9% which was statistically significant (p < 0.05). In group II four persistent uptake defects ( < 50% max.) out of six became smaller after therapy (in total 23 sgs. vs. 14 sgs). In conclusion: EECP has a benefit to left ventricular perfusion in patients with chronic coronary artery disease and anginal pain. This benefit could be substantiated objectively by scintigraphy and subjectviely (pain relief, reduction of the dosage of antianginal drugs and/or analgetics) although only a small number of patients was investigated so far.

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PMo487

PMo489

G~Mar~u~i~N~R~Petix~M~Si~ves~ri*~A.Arena*~A~Bart~etti~A~ecchi~G.Mangia~av~ri~ V.Mazzoni, A. Monopoli, F.Nassi, A.Talti, O.Terni, F. Venturi,A. Mennuti*, A. Bini. Cardiology Division, Empoli (Fi); * Nuclear Medicine Department, Prato.

MV G6mez. [ Coma-Canellla, FG Gallardo, JM Castro-Beiras. CIC Carlos III Servicio de Medicina Nuclear. Madrid Spain

EXERCISE Tc-99m SESTAMIBI MYOCARDIAL PERFUSION SPECT: WHICH RELATIONSHIP AMONG EXERCISE TEST RESULTS, THE EXTENT OF REVERSIBILITY ON SESTAMIBI SCAN AND LONG TERM PROGNOSIS ? In order to evaluate the relative prognostic power of some patterns of exercise test (EET) results and the extent of reversibility on MIBI scan, we followed 306 consecutive pts (230 m,76 f, mean age 58 y, 166 with prior MI) for >1 year (19 ±11 mos) after exercise MIBI myocardial perfusion SPECT. EET were performed off therapy on the symptom-limited protocol, defined as achievement of an heart rateZ-_85%of predicted or occurrence of angina (Ang) or ST depression (STd).On MIBI scans, average % of segments with reversible (%R) and irreversible (% IR) was considered (5 segments for pt; score 0-4). On follow-up, a major cardiac events (HCE) occurred in 24 pts (4 deaths and 20 MI or re-IM), with normal scan in 2/57 pts, fixed defects alone in 3/83 and with partially or total reversible defects (RD) in 191203. The results are shown in the table below: Pts (No) %R HCE %1R HCE (pta) (pts) NegativeEET 62 8.O6 3 tO l Positive EET isolated STd ,80 21.5" 6 6.25 1 Ang+STd 60 21.33" 5 13.33 0 Ang 35 20.57* 2 l 1.43 l early recovery < 6' 49 16.73 0 9.39 l * p < 0.05 late recovery a 6' 91 23.96" ll 8.77 0 vs other data Not diagnostic 69 1 1.01 3 t 6.8" 2 of same RPPmax_<20.000 104 20.38* 10 10.45 2 column RPPmax >20.000 202 14.13 8 13.14 3 EET~ 100W 116 21.3" t0 10.57 1 EEr >100W 190 12.9 8 11.91 5 No HCE occurred in 21 pts with negative EET. In 175 pts with positive EET, the cumulative probability of HCE did not differ according to EE'I" results and MIBI patterns. A significantly higher HCE rate was found in 91 pts with late recovery and RD than in those with early recovery and RD (logrank 0.01), in 68 pts with RPPmax ~ 20.000 and RD (logrank 0.02 vs pts with RPPmax >20.000 and RD) and in 116 pts with EET<100 W (logrank 0.02 vs pts with EET~100 W). In conclusion:l) a negative maximal EET with normal scan had a favorable long term prognosis;2) the pts with positive EET, with or without angina, had the same R% and prognosis, but those with late recovery were at higher risk of HCE;3) EET- derived parameters, as RPP max :~ 20.000 and EET<100 W, were associated with with a more extensive stress-induced R% and poor prognosis.

REVERSE REDISTRIBUTION OF THALLIUM-201 AFTER MYOCARDIAL INFARCTION The aim of this study was to assess the frequency of thallium-201 reverse redistribution pattern in patients with myocardial infarction and to evaluate its significance with respect to regional wall motion. METHODS: Study patients: The patient population consisted of 58 consecutive patients (53 male) which were diagnosed of myocardial infarction,. All patients underwent stress and resting thallium and radionuclide ventrieulography studies 3-4 weeks after infarction. Thallium images were quantitatively analyzed. The raw data polar maps for each patient were statistically compared with a normal data bank. According to the results of the quantitative study segments were divided in four categories: Normal segments (NS), fixed defect segments (FDS), reversible defect segments (RDS) and reverse redistribution segments (RRS). The definition of reverse redistribution required an increase of at least 5% in the perfusion defect in the delayed image and included both, segments with normal peffusion in the stress images that appeared as new defects on redistribution images and defects on stress images that appeared more severe at 3h images. The global and regional EF were calculated semiautomatically by computer analysis. RESULTS: A total of 174 segments were evaluated. According to the stress-redistribution pattern, segments were divided in four groups: 35 (20%) segments were NS, 26 (14.9%) segments were FDS, 90 (51.7%) segments were RDS and 24 (13.7%) segments were RRS, Regional contractility was as follows : NS: 52.8%±14. FDS: 38.1%±11.3. RDS: 38.7%±i7, land RRS: 41.9%±18%. Nineteen (79%) of RRS were associated with patency of the infare-related coronary artery. Only 4 of the R-R segments had severe hipokinesia. CONCLUSION: The pattern of reverse redistribution probably represents the effect of several mechanisms, and not all the regions demonstrating reverse redistribution phenomenon are alike, contractility in R-R segments is greater than the contractility in ischemic or scar segments. As previous reports have suggested, in our study reverse redistribution segments were subtended by a patent coronary artery. Thus, we conclude than R-R segments likely correspond to viable territories.

PMo488

PMo490

C.H Kao and J.K Lee, Departments of Nuclear Medicine, China Medical College Hospital and Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.

B.Caner, U.Uysal, C.Rezani, O.U~ur, L.Kostako~lu, N.Elahi, S.Kes, T.Aras, C.Bekdik. Hacettepe University Faculty of Medicine, Ankara, TURKEY

REVERSE REDISTRIBUTION DURING MYOCARDIAL PERFUSION IMAGING WITH DYPRIDAMOLE THALLIUM-201 MYOCARDIAL SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IN CORONARY ARTERY DISEASE.

DOBUTAMINE THALLIUM-201 MYOCARDIAL PATIENTS WITH LEFT BUNDLE BRANCH NORMAL CORONARI ARTERIES

Ninety-six of consecutive 1100 patients undergoing dypridamole TI-201 myocardial SPECT demonstrated the reverse redistribution (RR) phenomenon Twenty-six of the 96 cases (9 females, 17 males, ages: 37 78 years) who had accepted coronary angiographies were included in this study. Patients with previous coronary bypass, myocardial infarction or those who recevied thrombolytic therapy were excluded. Patients fasted overnight and all cardiovascular drugs were discontinued 3 days prior to the study. Coronary arteriography was performed using standard techniques and multiple views were obtained including obliques. An abnormal coronary angiogram was defined as a significant ( > 50%) coronary artery stenosis. RR was defined as > a 20% decrease in relative TI-201 activity between exercise and resting images (type 1), and included a perfusion defect apparent in the resting image, but not in the exercise image (type 2). In addition, RR was also defined to find a decrease in the size of the defects between the initial and delayed image. Ninety-six of the consecutive 1100 (8.7%) patients who underwent dypridamole TI-201 myocardial SPECT demonstrated the RR. Of the 28 cases analyze~, RR was present in 40 segments. Seventeen segments were in the RCA distribution and 17 in the LAD distribution, 6 in the LCX distribution In 22 segments of RR were type 1 In 18 segments of RR were type 2. Seventeen segments with RR were in the distribution of coronary arteries with abnormal angiograpNc findings. Of the remaining 23 segments, the angiographic findings were normal. In conclusion, RR also can happen in TI-201 SPECT after dipyddamole and easily appears in the territories of RCA and LAD. It does not absolutely indicate the presence of severe coronary artery disease or normal coronary arteries

1154

SPECT IN BLOCK AND

Dobutamine is a positive inotropic and chronotropic agent and is being widely used as a pharmacologic stress agent in patients unable to achieve maximal dynamic exercise test. The purpose of the current study was to d o c u m e n t the dobutamine induced false positive septal defect in terms of its frequency and extention on TI-201 myocardial SPECT in patients with left bundle branch block (LBBB).24 symptomatic patients with LBBB underwent dobutamine and rest TI-201 myocardial SPECT studies, Coronary angiographies were also performed within 38 days. Only those patients with normal coronary arteriograms (n=19; 16F, 3M) were included in the study. For each study, tomograms were divided into 19 segments and each segment was analyzed qualitatively regarding with the presence and type of the perfusion defect (reversible or fixed).Sixteen of 19 patients (84.21%) had false positive septal reversible perfusion defect and remaining 3 had normal images. Perfusion defect was confined to only septal area in 2 of 16 patients (10.52%) showing false positive perfusion defects, whereas a greater proportion of patients had septal defects extenting to the contiguous inferior, anterior and/or apical areas. Conclueion:Dobutamine myocardial scintigraphy in patients w i t h LBBB was m i s l e a d i n g for the diagnosis of coronary artery disease, since up to 84.21% patients had false positive septal perfusion defects extenting to c o n t i g u o u s inferior, anterior and/or apical segments in most of the patients.

• PMo491 J. Toft, S. All, A. Rab~l, K. Saunam~ki, Clin. Physiol. Nucl. Med and Cardiology, University of Copenhagen, Denmark.

Cardiovascular

PMo493 B. Hesse. Dept.s Rigshospitalet

SELECTION OF REFERENCE POPULATION (ref) FOR MYOCARDIAL BULL'S EYE (BUEYE) NORMAL DATA BASE: INFLUENCE ON ACCURACY IN CORONARY ARTERY DISEASE (CAD). We have recently shown in a myocardial MIBI SPECT study of 128 (76m/52f) subjects with low likelihood for CAD, with age groups from 18-79 years evenly represented that the relative activity distribution changed with age in men and that black-out defects in the CEqual program with its own ref (CEref) were more frequent than anticipated, espicially in the inferior wall in men. Purpose: To compare the accuracy of MIBI BUEYE interpretation with 2 ref and coronary anKiography as gold standard. Patients: 60 men and 18 women referred for suspicion of CAD. Methods: 2-day MIBI SPECT. After CEqual reconstruction and processing the BUEYE images were compared with the CEref and our own (RHref), above mentioned ref, the men being analyzed both age matched (<39,40-59,>59y) and as one group. A significant defect was defined as exceeding 10/20 pixels for m/f. Results: 51 of 78 patients showed identical defects with all 3 refs, in 27 cases CEref data differed from RHref. Subdividing RHref into age groups had virtually no effect.ln 7 cases the defects disappeared with CE->RHref, in 5 of them becoming true neg. in 2 false neg. In 5 other patients partially reversible defects became purely reversible, in 2 vice versa with CE->RHref. Accuracy was virtually unchanged. Conclusion: Selection of subjects for a normal data base in myocardial 8PECT is crucial for the appearance in a considerable number of patients. Reference limits should be adjusted according to the ref. and to the patient population.

F.Faccio,F.Patrois,F.Vigoni,A.Blasco. Department of Nuclear Medicine, Centre Cardiologique du Nord, S a i n t - D e n i s , France

E F F E C T OF T H E P R O N E P O S I T I O N O N TL-201 S P E C T OF PATIENTS WITH MYOCARDIAL INFARCTION. O u r o b j e c t i v e w a s to d e t e r m i n e , w h e t h e r t h e r e are differences in s i z e and depth of uptake defects, on TL-201 SPECT of p a t i e n t s ( P ) with myocardial infarction(MI), b e t w e e n p r o n e ( p r ) and supine(s) positions.Thirty-one male patients (mean a g e ± S D : 5 9 ± 1 1 y e a r ) w i t h c h r o n i c MI of k n o w n localization, were divided in 3 g r o u p s ( G ) : GI anterior; GII inferior; GIII lateral MI. We p e r f o r m e d p r o n e a n d s u p i n e TL-201 S P E C T in r e s t conditions. Q u a n t i t a t i v e a n a l y s i s w a s made. T h e l e f t v e n t r i c l e was d i v i d e d i n t o 20 s e g m e n t s . A s c o r e of 0-3 w a s assigned to e a c h segment, a c c o r d i n g to the m a x i m a l a c t i v i t y f o u n d in e a c h study(0=normal 7 0 - 1 0 0 % of the m a x i m a l a c t i v i t y ; 1=mild 50-70%; 2=moderate 30-50%; 3=severe 0-30%). Total number of abnormal segments represented the s i z e of the u p t a k e d e f e c t s , a n d the a d d i t i o n of s c o r e s , t h e depth. W e f o u n d that the size was significantly lower in GI and GIII,and the depth was significantly lower in all the groups, in p r o n e )osition.

GI n= 13 Size (mean +SD for P)

s=13.5 ± 2.1 pr=ll.6 ± 1.7"

GII n=10 s=9.3 + 2.5 pr=8 ± 3.4

Depth(mean

s=17.5 +4.1

s=ll ±3.5

+SD for P)

pr=15 ± 3.6*

pr=8,7 ± 3.8*

GIII n=8 s=10.5 + 1.7 pr=8.1 ±3.1" s=ll.1 ± 2,3 pr=9 ± 3.7*

*p < 0.05 ( A n a l y z e d by ~aired s t u d e n t ' s t-test) In c o n c l u s i o n , the s u p l n e p o s i t i o n i n c r e m e n t e d the size of d e f e c t s in a n t e r i o r a n d l a t e r a l MI; and the depth, w h e n the size w a s not d i f f e r e n t , in inferior MI. This could rise different i n t e r p r e t a t i o n s of p r o g n o s t i c .

PMo492

PMo494

T. Basoqlu, C. Coskun, i.Bernay, F. Tanyeri, M. Sahin, H Kahraman, A.E.Demircah. Ondokuz May=s University Hospital, Departments of Nuclear and Internal Medicine, Samsun - Turkey

A,L Ferrer-Antunes, B. Dies, J.Morais, N. Pontes, F.Gonc~alves, A.Cardosc, M.J.Ferreira, M.Silva, L.Provid6ncia, J.Lima. Nuclear Medicine and Cardiology Departments, University Hospital. 3049 Coimbra, PORTUGAL.

MYOCARDIAL PERFUSION SPECT IMAGING WITH TC99MTETROFOSMIN IN TYP-II DIABETES MELLITUS PATIENTS : A COMPARISON TO TL-201 SPECT, PRELIMINARY RESULTS.

ISCHEMIC HEART DISEASE WITH ANGINA IS NOT MORE EXTENSIVE THAN ASYMPTOMATIC ONE - TOMOSCINTIGRAPHIC STUDY.

Inhibition of Tc99m-Tetrofosmin uptake in rat ventricular myocytes by pharmacological inhibition of glucose utilization has been reported. The purpose of our study was (a) to evatuate the myocardial uptake of Tc99m-Tetrofosmin in the case of altered glucose utilization, (b) detection of myocardial ischemia in typ-II diabetes patients and compare the results with TI-201 findings. Fourteen dysrsgulated typ-II diabetes patients with elevated blood glucose levels (BG) were taken for analysis before any medical treatment ( 8 Male, 6 Female; Mean age = 50 ± 7yrs).ln 5 patients atypical chest pain with or without ST changes was present.12 patients were free of clinical and electrical signs of coronary artery disease. Same day protocols of Tc99m-Tetrofosmin stress ( 296 MBq ) / rest ( 888 MBq ) SPECT and Thallium-201 stress ( 74 MBq ) / rest re-injection ( 37 MBq ) SPECT studies were performed within three days. Blood samples for BG were taken just before Tetrofosmin stress study. Mean BG was 179 ± 78 mg/dl ( Normal Values = 60 -110 ). Both SPECT studies were compared using a 20-segments scoring method, in all patients, stress and rest Tc99m-Tetrofosmin imaging could be performed within the time intervals proposed by the manufacturer. Good myocardial uptake was observed and the whole-body distribution was unremarkable. In 4 of 5 symptomatic patients reversible ischemia was detected by TI-201 and in 3 of 5 by Tetro (24 segments versus 20).TI201 revealed reversible ischemia in 5 of 9 asymptomatic patients ( silent ischemia) and Tetro in 3 of 9 ( 24 segments versus 16 ). In all commonly detected ischemic segments, tetrofosmin reversibility was more significant than in TI-201 studies. There seems to be no substantial inconvenience in the realization of Tc99m-Tetrofosmin myocardial perfusion studies in patients with altered glucose utilization and high blood glucose levels. TI-201 was found preliminarily superior to Tetrofosmin in the detection of silent and symptomatic ischemia in typ-II diabetes patients which remains to be, investigated in Iarger patient populations.

The value of the symptoms to predict the severity of ischemic heart disease still remains a controversial issue. In the present paper the authors retrospectively analysed a series of 223 patients (pts) submitted to myocardial per'fusion tomoscintigraphy CSPECT"), all of them with a positive scan (defined by the presence of two adjacent segments with transient perfusion defect at least). We divide the studied population in two groups according to the presence or absence of angina (Gr A (With angina) - 105 pta "and Gr B (Without angina)- 118 pts). We analysed "SPECT" studies considering the number of fixed and partially reversed perfusion detects and with a perfusion score (0 - no perfusion; 1 - definitely hypoperfused; 2 - doubtfully hypoperfused; 3 - normal). Female gender was more frequent in Gr A pts (30.0% vs 18.6=/o; p=0.05) and a previous myocardial infarction was more frequent in Gr B pts (63.0% vs 17.0%; p<0.001). From the 223 analysed pts, we stressed 106 on a treadmill and submitted the remaining ones to a pharmacological stress test with dipiddamol. Exercise test variables were similar in both groups (peak exercise time, maximum and ratio of predicted maximum heart rate, peak systolic blood pressure, rate pressure product and induced angina). GrA GrB p v~ue Fixed defects (n) 2.52±3.34 3,75-~3,97 0.01 Transient defects (n) 4.45±2.78 4.38+_2.92 ns Perfusion score(stress) 2.02±0.63 1.85±0.75 ns Pertusion score(rset) 2.56±0.52 2.36±0.63 <:0.01 I~ s~ess~es~(%) 78.0±16.4 76.8±17.6 ns Conclusion: In spite of a previous myocardial infarction and a larger area of scar to be more impressive in asymptomatic patients, the amount of jeopardised myocardium is not related to the presence of angina.

1155

•

Cardiovascular

PMo495

PMo497

N. P. Sand, M. BOttcher, M. M Madsen, T. T. Nielsen, M Rehling, Aarhus University Hospital, Department of Cardiology, Department of Clinical Physiology and Nuclear Medicine and The PET Center, Denmark.

M. Koutelou t , V. Vassilikos 2, S. Papaioannou 2, V. Voudris 2, G. Pavlides 2, A. Manginas 2, A. Kouzoumi I, D. V. Cokkinos 2.

DIRECT COMPARISON OF AMMONIA-PET AND SESTAMIBISPECT PERFUSION IMAGES IN PATIENTS WITH SEVERE HEART FAILURE

CONTRIBUTION OF ADENOSINE THALLIUM SCINTIGRAPHY TO DECISION MAKING IN PATIENTS WITH U N S T A B L E A N G I N A

PET-scanning is well established for the detection of myocardial viability. Due to the limited availability of PET facilities it has been proposed to combine SestamJbi-SPECT with FDG-PET. Therefore, the aim of this study was to compare perfnsion scans using the two techniques. Twenty patients (mean age 57_+8 years, mean ejection fraction 25_+6%) with angiographically verified coronary artery disease were included. In random order Ammonia-PET- and Sesmmibi-SPECT scanmngs were performed. Two blinded observers scored a total of 400 segments on a 5-point scale in a 20 segment model of the left ventricle. PET and SPECT scans were evaluated using the same software program. Weighted kappa (K) statistics has been used for comparison. Segmental score-differenees (SPECT-PET) in % of the total number of segments are shown: 0 -1,0,1 > 2 < -2 No.Segm t: Anterior# 43 70 15 15 60 i Lateral# 63 87 1 I2 120 i Apical# 38 78 I5 7 40 [ 0.54# I4 2 80 . .Septal-apieal# . . . . . . . . . . . . . . . . . . . . . . . . .48 . . . . . . . 84 ..... Septal-basal+ 33 56 42 2 40 ] Posterior+ 35 72 25 3 60 t 0.32+ Overall 47 77 15 8 400 [ 0.41 # and + represent lc for pooled data of regional groups. PET and SPECT perfusion scans yield similar results, except for the basal septal and posterior regions, where SPECT tends to overestimate perfusion defects, most likely due to attenuation artifacts. Hence attenuation correction should be considered when combining FDG-PET and Sesmmibi-SPECT for diagnosing myocardial viability.

(pts) with stable coronary artery disease (CAD). The purpose of this study is to ¢x~:nine its safety and usefulness in decision making in pts with unstable angina (UA). Methods:. We studied 67 pts who presented with UA and underwent

/Nuclear Medicine Department. 21st Department o f Cardiology, Onassis CarcHac Sttrgery Center, Athens, Greece.

Adenosine (A) is widely used for Thallium (T1TM) scintigraphy in patients

adenosine T1201 scintigraphy (ASe) at a metha, time (MT) of 1 day post admission. All pts had coronary arteriography during the same admission. Pts were allocated by clinical decision aided by a strongly positive Asc (>2 reversible segments), to either intervention (CABG or PTCA) -Group A, or medical treatment - Group B. Resolts: Group A consisted of 40 pts who underwent coronary intervention (24 pts PTCA and 16 pts CABG) and Group B of 27 pts. The mean age for Group A was 63 ~: 10 years, and for Group B, 58:1:11 years. A history of previous myocardial infarction was present in 18 pts of Group A, and in 11 of Group B. There was no difference in cardiac performance (Ejection fraction for Group A 0.50 :k 0.08 and for Group B 0.49 -~ 0.10). The MT between the onset of symptoms and ASc was similar for both groups (1 day). We used a cou;.inuous fixed intravenous A infusion at a dose of 140 ¥/kgr/min during 6 minutes with 3mCi TITM being injected at the fourth minute. The MT between ASc and clinical decision was 6 days (1 - 126) and 2 days (1 - 28) for groups A and B respectively. In Group A 26 pts (65%) and 6 pts (22%) in Group B had two or more reversible defects in ASc (p=0.002). Also pts in Group A had higher prevalence of multivessel disease than Group B (2.3 vs 1.5, p<0.01). The sensitivity for ASe in detecting coronary artery disease for both groups was 87% and the specificity was 100%. There were no significant side effects in either group. At follow-up (MT 270 days) 1 pt in each group died. Conclusions: ASe is safe in detecting residual isehaemia in pts with UA, and provides important information for their management distinguishing pts who may benefit from intervention, or who can safely be treated medically.

PMo496

PMo498

B,Chrapko, A.Tarkov~ska, Department of Nuclear Medicine, Medical University in Lublin, Poland.

L.Pace, P.Perrone-Filardi, M.Prastaro, A.Cuocolo, F.Squame, P.P.Mainenti, T.Crisci, A.Soricelli, F.Piscione, M.Chiariello, M.Salvatore. Catt.6 Centro C.N.R. Medicina Nucleare, Catt. Cardiologia, Universit~ Federico II, Napoli, Italy.

EVALUATION OF LUNG/HEART(L/H) RATIO IN PATIENS WITH CORONARY ARTERY DISEASE (CAD), AFTER MYOVIEWOgMTC ADMINISTRATION.

Myoview99mTc (Tetrofosmin99~C) is a new myocardial perfusion agent, suitable for high-quality images. Because of its various biodistribution in the lungs we decided to test if L/H ratio measured after Myoview99mTe administration can be helpful for the assessment of left ventrieular function. The study included 30 patients with confirmed or suspected CAD. They underwent radionnclide gated bloodpool study and perfusinn myocardial SPECT at rest and during stress with Myoview99mTc. Additionally, two planar images in LAO 30-45°: early (5 minnt post injection) and delayed (50-60 minut post injection) were performed. The patients were divided into two groups: A with LVEF>50% - 15 pts & B with LVEF<-50% - 15 pts. To calculate the L/H ratio, 2 ROIs were defined: one within the left lung and the other within the normal myoeardium. Then L/H ratio was calculated from mean cts/pixel in these regions, for both rest and stress study (R:L/H and S:L/H respectively). According to J.F.Bureau stress/rest index (I:S/R) was calculated by dividing S:L/H by R:L/H. It was found that in both at rest and at stress conditions the L/H ratio was significantly higher in group B than in group A in early and delayed planar study as well as using the anterior projection frame obtained during the SPECT acquisition. On the other hand, hS/R was significantly higher in group B than in group A only in planar delayed images. The final conclusions: Myoview99~Fc L/H ratio may be helpful in the assessment of left ventricular function in CAD. For that purpose delayed planar images seem to be of the best value.

1156

EFFECTS OF CORONARY REVASCULARIZATION ON MYOCARDIAL REGIONS WITH THALLIUM-201 REVERSE REDISTRIBUTION The clinical significance of reverse redistribution (RR) on T1 imaging is still unclear. The aim of this study was to assess the effects of coronary revascularization (CR) on systolic function and T] uptake in segments showing RR at rest. We studiei 34 patients with chronic coronary artery disease (CAD) undergoing CR by rest-redistribution T1 SPEq before and after CR. Regional function was e v a l u a t e d by two d i m e n s i o n a l echocardiograph~ before and after CR by a 3 point scale (i= normal, 2= h y p o k i n e t i c , 3= a / d y s k i n e t i c ) . Myocardial segments w i t h abnormal systolic function were defined viable if systolic function score decreased ~i after CR. RR was defined as ~12% decrease in relative T1 uptake between rest and redistributior images. RR was found in 17 (50%) of 34 patients, corresponding to 38 (9%) of 408 segments analyzed. Of such segments, 16 (42%) had normal systolic function, ii (29%) were hypokinetic, and ii (29%) a/dyskinetic. Twenty-three segments underwent CR, and RR was no longer present in 83% of them; ir particular 4 hour T1 uptake significantly (p<0.05) increased from before (61±13%) to after (68±18%) CR. Of 22 dyssynergic segments with RR, 17 wer6 subjected to CR and 14/17 (82%) showed improved function at follow-up.These findings indicate that RR is a reversible phenomenon and it is associated with improvement of systolic function following CF in patients with chronic CAD.

•

Cardiovascular

PMo499

PMo501

V. Prassopoulos, J. Lekakis, A. Vezyrgianni, J. Germanidis, N. Sif'a1~is, Ch. Kalliontzi, Ch. Papamichael, Cb. Palaistides, P. Kostamis. Depts of Nuclear Medicine and Clinical Therapeutics, "Alexandra" Univ. Hospital, Athens, GREECE

K. Blaszykk, A. Baszko, M. Popiel, S. Grajek, I. Piszczek, M. Lesiak, A. Cie~li/Iski, M. Gembicki*, J. Sowifiski*,.

STRESS REST DOBUTAMINESPECT 99mTc-TETROFOSMINIs USEFUL IN IDENTIFYING PATIENTS WITH MULTIVESSEL DISEASE POST MYOCARDIALINFARCTION. -

Data on pharmacological stress with 99mTc-tetrofosmin imaging in identifying multivessel coronary artery disease post myocardial infarction are lacking. We examined 20 patients (pts) (mean age 56+10 years; 19 men, 1 woman, ejection fraction 43+12%) with maximal (10-40gg/kg/min) stress dobutamine 99mTc-tetrofosmin SPECT imaging. A 16-segment model was used for quantitative analysis of SPECT. Coronary arteriography revealed 43 diseased vessels (,50% diameter stenosis, 2.15 vessels/pt). First pass ejection fraction was measured at stress and rest during the tetrofosmin study. SPECT detected 34/43 diseased vessels (sensitivity 79%). There were 23 noninfarct related vessels and SPECT detected 15/23 (sensitivity 65%). Left anterior descending artery (LAD) was diseased in 18 pts and detected in 16/18 (sensitivity 88%); left circumflex artery (LCx) was diseased in 14 pts and detected in 8/14 (57%); right coronary artery (RCA) was diseased in 11 pts and detected in 10/11 (sensitivity 91%). There were 2 false positive results in the territory of RCA. In 8/20 pts (40%) first pass ejection fraction decreased at stress and 12/20 (60%) increased. In conclusion: Stress-rest dobutamine 99mTc-tetrofosmin SPECT is a reliable method in detecting multivessel coronary artery disease post infarction; SPECT has the lowest sensitivity for LCx disease. First pass ejection fraction during dobutamine stress and at rest is not helpful in identifying muhivessel disease.

Institute of Cardiology and Department of Endocrinology*, ~hnversity School of Medical Sciences, Poznah, Poland- PL ASSESSMENT OF ARTERY PATENCY USING Tc-99m-MIBI SPECT IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION

Patency of infarct related artery in patients (pts) with acute myocardial infarction (AMI) improves prognosis. Even modern fibrynolityc therapy in significant proportion of patients fails to restore adequate perfusion. Thus there is a need for non-invasive identification of patients who should undergo early angiography and revascularization. The aim of the study was to assess the usefulness of Tc-99m-MIBI SPECT for identification of occluded artery in pts after AMI. Forty two pts (age + SD: 49.7 +_9.7, F/M; 6/36) with a history of the first MI within the last 4 weeks who were qualified to coronary angiography were enrolled. Each patient underwent two-day dipirydamole-rest Tc-99m-M1BI SPECT Myocardial perfusion was assessed in 16 segments (seg) using a 5-point scoring system. Perfusion index (PI=Z score /n seg) was generated for each coronary artery territory. Coronary angiography revealed 3-vessel disease in 15 pts, 2-vessel in 19 and 1-vessel in 8 pts. Among 91 stenosed arteries, there were 33 (36%) occluded vessels Regions supplied by patent coronary artery had similar perfusion defect at dipirydamole study (2.85 + 1.39 vs. 2.45 + 1.30), but significantly lower at rest (2.44 _+ 1.33 vs. 1.82 _+ 0.94, p=0.03). This pattern was the strongest for LAD territory (2.76 +_ 1.33 vs. 1.55 + 0.42, p=0.003). Q-wave at ECG was related to significantly deeper perfusion defect of the related region regardless the artery patency. We conclude, that the deeper perfusion defect of the infarct region at Tc-99m-MIBI SPECT may indentify occluded coronary artery.

t| lO m r. ID x._

PMo502

PMo500 C Leth Petersen. UAndersen, E Frandsen, B Hesse, HDige-Petersen. Depts. Clinical Physiology & Nuclear Medicine.Glostrup & Frederiksberg Hospital, University of Copenhagen, Denmark. Myocardial flowpattern and release of vasoaetive hormones in patients with stable angina during exercise versus hyperventilation test. The study: Twenty patients with stable angina performed either an exercise or

a hyperventilation test followed by myocardial scintigraphy. Patients received no antianginal(or other) therapy during 48 hours prior to the study. None were smokers.Exercise was performed as a symptom limited exercise test on an bicycle ergometer. We used an exercise protocol starting with 25 W and incrementsof 25 W every 2 minutes. A 12-1eadECG and systolic blood pressure were measured every minute. At peak stress, 800 MBq technetium-99m of the flow tracer sestamibi was injected intravenously and 30 min later myocardial SPECT was performed. Accordingto our standard hypervemilation protocol the patient was asked to hyperventilate vigorously at a rate of 30 respirations per min for 6 min under continuousECG monitoring. Myocardial SPECT was performed 30 rain later. Before and at peak myocardial stress (hyperventilalion/exercise)blood samples were drawn. Plasma concentrations of adrenaline, noradrenaline, ANP, endothelin, renin, angiotensin [I were measured. Myocardial flowpattern was determined by scintigraphy using a computer method to detect and quantitate regional tracer uptake. Results:

Hyperventilation

Exercise

Rest 58 2.95 24 11 1.64 40 170

Stress 124 * 8.15 * 30 16 1.65 85 * 611"

Rest Stress Adrenaline (mmol/l) 34 40 Noradrenaline (retool/l) 1.48 2.05 * Renin (miU/l) 15 16 Angiotensin II (pmol/l) 10 10 Endothelin (pmol/l) 1.55 1.75 * ANP (pg/ml) 30 29 Ischemic score 156 156 (Median values). * P < 0.05 Conduslon: Hypervenfilation is not an ischemic stimulus in patients with stable angina. In contrast to exercise, hyperventilafion is a stimulus for endothelin release. On other vasoactive hormones the impact of exercise is far more pronounced than hyperventilation.

x._

A.Teresifiska, L.M.Brodzki, B.Szumilak, E.Gosiewska, Z Juraszyfiski, Z.Slipko, Institute of Cardiology, Warsaw, Poland MYOCARDIAL PERFUSION ASSESSMENT WITH Tc-99m-MIBI SPECT IN PREDICTION OF PERFUSION AFTER CORONARY ARTERY BYPASS GRAFTING The aim of this work is to present the correlation between the results of left ventricle [LV] perfusion studies performed before and after coronary artery bypass grafting [CABG]. Sixty eight pts were studied with standard 2-days stress/rest Tc-99mMIBI SPECT. These were pts with persistent or/and partially transient perfusion defects in pre-revascularisation [pre-rev] study. Among them, there were 23 patients with low resting LV ejection fraction (LVEF< 0.35), as was evaluated during LV contrast ventriculography. First SPECT study was performed 2-180 days pre-rev and the second - 20284 days post revascularisation [post-rev]. Study assessment essentially was qualitative (visual evaluation of LV sections and BULL'S-EYE MAPS by 4 experienced observers). Additionally, the results of quantitative normative evaluation of BULL'S-EYE MAPS were considered if they were reliable. Perfusion improvement was defined as increase of activity in underperfused territory, in stress or/and in rest

study. In pre-rev study, 13 pts had persistent perfusion defects only, 12 pts had persistent and partially transient perfusion defects and 43 pts had partially transient perfusion defects only. Altogether, 33 persistent perfusion defects and 76 partially transient perfusion defects were found. In post-rev study, in 29 of 33 (88%) of persistent defects perfusion has not improved or has deteriorated, and in 67 of 76 (88%) partially transient defects perfusion has improved. Conclusion: after carefull Tc-99m-MIBI SPECT evaluation, supported with quantitative approach (if possible): (1) persistent perfusion defects in pre-rev study identify the regions of myocardium with low probability of perfusion improvement after CABG; (2) partially transient perfusion defects in pre-rev study identify the regions with high probability of perfusion improvement after CABG.

1157

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Cardiovascular

PMo503

PMo505

O. Schillaci, F. Scopinaro, C. Moroni*, R. Tavolaro, R. Danieli, P. Cannas, R. Cassone*, A. Centi Colella, Sect. Nucl. Med. and *Int. Med., Univ. "La Sapienza", Rome, Italy.

R.

Tc-99m MIBI SPECT AFTER DIPYRIDAMOLE (DIP) ECHOCARDIOGRAPHY (ECHO) T E S T IN THE D I A G N O S I S A N D L O C A L I Z A T I O N O F CAD.

AMIR, E. DELCOURT, P.TRAN, R.CALAY CHU Andre VESALE,

W.

KOSTUCKI,

MONTIGNY-LE-TILLEUL,

S T R E S S DOBUTAMINE, STRESS D I P Y R I D A M O L E TESTING : COMPARATIVE EVALUATION

M.

GUILLAUME, BELGIUM

AND

EXERCISE

DIP infusion is largely used as an alternative to exercise in myocardial (myo) perfusion studies. However, DIP is routinely administered during ECG monitoring, w h o s e changes do not represent optimal m a r k e r s of myo ischemia. The aim of this study was to determine the accuracy of Tc-99m MIBI SPECT after high-dose DIP ECHO test in patients (pts) with suspected CAD. Sixty-seven pts (45 men, m e a n age 54 ± 8 years) with chest pain and no p r i o r myo infarction were submitted to T c - 9 9 m MIBI SPECT after DIP and at rest. For DIP imaging, T c - 9 9 m MIni was injected as soon as a wall motion abnormality was d e t e c t e d by "ECHO, or 2-4 m i n after the end of DIP infusion (up to 0.84 m g / k g over i0 min). The scintigraphic data were quantitavely analyzed. According to coronary angiography 21 pts had normal vessels, 19 had 1-vessel, 16 2-vessel and ii 3-vessel disease (stenosis >50%). The overall sensitivity (SE) and s p e c i f i c i t y (SP) of DIP Tc99m MIBI SPECT for CAD w e r e 97.8% and 90.5%, respectively. The SE and SP for detection of individual stenosed vessels were 86.9% and 92.3% (LAD 87.8% and 93.9%, LCX 78.3% and 97.7%, RCA 89.7% and 86.8%), respectively. In conclusion, DIP Tc-99m MIBI SPECT is a c c u r a t e in e v a l u a t i n g the presence of CAD and in the localization of stenosed coronary vessels; the association w i t h ECHO monitoring allows to improve the timing of tracer injection, based on a reliable and s p e c i f i c m a r k e r of myo ischemia.

The value of stress dobutamine 99-Tc-MIBI imaging was evaluated as a n o n i n v a s i v e diagnostic method for assessing coronary artery disease (CAD) by comparison to stress d i p y r i d a m o l e - t h a l l i u m SPECT in 18 patients (group I) and by comparison to exercise thallium SPECT in 16 other ones (group II). In t h e s e 34 p a t i e n t s who underwent coronary a n g i o g r a p h y (CA), s i m u l t a n e o u s E C G and e c h o c a r d i o graphic m o n i t o r i n g was also performed during stepwise dobutamine (DOB) infusion. Because of the high p r e v a l e n c e of CAD in these patients (2 patients with normal CA), the comparative p a r a m e t e r s c o n c e r n the d e t e c t i o n of l e s i o n with a diameter stenosis > 70 %. Whereas the overall sensitivity of DOB MIBI-SPECT were 88 % (28/32), these values for DOB ECG and e c h o c a r d i o g r a p h y w e r e 28 % (9/32) and 84% (27/32) respectively. When Don e c h o c a r d i o g r a p h y and MIBI-SPECT were evaluted together,the diagnostic accuracy reaches almost i00 % (31/32). In group I, overall sensitivity of dypyridamole (DYP) testing(O.56mg/kg over 4 minutes) and Don testing (up to 40 @ g / k g / m i n w i t h a d d i t i o n of 0.25 to ig of atropine in some p a t i e n t s ) were comparable: 82% (14/17) a n d 88% (15/17) respectively, but the capability of detection of one-vessel CAD is lower in both methods (5/8 versus 6/8). In group II, overall sensitivity of DOB testing was not s i g n i f i c a n t l y d i f f e r e n t t h a n that of e x e r c i s e testing 87% (13/15) and 93% (14/15) respectively, but the c a p a b i l i t y of d e t e c t i o n of o n e - v e s s e l CAD was clearly higher by exercise testing (4/7 versus 6/7). Significant ST segment depression on ECG was observed in 5/17 (29%) cases by Don compared to 2/17 (13%) by DYP in group I and in 4/15 (26%) cases by DOB compared to 7/15 (47%) by exercise testing. Despite the different hemodynamic effects, exercise, DOB and DYP SPECT imaging have high overall diagnostic values. The diagnostic accuracy of ECG was higher for exercise than for dobutamine or dipyridamole testing. One-vessel CAD s e e m b e t t e r d e t e c t e d by e x e r c i s e testing than by the two other tests.

PMo504

PMo506

A. Boz, B. Kamyalgm, N. De~er, O. Sancaktar, D. Kumbasar, F. GOng&, Departments of Nuclear Medicine and Cardiology, Akdeniz University, Medicine Faculty, Antalya, Turkey.

CJ. Demonceau, C. Vanhove, J. De Vuyst, D. Bladt, S. Dierickx. St Elisabeth Hospital, Zottegem, Belgium.

THE EVALUATION OF MYOCARDIAL PERTIJSION USING Tc99mTETROFOSMINBEFORE AND AFTER MECHANICALREVASCULARIZATION

O N E YEAR PREDICTION OF THE PATIENT OUTCOME AFTER A FIRST INFARCTION: VALUE OF THE BLOOD POOL GSPECT. The gated bloodpool tomography (GSPECT) gives the ability, not only to accurately measure the ejection fraction and the volumes of the 4 cavities, but also, by comparison with a normal database, to evaluate the extent and the depth o f a dysldnesia. We evaluate the place of these parameters in the evaluation of the 1-year prognosis of the patients medically treated after a first myocardial infarction. Eighty seven patients underwent during the first 15 days after infarction a GSPECT, an echocardiography, a SPECT at rest with Tc-MIBI and a bicycle ergometric proof. Their results as well as the clinical and enzymatic data were analysed. The prediction was made on the outcome of major as well as of global cardiac events during the first year following the infarction. The patients which underwent PTCA or bypass were excluded from the study. The GSPECT were analysed using a 4Dautomatic processor, controlled and eventually corrected by the experimentator. The data of the Tc-MIBI-SPECT were analysed according to the CEqual program, allowing quantification of the size and the depth of the perfusion defects. The best multivariate Cox model to predict the total cardiac events included the standard deviation of the intensity of the contraction of the LV on a pixel base (p= 0.01), the presence of diabetes (p= 0.02), the surface of the defect on the RV (p= 0.03), the active flow of the auricles ( p - 0.08) and the depth of the phase abnormality on the LAD territory of the left ventricle (p=0.08). For the major events, the best predictors were again the standard deviation of the intensity of the contraction (p= 0.0 I) and the contractility of the apex of the RV (p= 0.007). The informations coming from the other imaging techniques cannot be satisfactory included in the model, due to their weak correlations and/or double use. This study thus emphasises the importance of the measurement, by GSPECT, of asynchrony as well as the 4 cavities analysis for the prognostic of patients medically treated after infarction.

The aim of this study was to evaluate myocardial perfusion using Tc99mtetrofosmm, a new myocardial imaging agent, before and after mechanical revascularization (MR) achieved by intracoronary stent placement or PTCA. Twenty one consecutive patients (1 F and 20 M, mean age 55+10) were included in the study. All patients had angiographically significant Coronary artery stenosis (>70%); 5 had LAD, 9 had LCx and 7had RCA lesions. None of the patients had recent myocardial infarction. In 12 patients, intraonrenary stent placement and in 9 patients PTCA were successfully performed (<50% residual stenosis, >90% reduction of stenosis). One day exercise-rest Tc99mtetrofusmin SPET myocardial perfusion scintigraphy (185-296 MBq for exercise and 555-888 MBq for rest imaging) was performed before (1-4 days) and aRer (1 month) MR. SPET data analysis was based on one midventricular vertical long axis slice and three short axis slices. Basal, mid and apical short axis slices were divided into six segments and vertical long axis slice was used to evaluate apex. A semiquantitative segmental visual analysis technique with a five point scoring system was used. Image interpretation was performed by two different observers. 0--normal Tc99m-tetrofosmin uptake; l=equivocal or slight reduction of uptake that is not clearly abnormal; 2-~noderate reduction of uptake, usually implying significant abnormality; 3=severe reduction of uptake; and 4=absence of Tc99m-tetrofosmin uptake. Two or more segments _>2 score was considered abnormal. In 74 out of 399 segments, ischemia was detected before MR. After MR double product values and duration of exercise increased significantly (250.42_+40.32 vs. 271.57_+38.40 [MOO] and, 485_+148 vs. 529±119 sec, p<0.05). After MR, ischemia score of all patients were significantly reduced (p<0.001); and in 13 patients, exercise perfusion scores (EPS) improved to 0 or I. In 7 s'tent patients and in 2 PTCA patients EPS was 0 after MR. Our preliminary results may suggest that the improvement in EPS may be better in stent patients than in PTCA patients; further studies are required in this respect. In conclusion, Tc99m-tetrofosmin was considered a good and reliable agent in the evaluation of myocardial perfusion in stent and PTCA patients

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Cardiovascular

PMo507 D. Dao% M. Faraggi, R. Lebtahi, L. Sarda, C. Peker, D. Le Guludec, Nuclear Medicine, Bichat Hospital, Paris, France.

PMo509 Juan F. Batista, Julio Tain, Mercedes Borr6n, Osvaldo Pereztol, Beatriz P6rez, Rodolfo Stusser. Centro de Investigaciones CI/nica% Habana, Cuba.

WHAT IS THE MOST APPROPRIATE STRESS TEST FOR TL201 SPECT IN THE EVALUATION OF THREE VESSEL CORONARY ARTERY DISEASE (3VD).

ILMS)IONUCLIDE VENTRICULOGRAPHY WITH NITROGLYCERIN ~PROVES DETECTION OF LEFT VENTRICULAR DYSFUNCTION REVERSIBILITY IN PNIJENTS UNDERGOING CORONARY BYPASS SURGERY

The aim of this prospective study was to compare the performance of 3 different stress tests in the evaluation of CAD in patients (pts) with angiographically proven 3VD. Pts were assigned to exercise (E) if judged able to achieve a high level of E (GE, n=64), to dipyridamole (D) in the presence of a contraindication or inability to E (GD, n=15), to combined E+D if judged capable of achieving only a limited level of E (GE+D, n=44). The number of scintigraphic defects per scan was evaluated (heart=13 segments). Work level (watt) Target heart rate (%) Clinical positivity (%) ECG positivity (%) Number of defects Abnormal L/H* (%) Normal scintigraphy (*): p<0.001; ("): p<0.05;

GE GD 109 + 33* 74 + 13" 51 + 9* 28% 7% 55 27" 3.1 + 2 . 4 * 5.1 +2.7 66 13 " 27% " 6% ÷: L/H: lung to heart.

GE+D 87 + 34* 66 + 12" 50% " 59 5.7 +2.9 50 7%

D alone induces less ECG and clinical positivity, smaller scintigraphic TI-201 defects and more normal TI-201 scans in pts with 3VD. As compared to a high level of E, combined E+D presents similar results despite a lower level of work achieved. Conclusion: D is not accurate for the evaluation of 3VD pts. In contrast, the combined test E+D is as valuable as E in the evaluation of extensive CAD and should be preferred to D alone whenever feasible.

OBYECTIVE: The aim of this study was to assess the usefulness of nitroglyt;erin-radionucfide ventriculography to predict left venlricular dysfunction reversibility in patients referred to coronary bypass surgery. METHODS: Radionuclide ventriculography was done at rest and with previous administration of nitrodycerin on forty patients, with proven coronary onery disease and impaired left ventricular function (ejection l~'action Jess than 40%), demonstrated angiographicaUy, before their submissions to coronary surgery, without consider the radionucfide results. ]he radionuclide studies were repeated three months after revaseularization (± 15 days). The studied sample was divided before surgery according the rest-nitroglycerinradienuclide ventriculography results in two groups: Group one, of 26 patienls,with improvement of left venlricular function (increment of 5% or more in ejection fraction and/or wall motion abnormalities' recovery), and group two, of 14 patients, without relevant changes. RESULTS: Group one showed a lower incidence of patients with antecedents of myocardial infarction than group two before surgery. Also, ~oup one shoved an increment of the left ventrieular ejection fraction after ~rgery, while in group two were not found relevant changes (P~0.05). Reversible dcfects by nitroglycerin-radionucfide ventrieulography pfiol ~ revascularization correlated closely with the findings observed with this procedure at rest after surgery (Pg0.05). CONCLUSION: These findings suggest the usefulness of nitroglycerin-radionuellde ventrieulography to discriminate patients with impaired left ventrieular function, who will improve it after revasculafization from those who will not.

C O im C L_

PMo508

PMo510

~. Simon. E. Nitzsche, J. Martin, I. Barth, A. Geibel, F. Beyersdorf, E. Moser. Div. of Nucl. Med., Cardiovasc. Surg. and Cardiol., Univ. of Freiburg, Germany

V i d a l - S i c a r t V, Sol~ M, M a g r i ~ J ' , G a r c ~ a A, Fuster D, Muxi A, S e t o a i n J. Nuclear Medicine and Cardiology" Departments. Clinic de Barcelona. Spain. .THE R O L E

DIAGNOSIS OF LEFT V E N T R I C U L A R ANEURYSM MIBI SPECT FDG PET: COMPARISON ECHOCARDIOGRAPHY AND VENTRICULOGRAPHY

USING WITH

Background: In patients (pat) with advanced heart failure (LV-EF ~ 35%, NYHA III, IV) the preoperative diagnostic w o r k up of suspected left ventricular aneurysm (LV-AN) by echo and ventriculography (VG) frequently reveals different findings. In this prospective study, it was hypothesized that PET permits additional information to diagnose a LV-AN more accurately. M e t h o d s : We examined 12 pat (age 66±10 yrs, EF 29±5%). Echo, VG and hybrid PET were performed according to a standard protocol. The diagnosis of an LV-AN was based on the following criteria: Echo: regional dyskinesia; VG: systolic negative contraction; PET: perfusion defect, FDG Uptake<20% of the normalized mean uptake, compared to a data base of 10 normals. G o l d standard was the intraoperative finding of a circumscripte, not contractile outbouching of the lef~ ventricle. Results : VG Echo PET diagnosed preoperatively 2 5 5 confirmed intraoperatively 1 2 5 unconfirmed intraoperatively 1 3 0 undetected preoperatively 6 4 1 Intraoperatively we verified 7 LV-AN. In Ii of 12 pat PET findings showed good concordance with the intraoperative finding. In one pat with operatively verified LV-AN, PET revealed viable myocardium. Conclusion: PET may be helpful to diagnose a LV-AN in addition to echo and VG more accurately prior to surgery.

OF SESTAMIBI

GATED

SPECT

IN V I A B I L I T Y

Pavia

J,

Hospital

O

STUDIES

The i n v e s t i g a t i o n of ~ T c - s e s t a m i b i r e g a r d i n g myocardial v i a b i l i t y seems to conclude that it is a p e r f u s i o n agent that can m i s i n t e r p r e t necrotic segments. However, few studies have assessed its u t i l i t y when gated SPECT (GSPECT) is u s e d to evaluate wall thickening (WT). The aim of this study was to evaluate if the a d d i t i o n of a G S P E C T could improve the assessment of m y o c a r d i a l v i a b i l i t y in patients with m y o c a r d i a l infarction (MI). Patients and Methods: 31 patients (25 men, 58 y.o) with MI (20 Acute MI and ii Previous MI) were studied. GSPECT, isotopic v e n t r i c u l o g r a p h y and clinical e v a l u a t i o n were done at b a s e l i n e and at 6 months follow-up. G S P E C T a c q u i s i t i o n was p e r f o r m e d at 8 frames/cycle and r e g r o u p e d later tc o b t a i n the n o n g a t e d SPECT. Eleven segments were a s s e s s e d at the short-axis and the vertical long-axis m i d v e n t r i c u l a r slices. Segmental m y o c a r d i a l uptake was a s s e s s e d visually. Wall thickening (WT) was evaluated by means of visual assessment of wall b r i g h t e n i n g in end-systolic compared to e n d - d i a s t o l i c images. Results: 74 p a t h o l o g i c a l segments were observed. Of the 5 3 s . i n A M I group, 12 were reversible and so viables (ii with WT), and 41 were fixed defects (9 with WT). Of the 21 h y p o p e r f u s e d segments in PMI group 9 showed WT. At follow-up, p e r f u s i o n evaluation in the 18 h y p o p e r f u s e d segments with WT s h o w e d that 12 improved perfusion, 4 did not change and 2 worsened. Of the remaining 44 h y p o p e r f u s e d segments without WT, 2 improved perfusion, 29 did not change and 13 worsened. E j e c t i o n fraction in AMI group improve from 47.7 to 52.3 (p=0.018) but did not p r e s e n t significant changes in PMI group. Clinical e v a l u a t i o n w o r s e n e d only in 2 p. Presence of WT in stress GSPECT was predictive of r e v e r s i b i l i t y at rest in 43S.(IITP,32TN} and failed in 10S.(IFN, 9FP) o b t a i n i n g v a l u e s of S=91.6% and SP=78%. Presence of WT in h y p o p e r f u s e d regions was predictive of improved p e r f u s i o n at follow-up (PPV=S5.7%, NPV=87.5%). Conclusions: G S P E C T has been useful to diagnose viable segments in h y p o p e r f u s e d regions by means of wall thickening assessment. However, we think we must be cautious to take p r e s e n c e of WT as a sign of reversibility.

1159

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Cardiovascular

PMo511 ~ , H. AKIN, S. BUKET, C. SOYDA~, D. YOKSEL,Y. ATAY, i. DURMAZ, Y. DUMAN. Ege University, Depte of Nuclear Medicine, Cardiology, Cardiovascular Surgery, Izmir, Turkey. COMPARISON OF Tc-99m TETROFOSMIN AND THALLIUM=201 REINJECTION IN DIAGNOSIS OF VIABLE MYOCARDIUM The aim of this study was to predict the relative efficiency of two myocardial perfusion tracers, Tc-99m Tetrofosmin (TFM) and TI-201 in diagnosis of viable myocardium in patients (pts) with previous myocardial infarction (MI) in comparison with 2 Dimentional (2D) echocardiography (echo). Eighteen pts (15 men, 3 women, mean age=55) with previous MI and mean left ventricle ejection fraction = 30 ± 15% were studied by exerciserest-reinjection (RI) T1-201 and one day exemise-rest TFM cardiac imaging.Until now, 4 pts have been reevaluated after by-pass surgery. For each study, left ventricle was divided into 20 segments. Regional TFM and 71-201 uptakes were anaiyzed in a total of 360 segments by quantifying the percentage of uptake in 4 representative slices (>/75% = normal - <50% = severe), All pts were evaluated by 2D echo using a wall motion 0NM) score ranging from 1 (normokinetic) to 4 (akinetic). TFM Results: 250 segments were normal with >/75% uptake. There were 110 stress defects with ~<65% uptake, 35 were reversible (32%), 75 were fixed (68%). 36 of fixed defects had WM score 4 with uptake < 30%. Remaining defects had WM score 3±1 and mean uptake was 48±10%. ~-:~01 Result~ There were 121 stress defects, of these 38 were reversible (32%) with 55~:10% uptake, 16 were filled-in with RI (13%) and 63 were fixed (52%). 14 of 51 fixed defects had WM score 2±1 with 40±5 uptake. In g segments, TI-201 showed viability consistent with echo results while TFM uptake was <40%. In 6 segments TFM uptake was 1>55% while TI-201 uptake was <50% with WM=3. In eoneluaion, although both TFM and TI-201 were found sensitive in detecting significant coronary ischemia, TI-201 RI demonstrated better results in diagnosis of viable myocardium in segments with ~<45% uptake.

PMo513 E.ibi~, F.Berk,*M.Ozdemir, *T.Kural, G.Aras, A.Akin Ankara University, School of Medioine, Dept.of Nuclear Medicine, *Y~ksek Ihtisas Hospital, Dept.of Cardiology, Ankara I Turkey EVALUATING OF MYOCARDIAL VIABILITY DOBUTAMINE STRESS ECHOCARDIOGRAPHY RE I N J E C T I O N T I - 2 0 1 S P E C T IN P A T I E N T S ACUTE MYOCARDIAL INFARCTION

WITH AND WITH

Coronary angiography(CAG), dobutamine stress echocardiography(DSE) and stress-restr e i n j e c t i o n T I - 2 0 1 S P E C T ( T I ) w e r e p e r f o r m e d for evaluation of m y o c a r d i a l viability(MY) in 16 patients (pts) with non-complicated acute myocardial infarction(MI), b e t w e e n 7 and i0 days a f t e r MI. C A G r e v e a l e d s t e n o s i s o v e r 50% at L A D in pts, L A D + R C A in 7 pts, L A D + C x in 1 pt, L A D + C x + R C A in 1 pt n o r m a l c o r o n a r i e s in 3 pts. All pts (3) w i t h n o r m a l CAG s h o w e d M V in b o t h DSE and TI. Pts(4) w i t h L A D s t e n o s i s s h o w e d M V in b o t h DSE and TL for 3 pts w h i l e 1 pt had (+)T1 and (-)DSE for MV. Pts(7) with LAD+RCA l e s i o n s s h o w e d (+)results in b o t h DSE and T1 in 4 pts,(-) T1 and (+)DSE in 1 pt, (+)TI and (-) DSE in 1 pt, (-) r e s u l t in b o t h T1 and DSE in 1 pt for MV. Pts(2) w i t h L A D + C x and L A D + C x + R C A lesions had (-) r e s u l t in b o t h DBE and TI. Briefly, DSE for d e t e c t i n g M V was f o u n d to be in h a r m o n y w i t h T1 in 81.2% of 16 pts. On the o t h e r hand, DSE had 6.2% false[+} and 12.5% false(-) result. As a results, we c o n c l u d e that DSE have h i g h s e n s i t i v i t y for d e m o n s t r a t i o n of M V but s t r e s s r e s t - r e i n j e c t i o n T I - 2 0 1 SPECT is m o r e v a l u a b l e for having possibility of visual and q u a n t i t a t i v e a s s e s m e n t of m y o c a r d i a l v i a b i l i t y .

PMo512

PMo514

H.Maruno. M.Onoguchi, H.Toyama, K.Yoshioka, N.Komiyama, S.Ishiwata, H.Murata, D i v i s i o n of N u c l e a r Medicine, Toranomon Hospital, Tokyo, Japan

M. Giganti, C. Cittanti, P. Colamussi, L. Uccelli, S. Scarf6 °, D. Barbieri*, A. Piffanelli. Cattedra di Medicina Nucleare, Universit~ di Ferrara, Divisione di Cardiologia Ospedale di Canto°; Divisione di Cardiologia Ospedale di Comacchio*.

ASSESSMENT OF MYOCARDIAL VIABILITY USING Tc-99m TETROFOSMIN IMAGING, ECG-GATED SPECT AND FOURIER ANALYSIS. --COMPARISON TO R E S T - R E D I S T R I B U T I O N THALLIUM (TL) IMAGING-This study examined the ability of Tc-99m tetrofosmin (TF) imaging to detect myocardial viability, compared with rest-redistribution T1 imaging, in patients with chronic coronary artery disease. Forty-seven patients with regional wall motion (RWM) abnormalities (assessed with LVG) were s t u d i e d prior to CABG. Each patient underwent resting TF SPECT (including ECG-gated SPECT) and r e s t - r e d i s t r i b u t i o n T1 SPECT. Enddiastolic polar map (ED) was generated using ECG-gated SPECT and Fourier analysis. RWM was graded as normal, hypokinetic, a k i n e t i c or dyskinetic pro and post CABG with LVG or MUGA. Dysfunctional regions were considered viable when RWM improved by at least one grade after CABG. LVG or MUGA were repeated after CABG. The uptake in each of 9 s e g m e n t s per scan was s c o r e d as; 3=normal, 2=mildly reduced, l=severely reduced, 0=defective, and compared between TF and T1 images. In addition, regional m y o c a r d i a l uptake (rMU) was expressed as p e r c e n t a g e of peak m y o c a r d i a l activities. T1 uptake was e v a l u a t e d as early uptake (Tle), redistribution uptake (Tld), and the larger (Tlmax) between Tle and Tld. Of all 423 segments, 145 had both perfusien abnormality and asynergy. In the asynergic segments, the agreement b e t w e e n TF and Tlmax was 74%, and was higher than Tle (66%) or Tld (71%). O£ 84 asynergic segments in anterior or inferior wall, 53 were viable and 31 were nonviable. In these segments, the d i a g n o s t i c a c c u r a c y w i t h TF and T1 i m a g i n g in the detection of myocardial v i a b i l i t y was d e t e r m i n e d using rMU. Sensitivity Specificity Accuracy TF(ED) T1 TF T1 TF(ED) T1 Overall 87%(91%) 89% 97% 94% 90%(93%) 90% Anterior 88%(92%) 96% 100% 93% 93%(95%) 95% Inferior 85%(89%) 81% 94% 94% 89%(91%) 86% In the inferior segments, the diagnostic accuracy of TF was higher than T1. These data suggest that TF imaging could identify viable m y o c a r d i u m as clearly as TI, and that TF and ED p r o v i d e more accurate p r e d i c t i o n of myocardial viability than T1 in inferior wall.

1160

PERFUSION SPET WITH 99mTc-TETROFOSMIN VERSUS 2mTl FOR MYOCARDIAL VIABILITY DETERMINATION. Technetium99m-tetrofosmin has been proposed for perfusion myocardial imaging, and proved as useful tracer for detection of coronary artery disease. Aim of the study was to assess the possible role of 99mTctetrofosmine in myocardial viability identification in comparison with 201TI. Patients: a total of 21 patients aging from 58 to 75 yrs, with stabilized previous myocardial infarction (2-3 mo.), demonstrating a severe thallium defect persistent at redistribution (defined as < 50 % uptake of peak max activity PMA), with a good quality echocardiography (confirming the presence of regional wall motion abnormality) were studied. Spet acquisition and processing: Patients underwent Thallium stress /rest/reinjection scans, and 99mTc-tetrofosmin stress/rest scans. The data analysis was performed by two independent observers, with the following criteria: the left ventricle was divided in 21 segments; each segment was scored 0-4 (normal uptake >70%PMA; mild defect 70>60% PMA; evident defect 60>50% PMA; severe defect 50>40% PMA; no uptake: <40% PMA) by semi-quantitative analysis. The scans were compared to assess: 1) localization, extension and severity of coronary disease, 2) tetrofosmin/ Thallium concordance for topographic identification of disease (localization, extension), 3) segmental concordance normality/abnormality of perfusion, 4) segmental concordance, transient/permanent perfusion abnormality. Based on the scans comparison, each segment was classified as normal, ischaemic, viable, necrotic. Segment Thallium Tetrofosmin Tetrofosmin classification N° N° Concordance Normal 230 233 212 (92%) lschaemic 62 59 55 (88%) Viable 37 7 5 (13%) Necrotic 112 142 110 (98%) High concordance values were calculated between the tracers for localization and extension of normal myocardium, ischaemic areas and necrotic tissue. The sbgroup of segments matching the scintigraphic criteria for viabile tissue showed very low concordance data (see table). In conclusion, while terofosmin confirms its thallium-like behaviour in detection of CAD, it seems to underestimate the presence and extension of viable myocardium.

•

Cardiovascular

PMo515

PMo517

A.Akta~, B.Caner, U.Uysal,NG~latdL C Sasani Hacettepe and Ba~kent University, Department of Nuclear Medicine, AnkaraTURKWE

Y.Nomura K.Matsumura, K.Takeda, S.Murashima, M.Gotou, and T.Nakagawa. Department of radiology, Mie University School of Medicine, Mte, Japan

IMMEDIATE THALLIUM REINJECTION FOLLOWING STRESS IMAGING FOR DETECTING MYOCARDIALVIABILITY Myocardial perfusion scintigraphy with thallium has been established as an effective method to assess ischemic and in certain instances viable myocardium By using planar imaging technique, images taken 1 hr after immediate thallium reinjection has been sho~aato be comparable to those of 3 hr redistribution. The aim of this study was to clarify this issue by using SPECT technique. Sixteen patients with chronic coronaB, artery disease having at least 2 perfusion defects on postexercise imaging participated for this study All patients received thallium reinjection immediately follomng poststress SPECT accquisition and all had 1 hr, 3 hr and 24 hr redistribution imaging. The thallium myocardial tomograms were divided into 20 segment for each patient. A total of 52 segments were studied. Twelve segments showed reversibility on I hr imaging (%23). Of the remaining 413 segments, 13 shewed fill-in on 3 hr redistribution images (%25). On 24 hr imaging 12 additional segmentsshowedfill-in (%23). In conclusion, we say that when compared to 3 hr images, images taken 1 hr aller immediate reinjection underestimate the extent of viable myocardial segments and the incidence of late reversibility (24 hr imaging) is not reduced by the immediate reinjectien of thallium

COMPARISON OF 1-125 BETA-METHYL-BRANCHED FATTY ACID(BMIPP) AND THALLIUM-201(T1) U P T A K E IN RATS WITH RIGHT VENTRICULAR F A I L U R E . To evaluate myocardial metabolism of right ventricle(RV) in patients with pulmonary hypertension (PH) is clinically important. We compared 1-125 BMIPP with T1-201 uptake in a rat model of right ventricular failure (RVF) and evaluated myocardial fatty acid metabolism in RVF. Methods:Sprague-Dawley rats were given a single subcutaneous injection of the toxin monocrotaline (40 mg&g). At 3 weeks after treatment, mean pulmonary arterial pressure was higher than that in age matehed control rats (n=9) (36-+5 vs. 16_+3 mmHg, p<0.001), and all RVF rats had aseites. 1125 BMIPP (0.37 MBq) was injected to the RVF rats(n=6) and control rats(n=6) via the tail vein. TI-201 was injected t~ the RVF rats(n=3) and control rats(n=3.). The hearts were excised at 30 rain after injection, weighed and counted. R e s u l t s : T h e ratio of RV weight to body weight was significantly higher in RVF rats than in control (0A34_+0.005 vs. 0.056_+0.01 p<0.001). The uptake ratios of RV to left ventricle(RV/LV) and interventricular septum to LV(Septum/LV) show as follows: RVF t-test Control BMIPP RV/LV 0.77-+0.08 p<0.01 1.06-+0.18 Septum/LV 0.82+0.07 p<0.0t 0.98_+0.05 Tt

RV/LV Septum/LV

0.98_+0.12 0.95_+0.13

N.S. N.S.

0.95___0.14 0.97_+0.17

Histopathology of RV and septal wall in RVF rats showed hypertrophy of myocardial fibers, but no destructive change. Conclusion:tliese results of our study suggest that 1-123 BMIPP is a more suitable tracer for assessment in RV failure patients with PH compared with Tl-201.

PMo516

PMo518

L.Pace, P.Perrone-Filardi, M.Prastaro, A.Cuocolo, F.Squame, P.Vezzuto, A.Discepolo, A.Soricelli, F.Piscione, M . C h i a r i e l l o , M . S a l v a t o r e . Catt.E Centro C.N.R. M e d i c i n a NucleareCatt. Cardiologia, Universit& Federico II, Napoli, Italy.

T u r p e i n e n AK, Kuikka JT, V a n n i n e n E, U u s i t u p a M. D e p a r t m e n t s of Clinical P h y s i o l o g y and N u c l e a r Medicine, and Clinical Nutrition, K u o p i o U n i v e r s i t y Hospital, Kuopio, F i n l a n d

O P T I M U M T H A L L I U M - 2 0 1 U P T A K E T R E S H O L D TO IDENTIFY VIABLE MYOCARDIUM BY REST-REDISTRIBUTION SPET

A B N O R M A L M Y O C A R D I A L KINETICS OF 1-123H E P T A D E C A N O I D A C I D IN SUBJECTS W I T H IMPAIRED GLUCOSE TOLERANCE

Quantitative thallium-201 (TI) analysis using a 50% treshold is w i d e l y used to identify viable myocardium. However, this is an arbitrary treshold. In order to identify the best treshold we studied 34 patients with chronic CAD u n d e r g o i n g coronary r e v a s c u l a r i z a t o n (CR) by r e s t - r e d i s t r i b u t i o n T] SPET before and after CR. Regional f u n c t i o n was e v a l u a t e d by two d i m e n s i o n a l echocardiograph~ before and after CR by a 3 point scale (l= normal, 2= h y p o k i n e t i c , 3= a / d y s k i n e t i c ) . Of the 408 myocardial segments analyzed, 78 were a/dyskinetic. Akinetic myocardial segments were defined viable if systolic function score decreased A1 after CR. Of these, 54 underwent CR, and 26 improved function after CR and 28 did n o t . S e n s i t i v i t y - s p e c i f i c i t y curves were generated by v a r y i n g T1 uptake treshold. A 65% treshold uptake was identified as capable of best s e p a r a t i n g a/dyskinetic segments improving after CR from those not improving. Sensitivity was slightly lower with a 65% t r e s h o l d (81%) than w i t h a 50% t r e s h o l d (96%, p<0.05). On the other hand, specificity was higher (75% vs 21%, p<0.05) resulting in better accuracy (78% vs 57%, p<0.05) and positive predictive value (75% vs 53%, p<0.05), w h i l e n e g a t i v e predictiv( value was not different (81% vs 86%, p n.s.). These results demonstrate that a 65% T1 uptake treshold is preferible in order to separate viable from not viable dyssinergic myocardial segments.

D i a b e t e s is a s s o c i a t e d w i t h increased m y o c a r d i a l t r i g l y c e r i d e content. It is not known w h e t h e r m y o c a r d i a l fatty acid (FA) m e t a b o l i s m differs b e t w e e n n o n - i n s u l i n (NIDDM) and insulindependent diabetes (IDDM), and w h e t h e r such a b n o r m a l i t i e s are present even before overt diabetes. Therefore, we studied myocardial FA k i n e t i c s w i t h SPET and 1 - 1 2 3 - h e p t a d e c a n o i d acid (HDA) in m e n w i t h i m p a i r e d glucose tolerance (IGT; n=13), N I D D M (n=10), IDDM (n=8) and in a h e a l t h y control group (n=8). In the IGT group, m y o c a r d i a l b e t a o x i d a t i o n index was reduced by 53 % (4.6 ± 0.4 vs 9.7 ± 1.0 ~mol/min/lO0 g; m e a n ± SEM; p<0.01), H D A u p t a k e by 34 % (3.7 ± 0.2 vs 5.6 ± 0.3 % of i n j e c t e d dose; p< 0.01) and fractional amount of H D A u s e d for b e t a o x i d a t i o n (43 ± 4 vs 61 ± 4 %; p<0.05) c o m p a r e d w i t h the control group. The N I D D M group tended also to have l o w e r e d H D A b e t a o x i d a t i o n index, whereas p a t i e n t s w i t h IDDM had similar H D A kinetics as the control group. In conclusion, even before d i a g n o s i s of clinical diabetes, IGT is a s s o c i a t e d w i t h a b n o r m a l i t i e s in myocardial FA metabolism.

1161

C O

= m

C

O

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Cardiovascular

PMo519 G. Huanq, R.Y. Zhao, Y.F. Srlan, ~. Zhen, J-B i..i Y Yan, W.G.Liu. Dept. of Nuclear Medicine, Zhongshan Hospita_, Shanghai Medical University, Shanghai, P.R. of China. COMPARISON BETWEEN NITRATE TC-99m-MIBI A/qD TI-20! REINJECTION TOMOGRAPHY IN DETECTING VIABLE MYOCARDIUM. T h a l l i u m reinjection (TL-RI) and TC-99m-MIBI tomography after administration of nitrate (MB-N) improve the detection of viable myocardium. However, few paper directly compared the resulzs of TL-RI with MB-N. Resting/reinjection thallium tomography and same-days stressing/MB-N tomography were performed in 23 patients with myocardial infarction within 1 week. Of them 12 patients underwent PTCA in 2 weeks after the imagings and followed-up by echocardiography for 3 months. The method of same-days stressing/MB-N tomography is that TC-99m-HIBI is reinjected in 5min. after sublingual nitroglycerini (NTG) i m~ (MB-N) following.the .acquisition of postexercise MB imaging and MB-N was acquired at 1 hour after the reinjection. The left ventricle was divided into 9 segments and blindly evaluated by 3 independent observers based on a 4-poin~ seale(l=no uptake, 4=normal). Of 207 myocardial segments analyzed, 96 had abnormal reduction of Tc-99m-MIBI (ME) uptake on stressing imaging, of which 53 demonstrated improved MB uptake on MB-N and 57 had improved T1 uptake on TI-RI. There was no difference between TI-RI and M B - N . In 12 patients undergone PTCA, the predictive positive and negative values of TI-RI and MB-N were 81%, 83% and 78%, 86% respectively. These data suggested that MB-N, a simple and practicable approach can significantly improve the detection of viable m y o c a r d i u m in ischemia as well as TLRI.

PMo520 M.J. Claeys (1), B. Krug'(2), F.E. Rademakers (1), C.J. Vrints (1), J.Bosmans (1), V. Conraads (1), J.P. Snoeck (1), P.P. Blockx (2). Depts of Cardiology (1) and Nuclear Medicine (2), Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium. ADENOSINE MIBI SPECT UNDERESTIMATES POST INFARCTION ISCHEMIA DUE TO OVERESTIMATION OF INFARCT SIZE To assess whether underestimation of viability by Tc-99m sestamibi (MIBI) may affect the diagnostic accuracy of stress scintigraphy to detect ischemia within the infarct region, adenosine MIBI SPECT was performed in 51 patients(pts.) with recent myocardial infarction(MD and related to quantitative coronary angiography and dobutamine stress echocardiography(DSE). Both perfusion activity(on MIBI) and regional wall motion(on DSE) were analyzed on a 13 segmental left ventricular model. The infarct size was estimated scintigraphically by the number of segments with resting perfusion activity <50%, and echocardiographically by the number of akinetic segments during low dose DSE. A reversible perfusion defect within the infarct region(REV), was observed in 21 pts. A total of 37 pts. had a significant infarct related lesion (IRL >50% diameter stenosis), of which only 20 pts had REV. This resulted in a sensitivity of 54% and a specificity of 93%. The underestimation ot ischemia by MIBI occurred twice as much in pts. with an IRL ->65% and was mainly related to a scintigraphic overestimation of the infarct size: in pts. with IRL >50% and REV(n=20), the scintigraphic and echocardiographic estimation of the infarct sized matched well. However, in pts. with IRL >50% and non-REV(n=17), resting scintigraphy overestimated the echocardiographic infarct size by an average of 1.5 segments. pts. with IRL > 50 % diameter stenosis REV (20) non REV (17) p-value DSE +,n 16 11 p=NS 1RL ->65 % 8 14 p<0.05 infarct size echocardiography (E) 2.2 + 1.6 2.2 -+ 1.3 p=NS scintigraphy (S) 2.3 + 1.4 3.7 + 1.3 p<0.005 overestimation S -E 0.1 + 1.6 1.5 + 1.7 p= 0.01 ~, (DSE + = echocardiographic evidence of ischemia during dobutamine) Thus, in pts. with a recent MI, adenosine MIBI may underestimate ischemia mainly in regions supplied by a severely stenotic vessel, probably due to overestimation of the infarct size on the resting study.

1162

PMo521 P. Chouraqui, M. Shechter, S. Lifshitz, B. Rabinowitz, Z. Brill, E. Di Segni, Nuclear Cardiology Unit, Heart Institute, Sheba Medical Center, TeI-Hashomer and TeI-Aviv University, Israel.

SIGNIFICANCE OF DISTAL REVERSIBILITY IN INFARCT TERRITORY AS DETERMINED BY SPECT THALLIUM-201: A SIGN OF COLLATERAL FLOW WITH OCCLUDED INFARCT-RELATED CORONARY ARTERY. Following myocardial infarction, the assessment of the presence of flow within the infarct region may be of importance for therapeutic management and prognosis. The finding of combined proximal fixed defect and distal reversibility of thallium-201 (TI-201) uptake within the myocardial infarction (MI) territory is related to collateral flow supplying the territory distal to the occlusion of the infarct-related artery. In order to test the hypothesis, we performed stress-redistribution SPECT TI-201 studies in 69 consecutive patients following MI with completely occluded (65 patients) or critically stenosed Ml-refated artery (4 patients) at coronary angiography. Twenty-nine patients (Group A) demonstrated a reversible defect in the distal portion of the MI territory combined with fixed proximal defects, and 40 patients (Group B) had only fixed defects in the MI territory. Collateral flow to the infarct-related artery was observed by angiography in 28/29 patients of Group A and in none of Group B: (Sensitivity 98%; Specificity 100%; Accuracy 99%). Conclusion: The TI-201 uptake pattern consisting of combined distal reversibility and proximal fixed defect in myocardial infarction territory is a very accurate sign of collateral flow in patients with totally occluded or critically stenosed infarct-related artery.

PMo522 C.F~,se~. GGanafe, C.Landoni, G.I.uognani, Mlppolito, A.Bartorelli, ASavi, M.Pepi, M.GuazzJ, F.Fazio. INB-CNR, HS. Ra~ele, ~ of Cardiology"1.Mon~no", Universityof Mlan, Ilaly.

99mTc-MIBIREST,TL-201 REST~EDISTI=IBUTIONAND F18-FDG IN PATIENTS WFIH MODERATE LEFT VENTF~LE DYSFUNCTION UNDE~G PTCA Seventeen palier~with let ven1~deejeclon frac~on>40% candidate to PTCA were sUdied with SPET 99m-Tc MIBI rest, 201-TI rest/ red~lJb~on and PET 18FFDG. Global and regional ~nes~sof ~e left ver~de was s~died with biplane echoca~liography:theleltvenf~idewas dMded into 11 segmenls andthe relalJveregionalkinesiswas scored (5= diskJnesia;4= akJnesia;3= severe ipol4nesJa; 2= mild ipol4nesia;l= normo~nesia). Echo- and tomosdnlJgraphicimages were coregiste~d by sudace matching of trasmissive image& Among the 11 segments de|ned on echo-matched images, the one with ~e highest acA4ty at s~ess 99m-Tc MISI SPET was used as the reference for each s~dy (adMty=-100%). If >50% of the re~rence segment, 99m-To-MIBI, 181=FDG and 201-TI uptakes were considered signitcant The echccaEliogrephic fol~ow-up a~er PTCA did not show s~gni~ant improvementat 30 days (EF 56_+6%)or at 6 months (EF 56_-_+9%).Thirtyone segments (44%) irnproved their 14nests alter PTCA. Of these segments signiicant uptake was present in 27 br 99mTc-MIBIjn 28 for 201-]1 and in 26 for 18F-FDG. Considering the 38 segments without kinetic improvement, 99mTc-MIBI uptake was signiicant for 31 segments,while201-TIand 18F-FDGuptakewassigniJcantin 31 and 32 segments ~spec~vely. In conclusion, in the dass of palJen~ w ~ moderatelycompromised contrac~letuncton, 99mTc-MIBI, 201-TI and 18F-FDG,while dernons~ng the same behaviourdo not exhibit a dear prediclive value of cor~acgJle func~on recovery rater PTCA; pa~ent popula~onis then an highly relevant point to eslablish the accuracy of these diagnos~cprocedures.

•

Cardiovascular

PMo523

PMo525

J.J. Bax, J.H. Cornel, F.C. Visser, A. van Lingen, P.M. Fioretti. Free University Amsterdam, University Rotterdam, Netherlands.

E. Derebek,O. Kozan,H. Durak, O. Ergene, E. Ozbilek,G. Capa, A. Belgi, Y. Yurekli,B. Degirmenci,A.S.Dogan.DeNsof NuclearMedicineand Cardiology, School of Medicine, DokuzEylul University, Izmir, TURKEY.

COMPARISON BETWEEN FDG SPECT AND STRESS-REINJECTION THALLIUM SPECT TO DETECT VIABLE MYOCARDIUM. Thallium-201 imaging using a stxess-reinjection protocol and FDG imaging have both been proposed to assess viable myocardium. In the present study, we performed a direct comparison between FDG SPECT and thallium-201 slress-reinjection to assess viability. Also, we assessed the diagnostic accuracy of both techniques to predict improvement of contractile left ventricular function after revascularization. Seventeen patients with depressed ventrieular function (mean LVEF 38±11%), who were scheduled for revascularization, were included in the study. FDG uptake was compared with resting perfusion (assessed with early thallium-201 SPECT). On FDG SPECT, viability was defined by normal peffusion or by a peffusion-FDG mismatch. For thallium-201 stress-reinjection, viability was present when there was normal uptake, (partially) reversible uptake or an irreversible mild fixed uptake (>50% of normal activity). Contractile function was evaluated with 2D echo before and 3 months after revascularization. In the dyssynergic segments, the agreement for the detection of viability between FDG SPECT and thallium-201 stress-reinjection was 70%. FDG SPECT and thallium-201 stress-reinjection had a comparable sensitivity to detect functional recovery after revascularization (89% vs 93%), but the specificity of thallium-201 stress-reinjection was markedly lower (77% versus 43%). These data show a fair agreement between FDG SPECT and thallium201 stress-reinjection for the assessment of viability, although the results suggest that thallium-201 stress-reinjection may overestimate functional recovery after revascularizatian.

Tc-99m TETROFOSMIN I N F U S I O N IMAGING U N D E R THE EFFECT OF SUBLINGUAL N I T R A T E IN THE DETECTION OF VIABLE MYOCARDIUM.

Conventional stress-rest (ST-R) Tc-99m labeled myocardial imaging is suffered from underestimation of viability. The purpose of this study was to investigate the possible role of sublingual nitrate plus Tc-99m tetrofosmin infusion (N+lnf If) in the detection of viable myocardium. ST-redistribution (RD)-reinjection (RI)-Iate redistribution (L RD) TI-201, and R-ST-N +lnf Tc-99m tetrofosmin SPECT imaging were performed in 25 patients with fixed defect on conventional STRD TI-201 imaging. 3+ 1 mCi TI-201 was administered for ST and RI studies. Two days after R-ST Tc-99m tetrofosmin one-day imaging protocol (8 mCi for FIand 25 mCi for ST), 30 mCiTc-99m tetrofosmin was infused for 1-hour following 5 mg sublingual isosorbid dinitrate and N+lnf If imaging was performed. Each study was visually evaluated by two observers, scorring segmental uptake as 4 (Normal), 3 (Mild decreased), 2 (Moderately decreased) and 1 (Markedly decreased or absent). Any increment on RD, RI, L RD TI201 and R, N +lnf Tc-99m If images was the criterion for reversibilk"y. Of 103 fixed defects on conventional ST-RD TI-201 imaging, 17 were reversible on RI TI-201 images. Of 100 fixed defect on R-ST Tc-99m "If images, 15 were found reversible on N +lnf Tf images. We found great concordance (91%) between TI-201 RI and N +Inf Tc-99m Tf regarding reversibility. We conclude that N + Inf Tc-99m Tf imaging seems to be a promising method in the identification of viable myocardium.

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O

V) O Q.. PMo524

PTu526

L. Sarda, R. Lebtahi, N. Delahaye, Y. Petegnief, P. Weinman, M. Faraggi, D. Le Guludec. Bichat Hospital, Department of Nuclear Medecine, Pads, France.

M.Estorch, A.Flotats, R. Serra, A. Lizarraga, LI.Bern~, A.Catafau, I.CarriS. Department of N u c l e a r M e d i c i n e and Cardiology. Hospital Sant Pau. Barcelona, Spain.

ARE SIZE AND INTENSITY OF MYOCARDIAL MIBI-SPECT DEFECTS DEPENDENTON PATIENTPOSITIONNING(SUPINEOR PRONE)?

PROLONGED E X E R C I S E INFLUENCES M Y O C A R D I A L 1231M I B G UPTAKE.

Prone imaging has been proposed to avoid artefactual inferior defects. But its implications on the size and intensity of defects, which are two major prognostic factors, are unknown. Our purpose was to evaluate the effect of positionning on SPECT images. Two consecutive rest acquisitions (supine/prone) were performed l h after injection of Tc99m-MIBI (370 Mbq), in 2 groups of patients with known myocardial infarction ([VII), documented by angiocoronarography: antedor MI (G1; n=10), infedor MI (G2; n=10). Were computed the absolute values and their relative changes (RC) between the 2 SPECT of: 1/the number of pathologic segments (N) (total segments: 25), 2/ the size of the defect (S) determined on polar maps (uptake < 60% of maximal activity), 3/the uptake ratio: pathologic/normal area (P/N),

To assess the influence of p r o l o n g e d e x e r c i s e in cardiac sympathetic innervation, nine healthy u l t r a m a r a t h o n male runners (age 34±11 years) were studied after a four hours race and at rest w i t h 123I-MIBG. A f t e r injection of 185 M B q of 123I-MIBG, the athletes were r u n n i n g d u r i n g four hours, covering 45±8 Km. Planar and SPECT images of the thorax were a c q u i r e d at the end of race. Two w e e k s later, studies at rest were performed. A heart to m e d i a s t i n u m ratio (HMR) was calculated to q u a n t i f y MIBG uptake. Serum norepinephrine (NE) c o n c e n t r a t i o n was m e a s u r e d after the race and at rest. HMR at rest was 1.84±.16 and after the race was 1.70±.18 (p<0.005). Cardiac p a r a m e t e r s during the race were: heart rate increased from 70±8 b e a t s / m i n to 81±13 b e a t s / m i n (p=0.03), and b l o o d p r e s s u r e at rest was 130±14/84±8 and 128±24/78±ii after the race (p=NS). The level of NE at rest was 142±68 pg/ml and after the race was 156±49 pg/ml (p=NS). We conclude that myocardial 123I-MIBG uptake can be influenced by p r o l o n g e d exercise. A decrease in myocardial MIBG uptake is o b s e r v e d with p r o l o n g e d exercise without significant variations in the serum levels of NE. These results suggest that p r o l o n g e d exercise could increase washout and decrease cardiac uptake of MIBG, in relation to sympathetic nerve activation.

O tn O

13,,

NG1 SG1(%) PING1(%) NG2(%) SG2(%)PING2(%) Supine 10.7_+4.6 22.9_+15.6 57.8+-6.1 7.0_+1.9" 7.7_+5.2" 62.7+_5.4" Prone 8.6_+3.8 18.5_+13.8 56.6_+7.2 3.7_+2.0" 2.3-+3.0" 70.5+9.7* RC(%) 2.1+3.1 4.3+8.6 1.2-+2.5 3.3-+1.5' 5.4+3.7* -7.7_+6.4* p NS NS NS 0.00009" 0.001" 0.004" In 5 patients of G1 and 7 of G2, N vadation was superior to 2 segments. In G1, wall motion abnormalities studies were more concordant with supine than prone SPECT images in all 5 cases. In G2, a better agreement with supine images was found in 4/7 cases but an undesirable bowel activity was present in prone images. Conversely, a better concordance with prone imaging was found in 3 patients, without bowel activity. Conclusion: prone MIBI positionning induces a significant decrease in size and intensity of the inferior defects. This must be integrated for prognostic and viability studies. The presence of bowel activity may affect the accuracy of prone images.

1163

•

Cardiovascular

PTu527

PTu529

*S.Naqamachi,*S.Jinnouchi,*Leo G. Flores II, *H.Nakahara,*K.Watanabe,**T. Kurose,**S.Matsukura, *Department of Radiologyr ** Department of III rd Internal Medicine, Miyazaki Medical College, JAPAN

V, Podio, M.T. Spinnlsr, G. Canavese, A. Muni, A. Codegone, G. Bisi

1-123 MIBG MYOCARDIAL SPECT IN PATIENTS WITH DIABETES MELLITUS TYPE II; COMPARATIVE STUDY WITH VERSUS WITHOUT SILENT MYOCARDIAL ISCHEMIA

Effects of Myocardial Ischemia on Myocardial MIBG Uptake

Purpose: This study was u n d e r t a k e n to assess the e f f e c t of s i l e n t m y o c a r d i a l i s c h e m i a in the cardiac sympathetic i n n e r v a t i o n of d i a b e t i c patient(NIDDM) by using 1-123 MIBG SPECT. Methods:I-123 M I B G S P E C T was done in 8 normal subjects and 30 NIDDM patients. Data were acquired at both 20 m i n u t e s and 4 hours after intravenous injection of 180 M B q 1-123 MIBG. Tracer uptake was e v a l u a t e d v i s u a l l y on b o t h e a r l y a n d d e l a y e d images b y d i v i d i n g m y o c a r d i u m into 7 segments. S i l e n t m y o c a r d i a l i s c h e m i a was d e f i n e d as the p r e s e n c e of a reversible p e r f u s i o n defect on TI201 myocardial SPECT. M e a n value of visual uptake s c o r e of e a c h s e g m e n t s w e r e c o m p a r e d b e t w e e n normal control(n=8), NIDDM without silent ischemia [I(-),n=16] and NIDDM with silent ischemia [I(+),n=14]. Results: On e a r l y images, m e a n u p t a k e score of e a c h s e g m e n t w e r e s i g n i f i c a n t l y lower in I(+) g r o u p than I(-) group. These findings w e r e m o r e c o n s p i c u o u s on the d e l a y e d study p r o b a b l y due to e f f e c t of s i l e n t i s c h e m i a in the 1-123 M I B G retention ability. Conclusion: N I D D M with s i l e n t myocardial ischemia have s i g n i f i c a n t l y larger abnormalities in 1-123 M I B G uptake than N I D D M w i t h o u t silent m y o c a r d i a l ischemia. Silent m y o c a r d i a l i s c h e m i a a g g r a v a t e s cardiac autonomic nerve dysfunction in diabetes.

Numerous studies aimed at stratifying patients (pts) at risk after an acute myocardial infarction (MI) have postulated the importance of alterations in neural control mechanisms, in particular the functional integrity of sympathetic efferent fibers directed to the heart. Myocardial scintigraphy by mean of metaiodobenzylguanidine ([123W]MIBG), a norepinephrine analog known to concentrate in the adrenergic fibers, has been used to detect areas of sympathetic efferent denervation in pts after MI. However, it is not known whether sympathetic nerve function is damaged by myocardial ischemia. As a consequence it is difficult to define the time course of this impairment when the pedusion has been restored, in the present study we examined the regional MIBG uptake in pts with unstable angina before and after angioplasty (PTCA). We evaluated 9 male pts (age 59_+12)with angiographic evidence of significant (_>75% of vessel section) LAD stenosis; two pts had also non significant RCA stenosis.without present or previous MI, diabetes, congestive heart failure, systemic hypertension or renal failure. All pts received nitrates and aspirin, 6 pts had also Ca-channel blocking agents. No 8-blockers were used at the time of scintigraphic studies and during followup period. Before PTCA, all the pts underwent stress-redistribution thallium imaging (TI) and, a week later, MIBG scans. Stress and redistribution TI images were analyzed with standard diagnostic protocols; qualitative and circumferential quantitative analysis were obtained from MIBG images 4 hoers after injection. Five pts had antero-septal, 3 apico-septal and one septal TI reversible defect, with normal MIBG uptake, They underwent PTCA with good results. Scintigraphic and coronarographic studies were repeated 3 months after PTCA. In 8 pts with open coronary arteries, Tt and MIBG images were normal, in 1 pt with restenosis on the site of PTCA, TI imaging showed reversible defect, while MIBG uptake was normal. This study suggests that: 1. there is no impairment of sympathetic nerve uptake in pts with unstable angina and myocardial ischemia; 2. as the result, MIBG is useless in pts evaluation to predict restenosis after PTCA.

PTu528

PTu530

H. lino, T. K a m a d a , H . N o h a r a , M . M a t s u m o t o , I. Harada, Y . K o b a y a s h i , Y. Nagai, C. I b u k i y a m a , H . M a t s u m u r a * , K.Watanabe*, Tokyo Medical College, Department of Cardiology, Plastic Surgery*, Tokyo, Japan.

'J.B.Bader, 2H.P.Stoll, 2A.Heisel, iC.Alcxander, 2C. 0zbek, IL.Trampert, IA. Sehader, 2H.Schieffer and lC.-M.Kirsch

EVALUATION ELECTRICAL SPECT

OF MYOCARDIAL INJURY BY TL-201

DAMAGE DUE TO AND 1-123 MIBG

Objective: Cardiac complications a s s o c i a t e d with electrical injury were evaluated. M e t h o d s : Electrocardiogram, CK-MB, UCG, TI-201 a n d 1-123 M e t a i o d o b e n z y l g u a n i d i n e (MIBG) SPECT, and coronary arteriography(CAG) were performed in 7 patients w i t h electrical injury. Five of the patients were followed up with TI-201 and MIBG SPECT. Results : Electrocardiogram revealed transient Af, second-degree A-V block, ST depression, and sinus b r a d y c a r d i a in 1 p a t i e n t each. C K - M B level i n c r e a s e d in 2 patients. M i l d hypokinesis involving the anterior wall was observed in only 2 patients. CAG was normal in all patients. TI201 a n d M I B G SPECT s h o w e d abnormalities in 7/7 a n d 5/6 patients, respectively. D e c r e a s e s in accumulation were seen primarily in areas extending from the anterior wall to the septum. The degree of accumulation was less in M I B G when c o m p a r e d w i t h TI-201. S c i n t i g r a p h y f o l l o w up showed aggravation in 3 patients and remaining 2 showed improvement. Conclusions: i) ECG abnormalities are transient, a n d C K - M B i n c r e a s e does not r e f l e c t myocardial disorders. 2) W a l l m o t i o n r e m a i n relatively unaffected. 3) C o r o n a r y vessels remain intact. 4) TI-201 a n d M I B G SPECT are sensitive methods for d e t e c t i n g m y o c a r d i a l d a m a g e b y electrical i n j u r y w h i c h u s u a l l y involve the a n t e r i o r wall and septum. Sympathetic nerve dysfunction might be m i l d e r t h a n m y o c a r d i a l cell damage. 5) M y o c a r d i a l d a m a g e p r o g r e s s are s e e n in some patients.

1164

Cattedra di Medicina Nucleare - Universit& di Torino (I)

Departments of 1Nuclear Medicine and qntemal Medicine TIT, University Hospital Homburg/Saar-Germany. MIBG/MIBl-Scintigraphy Of The Myocardium In Patients Who Survived Malignant Ventricular Tachyarrhythmia. Provides The Information Of A Mismatch Between The Sympathic Myocardial Innervation And The Perfusion A Hint On Ahe Occurance And Outcome Of Severe Arrhythmia? Mismatch between cardiacperfusionand sympathic innervation may play a key role in the development of sudden cardiac death. Due to this hypothesis, we examined 17 patients (Its.) scheduled for implantation of an Intra Cardiac Defibrillator (ICD) due to malignant ventricular arrhythmia. The myocardial uptake of I23J-meta-todo-benzyl-guanetidin (MIBG) represents functional adrenergic ianervation, S~Tc-sestamibi (MIBI) uptake the cardiac perfnsion. Comparing both studies, a mismatch in the myocardial distribution hints an imbalance of sympathic innervation and thus potentially causing severe ventricular tachyarrhythmia. Method: 17 Pts. who survived a documented ventricular tachycardia underwent a combined MIBG/MIBI-Rest study. The myocardial distribution of MIBG was compared to that of the flowtracer M1BI. 360% SPECT-imaging of the heart was performed approximately 5h after the application of 250 Mbq MIBG followed by an i.v.-Injectiun of 450 MBq MIBI. Thirty rain. later - using the identical acquisition protocol - the resting perfnsion study was acquired. For both acquisitions a doubleheaded gammacamera with high resolution collimators (MULTISPECT 2, Siemens) was used. Results: The following graduation of mismatch patterns between perfusion (P) and sympathic innervatian (1) could be evaluated: 1° slight matching defects comparing MIBI (P) to MIBG accumulation (I): P > I 2 ° severe defects: P >> I 3 ° complete mismatch (no myocardial accumulation of MIBG) 2 of 17 Pts. with documented ventricular tachyarryhthmias showed slight (l°), 4 severe (2°) and II complete (3 °) mismatch between myocardial perfnsion and adrenergic innervation. Conclusion: Mismatch patterns between sympathic myocardial innervation and rest perfusion may help to identify Its. with increased risk for sudden cardiac death.

• PTu533

PTu531 .Ion,IL:WOrL[Ia. Jong-Doo Lee.. Nnmsik Chung, Yangsno Jang. Byung Sea Kim.*. jt~n,.' [G~an, Drmg-llun

Cardiovascular

Cha, Young-joan

L e e . Won-Ileum

Shim, Scung-Yun

Chn,

Sung-Soon Kim. Cardiovascular Center Yonsci University College of Medkirle, "Division

M.G. KoutelouI, G. Economopoulos2, S. Papaioanou3, A. Karoussoul, A. Kouzoumi1, A. Dritsas3, DN Cokkinos3. INudear Medicine Deparnnent, 2Cardiac Surgery Department, 31st Cardiology Dep~ment, Onassis Cardiac Surgery Center,Athens, Greece.

o[ Nuclear Medicine, **Department of Applied Statistics Yonsei Univcr'dty IOI)INF.- 123-METAIODO[WNZYLGUANII)[NI~

(MIIIG)

ECINTIGRAP[{Y: nEI.ATION

MIBG UIrI'AI
OF

MYO('ARI}IAL

MYOCARDIAh

\:ENTRICULAR SYSTOLIC AND DIAgTOLIC FUNC'I'IONAI. PAnAMETERS

CARDIAC SYMPATHETIC INNERVATION IS REDUCED FOLLOWING CARDIAC SURGERY WITH MYOCARDIAL COOLING.

IN

DILATED CAIIDIOMYOPATIIY

The

prognosis of patients with

dilated cardiolnyopnthy remains pbor. Doppler

evhncardingraphy and cardklc iodine-123-rnetaiodobenzy}guanidine (MnlG) myocardial stratigraphy are useful non-invnsive diagnostic moclalities to assess, the progn,~sis in

these

patients,

lllJwever, the relationship between

MIBG uptake and Doppfer

ecbocardiograi)hic variables was not weII investigated We analyzed the cardiac MIBG imaging in d0 patients with dilated cardiomyopathy and assessed b~tween ms,)cardkd 3.I[l/G upulke and left vcntricular(LV)

the corTeIati(m

systolic and diastatic

functional parameters assessed by transthoracic echocardiograpl W. MII~(; UlRake(DllM) was assessed as the ht'art(lD/mcdklstintmdM) rntlo measured on alrterl.r view im:u1v ohtahlt~t .1 hours after h/jectlon,

gaily and dcklyeg MnIG uptake of heart w~:re

significantly lower ill pndclK group ctnlqmrcd with normal contlol suhjects. There wcre no significant diffelences in hlng(L) and M utxake of NIII~G I)et~een the two grr~ups. I'nrly and dehlyc,d MILK; Ul)take ratios of the It/L and Ig*l were sivniricamtly Im~cr in patient group compared with those of normal crmtrol subjects. DIIM was significantly lower in patients widl NYHA functional class 3. ,t than those with NYHA functional class 1, 2 in patient group. There was. however, no significant difference of DIIM in

Iodine-123 metaiodobanzylguanidine(MIEG) imaging has been used to demonstrate regional sympathetic innervationof myocardial tissue in various clinical and experimental settings. Methods: We used MIBG to assess innervation in I0 patients (mean 63+8 years) who underwent cardiac surgery employing moderatehypothermia (32°C) cardiopulmonarybypass with cold blood cardioplegia and myocardial temperatureranging from [0 %-18 °(2 using cold saline irrigation (4 °C). Pts were studied 1 day prior and I week following surgery. MIBG uptake was quantified by heart/lung ratio on planar images 4-5 hours post injection. Regional uptake was estimated in 20 segments of the tomographic images by using a 4 point scoring system(0~ormal and 4--no uptake). ResuIts: Heart/lung ratio was decreased significantly following surgery (1.18_+0.32 to 0.764_-0, p=0.004). The total MIBG uptake score was increased (3.1+_3.2 vs 6.0+3.7 respectively for pro-and post-surgery, p=0.001). No correlation was found between the changes in the heart/lung ratio and time during which the hem was exposed to hypothermic by-pass. In conclusion, regional neuronal denervation expressed by MIBG uptake is reduced early after cardiac surgey. The precise mechanism of this finding needs to by elucidated, however it is possible that cooling of the myocardiumplays an importantrole.

palicnt grouD divklcd by the degree of mitrM regurgitation and LV diastolic fi!lin~

re | mllml

paucrn. There were no significant correlations between DIIM and other prognostic factors( LV end-diastolic dirnenskm. LV ej~_'ction fraction, peak velocity of earl:,' diastolic f(tlinglE velocity), deceleratinn time of E wave. cardiac output, pulmonary capillary wedge pressure, LV end diastolic pressure conclu,don, 1-123-MIBG scan

and

24hr urine norepineph6n,_q

is a useful nnninvasive

.0..i

In

imaging mc
as~ussm{'nt eft cHI'diac s3ml]:tthetic neuronal intc~irity in

padents

with

,.I..I

co

dilated

c;ircliomyopalh,; "['here were i1o si~ni[icat]t cQrrchlLions }>e[&VC'CnC[lFdlac MIBG u[nake

(/)

and other prop,nostic factors. The cardiac Mll]G uptake probably enll be utilized as nil indclmndcnt prognostic factor, hence it wc~uld be suggested that a large proslx~cdve

o 1,. e,i

clinical study i5 needed to consolidate these findings.

PTu532

PTu534

d_o~n~la, Jong-Doo Lee. Yangsoo dang, June Kwan, Namsik Chung. Young-Joan Lee, ~on-Heum Shim, Seung-Yun C h o , Sung-Soon K i m . Yonsei Cardiovascular Center. Cardiology Division.

A. Dtitsas1, M. Koutelou2, E. Efstathopoulos2, DV. Cokkinosi. list Department of Cardiology,~ratory, Onassis CardiacSurgery Center, Athens, Greece

ABgORMAL REGIONALSIXIPATHETICNEURO.K4L [N~EGRITY IN PATIENTS WITH CORONARY SPAS"I:ASSESSt[E'~T lfITH IODINE- 123-METAIODOBENZYLGUANIDI NE HYOC~RDIAL SCI,",Ti GRAPHY

i t has been suggested t h a t the sympathetic nervous system may piny an izportant role in the development of coronary spasm. Hocever. there has been no cardiac imaging modality t h a t has demonstrated abnormal sympathetic inncrvation in p a t i e n t s with coronary spasm. The purpose of t h i s study ~as to assess the presence and location of abnormal sympathetle innervation by iodine-123-metaiodobenzylguanidine(l-123-HIBO) single-photon emission computed tomography(SPECT) and evaluate the c l i n i c a l e f f i c a c y of 1-123-~IIBO SPECT in 16 p a t i e n t s with coronary spasm. Coronary spasm was documented by EC5 and/or by coronary angiography during coronary spasm induced by intravenous i n j e c t i o n of ergonovine mMeate. We a l s o examined 6 p a t i e n t s of atypical chest pain with negative intravenous ergonovine maleate provocation t e s t and 4 normal control subjects. The p a t i e n t s included in this study had neither organic coronary stencsis nor myocardial infarction. Regional defect of H[BG uptake was observed in the d i s t r i b u t i o n of perfusion in I2 of the 16 vasospasm-induced vesseIs. Normal uptake of NIBG was observed in the perfusion t e r r i t o r y in 62 of the 62 coronary a r t e r i e s not having spasm, The s e n s i t i v i t y and s p e c i f i c i t y of iodine-lE341[BO SPECT for" detection of coronary vasospasm i~ere 75~ and 100~, r e s p e c t i v e l y . These results sho~ed that iodine-123-HlBO SPECT is a feasible method with high s p e c i f i c i t y for predicting the coronary a r t e r i e s with spasm noninvasively. I t ~ould be suggested that, ~hen considering the false negative studies, sympathetic nervous dysinnervation may be related with ischemic i n j u r y as a result of coronary spasm.

QT DISPERSION IS ASSOCIATED WITH REGIONAL VARIATION BUT EJECTION FRACTION WITH TOTAL SYMPATHETIC NEURONAL INRERVATION 1N CORONARY ARTERY DISEASE QT dispersion reflects dispersion of veatricular refraetonness and represents a marker of arrhythmogenic potential in coronary arterydisease (CAD). In this study we examined whether QT dispersion is associated with regional variation of iodine-123 metaiodobenzylguanidine (MIBG) uptake which is an index of sympathetic neuronal innervation. Methods: Nineteen patients (pts) (mean age 61_-t-9 years) with angiogmphically documented CAD underwent an MIBG scan. MIBG aptake for each segment of the left ventricle (LV) was scored from 0 (normal) to 4(no uptake) and a total uptake score was derived as the sum of all segments. An objective score was also applied to each segment using the absolute coants/pixel deriving a ratio of maximal/minimal uptake per patient. QT dispersion was defined as the difference of maximum-minimum rate corrected QT across the 12 leads of an ECG. Results: Sixteen (84%) pts had a history of myocardial infarction, 8(42%) pts had 3 diseased vessels and the overall mean LV ejection fraction (EF) was 40+10%. LV EF correlated negatively with the total MIBG uptake score (r=-0.65, p<0.0t) but not with the maximal/minimal uptake ratio (r=-0.07, p~s). A borderline significant correlation was detected between total MIBG uptake and LV end-diastolic diameter derived by echo (I=0.48, p<0.05). Mean QT dispersion was 55+_27msec ranged from 20 - 120msec. QT dispersion correlated well with the maximal/minimal MIBG uptake ratio (r=0.69, p<0.001) but not with the total uptake score (r=0.14, p~s). In conclusion, overall sympathetic neuronal innervation expressed by MIBG total uptake correlates with EF and LV enlargement while differences in regional innervation expressed by maximal/minimal uptake ratio correlate with QT dispersion which is a marker of arrhythmogenicity.

1165

.I..I

O IX

•

Cardiovascular

PTu535

PTu537

N. Honda, K. Machida, M. Hosono, T. Mamiya, T. Takahashi, T.

H. S i n z i n g e r , M a r g a r i d a R o d r i g u e s , Susanne G r a n e g g e r , H. K r i t z , D e p a r t m e n t o f N u c l e a r Medicine, U n i v e r s i t y of V i e n n a , A u s t r i a

Kamano, A. Kashimada, H. Osada, Y. Shimizu, T. Iwase, H. Toyoda, and S. Kinoshita. SaitamaMedical Center, Department of Radiology, and Department of Internal Medicine IV B~4IPPAND

FIBRINOGEN

test whether

the cardiac

involvement

can be detected by

radionuclide imaging or not. Consecutive 16 patients with MD entered the study. There were 9 men and 7 women with age range of 31-58 years. None was in heart failure, and seven patients had first-degree AV block. T1-201, 1-123 BMIPP, and 1-123 MIBG SPET was performed 10-15 minutes (early] and 3

hours (delayed) after the injection of the radiotracers (iii MBq).

SPECT images were

read by consensus of 3 nuclear

medicine physicians blinded to clinical information. eye washout ratio was

calculated.

Bull~

All patients

showed

decreased accumulation or defects on all kinds of radionuclide imaging, most often in infero-posterior wall. Decreased accumulation and defect were found in 88/101(early/delayed imaging), and 10/5 segments on TI-201 SPET, respectively; 94/82, and 4/16 on BMIPP SPET; and 71/69, and 2/3 on MIBG SPET. However, the number of abnormal segments did net differ significantly (p<0.05) among the radiopharmaceuticals. Redistribution of TI-201 was observed in 5 segments, all in inferior wall. Mean Bull's eye washout ratio was 41 (SD 14.1)% for TI-201, 16.5 (i0.4) for BMIPP, and 24.4 (15.4) for MIBG. There was

no statistically significant difference of

these

ratios between mild and severe disease. In conclusion, cardiac radionuclide imaging involvement of MD.

may be

useful

to detect

cardiac

PTu536 S. Severi. R. Bettini °, R. Lovastc*, L. Visona '°, E. Lorenzi, Branz*, M. Camerani Departments: Nuclear Medicine, Cardiology °, Iafetctivoas disease* S. Chiara Hospital - Trento - Italy

LESIONS

PTu538 F.

123I MIBG C A R D I A C SCAN: AN USEFUL A P P R O A C H IN AIDS C A R D I O M Y O P A T H Y ASSESSMENT AND THERAPY PLANNING.

A great percentage of AIDS patients will develop during the illness an important myocardial disease that is more frequent with the improved survival. It is otherwise diagnostically very difficult to predict wich patient will present myocardial involvement with the in use modality. In our study we tested the utility of the 123I-MIBG SPET to evaluate the presence of sympathetic nervous system impairment in AIDS patients. The MIBG, generally linked with 123I, is a molecule analogous of norepinephrine that uses the same uptake and storage systems. Matherials and Methods: We studied 12 AIDS patients (9 males and 3 females average age 34 years) with 8-10 years of infection and CD4 < 100. The cardiologycal protocol was comprehensive of a clinical examination standard ecg and Echocardiogram with a follow up of 6 months. The Nuclear Medicine protocol was comprehensive of a 123I=MIBG and 99mTc Myoview SPET rest study (370 MBq and 740 MBq respectively). Results: The cardiologycal exam divided our casistic in 3 groups A) no clinical, ecg and echo signs, B) no clinical signs, mild ecg alteration (tachicardia and T wave voltage reduction), moderate echo alterations (segmental hypokinesia), C) evident clinical signs, pathologic ecg and echo. 6 months later we had no changes in A group, worsening of all the parameters in B group and no survival in the C group. The Nuclear Medicine results showed presence of one case of mild MIBI positivity in one patient with severe miocardial compromission and one false positive (an uremic patients) in A group, 3 diffuse hypoconcentration in B group and 3 marked hypoactivity in C group. We had 100% sensitivity, 85% specificity. In particular we were able to preditc and adeguately treat the B group patients whouse illness progression and therapy was,with our exam, significatively changed. Conclusions: The 123I-MIBG SPET has an high sensitivity and specificity in myocardial involvement detection in AIDS patients and gives the opportunity to~ diagnose the disease in an early stage when cardiac standard parameters and echo are not jet significant. Certainly the modality needs more validation with further studies in larger series but, at present, it seems as one of the more promising tool to detect an early myocardial compromission in AIDS patients.

1166

OF ATHEROSCLEROTIC

Elevated fibrinogen (F) is a r i s k f a c t o r f o r t h e development of a t h e r o s c l e r o s i s . F is i n c o r p o r a t e d i n t o t h e a r t e r i a l w a l l in a c t i v e s t a g e s o f t h e disease a n d is a c h a r a c t e r i s t i c f e a t u r e of t h e atherosclerotic p l a q u e as m o n i t o r e d b y m o r p h o l o gical, biochemical and immunological techniques. Only anecdotal information on the use and value of r a d i o l a b e l e d F is a v a i l a b l e so far. We e s t i mated the accumulation of 1 2 5 I - f i b r i n o g e n into the rabbit arterial (aorta, iliac artery) wall in 1 % - c h o l e s t e r o l fed New Zealand white rabbits after experimental lesioning using a Fogarthycatheter. 125I-fibrinogen uptake correlates with low-density lipoprotein-entry, the actual amounts b e i n g a b o u t 3 - 5 t i m e s h i g h e r in t h e r e s p e c t i v e segments. Lesioned (deendothelialized) areas exhibited a significantly (p~ 0.01) h i g h e r F uptake. There was an inverse correlation between vascular prostaglandin 1 2 - as w e l l as n i t r i c oxide-production a n d t h e a m o u n t of F. T h e s e findings indicate that F might be clinically u s e f u l to a s s e s s a r t e r i a l t h r o m b o t i c e v e n t s . Based upon these results we started a prospective t r i a l in 100 p a t i e n t s w i t h c l i n i c a l s i g n s of atherosclerosis comp@~ing sonography with radioimaging after I mCi ]zJI-fibrinogen. I m a g i n g is performed I and 4 hours after tracer application. R e a d i n g t h e r e s u l t s is b l i n d e d . 123I-fibrinegen is t a k e n u p b y t h e l o w e r l e g a r t e r i s > c a r o t i d a r t e r i e s . T h e f i n a l r e s u l t s of t h i s t r i a l ( c o m p a r e d to s o n o g r a p h y , p l a s m a f i b r i n o g e n and blood lipids) will be presented.

Cardiac involvement is a leading cause of death in patients with myotonic dystrophy (MD). The purpose of the study is to

myocardial

IMAGING

MIBG SPET FINDINGS IN MYOTONIC DYSTROPHY

E.Ibi~, N.0.KflGflk, S.Sava~*, S.Tuncer*, C.Ya~mur, K.M.KIr, G.Aras, G.Erbay, A.Akin. Ankara University, M e d i c a l School, D e p a r t m e n t of N u c l e a r M e d i c i n e and P h y s i c a l T h e r a p y * EVALUATION OF WITH RHEUMATOID

CARDIAC ARTHRITIS

FUNCTIONS

in

PATIENTS

The aim of this s t u d y was to d e t e r m i n e how the s y s t o l i c and d i a s t o l i c f u n c t i o n of left v e n t r i c u l e were e f f e c t e d in p a t i e n t s (pts) with rheumatoid a r t h r i t i s (RA). Rest radionuclide ventriculography (RNV)and echocardiography (ECHO) were p e r f o r m e d in 25 pts w i t h RA but w i t h o u t known c a r d i a c a b n o r m a l i t y , and in ii n o r m a l v o l u n t e e r s . Systolic and d i a s t o l i c f u n c t i o n s were a n a l y z e d u s i n g RNV and ECHO in pts w i t h RA and c o n t r o l s . M e a s u r e d m e a n v a l u e for e j e c t i o n f r a c t i o n s (EF) and d i a s t o l i c p a r a m e t e r s as Peak E j e c t i o n Rates (PER), Peak Filling Rates (PFR), Time to Peak Filling Rates (TPFR), Time to Peak E j e c t i o n Rates (TPER), u s i n g RNV were s h o w e d as in f o l l o w i n g table;

~:25) Control(ll)

E~ 60.3±5.9 57.1±3.8

PER PFR TPFR ITPER I 3.3_+0.6 12.8_+0.5 1162"8±533 1116"8±30"2 I 3.4i43.7 3.2-+0.6 122.8+~79 114.1±25.6

All f i n d i n g s in ECHO and RNV, e x c e p t PER and TPF, were in s i m i l a r range in b o t h pts w i t h RA and controls. But, prolonged TPF and decreased PFR (p<0.05) were found in pts w i t h RA. As a result, we c o n c l u d e that d i a s t o l i c a b n o r m a l i t y m a y be an e a r l y f i n d i n g of c a r d i a c i n v o l v e m e n t in pts w i t h RA, and d i a s t o l i c a b n o r m a l i t i e s m a y be d e t e c t e d in e a r l y stage of KA using RNV.

•

Cardiovascular

PTu539

PTu541

I. Cas~ns, V. Bodi, J. Sanchis, J. Ciudad, L. Insa. Nuclear Medicine and Cardiology Departments. Hospital Clinico Universitario. Valencia. SPAIN.

V.Sergienko, L.Samoilenko, 0.Fomiche~a, M.V$1@inskaya, E.Nassonov, ~u.Karpoy, . baraloiogy ~esearcn center, Moscow, ~ussla

REPRODUCIBILITY AND ACOHIh~CY OF LEFT VI~qTRICULAR EJECI~ON FRACTION AND VI~NrfRICLKAR VOLUMES DEr~I4Ff[NED BY ~CHOCARDIOGRAITIY AND RADICKqUCLIDE V~NTRICUT/X~RAPHY. To study left ventricular function in a group of 48 patients with a first AMI, we have assessed reproducibility and accuracy of left ventricular ejection fraction(EF) and ventricular volumes detern/ned by 2D-echocardiography(EC£O), equilibriura radionuclide ventriculography(RV) and cardiac catheterization(CASH) . We have obtained end-diastolic volume(~DV), end-systolic volume(ESV) and EF by ECHO at 6+3 days after AMI, by area-length method; by CA2H at 6+4 d~ys, by arealength method, and by RV at 11+7 days, b~ a count-based method with semiautc~atic selection of ROI, and for volumes, by Massardo method with manual selection of ROI. We obtained the same determinations 6 moths after AMI, by ECHO in 21 patients, by CATH in 22 patients and by 557 in 14 patients, with a total of 69 ECHO, 70 CATH and 47 RV. Correlations of EDV determined by ECHO and RV with CATH were r:.34(p:.02) and r:.56(p:.0001) respectively, for ESV were r:.53(p:.0001) and r:.71(p:.0001), and for EF, r:.55 (p: .00001} and r: .79(p:.00001). In the assessment of variability, the mean% error between two measurements of EDV by ECHO was 13+11%, with a correlation r: .96(p: .0001) , for ESV 20+ 18%, r--.90(p: .0001) and for EF 28+--32%, r:.80(p:.001).Dete~minations of EDV by RV showed a mean difference of 4.5+3.0% r:.96(p:.0001), for ESV 4.6+2.9%, r:.98(p:.0001) and f~r EF 1.9+I.0%, r:.98(p:.0001}. I_~ the case of CATH, mean differen ces were for EDV 11+13%, r:.94(p:.0001), for FSV 12+12%, r: .91(p:.0001) and for EF 2.5+2.3%, r:.99(p:.0001). In quantitation of EF and v~ntricular volumes, RV is more reproducible and shows better correlations with CATH, thus it must be the method of choice in serial assessment of patients.

EvaSuation 9~ m y o c a r d i a l per[usipn in antlpnospno±ipla synarome pa~len~s The association of arterial and/or venous thrombosis, recurrent fetal losses, thrombocytQpenia w~th.,high level of antipbospholipi ~ an~leoale%.~rA).~s .Known. as, a n ~ l p n o s p D o ± l p s a s y n a r o m e . ~Ar~)..., AYb IS q e i 1 g e a as seqgnaa
~I,~+ID~

aon0rmallsles.

A. S. Dogan,

Conclusion: Hyperventilation is a stimulus for release of noradrenaline and endothelin although it did not cause myocardial ischemia in patients with stable angina. The temperature of the inspired air has no significant impact on either myocardial flow pattern or hormone release.

±g~-ArA

~

PTu542

ST deviations in the exercise ECG were included. Patients performed two separate hyperventilation tests on different days: one with inhalation of cold (-22 C) air and one with inhalation of thermoneutral (+22 C) air. Myocardial flow pattern was determined by SPECT and severity scores were calculated. Blood samples taken at rest, after cold hyperventilation and after hyperventilation of thermoneutral air were analyzed for Adrenaline, Noradrenaline, Renin, Angiotensin-II, ANP and Endothelin-I. Results: Rest Cold stress Neutral stress ~Iormones: Adrenaline (retool/l) 0.33 0.38 0.33 Noradrenaline (mmol/l) 1.48 1.93 * 2.05* Renin (miU/l) 15 15 16 Angiotensin-II (pmol/l) I0 9 10 ANP (pg/l) 30 31 29 Endothelin-I (pmoVl) 1.49 1.68 * 1.74* $ PECT-severity-scnre: 156 239 156 N= 11 Medianvalues. * P < 0.05 (rest to stress)

ana

Our f~ndings.suggest that reduced MP reserve and MP abnormalities occur ~n 5ne most PS p}s. Probably, the microvascula F thrombosis ue 5o .Aign level APA consriDute to such

C Leth Petersen, U Andersen, E Frandsen, B Hesse, H Dige-Petersen. Depts. Clinical Physiology & Nuclear Medicine, Glostrup & Frederiksberg Hospital & Rigshospitalet, University of Copenhagen, Denmark.

Cold exposure is often described to provoke attacks of angina. AIM To describe the endocrine response together with myocardial flow pattern during a hyperventflation test with and without cold air inhalation in patients with stable angina.THE STUDY: Eleven patients with a history of myocardial infarction and ensuing stable angina and dynamic ischemic

~>i~,W)

Conclusion:

PTu540

Cold air inhalation during hyperventilation test in patients with stable angina: Impact on myocardial flow pattern and vasoactive hormones.

~WL

47 9+9,2 . MPL- (>27,5 MPL)~ All pts were in@eg~iga~ed , b~,. $CG-mgn~tor~ng, , .coronaro 7 anglograpn~ ~duqK~ns). ±m Nts. nag s~±gnD ~scn~ma,,~ pts na9 angina p@ctgr%s, ,4 P ~ g , g ~ ~revious nlstory o~ .myocaF~a~ ,ln/arct%qn <~$A~v coronary anglograpny on±y ~ p~s[z o~.tnem w~tn M%) had sSeno@?s of coronary grteries (CA)< 50%~ ~ pts naa in~act. CA, (~ of those had MI). SPEc~ 2ZIcTL stress te@t was pe~tomea in ~3 pts, 2ZI-TL
O. Ergene,

D. Kaya, E. Sayit.

Depts of N u c l e a r M e d i c i n e and Cardiology, Dokuz Eylul Univ.,Sch. of M e d i c i n e Izmir, Turkey.

TWO CASES OF CORONARY ARTERY FISTULA QUANTIFIED BY INTRACORONARY INJECTION OF Tc-99m MAA PARTICLES

This study is u n d e r t a k e n to e s t i m a t e the e x t e n t and location of a s h u n t t h r o u g h a coronary artery f i s t u l a s h o w n by c o r o n a r y a n g i o g r a p h y in p a t i e n t s with chest pain and normal appearing coronary arteries= One m C i T c - 9 9 m M A A p a r t i c l e s w e r e injected into t h e c o r o n a r y v e s s e l s o n w h i c h a f i s t u l a was s u s p e c t e d d u r i n g a n g i o g r a p h y . E x t r a m y o c a r d i a l a c t i v i t y was v i s u a l l y and q u a n t i t a t i v e l y e v a l u a t e d on p l a n a r images. Case i: 4 5 - y e a r - o l d f e m a l e w i t h a n g i n a had c o r o n a r y artery f i s t u l a on a n g i o g r a p h y . A f t e r i n j e c t i o n of l a b e l e d particles into the left main c o r o n a r y artery, m i n i m a l a c t i v i t y was n o t e d in the b r a i n a n d k i d n e y s , e x c l u d i n g a r i g h t - t o - l e f t shunt. T w o d i s c r e t e areas w e r e n o t e d in t h e left lung w i t h 15% uptake, c o n f i r m i n g a c o r o n a r y a r t e r y to p u l m o n a r y shunt. Case 2: 5 8 - y e a r - o l d m a l e w i t h ventricular arrhythmia on e x e r t i o n had a left c o r o n a r y f i s t u l i z a t i o n into the left v e n t r i c l e and a questionable right coronary artery fistula. L a b e l e d p a r t i c l e s w e r e i n j e c t e d into b o t h c o r o n a r y arteries. Images s h o w e d s i g n i f i c a n t e x t r a - c a r d i a c a n d p u l m o n a r y a c t i v i t y (31%) c o n f i r m i n g the a n g l o g r a p h i c a l l y s h o w n r i g h t - t o - l e f t shunt. T h e r e was also s i g n i f i c a n t a c t i v i t y in the l o w e r lung fields (27%), p r o b a b l y d u e to a c o r o n a r y to p u l m o n a r y fistula. I n t r a - c o r o n a r y i n j e c t i o n of T c - 9 9 m M A A particles is a s a f e m e t h o d for d e t e r m i n i n g the l o c a t i o n a n d m a g n i t u d e of a s h u n t f r o m c o r o n a r y arteries t h r o u g h a fistula d e t e c t e d d u r i n g c o r o n a r y a n g i o g r a p h y in a p a t i e n t with a n g i n a l s y m p t o m s and no s i g n i f i c a n t o b s t r u c t i v e coronary a r t e r y disease.

1167

•

Cardiovascular PTu545

PTu543 V.D.Tenedieva,V.P.Kulikovski,V.H.Amcheslavski Burdenko Neurosurgery Institute RAMS, Department of R a d i o l o g y , M o s c o w , R u s s i a . THE ~-ENDORPHIN LEVELS AND CARDIORESPIRATORY DISTURBANCES IN O P E R A T E D P A T I E N T S W I T H B R A I N T U M O R S S t u d i e s of t h e p o s s i b l e r o l e of ~ - e n d o r p h i n ( ~ - E ) in g e n e s i s of s e v e r e cardiorespiratory disturbances(CRD) in e a r l y o p e r a t i o n p e r i o d of p a t i e n t s with brain tumors were undertaken. T h e ~-E l e v e l s were evaluated b y R I A in a r t e r i a l ( A ) , peripheral(Vp) and jugular (Vj) v e i n b l o o d a n d c e r e b r o s p i n a l f l u i d (CSF) (i02 p e r s o n s ) .The o b t a i n e d d a t a were analysed taking into account the patient conditions which were estimated in b a l l s ( l - 5 ) in accordance with CRD(blood pressure and cardiac r a t e c h a n g e s , b l e e d i n g a n d its d e g r e e ) . S e p a r a t e ly t h e ~-E l e v e l a n a l y s i s in p a t i e n t s with brain edema(BE) was performed. Results have shown:l)the direct correlation in i n c r e a s e of ~-E l e v e l s in A,Vj,CSF in patients and clinical condition s e v e r i t y , e.g. t h e h i g h e s t ~-E l e v e l s w e r e m a r k e d in cardiac arrest and respiratory depression; 2)in contrast the ~-E levels in Vp decreased along with the patient worsening; 3)important f i n d i n g w a s t h e r e v e a l i n g of d e p e n d e n c e of h i g h e r ~-E l e v e l s and CRD with BE in c o m p a r i s o n with patients without BE b u t with CRD. In p a t i e n t s with BE but without CRD the ~-E levels were significantly higher only in C S F in c o m p a r i s o n with the patients without BE a n d CRD. T h u s , the received results prove the pathogenic role of hormonal and neurotransmittant ~-E i n f l u e n c e in CRD development especially in p a t i e n t s w i t h BE, a n d m a y s e r v e as a b a s i s for the u s e of d i f f e r e n t agonists and direct and functional antagonists of d i v e r s e ~-E r e c e p t o r t y p e s .

D.Cssar-a,G.~1 ~i ni,A.Avo~ro, C .CrL~paldi,C. S c o ~ o ,

F .Bella~ere and

C.Balzani. Nucleer Medicine Servioe,C~m~L%Oin~yService and G e r ~ Medicine De~t.I~onal Hospital and University of Padua,Italy. VENTRICULAR FUNCTION IN PATIENTS WITH INSULIN DEPENDENT DIABETES MELLITUS(IDDM):ROLE OF ADRENERGIC MYOCARDIAL INNERVATION.

l ' ~ of ~m/eloping c~l/~l~_ve he~Tt failure is associated with IDl:M.lhe aim of this study ~ms to co.lmre ~ c .yoce~niial i r r ~ ration assessed by 123-I-mlBGscintigr~dayand ~ f l e x sensitivity to LV £t/ac~on detscted by post extrasistolic potentiatdon (PESP) in ]II]M. 14 young II]DMpatients with no diabetic oomplicationand 10 contzols studied,all with n ~ LVI~ at rest.IDEM paldents were divided into 2 on the bssis of banc~ip isomelric exercise LVEF re~pma~: ~r~up A ~bnor~al and ~ B n~rmal ~ . L V E F ~ si~nificant/~ aft~m~ PESP in all patients (p
activity.

PTu544

PTu546

D. C a s a r a , G. S a l a d i n i , C. Dafermo, N. P i g n a t a r o , G. C a r d i n , NC. Capotale, B. Permutti. Nuclear Medicine Service,Cardiology Dept. and Internal Medicine Dept.Regional Hospital and University of Padova, Italy

A.M. Wiersema, W.J.G. Oyen, J.A. van der Vliet, K.E Pak~, B.A. Khaw', F.H.M. Corstens.

ROLE OF 99mTc-SESTAMIBI

SCINTIGRAPHY(MIBI)

LATED CARDIOMYOPATHIES(ADC)

IN ADVANCED DI+

AND IMPACT ON HEART TRANSPLAN-

TATION (HT). The aim of this study was to evaluate the MIBI results in patients (pts) with ~ and i~s i m ~ in ~ . MIBI results m m pared to oarona~ en~o~raphy,left,v e n ~ c u 1 ~ and e c h o c ~ l i s g ~ .

56 o c t a v e pts with ~ m sbJdied and f o l l ~ UP for 1-31 months. Pts were ol~-qtfisd ~ 3 ~:20 pts postinf~axvt(group A), 23 pts idiopa~c ( ~ u p B), 13 pts s e ~ with ncrml c¢~r~vien (~mup C). MIBI rest images ~ divided into 16 se~nents/pt (886 totsl segments) and segmental uptake was sooted from 0 (nomal) to 4 (no u ~ ) . In group A (320 sea,rots) uptah~ was:sooce 4 in 121 se~nents,scc~e3 in 40,sccre 2 in 35,soore 1 in 17,soore 0 in 107; in ~ B (368 s e ~ ) u p t ~ ~ : socl:,e 4 i n 29 segraent:s,~cr~e 3 i n 39, scot-e 2 i n 76, Bnoce 1 in41, soc~e0 in 183; in ~xJUp C (20BseB~ents) upts~e ~Bs: aoc~-e4 in 10 ~Bments, score 3 in 15,Bocre2 in 42, soore 1 in 17, Bcoce0 in 124. In group A bIIBlresults ~ r e in a~reemm~t,with o ~ n a r y stmmsis si~em aed a~ll mot~on r e ~ ahn~ties. ~ gr~p B and group C hhere ~ r e no si~nifica,t differences in uptake: in both gr~upa defects ~ere regional, less ¢ ~ i v e and less m ~ in o o n ~ with ~ A (p(O.Ol). Q~x~s ~e~e then divided on the basis ~ indication: in ~s~ap A, pts canclldatedto bI~ had a worse u p t ~ (p
1168

University Hospital Nijmegen, The Netherlands; MTTI, Malvern, PA, USA#; Northeastern University, Boston, MA, USA'. DETECTION OF ISCHEMIA AND REPERFUSION DAMAGE IN MICE WITH Tc-99m-GLUCARATE AND Tc-99m-PYROPHOSPHATE. Revascularization of ischemic limbs may result in tissue damage due to formation of oxygen-derived free radicals after reperfusion. For scintigraphic assessment of muscle damage, Tc-99m-pyrophosphate (PYP) has been suggested. However, this agent is less attractive since PYP reflects necrosis rather than actual ischemia. In contrast, the uptake of a new agent [Tc-99mglucarate (GLUC)] is more related to the degree of ischemia. In this study, both agents are compared in a mouse model of hindlimb ischemia/reperfusion. In anaesthetized, C57/BL6 inbred mice, ischemia was induced for 2,3 or 4 hr. After a reperfusion period of 15 min., 4 MBq Tc-99m-PYP or Tc-99mGLUC was i.v. injected (6 groups, 5 mice per group). One hr after injection, the mice were sacrificed and the reperfused and contralateral calf muscle and a blood sample were obtained. Reperfused-to-contralateral-musde and ieperfused-muscle-to-blood ratios were calculated. As shown in the table, Tc-GLUC showed significantly higher uptake (mean ± SEM) in the ischemic limb than Tc-99m-PYP at all time points (p < 0.05).

GLUC PYP

Reperfused-to-contralateral-muscleratio Repertbsed-muscle-to-bioodratio 2 hr. 3 hr. 4 hr. 2 hr. 3 hr. 4 hr. 10.7-+0.9 8.9_+0.9 8.6+1.1 2.0_+0.2 2.0_+0.2 I 8-+0.2 4.5+0.7 4.9_+0.4 4.54-0.4 1.2_+0.3 1.2_+0.1 1.2_+0.1

Not only the ratios for GLUC were higher, also absolute uptake was higher after the 3 and 4 hr. ischemia period (for GLUC 5.6_+0.8% and 4.4_+0.7 ID/g, and for PYP 2.7±0.3 and 3.4_+0.3 %ID/g, respectively, p < 0.05) In conclusion, GLUC shows higher uptake in reperfused muscle than PYP, indicating that GLUC better represents non-necrotic tissue damage. With GLUC, a potential agent has become available for noninvasive monitoring of interventions in the ischemia/reperfusion pathology.

• Endocrinology PMo547

Endocrinology

PMo549

Li.Bern~ A.Flotats, M.Estorch, A.Caix~s, M.Puig, J.Piera, A.Catafau, I.Carri6. Departments of Nuclear Medicine, Endocrinology and Surgery. Hospital de Sant Pau, Barcelona. PARATHYROID 99mTc-MIBI SCINTIGRAPHY: THE PRIMARY IMAGING TECHNIQUE TO ASSESS HYPERFUNCTIONAL PARATHYROID LESIONS.

We performed 99mTc-MIBI scintigraphy in a group of 39 patients suffering primary (n=32) or secondary (n=7) hyperparathyroidism. Parathyroid imaging was carried out using 99mTc-MIBI scintigraphy together with at least another imaging technique such as CT-scan, ultrasonography, MRI or Thallium 201/Technetium 99m substraction scintigraphy. Blood tests included measurements of total calcium and PTH. Confirmation was obtained surgically in all patients. 99mTc-MIBI scintigraphy correctly localized 31 of 32 adenomas, giving a sensitivity of 97%, higher than that of ultrasonography (75%), Thallium 2 0 1 / T e c h n e t i u m 9 9 m substraction scintigraphy (57%), CT-scan (41%) and MRI (33%). All ectopic adenomas (n=4) were identified preoperatively by 99mTc-MIBI scintigraphy, which significantly contributed to the correct surgical approach. Of 29 hyperplastic glands identified surgically and confirmed by pathological examination, 99mTcMIBI scintigraphy showed a positive image in 17 of them, corresponding always to the larger pathologic gland/s (sensitivity 58%, higher than that of the other imaging techniques). No false positive images were obtained with 99mTc-MIBI scintigraphy. In the preoperative localization of abnormal parathyroid tissue of patients presenting with hyperparathyroidism, 99mTc-MIBI s.cintigraphy may be the primary imaging technique.

T. Athanasoulis, Z. Anagnostopoulos, A. Vezirgianni, Ch. Kalliontzi, S. Gerali, P.Kostamis. Dept of Nuclear Medicine "Alexandra" University Hospital, Athens, Greece. PARATHYROID(PT) TO THYROID(T) RATIO(PT/T) CHANGEIN DOUBLEPHASETC99MSESTAMIBI PARATHYROID$CINTIGRAPHY(MIBI-SC) IN PATIENTS WITH COEXISTING THYRO(ONODULES(TN)

TN often coexist in pts with hyperparathyroidism (HP) resulting in false positive (F+) subtraction images. Many TN fade on delayed images (D) while some PT lesions, especialty hyperptasie (HY), fade as well. The aim of the study was to evaluate the hypothesis that PT/T change from early images (E) to a delayed image not later than 90 min, could be useful in these cases without significant loss of sensitivity. 29 pts with primary HP, 4 with secondary HP and 15 normal individuals (N-IND) with one or more cold TN were injected with 15 mCi Tc99m-sestamibi and E and O images were obtained at 15 and 60-90 rain. Then, with the pts being immobilized, 4 mCi Tc99mCH were injected and another set of images were obtained. Finally a Tc99mO4 image was created and then after movement correction and normalization two subtraction images were generated from E (SE) and D (SD). Count densities in two ROIs defined over suspected PT lesion (or TN in IV-IND) and normal thyroid tissue in E and D were utilized to denved PT/T or TN/T. When PT/T was increased over than 10% from E to D, MIBI-SC is considered [o be positive for PT lesion. Finally 28 adenomas (AD) and 19 hyperplasfic glands were found at surgery. In summary 24 AD and 13 HY were detected in the study and additionally Tcggm-sestamibi was accumulated in 9 pts' and 10 N-IND' solid and cold in Tc99mO4 images TN. The rest of TN were confirmed as cysts. SE was positive in all N-IND' TN (10t10),while SD in 7110and PTfT only in 3/10. Results of the pts' images were: SE AD 24/28 (86%) sensitivity H 13119 (68%) F+ (due to TN) 9

SD 24/28 (86%) 12119 (63%) 7

PT/T 24/28 (86%) 12/19 (63%) 2

These results indicate that 1) there is no significant loss of sensitivity when data are derived from the 60-90 min D. 2) Many TN are also detected in D resulting in F+ SD and thue the PT/T index is an useful adjunct, which in these cases, minimizes F+ and increases the overall accuracy in MIBI-SC.

In I::

O

= l

l::: In

o PMo550

PMo548 M. B. Tomas, M. O. Afriyie, J. N. Attie, C. J. Palestro. Division of Nuclear Medicine, Long Island Jewish Medical Center, New York

T. Athanasoulis, Z. Anagnostopoulos, A. Vezirgianni, Ch. KaUiontzi, S. Gerali, P.Kostamis. Dept of Nuclear Medicine "Alexandra" University Hospital, Athens, Greece.

SINGLE LATE PHASE SESTAMIBI VS SESTAMIBI SUBTRACTION SCINTIGRAPHY FOR PARATHYROID LESION LOCALIZATION.

COMPARISON OF TC99M-SESTAMIBI (MIBI) AND TC99M-TETROFOSMIN (TETR) IN PARATHYROID SCINTIGRAPHY(PT-SC)

We are prospectively comparing 99mTc-sestamibi with and without TeO4 subtraction imaging for preoperative parathyroid lesion localization in patients with hyperparathyroidism. 145 patients (101 females & 44 males), 24 - 87 yrs old, with histopathologic confirmation have been studied to date. Approximately 90 minutes following 10-15 mCi IV injection of 99mTcsestamibi, pinhole images of the neck are acquired followed by 5 mCi IV injection of 99mT¢O4 and additional neck images. Sestamihi and TcO4 images are background subtracted & normalized and a subtraction image generated. For both studies, focally increased uptake was considered positive. Among the 145 patients studied to date, there were 161 lesions: 133 patients had 1 lesion each, 4 patients had 2, 4 patients had 3, 2 patients had 4 & 2 patients had no parathyroid lesions. There were 134 adenomas (83%): 63 chief, 34 oxyphil, 22 mixed, 15 clear cell; 23 hyperplasias (15%): 6 chief, 3 oxyphil, 12 mixed, 2 clear cell; & 4 carcinomas (2%): 3 chief & 1 mixed cell. Lesions ranged from 50 - 9300 mg (mean: 1285mg). 51 lesions(32%) were eetopically located (39 superior & 12 inferior glands). There were 64 concomitant neck lesions (53 thyroid & 11 nonthyroidal). Results were:

The aim of the study was to compare MIBI and TETR in PT-SC in order to evaluate if TETR could be alternatively used in PT-SC. 12 paUetns (pts) with primary hyperparathyroidism (PH) were injected with 15mCi MIBI and early images were obtained at 15 min (MIBI-E), followed by two delayed images at 111and 2h (MIBI-D1)and ~MIBI-D2). Then with the pts being immobilized, 4mCi Tcg9mO4 were injected and another set of images were obtained. Finally a Tc99mO4 image was created and then after movement correction and normalization a subtraction image was generated from MIBI-E and Tcg£mo4 image (SUB-MIt31).We also calculated the count density ratio of suspected parathyroid lesion (PT) to normal thyroid (T) tissue in MIBI-E (MIBI-E PUT), MIBI-D1 (MIBI-D1 PT/T) and MIBI-D2 (MIBI-D2 PT/T). Within 2 weeks the same procedure was performed after injection of 15 mCi TETR and corresponding data were: (SUB-TETR), (TETR-E PT/T), (TETR-D1 PT/T) and (TETR-D2 PT/T). 12 adenomas where found after surge~/ Results for SUB-MIBI and SUB-TETR were identical as both detected 10/12 adenomas. No significant difference (NS) was found between MIBI-E PUT (1.25+0.33) and TETR-E PT/T (1.28+0.24). Results of count density ratios change were: TETR-E PT/T (1.28~-0.24)vs TETR-D1 PT/T (1.34+0.35) NS, TETR-E PT/T (1.28+0.24) vs TETRD2 PT/T1 (1.27+0.35) NS, MIBI-E PT/T (1.25+0.33) vs MtBI-D1 PTtT (1.46+0.42) (p=0.01) and MIBI-E PT/T (1.25+0.33) vs MIBI-D2 PT/T (1.51+0.55) (p=0.001). Although we need more data to confirm these findings, current results indicate than 1) TETR is an excellent alternative in PT-SC when subtraction technique is used. 2) TETR retention from PT is no significantly longer from T (as observed in MIBI studies) and so its usefulness in double phase study is questionable.

Sensitivity Specificity

Sestamibi

Subtraction

86% 87%

88% 88%

Sensitivity for adenomas was higher than for hyperplasias (95% vs 30% for sestamibi, & 97% vs 30% for subtraction). False positives for both were associated with thyroid abnormalities. Interpreted together, classifying studies as positive if either sestamibi or subtraction images were abnormal, sensitivity rose to 89%, specificity fell to 86%. In summary, single late phase sestamibi scintigraphy is sufficient for preoperative parathyroid lesion localization in the vast majority of patients. Subtraction imaging should be reserved for those patients with negative sestamibi images.

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• Endocrinology PMo551

MJ.Carroll, A H Chesser, L R Baker, W Shand, K E Britton. Departments of Nuclear Medicine, Nephrology and Surgery St. Bartholomew's Hospital, London EC1A 7BE, UK.

Tc-99m MIBI Imaging with Optimized Statistical Detection ,OSD, of Multiple Parathyroid Gland Hyperplasia,MPGH. There is as yet no satisfactory technique for imaging MPGH. A statistical change detection algorithm has been applied with this aim. We have developed an Accuracy Index based on the Kappa coefficient of agreement to determine the optimal significance level that should be used when interpreting significance probability maps to optimize the overall accuracy of parathyroid tissue detection. 15 patients with renal failure and abnormal parathyroid hormone levels received 80 MBq of Tc-99m pertechnetate with 400 MBq Te-99m MIBI after 10 minutes. Data were acquired into a 128 matrix with a zoom factor of 3.0. The statistical process comprises an initial pre-whitening stage to reduce the detrimental effects of structured background and interpixel correlation on the detection process. For every pixel a small centralized window or group ofpixels is extracted for the Pertechnetate and for the M1BI + Pertechnetate images and respective means and variances are calculated.The pooled t-test is used to derive a significance probability map for the differences between the respective images. Results : 44/54 glands found at surgery were detected using OSD giving an 81% accuracy. Among the gland size distribution detected were 11 glands 100mg or less, 4 glands 200mg or less and 2 glands 300rag or less. The main problem was overlap of glands appearing as one bigger gland on the OSD instead of two smaller ones. In conclusion OSD is a valid approach to MPGH and considered beneficial by the surgeon.

PMo552

M.Piga, PGBolasco, L.Satta, GL.Loi, P.Altieri, C.Mereu, A.Serra. A.Careddu, ANicolosi, A.Tarquini, S.Mariotti Departments of Nuclear Medicine, Endocrinology, Surgery, University of Cagliari. Department of Nephrology and Dialysis H S Michele - Cagliari 99mTe-SESTAMIBI P A R A T H Y R O I D S C I N T I G R A P H Y IN THE U R E M I C PATIENTS : EVIDENCE FOR LOCALIZATION OF A U T O N O M O U S GLANDS ( TERTIARY H Y P E R P A R A T H Y R O I D I S M ) The 99mTc-Sestamibi (MIBI) parathyroid scan as proposed by O'Doherty and Taillefer showed a low sensitivity (55%) in the detection of hyperplastic glands in the secondary hyperparathyroidism (SHP). The aim of the present study was to clarify the reason of this unsatisfactory sensitivity in SlIP as compared with the high sensitivity reported in the primary hyperparathyroidism. In 61 SHP uremic pts serum Ca, P, TSH, FT3, FT4, Calcitonin and iPTH were assayed togheter with thyroid and parathyroid echography and 99mTcO4 thyroid scan Doublephase parathyroid scintigraphy was performed after i.v.injection of 300 MBq of 99mTc-MIBI. 16 pts were subsequently submitted to parathyroidectomy. 46 pts were MIBI+ for almost one gland, 15 were MIBI-. Parathyroid echo size was greater in MIBI+ than the MIBIpatients (304 ± 1.7 cm vs 1.4 ± 05; p< 0.01) In the 16 subjects submitted to parathyroidectomy, 45 glands were removed (24 MIBI+). The mean volume of the MIBI+ glands were greater that of MIBI- glands (32 ± 5.5 ml vs 0 6 ± 0.3: p< 0.05). In individual cases, however, MIBIglands larger than contiguous MIBI+ glands were observed Paradoxical significative correlation between serum Ca and iPTH levels (r = 0.68 ; p< 0.005) were also observed in MIBI+ subjects~ On the contrary, as expected for SHP, the same correlation was negative in MIBI- pts On the base &these data we conclude that in SlIP MIBI scan identifies a subgroup of pts in whom parathyroid hyperplasia is evolving to tertiary hyperparathyroidism Pre-surgical localization of autonomous glands could be useful in reducing the chance of leaving in situ a significant amount of eutopic or ectopic hyperparathyroid tissue responsible of surgical failures 1170

PM0553 D. Sandrock, D. Mtiller, B. Kettner, V. Ivancevic, I. Reisinger, and D.L. Munz. Clinic for Nuclear Medicine, CharitY, Humboldt University, Berlin, Germany.

IMPROVED ACCURACY USING THE ADRENAL TO BACKGROUND RATIO IN MIBG SCINTIGRAPHY IN PATIENTS WITH SUSPECTED PHEOCHROMOCYTOMA. Aim of this study was to determine the extent of normal uptake in adrenals in MIBG scintigraphy using visual scoring and ROI technique in order to find a cut-off level between normal and pheochmmocytoma. Overall 50 patients (36 women, 14 men, aged 15 - 77 years, mean 52.3 years) with suspected pheochromocytoma were studied. Whole body scintigraphy in anterior and posterior view was performed 4 and 24 hrs after i.v. injection of 185 MBq 1-123-MIBG. Additionally, abdominal SPECT was done 24 hrs p.i. Adrenal MIBG uptake i) was scored visually and ii) ROIs were drawn over the adrenals, background, liver, heart, and lungs. In the 50 patients, 10 pheochromocytomas were found (proven by histology). On planar scans visual reading detected 6 and on SPECT images 8 of the 10 pheochromocytomas with a tracer accumulation >_ liver intensity with 3 false positive "hot spots" in SPECT. The ratio of (background corrected) pheochromocytoma count density to background count density was 2.6 +/- 1.7 (mean +/- SD) on planar images. Normal adrenals had a ratio of 0.4 +/- 0.2 (p < 0.001). Using a cut-off level of t.2 classified 3 pheochromocytomas falsely normal. On SPECT images the ratios were 5.7 +/- 3,7 (pheochromocytomas) and 0.9 +/- 0.5 (normal adrenals), respectively. Using a cut-off level of 2.6 failed to identify only I pheochromocytoma and classified all 90 normal adrenals correctly (overall accuracy 99%). Other ratios (adrenal/liver/heart/lung) yielded no better accuracy. There was no significant correlation between the ratios and age, sex, blood pressure or catecholamine / vanillylmandelic acid in blood / urine. We conclude that a cut-off level of 2.6 of the ratio adrenal to background using SPECT is superior to visual scoring.

PMo554 B Sb~Diro*, I Dormehlt, N Hugot, D Rossouw~, University of Michigan Medical Center, Ann Arbor, MI, USA*, AEC Institute for Life Sciences, University of Pretoria+ and National Accelerator Center, Faure, South Africa+ BIODISTRIBUTION OF 123-I lABELED VASOACTIVE INTESTINAL POLYPEPIDE (VIP) FRA(IM~k~ 1-12 IN BABOONS Intact VIP (28 peptides) labeled with lwe-I localizes metastatic colon cancer and other tumors. Small peptides are in general more rapidly cleared from the circulation and easier to label than large peptides. We examined the phar~ macokinetics of 123-I labeled VIP-I-12 fragment in balx~ns as a prelude to its ~ossible use in man. VIP-I-12 (Sigma) was labeled with 123-I using chloramine T. Purification was by SepPak C18, extraction by 20% acetonitrile in 0.1% trifluoroacetic acid and AGIX8 anion exchange resin. Purity by I£DLC was 92-89% and specific activity <3.3 pmol/MBq. Six male baboons (mean wt 28 Kg) were injected with 123-I-VIP-I-12 (mean 252 MBq range 222-285) and whole body dynamic scintigraphy obtained for 2 h~ static i~mges at 2,3,4,5,24 and 48 h, blood sanloled at 3,6,9,14,19, 24,34,39,44,48,54 min 1,2,3,4,5 h and cumulative urine collected over 48 h. We observed rapid clearance of 123-I-VIP-I-12 from blood and cardiac blood pool (TI/2 I0 and 14 rain) with urine excretion of 44% of activity by 48 h. In contrast to intact 123-I-VIP in man which shows relatively low liver and high lung uptake the 123-I-VIP-I-12 showed greater liver than lung uptake at all time points and siqnificant progressive biliary excretion. This biodistribution is similar to many other iedinated peptides. The availability of tyrosine containing VIP peptides permits study of VIP receptor bearing tumors with easily prepared, rapidly cleared 123-I tracers. Baboon studies reveal differences in biedistributien from the native intact peptide.

• Endocrinology PMo555

PTu557

C. J. Palestro and M. B. Tomas Division of Nuclear Medicine, Long Island Jewish Medical Center, New York

INDIUM-Ill PENTETREOTIDE IMAGING IN PATIENTS WITH SUSPECTED NEUROENDOCRINE TUMORS We retrospectively reviewed the results of In-1 ll-pentetreotide imaging in 18 pts, 10 women & 8 men 15-79 yrs of age with suspected neuroendocrine tumors. Pts were injected with ---6mCi of this tracer and underwent whole body and SPECT imaging approximately 24 hrs later. Final diagnoses included: pheochromocytoma (4), metastatic medullary thyroid carcinoma (3), familial paraganglioma (2 pts, 3 sites), gastrinoma (3 pts, 5 sites), earcinoid (1 pt, 4 sites), pituitary adenoma (1), small cell carcinoma(l pt, 4 sites), ganglioneuroma (1), pancreatic carcinoma (1), and normal pituitary gland (1). The overall sensitivity (n=25 sites) of the procedure was 76% (19/25). False negatives included 3/3 medullary thyroid carcinomas, and 3/4 pheochromocytomas. There were no false positive results in our population (100% specificity). A lower sensitivity for medullary thyroid carcinoma than for other neuroendocrine tumors has been previously observed, presumably due to a paucity of somatostatin receptors, so our results are not surprising. 2 of the 3 pts with medullary thyroid carcinoma also underwent 1-131 MIBG studies; both of these were also false negative. The poor sensitivity (25%) of pentetreotide imaging for detecting the 4 pheochromocytomas studied was somewhat surprising. A disadvantage of this technique is the intense normal hepatic and renal uptake of the tracer. 2 of the 3 false negative pheochromocytomas were in fact extraadrenal and both were located in the region of the renal hilum. The third false negative, though 8 cm in diameter, showed extensive necrosis. This pt (the only 1 with pheochromocytoma to undergo I-131 MIBG imaging) also had a false negative I-131 MI~BGstudy. The 1 true positive pheochromocytoma was a right adrenal lesion 3.5 cm in diameter, and 1800 mg in weight, which was clearly seen well above the right kidney. In the pt with small cell Ca, the procedure identified all 3 metastatic sites, and detected a lung lesion, presumably the primary, not identified with any other modality. In summary, our data suggest that a positive pentetreotide study indicates a very high likelihood that a neuroendocriue tumor is present (PPV = 100% in our population), while the significance of a negative study will vary with the type of neuroendocrine tumor being investigated.

G. Ronga, M. Filesi, G. Salerno, M. Ciancamerla, M . Chianelli, F. lorio, E. Procaccini, A. Signore S.S. Nuclear Medicine/Clinica Medica II-University "La Sapienza" of Rome THE ROLE OF 99m TC-MIBI IN THE FOLLOW-UP OF THYROID CANCER: COMPARISON WITH OTHER DIAGNOSTIC METHODOLOGIES In the last 2 years, many AA. tested usefulness of 99mTc-MIBI scintigraphy in the follow-up of differentiated thyroid carcinoma (DTC), with controversial results. In present work we explain our results and conclusions. We considered 32 cases of metastases from DTC (14 males/18 females; 23 papillary and 9 follicular; 20 131I uptaking and 12 not uptaking metastases). Diagnosis occurred by CT, t3'I-WBS and Tg results. After 99mTc-MIBI administration (10 mCi e.v.), during L-T4 suppressive flmrapy, planar images were acquired at~er 20', 120' and 240', and SPET after 120'. On 20 cases of ~1 uptaking metastases, 99mTc-MIBI detected them in 15 patients, with full correspondence with CT results: on the residual 5 cases, CT was positive in 2 pts. Out of 12 not 13~I uptaking metastases, 99mTc-M1BI showed sites of them in 4 pts and CT in 5 pts; in 7 cases both investigations were negative, and only high Tg level proved disease. CT and 99~Tc-M1BI sensibility were 68,8 % and 59,4 % without significative difference. In all the miliaric/smaller lung localizations, metastases detection was difficult or negative. No advantage was found using SPET imaging. In conclusion, our results indicate that 99raTc-MIBI scintigraphy is useful to dectet not 131I uptaking, and in long-term follow-up of ~3'I uptnking metastases, only for greater localizations, without L-T4 therapy withdrawal; it is useless in miliaric lungs metastases; 120' and SPET acquisition revealed useless; it cannot substitute usual investigations, but directs on further diagnostic choices, with a good cost/benefit ratio, if previously employed.

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PTu556

PTu558

O. U~urr L. Kostako~lu, B. Caner, N. G~ler, U. Uysal, N. Elahi, M. Halilo~lu, T. Aras and C. Bekdik. Hacettepe University Faculty of Medicine, Ankara, TURKEY

A.R. B6merI K.-J. LangenL,D. Simon2, HD. R6her~, H.W. M/iller-Cmrtner~. Institute of Medicine~, Research Center Jiilich, Department of General and Thoracic Surgery, University Diisseldorf, Germany

ID

ISOTRETINOINE INDUCED STAGNATION IN METASTASES OF A FOLLICULAR THYROID CARCINOMA

IX

MEDULLARY THYROID CARCINOMA FOLLOW-UP USING Tc-99m(V)-DMSA:COMPARISON WITH TI-201 AND Tc-99m-SESTAMIBI

Our purpose was to assess the i m a g i n g potentials of Tc-99m dimeroaptosuccinic acid (VDMSA), T c - 9 9 m - s e s t a m i b i (MIBI) and T I - 2 0 1 in detecting recurrent or m e t a s t a t i c medullary thyroid carcinoma (MTC). A total of 14 MTC patients underwent w h o l e body and SPECT imaging using a dual-head gamma camera. All patients had total t h y r o i d e c t o m y and had p e r s i s t e n t elevated serum calcitonin levels after the surgery. Scintigraphies were done 20 min after iii MBq of TI-201 and 555 MBq of MIBI injections and 2 hours following 370 M B q of V - D M S A injection. All patients had c o n t e m p o r a n e o u s C T / M R I and bone scans. Elevated calcitonin levels were used as a gold s t a n d a r d as to the p r e s e n c e of recurrent disease. CT, MRI and bone scan showed 42 metastatic lesions in 11 patients. In 3 patients all m o d a l i t i e s were false negative. M e t a s t a t i c sites, identified with each agent as compared with CT/MRI and bone scans were as follows;

Sensitivity Bone Soft tissue V-DMSA 24/26 (92%) 16/16 (100%) MIBI 12/26 (46%) 8/16 (50%) TI-201 5/26 (19%) !3/16 (18%)

Overall Sensitivity 40/42 (95%) 20/42 (47%) 8/42 (19%)

We c o n c l u d e d that TI-201 / MIBI have low sensitivities compared to V-DMSA for MTC and have limited value in the follow-up of these patients.

The vitamin A derivate Isotretinoine has shown antiproliferative and differentiation inducing effects in cell cultures of follicnlar carcinoma of the thyroid. Those effects include reactivation of the sodium-iodide cotransporter and slowering of cell growth. In one patient with follicular thyroid-carcinoma pT2 N1 MI after primary surgery and neck dissection in 5/93 muhiple non,resectable lung metastases were found. These showed no accumulation of radioiodine after ablation of the thyroid remnant in 3/94. F18-FDGPET revealed intense glucose hypermetabolism of the 10 most prominent loci with close-uptake ranos (DURs) between 5.1 and 8.4. In 5/95 thyreoglobnlin (hTg) levels were rising exponentially. Additional medication with Isotretinoine (Roaccutan R) 60 mg/die was started after several controls in 6/95. F I8-FDG-PET revealedDURs of 3.1-5.3 in the corresponding loci in 11/95. No measurable changes were found in chest X-ray and CT. Further development of hTg-levels is given below including a medication pause of 3 weeks. hTg

7000

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Isotretinolne 60 mgld

6000 5000 4000

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200030001000

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: 7194

= = =: 11194 3199

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=: = -- •1 11199 3196

Our results indicate that Isotretinoine is able to slow down growth of lung metastases of follicular thyroid carcinoma. Further research will show, if the sodium-iodide cotransporter is reactivated in vivo, thus giving a chance to cure irresectable tumors with radioiodine.

1171

O

• Endocrinology PTu559 A. Bockisch÷, R. Grrges*, Chr. Drahten* (+) Clinic for Nucl. Med., Univ. of Essen and (*) Clinic for Nucl. Med., Univ. of Mainz, Germany ARE ATHYROID PATIENTS SUFFERING FROM THYROID CANCER ON RISK TO INDUCE OSTEOPENIA BY SUPPRESSIVE LEVOTHYROXINE TREATMENT? Osteopenia induction by levothyroxine (LT4) medication because of benign thyroid disease has not been established so far. On the other hand it is well known, that hyperthyroidism may induce osteopenia. Therefore, we investigated, whether high dose LT4 medication, which is common in the treatment of thyroid cancer patients has the risk of o steopenia In a prospective study, we measured the bone mineral content (BMC) in thyroid cancer patients when included into the study and 12 months later (and often also after 6 month). The data were gained from the distal radius (pQCT), the lumbar spine, and the femur (DPA) and were normalized to the average reference value. The initial data for each patient were compared with the findings after (6 months and) 12 months for each of the measuring sites. We have complete data sets from 116 athyroid patients for 0 - 15 years of follow-up. We analyzed the correlation of the change of the BMC with the absolute values of the BMC and the correlation of both the change of the BMC and the absolute BMC with the LT4 dose, the LT4-serum level, age, sex, and the duration of the LT4 therapy. Results: The average BMC of our patients coincided with the average reference values in each of the three locations. The change during the study corresponded to the expected age-dependent change. There was no correlation of the BMC or the change of the BMC with any of the parameters mentioned above (r2 < 0.2 in each case). Especially, we did not find an increased loss of BMC in the early phase of medication or for postmenopausal women. In conclusion, an increased risk of developping osteopenia could not be established in our athyroid patients who were treated with the minimum LT4 dose, which guarantees a complete suppression of TSH secretion.

PTu562 D.Pop GJorcheva, V.Bogdanova, N. Slmova~ S.Mlceva-Risteska. S.Loparska Institute of Pathophyslology and Nuclear Medicine, Medical Faculty, SkopJe, MACEDONIA LEFT VENTRICULAR FUNCTION IN HYPERTHYROID PATIENTS, BEFORE AND AFTER TREATMENT, ASSESSED BY RADIONUCLIDE VENTRICULOGRAPHY Using the method of radionuclide ventdculography (RNV), we have examined left ventdcular (LV) function in 22 control and 26 hyperthyroid patients at rest, before and after treatment. We have analyzed following LV performances: ejection fraction (EF), ejection and filling pedod (EP,FP), peak erupting and peak filling rate (PER, PFR) and time to PER and PFR normalized for the EP and FP. The hyperthyroid state was characterized by a significantly higher values of PER (- 4.12 EDV/s vs. - 3.07 EDV/s in controls, p
PTu561

PTu563

I. Lauer, B. Meller-Rehbein, M. Baehre, E. Richter Clinic of Radiotherapy and Nuclear Medicine, Med. University of Luebeck, Germany

P l a z i ~ s k a 11., K r o l i c k i L., G r a b a n W. Department of ~!uclear M e d i c i n e ~ e d i c a l of W a r s a w (I F a c u l t y ) .

INFLUENCE OF URINARY IODINE EXCRETION ON UPTAKE AND HALF-LIFE IN RADIOIODINE TEST AND THERAPY Aim of this study was to investigate the influence of iodine supplementation measured as urinary iodine excretion (UIE) on uptake (Up) and half-life (tt/2) during radioiodine uptake test (RITe) and therapy (RITh). Methods: UIE was determined in 161 patients (focal autonomy (fA; n = 2 6 ) , multifocal autonomy (tufA; n = 9 7 ) , Graves' disease (GD; n = 3 8 ) ) o n the first and last day of RITe and n = 105 at 3 rd and 7 th day of RITh. UIE was measured using a colorimetric method (iodine catalysed decolorization of cerium sulfate solution) in pg iodine per g creatinine. The median of UIE was calculated and Up (RITe), tl/2 (RITe) and tl/2 (RITh), and set in relation to diagnosis and medication.

Results: Diaqnosis fA mfA mfA 0 mfA T. GD n 26 97 48 32 38 UIE 11 7 108 1 O0 114 84 Up 31 32 32 36 53 tl/2 5,2 6,6 7,0 5,4 4,7 RITh n 14 64 36 19 24 UIE 171 149 150 148 163 tl/2 5,5 6,1 6,2 5,7 5,1 [o without -, T with antithyroid drug] UIE was significantly higher in patients with tl/2 in RITe < 4 days (124 pgl/g creat., p
RlTe

1172

LITHIUM THERAPY

APPLICATION IN P A T I E N T S

School

ON T H E E F F E C T OF 1 3 1 - I WITH HYPERTHYREOSI5.

L a s t y e a r we p r e s e n t e d the r e s u l t s t h a t l i t h i u m bicarbonate application produce about 100% i n c r e a s e of t h y r o i d i o d i n e u p t a k e . T h e s e r e s u l t s s u g g e s t e d the p o s s i b i l i t y of the use of I i t h i u m in p a t i e n t s w i t h h y p e r t h y r e o s i s and low T 24 i o d ine u p t a k e ( 1 5 - 2 0 % ) b e f o r e 1 3 1 - I t r e a t m e n t . The a i m of t h i s r e p o r t is to p r e s e n t the g r o u p of p a t i e n t s (n=27) w i t h h y p e r t h y r e e s i s (Graves-Dasedow or a u t o n o m o u s a d e n o m a ) who had low i o d i n e u p t a k e and t h e r e f o r e t h e y r e c e i v e d lithium application before 131-I treatment.Time of o b s e r w a t i o n a m o u n t e d 1 - 1 . 5 y e a r s . L i t h i u m was g i v e n two d a y s b e f o r e and 5 d a y s a f t e r a p p l i c a t i o m of 1 3 1 - I . D o s e of the a c t i v i t y was c a l c u l a t e d individually a c c o r d i n g to d o s i m e t r i c formula. Our r e s u l t s as f o l l o w e s : - reccurrent hyperthyreosis in 5 p a t l e n t s . T h e sec o n d d o s e of 1 3 1 - I w a s e f f e c t i v e in all c a s e s , - early transient hypothyreosis (3-4 m o n t h s in d u r a t i o n ) w a s o b s e r w e d in 8 p a t i e n t s , - t h e r e are no p a t i e n t s - till n o w - w i t h s t a b l e hypothyreosis. In c o n c l u s i o n : we r e c o m m e d d the p r o t o c o l i n c l u d i n g lithium bicarbonate application in o a s e s in w h i c h a l o w i o d i n e u p t a k e l i m i t s the use of 1 0 1 - i in h y p e r t h y r o i d patients.

•

Gastroenterology

Gastroenterology PMo564

PMo566

C.H. Kao and C.K Huang, Departments of Nuclear Medicine and Division of Gastroenterology, Taichung Veterans General Hospital, Taichung Taiwan, R.O.C.

~

EFFECTS OF ANIMAL BUTTER AND VEGETABLE SOYBEAN OIL ON SOLID-PHASE GASTRIC EMPTYING IN PATIENTS WITH FUNCTIONAL DYSPEPSIA.

RE-EVALUATION OF THE CLINICAL VALIDITY OF ILEAL FUNCTION ASSESSMENT B Y MEASUREMENT OF THE ABDOMINAL RETENTION OF SeHCA T

Twenty-seven patients (3 females, 24 males; ages: 31-78 years old ~, with chief complaints of bloating and early satiety but with an endoscopic negative findings were considered for entry into the study. Patients with previous history of gastric surgery, endocrine, liver and renal diseases were excluded. Radionuclide labelled solid meals were used to evaluate gastric emptying (GE). A study meal was composed of 206.8Kcal - 9.2gin protein, 45gm carbonhydrate and 10gin fat (formula 1: animal butter - saturated 26.2% patmitic acid and unsaturated 29.1% oleic acid, 3.5% linoleic acid, 0.5% linolenic acid; formula 2: vegetable soybean oil - saturated 11.0% palmitic acid and unsaturated 23.4% oleic acid, 53.7% linoleic acid and 7.8% linolenic acid). Each patient received the formula 1 and 2 study meals on seperete days. GE was represented by the gastric retention ratio of the study meal at 90 min (RRg0), and calculated by the formula: residual radioactivity within the region of interest (ROI) covered the whole stomach at 90 min + the initial radioactivity within the ROI at 0 rain. A questionnaire was given to each patient after finishing each study meal to evaluate their symptoms during the test. The RR90 is 68.1 -+19.8% for formula 1 and 61.8-+18.4% for formula 2. There is no significant difference for the RR99 between formula 1 and 2 (a paired Student's t-test, P > 0.05). Of the 27 cases, 15 (55.6%) patient demonstrated increased RR99 from formula 1 shift to formula 2 study meal, and the remaining 12 (44.4%) patient's RRg0 decreased. In addition, neither the patients with increased RR90 nor those with decreased RR90 showed a difference of symptoms between the two study meals. Our data suggests that saturated animal butter and unsaturated vegetable soy-bean oil make no different influence for the gastric motility.

, K. Kosric, O Popovic, IS Markovic, V. Artiko, V, Obradovic, M.Matovic, Belgrade and Kragujevac Schools of Medicine/Clinical Centers, Departments of Nuclear Medicine

The aim of the study was to assess the ileal function in 79 patients [9 controls (CG), 5 ileal resections (IR), 4 after radiotherapy (RT), 6 Crohn disease (CD), 19 primary bile acid malabsorption (PBAM), 7 giardiasis before (Ga) and after therapy (Gb), 3 blind loop syndromes (BLS), 7 post-cholecystectomy diarrhoeic syndromes (PCCa) and 4 cholecystectomy without diarrhoea (PCCb), 5 iritabile bowel syndromes (IBS) and 10 different diarrhoeic syndromes (DS)]. 0.37 MBq of 75SeHCAT (Amersham) was administered orally and its abdominal retention (ARS) was measured by uncollimated gamma-camera after 3 h, 4 and 7 days, Results were expressed as percentage of fl st day value, Retent)on curves showed monoexponential decline and were fitted well by function y=e a-ox. Functions were calculated for all experimental cases as welt as t l/2 of SeHCAT AK Results:

groups CG IR RT CD PBAM Oa/Gb BLS PCCa PCCb 1BS DS

%ARS 4th day (x_+SD) 64.98+~21.23 6.73+4.36 l 1.31_+6.38 26.28+-18.33 2031-+1251 27.67/34.42_+95/5.7 5812+15.66 16.6+-11.9 50.23-+15 64 59.28+-2726 33.11+_24.22

%ARS 7th day

(x_+SD) 38.61+_15.64 2.08-+1.08 4.45+_3.00 7.05+-3.97 558±342 97/26.4+-43/57 20.07-+9.3 5.11-+3.59 18.95+276 3355-+9.54 19.41±12.95

t 1/2 (day) 5.36 1.87 2.27 2.77 268 3.1/53 4.34 2.65 324 5,22 3.84

signific. CD/ p<0.0] p<0.0l p<0.01 p<0.01 p<0.05 p>0.05 p<0.0l p<0 05 p>005 p<005

In summary:Tth day ARS results are devided in two groups: the first (CG, BLS,

PCCb, IBS and Gb) has ARS in physiological limits. The second (IP,. RT. CD, PBAM, La, PCCa and DS) has low ARK Although the method doesn't differentiate causes of malabsorption, its clinical benefit is to be able to prove-out &many ileal absorption disorders-the bile acid malabsorption, treated by specific cholestiramine therapy. ARS assessment is non-invasive and highly sensitive in vivo test of ileal function

PMo567

S.J. Wang, C.H. Kao, C.S. Chang, and GH. Chen. Taichung Veterans General Hospital, Taiohung, Taiwan

Josifovska T., Fjalling M., Friman S., Ekman M.. Institute of Pathophysiology and Nuclear Medicine, Skopje, Macedonia and Dept.s of N u d e a r Medicine, Transplnatation Surgery and R a d i a t i o n Physics, Sahlgrenska Hospital, GOteborg, Sweden

20 patients with reflux esophagitis (RE) by 24hr pH monitoring and scintigrapic findings were enrolled in the study. Patients with previous history of immunorheumatic, endocrine, liver and renal diseases were excluded. Another 20 normal volunteers were selected to compare. After I.V. 15mCi Tc-99m pertechnetate, sequential images of 1rain each were acquired for 30min. Saliva excretion was stimulated by 500mg vitamin C at 15rain post-injection. The 1st and 15th rain uptake ratios in major salivary glands: (the mean counts in ROIs of salvary glands) - (the mean counts in ROIs of background). The maximum excretion fraction of salivary glands for the sialogogue: [(the 15th rain mean counts in ROIs of salivary glands) - (the lowest mean counts in ROIs after the sialogogue stimulation)] + (the 15th rain mean counts in ROIs) x 100%. The results were tabulated as follows: Salivary Uptake Glands 1st Reflux Esophagitis Rt Parotid 2.3--+0.7 Lt Partoid 2.1-+0.7 Rt Submanibu~ar 4.1-+1.0 Lt Submanibular 3.8-+1.0 Controls Rt Parotid 3.4-+2.3 Lt Partoid 3.2-+2.3 Rt Submanibular 5~5--+3.4 Lt Submanibular 5.3-+3.2

ratios 15th

Excretion Fraction

4.6-+2.0 4.1-+1.1 5.1-----1.4 5.0-+1.2

50.1--+t4.6 50.1--+14.4 42.0+--12.4 42.2--+11.9

8.4-+5.4 8.1+-5.2 9.0--+5.0 9.1-+5.3

62.5-+12.5 60.9-+12.3 50.1 -+9.7 50.7-+9.6

RE vs controls, p<0.01 In conclusion, poor salivary functions in RE are confirmed by the quantitative sialoscintigraphy. Lack of enough alkaline saliva production to compensate the acid which reflux from stomaches into the esophaguses may result in esophagitis.

o

L.

COMPLICATIONS AFTER LIVER TRANSPLANTATION DIAGNOSED BY QUANTITATIVE HEPATO BILIARY SCINTIGRAPHY Hepatobiliary scintigraphy with imino-diacetic-acid derivatives is a sensitive indicator of hepatocyte function, hepatic blood flow and b i l i a r y drainage. The aim of the study was to evaluate the accuracy of h e p a t o b i l i a r y scintigraphy fn detecting rejection, hepatitis, vascular complications, biliary obstruction, and leakage after liver t r a n s p l a n t a t i o n . M a t e r i a l : The study group consisted of 35 liver transplanted patients w i t h suspected postoperative complications, 19 females and 16 males. 10 patients had rejection, 9 hepatitis, 6 vascular complications, 10 h e p a t o b i l i a r y obstrudion, and 6 had leakage. 6 patients h a d two ovmplications at t h e same time. The diagnoses were confirmed with biopsy, serology, US or angiography, c h o l a n g i o g r a p h y or reoperation, respectively. The h e p a t o biliary scans of 11 normal subjects were evaluated in the same w a y and served as the control. Method: 200 MBq 99mTc-IODIDA was given by iv injection. Acqusition w a s 10 sec/frame for 30 min followed by static images w h e n necessary. C l e a r a n c e rate (CIr) calculation and deconvolution analysis performed on timeactivity curves derived from blood pool ROIs and hepatic p a r e n c h y m a l ROls giving Clr, hepatic extraction fraction (HEF) and mean transit time

(MTT). Results: Rejection MEan (SD) Clr, % / rain 9 (4.6) HEF, % 33 (23.8) MTT, rain 14 (5.2)

¢..

o Q.

PMo565

THE SALIVARY FUNCTIONS EVALUATED BY QUANTITATIVE SALIOSCINTIGRAPIES IN PATIENTS WITH REFLUX ESOPHAGITIS.

co

Hepatitis

tO (4.3) 40 (19,7) 16 (2,5)

Vase. complic,

t0 (4.3) 67 (12,9) 16 (3,7)

Biliary obstruct.

13(4,6) 54(16.4) 18 (4,5)

Leakage

14 (6,7) 56 (31,1) 16 (4,1)

Normalsubj.

23 (2,5) 87 (6,7) 20 (4,9)

All patients with scans indicating obstruction or leakage had t h e complication confirmed by other methods and underwent surgical or other correcting intervention. Conduslon: Quantitative hepatobiliary s d n t i g r a p h y (CIr/HEF) will show hepatocyte disfunction, but not t he cause. Morphological complications w i l l be diagnosed with high accuracy. HBS is therefore recomended as the first diagnostic procedure w h e n liver graft dysfunction is suspected.

1173

O O a.

• Gastroenterology PMo568 t~st=i~ mnptyini (GE) =~1 timing oi i~,ulin ira,alien in imdi~-t=,=t,d ditbtticJ (ITD) M Sh*ta* a~d k E1-Tawil Dtpt M I~tomal bt*did~** and N~I*a* bl*dici~*, Cairo Uni~*sitF, EIFl~t

Ol~'li~== F~ndional pst,opazesis is a well ,e¢o~nized complication oi diabetes mellit~ that may lead to poe= glycemic ¢ont*ol d~e to disc~ei~a~¢ies between the ~set of i~suli~ action (OIA) s~d the zelesse of nutzie~ts i~to the i~testine, I~ the pzesentwo=kwe aim |el= • Ewlutto the zelationship of ~st,opazesis to patienb a p , so., GIT ~)~?i~ms, dlabetk e~mplie~io~s (~eu~op-athy) and dlabetle ea~t~ol, • Enmlt.ate the inflttence of stomach xelease of nutzient~ and liming of insdin i~e_di~ as a vnodibj'i~g factoz |o* blood ~lu~ose ¢ontzol, eO~*¢tiw o?timi=ation o| timing o[ i~suli~ i~j*dion ~o= =~.t~ i~dividual ~atimt u~i~gthe o~tion (tic'noo~ i~suli~ i~ettion • OIA -solid lagti,mo), Methods: GE oi Tc-99m labeled liquid and solid meals v~ze studied it, 112 lo~¢-sta~di~g ITD, as well a~ 46 ai~, so. a~d body mass- ~lteh*d h*althy vol~ttez~ as a cent*el, Ti~t adivity e u ~ = vctz* liPmtztt*d lot the i~stzi¢ azea LUinggeometxie vneav=of ~0 see. a~tezioz a~d posteliot Caverns camera xecozdi~¢~ duzi~g 2 h o ~ liquid a~d solid lag time (T lag) a~d T1/2 values were calculated allez eoneetion ioz T¢-99m decay, li=~ulls= Diabetics showed significantly delayed gastzic T1/2 foxboth liquid (0=45+0~14 rain) and ~oli~.~ (;L20±0;~6 rain) c~npazed to (0:8110;10 rnin) a~d (0:49_+0:15rain)of the ~ontzois ,es~ectively (p<0.05). This delaywas apl~azent i~ male pati~ts ,^dth olde~ age a~d len~x dttmtle~ o~ diabetes, who had ~st=0i~tetti~tl a~d pezi~he,al o* tatono~k @,~ptoms, ~y~¢ht~i--Iti~ of

i~s~lin i~edion time with the onset o~ the solid meal ,oloase f=om the ~to~a~h acco=di~g to the p=eviou~ ,qu~tion**suited i~ ~ig~i~ict~t ,eduxtion o~ ia,ti~¢ a~d 2h. post p*a~dial~lood gl~ose levelby SSmg/dl a~d 66 m~dl ZeSl~edivelyv¢ithbeite=~ly~e~ic¢~twl, C e r t i f y : Kadio~adide GE is a ph3~iol0gleal, o~ective method io~ i~dividaal optimi:ation of i~duli~ i~jectio~ time i~ :elation to meal that impzow glum'hie ~ontzol a~d ma.irnise b ~ i f i t oi i ~ d i ~ adios,

•

+

.

*

•

+

D Papapanagiotou*, T Mavromatls , H Glannopoulou , B Bursmos ,

C Alevizaki#, G Diamantopoulos*, M Kesse-Elia* •Dept of Nuclear Medicine, +3rd Surgery Clinic and #Dept of Medical Physics, ~ Hospital, Athens-Greece SCINTIGRAPHIC STUDY OF GASTRIC EMPTYING IN PATIENTS WITH VARIOUS TYPES OF GASTRIC OPERATIONS BEFORE AND AFTER ADMINISTRATION OF ERYTHROMYCIN It is well known that one of erythromycin's (EM) side effects is induction of gastric motility. The aim of the present work was to investigate the possible beneficial prokinetic effect of EM during the early postoperative period of gastric surgery in patients with delayed gastric emptying. We studied 16 patients (14 men and 2 women, mean age 53 y) with various gastroduodenal diseases. Nine of them had been submitted to truncal vagotomy and pyloroplasty (group A) and 7 to partial gastrectomy and gastrojejunostomy (group B). The effect of EM on gastric emptying was tested between 8-10 postoperative days. A standardized solid meal labeled with 500 pCi of Tc-99m sulfur colloid was consumed by the patient. The same meal was repeated the next day after the iv injection of 250 mg EM X 4. The patients were studied in the standing position with the large field of view gamma camera, with low-energy all purpose parallel-hole collimator. Images were acquired every 15 min for one hour and then every 30 rain for another hour. Gastric activity in an area of interest over the stomach was recorded on the computer• Tl/2 of gastric emptying was calculated from the data by a least square technique. Results: T1/2 of gastric emptying (min) before EM after EM range mean (SD) range mean (SD) 207-600 310 (120) 45-222 150 (71) 117-600 330 (206) 88-600 330 (244)

P** 0.001 0.4

Conclusion: A highly significant difference of the gastric emptying (T1/2 reduction about 50%) was noticed in the patients with intact stomach (group A) after EM infusion, while no difference of gastric emptying was observed after EM infusion in patients with partial gastrectomy (group B). A possible explanation for this difference is that EM may mimic the effect of motilin on gastrointestinal motility through a direct action on motilin receptors, located mainly in the gastric antrum. **Wilcoxon signed rank test

1174

J.Naumovski,N.Simova,G.Pilovski,E.Kovkarova Naumovski Medical Faculty,Skopje,Macedonia

-

SCINTIORAPHIC DETECTION OF CAUSTIC INJURIES OF UPPER CASTROINTESTINUM WITH Tc-99m SUCRALFATE An advanced approach to injuries of the upper gastrointestinum(UGl) includes several methods, which are chronologically determined in case of caustic lesions.The aim of this study is to evaluate the scintigraphy of UGI and to compare its value with endoscopy and radiography in the clinical estimation.Thirty patients with UGI injuries after a caustic ingestion were imagined with Tc-99m-DTPA-sucralfate and gamma-camera.They were divided in 3 groups according to the severity of the le-sions(l,ll,lll degree).Using the method of clinical test evaluation,sensitivity(Sn),specificity(Sj and accuracy(Ac) were determined in general and separately for esophagus,gaster and duodenum in the 3 groups. The scintigraphy of the studied group revealed a Sn--87.2~,Sp-89.4% and Ac--87.9% for the UGI.According to the severity of the injuries,the method showed an increase of Sn(68.O%,85.TZ,resp.97.3Z), a high SP in all(100~,80.gZ,88.6%) ,as well as Ac (82.2Z,84.2~,87.7%).The most incresing Sn with degree of the lesion is for the esophagus:l degree54.5%,ll-82.3Z,lll--93.]%(p 0.006;C2 0.37). The study shows a strong correlation between the accuracy of sucralfate scintigraphy and the degree of caustic damage of upper gastrointestinum.This method is inferior comparing to endoscopy,but the need for appropriate treatment choice of caustic injuries where invasive diagnostics is dangerous or impossible,force the application of noninvasive technics.

PMo571

PMo569

group A group B

PMo570

Erkan Vardareli*. TiHay Sangam**, llknur Ak*, Nesrin Seyman*, Hasan Ym,uz**, Emre Entok* Osmangazi University, Department of Nuclear Medicine* and Division of Gastroenterology**, TURKEY PORTASYSTEM1C SHUNT QUANTIFICATION BY PERTECHNETA TE PER RECTAL PORTAL SCINTIGRAPHY

Tc-99m

Per rectal portal scintigraphy is the best noninvasive method to measure the portasystemic circulation. Many different radionuclides and quantification methods has been used for determination ofportasystemic shunting (PSS). The most important factor is the selection of sampling-time in time-activity curves for determination of quantitative PSS index. The aim of this study is to determine PSS index in different times and to compare its with clinical and laboratory findings. In this study, PSS were evaluated in 25 patients vath liver cirrhosis and 10 healthy controls by rectal administration of 10 mCi Tc-99m pertechnetate through a thin polyethylene tube, Subjects were positioned supine under the detector of a gamma camera (GE 400 AC/T); fitted with a low energy general purpose collimator. Dynamic images were recorded using a computer (GE Starcam 40000 5 sec. interval for 25 rain PSS indices were calculated using the arms under time-activity curves generated by heart (H) and liver (L) regions of interest (ROls), expressed as percent H activity over the sum of H and L activity for the periods of 30 sec., I min., 5 rain. And at the end of the study (25 rain.) H/L ratio was calculated. Student's t-test and Spearman's correlation analysis were used for statistical analyses. Fair correlation was observed between the spleen and splenic vein size (r=0.543, p<0.05) and between portal vein and splenic vein size (r=O514, p<005). The nighest statistically significant difference was present at 30 sec. PSS index (p<0.001, t=8.02) comparing with patients and healthy controls. There was a good correlation between the 30 sec. PSS index and 1 rain. PSS index in patients with cirrhosis and controls. As a conclusion, per rectal portal scintigraphy using Tc-99m pertechnetate is a noninvasive, less expensive and readily available method for the evaluation of the fuctiunal state of portal circulation. But, for the quantitative determination, PSS index should be determined during the first transit of the tracer after the per rectal administration.

• Gastroenterology PMo572 A. TutuS;, K Giiven, M Nardah, T. Yolcu, M.T. Ercan, Department of Nuclear Medicine and Internal Medicine, Erciyes University, Medical Faculty, Kayseri, TURKIYE

PMo574 K. Bhargava*, S. Vasa, P. Rajvanshi, M. A f r i y i e , L. Zuckier, C.J. Palestro*, and S. Gupta. Liver Research Center and * D i v i s i o n of Nuclear Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, NY.

THE VALUE OF Tc-99m CITRATE SCINT1GRAPHY I N DISCRIMINATION B E T W E E N CHRONIC HEPATITIS AND CIRRHOSIS

Tc-99m-HEPATOCYTES: IN VIVO APPLICATION FOR DEMONSTRATING ORGAN DISTRIBUTIONS IN CELL RECIPIENTS.

Diagnosis and discrimination between chronic viral hepatitis and cirrhosis is essential since the therapy will depend on the histological difference. Current diagnostic method, liver biopsy, is invasive and potentially has morbidity and even mortality. The purpose o f this study was to determine the diagnostic value o f Tc-99m-citrate as a n e w inflammatory imaging agent, in discrimination of chronic viral hepatitis and cirrhosis. 550 M B q Tc-99m citrate was administered intravenously to 29 patients proved to be either chronic viral hepatitis or cirrhosis. 500 Kcounts planar spot images over the liver and lung were obtained at 3 hours post injection. A region of interest (ROI) was drawn over the liver, and second ROI was drawn over the lung as a background. Liver/lung ratios were calculated. Fourteen patients with chronic viral hepatitis showed remarkably increased uptake of Tc-99m citrate, while cirrhotic patients did not. The mean liver/ lung ratio was significantly higher in chronic viral hepatitis group compared to cirrhofics (3.05+1.99 versus 1.78+_0.35, p
Hepatocyte transplantation will be useful for novel cell-based therapies, q o define which vascular beds best support engraftment of transplanted hepatocytes, analysis of cell distributions is necessary. To facilitate noninvasive analysis in patients, we developed conditions for labeling isolated rat hepatocytes with Tc-99m. Hepatocytes could be labeled with tagging efficiency of up to 85% without loss of cell viability. When radiolabeled cells were transplanted vis spleen into normal rats (n=3), hepatocytes immediately entered the hepatic sinusoids and activity in recovered organs was primarily in liver (85% +-3%), less in spleen (13% +-3%), and least in lungs (1% -+0.5%). In contrast, when Tc-99m hepatocytes were injected into the spleen of rats previously subjected to portal vein constriction (n=3), a large amount of Tc99m activity simultaneously appeared in lungs (35% + 3%, p<0.001), consistent with portasystemic shunting. To localize transplanted cells, we used DPPIV + F344 hepatocytes as donors and syngeneic DPPIV rats as recipients. Transplanted cells containing histochemically demonstrable DPPIV activity survived indefinitely in the liver parenchyma of recipients. In contrast, when hepatocytas were deposited in the pulmonary vascular bed via femoral injection, significant Tc-99m activity accumulated in extrapulmonary organs due to cell fragmentation with DPPIV cell fragments observed in liver, spleen and kidneys. CONCLUSIONS: Labeling of hepatocytes with Tc-99m provided a convenient noninvasive method for demonstrating cell biodistributions. Cell survival was excellent after deposition into the hepatic sinusoids but not after deposition in to the pulmonary vascular bed. These findings will help advance hepatocyte transplantation.

tO |m e-

¢n I11 L-

O. PMo573 F. Barbano, G. Petracca Ciavarella, G. Polito, S. Modoni, E. Calo, G. Modola*, D. Facciorusso*, A. Giacobbe*, V. Frusciante. Nuclear Medicine and * Gastroenterology, "Casa Sollievo della Sofferenza", Scientific Institute, San Giovanni Rotondo (FG), Italy. PERITONEAL SCINTIGRAPHY IN HEPATIC HYDROTHORAX. Hepatic hydrothorax is a pleural effusion in cirrhotic patients, with or without ascites, and no evidence of cardiac or pulmonary diseases. Hepatic hydrothorax is an infrequent complication of cirrhosis (6%); pleural effusion is more frequent in the right side than in the left or both sides (often caused by TBC). The more widely accepted pathogenetic hypotesis is a communication between peritoneum and pleura through the tendinous portion of diaphragma. We evaluated 14 patients (gM and 5F, age range 42-74 yrs.) affected by cirrhosis. All the patients, on admission, showed dyspnoea and right pleural effusion; in 3 pts. a large amount of ascitic fluid was evident at the physical examination, in 2 pts a small amount of ascites was evident only by US, in the remaining pts US and physical examination did not show evidence of ascites. All the patients were imaged by scintigraphy, performed 10-15 rains. after the intrapedtoneal administration of 111 MBq of 99mTc-SC. Eight pts. shewed an early evident radioactivity in dght hemithorax; only in 1 patient, activity in right hemithorax was evident 1 hour after the administration; in the other five cases radioactivity remained in the peritoneum; however, after decompressive thoracentesis, radioactivity was evident in the pleural cavity. In order to confirm the location in the pleural cavity, the sulphur colloid scans were compared with the lung images obtained with intravenously injection of 74 MBq Tc-99m MAA. Two days later 37 MBq of 99mTc-SC was injected into the right pleural cavity. Static images aquired up to 120 mins. showed that the radioactivity remained confined in the pleural cavity. We conclude, therefore, that peritoneal scintigraphy is a specific and simple technique to demonstrate the peritoneal odgin of hydrothorax, the unidirectional flow between the two cavities and the pathogenetic role of diaphragmatic defect and respiratory dynamics.

!.__

PMo575 N.Molea,O.Goletti~,L.Bodei,E.Lazzeri,R.Balestril,F.Borsetti,E.Cavina t and R.Bianchi. Nuclear Medicine Center and Emergency Surgery Institute ~,University of Pisa, Italy.

o'1

O

IX LAPAROSOPIC APPROACH IN ABDOMINAL SURGERY: A SCINTIGRAPHIC EVALUATION

NEOPLASTIC

The introduction of diagnostic and therapeutic laparoscopy has leaded to a better capacity of staging and treating abdominal neoplasias. Neoplastic reimplantation along trocar passage is a frequent complication (4% out of over 1500 laparoscopic resections in colo-rectal cancer).This is due to tumor cell exfoliation during laparoscopic maneuvers,direct contact between tumor and abdominal wall,'cbimney" effect (cancer cell aerosol).Pneumoperitoneum (PNP) seems to be a particularly important etiologic factor.Simulating gallbladder tumor a scintigraphic study was performed in order to estimate causal role of PNP.26 patients affected by cholecystolithiasis and undergone a videolaparocholecystectomy (VLC) were studied.Patients were split into 3 groups: 1)VLC with PNP and cholecystis extracion without bag; 2)VLC with PNP and cholecystis extracion with bag; 3)GASLESS VLC and cholecystis extraction with bag.3ml of 99mTc-labeled erythrocytes (3mCi,lllMBq) were injected into gallbladder-bed.A front and a lateral image of abdomen were recorded 2 hours after VLC.Abdominal SPECT was performed in some cases.All patients treated with PNP demonstrated a large intraperitoneal diffusion of the tracer (see table below). PNP PNP+bag Gasless n=26 11 9 6 UT pos 10(90%) 7(78%) 5(83%) UT neg t(lO%) 2(22%) 1(17%) These results show a high radioactive contamination of ttmbelical trocar in patients treated with PNP.So the greatest risk of neoplastic cell diffusion is in laparoscopy performed with PNP and not in the gasless method.

1175

[] Gastroenterology PMo576

PMo578

Y.Kuniyasu~ Y.Niio, S.Hasebe, H.Shinohara, K.Uchiyama, M.Obuchi, K.Takizawa, M.Honda, and S.Satoh, Department of Radiology, Fujigaoka Hospital of Showa University, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227, Japan A NEW LIVER FUNCTION TEST WITH Tc-99m-DTPAGALACTOSYL HUMAN SERUMM ALBUMIN -COMPARISON WITH THE USEFULNESS OF SEVERAL FUNCTIONAL PARAMETERS -.

H.W Hendel, L. H~a~rd, T Andersen, BH. Pedersert LI Paloheimo, J.F Rehfdd, A Ootfi'edse~a, M H. Ramaussm Daloartment 0f Clinical Physiology & Nuclear Medicine, Hvidowe University Hospital. ABDOMINALFAT MAS,~ GLUCOSETOLERANCE,AND GALL BLADDERVOLUMEIN NON-DIABETIC OBESESUBJECTS

The hepatic receptor binding parameters obtained by several methods are LHL 15(hepatic uptake index), HH 15(clearance index), Ku of 1compartment analysis, Ku/Ke(3-compartment analysis) and Ku from Patlak's plot method which are all depending on the ROI size of the heart. A new parameter which can be obtained independently from the ROI of the heart, is evaluated from a clinical point of view. The new parameter of liver/body(L/B) ratio shows hepatic uptake ratio and is calculated from liver activity divided by whole body activity on Tc-99m-GSA whole body imaging. This parameter is compared with other receptor binding parameters. A total of 153 patients were studied. They were consisted of 88 patients with hepatocellular carcinoma and liver cirrhosis or chronic hepatitis, and 57 patients with chronic liver diseases. A bolus of Tc-99mOSA(185 MBq) was injected and following images were obtained anteriorly covering abdomen and lower thorax. The images were acquired for 20 minutes by a matrix of 128 x 128 on this study. Using these early phase data, the computed parameters were obtained and the new parameter was calculated from the static phase(30-40 minutes). The L/B ratios were correlated with the computed parameters and biochemical data of the liver function. The L/B ratio correlated well with albumin(r= 0.594), HPT(r=-0.678), KICG(r=-0.625) and other computed parameters ; HH 15(r=-0.870), LHL 15(r=-0.894) and Ku of Patlak's plot method( r=0.809). In conclusion: The L/B ratio is a new sensitive and promising parameter for estimating the prognosis and severity in various liver injuries. It can be obtained independently from the ROI size of the heart, as a simple, objective and reproducible parameter.

Baelqgrou_ntl & .aaras: Obesity is a major risk factor for gallstone formataon. Total body fat mass md its distribution are responsible for the metabolic ab errati0ns This study has assessed gallstone risk factors in obese subjects in rel~0n to total fat mass, fat distribution, and glucose and lipid metabolism. M(~hed~ In 57 non-diabetic subj eels without gallstones (mean b ody weight 1134kg~ total and intra-abdominal fat masses were measured resp e m v d y by dual X-ray absorptiametry, total bodyp0tassium counting ~nd abdominal CT scanmng. The lith0gen index was measured in aspirated bile The gall bladder v01ume was deterrraned by ultrasound and the ej ection fraction by dynarac ch01escinl~graphy. Plasma CCK concmtrati0ns during a meal were measured with a specific radioimmunoassay. Insulin sensitivity, oral glucose tolerance, and serum lipid c0ncmtratians were 3iso measured. Rmult= The ~all bladder volume in the fasting state correlated with intra-abdeminal fat mass (p = flOOd) and was increased in subjects with impaired glucose tolerance (41 vs 27 ml, p = 13.00I). The gall bladder motility was normal as juged by cholesdntigraphy CCK con caatratmns in plasma p caked later in 0b ese ;ubjeas. The lithogen index was ab ore 1 in all subj eas and correlated (r= 0.66) w/th total fat mass (10 = 0.04). Omdusi~s: An obese, glucose int01a'ant patient with intraabd0mmal fat accumulation is predisposed to gall stone formataon 0wing t~ supersaturated bile, large gall bladder volume, and a ddayed CCK resp0nse to food.

PMo577

PMo579

R. Linke, K Tatsch, W. Mfinzing, K. Hahn. Department of Nuclear Medicine, University of Munich, Germany

t.Grzukam C.Un'avar, M Mglazim@,lu, E Uyanlk, M. Burak, S.Erol, N.Yenice, T.Ozpaqacl. Okmeydam Hospital, [ztanbul, Turkey

QUANTIFICATION OF GASTRIC MOTILITY IN DIABETICS: A SENSITIVE METHOD FOR DIAGNOSING GASTRIC DYSFUNCTION?

THE IMPORTANCE SCINT[GRAPHY IN DYSFUNCTION.

Scinfigraphi¢ assessment of gastric emptying is an established method to prove gastrointestinal involvement in diabetes mellitus (DM). Quantification of gastric emptying (GE), however, points only indirectly to the underlying nerval dysfunction. Therefore, aim of this study was to investigate, whether quantitative analysis of gastric peristalsis might be a better parameter for detection of functional impairment due to DM. In 22 pts with insuline-depending DM and 15 controls conventional GE-studies (emptying rate, Tv2) were performed (400ml semisolid oatmeal labeled with 40 IvIBq Tc-99m sulfur-colloid, dynamic acquisition for 40 minutes, 64 x 64 matrix, LAO). Additionally, a short dynamic sequence (140 images ~i 3see) was acquired. The latter was used to generate condensed images, on the basis of which the amplitude and frequency of gastric contractions was determined by Fourier analysis. 6/22 diabetics showed normal GE (NE), in 16/22 GE was delayed (DE). Compared to controls in both groups significantly reduced contraction amplitudes were observed, even though this finding was more pronounced in pts with DE. There were no significant differences between controls and DM-pts regarding the frequency of gastric contractions. N Frequency p* Amplitude p* Empt.-rate p* *comparedto controls (rain-1) (%) (%lmin) Controls 15 3,1-+0,2 29-+ 8 2,8-+1,0 Diabetes(total) 22 3,3_+0,3 ns 12_+ 8 <.01 1,9_+0,8 <.01 Diabetes(NE) 6 3,4_+0,3 ns 16+13 <.05 2,9_+0,8 ns Diabetes(DE) 16 3,2_+0,3 ns 11+ 6 <.01 1,5+0,4 <.01 The results of our study suggest, that the contraction amplitude may represent a more sensitive parameter for the detection of gastric dysfunction than the evaluation of GE. This assumption is supported by the presence of reduced amplitudes despite GE is still in the normal range. Thus, quantification of gastric motility seems to be the preferable method for early detecting impairment of gastric function in patients with diabetes mellitus.

1176

OF THE

HEPATOB1LLARY SYSTEM DETECTION OF PYLORIC

It is known that pytoric dysfunction goes with enterogastric reflux (EGR). EGR is seen incidentally in hepatebiliary system scintigraphy (HBS). In order to evaluate the diagnostic value of EGR in the diagnosis of pytoric dysfunction, th/s study was planned Twenty patients, 12 female, aged 19 - 55 (30,5 -/+ 8.4), diagnosed as pyleric dysfunction with EGR on endoscopy were included to the study. A HBS with 5 mci Tc-99m HIDA was performed to all the patients, on morning times and in fasting state. Thirty minutes dynamic data and 60th, 90th., 120th.minute static images were obtained on anterior position. The activity accumulation on the area of stomach or on the left lateral side of liver, appearing after the first activity seen on duodenum was accepted as EGR. EGR determined by this way, divided into two subgroups comparing the stomach activity to the left lobe liver activity at 60th minute. Equal or higher stomach activities accepted as high degree EGR; Lower stomach activities could be determined in high contrast set up accepted as low degree ERG. ERG was found in only 10 out of 20 patients;. Six patients showed high degree, 4 patients showed low degree EGR. The sertsitivity of the HBS was 50 % in the diagnosis of EOR and pyloric dysfunction. On the patients with nonspecific gastrointestinal complaints, It is useful to lengthen the HBS to determine EGR and pylorJc dysfunction, on the tame and the contrast set up explained above, even though hepatic uptake and biliary excretion and passage were normal . The HBS is the only method to asses EGR on the patients unsuitable for an endoscopic examination; but, it can not be used for the screening of EGR and pyloric dysfunction with its low sensitivity of 50 %.

•

G a s t r o e n t e r o l o g y / H a e m a t o l o g y , Miscellaneous

PMo580 St. Lourens, M. Voigt, B. K. Adams Departments of Nuclear Medicine, Universities of Berne, Switzerland and Cape Town, South Africa; Liver Research Centre, University of Cape Town, South Africa GIANT HEPATIC CAVERNOUS HAEMANGIOMA SCINTIGRAPHIC PORTRAYAL OF PATHOPHYSIOLOGY SUPPORTS SURGICAL INDICATION In a prospective study of 45 patients (21 male), mean age 54 years (range 21 to 75) with hepatic mass lesions by 99rnTc erythrocyte pool scintigraphy, of 25 haemangiomas found in 18 patients, 13 were larger than 4 cm in diameter as assessed by US and/or CT. The great majority of hepatic cavernous haemangiomas are small, asymptomatic and discovered incidentally. While the size of haemangiomas ranges from a few millimetres to greater than 20 cm in diameter, in unselected autopsy and clinical series the majority are less than 4 cm in size. Lesions exceeding 4 cm in diameter have been defined in the literature as massive or giant cavernous haemangiomas. Clinical studies have reported symptomatology developing only in patients with liver haemangiomas exceeding 4 cm in diameter, associated with the exertion of pressure on or displacement of adjacent viscera and organs by these large lesions, or due to congestion, thrombosis or infarction with stretching and inflammation of Glisson's capsule. While the asymptomatic incidentally discovered hepatic cavernous haemangioma can safely be observed with serial studies, large symptomatic and complicated haemangiomas and even asymptematic lesions larger than 4 cm in diameter, should be considered for resection, owing to the increased incidence of central necrosis, acute haemorrhage into the lesion and possible rupture, either spontaneous or induced by blunt abdominal trauma. The large number of giant haemangiomas detected in this prospective study shows that this entity is not uncommon. Scintigraphy alone is effective in demonstrating the pathophysiology of these massive lesions, in particular the expanded vascular pool and extremeJy sluggish flow of blood and thereby the high potential for complications, Scintigraphy therefore provides a pathophysiological basis for the indication for excision, particularly in the context of asymptomatic lesions.

PTu582

N. Topuzovi~, * V. RupEi~, A. Rusid, B. Krstono~iE,L Karner, Departments of Nuclear Medicine and of *Itemodialysis, Osijek Clinical Hospital, 31000 Osijek, Croatia BLOOD VOLUME CHANGES AFEER LONG-TERM CORRECTION OF ANEMIA WITH RECOMBINANT H U M A N E R Y T H R O P O I E T I N (EPO) I N P A T I E N T S ON MAINTENANCE HEMODIALYSIS The purpose of this study was to evaluate blood volume changes in chronic hemodialysis patients after long-term correction of anemia with recombinant human erythropoietin (EPO). Twenty three patients (12 males, 11 females, mean age 38 _+ 10 years) with severe renal anemia (hematocrit < 0.25) and on hemodialysis (mean duration 5.8 _+ 3.7 years) were studied: (1) basally, before EPO treatment; (2) short-term, at the time when target hemoglobin (Hg) reached 100 g/l; and (3) long-term, after 12 months of therapy. Blood volume was measured with Tc-99m-labeled h u m a n serum albumin using the method adjusted and validated in our laboratory. At the beginning mean Hg was 72 + 7 g/l, increased to 110 _+ 11 g/1 during 3.7 _+ 1.4 months and was maintained thereafter. Redcell volume significantly increased from 11 _+ 2 to 15 + 3 ml/kg in short-term, and 14 _+ 3 ml/kg, p<0.0001, in long-term study. Plasma volume significantly decreased from basal 46 +_ 9 to 43 +_ 7 ml/kg in short term, p<0.02, and further decreased to 37 + 6 ml/kg in longterm study, p<0.001. In contrast, total blood volume remained unchanged in short-term study (57 + 10 vs. 58 + 9 ml/kg, p=NS), whereas in long-term study it was significantly reduced to 52 + 8 ml/kg, p < 0.001. In conclusion, red-cell volume increased within a short time after anemia correction in chronic hemodialysis patients, followed by a decrease in plasma volume, but total blood volume only decreased after a long-term treatment.

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Haematology, Miscellaneous PTu581 I. Brandhorst, B. Schulze, B. Backenkbhler, V. Jacobi, G. Hbr. Institute for ECT Imaging, Neu-lsenburg; and J.W.G.-University Hospital Medical School, Frankfurt; FRG. FUNCTIONAL BONE MARROW SCANNING, T4-LYMPHOCYTES AND LYSOCYME BLOOD LEVELS IN HIV* PATIENTS.

The static and functional bone marrow scanning using 99mTcHSAMM is well known as a good, noninvasive, one-step tool to evaluate the bone marrow status and its functional rethiculoendothelial parts. Furthermore, it is a simple procedure to find out focal lesions due to opportunistic tumors and/or infections. The aim of our study was to evaluate 1. the attachment, 2. the ingestion and 3. the degestion of HSAMMs on the sessile bone marrow macrophages in comparison to the "l'4-1ymphocytes and the lysocyme blood levels in HIV pts.. In 25 patients (22 males, 3 females, mean age 36 years [HIV*, LAS, AIDS]) we performed time activity curves of the bone marrow [ileo sacral region] over 40 min., starting with injection of 5,55 MBq 99mTc-HSAMM/kg BW. The time activity curves served for the calculation of {1}T½acc [min], {2}fl el [%] und {3}f2el [%]. For the normals (n=24) we found eadier the following data (mean/SD): {1}= 1,99/0,46; {2}= 4.14/1,33; {3}= 10,02/2,96. In our LAS pts. (n=12) we found for {1}= 2,87•0,57; {2}= 2.1110,44; and {3}= 6,13/1,77. In the 7 HIV* pts. still clinically unsuspected we showed already a moderate functional defect of the sessile bone marrow macrophages [{1}= 2,01/0,51; {2}--" 3.01/0,40; {3}= 8,11/1,61], and in 6 AIDS pts. the attachment of the HSAMM had not been finished until the end of the data acquisition with no chance to define {2}flel and {3}f2el. so far. Furthermore, in all over 6 pts. we found a pathological bone marrow status with expansion/focal defects. In our opinion these results show cleady the sense of functional bone marrow scanning in HIV* pts. to depict the early involvement of the macrophages in HIV infections, as the role oft the functional macrophage defect is still the most interesting point in this disease today, even for a possible later therapy controlling.

Q. PTu583

s._

Grillenber,qer KG, Heitmann M, Reske SN. Department of Nuclear Medicine, University Hospital, Ulm, Germany TC-99M-HMPAO LABELLED HUMAN PLATELETS: IMPROVED LABELLING PROCEDURE, IN VITRO RESULTS AND CLINICAL APPLICATION The lipophilic Tc-99m-HMPAO (hexamethylpropyleneamineoxime) complex has been developed originally for brain imaging. Due to a rapid incorporation into blood cells it can be used for the labelling of platelets for scintigraphic detection of thrombotic diseases or to determine platelet survival. The most important advantages over In-111 labelling are the easy availability of the radionuclide coupled with lower radiation doses on account of the shorter half-life. In this study we investigated the influence of the main labelling conditions on the labelling yield. Therefore we varied the temperature (room temperature or 37 °C), the incubation medium (buffer or normal saline), the incubation time (10, 20, 30, 40 min) and number of the washing steps (0x, lX, 2x). After centrifugation the activity bound to the platelets was determined by a gamma counter. The vitality of the labelled platelets was examined by collagen aggregation test and hypotonic shock reaction. Raising the temperature to 37 °C led to no significant increase in labelling yield whereas performing the reaction in normal saline was more efficient than in tyrode buffer. The reaction was almost completed after 30 rain and one washing step was sufficient to achieve a labelling yield of more than 83 % The in vitro tests showed a remaining vitality of about 70-80 %. In conclusion we were able to obtain a 20 % increase in the yield of Tc-99m-HMPAO labelling of platelets by optimizing the labelling conditions. The simple procedure takes not more than 90 min, can be realized aseptic and provides labelled ptatelets with high vitality. 1177

(/) 0 13.

•

Haematology, Miscellaneous

PTu584

PTu586

M. Pap6s, Z. Borb6nyi, L. Tr6n, A. CserMti, L. P~ivics, E. Ambrus, G. Varga, L. Csemay Albert Szent-Gy6rgyi Medical University, Department of Nuclear Medicine, 2nd Department of Medicine, Department of Radiology Szeged, DOTE PET Centre Debrecen, Hungary

D. Vassileva, E. Piperkova*, Y. Jechev, K. Nikolova. Department of Nuclear Medicine, National Centre of Clinical and T r a n s f u s i o n a l H a e m a t o l o g y , *National C e n t r e of Oncology, Sofia, Bulgaria.

FDG PET AND MIBI SPECT IN DETECTION OF RF~IDUAL TUMOR MASS IN LYMPHOMAS The diagnostic value of the FI8-FDG PET and Tc99m-MIBI SPECT was investigated for detection of residual tumor mass following the therapy in lymphomas. Five patients with Hodgkin disease (HD) and 3 patients with highgrade non-Hodgkin lymphoma (NHL) were examined. Following the therapy (combination of chemotherapy and radiotherapy in 6 and chemotherapy only in 2 of them), on the basis of CT investigations, residual tumor mass was suspected in all of the patients, confined to 19 regions. Clinical or laboratory activity signs were found in only four cases. PET investigations (multiple scans) of the suspected regions were carried out following administration of 222-518 MBq (365 MBq on average) F18-FDG. Early and late planar and SPECT studies were also applied, using 720-804 MBq (738 MBq on average) of Tc99mMIBI. PET and SPECT investigations were taken within a week. PET revealed active tumor mass in all of the patients, localized in 18 of the suspected 19 regions. Three occult lesions were also detected by PET. Pathological MIBI uptake, however, was found in only 5 patients (in 4 with HD, and in 1 with NHL). Lymph node involvement was detected confined to 3 regions. The size of the MIBI positive lymph nodes ranged in 2-5 cm. Two organ manifestations of HD (spleen and lung) were also visualized using MIBI. Conclusions: FDG PET examination is a beneficial tool for detection of residual tumor mass in HD and NHL patients following therapy. MIBI SPECT investigation can not replace the FDG PET in these cases,

111- In- O X I N E L Y M P H O C Y T E S C I N T I G R A P H Y PATIENTS WITH M A L I G N A N T L Y M P H O M A S

IN

In patients with malignant lymphoma, exact staging is very important for the treatment and prognosis of these patients. The purpose of the present research was to asses the sensitivity of 1 l 1In-oxine-labelled lymphocyte scintigraphy in the detectetion of malignant lymphomas. The lymphocyte suspenson was preparated by Polysep density gradient and labelled with 5,5-11,1 MBq 111-In -oxine. The images were performed on a DIACAM gamma camera (Siemens) 24 and 48 hours after intravenous injection of labelled lymphocytes. Planar scintigraphy and SPECT were carried out in 10 patients. All patients had been verified staged by histology and imaging methods (CT, chest X-rays, abdominal ultrasonography). In 9 of the 10 patients with non-Hodgkin's lymphoma a positive scintigram was obtaind. The one negative scan occurred in patient with palpable and enlarged lymph nodes. The mean target to background ratio calculated 24 hours after injection of 111-lnoxine-labelled lymphocytes was 3.2 (range 1,8-4,9). In one patient was detected additional, previously unsuspected lesion in abdomen. In 9 patients with a positive scan, the results could be compared with the data of conventional images. In conclusion, our results indicate the potential usefulness of the l 1 l-In-oxine-lymphocyte scintigraphy to visualize tumour involved lymph nodes and extranodal malignant tissues in patients with malignant lymphomas.

PTu585

PTu587

K. Nikolova, E. Piperkova*, U. Jechev, . D. V a s s i l e v a Department of Nuclear Medicine, National Centre of Clinical a n d T r a n s f u s i o n a l H a e m a t o l o g y , * N a t i o n a l C e n t r e of Oncology, Sofia, Bulgaria.

Lintunen P, Savolainen S Koponen I, Jokelainen 1, Liewendahl K* Department of Physics, Univeristy of Helsinki (POB 9, FIN-00014 Helsinki University), *Laboratory Department, Division of Nuclear Medicine, Helsinki University Central Hospital PLATELET KINETICS IN NORMAL SUBJECTS AND PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

67-GALLIUM - SPECT IN L Y M P H O M A WITH GASTRIC INVOLVEMENT ( P r e l i m i n a r y study). Accurate staging of Hodgkin's disease (HD) and nonH o d g k i n ' s l y m p h o m a (NHL) is i m p o r t a n t for treatment menagemeut.The gallium scan (GS) is significant indicator of disease activity. Both Hodgkin's disease and non-Hodgkin's lymphoma may involve gastric wall.Traditionaly fibrogastroscopy has been used to detect such involvement. The present study aimed to show the value of 67-galliumSPECT in lymphoma patients with gastric involvement. W e evaluated 30 patients with proven lymphomas using Oa67 citrate (17 with HD and 13 with NHL). All patients had b e e n verified histologically and staged by i m a g i n g methods. Whole body images were obtained at 48 h and 72 h after i.v. injection of 185 M B q (5 mCi) 67-Ga-citrate on a rotating g a m m a - c a m e r a D I A C A M ( S i e m e n s ).Due to increased 67-Oa uptake we identified 28 lesions and two of them were in gastric region.After that these lesions were verified by fibrogastroscopy as a gastric involvements.One of them was with H o d g k i n ' s desease and one - with nonH o d g k i n ' s l y m p h o m a . T h e 6 7 - G a s c a n f o u n d gastric involvement before other diagnostic methods. We can concluded that 67-Ga scintigraphy will be an useful and sensitive method for detecting gastric localisation of malignant lymphoma.

1178

Three healthy volunteers were studied with l 11-In-labelled platelets. Dynamic ima~ng was performed for 40 rain. The results from healthy subjects were compared with data on patients with ITP. The exchange rates between blood and spleen (liver) were calculated using compartmental analysis. Blood samples were taken at 15 rain, 30 min, 1 h and 3 h after the injection and thereafter 1-2 times dally for 5 days. To determine the mean platelet survival time a mono-exponential function was fitted to the blood data. The spleen/liver activity ratio was calculated as the geometric mean of anterior and posterior counts/pixel in ROIs. The mean blood platelet count in healthy subjects was (240+40)x 109 L"1 and in ITP patients (58+10)x109 L-l (n=21). The mean survival times were 175+6 h and 52+8 h, respectively. The mean spleen/liver ratios for normal subjects and ITP patients were 13-+4 and 8.5-+1.4 as calculated from data derived one hour after injection. The spleen/liver ratio decreased with time, but fluctuated during the first day after injection. Platelet recovery was higher for normal subjects (62-+4%) than for ITP patients (42+3 %). The peffusion index (area under blood curve up to maximum divided by area of spleen curve) was 4.3_+2.3 and 22_+4 for normal subjects and patients, respectively. Interestingly, the splenic and hepatic transit times as derived from deconvolution analysis were similar for normal subjects and ITP patients. It is concluded that platelet survival rime, recovery and compartmental transfer coefficients are clinically the most relevant parameters reflecting pathology of the platelets in ITP. More complicated models (deconvolution, complex compartmental) are error-sensitive because of difficulties in collecting optimal data matrixes and therefore a robust single mono-exponential model for platelet survival is clinically more reliable.

• PTu588 Irina A.Kuzminova, Institute of Medical Radiology, Department of Radiation Medicine

Haematology, Miscellaneous

PTu590 G Blomqvist, V Grill, M Gutniak, M Lindqvist, S Stone-Elander, L Widen. Departments of Clinical Neurescience and Endocrinology, Hospital, and Karolinska Pharmacy, Stockholm Sweden

AGE-DEPENDENT C H A R A C T E R I S T I C S OF LIPID METABOLISM DISTURBANCES IN PATIENTS, ~ O TOOK P~RT IN THE CHERNO3YL ACCIDENT CLEANUP in depth investigation of the serum lipid spectrum was performed in 152 men who took part in the Chernobyl accident cleanup in 1986-1987 and were exposed to ionizing radiation in the dose range of 10-25 cGy. All patients were divided into two general age groups, i.e. 30-39 years and 40-49 years. The characteristics of lipid metabolism disturbance was studied by determining and calculating the following biochemical parameters: general cholesterol, triglycerides, high, low and w e r y low density lipoproteins, and the cholesterol a t h e r o g e n e i t y coefficient. Comparative age analysis has shown that 66% of the patients of the younger age group (30-39 years) during I0 years after the accident are developing changes in lipid metabolism, w h i c h are c h a r a c t e r i z e d by a considerable increase of a t h e r o g e n i c lipoproteins (both low and v e r y low d e n s i t y ) , c h o l e s t e r o l and triglycerides under the b a c k g r o u n d of reduction of antiatherogenic lipoproteins (types IIa, IIb, IV of dyslipoproteinemia, which are not characteristic for this age group). In the p a t i e n t s of 40-49 years of age, 60% developed less m a r k e d disturbances of their lipid spectrum (IIa type of dyslipoproteinemia) though their incidence exceed 3.4 times the mean population standards for similar age group. Thus, the risk of early atherosclerosis development is higher in the persons e x p o s e d to small doses of ionizing radiation at a y o u n g e r age. Evalution of blood lipid s p e c t r u m can be r e c o m m e n d e d for early diagnosis of a t h e r o s c l e r o s i s in the follow-up of patients exposed to radiation from Chernobyl.

Karolinska

ON THE CONNECTION BETWEEN GLOBAL CMRglc AND CMRO2 The cerebral AV-differences of oxygen, glucose, and lactate have been measured in 14 healthy controls and 7 subjects with insulin-dependent diabetes mellitus. For the same subjects CBF was measured with positron emission tomography using [11C]fluoromethane as tracer. The AV-differences, and the metabolic rates of oxygen, glucose and lactate were compared between the subjects. It was found that the AV-differences of oxygen and glucose were not proportional, but the ratio between AVDO2 and AVDglc decreased with increasing AVDglc. A similar lack of proportionality was observed between global oxygen and glucose consumption. These data could be roughly described by the regression line CMRO2 = 15.0 + 0.37,CMRglc (r = 0.72). The results indicate that the fraction of glucose which is oxidized decreases with increasing total CMRglc. The lactate production was found to increase with increasing CMRglc but, in accordance with previous findings, only a small part of the discrepancy between glucose end oxygen consumption could be explained by the observed lactate production. The global decrease of the fraction of glucose oxidation, found in this study, is analogous to the corresponding regional effect which has been observed previously (1,2) by PET during regional stimulation of the brain. (1) P Fox et a[. Nonoxidative glucose consumption during foca~ physiologic neural activity. Science 341:462-464, 1988 (2) G Blomqvist et at. Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography. Acta Physiol Scand 151:29-43,1994

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PTu589 F. Barbano, G. Valle, S. Modoni, G. Polite, E. Perrone, G. Gorgoglione*, V. Frusciante. Nuclear Medicine and * Neurology, "Casa Sollievo della Sofferenza", Scientific Institute, San Giovanni Rotondo (FG), Italy.

PTu591

99mTc-DIPHOSPHONATE WHOLE BODY RETENTION (WBR) AND SCINTIGRAPHY IN CAMURATI-ENGELMANN'S DISEASE.

O l ~ i ' m ~ Standard te,:hniq~e ~ox _~ral,.~ti~ o5 tubal patenof indu,'/es H ~ t e ~ o ~ a t p m ~ p h y d lapa~os¢opes and ch=ornotubatio~. Hovmmvm,,all these techmque~ aze still ~e~ physiologic in that the con~za~t is int*od~ed th~o,.~h (ervi,~ ~ndez positix~e pzessuze, potentially dem~dzatmg tubal pate~,~ which may~ot be zele~,'~t to the ~em~al ph~iolo~c ~'ne:.hanim'noi ~pe~ tm~dez, In pzese~t workwe ai~ ~oz= oE*a.mi~atio~d ov~=ia~ ze~latio~ o~ f~mctio~alD.11opian tube patens'y, • Quanfificati~-, of mdiotzacez Fallopian tt&al tzansit tir~e (TTT) iv tooth ,wm~al a~d fen~ale~vAth ~m~.plai~ed i~eztility, • E~alu~tion of ft~ctional Fallopian tube ol~sfzu.¢tionas a possible ca,~e of ~e~plam~cl i~fe~tility, Mmthe~= Thb s t a y in¢l~led 1~5 female patienb with ~e~plsbed infe~tilih I a_~well a-~4-5a~-mat~hed ~--~t~ob,All paztidpants v~ze ~ul~e:_fed to ~sdien~lide HS~ b e ~ day~-16 d theizm~tzusI ~/~le~~ i ~ 1 0 MBq

Camurati-Engelmann's disease (also known as Progressive Diaphyseal Dysplasia-PDD) is a rare autosomal dominant hereditary disorder clinically characterized by painful and weak lower extremities, myopathy, waddling gait and cortical symmetric thickening and sclerosis of the diaphyses and metaphyses of the long bones. Exophtalmos, Raynaud's phenomen and hepatosplenomega~y are also frequently associated. Laboratory studies are usually unremarkable and diagnosis is generally reached on the basis of the radiologic features. Scintigraphic studies in PDD are limited to few cases and show increased tracer uptake in long bone shafts. We performed 99mTc-diphosphonate wole body retention (WBR) and scintigraphy in a 20-year-old woman with (both clinically and radiologically) proven Camurati-Engelmann's disease. The scintigraphic observed pattern showed an increased but roughly dishomogeneus increased uptake of the radiopharmaceutical in both upper and lower limbs long bone shafts. A value of 70.88% was observed at diphosphonate WBR studies (normal value ± sd = 47.0 + 8.12%) as a conseguence of the increased bone deposition. Thus diphosphonate WBR can be regarded as a simple, non invasive, safe and useful quantitative method to assess the activity of the disease. Further studies are in progress to evaluate diphosphonate WBR changes after therapy.

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h~tezosa).pin~:,scmti~aphic (MS$) evaiuati~, of fMlopm~, tubes patent:/" a~d ph.~iolo~v in ~orcnal a~d patients with ~e.plained i~feztility 0 Shawki* s~d A E1-Tawil

DeFt o50lo/C.%~~and N,J,:leaz Medicine, Cairo L~ive_zsity.E~%rpt

of Tc-9~ M A A of5-40F in dia~etaz placedon po~tezio*va~i~=l Jorni~,Sezial antenoz pelvic~aum~a cameza imaczs were obtained at 5 rnm, i-~tezv~Isap to o~e he~ and eve~/ho~ ~p to4 ho~s. A delayed 24ho~s ima~es,*~eretak~ if requ/~ed, l~sulb were zelated to the scno~zephicallydetern'i'ned d~,i~ant ~ollicle.

lZamlb: Dominaot follicle sided functional tubal patenqr wa~ observed i~ 48145 (97%) of nom~al ~{th ~,ea~ TTT 10-4 rain, as v~ll a~ ~4/18~ (40%) of patients with then mea~TTT]lO+_lOmim(p>0,O5), F~mctional Fallopia~ tube ,.~bstz,_,,'_ti,.,~,~s '~ ob~e~;,ed i~ 60% (8~/135) e5 pati~t.~ ~with ~e~plained infeztility. ~ = HSS isa si~ple,~ou-irwadve,sensitivea~dvalusble method fez

e~al~tion of Fallopia~ tube patentF and phy~iolo~ps"i~ patie~t~ with ,m~e~plainedinfe*tility,

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• Haematology, Miscellaneous PTu592

PTu594

(~etinkale, Mustafa Demir, Haluk B. Sayman, Fadd Ayan I. U. Cerrahpa~a Medical Faculty, Departments of Nuclear Medicine & Emergency and Burn Unit, lstanbul, Turkey O~uz

EFFECTS OF ALLOPURINOL, IBUPROFEN AND

K.M.Klr,*~.Dingel, E.~bi~, A.Akin, G.Tokuz,*Y.Z.M~ft~o~lu A n k a r a University, School of Medicine, Dept. of Nuclear Medicine, *Dept. of Urology, Ankara, Turkey

CYCLOSPORINE-A ON LOCAL MICROCIRCULATORY DISTURBANCIES DUE TO THE BURN INJURIES

R A D I O N U C L I D E P E N I L E B L O O D F L O W S T U D I E S IN THE D I A G N O S I S O F I M P O T E N C E D U E TO A R T E R I A L INSUFFICIENCY

This experiment was designed to study the reactions in surrounding area of injury that was leading to further necrosis in 24 hours after burn. During the inflammatory process of the bum, white blood cells, especially neutrophils adhere to or the emigrate through vascular wal]. Besides causing a partial obstruction of the vessel, they have also recently been implicated as a potential source of oxygen free radicals mediating injury in postischemic tissues. It has been postulated that free oxygen radicals contributed to the cellular damage in the zone of stasis. To prevent extension of burn size into the adjacent tissues, progressive microvascular damage was attempted to be reduced by different drugs in a rat model, lbuprofen, allopufinol and CyA were tested if this progressive isehemia could be prevented. Ibuprofen, besides being a cyc[o-oxygenase inhibitor, is also known to inhibit the release of oxidants from neutrophils and decreases lipid peroxidation. Allopurinol is a xaothine oxidase inhibitor that decreases oxidant release by the ischemia repeffusion injury. CyA probably is a modulating agent of neutrophil infiltration in acute inflammatory conditions. To evaluate the effect of these drags on microeirculation and perfusion of panniculus carnosus muscle underIying burned area, a radioactive agent, Te-99m M1BI was used. Capillary permeability was also studied by establishing wet and dry ratio of the full-thickness tissues taken from zone of coagulation and stasis. There was no significant difference between control and ibuprofen treatment groups in terms of Tc-99m-MIB1 uptakes. It was apparent that panniculus carnosus bad more per'fusion in interspaces of allopurinol and CyA treated groups when compared with control group.Though pretreatment with allopurino} and ibuprofen resulted in no significant reduction, CyA effectively reduced water content of burn sites compared with controls In present study, the results have showed that all drugs have some effects to prevent further ischemia and capillary compromise.

In order to evaluate the impact of radionuclide penile blood flow studies on the differential diagnosis of impotence, we studied 47 patients (Aged b e t w e e n 20 to 70) who had various causes of erectile dysfunction. Patients were injected stannous blood pool agent, 20 minutes later a tourniquet was applied to the basal p o r t i o n of the penis to prevent arterial inflow, 60 mg of papaverine hydrocloride was injected intracavernosally. Necessary lead shielding were applied around the penis. After 5 minutes 20 mCi of Tc-99m pertechnatate was injected and i0 minutes d y n a m i c images was started (Isee/frame). During the acquisition when p h a r m a c o l o g i c a l effect of p a p a v e r i n started, the tourniquet was released. At the same time 5 cc blood samples were withdrawn from antecubital vein. After completing the dynamic study, the injector which contain blood samples were imaged in same geometry. On dynamic images ROI's were drawn around the penis and time activity curves were generated and initial p o r t i o n of the curves which showing arterial flow were quantitated. Psycogenic impotent patients were used as a control group (No:lS), the values more then 20 m i / m i n / 1 0 0 g r tissue was accepted as normal. There was s i g n i f i c a n t l y lower blood flow values in patients who had arterial insufficiency (No:f3). There was good agreement between Doppler ultrasonography and radionuclide study results. As a result, radionuclide penile blood flow study is a simple, reliable and noninvasive test in the evaluation of impotence.

PTu593

PTu595

S. Glatz, Kotzerke J., Moog F., Kern P.*,Reske S.N. Department Radiology III (Nuclear Medicine) and Medicine*, University of Ulm, Germany POSITRON-EMSSION-TOMOGRAPHY WITH ISF-FDG IN EVALUATION OF ALVEOLAR ECHINOCOCCOSIS

Alveolar echinococcosis (AE) is caused by the parasitic cestode Echinococcus multilocularis. Clinical manifestations are due to proliferation of larval cyst masses with primary lesions in the liver. In spite of the low prevalence and incidence, AE is a severe disease with a high morbidity and lethal outcome if not treated adequately. Early detection of AE is impeded by the lack of distinct clinical symptoms and mainly relies on immunodiagnosis and standard imaging techniques (i.e. ultrasound, CT or MRI). A non-invasive technique to visualize parasite viability would greatly improve early detection and follow up of AE patients under chemotherapy. We thus examined the feasibility of 18FFDG-PET to assess increased glucose utilization in the liver caused by the parasite in eight patients who had well-documented AE with liver involvement demonstrated by US and CT. Diagnosis was confirmed by histopathology in all but one cases. PET scans were performed using a Siemens CTI (ECAT 931-08-12) PET Scanner. After fasting state of at least twelve hours 290 + 70 Mbq ZSF-FDGwere injected intravenously. Transmission scans were done in all patients using a 68Ga/rSGe ring source. Emission scans were performed covering the whole liver and reconstructed by Schmidlins iteration in eight steps. All patients showed focally ! radial increased 18F-FDG uptake in the parasitic liver masses. Six patients with extensive lesions showed additional central defect with marginal radial ~SF-FDG accumulation. Quantitative analysis was performed using standardized uptake values (SUV) which varies between 2,1 and 4,7 (mean 3,16). We conclude that 18F-FDG PET seems to be feasible for detection of metabolic active larval tissue. ~SF-FDG accumulation in granulation tissue represents a potential drawback of the method concerning specificity of AE detection which might be solved by using parasite specific radiopharmaceuticals in our further investigations

1180

K~M.KIr, F.Berk, *A.Er~gen , G.Aras, G.Erbay, A.Akin A~kara University, School of Medicine, Dept. of Nuclear Medicine,*Dept.of Plastic & Reconstructive surgery, Ankara, Turkey LYMPHOSCINTIGRAPHY IN THE E V A L U A T I O N O F L Y M P H A T I C F L O W C H A N G E S O N THE S K I N G R A F T S : AN EXPERIMANTAL STUDY A l t h o u g h there are many studies about arterial and venous flow changes in skin graft area, there is not enough study showing lymphatic flow changes. In order to study lymphatic flow changes, a total of 20 New Zeland rabbits were operated and 8x4 cm skin grafts were obtained on epigastric (Group I) and dorsal(Group II) area bilaterally. Tissue expansion technique were applied in i0 animals. After injection of 0.8 to 1 mCi T c - 9 9 m Dextrane subcutaneusly, a dynamic study obtained for 60 minutes (15 sec/frames) and static images were also obtained at 0,70,90 and 120 minutes. ROI's were drawn around the injection sites and the time activity curves were generated o n dynamic images. Same ROI's were drawn on each static images and decrease of r a d i o a c t i v i t y by the time indicating lymphatic flow were calculated for each area. Same study protocol were applied at baseline (2 days before operation), 0, 5 and 15 p o s t o p e r a t i v e days. A biopsy from the graft area was obtained at different time and e v a l u a t e d h i s t o l o g i c a l l y staining with ercein dye to show lymphatic channels. Lymphatic flows were decreased at 0 and 5th days of operation compared to baseline values and returned to baseline levels at 15th day. Decrease in lymphatic flow were more prominent in expanded skin graft areas. As a result lymphoscintigraphy may be used to determine skin graft outcome and prediction of fibrotie changes.

• Haematology, Miscellaneous/Infection PTu596 B.

Malkowski,

P.

Jurowski,

R.

Cos,

W.

Tryniszewski,

Z. Maziarz, A. Rozej. Dep. of Nuclear Medicine and Ophthalmology Military Medical Academy ,I/xlz, Poland. CAN THE POST TRAUMATIC PE~RFUSION ABNORMALITIES CAUSE 7HE DI~CES OF VISION. SPECT STUDIES IN OPHTHAI/
Infection PMo599 D.M. Goldenberg, C.M. Pinsky, F.L. Datz, S.J. Harwood, R.W. Quenzer, C. Hung, B.J. Barton, L. Lamki, Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Newark, NJ; Immunomedics, Inc., Morris Plains, NJ; Univ. of Utah, Salt Lake City, UT; Dept. of VA Medical Ctr., Bay Pines, FL; Univ. of New Mexico, Albuquerque, NM; Rancho Los Amigos Medical Center, Downey, CA; Dept. of Radiology, Div. of Nuclear Medicine, Univ. of Texas, Houston, TX, USA PHASE-III TRIAL RESULTS OF LEUKOSCAN IN THE IMAGING OF INFECTION AND INFLAMMATION Purpose and Methods: Multicenter clinical trials of over 300 patients with bone or soft tissue infection/inflammation have been conducted with LeukoScan®, a 99~Tc-labeledanti-granulocyte (NCA90) Fab" fragment (MN-3). Comparisons were made to white blood cell (WBC) imaging, and "truth" determined by histopathology or microbiological cultures. Results: Reliable imaging was obtained at early times (1-2 or 5-8 h), and no immune responses (HAMA) were found. In 176 patients with suspected osteomyelitis, LeukoScan showed a significantly better sensitivity than WBC imaging (87.7% vs. 72.6%; p=0.O03, McNemar's Test), whereas all other performance criteria were similar for the two methods. In a series of 50 patients with suspected acute atypical appendicitis, all 12 patients proven to have appendicitis were positive with LeukoScan. Of the remaining 12, 7 with positive scans had other abdominal inflammations, 3 had non-inflammatory conditions, and 2 were indeterminate, thus indicating a high sensitivity and specificity for lower abdominal infection/inflammation. Conclusion: This new imaging test appears to be safe, rapid, and at least as accurate as WBC imaging, without the risks attendant to handling patient blood.

c-

o

i m

eItl ID

PTu598

PMo600

RaVen A., Sugtargi6 J. Institute ofOncology, Ljubljana, Stovenia

J. C. Hun,q, S. Chowdhury, and B. P. Mullan

HISTORY OF NUCLEAR MEDICINE IN SLOVENIA

Nuclear Medicine, Department of Diagnostic Radiology, Mayo Clinic, Rochester, Minnesota, U.S.A.

The beginnings of nuclear medicine in Slovenia date back in the year 1954, when J.Satler at the Medical Clinic in Ljubljana first used radioiodine (131-I) for diagnosis. In 1955, L. Savnik at the Institute of Oncology in Ljubljana (IO) injected 198-Au colloid intraperitoneally for the treatment of malignant disease. These attempts gave rise to the departments of nuclear medicine at the University Medical Center and at IO in Ljubljana. After 1960, five nuclear medicine departments were established in different regional hospitals of Slovenia: in Slovenj Gradec (1960), Celje (1968), Maribor (1973), Sempeter near Gorica (1974) and Ankaran (1974). From 1954 to 1974, Slovene nuclear medicine, which was initially more or less a research-oriented activity, gradually developed into a clinically applicable science. Until 1970, the main radiopharmaceutical used for diagnosis and therapy was 131-I, while measuring and imaging equipment consisted of uptake probes and rectilinear scanners. 1970 marks the onset of a decade of rapid development induced by the introduction of radioimmune tests as well as by new devices such as gamma cameras, computers and Tc-generators. After 1980 this rapid progress has slowed down. Today, Slovenia with its 2,000,000 population has seven nuclear medicine departments, which were established before 1974.. Four of them have SPECT equipment. Annually, 45.000 radiopharmaceutical applications are performed for diagnostic and 500 for therapeutic purposes.

THE USE OF STABILIZED Tc-99m EXAMETAZIME TO RADIOLABEL LEUKOCYTES WITH THREE LEUKOCYTE SEPARATION METHODS

ID

The U.S. Food and Drug Administration recently approved a stabilized Tc-99m exametazime preparation with methylene blue and sodium phosphate buffer mixture. Although the methylene blue stabilizer extends the shelf life of Tc-99m exametazime to 4-6 hr post reconstitution, the dark blue appearance of the mixture of stabilized Tc99m exametazime and blood components makes it impossible to properly separate out the leukocyte button. The purpose of this study was to evaluate the feasibility of using stabilized Tc-99m exametazime to radiolabel the separated leukocytes employing one of the following three methods: volex sedimentation (VS), hypotonic lysis with sterile water (HL), or single density gradient FicolI-Hypaque (specific gravity=l.08 g/ml) with hypotonic lysis (FL). Isolated leukocytes from an 80-ml donor blood sample were mixed with 0.5-ml stabilized Tc-99m exametazime (~925 MBq, 125 I.Lgexametazime) and incubated at 25°C for 15 rain. After incubation, two washings with 3 and 9 ml of 12.6% ACD/NS (anticoagulant citrate dextrose, solution A, USP, mixed with 0.9% NaCI, v/v) were conducted to ensure removal of free activity without disturbing the white cell button. With the addition of 9 ml of 12.6% ACD/NS solution to the 1-ml bottom portion from the first washing, the supernatant of the centrifuged preparation was clear enough to be withdrawn. The labeling efficiency of labeled leukocytes with the VS, HL, and FL methods were 88.0+1.1%, 85.0+3.0%, and 86.9!-_4.2%, respectively (n=3). The in vitro stability studies (n=12) showed that 98.0!-_0.9% (VS), 97.7+1.0% (HL), and 98.4+0.8% (FL) of activity still bound to the cells during the 6-hr evaluation period. Cell viability of all labeled leukocyte samples was confirmed by the trypan ~oluestaining technique. In conclusion, leukocytes separated by the VS, HL, or FL method can be effectively labeled with stabilized Tc-99m exametazime by using two washing techniques. 1181

O IX

•

Infection

PMo601

PMo603

A . M . Catafau. A. Iranzo, A. Flotats, M. Estorch, L. Bern,5, J. Pujol*, J. Martf, I. Carri6.

NUCLEAR MEDICINE AND LEPROSY (L). Braga FJHN(1); Foss NT(2); Merchior Jr E(3); Tfouni E(4). Sec. de Medicina Nuclear. Centre of Image Sciences(1); Dermatology Div(2);The Ribeirg.oPrete School Meaicine; Health Secr(3); Chemistry Dep(4), Fac Phyl Science. USP Ribeir~toPreto BRAZIL.

Hospital de Sant Pau and MR Center of Pedralbes*. Barcelona, Spain. ROLE OF 201 -THALLIUM SPECT, CEREBROSPINAL FLUID PCR AND MR SPECTROSCOPY IN THE MANAGEMENT OF CNS LESIONS IN AIDS PATIENTS: PRELIMINARY RESULTS.

The aim o f this study is to evaluate the usefulness o f 201TI-SPECT, polimerase chain reaction for toxoplasm in cerebrospinal fluid (CSF PCR) and MR spectroscopy in distinguishing infections from tumoral processes (lymphoma) in AIDS patients with CNS lesions. Six AIDS patients who presented symptomatic CNS lesions have been studied (4m, 2f, mean age 3 5 . 5 + 6 . 2 yrs, mean time from HIV infection 5.8_+3.9 yrs, mean CD4# 31.6_+24). Empiric antitoxoplasm treatment was started upon their admission to the hospital. Data on toxoplasm serology (Tx serology), CSF P C R and 201T1-SPECT were obtained in all patients. Spectroscopy was available in 3 patients. SPECT was performed 20 rain after iv injection o f I48 MBq (4mCi) o f 201TI, using an Elscint-Helix cammera. Spectroscopy was performed using the P R O B E - S V method with a G E Signa-System 1.5 Tesla. Final diagnosis was established by response to treatment and/or histology. F o u r patients had a good response to antitoxoplasm treatment and positive Tx serology. One o f them showed 201Tt uptake in 1 of 2 CNS lesions seen at CT, with no further data in 1 month o f follow-up. T w o patients had a poor outcome. One o f them had positive Tx serology and showed 201T1 uptake in 1 o f 2 lesions seen at CT, but histology was not conclusive, showing gliosis. The remaining patient had negative Tx serology, but showed no 201TI uptake. This patient denied permission for biposy. Spectroscopy showed the same pattern in the 3 cases (1 with good response to treatment): Increase o f fat resonances and decrease o f normal metabolits. C S F P C R was negative in all cases. These preliminary results suggest a better role for 201TI S P E C T than for C S F P C R or M R spectroscopy in the clinical m a n a g e m e n t o f AIDS patients with CNS lesions.

L is a chronic infectious granulomatous disease caused by M,/cobacterium leprae, an intracelIulary parasite which has a strong positive nenrotropism. It is a milenary worldwide spread disease and is more frequently found in developing countries, Statistics vary between 1.8 and i2 million people affeted by L nowadays. Nearly all organs may be directly or indirectly affected by the disease, the skin being the most frequent site. We have already shown that Ga-67 concentrates in L lesions(l), Radioisotopic specific studies may be used to evaluate particular organs and systems. The aim of this abstract is to start using these specific studies in L patients (pts). KIDNEYS are frequently affected by secondary amyloidosis and renal function may be studied both with 99mTcDTPA and 99mTc-MAG~. We have studied 5 Iepromatous L pts with DTPA, both before and after treatment. In all cases, the arterial peak and the accumulation phase were reduced and the elimination phase was delayed in the pretreatment (PrT) evaluation. Studies were normal after therapy (POT,4 months). TESTES - 99mTcO4 studies were performed in 3 pts, before and after treatment. All of them were abnormal (increased bilateral blood flow and moderate bilateral uptake after 15 minutes) PrT. Studies were normal PoT (4 months). LUNGS - Authors still do not agree whether lungs may be affected by the bacillum or not. Nevertheless, in our previous study (1) it was shown that I pt had abnormal Ga-67 and gluco-heptonate lung uptake. LIVER AND SPLEEN - In a series of 10 pts, 99mTc sulphur colloid studies showed hepatomegaly (2 pts) and spIenomegaly (4 pts); in all of them the distribution was homogeneous indicating, probably, a reactienal process rather than infection by the bacillum. EVALUATION OF MUTILATION - Very frequent in the past, mutilation is still found nowadays, mainly in pts with long stories of the disease. We have studied 4 mutilated pts (2 without the nose and 2 without a foot)using 99mTc MDP, One of the foot-lacking pt had a discrete increase in the blood flow phase and normal uptake in the affected extremity but tibia uptake of MDP was heterogeneous and there was a focal moderate uptake abnormality in the distal third of the bone. The contralateral tibia was also abnormal with a focal uptake in the mid third of the bone. This indicated that the extremity of the mutilated leg was Iree of bacilli but there was disease in other areas of it. The nose-Iacking pts and the other thin-lacking pt had normal bone studies. IN CONCLUSION. specific nuclear examinations may be a good tool to evaluate the functional state of different organs and systems m L pts (t) Galliumscmdgraphyin Hansen'sdisease.Bragaet al. Eur J NuciMed. 1992

PMo602

PMo604

H.KAYA, M. ELEVLt, A.~OBANER, A. CEVIZ, A. YARAMI~, K. HASPOLAT, M OZAYDIN,

E. G. Eising,

Departments of Nuclear Medicine, Neurosurirgy, Pediatry and Pathology, Faculty of Medicine, Dicle University, Diyarbak~r, Turkey.

J. Sciuk

Clinic for Nucl. Ned., Univ. of Essen,

Germany

INVESTIGATION OF EFFICIENCY OF THE INTRATHECAL UROKINASE ADMINISTRATION WITH RADIONUCLIDE ClSTERNOGRAPHY IN THE HYDROCEPHALUS PROVOKED BY TUBERCULOSIS

PROBLEMS IN D E F I N I T I O N OF NORMAL RANGES IN ENZYME IMMUNO ASSAYS (EIA) DETECTING HUM/EN-ANTI-MOUSEANTIBODIES (HAMA) IN PATIENTS A F T E R A D M I N I S T R A T I ON OF MURINE M O N O C L O N A L A N T I - G R A N U L O C Y T E A N T I B O D Y NAB BW 250/183 ('MAGAB')

Tuberculous (tbc) meningitis is one of the serious complications of the tuberculosis and frequently resulted in hydrocephalus. In this study we aimed to investigate the efficiency of radionuctide cistemography (RCG) in patients with obstructive hydrocephalus provoked by tuberculosis, undertaken intrathecal urokinase therapy besides the anti-tuberculous (anti-tbc) therapy. Twenty seven patients diagnosed as tbc meningitis with physical examination and laboratory findings (ppd skin test, chest x-ray, lumbar puncture, biochemical and bacteriological finding's etc...) were included in this work. Their ages were 4 months- 8 years (average is 26.7 months). Cranial computerized tomography (CT) was applied to all patients before and after therapy. Although 18 patients had undergone only anti-tbc therapy, 9 patients had received intrathecal urocinase therapy (5000 or 10.000 IOU/kg) beside anti-tic therapy. Before and after urokinase therapy circumference measuring of the heads, cranial CT and RCG of all patients were performed. RCG was utilized after Jntrathecat injecting of 0.3 mCi of Tc 99m-DTPA and anterior, posterior, right and left lateral views were obtained at 1 hr, 3 hr, 6 hr and 24 hr post- injection with 3 min. static images. Counts per pixel were obtained over the total cranium, right and left hemispheres by drawing regions of interest (ROIs) at the anterior images, Before and after urokinase therapy percentages of the transition to the subarachnoid space (TSS percentage) were calculated in all patients, The difference between TOSS percentage of before and after therapy was statistically significant (p<0.05). Eighteen patients who received only antitbc therapy were indicated in ventriculo-peritoneal shunt operation because of the development of hydrocephalus, in spite of these, £ patients who received anti-tbc therapy + urakinase therapies were not indicated in shunt operation. We concluded that in early period of tbc meningitis development of neurological complications and hydrocephalus may be decreased with intrathecal urakinase administration besides anti-ibc therapy and CSF circulation is able to investigated easily with RCG.

HAM_A-development after a d m i n i s t r a t i o n of M_AGAB can damage later scintigraphical imaging by capturing the labeled M/Ib in the reticulohistiocytary system. EIA can help to detect H A M A in such patients. In this prospective, controlled study, our experiences with the EIA Enzygnost H A M A micro ® are reported. 30 patients underwent scintigraphy with 450 M B q MAGAB. H A M A titers were m e a s u r e d before and 24h, 14d, and 28d after a d m i n i s t r a t i o n of MAb (as lab results of inflammation). If a HAM/{ value exists before M A G A B administration, doubling of individual H A ~ - e l e v a t i o n has to be considered as significant HAM/~development (according to recommendations of manufacturer), w h i c h could be stated in one patient with persistent H/dVIA-elevation up to 28 days. But all patients didn't reach i~ times the positive standard (as recormmended normal range for patients without p r e c e e d i n g H/LMA determination) and showed normal tracer distribution. Therefore, the lack of H/hVaA-titer before actual scintigraphy diminishes sensitivity in HAMA detection. On the other hand, very high HAN_A titers with the risk of severe image alterations can be diagnosed without existing follow-up of }£A_M/~ titers.

1182

•

Infection/Lung

PMo605

PMo607

M. Liberatore*, AP. Iurilli*, F.Ponzo*, D. Prosperi*, L. Rizzo ° ,F Speziale°,P.Fiorani°,A.CentiColella * . *Dept. of Experim. Medicine, Section of Nuclear Medicine and °Dept.of Vascular Surgery, University of Rome "La Sapienza".

N.Prandlm, L.Massan , L.Feggi, A.Sclnavl , G.Massml . Dept of Nuclear Medicine, S.Anna Hospital Dept of Orthopaedic*, University, Ferrara - Italy

THE INFEclED M]RK)F~43RAL GRAFr:EVAI/IkTICN OF THE ~

I/,~F_,~(IJ 15"/"99ra~--Ht~.zO-~rx]:rn ~

OF

SCAN (r~E~s).

In selected cases, in situ graft replacement (IS
DbkGNOSlS OF BONE INFECTIONS RELATED TO AN ORTHOPAEDIC DEVICES: VALUE OF 99mTe-HMPAOLABELLED LEUKOCYTE SCINTIGRAPHY. Orthopaedic surgery causes postoperative alterations of bone marrow that are responsible of a specificity lack of leukocyte scintigraphy (LS) in the diagnosis of periprostheses infections. Some authors, using a combination with sulphur colloid, demonstrated an improved accuracy of LS In our experience LS 1 hour after iv injection - produces a better image of bone marrow and can substitute sulphur colloid combination Forty-three cases with suspect infection of orthopaedic devices were studied by LS: 33 hip and 1 shoulder prostheses, 6 with femur and 3 with rachis devices. Seventeen of the cases were studied with 99roTe sulphur colloid scintigraphy. MDP three phase's bone scintigraphy was performed in 26 patients. All the LS that satisfied one of the three following criteria were considered positive: a significant focal increasing of leukocytes in bone marrow in late imagings - 3 and 20 hours after injection - or every leukocyte's uptake in soft tissues, both in periprosthetic tissues or in regional lymph nodes. In all cases a bacteriological or clinical assessment was obtained: 21 devices were infected, and 22 were uninfected. The sensitivity and specificity of LS were of 100% and 95%, respectively with only one false positive case. LS and sulphur colloid showed concordant imagings in all but 3 cases: 2 resulted FP and 1 FN by sulphur colloid. Three phase's LS had an accuracy of (97%), higher than sulphur colloid combination (88%), and higher than bone scintigraphy alone (79%). Our method is accurate in diagnosing infections after orthopaedic implant of bony and joint's devices. Sulphur colloid combination can be avoided saving time and money.

C

D..

PMo606

PSu608

E. Varo~lu, H.. U s l u , A. ~ o l a k , O. B a y k a l Departments of Nuclear Medicine and Ophtalmology, A t a t f i r k U n i v e r s i t y , Medical S c h o o l , E r z u r u m - T u r k e y

CH. Kao and DL. Hung, Departments of Nuclear Medicine and Emergency, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.

T h e a i m of t h e p r e s e n t s t u d y w a s to e v a l u a t e t h e role o f q u a n t i t a t i v e T c - 9 9 m - H u m a n I m m u n o g l o b u l i n G (IgG) s c i n t i g r a p h y in t h e e v a l u a t i o n o f p a t i e n t s w i t h B e h q e t ' s a n d n o n - B e h ~ e t uveitis. T h i s s t u d y i n c l u d e d 13 B e h g e t ' s D i s e a s e a n d 8 n o n - B e h q e t p a t i e n t s w i t h uveitis. T h e age ranges of patients with Behqet's Disease and nonB e h g e t g r o u p were 3 2 . 4 _+ 1 2 . 2 a n d 2 9 . 8 i 18.2 y e a r s , respectively. T h e s t u d y w a s p e r f o r m e d by a d m i n i s t e r i n g 3 7 0 M B q T c - 9 9 m - IgG i n t r a v e n o u s l y a n d p l a n a r i m a g e s were acquired at the 1st and 3rd hours. For quantitative evaluation, eye/scalp indices were quantified using mean counts of drawing ROIs around e a c h eye a n d o n s c a l p . In B e h ~ e t ' s D i s e a s e , t h e m e a n e y e / s c a l p i n d i c e s were 1.49 _+ 0 . 2 4 a n d 1.57 _+ 0 . 5 3 a t the 1st and 3rd hours, respectively. However, nonB e h g e t g r o u p h a d t h e m e a n e y e / s c a l p i n d i c e s a s 1.81 _+ 0.31 a t t h e 1 s t a n d 1.78 + 0 . 3 2 a t t h e 3 r d h o u r s . T h e r e was a statistically significant difference between B e h ~ e t ' s D i s e a s e a n d n o n - B e h ~ e t g r o u p s w i t h r e s p e c t to e y e / s c a l p i n d i c e s (p<0.05). A s a c o n c l u s i o n , s i n c e lgG uptake of non-Behqet uveitis was greater than that of B e h g e t ' s uveitis, T c - 9 9 m - I g G s c i n t i g r a p h y m a y be u s e f u l in the differential diagnosis of Behget's uveitis from non-Bchget ones.

O

s.._

Lung

THE QUANTITATIVE EVALUATION OF OCULAR INFLAMMATION IN BEHI~ET'S D I S E A S E A N D NONBEH(~ET UVEITIS WITH Te-99mHUMAN IMMUNOGLOBULIN O SCINTIGRAPHY

c-

s._

LUNG VENTILATION AND ALVEOLAR PERMEABILITY IN PATIENTS WITH PARAQUAT INTOXICATION USING Tc-99m DTPA RADIOAEROSOL INHALATION LUNG SCINTIGRAPHIES AND PREDICT THEIR OUTCOMES.

Thirteen patients with acute paraquat intoxication (4 females, 9 males, ages: 18-64 years) were included and immediate Tc-ggm DTPA radioaerosol inhalation lung scintigraphies were performed to evaluate the lung ventilation (LV) and alveolar permeability (AP). Meanwhile, 12 normal volunteers (2 females, 10 males, age: 22-75 years) were studied for comparison. Art of the subjects' chest x-ray findings were normat. The equilibrium LV images were visually interpreted according to the presence or absence of inhomogeneous distribution, inverted base to apex gradient, and segmental defects. The results showed that only 2/13 (15.4%) patients showed significantly abnormal LV image findings, but 11/13 (84.6%) cases were normal. Time-activity curves of Tc-99m DTPA radioaerosel clearance were generated over the right lungs (to avoid interference from stomach activity on the base of the left lungs) to evaluate AP. A power exponential fitting routine was then used to calculate the clearance half time (r1/2) in minutes for the right lungs. The TlI2 in normal volunteers was 94.6_+ 19.1min (56.4-134.6rain). Of the 13 patients, onty 4 (30.8%) had a normal Tl/2 and 9 (69.2%) had a shortened Tl/2. However, none of the 13 cases had a prolonged Tl12 All of the 9 cases with shortened Tl/2 demonstrated abnormal findings in the follow-up pulmonary function test, and 2 of the 9 cases were expired finally. In addition, inverse trend was found between T1./2 with the amount of paraquat intake. However, this trend were not statistically significant. These results indicate that Tc-99m DTPA radioaerosol inhalation lung scintigraphies may sensitively evaluate the lung damages and accurately predict the outcomes in patients of paraquat intoxication.

1183

,4~

(/)

0 la.

• Lung PSu609

PSu611

S.J. Wan~9, C.H Kao, and G.L. Wu. Department of Nuclear Medicine and Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.

W.Y. IAn, M.N. Chen and S.J. Wang. Department of Nuclear Medicine, Taiehung Veterans General Hospital, Taichung, Taiwan.

ABNORMAL PULMONARY FUNCTION TESTS, ALVEOLAR PERMEABILITY AND LUNG VENTILATION IN WOMEN WHO INTAKE SAUROPUS ANDROGYNUS TO REDUCE THEIR BODY WEIGHT.

RADIOAEROSOL INHALATION LUNG SCINTIGRAPHY IN DETECTING SEQUENTIAL PULMONARY EFFECTS AFTER RADIOTHERAPY The tung is one of the most sensitive organs to irradiation. However, the sequent changes, especially the earliest effects, in humans alter irradiation of the hmg are still unclear. In this study, we employed Te-99m DTPA aerosol inhalation hmg scintigraphy (AILS) to evaluate the serial pulmonary changes after radiation therapy in patients with breast cancer. Thirty-nine female patients diagnosed with fight breast cancer were included in this study. All patients underwent simple masteetomy, and post-operative radiation of approximately 50 Gy. None of the patients had habit of smoldng. AILS was performed in supine position. All subjects were told to inhale for 2-3 minutes from a commercial hmg aerosol delivery unit containing 7400 MBq Tc-99m DTPA. Data was colleeted for 30 minutes using a large field computerized gamma camera over the posterior view. The degree of lung damage was presented as the clearance rate (k; %/rain) calculated from the time-activity curve. Only the fight hmg was used to analyze clearance in order to avoid interference from stomach activity on the left side. We divided the patients into three groups according to the intel"val of time between the date of irradiation and the AlLS. In addition, 10 age-matched no1~al women were included as the control group. The results are tabulated as follows:

The use of Sauropus androgynus, a Malaysian food, to reduce weight first happened fashionally in Taiwan since 1994. Some of them developed respiratory distress including dry cough, exertional dyspnea, and even resirtory failure gradually. We investigated the subjects with chest X-ray (CXR), pulmonary function tests (PFT) and Tc-99m DTPA radioaerosol inhalation lung scintigraphies (RILS) which were used to evaluate the lung ventilation (LV) and alveolar permeability (AP). One hundred and four nonamoking females (ages: 18 60 years) was included. Of them, 42 females had resiratory symptoms. Ninety-one females received RILS and 100 females underwent conventional PFT. The results showed [1] all of the cases had normal CXR. [2] 50 patients with abnormal RILS including impaired AP - shortened Tl/2 of Tc-99m DTPA radioaerosols (n = 30), abnormal LV - multiple, focal and subsegmental tracer accumulation or hypoventialtion (n = 40) and both (n = 16). [3] only 19 females had abnormal ventilatory impairment in PFT including obstructive type (n = 14), restrictive type (n = 1) and both (n = 4). Besides, the patients with respiratory symptoms had lower FEVl (P =0.001), FEVl/FVC (P < 0.001), PEF25-75% (P = 0.001), VC (P = 0.002), DLCO (P = 0.009). [4] The amount of dosage was 2.67 -+ 1.89 Kg in recorded 75 cases, and the dosage was roughly correlated with FEV1 (r = 0.38), FEVl/FVC (r = 0.43), PEF25-75% (r = 0.47), VC (r = 0.28) but not with AP, DLCO and TLC. In conclusion, taking Sauropus androgyrus can result in lung injury, manifesting as obstructive ventilatory impairment (shown in PFT and LV) and increased lung epithelial permeability symptomatically or asymptomatically. The Tc-99m DTPA radioaerosol inhalation lung scintigraphy is a sensitive test to detect the mild lung injury. However, the conventional PFT only disclose it in severe cases,

The results suggest that lung damage does occur in the first three months and become worse in 3 to 9 months post approximal 50-C-y irradiation. After 9 months, the clearance rate declines markedly which may result from the recovery of lung tissue from acute irradiation damage or from pulmonary fibrotic change al~er radiation therapy, or from a combination of the two.

PSu610

PSu612

S=_Jc_W._an 9 and C.H. Kao. Veterans General Hospital, Taichung, Taiwan.

N.Kanzaki, T.Akita, S.Dendo, R.Soda, T.Okada, Y,Tanimoto, A.Tamaoki, K.Takahashi, M.Kibata, Y.Hiraki. Department of Radiology, National Sanatorium Minami Hospital, Okayama, Japan

Evaluation

of Lung Ventilation and Alveolar Permeability in Amphetamine Abusers using Tc-99m DTPA Radioaerosol Inhalation and Xe-133 Ventilation Studies. Drug abuse has reached an epidemic level in Asian conutdes, with amphetamine being the most popular cause. The mechanism by which amphetamine vapors and pyrolysis products can injure the lung have not been well defined. In this study, we evaluated 23 amphetamine abusers with radioaerosol inhalation alveolar permeability (AP) and lung ventilation (LV) studies. 18 control subjects (12 nonsmokers and 8 smokers) were also studied for comparsion. Our studies revealed none of 23 drug abusers showed significant abnormal LV image finding. The degree of AP damage was presented as the half-times~-l/2) of the time-activity curves of Tc-99m DTPA radioaerosol lung clearance from dynamic lung images. The Tl/2 for the 7 nonsmoking amphetamine abusers (61.5 ± 18.3 min) were longer than for the 7 smoking amphetamine abusers (27.9-+ 16.9 rain) and 9 smoking amphetamine plus heroin abusers (33.5 -+ 216 min). T1/2 for the nonsmoking amphetamine abusers was significantly shorter (P<0.O01) than for the nonsmoking control group (123.8±28.7 minutes). Tl/2 for the smoking drug users was similar to that of the smoking control group (33.1 17.8 minutes) inverse trends were found between Tl/2 with the amount of amphetamine usage per day and duration of use for all three groups of drug users. These trends between T1/2, however, were not statistically significant. No trend was found between Tl/2 and the time between last amphetamine use and imaging. Our study indicate that Tc-99m DTPA radioaerosol inhalation lung scintigraphies may provide s sensitive and useful assay to evaluate the physiologic effects of amphetamine inhalation in the lung.

No. Time after irradiation Age (yrs) Clearance rate(%/min)_ Control I0 50.6-+6.9 0.73 ±0.13 Group 1 I2 <3 months 49.9-+9.9 0.94_+_024 Group 2 16 3 to 9 months 48.8_+2.8 1.i I-+0.39 Group 3 l I > 9 months 47.9_+7.8 0.69_+0.2I The clearance rates were compared using the Mann-Whimey U rest. Control and Group l: P value = 0038 Group ! mid Group 2: P value = 0.298 Control and Group 2: P '¢aine = 0.002 Group i and Group 3: P value = 0.021 Control and Group 3: P value = 0.401 Group 2 and Group 3: P value= 0.001

Okayama

DOES 1-123MIBG REALLY A C C U M U L A T E IN THE LUNG B R O N C H I A L A S T H M A C O M P A R E D T O O T H E R DISEASES ?

OF

Bronchial asthma is a multifactional disease and many causes are postulated. The cause of bronchial asthma remains unknown. Damaged post-synaptic /3-receptor of the pulmonaly sympathetic system is one of them. 1-123MIBG is a biochemical marker which could monitor pulmonary norepinephrin (NE) metabolism. The aim of this study was to evaluate lung 1-123MIBG uptake in patients with bronchial asthma. A aliquote dose of 111MBq of 1-123MIBG was administered intravenously. 1-123MIBG planar images were obtained twice 15 min(early) and 3 hours (delayed) after injection• 1-123MIBG lung uptake was assessed in 13 patients with bronchial asthma without myocardial perfusion abnormalities (age 4 8 ± 1 5yrs, average+SEM ; 5M, 8 F ), 30 patients with ischemic heart disease (69+_13yrs ; 22 M, 8 F )and 13 controls (67___18yrs ; 5 M, 8 F). Patients complicated with diabetis mellitus were excluded. 1-123MIBG lung uptake was quantified by a lung-to-mediastinum ratio (LMR) on early and delayed images and lung clearance rate (CR) was calculated from both images. In patients with bronchial asthma, both early and delayed LMR did not show any difference to controls, but lung CR (%) was significantly increased (P
• PSu613 H.Hadjikostova, M.H.Denninger, France.

Lung

PSu615 F.Bonnin, G.Jebrak, P.Seknadji, B.Bok. H6pital Beaujon, Clichy,

H.KAYA, A.QOBANER, S. OTQU, M. OZER, D. TOK, T. A. BALCI, A.~AHIN. Dicle University, Department of Nuclear Medicine, Pediatric Surgery and Anaestesiology, Diyarbaklr, Turkey.

WILL D-DIMER TEST (DDT) MODIFY THE INDICATION OF LUNG SCINTIGRAPHY (LS) IN PULMONARY EMBOLISM (PE)? DDT, identifying fibrin degradation products, was assessed in a prospective unselected series of 88 consecutive patients referred to LS for suspicion of PE. This series was also used to intercompare several ways of performing and reading LS images. The final diagnosis (truth) was made independently by a separate panel with all available information including evolution but the result of DDT. DDT was d e t e r m i n e d by ELISA (n<500ng/ml). LS including perfusion (Q) and pseudo-ventilation (Technegas) (V) views were classified a c c o r d i n g to PIOPED criteria i) by the physician on duty 2) retrospectively by a blinded panel for Q and Q+V. Gathering probable (9+,27-) and certain (12+,36-), a positive (P) (21) or negative (N) (63) diagnosis of PE could be achieved in 84 patients, the prevalence of PE being 0.25. Only one false negative was noted on DDT (Se=0.95) and 42 false positives (Sp=0.35) resulting in a PPV of 0.33 and a NPV of 0.96. The proposed threshold for positivity was confirmed by ROC analysis. Emergency and retrospective interpretations of LS were very close (paired t-test: p=0.18). Reading V+Q was more conclusive (the number of "undeterminate" cases dropping down from 35 to 15) and on a subjective scale much easier (p<0.0001) than that of Q alone. In only a minority of cases, PE may be excluded with reasonable safety if DDT is normal, resulting in significant time and money savings. Once prescribed, LS should always include V and Q images.

EVALUATION OF THE EFFECTS OF ACUTE HEMORRHAGIC SHOCK IN LUNG CAPILLARY CIRCULATION BY Tc- 99m-MAA PERFUSION SCINTIGRAPHY Tissue hypoxia is considered to be the most important factor to the mortality and morbidity in the patients with acute hemorrhagic shock. The mechanism of cellular hypoxia during hypovolemia may include decreases in peripheral oxygen transport and microcirculatory abnormalities. The present experimental study examines the hemodynamic efficiency of autologous blood and saline in hypovolemic shock by using Tc 99m-MAA. Forty male, Sparaque Dawley rats (250-275 gr.) wer e chosen as the animal model and they were sedated with intramuscular ketamine (25 mg/kg). The animals were divided randomly into four groups and 10 of them were accepted as a contro ! group. In all groups, carotid artery was canalated., Systemic arterial pressure and body temperature were monitored continuously during the procedure.In groups A, B and C. these parameters were recorded prior to and at five minutes intervals following hemorrhagie. In group A, B and C, systolic blood pressure decreased to 25 mmHg from110-132mmHg. This shock period was terminated after 45 minute. Then resuscitated by heparinized autologous blood (in group A), autologous blood in oxale acetic acid (in group B) and saline (in group C) were done. After the correction of hypovolemia, all animals were injected 100 micro Ci (0.1 cc) Tc 99m-MAA via penil vein, At 15 minutes and 5 hours post injection, 3 minutes static images of posterior position of the lungs were acquired by gamma camera fitted with low energy paralel hole collimator. Two regions of interest (RIO) from the right and left lungs. The Tc-99m MAA clearance rate in lung was determined at 5 hours post injection. Clearance was obtained as 52.0 % in control group, 50.5 % in group A (p>0.05), 4 5 . 1 % in group B (p<0,05), 37.6 % in group C (p<0.001). This result shows that heparinized autologous blood has more significant improvement than blood with oxalacetic acid and saline in lung capillary circulation.

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PSu614

PSu616

S. Pavlovid D. Sobid-Saranbvid, D. Jovanovid, G. Radosavljevi6, W. Ussov, Institute of Nuclear Medicine, CCS, Belgrade, YU, Laboratory of Nuclear Medicine, Tomsk, Siberia, Russia

MF Botelho, JJP de Lima, MA Marques, C Gomes A Silva. Dpt. Biofisica e Processamento de Imagem/IBILI/Fac. Med; Dpt Electro. e Telecom/ Univ. Aveiro; Centro de Pneumologia da Universidade de Coimbra

UTILITY OF TI-20I AND 99m-Tc-MIBI 1N LUNG CANCER NECROSIS DETECTION

STUDY OF THE ALVEOLAR PERMEABILITY USING T H I N 9 9mTc-HMPAO AEROSOLS

T1-201 and 99m-MIBI do not accumulate in necrotic tissue and thus represent agents of tumor viability. We performed T1-20I or 99mTcMIBI planar scintigraphy in 44 patients (pts) with solitary pulmonary nodule or masses in order to assess the frequency of tumor necrosis. One month after performed therapy the chest X-ray was used to evaluate the response of primary lesion to radiotherapy or chemotherapy Twenty pts (group l) were injected with 74 MBq of TI-201 and 24 pts (group2) with 370 MBq of 99mTc-MIBI. Anterior and posterior thoracic images were acquired 20 rain. after injection for 500000 counts per view. In group 1 small cell lung cancer (SCLC) was histologically proven in 4 pts and nonsmall cell lung cancer (NSCLC) in I6 pts, whereas in group 2 of pts SCLC was found in 5 pts and NSCLC in 19 pts (p>0.05). In the first group 18/20 pts (90%) were found true positive and in 4 out of 18 tree positive focal uptake with central necrosis was detected (3 squamous cell and ] adenocarcmoma). In the second group 20/24 pts (83%) were found true positive and focal uptake with central necrosis was found in 5 out of 20 true positive findings (25%). In 4 out of those 5 pts squamous cell lung cancers were proven and l patient was with adenocarcinoma Chemotherapy was performed in t6 pts in both group, radiotherapy in 4, four pts were operated and 20 pts had symptomatic therapy only for extensive primary or secondary lesions. One month after chemotherapy or radiotherapy 5 out of l l pts with focal TLC-201 or 99mTc-MlBl accumulation without necrosis showed decreased tumor volume on chest X-ray film, whereas 8/9 pts with central necrosis were considered nonresponders by chest X-ray. Conclusion: TI-201 and 99mTc-MIBI detected tumor necrosis in 20% (9/44) pts in primary lung lesion. Necrosis may be one of causes for the lack of response to therapy in those patients.

The use of thin radioactive aerosols makes possible to evaluate indirectly the pulmonary epithelial permeability which is altered in a number of lung pathologies with interstitial compromise. The local evaluation of the mean disappearance times of the aerosol activity deposited in the deep lung areas allows the generation of permeability parametric images which, normalized to a previously adopted colour scale have information about the local alteration of the alveolar capillary barrier permeability. A method for the production of very thin aerosols using low surface tension mother solutions and appropriate ultrasound frequencies was developed. Urea was used as the surface tension agent. Particles size averaging 0.2 lam are obtained. After the nebulization, posterior view acquisition of the activity data by a gamma camera-computer system was carried out. A sequence of 64x64 images with 10 sec individual collection times and a total of 20 rain is acquired. With this information, pixel activity/time curves are obtained in the computer and the mean disappearance times (local and regional) are calculated and further available together with the parametric images. The method has been used to study a group of 5 normal controls and 10 patients with pulmonary fibrosis. Decay curves with two exponential components are observed in all the cases studie& When compared with the results of the normal controls, the pathological cases show an increase in the mean decay time in the first exponential term and a decrease in the second component. The results suggest that the first exponential component is related with the alveolo-capillary cellular membrane itself and the second exponential term with intercellular phase.

1185

I1)

O IX

• Lung PSu617

PSu619

G Panoutsopoulos, C Batsakis, G Tourkochoriti*, I nias, D Bofos*, J Christacoponlou. Dept of Nuclear Medicine, *5th Dept of Pulmonary Medicine, "SOTIRIA" Chest Hospital, Athens-HELLAS.

V. Podio,I. Masaneo,T. Angusti,A. Francini,G. Picciotto*,A. Sargiotto*,E. Aluffi°, G. 8isi

INGUINAL LYMPH NODE EVL~GINGWITH GA~;%CITRATEIN PATIENTS WITH SARCOIDOSIS. A THIRD TYPICAL COMMON PATTERN. The aim of the study was to evaluate the possible presence of ancillary findings on Ga-67 scintigraphy enhancing its diagnostic accuracy in the evaluation of sarcoidosis. The already described Panda(P) and Lambda(L) patterns are not always typical concerning the shape of the L and the degree of uptake of the P. Moreover, the P pattern even with bilateral symmetrical hilar lymphadenopathy on the chest x-ray, although highly suggestive of sarcoidosis, is not quite specific. We retrospectively evaluated 381 consecutive abnormal Ga-67 scintigrams of 346 patients with sarcoidosis, diagnosed mostly by biopsy or by typical x-ray findings supported by elevated SACE levels and bronchial washing's cytology. The scintigrams were performed, either during initial diagnosis, or follow-up and disease reactivation, 48 h post IV injection of 111148 MBq Ga67-citrate. In the first 303 of the scintigrams spot views of the head and the thorax had been obtained. The last 78 studies (74 patients), which were whole body- images in anterior view (three peaks window, >1500 Kcts/view), were analysed. The P pattern was seen in 48 out of 78 scans (61%) but only in 17 of them (35%) was intense. On the other hand, although in 63 studies hilar or mediastinal lymph node uptake was seen (81%), only' in 37 scans (47%) the typical L pattern, concerning the shape and regardless of the degree of the uptake, was present. In 32 cases (41%) inguinal lymph node uptake was seen (a typical thin chain of usually 2-4 small lymph nodes), mostly bilaterally symmetrical (n=25, 33%) and rarely unilateral (n=7). This symmetrical inguinal pattern was observed with typical P and/or L patterns in 9 cases, with an atypical appearance of them in 13 cases and with neither of these patterns in 3 cases. Diffuse lung parenchymal uptake (faint to intense) was noted in 15 cases. Finally a few scintigrams showed a variety of abnormal findings e.g. focal lung uptake, unilateral axillary lymph nodes, etc. In conclusion one out of three patients with sarcoidosis and abnormal Ga-67 scindgram presents atypicaI s}anmetrical inguinal lymph node pattern, which may help in the diagnosis of sarcoidosis, especially in the case of at3.pieal Panda and Lambda patterns.

Silent Pulmonary Embolism: High Prevalence in Patients with Deep Venous Thrombosis

Cattedra di M~dicina Nuc/eare- Universit# d~ Torino (1), *Servizio di Medicina Nucleate e °Medicina d'Urgenza - Ospedale Molinette di Torino (f)

Pulmonary embolism (PE) is a frequent complication of deep venous thrombosis (DVT); unfortunately PE could remain unknown since often it occurs asymptomatically. The aim of fhis study was to evaluate scintigraphic lung perfusion pattern in patients with DVT assessed by Doppler ultrasenography. We examined 141 consecutive patients with DVT referred to our Emergency Department. Among these patients, 60 complained signs or symptoms suggestive of DVT, 23 of PE and 58 of both DVT and PE. All patients underwent 99mTc-MAA lung perfusion scan within few hours after admission, According to modified Biello's criteria, scintigraphic patterns were suggestive of high probability of PE in 79/141 pts (56%), of intermediate probability in 25/141 pts (18%) and of low probability in 24/141 pts (17%); 13/141 pts (9%) had normal scan. Among the 60 patienfs with symptoms of DVT and no clinical signs of PE, 35 (50%) had lung scan pattern suggestive of PE (high or intermediate probability). In our experience, in all patients with DVT lung scanning is mandatory, even if they are asymptomatic for PE.

PSu618

PSu620

F.Roqowski, I.Skiba-Choifiska, E.Jaroszewicz, A.Citko, BKiersnowskaRogowska *, D.Jurgilewicz, EOczeretko, T.Budlewski. Departments of Nuclear Medicine and Haematology*, Medical Academy, Bia~ystok, Poland

T. Bury (I), P. Paulus(Z~, T. Weber (z), M.F. Radermecker (I), P. Rigo (2). (i) Pneumology Dept, (2) Nuclear Medicine Dept, CHU Sart Tilman, Liege, Belgium.

THE INFLUENCE OF IMMUNONEUTRALIZATION OF INTEGRtN CD18 AND IMMUNOGLORULIN CD54 ON THE COURSE OF RAT ARDS-LIKE LUNG INJURY. The studied model of rat lung injury was induced by the combined of administration of lipopolysaccharide (LPS) and platelet activating factor (PAF) (Rabinovici et a1.1993.). The experiments were conducted on 22 male Wistar rats devided into the following groups :control (n=6), LPSPAF(n=6), LPS-PAF+mAb to CD18(n=3), LPS-PAF+mAbCD54 (n=3), LPS-PAF+mAbCD18+mAbCD54(n=4). At time 0, either saline (control) or LPS-PAF were injected into the femoral veins. In the last three groups of rats, monoclonal antibodies (Serotec, England) to studied adhesion molecules were infused 10 min. before LPS-PAF (Sigma, USA) administration. Three hours later each rat received on intravenous injection of a mixture of Cr-51 (Polatom, Poland) tagged erythrocytes(RBC), Tc-99m-HM-PAO-labeled leukocytes (IZINTA, Hungary) and J-125 labeled bovine albumin ( I C N , USA). At exactly l h later, the rats were killed. The lungs were dissected and weighed and together with blood samples their radioactivty were determined in a scintillation spectrometer and after drying lung wet-to-dry (W/D) weight ratio were calculated. The degree of lung injury was measured by increased accumulation of Tc-99m-labeled rat granulocytes, vascular permeability (J-125-albumin leakage), haemorrhage (extravasation of Cr-51-RBC) and interstitial oedema (W/D). Obtained results showed significant increase W/D ratio, albumin-J-125 leakage, accumulation of Tc-99m-leukocyte and haemorrhage Cr-51-RBC after LPS-PAF administration in comparison to control. Monoclonal antibodies to CD18 particulary given together with mAb to CD54 nearly norrnalised above parameters except the leucocyte accumulation wich remained unchanged. The above results indicate that integfin CD18 and immunoglobulin CD54 play a more important role in determining the degree of activation, rather than the number of neutrophils in the lung after LPS-PAF administration. Isotopic methods proved very useful for quantitative estimation of lung injury in the model of study.

EVALUATION OF PLEURALDISEASES : PRELIMINARY REPORT

1186

B Y F D G - P E T IMAGING

Positron emission tomography (PET) with 18fluoro-deoxyglucose (FDG) is an accurate method for differentiating benign from malignant disease. We investigated the utility of FDG-PET for the diagnosis of pleural disease in 25 patients. PET study was performed in each subject before an invasive procedure was proposed to confirm the etiologic diagnosis. PET data were analysed by visual interpretation of coronal, sagital and transverse slices. Sixteen patients had a malignant pleural disease and nine had a benign disease. All patients with histologically confirmed malignant disease (3 mesothelioma, 13 metastatic lesions) have shown FDG uptake within the pleural thickening which was intense in 14 cases and moderate in two cases. PET imaging has shown the absence of FDG uptake and correctly categorized 7 non malignant lesions (4 parapneumonic effusions, 1 pleural fibroma, 1 benign asbestos pleural disease, 1 benign neurofibroma). Two patients with infectious pleural diseases (I parapneumonic effusion, 1 tuberculous pleuritis) have a moderate and localised FDG uptake. Conclusion : our results suggest that FDG-PET- is an effective tool in the evaluation of some pleural diseases. Further studies are needed to validate our preliminary descriptions and to develop quantitation programs.

• PSu621 P.Sorce, G.Gusso, R.Spaziante, R.Zecchin, F.Mazza*, F.De Conti*, M.G.Boceieri*, W M a m s °. Department of Nuclear Medicine, *Division of Pneumology and °Institute &Anatomy - Hospital of Pordenone, Italy

Lung/Nephrology

PMo623 W i t h d r a w n by author

')9~Tc-MIBI and pulmonary masses: to be or not to be?

The aim of our work was to evaluate the potential role of 9~Tc-MIBI seintiglaphy in differentiatingthe nature of pulmonary masses, X-ray and/or CT detected and all histologicaUlyproven. SPET studies were performed 30 rain. and 180 rain. p.i. of 740 MBq of Tc-99m MIBI in 133 pts (109 M and 26 F; age ranging 28-81 years), of which 97 affected by malignant tumoral lesions (35 adenocarcinomas, 40 epidermoid carcinomas, 7 small cell carcinomas, 1 cancerabscess, 1 large cell carcinoma, 4 adenosquamous carcinomas, 3 carcinoid, 1 sarcomatoid mesotheliorna, 5 metastases), 10 by benign tumoral lesions (8 condroid hamartomas, 1 solitary fibrous mesothelioma, 1 epithelioid haemangioendothelioma) and 26 by benign (infectious) diseases (3 sarcoidosis, 4 thc, 3 silicosis, 1 abscess, 10 bronchopneumonitis, 5 flogistic outcomes). Studies were interpreted indipendentely by three nuclear medicine specialists and results were expressed as + (clearly positive uptake), - (no uptake) and +/- (mild uptake or significantintensity decrease in the late scan vs the early one). Results were: Early acquisition Late acquisition + +/+ +/Malign. turn lesions Benign turn. lesions Non tumoral lesions

99% 60% 54%

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80.5% 30% 31%

15.5% 23%

4% 70% 46%

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Data showed a high percentage of positive MIBI uptake in malignant tumoral lesions, while a higher percentage of'No uptake" was observed, both at early and late scans, in the non neoplastic group. In conclusion, pulmonary SPET with 9*"Tc-MIBI is a non-invasive method surely useful in the clinical diagnosis and staging of lung neoplasms but still doubts remain about its effective usefulness in differentiatingthe nature of the masses.

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PMo624

Marian J. Surma Nuclear Medicine Department, Medical University, L6di, Poland ANALYSIS OF ERRORS OF ONE- AND M'ULTI-SAMPLE 99mTcEC PLASMA CLEARANCE DETERMINATION Value of clearance is burdened with an error resulting from: inaccurate fit of regression functions to the data obtained from measurments, imprecise pipetting and inaccurate measurements of time at which the blood is sampled. The error may be estimated in two ways: 1. Calculating the total diffrential of the formula defining the clearance and utilizing the variances of the participating quantities. 2. Repeating a number of times the determination of the clearance and directly calculating the mean and standard deviations from the results. As measuring the clearance several times is not feasible, both for physiological and ethical reasons, multiple ,,determinations" were performed in a computer experiment, using Monte Carlo simulations at assumed different accuracy of pipeting and time of blood sampling This experiment provided an alternative method for error estimation of the renal 99mTc-Ethylenedicysteine plasma clearance by a complete method (9 blood samples) and a simplified one sample procedure. The results indicate that the relative error of the clearance determination by multisample method is practicly constant above CI values of 150 ml/min and amounts to ab :k3-4%. For values below 150 ml/min the error increases and reaches ±12% at C1=70 ml/min. The one sample method is less accurate and drops from ±8-9% at 550 ml/min to ab ±25% at 70 ml/min. Moreover, for the multisample method the error estimated from total differential exceeds that obtained from Monte Carlo procedure by a factor of 2 to 3. For the one sample clearance determination both error estimates yield similar results. For both methods of clearance determination this is inaccurate pipetting that makes a dominant contribution to the overall error. For monitoring of patients condition this is the muhisample method that should be employed The use of one sample method shouId be limited for screening tests and for obtaining additional information, supplementing the dynamic scintigraphic studies.

Levent Kabasakal. Tanju Yusuf Erdil, Meltem Ayaz, Saadet Amy, Kerim S0nmezo~lu, Bedii Kanmaz, U~ur Olk~i, llhami Uslu, Haluk B. Sayman ¢etin Onsel.

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Cerrahpa~a Medical Faculty, Nuclear Medicine, Istanbul Turkey.

IX

EVALUATION of Tc-99m-ETHYLENEDICYSTE1NE (EC) in ANURIC HEMODIALYSIS PATIENTS Tc-99m-ethylenedicysteine is a new renal tubular agent. Clinical studies have shown that EC has superior biological and clinical characteristics as compared to those of MAG3. However, clinical experience with EC is relatively limited. The aim of the present study was to evaluate EC in anuric hemodialysis patients and compare the results with those of OIH. For this purpose 10 patients were selected. Plasma clearances of OIH and EC were obtained simultaneously by using open two-compartment model. After injecting 3 7 MBq Tc-99m-EC and 16 MBq 1-131-OIH 13 blood samples were obtained for a duration of 180 min and plasma samples were counted. Mean plasma clearances of EC and OIH were 7.5:~3.6 ml/min and 12.7±4.4 ml/min (p<0.05), respectively with a range of 418 ml/min and 7-24 ml/min. EC/OIH ratio was calculated to be 0.55±0.26 Volume distribution of EC and OIH were 23.5±12 L and 15.7±7.2 L respectively (p<0.05). The plasma half iife was found to be longer for EC as compared to that of OIH (836±525 min and 662±398 min p>0.05). In anuric patients renal clearance is not expected so this study suggested that extrarenal clearance of EC is less than extrarenal clearance of OIH and EC clearance may be more suitable in patients with deeply impaired renal function

1187

• Nephrology PMo625 S.Fant~, M.Dondi, A.Romeo, M.Mareago, C.Corbelli, F.Fallani, A.Palermo, ILGalassi, S.Zoboli, R.Franehi, N.Monetti. Dpt of Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna; Dpt of Nuclear Medicine, Ospedaleper gli Infermi, Faenza; ITALY EVALUATION

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TECHNETIUM-99M-ECD

AS

RENAL IMAGING AGENT, Technetium-99m-bicisate (ECD), commercially known as Neurolite (DuPont) and currently used as brain perfusion tracer, has a fast metabolism after injection to polar end products which are rapidly excreted through the kidneys. ECD may therefore be suggested as a potential tracer for renal scanning, as confirmed by preliminary data in animals. The present study aimed at evaluating ECD as renal imaging agent in humans. Sequential renal scintigraphy (10 see/frame for 20 rain after injection) was dynamically recorded in 22 patients referred for brain SPECT. No patient had a history, clinical symptoms or laboratory signs of nephro-urologic disease. In all patients ECD provided a clear imaging of the kidneys. The radiotracer showed homogenous uptake in the parenchyma; pelvi-calyceal system was visualized 5-8 minutes after injection and ureters were also frequently observed (15/22 pts). The radiotracer, however, showed a prolonged transit through the kidneys (mean parenchymal transit time = 396 + 98 sec). Relevant ECD uptake was observed in the liver; a variable amount of activity was also found in the spleen (early frames) and in the bowel (5/22 pts). Significant asymmetry of renal uptake was found in 2 patients: a renal scintigraphy with Te-99m-MAG3 confirmed in both cases the presence of unsuspected asymmetry of relative renal function. Our data indicate ECD has interesting properties as renal imaging agent, but can not be indicated as a replacement for conventional renal tracer for several reasons (complex kinetics, extra-renal uptake). A possible role may be suggested, however, for performing renography during injection of ECD for brain studies: this approach might add useful information for the assessment of renal function in selected patients.

PMo627 M. Rehling and L.E. Nielsen. Aarhus University Hospital, Section Skejby Hospital, Department of Clinical Physiology and Nuclear Medicine, Aarhus, Denmark. LESS PROTEIN BINDING OF 99mTC-DTPA COMPARED WITH 51CrEDTA AND 1251-IOTHALAMATE 99mTc-DTPA, 51Cr-EDTA and 125I-lothalamate are widely used for measurement of the glomemlar filtration rate (GFR). 99mTc-DTPA has the adventage of being suitable also for imaging and split function measurement. However, it has often been emphasized that commercial DTPA-preparations sometimes contain impuraties that bind to plasma protein, causing errors in GFR measurement. The often very different protein binding results that has been published may be due to true differences, but it may also be due to the various techniques that have been used for determination of protein binding. We have studied the in vitro protein binding of the three radiopharmaceuticals we use for measurement of GFR: 99mTc-DTPA, 51Cr-EDTA and 1251Iothalamate (all three from Amersham). Protein binding was investigated simultaneously with the same technique in the same plasma. Protein binding was determined by ultrafiltration (Centrisart 1, cut of 10000, Sartorius, Germany) after in vitro incubation in patient plasma at room temperature for 40 min. The following fractions (%) of activity were bound to proteins (mean of 16 (± SEM)): 99mTc

51Cr

1.47 (--,-0.42)

4.45 (--.0.38)

125I 3.96 (±0.40)

The protein binding of 99mTc was significantly smaller than the protein binding of 51Ct and 125I (p<0.05). Conclusion: All three radiopharmaceuticals can be used for measurement of GFR but 99mTe-DTPA is the most suitable.

PMo626

PMo628

C. R u s s e l l , E. D u b o v s k y , D i v i s i o n of N u c l e a r M e d i c i n e , U n i v e r s i t y of A l a b a m a H o s p i t a l ; N u c l e a r M e d i c i n e S e r v i c e , V.A. M e d i c a l C e n t e r - - B i r m i n g h a m ; B i r m i n g h a m , AL, U S A

A.G. Irwin. R. Barlow, J.E. A g n e w Hilson. Royal Free Hospital and M e d i c i n e , London, UK.

E F F E C T O F A R T E R I O V E N O U S D I F F E R E N C E IN M E A S U R I N G RENAL FUNCTION BY SINGLE-INJECTION PLASMA CLEARANCE Introduction The d i f f e r e n c e b e t w e e n a r t e r i a l a n d v e n o u s b l o o d s a m p l e s h a s l o n g b e e n r e c o g n i z e d as a s o u r c e of e r r o r in r e n a l c l e a r a n c e m e a s u r e m e n t s . H e r e w e estimate the error when using the single-injection m e t h o d w i t h T c - 9 9 M D T P A a n d T c - 9 9 M MAG3. Methods E r r o r e s t i m a t e s for a r t e r i o v e n o u s d i f f e r e n c e w e r e calculated by two models: a delay time model and a peripheral two-compartment model representing the arm of t h e s u b j e c t , a p p l i e d t o T c - 9 9 m D T P A d a t a f r o m 40 s u b j e c t s a n d T c - 9 9 m M A G 3 d a t a f r o m 19 subjects. Results The two m o d e l s g a v e q u a n t i t a t i v e l y s i m i l a r r e s u l t s . T h e e r r o r in c l e a r a n c e i n c r e a s e d (as a p e r c e n t a g e of t h e m e a s u r e d value) w i t h i n c r e a s i n g c l e a r a n c e , t o a m a x i m u m of 2% for T c - 9 9 m D T P A a n d 1% for T c - 9 9 m M A G 3 at h i g h n o r m a l r e n a l f u n c t i o n . H o w e v e r , t h e e r r o r in c o m p a r t m e n t a l p a r a m e t e r s o t h e r t h a n c l e a r a n c e w a s as h i g h as 20%. Conclusions The e r r o r in T c - 9 9 m D T P A o r T c - 9 9 m M A G 3 c l e a r a n c e c a u s e d b y a r t e r i o v e n o u s d i f f e r e n c e is s m a l l a n d can be n e g l e c t e d w h e n s a m p l i n g t i m e s are a p p r o priate. A m e t h o d of c o r r e c t i o n is p r o p o s e d for other compartmental parameters, based on a twoc o m p a r t m e n t m o d e l r e p r e s e n t i n g t h e a r m of t h e subject.

1188

a n d A.J.W. School of

CAN SINGLE SA~LE (CHRISTENSEN-GROTH) C r - 5 1 E D T A G F R E S T I M A T I O N B E U S E D IN P O O R R E N A L F U N C T I O N ?

In order to instigate a s i n g l e - s a m p l e m e t h o d for measuring GFR on our department, we have i n v e s t i g a t e d a s i m p l i f i c a t i o n of the C h r i s t e n s e n and G r o t h m e t h o d s u g g e s t e d b y W.S. W a t s o n (Eur J N u c l M e d 1992; 19:827). Our aim was to v a l i d a t e t h i s m e t h o d u s i n g real c l i n i c a l data. O u r r o u t i n e m e t h o d for G F R e s t i m a t i o n is the slope-intercept method using 3 blood samples taken at about 2, 3 and 4 hours after i n t r a v e n o u s i n j e c t i o n o f 0.9 2.6 M B q C r - 5 1 EDTA. Our dataset was derived from 200 consecutive patients having routine GFR estimations. Only 3 studies were rejected from t h i s e x e r c i s e as b l o o d s a m p l e c o l l e c t i o n was incomplete. 29 p a t i e n t s (aged 1-88 years) had a slopeintercept G F R of < 30 m l / m i n (range 4-29 ml/min). B a s e d on a sample t a k e n at 4 hours, the single-sample method was compared with the slope-intercept m e t h o d for t h e s e p o o r r e n a l function patients. In all c a s e s t h e s i n g l e s a m p l e m e t h o d a l s o g a v e a G F R < 30 ml/min. C o r r e l a t i o n b e t w e e n the two m e t h o d s for t h e s e 29 p a t i e n t s was g o o d (r = 0.79, p < 0.001). However, out of 14 p a t i e n t s w i t h s l o p e - i n t e r c e p t G F R v a l u e s o f 10-20 ml/min, 4 gave single s a m p l e r e s u l t s > 20 m l / m i n (mean 2 4 . 5 ml/min, range 22.6 - 25.6 ml/minl. W e c o n c l u d e t h a t the s i n g l e - s a m p l e m e t h o d can reliably indicate poor renal function but that d e t a i l e d values in the 10-20 m l / m i n range s h o u l d b e i n t e r p r e t e d w i t h caution.

• Nephrology PMo629 M~ller M.L., Widding A. Departments of Clinical Physiology and Nuclear Medicine, Frededksberg Hospital, and Rigshospitalet, Copenhagen.

PMo631 C. Van de Wide K. Everaert, JP Van Haelst, M. Simons, H. Vereecken, RA Dierckx. University Hospital Gent, Belgium.

REPRODUCIBILITY OF ~TC-MAG 3 - COMPARED TO 9~TC-DTPA RENOGRAPHY: DAY TO DAY VARIATION IN ESTIMATES OF RENAL FUNCTION.

DOES RECIRCULATION OR A BLOCK OF TUBULAR TRANSPORT OF DMSA CONTRIBUTE TO THE DIFFERENCE IN DIFFERENTIAL RENAL FUNCTION AS MEASURED BY D'rPA AND DMSA FOLLOWING COMPLETE UNILATERAL RENAL OBSTRUCTION : A RAT MODEL.

Many departments of nuclear medicine have substituted ~9=Tc-DTPA renography with 99~"Tc-MAGz renography as the method of choice for determination of parameters of renal function. This is primarily due to the much higher kidney uptake of MAG 3 compared to DTPA, resulting in an improved signal to noise ratio. It would therefore be expected that the reproducibility of the parameters of renal function determined by ~r"TCMAG 3 renography would be better than when determined by ~=Tc-DTPA renography. The day to day variation of ~mTc-MAG3 renography was determined in 17 patients with a wide spectrum of S-creatinine values and stable kidney function. The tests were performed with an interval of less than 5 days. These results were compared with an eadier study performed in 27 patients in whom day to day variation of ~r~Tc-DTPA renography had been estimated. The method used for determination of renal function parameters were the same for the two tracers. From the uptake phase of the renograms and the bolus passage through the kidneys, the relative uptake function, the single kidney MAG: or DTPA clearance (GFR), the single kidney renal plasma flow (RPF) and the single kidney MAG: or DTPA extraction fraction (filtration fraction) were calculated. The coefficient of variation for the different parameters were (MAGJDTPA): Relative uptake function 5.3% t 2.9% (p<0.05), single kidney MAG 3 clearance/single kidney GFR 12.4% / 7.8% (p<0.01), single kidney RPF 20.2% / 15.8% (n.s.), single kidney MAG3 extraction fraction/single kidney filtration fraction 22.1% / 15.7% (p<0.05). Conclusion: These results show that though the signal to noise ratio in ~mTc-MAG~ renography is much higher compared to ~mTc-DTPA renography, the parameters of renal function estimated by 99=Tc-MAG3 renography has a significantly larger day to day variation, probably explained by a greater biological variation in RPF and tubular function compared to the variation in GFR. This should be considered when performing comparative or interventional studies.

The consistently higher differential renal function (DRF) values of obstructed kidneys estimated by Tc-99m DMSA when compared to Tc99m DTPA (Kelleher et al., Br J Urology, 1993) in a complete unilateral renal obstruction (CURO) multipapillary kidney model may be an Upper Urinary Tract Pressure (UUTP) dependent phenomenon. To provide indirect evidence for this hypothesis and to exclude recimulation and/or a block of intratubular transport of Tc-99m DMSA as possible alternative explanations, a prospeclive study was performed using a CURO unipapillary rat model. In this setting, after 12-24 h post obstruction, UUTP may be considered normalized, ftence, little difference in DRF as measured by Tc-99m DMSA and Tc-99m DTPA would be expected. In 8 female Wistar rats, Tc-99m DMSA 24h renal uptake values were obtained prior to complete obslruction of the right ureter, serving as reference values. 24 h after obstruction, Tc-99m DTPA (0,5 met) renography was performed, followed by the injection of Tc-99m DMSA : 0,5 mCi in 4 rats and 20 mCi in 4 other rats. Subsequently, Tc-99m DMSA renal uptake measurements were performed at 24 hrs in all rats, whereas in the 4 rats having 20 mCi of Tc-99m DMSA injected, renal uptake was additionally measured at 48 and 72 hrs. Using a Student t test, no significant difference in the interpretation of DRF after obstruction as measured by Tc-99m DMSA and Tc-99m DTPA was found (p>0,2). Additionally, using a paired t-test, no statistically significant difference between DRF of the obstructed kidney as measured by Tc-99m DMSA at 24hrs., 48 hrs. and 72 hrs was found (p>0,2).These data may indirectly support the hypothesis put forward. Furthermore, in the absence of a statistically significant difference in DRF as measured by Tc-99m DMSA at 24h, 48 h and 72 h, recirculation ofTc-99m DMSA as wett as a block of tubular transport are less likely to contribute significantly to the difference in DRF.

c-

o

|m

eID ID x.._

O., PMo630 C De Sadeleer,(2 Van de Wiele K. Everaert, M Simons,RA Dierckx. University Hospital Gent, Belgium.

PMo632 C. Russell, M. Japanwalla, S. Khan, J. Scott, E. Dubovsky, University of Alabama Hospital and V.A. Medical Center-Birmingham, Birmingham, AL,

EFFECT OF DOUBLE BACKGROUND CORRECTION ON DIFFERENTIAL RENAl. FUNCTION AS ESTIMATED BY Tc-99m DTPA, USING Tc-99m DMSA AS GOLD STANDARD

MEASUREMENT OF RENAL VASCULAR TRANSIT TIME AND TUBULAR TRANSIT TIME DISPERSION FOR Tc-99m MAG 3

USA

A retrospective stucly was performed to evaluate : 1) the frequency of differences in DRF (•DRF) expressed as percentage (<5%, between 510% and >10%) as measured by Tc-99m DMSA and Tc-99m DTPA 2) the value of both the am~dratio method ( perimnal ROI + integral method) and the double background correction method (Piepsz el al., JNM 1990) using Tc-99m DTPA as compared to the Gates method in determining DRF. For both aims, Tc-99m DMSA 24h non-depth corrected renal uptake was used as gold standard. Over a period of 2 years, 246 pts referred fro"renal fnnction evaluation were included. There were 130 men (g age 21.6 yls, range 2w-71yrs) and 116 women (!J age 28.2 yrs, range I m-75yrs). In all patients, DRF (R/R+L and L/L+R kidney function) was measured using Tc-99m DTPA (Gates method) and Tc-99m DMSA 24h renal uptake (At between both examinations=24-26b). Additionally, in those patients showing a diflhrence > 10% (non physiological wu-ialion) in ADRF , the area ratio medmd and double background correction method were perfl)rmed. ADRF (Gates) was <5% in 140 pts (57%),.between 5 and 10% in 56 pts (23%)and >10% (l-t 15.03%, SD 5.47%, range 10.59-30.29%) in 50 pls (20%). Using the area/ratio method, A DRF varied from 1.6% to 10.53% (It 4.37%, SD 2.84%) whereas zX DRF using the double background col'ruction varied from 0.47% to 10.16% (it 3.04%, SD 1.47%). In conclusion : 1) using the Gates method, in a large fraction (20%) of patients, differences for aDRF > 10% may be lbund, 2) using Tc-99m DTPA, the double background correction method as suggested by Piepsz et al. allows a more accurate assessment of DRF when compared to the Gates method.

x.....

ID O

Purpose: Renal transit time usually refers to tubular transit time, as introduced by Taplin. However, other transit times have also been defined and reported to have diagnostic value. Here we examine the vascular transit time V T T (similar to that of Rutland) and the dispersion of tubular transit time TTTD (similar to the mean transit time index of Britton) in a group of 30 patients having baseline and ACE-inhibitor T c - 9 9 m MAG 3 renography prior to arteriography. Methods: A same-day low-dose high-dose protocol was used for renography, with only the postcaptopril dose high enough for VTT calculation. Results: Precaptopril, the Spearman rank correlation coefficient for TTTD was p=0.52 (n=53 kidneys, p <0.0002). Postcaptopril, for TTTD, p=0.54 (n=49 kidneys, p <0.0002); for VTT the value was p=0.18 (n=32 kidneys, p not significant). Spearman's p is simply the correlation coefficient calculated from rank in list, which allows nonlinear correlation.) For comparison, the same statistics were calculated for Taplin's original measure of transit time, the time from injection to maximum count rate. Precaptopril, for peak time, p was 0.47 (n= 53 kidneys, p <0.001). Postcaptopril, p was 0.39 (n=50 kidneys, p <0.01). Conclusion: These findings confirm the diagnostic value of TTTD but not of VTT. TTTD c o r r e l a t e d better than peak time with the arteriographic findings.

1189

• Nephrology PMo633 J.J. Hvistendahl, T.S. Pedersen, M. Rehling, E.B. Pedersen, J.C. Djurhuus, J. Froki~r. Institute of Experimental Clinical Research and Department of Nuclear Medicine, Aarhus University Hospital, Denmark. RENAL HEMODYNAMIC AND HORMONAL EFFECTS OF LOSARTAN IN PIGS WITH UNILATERAL URETERAL OCCLUSION. Ureteral obstruction (UO) is associated with an enhanced de novo generation of angiotensin II (AII) from the ipsilateral kidney. We investigated the renal hemodynamic and functional role of the non-peptide angiotensin II antagonist losartan. Female pigs of the Danish land race (35 kg) were operated on, and catheters placed in both renal veins by x-ray. Losartan (2 mg/h/kg b.w.)(n=8)or vehicle (n=6) was administrated to pigs with UO for 8 hours. The following parameters were measured: Bilateral renal blood flow (RBF) by ultrasound transit time, glomerular filtration rate (GFR) in both kidneys (as the renal e x t r a c t i o n of 51Cr-EDTA times the renal plasma flow), ipsilateral pelvic pressure and blood pressure. In addition plasma levels of renin, AII and aldosteron (Aldo) were measured. The results showed that ipsilateral RBF was unchanged in the losartan-treated pigs. However, contralateral RBF increased significantly temporarily from 149±8 to 188±4 suggesting an AII dependent modulation of contralateral RBF during UO. Losartan did n o t change ipsilateral or contralateral GFR response. Plasma AII increased significantly in both groups (5-50 pmol/l), but in the losartan-treated animals plasma Aldo was significantly reduced indicating effective blockade of the ATI receptor. In conclusion the anticipated decrease in ipsilateral RBF and GFR was not affected by losartan suggesting that AII is not the only mediator of obstructive renal vasoconstriction.

PMo634 K. Everaert, C Van de Wiele J. Van de Voorde, J. Delanghe, W. Oosterlinck, R.A. Dierckx. University Hospital Gent, Belgium Tc-99m DMSA ABOLUTE RENAL UPTAKE, URINARY ~-NAG ACTIVITY AND TUBULAR PROTEINURIA AS PARAMETERS OF SEVERITY OF TUBULAR DAMAGE FOLLOWING BILATERAL PARTIAL OBSTRUCTION IN RATS. To evaluate the usefnlnes of combined Tc-99m DMSA scintigraphy, tubular pmteinuria and urinary [3-NAG (beta-N-acetyl glucosa-minidaseactivity) in determining the duration (old or recent) and the severity of tubular damage following bilateral partial obstruction in rats, a prospective study was performed. Twenty-two female whistar rats (190230 g) were included in the study. In eight non-obstructed rats, Te-99m DMSA 24h renal uptake, urinary [~-NAG activity and proteinuria were measured, serving as reference values. The 14 remaining rats underwent a bilateral partial obstruction (BPO) using the method by Ulm et al. Subsequently, Tc-99m DMSA 24h renal uptake measurements were performed l(tl) and 6(t2) weeks following obstruction. Additionally, in all 14 rats, every morning, 5 days a week during a 7 week period, urinary samples were collected and urinary NAG activity and tubular proteinuria measured. The decrease of absolute Tc-99m DMSA uptake at t2 was correlated with NAG activity and tubular proteinuria. Both urinary" NAG activity and tubular proteinuria were significantly higher immediately after BPO (45.5.+28.2 U/mg creat, vs. 58.1.+25.8 Umg creat.(p<0.04) and 39.8_+110.9 mg/mg creat, vs. 108.8-+ l l8.2mg/mg) and remained so for 2-3 weeks. After 2 weeks there was a tendency to normalisation. The decrease of absolute Tc-99m DMSA uptake at t2 of the right (RK) and left kidney (LK),( 27.6-+7,1% RK and 27.4_+7.7% LK vs.13.03_+6.8 RK and 24.4% .+9.95 LK) correlated (r=0,5) with the increase of [3-NAG activity and tubular proteinuria. In conclusion,the combined use of Tc-99m DMSA, urinary p-NAG activity and tubular proteinuria allows estimation of the duration (<2-3 weeks onset, if urinary 13-NAG and tubular proteinuria m'e elevated) and severity of tubular damage following BPO in rats.

1119o

PMo635 N. Czech 1, U. Huebner 2, k. Pollak 1, M. Baehre 1, E. Richter 1, 1Clinic of Radiotherapy and Nuclear Medicine, 2Clinic of Pediatric Surgery, Medical University of Luebeck, Germany RELIABILITY OF FUNCTIONAL RENAL SCINTIGRAPHY WITH 1231-HIPPURAN IN EXTREME UNILATERAL HYDRONEPHROSIS OF INFANTS Introduction: Despite numerous clinica~ trials which proved the reliability and precision of the assessment of renal function by scintigraphic means there still remains some scepticism on the pediatric's side regarding the obtained values especially in cases of severe hydronephrosis. Therefore, the preoperatively measured unilateral kidney function (UKF) determined by renal functional scintigraphy was compared with the postoperative excretory capacity (PEC). Patients and methods: 55 infants with a unilateral hydronephrosis III ° due to ureteropelvic or ureterovesical junction stenosis were included. The range of age at the time of operation varied from nine days to 10 years. Renal sequential scintigraphy was performed in all cases preoperatively and in 22 cases postoperatively, using 1231-hippuran (minimum 5 MBq, maximum 10 MBq; 1 MBq/kg body weight) after 30 minutes followed by injection of furosemide (0,5 mg/kg body weight). PEC was measured separately for each kidney by renal urine volume and specific gravity via catheterization of ureter and bladder. Results: a) 43 of 55 infants with a preoperative UKF of the hydronephrotic kidney in the range of 40-59 % (median 47 %) also presented a normal unilateral function in the PEC within 5 days. b) A delayed normalisation exceeding 5 days was observed in 12 cases with preoperative pKF between 12-37 % (median 3 1 % ) . c) tn 14 of 22 children who were investigated twice surgery did not alter the scintigraphic results significantly. [n the remaining 8 patients with a UKF ranging from 15-48 % (median 38 %) the follow-up scan shewed recovery of function of more than 5 %. Conclusions: There is no doubt that 1231-hippuran renography provides reliable results and no overestimation even in cases of unilateral hydronephrosis caused by ureteropelvic or ureterovesical junction obstruction. Renal 1231-hippuran scintigraphy is the most important preoperative diagnostic method.

PMo636 I. Szilv~isi, K. Buga, E. Szule', Z. Nagy Dept. of Nuclear Medicine and Dept. of Urology', Haynal University, Budapest

COIV[PARISON OF INDIRECT DYNAMIC RADIONUCLIDE CYSTOGRAPHY AND NON-ISOTOPE UROFLOWMETRY IN PATIENTS WITH LOW URINARY TRACT DISORDERS The aim_of our study was to validate indirect dynamic radionuclide cystography (DRC) by comparing with the standard gravimetric uroflowmetry (UFM). 12 patients with various urodynamic distrurbances were examined. Methods: after hydration and voiding conventional dynamic renal scintigraphy was performed after i.w injection of 100 MBq of Tc-99m-ethylenedicysteinate (EC). After the renal study all the patients underwent DRC and UFM simultaneously. Patients were sitting on the gravimetric uroflowmetric apparatus connected to a microcompter in front of a LFOV digital gamma camera. Pre-(and post-)voiding 15 s static images were taken. Dynamic study was started, 2 seconds frames in 128x128 matrix were collected for 5 minutes. Parameters defined by renography were: Tmax, T 1/2 of the descending phase, parenchymal and total mean transit time values. Parameters of the DRC were: total voiding time (TVT), maximal and average emptying rate in per cent of the bladder-volume (MER and AER) of the bladder defined by analysing activity-time curve &the bladder. Residual volume &urine in the bladder was calculated too. Parameters of the UFM were: TVT, MER, AER in ml/minParametric images & t h e bladder during micturition were also created. Results: close correlation was found between values determined by isotopic and non-isotopic method for all three dynamic parameters. Our conclusions: UFM is essential to diagnose and characterize urodynamic disorders. Dynamic renal seintigraphy should be performed in this group &patients for evaluating renal parenchymal funtion. ARe~renography the DRC is a simple and - based on our preliminary results seems to be a - reliable technique for follow-up studies of micturition dynamics. The radionuclide method is useful in detecting vesico-ureteral reflux and calculating residual volume.

•

Nephrology

PMo637

PMo639

A. Pe~ari~, Z. Petrovi~, A. RaVen, I. Slodnjak, University Medical Centre Ljubljana, Department of Nuclear Medicine

PF Kao 1, KY Tzen 1, CB Shieh 2, DL You I 1 Department of Nuclear Medicine, Chang Gung Memorial Hospital and 2 Department of Pediatric, Taipei Municipal Hospital, Taipei, Taiwan, Republic of China.

CYCLIC DIRECT RADIONUCLIDE CYSTGRAPHY IN COMPARISON WITH CONVENTIONAL (ONE CYCLE) CYTOGRAPHY Vesicouretal reflux (VUR) is the most common abnormality found in children with urinary tract infection (UTI) .According to different authors it is present in 22% to 52% of the children with UTI. It's detected by X-ray voiding cystourethrography (VCU) or by radionuclide voiding cystography (RVC). The purpose of this study was to establish the sensitivity of cyclic direct radionuclide cystography in detecting VUR in infants and small children and to compare it to the conventional (one cycle only) RVC. 428 patients (with 856 renal units) were included to the study. Cyclic RVC was performed in all cases. The age of the patients ranged from 4 months to 7 years. Children were catheterised under aseptic conditions using a small fringe aspiration catheter (outer diameter 3.3/2.4 mm) and the bladder was ~mptied. 99~Tc-O4 was added to sterile isotonic-saline in concentration of 40-80 Mbq/1000 ml warmed to normal body temperature and bladder was slowly filled to maximum capacity. Child voided around the catheter which was not removed. The second filling through the same catheter was started shortly after the first voiding. A gamma camera with low energy all purpose collimator was used and the data were recorded continuously from the beginning of the first cycle until the end of the second voiding at a rate of 1 frame/5s in supine position in posterior projection in matrix 64 x 64. Our results showed that cyclic RVC detected 43% more VURs than conventional (first cycle only) RVC. Therefore we recommend its use as a standard procedure instead of the conventional RVC.

RENAL CORTICAL SCAN IN PEDIATRIC PATIENTS OF ECTOPIC KIDNEY In a large scale school children renal sonography survey, over 300 cases of nonvisualization of one side of kidney was referred to do Tc-99m DMSA renal cortical scan. Among these cases, 60 cases of ectopic kidney were found. In this work, we try to clarify some characteristics of the ectopic kidney based on these pediatric patients. These patients include 34 females and 26 males. Their age ranged 6 -16 years old. Forty-two cases of ectopic kidney were from the right side and 18 cases were from the left side kidney. Eleven of these cases were initially diagnosed as renal agenesis by sonography. These 11 cases included 2 crossed ectopic fusion kidneys and 1 thoracic kidney. The rest of the 57 ectopic kidneys located caudal to the normal renal fossa to the lower abdominal region. All of the ectopic kidney combined with malrotation which can be well recognized from the orientation of the renal pelvis and the shape of the kidney. The size and the relative function of all of the ectopic kidneys but 2 were smaller than the contralateral side of the kidneys. The size ratio of ectopic kidneys to the contralateral ones was 0.803 +/- 0.168 (mean +/- SD ), and the relative function ratio was 0.637 +/- 0.196, respectively. In conclusion, the renal cortical scan can help to find out the ectopic kidney when kidney tissue was not found by the sonography. The Tc-99m DMSA is specifically taken up by the renal cortical tissue. The renal cortical scan can determine the size, location and relative function of the ectopic kidneys which were valuable for these pediatric patients. These patient should be advised to avoid violent exercise and abdominal trauma,

c~ 0 C c~ s_

PMo638

PMo640

A l e x a n d e r Smokvina, Department of N u c l e a r M e d i c i n e , Clinical Hospital Center, Rijeka, Croatia

J.R.Buscombe~ K.Rosenfeld, P. Sweny, A.J.W,Hilson Departments of Nuclear Medicine, Radiology and Nephrology, Royal Free Hospital and School of Medicine, London NW3 2QG, UK.

THE RENAL TRANSPLANT PERFUSION INDEX: IMPORTANCE OF THE A R T E R I A L A N D RENAL CURVES TIME SHIFT CORRECT ION A t different times following surgery and during v a r i o u s complications, 119 studies w e r e perfor~led on 57 p a t i e n t s . In m a n y p a t i e n t s studies w e r e repeated several times. T w e n t y three studies w e r e p e r f o r m e d in as m a n y patients, in whom a normal function of the t r a n s p l a n t e d kidney w a s e s t a b l i s h e d by other d i a g n o s t i c m e t h o d s and retrospective analysis. Comparison was m a d e of the perfusion index results obtained by the Hilson et al. m e t h o d from 1978 and the ones o b t a i n e d by m y own m o d i f i e d method, which for calculating the index also takes into account the time d i f f e r e n c e in appearance of the initial p o r t i o n s of the artery and kidney curves. The arterial region of interest w a s p o s i t i o n i n g over the distal part of the aorta. The reliability of one or the other m e t h o d tested by simulated time shift of the p e a k of arterial curves shows that the deviation p e r c e n t a g e from the m a i n index value in the u n m o d i f i e d m e t h o d is 2 - 5 times g r e a t e r than in the m o d i f i e d m e t h o d . The normal value of the p e r f u s i o n index applying the m o d i f i e d m e t h o d is 91-171 .

SCARRING IN RENAL TRANSPLANTS IDENTIFIED BY Tc-99m DMSA SPECT Kidneys transplanted into patients are susceptible to scarring from infection for two main reasons. The host may have sufficient immunosupression to reduce their ability to eradicate infection and as the transplant is often placed in the pelvis the ureter is much shorter than with native kidneys may not show peristalsis. Planar Tc-99m dimercaptosuccinic acid (DMSA) imaging is of limited use as photons from the posterior wall of the transplanted kidney are attenuated by the pelvic bones. Therefore this study was performed to determine if tomographic Tc-99m DMSAimaging could identity renal cortical defects consistent with scars and the relationship of the defects seen to the presence of vesico-ureteric reflux. 23 patients with proven urinary tract infection (mean age 26, range 1067, 4 male) with transplants in situ for 1-17 years (mean 7 years) were studied. Tomographicimaging was performed with atwo headed gamma camera 2.5-3 hours after administration of 74MBq Tc-99m DMSA. Tomographic data was displayed as orthogonal slices and a 3D volume rendered image. All patients also underwent an X-ray micturaling cystogram. The kidneys of 17 patients showed cortical defects consistent with scarring in 7 of these transplants more than 3 renal cortical defects were seen. Comparison with results of cystography is given in Table 1 reflux on cystoqraphy present absent Scarring on Tc-99m DMSA present 9 8 absent 2 4 Of the 8 patients with no cystographic evidence of reflux, three had 3 or more scars denoting significant renal cortical damage. Therefore Tc-99m DMSAtomography is recommended in all renal transplant recipients with proven urinary tract infection

1191

c~ 0

• Nephrology PMo641

PMo643

A.~obaner, H.Kaya, M.Ozer, S.Ydmaz, D Tok, F.Y=ldlz, A. ~ahin Depatments of Nuclear Medicine, Pediatric Surgery, Anesthesiology and Reat~imation and Pathology, Bfastetis#e,Diele University, Diye,'baktr, Turkey.

B. Ma_ikowski. Z. Maziarz, J. Zelechowski, E. Miekos, w. Tryniszewski. Dep. of Nuclear Medicine, Radiology and Urology Military Medical Amademy, Lodz, Poland

EVALUATION OF THE EFFECTS OF THE ACUTE HEMORRHAGIC SHOCK IN ISCHEMIC TUBULAR DAMAGE BY Tc 99m-DMSA UPTAKE SCfNTIGRAPHY Kidneys are one of the most sensitive organs to hemorrhagic shock hypoxia causes ischemic tubular damage that occurs in tubular cells. The aim of the present study is to determine the intensity of ischemie acute tubular necrosis (ATN) by Tc 99m-DMSA percentage uptake scintigraphy beside the conventional techniques like biochemical and histopatologieal investigation. Frothy male, Sprague Dawly rats ( 3.5 mounts old, 250-275 gm in weights) were chosen as the animal model and they were sedated with intramuscular injection of ketamin (25 mg/kg). The rats were divided into four group randomly (A, B, C) and 10 of them were accepted as the control group. In all groups, carotid artery was canulated and during the procedure, systemic arterial pressure and body temperature were monitorized continuously and in Group A, B and C, these parameters were recorded prior to and at 5 min intervals following hemorrhagie. In group A, B and C, systolic blood pressures were decreased to (mean) 25 mmHg from (mean) 110-132 mmHg. This shock period was lasted about 45 rain. Then rats were resuscitated by heparinized autelogous blood. After the correction of hypovolemic shock, Tc-99m DMSA percentage uptake scintigraphy were performed to group A (8 rats) at second day, to group B (8 rats) at eighth day and second day, to group C (7 rats) at twenty-first day. At the same days, BUN and blood creatinine levels of rats were determined. Tc-99m DMSA percentage uptake values were 25.4 in control group, 14.4 in group A (t=30.6,p<0.001), 20.4 in group B (t=11.1, p<0.001) end 22.8 in group C (t=7.3,p<0.001). BUN and blood creatinine levels were respectively 44.8 mg/dl and 0.46 mg/dl in control group and 59.6mg/dl (p<0.001) and 0.65 mg/dl (p<0.001) in group A. However, there was no statistically significance between control group and group B and group C. In the histopathologic examination, there were the tubular cell swelling, narrowing in the proximal tubules lumens and epithelia cell desquamations on the second day: there were tubular degeneration and regeneration, partly tubulorrhexis in the same areas on the eighth day; tubular regeneration and the casts in tubules lumens of the periglomerular areas and tubular regenerations were clearly observed on the twenty-first day. In conclusion, Tc 99m-DMSA percentage uptake scintigraphy was superior to the biochemical techniques for evaluating the ischemic ATN in acute hemorrhage shock

SCYNTYGRAPHIC EFFICIENCY ASSESSMENT OF THE SCII~RUIHERAPY OF THE VARICIN2EI~. Sclerotherapy is one of a few methods of varicocele treatment. It is efficiently cheap and quick and can be used without patient's hospitalisation. The efficiency of this metb~2d can be assessed by angiographical ~ t i e n or by scyntygraphical studies. The latter method is cheaper non invasive and easier to do than traditional agiographical

study. In 1995 we made 12 sclerotherapies of the varicoceles and controlled them by using scyntygraphy. The radioisotope studies had been made beforehand, two days after and two months after sclerotherapy. Angioscyntygraphy was made in the supine patient's position by bolus injection 99 m Tc and I00 sec. acquisition in the region of perineum. In the 40 th sec. of study patients made the Valsalva test. The static acquisition using "in vivo" labelled e r y t ~ e was made one hour after injection of the radioisotope. In the studies before sclerotherapy we found the typical changes of varicocele. After therapy we confirmed nornml flow and absence of hot spots in the static studies. Other studies confirmed normalisation of the function of the testis. Gonclusions. I, Scyntygraphy studies can be use for monitoring patients after sclerotherapy of the varicocele. 2. Dynamic and static studies should be made together because of increasing sensivity of the test.

PMo642

PMo644

Jakgi6 t~, Beatovi6 S, Mid"h5 S, Tulid C, Radojkovi6 S, I-{an R, Institute of Nuclear Medicine, Clinical Centre of Serbia, Belgrade, Yugoslavia.

u o O L O T T I O.*, G A V A R U Z Z I G.*, A R E N A F.+, P E R A C C H I A G.+, C O R T E L L I N I P.+

SCROTAL SCINTIGRAPHY IN DIAGNOSIS SUBCLINICAL VARICOCELE IN INFERTILE MALES Varicocele is the most c o m m o n

OF

correctable cause of male

infe~ility. Minor vascular changes have similar adverse effect on spermatogenesis as the major ones. The purpose of the study was to evaluate the use of scrotal scintigraphy in early diagnosis of small, arduously detectable, subclinical varicocele, especially in the right hcmiscotum. Scrotal blood pool scintigraphy, with erythrocytes in vivo labelled with 175 M b q 99mTc, was performed in 275 infertilepatients with suspected varicocele. If dearly defined focal zone of increased activityon the static 500 K C image was observed, the finding was considered as positive. Scintigraphy detected varicocele in 223 patients ; in 99 unilateral and in 124(56%) bilateral. Clinical examination revealed varicocele in 195 patients , unilateral in 140 and bilateral in 55(28%). Total incidence of scintigraphlcally positive findings

was 347(63%) varicocelcs in 550 ex~mlned hemiscrotal regions in comparison of 250(45%) by clinical examination. Sensitivity and specificity of clinical examination comp~ed with scintigraphy

were 62,5% and 84%, respectively. Rate of (130/347) false negative results (37,5%) were clinically missed subclinical varicoceles. In group of 19 patients scintigraphic and clinical results were compared with pbiebography ; sensitivity of scintigraphy and clinical examination was 84% and 60%, respectively. In conclusion: clinical examination is not sufficiently sensitive in diagnosis of varicocele, particularly for detection of subclinical and bilaterallesions.Scrotal scintigraphy should be routinely applied in selection of infertilepatients for correction of varicocele.

1192

*Servizio di Medicina Nucleare, Azienda Ospedaliera di P a r m a + D M s i o n e di U r o l o g b , Aziendo Ospedaliera di Panma

RADIOISOTOPIC PENOGRAPHY IN DIFFERENTIAL DIAGNOSIS OF IMPOTENCE We pertbrmed dynamic seintigraphy of the penile brood flow using Tc99m m v/re labelled red blood cells and pharmacological induced erection m order to determine its role as screermN test for vasculogenic impotence and to differentiate arte~iogemc from venogertic insufficiency, conelating this test with the other methods used for dia~losis impotence. We studied the penile blood flow during pharmacolo~cal induced erection in 7 aoimal potent vohmteers and in 60 impotent patients acquiring, after treeing labelled red blood cells in rive v~dth 185MBq of Tcgqm, a two hours study 0 flame/minute) with an injection of 20ug of PGE1 into the corpus cavenaous at the twentieth minute. Before lmdergoing radioisotopi¢ e×amination all patients were questioned about their medical histo D' and tmdetwent a phisical exareination, hormonal assay, mtraeavemous ~iection of prostaglarmle E 1 ~xdth self sthnalafion, color duplex doppler ~fltrasonogTaphy and, if a venous leak was sospected, d~amic infusion eavemosometly and cavernosography. After titese tests patients resulted as follows: 28 pts presented psycogenJc impotence, 22 pts artefiogenie and l 0 pts venogenic hnpotence. 7he radioisotopic time/activity craves were as tbllows: the ones obtained in fl~e patients with psycogenic hnpotence mid m the healthy volunteers showed a greater and more rapid increase, reaeNng a peak followed by a plateau or a gradnal descent ]tle cm~'e obtained in pafienls with arlenogenic impotence showed a slower increase, wMe the venogenic ones presented lower peak levels followed by a more rapid decrease. The scintimaphic results were in aNcement with the ones obtained by tile other lesIs in 56/o0 (93%1 patients. We cormlude that radioisotopic erection penogram is a simple, less invusive ~gl(I asefiN screening test to identity," vascMogenic impotence and to differentiate urteliogemc fi'onl venogemc patbolo~'.

• Neurology Neurology PSu645

PSu647 V. Leduc (1), p. Lecouffe (2), F. Pasquier (3), L. Defebvre (I), A. Dest~e (t), M. Steinling (2), Departments of Neurology A (1) and C (3) and Nuclear Medicine (2), CHRU Lille, FRANCE.

P-0 Kotzki, J Tcuchon, F Lyonnet, H Collet, R Genin, D Mariano-Goulart, M Zanea and M Rossi. Service de MBdecine Nucl@aire, HBpital Lapeyronie, Montpellier, France. VALUE OF SEMIQUANTITATIVE HIPPOCAMPUS SPET MEASUREMENTS IN OLDER PERSONS WITH AND WITHOUT ALZHEIMER'S DISEASE. Bilateral perfusion deficit in the posterior temporoparietal areas is the "classical" SPET appearance in AD. However, this pattern occurs only in a minority of mild AD patients. Some authors have suggested that the disease begins in the entherinal cortex and spread to involve the hippocampus. In this study the value of semiquantitative hippocampus SPETHMPA0 measurements was examinated in older with and without AD.

Four groups of patients were studied. Group:l: BB patients without memory loss (MMSE 28; Bg±10y).Group 2: 29 patients with memory loss (MMSE=27±I; 71±10y). Group 3 : 3 5 patients with mild AD (MMSE=21±3; 71±7y). Group 4: 20 patients with severe AD (MMSE=II±5; 71±5y). SPET images were acquired with a dual detector camera. Circular R0I were manually positioned on the frontal (F), posterior parietal (PP) and posterior temporal (PT) cortices. After reorientation parallel to the insular-axis, hippocampus ROI(H) were delimited on coronal slices. The cerebellar cortex was taken for normalization. The group differences were evaluated using ANOVA. For PP, PT and H, we found a progressive and significant decrease of activity between groups, but hippocampus were not m~re discriminant than parietal dans temporal cortices. Nevertheless, the inter-group discriminations were significant ly increased by combining PP or/and PT with hippoeampus ratio. Variations of frontal activity were not significant, but frontc-parietal and fronto-temporal ratio clearly discriminated olders persons without (groups 1 and 2) and with AD (groups 3 and 4). In conclusion: hippocampus were not more sensitive than posterior parieto-temporal cortices in differentiating normal elderly from mild AD, but best discriminations were obtained by adding hippocampus to posterior parietal and posterior temporal cortices.

COULD HMPAO-TC SPECT STUDY DIFFERENTIATE DIFFUSE LEWY BODY DISEASE FROM ALZHEIMER'S DISEASE ? Diffuse Lewy Body Disease (DLBD) typically associates a parkinsonian syndrome and a cortico-subcortical dementia. Clinical diagnosis is difficult, especially differential diagnosis with Ahheimer's Disease (AD) with extrapyramidal features. The aim of the present study was to evaluate the contribution of SPECT in this difficult diagnostic situation. A 99mTc-HMPAO SPECT study was performed in 14 patients with probable DLBD according to Byrne's and to Mc Keith's diagnosis criteria and in 19 patients with probable AD according to the NINCDS-ADRDA criteria. The mean age, disease duration and MMS didn't differ between the 2 groups. SPECT was performed with a dedicated fast rotating SPECT system TOMOMATIC 564 (Medimatic Coperthague). HMPAO uptake was mesured in 10 pairs of Regions of Interest (ROI) drawn on a slice located 6 cm above the orbito-meatal plane, eg: fronto-internal (FI)0 fronto-lateral (FL), fronto-posterior (FP), temporo-insular (TI), temporoparietal (TP), temporo-parieto-occipital (TPO), parieto-oecipital (PC), occipital (OC), lenticular (L), and thalamic (TH). Tracer uptake was expressed as cortical / mean cerebellar activity ratios. Statistical analysis was performed with a Mann and Withney test. We found a significant difference in the tracer uptake in the 3 frontal pairs of ROI (FI, FL, FP). Discriminant analysis applied to these 3 pairs of ROI was able to correctly classify 11 patients of the DLBD group (78.6 %) and 14 patients in the AD group (73.7 %). A predictive analysis applied to the 6 uptake ratios of a new patient determines a predictive score classifying the patient either in the DLBD group or in the AD group. To conclude, SPECT appears to be usefull in the differential diagnosis between DLBD and AID.

O

im

C

t_

PSu646

PSu648

J. A.

S. Vidal-Sicart F. Lomefia, T. Soler, A. Catafau, FJ Setoain, N. Vila, J. Pefia*, R. Herranz and R. Blesa. Hospital Clfnic and Hospital del

Arbizu L. Rubio, R. Laru~be*, M.J. Garcia-Velloso, Villas, ~. Martinez-Lage*, J.A. Richter. Departments of Nuclear Medicine and Neurology*. University Hospital of Navarra School of Medicine. Pamplona. spain. COGNITIVE FUNCTION HEIMER DISEASE.

AND

SPECT

IN

DIFFERENT

STAGES

OF

ALZ-

In order to evaluate the relationship between perfusion brain SPECT and specific cognitive functions as well as the possible influence of the illness severity on them, 34 dementing pts clinically diagnosed as probable Alzheimer disease (AD) according to N I N C D S - ~ P ~ A criteria were studied. Additionally 12 elderly subjects were studied as control group (CG). A semieuantitative analysis of 99mTc-HMPAO-SPECT images was made in 22 cortical ROls referred to cerebellum. Both CG and AD pts carried out the neuropsychological (NPS) battery of C B P ~ D protocol. Relation between cognitive test and SPECT indexes was assessed by performing contingency analysis including related statistics according to the different parameters analysed. AD pts were classified according to MMSE score as 16 mild AD (n~AD)and 18 moderate AD (~%D). All the N P S test, except the Boston na/ning test, demonstrated significant differences between CG, ak~D and ~i~/9. Bilateral temporal and parietal perfusion indexes showed significant (sg) differences between CG and MAD and between and M~D. However, only the right posterior temporal index showed a sg hypoperfusion between CG and ~u%D. Frontal hypoperfusion was sg in the right side between CG and n ~ and between n ~ and ~ in the left. Learning and short term memory impairment were statistically related to bilateral temporal and parietal deficits. Learning memory lost showed a sg relation to left frontal as well. Praxis dysfunction was related to bilateral temporal deficits. Cortical perfusion was not related to naming test and executive function. When comparing both groups of parameters in the nu~D pts, similar sg relations were obtained more selectively in temporal ROIs. NPS test of memory and praxis were superior to SPECT in discriminating mAD and M A D pts from controls. Nevertheless, temporo-parietal hypoperfusion is mainly related to the above cognitive disfunction in AD pts even in the mild disease.

Mar. University of Barcelona, Spain. ROLE OF 99rnTe-HMPAO SPECT IN TIlE EARLY DIAGNOSIS OF FRONTO-TEMPORAL DEMENTIA Aim: To asses the usefulness of 99mTc-HMPAO brain SPECT in the early diagnosis of frontal dementia. Methods: A longitudinal study was performed in 13 patients with clinical suspicion of fronto-temporal dementia (9 female, 4 male; mean age 66+7.3 y, years of education 8.5+1.9 y). All the patients were initially tested for the presence of frontal symptomatology using a frontal symptoms scale (FSS, score 0-30 points), and underwent both MRI and HMPAO SPECT. At the end of the follow-up period (26___6 mo.) patients showed a mean Minimental score (Folstein) of 5.4+8.3, and were re-evaluated by the FSS. Results: Initially the mean FSS score was 7.3+4.6. Atrophy on MRI and perfusion defects on SPECT were scored as +(mild), + +(moderate) and + + +(severe). MRI showed bilateral frontal and/or left atrophy: 7 temporal (+), 4 fronto-temporal (+ +) and 2 fronto-temporal (+ + +). SPECT showed perfusion defects: 2 left temporal (+), 2 left frontotemporal ( + + ) , 4 bilateral frontal and left temporal ( + +), 3 bilateral frontal and left temporal ( + + + ) , 1 left fronto-temporal ( + + + ) and 1 right fronto-temporal ( + + + ) (corresponding to a depressed patient, Yesavage score: 26). No relationship was found neither between MRI and SPECT findings nor between FSS score and SPECT (X 2 p>.05). However, a significant relationship was found between the mean FSS score at the end of follow-up (16.6+6.4) and the perfusion defects initially detected. Conclusions: SPECT pattern in fronto-temporal dementia shows bilateral frontal and left temporal perfusion defects. Perfusion defects are more severe than MRI abnormalities, and not related to atrophy. 99mTcHMPAO SPECT can detect early functional changes in patients with fronto-temporal dementia.

1193

d~

O n

• Neurology PSu649

PSu651

A,Tutu~*N.Ku~u,S.Sofuo~lu,M.Nardall*,A.$imsek, F.Karaaslan, A.S.G~nQI

M Schreckenber~er 1, O. Sabri 1, M. Mull2, U. Cremerius 1, M. Schwarz 3, A. Thron 2, U. Buell 1 Departments of Nuclear Medicine 1, Neuroradiology 2 and Neurology3, Aachen University of Technology, Aachen, Germany

Erciyes University School of Medicine, Departments of Psychiatry and Nuclear Medicine*, Turkey TR2kNSIENT FRONTAL HYPOPERFUSION IN SPECT ALCOHOL WITHDRAWAL SYNDROME

IMAGING DURING

The aim of this study was to test the hypothesis that a homogenous population of patients with alcohol dependence, in terms of their physical-nutritional and cognitive functional condition, have some rCBF changes during the alcohol withdrawal syndrome and these possible changes will normalize after recovery from withdrawal symptoms. The study group consisted of 15 male patients (mean±SD age: 41.53± 10.37) who met DSMIV criteria for alcohol withdrawal syndrome . None of them had a gross cognitive impairment. They had no history of major systemic disease or head trauma. Brain CT scan was performed on a 600 XT (Toshiba, Japan) in all subjects. No subject had any significant structural changes in CT scan. Regional cerebral blood flow images were obtained by SPECT using Tc-99m NMPAO (Ceretee, Amersham, Intl) as a radiotracer and with a single head camera both during the withdrawal syndrome and in remitted state of patient without taking any drug. Student's t test (paired) was used for comparison of data obtained at two different times. We found significantly lower LF/LH ratio (Left frontal to left hemisphere) during the withdrawal period(mean:0.957) compared to that of the recovery period (mean:0.989) (t=2.23 p<0.05). RF/W(Right frontal to whole brain) ratio was also lower during the withdrawal (0.954) compared to that of the recovery period (t:2.15 p<0.05). In conclusion, our data support the hypotesis that perfusion of the frontal lobes reduces during the alcohol withdrawal probably due to the increased circulating cateeholamine levels, and it tends to be normalized after recovery from alcohol withdrawal syndrome.

REGIONAL MORPHOLOGICAL/FUNCTIONAL MATCH/MISMATCH IN CEREBKOVASCULAR DISEASE (CVD): A COMPARISON OF REGIONAL PEP.FUSION AND ITS RESERVE TO CT FINDINGS IN 104 PATIENTS. Cerebral ischemia may be caused by thrombembolic (territorial or striato-capsular) or hemodynamic (terminal supply area, watershed) infarction or by ischemia due to various reasons (TIA, PRIND). Since this classification has mainly been gained from morphological criteria (e.g., CT), theological aspects often remain underestimated. Since, however, both clinical presentation and prognosis may depend on such aspects, it is of interest to evaluate origin and frequency of a mismatch pattern indicating areas of disturbed perfusional conditions not yet morphologically altered, in the vicinity of a morphological defect (MD). We investigated 104 patients (mean age 56 years ~: 17,8 y.) with chronic CVD to compare sizes of MD in CT to sizes of perfusion deficit (I'D) or to extent of exhausted cerebral perfusion reserve (CPR) in combined flow/volume-SPECT. Flow conditions of the extracranial vessels were examined by Doppter ultrasonography SPECT was done in two steps, viz. to examine cerebral perfusion pattern (400 MBq 99mTc-HMPAO) and to image regional cerebral blood volume (in-vivo labelling of red blood cells, 740MBq 99mTc). CPK was obtained from dividing the images (perfusion : volume). An actual CT (no contrast enhancement) was taken to scrutinize for MD (except lacunes). Two experienced observers categorized the defect/deficit size-relations ofMD, PD and CPR into 1. CT/SPECT-mismateh category A (no MD, no PD, CPR reduced) or category B (PD>MD) or 2. CT/SPECT- match category C (PD=MD) The results were: CT-result/clinical findine;s

categ.:

Mismatch A

Mismatch B

Match C

thrombembolic: - territorial infarclions - striato-capsular infarctions

(n=50) (n=16)

12 (24%) 6 (38%)

38 (76%) 10 (62%)

hemodynamic: - terminal supply area infarctions

(n=17)

clinically reversible (TIA/PRIND) (n=l 1) 9 (82%) tOcases unclassifiedbecauseof additiona] findings

15 (88%) 2 (18%)

2 (12%)

The CT/SPECT mismatch (A,B) was found in 93% of the patients (26/28) with hemodynamic pattern and TIA/PRIND resp, or in 27% of patients with thrombembolic infarctions (18/66; p<001) A match (C) ocurred in 73% of thrombembolic (48/66) or in 12% (2/17) of hemodynamic cases (p<0.0I) Thrombembolics revealed high-grade ACl-stenosis or obliteration in 78% (14/I 8) of mismatch or in 46 % (22/48) of match eases (p< 0.025) From these data we conclude that mismatch prevails significantly in hemodynamic, match in thrombembotic presentations FlowF'Colume-SPECT yields valuable additional assessment of cerebral perfusion conditions in 47% (A and B) of a cerebral ischemia by illustrating presence and extent of a theological penumbra, which is supposed to be an area of further ischemic events CPR is effective in cases with reversible ischemia, even if no MD is present.

PSu650

PSu652

Y.Koshi, S.Kitamura, A.Nagazumi, O.Sakayori, T.Komiyama, Y.Komaba, T.Tuganezawa, A.Terashi, Nippon Medical School First Hospital, SecondDepaCcment of Internal Medicine, 3-5-5 lidabashi Chiyoda-ku, Tokyo, Japan REGIONAL CEREBRAL BLOOD FLOW AND PERIVENTRICULAR HYPERINTENSITY IN SILENT CEREBRAL INFARCTION --COMPARISON WITH DEMENTED CASES-Purpose : In order to investigate relationship between rCBF and the white matter lesions on MRI in silent cerebral infarction (SCI), m u l t i infarct dementia (MID),We performed magnetic resonance imaging (MRI) and measured regional cerebral b[oodflow (rCBF) quantitatively in the cerebral cortices and white matter using ~z31-1MP autoradiography method(IMP ARG method) and single photon emission tomography (SPECT) Material and Methods : 44 patients with silent cerebral infarction (SCI group), 22 patients with multi-infarct dementia (MID group), and 20 control subjects without periventricular hyperintensity (PVH) and lacunar infarction on MRI (CL group) were studied. Regions of interest (ROts) on rCBF images were set in the frontal(F), temporal(T), parietal(P), occipital(O) cortex, and the cerebral white matter(W). The severity of PVH on MRI T2-weighted image was evaluated to 4 grades(grade 0- 3). Results : 1 ) rCBF in the white matter and cerebral cortices except the occipital cortex in SCI group was significantly low compared with CL group (rCBF ratio to CLgroup : W 0.87, F 0.88, T 0.88, P 0.87, O 0.92). 2) rCBF in thewhite matter and cerebral cortices, especially i n the white matter and frontal cortex, in MID group was significantly low compared with SCi group (rCBF ratio to CLgroup : W 0.69, F 0.71, T 0.74, P 0.74, 0 0.82). 3) the mean grade of PVH in MID group was significantly high compared with that in SCI group (SCI 0.98 vs MID 2.45). 4) The severity of PVH was significantly correlated with each rCBF in the white matter and cerebral cortices, especially in the white matter and frontal cortex. Co n c I usi o n : Our findings suggest that the quantitative measurement of rCBF by IMP ARG method is useful for the follow-up study in the patients with silent cerebral infarction as well as the evaluation of the severity of PVFI on M RI.

M M i t j a v i l a * , C Bas, E N a v a s * * , V P i n t a d o * * , J S a n M i l l ~ n & , A G ~ . P a r r a , A C r e s p o . N u c l e a r M a d i c i n e , ** I n f e c t i o n s d i s e a s e and & R a d i o l o g y d e p a r t m e n t s , H R a m r n y Cajal, Madrid. *Nuclear Medicine, H.U. G e t a f e , M a d r i d . Spain. I N T R A C R A N E A L M A S S L E S I O N S IN A I D S P A T I E N T S : V A L U E OF T I - 2 0 1 B R A I N SPECT. T h e i n c i d e n c e of i n t r a c r a n e a l (CNS) l y m p h o m a is increasing in AIDS patients, current imaging modalities are n o t r e l i a b l e for d i f f e r e n t i a t i n g t u m o r f r o m o t h e r c o m m o n n o n n e o p l a s t i e lesions, s u c h as t h o s e s e e n in t o x o p l a s m o s i s (txpl). T h e p r e s e n t study evaluates the use of TI-201 SPECT in i d e n t i f y i n g CNS t u m o r in p a t i e n t s w i t h AIDS. 32 A I D S p a t i e n t s p r e s e n t i n g w i t h CNS m a s s l e s i o n s underwent further evaluation with T1-201 brain S P E C T . A s t u d y w a s i n t e r p r e t e d as p o s i t i v e for t u m o r if t h e r e w a s i n c r e a s e d u p t a k e of T I - 2 0 1 in a l e s i o n s e e n on c o m p u t e d t o m o g r a p h y a n d / o r m a g n e t i c r e s o n a n c e . 20 p a t i e n t s w i t h n o T I - 2 0 1 u p t a k e h a d tumor excluded as final d i a g n o s i s (7 c a s e s of txpl., 3 progressive multifocal leucoencephalopathy, 1 v a s c u l i t i s , 2 a b s c e s s e s , a n d 4 g r a n u l o m a s , a n d 5 p a t i e n t s d i e d w i t h o u t d i a g n o s i s ) . 12 p a t i e n t s s h o w e d focal T I - 2 0 1 u p t a k e . 5 of t h e m h a d e i t h e r b i o p s y or e e r e b r o e s p i n a l fluid analysis proving l y m p h o m a , and 5 p a t i e n t s w e r e d i a g n o s e d of l y m p h o m a in the clinical and radiologic follow-up. The d i f f e r e n c e b e t w e e n t h e s e two s e t s of r e s u l t s w a s statiscally significant (p<0.001, Fisher exact test, t w o t a i l e d ) . 2 p a t i e n t s w h i t h i n c r e a s e T I - 2 0 1 uptake died without diagnosis, 1 of them had R h o d o c o c u s i n f e c t i o n a n d the o t h e r was d i a g n o s e d of tuberculoma 2 months before the scintigraphy was performed. T h i s s t u d y s u g g e s t that T I - 2 0 1 b r a i n S P E C T is a u s e f u l , n o n - i n v a s i v e m e t h o d of d i f f e r e n t i a t i n g CNS lymphoma from other nonneoplastic e t i o l o g i e s in A I D S p a t i e n t s . T I - 2 0 1 b r a i n S P E C T can a c c u r a t e l y ~uide therapy and obviate the need for most b i o p s i e s in t h e s e p a t i e n t s .

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• Neurology PSu653

PMo655

Otte A, Roelcke U, Curt A, Missimer J, Dietz V, Mueller-Brand J, Leenders KL. Paul Scherrer Institute, Villigen; Swiss Paraplegic Center,University Hospitals Zurich, Basel and Freiburg

K.Kawaba~a. H. Tachibana, Y. Tomino, M. Sugita, M. Fukuchi* 5th Department of Internal Medicine and Department of Nuclear Medicine ~, Hyogo College of Medicine, Nishinomiya, JAPAN

BRAIN FLUORODEOXYGLUCOSE CONSUMPTION IN PARAAND TETRAPLEGIA FOLLOWING SPINAL CORD INJURY (SCI)

Introduction: Spinal cord injury (SCI) may result in damage to neurons efferent or afferent to the brain followed by loss of sensorimotor function. The relevance of this de-afferentiation state for the cerebral organization of motor systems is not understood. Patients/Methods: Using positron emission tomography and F-18fluorodeoxyglucose, the global and regional cerebral metabolic rate of glucose (CMRGIu) was investigated at rest in 11 patients with persisting paraplegia (n=7) or tetraplegia (n=4) (age 31_+11 years [mean_+SD]) following SCI and in 12 healthy control subjects (CON; age 34_+11 years). Statisitical Parametrical Mapping (SPM) was applied to compare both groups on a pixel by pixel basis. To allow interindividual comparisons, absolute regional CMRGIu values were normalized by the individual level of global CMRGlu (regional glucose metabolic index [GMI]). Results: The global CMRGlu was lower in SCI patients (33.2+7.8 mmol/I00ml/min) compared to CON (43.3_+6.9, p=0.015, Mann Whitney U-test). At a significance level of p<0.01, SPM revealed relatively higher glucose metabolism bilaterally in the supplementary motor area, anterior cingulate, and globus pallidus. Relatively reduced glucose metabolism was observed in both cerebellar hemispheres. In contrast, GMI values for the motor cortex, putamen and thalamus were in the same range for both groups. Conclusions: The presented results suggest that brain areas involved in attention and movement initiation may tend to compensate ineffective projection of pyramidal neurons to alpha-motoneurons. Decreased cerebellar glucose metabolism may reflect reduced activity of cerebrocerebellar loops associated with movement control.

1-123 IOMAZENIL SPECT IN PARKINSON'S DISEASE 1-123 Iomazenil (IMZ) is a new agent developed for SPECT of brain benzodiazepine (BZ) receptor binding. BZ receptor and gammaaminobutylic acid (GABA) receptor comprise a receptor complex in the cerebral cortex. Therefore BZ receptor binding of 1-123 IMZ will provide indirect, information regarding (]ABA receptor. Since GABA receptors have been reported to be decreased in the Parkinsonian brain, 1-123 IMZ binding might decrease with the progression of Parkinsons disease (PD). The aim of the present study is to examine the relationship between cerebral benzodiazepine receptor binding and clinical parameters, i.e., age, duration of illness, motor disability and intellectual status of patients with PD. We studied 15 patients with PD using SPECT and 1-123 IMZ. SPEGT scan was performed with a single-head gamma-camera system (Staream 3000XCfI', General Electric Co.) three hours after intravenous injection of 1G7MBq of 1-123 [MZ, The ratio of the 1-123 IMZ SPECT count in the cerebral cortex to that in the cerebellum was calculated as the binding potential index (BPI) in the upper frontal, lower frontal, temporal. occipital and parietal cortices. In all studies performed, there was no correlation of BPI with age, duration of illness or mental stares evaluated by Mini-Mental State. examination However. the BPI in each cerebral cortex, except the upper frontal cortex, was significantly correlated with motor disability evaluated by Yahr's stage (P<0.05, in each cortex). The BPI in the upper frontal cortex showed the same t~n(lency (P=0.08) but did not reach the significant level. These results suggest that the GABA/BZ receptor complex in the cerebral cortex of PD patients is impaired in proportion to the severity of motor disability, and that I-]Z3 IMZ is uselul tbr evaluating the pathophysiological condition in PD.

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M. Otsuka, Y. Ichiya,Y. Kuwabara, M. Sasaki, T. Yoshida, T. Fukumura, M. Kate, and K. Masuda. Kyushu University, Departments of Radiology and Neurology, Fukuoka, JAPAN.

J.-L. Baulieu, P. Emend, A.-M.Dognon, L. Garreau, S. Chalon, M. Boazi, Y. Frangin, J.-C. Besnard, D. Guilloteau. INSERM U316, Laboratoire de Biophysique M6dicale et Pharmaceutique, Tours, France

DIFFERENTIATION BETWEEN MULTIPLE SYSTEM ATROPHY AND PARKINSON'S DISEASE BY F-18-DOPA AND F-18-FDG PET. Striatal F-Dopa uptake and brain glucose metabolism were studied by PET with F-t8-L-dopa (KD) and F-18-FDG in 9 patients with multiple system atrophy (MSA) and 15 patients with idiopathic Parkinson's disease (PD). Five of the 9 MSA patients were diagnosed as having olivopontocerebellar atrophy, 2 were with striatonigral degeneration, while 2 demonstrated Shy-Drager syndrome. The FD uptake ratios to the occipital cortex in MSA at 120 rain were 2.07-t-0.31 (mean--SD) and 1.96-t-0.29 in the caudate and putamen, which decreased from the controls (2.72 ±0.11,2.71 ±0.10). Those in PD were 2.07±0.36 and 1.74--+0.24, which also decreased, but a decrease in the putamen was larger than in the caudate. The candate-putamen index (CPI)(%), calculated by a formula based on the difference in the uptakes of the eaudate and putamen divided by the caudate uptake, indicated 5.6-+ 4.6 in MSA and 14.8-t-5.4 in PD. The CPI for all PD patients showed more than 7, the mean+2SD for the controls, and the CPI for 3 MSA patients showed more than 7 (accuracy: 88%). The glucose metabolism for each region in PD showed no difference with the controls. The frontal, the temporal and the parietal cortical metabolism and the caudate, the putaminal, the cerebellar and the brainstem glucose metabolism in MSA decreased significantly from the controls. However, as the glucose metabolic rates in such regions of each patient were overlapped in the two groups, the accuracy by the FDG study for the differentiation was lower than by the FD study. The putaminal metabolic rates, for example, in all PD patients showed more than 6.0 (mg/min/tOOml), and 5 MSA patients showed more than 6.0 (accuracy: 79%). In addition, the combination of the two methods did not improve the accuracy. The glucose metabolism is useful for evaluating the metabolic or functional activity in each region of the brain, and the FD study, which is specific to the dopamine system, seems to be more useful for the differentiation between MSA and PD.

IN VITRO A N D IN VIVO EVALUATION OF I3-CDIT, A NEW

COCAINE CONGENER FOR DOPAM1NE TRANSPORTER SPECT IMAGING WITH HIGH SPECIFICITY AND VALUABLE KINETIC The aim of this work was to improve the 13-CIT properties (slow uptake, affinity for both dopamine and serotonin transporters) by structural changes in the tropane structure at the phenyl substituent for higher affinity and at the nitrogen substituent for higher specificity. A promising ligand was synthetized: 2f3Carbomethoxy-3g-(3',4' diclorophenyl)-8-(3-iodo-prop-2E-enyl) nortropane (13-CDIT). No carrier added B-CDIT has been characterized in vitro and in vivo in rats and monkey in comparison with [3-CIT. Monkey study was performed using a brain dedicated SPECT camera (Ceraspect* D.S.I.) 30 minutes after 1.3 mCi 1231 [3-CDIT injection. In vitro inhibition studies revealed that /:;-C1T and [3-CDIT inhibited in the same order of magnitude the binding of GBR 12935 (Ki=27.5 nM and 29.0 nM respectively). By contrast, in vitro competition studies using, paroxetine showed that [,',-CIThad a greater affinity for the serotonin transporter than 13-CDIT (Ki=3.12 nM and 50.0 nM respectively). In vivo studies on rats revealed that/3-CDIT had a high and fast uptake in the striatum reaching a maximum about 1 hour post injection. According with in vitro and in rive results, [3-CDIT showed excellent imaging quality on rat autoradiography. The monkey basal ganglia were perfectly imaged by SPECT and the ratio of basal ganglia to brain, cerebellum and face were repectivelly equal to t .55, 1.70 and 3.97. In conclusion, it seems that the combination of an aromatic and a nitrogen substitution will improve the properties of tropane derivatives and result in new cocaine congeners for dopamine transporter imaging and quantification, with high specificity and valuable kinetic.

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• Neurology PMo657 E.G. Eising:, H.-H. Coenen:, T. M u e l l e r z, J. rahati ~, W. Kuhn 2, C. Zander:, H. P r z u n t e k 2

PMo659 Fa-

:Clinic for Nucl. Med., Univ. of E s s e n and 2Dept. of Neurology, Univ. of Bochum, G e r m a n y C L I N I C A L E X P E R I E N C E S W I T H I123-2 5 - C A R B O M E T H O X Y - 3 g-(4-IODOPHENYL)-TROPANE (I123-5-CIT) IN P A T I E N T S W I T H DE N O V O - P A R K I N S O N I S N .

S. Dresel, K.Tatsch, Th.Pfluger, T.Mager #, K.Hahn Departments of Nuclear Medicine and #Psychiatry, University of Munich, Germany IMPROVED ANALYSIS OF THE DOPAMINE D2-RECEPTOR STATUS BY IMAGE FUSION OF IBZM-SPECT AND MR DATA: P H A N T O M STUDIES AND FIRST CLINICAL RESULTS

In conclusion, I I 2 3 - B - C I T seems to be a prom i s i n g tool in i m a g i n g of u n t r e a t e d p a r k i n s o n i a n patients.

The exact alignment of regions of interest (ROI's) is essential for correct evaluation of the doparmne D2-receptor status with IBZM-SPECT. Problems particularly occur when reduced binding of the ligand is evident. Goal of this study was to improve semiquantitative analysis using the information of both the functional (IBZM-SPECT) and morphological (MR) method. For this purpose we performed phantom studies and investigated patients presenting with different binding characteristics. SPECT data were obtained in a brain phantom (high and low target/non-target ratios) and in 9 patients (185 MBq 1-123 IBZM, Picker Prism 3000). MR examinations were achieved using TI-, T2- and rOton density-weighted images (Siemens, Magnetom SP 4000). Image sion was performed using a 3D-interactive fusion algorithm. For semiquantitattve evaluation striatum/frontal cortex (S/FC) ratios were calculated in the fusion data sets and compared to the conventional SPECT evaluation (normal > 1,8). ROYs based on the fusion images were smaller and delineated only the central, hottest area. Consequently, ROI's of the SPECT images were systematically too S/FC ratios (mean values)l Fusion ] SPECT large and the calculated Phantom high /2.45 12.2 S/FC ratios too low. This Phantom low [ 1,5 t 1.2 finding was observed in Normal (n=3) I 1.92 12.03 phantom and patient studies and was par- Slightly reduced (n=3) 1.6 I 1.56 ticularly present in cases Markedly reduced (n=3) 1.33 1.13 of low target/non-target ratios. The overestimation of structure size by SPECT is a known problem of this methodology (e.g. different spatial resolution compared to MR,partial volume effect, scatter, collimator penetration) compromising efforts of quantification. Our findings suggest that image-fusion of IBZM-SPECT and MR data enables to define ROI's more reliably, particularly in cases with markedly reduced binding of the ligand. An objective definition of the location and size of ROI's may result in more precise findings in primary examinations and will allow reproducible data evaluation in individual follow up studies.

This a b s t r a c t reports our p r e l i m i n a r y results w i t h S P E C T - i m a g i n g of d o p a m i n e t r a n s p o r t e r s u s i n g the cocaine analogue I 1 2 3 - 5 - C I T in p a t i e n t s with u n t r e a t e d (de novo) p a r k i n s o n i s m . In 23 p a t i e n t s w i t h clinical s u s p i c i o n of Parkinson's d i s e a s e and 15 h e a l t h y controls, SPECTi m a g i n g of d o p a m i n e t r a n s p o r t e r s was p e r f o r m e d i, 4 and 24 hours after i n j e c t i o n of 180 M B q of I123-5-CIT. None of the p a t i e n t s resp. c o n t r o l s had b e e n t r e a t e d b e f o r e with n e u r o l e p t i c a l drugs or any other p h a r m a c e u t i c a l s w i t h known b i n d i n g to the dopamine t r a n s p o r t e r s . C l i n i c a l symptoms are staged b y scales of H o e h n - Y a h r (HYS) and UPDRS. Comparing to the controls, a significant (p<0.01) d e c r e a s e of t r a c e r uptake in p a r k i n s o nian p a t i e n t s can be s t a t e d e a r l i e s t on 24 h p.i.-studies (exception: p a t i e n t s with HYS grade I). Tracer uptake d e p e n d s s i g n i f i c a n t l y on duration of disease (p<0.05) but not on age. High significant (p<0.005) correlations of I I 2 3 - ~ - C I T uptake comparing to UPDRSand HYS values (especially symptoms of rigor and akinesy) can be seen.

PMo658

PMo660

D.C. Costa Z. Walker, S. Gacinovic, A.G.M. Janssen, P.J. Ell, and C.L.E. Katona, UCL Medical School, London, UK and Cygne by, Eindhoven, The Netherlands.

..CantinhoG, Leite/viM, Coelho MH, Pena H, SampaloC Ribeiro C, CastroCaldasC, Godir~oF last,de MedicinaNuclear,Fac,de Mediciandc Lisboa;S. de Neurologia Hospital de Santa Maria. Ressonancia Magndtica de Caselas, Lisboa, Portugal

DOPAMINE D2 NEURORECEPTOR DEREGULATION IN LEWY BODY DEMENTIA HAS LEFT HEM/SPHERE PREDOMINANCE.

123I IBZM SPECT IN PARKINSONIANSYNDROMES COMPARATIONWITH APOMORPHINETEST IN DIAGNOSTICCAPACITY

In this study we investigated the dopamine D2 neuroreceptor availability in the striatum of 46 age matched individuals: 15 Lewy Body Dementia (LBD), 13 Alzheimer's disease (AD), 3 drug naive Parkinson's disease (PD) patients and 15 normal volunteers (NV). Single photon emission tomography (SPET) with the SME 810 was carried out 1.5 to 2 hours post-injection (i.v.) of approximately 185 MBq of 123I-iodobenzamide (IBZM). Regular and circular regions of interest were employed to calculate average caudate nucleus (CN) over lentiform nucleus (mainly putamen -P), as well as caudate nucleus and putamen over frontal cortex (Fc) radioactivity ratios for both hemispheres. Analysis of variance was performed using the SPSS/PC software. The results shown as mean (1SD) in the table below demonstrated clear deregulation of the D2 dopamine neuroreceptors between caudate nucleus and putamen in LBD patients compared to norruals and AD, more marked on the left hemisphere (L). The only difference between LBD and PD (small sample) was the left hemisphere predominance observed in the LBD population with a non-significant trend to left putamen upregulation. CN/P CN/Fc P/Fc n R L R L R L LBD 15 0.97 0,92 1.57 1.58 1.60 1.70 (0.09) (0.07) (0.24) (0.24) (0.22) (0A9) AD 13 1.03 1.07 1.60 1.72 1.57 1.62 (0.12) (0.17) (0.16) (0.21) (0.18) (0.15) PD 3 0.93 0.94 1.48 1.53 1.61 1.66 (0.11) (fill) (0.09) (0.23) (0.15) (0.04) NV I5 1.08 1.08 1.73 1.74 1.62 1.63 (0,11) (O.10) (0.18) (0.18) (0.19) (0,16) In conclusion, the left hemisphere predominance of the dopamine D2 neuroreceptor striatal deregulation which correlates with the presence of hallucinations may be the differential between LBD and PD. Further work with bigger sample of PD patients is already underway.

Differential diagnosis betweenParkinson disease (PD) and Parkinsonian Syndromesis important in view of the difference in prognosis and therapy, however clinical distinction is sometimes hard to achieve. X Ray CT, MRI and apomorphine test contribute to the differential diagnosis, however functional imaging of striatal dopamine D2 receptors in vivo sesans promising. To compare the discriminating power of the apomorphinetest, high field (1.5 T) Cranial MRI and n3I-IBZMSPECT were our objective. Methods - Two groups of patients were studied. Group A (5 pts) with Purkinson's disease according to the "UK brain bank" criteria and Group B (7pts) with non Parkinson's disease: Progressive Supranuclear Palsy (PSI'): 2 pts, Multiple System Atrophy (MSA): 3 pts, OlivopontoCerebellar Atrophy type of MSAOPCA (1 pt) and Corticobasal Degeneration (CBD) 1 pt. Both groups were submitted: 1. Clinical neurological examination according to Unified Parkinsen's Disease Rating Scale (UPDRS). 2. Apomorphinetest with dosages of 3 to 10 mg until positive response (improvement of 25% in section III of UPDSR) or if intolerable adverse effects appear. 3. 123I-IBZMSPECT with 185 MBq in a two head Camera (GE Optima connected to a Star 4000I). Studies are acquired 90 rain, after e.v. administration, in 64x64 matrix 64 views of 30 seconds each. Semiquantificationof D2 receptors binding potential was obtained after reconstruction of transaxial slices and ratio of basal ganglia / occipital cortex (OC) counts were obtained. 4. High field cranial MRI with VEMP (DP / T2) axial and MEMP (T1) sagital sequencestovisualisebasalgangliastructuresand irondeposits. Results- UPDR S $¢qre:Group A :41 / Group B: 85;AtmmorDhine te~t:Group A: improvement50% / Group B: improvement4% in dosagesof 3 and 5 rag.With 10 mg onlyadverseeffectsappear;123MBZM SPECT: Group A: BG/OC = 1.420+ .057 / Group B: BG/OC = 1A40 _+.117. If we accept a cat-off point of 1.35 for BG/OC ratio we have 100% sensitivity and specifity. Same values for apomorphine test if we accept the classic 25% improvement.MRI results are being processed. Conclusions - In our population, both apomorphine test and Im-IBZM SPECT yield similar good results. Apomorphine test was considerably cheaper, but was a more unpleasant procedure for patients,

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• Neurology PMo661 D. Salvo *r M. Baratti **, S. Calzetti ***, D. Seraflni *,

PMo663

G. Bizzarri * * * , A. Negrotti * * * , F. Solim~ **, A. Versari * • Nuclear Medicine and ** Neurology depts., S.Maria Nuova Hospital of Reggio Emilia ; *** Neurology dept., University of Parma

PLyczak, P.Lass_ M.Sygitowicz, M.Taraszewska, E.St~piefiKocmiel, EMierzejewska, M.Dubaniewicz, G.Romanowicz, KMizan, JM. Stomifiski Medical University and Navy Hospital, Gdafisk, Poland

IBZM-SPECT PARK1NSON'S COMPARISON

BRAIN PERFUSION DEFECTS AFTER CRANIO-CEREBRAL TRAUMA ASSESSED WITH 99mHMPAO SPECT AND AMINOPHYLLINE TEST

IN PATIENTS WITH DISEASE: EARLY AND

"DE NOVO" LATE ONSET

It is still unclear if in the early stage of Parkinson's disease (PD) there is a change in D2 receptors functional state and density, visualized by IBZM SPECT, because of the poor homogeneity for age and therapy of the recordered cases. The aim of the study is to know if the age of PD onset is a critical factor for the D2 receptor evaluation in pts with PD at the early phase.We studied 6 normal subjects (m/f 5/I, mean age 62 yrs, range 48-73 yrs) and 20 parkinsonian pts ( m/f 15/5, mean age 62 yrs, range 41-81 yrs ) with duration of disease less than 4 yrs, Hoehn-Yahr stage I-III, without past L-dopa or dopaminomimetic treatment, with negative TSA Doppler and brain CT or NMR.. Pts were divided in 2 groups according to the age of PD onset ( groupl: > 70 yrs; group 2: < 70 yrs ). Brain SPECT was performed 90-150 rain. after i.v. injection of 123I-IBZM ( 185 Mbq ). In a semiquantitative approach, a ratio was calculated between mean counts in a ROI on the basal ganglia and the cerebellum. The results were: Total Group Group 1 Group 2 Normals(n=6) 1.72+-0.14 (n=3)1.65+-0.01 Oz=3) 1.80+-0.18 Patients (n-20) 1.7I+-0.24 (n=8) 1.50+-0.15 *^ 0~=12)1.85+-0.17 *p< 0.01 compared to normals "p< 0.001 compared to group 2 These results indicate that late onset ofPD ( >70 yrs ) is associated to a reduction of D2 striatal receptors IBZM uptake compared to pts with appearance of disease before 70 yrs and to normals. It could be a consequence of an age correlated dopaminergic function loss, as in normal people too, and a reduced receptorial postsynaptic function caused by disease.Uptake index of pts with onset of PD before 70 yrs is comparable to healthy controls.

Cerebral perfusion alterations immediately after head trauma are fairly well described, but we know little about the remote effects of craniocerebral trauma, together with cerebrovaseular reactivity. The aim of the study was to assess regional brain perfusion in different periods after trauma together with reversibility of changes after aminophylline, an agent known to produce an inverse-steal phenomenon in hypoperfused brain areas. We performed 48 brain SPECT studies with a single-head DIACAM rotating gammacamera in 24 patients, 14 men, 10 women, age: 19 - 64 yrs, between first day to 5 years after closed eranio-eerebral trauma. The study was repeated 2 days later, after i.v. injection of 0.25 of aminophylline. Results: we found cerebral perfusion assymetries in 23/24 patients; in 7/8 patients in a remote period (12 months or more) after trauma. Simultaneous CT scanning revealed focal abnormalities only in 5/18 patients. Assymetry index (AI) in hipoperfused areas varied between 7 - 22 %, mean 12.8 _+ 2.9 %. Bifocal assymetries of cerebral perfusion on the axis: coup - eontre coup was seen in 15 patients (62.5 %), multiple assymetries in 5 pts. (20.8 %). The aminophylline test increased HMPAO accumulation in hypoperfused areas in 10 patients (41.6 %), mean by 6.3 _+2.8 %, no change was seen in 14 (58.4 %). Comments: the authors conclude the long-lasting alterations of cerebral perfusion after cerebral trauma. We postulate the usefulness of aminophylline test in the assessment of perfusion reserve in posttraumatic period and usefulness of brain SPECT scanning in the clinical and medico-legal assessment.

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B. Beuthien-Baumann1, B Kunath2, J. Pinkert ~, U. Reunerz, H. Linemann1, M. Obert 3, E. Will3, J. Steinbach3, B Johannsen3, W.-G. Franke 1. ~Nucl. Med.,ZNeurology, Univ Hosp. Dresden,~Research Center Rossendorf, FRG

I.Pustovrh, B.Pustovrh, P. Predi~, *D. Dodig HOSPITAL CEIJE, SLOVENIA, *UNIVERSITY HOSPITAL "REBRO", ZAGREB, CROATIA

CEREBRAL MRGluc AND PERFUSION PATTERN OF PATIENTS W I T H MYOTONIA DYSTROPHIA (MD) Apart from muscle symptoms, cfinical signs of MD often include altered glucose metabolism, an increased tendency to sleep, and intellectual impairment of various grades. To address the question whether the cerebral symptoms are related to an impaired cerebral glucose utilisation (MRGluc) and/or altered regional cerebral perfusion (rCP), 6 female patients (pats.) age 27 to 56 years (median 49 years) underwent PET-scanning on a POSITOME IIIp after injection of 185 MBq 18F-FDG and SPECT after injection of 750 MBq 99mTc-HMPAO on a triple-head camera equiped with fan beam collimators. For comparison, on 2 transaxial PET-slices (level 1 including basal ganglia (BG) and thalamus (Thai), level 2 located 3 cm above level I) circular regions of interest (ROI) where drawn on representative areas of frontal-, temporal-, parietal cortex, BG, Thai and white matter, rCP of corresponding SPECT-slices was semiquantitatively analysed for 12 regions per slice using a semiautomatic software. In PET and SPECT, no left-to-right asymmetry within each pat. was observed. The MRGluc of cortex, BG and Thai was on the same individual level in 5 pats., 1 pat. showed lower values in the parietal cortex than in the rest of the grey matter structures. Assuming 30-35 rtmol/100ml/min as a normal mean value for grey matter MRGluc for this type of PET-scanner, 3 pats. had mean values of 28,7 ± 2,7 lamol/100 ml/min; 2 pats. of 24,8 ± 3,5 ~tmol/100 ml/min, and 1 pat. was markedly decreased with 18,3 ± 1,8 gmol/100 ml/min. White matter ROIs showed a mean value of 17,0 ± 1,4 gmol/100 ml/min in 1 pat., 10,7 ± 1,6 gmol/100 ml/min in 3 pats., and 7,8 ± 1,3 gmol/100 ml/min in 2 pats.. In SPECT, 1 pat. showed a symmetrically decreased rCP of the frontal cortex without regional impairment of MRGIuc. In the remaining studies, no regional perfusion defects were observed In this small group of pats. with MD a marked heterogeneity of the cerebral MRGluc between individual pats. was observed. When MRGIuc was impaired, no singular brain structure but the MRGIuc of the whole brain seemed to be altered without evidence of local perfusion disturbances.

ROLE OF THE INDEX TUMOR/BACKGROUND IN DIAGNOSIS OF BRAIN TUMORS WITH SPECT TC 99m MIBI IMAGING

The purpose of this study was to stablished the optimal index tumor/background for diagnosis brain tumors with Tc 99m MIBI SPECT imaging. Brain SPECT was performed in 233 patients one hour after the intravenous injection of 370-740 MBq Tc 99m MIBI. All tumors were confirmed with other neuroimaging methods ((ST, MRI) and/or histology. When we used index tumor/background 1,8 there was sensitivity 96,9% and specifity only 82,9%. At index tumor/background 2,2 the sensivity was 93,9% and the specifity 94,5%. At index tumor/background 3,0 the sensivity was 71,9% and specifity 97*. In gliobiastomas multiforme there was indexis betwen 2,7- 31,6 in anaplastic astrocitomas betwen 2,3- 8,2, in gliomas 3,2- 4,8, in meningeomas 2,2 -8,7 and in metastases 2,8- 5,0. Amongh the false negative results there was oligodendroglioma and neurinoma neuri acustiei; amongh false positive results there was several cases of multiple sclerosis and some ishemieal brain lesion. With this study we established index tumor/background 2,2 as limith for diagnosis brain tumors.

1197

O IX

•

Neurology

PMo665

PMo667

RJ Meijer, D Hasan, J van Peski, R Valkema, PJ Koudstaal, EP Krenning Dept. of Neurology and Dept. of Nuclear Medicine University Hospital Rotterdam Dijkzigt, The Netherlands

F.J.Setoain F.Lomefia, S.Arroyo*, A. Catafau, S.VidalSicart, L. Torner*, X.Pavfa, J.Setoain. Departments of Nuclear Medicine and Neurology*. Hospital Cl~nic. Barcelona. Spain.

CEREBRAL UPTAKE OF 9~mTcBICISATE AND ~gmTCHMPAO IN ACUTE STROKE Background: Recently,ggmTc Bicisate (Neumlite) has been promoted as a new agent for measurement of regional cerebral blood flow (rCBF). Although a good correlation between the distribution of 99mTC Bicisate and rCBF was found in normal individuals, a few studies suggested that 99roTe Bicisate cannot detect hyperperfusion in infarcted brain tissue. However, no direct comparative study has been performed on differences in cerebral uptake of 99mTc Bicisate and the established rCBF tracer 99mTc HMPAO (Ceretee) in acute ischemic stroke. Methods and Results: Twelve patients with an acute ischemic stroke were entered in this study. The cerebral uptake of both tracers was detected by a three headed SPECT camera (Picker, Cleveland, Ohio). Each patient underwent a ~9mTc 8icisate and a ~9'nTc HMPAO study• Images obtained from each study were matched (registered), voxel by voxel, using reorientation software (Nuclear Diagnostics, Stockholm, Sweden)• Tracer uptake was normalized to the highest uptake in the cerebellum. Regions with increased tracer uptake (indicating luxury perfusion) on the gg~nTC HMPAO images were compared to corresponding regions on the 99rnTcBicisate images. In addition, regions with decreased 99r"Tc Bicisate uptake and regions in normal gray matter end in normal white matter on the sgmTcBicisate images were compared to corresponding regions on the 99rnTe HMPAO images. Statistical analysis was performed by means of ANOVA with repeated measures. We found no differences in cerebral uptake of ~gmTcBicisate and 99raTe HMPAO in the normal gray matter (p=0•68), normal white matter (p=0.65), and in regions with decreased uptake (o=0.46). In contrast, a significantly lower uptake of °9~Tc Bicisate was found in regions with increased uptake of 99mTc HMPAO, the latter indicating luxury perfusion (p=0.001). • 99rnTc Bmtsate •• Conclusion: In patients w~th acute stroke, cannot detect luxury perfusion. This could be probably explained by the fact that in contrast to 99r~Tc HMPAO, cerebral uptake of S~=Tc Bicisate depends not only on rCBF but also on cerebral metabolism, the latter being absent in infarcted tissue

PMo666 1

2

1

. . . .

1 1

BLOOD OXYGENATION LEVEL DEPENDENT FUNCTIONAL M R I THE BRAIN DURING NORMO- AND HYPOCAPNIA Hyperventilation is known to reduce cerebral blood flow by decreasing the arterial Pco2- Arterial oxygen saturation is near 100% during normocapnia and can not be increased by hyperventilation. Thus hyperventilation leads to an increase in oxygen extraction and therefore to a reduction of cerebral oxyhemoglobin. It was our aim to measure this effect in normal volunteers using a blood oxygenation level dependent (BOLD) echoplanar magnetic resonance imaging technique (EPI-MRI). A total of 12 experiments was performed in three volunteers. Five non adjacent brain slices were measured 10O times by EPI-MRI. The effective repetition time was 1 second. Endexspiratory Poe2 was monitored continuously. During the first 40 measurements subjects breathed normally. Then vigorous hyperventilation was initiated decreasing Poe2 from 35-38 to 19-22 mmHg within 20 seconds. Regions of interest were drawn to detect signal intensity changes in cortex, striatum, thalamus and white matter. Signal intensity decreased by 5-10% immediately after the onset of hyperventilation in cortex, striatum and thalamus of all subjects. There was a delayed and smaller decrease in white matter as well. A representative example is given in Fig. h OF

o~ 106 104

1 | --

,J~ _ N~ *

temporal lobe

~, lo2 "~ 100 '98

Start of H

V

/

~

~

94

o 20 40 60 80 100 Hyperventilation-indueed signal reduction in gray matter probably reflects

increased deoxyhemoglobin concentration. Since energy demand is lower in white matter, the effect was smaller and delayed in this compartment. The approach introduced here may help to elucidate the temporal aspects of physiological changes during hyperventilation. 1198

The aim was to determine amobarbital distribution with HMPAO brain SPECT and whether SPECT could clarify the changes in cerebral blood flow that happen after intracarotid amobarbital (IA) injection or Wada test. Material and methods: IA test was performed in 13 patients with intractable temporal (T) lobe epilepsy prior to surgery. V i d e o - B E G localized seizure foci in right T lobe in 5 patients and in left T lobe in 8. Right-side language dominance was observed in 6 patients, left-side dominance in 3 and in 4 patients it was bilateral. Following catheterization of the internal carotid artery (ICA), 125 mg of amobarbital were injected in the ICA on the side of the seizure focus. 740 MBq of HMPAO-Tc99m were injected i.v. just when patients developed contralateral hemiparesis. An interictal SPECT with the same dose had been performed p r e v i o u s l y and was used as a baseline SPECT. Regions of interest were drawn in both SPECTs in order to semi-quantify the p e r f u s i o n changes between Wada and baseline SPECTs. Results: H y p o p e r f u s i e n on the side of the IA injection, p r e d o m i n a n t l y on anterior and middle cerebral arteries territories and crossed cerebellar diaschisis were detected. H y p o p e r f u s i o n after IA injection was statistically significant in frontal, posterolateraltemporal, occipital and cerebellar regions (t-test p<0.05), but it was not significant in mesial temporal cortex, where a reduction of perfusion were seen only in 5/13 patients (38%). The SPECT findings were the same if IA injection was performed or not on the dominant hemisphere (ANOVA). Conclusion: Brain SPECT with intravenously injection of HMPAO can represent brain perfusion changes due to decreased neuronal activity during Wada test. It could assist to know which areas of the brain have been anesthetized.

PMo668 1

M.Weckesse?. S. Posse, S. Dager, JS. Shah, H.-W. Muller-Gartner Inst. of Med., Res. Cent. Jt~lich, Germany, 2Depts. of Psychiatry and Behav. Sci., Radiol. and Bioengeneering., Univ. of Washington, Seattle, USA

~5

EVALUATION OF BRAIN PERFUSION CHANGES WITH HMPAO-Tc99m SPECT DURING WADA TEST

DG.Pavel, A. Manasrah, K Manickam, Q Lin, V. Ibanez. University of Illinois Medical Center, Chicago IL and Laboratory of Neurosciences, National Institute &Aging, NIH, Bethesda MD, USA. BRAIN SPECT EVALUATION USING THE STATISTICAL PARAMETRIC MAPPING (SPM95) METHOD. For the clinical evaluation of brain SPECT a standardized quantification method is highly desirable. SPM95 is a widely used method in PET imaging and we have evaluated the practicality of its use in paired SPECT images. Method: SPECT acquisition was performed on a Picker t)rism 3000 with high resolution fan beam collimator in 128x128 matrix. Reconstruction and oblique reorientation generated a cubic voxel size averaging 2.2 m m . The entire brain volume was then transferred to a Sun Unix workstation for a preprocessing sequence of matrix equalization, realignment and editing out of scalp and skull activity. Using the SPM95 sequence a final realignment is done followed by normalization to the Talairach space, smoothing and statistical evaluation. The patient data consisted of pairs of images obtained from the same patient before and after Diamox ,or from longitudinal followups. These data were compared with paired normal studies. Results : abnormality maps of each individual pair component were obtained, as well as maps of the difference between pairs. These maps are presented in terms of the statistical significance &change for peak height and spatial extent. A comparison was made with the standard interpretation based on the availability of color displays of orthogonal slices, and surface activity maps. The objective evaluation and statistical quantification provided by SPM enabled an easier and more reliable interpretation of the images and flagged areas of otherwise ambiguous interpretation. In conclusion, with adequate preprocessing, SPM analysis of brain SPECT images is feasible and provides an'objective standardized way of quantification with great potential for increased accuracy in the interpretation of paired studies.

•

Neurology

PMo669

PMo671

F.Tranquart, , L.Barantin, E.Saliba, S. Cantagrel, S.Akoka, JL Baulieu - I N S E R M U316 - 37044 T O U R S C6dex

I.Podreka*, Ch. Baumgartner, A. Olbrich, E. Punz*, T. Heller*, S. Asenbaum, W. Serles, U. P i e t r z y k * * , G. Lindinger, S. Lurger, G. Almer, E. Paparaia, T. Br~cke, *Neurologische Abteilung KA Rudolfstiftung, Neurologische Univ. Klinik und Klinik f~r Nuklearmedizin Wien, **Max Planck I n s t i t u t f~r N e u r o l o g i s c h e F o r s c h u n g K d l n

CONTRIBUTION OF 99mTc TOMOSCINTIGRAPHY AND QUANTITATIVE MRI TO THE DIAGNOSIS OF PERINATAL HYPOXO-ISCHEMIA In neonates neurosonography is considered as a useful method to objective brain ischemic lesion, but an earlier detection of brain injury needs to perform quantitative images using metabolic imaging techniques such as magnetic resonance imaging (MRI) or SPECT. We further evaluate nuclear medicine and MRI techniques in neonates with clinical suspected brain injury. 12 neonates (gestational age of 35 +/- 2 weeks) underwent 99mTc-ECD SPECT (74 MBq) using annular crystal SPECT system (Ceraspect, DSI instruments; 64 slices, 1.67 mm thick) and quantitative MRI with real T2 calculated images (Bruker Biospec 2.35T; TR / TE 3000/30-150 ms; 7 slices 5 mm thick). These results were compared to psychomotor tests (Griffith test) performed at 12 months. This study objectives an earlier detection of ischemic areas by T2 calculated images in comparison to T2 weighted images in all eases. The areas of hypoperfusion objectived by SPECT were larger than the ischemic areas detected by MRI, even quantitative, especially in occipital regions (5 cases). In three cases, an hypoperfusion of thalami was observed despite absent ischemic detected lesions on MRI. The overall sensitivity and specificity was respectively 100 % for both methods and 75 % for MRI and 82 % for SPECT related to the brain development abnormalities at 12 months assessed by the Griffith test. In conclusion, this preliminary study indicates that 99mTc-ECD could be performed in neonates without inconvenient. This method gives additional informations on brain injury to quantitative MRI.

PMo670

G.- J. Meyer, R. H(Sfs, W. Butcher1, J. van den Holt', H. Hundeshagen Abteilung Nuklean~edizin und spezielle Biophysik der Medizinischen Hochschule Hannovcr THE RATE CONSTANTS OF L -11C-METHIONINE TRAPPING IN GREY AND WHITE MATTER OF THE CORTEX AND IN THE CEREBELLUM In 75 patients, who were examined for malignant processes in the brain by positron emission tomography and L -11C-methionine we determined the rate constants of methionine trapping in various brain regions. Quantitative analysis was performed using the Gjedde-Patlack method. Bleed samples were obtained from surface veins of heated hands in all examinations. For the analysis of rate constants in normal brain, regions of interest were placed in areas which according to CT, MRI and PET were opposite and at least 5 cm apart from any confirmed or suspected malignant process In order to analyse any effect of the established or suspected disease on the data in normal brain regions, patients were grouped in three classes: Patients with highly malignant processes (n=24) patients with mildly malignant processes (n=30) and patients without malignant processes (n=21). The rate constants were determined in all three groups according to the same criteria. No significant differences were found in the three groups. The rate constants in grey and white matter as well as in cerebellum varied by +37% in all three groups. The mean values are 0,029 rain -1 for grey matter, 0,0157 rnin -1 for white matter and 0,0282 min -1 for the cerebellum The differences in the brain regions are typical and correlate significantly in all three patient groups. Other brain structures with significantly elevated rate constants are the occipital visual cortex and the piluitary gland. The individual right left symmetry varies by 4,9%+4,4%. The ratios of grey over white matter and grey matter over cerebellum are very stable in all three patient groups with an overall variability of only 10 %. The larger inter-patient variability is due to individual differences in the systemic methionine concentration, which, on average, is in the order of 21 ~tmol/I, but may vary more than twofold with the nutritious status. Current investigations analyse the effect of changes in the systemic amine acid concentration on the rate constants. The results confirm that rate constants of amino acid trapping in brain and especially the ratio of these constants in grey and white matter are a stable physiological parameter. Knowledge of its variability in normal brain tissue is a prerequisite, however, before it can be used as a tool for the detection of pathopysiological states.

ICTAL U N I - OR B I T E M P O R A L r C B F I N C R E A S E WITH INTERICTAL TEMPORAL SPIKE ACTIVTY

CORRELATES

In this i n v e s t i g a t i o n we c o m p a r e d the % - i n c r e a s e of n o r m a l i z e d rCBF values (mean cts of R O I / m e a n cts of all ROIS) between ictal and interictal HMPAO-SPECT studies with interictal video-EEG results (recorded o v e r 5 days). 15 p a t i e n t s (3 m, 12 f, 24-50 y e a r s of age) s u f f e r i n g f r o m t e m p o r a l lobe e p i l e p s y (TLE) w e r e investigated. 5 patients h a d p u r e u n i l a t e r a l spike a c t i v i t y (SA), 5 cases c l e a r b i l a t e r a l SA and 5 less p r o n o u n c e d b i l a t e r a l S A (1-9% o n one side versus 91-99% on the other). U n i - or b i l a t e r a l r C B F i n c r e a s e w a s a l s o o b s e r v e d on ictal SPECT. 107 ROIS w e r e d r a w n on nine 10.3 m m t h i c k c o r e g i s t e r e d cross sections. A n ictal to baseline rCBF increase above 12% in a ROI was c o n s i d e r e d as significant. T h e s u m of t h e s e R O I volumes (voxel=O.123cm3) and %-rCBF increases was calculated. Ratios between left/right (l/r) interictal %EEG-spike activity, the sums of i/r ROI v o l u m e s and % - r C B F i n c r e a s e s w e r e obtained. C o r r e l a t i o n and r e g r e s s i o n analysis gave f o l l o w i n g results: E E G i/r ratio x V o l u m e i/r ratio r=0.883, p<0.001, y=0.461x+0.162; EEG i/r ratio x %increase I/r ratio r=0.947, p
PMo672 S. Vinjamuri, S. Woods, J.S. Grime, M. v.d. Broek ~, K. O'Driscoll ~ and N. Critchley. Department of Nuclear Medicine, Royal Liverpool University Hospital eno ~Braln lnju~'y Rehabilitation Centre, Rathbone Hospival~ LivePpool, UK. TRAUMATIC BRAIN INJURY (TBI) IN YOUNG PATIE~TS. SPET STUDY WITH 99Tom HMPAO. 46 young patients (mean age 34 years) with a past history of moderate to severe TBI who require specialist rehabilitation services underwent cerebral perfueion studies and single photon emission tomography using 500 MBq 99mTc HNPAO following standard acquisition protocols. These were performed at least 6 months after the initial traumatic episode (at optimum score on Glasgow Outcome Scale). Visual Reporting (VR) was done by two nuclear medicine physicians and semi quantification (SQ) was carried ou~ using large regions of interest (ROI) for each lobe and normaliaazion to cerebellum. A cohort of 21 studies in normal patients was used as the reference. Results VR and SQ showed abnormal frontal lobe perfusion in 35 of the 92 frontal lobes, i.e. 40% of the frontal lobes were abnormally perfused. There was good overall concordance of 85% between VR and SQ (positive concordance 76% and

n e g a t i v e 9%). Conclusion i. in TBI, 40% of frontal lobes are abnormally perfused. 2. Abnormalities not directly related to primary traumatic site are more common. 3. The role of SQ in patients with neuropsychologieal abnormalities and negative concordance requites further assessment.

1199

e" 0 |l e,,

l/} o,. (D o 0.

• Neurology PMo673

PMo675

CYO Won~. D Chyatte, A J Furlan, RT Go, EQ Chen, WJ Maclntyre, GB Saha, S Raja, D R NeL%mann, R C Brunken, S Khandekar, SA Cook. Departments of Nuclear Medicine, Neurosurgery, and Neurology. C l e v e l a n d Clinic Foundation, Cleveland, Ohio 44195, USA. MEASUREMENT OF VASOMOTOR RESERVE (VMR) USING SINGLE-DAY STRESS PERFUSION BRAIN SPECT: A PROSPECTIVE STUDY.

C S. Raia. T. Desudchit, E.Q. Chen, C.Y.O. Wong, H. Morris, H.O. L~ders, W.J. MacIntyre. G.B. Saha, R.T. Go. The C l e v e l a n d Clinic Foundation, Cleveland, O h i o 44195, USA.

The purpose of this study is to evaluate the incidence of compromised VMR in anterior circulation (AC) from patients with cerebrovascular disease. Single-day split dose acetazolamide stress cerebral perfusion(Q) SPECT images from 46 consecutive patients (pts) referred from neurosurgery or neurology who had cerebral angiogram (CA), MRA or carotid Doppler were analyzed. Seven pts were excluded because 5 had significant disease in posterior circulation by CA and 2 had prior AC encephalomyosynangiosis. Stenosis ~70% in AC, either unilateral(U) or bilateral(B), was defined as abnormal(ABN), otherwise normal (NL). The pair of SPECT images were interpreted using semiquantitative 10% color scale, assisted by a quantitative polar map which reveals the relative changes in VMR (>10% decrement(dec)was defined as positive, otherwise negative). The results are: Group I: Carotid stenosis(CS) C${%) P t s A B N N L B a s e l i n e ( 0 dec)

8 5 9 6

0

<70 U>70 B~70

0 0 9 12

16 10 9 0

0 0 6 7

No VMR dec(-)

(0%) (0%) (67%) (58%)

16 i0 8 5

4 5 2

(100%) (100%) (89%) (42%)

No VMR dec(-)

0 5 4

8 2 (25%) 0 (0%) 8 (100%) 5 5 (100%1 3 (60%) 5 (i00%) 0 4 (100%) 4 (100%) 0 (0%) Conclusion: l)the single-day stress brain test is feasible and accurate compared to a separate-day protocol*, 2) there is a significant difference in incidence of baseline Q dec and VI4R dec(p=0.035), 3) the high specificity of the test is useful for deciding medical therapy, and 4)the VNR dec (+ve. test) reveals the inadequacy of collateral circulation, thus suggesting the need for revascularisation. Further study on outcome is in progress. *Radiology 1992;182:461-466.

INTRACTABLE SEIZURES A N

We have prospectively evaluated the utility of FDG 511 key 8PBCT as compared to PET in pts with intractable seizures using (AI). Fourteen pts with intractable seizures were studied with FDG SPBCT and PET. All sPEnT scans were obtained within I hr of PET scanning on a triple headed gamma camera equipped with 511 key collimators. The reconstructed SPECT and PET images were coregistered using AIR software (Roger Woods). Eight homologous regions were fitted to the PET images using a standardized template, and then transferred to the SPECT images. Count based AIs were obtained from PET and SPECT. The correlation coefficients (CO)and the standard error of estimate(SE) are as follows. CC

V24R d e c ( + )

0 (0%) 3 (30%) 6 (67%) i0 (83%)

Group II: Intracranial stenosis (IS) IS(%) P t s A B N N L B a s e l i n e (0 dec] V M R d e c ( + ]

<70 Uz70 B~70

F-18 FDG 511 keY SPECT A N D PET IN ASlq4METRIC INDEX (AI) C O R R E L A T I O N

BE

CC

SE

Frontal 0.87 8.82 Occipital 0.71 5.28 Parietal 0.87 8.48 Insular 0.75 11.57 Ant temp 0.76 8.56 Cerebellar 0.52 53.14 Post temp 0.69 14.9 Basal gang 0.37 6.69 All region 0.81 21.4 Good correlation was observed in frontal, parietal and temporal cortex. The poor correlation in the basal ganglia is felt to be due to partial volume effects, while the weak correlation in the cerebellum, post. temporal and occipital regions are conjectured to arise from differences in attenuation and scatter corrections applied in the two techniques. Our data suggests that FDG 511 keY SPECT is promising in the evaluation of seizure pts. Further refinements in attenuation and scatter correction may be necessary before its routine use.

PMo674

PMo676

H.Stevens I'3, Ch. Vd Wiele I, P. Santens l, J. De Reuck 2, H.M.L. Jansen ~'2, R. Dierckx I, J. Korf ~ . IDept. Nuclear Medicine and ZNeurology University Hospital Ghent, Dept Biological Psychiatry University Hospital Groningen. STCo A N D T ~ 9 - m H M P A O LABELED LEUCOCYTES SPECT IN VISUALISING CEREBRAL ISCHEMIA. Following stroke,

H. Barthek I. K~impfer, C. Dannenberg, S. Bettin, A. Seese, W.H. Knapp Department of Nuclear Medicine, University of Leipzig, Germany

there

is

an

influx

subsequently Since

both

influx Pat

of

followed processes

these Tc

l(g) 2 (v)

calcium

may

be

Co

~0t

-

45-90

by are

in

ischemic

leucocyte

infiltration.

characterized

by

infiltration we HMPA0 labeled

-

95-95

+

+

30-40

presented

4(me)

+

+

25-25

5(mu)

+

+

45-85

compare the results of both SPECT and Co-57

6(r)

+

+

65-65

7(s) +

+

75-80

+

70-85

9(h)

70-90

cerebral

artery

SPECT.

The

u s e d TC99-M leucocytes

aims

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study

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respective leucocyte SPECT and

to compare the SPECT findings with clinical improvement as s c o r e d b y t h e Orgogozo present, scan

infarcts

were

scale (ACt) . A t 9 p a t i e n t s w i t h CTpositive middle included

in

the

study. Leucocyteand Co-SPECT (interval 2-4 days) were performed using a double headed gamma camera. All scans were performed within 1-3 w e e k s of o n s e t of f i r s t s y m p t o m s . T h e p r e l i m i n a r y findings suggest that both Tc-99m HMPA0 labeled leucocyte and C0-57 SPECT may be useful for visualizing the inflammatory changes in ischemic brain damage. Furthermore, tend

1200

to

the

concur.

results

of b o t h

imaging

IMPROVEMENT OF RADIOCHEMICAL PROPERTIES AND IMAGE QUALITY IN BRAIN SPET BY STABILIZATION OF Tc-99m-HMPAO WITH METHYLENE BLUE

Calcium-

visualized using C o -57 as a Calcium analogue. To visualize the leucocyte

3 (b)

8(n)

tissue,

techniques

Tc-99m-HMPAO is being widely used for imaging of local cerebral blood flow (ICBF). Rapid decomposition of this agent, however, may result in high backround activity and compromize quantitation of ICBF. Therefore, approaches to stabilize the compound have been developed. We report on the effects of methylene blue (MS) on in vitro stability and in vivo distribution. 30 minutes after preparation 400-600 MBq Tc-99m-HMPAO, unstabilized or added with MB, were injected in 35 and 20 patients, respectively. Assessment of image quality: (A) Quantitation: ratio between counts / pixels corresponding to brain and scalpe (Qs) or to brain and nose (QN), respectively. (B) Visual scoring of image quality (0 = bad, 3 = excellent) and backround activity (0 = low, 3 = high) by 3 independent observers. Measurement of radiochemical stability in vitro with 3 chromatographical methods. Results: The following table shows the percent integrity of the complex. time after reconstitution 5 min 30 rain 1h 2h 6b Tc-99m-HMPAO [%] 95.1 80.3 70.0 62.4 25.0 MB-Tc-99m-HMPAO [%] 94.3 93.9 93.3 91.6 87.5 p n.s. <0.01 < 0.001 In vivo quantitation: Qs (m.v, f SD) differed significantly between studies using MB-Tc-99m-HMPAO (3.46 +_ 0.38) and studies using Tc-99mHMPAO (3.02 + 0.37; p < 0.01), QN for MB-Tc-99m-HMPAO 2.24 _+0.28 and for the unstabilized complex 2.08 + 0.33 (p = 0.09). Visual scores of image quality: MB-Tc-99m-HMPAO 2.17 _+ 0.56 and Tc-99m-HMPAO 1.80 _+ 0.71 (p < 0.05), backround activity 1.50 _+ 0.68 and 2.10 _+ 0.76 (p < 0.01). Conclusion: Stabilization of Tc-99m-HMPAO with MB definitely improves image quality in ICBF-SPET by reducing the amount of decomposition products that contribute to considerable extracerebral activity.

• Neurology PMo677 C. Darmenberg, A. Bosse-Henck, H. Barthel, S Bettin, B. Sattler, W.H. Knapp. Departments of Nuclear Medicine and Internal Medicine, University of Leipzig, Germany. BASBLIN]3 AND ACTIVATION STUDIES USING Tc-99m-ECDSPECT IN PATIENTS WITH SEVERE, SLEEP APNEA SYNDROME Severe sleep apnea syndrome (SAS) may result in cognitive dysfunction. The present study deals with the question whether there are characteristic cortical perfusion deficits in patients with severe obstructive or central SAS, and if so whether they are caused by atrophy or decreased neuronal input. Patients: n = 25, 20 with severe obstructive and 5 with predominantly central SAS. Baseline study with 600 MBq Tc-99m-ECD (CERASPECT; ADAC Lab.). Six patients had additional vasoactivation (0.5 g acetazolamide) and four patients cognitive activation studies (labyrinth task). Tomograms were visually classified by 3 experts (7 scores, 0 = normal, 3 = severe defect). Baseline study: 8/25 (= 32%) of the patients had abnormal cortical activity uptake. In obstructive SAS 6/20 (= 30%) pts. had deficits located in frontal cortices. In central SAS no predominant pattern was found. Vasoactivation: There were no significant changes in scores compared to baseline studies (p>0.05) in pts. with obstructive SAS. Cognitive activation: significant increase in scores in frontal, temporal and parietal cortices. Mean values of scores in pts with obstructive SAS are given in the table: frontal

Baseline Cognitive activation

0.89 _+0.81

1.54 _+0.98 Vasomotor activation 1.21 _+1.01

temporal 0.81 _+0.78 1.38 __+0.93 1.13__+0.91

;parietal 0.84 _+0.82 1.46 __+0.99 0.84__+0.87

Conclusion: A considerable percentage of patients with severe SAS show cortical perfusion deficits; characteristic patterns are found in obstructive SAS These abnormal flow patterns are enhanced when patients undergo cognitive activation.

PMo678 D. BecerraGareia, R. Cortds1, L Lumbreras, R Nieto, B Fern~dez, O. PadiUa, M. Sfiinz1, JJM Sampere. Serviciosde MedieinaNucleary OtorrinolaringologiaLHospital Universitario. Granada. SPAIN. [99mTc]HMPAO ACTIVATIONBRAIN SPECT IN COCHLEARIMPLANTED.

Brain activationstudieswith [99mTc]HMPAO have been apply in the location of functional anditive areas during the electrical stimulation of the auditive nerve, Promontory Test, (LeScao, 1993). The purpose of our work is the study of the variations of regional corticocerebralperfusionin temporal and parietal areas after auditory stimulus in cochlear implanted patients. For this was practiced a brain SPECT with [99mTc]HMPAO in 5 rigth handed patients with cochlear implant and in 4 healthy volunteers, on basal conditions as well as aRer stimulation with a Words Test to 50dB Hearing Level. It was calculated the Activity Index (AI) for each Regionof Interest(ROI) normalizedby cerebellum and thereinaffer the Variation Index (VI) for each ROI: IV=R poststimulation-R prestimulation/R prestimulation Temporallobeincrease(%)

ParietalROlincrease(%)

Left

Right

Left

Controls(n=4)

11.3

17.07

7.5

Right 6.1

Implanted(n=5)

7.43

7.41

3.17

4.53

Mann-WhitneyU

0.4795

0.1573

0.1573

0.4795

In our preliminary results, brain activation SPECT with [99mTc]HMPAO in healthy subjects and in cohlear implanted patients have shownthe increasein the captation after auditive stimulation with Words Test in temporal areas and in smaller degree in parietal areas, probably related to their participation in the associative areas. Though it is appreciated a greater middle increasein normal subjects that in implanted patients, probably due to the presence of a small residual functional injury in the group of patients, the size of our samplestudieduntil the present,not allows us to establish statistical differences. Theseresults are in conformity with the described in PET studies (Ito 1990, Hergoz 1991, Ohyama 1993) in those which describes a progressive reactivatiouof the secondaryand primary auditive areas after cochlear implant.

PMo679

MC Lee, D.S. Lee, J M Jeong, J - K Chung, C - S Koh. Seoul National University Hospital, Department of Nuclear Medicine, Seoul, Korea METABOLISM/VIABILITY MISMATCH IN THE ISCHEMIC BRAINS OF MIDDLE CEREBRAL ARTERY(MCA)-OCCLUDED RATS T o find out ischemic b u t viable brain regions, we did triple imaging with F - 1 8 - F D G and T c - 9 9 m - g l u c a r a t e autoradiography(BAS, Fuji) and 2,3,5-tirphenyltetrazohum chloride(TTC) staining. In rats with M C A occlusion two g r o u p s with M C A occlusion with or without reperfusion were sacrificed 24 h o u r s after occlusion with thread t h r o u g h internal carotid artery. In the regions of T T C staining, T c - 9 9 m - g l u c a r a t e w a s not uptaken. In the regions of T T C nonstaining, T c - 9 9 m - g l u c a r a t e w a s more with reperfusion group. In the occlusion group without reperfusion, T T C and F - 1 8 - F D G staining w a s m a t c h e d in m o s t areas. (n=5) Tc-99m-glucarate w/o r e p e r f u s i o n 1.2 + 0.4

F-18-FDG 2.4 + 0.9

1.8 + 0.9

with reperfusion

2.8 + 0.4

1.4 + 0.4

2.4 + 0.9

TTC

However, in reperfusion group, there w a s m i s m a t c h e d regions. In the regions with T T C nonstaining we found area of intermediate F - 1 8 - F D G uptake. A n d also in the regions with T T C staining, w e found areas of decreased F - 1 8 - F D G uptake. W e conclude that there is m i s m a t c h as a phenomenon after M C A occlusion and that triple imaging could elucidate t h e nature of m a t c h or m i s m a t c h of metabolism and viability.

g) c=O m 4=1

t~ c-

4=i

O.

PMo680

h=

E. T e d e s c h i * S.G. Hasselbalch, G. Waldemar, M. J u h l e r °, P. Hegh, F. G j e r r i s °, O.B. Paulson. *CNR, N u c l e a r M e d i c i n e - U n i v e r s i t y "Federico II", Naples - Italy; Neurology and °Neurosurgery Rigshospitalet, C o p e n h a g e n - Denmark. REGIONAL CEREBRAL GLUCOSE METABOLISM IN N O R M A L PRESSURE HYDROCEPHALUS BEFORE AND AFTER SHUNT A i m of this study was to c o r r e l a t e the p a t t e r n s of regional Cortical Glucose Metabolism (CGM), m e a s u r e d w i t h PET-FDG, w i t h the r e s p o n s e to shunt operation in patients with Normal Pressure Hydrocephalus (NPH). E l e v e n p a t i e n t s w i t h clinical and h y d r o d y n a m i c c r i t e r i a for N P H and Ii h e a l t h y subjects of comparable age underwent Magnetic R e s o n a n c e (MR) and P E T - F D G i m a g i n g of c o r r e s p o n d i n g b r a i n slices. D u r i n g the shunt operation, a right frontal brain b i o p s y was o b t a i n e d in all p a t i e n t s and, in 8 of them, also post shunt M R a n d P E T - F D G studies. CMG values w e r e c a l c u l a t e d u s i n g S o k o l o f f model in ROI's p l a c e d on MR and t r a n s f e r r e d to PETFDG axial slices. In respect to controls, NPH p a t i e n t s showed a s i g n i f i c a n t p r e - s h u n t global C G H reduction (p<0.05 at t-test), with highly heterogeneous interindividual distribution. D i f f e r e n t p a t h o l o g i c p r o c e s s e s w e r e found in the biopsy: Alzheimer's changes (AC, 4 cases), cerebrovascular disease {CVD, 2), no specific p a t o l o g y (NSP, 5), w i t h no c h a r a c t e r i s t i c m e t a b o l i c pattern. A m o n g the 8 p a t i e n t s w i t h f o l l o w - u p scans, those 3 (2 AC, 1 NSP) w h o b e n e f i t t e d from shunt increased their CGM values in respect to the p r e s h u n t study, w h e r e a s the 5 cases (i AC, 1 CVD, 3 NSP) w i t h w o r s e n e d or u n c h a n g e d clinical status s h o w e d a m a r k e d d e c r e a s e in CGM. T h e s e p r e l i m i n a r y data suggest that NPH can be associated with different brain pathologies and that PET-FDG patterns after successful shunting express the functional consequences of the improved brain hydrodynamics, regardless of the associated p a t h o l o g i c process.

1201

ID 4,=1

O

n

• Neurology PMo681

PTu683

!i;.Ar-;en]~au]a, T. L~,~dcke, W. Pi ~ker, I .Podr eka, Departments of Neurology and Nuclear Medicine, U n i v e r s i t y of Vietma, W a h r i n g e r G£rtel 18-20, A - 1 0 9 0 Vienna, A u s t r i a

C.A. Buchpiguel, R.M.F. Valerio, k.Y.ltaya, E . M Yacubian, S.K.N Marie, A. Palmini, F.H. Hironaka. Centro de Medicina Nuclear & Neurological Clinic of Sgo Paulo University Medical School, Brazil.

IM/kGING OF CEREBRAL BLOOD FLOW WITH [99mTC] H N P A O AND [~9°TC]ECD - A COMPARISON The aim of t h e p r e s e n t study was to c o m p a r e the regiollal c e r e b r a l distribution of two co$~mercia I ly available blood flow tracers, of H M P A O and ECD, r e s p e c t ively. Methods: S P E C T i n v e s t i g a t i o n s were p e r f o r m e d twice on a Siemens Mult i!:;pect 3 c a m e r a in i7 p a t i e n t s (4 female, i~ male, mean age 71y) with different neurological disorders except akute stroke, using [ TC ]H N P A O as well as [ '=Tc] ECD. After colegistration of the two studies 71 regions of interest (ROI) were drawn manually on 8 slices coverillg su~rd alld inf r a t e n t o r i e l l areas ill one stu;ing a p a i r e d t-test. Results: ~ i g n i f i c a n t d i f f e r e n c e s of t h e s e ratios w i t h t -values r a n g i n g f~ om 2.4 to 5.9, p at least <. 05, w e r e found in tile c e r e b e l l u m and in the b r a i n s t e m , t lie o c c i p i t a l , f roIlt O and temporobasal and the t e m p o r o m e s i a l c o r t e x {f.e. right side t-4.1, p<.003) a:; well as in the thalantus w i t h h i g h e r v a l u e s in ti~e HMPAO SPECT study. In c o r t i c a l regions in u p p e r layers (frontal and p a r i e t a l ) higher values were o b t a i n e d in the ECD S P E C T study (f .e. left frontal t=5.9, p, .0004). Di~;cussion: In the present i n v e s t i g a t i o n a d i f f e r e n t regional distribution of H M P A O and ECD could be demoi~strated. This f i n d i n g indicates, that v i s u a l and s e m i q u a n t at ive e v a l u a t i o n s of ECD and H M P A O SPECT s t u d i e s c o u l d not be c o m p a r e d and that a d i s t i n c t i n d i c a t i o n s h o u l d be set for e a c h one of the tracers.

B R A I N S P E C T I M A G I N G IN N E U R O N A L M I G R A T I O N D I S O R D E R S . A Electrographic and Neuroimaging Correlation.

PTu682 E. Alper, B. Taneli, E. Selcoki, S. Taneli, A.T. Akbunar, B. Erkal, A. Ceylan, N. Konuk, K. Yazici, [ Bilgin. Uludag University Medical School, Departments of Nuclear Medicine and Psychiat~', Bursa, TURKEY.

Tc-99m-HMPAO CEREBRAL SPECT 1N PARANOID AND DISORGANIZED SCHIZOPHRENICS COMPARED WITH NORMAL CONTROLS

The aim of our study was to investigate paranoid and disorganized subtypes of schizophrenia with respect to their underlying regional cerebral blood flow (rCBF) changes and to compare them with age matched normal controls using Tc-99m-HMPAO brain SPECT at rest. Twenty patients (pts) with paranoid schizophrenia (PS) (mean age 33:1:9)and 14 pts with disorganized schizophrenia (DS) (mean age 29±7) were recruited together with 17 healthy volunteers (mean age 32+12). Eight out of 20 (40%) pts with PS were drug-naive versus 6 out of 14 (43%) pts with DS; all the other patients were under neuroleptic medication. SPECT was performed 1 hr after i.v. administration of 740 Mbq Tc-99mHMPAO (GE 3200, LEHR, 32 min acquisition). Studies were interpreted visually and semiquantitatively, blinded to clinical history. Square regions of interest 4x4 pixels drawn over inferior and superior frontal, inferior and superior parietal, temporal, occipital regions and basal ganglia were used to obtain activity ratios in axial slices, taking cerebellum as reference. Scans were visually read as normal for 2 pts with PS, 6 pts with DS and, for all controls. Eighteen pts with PS had rCBF deficits: bilateral frontal (n=3), left frontal (n=6), bilateral frontal with temporal or parietal (n=5), left frontal with temporal and parietal (n=l), temporal (n=2), and parietal (n=l). Eight pts with DS had rCBF deficits: bilateral frontal (n=6), left frontal (n=l), and bilateral frontal with parietal (n=l). Pts with PS showed a significant reduction of perfusion in the left superior (13=.03) and inferior frontal (1o=.02) cortex and basal ganglia (p=.001) compared to normals. Pts with DS had significantly lower rCBF than did normals in all but occipital regions (p<.01). The only significant difference between the 2 subgroups o£ schizophrenia was the lower rCBF in the right inferior frontal cortex in pts with DS than in pts with PS (13=.03). Results from our sample of patients suggests that, at rest, both paranoid and disorganized subtypes of schizophrenia is commonly associated with rCBF deficits in the frontal cortex; right inferior hypofrontality occurring relatively more frequently in the disorganized subtype.

1202

Neuronal Migration Disorders (NMD) are highly epileptogenic and are characterized by focal repetitive epileptiform discharges which frequently manifest in the form of ictaMike activity during interictal E E G However, controversies still exist regarding the intrinsic epileptogenicity of these cortical dysplastic lesions. The purpose of this study was to investigate the association between the rCBF pattern and the intrinsic epiteptogenicity o f NMD. Twenty two patients with a confirmed MP,I diagnosis of NMD were studied. The SPECT images were obtained with a single-head tomographic camera equipped with a low energy-high resolution collimator. All patients received the I-IMPAO injection in the interictal clinical state and under continuous video-EEG recording. The EEG patterns were analysed atleast for 5 min after the injection. The EEG recording at the time of I-IMPAO injection showed continuous electric discharges (ictal-like state) in 12 and interictal pattern in 10. All 10 patients with interictal EEG showed hypoperfusion or normal pattern on SPECT. In contrast, 6 from 12 patients who presented ictaMike activity on EEG showed increased rCBF in the epileptogenic focus. The remaining SPECT studies showed hypoperfusion in 5 and normal finding in 1. These preliminary results suggest that the metabolic boundaries of interictal to ictal transition are blurred in NMD. Dysplastic lesions often generate focal repetitive discharges which do not always correlate with hyperperfusion on interictal SPECT studies.

PTu684 S. Erdem, B. Veznedaro~lu, M. Argon, 0. Bilkay, A. Dirlik,

Y. Duman, R. Saygzlz. Departments of Nuclear Medicine and Psychiatry Ege U n i v e r s i t y Izmir Turkey TC99m HMPAO BRAIN SPECT IN PATIENTS WITH DEFICIT AND NONDEFICIT FORMS OF SCHIZOPHRENIA Patients with schizophrenia have been shown to e x h i b i t f o k a l abnormalities of regional cerebral blood Flow (rCBF). The aim of t h i s study was to c o r r e l a t e the findings on Tc?gmHMPAO SPECT with the d e f i c i t and n o n d e f i c i t subtyps in schizophrenia. Thirthy nine patients (23 males, 16 females) Fulfilling the DSM-III-R criteria for schizophrenia were investigated and their quantitative brain perPusion compared with 12

healthy normal volunters (7 males, 5 females). 17 out of 39 pts had d e f i c i t symptomps (according to Neurological Evaluation Scale). 15 min. a f t e r i n j e c t i o n o f 740 MBq Tc99mHMPAO rCBF was evaluated with a double head SPECT gammacamera A f t e r reconstruction with a Harm f i l t e r and a t t e n u a t i o n corr e c t i o n r e g i o n / c e r e b e l l a r average p i x e l count r a t i o s were obtained by drawing ROIs over cerebral cortex and basal ganglia and were compared to 12 c o n t r o l s . The p a t i e n t s with n o n d e f i c i t symptomps were not s t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e s f o r rCBF(P~O.05). The pts. with d e f i c i t symptoms were shown decreased rCBF i n the f r o n t a l lobes ( b i l a % e r a l ) , t h e basal ganglia ( b i l a t e r a l ) and the r i g h t temporal lob (p
• Neurology PTu685

PTu687

F. Chierichetti, *G.L. Bianchin, *A. Vallerini, P. Zanco, A. Fini, L. Vettorato, * G Salce, R. Bergamin, G. Ferlin, Nuclear Medicine Dpt, Castelfranco Veneto and *Psychiatry Dpt ULSS 8 - Italy

E. Klemm, *A. Friederici, L. Pavics, A. Piotrowski, F. Grfinwald, C. Menzel, EL Palmedo, EL Bender, K. Hamad, EL-J. Biersack. Department of Nuclear

18F-FDG PET IN D E T E C T I N G DIFFERENT CLINICAL PATTERNS OF OBSESSIVE-COMPULSIVE DISORDER (OCD) Many Authors (Baxter et al. 1987, 1988; Nordhal 1989; Swedo 1989) have studied by 18F-FDG PET patients (pts) affected by O C D without focalizing that it has different clinical patterns (e.g. obsessions without compulsions) and often depression, too. Aim o f our study w a s to investigate O C D in its various clinical phenomenons. Methods: we performed 18F-FDG PET in 15 OCD p~s (diagnosis according to D S M IV) and 6 age-matched healthy controls. A m o n g the pts 3 o f them were drug-naive, and the other were drug-free for at least 4 weeks. All pts were divided into: g r o u p A (5 pts with obsessions without compulsions), g r o u p B (5 pts with both obsessions and compulsions), g r o u p C (5 pts with O C D and depression). P E T data were evaluated by semi-quantitative method (each cortical and subcortical a r e a / ~ 3 A , mean brain activity) and statistical analysis. Results: in g r o u p A, hypometabolism in left upper frontal (p = 0.05) and right (p = 0.022) and left (p = 0.047) upper temporal cortex. In g r o u p B the frontal lobes, except the orbito-frontal regions, were hypometabolic (p < 0.05). G r o u p C showed significant hypometabolism in left upper frontal (p - 0.009) and right medium frontal (p = 0.036) cortex. Conclusions: 18F-FDG PET seems useful for the comprehension o f the different clinical patterns in OCD, but, from our even preliminary experience, we can do some considerations. It has been reported an involvement o f temporal cortex during the imaginary exposure to the critical stimulus (Zohar et at. 1989) and we found it in pts with obsessional status. Moreover, it is interesting our report o f lesser frontal involvement in O C D and depression than reported in depressed pts (Baxter et al. 1989). This may suggest that depression, in our pts, is not endogenous but reactive to the disease.

Medicine, University of Bonn, 53105 Bonn, and *Max-Planck-lnsti~ute for Cognitive Neuroscience, 04103 Leipzig, Germany SYNTACTIC AND SEMANTIC LANGUAGE STIMULATION EVALUATEDD BY MEANS OF Tc-99m-ECD AND HIGH RESOLUTION SPECT ACTIVATES DIFFERENT CEREBRAL STRUCTURES

Despite of the importance to activate syntactic knowledge in relating words functional imaging studies on language mainly have focussed on .processing of isolated words rather than sentences. Former brain lesion studies suggest a different processing of semantic and syntactic structures. We evaluated r3~male volunteers (mean age 32.0, range 23 to 46 years) who were all right handed by means of SPECT and Tc-99m2ECD (ethyl cysteinale dimer) 'as a tracer. The stimulus was to listen either to content words (semantic condition) or to short phrases containing no lexical, but only grammatical information (syntactic condition). SPECT-images were acquired using a dedicated brain imaging system (FWHM 6 - 7 nun). Following the resting acquisition after intravenous rejection of 550 MBq (15 mCi) Tc-99m-ECD stimulatton was performed either with the semantic stimulus or the syntactic set binaurally over a period of 5 minutes and 39 seconds. The second dose (860 MBq, 23 mCi) was slowly injected during this period, thus representing the cerebral perfusion pattern during stimulation. The SPECT results were evaluated both semiquantitatively and visually. Quantitative data were related to the baseline set by calculating the per cent increase or decrease of counts per voxel normalized to the whole brain activity in the stimulation study. Thus, each subject served as his own control. -Different activation patterns were observed when comparing the two conditions. Hypetperfusmn was seen in the following areas: SYNTAX (n = 5): All five snj~rior temporal gyrus (1 left, 3 fight, 1 both sides), 3 superior frontal gyms (right), inferior frontalis gyrus (2 right, 1 left), and 4 insula (2 left, 2 nght). Moreover, two subjects had hyperfuston within the gyros postcentralis (1 lefi, I right). SEMANTIC condition (n = 8): 7 subjects had hyperperfusion of the medius frontal gyrns (4 right, 3 left), 5 of the superior frontal gyms (3 right, 1 left, 1 both sides), the precentral gyrus (2 right, 2 both sides) and the medius temporal gyms (2 both sides, 1 left), 6 of the postcentral gyms (4 right, 2 both sides), 5 of the iusula (3 left, 2 both sides), and 5 of the cuneus (3 right, 2 both sides). - The results of the syntactic stimulation agree well with experiments demonstrating disabled syntactic processing following lesions of Broca's area and the iusnla and suggesting the iusula to be a relevant in syntactic (and semantic) processes. The semantic stimulation reflects involvement of both hemispheres, more prominent on the fight side. The hyperperfused regions are not the primary language areas. These findings are canslstent with other studies using PET or SPECT which report activation outside these areas and conclude that semantic processes may be distributed over a network of brain regions.

co |m

,,k,a

t~ e-

,i,,a

e~ PTu686

PTu688

C. Dannenberg, H. Barthel, D. Zedlick, S. Bettin, A. Seese, W.H. Knapp. Departments of Nuclear Medicine and Psychiatry, University of Leipzig, Germany.

S. J i n n o u c h i , S. N a g a m a c h i H. N a k a h a r a , T. O h n i s h i , S. Futami, L. F r o l e s II, K. W a t a n a b e , Y. U s h i s a k o * . D e p a r t m e n t of R a d i o l o g y a n d O t o r h i n o !aryngology*, M i y a z a k i M e d i c a l College, J a p a n

COGNITIVE ACTIVATION USING Tc-99m-HMPAO-SPET IN PATIENTS WITH DEPRESSIVE DISORDERS AND IMPAIRED COGNITIVE FUNCTION Depressive disorders in elderly patients are often associated with impaired cognitive function. Both depression and neurodegenerative disease are paralleled by cortical perfusion deficits. This study deals with cognitive activation as a potential means to differentiate both entities. A total of 32 patients with impaii'ed cognitive function were enrolled in the study, 16 with Geriatric Depression Scale (GDS) values < 10 = group I (Ia: CT with atrophy, In: without atrophy), 16 with GDS value > 10 = group lI (lIa: CT with atrophy, IIn: without atrophy). Control group (only baseline) with n = 15. SPECT: dual-head camera, 500 MBq Tc-99m-HMPAO under baseline conditions and during cognitive activation (labyrinth task). For activity quantitation cortico-to-cerebellar counts ratios (c/c) were used. Normal range: Mean value of controls + 2 SD. Q = activation/baseline c/cratio. Baseline: 12/24 (= 50 %) pts. of groups Ia, lln, II a showed prefrontal cortical activity deficits, 6 out of these pts. had additional temporal deficits. Significant inter -group differences were observed only between groups I n and I a. The cognitive activation studies, however, produced Q values that differed significantly between groups I a and I1n (*p < 0.05; ** p < 0.01): Q frontal lateral Q temporal left Q temporoQ parietal left left parietal 0.99+__0.11 0.95+0.05 0.97+0.10 0.95 + 0.06 ]n la 0.89 +- 0.08** 0.88 _+0.03** 0.93 _+0.06* 0,88 +_0.06** 1.05 _+0.08** 1.02 ± 0.07** 1.05 _+0.09* 0.99 -- 0.08** IIn II a 0.97+0.14 0.93±0.17 0.94±0.20 0.95_+0.07 Conclusion: Patients with probable neurodegenerative disease and those with probable depressive disease according to neuropsychological testing and CT do not significantly differ in baseline ICBF-SPET. Under cognitive activation, however, there are characteristic changes in ICBF patterns for both groups.

REGIONAL CEREBRAL ACTIVATION STIMULATION IN P A T I E N T S W I T H USING Tc-99m ECD SPECT.

DURING COCHLEAR

AUDITORY IMPLANTS

We evaluated a p o s s i b l e c h a n g e in t h e r e g i o n a l c e r e b r a l b l o o d f l o w (rCBF) in the a u d i t o r y a r e a s of t h e b r a i n d u r i n g stimulation of a c o c h l e a r implant using Tc-99m ECD SPECT. The rCBF was measured during rest (baseline) and during a u d i t o r y s t i m u l a t i o n b y p r e s e n t i n g simple s o u n d to the ear with the implant (activation) in f o u r patients. F o r b a s e l i n e study, 370 M B q of T c - 9 9 m ECD was injected at r e s t a n d S P E C T d a t a w e r e a c q u i r e d for 20 m i n u t e s . J u s t a f t e r the b a s e l i n e s t u d y 740 M B q of E C D w a s i n j e c t e d d u r i n g s o u n d s t i m u l a t i o n for a c t i v a t i o n study. Image d a t a w e r e acquired using a three-head gamma camera system ( P R I S M 3000, Picker) w i t h l o w e n e r g y u l t r a - h i g h r e s o l u t i o n fan b e a m c o l l i m a t e r s . SPECT data was subtracted. T h e c h a n g e r a t e s of r C B F in v a r i o u s a r e a of the b r a i n w e r e c a l c u l a t e d w i t h a formula; (mean count on activation mean count on baseline) / baseline x i00 (%) . In a l l f o u r p a t i e n t s r C B F of the t e m p o r a l lobe e s p e c i a l l y the s u p e r i o r t e m p o r a l g y r u s a r e a i n c r e a s e d o v e r 10% during auditory stimulation. W e c o n c l u d e d that T c - 9 9 m E C D S P E C T c o u l d e v a l u a t e the r C B F c h a n g e s in a u d i t o r y activation s t u d y in p a t i e n t s with c o c h l e a r implants.

1203

O

• Neurology PTu689

PTu691

P.V6ra*,**, B.Farman*, JL.Sti6venart*, I.Gardin*, MO.Habert***, O. de Dreuille**, M.Bourguignon**, B.Bok*. Department of Nuclear Medicine, *Clichy, **SHFJ-Orsay, ***CHSA, Paris.

P. Bartenstein 1, A.S. Mrger 1, T. Kaufmann 2, A. Bethele 2, S. Ziegter 2, B. Conrad z, M. Schwaiger t, T.R. T611e2 Dept. of Nuclear Medicine I and Neurology 2, Techn. Univ. Miinchen

INDIVIDUAL LOCALIZATION OF ANTERIOR AND POSTERIOR COMMISSURES ON BRAIN SPECT PERFUSION IMAGES

PET IMAGING OF CEREBRAL RESPONSE TO TONIC HEAT PAIN

Thus, this semi-automatic method results in reproducible and accurate stereotactic localization of SPECT perfusion abnormalities. This method can be used routinely for repeat follow-up studies in the same subject as well as in different individuals without requiring SPECT-MRI coregistration

Aim: PET techniques have identified some principal cerebral structures of a central network that is activated during pain. The aim of this activation study was m investigate interindividual differences in the processing of tonic heat pain. Methods: 6 healthy maly volunteers were stimulated with contact heat placed against the right forearm, delivering either continous 37°C (neutral), or repetitive heat pulses (30 min, amplitude 2c) with a temperature 3°C below (warm) or I°C above (noxious heat) the individual pain threshold for 5 min. Repeated rCBF measurements were performed using a H20-15 bolus technique (3D-mode; measured attenuation). For every experimental condition 4 scans were obtained during the last minute of stimulation. Tracer counts were normalized to the global mean. Differences between the conditions averaged within and accross subjects were expressed in Z-scores. The significance threshold 0.05 was allowed adjusting for multiple comparisons. The individual Z-score images were overlayed to the individual MRI. For accross subject comparison sterotactic normalization was performed. Results: All subjects rated the noxious heat stimulus as painful (VAS rating = 6.4) and the warm stimulus as not painful (VAS rating = 0.2). The single subject analysis revealed a high degree of variability in cortical activation patterns. Statstic parametric mapping accross subjects showed a consistent activation (specific for noxious heat) only in the brainstem/PAG, contralateral somatosensory cotrex (S1) and posterior cingulate gyrus (BA 23). The inferior frontal lobe (BA 11,47) and the basal part of the temporal lobe (BA 20,38) were activated bilateraly but predominantly on the contralateral side. Thalamic activation was very variable across subjects and only significant in comparison between noxious heat and neutral stimulation. One subject showed intense increase in rCBF of the Hypophysis. Conclusion: Tonic heat pain activates a set of central structures common to all subjects. However the extent and localization of brain structures involved in pain processing is highly variable from person to person.

PTu690

PTu692

J.Pinkert ~, l.Gerdsen2, R.Frtzsch3, L.Oehme1, U.Neumann4 and W.-G. Franke~ Technical University Dresden, Depts. of Nuclear Medicine1, Psychiatry2, Neurology3 and Radiology4

H. Sumiya, M. Nakamura, A. Ichikawa, S. Tsuji, K. Kinuya, N. Tonarm, f. llhiki, and Y. Koshino, Departments of Nuclear Medicine and Neuropsychiatry, Kanazawa University, Kanazawa, Japan

A semi-automatic method was developed to determine the anterior (AC) and posterior (PC) commissures on brain SPECT perfusion images, and then to draw the proportional anatomical Talairach's grid on each axial SPECT images. This method does not require SPECT and MRI coregistration, but only MRI measurements on hardcopies. First, the AC-PC line was defined on SPECT images from the linear regression of four internal landmarks (frontal pole, inferior limit of the anterior corpus callosum, sub-thalamic point and occipital pole). Second, the SPECT position of AC and PC points on AC-PC line was automatically determined from measurements made on hardcopies of MR images of the patients. Finaliy, a proportional Talairach's grid was automatically drawn on each axial SPECT images. To assess the accuracy of AC and PC points localization, co-registered 99mTc-HMPAO-SPECT and MR images from 11 subjects were used. The mean displacements between estimated points on SPECT and true points on MRI (Ax, Ay in axial plane and Az the axial level) were calculated. The mean displacements were (in mm) for AC: Ax = -1.4+_1.8; A y = - 1 . 7 + 3 . 3 ; A z = - l . l + 2 . 5 and for P C : A x = - I . 8 + I . 8 ; Ay = 0.3+3.2; Az = -1.3+2.7. These displacements represented an error less than 5 mm at the anterior or posterior pole of the brain or at the vertex. Mean displacements did not differ significantly between intra and inter-observers comparisons.

FUNCTIONAL FRONTAL EYE FIELD IMPAIREMENT DURING SMOOTH PURSUIT EYE MOVEMENT IN SCHIZOPHRENIC AND DEPRESSIVE SUBJECTS An increased number of saccadic intrusions during smooth pursuit eye movement (SPEM) has been frequently observed in schizophrenicpatients (6080 %) and with tower incidence also in non schizophrenic psychiatric patients (30 %). In our ongoing trial we performed activation studies using high resolution ECD SPECT and compared the results with resting patterns to evaluate a possible functional disturbance of the frontal eye field (FEF) which is supposed to be involved in SPEM performance and cortical saccadic control. 15 schizophrenic and 14 depressive pts. were diagnosed according to DSM-IV criteria. Psychopathological symptoms were assessed on the BPRS, SANS, SAPS and Hamilton Depression Rating Scale. Electrooculographic and neuroophthalmological examinations were carried out in all pts. 750 MBq Tc-99mECD were intravenously given and SPECT studies (40 s / frame, 64 frames at a 64x64 Matrix) were accomplished 1 h after injection under resting conditions and following an activation with an horizontally oscillating visual target. Neuroaedvatlon images were calculated by subtracting resting from activation patterns. The activation pattern of all calculated neuroactivation images was visually analysed using a score comprising four categories from ,,no activation" to ,,strong activation" and by comparing rCBF values by statistical parametric mapping (SPM95). SPECT images were matched with MRI data for identifying anatomical structures. The calculated neuroactivation images showed hot-spots caused by elevated rCBF under neurostimulation in the primary visual cortex, unilateral frontal (FEF), posterior parietal cortex and to a smaller extent in the basaI ganglia, thalamus and cerebellum. Reduced rCBF was observed under stimul.ation in several subjects presenting an increased number of saccadic intrusions. In addition the enhancementof rCBF in the FEF was found to be lower for the schizophrenic group compared with depressive pats. (p<0.05). This might indicate an impairement of the FEF to suppress inappropriate saccades towards a visual stimulus. Our data confirm also the possibility to visualize functional well defined areas of the ocular motor system with SPECT lay using a specific task designs.

1204

AVAILABILITY OF BENZODIAZEPINE RECEPTOR SPECT I M A G I N G USING IODINE-123 IOMAZENIL IN P A T I E N T S WITH PARTIAL EPILEPSY: COMPARISON WITH CEREBRAL BLOOD FLOW SPECT IMAGING Benzodiazepine receptor SPECT imaging using Iodine-123 iomazenil (IMZ) was evaluated the detectability of epileptic focus in patients with partial epilepsy in comparison with cerebral blood flow (CBF) SPECT imaging. Twenty-four patients (12 male and 12 female, a mean age of 34.1_+10.9 yr) with partial epilepsy underwent CBF SPECT and IMZ SPECT. Every patient had focal symptoms. Epileptic focus was determined by repeated interictal EEGs and sphenoidal EEG recording. SPECT scan was performed 3 hours after the intravenous injection of IMZ (111 - 167MBq). IMZ SPECT images were assessed visually to detect epileptic focus and were compared with interictal CBF SPECT images in each patient. Focal decreased IMZ uptake was detected in 13 patients (54.2%) and focal hypoperfusion was detected in 12 patients (50.0%). Concordance with epileptic focus was obtained in 11 areas (84.6%) in the 13 decreased IMZ uptake areas and 9 areas (75.0%) in the 12 hypoperfusion areas. In conclusion, detectability of epileptic focus of I M Z SPECT is similar to that of CBF SPECT. Either IMZ SPECT or CBF SPECT can be used for detecting epileptic focus in patients with partial epilepsy.

•

Neurology

PTu693

PTu695

C Lamy-Lhullier~, P h Derambureb, E. Josienb, V. Leduc~, M Steinlinga; Departments of Nuclear Medicine (a), Clinical Electrophysiology (b) and Neurology (c) ; CHRU ; 59037 LILLE Cedex ; France

Cluckie A, Slca%ka p, Ellam S, Buxton-Thomas M, Nuclear Medic/m~ DepaLh,~,t, Kings College Hospital, London, UK. A~%LYSIS QF ACUTE STI~:~E S ~ T SCANS ~q!gG A V(X/a4E ]K%.g~D ]i~ ~ G N ~'f~GD A~D A NC~MAL T ~ A T E . ~jective: The aim of this study is to evaluate the application of comparing acute SPET stroke scans to a normal t~,plate as an aid i~ interpretation. Volt~e based image registration techniques %~re used to align SPET scans to a normal tEmiolate which was produced from 16 controls (7M, 9F, mean age=64 years). P a ~ & method: 20 consecutive acute non-hammmrhagic stroke patients were included in the study(llM, 9F, mean age=66years). All patients und~m~ent CT and SPET scanning within 72 hours of onset o~ their stroke. SPET scans were registered to a common orientation and size on a Hermes w~rkstation using a hybrid volume registration method based on principal axes and iterative downhill-si,101e~ minimization of count difference. Data Analysis: Patient SPKT scans were initially repmrted visually by a Nuclear Medicine physician who identified if a cortical perfusion deficit was present and d e ~ e d its location and size(small, medium, large). In addition, p a t i ~ t scans registered to the normal template and a subtracted image was prcduced to allow visualisation of areas of reduced perfusion. This ~ a g e was used to identify a "seed' for the region growing software to enable the volume of the perfusion defect to be est/mated. Results: ~ e aut2mated registration was suocessfully applied in al] cases. Cortical perfusion deficits %~re identified in eleven patient scans. These w~re visually graded as small(36%), medium(46%) c~ large(18%). The mean volume of the cortical pe~fusion deficit estimated tlsing the region growing software was ll.2cm 3 (small), 70.8c~ 3 (medi~) and 95.7cm 3 (large). Of the nine patient scans where no cortical perfusion deficits %~re identified visually, two scans d~onstrated subcertical perfusion deficits when subtraction frmm the normal template was perfcmmed. These were confirmed retrospectively on the CT scan reports. Conclusion:This pilot project demm~strat~ a method of analysis that may provide an automated and reproducible technique for identifying perfusion deficits in ccmtical and subcortical regior~ in acute non-hemorrhagic stroke patients.

ICTAL ECD Tc SPECT IN REFRACTORY PARTIAL EPILEPSY : ABOUT SOME METHODOLOGICAL ASPECTS. lctal SPECT studies of patients with refractory partial epilepsy are very difficult to performed with HMPAO T c The aim of this study was to discuss the results ofictal and interictal SPECT with ECD Tc. This tracer has a much longer stability than HMPAO Tc, and doesn't require an extemporaneous preparation. So that the injection can be performed more quickly after the onset of seizure. Patients (n = 22) were candidates for epilepsy surgery. They all had neuropsychological evaluation, video EEG monitoring and per-ictal and inter-ictal SPECT. SPECT images were performed on Tomomatic 564. Interictal scan was performed after intraveinous administration of 555 MBq ECD Tc. Per-ictal scans were performed with injection of radiotracer (740 MBq ECD) less than 40 sec after the electrical onset of the seizure. SPECT started between 60 mn and 225 mn (mean : 120 mn) after the injection. A semiquantitative study was performed by normalizing ECD Tc uptake pixel by pixel to cerebellar uptake. After electroclinical confrontations ictal ECD Tc SPECT appears to be very helpful in the determination of epileptic focus whereas inter-ictal ECD Tc SPECT seems to be less contributive. However, several problems have to be stressed : i) washing out must be accounted for the data analysis and mean time between injection and scans must be similar, ii) the repartition of ECD is different from HMPAO Tc, iii) the usual hyperfixation of occipital lobes impedes providing valuable datas in cases of occipital seizures. These preliminary results suggest that ECD SPECT may be an useful additional procedure in the evaluation of partial epilepsy. Comparisons with results of Neurosurgical treatments (when possible) and follow-up are now need.

u~ t-

O

m ~

t~ C u~ t._

O. PTu694

C Lamy-Lhulliera, F Duboisb, S Blond~, M Steinlinga; CHRU ; Departments of Nuclear Medicine (a), and Neurosurgery (b) 59037 LILLE Cedex ; France VALUE of 99~Tc-SESTAMIBI IN DISTINGUISHING RADIATION NECROSIS FROM BRAIN TUMOR RECURRENCE MRI or Computed Tomography does not always provide reliable informations for differential diagnosis between cerebral radiation necrosis and recurrent brain tumor. Some SPECT studies have emphasized the potential interest of Technetium-99m Sestamibi (MIBI) in this difficult differential diagnosis. The aim of this study was to compare MIBI SPECT results with histological findings. Thirteen patients with pathologically proven brain tumor (low grade glioma : n=5, high grade glioma : n=4, otigodendroglioma : n : l meningioma : n=l, lymphoma : n=l, ependymoma : n=l) were included in this one year study 12/13 were supratentorial tumors. After surgical treatment or radiation therapy, suspicion of recurrence was based on new clinical symptoms and inconclusive changes in MRI. SPECT was performed using a Tomomatic 564 one hour after iv administration of 370 MBq of MIBI. The choreid plexus index (PI) was computed as the ratio of counts in the lesion to those choroid plexus and the Mirror Index (MI) as the ratio of counts in the lesion to those in the controlateral mirror region. The PI values ranged from 0.5 to 2 and the MI ranged from 2 to 8. Using 0.5 as cutt off value for PI led to the diagnosis of recurrent tumor in 7 patients and of radiation necrosis in 6 patients. Histological results confirmed the diagnosis of recurrent tumor in 3/4 patients and of radiation necrosis in 3/5 patients. False negative results were obtained in a haemorrhagic brainstem tumor and in a necrotic lymphoma. But, using 2 as cut off value for the MI, we identified correctly the recurrence from radiation necrosis Histological results are still unknown for 4 patients. Conclusion : this study suggests that MIB1 may play an important role in distinguishing recurrent tumor from radiation necrosis However, some limits of the method have to be stressed, particularly in the infratentorial localization and necrotic tumoral evolution

PTu696 A. Bottoncetti A. Pupi U. Meldolesi D i p a r t i m e n t o di F i s i o p a t o l o g i a Clinica U n i v e r s i t 6 di Firenze, Italy B R A I N FIRST-PASS E X T R A C T I O N NCQ-298.

I,.

(E) OF THE D 2 - T R A C E R

NCQ-298 is a D 2 - 1 i g a n d that can be c o n s i d e r e d a t r a p p e d tracer (Kd 0.019 nM). To m e a s u r e receptor density in humans, SPECT data o b t a i n e d w i t h t r a p p e d tracers can be a n a l y s e d by the Patlak plot if the ratio [binding r a t e ] / [ i n f l u x rate (KI)] of the tracer is an intermediate one. K1 of NCQ-298 and rCBF w e r e m e a s u r e d by the fractionation method. E was c a l c u l a t e d as the ratio KI/rCBF. Five male S p r a g u e - D a w l e y rats w e r e anaesthetised, tracheotomized and artificially v e n t i l a t e d w i t h a h a l o t h a n e - o x y g e n mixture. Both femoral arteries w e r e cannulated, and through the right external c a r o t i d artery a c a t h e t e r was a d v a n c e d into the left heart v e n t r i c l e for the injection of the tracers. A m i x t u r e c o n t a i n i n g 9 9 m - T c - m i c r o s p h e r e s (15 ~ diameter, 0.5 mCi, 1.5 m i l l i o n of p a r t i c l e s ) , 1 3 1 - I - H i p p u r a n (5 ~Ci, to estimate the i n t r a - v a s c u l a r content of tracers) and 125-I-NCQ298 (2 ~Ci) was injected in a total v o l u m e injection of 0.i ml. Six seconds post injection, the rats were d e c a p i t a t e d and the pump controlling the arterial sampling was s i m u l t a n e o u s l y stopped. Cortex, basal g a n g l i a and cerebellum + samples were taken. +++ + The K1 values of NCQ298 were linearly ~ + dependent on 0.8. .-rCBF(slope 0.33, intercept -0.03). E value was 0.342 ± 0.0123 (mean ± sem). 0.4. The intermediate E value of N C Q - 2 9 8 is a data in favour of the possible use of K~F ~n~n~ 0 : ":-------, , Patlak plot to evaluate D2 receptor 0 1 2 3 4 density w i t h NCQ-298.

+, f+ }+}+g

1205

(b u) O 13.

• Neurology PTu697

PTu699

E. Klemm, *H. Urbach, A. Piotrowski, *D. Brechtelsbauer, **C. Pohl, F. Grfinwald, *L. Solymosi, ***P. Hfiek, H.-J. Biersack.

FRANCOIS-JOUBERT A.*, B E R G E R F.**, N O E L L E B.**, GRAND S.****, BENABID A.L.***, COMET M.* *Nuclear Medicine **Neurology ***Neurosurgery * * * * M R I u n i t - CHU A. M i c h a l l o n BP 2 1 7 X - F 3 8 0 4 3 G R E N O B L E C e d e x - FRANCE

Departments of Nuclear Medicine, *Neuroradiology, **Neurology, and ***Oto-Rhino-Laryngology, Universityof Bonn, 53105Bonn, Germany CORRELATION OF ANGIOGRAPHY, TRANSCRANIAL DOPPLER SONOGRAPHY AND HIGH RESOLUTION SPECT USING Te-99m-HMPAO FOR THE DETECTION OF HEMODYNAMIC CHANGES DURING THE INTRACAROTIDAL BALLOON TEST OCCLUSION Surgical management of ICA aneurysms, large skull base or neck tumors often requires permanent occlusion of the internal carotid artery (ICA). To predict the hemodynamic tolerance of permanent ICA occlusion an lntracarotidal balloon inflation (BTO) is widely used. Since 5% - 20% of the patients pass a BTO without neurologic symptoms, but develop a hemo~marnic infarction with permanent occlusion, BTO often is combined with vVmTc-HMPAO-SPECT. We evaluated 56 patients (58 investigations, 35 males, 21 females) with neck tumors (n = 3'*, skull base tumors (n = 17), or giant aneurysm (n = 5). The mean age was 54 years (range 13 - 75 years). Ten minutes after i.v. injection of acetazolarmde a double lumen balloon catheter was inflated in the cervical ICA for 10 minutes. Transcranial Doppler sonography (TCD) signals were continuously monitored. 740 Mbq (20 mCi) Tc-99m-HMPAO were injected following the balloon inflation. Asymmetries of HMPAO uptake were assessed both visually and quantitatively. Quantification was performed using a semiautomatic cortical peel technique applied to the various cerebral-artery territories within l0 predifined slices. Patients with neurological deficits had t-IMPAO uptake side differences from 30 - 50 % (anterior and middle cerebral artery) or TCD mean velocity decreases ranging from 30 % - 70 % as comPoared to baseline values. Patients with HNIPAO uptake differences > 20 ~ (same territories) or a TCD decrease > 30 % were assessed to carry a high risk of hemodynamic infarction after permanent occlusion. We conclude that Tc-99m-HMPAO-SPECT during balloon test occlusion of the internal carotid artery is a sensitive tool to define various risk groups, but has to be combined with TCD monitoring reflecting the different hemodynamic changes after balloon occlusion and taking into account the time of injection of the tracer following the occlusion, and the angiographic findings during the procedure. Furthermore, right/left uptake differences shouldbe analyzed with respect to the various cerebral territories instead of calculating only whole-hemispheric ratios.

PTu698 L.O. Kapucu, A. Kuruo~lu, Z. Ankan, M. 0nlfi. Departments of

Nuclear Medicine and Psychiatry, Gazi University, Ankara-Turkey. REVERSIBLE CEREBRAL BLOOD FLOW ABNORMALITIES IN PATIENTS WITH EATING DISORDERS STUDIED BY 99mTcHMPAO SPECT METHOD. Despite the growing number of studies on eating disorders, several aspects still remain ill defined. Imaging studies and electrophysiolegical data are scarce, which preclude widely accepted conclusions. In this report we present three patients with eating disorders, investigated with electroencephalography (EEG), cranial computerized tomography (CT) and SPECT. One patient was a 19 year-old female with a diagnosis of bulimia nervosa for the previous 4 years. She had no anorectic symptoms. The other two who were aged 16 and 18 years had anorexia nervosa with bulimic symptoms, with a disease duration of 1.5 and 2 years respectively. SPECT studies were performed following intravenous injection of 592-666 MBq 99mTc-HMPAO. Transaxial, sagittal, and coronal slices were obtained. SPECT results were evaluated by both visually and semiquantitatively. The mean counts/pixel was calculated for 11 regions of interest on 8 sequential transaxial slices and two for the cerebellum. Region/cerebellumratios were obtained. For each region normalized ratios were used to obtain side to side % asymmetry index between pre-treatment and posttreatment studies. While no patients showed CT and EEG abnormalities, the two anorectic patients had bilateral frontal, frontoparietal, parietal, frontotemporal hypoperfusion especially more prominent on the left side, in pretreatment SPECT examination. The patient with bulimia nervosa had normal findings in SPECT study. Following the treatment program lasting a year, and during when all patients remained free of symptoms for at least 3 months, SPECT studies were repeated with the same dose of 99mTc-HMPAO, revealing normal findings. For visually detected abnormal regions the asymmetry between pre-treatment and post-treatment SPECT studies ranged from 3 to 7 %. Although this reversal of cerebral low flow may partly be explained b y the changes in the eating habits, other yet unknown mechanisms should also be considered.

1206

S E S T A M I B I SPECT D I S C R I M I N A T I O N VS H I G H OR LOW GRADE GLIOMAS.

OF

RADIONECROSIS

99mTc-Sestamibi b r a i n S P E C T has b e e n u s e d for patients suffering from brain tumors to discriminate low v e r s u s h i g h g r a d e g l i o m a s but what about r a d i o n e c r o s i s ? We have s t u d i e d 34 high grade, 7 low grade a n d 5 r a d i o n e c r o s i s lesions. P a t h o l o g i c a l p r o o f at the time of the S P E C T was o b t a i n e d in 31/34, 3/7, 2/5 p a t i e n t s a n d c l i n i c a l and MRI results in the o t h e r s . An i n d e x w a s calculated for e a c h p a t i e n t as the ratio of l e s i o n ' s ROI counts to c o n t r a l a t e r a l R O I counts. Results (m±sd) for group i, 2 and 3 are r e s p e c t i v e l y 61.9±49.0, 16.6±26.7, and 6.8±11.5. C h o r o i d p l e x u s e s and p i t u i t a r y gland w e r e t a k e n as i n t e r n a l control region (ROI) so t h a t t w o other ratios were c o m p u t e d for each S P E C T s t u d y : l e s i o n to p l e x u s and lesion to p i t u i t a r y gland. For the 3 ratios we c o u l d e a s i l y s e p a r a t e h i g h f r o m low grade groups (p<0,001) but o n l y r a t i o s to p l e x u s or to p i t u i t a r y g l a n d w e r e a b l e to separate low g r a d e from radionecrosis groups (p<0,05). H o w e v e r some b o r d e r l i n e v a l u e s i n d u c e d an o v e r l a y i n g of the r a t i o s e s p e c i a l l y w i t h the t u m o r to noise ratio. W i t h a p l e x u s r a t i o ' s u p p e r level of 0,09 and 0,95 for r a d i o n e c r o s i s a n d low grade respectively, only 5 patients (11%) w e r e wrongly classified (3 in h i g h group, 1 in e a c h other). We think that those n e w i n d e x e s w i l l be v e r y h e l p f u l to d i f f e r a n t i a t e r a d i o n e c r o s i s f r o m low or h i g h grade tumors.

PTu700 V.Krymski,A.Lysachev, T.Kotelnicova,O.Soboleva B u r d e n k o N e u r o s e r g e r y Institute, D e p a r t m e n t of R a d i o l o g y , Moscow, R u s s i a R E G I O N A L C E R E B R A L B L O O D FLOW U S I N G 99Tc H M - P A O S P E C T M E T H O D IN P A T I E N T S W I T H S E V E R E H E A D T R A U M A IN THE L O N G T E R M P E R I O D Cerebral blood perfussion (CBP) u s i n g 9 9 T c H M - P A O S P E C T m e t h o d s t u d i e d in 20 pts after s e v e r e h e a d trauma(HT) d u r i n g 1-5 years. The SPECT r e v e a l e d : all p t s ( 2 0 / 2 0 ) had regional CBF d i s t u b a n c e s in e x a m n a t i o n period. H y p o p e r f u s i o n a r e a a l w a y s surrounded contusion lesion that r e v e a l i n g CT but hypoperfusion a r e a was c o n s i d e r a b l y m o r e t h a n a v o l u m e of c o n t u s i o n l e s i o n (i0/i0) . C o n t u s e d a n d h y p o p e r f u s i o n areas l o c a l i z e d in b a s a l r e g i o n s of frontal and temporal lobes more often (8/10). SPECT did not s h o w CBF d i s t u r b a n c e s on the side of the removed subdural hematoma in pts(5/5) w i t h o u t d a m a g e of b r a i n t i s s u e and local n e u r o l o g i c a l deficit. Hypoperfusion area was r e v e a l e d on the o p p o s i t e of the a f f e c t e d side in a c c o r d a n c e w i t h EEG c h a n g e s (3/4). In these pts CT changes were not presented on the side of hypoperfusion area. In pts (4/4) w i t h long coma in a c u t e stage of the HT and g o o d o u t c o m e in late period specifical disturbances of CBP w e r e not found. After plastic closing cranial defect (i0/i0) c h a n g e s in n e u r o l o g i c a l state a n d S P E C T w e r e not o b s e r v e d a f t e r two p o s t o p e r a t i v e weeks. However it is not clear h o w c l o s i n g of c r a n i a l d e f e c t i n f l u e n c e on CBP in l o n g t e r m p e r i o d a f t e r operation. Our investigation indicates that disturbances of CBP r e m a i n for long time a f t e r the h e a d trauma. H y p o p e r f u s i o n areas o c c u p y w i d e regions of the brain and can lead to the d e v e l o p m e n t of t r a u m a t i c disease.

• Oncology Oncology

PSu701

PSu703

P. Paulus. A. Sambon, T. Benoit, J.M. Deneufbourg, P. Moreau, P. Rigo, University Hospital, Sart Tilman, Liege, Belgium

P. Magnani, C.Messa. G.Trifirb, G.Rizzo, A.Carretta, A.Vanzulli, G.Lucignani, A.Del Maschio, P.Zannini, MC.Gilardi, F.Fazio. INB-CNR, Istitulo Scientifico H S.Raffaete, Universita. di Milano, Milan, Italy.

POSITRON

STAGING OF NON-SMALL CELL LUNG CANCER WITH FDG PET AND CT IMAGE FUSION. The staging of bronchial carcinoma (T) is currently based on CT, mediastinoscopy (MDS) and transbronchial mediastinal lymph-nodes (N) biopsy.The accuracy of CT in assessing N involvement, based on node size, is reported to be 50-60%, while that of FDG/PET, based on tracer uptake, is reported to be 80-90%. The synergistic use and fusion of FDG/PET and CT images, by combining the spatial resolution of CT and sensitivity of PET, may improve the accuracy of the assessment of the mediastinal N involved and avoid MDS. To assess the usefulness of CT-FDG/PET image fusion for N staging, 9 patients with a lung lesion were studied with both methods. Methods: FDG studies were performed with GEAdvance PET tomograph and dynamic scanning for 1 hour after i.v. inj. of 290 MBq of the tracer. Lesions were considered positive when FDG uptake was judged to be greater than blood pool activity at visual inspection by two independent observers. Spiral CT was performed with a Toshiba scanner. CT and PET scans were interpreted separately and after fusion. Results of both scans were compared with histological diagnosis. Results: As for T detection, either CT or PET showed 8 true positives (TP) and 1 false positive (FP). As for N staging, CT scored 3TP, 1 true negative (TN) and 5 FP; FDG/PET before registration scored 5 TN. tn the remaining 4 pts a hypermetabolic area was detected which could be due to nodes, blood pool or primitive tumor. CT-PET fusion images of these patients diagnosed 3TP, and 1 FP. Conclusions: FDG/PET is more accurate than CT in staging disease; PET-CT coregistration further improves the accuracy of stagir,g. FDG quantification and follow-up may clarify FP findings.

EMISSION

TOMOGRAPHY WITH IN T H E D E T E C T I O N O F L Y M P H NODE I N V O L V E M E N T A N D R E C U R R E N C E S IN H E A D AND N E C K C A N C E R : H I S T O P A T H O L O G I C A L CORRELATION. We performed a retrospective study to evaluate the role of FDG-PET in the detection of primary tumor, lymph node involvement and recurrences in head and neck cancer patients. We studied 26 patients who underwent clinical examination, computed tomography (CT) and FDG-PET within 2 weeks. All patients were operated on and the staging results were correlated with the histopathological examination of the surgically resected piece. 19 patients were evaluated at the time of diagnosis for the detection of the primary tumor and lymph node involvement. With FDG-PET, the primary tumor has always been detected and the absence of metastatic lymph nodes has been correctly interpreted in 11/14 patients. We deplore 3 false positive results but FDG-PET allowed the detection of an involved heternlateral lymph node in 1 patient with a piriform sinus tumor not detected by clinical examination and CT. Microscopic foci were missed by FDG-PET in two cases but were also undetected by CT and clinical examination. FDG-PET appears to be more efficient in the detection of recurrences. Among the 7 patients studied when a relapse was clinically suspected, FDG-PET correctly evaluated the extent of the recurrence in all patients and, in one case, FDG-PET was the only technique to demonstrate a mandibulary relapse after surgery and radiotherapy. Our retrospective study suggests that FDG-PET has a relatively limited and targeted role in the staging of head and neck cancer at the initial diagnosis but is more relevant in the detection of recurrences when anatomical structures have been modified by previous surgery and/or radiotherapy. FLUORODEOXYGLUCOSE

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PSu702

PSu704

T.Ohlsson 2, E.Brun~, K.Erlandsson 2, G.Holmstr~m 2, E.Kjell6nl~ A.Sandell2,j. Tennvall I, J.Wennerberg 3 E.Wing~rdh 2 . Depts.of Oncology l, Radiation Physics ~ and Oto-Rhino-Laryngology 3, University Hospital, Lund, Sweden.

S. Maurea, W. Acampa, P. Varrella, S. Lastoria, C. Mainolfi, H. Wang, P. Fimiani, MR. Panico, G. Abbate, M. Salvatore. Nuclear Medicine and Hematology, Istituto Nazionale dei Tumori, Universith degli Studi "Federico II", CNR, Napoli, Italy

EARLY CHANGES I N 2 1 8 F D G AND DNA P R O F I L E D U R I N G R~IATION CANCER.

OR CHEMOTHERAPY

OF ADVANCED

HEAD AND NECK

Tke possibility of predicting outcome of treatment could direct us from unfavorable treatment and thereby avoiding unnecessary side-effects. We have investigated the glucose-metabolism by initial uptake and early changes in 2 18FDG-PET, and also changes in the DNA profile during the initial treatment with radiation or chemotherapy. Ma.terials and methods. 12 males with squamos cell carcinoma of the head and neck, tumour stages Ill-IV, 21-72 years of age (median 55 ) were included, f r o m M a y 1993 to April 1994. 9 patients started with hyperfractionated radiotherapy,l.6 Gy twice daily, 3 with chemotherapy, Cisplatinum I00 mg/m 2 i.v. day 1 and Fluorouracil I00 mg/m 2 i.v. days 1-5. PET scanning and fine-needle biopsy, of palpable, histologically proven lymph node metastases, was performed before start of treatment (3-10 days before) and after ccmpleting the first chemotherapy cycle or after 5-11 days of radiotherapy, viz.after 16-35 Gy. Results and conclusion. Elevation of 2 18FDG uptake was seen in all but two primary tumours, one of the primary tumours beeing small(< 7 ngn), the other was > 20ram, with a low uptake. The uptake was generally higher in pzimaries than in corresponding metastases. A high uptake in the first PET examination and a low decrease in the second one correlated to a lesser degree of local tumour control after completed therapy. Of 12 examined biopsies 9 were evaluable with flow cytometry. 5/9 had initially non-diploid tumour cell pcpulations and in 4 of these the non-diploid population had disappeared at the time of the second examination. Feulgen stained static measurements revealed that in some of these cases non-diploid cell populations remained in the second biopsy.

Tc-99m MIBI IMAGING IN THE EVALUATION OF PATIENTS WITH LYMPHOMAS: COMPARISON WITH GALLIUM-67 AND F18 FDG PET STUDIES Tc-99m MIBI imaging has been proposed to assess patients (pts) with different malignant tumors. However, the role of this technique in lymphomas has not been yet established. We directly compared the results of Tc-99m MIBI whole-body imaging in 18 pts with proven lymphomas (11 non-Hodgkin and 7 Hodgkin) with those of gallium-67 citrate (n=12) and those of fluorine-18 deoxyghicose (FDG) PET (n=lO) studies. Tumor lesions were localized on the basis of clinical examination and/or radiological imaging findings. When MIBI and gallium images were compared, a total of 26 tumor lesions (3 neck, 2 abdomen and 8 mediastinum lymph nodes, 1 jejunum, 8 skeletal and 4 soft tissue) was analyzed in 9 pts; in 3 of these pts, a total of 11 unknown lesions was discovered on MIBI and gallium images. The other 3 pts were disease free. The diagnostic accuracies of MIBI (93%) and gallium (90%) imaging were comparable. When MIBI and FDG PET images were compared, a total of 25 tumor lesions (7 neck, 2 abdomen and 11 mediastinum lymph nodes, i jejunum and 4 soft tissue) was analyzed in 9 pts; in 1 of these pts, 3 unknown lesions were discovered on MIBI and FDG images. The other patient was disease free. While the diagnostic accuracy of MIBI was 85%, that of FDG was 100%. In a patient with multiple abdominal nodular lesions (liver, spleen and lymph node) by Hodgkin disease, MIBI, gallium and FDG images were compared; in this case, while no MIBI uptake was observed in tumor lesions, gallium and FDG activities were clearly abnormal. Thus, this study suggests that MIBI and gallium scans may provide comparable diagnostic information in pts with lymphomas; however, MIBI shows better imaging quality. Conversely, MIBI scan is slightly less accurate compared to FDG. The intense activity of MIEI in the abdomen (liver, spleen and bowel) may obscure lymphoma lesions located in the lower chest and in the abdomen.

1207

111

O

• Oncology PSu705 R.P. Bourn, E. Weidmann, S. Adams, A. Hertel, B. Knupp, S. Eisner, P.S. Mitrou, D. Hoelzer, G. H&. Departments of Nuclear Medicine and Internal Medicine, Goethe University Medical School, Frankfurt/Main, Germany. SERIAL WHOLE BODY FDG-PET COMPARED TO CONVENTIONAL DIAGNOSTIC IMAGING IN PATIENTS WITH MALIGNANT LYMPHOMAS: RESULTS OF A PROSPECTIVESTUDY. Purpose: To investigate whether F-18 FDG PET may be able to replace conventional staging by a number of examinations such as CT scans, ultrasonography, x-ray of thorax, abdomen/GI tract, and skeletal/Ga-67 scintigraphy in patients with malignant lymphomas and, thus, may safe substantial efforts without increasing or even decreasing costs, we prospectively studied patients (pts) before treatment, after 3 or 4 cycles of chemotherapy and after completion of radio-/chemotherapy. So far, 18 pts were entered into the study. 2 pts, suggested to have lymphomas by PET and CT, had to be excluded, because histology revealed tuberculosis. Of tile remaining 16 pts, 9 had Hodgkin's disease (8 nodular sclerosing, 1 mixed type) and 7 Non-Hodgkin's lymphomas (2 large cell anaplastic, 1 MALT, 1 T-zone, 1 B-lymphoblastic, 1 B-cell and 1 cb-lymphoma). Results: At diagnosis, in 3/16 cases the different examinations corresponded completely. In 9/16 pts, the procedures showed different results (more involved lymph nodes and regions demonstrated by PET in all of these cases), not influencing tumor stage or treatment. In 4 pts there were differences concerning the stage: l. a malignant pleural effusion demonstrated by CT but not by PET; 2. lymphoma of the lung and 3. spleen involvement shown by PET but not by other exams 4. an infradiaphragmatic nodule described by PET, which turned out to be supradiaphragmatic by CT scan. 9 pts were studied after 3 or 4 cycles of chenmtherapy and 3 pts after finishing ehemo/radiotherapy. The latter and 4/8 patients after chemotherapy had CR in all procedures. Of the remaining 4 pts 3 had CR by CT, but showed hypermetabelie lymph nodes by F-18-FDG. One MALT lymphoma described to have residues of lymphoma in the liver and the colon and CR in the stomach by PET was demonstrated to have only partial remission in the stomach. In conclusion, the data so far demonstrate at least comparable results using PET or all ether conventional diagnostic procedures for primary staging and a higher diagnostic accuracy of PET in evaluation of therapy response.

PSuT07 AR. B6rner I M "Weckesser~, H Herzog ~, W. Audretsch 2, M. Rezai 2, H.W. MOller-G~rtner I. Institute of Medicine ~ , Research Center J~lich, and Dept. of Senology 2, Cityhospitals Dtisseldoff, Germany. FIg-FDG-PET IN BREAST CANCER: EARLY O R LATE I M A G I N G FOR BETTER M E T A B O L I C I N F O R M A T I O N ? In primary carcinoma of the breast preoperative chemotherapy is useful to obtain better cosmetical results and to resect larger margins to vital tumor tissue. MR/ gives good anatomical information on basis of hypervascularisation, but hypervasularisation is the first feature to resolve after chemotherapy. There is a need for imaging procedures giving precise information on hypermetabolic residual tumor before surgery. Twelve patients with breast cancer of_>3 cm in diameter were studied with PET after injection of 20 mCi (740MBq) FId-FDG 1. for 90 rain. and 2. from 180-240 rain. All patients were fasted for at least 12 hrs. Iterative reconstruction and 3-D-reprojections were calculated, displayed and evaluated for both scans. In all patients hypermetabolism of the primary tumor was observed with dose-uptake rations (DUll) ranging from 7.2 to 12.5 and tumor/nontumor ratios (T/NT) of 2.2 to 3.7 at 1.5 hrs. Early scans (-l.Shr) showed hypervasularisation in normal, inflammatory and mastopathlc breast tissue comparable to MRI-mammograms. In one patient with inflammatory carcinoma the whole breast seemed involved. With time after injection no relevant changes were found in DURs, but loci were more prominent in 3hr scans due to lower background and showed improved delineation from non-cancerous tissue. T/NT ratios increased to 5.4-108. No normal breast tissue, large veins or muscles except myocardium were visible in the 3hr scans in contrast to 1.5 hr scans. The patient with inflammatory carcinoma had 3 clearly contrasted loci at 3 hrs p.i.. These preliminary results indicate that Fld-FDG-PET started at 3 hr p.i. is able to provide pure metabolic information that cannot be obtained by any other method. It is superior to early scanning in terms of target/nontarget ratios and differentiation of malignant vs. inflammatory or benign changes.

PSu706 AR. B0rnerl., M. Weckesser l, F. Weise I, H. Herzog l, U. Nitz 2, H.G. Bender 2, H.W. Maller-Gartner 1. Institute of Medicine ~, Research Center J(ilich, University Clinic for Gynaecology and Obstetrics 2, University DOsseldorf, Germany

PSu708 L.G. Strauss ~, L. Schad', A. Dimitrakopoulou-Strauss', M. Knopp ~, R. Engenhart ~, U. Haberkorn', F. Oberdorfer ', J. Doll', G. van Kaick'. 'German Cancer Research Center, Heidelberg, 2University Clinic for Radiotherapy, Heidelberg, Germany

F I g - F D G PET IN OVARIAN CANCER

POSITRON EMISSION TOMOGRAPHY (PET) AND MAGNETIC RESONANCE IMAGING (MRI) 1N PATIENTS WITH BRAIN TUMORS RECEIVING RADIOTHERAPY.

Ovarian cancer is rare, but prognosis of patients with ovarian cancer is poor because of late diagnosis and widespread metastatic disease in more than 70 % of patients. Fourteen patients with ovarian cancer Figo III and IV were examined with F18-FDG-PET after surgery and first three courses of adjuvant chemotherapy. All patients were diagnosed disease-free by computed tomography. Overnight fasting patients were injected with 20 mCi (740 MBq) F18-FDG. They were asked to drink 2 I of mineral water and had static scans of the abdomen and pelvis three hours later after emptying the urinary bladder. Iterative reconstruction and 3D reprojections were used for analysis. In 13 of 14 patients a focal glucose hypermetabolism was found. It was identified as local recurrence in 3, as lymph node metastases in 8 and as both in 2 cases. No false positive results were obtained. Only one patient was staged disease-free by all methods. Diagnoses were confirmed at second-look surgery in 13 cases. PET didn't show micro metastases of the omentum majus in one patient. One focal hepatic lesion showed no F18-FDG accumulation and was not removed at surgery. A comparison of F I8-FDG images to CT scans showed that all involved lymph nodes were <1.2 cm in diameter. Local recurrence was taken for scarring or altered anatomical set-up aRer extensive surgery. Size of the local lyrnph nodes is not an appropriate criterion for diagnosing metastases. FI8-FDG PET is not able to identify micro metastases, but reveals macro metastases in a large percentage of patients with ovarian cancer. These preliminary results show that FDG PET is able to indicate location of relapse or metastases in ovarian cancer patients thus giving early clues to surgery and intensified radiochemotherapy.

1208

The correlative assessment of PET and MRI studies necessitates common land marks. This is important in particular for the radiotherapy of brain tumors. Vital as well as necrotic tumor tissue must be idenfied and associated with mqrphological structures. We used an individual, dedicated head mask and a stereotactic device in patients scheduled for radiotherapy due to brain tumors. External marks were used during the imaging procedures and evaluated with a software program in order to correlate the corresponding cross section levels. The MRI examination was dynamically performed in each patient using the intravenous application of contrast material (Gd-DTPA), parameter: TR=170 ms, TE=5 ms, FL=900, RFOV=160*270 mm2, MA=128"256, TH=5 ms, 15 sections, acquisition time 22sec). Double tracer PET studies were performed with O-15 labeled water (1550-3600 MBq, 8"1 minute images) and F-18-Deoxyglucose (FDG, 240-360 MBq, 19 images, total acquisition time 60 min). The PET images were corrected for scatter and attenuation and iteratively reconstructed with an matrix of 256*256. identical ROIs were used for MRI and PET and time-signal and time-activity concentrations were calculated. Furthermore, models (two and three compartment) were used for the quantitative evaluation of the MRI kinetics, for O-15 labeled water and FDG. The preliminary evaluation of the ongoing study comprises 5 patients. The spatial error was less than 3 mm in all patients. All tumors were well delineated in the MRI images. The PET data demonstrated in 2 patients inhomogenous tumor tissue with hypo- and hypermetabolic areas, which were associated with hypo-and hyperintense regions in MRI. The quantiative evaluation gave evidence for a two compartment distribution of Gd-DTPA in tumors. The FDG accumulation was not clearly associated with the contrast material kinetics.

•

Oncology

PSu709

PMo711

U.B.BadeL =W.Reiche, tA.Schaefer, 'C.Alexander, 'L.Trampert, ~W.Feiden,4J.R.Moringlane,aU.Piepgras,*M.Eisenhutand xC.-M.Kirsch Department of ~Nuelear Medicine, :~leuroradiology, ~Neuropathology, qqeurosurgeryand *Dept. of RadiopharmaeyUniversityHospital Heidelberg, UniversityHospitalHomburg/Saar-Crermany.

Saadet Atay, (~etin C)nsel, Kerim S0nmezo~lu, Bedii Kanmaz, Haluk Sayman LevenfK&basakal, Zeynep Do~ruca, A. Fuat Yapar, Musa Hamidi, O. Fehmi YardL Ebru AIkan, ham Uslu

Comparison Of 18-FDG PET And 123-J ~z-Methyltyrosine SPECT With CT And Mill Findings In Patients With Primary Brain Tumors

OUTCOME OF DIFFERENTIATED THYROID CANCER TREATED AT THE CERRAHPASA MEDICAL FACULTY

18-FDG PET data and 123-J a-Methyltyrosine SPECT (IMT) were compared with CT/MRI findings and correlated with the histopathological result gained by stereotactic biopsy. Thus we tried to answer the question whether metabolic neuroimaging provides further diagnostic information in patients with gliomas. Thirteen patients underwent a PET and SPECT study. PET acquisition of the brain followed 30 min. after injection of 200 MBq FDG with a Siemens ECAT-ART PET-Scanner. One hour after application of 250 MBq IMT a SPECT-study with a double headed gammacamera with high resolution collimators (Multispect 2 Siemens) was acquired. While localized gliomas showed -depending on the grade of the tumor- no, low or high FDG accumulation in the PET study, all tumors had an intensive IMT uptake (12/13). In 1 case a diffuse spreading and infiltrating glioma could not be either visualized by both methods. As a result of this study IMT-SPECT in brain tumors shows an excellent tumor to brain ratio and therefore pathological findings like recurrence can easily be visualized. The comparison of FDG-PET and IMT-SPECT findings supports in vivo tumor grading as well as change of grade and early detection of tumor-recurrence during follow up.

Cerrahpa§a Istanbul

Medical

Faculty,

Nuclear Medicine

Department,

A retrospective clinical and pathological study was carried out in 849 patients (female 663, male 186 ) with differentiated thyroid cancer treated at The Cerrahpasa Medical Faculty from 1968 to 1994. The mean follow-up period was 6.10+4.4 (range 124) years. The histologic diagnoses were 361 (43%) papillary carcinoma, 288 (33%) mixed papillary/follicular carcinoma, 172 (%21) follicular carcinoma and 28 (%3) H(irthle cell carcinoma. The overall mean age was 43.6+16.7 years. Two hundred sixty six patients (44%) were under 40 years. There were 174 patients with occult cancer 5 had regional lymph nodes involvement. Operations were conservative in these patients. All patients were underwent surgical treatment. In whom 95% patients were total or near total thyroidectomy. Thirteen patients had distant metastases to bone and lung at the time of 1-13l therapy. One hundred thirty eight patients were followed with only suppression therapy. Of 652 patients were treated with 1311after operation and TSH suppressive therapy. Of 652 patients 409 (%63) had total ablation after 1311 < o therapy. The ablation doses of 131 I were _10OmCi for 256 (39.3~/o) patients, 100-200mCi for 105 (16.1%) patients and more than 200mCi for 48 (7.4%) patients. Thirty two patients had recurrence of 1311concentrating tissue after initial total ablation, The reccuronce rate was significiantly higher in patients over 40 years. Thirty two patients died due to the thyroid cancer. There were no deaths in patients with occult cancer and when total ablation was accomplished during the follow-up period, No significant secondary effects of radioiodine treatment was observed in this series.

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PSu710

PMo712

T. K u w e r t 1, B. Woesler 2, C. M o r g e n r o t h 2, P. Matheja 1,

Ch. Ehrenheim, J. Fischer, S. Sophocleous, G. netting, H. Hundeshagen

S. Palkovic 2, B. Vollet 1, W. Brandau 1, M. Schiifers 1, H. W a s s m a n n 2, O. Schober 1 , D e p a r t m e n t s of (1) Nuclear

Department Nuclearmedicine, D-30623 Harmover

i.._ Medizinische Hochscbule Hannover,

=I~

LONG-TERM FOLLOW-UP AND THERAPEUTIC RESULTS IN PATIENTS WITH LOW RISK DIFFERENTIATED THYROID CARCINOMA

0..

Medicine and (2) Neurosurgery, WWU Miinster, Germany. GLUCOSE METABOLISM AND AMINO ACID UPTAKE IN BRAIN TUMORS It is still unclear whether the study of amino acid uptake offers advantages over the measurement of glucose metabolism for the diagnostic workup of patients with brain tumors. It was therefore the aim of this study to compare glucose metabolism with amino acid uptake in these neoplasms. Methods: The study comprised 19 patients with brain tumors including seven patients with high-grade gliomas, five patients with metastases, four patients with low-grade gliomas, and three patients with low-grade non-gliomatous brain tumors. Glucose metabolism was studied using the PET camera ECAT EXACT 47 and F-18-fluorodeoxyglucose (FDG); amino acid uptake was measured with the triple-headed SPECT camera MULTISPECT 3 and iodine-123-a-methyl tyrosine (IMT). For both techniques study specific discrimination thresholds were defined as those values of uptake that differentiated best between high-grade tumors, i.e. high-grade gliomas and metastases, and lowgrade tumors, i.e. low-grade gliomas and benign non-gliomatous neoplasms. Results: The correlation between the tumor-to-slice ratio of IMT uptake (RIMT) and the tumor-to-gray matter ratio of FDG uptake (RFDG) was low, but significant (r = 0.61; p < 0.01). Using thresholds of 0.8 for RFDG and 1.8 for RIMT the accuracy values of PET and SPECT for differentiating between high-grade tumors and low-grade tumors were 17/I9 (89 %) and 13/19 (68 %), respectively. Conclusions: Glucose metabolism and amino acid uptake are loosely, but significantly correlated in brain tumors. In a heterogeneous group of patients with brain tumors FDG-PET may be superior to IMTSPECT for the non-invasive evaluation of malignancy grade.

Aim of the study was to determine the frequency of local recurrences and distant metastases and their risk factors in pts with low risk differentiated (follicular or papillary) thyroid carcinoma pT1NoM 0 or pT2NoM0. We overlook about 2200 patients with thyroid carcinoma since 1966, and 740 pts (30%) belong to the low risk groups pTtNoM 0 or pT2NoM0. The incidence ranges about 140 pts per year in our area. The homogeneity of our group is given by strict criteria for the histologic diagnosis and tumor staging according to the TNM system. Diagnostic and therapeutic procedures vary in exceptional cases only. Serological, scintigraphic and othei examinations are repeated in regular time intervals. Tumor markers (hTg and antibodies), J-131 whole body scan, iodine contamination, T1-201 and Tc-99m MIBI scans as well as bone scan, ultrasound, x-ray, CT, and MRI are included. It is of special interest which of these procedures is the earliest and the most reliable to detect rumor recurrence or metastases in pts with low risk tumor. A total number of 52 pts out of 740 pts died. 65 local recurrences (lrec) or metastases (met) were diagnosed in 41 pts (%) (4 pts pT1NoM0, 37 pts pT2NoM0), 11 of them died (1 pt pT1NoM0, 10 pT2NoM0), but only 3 due to the tumor disease. First diagnostic hint to tumor recurrence or metastases was given by the tumor marker hTg in most cases. The pts" age at the onset of the disease influences the prognosis, especially in pts with follicular carcinoma, and further the tumor size. No prognostic value was stated for pts" sex, surgical method (total, subtotal) and tumor growth characteristics (uniVmultifocal). We propose a tight follow-up programme even for low risk tumor patients including routinely performed hTg and ultrasound with selective use of additional diagnostic specialities to warrant best patient care.

1209

(/)

0

• Oncology PMo713

PMo715

S.Tasi6, ~.Perovi6,

S.Djurica,S.Pendi6

Institute for Radiology and Oneology Serbia Department

of Nuclear Medicine

FOLLICULAR AND PAPILLARY THYROID CARCII{OMA: A RETROSPECTIVE STUDY , ON io5~ CASES In Institute for Radiology and Oncology SRS,699 patients of average age o£ 42 years,suffering from Papillary as well as 555 of average age o£ g6 years with Follicular thyroid oarcinoma,£ollo wed up 1-54 y. and 1-45 y~respectively,have been studied.Females suffered from thyroid carcinoma /TC/ more frequsntly/79%/than males/21%/,giving 3.7 : i relationship.At the time o£ diagnosis o£ FC 162/555 patients were younger than 45 y, with I stage in 156/162 of them and 6/162 with II stage of disease/TNMl/oln 195/355 other peopis/45y et more/ with FC,I stage in 12/193 was proved,but II and III stage in 135/193 and 5o/19 IV stage of disease in 16/195 was confirmed. At the time of diagnosis of PC ~o9/699 pts.were younger than ~5y.l stage has been confirmed in 4o3/~o9,11 stage in 6/4o9 pts.Elder than ~5y /29o/699/suffered from PC in I stage 12/29o,ll stage 156/29o,III stage 116/29o and 6/29o in IV. An objective basis for treating FC amdPC,a prognostic factors,quantifying clinical,histologie and therapeutic parameters was established with prognostic implications. Age~t~mor size,local inv asion,distant metastasis ,surgery,degree of tumor differentiation,presence of capsular and vaseulan invasion,cellular atypia,showed prognos tic value for survival. Overall mortality in followed group has been 26/699 in PC group and 56/555 in FC, respectively.

A. Spanu, M.K. Solinas, A. Falchi, S. Nuvoli, M.D. Azzena, A. Serra, C. Bagella, A. Masts, P. Solinas, M. Piga and G. Madeddu. Depts. of Nuclear Medicine. Universities of Sassari and Cagliari. Italy.

Tc99m-SESTAMIBI (MIBI) AND Tc99m-TETROFOSMIN (TF) IMAGING IN DIFFERENTIATED THYROID CARCINOMA (DTC). Tc99m-MIBI and Tc99m-TF have been reported to localize in malignancies including thyroid cancer.To further evaluate the usefulness of these non specific radiotracers in the lollow-up of DTC to early detect local and distant recurrences, we studied 97 pts, 70 F and 27 M, aged 19 to 71 yrs, previous}y submitted to total thyroidectomy and to radioiodine therapy for papillary (77 cases), follicular (16 cases) and Htirlle cell (4 cases) carcinomas.In all pts on suppressive L-tiroxine treatment, whole body,neck and chest planar and SPET images were acquired 15 rain after i.v. 740 MBq injection of MIBI in 74 cases and of TF in the remaining 23. MIBI and TF images were compared to conventional 1311-WBS and to Tg serum levels, both the latter evaluated in withdrawa} of T4.1n all 79 patients with low Tg (<3ng/ml) and negative 1311WBS, MIBI scan performed in 61 cases and TF scan in the remaining 18 were concordantly negative.Likewise, 9 pts with high Tg and positive 1311WBS had also positive findings at MIBI (7 cases) or at TF 12 cases) scans.However, in 5 of these pts, MIBI and TF identified more local and lung lesions in respect of 1311-WBS and this was confirmed at therapeutic radioiodir~e scanning.Finally, in 9 pts with high Tg and negative 131t-WBS, only MIBI in 6 cases and TF in the remaining 3, localized local, lung and bone metastases which were also detected by other imaging methods or by surgery.Of 18 MIBI or TF positive pts, only SPET detected metastases in 4 cases while it identified more lesions than planar images in a further 7. Our data suggest that either MIBI or TF scans, mainly by SPET, could find a large use in the follow-up o! pts with differentiated thyroid carcinoma to clarify high serum Tg conditions; moreover, these methods could also reduce the frequency of 1311-WBS in those cases in which the two tracers persist negative in concordance with low Tg and negative radioiodine scan.

PMo714

PMo716

K. Mainz, St. Miiller, W. S o n n e n s c h e i n , Chr. Reiners, J. S c i u k Nuclear Medicine, University Essen, F R G

E. Varo~lu, G. Ak~ay, H. Uslu, C. Gflndogdu D e p a r t m e n t s of Nuclear Medicine, Endocrinology a n d Pathology, Mat/irk University, Medical School, E r z u r u m - T u r k e y

THE INFLUENCE O F T H E L O C A T I O N OF T H Y R O I D C A N C E R M E T A S T A S E S ON T U M O R D E T E C T A B I L I T Y WITH THALLIUM-201

Tc-99m-TETROFOSMIN SCINTIGRAPHY IN THE DIFFERENTIATION OF MALIGN FROM BENIGN THYROID NODULES

TI-201 scintigraphy has an established role in the follow-up of thyroid carcinoma. For the diagnosis of p u l m o n a r y and other distant metastases, however, the results are sometimes disappointing, but no data are available in the literature. In a retrospective study (1988-1994), we analyzed the diagnostic a c c u r a c y of Tl-201 s c i n t i g r a p h y in 162 patients; there were 41 patients with oncocytic (Hurthle cell) carcinomas. After injection of 75 M B q Thallium-201-chloride, we performed planar whole b o d y scans, followed by a S P E C T e x a m i n a t i o n of the chest. All patients had clinical examinations, serum t h y r o g l o g b u l i n levels, ultrasound examinations of the neck, and chest X-rays. The diagnosis was validated by surgery or follow-up over at least 1 year; 19 patients had to be excluded because of incomplete validation. All TI-20Iscintigrams were reevaluated by an experienced observer, blinded to the clinical data, and the likelihood of tumor in the neck, the mediastinum, the lungs, and the skeleton was rated on a scale from 0 to 4. The tumor detectability for lymph node and mediastinal metastases was compared to other metastatic locations (lung and bone) by ROC-Analysis using the bivariate binormal model. The R O C - a n a l y s i s gave an overall sensitivity of 7 5 % (95% c o n f i d e n c e interval 6 5 - 8 4 % ) at a specificity o f 90%. At a fixed specificity of 90%, the True-Positive-Fraction test showed a significant difference (p<0.01) between the sensitivity of 88% (95% confidence interval 7 6 - 9 4 % ) tbr cervical and mediastinal metastases and of 58% (95% confidence interval 4 2 - 7 3 % ) for other metastases. The thallium-201 scintigraphy is a valuable diagnostic method in the follow up of differentiated thyroid cancer, especially for cervical and mediastinal lymph node metastases. The detectability of metastases in other locations is substantially inferior.

1210

T e c h n e t i u m 9 9 m - t e t r o f o s m i n h a s been p r o p o s e d for m y o c a r d i a l imaging a n d it also a c c u m u l a t e s skeletal muscle, liver, spleen, breast tissue, kidney a n d normal a n d pathologic thyroid tissue in proportion to regional perfusion. We evaluated Tc-99m-tetrofosmin u p t a k e of n o d u l a r thyroid disease a n d c o m p a r e d with Tc-99mp e r t e c h n e t a t e s c i n t i g r a p h y a n d h i s t o p a t h o l o g i c findings for the differentiation of malign thyroid n o d u l e s from the benign lesions. Thirty six p a t i e n t s (28 females a n d 8 males, aged from 18 to 58 years) were included to the study. All patients h a d solitary a n d / or multiple thyroid nodules. T c - 9 9 m - p e r t e c h n e t a t e 100 Mbq w a s injected intravenously, 2 0 m i n u t e later a n a n t e r i o r p l a n a r image w a s obtained for 5 m i n u t e s , After 48 h o u r s , 3 7 0 MBq Tc-g9mTetrofosmin was injected intravenously a n d anterior p l a n a r images for 5 m i n u t e s at the 15th m i n u t e a n d 1st h o u r were also obtained. All of p a t i e n t s h a d n o d u l a r y goitre d i s e a s e in p h y s i c a l a n d ultrasound examination. Tc-99m-pertechnetate scintigraphy showed t h a t 28 patients h a d cold nodules, w a r m nodules in 4 a n d hot n o d u l e s in 4, In cytopathologic e x a m i n a t i o n , 5 patients h a d differentiated thyroid c a r c i n o m a (3 follicular carcinoma, 2 papillary carcinoma), 23 p a t i e n t s h a d thyroid a d e n o m a , one patient h a d Riedel thyroiditis a n d 7 p a t i e n t s h a d follicular cyst. In the early phase Tc-99m-tetrofosmin scintigraphy, 19 of 28 patients with cold nodules ( 67,8 % ). one of 4 patients with hot nodules ( 25 % ), all of 4 patients with w a r m nodules / 100 % } did not s h o w tetrofosmin uptake. In the late phase, 20 of 28 patients with cold nodules ( 71.4 % ), one of 4 patients with hot nodules ( 25 % ), all of 4 p a t i e n t s with w a r m nodules ( 100 %) also did not have tetrofosmin uptake. The sensitivity of Tc-99m-tetrofosmin scintigraphy for differentiating malign from benign nodules were calculated a s 75 % a n d 80 % for early a n d late phase, respectively. We did not calculate specificity rate of t h i s m e t h o d b e c a u s e we h a v e not a n y t r u e negative a s s e s s m e n t in o u r cases. In the present study, we concluded t h a t Tc-99m-tetrofosmin m a y be a n alternative scintigraphic method to TI-201 a n d Tc-99m-MIBI scintigraphy for differentiating malign from benign thyroid lesions

• Oncology PMo717

PMo719

I.Saletnich, M.Salvatori, B.Rossi, M.C.Garganese, M.Marciano, V.Rufini, L.Troncone D e p a r t m e n t of N u c l e a r M e d i c i n e - S a c r e d H e a r t Catholic University - R O M E P U L M O N A R Y A N D B O N E M E T A S T A S E S IN D I F F E R E N T I A T E D THYROID CANCER (DTC): UNIVARIATE AND M U L T I V A R I A T E A N A L Y S I S OF P R O G N O S T I C F A C T O R S . The prognostic value for distant metastases development of the f o l l o w i n g v a r i a b l e s in 804 p a t i e n t s w i t h D T C t r e a t e d in the 2 6 - y r p e r i o d from January 1969 to December 1995 was evaluated by univariate ( C h i - s q u a r e a n d T-test) and multivariate (logistic r e g r e s s i o n stepwise mode) a n a l y s i s : sex (204 male, 600 female), age

O. Schillaci, C. Moroni*, R. Tavolaro, R. Danieli, V. Picardi, A. B o s s i n i * , R. C a s s o n e * , F. S c o p i n a r o , Sect. Nucl. Med. a n d *Int. Med., Univ. "La S a p i e n z a " , Rome, Italy.

at d i a g n o s i s (451~45 a n d 3 5 3 > 4 5 yrs), h i s t o t y p e (620 p a p i l l a r y a n d 184 f o l l i c u l a r form), t u m o r size (TI=189, T2=433, T3=62, T4=120) and lymph node involvement at d i a g n o s i s (168 p o s i t i v e , 636 n e g a t i v e ) . Statistical analysis identified older age (p<0.001), follicular histotype (p<0.001), tumor size T3-T4(p<0.001) and lymph node involvement (p<0.0001) as s i g n i f i c a n t n e g a t i v e prognostic factors while sex has less significativity (p<0.05). Tumor size and lymph node i n v o l v e m e n t are the best p r e d i c t o r s for the p r e v i s i o n of a 15yrs disease free survival (DFS) after surgery (p<0.01). Particularly, 15yrs DFS in 60% of pts w i t h lymph node i n v o l v e m e n t and tumor size T3-T4 vs. m o r e than 90% of pts w i t h o u t lymph node and tumor size T~-T2 was observed. Finally, lymph node involvement seems to be the only prognostic f a c t o r a b l e to f o r e c a s t with high probability the development of a specific m e t a s t a t i c s i t e (lungs).

A NEGATIVE DIPYRIDAMOLE EXCLUDES SIGNIFICANT HYPERTENSIVE PATIENTS

(DIP) T C - 9 9 m M I B I S P E C T EPICARDIAL CAD IN WITH CHEST PAIN.

In h y p e r t e n s i v e p a t i e n t s (pts) w i t h c h e s t p a i n the noninvasive diagnosis of CAD is an important clinical concern because all exercise-dependent tests show limited feasibility and diagnostic accuracy. The a i m of t h i s study was to d e t e r m i n e the diagnostic value of T c - 9 9 m MIBI SPECT after high-dose DIP ECHO test. At coronary angiography 22 p t s h a d s i g n i f i c a n t epicardial (ep) C A D ( s t e n o s i s A 70% of at l e a s t o n e m a j o r vessel), a n d 4 out of 18 p t s w i t h n o r m a l ep vessels showed slow coronary flow. F o r ep C A D detection, DIP Tc-99m MIBI SPECT sensitivity was 95.5%, specificity 72.2.%, positive predictive value (PV) 80.8% and negative PV 92.9%. Reversible perfusion defects were detected in the 4 pts with patent major c o r o n a r y a r t e r i e s b u t r e d u c e d f l o w v e l o c i t y of angiographic contrast medium, due to microvascular disease. In conclusion, these results indicate that significant ep C A D in h y p e r t e n s i v e pts with chest pain is u n l i k e l y when DIP Tc-99m MIBI SPECT is negative. When scintigraphy is positive, either ep or small-vessel CAD is possible.

tO 4.J t-

PMo718

PMo720

P. Bert¢lli, M. Cintorino*, L. Burroni, A. Vella, D. Volterrani, S. Lazzi*, and A. Vattimo, Nuclear Medicine Unit and Institute of Pathology*, University of Siena, Italy.

K. Melis, J. Kunnen*, A. Vervaet, J. Vandevivere, L.L. Mortelmans* Departments of Nuclear Medicine and Radiology*, General Hospital Middelheim, ~d]twerp, Belgium.

AUTONOMOUSLY FUNCTIONING THYROID NODULE BEARING H~RTHLE CELL TUMOR: ITS DETECTION WITH Tc99mSESTAMIBI Thyroid scintigraphy with Tc99m-Sestamibi (MIBI) has been suggested to visualize extranodular thyroid tissue suppressed by a autonomously functioning thyroid nodule, in alternative to endogenous TSH stimulation. In a series of 82 pts with a clinical and biochemical hyperthyroidism due to a hot nodule previously detected by a scintigraphy with Tc99m, a single injection dual phase scintigraphy (SIDPS) with MIBI (15-30min and 34hrs p.i.) was performed. A visual score of extranodular uptake in comparison with nodular uptake has been done. Nodular-to-thyroid uptake ratio (N/T) in the early and late images and washout rate from the nodule (WON) and the thyroid tissue (WOT) were also measured. Histopathology was obtained in 26 operated pts. In 11 pts (Group A) the early image showed a good uptake of MIBI in the nodule and a poor uptake in the extranodular tissue; the late image showed a persistent uptake in the nodule with fading activity in the extranodular tissue. In 6 operated pts histopathology demonstrated a Httrthle cell tumor (HCT). In 71 pts (Group B) the early image showed a good uptake both in the nodular and extranodular tissue with fading activity in the late image in both areas. In 20 operated pts histopathology revealed a benign adenoma.

CAPTOPRIL RENOGRAPHY : FIRST LINE INVESTIGATION IN THE EVALUATION OF RENOVASCULA]~ HYPERTENSION. Goals: evaluation of the value of captopril renography in the detection of hemod]rnamic significant renal artery stenosis (RAS), in comparison with renal angiography. Patients and methods: Baseline and post-captopril studies were performed with 99~ Tc DTPA in 251 patients (123 men and 128 women) with suspicion of renovascular hypertension (RVH). Captopril (50 mg) was given orally in a fasting condition. ACE-inhibitors and diuretics were discontinued at least 2 days before the study. Clinical parameters as serum creatinine, blood pressure levels, and drug treatment were recorded. Kidney images were acquired using a gamma camera computer system in a time sequence of 20 min at a rate of 1 frame/20 sec after a bolus injection of 370 MBq. ROI's were traced over the 2 kidneys on cumulative images 2 min after dose injection and used for calculation of activity-time renographic curves and separate GFR. In 71/251 (28%) an intra-arterial digital subtraction angiography (DSA) of the renal arteries was performed. Data-analysis: visual renographic analysis, time to peak activity (Tmax), relative individual kidney uptake index, and absolute individual kidney clearance were evaluated as diagnostic parameters to be used in a grading system proposed by the Consensus Committee on RVH, resulting in high, indeterminate or high probability for RAS. DSA was read as significant (>50% stenosis) or non-significant IS 50% stenosis). Results ~enograpny vs anglograpny Non slgnltlcant ISlgnitlcant I !Low proDabi±lty 115 21 Zndetermlnate proDaDl±lty122 Hlg~ proDabllzty 12 )iscussion: our results snow that captoprl± renograp~y is a very sensitive investigation in screening for P~AS. False positive results were largely due to different hydration. As 10/32 patients with indeterminate probability had an angiographically proven significant RAS, patients with high as well as with indeterminate probability will proceed to angiography.

ffl

0

Group A Group B

early N/T 2.98_+2.11 2.60_+1.30

late N/T 5.46-+4.84 1.77_+1.10

WON 17.16_+5.23 26.31-+2.75

WOT 24.55_+5.23 23.11-+3.69

The rate of malignancy in AFTN is very low and in such cases there is not discrepancy in the uptake of Tc99m and radioiodine. Our data demonstrate that SIDPS is able to detect hot nodules beating the HCT. The persistent uptake of MIBI is related to crowded mitochondria. This pattern of HCT could explain those cases able to retain radioiodine, since usually HCT born in cold nodules does not.

~0

1211

• Oncology PMo721

PMo723

V.B.Sergienko, E.N.Khodareva, Institute of Clinical Cardiology, Cardiology Research Center, Moscow, Russia.

S.Naqamachi,S.Jinnouchi,Leo G. Flores II, H.Nakahara,T.Ohnishi,S.Futami,K.Watanabe, Department of R a d i o l o g y , Miyazaki Medical College, Miyazaki, JAPAN

CAPTOPRIL RENAL SCINTIGRAPHY IN THE DIAGNOSIS & MANAGEMENT OF RENOVASCULAR HYPERTENSION. The aim of our study was to determine the diagnostic value & the ability of radionuclide ACEl-test to reveal the presence of angiotensine-2 dependent renovascular disorder (RVD) & potentially reversible RVH in patients (pts) with severe arterial hypertension & renal artery stenosis (RAS). 54 hypertensive pts. were evaluated. Evidence from angiography showed RAS > 50% in 39 of them ( 10 pts with bilateral RAS - [BRAS], 29 unilateral RAS [UP,AS] ). 15 pts without any RVD were estimated as a control. Renal scintigraphy with 131I-OIH & 99m-Tc-DTPA was performed in every case at baseline conditions & after ACEI (25 mg. captopril per os). The total & split ERPF & GFR were measured with a single compartment radiotracer infusion clearance. Also were evaluated time-activity curves & hypotensive effect of ACEI. In 32 pts, who underwent surgery treatment, preoperative studies were correlated with blood pressure (BP) outcome after revascularization. Normalization or improvement of BP control after surgery were documented in 22 of them, poor BP outcome (failure) was identifyed in 10 pts. The results of our investigation showed increased sensitivity & specificity after ACEI in all group ofpts, from 72%-80% to 85%-93% respectevely. In patients with URAS sensitivity increased from 72% to 90%, in BRAS didn't change (70%-70%). In pts with good BP response after surgery sensitivity of renal scintigraphy after ACEI in detection RAS increased from 73% to 95%, in failured pts from 50% to 60%. The drop in BP after ACEI was more significant in cured pts. & URAS , but it hadn't diagnostic value. However, positive scintigraphic test features, specific for RAS, were obvious only in 72% URAS pts, 30% BRAS pts, 95% cured or improved pts & in 30% of failured pts. On the basis of this data scintigraphic ACEI-test appears to reliably increase the diagnosis of RVH & especially predict BP response to revaseularization with some limitation in BRAS pts & in pts without improvement of BP control after surgery.

COMPARISON OF Tc-99m MIBI AND TI-201 SPECT IMAGING IN PRIMARY LUNG CANCER A N D M E D I A S T i N A L LYMPH NODE METASTASIS

Purpose:The a i m of the p r e s e n t s t u d y is to c o m p a r e the effectiveness of T c - 9 9 m MIBI and TI201 chloride for detecting primary lung cancer and mediastinal lymph node metastasis Methods:Cases were twenty-one p r i m a r y lung cancer (>1.5 cm) h i s t o l o g i c a l l y c o n f i r m e d and e i g h t e e n mediastinal metastatic lymph nodes (>i.0 cm) d i a g n o s e d b y c h e s t CT. Dual-isotope SPECT performed at both 20 min and 240 min postinjection of 600 M B q T c - 9 9 m M I B I a n d 148 M B q T I - 2 0 1 chloride. The image was interpreted as positive if there was significant tracer uptake in accordance with tumor or metastatic lymph nodes. Results: S t r o n g TI-201 u p t a k e was shown in all p r i m a r y tumor on b o t h e a r l y a n d d e l a y e d images (100%), whereas Tc-99m MIBI uptake were shown only in 16 of 21 (76.2%) on e a r l y images and in 14 of 21 (66.7%) on d e l a y e d images. M e t a s t a t i c lymph nodes showed TI-201 uptake in 16 of 18 (88.9%) on both early and delayed images. Tc-99m MIBI uptake was noted in 14 of 18 (77.8%) on early studies and 12 of 18 (66.7%) on delayed studies. Conclusion: Both Tc-99m MIBI and TI-201 SPECT can be helpful in detecting lung cancer and mediastinal lymph node metastasis, a n d the s e n s i t i v i t y was higher in TI-201 SPECT. In MIBI SPECT, early images was more effective than delayed images.

PMo722

PMo724

D.A.Merzliakov, S.L.Stukanov, S.A.Kolomietz, I.GFrolova, S.A.Velichko, BN.Zyrianov,WYu.Ussov Tomsk Institute of Oncology, Siberia,RUSSIA

A. Tutus, M. Nardab, I. Cralmez, G. Silov, M. Kibar, E. Karahacto~lu. Departments of Nuclear Medicine and Psychiatry. Erciyes University Medical School, Kayseri, Turkiye.

PENTOXYFILLINE IMPROVES [CANCER /BACKGROUND] UPTAKE RATIO IN 9$mTc-MIBI LUNG SPET STUDIES. Usually g9mTc -MIBI scanning for visualising of cancer is performed at rest without pharmacNogical stresses. In the study we aimed to test whether cancer/background ratio can be increased pharmacologically. In 10 patients with lung cancer of T2N0-2M0-1 stages 99mTc -MIBI SPET study was performed before start of any treatment and in three days thereafter, combined with infusion of 10 ml of 2% solution of pentoxyfilline. Each time 99mTc -MIBI SPET was performed using 740 MBq of the agent, with reconstruction of 2 cm slices from 64-128 projections/360 ° of rotation. Simultaneously blood samples were taken for 10 min after injection of 99mTc -MIBI for quantification of blood clearance of the agent. Uptake of 99mTc-MIBI in lung cancer was quantified as [Cancer~Background] and [Cancer/Myocardium] ratios of average uptake in the region of interest. The following results were observed :

Rest Lung cancer/ Background

Pentoxyfilline test

ranges 1.26 - 1.94 mean 1.52 (sd O.11) p < 0.01 vs. rest Lung cancer/ ranges 0.36 - 0.53 ranges 0.34 - O. 57 Myocardium mean 0.43 (sd 0.05 ) mean0.44 (sd 0.06 ) p > 0.05 vs. rest Pentoxyfilline significantly accelerated both quick and slow components of ggmTc -MIBI blood clearance. Pentoxyfilline-induced increase in 99mTc-MIBI correlated negatively with dimensions of cancer nodule. Thus, pentoxyfilline stimulates blood clearance of 99mTc-MIBI, facilitates uptake of the agent in cancer tissue and therefore improves the [Lung cancer/Background] uptake ratio in SPET studies Pentoxyfilline should be further tested as agent for routine combination with 99mTc-MIBI in lung cancer diagnostics, in particular when early stages of cancer are supposed.

1212

ranges 1.18 - 1.49 mean 1.40 (sd 0.09)

E V A L U A T I O N OF P R I M A R Y LUNG C A N C E R W I T H Tc-99mTETROFOSM1N 1N C O M P A R I S O N TO Tc-99m MIBI UPTAKE Technetium-99m-tetrofosmin has become available for myocardial perfusion imaging. The tumour-seeking properties of the routinely used myocardial perfusion agents T1-201 and Tc-99m MIBI are welI known. In fact, tetrofosmin and MIBI have some properties in common. The aim of the current study was to investigate whether Tc99m tetrofosmin has a diagnostic role in lung lesions and it has any advantages over MIBI or not. Both Tc-99m tetrofosmin and Tc-99m MIBI studies were performed in 20 patients with primer bronchial carcinoma, 5 patients with benign pathologies and 10 controls. The malignancy oftumours was confirmed by the results o f pathology. The images were evaluated visually and also quantitatively. Lesion/ contralateral normal lung ratios were calculated, 30 min after the injection of 555-740 MBq Tc-99m tetrofosmin and Tc-99m MIBI with a period o f 48 hours. The mean tumor uptake ratio was slightly higher with Tc-99m MIBI than Tc-99m tetrofosmin. 18 out of 20 patients with primary lung malignancies demonstrated pathologic uptake on planar imaging. Three types pathological uptake pattern were observed visually. No abnormal activity accumulation was detected in benign lesions. The overall sensitivity in the lncalisation of primary tumour was 90% on planar imaging for both study. The demonstration of central tumour necrosis as a hypoactive area indicates Tc-99m tetrofosmin accumulates in viable tumour tissue only, as has also been described for MIBI in malign lung lesions. In conclusion Tc-99m tetrofosmin has quite similar properties and equivalent sensitivity with MIBI. Additionally Tc-99m tetrofosmin has advantage of no sternal activity and it can be labeled with Tc-99m at room temperature as compared to sestamibi which requires heating for approximately 20 rain.

• PMo725

Oncology

A. Tutus, h4'. Kibar, G. Silov, M. Nardah, M. Kula, T. Yolcu, I. Gt~lmez, K. Attila, Departments of Nuclear Medicine and Internal Medicine, Erciyes University,Medical Faculty, Kayseri, TORKIYE

PMo727 T.Atasever_, G.Vural, N.Cetin, N. Gok¢ora, C. 0zturk, M.0nlU. Gazi University Faculty of Medicine, AnkaraTi)rkiye

EVALUATION OF MALIGN LUNG LESIONS WITH Tc-99m TETROFOSMIN tN COMPARISON TO THALLIUM-20I AND Tc-99m MIBI

EVALUATION OF M A L I G N AND BENIGN LUNG LESIONS WITH Tc-99m TETROFOSMIN

Thallium-20l has achieved widespread acceptance in clinical oncologic imaging, but problems due to cyclotron production and poor energy characterisation are significant disadvantages of this agent. Tetrofosmin can be labeled with Tc-99m at room temperature as compared to sestamibi which requires heating for approximately 20 minutes. The aim of this study was to investigate the diagnostic role of Tc-99m tetrofosminin malign lung lesions and to compare the resultswith Te-99m MIBI and TI-201. This study was carded out on twenty patients (18 men, 2 women, mean age 61.31_+9.1 yr) with primary bronchial carcinoma (10 epidermoid ca., 6 small cell ca., 2 adeno ca., 2 undifferentiatedlarge cell ca.). The imageswere evaluated visually and also quantitatively. Lesion / contralateral normal lung (LfNL) ratios were calculated 30 minutes after the injection of 740 MBq Tc-99m tetrofosmin, Tc99m MIBI and 180 minutes after'the injection of 111 MBq TI-201. While MIBI and tetrofosminstudies had two false negative results, there were three false negative results for TI-201 study. The mean tumor uptake ratios ofTc-99m tetrofosmin, Tc-99m M1BI and T1201 were ] .40_+0.024. 1.46_+0.020, 1.67_+0.16 respectively. The L / NL ratio was slightly higher with MIBI and TI-201 than tetrofosmin, however MIBI and tetrofosminappears same sensitivity in malign lung lesions. For this reason we concluded that telrofosmin is a promising agent in the evaluation of malign lung lesions.

The purpose of the study was to evaluate the Tc-99m tetrofosmin uptake in malign and benign lung lesions. Study population consisted of 21 cases of primary lung cancer (I0 squamous cell, 5 small cell, 4 adeno and 2 large cell carcinoma) and 9 benign lung lesions (4 pneumonia 3 tuberculosis, I infected bronchiectasis and I bronchiolitis obliterans). The smallest malign lesion size determined from CT was 3 cm, Anterior and posterior planar thorax images were obtained 30 minutes after iv injection of 740 MBq Tc99m tetroJ'osmin. Visual and quantitative evaluation was performed. For quantitative evaluation regions of interest were drawn on the lesion area fL) and contralateral nonlesion area (N). Out of 21 malign primary lung lesions 19 (90%} showed Tc-99m tetrofosmin accumulation, One squamous cell and an adenocarcinoma did not show tracer uptake. 4 of the 9 (44%) benign lung lesions including three pneumonia and a case of active tuberculosis showed also uptake. The mean !L/N) ratios for malign and benign lesions were 1.63+029 and 1.64+_0.I9 respectively. L/N ratios of malign and benign lesions as well as various histological types of lung cancer did not show difference (p>0.05}. As a conclusion Tc-99m tetrofosmin showed high sensitivity (90%) in detecting malign lung lesions but it revealed lower specificity (55 %).

(/) C O

|mm

r= (I) (n Q.

PMo726

PMo728

T. Ba~oglu, C. Co~kun, i.Bernay, M. ~ahin, A.Talu, L.Erkan Ondokuz Maym University Hospital, Departments of Nuclear Medicine and Pulmonology, Samsun - Turkey

A. Spanu, F. Ginesu, G. Dettori, P. Pirina, A. Farris, A. Porcu, A. Falchi, ME. Solinas, S. Nuvoli, M.D. Azzena and G. Madeddu Depts. of Nuclear Medicine, Respiratory Diseases, Surgery and Oncology. University of Sassari. Italy

EVALUATION OF T99M-TETROFOSMIN UPTAKE IN BENIGN AND MALIGNANT LUNG LESIONS Accumulation of the recently developed myocardial perfusion agent Tc99m-Tetrofosmin (TF) in malignant tissues including lung tumors has been reported by various authors. The objective of our study was to evaluate (a) the uptake and kinetics of this tracer in benign and malignant tung lesions, (b) the effect of radio- and/or chemotherapy on Tc99m-Tetrafosmin uptake in malignant lung tumors. A total of 40 patients with well-diagnosed lung lesions ( 33 untreated malignant tumors, 7 benign lesions) were included in the study. An initial 30minute dynamic acquisition and following static images were obtained in all patients after intravenous injection of 740 Mbq TF. Lesion / contralateral normal lung (L/CN), heart / lesion (H/L) , and heart / contralateral normal lung (H/CN) ratios were calculated for 5-10,25-30 and 85-90 minutes p.i. Tracer washout in the lesion at 30 minutes postinjection (p.i.) was determined. There was visibly increased TF uptake in 29 of 33 malignant tumors. Mean uptake ratios were : n=29 5-10 min.p.i 25-30 min.p.i. 85-90 min.p.i. L/ON 1.37 _+0.24 1.33 ± 0.23 1.30 + 0.21 H/L 1.84 +_0.38 1.96 _+0.37 1.93 +_0.54 H/CN 2.46 _+0.36 2.56 + 0.37 2.38 + 0.58 All H/L ratios were significantly different from H/CN ratios (p<0.05). Mean TF washout in 29 malignant lesions at 30 minutes p.i. were 27.9 % + 6.7. In nine patients, acquisitions could be performed after therapy. Significant decrease of TF uptake was observed in five patients with squamous cell carcinomas (SCC). 2 patients with SCC showed no difference of TF uptake after therapy. In remaining 2 patients, both with small cell carcinomas, increase of tracer uptake was observed. In one patient, bone and soft tissue metastasis, in another multiple bone metastasis could be detected. In 2 of 7 benign lesions (tuberculosis and empyema), TF accumulation was observed: Mean WCN ratio at 25-30 and 85-90 rain pJ. were 1.38 _+0.04 and 1.43 + 0.02 respectively. Mean 30-Minute washout rate was 23.3 % _+ 4.3.The sensibility of TF in the detection of malignant lung lesions in our study was 88 % , being within the range reported for Tc99m-SESTAMIBI (65%-96%).1ts specificity was calculated as 71%.

Tc99m-TETROFOSMIN DETECTION.

SCAN IN LUNG AND BREAST CANCER

Tc99m-Tetrofosmin (TF) is a myocardial periusion imaging tracer whose uptake has also been described in malignant tumors. To further evaluate TF scan role in detecting neoplastic lesions we studied 30 male pts with lung NSCLC (LC) and 15 females with breast cancer (BC). LC included 26 pts with primary cancer, 23 before surgery and 3 already operated (2 NED, 1 with mediastinal metastases) and 4 pts with secondary tumors; BC included 14 pts belore mastectomy (4 of these had previously undergone excisional biopsy) and 1 mastectomized advanced disease (AD). Six pulmonary and 4 mammary benign lesions were also investigated. In all pts, planar and SPET images were acquired 15 rain. after 740 MBq TF injection. TF scan was positive in both planar and SPET in all primary LC and in 3/3 bone metastases while only SPET detected mediastinal lymph nodes in 12/12 cases including the already operated pt; TF scan was negative in the 2 NED pts. The 4 secondary tumors were also detected by TF, but only 2 by SPET. In BC pts marked TF uptake was detected by SPET in 10/10 primary non operated tumors, while planar images were positive in only 6 cases. Moreover, only SPET identified bone and mediastinal metastases in 2/2 pts, including the AD mastectomized patient as well as neoplastic lymph nodes in 3/7 affected pts; however, negative malignant lymph node size, at surgery, was < 1 cm . TF uptake was also observed in 2 benign axillary lymph nodes. TF did not accumulate in the perinodular tissue nor in axillary lymph nodes of previously biopsy excised pts, according to histology after mastectomy. Both pulmonary and mammary benign tesions were all TF negative. Tc99m-Tetrofosmin could represent a new tumor agent to detect primary and metastatic lung and breast cancers, given the high sensitivity and specificity observed in our cases; moreover, SPET imaging represents the more accurate diagnostic tool.

1213

(I,) (/) o 13.

• Oncology PMo729 J.L. Moretti, F. Tamgac, S. Piperno-Neumann, N. Sail, J.M. Rocchisani, J.L. Breau. Universit6 Paris 13, Bobigny, France PLANAR S C I N T I G R A P H Y W I T H Tc-99m S E S T A M I B I , TI-201 A N D In-111 O C T R E O T I D E IN L U N G C A N C E R : AN I N D I C A T O R OF C H E M O T H E R A P Y RESPONSE Ten patients (9M, 1 F, mean age: 56-+7 yrs) with primary lung cancer (7 small cell lung cancer, 2 adenocarcinoma, l squamous cell) were studied before and after 3 courses of chemotherapy by planar scintigraphy (Sc 1 and Sc2). T1-201 (TI) (125 MBq) and Tc-99m Sestamibi (MIBI) (580 MBq) planar imaging was performed on thorax 15 rain. p.i. and In-111 Octreotide (OCT) (160MBq) 4 hr. and 24 hr. p.i. The 14 lesions belonging to the 10 patients were visualised by all the tracers. Tumor activity was measured using tumor uptake over background ratio (T/B). The ratio of TIB(MIBI)/T/B(TI) were calculated. Lesions having MIBI/TI _> 1 (10 lesions) showed an objective response to chemotherapy (complete=6/10, partial=4/I0) assessed by clinical, radiological and biological examinations. The 4 lesions who had MIBI/TI < 1, were no responder. Tumors resistant to chemotherapy may wash-out MIBI via Pgp 170, conversely to TI which is only perfusion related. Thus MIBI/TI ratioI (no responder) (responder) OCI" n=4 n=10 uptake 4hr I 24hr 4hr r 24hr Scl 1.4-+-0.2 1.6_+0.2 1.6_+0.5 1.8_+0.7 sc2 1.5_+0.3 1.7_-+0.1 1.2_---83.2 1.3_+0.1 Conclusions: In lung cancer; 1- In-111 Octreotide uptake was related to the tumor evolution after chemotherapy; 2- MIBI/TI may have a predictive value of chemotherapy response.

PMo731 LKostako~lu, P.0.Klrath, N. Elahi, U. Uysal, D. Uzal, N.C. Giilaldi, E. Baltah, E. 0zyar, B. Caner, T. Aras, O. U~ur, L. Atahan, C.F. Bekdik. Haeettepe University Medical Faculty, Department of Nuclear Medicine, Ankara, Turkey. DIAGNOSTIC POTENTIAL OF TC-99M-TETROFOSMIN (TETRO) IN THE DETECTION OF MALIGNANT TUMORS: COMPARISON OF THE RESULTS WITH TI-201 IMAGING. Our aim was to evaluate the diagnostic value of Tetro in patients (pts) with various types of malignant tumors (tm) as compared with T1-201. A total 90 sites were evaluated in 75 pts of whom 34 with primary brain tin, 20 with breast cancer, 15 with nasopharyngeal cancer (NPC), 6 with bone and soft tissue tm (B&ST) were included in the study. Spot and/or SPECT iniages of the relevant area were obtained 30 rain. after the injection of 111 MBq of TI-201 and 555 MBq of Tetro using a dual-head gamma camera. All studies were correlated with concomitant radiographic studies such as mammography (Mammo) and ultrasonography (US) in pts with breast cancer, and/or CT/MRI in all others All visually detectable lesions on scintigraphy were considered positive for disease. Tm/baekground (T/B) ratios were calculated. TI-201 imaging was false negative in I6 pts (6 pts with NPC, 6 pts with low grade astrocytoma, 4 pts with breast Ca). Tetro was false negative in 4 pts with low grade astrocytoma;TI-20l was also false negative in these 4 pts. The results are as follows (True positive:TP, True aegative:TN, False positive:FP, False negative (FN); TETRO TI-201 TP 62 73 TN 12 12 FP 0 1 (brain lm) FN 16 4 (brain tms) Sensitivity 79 % 95 % Specificity 100% 92 % Accuracy 82 % 94 % T/B ratios were as follows; Brain Tm 2.67+1.8 9.05_+6. l Breast Ca 2. t9_+1.2 2.11+1.5 NPC 2.33-+0.7 2.65+0.7 Bone & ST tm 2.21+0.7 2.12_+0.5 Except for primary brain tumors there was no statistical difference between T/B ratios of T1-201 and Tetro imaging (p >0.1). The sensitivity and accuracy of Tetro imaging proved superior to TI-201 in the detection of malignant tumors. We conclude that although its sensitivity for low grade brain tms is low, Tetro should replace TI-201 in tm imaging for its superior imaging properties.

PMo730

PMo732

H KAYA, A (,20BANER, R. I~IK, A. SENYiQJIT, S. YILMAZ, M COSKUNSEL

L.Kostako~lu, U. Uysal, E. Ozyar, N. Elahi, B. Caner, T. Aras, 0. Ugur, L. Atahan, C.F. Bekdik. Hacettepe University Medical Faculty, Department of Nuclear Medicine, Ankara, Turkey.

Deparments of Nuclear Medicine and Chest and Tuberculosis. Dicle University of Dicle, Diyarbaktr, Turkey. TETROFOSMIN ACCUMULATION IN THE MALIGN PLEURAL MESOTHELtOMA. Pleural malign mesothelioma (PMM) is a malign disease characterized by plevral mass (or thickening) and effusion after a long latent period with the exposure to asbest fibres. In patients with PMM, intrathorasicthe space and thorasic wall involvement is the important factor affecting the operative procedure. Our aim in this study was to determine single and/or multiple involvement of PMM with thorasic SPECT using Tc 99m-tetrofosmin and to compare thorasic SPECTwith thorasic CT. Sixteen patients were involved in this study. Thorasic CT and thorasic SPECT was performed to all patients.Thorasic SPECT was obtained at 20 min after intravenous administration of 20 mCi of Tc99m-tetrofosmin. With thorasic CT, 12 of the patients (75%) had single thorasic mass lesion but only 3 of them (19%) had multiple lesions at the thorasic wall and in the intrathorasic space. However, thorasic SPECT using Tc-99m tetrofosmin determined that all of the patients (100%) had involvement of PMM and besides this, there were multiple involvement of thorasic wall and intrathorasic space in l0 of them (62%). In conclusion, this study suggests that Tc-99m tetrofosmin thorasic SPECT was more sensitive than thorasic CT for detection of single and/or multiple lesions of PMM and might be used for selection of patients to operation.

1214

MONITORING RESPONSE TO THERAPY USING CONSECUTIVE TL-201 AND TC-99M-SESTAMIBI (MIBI) SPECT IN PATIENTS WITH NASOPHARYNGEAL CARCINOMA (NPC). There is a great demand for a satisfactory imaging tool in monitoring response to treatment and differentiating post-therapy changes from residual disease (liD) in patients (pts) with NPC. We attempted to assess the value of TI-201 and MIBI SPECT in monitoring disease regression/progression as compared with CT/MRI fmdings in pts with NPC undergoing chemotherapy and/or radiotherapy (C-RT). Thirteen pts (age range: 13-75, mean: 44) underwent consecutive SPECT imaging using a dual-head gamma camera after the injection of 111 MBq of TI-201 and 555 MBq of MIBI prior to C-RT, 3 months and 6 months following C-RT. A total of 78 SPECT studies were correlated with concomitant CT/MR/ studies. Tumor/background (T/B) ratios were obtained on coronal slices. Visually detectable lesions in the region of nasopharynx (NP) and cervical lymph nodes (LN) were considered positive for RD. The combination of repeat MILl scans, endoscopic examination and clinical evaluation performed 9-12 months after completion of C-RT was the gold standard for the presence of disease. One pt died 4 months after completion of C-RT and 4 pts developed bone metastases. Twelve of 13 pts who had 6-month follow-up had remission of disease in their primary sites. Accuracy rates in the detection of RD in the NP and LN are as follows; TI-201 MIBI CT/MRI NP% LN% NP% LN% N'P% LN% Baseline 100 70.0 100 90.0 100 100 3 months 41.6 87.5 58.3 94.1 30.0 69.2 6 months 60.0 90.9 90.0 90.9 62.5 90.9 TI-20I and MIBI failed to show bone metastases in 2 pts. MIBI SPECT proved superior to both TI-201 SPECT and CT/MRI on either 3 or 6 month follow-up in predicting complete remission verified 9-12 months following completion of C-RT (negative predictive value: 95 %). In pts achieving complete remission, 3-month follow-up T/B ratios showed a 33% - 67% decrease from those of baseline. In conclusion, MIBI SPECT proved promising in predicting response to C-RT in pts with NPC, however, its value in detecting bone metastases is low. Its potential clinical utility in pt management should await the results of a larger study.

• Oncology PMo733 L. Rettenbacher*. J. Koller+, G, Galvan*, *Department of Nuclear Medicine and Endocrinologyand +Department of Dermatology, Salzburg State Hospital,Austda

PMo735 Giammarile F, Thiesse Ph °, Desuzinges C, Frappaz D ~, Becker F°, Kaemmerlen po, Chauvot P.

DETECTION OF MALIGNANT MELANOMA WITH THALLIUM 201 S C I N T I G R A P H Y

MIBG-SPECT

NUCI,I~ARMEDICINt', RADIOI,()GY° AND PEDIATRIC'* DEPARTMENTS CENIRE LEON BERARI). LYON (F) AND

CT-SCAN

IMAOE

FUSION:

WORK IN

PR( )GRENS IN CIIILI)t tOOD NEUROBLASTOMA

Thallium-2Ol accumulates well in various malignant tumors, but there is no clinical study with TI-201 scintigraphy and melanoma metastases. Methods: 50 patients with suspected melanoma metastases were studied after intravenous injection of a mean tracer activity of 100 MBq TI-201 chloride. We performed sequence images up to 5 minutes (15 sec / image) and immediate whole body images with an Elscint Helix double head camera and a high- resolution collimator. Results: Of 29 patients with metastatic melanoma confirmed by histology, metastases were detected in 23 patients using TI-201 scintigraphy. The tumor / background ratio ranged between 2.0 and 4.5 (mean 3.2 ). Three false negative findings were lymph node metastases with tumor / background ratios of 1,5 and 1.3 and there was one false positive finding of an inflamed lymph node. Upon analysis of the patients with metastases larger than 2 cm, we found a sensitivity of 88 % and a specificity of 95 %. This does not apply to patients with abdominal metastases, since there were no such patients in our study. Only a few cutaneous metastases smaller than 1 cm could be detected. The optimum time for imaging was 2 - 5 min post-injection. Conclusions: These data suggest that the TI-201 scintigraphy is an accurate method for the detection of melanoma metastases. The short waiting period after injection and the lack of side effects qualify this method as a routine investigation.

Purpose: l. To combine the specific and functional (mIBG) with the high-definition and morphological (CT) information in neuroblastoma. 2. To test the feasibility in children with altered clinical status. 3. To evaluate the diagnostic efficacy of the fusionated data. Patients and Methods: From Sept. 95 to Feb. 96, 16 children with neuroblastoma of the trunk were studied. The patients received an intravenous administration of 4 MBq/kg 131I-mlBG or 8 MBq/kg 123I-mlBG. SPECT was focused on pathological mIBG uptakes detected on planar views Volumic CT acquisitions used 5 mm slices with extended helix and overlapped reconstruction. CT scan and mIBG SPECT were performed on separate days. During the exams, four muhimodality radiographic markers filled with radioiodine were sticked on the skin and immobility were obtained with usual i.v. sedation. Results: Image quality was excellent in every case, without motion artifacts on both CT or SPECT. Concordance of each external marker was reached in every case. The centers of mIBG uptakes correlated well with the centers of morphological lesions, whenever visible on CT scans In 3 cases, the most functional parts of the tumor could be located before diagnostic biopsy. Doubtful topography of mIBG uptakes facing adjacent organs could be precisely located with fusion in 6 patients. In one case, image fusion permitted to distinguish two liver metastasis evident as a solitary uptake on mIBG scan. One doubtful abnormality on CT scan did not corresponded to pathological mIBG uptake and were therefore assigned to be a post-surgical scar. Conclusion: These preliminary results show that technical management is feasible in sick children and improvement of clinical information was provided in most cases. Acknowledgment:This work is supported lW a grant o f the A.R.C. (Association

e-

O

|l

c-

pour la Recherche sur le Cancer). The image Jhsion software was kindly furnished h v PICKER I,VTER.~4 TIO.VAL Inc.

PMo734 Desuzinges C, Giammarile F~ Brunat-Mentigny M*, Chauvot P. NUCLEAR MEDICINEAND PEDIATRIC* DEPARTMENTS CENTRE LEON BERARD. LYON (F) CLINICAL INTERESTOF 201 TL SCAN IN PRE-SUROICAL EVALUATION OF OSTEOSARCOMA: A COMPARISONWITHBONE SCAN AND MRI

Aim : In order to evaluate histologic response to chemotherapy, a total of 15 patients (9 males and 6 females) with osteogenetic sarcoma were studied.

Methods : TI scintigraphy (TS), immediately followed by a three phase bone scan (BS), were performed at diagnosis, after three treatment and in the pre-surgical evaluation. All patient underwent MRI at diagnosis and in the pre-surgical evaluation. TI uptake index, BS parameters, MRI findings and histological results were compared. Results : The areas of signal intensity alteration on MRI corresponded to those of increased T1 uptake. However, the same areas not always corresponded on delayed BS images. 7/10 of the "good responders" (more than 95% of tumor necrosis) presented at diagnosis a high T1 uptake with regard to the contralateral side (associated with an increased uptake in first phases of BS) but also an important regression of T1 uptake in the following TS. The 5 "bad responders" presented at diagnosis a low T1 uptake with variable evolution. No general rule could be defined with BS parameters.

Conclusion : This preliminary study showed that TI uptake index is a good prognostic factor of therapeutic efficacy, mainly if it is high at diagnostic TS. In this case it seems more useful than BS parameters and at least equivalent to MPd findings.

PMo736 Sabahat inamr Aytug 0ner, Tamer Atasever, Nazan Gtinel, Nahide Gbk~ora and Mehmet T. Kitap~:=, Gazi University Medical Faculty, Departments of Nuclear Medicine and Oncology, Ankara, Turkey. THE PRELIMINARY RESULTS OF SCINTIMAMMOGRAPHY WITH Tc-99m MDP IN BREAST CANCER There is growing interest in scintigraphic evaluation of suspicious breast masses. In addition to the tumour-localizing agents such as TI-20I and Tc99m sestamibi, early imaging with Tc-99m MDP has been proposed for the differential diagnosis of breast lesions. In this preliminary study, doublephase (15 min and 4 hr) breast imaging with Tc-99m MDP was evaluated during presurgical bone scintigraphy in patients at high risk for breast cancer (Group 1, n=14) and patients with indeterminate mammographic findings (Group 2, n-l l). Lateral breast images were acquired at prone position using a special table. Focal increased MDP uptake in tumour localization was considered positive. Visual and quantitative (tumour to background ratio) results of scintimammography were compared with radiological (mammography with ultrasonography) and histopathological results. Out of 14 malignant breast lesions (Group 1), 11 were invasive ductal carcinoma and 3 were invasive lobular carcinoma. There were 7 fibroadenomas and 4 fibrocystic diseases in Group 2. In Group 1, tumour to background ratios (mean_+lSD) were 2.26+1.36 and 1.75_+0.49 for early and late phases, respectively, but there was no statistically significant difference. Benign breast lesions (Group 2) did not show any MDP accumulation. The diagnostic sensitivity and specificity of scintimammography was 83% and 100% in the early phase and 78% and 100% in the late phase, respectively. Radiological interpretation showed 90% sensitivity and 63% specificity. In three patients, scintigraphic images defined turnout limits better than clinical and radiological assessments. As a result, scintimammography with Tc-99m MDP seems to be a highly sensitive and specific method in the differentiation of breast lesions. This method can be useful in patients with suspicious radiological findings. Also, it can be added to routine presurgical bone scintigraphy as a diagnostic tool.

o

• Oncology PMo737

PMo739

V.Papantoniou 1, P.Karganzis2, A.Stipsanelli1, AArka 1, A.Keramopoulos 2, P.Kostamis 1 1Dept. of Nuclear Medicine and Therapeutic Clinic "Alexandra" Hospital, University of Athens, 2Dept of Obst. and Gyn. "Alexandra" Maternity Hospital, University of Athens.

R.Aurisch, H.Winter, D.Kornrumpf, D.L.Munz, Humboldt U n i v e r s i t y Berlin, Germany, Charit~ Hospital, D e p a r t m e n t of N u c l e a r M e d i c i n e

TECHNETIUM-99m(V) DIMERCAPTOSUCCINICACID[Tc99rn(V) DMSA]iN THE DETECTION OF PRIMARYBREASTCANCER,PRELIMINARYRESULTS

E L E C T I V E R E M O V A L OF L Y M P H PATHS A N D N O D E S GUIDED BY L Y M P H O S C I N T I G R A P H Y IMPROVES THE PROGNOSIS OF PATIENTS W I T H M A L I G N A N T MELANOMA(MM)

The aim of this study was to evaluate the usefulness of Tc99m-(V)DMSA in the detection of breast lesions and its possibility to differentiate benign from malignant disease Methods: 20 women (mean age ±SD 57±159), with suspicious findings on physical examination and/or mamographies, were studied. Anterior and oblique views of the breast in time intervals 1) 15-50 min and 2) 60-150 min after administration of 16-22 mCi of Tcg9m-(V) DMSA were performed in an upright position. 7 women with medullary thyroid cancer without breast metastases where used as control group. Tumor to background ratio (T/B) was also performed and CEA 15-3, CEA levels were determined. Scintigrams and mammographies were compared with biopsies Results: Tumor size ranged from 0,8-4,3 cm (m±SO=2,28+_1,21cm). Breast cancer was histologically confirmed in 13 lesions (65%), while benign abnormalities were rotundin 7 lesions (35%). Marnmography in breast cancer was positive in 9 cases (69%) indeterminate in 2 cases (15%) and negative in 2 cases (15%) Tcggm-(V)-DMSA scintimammography had a sensitivity of 85% (11TP, 2 FN), a specificity of 67% (7 TN, 1 FP) an accuracy of 85%, a PPV of 91% and a NPV of 77% in the ir,terva115-50 rain, while between 60-150 rain had a sensitivity of 92% (12 TP, 1FN) a specificity of 75% (6 TN. 2 FP) an accuracy of 81%, a PPV of 85% and a NPV of 65%. ]/B ratio was found for malignant lesions (m+SD): 1,97_+0,37in 15-50 rain, and 2,01±05 in 60-150 rain, while for the adjacent normal breasts 1,16±0,10and 1,17_+0,14in the same time respectively. Benign lesions had a T/B: 1,29±0,26 and 1,37±0,37 and the adjacent normal breast: 1,17±0,12 and 1,06±0,03, both for early and delayed phase. Control group had a T/B ratio: 1,14±0,102.As true positive were comidered these lesions with a T/B ratio >1,5. The 2 false negative had a T/B ratio 1,35 and 1,42.The last became positive in the delayed image while the other reached the limit (1,5), and was an "in silu" ductal carcinoma. In all but one case with osseous metastases, Ca 15-3 and CEA levels were normal. Osseous metastases were also depicted with a T/8 ratio similar to that obtained with Tc99m MDP. Conclusion: Tc99m-(V) DMSA appear to be a highly sensitive, specific and accurate breast tumor seeking agent and a promising test in the investigation of breast abnormalities.

Since 1984 at our clinic m e l a n o m a surgery (in cases of m o d e r a t e and h i g h risk) involves the p r o p h y l a c t i c removal of regional lymph nodes and lymphatic transit paths. The l y m p h o s c i n t i g r a p h y is able to find out the individual l y m p h ' f l o w pattern. This m e t h o d is not g o i n g to identify metastases, but to identify the areas of greatest r i s k for c o n t a i n i n g occult metastases. Patients: 275 pts. w i t h truncal M M (160 men, 115 women) of c l i n i c a l s t a d i u m I (according to p T - c l a s s i f i c a t i o n : pTl 1 6 % ~ p T 2 14%, pT3 51%, pT4 19%). F o l l o w - u p of at least 5 years. Method: I n t r a c u t a n e o u s i n j e c t i o n of Tc-99mn a n o c o l l o i d s in small deposits a r o u n d the tumor or scar (in case of p r e v i o u s d i a g n o s t i c tumor excision). D u r i n g 30 to 60 m i n p.i. the m o v e m e n t of the r a d i o t r a c e r was c o n t i n u o u s l y r e g i s t e r e d by a large field g a m m a camera and m a r k e d in two different views on the skin of the patient. Results: In all p a t i e n t s the u n e q u i v o c a l i d e n t i f i c a t i o n of lymph ways and nodes was possible. In many cases the d r a i n a g e p a t h was s u r p r i s i n g (6 p t s . e x c l u s i v e l y to t h e c o n t r a l a t e r a l s i t e ) . T h e consequent r e m o v a l of t h e r e g i o n a l l y m p h n o d e s a n d p a t h s b y t h e surgeon - possible on the basis of lymphoscintigraphic information - improved the p r o g n o s i s of pts. w i t h M M c o n s i d e r a b l y : In comparison with the pre-lymphographic era ( b e f o r e 1984, w i t h o u t e l e c t i v e d i s s e c t i o n of lymph nodes and vessels) the 5-year survival r a t e i n c r e a s e d f r o m 57% (men) a n d 7 4 % (women) to 7 7 % a n d 81%, r e s p e c t i v e l y .

PMo738

PMo740

R. Piipers. S. Meijer*, O.S. Hoekstra, GJ. Collet*, G.LJ. Teule. Dpts. of Nuclear Medicine and Surgical Oncology*, Academisch Ziekenhuis van de Vrije Universiteit, Amsterdam, The Netherlands.

M. Cimitan. E. Borsatti, V. Zagorela, C. Saccoa, R. Ruffo Department of Nuclear Medicine and Diagnostic Ultrasound, aDivision of Medical Onoology, Centro di Riferimento Oncologico, IRCCS Aviano (Italy)

PITFALLS 1N SENTINEL NODE DETECTION IN BREAST CANCER AFTER EXCISIONAL BIOPSY. Sentinel node (SN) biopsy using radioguided surgery is a promising method to select breast cancer patients (pts) without axillary lymphatic involvement. In 39 consecutive pts we evaluated the effect of previous excisional (EB, 11 pts) and core biopsy (CB, 28 pts) on lymphoscintigraphy and feasibility of SN identification in the axillary specimen using a handheld gamma probe. Eighteen hours after injection of Tc-99m colloidal albumin (40 MBq in 4 ml) lymphoscintigraphy revealed 1-3 axillary loci in 7/I 1 and 26/28 pts, respectively (Xz, P<0.025). In 2 of the negative EB pts a cavity filled with seroma and tracer was encountered intraoperatively. The tracer content of the SNs, as determined with the probe, was not significantly different in both groups (10 sec ex vivo cts: CB 431+553, EB 610±837). Compared to lymphoscintigraphy, the gamma probe search of the axillary specimens revealed no additional labeled nodes. The SNs retrieved from the axillary specimens (gamma probe guidance) revealed micrometastases in 1/7 and 9/26 pts, respectively. False negative SN biopsies did not occur in either group. In 2/4 EB pts with negative scintigraphy lymphatic metastases were found. Conclusion: Scintigraphy correctly predicted feasibility of gamma probe guided SN retrieval independent of previous diagnostic biopsy procedures. However, successrate of SN identification appears to be lower following EB.

1216

KVAL~%TR~ ~ . ~ ~ M£Ka'am~S ~ (MDR) rmza. 23 pts with Hodgkin's disease (HD) and 6 pts with non-Hodgkin's lymphcma (h~L) ~der~_nt Tc-99m-~BI and Ga-67 scintigraphies before treahnent as a baseline ttmour imaging for a better ~ t of lymphawas and to determine if tumour oells overexpressed the multidrug resistance factor responsible for the decreased accumulation of Tc-99m-MIBI. Six other pts with HD and 5 with h~qL~ evaluated after treatment for diagnosis of recurrenoe and for imaging of ~ ir~%~cedby cherother~oy. Scintigraphies were obtained by a S o p h i a DSX lh after injection of 740 MBq of Tc-99m-MIBI with a LEV~q collimator, and 72h after injection of 222-296 FBq of C~-67 using a collimator and all the three photon peaks of gallium. All TC99m-MIBI and Ga-67 studies i n c ] , ~ anterior planar images with a preset count of 1500000 (512x512 matrix) followed by a SPET of the thorax (including head and neck) and ~ (3 cases), in a 128x128 matrix with a 360 ° acquisition and 64 steps. ~he results were then ccnpared with radiological and biopsy data. In the ~ cases, before treatment, Ga-67 scintigraphy visualized 39 sites of increased ~ptake (sensitivity 100%) c ~ to 28 with Tc-99m-MIBI; after treatment, C~-67 still revealed a greater number of sites (9) of increased uptake than did Tc-99m-MIBI (5). In the NHL cases, before treatment, Ga-67 visualized ii sites of increased uptake (sensitivity 79%) ccmpared to 8 with TC-99m-MIBI; after treatment, increased Ga67 ~ptake was seen in all 7 residmal masses whereas increased TC-99m-MIBI tlotake was shown in only 4. TC-99m-MIBI uptake, expressed as tumour/background (T/B) ratio, was always lower (range 1.05-1.65, mean 1.26) than that of Ga-67 (range 1.303.90, mean 2.27). Despite the low TC-99m-MIBI accumulation within iMRohsnas, in evaluating residual masses after therapy, a lack of TC-99m-MIBI uptake compared to the increased Ga-67 uptake would be related to FIR overexpression.

• Oncology PMo741 R. BARONE, M. CHIANELLI, U. BOTTONI, S. J. MATHER, A. LATIN!, D. INNOCENZI, S. CALVIERI and A. SIGNORE. Nuclear Medicine, Clinica Medica 2 and Clinica Dermatologica, University "La Sapienza", Rome, Italy. St. Bartholomew's Hospital, London, UK. IN VIVO DETECTION OF LYMPHOCYTIC INFILTRATION IN MELANOMA USING 99mTc-lL2. Cutaneous melanoma is characterized by a local lymphocytic infiltration and it has been reported that higher degrees of infiltration are characterised by better prognosis, probably related to a greater immune response against the tumour. This has prompted the therapeutic use of IL2 as an immunostimulant in these patients. 99mTc-lL2 is a radiopharmaceutical that binds in vivo to activated T limphocytes homing in infiltrated tissues. The aim of this study was to evaluate whether 99mTc-lL2 scintigraphy can detect, in vivo, different degrees of tumour infiltration. We report the preliminary results of 99mTc-lL2 scintigraphy in 9 patients with clinical diagnosis of cutaneous melanoma. Planar gamma camera images over known sites of the tumour were acquired one hour after the injection of 2mCi of 99mTc-lL2 labelled as previously described. All patients with primitive melanoma underwent surgery and histological evalutation of the tumour was performed to assess tumour grading and inflammatory infiltration. Lymphoscintigraphy and immunoscintigraphy with anti-melanoma MoAbs were also performed. Lymphocyte subsets and NK activity were studied in most patients, An accumulation of 99mTc-lL2 was observed in primitive and metastatic lesions although of different degree. In one patient with negative 99mTc-lL2 scintigraphy, histological evaluation demonstrated absence of melanoma lesion (angioma). Tumour uptake of IL2 was correlated with other immunological and histological parameters, Results of this study indicate that 99mTc-lL2 can detect lymphocytic infiltration in melanoma lesions suggesting the use of this radiopharmaceulical for the selection of patients who may benefit from IL2 immunotherapy.

PTu743 A. B E R B S.ANCIDEI,G.VALENTINI,E. NUCLER MEDICINE SERVICE OSP. M A C E R A T A -AZ. U S L 9 M A R C H E - I T A L Y

BRIANZONI

IIlINPENTETREOTIDE SCAN IN PHARMACOLOGICAL F O L L O W - U P OF G E P N E U R O E N D O C R I N E TUMORS PATIENTS.

We investigated if a second InP scan can provide further clinical and/or biological informations in the m a n a g e m e n t of a group of d i a g n o s e d G E P patients submitted to long term octreotide treatment. We

studied

10

patients

(4

females,

6 males,

age

46-76 yy) with proved GEP (4 gastrinomas,3 carcinoids, 1 MEN II syndrome, 2 nonfunctioning islet cell carcinomas). Seven were studied after surgical treatment (primitive tumor or symptomatic metastasis ablation); 3 were d i a g n o s e d by liver lesions biopsy. First InP s c a n w a s performed before standard octreotide therapy start; a second s t u d y w a s c a r r i e d o u t 4 - 1 8 m o u n t h later. The s c i n t i g r a p h y c findings (presence a n d number of localizations) were matched with s e r u m markers leveles (S), conventional imaging modalities (I), clinical status (C) and scored (unmodified (U); p r o g r e s s i o n (P); reduction (R).

InP

U P R

S U P R 31 2 2 2

I U P R 43 -

1 2

C U P R 3 1 2 2 1 i# p e r f o r m e d an

onset of low glucose tolerance; additional InP scan 5 mo after therapy unmodified). Concordance levels: InP/S: (#:

stop,

50%; InP/I: 50%; InPIC: 30%. O u r d a t a s h o w e d l o w correlation between InP d a t a and other parameters in the pharmacological treatment m o n i t o r i n g , discouraging the I n P s c a n u s e in G E P p a t i e n t s f o l l o w - u p .

th ciO m .l,I

t~ e'-

e~ PTu742

S.Fanti, A.Chiti, B.Bellanova, P.Tomassetti, M.Migliori, A.Romeo, S.Zoboli, G.Savelli, E.Bombardieri, N. Monetti.

Dept of NuclearMedicine, lstituto Nazionale Tumori,Milano Dept of NuclearMedicine, S.Orsola-MalpighiHospital, Bologna; Italy ROLE OF In-111-PENTETREOTIDE (OCT) IMAGING IN STAGING AND FOLLOW-UP OF NEUROENDOCRINE GASTRO-ENTEROPANCREATIC TUMORS (GEP) AND CARCINOIDS Aim of this study was to assess the effectiveness of OCT imaging in staging and follow-up of neuroendocrine GEP and carcinoid tumors. Our series included 78 patients (pts) with known (59 cases) or suspected (19 cases) GEP tumors or carcinoids. Planar and SPET images were acquired after i.v. injection of 200-250 MBq of OCT. In all pts the diagnostic work up included at least 2 other imaging procedures: computed tomography (CT) in 65 pts, ultrasound (US) in 63 pts and other procedures in 50 pts. A pathologic diagnosis was obtained in 66 pts (38 carcinoids, 9 gastrinomas, 9 pancreatic tumors, 10 other tumors), while in the remaining pts diagnosis was based on clinical and follow-up data. Our findings were as follows: OCT CT US Primary tumor 22/27(81%) 13/21(62%) 11/19(58%) Metastases 38/42(90%) 29/41(71%) 26/35(74%) In 17/78 pts (22%) OCT was the only diagnostic procedure able to correctly identify lesions confirmed later. The therapeutic plan was modified on the basis of OCT findings in 16/78 pts (20%). In the remaining cases OCT was effective in supporting the findings of other diagnostic procedures. We can draw the conclusion that OCT is effective in staging and follow-up of GEP and careinoid tumors and has to be considered an essential diagnostic procedure in these neoplastic diseases.

PTu744

x.._

A.Romeo, B.Bellanova, S.Fanti, A.Chiti, S.Zoboli, P.Tomassetti, M.Migliori, P.Zagni, E.Bombardieri, N.Monetti. Dpt of Nuclear Medicine, Policlinico S.Orsola-Malpighi, Bologna; Dpt of NuclearMedicine; Istituto Nazionale Tumori,Milano; ITALY COMPARISON OF SOMATOSTATIN RECEPTOR SCINTIGRAPItY AND BONE SCAN TO DETECT BONE METASTASES OF NEUROENDOCRINE TUMORS. Somatostatin receptor scintigraphy (SRS) with 11 lIn-Pentetreotide has been reported to be accurate for detecting lesions (primitive tumor and metastases) of neuroendocrine tumors (NET). In this study we compared the results of SRS and conventional bone scan (BS) for identifying bone metastases of NET, 16 patients with hystopatholosic diagnosis of neuroendocrine tumors were studied (4 medullary thyroid carcinoma, 6 earcinoid, 4 pancreatic tumors, 2 ectopic Cushing). All subjects had clinical, laboratory or radiological data suggestive of possible bone metastatic disease. After i.v. injection of 150-250 MBq of l l l I n Pentetreotide planar images were acquired at 4 and 24 hours and SPECT at 4 hours; within one week all patients also underwent whole body bone scan performed 2.5 hours after receiving 550-750 MBq of 99mTc-MDP. In 9 patients both SRS and BS ruled out the presence of metastatic bone disease (6 pts with SRS- and BS-; 2 pts with SRS- and BS+ but "likely non metastatiC'; 1 pt with SRS+ and BS+ at site of a recent bone fracture): in all 9 cases radiological and follow-up data confirmed the absence of bone metastases. In 6 patients both scans were positive (SRS and BS gave similar findings in 2 cases, while in 3 pts BS demonstrated more lesions and in 1 case SRS revealed more lesions). In the remaining patient (affected by pancreatic tumor) BS only revealed bone lesions while SRS was negative: the presence of bone metastases was radiologically confirmed. In conclusion our findings confirmed SRS is useful for detecting bone metastases of/gET: SRS sensitivity, however, was found not superior to conventional BS. As our data are not concordant with previous reported data and based on a limited group, further investigations are required to fully address this issue.

1217

O

el

• Oncology PTu745

PTu747

c. Giannakenas D. Apostolopoulos, A. Chondromaras, H.P. Kalofonos, T. Petsas, Ch.Scopa, E. Tzorakelefterakis, P.J. Vassilakos. Depts of : Nuclear Medicine, Oncology, Radiology, Cytology & Surgery, University Hospital of Patras - Dept. of Nuclear Medicine, "St. Andraas" General Hospital, Patras-Greece

P.J. van den Anker-Lugtenhurg, R. Valkema, H.Y. Oei, B. L6wenherg and E.P. Krenning. Erasmus University and University Hospital Rotterdam, Dr. Daniel den Hoed Cancer Center, Rotterdam; The Netherlands. Departments of Haematology and Nuclear Medicine.

SClNTIGRAPHIC IMAGING OF SOMATOSTATIN RECEPTORS IN SARCOMAS PURPOSE : Current literrature provides a very small number of references relating to the scintigraphic imaging of sarcomas. Our aim in this continuing study is to investigate the efficacy of mln-DTPAOctreotide (OC) in imaging these relatively uncommon tumors. METHOD : To date we have studied 12 patients with known sarcomatous lesions, 6 females and 6 males, mean age 59y. All the patients had known lesion as demonstrated by other modalities e.g. CAT, U/S. Following the IV injection of 2,9 - 4,2 mCi of OC, planar and in a few cases SPECT imaging was done at 4_+1 hr and 20_+2hr respectively. Histologic verification was obtained in all cases, either from FNA or from surgically removed tissue. The histologic typing and the scintigraphy results are seen in the table below. RESULTS : Positive imaging was observed in 10/12 cases (83,3 %). Of the 2 negatives both were false negative. It should be noted that one )atient had completed chemotherapy a few days prior to scintigraphy. )ccult lesions were demonstrated in two of the patients. Histologic type (n) Scan Results Fibrosarcoma 1 1 (+) Embryonic rhabdomyosarcoma 1 1 (+) Leiomyosarcomas 2 1 (+) / 1 (-) Liposarcomas 2 2 (+) Uterine sarcoma 1 1 (+) Osieosarcomas 2 2 (+) Chondrosarcoma 1 1 (-) Neurogenous sarcoma 1 1 (+) Total 12 10 (+) / 2 (-1

SOMATOSTATIN RECEPTOR AND 67-GALLIUM SCINTIGRAPHY IN MALIGNANT LYMPHOMAS. We performed a prospective comparative study in which somatostatin receptor (SS-R) and gallium (GA) scintigrams were evaluated blindly to each other and to all other staging information. Three patients with Hodgkin's disease and eight patients with non-Hodgkin's lymphoma were investigated. SS-R scintigraphy was performed after i.v, injection of [llI-ln-DTPA-D-Phe-l]-octreotide (220 MBq). Planar images were recorded 24 and 48 h post-injection (p,i.) and 24 h SPECT of the upper abdomen was done in all patients. One week after SS-R scintigraphy high dose GA scinfigraphy (296 MBq) was performed. Planar images were obtained 48 h p.i. and in all patients 48 h SPECT of the thorax and abdomen was performed. The blindly read scans were compared with standard staging procedures including physical examination, chest X-ray, CT scans, ultmsonograpby and bone marrow biopsy, The patient-based analysis yielded an overall sensitivity of 73 % for SS-R scintigraphy and 45% for GA scintigraphy. 8/11 patients were true positive, three were false negative on SS-R scintigraphy. On GA scintigmphy 5/11 patients were tree positive and six false negative, The lesion-based analysis showed different results. With standard staging procedures a total of 32 lesions could be identified, The overall sensitivity for SS-R scimigraphy was 17/32 (53%); t0/15 (67%) in the supradiaphragmatic region and 5/13 (38%) in the infradiapbragmatic region. The overall sensitivity for GA scinfigraphy was 10/32 (31%); 5/15 (33%) in the supradiaphragmatic region and 5/13 (38%) in the infradiaphragmatic region. CNS infiltration in one patient was apparent on SS-R scintigraphy but negative on GA scintigraphy. The sensitivity for bone marrow infiltration was 1/3 (33%) for SS-R scintigraphy and 0/3 (0%) for GA scintigraphy. SS-R scintigraphy visualized six previously unknown lesions in four patients, two of these lesions were also visualized by GA scintigraphy. As a result the clinical stage was upgraded by SS-R scimigraphy in two patients. In general the interpretation of the SS-R scan was easier because of its lower background radioactivity. These preliminary data show that the results of SS-R scintigraphy are at least comparable to GA seintigraphy. A prospective study in a larger group of patients is in progress.

CONCLUSIONS : From the available data, 111In- DTPA-Octreotide appeam to have properties which lead to a new indication for its use. The study continues.

PTu746 A.C. Kole ~2, J. Pruim 1, A.M.J. Paans ~, O.E. Nieweg 2&3, H.J. Hoekstra 2, H. Schraffordt Koops 2, W. Vaalburg 1. ~PET center, 2Department of Surgical Oncology, Groningen University Hospital, Groningen and 3Department of Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands. THE CORRELATION BETWEEN STANDARDIZED UPTAKE VALUE A N D Q U A N T I F I C A T I O N OF PROTEIN SYNTHESIS RATE USING L-1-[11C]-TYROSlNE PET IN SOFT TISSUE S A R C O M A S The aim of the study was to investigate the correlation between standardized uptake value (SUV) and protein synthesis rate (PSR) using PET with L-1-[11C]-tyrosine (TYR) in patients with soft tissue sarcoma (STS). With the SUV analysis, arterial cannulat[on is not necessary and the study duration can be shortened, making PET research less of a burden for patients with cancer. T w e n t y - f o u r patients with STS were studied before receiving any therapy. A dose of 3 0 0 MBq (85-380) TYR was given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. The mean and maximum tumor protein synthesis rate (PSR) and the PSR in contralateral normal muscle tissue were quantified using the method described by Willemsen et al. From a 20-minute frame, 30 minutes after injection, SUVs were calculated based on body weight, body surface area and lean body mass, and corrected for plasma tyrosine. A significant but moderate correlation between PSR and SUV was found. Correlation-coefficients (r) varied between 0.67 and 0.88 (p
PTu748 E. P i p e r k o v a , A. G r u e v a , L G a v r i l o v , E. A l e x a n d r o v a , A. M i l e v , D. F a n a r i o t o v . National Oncological Centre-Sofia 1756, Bulgaria. C L I N I C A L A P P L I C A T I O N OF T H E R E C E P T O R - S C I N T I G R A P H Y W I T H 111-In-PENTETREOTIDE IN B R E A S T C A N C E R STAGING. Limited information is available on the s o m a t o s t a t i n - r e c e p t o r detection in breast cancer (BC), The aim o f this study was to evaluate the potential use o f 111-In-pentetreotide scintigraphy in preoperative BC staging. The study included 12 w o m e n , a g e d 30-64. In all patients l l l - I n pentetreotide scintigraphy was done after physical examination, m a m m o g r a p h y and sonography with fine-nidle biopsy and oar data were verified hystologically after surgery. Planar images in anterior view and/or S P E T were obtained immediately, 15 min, 4, 2 4 a n d 4 8 h o u r s after application 111-In-pentetreotide (OctreoScan-Mallinckrodt),activity 110220 M B q on a D I A C A M g a m m a - c a m m e r a (Siemens). In two out o f six suspected BC-patients (pts) 111-In-pentetreotide scans were positive and tumour/symetrical area (T/S)-index was higher than 2,75. In the other four pts verified as benign fibroadenomas negative scans were obtained. In four of other five pts with previous BC diagnosis without palpable regional l y m p h nodes (N) the axillar N-metastases (in 2 o f these pts) were visualized as well as the breast tumour. Recurrent receptor-positive tumour was detected in one case.Invasive ductal c a r c i n o m a was m o r e readily seen (7 pts) than invasive lobular (lpt) cancer. The verified results of the 111-In-pentetreotide scintigraphg are summarized in the table: 111-In-pentetreotide true-positive True-negative False-negative tumour detection scan scan scan BC Recurrent BC Regional N

6 1 2

4

1

Somatostatin-receptor scintigraphy is sensitive ( 9 0 % ) , high specific ( 1 0 0 % ) and accurate ( 9 3 % ) n o n - i n v a s i v e i m a g i n g m e t h o d for BC diagnostic. The clinical application o f 111-In-pentetreotide scintigrapy could be an impact in breast cancer staging, quite important for the treatment strategy and the survival of this disease. (sup. by MEST, N.F "Scientific researches" N 437/94)

• Oncology PTu749

PTu751

S.Lastoria, P.Muto, W.Acampa, C.Carac~, E. Vergara, P.Varrella, J.Lister-James, M.Salvatore. National Cancer Institute and Nucl.Med. Cent. C.N.R. N a p o l i and D i a t e c h Inc., Londonderry, NH.

T.M. Beh/, F.G. Wolf2, D.L. Munz j, D.M. Goldenberg 3, W.S. Becket "=. Departments of Nuclear Medicine of the Universities of G6ttingen ~ and Erlangen -~, Germany; Garden State Cancer Center at the Center for Molecular Medicine and Immunology3, Newark, N J. USA.

IMAGING SYNTHETIC

OF MELANOMA PEPTIDES. The

WITH

99mTC

LABELED

a i m of t h i s s t u d y w a s to evaluate the diagnostic accuracy of somatostatin-receptors-scintigraphy (SRS) u s i n g a n e w s y n t h e t i c p e p t i d e P829 l a b e l e d w i t h 99mTc in p a t i e n t s w i t h m e l a n o m a . SRS w i t h 99mTc P 8 2 9 w a s p e r f o r m e d in 21 p t s a c q u i r i n g the s t u d i e s w i t h i n 24 hrs. T h r e e p t s w e r e s t u d i e d at d i a g n o s i s , 19 during the follow-up (4 of t h e m w e r e d i s e a s e free). M e t a s t a t i c d i s e a s e to l y m p h o n o d e (n ° i0 pts), to s u b c u t a n e o u s t i s s u e (n°14), l u n g s (n°3), and skeleton (n°3) as well as primary localizations were detected. On a per patient b a s i s the s e n s i t i v i t y of SRS w a s 88%, o n a p e r site b a s i s the s e n s i t i v i t y w a s 9 0 % . I n 5 c a s e s SRS results were compared with PET-FDG findings showing no differences in t h e s t a g i n g of the disease. Based on autoradiographic i m a g e s the d e n s i t y of of P829 u p t a k e is c o n s i d e r a b l y h i g h e r in subcutaneous, pulmonary and lymphonodal metastases than in hepatic or bony ones. A u t o r a d i o g r a p h y w i t h 99mTc P829 a l s o d e m o n s t r a t e d b i n d i n g to b o t h m e l a n o c y t e s a n d to i n f i l t r a t e d (activated) lymphocytes and the number of l y m p h o c y t e s v a r i e s a c c o r d i n g to the a n a t o m i c a l s i t e ( s u b c u t a n e o u s n o d u l e s > l y m p h n o d e s > bone). Therefore, the magnitude of uptake seems i n f l u e n c e d b y the n u m b e r of a c t i v a t e d l y m p h o c y t e s i n f i l t r a t i n g the l e s i o n as w e l l as b y the d e n s i t y of r e c e p t o r s expressed by melanoma cells. We c o n c l u d e t h a t SRS is u s e f u l to a c c u r a t e l y s t a g e m e l a n o m a as it h a s the p o t e n t i a l to d e t e c t s m a l l lesions (
IMMUNOSCINTIGRAPHY OF CEA-EXPRESSING CANCERS WITH 99mTcLABELED COMPLETE AND FRAGMENTED MONOCLONAL ANTIBODIES: META-ANALYSIS OF THE EXPERIENCE AT TWO GERMAN UNIVERSITIES The aim of dais study was to retrospectively analyze the experience of two German university departments with respect to immunoscintigraphy of CEA-expressing cancers with complete and fragmented, directly 99mTc-labeled, monoclonal anti-CEA antibodies. A total of 295 patients with CEA-expressing cancers (among them colorectal, gastric, urinary bladder, lung, breast, endometrial, ovarian and medullary thyroid cancers) were examhled between 1988 and 1996 at the Universities of G6ttingen and Erlangen. They were studied with 555 to l I 10 MBq of the monoclnnal anti-CEA antibodies BW431/26 IgG (Behringwerke, Marburg, FRG) [n=2081, F023C5 F(ab'),/Fab" mixture (Sorin Biomedica. Sahrggia, Italy) [n=65; 27 of them compared intraindividually to IgG], and IMMU-4 Fab" (lmmunomedics Inc., Morris Plains, NJ, USA) [n=22]. Imaging was performed from 1 to 24 h p.i., kinetic data were obtained from imaging, blood samples, and gel filtration chromatographic analysis of labeled serum compounds. Half-lives in blood were related to the molecular weight of the respective MAb: IgG showed a mean serarn tv: of 36 h, F(ab'h fragments of I6 h, Fah ~ of 4 h. lgG had a pronounced uptake in the liver (16% of the injected dose at 24 h p.i.), whereas with fragments, renal accretion was predominant (18% at 24 h p.i.). Accordingly, the sensitivity in the detection of liver metastases was lowest with lgG (44%), similarly high for both fragments (73 and 80% for F023C5 and IMMU-4, respectively), although the mean absolute tumor uptake at 24 h p.i. was approximately 2.5-fold higher with IgG than with fragments (2x10 2 versus 8xl0 -3 % ofinj.dose/g). The detection rates of local recurrences and peritoneal carcinomatoses were high with all three antibodies (> 90%), clearly superior to computed tnmography, whereas the sensitivity for the detection of lung metastases was low (< 20%). In planar scans, only 42 % of lesions could be visualized as compared to' SPECT data. Imaging was possible with fragments already at 4-6 h p.i., whereas 24-h scans were mandatory with IgG. Approximately 32 % of patients developed HAMA after a single administration of IgG, as compared to none of the fragmenl patients (0%). Previously unsuspected lesions were found in approximately 25 % of patiema (no significant difference between IgG and fragments). These data indicate that immunoscintigraphy can yield useful clinical information which is complementary to conventional radiological techniques. The use of SPECT is mandatory. Fragments seem to have an advantage over IgG with respect to their higher sensitivity in the liver, the possthilty of earlier imaging and their lower immunogehicity.

ltl eO

i i

rID t_

PTu750

PTu752

A.Ei~ *, A.Anderss~n **, K.Dahlstre~ **, A.Rab~l *, M.Jensen *, K.T.Drzewiecki **. Dept. of Clin.Phys.& Nucl.Med. * and Dept. of Reconstructive Surgery **, Rigsbospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

A. Spanu, A. Farris, C. 8agella, A. Masia, A. Falchi, S. Nuvoli, M.E. Solinas, P. Sulas, A Marrosu, M.D. Azzena and G. Madeddu. Depts. of Nuclear Medicine and Oncology. University of Sassari. Italy

M~LIGNANT MELANOMA: FDC--PET IN DISCOVERING SILENT METASTASES °

Correct staging is crucial for management and prognosis for patients with malignant melanoma. We performed 29 whole-body PET scans with fluorise-18-fluorodeoxyglucose (FDG) on 26 patients with malignant melanoma, clinical stage II (local recurrence, in-tr-dr~it and regional l y r e node metastases) and stage III (metastases to other sites than stage II ). 30 minutes after intravenous injection of 400 MBq FDG the patients were scanned (t~hrance, Gener~Ll Elestrics) with a 15 cm Field of View and a resolution of 4-5 ,In. The resulys were compared to those found by corr~etional methods (clinical exaninotion, CT, US, X-ray and blood sa,ples) and to histology. RESULTS: PET detested 35/37 foci (95%), conventional methods could detect 30/37 (81%). PET failed to show one subcutaneous and one reginal ly.pbe node, which were both found by clinical examination. Conventional m e ~ missed 4 pulmonary and 2 abdominal lesions besides one distant lymphe node metastases. CONCLUSIONS: FDG-PET is superior to conventional methods i n detecting v i c e r a l s i l e n t melanoma metastases. FDGi s an accurate methode t o detect w / d e s p r ~ ~taustases f o r avoiding m u t i l a t i n g surgery o f no b e n e f i t . FDG-PET i s u s e f u l as st~pplementary t o c l i n i c a l examination

in melanoma staging.

THE USEFULNESS OF MALIGNANT MELANOMA_

S-100

PROTEIN

IN

MONITORING

S-100 protein has been ascertained both in the tissue and in the serum of patients affected by different types of tumor such as melanoma, glioma, schwannoma and neuroblastoma. In this study we assayed S-100 protein by IRMA (Byk-Sangtec 100; upper limits 0.2 t~g/L) in the serum of 36 patients, 24 F and 12 M, aged 21 to 76 yrs, who had previously undergone surgery for cutaneous melanoma. According to AJCC criteria the patients, at the first observation, were classified as stage I in 19 cases, stage II in 5, stage HI in 4 and stage IV in 8. All stage I-II patients were NED, white 3/4 stage III patients had partial disease regression (R), after lymph node excision and/or chemotherapy, and the remaining one, disease progression (P). Of stage IV patients, 3/8 were R and 5/8 P after treatment. S-100 was under cut-off in all stage I-II NED patients; low levels of the marker were also found both in 3/3 stage Ill R patients end in the remaining 1 P, who had one small size axillary lymph node (< 0.8 cm), as well as in 3/3 stage IV R patients. In all 5 stage IV P patients, S-100 was elevated. In the follow-up of 7-51 mths, 4 stage 1-11 NED patients developed metastases and the marker markedly rose in 2 of them while it was under cut-off in the remaining 2 with only brain metastases; in the 2 latter, S-100 measurement in CSF could presumably give additional information. The marker also increased in 3/4 stage III patients, 2 previously R and 1 P, who underwent metastases. The eight stage IV patients had disease progression and S-100 was elevated in all of them. These data seem to suggest that S-100 may play a role in malignant melanoma since it showed high sensitivity in our cases to distinguish between advanced and inactive diseases; moreover, the marker may be useful in follow-up for an early detection of metastasis and an evaluation of response to treatment.

1219

ID Itl O el

[] Oncology PTu753

PTu755

A.R. Casu, A. Farris, I. Vannucchi, M. A. Foddai, A. Marrosu and G. Madeddu. Depts. of Nuclear Medicine and Oncology. University ot Sassari. Italy.

A~ D ' A ~ a ~ R~ Bartoletti" F, Travaglini ^ $. Paladini and G.CtppeUi ^ Nttclear Medicine Unii, Clinical Urology Inst~tu~ Flere/~e, lmly

THE USEFULNESS OF CA195 IN COLORECTAL CANCER CA195 is a circulating tumor associated antigen that has been identified in pts with malignancies, mainly o| the gastrointestinal tract. To further investigate the role of CA195 in colorectal cancer, to detect early recurrences and to monitor metastatic disease, we assayed the marker in the serum of 155 affected pts by IRMA (cut-off: 10 U/ml) and simultaneously also CA19-9, CEA and TPA. At the tirst observation, 80 pts were classified as stage I-II with apparently inactive disease (NED), 75 as stage Ill-IV with advanced disease (AD); in the latter group 38/75 had disease progression (P) and 37/75 disease regression (R). CA195 was above cut-off in 16.2% of NED pts while CA19-9, CEA and TPA were in 8.7%, 6.2% and 13.7% o| cases, respectively. In AD pts, CA195 was high in 73.7% of P pts and in 13.5% of R pts, CA19-9 in 60.5% and 5.4%, respectively, both CEA and TPA in 71% and 8.1% ol cases. Combined CA195 and CEA use showed the best result (sens. 89.4%, spec. 82.5%). A follow-up of 8-46 mths could be performed in 134 of the pts (80 NED, 23 P, 31 R at the first observation). Twelve NED pts developed metastases and CA195 rose in 9/12 (6/9 with initially low marker levels and 3/3 with high values) 2-3 mths prior to metastasis appearance; CA19-9 increased in 8/12 and CEA and TPA in 10/12 cases. In AD pts there was disease progression in 7/31 R and in 22/23 P and CA195 became high in 4 R and further increased in 21 P; CA 19-9 was elevated in 4 R and in,16 P, CEA and TPA in 5 R and in 20 P, respectively. In the only pt with disease remission, all the markers, initially high, fell under cut-off. Our results show that serial CA195 measurements may be useful in colorectal cancer to identity early recurrence in apparently NED pts; in addition, the marker may play a role to evaluate tumor response to treatment since its increase or decrease corresponded to progression or regression disease in most of our cases. Combined use of CEA may provide better information.

Free PSA / Total PSA RATIO : A NEW TOOL FOR D~'TIAL DIAGNOSIS OF PROSTATIC CANCER ]ntreductiea : PSA is a serine protease wich farms complexes wiflt different attti~protea~s. In serum, the major portion of PSA is oamplexed with ACT, while the rest is free. "['here are large variation between indlvidttaJs of the prQlmrtien of frte-PSA to PSA-A.CT complex, and between benign and malignm~ prostatic disease, Subje~'ts and method : Total PSA and Free P ~ ( Hybritet-h Tandem ) were determined in 139 samples: - 3I from subjec~ with prostatic canter (CAP], - 76 from subjects with ~ hypertruphta (BPH) - 32 from subjects with benign prostatic pa@tolegies. Biops~-~ were treed to cen/h~m the diasnests ofall cases. Results : the comparison between total PSA and I~'ee/Total PSA ratio results has been made by R.O.C. analysis. Using all PSA vah~s the ROC curve is better than the ROC curve of Fre~rota! PSA ratio,while w i ~ PSA values between 4 and 20 ng/ml the ]LR"ree,fI'efad P S A ratio shows the best diagnostic. In table 1 are reported th~ value~ obteined t~lng a cut-off af 18%, Table g SensitivitT 80.0% SpeciftciVy 62.7% Effi~emy 69.8% True positive predictive value 60.0% True negative predictive value 81.8% Cottclus~n: In prostate pathology~measurement af total PSA alozte aBews a poor discrimination between BP}] and cancer in 4 - 20 ng/ml range of total PSA valme~The addition of free PSA ~t combination with total PSA value improves the discrtmiemtian between BP}T and CAP cases.

PTu754

PTu756

MI, Martinez, M.T. Allende, M Suarez Hevia*, J.M. Abascal*, MJ., Nufiez, AAIba, R. Abascal* and A. Ruibal. Nuclear and Urology* Services. Hospital General de Astudas. Oviedo.Spain.

V.Zaichick, A.Tsyb, Medical Radiological Research Centre, Obninsk 249020, Russia

SERUM PSA FREE/TOTAL RATIO IN THE DIFFERENTIAL DIAGNOSIS BETWEEN PROSTATIC PATHOLOGIES. OUR PRESENT EXPERIENCE WiTH 146 CASES. In order to study its behaviour and clinical usefulness, we have measured by an IRMA assay (Tandem-r Hybntech) the seric levels of free (F) and total (T) PSA in 91 patients with benign prostatic hypertrophy (BPH) and 55 with prostatic adenocarcinomas (PC), all with histological confirmation. We observed statistically significant differences (p: 0.01155) in FFF PSA ratio between BPH ( r : 6.9-66.7 ; pt25: 15.8; pt50: 21.7; pt75: 30.2) and PC ( r: 3.1-157; pt25: 9.6; pt50: 16.7; pt75:30.8 ) samples. We not observed differences in F/T PSA in BPH patients classified according to US volume (> 50 cc: r: 10.5-48; median 23.1; <50cc: r: 7.9-66.7; median: 21.7), but the F and T PSA levels were higher (p:0.0001) in BPH >50 cc (r:0.4-5.1; median 1.3 ; r: 1.6-26.5; median 5.3) than in those < 50 cc ( r:0.33-1.6; median 0,7; r: 0.6-8.7; median 3.8). In PC patients we not observed statistically significant differences on FFF PSA, FPSA and T PSA values when those were classified according to glandular volume (> ( r: 6.1-56.5; median 14.3 ; r: 0.05-8.2; median 1.5 ; r: 0.3-87; median 10.5) ) and < 50 cc (r: 3.8-157; median 16.5; r: 0.05-6.3; median 1.1 ; r: 0.1-65.4 ; median 5.5) ) ; nevertheless, FIT PSA ratio were statistically higher (p:0.06181) in PC patients undergoing hormonal treatment ( r: 3.8-67,3 ; median 23.7: pt75: 38.1) than in those without any treatment ( r: 3.1-157; median 14.3 ; pt75: 19.6) . The best cu-off for F/T PSA was established in 20% and when we compared the behaviour of TPSA and F/TPSA, using as cut-offs 6 ng/ml and 20% respectively, we obtained better results with F/T PSA (Sensitivity : 62.9% vs 50 % ; Specificity :48.6% vs 51.4 % ; +PV: 64.2% vs 60% ; -PV:47.4% vs 41.3% ; Efficacy : 57.1% vs 50.5% ) Likewise, FfT'PSA was slighty better parameter than TPSA in prostatic patients with TPSA between 4 and 12 ng/ml. Our present results, with few number of cases, led us suggest that F/T PSA seem to be better than TPSA ratio as a parameter for the differential diagnosis of prostatic diseases.

1220

NUCLEAR METHODS OF CHEMICAL ELEMENT ANALYSIS IN BODY TISSUE AND FLUIDS FOR CANCER DIAGNOSTICS For more than 25 years studies on chemical element contents in human body tissues and fluids have being carried out in Medical Radiological Research Centre. Modern nuclear methods i n c l u d i n g neutron activation analysis (NAA), gamma-activation analysis (GAA) and some others are used to determine elements for the normal and pathology including oncologic diseases. The main aim of the investigation is to search new methods for both estimation of body state and differential diagnostics of malignant and benign tumours in particular. Samples obtained under clinical conditions (puncture biopsy and resected materials) were used to analyse 25 major and trace elements, such as Ag, Br, Ca, Cl, Co, Cr, Cu, F, Fe, H, Hg, I, K, Mg, Mn, N, Na, P, Rb, S, Sb, Sc, Se, Sr, Zn in tumours and surrounding tissues. It was shown that information about contents of thyroid iodine, prostate zinc, bone and breast major elements can be successfully applied in diagnostics of malignant and benign tumours of these organs. The new methods of diagnostics were based on the data obtained. Tumour elements were analysed both in vitro (materials of puncture or aspiration biopsies) and in vivo. The accuracy, specificity and sensitivity of diagnostic tests ranged from 80 to 98%. These methods have been successfully tested under clinical conditions of the Centre.

•

Oncology

PTu757

PTu759

II.Takahashi~.~,S.~aeda" , N.Ta=ahashi~,ll.Oika~a",T.Yoshioka',S. Endu=~, II.Got#' ~,S.Ilayasaka=~,L~akui'~,T. Saito~,Inst.of Development,kgingand Cancer,Tohoku Oniv.,Bept.of Clinical Ontology', ~aiya Ilospital ~, Japan.

U. H a_b¢_rkorrL A. Altmann, I. Morr, F. Oberdorfer, G. van Kaick. Dept. o f Oncological Diagnostics and Therapy, G e r m a n Cancer Research Center, Heidelberg, Germany.

EXPERIMENTALSTUDIESON ~*FOGUPTAKEOF THE ~YOCARD1U~,ECGAND HISTOLOGICALFI~tnCS in DOXORUBICIN-AgIIINISTERED RATS 2-deoxy-2-[lSF]fluoro-D-glucose(~F~) has been used as a tracer for detecting cancer or analysing the brain and myocardiumfunction.This report deals with the possibility to detect dysfunction ot the myocarditmunder chemotherapywith an anti-cancer agent, Oexorubicin(NR). which often induces cardiotoxicity clinically, by comparing to electroeardingraphic(ECG) findings and histological ones especially by electron ~icroscopy in DXR-administeredrats. Since it was known in our experiment that a single optimal dose inducing *SFOGuptakedecrease in the heart ~as 4.25~g/kg of DXR, this dose of the agent was administered into rats. On days 1,3,~ and ? after DXR injection, the animals were sacrificed one hour after intravenous injection of ~BFOGat the dose of 20#Ci. The distribution of ~sFN; in the heart was measured by auto-coma counter and expressed by g injected dose/g tissue. The uptake value off'FOG in the heart of OXR-administeredrat mas compared to that of control nomal rat without OXgadministration and the uptake-ratio was defined as follows: ~ptake-ratio=[ injected dose/g tissue of the heart(DXll-administered)/[meanof g injected dose/g tissue of the heart (not DXR-administered)]. Limb lead ECGwas examined. The rat hearts were examined by light microscopyand offered for examination by electron ~iCFOSCOpy. The uptake-ratio after administration of 3XR at the dose of 4.25ag/kg was the Io~est(0.35) on day 3 and recovered to the normal range on days 5 and 7. Heart rate, PR interval, QRS complex, ST interval, QT interval and T wave height did not change at any day. No change was observed by light microscopyat any day. By electron microscopy, on day 1 a slight s*elling of the mitochondria was observed but no change in cristae.The sost swelling like aneurysma in the mitochondria was observed on day 3. On day 7, s~elling of the mitochondria ~as hardly observed ~yocardiu~ uptake of t~FDCin rat decreased, and the uptake-ratio showed the nadir on day 3 and recovered to the nomal range on day 7 after ~XR administration. Sensitivity to detect '~FOGuptake changes ~as higher than those on ECC and histological examination by light ~icroscopy. Changepattern of '~F~Guptake in course of time after OXRadministration corresponded to that of the =itochondria ~hich is the area producing energy by electron microscopy. By utilizing a shortlived positron e~itter,~"Fl)G, Dig-induced eardiotoxicity may be noninvasively predicted in teris of the change of myocardial images by PET.

M E T A B O L I C EFFECTS O F G E N E T H E R A P Y IN MORRIS H E P A T O M A CELLS. This in vitro study was performed to investigate the application o f positron emission t o m o g r a p h y (PET) with tracers o f t u m o r metabolism for monitoring o f gene therapy with the suicide gene H S V thymidine kinase (HSVtk). Morris hepatoma cells were transfected with a retroviral vector bearing the H S V t k gene and different clones were established by selection with the neomycin analog G418. Thereafter uptake measurements were done in a tk-expressing cell line and in control cells (bearing the empty vector) using fluorodeoxyglucose (FDG), 3 - 0 methylglucose, AIB and methionine in the presence o f different doses o f ganciclovir. These experiments were done up to 48 hours after the onset o f therapy. The values were then expressed as Bq/well or as Bq/105 cells. During therapy a decrease o f the uptake/well for all tracer was seen in the tk-expressing cell line. A normalisation to the viable cell number showed an increased uptake for F D G and 3-Omethylglucose up to 195%. Experiments with different amounts o f tk-expressing cells and control cells showed that these effects were dependent on the percentage o f tk-expressing cells. The AIB uptake decreased to 47%. The intracellular methionine was decreased in the acidinsoluble fraction (to 17%) and increased in the acid-soluble fraction (to 150%). These data show that these PET tracer m a y be applied for therapy monitoring o f gene therapy with HSVtk. The increase in F D G and 3-O-methylglucose uptake in vitro is interpreted as stress reaction o f the t u m o r cells, whereas the amino acid data indicate an inhibition o f protein synthesis as well as o f the transport o f neutral a m i n o acids.

ffl

cO =m t~ e-

,l,,a

ffl L-

I3.

PTu758

PTu760

U. Haberkorn, M. E. Beltemann, I. M o r r , L. Gerlach, J. Doll, H. Trojan, J. Blatter, G. van Kaick. G e r m a n Cancer Research Center (dkfz), Heidelberg, G e r m a n y and Lilly Deutschland.

L.G. Strauss', U. Haberkorn 1, R. Schosser2, 5.1. Ziegler ~, A. DimitrakopoulouStrauss ~, F. Oberdorfer ~, G. van Kakk 1. ~German Cancer Research Center, Heidelberg, Germany, 2Department of Experimental Surgery, University of Heidelberg, Germany, 3Department of Nuclear Medicine, University of

C H A N G E S IN T U M O R M E T A B O L I S M A F F E R T H E R A P Y O F PROSTATE ADENOCARC1NOMAS WITH GEMCITABINE. This study was performed to investigate the effects o f the new chemotherapeutic agent gemcitabine (2'2'-difluordeoxycytidine) on glucose transport and metabolism in prostate c a r c i n o m a cells. After transplantation o f rat prostate a d e n o c a r c i n o m a cells (Dunning R3327, subline AT1), d y n a m i c PET measurements with fluorine-18-deoxyglucose (FDG) were p e r f o r m e d in 15 animals prior and 24 hours after therapy with 90 m g / k g ( n = 8 ) or 180 m g / k g ( n = 7 ) gemcitabine. One day after therapy the animals received a simultaneous injection o f F D G and H-3-thymidine. After the P E T study the incorporation o f tritiated thymidine into the D N A was determined. In vitro measurements o f the F D G , 3-O-methylglucose and tbymidine uptake were performed immediately and 4 hours after 24 h incubation with different doses o f gemcitabine. Eleven tumors were evaluable by a compartment analysis. Eight o f these showed an increase in K1, k2 and k3. The incorporation o f thymidine into the D N A o f treated tumors showed a 80% decrease as compared to a control g r o u p with no correlation between F D G uptake and thymidine incorporation. In the cell culture experiments a dose-dependent increase o f F D G (up to 175%) and 3-O-methylglucose (up to 305%) uptake was demonstrated. The thymidine uptake showed a decrease to 21% in the acid-insoluble fraction and an increase up to 337% in the acid-soluble fraction. Shortly after therapy with gemcitabine the t u m o r cells react with an increase o f the F D G and 3-O-methylglucose uptake, indicating an increase o f glucose transport. These effects may be part o f cellular stress reactions after exposure to chemotherapy with gemcitabine. The decrease o f thymidine incorporation into the nucleic acid fraction reflects the effects of the drug on D N A synthesis.

k,,

Munich: G~rmany.

EXPERIMENTAL STUDIES OF LIVER PERFUSION USING O-15-WATER AND POSITRON EMISSION TOMOGRAPHY (PET). 0-15-water is one of the tracers used for the quantification of tissue perfusion. The quantification of liver perfusion is complicated due to the double blood supply of the organ and only limited data exist about the tracer kinetics and blood flow. We used PET and O-15-water in animal experiments for the quantitative evaluation of liver tissue perfusion, O-15-water was intravenously injected in 7 dogs and dynamic data were acquired for 8 minutes. Following the 0-15 application radiolabeled microspheres were injected via the hepatic artery and portal vein to quantify the organ blood flow. These data were used for reference. The PET data were scatter and attenuation corrected and iteratively reconstructed with a matrix of 256*256. The images were evaluated with a ROI technique and standardized uptake values (SUV) were calculated. Furthermore, a two compartment model was applied to the PET data. We noted no significant correlation between the SUV for the liver parenchyma 5 min after O-15-water injection and the total blood flow. In contrast, a significant positive correlation was found for the SUV and the arterial blood flow, while a negative correlation existed between the SUV and the portal flow. The multiple regression function for the liver SUV (dependent var.) and the specific arterial and portal flow demonstrated that the accumulation of 0-15-water was increased at high arterial flows and decreased at high portal flows. The model data showed, that Kt paralleled the arterial flow while k2 was associated with the portal flow. The SUV ratios liver/aorta could be used to estimate the specific portal flow (r=0.78), while no correlation was observed between the ratios and the specific arterial flow. Total blood flow could be calculated with an multiple linear regression function and the SUV for the liver parenchyma and aorta. The results show, that images following the intravenous injection of 0-15water do not reflect the total blood flow in the liver parenchyma. Calculations of the total blood flow can be based on a multiple linear regression function and SUV measurements of the liver parenchyma and the aorta.

1221

(1) ,¢,,a O IX,

• Oncology PTu761

M. Sahin, I. Bernay, T. Ba~o~lu, T. Onen, C Co~kun, T. Yahn*, A.E. Demirqah. Ondokuz Mayls University Hospital, Departments of Nuclear Medicine and Radiology*, Samsun, Turkey. EVALUATION OF METASTATIC BONE LESIONS WITH Tc-99m MDP AND Tc-99m (V) DMSA The aim of our study was to assess the value of Tc-99m (V)DMSA scJntigraphy in metastatic bone lesions in comparison with Tc-99m MDP scintigraphy. A total of 15 patients were studied, including 5 patients with breast carcinoma, 4 patients with prostatic carcinoma and 6 patients with lung carcinoma. Whole body bone scanning was performed 3 hours after i.v administration of 740 MBq Tc-99m MDP using a standard imaging protocol. Two days later, Tc99m (V) DMSA whole body images were obtained 4 hours aEer i.v. administration of 555 MBq Tc-99m (V) DMSA in the anterior and posterior projections. All of the scans were evaluated qualitatively. The presence of metastatic disease was determined by scintigraphic patterns, clinical and scintigraphic follow-up and local radiography. In all patients, bone scintigraphy showed multifocal increased radioactivity, asymmetric distribution and location mainly in the axial skeleton. Most of the scans showed matched areas of increased accumulation of Tc-99m MDP and Tc-99m (V) DMSA. Traumatic or degenerative sites, except one patient, showed no accumulation of Tc99m (V) DMSA, whereas an intense accumulation of Tc-99m (V) DMSA was observed in all metastatic foci. One patient with intense Tc-99m (V) DMSA accumulation had a costal trauma due to operation at that site. The results of our study showed that Tc-99m (V) DMSA scintigraphy might increase the specificity and usefulness of bone scan in the evaluation of metastatic disease by excluding the degenerative and traumatic sites.

PTu763 P.Prcdi~, *E.Gregori~, B.Pustovrh, G.Venin~ek, D.Hrastnik HOSPITAL CELJE, *HOSPITAL IZOLA, SLOVENIA

WB AND SPECT SCINTIGRAM WITH Tc-99m-MIBI IN THE DIAGNOSIS OF BREAST CANCER

The isotopic mammography with Tc-99m-MIBI is gaining recognition as a reliable method to diagnose the breast cancer. It is to expect that Tc-99m-MIBI will also be accumulated in bone metastases of the breast cancer. 27 female patients with breast cancer or its relapse and bone metastases underwent SPECT scintigraphy of the breast, and whole body (WB) scintigraphy with 370-550 MBq of Tc-99m-M1Bt. After 2 - 3 days WB scintigraphy of the skeleton was repeated with 370-550 MBq of Tc-99m-DPD. In all patients, SPECT with Tc-99m-MIBI of breasts detected an increased focal accumulation in one only or both breasts while WB scintlgram detected multiple focal points in the whole skeleton. The repeated WB scintigram with Tc99m-DPD detected multiple focal points in the same regions of the skeleton as with Tc-99m-MIBI. Conclusion: In combination, scintigraphy with Tc-99mMIBI and WB scintigraphy of the skeleton with Tc-99mDPD enable us to very reliably diagnose bone metastases in the breast cancer.

PTu762 Ju.E flannel, EM Slonimskaya, SL Stukanov, SA Velichko, WYu Ussov. Tomsk Institute ofOnclogy, Savinykh 12, Tomsk, Siberia, RUSSIA

PTu764 Levent Kabasakal, Musa Hamidi, Canan Akman, GLil Ersava,~, Bedii Kanmaz, Aycca AltuO, Nermin Erkman, Cavit Ni~li, and (~etin (~nsel.

QUANTITATIVE GAMMA-IMAGING FOLLOW-UP THERAPY IN MAMMARY CANCER USING 99roTe -MIBI.

Cerrahpa~a Medical Faculty, Department of Nuclear Medicine and Radiology

OF

Although 99mTc-MIBI has been used for diagnosis of primary neoplasm and metastases in mammary carcinoma (MC), it has not been routinely employed for control of treatment of MC. Extraction fraction and regional uptake of 99mTc-MIBI in mammary gland and metastatic axillar lymph nodes were quantified in women with MC when following-up combined radiation&chemotherapeutical treatment. Fifteen women with cytologically proven MC and seven coronary heart disease patients as controls were referred for the study. We acquired dynamic frames of mammary uptake of 99mTc-MIBI after intravenous injection (570 MBq) simultaneously with half-minute sampling of aIterialised venous blood and thereafter did planary scans and SPET of 99mTc-MIBI uptake. Extraction fraction was determined from MC regional time-activity curve deconvolved with input curve obtained from arterialised venous samples. Results were as follows Control Patients with mammary cancer Indices subjects n=15 n=7 pre-treatment post-treatment 99mTc-MIBI 0.87, sd 0.l 1 0.43, sd 0.07 !extraction fraction in 0.04, sd 0.02 p < 0.05 mamma Mamma/Myoc 0.06, sd 0.04 0.19, sd 0.05 0.10, sd 0.05 p < 0.02 Lymph node/ 0.07, sd 0.08 0.17, sd 0.06 0.12, sd 0.04 Myoc p<0.05 p are given in comparison with pre-treatment values Early post-treatment decrease of 99mTc-MIBI extraction in mammary gland concomitant with decrease of 99mTc-MtBI uptake in lymp nodes predicted absence of MC relapse, in particular after radical surgery performed later in the patients. Thus, 99mTc-MIBI provides independent clinically relevant indices for follow-up and prognosis of treatment in MC.

Tc-99m-MIBI SCINTIMAMOGRAPHY COMPARED WITH MAMMOGRAPHY/ULTRASONOGRAPHYCOMBINATION AND MRI IN DIAGNOSIS OF BREAST. CANCER: PRELIMINARY REPORT MIBI has been shown to accumulate in malignant lesions and can be used in the diagnosis of breast cancer. We conducted a study to evaluate the value of prone MIBI imaging in diagnosis of breast cancer and compared the results with those of mammography/ultrasonog raphy (Mmg-US) combination and magnetic resonans imaging (MRI). For this purpose 24 patients with suspected breast lesions were included to the study. All patients underwent a prone MIBI breast imaging and Mmg-US investigation. MRI was performed in 13 patients. After injection of 740 MBq Tc99m-MIBI 3 planar images were obtained 15-30 min later from left and right lateral and anterior projections. Lateral breast images were obtained with a zoom factor of 2 and all 3 images were preset 10 min. Malignant lesions were proven in 17 patients and benign lesions were proven in 7 patients. Malign lesions were detected with MIBI in 15 of 17 lesions ( sen. 88%) and 7 of 7 benign lesions (spe. 100%). The smallest identified lesion was 1 cm. Mmg-US identified 21 malign lesions and 3 benign lesions. However, 4 benign lesions were identified as malign with Mmg/US (sen 100% and spe.43%). MRI detected 10 malign lesion however 1 of them was proven to be a benign lesion. In 2 patients MRI was detected benign lesions (sen. 100%, spe 75%). Accuracy of diagnostic modalities were 92%, 83% and 92% for MIBI, Mmg-US and MRI respectively. Positive predictive values for MIBI, Mmg-US and MRI were 100%, 81% and 90% respectively. Negative predictive values were 78%, 100% and 100%, respectively. Although patient population was highly selective, this preliminary report suggested that MIE~Ibreast imaging is a valuble modality which can be used in separation of malign and benign lesions and the results are seem to be comparable with those of MRI imaging.

• Oncology PTu765 H. Palmedo, A. Scho~burg, F. Gr~n~ald, C. Menzel, S. Werling, T . E b e l ~ P. M a l l m a n n , T. Bultmann, R. Otte, H.J. Biersac~. Departments of N u c l e a r Medicine, G y n e c o l o g i c , Pathology-, University Bonn, Germany. SCINTIMAMMOGRAPHY WITH MAMMOGRAPHY

WITH TC-99M MIBI: AND MR-MAMMOGRAPHY.

COMPARISON

The aim of the study was to compare d i a g n o s t i c a c c u r a c y of s c i n t i m a m m o g r a p h y (SMM) in detection of breast cancer with mammography (M/M) and m a g n e t i c r e s o n a n c e imaging (MRI). 56 p a t i e n t s w i t h suspicious lesions d e t e c t e d by p a l p a t i o n or MM were enclosed. In all p a t i e n t s SMM, MM and MRI as well as excisional biopsy were performed. For MRT, a dedicated breast coil was u s e d and d y n a m i c sequencies with and w i t h o u t g a d o l i n i u m a p p l i c a t i o n were performed. 5-10 min. after the injection of 740 M B q Tc-99m MIBI in the arm c o n t r a l a t e r a l to the suspicious breast prone SMM was performed. There were 43 palpable and 13 non-palpable lesions (6-80 mm). Breast cancer was confirmed by histopathology in 27 of the patients (22 palpable). In palpable breast lesions, all m e t h o d s showed high sensitivity (SMM 91%, MM 95%, MRI 91%) but SMM demonstrated significantly higher specificity. In comparison to MM/MRI, t w o / o n e additional carcinomas could be d i a g n o s e d by s c i n t i m a m m o g r a p h y . For p a l p a b l e breast lesions, diagnostic a c c u r a c y of SMM is superior to MM and MRI. By the complementary use of scintimammography, s e n s i t i v i t y for the detection of breast cancer and m u l t i c e n t r i c disease can be increased.

PTu767 V. Ivancevic, S. Marnitz, K.-J. Winzer, H.-U. Aldinger, I. Reisinger, J.M. M[Jller, and D.L. Munz. Clinics for Nuclear Medicine and Surgery, Charite, Humboldt University, Berlin, Germany. INTRAINDIVIDUAL COMPARISON OF T c - 9 9 m SESTAMIBI AND Tc-99m TETROFOSMIN IN PRONE AND SUPINE SCINTIMAMMOGRAPHY To investigate, if Tc-99m Tetrofosmin (Te) can be an alternative to Tc-99m Sestamibi (Mi) in scintimammography, we performed a prospective intraindividual study with both agents. Forty-four patients with 48 tumours, clinical/mammographical suspicion of breast cancer and subsequent surgical proof (34 malignant, 14 benign tumours) were enrolled and injected with Te and Mi (750 MBq each) within a week. Planar images in multiple views were obtained with a dual-head gamma-camera in the supine and prone positions starting 5 min p.i. SPECT was performed in the prone position after 30 min. The scans were read independently by two experienced and blinded observers. The results according to turnout stage are summarized as follows: True pos. False pos. False neg. n Te Mi Te Mi Te Mi Tis 3 1 1 1 0 2 2 T1 21 9 10 2 2 12 11 T2 ,T3 10 10 8 0 0 0 2 The site-by-site sensitivity for turnouts _T2 100% and 80% for Te and Mi, respectively. Positive predictive values were 77% and 85% for tumours T2 100% each for Te and Mi, respectively. In conclusion, Te and Mi revealed similar diagnostic characteristics. Sensitivity more than positive predictive values depends on tumour stage. For tumours
C O im C L_

PTu766

PTu768

S. Severi, B. Brancato °, M. F. Mauri*, E. Lorenzi, M. Bonzanini*, M. Camerani Nuclear Medicine, Radiology °, Pathology* S.Chiara Hospital - Trento - Italy

O. Schillaci F. Scopinaro, R. Danieli, R. Tavolaro, V. Picardi, P. Cannas, M. Ierardi, A. Centi Colella, Sect. N u c l e a r Medicine, Dept. Exper. Med., Univ. "La Sapienza", Rome, Italy.

99MTc MIBI M A M M O S C I N T I G R A P H Y (MSMIBI) IN BREAST C A N C E R : IS ITS SENSITIVITY R E L A T E D TO H I G H C E L L U L A R I T Y AND W I C H IS ITS R O L E IN L O C O R E G I O N A L INVASIVITY E V A L U A T I O N ?

Tc-99m TETROFOSMIN (TF) S C I N T I M A M M O G R A P H Y ACCURACY IN PATIENTS WITH SUSPICION OF (BI C A N C E R (C) A N D C O M P A R I S O N W I T H T c - 9 9 m

In order to evaluate the correlation between cellular density and MSMIBI sensitivity in tumor detection and MSMiBI ability in diagnosing the locoregional invasivity we studied 32 highly mammographic suspected patients with indication for open biopsy. Materials and methods: before surgery we injected intravenously 740 MBq of MIBI and acquired, after 15 minutes, 6 static views (2 anteriors, 2 laterals and 2 anterior oblique), 2000 Kcounts each. The cellularity evaluation was studied in the surgical specimens by morphometrical analysis. For each case, the histological section showing the maximum diameter of the lesion was identified and an automatic measurement of the mean percentage of cellular areas / acellular areas ratio was performed using color image analysis. Results: The lesions were 25 invasive ductal carcinomas, 2 invasive lobular and 5 intraductal carcinomas. The MS-MIBI showed 25 true positive (TP) and 7 false negative (FN) results, with sensitivity of 78%. All FN lesions had a macroscopical diameter less than 12 mm and showed a mean percentage of cellular areas of 17.65%. The overall mean percentage of all TP lesions was 27.34%. The only six TP lesions with a diameter ranging between 10 and 15 mm, showed a mean percentage cellularity of 37.68%. In the 30 patients with surgical lymphnodes exploration we had a positive tracer concenUation in 10 cases; 2 of them were false positive and 2 false negative. The 2 false negative were related to a minimal lymphnodes involvment. In 1 case we could detect a positive sopraclavear involvement while all the other metastases were referred to axiltary invasion. Versus lymphnodes involvement, MS-MIBI showed a sensitivity of 80% and a specificity of 90%. Conclusions: T h e MSMIBI has an high sensitivity in turnout detecting and the correlation with the morphomeWical analysis has demonstrated a better answer in high cellularity territories, the turnout size is otherwise the critical parameter. There is also a good sensitivity in invasivity localizing lesions, this aspect needs a confn-m by studies in larger casistic, but it seems to be one of the more promising indication of this modality.

SMM with Tc-99m MIBI has been r e c e n t l y p r o p o s e d as useful method for BC detection. T c - 9 9 m TF, like Tc-99m MIBI, is a lipophilic cationic complex, and similiar uptake (up) mechanisms have been suggested. The aim of this study was to evaluate the role of T c - 9 9 m TF SMM in patients (pts) with suspicion of BC, and to compare the data o b t a i n e d with T c - 9 9 m MIBI SMM. Fifty-two pts w i t h m a m m o g r a p h i c a b n o r m a l i t i e s were studied with T c - 9 9 m TF SMM. In 18 of them also Tc-99m MIBI SMM was performed. Dynamic (d) images (20 of 1 min/each) w e r e a c q u i r e d starting immediately after the injection of the radiopharmaceutical (740 MBq i.v.). Planar images (6-8 min/each) were obtained from lateral and anterior v i e w following the d study. Final diagnosis was a c h i e v e d by histology. A total of 56 B lesions w e r e considered: the sensitivity (SE) of Tc-99m TF SMM for BC detection was 92.6% (25/27) and the specificity (SP) was 93.1% (27/29). A x i l l a r y lymph node involvement (ALNI) was present in 15/27 pts with BC: SE of Tc-99m TF SMM was 73.3% (11/15) and SP was 100% (12/12). In pts studied with both tracers (tr) no up was observed in i0 benign B lesions; both tr d e m o n s t r a t e d focal up in 8 BCs and in the axilla of 3/5 pts with ALNI. W h e n present, the tumoral up of both tr was very fast (1-2 min). In conclusion, our results suggest that T c - 9 9 m TF SMM is an a c c u r a t e m e t h o d for d i a g n o s i n g BC and ALNI, and an useful a l t e r n a t i v e to Tc-99m MIBI as a complement to mammography.

(81424): BREAST MIBI.

1223

O

• Oncology PTu769

PTu771

Juan F. Balista, Mar/a E. Solano, Juan P. Oliva, Jos~ L. Rodriguez, Elvia SAnche7~l_AzaroBell. Centro de Investigaciones Clinicas, Habana, Cuba.

H. P a l m e d o , 2 H ~ B e n d e r ~ A. Schomburg, F. G r ~ n w a l ~ , D. I n d e f r e i , T. Ebel , M. Bangard, P. Mallmann-, B. Overbeck, H.J. Biersack. ~epartments o~ Nuclear Medicine, Gynecologie ~ , PathologyU n i v e r s i t y of Bonn, G e r m a n y

TECHNETIUM-99M-TETROFOSMIN SC1NTIM,MX4[MOGRAPHY IN PALPABLE BREAST MASSES

COMPARISON DIAGNOSIS

Background: Several radiopharmaceuficals such as Tc-99m-Meto.,disobutil-Lsonilrile, Tc-99m-MDP, Gallium Citrate and Thallium Chloride have been tested for the detection of breast cancer and lymph node involvement. To date, only one report has been published related with the uptake of Tc-99m-Telrofosmin in one patient with breast cancer. The aim of flfs exploratory study was to assess the usefulness of scin'~rmmmogmphyusing Tc-99m-Tetrofosmin for detection of palpable breast tumors due to its potential capabili~ to discriminate malignant of no malignant lesions. Methods: Nine patients with palpable masses were studied, seven with positive diagnosis of malignant lesions, and two diagnosed of no maSgnant, determined by fine needle aspiration (FNA) biopsy cytology. Each patient received 25 mCi of Tc-99m-Tetrosfosmin intravenously, obtaining three planar prone views in right and left lateral, and anterior positions that included the axiUary region visualization. Results: Scintimammography showed an increase of the focal uptake of the tracer in seven patients with positive FNA results, wide not showed that increment in the two patients with negative FNA results. Conclusions: These findings suggest that Tc-99m-Tetrosfosmin coitld be a promising ladiophannac~utical for detection and discrimination of the natur¢ of palpable breast tumors. Further, larger studies should be made to confirm these results.

OF PET UND SCINTIMAMMOGRAPHY OF BREAST CANCER.

FOR

T h e a i m of t h e s t u d y w a s to c o m p a r e d i a g n o s t i c a c c u r a c y of F D G - P E T and T c - 9 9 m MIBI s c i n t i m a m m o g r a p h y (SMM) for t h e d e t e c t i o n of b r e a s t c a n c e r . A t o t a l of 17 p a t i e n t s w e r e s t u d i e d by SMM and t h e f o l l o w i n g d a y by PET. i0 m i n p.i. of 740 M B q T c 99m MIBI, planar and SPECT images . in p r o n e position were performed. Emissiontomographic s c a n s w e r e a c q u i r e d 60 m i n p.i. of 370 M B q F-18 DG in t h e a r m c o n t r a l a t e r a l to the s u s p i c i o u s b r e a s t . A t t e n u a t i o n c o r r e c t i o n was d o n e by t r a n s m i s s i o n scans. In all p a t i e n t s , h i s t o p a t h o l o g i c a l results of the suspicious lesion were achieved. From ii p r i m a r y b r e a s t cancers (mean s i z e = 2 9 m m , r a n g e 7-50mm), PET as w e l l as S M M w e r e positive in 8 c a s e s ( s e n s i t i v i t y 91%), in two l o c a l r e c u r r e n c e s (size < 8mm), no m e t h o d w a s dia g n o s t i c . F r o m 6 b e n i g n a l t e r a t i o n s of t h e b r e a s t (3 fibrocystic lesions, 2 fibroadenomas, 1 chronic inflammation), PET and S M M w e r e f a l s e p o s i t i v e in one p a t i e n t w i t h f i b r o a d e n o m a (specificity 83%). From 5 patients with axillary m e t a s t a s e s , P E T d i a g n o s e d lymph n o d e m e t a s t a s e s in all cases, s c i n t i g r a p h y in o n l y 4 cases. T h e m e a n F D G - S U V for b r e a s t c a n c e r was 40.2 (range 9.7-75) a n d t h e M I B I r a t i o of t u m o r t o n o r m a l b r e a s t t i s s u e w a s 2.0 (range 1.43 to 3.1). For malignant tumors, the MIBI ratio was always h i g h e r t h a n t h e r a t i o for the f a l s e p o s i t i v e fibroadenoma (what w a s not t r u e for PET in one case). D i a g n o s t i c a c c u r a c y of PET w i t h FDG is not s u p e r i o r to s c i n t i m a m m o g r a p h y w i t h T c - 9 9 m M I B I for d e t e c t i n g b r e a s t cancer. However, PET s e e m s to be m o r e s e n s i t i v e t h a n s c i n t i g r a p h y to d e t e c t l y m p h n o d e m e t a s t a s e s of the axilla.

PTu770

PTu772

C. Zerva, C. Sabali, D. Kiriaki, E. Kitsou, I. Gogas, and V. AIevizou. Dept. Nucl. Med. and 2nd Surgical Clinic, "Laiko" Gen. Hospital, Athens, Greece.

,|.L. Moretti, H. Azaloux, D. Boisseron, J.C. Kouyoumdjian, B. Boissier, S. Piperno-Neumann, J.R. Vilcoq. CHU Bobigny, Fort-de-France, Cr4teil, Institut Curie, PARIS FRANCE.

Tc TETRAFOSMIN IMAGING IN BREAST TUMOURS SUSPICIOUS FOR MALIGNANCY. Thirty six women with clinically suspicious breast lumps were studied 1-4 days prior to surgery. I.V. injection of 370Mbq nfTc Tetrafosmin was followed in 20 patients by 3min planar images at 60min postinjection, and [r~ t6 pat}ents at 30rain postinjection. In 3 of these latter patients the 3Omin imaging was preceded by a dynamic study of 20xl rain images. The myocardium was always included in the field of view in the image of the left breast Images were aquired with the patient rotated 30 degrees to the left and then to the right to provide breast images without chest wall interference as much as possible. The analogue film and the digital images were viewed and count rates in suspicious areas compared with normal areas in the same breast, in the opposite breast and with myocardial counts. The results were marked as positive or negative by two observers in ignorance of the histological diagnosis and the histological result including tumour type was recorded later. Thirty one of the36 scan results were in agreement with the histologi-cal findings (23 true positives and 8 true negatives ). There were 4 false negatives, two of which were histologically "microscopic" tumors, and 1 false positive in a patient who had bilateral globally dense breasts on the scan. The sensitivity of Tc Tetrafosmin breast scans in the detection of malignant breast tumours was 85% and the specificity 88% in this series. The dynamics of Tetrafosmin uptake in tumour and the myocardium were compared and the count rate parameters are discussed in relation to tumour histology and scan timing. Breast scanning with Tc Tetrafosmin seems to have a good sensitivity and high specificity for the detection of malignant tumours of the breast.

1224

THE

PRIMARY BREAST CANCERSESTAMIBI IMAGING : ITS RELATION TO PgP 170 MULTIDRUG RESISTANCE. The aim of this preliminary study was to evaluate retrospectively T c 99m Sestamibi scintigraphy in relation to the presence of a 170 kD Pglycoprotein (Pgp) ,which is an expression of multidmg resistance in patients with primary breast cancer. Fifteen women (age range 37-76) were referred for clinically suspicious breast lesion assessed by mammography and echography, confirmed by fine needle aspiration cytology and pathology after surgery. Scintimammography was performed 30 rain postinjection of 500 MBq 99mTc-Sestamibi. Three planar anterior and oblique images were obtained in supine position. Excised tumors were assessed for cytosolic CA 15.3, Estradiol (RE) and Progesterone (RP) Receptors and Cerb B2 / Neu determination. Mammography was positive for malignancy in 14/15 with one true negative and one false positive case. Echography was positive for malignancy in 13 patients with one true negative, one false negative and one false positive case. Pathology revealed that only 13/15 patients had malignant tumors. The two benign tumors were sestamibi negative and Pgp positive. Sestamibi scintigraphy was found positive in 10/13 malignant lesions (9/10 infiltrating ductal carcinoma). Two of the three lesions with false negative scintigraphy were Pgp negative and their histology were respectively invasive lobular carcinoma and mucinous adenocarcinoma. The third false negative lesion was a positive Pgp infiltrating ductal carcinoma, Cerb Neu negative, CA 15.3 RP and RE positive. This preliminary study confirms that chemotherapy resistance which can occur in P- glycoprotein positive primary breast tumor can be a cause of negative sestamibi scintigraphy.

• Oncology PTu773

PTu775

J. Pasqnier*, O. Chinot**, I. Brenot-Rossi*, H Dufour**, I. ImberMoscht*, R. Sauvan*, F. G-risoli**, I~dmt Paoli-Calmet~, DlX de M~lecine Nucl~ite* et Centre Hospitalier Univemituire de la Timone, Dpt de Neurochimrgie**, Marseille, France.

N.C.M. Galaldz. h. Kostako~lu, Hayran~ L. Atahan, C.F. Bekdik. Hacettepe University Medical Medicine and Radiation Oncology,

CLINICAL RELEVANCE OF 99mTc-SestaMIBl (MIBI) IN COMPLEMENT TO CONVENTIONAL NEURO-IMAGING IN THE FOLLOW-UP OF THE GLIOMAS. 99mTc-SestaMIBI has been proposed to accurately appreciate malignancy of gliomas. Objeeti',,,e of this study was to evaluate in which clinical setting MIBI could add to conventional neuro-imaging (CT and/or MR]) in the follow-up of

SEMI-AUTOMATED QUANTIFICATION OF BRAIN TISSUES AFTER RADIOTHERAPY

gliomas. Study was performed on 42 pts (median age 50,5 yrs ; range 23-69). Histology included 28 malignant gliomas, 5 ~aplastic oligodendrogliomas, 2 anaplastic ependymomas, and 7 benigns gliomas. Brain SPECT has been performed 30 mn after 740 MBq IV of 99mTc-SestaM]BI (Helix-Elscint gamma-camera, FanBeam collimators, 64x64 matrix, acquisition time 20 mn, Metz filter, attenuation coefficient : 0.08). Tumor fixation level (T) has been compared to hypophyse (H) and positive level was considered for ratio T/H over 0.35, Fifty MIBI were evaluated, with two brain SPECTs performed for 8 pts. Benefit of M1BI was considered if MIBI imaging added information to conventional imaging (CT and/or MR/) in the follow-up of patients. Concordance of MIBI and CT/MRI was observed in 36 cases (72%) while discordance ocoured in 14 eases (2g%). With a mean follow-up of 11.1 months (range 3-15.5 months), results of MIBI were considered as true positive (residual tumor or rceurrence or malignant transformation) in 23 cases (46%), as true negative (no malignant detectable tumor) in 19 cases (38%). False negative MIBI was observed in 8 cases (16%), with CT/MRI contrast enhancement diameter less than 12 mm in 5/8 cases. No false positive was observed. In gliomas, MIBI sensibility was 74°/o, with a specificity of 100% in this gliomas population, and an accuracy of 84%. We considered benefit of MIBI over CT/MRI, in three clinical settings. Benefit of MIBI was observed -1- in 4/11 cases (36%) in the follow-up of benign gliomas or anaplastic oligodendrogliomas -2- in 13/23 cases (57%) in the evaluation of residual tumor after surgery -3-in 11/16 cases (69%) in the follow-up of malignant gliomas (mainly for suspicion of recurrence). Conclusion : MIBI imaging may help in the follow-up of patients with glioma, pasticulary when CT/MRI is not conclusive in the evaluation of a malignant component, despite its low sensitivity for small residus.

D.

Uzal,

U.

Uysal,

Faculty, Departments 06100 Slhhiye, Ankara,

DECREASE

IN

N.

Elahi,

M.

of N u c l e a r Turkey.

PERFUSION

IN

NORMAL

We attempted to ascertain the adverse impact of conventional (Co-60) radiotherapy {cRT) on the p e r f u s i o n of n o r m a l brain tissue in relation to the radiation doses d e l i v e r e d to the patients (pts} w i t h p r i m a r y brain tumors. F o l l o w i n g s u r g e r y iS pts w e r e p l a n n e d to u n d e r g o cRT for a total dose of 5100-6400 cGy. All pts had Tc-99m-H~PAO SPECT study p r i o r to cRT (basal), 15th and 30th days of RT as well as 1,3, and 6 months (in 3 pts) following RT. SPECT imaging w a s p e r f o r m e d using a dualh e a d gamma-camera, 30 see/frame, 128 frames in an e l l i p t i c orbit. After reconstruction of images, the entire set of transverse slices were d i v i d e d into 4 regions as frontal, parietal, occipital and temporal u s i n g a computer software program. A 8

R

L

was done on a total of 1616 regions with a mean estimated thichness of 3 cm in i01 studies to determine left to right ratios. Interregional difference of at least 10% was considered abnormal. Corresponding dose levels were determined from isodose curves used for cRT planning.

After elimination of tumor location, Spearman's correlation test was applied to all regions that showed i0% decrease in perfusion. There were S0 normal brain regions that s h o w e d d e c r e a s e d p e r f u s i o n a f t e r cAT. Of these, 74 regions r e c e i v e d >500 cGy (p<0.05). The p e r c e n t decrease in p e r f u s i o n was s i g n i f i c a n t l y higher (mean 22.54~9.85} in areas irradiated with doses >3000 cGy. In conclusion, cRT has a d v e r s e impact on the p e r f u s i o n of normal brain tissue for doses >500 cGy. Our findings justify that pts with small and l i m i t e d lesions s h o u l d be t r e a t e d w i t h s t e r e o t a c t i c techniques in order to minimize the adverse effects of cRT on normal tissues. On the other hand, pts with tumors >3 cm who c o u l d not be candidates for stereotactic techniques, r a d i a t i o n fields s h o u l d be re-evaluated after doses of $3000 cGy to lessen the unwanted effects of cRT.

PTu774

PTu776

G. Mariani, A. Lasku, E. Baiza, B. Gaggero, C. Motta, G. Calcagno, A. Dorcaratto, G. Viale and L. Zardi. Nuclear Medicine Service, DIMI, and Institute of Neurosurgery, University of Genoa; National Cancer Institute (IST); Genoa (Italy).

R. Valkema C.H.J. van Eijck, A.E.M. Reijs, J. van Peski, E.P. Krenning. Departments of Nuclear Medicine and Surgery, University Hospital, Rotterdam, The Nethedands.

TUMOR TARGETING POTENTIAL IN NUDE MICE OF THE RADIOIODINATED MONOCLONAL ANTIBODY BC-I DIRECTED AGAINST ONCO-FETAL FIBRONECTIN The lgGa monoclonal antibody (MoAb) BC-I detects a human fibronectin isoform (B +) containing the ED-B oncofetal domain. This antigen has extremely restricted distribution in normal adult tissues and high expression in fetal and tumor tissues, and it represents therefore a novel marker of angiogenesis. We studied the biedistribution of MoAb BC-1 (labeled with ~25I by the iodogen technique) in a total of 21 nude mice bearing two human tumor implants simultaneously, the U87MG high-grade astrocytoma and the SKMEL28 melanoma lines (one in each flank). The MoAb, radio iodinated at the specific activity of 370 MBq/mg, was injected either intraperitoneally (i.p.) or intravenously (i.v.), and the complete organtissue biodistribution was measured at 24, 48 and 72 hours after tracer administration. ~+-SI-BC-I showed favourable uptake in the human tumors implanted in nude mice, as follows:

U87MG (i.p.) SKMEL28 (i.p.) SKMEL28 (i.v.)

Tumor uptake (% dose/oram) 24 fir 48 hr 72 hr 4.89-+0.84 4.80-+0.58 5.27_+0.48 3.02_+0.22 3.21_+0.35 2.32._+_0.28 3.49-+0.25 3.18_+0.22 2.36-+0.35

The higher and more stable uptake of radioiodinated MoAb BC- 1 in the astrocytoma tumors reflected the higher expression of the oncofetal fibronectin in the U87MG than in the SKMEL28 tumor implants, as visualized by immunohistochemistry. Nonspecific uptake in the bone marrow, skeletal muscle, etc. was much lower than in both types of tumors. The experimental results obtained in this study point out the favoraNe tumor targeting potential of the radiolabeled BC- I MoAb, a useful marker of angiogenesis induced by cancer.

O

am

L_

FLUORINE-18-DEOXYGLUCOSE (18-FDG) SINGLE PHOTON EMISSION TOMOGRAPHY FOR THE DETECTION OF CANCER

Aim: Positron emission tomography (PET) using 18-FDG is a sensitive method to detect cancer lesions, useful for discriminating cancer from benign lesions and for the early detection of metastases. Our purpose was to study the feasibility of 18-FDG single photon emission tomography (SPET) for the detection of such pdmae/and metastatic cancer. Patients and methods: A 3-head SPET camera (Picker Prism 3000) was fitted with ultra high energy collimators. Nine patients with known or suspected pancreatic cancer, two with suspected recurrence of colorectal cancer and one with oesophageal cancer were investigated 45 min. after injection of 185 MBq 18-FDG. Four acquisitions in continuous rotation over 360 ° were obtained in 30 min. and added to each other, followed by reconstruction after filtering with a low-pass filter. In one patient dual isotope acquisition was performed using 55 MBq of Tc-99mcolloid to identify the liver. The SPET results were compared with conventional imaging in all 12 and with histology in 9 patients. Results: SPET with 18-FDG showed low intensity uptake in 4 of 4 primary pancreatic adenocarcinomas, 1 of 1 neuroendocrine pancreatic carcinoma, 1 of 1 oesophageal carcinoma, and 1 abdominal tumor which appeared to be metastasis of an unknown primary. Also, in 1 of 2 patients with chronic inflammation of the pancreas faint uptake was noted. In one patient with local recurrence of rectal carcinoma intense 18-FDG uptake was seen. One patient with recurrence of colonic carcinoma showed multiple liver lesions, subsequently confirmed with CT. In 3 patients with pancreatic malignancies 18-FDG SPET showed equivocal liver lesions, in 1 clear liver lesions and in 3 abdominal metastases, all confirmed with conventional methods. Equivocal liver lesions in the patient with an unknown primary could not be confirmed. The contrast between lesions, liver, and background was low in most cases. Conclusion: The image quality of 18-FDG SPET in the current setting is less than the quality known of PET, with low lesion to background contrast. Many lesions were detected, however. The actual place of this technique and of coincidence detection for oncology will be evaluated in the near future.

1225

O

• Oncology PTu777

PTu779

L.J.M. Rijks, P.J.M. Bakker, C.H.N. Veenhof, G.J. Boer, K. de Bruin, A.G.M. Janssen, E.A. van Royen, Departments of Nuclear Medicine and Medical Oncnlogy, Academic Medical Centre, Amsterdam,The Netherlands; Cygne BV, Technical University, Eindhoven, The Netherlands.

Susan Me~;hdadi~.Ulrike MossbacherLMargarida Rodrigues~.J. Flores~. H. Pchamberger2, H. SinzingeP Departmentof NuclearMedicine~and Departmentof Dermatolo~2. Universityof Vienna. Austria

IMAGING OF RECURRENT OR METASTATIC BREAST CANCER WITH THE ESTROGENRECEPTOR SPECIFICLIGANDZ- [I-123]MIVE. The Z-isomer of llg-methoxy-17cx-[I-123]iodovinylestradiol (Z-[I123]MIVE) shows excellent estrogen receptor binding properties in both rat and human mammary tumour tissue in vitro as well as in a rat tumour model in vivo. In human volunteers Z-[I-123]MIVE reveals a low lung retention, rapid hepato-biliary excretion and diffuse uptake in normal breast tissue. In this study Z-[I-123]MIVE was investigated as specific radioligand for imaging of estrogen receptors in metastatic breast tumours. Anterior and posterior whole body scans were made of 14 women with radiologically or scintigraphically confirmed recurrent or metastatic breast cancer (age 34 - 7l years) at several time points (up to 24 h) after i.v. injection of 150 MBq Z-[I-123]MIVE (SA 200 MBq/nmol). Quantification was performed by the "regions of interest" method. The results were expressed as lesion-to-backgrounduptake ratios. Low lung uptake and rapid hepato-biliary excretion allowed early imaging of the thoracic region. Analysis of the abdominalregion was impeded by bowel excretion. Focal accumulationof Z-[I-123]MIVEwas detected in known local recurrences and metastases in the lungs, liver, bone, brain and lymph nodes. The lesion-tu-backgrounduptake ratios increased over time. At 4 - 6 h after injection the ratios were in the lungs e.g. 3.5, liver 3.2, lymph nodes 3.6, sternum 2.2, os ilium 3.7, pelvis 2.7, os pubis 9.7, and local recurrence 2.8. There was also high accumulation of Z-[I-123]MIVE in the thoracic region of two patients with known pleuritis carcinomatosa and lymphangitis carcinomatosa (uptake ratios 3.9 and 4.8 at 4 h after injection). Receptor specificity of tamour uptake of Z-[I-123]MIVE was established in 6 patients who were studied a second time 2 - 3 weeks after initiation of anti-estrogen (tamoxifen) therapy. No Z-[I-123]MIVEuptake was seen anymore in any of the lesions. This was due to receptor blockade by the anti-estrogen, indicating that Z-[I-123]MIVEuptake was indeed estrogen receptor-mediated. In conclusion,Z-[I-123]MIVEaccumulates specifically in recurrencesand all metastases (bone, liver, lung, brain and lymph nodes) of breast cancer.

LOW-DENSITY L I P O P R O T E I N B I N D I N G AND MELANOMA: POSITIVE IN-VITRO BINDING, BUT NEGATIVE IN-VIVO IMAGING RESULTS Cholesterol metabolism is involved in cancer growth.Various malignant tissue shows increased LDL-binding. We therefore examined, whether human melanoma exhibits enhanced In111- LDL-binding in-vitro and whether_this property could eventually be used for In-II1-LDL in-vivo imaging. Autologous LDL were separated from 8 healthy volunteers (6 males, 2 females, aged 31-47 years) by means of ultracentrifugation. Labeling was done using complexing with DTPA. A dose of 25-35 MBq of I n - l l l - L D L was injected intravenously, imaging was performed immediately and after 4 as well as 20 hours. In all patients recurrences were proven by at least 2 other methods. Scintigraphic imaging, however, revealed in none of the patients in none of the proven locations positive findings. No false positive images were obtained either. Human melanoma tissue ( n=6 ) obtained from surgery showed high In-lll-LDL-binding. These clinical findings, however, indicate that although in-vitro Inl ll-LDL-binding studies show a high number of LDLreceptors, this in contrast to other malignant ~rnors seems to be insufficient to allow receptor scintigraphy for primary and/or secondary melanoma visualization.

PTu778

PTu780

G.Ferlin, D.Rubello, SPedrazzoli °, F.Chierichetti, P Zanco, AFini, R.Bergamin,CPasquali ° Nuclear Medicine-PET Center, °Surgical Phatology, Hospital of Castelfranco V.to (TV), Italy. ROLE OF FDG PET IMAGING IN DIAGNOSIS OF PANCREATIC DISEASE: PRELIMINARY REPORT. Several new imaging procedures have been developed during the past 2 decades for detection of pancreatic cancer (PC): US, CT, MR, endosonography, diagnostic laparoscopy combined with laparoscopic US give very good and detailed morphologic informations. A diagnostic problem that has remained unsolved is the differential diagnosis between focal or diffuse pancreatitis (PA) and PC. Recently PET with FDG has given encouraging results in diagnosis and staging of PC (Bares R i993). Methods: since May I995, 20 pts (14 M, 6 F) with a pancreatic mass have been prospectively investigated with FDG PET, US, CT and/or MR. Diagnosis was confirmed in 17 pts, by surgical exploration (11 pts) or by percutaneous FNA (6 pts): 7 adenoca., 1 cystoadenoca., 3 malignant pancreatic endocrine tumours (1 of them associated with 3 duodenal gastrinomas), 1 lymphoma, 1 malignant duodenal somatostatinoma, 1 renal cancer metastatic to the pancreas, 2 chronic PA, 1 normal pancreas (false positive mass revealed by US, CT and MR) PET imaging was performed 60 min. after i.v. injection of FDG 12 mCi in condition of overnight fasting. Trasmission scanning was also obtained to correct for attenuation and to calculate the SUV in areas &focal tracer uptake Results: in all the 13 pancreatic neoplastic pts, PET correctly localized the primary lesion (bifocal in I case); in addition, metastatic regional nodes were seen in 4 cases, liver metastases in 2 and peritoneal spread in 2. SUV ranged from 2.8 to 13; the higher values were found in an undifferentiated PC. PET resulted negative in the slow growing tumours (metastatic duodenal somatostatinoma and gastrinomas) and in all non neoplastic lesions. Conclusions: in our first experience PET seems to give promising results in evaluation of malignancy of pancreatic masses.

P. GRIES, E.G. EISING, M.E.SCHEULEN*, J. SCIUK

1226

Klinik far Nuklearmedizin and Tumorforschungszentrum*, Universitat GHS - Essen, Hufelandstr. 55, GERMANY

I N F L U E N C E OF HIGH DOSE A N T H R A C Y C L I N C H E M O THERAPY ON THE MYOCARDIAL EJECTION AND FILLING RATES ASSESSED BY GATED BLOOD POOL SCINTIGRAPHY The assessment of the left ventricular ejection fraction (LVEF) is a relevant method in the evaluation of cardiotoxicity induced by anthraeyclins. The aim of the study was to test whether peak ejection or peak filling rates (PER and PFR) can lead to an earlier detection of myocardial damage and to test a differential cardiotoxicity of adriamycin versus epimbicin. We performed 177 gated blood pool scintigmphies in 43 patients (28 males, and 15 females), 133 among them also in ergometric stress conditions. Twenty three patients received adriamycin (group l) and 20 epirubicin (group II). We found no significant difference in the LVEF between both groups neither under stress nor at rest (EFS and EFR) before the first therapy administration. A principal component analysis showed a comparable stronger weight for the PER and PFR than for the EFS and EFR. In addition, the analysis of variance showed a stronger alteration of the PFR at rest (p<0.03), of the PER under stress (p<0.01) and of the on the heart rate (HR) and LVEF normalized rest parameter LVEF*HR/PFR (p<0.0004) in the group l than in the group It. The present study shows that the myocardial motility parameters and especially the diastolic function (PFR) at rest, lead to a more sensitive recognition of a myocardial pump dysfunction than simply the EFS and EFR. Moreover it tends to proove a stronger carditoxicity of adriamycin compared to epirubicin.

•

Oncology/Paediatrics

PTu781

PTu783

L. Fonseca 1,2, C. Maliskal,2, E. Pinto2, L. Castro2, M. Bemardo-Filho2. 1- Departamento de Radiologia, Universidade Federal do Rio de Janeiro, 2- Instituto Nacional de C~.ncer Rio de Janeiro, ILl, Brasil

Z. (Szcan, 8- ~;alkavur*, G. Erenel, 8. Targan*, H. Akin, F. Atllhan*, Y. Duman. Ege University Medical Faculty Nuclear Medicine Dept and *Beh~et Uz Children's Hospital CliNc of Oncology ,Izmir, Turkey

THE OESOPHAGEAL RECONSTRUCTION SURGERY STUDIED BY DYNAMIC SCINTIGRAPHIC METHODS 1N ONCOLOGIC PATIENTS.

PRELIMINARY CLINICAL EXPERIENCE WITH Tc 99m MIBI SCINTIGRAPHY IN CHILDHOOD NEOPLASIA

Nuclear medicine is a very useful tool to evaluate the performance of normal function as well as the effects of disease of the gastrointestinal tract. Such studies have also proved useful in monitoring the effects of drug or surgical intervention and in the assessment of delivery systems for orally administered pharmaceutical formulations. We have studied the oesopbageal transit and the gastric emptying in the monitoring of the effect of oesophageal reconstruction surgery. Oncologic patients (19) were evaluated after oesophageal reconstruction surgery with gastric (group II - 14 patients) or colonic tube (group III- 5 patients) and they were compared with 15 healthy volunteers (group I - control) using scintigraphic process with liquid food mixed with a radiopharmaceutical (sulfur colloidal labeled with 99mTc). In the evaluation of the oesophageal transit, the patients (supine position) have received, orally, the radiopharmaceutical in liquid food and dynamic images were obtained with 05 sec intervals during 2 rain (in the processing of the images, the neotube was divided in three segments). The gastric emptying was also performed 2 days after oesophageal transit in the same patients using solid food (egg sandwich) with the same radiopharmaceutical and the images were obtained with 1.0 min intervals during 60 min. In the oesophageal transit studies there were no significant statistical differences among the three groups (I, II, III), when we have just considered to two (superior) of the three segments, as oesophagus, showing that the distal neotube works just like the stomach of normal volunteers. In the emptying studies the values of the T1/2 of the patients were much faster than those of the control (p < 0.05). However, when we compare the T1/2 of the group II with that of the group III we found no significant differences. We concluded that these nuclear medicine methods can be useful in monitoring the surgical reconstruction of oesophagus.

This study was planned in order to make a preliminary assessment of Tc 99m MIBI scintigraphy in pediatric neoplasms with emphasis on tumor detection and follow up of posttherapeutic changes. Until now, totally 18 children (aged 22 mo to 16 yr), 13 at initial presentation and 5 at post-therapy period covering 5 lymphoma, 3 astrocytoma, 2 medullablsstoma, 2 osteosamoma, 2 Ewing's sarcoma,1 Wilme' tm, 2 Rhabdomyossrcoma and 1 retinoblaetoma were studied. All patients underwent planar and/or SPECT imaging 10-30 min after =v injection of 7.4 MBq/kg Tc 99m MIBI as well as other imaging studies including CT and NMR. Images were evaluated visually and quantitatively using ROle over lesion site and contralateral normal tissue. There was quite variable uptake of MIBI in these different types of tumors with the highest ratio in bone sarcomas followed by brain tumors. The mean iesion/contralateral (L/C) uptake was 2.18-+1.09. Patient with metastatic Wilms' tm and 4 cases with a suspicion of local residual viable tumor showed no abnormal activity accumulation. The final diagnosis of these 4 cases has not been confirmed by biopsy until now. This preliminary data indicates that, many pediatric tumors may show Tc 99m MIBI affinity with a wide range in uptake degree. The physical properties of Tc ggm allow this agent to be alternative to Ga 67 and TI 201 inpediatric oncology. However it seems that further studies in large series are required in order to determine the tumor types in which Tc 99m MIBI scintigraphy has a value in patient management.

u~ cO =m d~ d~

eG) t_

Paediatrics PTu782

PTu784

E.Le Stanc*, F.Bonnin*, H.Lottmann**, C.Loirat***, Y.Aigrain**, B.Bok*. *Service de M6decine Nucl6aire hSpital Beaujon, Clichy. Services de Chirurgie** et de N6phrologie***, h6pital R.Debr6, Paris. FRANCE.

Mustafa Yddmm, GDlin Vural, TiJrkiz Gi~rsel, GiJlyDz 6ztGrk, Ozlem Kapucu, Tamer Atasever, Nahide Gbkgora. Gazi University Departments of Nuclear Medicine and Pediatrics Ankara - Ti~rkiye

THERAPEUTIC CONSEQUENCES OF DIVERGING INTERPRETATIONS OF DIURESIS RENOGRAPH¥ (DR) IN BABIES. Numerous methods have been p r o p o s e d to interpret furosemide response curves of DR and may lead to diverging conclusions and therapeutic decisions. A series of 82 asymptomatic babies (<9 months of age) were consecutively referred to our institution for 99 hydronephrotic kidneys diagnosed by u l t r a s o n o g r a p h y before birth. All DR required the injection of furosemide. DR was performed using a standard protocol: adequate hydratation, 15 to 19 M B q of 99mTc-MAG3, img/kg of furosemide. In all cases, one qualitative interpretation and 12 quantitative indexes (including 6 differents m e t h o d s for c a l c u l a t i n g TI]2) were d e r i v e d from the same a c q u i s i t i o n data and i n t e r c o m p a r e d u s i n g K a p p a test. Three categories were determined: no obstruction (NO), indeterminate (I) and obstruction (O). Qualitative interpretation resulted in 10.5% of (O) a n d 47.7% of (1). U s i n g the 12 q u a n t i t a t i v e indexes, (O) varied from 9.3 to 75.6%, (I) from 4.6 to 59.3% and (NO) from 11.6 to 77.9%. S t r i k i n g differences were also observed in the same patient. w o u l d this c l a s s i f i c a t i o n be the b a s i s of a surgical decision, these discrepancies might lead to dramatically different attitudes, although the same a c q u i s i t i o n data in the same patient w e r e used. No gold standard exists to really assess the d i a g n o s t i c v a l u e of each one of the m e t h o d s assessed. Therefore, a b e t t e r k n o w l e d g e of the n a t u r a l h i s t o r y and e v o l u t i o n of a s y m p t o m a t i c kidney is required, as well as standardization of interpretation criteria.

BRAIN PERFUSION SPET IN T R E A T E D PATIENTS WITH A C U T E L Y M P H O B L A S T I C LEUKEMIA(ALL)

Q. t_

The aim of the study was to evaluate brain perfusion in treated patients (pts) with ALL and to compare SPET findings with the results of MRI. Sixteen children (6 female,10 male) age between 619 (mean: 12+0.7) with ALL underwent SPET and MR imaging one or two years after cessation of therapy . Nine of 16 pts were high risk (HR), the rest of 7 were low risk (LR).Patients w e r e administered UKALL-X chemotherapy scheme. HR group only received high dose (> 2gr) methotrexate (MTX). All pts also received cranioradiotherapy, between 1800-2400 cGy dose. SPET studies were performed following i.v injection of (370-555mBq)Tc99m HMPAO, transaxial, coronal, sagittal slices were obtained using dual headed camera. Interpretation of the SPET scans was performed qualitatively by reviewing the images on a computer screen as well as recorded hard copy films independently by two experienced physicians. Patients treated low dose MTX had normal SPETand MR findings. Five of 9 pts (55%) treated with high dose MTX had abnormal SPET findings.These abnormalities were of relative hypoperfusion, bilateral frontal regions were the most frequently involved,being hypoperfused in three pts. MR findings of these three pts were normaI.SPET findings of one patient who had cerebral and cerebellar atrophy in MR imaging showed relative hypoperfusion in both parietal,temporal,occipital and cerebellar regions. Perfusion of the frontal cortex of the same patient had been reserved. The last patient had globally abnormal pertusion pattern in SPET showing low and nonhomogenous uptake.The MR imaging of this patient was interpreted as leukoencephalopathy. Although these brain perfusion abnormalities could be partly explained by the chemotherapeutic scheme and dosage of MTX. Pathophysiology of this abnormalities needs further investigations. 1227

4~

03

O a.

•

Paediatrics

PTu785

PTu787

B. Brans, G. Laureys, M. Simons, R.A. Dierckx University Hospitals of Ghent and Antwerp, Belgium

B Ljung and R Sixt Pediatric Clinical Physiology, Children's Hospital, S - 4 1 6 85

STAGE IV NEUROBLASTOMA: SIGNIFICANCE OF EVOLUTION OF METASTATICSITESON EARLYMIBG SCAN MIBG scintigraphy is an established diagnostic parameter in the follow-up of stage IV neuroblastoma. To assess the prognostic significance of early MIBG scan changes, we studied 14 children ( 9 boys, 5 girls, m e a n age 53 mo) treated w i t h p r i m a r y c h e m o t h e r a p y between N o v 1987 and Febr 1994. 1-123 MIBG scan findings at diagnosis were c o m p a r e d w i t h the 1-123 MIBG scan performed 2-3 m o n t h s after the start of chemotherapy. MIBG-CR was considered as complete response w i t h disappearance of metastatic lesions on MIBG, MIBG-PR as partial response or i m p r o v e m e n t of lesions in intensity of uptake and MIBG-NR as no change or worsening. Table 1 lists these categories v e r s u s the e v o l u t i o n of the disease to date ( m i n i m a l follow-up 36 months): disease free (DF), residual metastatic disease (RD), progressive disease (PD) and death of disease (DD) with their respective interval in m o n t h s , including p r o g r e s s i o n free interval. DF: RD: PD~ DD:

MIBG-CR:3/14 113 (36) 1/3 (99) 1/3 (30) 1/3

MIBG-PR:8/14 018 2/8 (70; 37) 6/8 (15;18;35;14;10;10) 6/8

MIBG-NR:3/14 0/3 115 !37) 2/3 (16;26) 2/3

A CR was more often associated with a disease free state and a b s e n s e of r e s i d u a l or p r o g r e s s i v e metastatic disease. A t t h o u g h the n u m b e r of patients m a y be considered small, these findings suggest that the early MIBG scan m a y contain prognostic information, useful in treatment planning.

G~teborg,

ESTIMATION OF G L O M B R U L A R FILTRATION R A T E IN CHILDREN WITH RENAL INSUFFICIENCY: COMPARISON BETWEEN SINGLE INJECTION PLASMA CLEARANCE AND URINARY CLEARANCE. Examinations in c h i l d r e n should provide accurate information without unnecessary discomfort to the child. Urinary clearance is o f t e n r e g a r d e d as t h e most accurate method to estimate g$omerular filtration rate (GFR) in uramic patients. However, this method includes bladder emptying, e i t h e r b y v o i d i n g or b y m e a n s of a b l a d d e r catheterr which can be a problem in p~diatric patients. Aim: To find out if e s t i m a t i o n of Cr 51 EDTA single injection plasma clearance with prolonged blood sampling is a c c u r a t e e n o u g h t o b e a n a l t e r n a t i v e to s i n g l e i n j e c t i o n r e n a l c l e a r a n c e . Material: 54 e x a m i n a t i o n s were performed in 33 children with renal insufficiency. Medium age was 7,8 y e a r s (range 0,5 - 1 8 , 2 ) . Methods: Single injection plasma clearance with blood sampling 5, 15, 60, 90, 120, 180 end 240 min after injection o f Cr 51 E D T A . T w o u r i n e s a m p ling periods of a p p r o x i m a t e l y one hour each to calculate single injection urinary clearance. Bladder emptying was checked by sonography. Results: Collection of u r i n e w a s c o n s i d e r e d adeq u a t e in 34 of t h e 54 e x a m i n a t i o n s . Total plasma clearance (mean±SD)

was 25,5 ± 12,4 ml/min/l,73 m 2 BSA and urinary clearance 22,7 ± 13,6 with

a r e s i d u a l SD of 2,2 m l / m i n / l , 7 3 m 2 (r=0.98) . Conclusion: Total plasma clearance measurement with a prolonged blood sampling period seems to be a reliable method to estimate GFR in children with s e v e r e l y d e c r e a s e d renal function.

PTu786

PTu788

F.Tenenbaum1, JE.Toublanc 2 Y.Chapuis l, P.Helardot2, A.Louvel 1, ~ o m b e 3, A. I~get4", B. Richard1. H6pital Cochin1 h6pital St Vincent de Paul2, Institut G.Roussy3, h6pital Necker4, Paris, France.

C a n e l a T, Servei de Unitat de Hospitals

Roca I, Lifian S*, Cobos N~, Aguad~ S, Porta F Medicina N u c l e a r Pneumologia Pedi~trica" Vall d'Hebron. B a r c e l o n a

R E G I O N A L LUNG P E R F U S I O N Q U A N T I F I C A T I O N

PAPILLARY THYROID CARCINOMA WITH ADRENAL METASTASIS ARISING IN A NEONATAL GOITRE ASSOCIATED WITH MATERNAL AUTOIMMUNE THYROIDITIS. A newborn male child presented with a goitre and mild hypothyroidism at birth in 1987 (TSH: 38 mU/ml). The child's ultrasound and scintigraphy visualised nodulesand the perchlorate discharge was positive. T4 treatment was given. After the first year of life and T4 withdrawal,the child was still hypothyroid and T4 was reinstituted. His mother was discovered at birth to have autoimmunethyroiditis. Initially the presenceof positivethyroglobulin, microsomal and cytotoxic antibody titres in the mother and child suggested that child's hypothyroidismwas due to maternal transplacentally transmitted antibodies. But over the years,the antibodies became negativeand the goitre grew, became more heterogeneousand T4 was no longer effective. This ted to a total thyroidectomy 8 years after birth. Histology revealed a large and diffuse papillary carcinoma invading almost all of the gland with only one mediastinal metastatic lymph node. A radioiodine treatment was performed (TSH: 220mU/ml, Thyroglobulin:30Iag/1). The post-therapeutic scan showed thyroid remnants and a radioactive uptake in the left adrenal area. This uptake correspondedto a left enlarged adrenal gland on CT scan (15 ram). Faced with this unusual but possible metastatic localization, adrenal surgery was performed with an intra-operative probe I0 days after iodine treatment. The probe detected significant count rates over the adrenal lesion which droppedto background level after excision. Histology confirmed the adrenal metastatic lesion In this case, every finding is unusual. A unique metastatic localization of papillary carcinoma in the adrenal gland is rare. It has neverbeen reported in a child, nor has a diffuse, invading papillary carcinoma of the thyroid. The genesis of a neonatal goitre induced by the mother's thyroiditis is puzzling and a very rare event. The carcinomawas probablypresent at birth asshown by the highly abnormal initial scintigraphyand ultrasonography.In the light of this case, a heterunodularthyroid at birth should be explored because of risk of malignancy.

1228

Sweden.

IN C Y S T I C FIBROSIS

In Cystic Fibrosis, the lung involvement evolves more as a regional than a diffuse disease. For the clinician, it is helpful to have information about a local progression of the disease: intensive treatments, such as new antibiotic administrations or even surgical operations, can be very effective. Clinically, lung regional improvement has the greatest importance for stopping or delaying the progression of the disease. The purpose of the study is to compare the lobar lung perfusion with the clinical evaluation of the disease. To value the lobar perfusion (Q), we calculated a lobar perfusion score, in which each lobe (including lingula) has been quantified in the lung perfusion scan as follows: lnormal, 2-heterogeneous Q, 3-mild hypoperfusion (< half lobe), 4-severe hypoperfusion (> half lobe), S-no lobar Q. The lobar perfusion score describes the values obtained in the 6 lobes (including lingula), giving, as described above, each lobe a number between 1 and 5, and the global addition is 6 to 30. We have compared the lobar perfusion score with the clinical evaluation and clinical (Shwachman), functional (EFR) and radiological (Crispin-Norman) scores. In 50 children (X 12,7 years, 15 boys, 35 girls) with variable lung involvement due to cystic fibrosis, we found a significant correlation between the global value of the lobar perfusion score and all the other scores (clinical, functional and radiological)(p<0.001). In front of the global evaluation obtained with the absolute value of these scores, the lobar perfusion score offers to the clinician information about the regional progression of the disease. In many cases, the global score can suggest a mild disease, but the lobar evaluation may show a severe local hypoperfusion. In these cases, children with a severe localized disease (unilobar, unilateral) and with a p r e s e r v e d perfusion in the contralateral lung (or the others lobes), the evaluation by means of the lung scan is crucial, and the patient may benefit from an intensive antibiotic treatment, or even from a surgical operation.

•

Paediatrics

PTu789

PTu791

M. Pruckmayer, S. Zacherl, M. Scblemmer, B. Mosing, T. Leitha, University Clinics for Nuclear Medicine & Paediatrics, Vienna, Austria

T.Atasever, A Haznedare~lu, B. 0kudan, N. Gok~ora, N. Buyan. M. OhiO. E. Hasano~lu. Gazi University Faculty of Medicine Departmen~ of Nuclear Medicine and Pediatrics Ankmrm-TORglYE THE FIRST URINARY TRACT [NFECT[0N (UTI) IN CHILDHOOD: ROLE OF Tc-99m DMSA SCAN

UTILITY OF LUNG PERFUSION SCITIGRAPHY TO ASSESS ABNORMAL DISTRIBUTION OF PULMONARY BLOOD FLOW IN CHILDREN WITH CONGENITAL HEART DISEASE AFTER GLENN SHUNT OR FONTAN PROCEDURE. Glenn shunt or Fortran procedure may be associated with abnormal pulmonary blood flow patterns and the development of pulmonary arteriovenous fistulae. Methods: This study assessed the pulmonary and total body blood flow utilizing the microsphere technique by sequential injection of Tc-99m microspheres into an upper and lower limb vein and performing conventional lung imaging in 4 projections and anterior and posterior total body scans in 45 patients with either Glenn shunt and/or Fontan procedure. The right-to-left shunt volume was quantitated by calculating a brain+kidneys / lungs ratio and compared to values additionally calculated from the total body scans. Results: In 29/45 patients the blood from the superior vena cava was preferentially drained into the right lung (range 70 to 84%). The inferior venous system was distributed equally between both lungs. In a subgroup of patients a remarkable perfusion pattern could be identified that was not known after pulmonary angiography or doppler sunography: 7/45 patients showed a hypoperfusinn of the right or left upper lobe after injection into the arm vein, and a corresponding hyperperfusion when injected into the foot vein. All these patients had a palliative Blalock Taussig shunt prior of either the Glenn or Fontan procedure and had presumably developed arterial strictures at the site of the initial surgery. Conclusion: Lung perfusion scintigraphy can be of great assistance to detect abnormal pulmonary blood flow patterns and to assess right-to-left-shunt-volume in children after Glenn or Fontan procedure.

This prospective s t u d y a i m e d to e v a l u a t e the r o l e of T c - 9 9 m D M S A s c a n n i n g in the o h i l d r e n w i t h r e c e n t o n s e t of s y m p t o m s of U T I . D i a g n o s i s of UTI was c o n f i r m e d b y t h r e e u r i n e c u l t u r e s . P a t i e n t p o p u l a t i o n was c o n s i s t e d of 4 8 c h i l d r e n (41 f e m a l e a n d 7 m a l e ) w i t h o u t k n o w n p r e v i o u s UTI, a g e d b e t w e e n 3 m e a n d 15 yrs w i t h a m e a n age of 5.6 y r s . T o - 9 9 m DMSA planar and SPECT images were obtained within 5 days of d i a g n o s i s . O n e or m u l t i p l e c o r t i c a l d e f e c t s were s e e n in 14(29%) p a t i e n t s w i t h p l a n a r a n d 15(31%) patients with SPECT imaging. T e n of the fifteen(66%) patients with abnormal DMSA soans w e r e o l d e r t h a n 5 y r s . A m o n g the 15 o h i l d r e n w i t h f e v e r ~38 o a n d c o n s i d e r e d a c u t e p y e l o n e p h r i t i s (APN) on c l i n i c a l g r o u n d s , 9 ( 6 0 % ) s h o w e d a b n o r m a l T c - 9 9 m D M S A s c a n f i n d i n g s . O n the o t h e r h a n d 6 of the 33(18%) patients without fever and c o n s i d e r e d as l o w e r U T I a l s o r e v e a l e d p a t h o l o g y on D M S A s c a n . A f t e r t r e a t m e n t 3 m o n t h s later, I0 of the 15 a b n o r m a l s c a n s w e r e r e p e a t e d ; 4 did completely normalize, 2 showed partial recovery a n d 4 r e v e a l e d c o n s t a n t l e s i o n s in b o t h p l a n a r and S P E C T study. O n l y 3(7.5%) of the 40 p a t i e n t s s h o w e d V U R w i t h v o i d i n g o y s t o - u r e t e r o g r a p h y and two of these r e v e a l e d a b n o r m a l scan findings.As a c o n c l u s i o n , the first UTI may cause renal parenchymal damage in ohildood with a oonsiderable frequency. Older pediatrio age g r o u p s are a l s o s u s c e p t i b l e to r e n a l parenchymal involvement.Tc-99m DMSA scan preferably SPECT i m a g i n g s h o u l d be a r o u t i n e e x a m i n a t i o n in the f i r s t U T I w i t h a n d w i t h o u t c l i n i c a l f i n d i n g s of

C 0 |m C

APN.

PTu790

PTu792

E. Sawt*, H. Durak*, E. 0zbilek*, E. Dirik**, Y. EroOlu**, N. Uzuner**, O. Anal**, B. B0y0kgebiz**, N. Qevik** Dokuz Eyl01 University S .chool of Medicine, Department of Nuclear Medicine* and Pediatrics**, Izmir, TURKEY

P.Orellana, P. Baquedano, C.Garcia, E. Lagomarsino, Cavagnaro,E. Olea. Nuclear Hedicina. Catholic University of Chile.

BRAIN SPECT IN RARE N E U R O L O G I C DISORDERS OF CHILDHOOD

Brain perfusion patterns of seven pediatric patients were investigated. The diagnoses were adrenoleukodystrophy (ALD) in one, LandauKleffner syndrome (LKS) in three, neuronal ceroid lipofuscinosis (NCL) in three. The healthy brother of a NCL patient was also studied. Brain perfusion SPECT was performed 30 minutes after I.V. administration of 222-370 MBq Tc-99m HMPAO, Using a three headed gamma camera equipped with high resolution collimators, 128 images of 35 seconds duration in 64 x 64 matrix were obtained over 360 degrees. Decreased perfusion was noted in the left temporal cortex of all LKS patients and in the left frontoparietal cortex of one patient with hiparkinetic behaviour. Degree of regional cerebral perfusion impairment did not correlate with the severity of clinical and EEG abnormalities. In the ALD patient decreased perfusion was observed in both superior temporal and parietal cortices, right occipital cortex, left frontal cortex and right cerebellum. Brain SPECT revealed more extensive involvement than MRt. In two of three patients with NCL, widespread cerebral perfusion impairment was most prominent in the occipitat cortex, posterior parietal cortices and cerebellum. The other NCL patient had hypoperfusion in the primary visual cortex and cyngulate gyrus. The extent of perfusion impairment correlated with clinical status. Brain perfusion of the healthy brother of the NCL patient was normal. Our findings show that Tc-99m HMPAO brain perfusion imaging has a potential value in the evaluation of these disorders and in determining the extent of brain involvement.

F.

ANTENATAL HYDRONEPHROSIS: DIURETIC RENOGRAPHY WITH Tc99m MAG3 DURING THE FIRST WEEKS OF LIFE In order to avoid progression of renal damage , the proper diagnosis and treatment of obstructive uropathy (OU) in newborns (NB) 0 is Important.We report our initial experience with the use of diuretic renography (DR) with Tcggm MAG3 in 15 full-term NB with antenatal hydronephrosis that persisted postnatal ly, performed during the first 20 days of llfe (l-2e days). A dose of 37-74 MBq of Tc99m MAG3 was injected in an hydrated neonate and 15-2@ minutes later, furosemide was administered in a dose of 1 mg/kg. Scintigraphic results were correlated with clinical and radiological follow-up. Among the 15 NB there were 27 renal units (RU). OU was demonstrated in 9 RU, one ectopic ureterocele in a double collecting system (DCS), 6 ureteropelvic junction obstruction (UPJO) and 2 posterior urethral valves. DR showed an obstructive pattern, without laslx response, in four of them (3 UPJO and 1 ectoplc uretorocele in a DCS). In the remainder 5 RU with OU was not possible to obtained an excretory curve due to poor renal function.Hydrouephrosis was observed during DR in 6 RU, and OU was ruled out in all of them. The excretory pattern was normal in the II normal RU and in the inferior moiety of the patient with DCS. Tc-99m MAG3 can be use in NB with accuracy in the assessment of urinary tract dilatation, even during the first days of llfe. We recommend the use of DR with Tc99m MAG3 in every NB with suspected urinary tract anomalies while the NB are admitted in neonatal or maternity facilities because its lower cost, availability and better evaluation by a multidlsciplinary team. At the same time, the early diagnosis allows an opportune treatment, avoiding progression of renal damage.

1229

0

0

•

Paediatrics/Radionuclide Therapy Radionuclide Therapy PSu795

PTu793

1 1 2 3 . 4 J.Kasalick~ ,V.KrajskA ,JlBro~ ,R.Kop~ek ,A.Nestaval , Repartments4of Nucl.Med., IKEM,Prague, ~.Bad@jovice, -0sti n.L., Chomutov,Czech Republic

M. Keys, i, &artlmva*,A Sankay~, N. E_rkmen.O. Altun, F. O. Gtim0.,~er,A. Alemdar,T. F. ¢ ~ m ~ O. Pekindil Trakya UnivexsityFaculty of Medicine, Edime *Kocaeli University Faculty of Medicine,TORK~YE

THE EFFECT OF 15~Sm-EDTMP ON PAINFUL BONE METASTASES; COMPARISON WITH 5~SrCI. 39 patients with skeletal cancer metastases (19x prostatic, 8x breast,6x lung,2x Grawitz,2x colorectal and 2x o t h ~ 3 cancers) received intravenously 30.75+0.89 MBq/Kg of SmEDTMP (Lacomed,Prague).Standard hematologic and biochemical investigations done before,3 days and one month after treat~Rnt did not re~eal any significant changes.Both previous ~m ~33 Tc-MDP and Sm-EDTMP skeletal seintigraphies (carried out 6 hours after adminis~Dtion) agreed well.There was a rapid blood clearance of "~Sm-EDTMP within first two hours together with nearly complete urine elimination 12-24 hours after dosage.Beneficial resists were compared with a group of 109 patients treated by SrCI (Metastron,Amersham),suffering from similar skeletal metastatic cancer diseases, predominantly of prostatic,breast and lung origin. The analgetic effect was evaluated according to subjective f e e ~ g s of patients and actual demand of analgetic drugs. In --~Sm-EDTMP group 4 patients (10.5%) did not reveal any improvement,in 19 patients (50.0%) the effect was mild or transient (within one month),12 patients (31.6%) had marked pain decrease and 3 patients (7.9%) were without any bone pain. Differences in response according to cancer£~ype were not remarkable. In contrast only 1 patient after ~-SrCI was without any improvement,transient and/or mild decrease of pain was observed in 21/109 patients (19.3%),marked pain decrease during observation period was in 60/109 patients (55%) and 29/109 patients were without any bone pain (2&8%). It is concluded that analgetic effect of 153Sm_EDTMP is 89 milder as compared with SrCI but its accumulation in metastases could be excel~ntly demonstrated by sciatigraphy ~m and therefore repeated Tc-MDP scintigraphy omitted.

DETECTION OF CEREBRAL PERFUSION DEFECTs IN CEREBRAL PALSY BY SPECT The pro@nosmin chickenwith¢etebn~palsy emlmnely variable. Although by defmi~on cerebral palsy i~ nonprogresive,i~ manifestationscan change over time. This neee~ity is cmgoing rcsssesment and monitoff.g to mmdmJze func~don and present secondary impairments, However, current diagnostictc~hmqucslmv¢ oRgn limited valu=.Tc-99m H M P A O is now widelyused as a toolto ewluate [egional cerebral blood flow. In flm study, Tc-99m H M P A O cerebralSPEC'T was ~zied out in 12 childwith cerebralpalsy (5 tetrapleg~ 2 dilxt¢~ 2 hem'lipl~ 3 d y ~ ageat 4 to 17).Rightleft asymmetries in tracer uptake and corticocerebel~r (C/Cb) ratios of activity were analysed for quamitation. Decreased C/Cb ratios were found in bilateral semowmoter exmcx in 3 patients with tetrapleBia and 2 with diplegiaand m left~.~3,motor cortex m a patient

with t ~ i ~ . ~ ~ rod/or a~ymme~ic C~'% r ~ (P, ~, 1", O) were fmmd in all of tetr~l~giaand dipl~a l ~ m t s ~ d l~i~ts with di,~m~a. Multiple bilmemldecreased C/Cb miles were obtained in a im~mt with MR h e w and mi~o¢¢phali. Bilateral

t m a ~ fro), ~ m (Po), o~,ipi~ (o) and ~l~t ~rfferiorfrontal(RID ~ ¢ ~ d C/Cb ra~os w=e fo~td in a patient with d~ht hemJp~(~ and cerebral atrophy. In tim ~udy, right-left asymmetlies in tracer up~d~ewere not found vahatble.Ourresults suggest timt Tc99m HMPAO SPECT,e s p e ~ quantitativecalculation,is valmble complmmtmy dia~ostic tool for evalua~on and fonow up m pstmss with ~ m b m l palsy.

PSu796

PTu794 Algnatov, !,Christozow, D 8obev U~,;vel~ity o[ Mc.xJk.hre, U~ve~~ity t {o~Jita|"Queel ~Gk)va~,, t,f',3u[ia DIFFERENTIAL DIAGNOSTIC PO~SI6iLiHES OF WI-t()LF-~O[Y~ SCINTIOP,APtW OF EWING'S SARCOMA IN CHII.DREN

bONE

Iwenty s~x oh,tires with Ewing's sarcoma , kern b to 18 years ot aqe. histofogioally verified, were examined and ~'e.ated in Clinic of paediatrie oi1~.xthaemafoIogy. The following diagnostio methods were us6~l : CT, tung arid bone X-rays, bone seintigraphy and tumoer markers. Neuroblesthma with Ix)he metastases, ostengenic sarcoma, Langerhans cell hi~ocytosia and osteomielitis were disouseed as differential diagnosed possibilities. In diagnostic plan the porte seintigraphic examinations in those oases were predominant. Sointigmphy was done on gamma camera with oeteotrophio compound 85~Srohloride, administrated i.v. at activity 95-150 p.Ci ( 3.5-5.5 MBq) on 24-th h. In all oases with negative results the suspected bones were alternatively examined with 99m-]b-oeteotrophio phosphate COmpOunds (PYP,MDP) on 8-4 th h. after administration at activity 6-8 mCi ( ?'22-296 MBq). In all Children with EwirKj's sarooma the bot~ seintigraphy with 85-Sr-ohloride was negative, due to the rto~ oeteogenie character of the sarcoma. On the contrary-the bone seirdigraphy with 99m-Te -phosphate COmpOunds imaged positively the pdmary tumour, and in 3 pie the neoplastic processes was demonstrated wilt= bone disseminaii(m iu 5 pB suspected fOr Ewing's sarcoma, the hone seint~jraphy with 85-Sr-eh~6de was pOsitive and the bone biopSy confirmed osteogenic sarcoma, which made the rest seintigraphic examina~ons unnecessary. Co.¢lUtiO.~_ : 1/. The scintigraphy wffh both alter;~at~m bone (~mpo.,'."![ give~ good possibilities fol diflerential diagnosi~ o( Ewi,~'~ ~,~,,o ~,~, oeteogenio saroon%~ In children . 2/. P,one ..~Antigraphy wi.~ .'Cam.i t phosphates has sensibility for detecting the dlssemir~ation of the ;~:mm:; p=o~;esa. 3/. The combined soi=mgmphy with both oOmpoends iv~ole~se~ the s[~fio~y of bone sointJgraphio imaging in disgr#sis of Ew!ryj's ~erc~m= (94%). 4/. Bone soin~graphy with ~m-To- phosphates is posi;ive seaYly O months before bone X-ray visualisation. 5/.The presurgioal seinugfapl,c diagnosis of Ewing'a sarcoma gives pOssibilities for speoifio chemotherapy for reduction of the pdmaW tumour sizes, before surgical tre.atment.

1230

H . P a l m e d o , H. Bender, P. M a l l m a n n 2, F. Grfinwald C. Dierke-Dzierzon-, S. Guhlke, K. Hamad, K. R e i c h m a n n , H.J. B i e r s a c k . ~ e p a r t m e n t s of N u c l e a ~ Medicine, Gynecologie~ Anesthesiology ~ U n i v e r s i t y of Bonn, Germany. PALLIATIVE THERAPY WITH RE-186 HEDP FOR PAINFUL BONE METASTASES OF BREAST CANCER. For p a t i e n t s w i t h m e t a s t a t i c p r o s t a t e cancer, it h a s b e e n s h o w n t h a t R h e n i u m - 1 8 6 H E D P can d e c r e a s e i n t e n s i t y of m e t a s t a t i c b o n e pain. T h e a i m of t h i s s t u d y w a s to d e t e r m i n e the e f f i c a c y of p a i n p a l l i a t i o n w i t h R h e n i u m - 1 8 6 H E D P in p a t i e n t s w i t h b o n e m e t a s t a s e s d u e to b r e a s t cancer. 24 patients with multiple, painful bone m e t a s t a s e s r e c e i v e d 30 i.v. i n j e c t i o n s of 1295 M B q R e - 1 8 6 HEDP. Patients had undergone x-ray therapy of main metastases and were taking analgesics regularly. To prove significant a c c u m u l a t i o n of R e - 1 8 6 H E D P in o s s e o u s m e t a s t a s e s a T c - 9 9 m M D P s c a n a n d a R e - 1 8 6 H E D P s c a n of the whole body was performed before and after therapeutic injection. D e v e l o p m e n t of p a i n w a s e v a l u a t e d by s t a n d a r d i s e d q u e s t i o n n a i r e s , a VAs c a l e and d o c u m e n t a t i o n of a n a l g e s i c s intake. 14 p a t i e n t s d e m o n s t r a t e d m o d e r a t e to s i g n i f i c a n t r e s p o n s e to p a i n therapy. A s i g n i f i c a n t relief of p a i n w a s o b s e r v e d in 8 p a t i e n t s . T h e i n t e r v a l of p a i n r e d u c t i o n was 2-12 w e e k s w i t h an a v e r a g e of 4.5 weeks. 3 patients who took non-opiate analgesics by need could renounce on any a n a l g e s i c s for s o m e weeks. We o b s e r v e d a f l a r e e f f e c t in 27%, a t h r o m b o c y t o p e n i a in 27% and a l e u k o z y t o p e n i a in 10% of the patients. R e p e t i t i v e t h e r a p y w h i c h was p e r f o r m e d in 4 p a t i e n t s s h o w e d s i g n i f i c a n t p a i n r e l i e f in all of the cases. We conclude that therapy with Re-186 HEDP i m p r o v e s p a i n s i t u a t i o n in 60% of p a t i e n t s w i t h m u t l i p l e b o n e m e t a s t a s e s due to b r e a s t c a r c i n o m a . If p a t i e n t s are not m y e l o s u p p r e s s e d d e c r e a s e of l e u k o c y t s and t h r o m b o c y t s is v e r y moderate.

• Radionuelide Therapy PSu797 V. Beauchat T. Prangere, D. Huglo, X. Marchandise, M. Steinling Department of Nuclear Medicine CHRU LILLE, 59037 LILLE, FRANCE

RELATIONSHIP BETWEEN PAINFUL, BONE MINERAL DENSITY AND 99MTC-HDP UPTAKE IN PATIENTS TREATED BY STRONTIUM 89. Strontium 89 (Metastron®, Amersham) is an effective agent for palliation of pain due to bone metastases from prostate carcinoma. Sometimes, there is a dramatic decrease in Tc-99m HDP uptake in the metastatic deposits few months after this treatment. The aim of this study was to follow up simultaneously pain, Bone Mineral Density (BMD), and quantitative bone scintigraphy (QS). Material and methods : Pain, BMD and QS were studied before and three months after strontium therapy. The pain was followed by a subjective and an objective protocol. The BMD, measured by dual photon absorptiometry and QS were performed on the lumbar spine with metastases. Results : 9 patients (P) have been treated No worsening of symptoms were reported. 3 P became pain free, 2 noted no improvement response, 4 noted decrease of pain. BMD were performed in 7 P and QS in 5. In most cases (6/7 P), BMD of the spine increased at~er treatment (3.08 to 121%). 4/5 P showed a decrease of HDP uptake (-57.2 to -3.44 %) when BMD increased and clinical status improved. One increase of uptake (+24.42%) was seen when BMD decrease(-3.41%). Conclusion : QS prove that HDP uptake decrease in Strontium therapy. Nevertheless, BM]) increase. The efficacity of Strontium 89 may be a direct but incomplete action on osteoblastic skeleton dysfunction.

PSu798 K. Liepe, R. Hliscs, A. Ktthne, J. Kropp, W G . Franke Department of Nuclear Medicine, Dresden University of Technology, Germany

EXCRETION RATE AND H E M A T O L O G I C A L TOXICITY FROM Re-186-HEDP AND Sr-89 IN THE PALLIATIVE T R E A T M E N T OF METASTATIC BONE PAIN In recent years Sr-89- and Re-186-HEDP-therapy (Sr/Re-T) played an increasing role in treatment for pain relief in bone metastatic disease. In this investigation we evaluated the influence of Re-186-HEDP or Sr-89 on pain relief, reduction of analgesic consumption, and impairement of bone marrow function. Following Re-186-application, three blood samples within the first three hours were taken and urin was collected within 48h, divided in 6 portions, to determine the excretion rate. Eleven patients (pts.) with bone metastases of prostate-, breast-, lungand bladder-ca were treated (3 treatments with 150 MBqm Sr-89, 10 treatments with 1285 MBq Re-186-HEDP). After 3 resp. 6 months two pts received a second treatment with the same radionuclide (St/Re). Blood counts were taken weekly for 6 weeks. Results: Both pts. with second therapy and two other pts. died within 6 weeks after application So that in total 9 observation periods of 6 weeks were evaluated. 66% of pat were able to reduce their analgesic intake. 44% of pat. reported a signifikant, 44% a minor improvement of life quality (raise of Karnovsky-index of ave. 6 pts (range 4-12). No difference was observed between Sr- and Re-therapy, although the number of Sr-therapy was very small. The excretion-rate of Re-186 in the urin was 6I% within 48h of the total activity administered. On average, the hemoglobin decreased 14%, leucocytes 28% and platelets 33% within the 6 weeks after therapy In conclusion with this treatment regime most of our patients experienced an improvement of life quality without induction of serious bone marrow reduction.

PSu799 E.Olea, MC.Gil, M.Tomic, G.Araya, M.Chandia, J.Quintana, LPinto, P.Orellana, J.Nagel and V.Ortiz. Nuclear Medicine, Catholic University and Chilean Comission of Atomic Energy. Santiago, CHILE. 153Sm-EDTMP LOCALLY PRODUCED IN THE TREATMENT OF METASTASIC BONE PAIN. lS3Sm-EDTMP was obtained from enriched 152Sm irradiated at a research 5 MW reactor and labelled at a molar ratio of 15:1; pH 7.5. Biodistribution, autoradiography, and radiochemical purity test were done for evaluation. 40 patients were treated with 37 - 55 MBq/kg weight of 153Sm-EDTMP. Bone scans with 99mTc-HMDP were obtained prior and after treatment. Every patient was hidrated orally and IV ( 5cc/kg ). In 8 patients blood and urine samples were collected every 30 min by 6 hours.. Whole body Samarium images were obtained at 3 and 24 hours after inyection. Results: Blood clearence 48 - 62 min Urinary excretion 42 - 67% inyected dose Liver/BKG 1.3 - 2.1 Met./nl. bone 153Sm-EDTMP 3.7 - 5.4 Met./nl. bone 99mTc-HMDP 3.6 - 4.8 Bone pain desappeared in 18 patients; decreased important in 9; partial in 12 and no response in one. Treatment was effective between 1 - 7 months. Follow-up during 17 months. 17 patients received more than one dose. In 23 patients we observed mild medullary depression, No liver toxicity was found. 4 patients received previously a Metastron dose wihtout result. We believe that 153Sm-EDTMP is a very good option to treat metastatic bone pain in those countries were a reactor is available and at a very affordable price.

co |m t~ e"

O. PSu800 M. Winderen, l , K.Breist¢~lz, I.Kj0nniksen3,0.Berlin4 and ~. Fodstad z I Dept. of NucL Med. and 2Tttmor Biology. The Norwegian Raditma Hospital. ~ DeFt. of Pham~acy, The National Hosp., Oslo, Norway and 4 DepL of Or~opaed., Sahlgren Hosp., Univ. of Gothenburg,, Sweden.

IS3Sm-EDTMP

TREATMENT

OF

SPONTANEOUS

LUNG

METASTASES F R O M KRIB HUMAN OSTEOSARCOMA CELLS GROWING INTRATIBIALLY IN NUDE MICE.

The v-Ki-ras oncogene transformed human osteosarcoma cell line (KRIB) represent a model for the major clinical problem with incurable lung met4

.

.

.

.

.

.

astases, when lxl0 KRIB-cells are rejected m the tibia of nude rmce (1). 99mTc-MDP was investigated for imaging and organ-uptake, and 153Sm-EDTMP was used for therapeutic purposes, in this model. Methods: 14 days after cell inoculation, animals were treated intra-

venously with 400, 800 or 1600 MBq/kg 153Sm-EDTMP. 99mTc-MDP was given 2 hours before the animals were sacrificed. Results: The control-, and treatment animals, developed palpable tibia tumor after a mean period of 35, 42, 44 and 47 days respectively. A moderate tumor uptake was seen on the tibial bone scans, while no lung lesions with increased uptake of 99mTc-MDP could be demonstrated. Conclusion: Treatment with the bone-seeking agent ~S3Sm-EDTMP gave

a dose-dependent delay in tumor growth in the KRIB spontanous lung metastasis model, both of the primary tibial tumor and lung metastases. References: 1. Berlin.Oet al. Developmentof a spontanousmetastasismodel of HumanOsteosarcomatransplantedorthotopicallyinto bone of athymiemice. Cancer Res. (1993) 53: 4890-4895.

1231

O IX

•

Radionuclide Therapy

PSu801 C.G. Diederichs, M. Mfiller*, S. Glatz, J. Kotzerke, H.-J. Brambs*, S.N. Reske. Departments of Nuclear Medicine and Diagnostic Radiology*, University of UIm, Germany COMPARISON OF THREE PHASE BONE SCINTIGRAPHY AND DYNAMIC MRI FOR ASSESSING ACTIVE SYNOVIALITIS PRIOR TO RADIOSYNOVIORTHESIS OF THE KNEES. Purpose: To compare the degree of inflammatory joint changes in scintigraphy and MRI. Methods: 14 patients with clinical arthritis of one or both knees were evaluated with 99m-Tc MDP-Scintigraphy (perfusion, whole-body bloodpool, 3h static) and MRI (fast Tlw coronal GE sequence before and 1, 2, 3, and 8 rain. after iv. Gd application). Post contrast MR images were subtracted from pre contrast. A four scale visual analysis of the images based on MDP / Gd uptake and morphology was performed (no / slight / intermediate / intense arthritis). The results were compared using a 4 x 4 contingency table. Results: Arthritis was best seen with blood-pool phase and subtraction MR images 3 min following Gd-administration. Visual rating was concordant with 19 kees. MRI-scoring was higher by one with 3 and lower by one with 6 knees. No patient with normal MRI had typical pathologic scintigraphic findings. One knee was normal in scintigraphy and showed slight spotted synovial enhancement in MRI. Concomitant subchondral ostoeporotic osteopathy of the tibia (two patients) was more clearly differentiated with MRI. Disease of other joints was well seen with whole-body blood-pool scintigraphy, but not with MRI due to its small field of view. Conclusion: These results imply that there are no significant differences between scintigraphy and MRI concerning detection and rating of synovitis. Concomitant pathologic conditions may be seen with MRI more clearly, and a larger number of joints may be simultaneous assessed with whole-body scintigraphy.

PTu803 I. Novak-Hofer, F. Carrel, K. Zimmermann, H. Amstutz*, H. Maecke** and P.A. Schubiger Radiopharmacy Division, Paul Scherrer Institute, CH-5232 Villigen; *ZLB, Swiss Red Cross, Bern and **Dept.of NuclearMedicine,KantonsspitalBasel 67-Cu-LABELED MAB chCE7 AS A P O T E N T I A L THERAPEUTIC AGENT FOR NEUROBLASTOMA Neuroblastoma (NB) relapses may appear as solid tumor and/or bone marrow infiltrations, become refractory to chemotherapy and have poor prognosis. As only minor therapeutic success has been achieved in such cases, new therapeutic options have to be evaluated. MAb chCE7 is a chimeric antibody against an NB-associated cell surface protein which is internalized into its target cells. Diagnostic imaging using 131-I-chCE7 shows its rapid and strong uptake into bone marrow metastasis with low unspecific uptake in normal tissues. We plan to use 131-I-chCE7 for therapeutic applications in such cases and in this context we are also evaluating the use of MAb chCE7 labeled with the beta particle emitting potential therapeutic nuclide 67-Cu. MAb chCE7 is derivatized with macrocyclic amine ligands and labeled with 67-Cu to a specific activity of 0.5-1.0 mCi/mg. Such preparations are fully immunoreactive and biodistributions in nude mice bearing NB xenografts show high and stable tumor uptake over 5 days. Compared with 131-I-chCE7, prolonged retention of radioactivity in tumors is found as well as superior tumor to blood ratios. Analysis of metabolites shows that radioactivity in tumors is present both in form of MAb-antigen complexes and low MW metabolites. The results indicate that our earlier observations on retention of low MW 67-Cu-labeled metabolites and "wash out" of iodotyrosine in case of radioiodinated chCE7 made in NB cells in culture extend to the in vivo situation. This property, together with low levels found in normal tissues and the more favorable radiation characteristics of 67-Cu compared with 131-1 make 67-Cu-chCE7 a potentially very effective therapeutic agent.

PSu802

PTu804

T.M. Behr R.M. Sharkey, M.E. Juweid, R.M. Dunn, Z. Ying. J.A. Siegel, D.M. Goldenberg. Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Newark, N J, USA.

M~.R_OELANDTS MD*, M S T E G E N MD**, H.NGUYEN ME)*, S.SIMON*, M.GUERCHAFT , A.VERBIST , and J.FROHLING,MD * Department ofradiooncology, Institut J.Bordet, Brussels, BELGIUM **Departement Antonome des Radio-Isotopes, Centre Hospitatlier Etterbeek-lxelles Brussels, BELGIUM

FACTORS INFLUENCING TUMOR DOSES IN THE RADIOIMMUNOTHERAPY WITH ~II-LABELED MURINE AND HUMANIZED ANTI-CEA AND ANTIMUCIN MONOCLONAL ANTIBODIES

IMPROVEMENT OF RESOLUTION OF BREMSSTRAHLUNG-SPECT I M A G I N G W I T H 32 P H O S P H O R U S USING A P I N H O L E C O L L I M A T O R Direct imaging and volume quantification can be performed after therapeutic administration of high dose colloidal 32P chromic phosphate by BremsslratdungSPECT. Usually medium-energy parallel hole collimators are used for this purpose but the resolution remains relmvely low. Thus this method fails to give reproducible results for volume smaller than 30-50ml. The aim of the present study is to demonstrate the feasibihty o f high resolution imaging and volume quantification with SPECT using the pinhole collimator. There are two mum advantages using this collimator: it provides a higher resolution for a small organ, moreover its physical characteristics allow high energy shielding. Its low sensllavity can be compensated by using large energy windows. We report here the results o f a preliminary study on volume measurement performed on phantom. SPECT acquisition were performed using a 4 m m aperture hole, and a 15 cm focus pinhole collimator on an Elseint's apex 415 gamma camera. The energy windows was 90KeV to 210 KeV. Thirty images o f 60 seconds were acquired for a 180 ° acquisition. Data were stored in a 128x128 matrix. Transaxial slices were reconstructed using a dedicated algorithm that allows unparallel backprojection. METZ filter of the third order was used for both prefiltermg and reconstruction.. The rotation radius was 22 +/- 0,5 cm.. In these conditions the measured FWHM was 9 m m compared to 2.5cm when using the parallel hole collimator with a rotation radius o f 25urn. SPECT acquisition was performed on 3 vials (0.7, 16.2 and 48.3ml ) containing 10 mCi (370 MBq) of 32P in solution. Four cylindrical acrylic phantoms of 40, 80, 120 and 160 m m diameter were used as scattering media. Volume qtnmtificafion was performed using full automated algorithm. Background level was estimated at 25% on preliminary studies. VOLUME OF MEASURED MEASURED MEASURED MEASURED THE VIAL (160mm O (120ramO (80mm O (40mm O t

Achieving sufficiently nigh radiation doses is probably the key for therapeutic success in the radinimmunotherapy of solid tumors. Therefore. the aim of this study was to examine which factors influence tumor dosimetry in CEA-expressing cancers. Data from a total of 119 tumors in 93 patients with CEA-expressing cancers (e.g., colorectal, lung, breast, ovarian, pancreatic, and medullary thyroid cancers) were analyzed. They underwent therapy with the ~3~I-labeledlgG~ anti-CEA antibodies NP-4 (K~=10aM") or M'N-14 (Ka=I09M'I), its humanized form hMN-14, as well as the anti-colon-specific antigen-p (CSAp) antibody, Mu-9. For dosimetry, the biodistributiun, targeting kinetics and cumulated activities of tumors and organs were determined from imaging (planar and SPECT) and blood clearance data from 4 to 240 hr p.i. Doses were calculated according to the MIRD scheme. With both anti-CEA Mabs, tumor uptake increased with decreasing size, and ranged from 10.3 to 1% ID/g, whereas no such relationship was found for Mu-9, which recognizes a mucin antigen that is more abundantly present in partly necrotic tissue. Tumor uptake was identified as the most important factor determining the radiation dose to the ~ n o r (r0.91 ), with the biological t~ of the antibody in the tumor being of secondary importance (1"=0.51). Doses ranged from 1 to 220 cGy/mCi. At comparable masses, colorectal and medullary thyroid cancers had significantly higher tumor uptakes, as well as tumor-to-red marrow dose ratios, than other cancer types (p<0.01 ). Maximal tumor uptake occurred at 4 to 48 h post injection, depending on the blood-T/:. MN-14 had longer biol. tumor t,/=sthan NP-4, which probably reflects MN-14% higher affinity. HAMA altered the overall pbarmacoldnetics by increasing the serum and whole-body clearance, thereby decreasing the tumor uptake and minor-to-non-minor ratios. Anti-"human" (anti-idiotypic) antibodies ("HAHA") did not compromise antibody biodistribution, but exclusively affected tumor uptake. In mdioimmunotherapy, tumor uptake appears to be the most important dose-detemrining factor. Differences in antibody affinity are reflected by differences in the biological tv,, not the absolute uptake. HAHA hinders tumor targeting without alteration of overall pbarmacokinetics. Especially favorable conditions for anti-CEA antibodies seem to prevail in colorectal cancer patients having minimal disease, as well as in medullary thyroid cancer, where cytotoxie tumor doses might be expected. Anti-mucin antibodies (e.g., Mu-9) may have a particular advantage in the treatment of patients with larger colorectal tumors. (Supported by DFG grant Be1689/1-1/2 and by USPHS grants CA39841 and CA54425.)

1232

(ml)

48.3 16.2

phantom)

phantom

phantom)

phantom)

I

49 46 43 41 16.6 16.3 16.5 16.6 I I 3.7 4.9 4.7 5.1 4.9 I There was a g o o d agreement between real and measured volumes for medium volumes. Small volumes were slightly o v e r - e s ~ e d . This could be partly explained by the average travel o f electrons out of the vial. The most critical parameter for the precision o f the volume measurement was the rotation radius, a 5mm error is associated with a 20% error in volume. These preliminary results demonstrate a better accuracy in volume quantification in the range of 5 to 50cc. As tumor volumes o f head and neck cancers often fall in that range, the determination of volume distribution of colloid-32P during infuslonal brachytherapy should preferably be done with this technique, giving a more precise dosimetry.

• Radionuclide Therapy PTu805 Zadravec Zaletel L., An~i6 J., Petri~-Grabnar J., ~ugtargi~ J., Jereb B., Movrin-Stanovnik T. Institute ofOncology, Ljubljana, Slovenia

PTu807 W i t h d r a w n by a u t h o r

J- 131 MIBG TREATMENT OF NEUROBLASTOMA The survival of patients with advanced neuroblastoma is poor. In order to improve these results, therapy with J-MIBG was also tried. However, the experience with this treatment is still rather limited which renders any conclusions on its effectiveness questionable. Between 1986 and 1984, 6 neurobalstoma patients - 3 girls, 3 boys 22 months to 8 years of age, were treated with J-MIBG at the Institute of Oncology in Ljubljana. At the beginning of therapy, all patients had disseminated disease with metastases to the bone marrow (6/6), bone cortex (3/6), orbit (2/6), distant lymph nodes (2/6), liver (2/6) and testis (1/6). They received 1-4 courses of JMIBG therapy with doses 24 to 200 mCi per course. Reduction of tumor burden was observed in three patients. The remaining three patients, all in the terminal phase of disease, presented with pain relief and improved general condition. Thrombocytopenia and leukopenia occurred in all patients approximately one week after therapy, and persisted for at least three weeks. Leukopenia was mild in all patients while thrombocytopenia was mild in 2, moderate in 2 and severe in 2 patients. There were no acute complications during treatment and no impairment of renal function observed. Therapy with J.131 MIBG exerts a cytoreductive effect on neuroblastoma and is well tolerated. This therapy could improve the prognosis of patients with neuroblastoma.

e'|mO t~ e"

L_

PTu806 G. Ronga, M. Filesi, L Mango, R. Barone, M.Chianelli, E. Procaccini, G. Ventroni, A. Signore and * I. Baschieri S.S. Medicine Nuclear/Clinica Medica II- University "La Sapienza" of Rome. * Medicine Nuclear Dpt-University of L'Aquila m I THERAPY AND THYROID CANCER: RELATIONSHIP BETWEEN SURVIVAL AND HISTOLOGY We reviewed our casistics of 1459 patients with thyroid cancer (312 follicular- FC, 931 papillary- PC, 57 anaplastic, 25 medullary, 130 other forms; 374 males and 1085 females; follow-up to 32 yrs). Out of them, 1085 were treated with 131I for post surgical thyroid remnant ablation and/or metastases. We calculated survival curves according to histologic type, independently from presence and sites of metastases, and their 13~1uptaking ability. In PC cases, with 128 local (lymphonodal) and 114 distant metastases, 36.0% of which not ~3~I uptaking, 79.3% of patients were treated and following survival rates were observed: 97.2%, 95.3%, 94.0% and 92.3% respectively after 5, 10, 15 and 20 yrs; in FC cases, with 29 local and 78 distant metastases, 14.1% of which not ~3~Iuptaking, 74.4% of patient were treated, and observed rates were 93.6%, 90.3%, 82.6% and 80.3% at same times. Comparing both data series, a significative difference was found (p<0.001). In anaplastic cases, survival rate at 5th yr was 21.6%: only 4 not metastatic patients survived for a longer time. In FC cases, we fotmd a greater incidence of distant metastases that are, neverthless, more able to concentrate radioiodine; in PC cases the greater incidence of both local metastases and not [311uptaking metastases doesn't seem to influence survival in the negative. Therefore, in both histologic types we observed a good life expectancy, also for its quality, whenever the metastases are radioiodine uptaking and treated.

PTu808

X--

B. Meller-Rehbein I. Lauer, M. Baehre, E. Richter Clinic of Radiotherapy and Nuclear Medicine, Med. University of Luebeck, Germany

INFLUENCE OF RADIOIODINE THERAPY ON IODINE EXCRETION While effects of the individual iodine intake on kinetics of 1311 in radioiodine therapy (RITh) are well known, there is little information about influences of RITh on the turnover of cold iodine. Since there might be consequences for subsequent RITh's, we studied the influence of RITh's on iodine turnover in a prospective study. Methods: In 105 patients with benign thyroid diseases (multifocal autonomy (n = 64), focal autonomy (n = 14), Graves' disease ( n = 2 7 ) ) , urinary iodine excretion {UIE) was determined on the first (Te 1) and 4 th day (Te 4) of radioiodine uptake test (RITe), the 3 rd (Th3), 7 th day (Th 7) and four weeks (4W) after activity application and 6 months after RITh (6M). Therapeutic activities were planned individually depending on kinetic data of the RITe, scintigraphy and ultrasonography. Iodine excretion in urine was measured by a colorimetric method (iodine catalysed decolorization of cerium sulfate solution). UIE was calculated as gg I/g creatinine to consider different states of hydratisation. Additionally, thyroglobulin (TG) was measured at Te 1 and 4W (n = 23). Results: No significant changes of UIE were found during the test so that the mean test UIE (mT) could be calculated. Median Te 1 Te¢ mT Tl't3 Th 7 4W 6M UIE Lug I/g creat.] 91 95 94 145 166 170 132 n 105 105 105 105 105 105 38 TG [pg/I] 73 134 When compared with mT, UIE was significantly increased (Wilcoxon Test) at Th 3, Th 7, 4W (p < 0 . 0 0 0 1 ) and 6M (p < 0 . 0 0 1 ) and between Th 1 and Th 2 (p < 0 . 0 5 ) . UIE (4W) was enhanced at target volumes > 14ml (M = 200 pg I/g creat., p < 0 . 0 5 ) . The rise of TG was significant (p < 0 . 0 0 1 ) and dependent on UIE. Conclusions: Radioiodine therapy increases urinary iodine excretion and TG concentration for months. These effects seem to reflect the damaging of thyrocytes. Consequences for valid planning of subsequent radioiodine therapies can be expected. 1233

O IX

•

Radionuclide Therapy/Physics and Instrumentation

PTu809 B.Karayalgln, 0.Karayalgln, A.Boz. F.Gflng6r, A.Ozdemir, B.Tflrk, G.Kagar, F.Tungdemir, I.Baltao{lu, F.¢iftgi, M. Akaydzn, Medical School of Akdeniz University, Departments of Nuclear Medicine, Endocrinology, Surgery, Antalya, TURKEY. F R A C T I O N A T E D LOW DOSE 1-131: IS IT EFFECTIVE IN THE A B L A T I O N OF RESIDUAL T H Y R O I D TISSUE? The aim of this study is to determine the success rate of fractionated low dose 1-13! (FLDI-131) in the ablation of residual thyroid tissue in patients with d i f f e r a n t i a t e d thyroid cancer. 31 patients (30 F, 1 M, age:17-73; 15 papillary, 12 follicular, 4 mixed thyroid cancer) who underwent near total or subtotal thyroidectomy were included in the study. 30 mCi 1-131 was given in 2-3 months intervals until 5 mCi 1-131 whole body scintigraphy showed no visual uptake in the thyroid region. Successful ablation was achieved in 27 patients (87%). A single dose of 30 mCi 1131 resulted in ablation of 6 patients (22%). 6 patients (22%) were ablated by 60 mCi, ii (41%) by 90 mCi; 2 (7.5%) by 120 mCi and 2 (7.5%) by 150 mCi 1-131. i0 of 12 patients who were a b l a t e d by 30-60 mCi, had TSH levels greater than >30 mIU/ml. In conclusion FLDI131 therapy may be an alternative to conventional single high dose ablative therapy, since it does not require hospitalization of the patients, has comparable success rate and prevents u n n e c e s s a r y exposure of high radiation dose to these patients.

Physics and Instrumentation PSu811 N.B~dlani and N.M.Spyrou. Radiotogic Sciences Dept., FAHS, Kuwait University and University of Surrey, Guildford, UK.

A MODIFIED SECOND DERIVATIVE METHOD TO CORRECT FOR THE SYSTEM EFFECT IN CARDIAC PHANTOM DETERMINATION A cardiac phantom of 12.5 mm homogeneous wall flfickness was filled with Tc-99m and the background was 10% of the cardiac w~dl activity. SPECT data were acquired tbr 180° using 1282 matrix (pixel size of 3.2 mm) at two energy windows, one at the full energy photo-peak and one in the scattering region. Another set of data using s a n e p:u'amcters but tbr u 642 matrix was also acquired. Reconstruction of the data was p,zrlbrmed with and without: 1)scatter correction, 2)background correction and 3)attenuation correction. The mid short axis slice was used to measure the w~dl thickness. A horizontal profile passing through the middle of tile slice was generated and tile FWHM was taken to be the wail thickness of each wall. The second derivative of each profile was used to correct for the system effect. The measured wall thickness was found to be: 1)26 nm~ and 32 n~n for 128 and 64 matrix, lespectively, when no correction was applied, 2)22 mm and 26 nma when background correction was applied, 3)22 nma and 26 nun when scatter correction was applied, and 4)26 rI~n and 32 n~n when attenuation correction was applied using a homogeneous map for both coefficients 0.012/mm and 0.015/mm. Finally, the wall thickness measurement was 13±0.6 mm in any of the above mentioned puratllutei's whcs the negative second derivative values were applicd. As a tvsuit of the work it is shown that the second deriwltive method can ~ a corrective procedme for the system effect.

PTu810

PSu812

Nikolai I. Pilipenko, Yan Ed. Vikman, Valery G. Nesterov, Kharkov Research Institute of Medical Radiology (Ukraine), Department of Nuclear Medicine and TJ-Itrasound Diagnostics ULTRASOUND AND RADIONUCLIDE DIAGNOSTICS OF PORTAL HYPERTENSION a. In the last years the problem of portal hypertension (PH) has become more actual in consequence of new possibilities of practical medicine in diagnostics of liver diseases. The most frequent causes of PH is cirrhosis of various genesis. Differential diagnosis of cirrhosis and other chronic liver diseases is possible by revealing of PH-syndrome only. b. With the aim of evaluation of ultrasound and radionuclide methods effectiveness 54 patients with diffuse liver lesions were investigated by using of ultrasound t o m o g r a p h y a n d radionuclide splenoportography with 99m-Tc-MAA (intraspleen injection). 17 patients were investigated before and after surgical treatment (spleen-kidney anastomosis). c. Ultrasound tomography and Dopplerography with high resolution equipment allowed to determine direction, linear velocity of bloodflow in the portal vena system and vessels diameters. Radionuclide splenoportography allowed to evaluate the level of portocaval bloodthrow. These data help to establish indications or conraindications to the operation. d. The quantitative date of ultrasound and radionuclide investigations were compared with results of direct measurements of blood pressure in the portal vena system during surgical treatment. High degree of the correlation was demonstrated.

K.Rudzkz,

1234

S.Nowak, T.M.Sadowski*,

J.RudzKa

Dept. of Nuclear Medicine, Katowice, Poland *Div. of Biomedical Electronics, Gliwice, Poland A P P L I C A T I O N OF A R T I F I C I A L N E U R A L NETWORKS FOR THE LEFT-TO-RIGHT CARDIAC SHUNT C L A S S I F I C A T I O N Artificial neural networks (ANN) seem to be a p r o m i s i n g p r o c e s s i n g tool for analysis of some diagnostic procedures. The purpose of our study was to develop ANNs capable of recognising the left-to-right shunt size from radiDnuclide first-pass studies and to evaluate their diagnostic accuracy. ANNs containing 3 layers of processing elements were used. Two randomised series of the pulmonary time/activity curves of different shunt size (determined according to Maltz and Treves as a reference method) were used: 60 curves for training and 60 curves for checking the results. The trained ANNs were also tested by direct analysis of 30 first-pass studies (each study contained 60 images). The time/activity curves were automatically generated for each pixel of the scanned area and evaluated by ANNs. The result was displayed as a colour x-y map. The correct c l a s s i f i c a t i o n of shunt size was 98.3% by the trained ANNs. Besides, m a p p i n g the classification results in the first pass study made it possible to visualise the region of pathological blood flow and the extent of shunting. Conclusion. The ANNs are an effective and efficient tool helpful in classification of the left-to-right cardiac shunts.

• PSu813 J. van den Hof_f, W. Burchert, H.-G. Wolpers, G.-J. Meyer, H.Hundeshagen. Dept. of Nuclear Medicine, Medical School Hannover, Germany VISUALIZATION AND QUANTIFICATION OF THREEDIMENSIONAL M Y O C A R D I A L WALL M O T I O N W I T H GATED PET

Evaluation of local myocardial wall motion yields important information for assessment of myocardial viability. Combination of a dynamic study with a gated scan offers the possibility to correlate regional wall motion and regional metabolic activity. We present a procedure which combines quantitative assessment of the 3D wall motion with an animated pseudo 3D visualization. Methods: In our approach, the left ventricular wall is identified directly in the transaxial images. Delineation of the wall proceeds via a weighted radial maximum intensity projection. The weighting is derived automatically from the local averages of ventricular radius and wall thickness. The resulting myocardial surface is smoothed bilinearily, resulting in a stable identification of the left ventricular wall even in infarcted areas. Results: With this approach one obtains from an ECG gated investigation a data set which describes the regional 3D motion of the complete left ventricle. For quantitative evaluation of the wall motion these data are recoded into polar maps of regional wall motion amplitude or regional ejection fraction. In order to enable correct area determination we use a faithful mapping of the individual myocardial surface for polar map generation. Visualization is performed with an animated pseudo 3D display of the derived surfaces. Regional metabolic rate, wall motion amplitude, or ejection fraction is used for colour coding of the myocardial surface in this display. Conclusions: The animated display of the heart motion offers a significant improvement for evaluation of motility as compared to conventional 2D approaches. The correlation of regional metabolism and motility further improves the detection of viable myocardium.

Physics and Instrumentation

PSu815 A. Stani~i~. D. Ivan~evi~*, S. Popovit*, Z. Milas**, V. 0apkun Department of Nuclear Medicine, Clinical Hospital, Split, *Clinical Department of Nuclear medicine and Radiation Protection, University Hospital, Zagreb, **Faculty of Engineering, Split, Croatia OPTIMIZING DILUTION

GAMMA

VARIATE

FIT

TO

ISOTOPE

CURVES

A mathematical function of the form C(t)=K.(t-AT)et.e-(t-AT)l[3, called a gamma variate, has been extensively used for curve fitting in nuclear medicine. It is still felt to be the best way of curve analysis in patients with left-to-right shunts in studies with a good bolus injection. We noticed that symmetry of gamma variate function curve, as expressed through its time proportions, is influenced only by the parameter c~and not by the parameter 13. This principle was incorporated in a new method of gamma variate fit. It is characterized by primary variations of c~ values, while the values of parameter 13,constant K, and appearance time (AT) are only adjusted to give the gamma variate function curve closest to experimental data. The new method was applied to 51 isotope dilution curves which were also fitted with a gamma variate using a least squares technique. These curves were generated for the right lung region of interest in patients of predominantly pediatric age group referred to radionuclide angiocardiography for evaluation of cardiac murmur. The dilution curves were normal, i.e. without signs of a leftto-right shunt. The quality of the fit was significantly better with the new method. The average coefficient of variation was 2.97 +0.82% for the new method versus 3.85 --+1.33% for the least squares fit (p<0.001). A real problem with the least squares technique was present in cases where a large difference in c~values between the two methods existed. The quality of curve extrapolation, which is of utmost importance in the left-to-right shunt analysis, is also affected.

(n cO |m t~ t,ID

ID L_

O.

PSu814

PSu816

C. Kwark, Y.W. Park, D.S. Lee, J.Y. Ahn, J.M. Jeong, B.H. Oh, J-K. Chung, M.C. Lee, J. Set, C-S. Koh, Seoul National University Hospital, Department of Nuclear Medicine and Internal Medicine, Seoul, Korea

F. Hermansen, S.D. Rosen, F. Fath-Ordoubadi, J.S. Kooner, J.C. Clark, P.G. Camici, A.A. Lammertsma. Cyclotron Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.

OPTIMIZATION OF QUANTITATIVE REGIONAL MYOCARDIAL BLOOD FLOW ESTIMATION USING RB-82 DYNAMIC MYOCARDIAL PET AND ADAPTIVE DOUBLE INTEGRATION METHOD. Quantitative measurements and parametric images of regional myocardial blood flow(rMBF) with dynamic myocardial PET have been introduced using the graphical analysis (GA) by Patlak et al and double integration method(DIM) by Mejia et aI(JNM, 1994). This study investigated an adaptive double integration method(ADIM) utilizing the slope of GA as the volume of distribution(Vd), where Vd is retrospectively applied to DIM. Using computer simulation, the relative performances of GA, DIM, and A D I M were evaluated. Rb-82 Rest/Dipyridamole stress dynamic myocardial PET scans for patients with coronary artery disease(CAD) were performed with thirty-five dynamic frame sequence(5sec x I0, 10see x I0, 20see x 15). With the left ventricular time activity curve(TAC) as an input function, 128x128 pixel TACs were processed with GA, DIM, and A DIM, respectively, rMBF parametric images were composed using the three K values. The results showed that the flow estimates from ADIM were closer to the true flow values than those from GA and DIM in computer simulation, and they reflected the rest/stress changes in rMBFs better than GA and DIM, even with the poorly perfused Rb-82 myocardial PET images. Also the parametric imaging by ADIM showed much lesser failure rate than GA and DIM, which led to relatively uniform myocardial parametric images. We conclude that ADIM could be useful as an easy-to-use, reliable rMBF estimator.

MEASUREMENT OF MYOCARDIAL BLOOD FLOW AND TISSUE FRACTION IN SEPTUMWITH [O-15]WATERAND PET

Myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of myocardium perfusable by water, can be measured using PET and [0-15]C02 or [0-15]H20. The method using [0-15]C02 is noninvasive but overestimates TF in septum. In contrast the [O-15]H;O bolus method with arterial cannulation is accurate but invasive. The purpose of the present study was to develop a method which circumvents both problems. Methods: ii patients with coronary artery disease and 4 normal subjects were studied. Following bolus injection of [0-15]H20, time-activity curves were obtained for septum and left and right ventricular cavities. Non-linear regression with a four-parameter model was used to determine MBF and TF, fitting for spill-over from both left and right ventricular cavities. The results were compared with those obtained with [0-15]C02 inhalation and the usual three-parameter model, fitting for spill-over from the left ventricular cavity only. R e s u l t s : The four-parameter model applied to bolus [O-15]H20 scans was stable. In contrast to [0-15]C02, TF in septum was similar to that in the rest of the myocardium. MBF values were similar for [0-15]H20 and [0-15]CO2. However, the precision of MBF in septum was significantly higher for [0-15]H20. C o n c l u s i o n s : MBF can be measured with a bolus injection of [0-15]H20 without the requirement for arterial cannulation. This eliminates the overestimation of TF in the septum where it gives higher precision for MBF than with [0-15]C02.

1235

ID O IX

•

Physics and Instrumentation

PSu817

PSu819

G BlomqvisI Department of Glinical Neurosoience, Experimental Alcohol and Drug Addiction Section Karolinska Hospital, Stockholm, Sweden

V.U Cheng~i. C.C. Nimmon.and K.E. Briuon. Departmen t of .Vuclear ~ [edicine and the l( "RF 5,)~clear 3 iedicine Group, St. Bartholomeu, 's Hospital, London ECIA 7BE, UK.

MEASUREMENT OF CEREBRAL METABOLIC RATES WITH POSITRON EMISSION TOMOGRAPHY - TREATMENT OF TRACER LOSSES For many labeled compounds used in positron emission tomography labeled metabolites are lost from the tissue. These losses can be treated in different ways : by fitting loss rate constants, by measurements, or by ignoring the process. For example using [1-11C]glucose, one type of loss occurs in the main branch of the metabolic process where oxidation causes loss of [11C]CO2 from the tissue. Another type of loss occurs in a metabolic side-branch where [11C]lactate is lost as an effect of nonoxidative glucose metabolism. Another example is [11C]leucine, which is incorporated into proteins (with no tracer loss) but is also metabolized with subsequent loss of [11C]CO2 from the tissue. The influence of different types of losses on the measured metabolic/ incorporation rates has been investigated. Using [1-11C]glucose, the average rate of loss of [11C]CO2 from the human brain was measured in a number of subjects and a rate constant for the loss was fitted. Without correction for this loss, the rate of glucose oxidation was found to be underestimated by 20%. An attempt to fit a loss rate without utilizing the measured loss, resulted in a 12% underestimation of the rate of glucose oxidation. The loss of [121C]lactate was also measured and two rate constants, describing the production and loss of this compound, was fitted. By ignoring this loss, the rate of glucose oxidation was found to be underestimated only by 3%. An attempt to fit rate constants for production and loss gave very unreliable estimates of these constants, although the variability of the corresponding estimated rate of glucose oxidation was found to be small. By simulations it was found that losses from a metabolic side-branch has a minor effect on the estimated metabolic rate in the main branch, if the pool in the tissue of labeled metabolites in the side-branch is small, or if this pool relatively rapidly reaches equilibrium with the tracer in the plasma. With prolonged measuring time, the estimate of the metabolic rate in the main branch becomes less sensitive to losses in the side- branch.

PSu818 ~ , A. Champailler. Centre d'Imagerie Nucl~aire, Polyclinique Beaulieu, Saint-Etienne, France

To reduce the problems inherent in SPET data reconstruction, a technique based on the mathematical description of raw tomographic projections has been developedwith the aim of quantitation. The user identifies the object that is to be segmented. A seed pixe] within this starts offan edge detector that provides a least squares fit to the edges of the chosenobject according to an assumed ellipsoid or irregular shape. The body outline and the backgroundcontribution are estimated. Copies of these are produced in a new data set to form the basis of a Monte Carlo subroutinethat takes into consideration attenuation, noise, Modulation Transfer Function and time variance of activity within the segmentedobject. This subroutineiterates to a point where the simulateddata closely approximatesthe original data for only the delineated object. This "image surgery" provides a quantitative clinical tool This algorithm, for which a patent application has been filed, has been tmplementedoo a HERMES workstation (Nuclear Diagnostics Ltd). It has the potential to determine volume, activity and chronological changes in SPET data without reconstruction. Refinement and validation of the method are currently being undertaken.

PSu820

B.M. Dohmen, R. Bares, M. Holtsteger, U. Buell. de

FIRST PASS BOLUS S A M P L I N G R E Q U I R E M E N T S

Gamma v a r i a t e functions are w i d e l y u s e d to m o d e l first p a s s t r a n s i t curves in n u c l e a r m e d i c i n e . T h e o r e t i c a l v a l i d i t y of the g a m m a v a r i a t e m o d e l for t r a c e r d i l u t i o n curves has p r e v i o u s l y b e e n derived and various fitting methods have been suggested b u t little a t t e n t i o n has b e e n p a i d to the s a m p l i n g r e q u i r e m e n t s of this model. F r o m a t h e o r e t i c a l f r e q u e n c y a n a l y s i s we s h o w that t h e frequency s p e c t r u m is not band-limited, thus t h e N y q u i s t c r i t e r i o n can t h e o r e t i c a l l y n e v e r b e s a t i s f i e d . N e v e r t h e l e s s we s u g g e s t t h a t t h e a m p l i t u d e at t h e f r e q u e n c y c u t - o f f s h o u l d b e lower that an a r b i t r a r y t h r e s h o l d £. We d e r i v e then a formula r e l a t i n g the s a m p l i n g interval Ts to the t i m e - o f - m a x i m u m M and the r a t i o k b e t w e e n the ordinate at 2M and the ordinate at M (M and k are easily estimated by a simple visual inspection): ~ . M . ( i n 2 - 1) Ts < i n k ~E( In 4 - 2)/(1 - in 2k)_ 1 S i n c e it a p p e a r s f r o m t h i s f o r m u l a t h a t f o r £=0.01, a Ts of 0.3 times M w i l l s a t i s f y t h e condition over n e a r l y all the realistic values of k, a practical guideline can then b e suggested: M must be at least the 5th sampled point, s t a r t i n g from the t r a c e r a p p e a r a n c e time. This g u i d e l i n e agrees with other experimental works and could be a p p l i e d to any b o l u s sampling, even if the g a m m a v a r i a t e f o r m a l i s m is not a c t u a l l y needed.

1236

CONSTRAINED HOLISTIC IMAGE MANIPULATIONAND ENHANCEMENT USING RAWDATA ANALYSIS(CHIMERA).

Department of Nuclear Medicine, University of Technology, Aachen, Germany. FDG-UPTAKE BY BLOOD CELLS: CORRECTION OF THE EFFECT ON ARTERIAL INPUT FUNCTION CALCULATED FROM DYNAMIC PET-DATA. Non-invasive determination of arterial input function from dynamic PET data (aorta/left ventricle) could be used as an alternative to sequential arterial blood sampling. However, various corrections are necessary to obtain valid data. Particularly with PET only .FDG concentration in the whole blood could be measured while real input function depends on plasma FDG. The aim of the presented study was to evaluate FDG-uptake by blood cells and its potential effect on calculated plasma radioactivity. In 19 patients ratio of cellular and plasma FDG-concentrations in-vivo was calculated from arterialized blood samples sequentially drawn 5 to 40 min. after FDG injection. To investigate the kinetics of FDG exchange between plasma and blood cells ['°F]-FDG was added to blood samples and FDG-enriched blood cells were mixed with autologue plasma. The radioactivity of cellular compartment and plasma was sequentially measured for 60 minutes hereafter. These in vitro tests revealed rapid cellular FDG uptake. Even in the first sample, drawn immediately after mixing FDG and blood for 1.5 minutes,. the final blood cell/plasma-ratio of 0.8 was observed. This steady state value was also found in vivo. The cellular effiux was fast, too, and appeared to be completed after mixing plasma and FDG-loaded blood cells. The measured ratio was 1.0, indicating that 10% of the FDG had been fixed in the cellular compartment. Applying a ratio of 0.8, real plasma FDG concentration [Cp~] can be calculated from the blood value [Cs] derived from scan data and the hematocrit according to the formula: Cpi = CB/(1-0.2*HCT). Comparing the calculated arterial input function with the results from arterialized blood samples the difference between both values was reduced about 5%. We conclude, that there is considerable and rapid FDG-uptake in circulating blood cells. Correction can be achieved by the presented formula, which may allow for improved arterial input data derived from PET scans.

•

Physics and Instrumentation

PSu821

PSu823

M. S&mal I,H. B e r g m a n n 2'3, M. K & r n ~ 4,J. V o s & h l o I,M. E c k h o l t 2'3, M. Scha-ffarich 2 iCharles Univ. Prague,CZ, 2Vienna Univ.,A, 3 L . B o l t z m a n n I n s t . N u c l . M e d . , V i e n n a , A , 4Acad. S c i . C z e c h R e p . , C Z

Ph. Decostre, Service de M6decine Nucl6aire, H6pitaux Civils du CPAS de Chaderoi, JUMET, BELGIUM

M E A S U R E M E N T OF C O M P A R T M E N T A L V O L U M E S U S I N G F A C T O R A N A L Y S I S OF D Y N A M I C S C I N T I G R A P H I C D A T A IN FEW S I M U L TANEOUS PROJECTIONS

ESTIMATION OF THE STEADY STATE DISTRIBUTION VOLUME OF TECHNETIUM 99m - DTPA FROM A 20-MIN CAMERA RENAL STUDY AFTER SINGLE BOLUS INJECTION. If several methods have been reported to estimate the total steady state distribution volume of diffusible tracers in open systems (VDSS), no simple reliable one has is fact been proposed, accuracy being only obtained with technically laborious methods. The present method applies the properties of the peripheral organ distdbution volume (PODV), in mammillary systems, as previously described. By PODV transformation of the 2O-min renograms, a continuous excretion time curve is estimated whose validity is studied in 57 patients by comparing actual and predicted bladder 20-min content (r = 0.96) and a continuous retained dose time curve is derived. At any time, the distdbution volume, VD(t), of the injected dose is, by definition, the inverse of the plasma concentration time curve. In open systems, when plasma concentration is expressed in fraction of the injected dose per liter, VD(t) diverges and eventually tends to infinity. When plasma is expressed in fraction of the dose retained, its inverse, VDret(t), uniexponentially tends to an asymptotic plateau as in a closed system. The total tracer content of the "closed system" may be calculated by inverse PODV transformation and clearly shows a maximum. Theoretically, at the time of maximum, VDret(t) represents the true VDSS. In 792 patients with no oedema, the method gives a mean total 9gmTc-DTPA VDSS of 14.2 _+2.8 % of body weight (with a mean correlation coefficient between experimental and fitted VDret(t) of 0.97 + 0.03). In a subset of 15 patients, a biexponential fit of the plasma concentration curve and the proposed dose retained method give respective values of 14.6 _+ 3.2 and 14.8 + 2.9 % of the body weight (good Correlation of the individual values with r = 0.97). The proposed original algorithm allows VDSS estimation from a routine 20-min renal study, after single bolus injection of a diffusible tracer such as 9gmTc-DTPA, without the need of multiple plasma samples.

In d y n a m i c s c i n t i g r a p h y , the pixel values in images r e c o r d e d in c o u n t s can be c o n v e r t e d into v o l u m e units e i t h e r by s a m p l i n g of the c o n t e n t or by m e a s u r e m e n t of the v o l u m e of i n d i v i d u a l c o m p a r t m e n t s . In p r a c tice, however, s a m p l i n g is d i f f i c u l t and l i m i t e d to blood, whereas standard tomographic techniques are toe slow to a l l o w the a c c u r a t e v o l u m e m e a s u r e m e n t of c o m p a r t m e n t s w i t h a short t r a n s i t time. The a u t h o r s p r o p o s e to o v e r c o m e the p r o b l e m w i t h the help of factor analysis. The s t a n d a r d i z e d pixel values in factor images are p r o p o r t i o n a l to the local pixel v o l u m e s of the s e p a r a t e c o m p a r t m e n t s . The factor images, however, c a n n o t be t r a n s f o r m e d d i r e c t l y into the units of v o l u m e b e c a u s e n e i t h e r the m e a n pixel v o l u m e nor its v a r i a n c e are known. In principle, if a single pixel v o l u m e w o u l d be available, the c o m p l e t e factor image c o u l d be c o n v e r t e d into the units of volume, and the c o r r e s p o n d i n g factor curve into the units of c o n c e n t r a t i o n . In order to v e r i f y this concept, p h a n tom e x p e r i m e n t s have b e e n p e r f o r m e d s i m u l a t i n g a dynamic s c i n t i g r a p h i c s t u d y r e c o r d e d in few s i m u l t a n e ous p r o j e c t i o n s . Factor images of r e s p e c t i v e c o m p a r t ments were e x t r a c t e d from data in e v e r y p r o j e c t i o n . In each factor image, the pixel v o l u m e s c o r r e s p o n d i n g to the row m a x i m a of pixel values have b e e n calcul a t e d u s i n g the factor images in a d d i t i o n a l p r o j e c tions. The e x p e r i m e n t s w i t h m a t h e m a t i c a l and p h y s i c a l phantoms r e s u l t e d in the a d e q u a t e r e c o v e r y of the compartmental volumes and concentrations. Problems r e l a t e d to b o t h a t t e n u a t i o n and the n u m b e r of p r o j e c tions are d i s c u s s e d .

C |O m 4.J

C

t_

PSu822

PSu824

C. Vanhove, G. Demonceau, K. Suenart, J. De Vuyst, H. Colaert, C. Monte. St Elimbeth Hospital, Zottegem, Belgium

L.Tellmann, H.Herzog, R. J. Seitz*, G. Schmitt, H. W. Miiller-Giirtner, Institute of Medicine, Research Centre Jiilich, Department of Nuclear Medicine and *Department of Neurology,Heinrich-Heine-Unlversity,Germany

COMPARISON OF 2 METHODS FOR THE AUTOMATIC DETECTION OF CEREBRAL LESIONS IN SPECT.

CALCULATION OF QUANTITATIVE RCBF-IMAGES BASED ON SINGLE-SCAN IMAGES AND A COMMON LOOK-UP-TABLE Recently we suggesteda combined single-scanacquisition and dynamic analysis of O15-butanol data to obtain rCBF-images for studies of neuroactivation (H. Herzog, JCBFM in press). This approach converts butanol images into parametric rCBF-images using a look-up-table which is obtained by individual arterial blood sampling. To simplify the method by avoiding arterial blood sampling we investigated the use of a common look-up-table. PET data were recorded in a group of normal volunteers (n=7) who were scanned six times followingbolus injections of about 1500 MBq OlS-Butanol using a GE PET scanner PC4096+. One scan was performed at rest, during the other scans different kinds of finger movements were performed. First, quantitative rCBFimages were calculated with an individual look-up-table for each subject (indLOT). Second, the individual look-up-tables were replaced by a common look-up-table (comLUT) being the mean of all (42) individual ones. In order to take into account differences in injected activity comLUT was calibrated to the injected activity and alternatively normalized, so that the whole brain CBF was 50 ml/mirdl00g. - Whole brain 15%-isocontour-ROIswere calculated for all images. A group analysis for one task of the motor study was done with the Computerized-Brain Atlas (CBA) (Thurfjell, 1991) followed by a statistical analysis (t-test-statistic with global standard deviation). After calculation of the indLUT and the calibrated comLUT-images the 15% ROI-CBF was 58.6-.15.9 ml/min/100g (mean-*SD)and 61.4+20.8 ml/min/100g respectively. Normalized comLUT resulted in 44.8±6.9ml/minl100g. Compared to the indLUT data, the maximum values in the case of calibrated comLUTs were only 5% higher and those obtained with normalized comLUTS were 30% lower. The standard deviation was in the same range for all data. - Group analysis of the data in the activated motor area showed a mean t-value of 10.7-.5.15 for the indLUT images in comparison with 8.46-*4.84 for eomLUT and 9.18±4.32 for the normalized comLUT. These findings were significant (p<0.001) for all methods used. In conclusion,the use of a commonlook-up-table for the calculation of quantitative rCBF-images yielded similar results in the statistical outcome of a group analysis. Therefore, the advantages of butanol for quantifying rCBF can be kept even without measuringthe arterial input function in each subject.

The efficiency of two methods for the the automatic detection of lesions in brain SPECT was compared, using the clinical data and the CT-scanner as a reference. In the first method, after detecting the mid-sagittaI plane and assuming left-right symmetry along this plane, a lower and an upper percentiles were defined, allowing the classification of the cortex in zones of low, normal and high flow. The second method compares the brain SPECT images, after geometric and gray value transformation into a standard coordinate system, with a normal database depending of age. Voxels deviating more than two standard deviations were classified as low or high perfudon areas. In this study, 206 patients suffering from CVA or TIA were included. ASPECT and a CT-scan were realised within 3 days after the attack. Acquisition starts 10 minutes after injection of 15 mCi of Tc-HMPAO. The images were realised on a 3-headed camera in a 128x128 matrix, 25 sew step, 90 steps on 360 °. After backprojection with adaptative filters, the images were fully automatically processed by both methods and the results visually assessed. Agreement b~ween both methods occured in 155 cases (75%). In 36 of the remaining 51 patients, the localisation of the lesion based on clinical history and CT-scan was not possible, resulting from equivocal symptoms and no clear lesion on CT. For the other 15 cases, 9 were correctly diagnosed by database comparison against 6 by the percentile method. In conclusion, the database comparison seems to be the prefered method for the automatic detection of brain lesion: the risk ofmisrepositioning and distorsion of the tomographies is low, compared to the false detection occuring from physiological variations (temporal asymetry, variations with age, _.) and the underestimation of zones of hlgh flow (only about 20% of our zones of high flow have an activity higher than these of the cerebellum).

L

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Physics and Instrumentation

PSu825

PSu827

F. Bengel, N. Avril, S. Ziegler, M. Herz, M. S c h w a i g e r N u k l e a r m e d i z i n i s c h e Klinik, K i i n i k u m r. d. Isar, T e c h n i s c h e Universitfit Miinchen, G e r m a n y

MGriessmeier, F.Sonnenberg, M.Weckesser, K Ziemons, K-.J. Langen, H.-W. M/aUer-CC&~ner.Institute of Medicine, Research Center Jfilich, Dep. of Nuclear Meal, University of DOsseldorf, Germany

R E G I O N A L C O M P A R I S O N OF C O N T R A S T VALUES IN A T T E N U A T I O N - C O R R E C T E D AND N O N - C O R R E C T E D WHOLE-BODY-PET IMAGES Staging and sensitive detection of tumor lesions in oncology are the main purposes of whole-body-PET imaging. The need of measured attenuation correction is discussed controversially, since quantification of tracer uptake is not the main issue. This study was performed to evaluate the effect of attenuation correction in whole-body-PET imaging protocols using F-18FDG. An ECAT-EXACT-PET-scanner was used with a whole-body-protocol including at least 3 bed positions, emission scans of 9 minutes per bed position and consecutive post-injection transmission scans (10-12 minutes, approx. 50 million counts per bed position). Uncorrected and attenuation corrected transaxial images were reconstructed by filtered backprojection (Hanning-filter, 0.4 cutoff-frequency). We analyzed a total number of 79 areas of focally increased FDG-uptake from images of 24 patients with several malignancies. 17 foci were located in the head/neck-region, 43 in thorax, 12 in abdomen and 7 in pelvis. In transaxial slices, a ratio of focal to background counts (f/b-ratio) was calculated using ROI-technique. F/b-ratios of average ROI-counts were significantly higher for uncorrected images in every bod~¢ region (p<0.01). images f/b total I f/b hd/nk I f/b thor I f/b abd I f/b pelv uncorr 4.4_+2.9 4.1+_1.8 I 4 . 2 + 3 . 0 [ 4 . 4 + 3 . 9 I 5 . 8 + 3 . 1 1 attcorr 3 . 0 + 1.3 2 . 5 + 1.0 3 . 2 + 1.3 2.7_+ 1.4 3.4+_1.3 Attenuation corrected images generally provided a lower target / background-ratio. This effect seems to be independent of focus localization. However, inhomogeneity of transmission scans may lead to additional noise in the attenuation corrected images independent of body regions. Also, miscorrection due to residual activity during transmission measurement might decrease contrast values. Our data suggest that attenuation correction in whole-body-PET using transmission scans with limited statistics yields lower contrast values in every body region. This may result in a decreased sensitivity for visual image analysis.

I M P R O V E M E N T OF SPECT Q U A N T I F I C A T I O N IN SMALL BRAIN STRUCTURES BY USING E X P E R I M E N T BASED RECOVERY-COEFFICIENT CORRECTIONS One of the major problems in SPECT-quantification is the underestimation of radioactivity concentration in small objects due to limited spatial resolution. This error may be compensated for by using recovery-coefficient (RC) correction algorithms. The aim of this study was to investigate the accuracy with which activity in small brain structures such as the hippocampus can be quantified. Glass cylinders with diameters of 1 to 40 mm filled with constant activity concentrations of Tc-99m were measured under constant conditions. The 'Dual Energy Window' technique[ 1] was applied for scatter correction and attenuation was corrected using transmission scans. ROls using the known tube diameter were placed on the objects in the reconstructed SPECT images. RC was determined by comparing average activity inside the region to the reference region ( D r y = 40ram). Changes of the RC with object size are shown in Fig. 1. The resuks of the correction procedure are shown in Fig.2. After correction the relative mean activity concentration was 1.0a: 0.08 for an object diameter above or equal to 5mm Without correction, the apparent activity concentration was strongly depend on object size. This method helps to improve Re Figure1 Figure 2 the quantification , . of brain SPECT 0,s especially in small spheroid

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campus if coregistered anatomical information (MRI) for determine object size is available. [l]: R.J. Jaszczaket al., J. Nucl. Med. 25, 1984

PSu826

PSu828

J. Yang, J.T. Kuikka, E. Vanninen, E. Lgnsimies, Kuopio University Hospital, Department of Clinical Physiology, F1N-70210 Kuopio

T.Ichiham, N.Motomara, T.Nakagawa, H.Maeda, K. Yamakado, K.Matsumura, K. Takeda. TOSHIBA Medical Engineering Laboratory, Tochigi-ken, Japan. Mie University School of Medicine, Mie. Fujita Health University School of Health Sciences, Aiehi.

C O M P A R I S O N OF BRAIN P E R F U S I O N SPET W I T H AND WITHOUT A DUAL-PHOTOPEAK SCATTER CORRECTION Scattered photons add a low-frequency background to the SPET images and thus degrade the signal-to-noise ratio. In addition, scatter makes difficult to perform accurate attenuation correction. The aim of the study was to evaluate the clinical usefulness of scatter correction in high resolution brain SPET scans. The basis for the dual-photopeak window method of scatter correction has been previously presented and tested (J Nucl Med 1992; 33:605-612). To obtain the regression relation between the scatter fraction and the ratio of the number of counts detected in two equally wide subwindows, a point source of Tc-99m was imaged in a plexi glass cylinder (diameter of 20 cm and thickness of 10 cm) using a Siemens MultiSPECT 3 gamma camera with fan beam collimators. The regression parameters were calculated and stored onto the scatter correction subroutine for further clinical applications. Twelve patients with SAV were studied with dual-window SPET scans after iv. injection of 550 MBq of Tc-99m-ECD. Signal-to-noise ratios of the original (sum-window) and scatter corrected images were calculated for the cerebellum, hippocampus, prefrontal, temporal, occipital, frontal and parietal cortices as well as for the basal ganglia and thalamus. White matter served as a reference region. In addition, 2 nuclear medicine experts visually scored these image sets: 0 = no visible difference and 1 = clearly visible difference. Signal-to-noise ratios of the scatter corrected images were 6-9 % higher than those of the sam-window ones. The visual score showed that 8/12 scatter corrected images had a higher score and especially the basal ganglia and thalamus visualized more clearly. The potential clinical utility must await the results of larger, interlaboratory studies.

1238

A~ATION COMPENSATED DYNAMICLIVER SPECT USING SHEET LINE SOURCE TRANSMISSIONCT frCT) AND TEW SCATTER COMPENSAT/ON

We have investigated using the triple energy window ('IEW) scatter compensation method with an uncollimated sheet source as a way of reducing scatter to improve the accuracy of the attenuation coefficients. A new TCT flood source was designed using a fluoroplastic tube which is a 50m long, 1ram internaldiameter( total capacityof 40ml) and housed in 5mm interval slits on a plastic plate ( rectangular shape with a size of 68cmx54can and thickness of 7ram ). For TCT measurement, this sheet line source (fiUed with 25 mCi of Tc-99m) was attached to the collimator face on one head of a TOSHIBA GCA-7200A dual headed SPECT gantry having a 55 x 40cm SPECT/TCT field of view. The camera size is sufficiently large to cause no truncation of the transmission md emission dam for larger patients. Seven rods ( 8cm long 3cm in diameter) in water fdied cylindrical phantom (20era long 20cm in diameter)were used to evaluate the accuracyof activity measurementsin 30-s dynamicSPECT scanning using high-resolution low energy collimators. Each rods was loaded with different activity (range,0.32 - 2.1,u Ci/ml) of Tc-99m. TEW method was used for scatter compensation of the transmission and emission data. SPECT images were reconstructed with attenuation compensation using a 2-iteration Chang algorithm modified for a nonuniform attenuation map. The measm'edattenuation coefficients of water in TCT image of this phantom was 0.14 (l/cm). Preliminary clinical evaluationswere performedfor 5 patients and 1 normal volunteer. After intravenous injection of 5 mCi of Tc-99m GSA, serial 30-s SPECT data were acquired for 20 rain. The time-activity carve(TAC) measured from cross-calibrated SPECT data(/z Ci/voxel) over the heart was normalized with the 10-min venous sample concentration (/zCi/m0 and was used as the blood clearance curve. The TAC for the entire liver was measuredfrom eross-ealibratedSPECT data (g Ci/voxel) of the entire liver. Hepatic clearanceand nonspecificvolume of distribution weredeterminedusing the Rufland(Paflak plo0 method.The hepatic excretion rate was determinedfrom analysis of liver kinetics basedon a 1-compartmentmodel with 3 panuneters. The results of the phantom studies showed good linearity and accuracy in activity measurements using 30-s dynamic SPECT. The proposed measurements method is thought to be useful for evaluation of hepatic resen,e in clinical use.

• PSu829

G. Glatting, M. Rentschler S.N. Reske, Univereit~t UIm, Abteilung Nuklearmedizin, Germany. THEORETICAL MODEL FOR THE ASSESSMENT OF DETECTABILITY OF SMALL LESIONS DEPENDING ON LESION SIZE AND LESION CONTRAST FOR 2 D - A N D 3D-PET Purpose of the study was to quantitatively determine the gain in sensitivity for the detection of small lesions by 3D positron emission tomography (PET) versus 2D-PET. A mathematical phantom of a tumor of cubic form having an elevated activity level imbedded in a constant activity background tissue was investigated. After deterioration of the mathematical phantom due to the finite resolution of the imaging system (ECAT EXACT HR+, CTI/Siemens, Knoxville, FWHM(x,y,z) = 5mm, 5mm, 4.6mm), statistical description of the error introduced due to absorption correction and calculation of the resulting voxel (size = 5 x 5 x 2.5 mm 3) activity contents, a statistic test (tTest) was performed in order to decide if the elevation of voxel values due to the tumor was statistically significant (5%). The dependence on tumor to background contrast c and on tumor volume v was investigated for sensitivities s of 2D and 3D data acquisition (s2D = 200 kcps/p, Ci/ml, s3D = 1130 kcps/#Ci/ml). The increase of sensitivity allows for fixed contrast the detection of lesions reduced in volume by a factor of 1.6 if absorption correction is measured in 2D mode. If all measurements would be performed in 3D mode an increase by a factor sqrt(s3D/s2D) = 2.4 would be possible. In conclusion the gain in sensitivity due to 3D-PET allows the detection of structures smaller by a factor of 1.6 for the ECAT EXACT HR+ PET.

Physics and Instrumentation

PSu831 C. S&nchez Catas~s i , M. Rodriguez Castillo 2 , R. Galvizu ~ and N. Rodriguez i, (I) International Center for N e u r o l o g i c a l Restoration, Havana, Cuba. (2)Institute of Oncology, Havana, Cuba. A NON-STANDARD IMAGE ACQUISITION M E T H O D TO IMPROVE SPATIAL RESOLUTION IN CEREBRAL PERFUSION SPECT STUDIES WITH A SINGLE-HEAD GASS4A CAMERA.

A n o n - s t a n d a r d images a c q u i s i t i o n m e t h o d to improve spatial r e s o l u t i o n in cerebral p e r f u s i o n SPECT studies w i t h a s i n g l e - h e a d gamma camera was developed. The i m p r o v e m e n t is a c h i e v e d by r e d u c i n g the radius of rotation, keeping all the b r a i n inside of the field of v i e w w i t h o u t the shoulder interference and m e e t i n g the condition, pixel size ~ FWHM/3. The m e t h o d is as follow: The c a m e r a - c o m p u t e r AI)C converters allows a c q u i s i t i o n in a s t a n d a r d m a t r i x format of 256x256 pixels. For this m a t r i x format, without zoom and e x c l u d i n g the last column and row, it is possible to define a c o m p r e s s i o n t r a n s f o r m a t i o n to reduce the original m a t r i x to n o n - s t a n d a r d format of 85x85 pixels. A 64x64 submatrix is p i c k e d up from each p r o j e c t i o n to form a new set of 64x64 images in such a w a y that no change in the axis alignment and the centre of rotation is introduced, w h i c h can be b a c k p r o j e c t e d using standard software. With this m e t h o d it is p o s s i b l e to reduce the radius of rotation to 16 cm and to obtain a t o m o g r a p h i c spatial resolution of 16 mm, 3.5 m m less than the standard m e t h o d used in our laboratory. This procedure was i m p l e m e n t e d for a gamma camera Siemens ZLC 3700 i n t e r c o n n e c t e d to a p e r s o n a l c o m p u t e r b a s e d a c q u i s i t i o n and p r o c e s s i n g s t a t i o n and has been v a l i d a t e d through J a s z c z a k p h a n t o m studies and b r a i n p e r f u s i o n studies of normal and p a t h o l o g i c a l cases. The metho~Od~i@ simple and it has the advantage of not introducing any complex or costly hardware implementations.

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PSu830 A.M. Scheff, J.J. Kozar, J.R. Saffer, A. Sherman. U n i v e r s i t y of P e n n s y l v a n i a M e d i c a l Center, D e p a r t m e n t of R a d i o l o g y NEUROSPECT DEDICATED

OPTIMIZATION TRIPLE HEAD

IN THE CAMERA

ABSENCE

OF

A

Puroose: This study was p e r f o r m e d i) to d e t e r m i n e w h e t h e r a c c e p t a b l e SPECT b r a i n imaging c o u l d be p e r f o r m e d w i t h single or dual h e a d cameras, and 2) what factors w o u l d o p t i m i z e the image q u a l i t y r e l a t i v e to a s t a t e - o f - t h e - a r t triple head camera. Methods: T o m o g r a p h i c a c q u i s i t i o n s of J a s z c z a k and H o f f m a n 3D b r a i n p h a n t o m s were o b t a i n e d on single, dual and t r i p l e h e a d cameras, with LEAP, high r e s o l u t i o n (± m a g n i f i c a t i o n ) , and f a n b e a m c o l l i m a t o r s (20 mCi, 30 mins, 23-27 Kcts/seo) . The data sets were p r o c e s s e d with a low pass filter u s i n g c u t o f f f r e q u e n c i e s that m a x i m i z e d r e s o l u t i o n of J a s z c z a k c o l d spheres and gave c o r t i c a l definition. Results: U s i n g the triple h e a d camera w i t h u l t r a high r e s o l u t i o n f a n b e a m c o l l i m a t o r s as the gold standard, the single h e a d camera with high r e s o l u t i o n p a r a l l e l - h o l e c o l l i m a t i o n (± m a g n i fication) was s u p e r i o r to the fixed dual head camera w i t h f a n b e a m or p a r a l l e l - h o l e collimation. This is most l i k e l y due to d i s t a n c e d e g r a d a t i o n by the larger radius of r o t a t i o n r e q u i r e d to clear the table and p a t i e n t ' s shoulders. Studies are in p r o g r e s s w i t h v a r i a b l e angle dual h e a d cameras and p a t i e n t s w i t h f i x e d b r a i n lesions. Conclusion: N e u r o s p e c t p e r f o r m e d with a single h e a d A n g e r c a m e r a can be o p t i m i z e d to p r o v i d e h i g h q u a l i t y c l i n i c a l studies. High r e s o l u t i o n c o l l i m a tion, t i g h t radius of rotation, no p a t i e n t motion, and c u s t o m i z e d p r o c e s s i n g improve image quality.

O,.

PSu832

t._

O.Zoccarato,R.Campini,FM.Fringuelli,R.Giubbini "Salvatore Maugeri" Foundation IRCCS Rehabilitation Institute Of Veruno - Nuclear Medicine Service BODY CONTOURING(BC) AND CIRCULAR ORBIT (CO): COMPARISONBETWEEN TWO SPETACQUISITIONMETHODS.

Technological improvement in new gamma cameras offers different modalities of SPET acquisition. Aim of this work was the evaluation of the effects of different acquisition orbits on SPET studies in terms of contrast and detectability of cold lesions. The studies were performed using a dual headed camera (Elscint Helix) equipped with body contouring option and HR collimator. After the evaluation of tomographic uniformity in both conditions, we compared the results of CO and BC acquisitions (128 matrix size - 3 ° angular step, 360° and 180" angular range ) by two different phantoms: Data Spectrum SPET phantom (cold rods ranging between 25.4 and 9.5 mm) and cardiac phantom with circular cold lesion (30ram diameter) located on the anterior and lateral wall. During the CO the acquisition radius (AR) was 20.3 cm for both phantoms; during BC the AR ranged between 20.3 and 13 cm for the SPET phantom and 20.3 to 10.3 cm for the cardiac phantom. A parametric Wiener filter (0.6 - 11) was used in filtered back projection; the slice thickness was 14mm. The data obtained by the tomographic phantom showed strict dependence of the intrinsic uniformity of the camera particularly during BC acquisition. The SPET phantom showed better spatial resolution using BC (9.5 mm ) rather than CO (11.1 ram) modality. In cardiac phantom no significant differences were found in lesion detectability with both in 180 and 360° angular range. The contrast values, evaluated by angular profiles on the short axis slices, was higher using BC acquisition as shown below: anterior lesion BC CO lateral lesion BC CO 360° 0.72 0.67 360° 0.79 0.66 180° 0.77 0.76 180° 0.79 0.76 In conclusion the BC acquisition method seems to improve both spatial resolution and contrast when compared to conventional CO acquisition. The contrast improvement seems to be more significant with 360°, BC modality requires more severe quality control criteria to prevent the amplification of residual field nonuniformity.

1239

O 13.

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Physics and Instrumentation

PSu833 G. Glatting, M. Rentschler, J. Kotzerke, S.N. Reske, Universitat UIm, Abteilung Nuklearmedizin, Germany. ENTROPY AND CORONARY ARTERY DISEASE (CAD): ROCANALYSIS OF Tc-99m-MIBI-SPECT AND Rb-82-PET Purpose of the study was to quantify the information gain for the measurement of regional perfusion by Tc-99m sestamibi (MIBI) SPECT und Rb-82 (Rb) positron emission tomography (PET) compared to coronary angiography. The information gain due to the measurement is described by the entropy S = - %i p(i) In(p(i)/m(i)). p(i) are the measured and m(i) the expected values for normal myocardial segments i. 55 patients (age: 58 _+10 y, 11 women, infarcted: 42, 1-,2-,3-vessel disease: 6,14,29) were investigated with respect to the value of entropy under rest and stress (0.7 mg/kg dipyridamot). For both methods a receiver operating characteristic (ROC) analysis was performed by comparison with the gold standard of quantitative coronary angiography (>70% stenosis) for LAD, LCX and RCA perfusion territories. The area under the ROC curve is used as parameter for the efficiency of both methods. The standard deviation of the entropy values of MIBI-SPECT is twice that of Rb-PET (as consequence of the (undesired) information about the absorption in the patients). The areas under the ROC curves for stress and rest are: stress/rest LAD kCX RCA [ MIBI-SPECT 0.77/0.67 0.74/0.67 0.76/0.73 Rb-PET 0.91/0.68 0.76/0.67 0.85/0.78 Both methods differ significantly (p<0.01) in the LAD territory. No difference in resting perfusion is found between Rb-PET and MIBI-SPECT. We conclude that inducible ischemia is detected more sensitively with Rb-PET in LAD- and RCA-territories.

PSu835 1,2

.

1

E.YakoumakJs , N.Baztatis, A. lissimopoulos , X.Geronikola I I 5 2 IrapalJ , E.Drakou , S ~ S h u k l a , Ch.ProukakJs . I Dept. of Nuplear Med.Saint Savvas Hosp.Athens, , Dept. of 5 Med.Physics UnJv.or AtheesZ,Nuel. Div. Osp. S.Eugenia Roma .

OPTIMUM CONDITIONS FOR BREMSSTRAHLUNG IMAGING IN YTTRIUM-90 AND STRONTIUM-B9 CHLORIDE RADIOISOTOPIC THERAPY Yttrium-90 and Strontium-89 two pure beta emitters, are attractive r a d i o n u c ] i d e s For radJoJsotopJc therapy i n oncolo-

gy. Therapeutic management r e q u i r e s q u a n t J t i v e high q u a l i t y imaging to measure the pharmacokinetics o f the radJonuc ] i d e i n t h e p a t i e n t f o r d o s i m e t r l c c a l c u l a t i o n s o r Lo p r e d i c t the c l i n i c s ] response o f treatment.. However, accurate q u a n t i t a t i o n of radionuc]ide by bremsstrah]ung imaging Js difficult because of poor image quality that results From septa] penetration and secondary scatter to the high bremsstrah]ung energies. METHOD: Using a Liver-slice Fandom, sensitivity, resolution and source to background ratio of the detector gamma camera system For 90y and 89Sr bremsstrahiung were investigated for various collimators and energy windows in order to determine optimum conditions for imaging. RESULTS: The sensitivity Jn air was almost three times greater for the LEAP than for M.E. and 1.5 times greater For the H.E. than for the H.E. co]lJmator. For the same energy window, system resoJutJon was almost equal for M.E. and H.E. collimator and extremely better than LEAP collimator. Therefore, N.E. collimator with an energy window 50-150 KeV For 8gSr and 50-110 For 90y was the optimal selection For achieving a clinical compromise between sensitivity and resolution. Using the above optimal conditions we obtained high quality s c J n t J ~ a m for patients w~t.h 89Sr bone metastasis therapy and -~Y silicate askJtes therapy.

CONCLUSION: The r e s u l t s of t h i s study suggest, that reasonable accuracy can be achieved Jn c l i n i c a l radJoJsotopJc therapy using 90¥ and 89Sr-Bremsstrahlung imaging.

PSu834

PSu836

M.H. Huang, H.J. Ding, C.C. Yang, C.Y. Chia, R.C. Yang. School of Technology for Medical Sciences, Department of Physiology and Department of Nuclear Medicine, Kaohsiung Medical College, Kaohsiung; Taiwan, R.O.C.

~ , A.E.M. Reijs, J. v. Peski, E.P. Krenning. Department of Nuclear Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands.

QUANTITATIVE ASSESSMENT OF UPTAKE MECHANISM OF TECHNETIUM99M-PERTECHNETATE AND TECHNETIUM-99M-MDP IN INDUCED OSTEOARTHRITIS OF RATS

Osteoarthritis induced in eighty mature rats by serial intra-srticular injection of Papain (3.Smg/kg) ever the right knee, on the first, fourth, and seventh days of the test, and equal volume of normal saline were injeqted into left knee as controls. The severity of induced arthritis of each group was observed by bone scans after subcutaneous injections of technetium-99m pertechnetate (i.0 mCi/kg) over the neck after a lapse of 24 hours and 1,2,4,6 and 8 weeks from the first intra-arcicular injection of papsin. After the bone scan, X-rays of bilateral knees were taken and the radioactivity ratio of the right to left knee of each rat was measured as an index of the severity of osteoarthritis. A teach stage of progression, a rat was sacrificed and bilateral knee sections were performed for further pathological evaluation and autoradiography.The results were compared with the changes of radioactivity ratio and X-ray findings. The results revealed that the bone scan was well correlated with the pathological change and this method can detect osteoarthritis change earlier than joint X-ray. It was suggested that the bone scan with technetium-99m pertechnetate is a useful method for the early diagnosis of osteoarthritis in rats.

1240

REMOTE ACCESS OF PATIENT DATA THROUGH LOCAL WWW SERVER.

The World-Wide Web (WWW) is commonly described as the universe of network-accessible information. WWW-browsers (viewers) appeared to be useful at our department for home viewing of patient data. This approach has a number of advantages. Most WWW-browscrs are free; they have the same Graphical User Interface (GUI) on several hardware platforms; and the user has the ability to introduce a new data type, such as an image in Interfile, DICOM or proprietary format, and specify a viewer or other program which can handle this type of data, such as GammaPC whmh can handle Interfile and some proprietar]( formats. If it is neccesary to convert the data to another format, hke TIFF, it can be done automatically on both the server and browser side. Instead of just sending files, which contain the requested data, the server may also spawn external programs that send the requested data. In this way, data from Hospital Information Systems (HIS) and databases can be made available through WWW and conversions can be done on the fly. In our hospital, users can access data trom the HIS and the Nuclear computer systems via WWW. They do not have to deal with transferring data using FTP, Kermit or ZModem and converting them afterwards by using separate utilities. They also do not have to use expensive ISDN-lines in order to run high-bandwidth X-Windows-applications, just for viewing images at a reasonable speed. l h e r e is a caveat though. If the WWW-server is reachable from the Internet, then security measures must be taken. The problem here is the fact that most security schemes WWW-servers support are useless, because IP-addresses can be faked and all data travelling through the Internet, like passwords and patient data, can be made visible with appropriate tools. All data travelling through the Internet should be encrypted. As encrypting and decrypting are examples of converting data, it should be -feasible to encrypt at the server and decrypt at the browser and vice versa. A popular encrypting tool which appears to be full-proof so far is Pretty Good Privacy (PGP). Of course It is safer to keep WWW-servers local: not reachable from the Internet. In order to still be able to access protected data, we have installed a modem-pool with a call-back facthty. We recommend using the PPP-protoco], as this sets up IP-addresses and several communication parameters automatically. Our conclusion is that WWW has proven to be very useful.

•

Physics and Instrumentation

PSu837

PSu839

¢~lia Hindorf, Sven-Erik Strand, Magnus Tagesson, D i v i s i o n of R a d i a t i o n Physics, Lund U n i v e r s i t y Hospital, S-221 85 Lund, Sweden

J. Lear, J. Pratt, N. Trujillo. Division of Nuclear Medicine, University of Colorado Health Sciences Center, Denver, CO USA

ACCURACY IN P H Y S I C A L PARAMETERS FOR A B S O R B E D DOSE C A L C U L A T I O N S ON CELL- AND S U B C E L L U L A R LEVELS FOR ELECTRON EMITTING RADIONUCLIDES

R E D U N D A N T A R R A Y OF I N D E P E N D E N T DISKS (RAID): P R A C T I C A L O N L I N E I M A G E A R C H I V I N G FOR N U C L E A R MEDICINE

Purpose: D i f f e r e n t m e t h o d s to calculate absorbed d o s e for e l e c t r o n s emitted from r a d i o n u c l i d e s on celland s u b c e l l u l a r levels in r a d i o n u c l i d e therapy h a v e been studied and the accuracy in the p h y s i c a l p a r a m e t e r s have been evaluated. Method: Absorbed fractions for monoenergetic electrons with energies between 0.5 keY and i0 M e V for sphere d i a m e t e r s b e t w e e n 2 ~m and 14 ~m, were c a l c u l a t e d w i t h a s e m i e m p i r i c relationship (used in several publications for absorbed dose calculations) and compared to a commonly used dose p o i n t kernel. D i f f e r e n t energy loss data were compared. Results: The a b s o r b e d fractions calculated w i t h the semiempiric relation, shows larger values than the dose point kernel. For example for ¢=i0 ~m and E=I00 keV, the d i f f e r e n c e is 20 %.The semiempiric r e l a t i o n s h i p u n d e r e s t i m a t e the energy loss of e l e c t r o n s by up to 30 % for energies between 20 eV
While various methods exist for long term archiving of nuclear medicine image data, none support rapid on-line search and retrieval of information. Redundant array of independent disk (RAID) technology has been used for this purpose with mainframe computers, but until recently, operating system and hardware limitations precluded its use on personal computers used in nuclear medicine data acquisition. Using a proprietary controller, we assembled a RAID system using ten, 9 gigabyte drives housed in two subsystems. After allowing for the parity information needed to assure redundancy, available storage totaled 72 gigabytes. The 72 gigabyte space was then separated into eighteen, 4 gigabyte partitions to comply with personal computer requirements. In this manner, only two computer SCSI addresses were needed to access all data. The system was then connected to a Macintosh file server that supports 10 nuclear medicine acquisition and processing computers. Total cost was less than $40,000. System reliability was tested by removing and replacing a drive while the system was in operation. The data from the replaced drive could be reconstructed in approximately 30 minutes, even while the system remained in use. All studies (50,000) acquired over a seven year period were archived in the system. Based on patient name / number and study date, information could be located within 20 seconds and retrieved for display and analysis in less than 5 seconds. Based on a caseload of 10,000 per year, approximately 10 years of image data can be stored by the system. RAID systems, if assembled properly, can support long term storage of nuclear medicine image data in a safe (redundant) manner while allowing nearly instantaneous access to studies.

e'O =I~

C s._

PSu838 J.Ricke L.Kleinholz, H.Amthauer, T.Schumacher, J.Thomsen, C.Zielinski, T.Liebig, C.Stroszczynski, H.Eichst6dt, R.Felix Strahlenklinik und Poliklinik, Virchow-Klinikum Berlin TELENUCLEARMEDICINE AND TELERADIOLOGY: PRINCIPLES OF AN ELECTRONIC PATIENT RECORD AND EFFICIENCY OF COMMON NETWORKS Purpose: Principles of an electronic patient record and access with PC are described. Networks used (ISDN/Ethernet) are tested for efficiency. Methods: Linked with a digital hospital infrastructure, a distributed management system forms the electronic patient record using the principles of an index card system. It offers on-line access to all clinical information systems with standard interfaces, e.g. HL7, EDI, SQL, Dicom. A Multimedia PC for review uses WWW-teehnology to browse patient data and a proprietary viewer for Dicom or ACRNEMA images. Physicians are offered role based access to the electronic patient record and teleconsultation via ATM, Ethernet and ISDN hospitalin- and externally. During videoconferences, documents or images can be visualized with a document camera. Results: Time for access to the electronic patient record was measured in 20 cases. Via ISDN, access with an overview of examinations and reports in the record took 41s (Standarddeviation SD 2s), via Ethernet 19s (SD 4s). Visualization of reports and 58 images (incl. CT, ACRNEMA transformed to GIF) via ISDN 3min 31s (SD 4s), via Ethernet 37s (SD 3s). Retrieval of an ACRNEMA image in original format took an additional imin 20s (SD 0,9s) via ISDN and 6s (SD 2s) via Ethernet. Conclusion: Inexpensive PC based systems are well capable to visualise multimedial patient records. Ethernet serves well for hospital internal communication, ISDN is a feasable tool for external data transfer and teleconsultation. The technology used improves communication between nuclearmedicine and clinical partners.

t3..

PMo840

s_

C. Falc6n I. D. ROS1, I. Juvells 2, J. Pavia 3 tLab. Biophysics and Bioengineering, 2Lab. Optics. University of Barcelona. 3Dept. Nuclear Medicine, Hospital Clinic P., Barcelona, Spain. IMAGE QUALITY IN SPECT. COMPARISON OF ITERATIVE ALGORITHMS USING FIGURES OF MERIT. ART and MLE have been intensively studied in the last few years for the iterative reconstruction of SPECT images. The aim of this study was to assess image quality as a function of the number of iterations. For this purpose four figures of merit (FOM) were used: the correlation coefficient between the pattern and the actual reconstruction (CC), the background coefficient of variation (CV) and the contrast (CON) and signal-to-noise ratio (SNR) of each ROI. CON and SNR were defined as: CON=(S-B)/(S+B), SNR=(S-B)/aB, (S: signal, B: background). A relaxation parameter with a value of 0.1 was used in ART and an acceleration factor of 2.0 was employed in MLE. The study was carried out using a simulated chest phantom which included lungs(L) (CON = 1) and a hot circle (C) (CON=0.5). Scattering, non uniform attenuation, noise and PSF were taken into account in projections and in the reconstruction process. Total counts in projections were 4xl0 s. The results over 10 runs showed that CC reached a maximum for I 1 iterations in ART and 28 in MLE. The values of FOMs were: lter 11

CC 0.93

CV 24.8

CONL

CON

SNRL

SNRC

0.82

0.40

3.64

5.46

28

0.93

29.4

0.78

0.44

2.97

5.37

1

0.82

26.9

0.21

0.42

1.31

5.46

where the last row corresponds to the values obtained after the filtered backprojection with a Metz filter and correction of attenuation using the Chang method (with an uniform attenuation coefficient). On the basis of our results ART and MLE appear to be equivalent with respect to FOMs and attain better values than filtered backprojection. 1241

(/) 0 O.

•

Physics and Instrumentation

PMo841

PMo843

M. Lyra, Skouroliakou K., Pappas D*, Tsoukas T.**. Areteion Hospital, University of Athens, Department of Nuclear medicine. *General Air-Force Hospital, Department of Nuclear Medicine. **Deree College, Athens.

B. K a s a l , S. Lon~ari~, D. D o d i g Clinical H o s p i t a l C e n t e r - Rebro, D e p a r t m e n t of N u c l e a r M e d i c i n e a n d R a d i a t i o n Protection, Z a g r e b , Croatia

EVALUATION OF THREE DIMENSIONAL DISPLAYS IN NUCLEAR MEDICINE Single Photon Emission Computed Tomography has now become routine in most nuclear medicine laboratories The most common form of display of SPECT data is a two dimensional mode using an interactive programme that allows the user to view a 3D dataset one slice at a time. This type of display does not provide an accurate idea of the size and shape of the organ in three dimensions. Therefore with the computer technology development, there is an obvious tendency towards the use of three dimensional displays. The -{-camera we use (GE Starcam) offers the option of full three dimensional displays using three methods of reconstruction, namely distance, angle and threshold shaded. At all instances we can apply a gradient shading on the three dimensional images produced. According to the type of the scan (heart, brain, liver, bone e.t.c.) we tried to optimize the three dimensional images by using appropriate reconstruction filters and attenuation correction algorithms. By ROC curve analysis we statistically evaluated the diagnostic quality of three dimensional images of different organs and estimated the specificity of the method. Compared to the SPECT slice method the 3D reconstruction method proved to be a valuable tool contributing to more confidential diagnostic results.

PMo842 Pinheiro M.J., .Correia L., Gramaxo M.I. Department of Nuclear Medicine, Oporto Medical School and Portuguese Oncology Institute, Portugal A FRACTAL UNIFORMITY

APPROACH

TO

TEST

GAMMA

CAMERA

Quantitative measurements of gamma camera uniformity are processed by a variety of performance parameters described in the literature and used in all the Nuclear Medicine Departments. This parameters are related with the planar gamma camera performance and they are established using statistical concepts concerning the static matrix. In this work, the acquisition matrix is modified by a rule (Iterated Function System) and lead us to a fractal view in two different directions: hot and cold areas. In the collection of mappings obtained with these rules the properties of self similarity and independence are maintained. Iteration of these mappings results in convergence to the fractal attractors of the Iterated Function System. An index of uniformity is defined using the two collections of generated mappings. The method was tested in theoretical matrices and in real acquisition matrices using a central field of view of 2500 pixels with the mean pixel count of 4000 counts. The process was tested in several configurations. In all these configurations we calculated the fractal index and all the indices generally used (NEMA index, Cox and Diffey index). This new index was compared with the others and we conclude it is more sensitive and contains more information about the uniformity matrix.

1242

GAMMA CAMERA FWHM AS MEASURED BY BAR PHANTOM AND FOURIER SPECTRUM ANALYSIS S p a t i a l r e s o l u t i o n of a g a m m a c a m e r a is u s u a l l y a s s e s s e d b y i m a g i n g a b a r p h a n t o m , w h i c h is a r a t h e r subjective approach. For better results more than one o b s e r v e r s h o u l d b e involved. O n t h e o t h e r s i d e t h e r e a r e e x a c t m e a s u r e m e n t s u s i n g a line s o u r c e of radioactivity. T h i s l a t t e r m e t h o d i n v o l v e s u n p l e a s a n t filling of a line s o u r c e , p o s s i b l e p r o b l e m s w i t h c o n t a m i n a t i o n , activity c o r r e c t i o n s for d e c a y if m o r e m e a s u r e m e n t s a r e to b e d o n e , etc. So m e a s u r e d F W H M s of a c o l l i m a t e d g a m m a c a m e r a a r e valid only for n a r r o w s t r i p s o n t h e d e t e c t o r face a n d , if a n a v e r a g e F W H M is w a n t e d , m o r e m e a s u r e m e n t s a r e to b e d o n e . T h e l a s t r e m a r k h o l d s for "edge' m e a s u r e m e n t s too a n d a m e t h o d w h i c h w o u l d give a n a v e r a g e FWHM is d e s i r a b l e . I n t h i s w o r k t h e r e s u l t s of e x p e r i m e n t s a r e g i v e n w h i c h s h o w t h a t it is p o s s i b l e to c a l c u l a t e t h e a v e r a g e FWHM of a g a m m a c a m e r a b y s i m p l y i m a g i n g a b a r p h a n t o m . FWHM and an index calculated from the F o u r i e r s p e c t r u m of t h e slice t h r o u g h t h e b a r p h a n t o m image show a simple continuous and monotonous r e l a t i o n s h i p . A s t h e F W H M is i n c r e a s e d b y a n y m e a n s (in t h i s w o r k b y c o n t r o l l e d a d d i n g of P e r s p e x plates), t h e i n d e x is d e c r e a s e d a n d t e n d s to zero w h e n t h e b a r s b e c o m e j u s t r e s o l v a b l e or invisible. T h e r e s u l t s h a v e b e e n d o u b l e c h e c k e d b y c o m p a r i n g to c l a s s i c a l line source method and good agreement has been found. Possible influences on the results are discussed. T h e m e t h o d h a s b e e n f o u n d v e r y s i m p l e to u s e a n d , a s m o s t of it is p e r f o r m e d b y c o m p u t e r , t h e j o b c a n b e d o n e b y a n y t e c h n o l o g i s t a n y t i m e w h e n n e e d e d . It is e x p e c t e d t h a t t h e m e t h o d itself is n o t d e p e n d e n t o n t h e g a m m a c a m e r a u s e d , w h i c h is n o w u n d e r i n v e s t i g a t i o n .

PMo844 D. Lan,qe, U. Noelpp ~. Dep. of Nuclear Medicine, Universitiy of Heidelberg, FRG # Dep. of Nuclear Medicine, University of Berne, Sw tzer and EXPERIMENTAL QUANTIFICATION OF IMAGE CONTRASTREDUCTION DUE TO SCATTER AT AND PENETRATION OF COLLIMATOR-SEPTA The contrast-reduction of images depends on photons transversing the collimator outside collimation rules. Photons penetrating the septa of the collimator have identical energies compared to collimated photons. Their contribution to the image countrate is independant of the window setting. Photons scattered at large angles can be distinguished due to their reduced energy. An experimental setup is presented to quantitate the contrastreduction just by simply measuring the countrates of imaged pulses of a point source. Method: Collimators are investigated with point sources at a distance 12 cm from the surface. Collimated photons are totally suppressed by a special shielding material. Systematic variation of the absorber dimension allows to extrapolate the counting results to the realistic image countrate of an unshielded source. Results: Scattered photons produce 1 - 2 % of the whole image countrate depending on the lower level of the window. It does not depend significantly on the type of collimator. The penetrating countrate is lowest for Tc-photons and Tc-longbore collimators ( 1 - 2 % resp. ), increasing from 10 % for Tc-99m (HiRes collimator) up to 50 % for 364 keV photons (400 keV collimator) and tremendeously to 54 - 73 % for 511 keV photons (511 keV collimator), resp. Conclusions: Penetration is highly underestimated reporting only the penetrability of one collimator-septum Planar projection images of 511 keV photons measured with state of the art collimators include ,,real" collimated pulses only at a level 1 out of 2 to 4, i.e. 27 - 45 % of the countrate in the best case - in air.

• Dosimetry and Radiation Biology Dosimetry and Radiation Biology PSu845 Fabrice Perin. Laurence Routledge, Grrard Normier#, Thierry Baussant#, Alain Le Pape. Biophysique Cellulaire et RMN, CNRSInserm U31& Tours and # Pierre Fabre Mrdicaments, Boulogne, France. CHARACTERIZATION OF THE IN VIVO BEHAVIOR OF THE J001 ACYLATED POLY-(I,3)-GALACTOSIDE I n t r o d g e t i o n : The aim of this study was: i) to investigate the pharmacokinetics and, biodistribution of the J001 molecule which is a macrophage targeting agent dedicated to inflammation imaging and ii) to characterize the radioactive forms in plasma and urine. Methods: J001 was labeled either with 99mTc or 3H (mild oxidization of the galactopyranose residues by galactose oxydase followed by reduction with 3H-borohydride). Radiochemical purities were 98% and 95% respectively. Male Wistar rats were intravenously injected with either 1.2 MBq 3H-J001 or 37 MBq 99mTc-J001. Organs, blood, urine and feces samples were serially collected throughout the study up to 10 days after injection for tritium experiments. Radioactivity of each sample was measured. Serum and urine were analyzed by exclusiondiffusion radioHPLC. Results: For 99mTc-J001, blood pharmacokinetics fitted with a two compartment model (T1/2ct =35 min; T1/2 13=8h). Target organs were essentially the liver (11%) and the kidne3/s (9%). The molecule was excreted mainly via urine (20% during the first 3h, 25% over a 24h period) with negligible excretion in feces. HPLC analysis of urine showed that 99mTc radioactivity was eliminated as a J001 metabolite corresponding to 99mTc-pyrophosphate with some (<10%) reduced Tc and TcO4- resulting from reoxidization. In serum, in addition to the 99mTc-J001 peak, labeled albumin resulting from transchelation (15%) and reduced Tc (5-10%) were observed 30 rain after i.v oh the HPLC profiles, Following injection of 3H-J001, 10% of the injected dose was found in liver and 2°2% in kidneys. Radio-HPLC of serum evidenced a progressive metabolization of the molecule with time: metabolites of 9 kD MW after 30 min, <2 kD of MW after 12-24h, then only micromolecular labeled fractions were detected on chromatograms.

PSu847 Z. Szybi~ski, P.~Ilko, Z.qic~Jiadomski Jagie]~onian University, Collegium ;~edicum, Cbair and Oepartnent of Endocr~nilo~y, Institute of Physics, Craco'% Poland THYROTO OOSINETRY AFTER CHERNO~YL ACCIDENTTN IOOI~4E

OFFICIEHT AREAS.

Thyroi:i dosimetry after Chernoby! accident in near and Far fie!ds is essential for calculation of the thyroid cancer risk coefficient due to radiation. The most recent variant or the mu!ticompartment dilution type kinetic model of iodine was created by Johnson, assumed that parameters reflpctin~l the transfer of iodice From the inorganic poe? into the bladder are fairly independin 0 of age, weight and are not qreatly affected by changes in the dietary intake of iodine. This value approximates the avaraoe values summarized by ICRP's Task Grouo on Reference ~an. However nationwide study or iodine deficiency in Poland preformed in 1999/i995 disvovered that Jn the Sudeten and Carpathian areas the northeastern part of Poland 40-80 % of children 6-13 years old had urine iodine concentrations within i-5(] ~0/!. AFTER Ohernoby! accident, Krak~w and Nowy S~cz districts represented one of the most contaminated areas in Poland. Radiation dose to the thyroid calculated acoordino to Johnson's formu!a depends reciprocally and expotentially on daily iodine intake. Therefore it may by assumed that "committed thyroid dose equivalent" (etde)in an iodine deficient area is significantly understimeted. To verify this hypothesis we carried out with Institute of Nuclear Physics in Krak6w a new calculation of ctde on the basis of real values of iodine intake in schoolchildren 6-13 years old. Calculated radiation dose to the thyroid was about twice higher than the estimated before for southern Poland and in the group of ane year old children ranged 30-80 mSv.

co

i m i

,¢.,,

t~ rID ID f2.

PSu846

PSu848

L. Maffioli, E. Adobati, C. Lequaglie, V. Mongioj, M. Gasparini, E. Seregni, D.R.M. Negri, S. M~nard, E. Bombardieri. lstituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy

E. Miot-Noirault*, S. Dclacroix# A; Mazal#, F. Lacmix#, F. Lafortone#, S. Akoka,* A. L¢ Pape*. * Laburatoire de Biophysique Cdlulalre et RMN-INSERM U316/CNRS-2bis,bd TonneUr-37032 Tours Crdex. # Centre de Protonthrrapie d'Orsay-FRANCE.

BIODISTRIBUTION AND PHARMACOKINETICS OF ][-131 MINT5: A NOVEL ANTI-EGF RECEPTOR MONOCLONAL ANTIBODY. The EGF receptor (EGFR) is overexpressed in 90% of spinocellular lung cancers and in 50% of lung adenocarcinomas. In this work we evaluated the biodistribution and the kinetic behaviours of MINT5, a novel monodonal antibody (MAb) generated against the human EGFR. MINT5 is a routine MAb (IgG1) produced at our Institute. Under thyroid blockage conditions 6 patients affected by non-small cell lung cancer stage III-IV were i.v. injected with 185 MBq (0.5 rag) of radioiodinated IgG1 or its F(ab')2 fragment (mean specific activity = 362 MBq/mg). All patients underwent whole body immunoscintigraphy (R.IS) at scheduled times (2, 6, 24 hours and, daily up to 5 days) after injection. ROIs were drawn over several organs to evaluate biodistribution. The pharmacokinetics was evaluated on blood samples sequentially collected starting at 0', 15', 30', 1, 1.5, 2, 6, 24 hours and daily up to 5 days after injection. No adverse reactions were observed after MAb administration. The elimination half-life (T~AI3) calculated from plasma clearance curves ranged from 21 to 50 hours for the whole MAb and from 13 to 19 hours for its F(ab')2 fragment. Images showed an early and intense hepatic uptake (17.4% I.A. at 1 hr), mainly due to the binding of MINT5 to the hepatocyte EGFRs. These results indicate that MINT5 F(ab')2 shows better biodistribution and kinetics behaviours than the whole molecule. Since the hepatic uptake can be saturated, we are now recruiting patients who will receive at least 20 mg of cold MINT5 prior to injection of 13 II.MAb. This work has been partially supported by AIRC - CNR ACRO project.

Q U A N T I T A T I V E MR IMAGING AS A MONITOR OF LESIONS IN T H E PIG BRAIN AFTER PROTON RADIATION THERAPY. A large animal model has been developed for the investigation of central nervous system response to proton irradiation using magnetic resonance imaging in a quantitative manner. Quantitation of T2 relaxation time was used to monitor the radiation lesions in the pig brain as an indicator for histologic injury as a function of time and dose. For 6 months, we monitored T2 value and the histological changes as the radiation injury progressed through these stages. A total of 14 Male Meishan pigs was studied: 9 irradiated animals and 5 unirradiated controls. A high-dose single-fraction irradiation was delivered to the right hemisphere (40 X 35 nun port), using a 80 MeV proton beam and a 1.83 Gy/min dose rate. Three groups of three animals received 25, 40, and 60 Gy at the 90% isodose respectively. "Spin echo" scans were performed to obtain T2-weighted images, using a 2.35 Tesla Proton Imaging System and a 700 ~m pixel resolution. T2 relaxation time was measured in three regions of interest, within the irradiated and contralateral hemispheres. Histology was performed at various stages of injury, in order to correlate T2 changes with radiation pathology. T2 values were observed to increase after proton therapy; the time course of T2 increase coud be divided into three phases: a transient phase (1 week long) associated with a slight inflammatory process, and two more long-lasting phases (3 to 12 weeks) associated with vascular and tissular lesions respectively. These three phases were observed to be dose dependent for both rapidity of onset and severity. T2 values were becoming higher when the radiation dose increased~ For the three high doses used( 25, 40 and 60 Gy), the higher T2 values (at the maximum of its increase) could be given'by a linear regression fit. These results agree with those obtained after electrons irradiation (1-3). From our results, T2 relaxation time measurements would be a powerfull tool to evaluate tissular radiation-induced complications at their initial stage of development. (1) AJNR 16:79-85,1995. (2) Int.J.Radiation.Oncology.Biol.Phys. 32:121-128, 1995. (3) AJNR 17,May 1996,In press.

1243

ID O 13.

• Dosimetry and Radiation Biology PSu849

PSu851

M. C. Siqueira l, F. Morgado 2, M. E. Camilo 1, M. C. de Moura 1, Centre of Gastroenterology 1, Department of Neurology2, Faculty &Medicine, Lisbon, Portugal

A. Kraoivnv. L. Belo~urova. S. Pughcar

RADIOENZYMATIC METHOD 14C ACETYL-COENZYME A

POSITIVE RADIOMODIFYING EFFECT OF NEW BIOLOGICALLY ACTIVE FOOD ADDITION MADE OF BLACK SEA MOLLUCK

Kharkov Research Institute of Medical Radiology,Department of Radiation Medicine

OF L-CARNITINE WITH

L-carnitine plays a major role in the transport of the activated long-chain fatty acids for [%oxidation in the mitochondria. The carnitine deficiency has been associated with depressed long-chain fatty acid oxidation. The aim of this study was to determine the plasma concentrations of carnitine and its metabolites in patients with myopathic diseases. The study comprised 11 healthy volunteers and 11 patients with neuromuscular impairment. Blood sample was drawn in each subject after overnight fast. The plasma concentrations of free carnitine, short-chain and long-chain acylcarnitine were determined by employing radiochemical enzymatic method. The values were calculated from solutions of L-carnitine chloride. For the control group, free carnitine, short-chain and long-chain acylcarnitine had the following mean values: 32.6±4.95 btM, 4.12±0.95 btM and 1.73±0.15 p.M. The patients with mitochondrial myopathy diseases were divided in two groups: the first group (N=6) had values within the normal range and the mean values were 31.44±3.72 ~tM, 3.52±1.56 IxM and 1.68±0.08 txM, the second group (N=5) had the mean values below the normal range: 18.34±4.74 btM, 2.98±0.81 txM and 1.32±0.11 [aM for free carnitine, short-chain and long-chain acylcarnitine, respectively. In conclusion, this method is suitable for accurate determinations of carnkine and its metabolites in blood plasma in patients with mitochondrial myopathic deficiency.

Radioblological experimental study on 300 rats 0NIstar line) and 500 mice have been performed with the aim to estimate the degree of radlomodlfylng and curing effect of Black Sea mollusk (Mytllus galloprovlnclalis) meat extract, The doses of X-Irradiation were 2,0; 4,0 and 6,0 Gy. Posttlve effect of extract addition to food was shown for X-ray doses of 4,0 and 6,0 Gy, based on blood-forming stimulation, antloxldant and adaptogenous action of extract, Rates of survival In the mane groups of rats and mice were 2 times higher then In control groops (70-80~o of survived animals against 30-40% In control at the 6,0 Gy dose), The mollusk meat extract had to be recommended for use as food addition for radiation-risk group persons,

PSu850

PSu852 J. Lepei, P. Dzdrik M. Messingerova: Department of Nuclear Medicine, Regional Hospital - Bansk~ Bystrica, SLOVAKIA.

F. Montra~crs, C.Rousseau, M. Scddiki, N. Younsi N, K. Kcrrou, J.N. Talbot. Service de Mddecine Nucldaim, h6pital Tenon, F75020 Paris, France

EVALUATION THE EXPENDITURES AND EFFECTIVE USE OF RADIOPH~,RMACEUTICALS BY NEW METHOD.

EVALUATION OF THE FREQUENCY OF MISADMINtSTRAT1ON OF 99mTc-HMDP IN WHOLE BODY BONE SCANS AND ESTIMATION OF THE ACTIVITY REMAINING IN THE INJECTION SITE

The prices of radiopharmaceuticals (RF) represents, no

We rexiewed the whole-body bone scans performed with a dual head camera in 490 patients from july to december 1995 in order m evaluate the frequency of misadministration (partial extravasation of the intravenous dose) of 99mTc-HMDP and to estimate the activity remaining at the site of injection 2h30 post direct IV injection using a leaded syringe. Methods The absence of visuali/ation of the injected site led to the conclusion of absence of misadministration. In case of visualization of the injection site, we determined the corresponding activity by comparison with phantom acquisitions (using geometric mean of counts) and the percentage of relained activity in protxwtion of the injected activity (decay taken ink) account). Results The site of injection was visualized in 155 cases corresponding to a frequency of misadministration of 32% (155/490). On these 155 visualized sites, 46 were masked by lead and consequently could not be quantified. remaimng [ .02-.5 .5-1 1 10 11-50 51-70 71-130 131-150 rm~ge [ acti~it} (MBq) u (109) 52 12 27 11 5 1 l .02 145

/

c.',~/injected [ .04-1 activi~}'~c4.,) n (109) 79

1-2

3 10

11-15

16-20

21-30

ll

lI

4

3

1

range ] .04-27

I

Conclusion These results show that misadministration of 99mTc-HMDP is not rare but correspond in the majority of cases to weak activities. However, in unfrequent cases, the remaining activity may be as high as 145 MBq (27% of the administered activity) without any clinical sign or complaint from the patient. 1244

negligible part of costs for nuclear medicine delSartments. F o r management of laboratories, particularly in private practice, it is important to analyse costs and economical consumption of RF. Due to different physical half-life of radiotracers and other variables this evaluation is difficult. We developetl software fol: e v a l u a t i o n t h e expenditures and effective utilrsation of all radiotracers and pharmaceuticals. We s u g g e s t e d the new Philosophy for evaluation of this rather c d m p l i c a t e d data.-Routinely measured activity of vial and injected doses with b o o k keeping system to enable software to generate some global parameters describing the economy of management and individual data for evaluation of all radiopharmaceutical~. The system ameliorate planing of the patients studies and to ordering of RF. The program is easy to understanding and obviously represent results by graphs and windows. In our department were used this method during 3 years. Global price of RF were rose by index of 1.5 during that period. In comparison with 1992 were economised more then 3500 USD per year. Mean value of supposed index ERAI (economy of radiopharmaceuticals index) risen from 0.58 to 0.92 and price of RF per application changed minimally. We conclude that this approach is useful for decision process in RF utilisation and retrospective analysis for management of the nuclear medicine departments.

•

Dosimetry and Radiation Biology/Radiochemistry and Radioassays

PSu853 Larysa L.Stadnyk, Leonid Z.Kalmykov. Kharkiv Reseach Institute of Medical Radiology. Department of Dosimetry and Radiation Safety

Radiochemistry and Radioassays PSu855 S.J. Yeh , C.P. Lin, B.T. Hsieh, W.Y. Lin, S.J. Wang. National Tsing Hua University, Institute of N u c l e a r Energy R e s e a r c h and T a i c h u n g Veterans General Hospital, Taiwan, R.O.C.

THE LEVELS OF OCCUPATIONAL E X P O S U R E A N D R I S K ESTIMATES FOR STOCHASTIC EFFECTS OF RADIATION FROM DATA OF CENTRALIZED SERVICE OF PERSONAL DOSIMETRIC CONTROL OF MEDICAL RADIOLOGISTS IN THE UKRAINE Close control over the doses of staff exposure and performing unjustified exposure limitation measures are important constituents of the radiation safety assurance during work with medical radiation sources. Centralized service of personal dosimetric control (PDC) of medical radiologists in the U k r a i n e has operated for more than 15 years. The number of medical workers c o v e r e d b y centralized service of PDC is about 4500 persons. A considerable amount of information on collective and mean annual doses of staff exposure, on doses dynamics during observation years, on personal annual dose distribution for different types of work with radiation sourses in medicine and among different occupational groups has been accumulated. Critical groups have been separated and risk of somatic and genetic effects has been assessed. Mean annual doses of medical radiologists were 1.3 - 2.5 mSv and doses of medical roentgenologists were 1.0 - 4.1 mSv. According to the mean annual dose level and to the fraction of persons obtaining doses more than 0.3 MAD ( 15 mSv ) the critical groups were separated from medical radiologists performing radiotherapy with enclosed sourses of gamma radiation. Mean annual doses of handlers of radioactive substances and radiomanipulation paramedical personnel exceed or approach 0.i MAD (5.2-8~5 and 2.2-5.0 mSv). Risk of somatic and genetic effects comprises no more than 1 % of natural frequency. Further optimization of radiation protection during work with medical radiation sources should be aimed at the reduction of dose loads in the professional groups of higher risk and cost-benefit analysis.

showed that high labelling e f f i c i e n c y was o b t a i n e d in each preparation. A l t h o u g h the b e h a v i o r of these R e - 1 8 8 - S n - H E D P complexes was quite similar, but the b i o d i s t r i b u t i o n p a t t e r n of carrier free Re-188Sn-HEDP was v e r y m u c h different.

PSu854

PSu856

JM. Marti-Climent, I. Pe~uelas, JA Richter, PETCUN Center. Department of N u c l e a r Medicine, Univ e r s i t y H o s p i t a l of Navarra School of Medicine. Pamplona. Spain.

F. Perin. E. Miot-Noirault, G. Normier#, A. Le Pape, Biophysiqu~ Cellnlaire et RMN, Inserm U316, Tours and # Institut de Recherche Pierre Fabre, Lab~ge, France.

R A D I A T I O N P R O T E C T I O N IN A CLINICAL PET CENTER

SCINTIGRAPHY OF INFLAMMATION: OPTIMIZATION OF 99roTe-J001 IMAGING IN EXPERIMENTAL ARTHRITIS

The radiation p r o t e c t i o n a r o u n d a PET Center depends on its level. The objective of this study is to present radiation protection elements around a clinical PET Center e q u i p p e d with a Cyii clone 18/9 IBA cyclotron, five targets ( C, 13N, 15O, 18F-, [18F] F2), a c o m p l e t e r a d i o c h e m i s t r y laboratory (with fully automatic synthesis modules) and a ECAT-EXACT HR+ Siemens PET scanner. The following radiation p r o t e c t i o n elements w e r e considered to reduce and prevent r a d i a t i o n risks to personnel and public: (i) Shielding: in the cyclotron vault (1.8-2 m concrete), hot cells (6 cm Pb), laboratory, Scanner and a d m i n i s t r a t i o n rooms. (2) Specially designed lead p r o t e c t o r s for h a n d l i n g and transporting r a d i o a c t i v e m a t e rials. (3) C o m p u t e r controlled v e n t i l a t i o n system in areas were radioactive gases are used (air r e n o v a t i o n s per hour, underpressure, g a m m a radiation detectors in smokestacks connected to the central control system), c o n s i d e r i n g a possible accident. (4) A d m i n i s t r a t i o n and evacuation of radioactive gases to the patient. (5) Radiation detectors: gamma and neutron area monitors, p o r t a b l e survey meters, c o n t a m i n a t i o n detectors, hands and feet detector, direct reading p e r s o n a l dosimeter and w h o l e body and ring t h e r m o l u m i n i s c e n c e detectors. (6) Safety interlocks and r e s t r i c t e d access to c o n t r o l l e d radiation areas, especially to the cyclotron vault. (7) Procedures for h a n d l i n g activities as high as 2000 mCi of 18F-. We remark the special c h a r a c t e r i s t i c s of a fully equipped clinical PET Center to ensure radiological protection of personnel and public.

THE EFFECT OF R E A C T I O N CONDITIONS ON PREPARATIONS OF RHENIUM HYDROXYETHYLIDENE DIPHOSPHONATE COMPLEXES D i p h o s p h o n a t e s labelled w i t h T e c h n e t i u m - 9 9 m were w i d e l y used as b o n e - s e e k i n g agents. Rhenium-186 h y d r o x y e t h y l i d e n e d i p h o s p h o n a t e has also been shown to localized in m e t a s t a t i c foci w i t h i n bone in a m a n n e r similar to T c - 9 9 m b o n e - s e e k i n g agents. U s u a l l y in the p r e p a r a t i o n of diagnostic T c - 9 9 m r a d i o p h a r m a c e u t i c a l s the concentrations of Tc were at

tracer

level

(~i0 ~7

M).

But

for

Re-186

r a d i o p h a r m a c e u t i c a l s large amounts of carrier (~10 -3 M) exist, w h i c h may s i g n i f i c a n t l y affect the p r e p a r a t i o n of Re-Sn-HEDP. In this study Re-188 was u s e d as a tracer of Re. The effects of pH, amounts of reluctant and concentrations of Re carrier on the p r e p a r a t i o n of R e - S n - H E D P has b e e n investigated. R e - 1 8 8 - S n - H E D P have been p r e p a r e d by r e c o n s t i t u t i o n of the kit of lyophilized m i x t u r e of HEDP, tin chloride w i t h a radioactive solution of p e r r h e n a t e in saline. The total c o n c e n t r a t i o n of Re present was this work is on the order of 10 -7 to 10 -2 M° The results

0 |m 4~ 4~

C (D 0~ Q.

J001, an acylated poly-(1,3)-galactoside purified from the membrane of K. pneumoniae, associates electively with macrophages (M~) via binding to CD14 and CD1 lb molecules. Labeled with 99roTe, J001 constitutes a probe for the scintigraphic imaging of inflammatory lesions. The objectives of our study were to define an optimal protocol for 99mTcJ001 imaging and also to document the specificity of J001 scans in arthritis. Indeed, in addition to Me) recruitment, inflammatory process is characterized by an increase in vascular permeability and occurence ot edema likely to lead to non-specific concentration of J001 in lesions, whatever the intrinsic specificity of the probe. Methods: In NewZealand rabbits with moderate antigen-induced arthritis, a dose-range study was conducted using specific activities (SA) ranging from 370 to 11840 MBq.mg-I while the i.v. injected activity was constant (37 MBq per animal). For each preparation, radiochemical purities (RP) were determined together with in vivo stability of the 99mTc-J001 complex (using radio-HPLC of serum sampled lh post-injection). Images were acquired at 2, 3 and 4h, the data analysis being done with region-ofinterest method and Student's t test for statistical analysis. Moreover, J001 scans were compared to scintigrams obtained after i.v. injection of 99mTcO4" (tracer of edema), 99rnTc-albumin nanocolloids (vascular) and 99roTe-J001 relieved of radioactive colloidal fraction likely to be generated due to J001 amphipathic properties and use of SnF2 for the labeling. Results: For SA>5920 MBq.mg-1, RP degradations and in vivo 99mTc transchelafion to albumin were .noted. To prevent significant in vivo transchelation and hydrolysis likely to impair imaging specificity, the optimal SA was found to be 1480 MBq.mg-1 corresponding to 25 ~tg of injected J001 (p<0.001). Better lesion-to-healthy tissue contrasts were obtained at 3h. Results obtained with the various traeers support the hypothesis that M# targeting is the main factor involved in the J001 imaging of arthritis, with limited contributions of edema and vascular disturbances (9<0.02). Eur J Nucl Med 1996; 23: 61-68.

1245

4~

0 0.

• Radiochemistry and Radioassays PSu857

PSu859

El. Cynowska,* J.M. Stomifiski,* J. Wyrwifiski,** K. Kurowski.*** J.Skokowski,*** P. Lass** *Dept.of Pneumonology, ** Dept. of Nucl.Med., *** Dept. of Thoracic Surgery., Medical University of Gdafisk, Poland

A. Garc[a-Burillo, G. Encabo, T. Canela, M. Soler, S. Aguad6, D. Garcla-Pdrez, JA de Tortes. Hospital General Universitari Vail d'Hebron. Barcelona, Spain. NMP22: A TUMOR MARKER FOR TRANSITIONAL VESICAL CARCINOMA.

Can we improve diagnosis of lung cancer using IRMA Cyfra 21-1 ? The IRMA Cyfra 21-1 assay is a test which measures in serum fragments of cytokeratin 19. C~okeratin t9 is s specific protein of simple epitheliums and expressed also in lung cancer tissues . The aim of our study was to assess clinical value of Cyfra 21-1

immunoradiometfic assay from Cis bio

international for lung cancer. We evaluated this marker in 196 patients with lung cancer I 167 NSCLC and 29 SCLC/. Using a cut off level of 3.3 ng/ml sensitivity for all patients was 37% but 24% for SCLC and 39% for NSCLC. In NSCLC patients concentration of Cyfra 21-1 tended to be associated with tumor size and significantly correlated with

lymph node involvement / Kruskal-

Wallis test/. Sensitivities for tumor burden were respectively T2 - 27% T3 48%, T4 - 67% and NO - 22%, N1 - 34%, N2 - 51%, N3 - 82%. Significantly higer level / p< 0.0001 / was elevated in group with metastases M1 / median 18.9 ng/ml / as compared patients without metastases M0 /median 1.89 ng/ml/. Sensitivity in these groups were 85% and 32% respectively. In NSCLC patients positive Cyfra 21-1 levels were observed in 19% of stage 1, 15% of stage II,

Introduction: The nuclear matrix is a three dimensional protein structure in the nucleus that functions as the structure for organizing the genome. Nuclear matrix proteins had been shown to vary by cell type, stage of differentiation, cell cycle and type of cancer. They are released into the body fluids through cell death or apoptosis, making them suitable targets for immunoassays. Aim: To determine role of NMP22TM as an indicator of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. Population: We have collected urine samples from 66 patients with surgically treated transitional cell carcinoma and from 31 normal healthy volunteers. We performed an enzyme immuneassaydeveloped against a nuclear matrix protein called NMP22r~ (Matritech NMP22TM Test Kit), This nuclear protein is found in epithelial ceils and it's level of expression is 10 fold greater in cancer cells than normaI cedis. Results: NMP22 values in normal healthy volunteers was 3.8 4- 1.6 U/ml (range 1.6-7.2). We established the cut-off level in 7.2 U/ml (percentil 96). The NMP22 mean value in the patients was 19.8 ± 39.8 U/ml (range 2,2-227) (p =0.0015). 27 out of them (41%) presented with values higher than 7,2 U/ml. 40 patients whithout tumor on follow*up cytoscopy showed a NMP22 mean value of 8.8 + 10.8 U/ml (range 2.2-65.6) against 26 patients whith tumor evidency on follow-up cytescepy who had a NMP22 mean value 34.6 -+ 59.6 U/ml (range 2.2227) (p =0.0385). The sensibility of the assay was 54%, specificity 67 %, PPV 52 %, NPV 69% and global value 68%. Conclusions: NMP22 value can predict a patient's disease status and it can be usefull in the early diagnosis of recurrence, better and with a higher sensibility than citelogy. It's a quantitative, non-invasive enzyme immunoassay that can avoid the subjectivity of citology. Further studies are warranted to determine the cost effectiveness of NMP22 and it's impact on the patients' quality of life.

36% of stage IIIA, 63% of stage IIIB and 85% of stage IV. Consequently, the marker was significantly lower in patients who were

operated upon when

competed with unresectable ones / p< 0.O001/. IRMA Cyfra 21-1 is clinicaly useful. In NSCLC concentration of Cyfra 21-1 correlate with the stage of disease. High levels and the highest sensitivites were observed in patients with metastases.

PSu858

PSu860

Luca Giovanella, Luca Ceriani, Bianca Beghe'*, Mauro Bandera* and Giuseppina Roncari

G. Encabo, A. Garcfa-Burillo, T. Canela, M. Soler, S. Aguad~, J. Morote. Hospitals Vail d'Hebr6n. Barcelona. Spain.

Nuclear Medicine Centre and *Pneumo/ogy Division- Regional Hospital of Varese, Verese (Italy) Immunoradiometric assay of neuron-specific enolase (NSE) and soluble fragment of eytokeratin 19 (Cyfra 21.1) in small cell lung cancer (SCLC): clinical results and biological hypothesis BaekgroundNSE is a well-known marker for the biochemical support of clinical evaluation and follow up of SCLCImmunoistochemical studies demonstrated that all lung cancer subtypes can express both neumfilaments and cytokeratins and particulady SCLC variants can express only cytokeratins. Cyfra 21.1 immunoassay detect the soluble fragments of cytokeratin 19, particularly expressed by tung cancer. AimEvaluation of the diagnostic performance of NSE, Cyfra 21.1 and their combination in SCLC and correlation between markers serum levels, disease extension and prognostic stratification. Material and methods62 pts.with histological diagnosis of SCLC entered in the study: 28 have limited disease (LD) and 34 extensive disease (ED). Tumor markers were assayed by IRMA methods (Prolifigen NSE Ab

Sangtec, Bromma, Sweden and ELSA Cyfra 21.1 CIS Biointernational, France),We evaluate the sensitivity of the markers at a 95% pre-fixed specificity in a control group of 100 patients affected by chronic obstructive disease of the lung.The Mann-Whitney U test was employed to evaluate the correlation between markers and disease extension and the prognostic value of NSE and Cyfra 21.1 was tested by univadate and multivariate analysis. ResultsNSE demonstre a sensitivity of 0.52. 0.42 and 0.62 and Cyfra 21.1 of 0.61, 0.64 and 0.59 in all cases, LD and ED cases, respectively. The markers combination have an overall sensitivity of 0.80 (0.78 LD and 0.82 EO).Our data demonstre a correlation between SCLC extension and NSE serum level (p=0,001) only. On the other hand log-rank (p=0.001) and Cox's model (p=0.003) analysis showed that Cyfra 21.1 is superior to stage and NSE as prognostic parameter. Discussion and conclusionsNSE and Cyfra 21.1 have a comparable sensitivity in SCLC but NSE only is useful in the disease staging. On the other hand Cyfra 21.1 is a valuable prognostic marker: this finding could be related to a relative major de-differentiation of the cancer cells or to a presence of epithelial cells in SCLC tissue. In conclusion Cyfra 21,1 can be useful in the SCLC patients stratification and therapeutic planning.

1246

BEHAVIOUR OF FREE AND PATHOLOGY.

TOTAL

PSA RATIO

IN

PROSTATIC

Introduction. PSA has been converted as the gold tumor marker in prostate cancer management and it is very usefull in the early diagnosis of this neoplasm. Cuantification of free and total PSA ratio in equimolar form can provide an incresase of specificity in a range of PSA where a great overlap exist in patients with BHP and Pca. Objective. To analize the behavior of free and total PSA ratio in patientes with prostatic pahology and it clinical implication. Matherials and methods, We evaluate free and total PSA levels and its ratio in 319 patients cIasified as 128 BPH (30 of them complicated BPH), 60 new diagnosed Pca (27 M0 and 33 M1) and 131 treated Pca (79 in CR-PR and and 52 in P). We performed sextant biopsies by ultrasonography in all patients with new diagnosis when a suspicious rectal examination or total PSA higher than 4 ng/ml except in patients with complicated BPH. PSA cuantifications were performed by Tandem ® and Tandem free" PSA (Hybtritech) and its ratio was calculated in percentage. Results. Mean free/total PSA ratio was 21.1 in BPH and 7.9 in new diagnosed Pca patients (p<0.0001), In BPH group it was 22.1 in non complicated and 17.9 in complicated BPH (p ns). In new diagnosed Pca group it was 8.9 when MO and 6.7 when M1 (p ns). In treated Pca patients it was 37.5 when CR-PR and 9.1 when progression (p<0.0001). Of the 56 patients with new diagnosis and total PSA between 4.1 and 20 ng/ml, 34.6 of ncBPH (9/24) and 31.6% of cBPH (6/19) had a free/total PSA ratio higher than 18% while all Pca patients (13/13) had this ratio under 18%. Conclusions. Free and total PSA ratio was significantly higher in patients with BPH than new Pca. It was similar in patients with non complicated and complicated BPH. It was similar in new Pca patients MO and M1 and it was significantly lower in treated Pca patients with progression related to those with clinical response. Aplication of 1 8% ratio can provide an increase of diagnostic specificity when torn) PSA range from 4.1 an 20 ng/ml and in this serie it couId avoid 34.6% of biopsies without any decrease in diagnostic capacity.

•

Radiochemistry and Radioassays

PSu861

PSu863

G. Encabo, A. Garcfa-Buri~lo, T. Canaia, M. Solar, S. Aguad~, J A Lorente, J Morote. Hospitals Vail d'Hebron. Barcelona, Spain

M. G y s e m a n s ( 1 ) ,

VALUE OF BONE ALKALINE PHOSPHATASE (BAP) IN STAGING AND FOLLOW-UP OF PROSTATE CANCER OBJETIVES: To analize the value of BAP in prostate cancer patients to determine whether or not can provide valuable additional information to PSA, regarding the degree of skeletal involvement of prostate cancer as in follow-up of disease. MATERIAL AND METHODS: BAP and PSA serum concentrations were determined in 235 prostate cancer patients included in t w o groups: 140 newly diagnosed untreated prostate cancer patients (72 M 0 and 68 M1-4). Extend of disease (EOD) was stablished according to bone scan criteria proposed by Soloway et al. in 7 2 M 0 , 17 M 1,21 M2, 22 M3 and 8 M4, and 96 follow-up treated prostate cancer patients (65 M 0 and 31 M1-4}. In M 0 patients, 9 had local progression, 5 lymph node progression and 7 hone spread (mean follow-up 56.4 months). Cut-off values for both markers and cl{nical efficacy according to state of disease were determined. RESULTS: BAP was more efficient than PSA in predicting positive bone scans and its level was significantly related to EOD whereas PSA was only able to distinguish between M 0 and M1-4. The highest efficiency to predict a positive bone scan was found for BAP cut-off value between 2 0 and 30 ng/ml, leading to negative and positive predictive values (NPV and PPV) of 98.2 and 92.6%. Combination of BAP and P S A < 2 0 ng/ml yielded NPV and PPV of 100 and 98.5%. In follow-up, mean BAP in M 0 patients was 10 ng/ml and 50 ng/ml when bone scan became positive (p < 0 . 0 0 0 1 ). NPV and PPV for BAP 20 ng/ml were 97.2 and 2 8 % (Odds Ratio 8.3). PSA cannot distinguish between lymph node progression and bone spread during follcw~up (p = 0 . 1 4 6 5 ) . In 31 M1-4 patients, 55% had BAP rise after three months of hormone blockage. BAP was significantly higher in stable or progression disease (198 and 2 5 4 ng/ml) in front of partial or complete response (45 and 33.5 ng/ml). PSA cannot distinguish between partial response and stable disease. However, a significant correlation was observed in longitudinal study between BAP and PSA concentrations in 5 7 . 5 % of cases. CONCLUSIONS: BAP is more efficient than PSA in detecting and predicting extension of bone disease in prosta'te cancer patients. BAP and PSA < 2 0 ng/ml let us foretell a negative bone scan. In follow-up, BAP can statistically distinguish between lymph node and bone dissemination; when PSA level increases, BAP> 20 ng/ml is useful to point out bone scan performance.

(i) (2)

J. M e r t e n s ( 1 ) ,

J. L e y s e n ( 2 )

VUB-cyclotron,Brussels,Belgium Janssen Research Foundation,Beerse,Belgium

SYNTHESIS

OF

II25-LABELED

I-(2-METHOXY-4-IODO-

PHENYL)-4-[4-(2-PHTALIMIDO)BUTYL]PIPERAZINE 4-II25-NAN-190, A POTENTIAL RADIOLIGAND FOR 5-HTIA RECEPTOR.

OR THE

Brain 5-HTIA receptors have been implicated in various neurological and psychiatric disorders s u c h as anxiety, depression, sleep and eating disorders. NAN-190, an arylpiperazine analogue w i t h h i g h a f f i n i t y f o r t h e 5 - H T I A r e c e p t o r , is a potentially useful precursor for the development of a r a d i o i o d i n a t e d 5 - H T I A r e c e p t o r tracer. For the incoporation of a r a d i o i o d i n e in t h e l-(2-methoxyphenyl)piperazine moeity (MPP) of N A N - 1 9 0 t w o s y n t h e t i c m e t h o d s w e r e c o m p a r e d : i__~. direct electrophilic radioiodination using chloramine T or p e r a c e t i c acid (H202/HOAc) as o x i d i z i n g a g e n t a n d 2__~.n u c l e o p h i l i c C u + a s s i s t e d *I for Br exchange in acidic and reducing m e d i u m . M P P a n d N A N - 1 9 0 as w e l l a s t h e i r 4 - B r analogues (custom made) w e r e u s e d to e v a l u a t e the efficacy of the labeling methods. E l e c t r o p h i l i c r a d i o i o d i n a t i o n w a s c a r r i e d o u t at 25 °C f o r 15 min. r e s u l t i n g in a l l c a s e s in a m i x t u r e of * I - c o m p o u n d s w i t h l o w l a b e l i n g y i e l d (~16%/*I-comp.) and therefore proved to be unsuitable. The nucleophilic *I for Br e x c h a n g e on 4 - B r - M P P and 4-Br-NAN-190 was performed at 140 °C d u r i n g 60 min. yielding 71 and 60% respectively of t h e 4-*I-compounds. Using the latter labeling method and after RP-HPLC purification followed by minicolumn recovery >99% p u r e 4 - I I 2 5 - N A N - 1 9 0 c o u l d be o b t a i n e d . The in v i t r o evaluation of 4 - I I 2 5 - N A N - 1 9 0 is p r e s e n t l y b e i n g c a r r i e d out.

C 0 =l.a

C 0 0

PSu862

PSu864

A.Zissimopoulos, N.Baziotis, X.Geronikola-Trapali, P.Thalasslnou, E.Drakou, E.Yakoumakis. Nuclear Medicine Dept Greek Anticancer Inst. "St.Savas" Hospital, Athens, Greece.

D. T e r r i e r e ( 1 ) , A. H e r m a n n e ( 1 ) , J. M e r t e n s ( 1 ) , J.E. L e y s e n ( 2 ) . (1)VUB-Cyclotron,Brussels, Belgium. ( 2 ) J a n s s e n R e s e a r c h F o u n d a t i o n , B e e r s e , Belgium.

EVALUATION OF THE SERUM CA 549, CA 27-29, S.A.P. AND CA 15-3 TUMOR MARKERS LEVF]~S IN PATIENTS WITH BREAST CANCER. CORELATION WITH BONE SCINTIGRAPHY.

RADIOSYNTHESIS OF A N E W R A D I O B R O M I N A T E D LIGAND F O R 5HT2 R E C E P T O R S , A P O T E N T I A L T R A C E R F O R PET.

AIM : The aim of this study was the evaluation of CA 549, CA 27-29, Skeletal Alkaline Phosphatase and CA 15-3 serum levels in patients with breast cancer in several stages and the corelation with the results of bone scintigraphy. PATIENTS AND METHOD : We studied 168 patients with breast cancer 159 women and 9 men (mean age 61,3 years) in several stages . Also we studied 52 healthy individuals (blood donors) to estimate the cut-off value. All the patients had a bone scan. The method we used was the RIA and immunoradiometric assay (IRMA) with kits CA 549, SAP (Hybritech) CA 27-29 (Biomira), CA 15-3 (BYK Sagndec). RESULTS : The cut off value was for the CA 549 12, 5 U/ml, CA 27-29 18 U/ml, SAP 12 ~g/l, CA 15-3 30 U/ml. CA 549>12,5 CA 27-29>18 SAP>I2 CA 15-3>30 Pati~qts with hh=93 18/93 19% 8/93 9% 11/93 12% 10/93 11% no h ~ e metastases Pat/ents with Nc~75 43/75 58%0 55/7574% 44/75 59%0 59/75 79% ~me metastases High levels of CA 27-29 SAP and CA 15-3 were found in multiply bone metastases. CONCLUSIONS : CA 15-3 and CA 27-29 are the more sensitive tumor markers in the follow up of patients with breast cancer. High levels of SAP were found in osteoblastic activity in multiply bone metastases. The high CA 549 levels in patients with no metastases may be an early indication of disease r e c u r r e n c e . T h e combination of these tumor markers did not give more significant information than each of them separately.

I--

Recently radioiodo-4-amino-N-[l-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2methoxybenzamide w a s d e c r i b e d as a r a d i o l i g a n d s h o w i n g h i g h a f f i n i t y a n d s p e c i f i c i t y for 5 H T 2 A r e c e p t o r s ( 1 ) . I n v i t r o de b i n d i n g s h o w e d t h e n o n radioactive 5-bromobenzamide analogue to have the same binding properties (2). T h e r e f o r e an appropriate radiobromination method was developed. As t h e 5 - p o s i t i o n on t h e b e n z a m i d e g r o u p is the deactivated for n u c l e o p h i l i c exchange nuc l e o p h i l i c s u b s t i t u i o n h a s t o be a p p l i e d . Br77 o b t a i n e d by ~ - i r r a d i a t i o n of A s 7 5 - o x i d e f o l l o w e d by i o n - e x c h a n g e recovery was used for optimalisation. When using the peracetic acid method or a s l i g h t m o d i f i c a t i o n of it, a r e g i o s e l e c t i v e r a d i o b r o m i n a t i o n on t h e 5 - p o s i t i o n w a s o b s e r v e d , but the labelling yield was limited to 20%-30% a n d d i f f e r e n t s i d e p r o d u c t s w e r e g e n e r a t e d .When using hydrogenperoxide/acetic acid the radiobromination is q u a n t i t a t i v e resulting in 85% s u b s t i t u t i o n on t h e 5 - p o s i t i o n a n d 15% on t h e 3p o s i t i o n . T h i s m e t h o d is p r e f e r r e d as c o u p l e d to H P L C s e p a r a t i o n a n d m i n i - c o l u m n r e c o v e r y it allows an o v e r a l l y i e l d of 7 5 - 8 0 % of n.c.a. 5-radiobrominated analogue with a radiopharmaceutical p u r i t y of >99%. 1,2. J. M e r t e n s , D. T e r r i e r e , V. Sipido, W. Gommeren, P.M.F. J a n s s e n , J.E. L e y s e n , J. Lab. Comp. & R a d i o p h a r m . , 34, 7 9 6 - 8 0 6 (1994).

1247

0 u) 0 a.

II Radiochemistry and Radioassays PMo865

PMo867

K. N~gren*, C. Halldin, C. Lundkvist, A. Eriksson, L. Farde. *Radiopharmaceutical Chemistry Laboratory, National PET Center, Turku, Finland and Karolinska Instituter, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden

M. Haaparanta, R. Paul l, J. Bergman, K. Aho and O. Solin, Turku PET Center, Tykist6katu 6, Turku, Finland, iEli Lilly Finland

CHIRAL HPLC SEPARATION OF (-)-(L)- AND (+)-(D)-[C-11]NOREPINEPHRINE FOR PRECLINICAL PET EXAMINATIONS. The potential of PET for the study of the sympathetic nerve system in the heart has been demonstrated using the false neuro-transmitter [C-11]HMED. This tracer has a very high affinity for the uptake-1 system, which causes the net tissue uptake of MHED to be highly flow limited. The predominant endogenous transmitter of this nerve system is (-)-(L)norepinephrine ((-)-NE). (-)-[C-11 ]NE should be advantageous as a tracer as it would mimic the myocardial uptake of the true transmitter, i.e. uptake by the uptake-1 system followed by storage in the synaptic vesicles. Racemic (±)-[C-11]NE has recently been prepared from [C-11]nitromethane, and its uptake in the primate heart was examined by PET (Farde et al., 1994). Selectivity for the sympathetic innervation was demonstrated by an 80% reduction of myocardial uptake upon pretreatment with desipramine. As the uptake in the synaptic vesicles is highly stereospecific, an even higher selectivity would be expected for enantiomerically pure (-)-[C- 11 ]NE. Separation of (±)-[C-1 liNE was performed on a Chiral-CBH 150xl0mm, 5 ~m column (ChromTech AB) using a sodium phosphate/EDTA/ethanol mixture. (-)- and (+)-[C-11]NE eluted at 9 and 15 min, respectively, at a flow rate of 4 mL/min. The radiochemical purity was higher than 98%, and the optical purities were 100 and >98%, respectively. The decay corrected yield of each enantiomer was about 5% within a total synthesis time of 85-90 min. The amount of radioactivity obtained for each enantiomer is sufficient for preclinical animal PET evaluation.

Farde, L. et aL, (1994) Eur. I NucL M e t 2h345-34Z

PMo866 Grillenber,qer KG, Haitmann M, Reske SN Department of Nuclear Medicine, University Hospital, UIm, Germany STUDIES ON SEPARATION OF F-18 FLUOROURACIL, F-18 FLUORODEOXYURIDINE AND POSSIBLE SYNTHETIC SIDE PRODUCTS BY REVERSED PHASE RADIO-HPLC

5-[l~F]-Fluorouracil (laFU) is frequently used in PET studies evaluating the uptake of the labelled cytostatic agent in tumors and metastases in order In predict individual response rates to FU chemotherapy. The use of 5-[18F]-fluorodeoxyuridine (lSFdUrd) can provide an index of tissue proliferation via increased transport and increased intracellular phosphorylation and incorporation into RNA. The main contamination of laFU preparations generally consists of unreacted uracil (Ura) which is initially used in large excess and which can only be removed chromatographically. The corresponding side products in 18FdUrd synthesis are deoxyuridine (dUrd) and uridine (Urd). In this study we examined the separation of these five compounds by high performance chromatography (HPLC) using different reversed-phase columns and varying the eluent and the pH value. The eluent consisted of a sodium phosphate buffer with pH values of 6.0-8.0 suitable for injection to patients. Detection of the peaks was performed photometrically at 260 nm. Order of elution was in every case FUra
2-(18F)FLUORO-2-DEOXY-D-GALACTOSE: UPTAKE AND METABOLISM IN HEALTHY AND CIRRHOTIC RAT LIVER We have studied hepatic function in a CCl4/phenobarbital induced liver cirrhosis model of the rat. The metabolites and uptake of 2[18F]fluoro-2-deoxy-D-galactose ([18F]FdGal) in organs of healthy and cirrhotic rats (n=7) were determined e x vivo. Uptake in brain and kidney of cirrhotic rats did not differ from controls. In contrast the uptake in cirrhotic liver was decreased. Metabolites of [18F]FdGal ([18F]FdGaI-IP and UDP-[18F]FdGal) from the liver, brain and kidney homogenates were analysed. In the brain and kidney of healthy and cirrhotic animals there were no significant differences between the amounts of these metabolites. In the cirrhotic liver the amount of [18F]FdGaI-I-P was increased and the amount of UDP-[18F]FdGal was decreased as compared to healthy animals. The uptake in various organs correlated with the relative amounts of metabolites. The extent of liver damage as assessed by histology did not correlate either with uptake or metabolism of [18F]FdGal. We conclude that [18F]FdGal metabolism is disturbed in cirrhotic rat liver. The decrease in UDP[18F]FdGal may reflect galactose-l-phosphateuridyltransferase (GALT) deficiency in cirrhotic liver.

PMo868 G. Westera. J. T. Patt, *D. Bertrand, K. Jankowski, P. A. Schubigcr. Division of Nuclear Medicine, University Hospital, ZLirich, *Departement of Physiology, CMU, Geneva, Switzerland N-[llc]METHYLEPIBATIDINE: A PROMISING LIGAND FOR THE NEURONAL NICOTINIC RECEPTOR. Epibatidine is a naturally occurring alkaloid, which has very high affinity and specificity towards the neuronal nicotinic acetylcholinc receptor (nAChR). Appropriately labelled derivatives thus might present the opportunity to study the role of these receptors in smoking, Ahheimers and Parkinsons disease etc. N-Methylepibatidine was prepared from raeemic epibatidine by methylation with methyliodide. Carbon-ll was introduced into epibatidine by methylation with []IC]Mel. The sensitivity of nAChR towards this derivative was compared with +-epibatidine by electrophysiologieal methods. The receptor was reconstituted in Xenopus oocytes with the major brain subanits c~4132, the most sensitive nAChR to this class of compound.

The sensitivity of nAChR to methylepibatidine is four times lower than that towards +-epibatidine. We studied the biodistribution in mice: Uptake of the compound was highest in the brain, except for the liver and kidneys: % of the injected dose/g after 5 min. (mean of 3 animals): brain 4.29%, blood 0.82%, liver 4.95%, kidneys 6.17%, spleen 3.70%, lungs 2.96%, heart: 1.29%, stomach: 2.70%, GItract 1.55%, muscle 1.27%. Blood/brath ratio 5.2. N-[llCJMethylepibatidine is a promising nAChR PET ligand.

•

Radiochemistry and Radioassays

PMo869

PMo871

U. Schwarz 3, G.Wunderlich 1, R.Brossmer 2, W.-G.Franke 1 ~Universit&tsklinikum, Klinik for Nuklearmedizin, Fetscherstr.74, 01307 Dresden, Germany; 2 Universit&t Heidelberg, Institut f0r Biochemie II, 3 NIH, National Cancer Institut, Bethesda, USA

F. Perin, A. Le Pape, D. Laurence #, I. Savary, S. Bernard #. Biophysique Cellulaire et RMN, CNRS-Inserm U316, Tours and # Pathologic Infectieuse et Immunologic, INRA, Nouzilly, France.

Radiohalogenated neuraminic acid derivatives for enzymatic labelling of glycoproteins

TECHNETIUM-99M LABELING OF MICROORGANISMS FOR THE DYNAMIC IMAGING OF BACTERIAL DISSEMINATION.

For labelling outside of the antigen binding site we suggest a new method to introduce radioactive halogens into the oligosaccharide chains of antibodies based on the enzymatic transfer of the labelled synthetic neuraminic acid derivatives. The advantage is the absence of oxidizing or reducing agents which guarantees that the antibody structure remains intact. The terminal groups of the saccharide structures in the Fc-part are preferable for such labelling reactions. Monoclonal IgG antibodies show a wide heterogenecity of oligosaccharide structures, but they contain only three different terminal groups based on a GIcNAcGaI-NeuNAc unit. Sialyltransferases allow the transfer of neuraminic acid derivatives modified in position 5 (5-SNA) and 9 (9-SNA) with salizyl residues. Especially after a modification in position 9, the sialyltransferases enable the transfer of sterically demanding substituents into the oligosaccharide chains of glycoproteins. The results indicate that sufficient accetor groups (Galactose) must exist or created bevor. Unmodified IgG was not labelled in an acceptable short reaction time. The transfer after galactosylation of IgG shows that this way is suitable to obtain acceptor sites for transfer of sialic acids. The best transfer results were obtained after cleavage of bound neuraminic acid. This method results in yields up to 90% in one hour. In all these labelling reactions no decomposition of 9-SNA was observed. Similar results were found for iodinated 5-SNA and for fluoresceinylated neuraminic acid. For estimating the immunological activity of such a labelled product we used a goat anti mouse antibody which was detected after the binding on immobilized mouse IgG. As expected, the immunreactivity was not influenced by these modifications.

Essential informations about the development of infection or induction of the immune response of the host could potentially be derived from the knowledge of the dissemination process occuring shortly after a bacterial infection. We therefore developped a procedure for 99roTe-labeling of bacteria and applied it to Salmonella abortusovis (SAO). Bacteria growing on solid trypticase soya agar at 37°C were harvested, placed in 5 ml 0.9% NaC1 and centrifugated (30 min, 1200 g, 4°C). The pellet was resuspended in 1 ml saline and 2 ml of a 40 ~tg.m1-1 SnF2 solution (optimized concentration) was added. After addition of 650 MBq 99roTe pertechnetate, the preparation was stirred and incubated 20 min at 37°C. Three successive centrifugations (30 min, 1200 g, 4°C) were then performed in the presence of 0.25 mg.ml-1 ascorbic acid. The final pellet was resuspended in 400 gl saline.This technique provides a 30% labeling yield. Viability of 99mTe-labeled bacteria was assessed by flow cytometry using rhodamine 123 as fluorochrome and was demonstrated to be unchanged. Turbidimetric measurements showed only a slight increase in the growth rate for radiolabeled bacteria (doubling time of 110 min v s 71 rain for control cells). Incubation of radiolabeled bacteria with pronase, saponine and urea suggested that 99mTc localization was mainly intra-cellular but the lack of an agent able to cleave lipopolysaccharide do not allow to completely exclude a membrane fixation for 99mTc. As a test to evaluate the usefulness of radiolabeled bacteria, we investigate whether scintigraphic imaging could be done to non-invasively document the spatial and temporal patterns of the in vivo dissemination of SAO in slieepo Virulent (15/5)and attenuated (Rv6) strains of SAO were radiolabeled and injected subcutaneously (108 cells) between the two parts of the left and right rear hoofs respectively. Using this well-characterized model of bacterial dissemination, we have shown that scintigraphy of 99mTc-labeled bacteria could provide new insights as compared to usual experiments (e.g. cannulations of lymphatic vessels or lymph nodes biopsies) to study infection.

PMo872

Sobal G., Menzel E J. Department of Nuclear University of Vienna.

LF.W. Ni!sen. A.D. van het Schip, H.G. IJzerman, M.H.K.J. Linsen, B.A. Zonnenberg, D.W. Rook, J.R.W. Woittiez, B. J. T. Nieuwendijk and P.P. van Rijk. Dept. of Nuclear Medicine, University Hospital Utrecht and Energie Centrum Nederland, Petten, The Netherlands

Institute

of Immunology,

BINDING STUDIES WITH GLYCATED 125I-AGE-ALBUMIN AS MODEL FOR AGE-RECEPTORS (RAGES) 1N DIABETES.

Non-enzymatic glycation of proteins is accelerated in patients with diabetes mellitus. It causes the formation of advanced giycosylation end products (AGE) which bind to endothelial cells end / or monocytes changing their functional behaviour in a way which could contribute to the pathogenesis of diabetic angiopathy.In this study we describe binding studies performed with the ligand 125-Iodine AGE-Bovine Serum Albumin (BSA) to demonstrate the presence of AGE-receptors (RAGE) on endothelial cells from human umbilical vein cells (HUVEC) and monocytes/macrophages from peripherai blood. Labeling with 125-iodine was performed according to the method of McConahey and Dixon. The influence of cell activation by lipopolysaccharide (LPS) or cytokines (TNF) was investigated. Seatchard analysis of binding data was performed. We found on HUVEC 3.0xl06RAGE/cell and K~ =2.5x10SM as compared to TNF-activated HUVEC with 67x10 RAGE/ceU and Kd=l 25x10 M. In case of monocytes we found l.lxl05 RAGE/monocyte and Kd= 0.7xl 0tM.Aetivated monocytes had 3.7xl 06 RAGE/cell with a Kd=0.27x10~SM. Thus, activation with LPS or TNF resulted in a clearcut increase of RAGE numbers on endothelial cells and monocytes It is well known that RAGEs are expressed in atherosclerotie lesions, causing accumulation of AGEs.Therefore our results may be used to create an imaging method for RAGEs on arterial tissue to evaluate and quantitate AGE-receptors in diabetes patients developing atherosclerosis.

lmall

t~ cO

O O.

PMo870 Medicine,

cO

x_

IRRADIATION OF HOLMIUM-165-POLYLACTIC ACID MICROSPHERES (HO-165-PLA-MS) FOR RADIOTHERAPYOF HEPATICMALIGNANCIES The intra-arterial use of radioactive microspheres of poly lactic acid (PLAMS) for internal radiotherapy of liver metastases has the potential of overcoming the disadvantages of external beam radiation which is limited by the radiosensitivity of healthy tissues. PLA-MS loaded with holmium166 are biocompatible, biodegradable and have a near plasma density of 1.3 g / c m 3. Neutron activated holmium-166 (T1/2=26.8 h) is a p-emitter (Emax=1.84 MeV) and emits "/-photons (81 keV) which can be used for imaging. Irradiation of Ho-165-PLA-MS was performed in a high flux nuclear reactor. Irradiation parameters were investigated to produce stable Ho-166PLA-MS with high specific activity. Methods: For incorporation into PLAMS, a Ho-165-trisacetyI-acetonate complex was prepared by a newly developed method. The spheres were collected on metal sieves. Samples of 50-600 mg microspheres with and without holmium-165 were irradiated in a high flux nuclear reactor at variable flux and irradiation time. The samples of microspheres were placed in vials of quartz, polyethylene and polypropylene. Results: The PLA-particles with 10% Ho-165 incorporation had less irradiation damage than spheres without holmium incorporation. Spheres irradiated in polyethylene or polypropylene vials had less irradiation damage than in quartz vials. Damage increased with increasing quantities of spheres and irradiation time. For therapeutical use an activity of 7.4 GBq is required at the moment of administration (at end of bombardment 14.8 GBq).This amount can be produced by irradiation of 516 mg Ho-165-PLA-MS during 1 hour in a polyethylene vial at q0=5.1013 n/cm2.s. After irradiation the spheres remain spherical. Maximum leakage of Ho-166 after 192 hours incubation at 37°C in phosphate buffer, plasma and liverhomogenate is < 0.5 %. The MW of the PLA was reduced from 89242 to 6298 daltons after irradiation. Conclusion: Production of therapeutic amounts of stable Ho-166-PLA-MS is feasible.

1249

O O rl

• Radiochemistry and Radioassays PTu875

PMo873

RD Gunasekera, AB Mostafa, A Notghi, LK Harding, City Hospital NHS Trust, Birmingham, U K TETROFOSMIN ABSORPTION ONTO SYRINGES: IS IT SIGNIFICANT? Tc-99m tetrofosmin is a widely used myocardial agent. We found that a variable amount & t h e radioactivity is absorbed onto some syringes. When appropriate syringes are not used, the reduction in the administered activity may result in poor quality images. The residual activity in the.syringes following tetrofosmin injections were measured in 75 patients using 3 brands of syringes and compared with MDP, DTPA, pertechnetate & MAA. The amount absorbed to the plastic syringe barrel and rubber plunger before and after wash out was measured at different time intervals. There was significantly higher residual tetrofosmin activity in some brands of syringes. Most of the absorption occurred within 10 minutes of preparing the injection. The percent of absorption onto the syringes was not dependant on the initial activity. The activity was absorbed onto the plunger with tetrofosmin but not with MAA as shown in the table below: Syringe tTpe B-D $henvood Braun

% residual of the initial activity 250 MBq 750 MBq plunger activity MAA plunger tetrofos, tetrofos, tetrofos, activity MAA 19.3±5.2 16,2±2.6 6.2±I.2 14,3±4 I,t±0.4 15.1±5,1 11.5±2.3 3.8+0.9 15.5±5 0.9±0.4 7.1±5.0 5,1±2.0 0.9±0,3 13.3±3 1.1±0.4

There is significantly less tetrofosmin residual activity in "Braun" syringes compared to 'Becton-Dickinson'(B-D) and 'Sherwood' syringes. Therefore "Braun" syringes are recommended for Tc-99m tetrofosmin injections.

B. L. Faintuch,M.A.T.M.Almeida ,E .Muramoto,O. G. Carvalho,E. B. Araujo,Dept.Radiopharmacy,Institute of Nuclear and Energetic Research (IP~N/CNEN) ,University of Sao Paulo,Sao Paulo,SP, Brazil 9~c-N-ACETYLCYSTEINE LZ~.LING AND BIODISTRIBUTION N-Acetylcysteine (NAC) is a recognized antioxidant,mueolytic and c h ~ r e v e n t i v e amino acid.Unlike cysteine,it has not been well studied as a poten£ial radiopharmaceutical for clinical use.AJmJ_ng at the labelling of this molecule with Tc-99m,a ecmplex was prepared by the reducticn of 99mrco4 with stannous chloride,in the presence of the ligand Radiochemical purity of the product was confirmed by TLC-SG using acetone and 0.9% saline as solvents.Animal studies were performed in male Wistar rats (n=48) .After administrat ion of 100 uCi of the tracer,lots of 6 animals were sacrificed at respectively 1,5,10,15,30,60,90 and 120 minutes.Dis tribution was determined in kidney, liver ,heart, lung, spleen, stomach,small ~ l a r g e bcwel,mus~le,blood and plasma.Label ling yield of ==~LTc-NAC was 97.6 - 1.1% (n=10).The highest concentration of the dose/g tissue was found in ~hekidney, with a peak at 90 minutes (21.9 - 4.5%).Lower but significant values were observed in lung,heart,liver and other viscera,with the highest findings corresponding to the first minutes,followed by slow reduction.~lood clearance of ==LLTc -NAC was fast,decreasing from 29.9 - 8.8% i~ the first minute to 18.2 - 5.8% at five minutes,and 1.8 - 0.4% after two hours.Plasma end whole blood activities were qui~e similar, a ~ protein binding (TCA precipitation) was 5 5 9 ~ - 6.2%. It is concluded that: i) Labelling of NAC by ~aTc was achieved by a convenient and highly successful procedure; 2) The kidney was identified as the preferredtsx/et organ, but distribution to all principal structures had acceptable concentrations; 3) The rapid blood clearance and probable active metabolic role of this amino acid in n%~ny tissues suggest potential applications not only for renal imaging, but also in the diagnosis of malignant tumors.

PMo874

PTu876

D. Sorger, R. Schliebs, S. RoBner, l. Kiimpfer, J. Heinicke, W. H. Knapp. Department of Nuclear Medicine and Paul Flechsig Institute for Brain Research, University of Leipzig, Germany

• 1 , 2 P.Komarek , I.Klezsner ~ M . K o n o p k o v a ,3 , I.Kom~rkov~ 4 P o s t g r a d . M e d . School; Clin.Nucl.Med., Kr~lovsk@ V i n o h r a d y Univ. Hosp.; 3Inst. Clin. and Exp.Med.; 4State I n s t . D r u g Control, Prague, C z e c h R e p u b l i c

TARGETED IMMUNOLESION OF RAT BASAL FOREBRAIN CHOLINERGIC SYSTEM - A MODEL TO EVALUATE THE PERFORMANCE OF RADIOIODINATED QNB IN THE DETECTION OF CHANGES 1N CORTICAL MUSCARINIC ACETYLCHOLINE RECEPTORS IN VIVO lodo-quinuclidinylbenzilate(IQNB) has been shown to be a potential ligand of muscarinic receptors in autoradiography, in vitro and in rive. The role of perfusion in activity distribution has not yet been clarified. We propose an animal model to evaluate effects of receptor changes in vitro as well as in vivo with an independent measurement of the influence of perfusion. Immunolesion was achieved in 5 adult male Wistar rats after sterotaxic injection of approximately 4 ~g of 192IgG-saporin into the left lateral ventricle. After seven days in vitro studies were performed with M1- and M2-specific radioligands (3H-pirenzepine and 3H-AF-DX 384, resp.). Imaging in vivo was performed at least one week after immunolesion following simultaneous injection of 800 MBq Tc-99m-ECD and 2 MBq (I[25)-IQNB (specific act. - 40 TBq/mmol). Cryocut sections of brain were prepared 2 h p.i. Results: Binding parameters of (l-125)-IQNB (K D - 1.9 nM; Bmax = 580 + 76 fmol/mg protein) are in the same order as those of (H-3)-QNB. In vivo autoradiography revealed activity distribution similar with contact autoradiography as early as 2 h p.i. Loss of cholinergic projection fibers in immanolesioned rats was accompanied by a 20 % increase of M1 and M2 specific ligand binding in frontal cortices. Our first results with doubleautoradiography support the view of an increase of muscarinic receptors in contrast to local perfusion. Conclusion: lmmunolesion in rat brain appears to be an adequate model to mimic chollnergic neuronal disease and, therefore, to evaluate potential radiollgands for in vivo studies. (I-125)-IQNB in vivo distribution is highly M 1,2-receptor specific and, 2 h p.i., largely independent of local perfusion.

1250

pREPARATION

OF

99mTc-HUMAN

I~MUNOGLOBULIN

USING

PHOTOACTIVATION

The aim of the study was to assess the photochemical effects of ultraviolet (UV) light on biologically active substances usable for radionuclide diagnosis. Human immunoglobulin (a 5.5% solution containing min. 95% of monomer and dimer of IgG) was irradiated with UV light at 254 nm and labelled with technetium (99mTc) by reducing 99mTc pertechnetate with stannous chloride or using a redox polymer (RP SP-C25). The radiochemical purity of 99mTc-IgG was evaluated using paper and/or Sephadex G-50 column chromatography. Labelled IgG biodistribution was determined in rats with experimentally-induced inflammation at 4 and 26 h after administration by means of 99mTc activity counting of isolated organs and tissues or by planar gamma camera imaging. Irradiated IgG shows a higher labelling efficiency of 99mTc (98%) compared to non-irradiated IgG (95%). UV light has a beneficial effect on 99mTc-IgG stability. There was a significant increase in the stability of the kit prepared using redox polymer (by 20%) and IgG with stannous chloride (by 10%). Irradiation of human IgG increases 99mTc uptake into sites of inflanumation more than three times. UV light can be used in formulating protein-based radiopharmaceuticals in order to improve their bioavailability in n u c l e a r medicine diagnostic imaging.

• Radiochemistry and Radioassays PTu877 L. Uccelli, C. Bolzati, A. Duatti, M. Giganti, R. Pasqualini, A. Piffanelli, University of Ferrara, University of Bologna, Italy, CIS bio international, France. TECHNETIUM-99m RADIOPHARMACEUTICALS CONTAINING A FERROCENEDITHIOCARBOXYLATE LIGAND Metallocenes have been used in therapy due to their cellular toxicity. With the aim to obtain an analogous Tc-99m derivative, we describe here the preparation of a Tc-99m complex with the ligand ferrocenedithiocarboxylate, which was obatined from ferrrocene by attaching a thiocarboxylic functional group to one cyclopentadienyl ring. The ligand was reacted, at tracer level, with a Tc-=N group and the formation of two products was observed. The first, more lipophilic product was characterized as the neutral, disubstituted complex containing a Tc-=N group coordinated to two ferrocenedithiocarboxylate ligands through the four sulfur atoms of the two thiocarboxylic group. In this complex, the two iron(lI) centers do not change their oxidation state upon coordination. The other product has been characterized as the cationic, mixed valence Fe(II)-Fe(III) species containing two ligands coordinated to a Tc=-N group through the same thiocarboxylic group. In this complex, the iron atom of one ferrocenedithiocarboxylate ligand has increased its oxidation state, giving rise to a mixed-valence compound. By a suitable choice of the reaction conditions, it has been possible to obtain each products separately and in high yield. In particular, the use of tertiary phosphines as reducing agents favoured the formation of the neutral complex, while the mixed-valence complex formed in higher yield using Sn(II) as reductant. In vitro incubation of these complexes with blood samples showed that they are unstable and easily undergo exchange of the ligands by blood proteins. This result was confirmed by biodistribution experiments in rats.

PTu879 M. L~izni~ek, A. L~izni~kov~i,F. Budsk~, Faculty of Pharmacy, Charles University, Hradec Kr~ilovr, and Nuclear Research Centre, Re~, Czech Republic 99mTc-DTPMP AS AN ALTERNATIVE TO 99mTc-MI)P IN BONE IMAGING Within the framework of new bone-seeking radiopharmaceuticals development, the pharmacokinetics and biodistribution of 99roTecomplexes with methylenediphosphunate (MDP) and diethylenetriaminepenta/methylene phosphunate/ (DTPMP) were compared in rats. Distribution and elimination characteristics of both complexes were similar, small differences were mainly due to the different binding to plasma proteins. Relatively rapid blood radioactivity-time decrease was a result of both bone uptake and kidney elimination (by the mechanism of glomerular filtration), which compete in the disappearance of the complexes from the blood. Both chelates under study exhibited high bone uptake and long-term retention of radioactivity in the skeleton. Higher protein binding of 99mTc-MDP is probably the reason for its insignificantly higher bone uptake in comparison with 99mTc-MDP. No significant cumulation in non-osseous tissues and organs was found. A more rapid time decrease of blood and muscle radioactivity after 99~TeDTPMP resulted in an accelerated non-osseous tissues background clearing when compared to 99~Tc-MDP. It means that the waiting lime for bone scintigraphy may be shorter for 99mTc-DTPMP as for 99~TcMDP. Another advantage of 99mTc-DTPMP is its much higher stability in comparison with 99mTc-MDP, which could reduce the complex degradation and perteclmetate liberation in the body.

q) cO

i m

63 ell)

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PTu878 N. Dezutter, T. de Groot. H. Vanbilloen C. Boonen, B. Cleynhens, A. Verbmggen Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U.Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuven, Belgium

PTu880 Fabrice Perin, Laurence Routledge, Grrard Normier#, Alain Le Pape, Biophysique Cellulaire et RMN, CNRS-Inserm U316, Tours and # Institut de Recherche Pierre Fabre, Lab~ge, France.

COMPARISON OF 99mTC-L,L-PROPYLENEDICYSTEINE AND 99mTC-L,L-ETHYLENEDICYSTEINE

INFLUENCE OF THE 99mTc-LABELING CONDITIONS ON r i l E BIOLOGICAL AND PHYSICO-CHEMICAL PROPERTIES OF J001

In this study we have investigated the influence of the replacement of the ethylene moiety in 99~Tc-ethylenedicysteine (99~Tc-EC) by a propylene moiety on the physical and biological properties. PC = HS-CHz-CH(COOH)-NH-CHz-CH2-CH2-NH-CH(COOH)-CH2-SH EC = HS-CH2-CH(COOH)-NH-CH2- CH2-NH-CH(COOH)-CH2-SH 1,3-Propane-di-S-benzyl-L-cysteine was synthesized by reaction of Sbenzyl-L-cysteine with 1,3-dichloropropane at elevated temperature. The thiol groups were deprotected with sodium and liquid ammonia. The resulting propylenedicysteine (PC) was directly labelled with 99~Tc at pH 12. The reaction mixture was analysed by reversed phase HPLC. Whereas labelling of EC results in a single radiochemical species, upon labelling of PC two 99roTe-complexes(A and B, as eluted from HPLC) are formed in a 3/1 ratio, probably two isomers with the central propylene carbon atom syn or anti to the oxotechnetium core. These isomers show a slow interconversion at pH 2.5 but are stable at neutral pH. In mice, both conformers of 99"Tc-L,L-PC showed a lower urinary excretion (respectively 46 % and 63 % of i.d. for A and B, at 30 min p.i.) than ~Tc-L,L-EC (94 %) and a higher renal retention. Hepatobiliary uptake ofg~Tc-L,L-PC was much higher (32 % ofi.d at 30 rain p.i.) than for 99~Tc-L,L-EC (2 %). In a baboon, isomer A of 99~Tc-PC was excreted rapidly in the urine without visualisation of liver or intestines, but its plasma clearance was only 34 % of OIH clearance, as compared to 75 % in the case of 99mTc-EC. These results demonstrate that also the length and orientation of the alkylene bridge between the two amines are important for the interaction of this type of compounds with the renal tubular transport proteins.

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ID O

J001 is a 25 kDa acyl poly-(1,3)-galactoside derived from a serie of molecules selected for their macrophage (M~) activation properties. Based on structure-activity relationship studies, this molecule has been optimized for scintigraphie applications, preserving its capacity to bind electively M~s but eliminating its immuno-pharmalogical activities. To achieve a functional imaging of inflammation via M~ visualization, minimal labeled colloid content and high in vivo 99mTc-J001 stability are strictly required. Our aim was therefore to establish an appropriate injectable radiopharmaceutical kit for the first clinical study. Optimization of the radiolabeling conditions has been achieved from a serie of pilot freeze-dried formulations evaluated for labeling efficiency, in vitro and in vivo 99roTe-J001 stability, colloid formation. Biodistribution of the formulations in rats was systematically studied, their imaging performances being evaluated in a model of inflammation i.e. immunological arthritis in rabbits. The labeling yield was determined by paper radiochromatography while the in vitro stability was studied by exclusion-diffusion radioHPLC analysis of the preparations submitted to 99mTc competitors such as DTPA. To document in vivo stability, radioHPLC was performed on rat serum collected lh after injection of 99roTe-J001 preparations. Colloid formation in each pilot lot was documented using autocorrelation spectroscopy and multi-angle laser light scattering while radioactive colloids (the only species to be considered for a radiopharmaceutical) were assessed based on liver Uptake in biodistributton studies. Our optimization of the preparation of 99mTc-J001 has resulted in the formulation of a one-step labeling kit (a single vial containing 1.0 mg J001, 80 I~g SnF2 and 1 mg NaC1) that gave contrasted images of joint inflammation in rabbits. This optimized formulation provides usually labeling efficiencies >98%, in vivo 99mTc transchelation on serumalhumin less than 15% and minimal colloids formation to achieve specificity of the J001 imaging.

1251

12.

• Radiochemistry and Radioassays PTu881

PTu883

H. Mfihlensiepen, M. Cremer, K.-J. Langen, H.-W. Mtiller-G~rtner Institute of Medicine, Research Center J~lich, Germany.

H. Wolf, C. Nacke, K. Kaiser, B. Frieling, S. Tinnemeyer, W. Brenner, K. H. Bohuslavizki, M. Clausen, E. Henze. Clinic of Nuclear Medicine, Christian-Albrechts-University of Kiel, Germany

DIFFERENTIAL EXPRESSION OF AMINO ACID CARRIERS IN GL1OMA CELLS DEPENDING ON GROWTH RATE

The amino acid [methyl-C-11]-L-methionine (MET) is used for the diagnostic evaluation of cerebral gliomas with PET. It has been shown that transport represents a dominating factor in the uptake process of MET into glioma cells. This study investigates the Michaelis Menten kinetics of MET transport in slowly and rapidly proliferating cells and the corresponding expression of the L 1- and A-amino acid carriers. Glioma cells type 86-HG 39 in culture were incubated for 1 minute with [methyl-H3]-L-MET at substrate concentrations of 10"6 to 10-3 mol/L L-MET in the exponential growth phase (day 3) and after reaching a plateau phase (day 8). Experiments were repeated after specific inhibition of the Ll-amino acid carrier by 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCtt) and of the A-carrier by 2(methylamino)-isobutyric acid (MeAiB). Vm,× of MET transport decreased from 660 + 186 gmol/106 cells/min in the exponential growth phase to 46.2 _+ 26.4 p.mot/106 cells/min when the cells entered the plateau phase (mean + sd, n = 4, p<0.05). The Michaelis constant K m showed no significant change (4.83 _+2.89 mmol versus 2.29 _+0.56 retool, n = 4, n.s.). Inhibition of the Ll-carrier by BCH induced a 68.8 + 4.4 % (n=3, p<0.001) reduction of transport in proliferating and a 68.5 _+6.4 % (n=3, p< 0.001) reduction in plateau phase cells. Inhibition of of A-carrier transport by MeAiB caused 22.1 + 5.0 % (n = 3, p<0.01) decrease of transport in proliferating cells and 11.3 _+ 13.0 % (n = 3, n.s.) in plateau phase cells. The results indicate that increased MET transport in proliferating glioma cells is due to an increased amount of carrier proteins (Vm~x). The substrate affinity of the carrier (Kin) remains nearly unchanged. Furthermore, in proliferating cells the A-transporter gains a considerable part of the transport capacity.

UPTAKE OF TC-99M TETROFOSMIN, TC-99M SESTAMIBI AND TL-201 IN CHEMOTHERAPY SENSITIVE AND RESISTANT TUMOUR CELL LINES Tc-99m tetrofosmin, Tc-99m sestamibi and T1-201 are used as tumour tracers. The purpose of this study was to compare their uptake in differential chemotherapy sensitive and resistant carcinoma cell lines. Monolayers of four sensitive cell lines (breast, gastric, ovarian carcinoma and melanoma) and two resistant gastric carcinoma lines were incubated for 1 h with 10 kBq of tracer. The uptake is expressed in % of activity added and normalized to 1 million cells. All results are given as mean + 1 s.d. (n = 10 / test) at lh. T1-201 uptake remai4 N breastca, sens. ned nearly constant -~ t IB gastri ......... at 1 % in all cells o [ IB gastricca,res. (seen in figure). In 2 31 Im gastri........ I~_ t~ ovanao oa.sens. ~ens sensitive cells tetro- ~ [ melanoma, f°smin uptake ~ between 0,9 %varied and ~ i2 o ~ 2 , 1 % , while sestamibi uptake ranged from 1,7 % to 3,6 %. In the two resistant cell lines the uptake of tetrofosmin and Tc-97m tetrofosmin Tc-99m sestamlbi TI-20I sestamibi is definitely reduced when compared to the sensitive cell lines. Tetrofosmin showed an uptake of only 0,5 % resp. 0,7 % and sestamibi of 0,6 % resp. 1,2 %. In conclusion, Tc-99m sestamibi showed the highest uptake in 4 of 6 cell lines and both, Tc-99m sestamibi and Tc-99m tetrofosmin, are dependent on the status of the tumour cells.

PTu882

PTu884

E. Seregni, C. Botti, S. Nerini-Molteni, S. Massaron, A. Martinetti, L Ferrari, L. Maffioli, C. Paseali, A. Bogni, F. Crippa, C. Lombardo, F. Remonti, E. Bombardieri National Cancer Institute o f Milan

H. Wolf, K. Kaiser, C. Nacke, B. Frieling, St. Tinnemeyer, K.H. Bohuslavizki, W. Brenner, M. Clausen, E. Henze Clinic of Nuclear Medicine, Christian-Albrechts-University of Kiel, Germany

UPTAKE OF 99mTe-SESTAMIBI, 99roTe TETROPHOSMINE, 99mTcMEDRONATE, 18F-FDG IN MCF7 BREAST CANCER CELL LINE

UPTAKE MECHANISM OF TECHNETIUM-99M-TETROFOSMIN IN TUMOUR CELL CULTURES

Aim o f the study." several radiolabelled pharmaceuticals are currently proposed

The myocardial peffusion tracer Tc-99m-tetrofosmin is also used as a tumour tracer. But little is known about the uptake mechanism in tumour cells. Therefore, the purpose of this study was to evaluate fundamentals of the uptake mechanism of Tc-99m-tetrofosmin in various tumour cell lines. Cellular accumulation of Tc-99m-tetrofosmin was measured at 8 different incubation times (30 min to 4 h) with 10 kBq / culture tube and 2 - 4 millions of breast, gastric and ovarian carcinoma cells. The effect of temperature (37 °, 20 °, 4 ° C), dose of metabolic inhibitor 2-,4-dinitrophenol (DNP, 1 and 0.2 mmol/1) and of activity concentrations on uptake was determined at 1 h of incubation time. The values are normalized to the activity added and to one million cells and corrected for the number of viable cells, expressed as %. Tc-tetrofosmin showed increasing uptake kinetics in every of the three cell lines for up to 4 h of incubation time. The uptake was independent of activity concentration (in the medium). Lower temperatures and addition of DNP at 37 ° C decreased the uptake. The results for the 1 h-uptake are given in the table.

as tumour detectingagents for breast cancer. The aim of this study is to evaluate in vitro the incorporation of IgF-FDG and 99roTe-chelates (SestaMIBI, Tetrophosmine, MDP) in the MCF7 mammary carcinoma cell line both in basal conditions and in differentphases of cell growth. Methods: the kinetics of MCF7 growth was obtained by growing 150,000 cells/well in RPMI 1640 supplemented with 10% FCS, 1% L-ghitamine, sodium-pyruvate, penicillin/streptomycin, vitamins, non-essential aminoacids and 150 mg/dl glucose. During the experiment of 18F-FDG incorporation an activity of 5 p.Ci was added to 500,000 cells which were incubated for 60 min. at 37°C in the same medium containing a physiological glucose concentration. As regards 99roTe-chelate incorporation, an activity of 401xCi was added to 500,000 cells resuspendedin the same medium supplementedwith Hepes 1.2% and the incubation lasted 30 rain. at 37°C. Unbound activity was washed twice with cold PBS. Results and conclusion: 99mTc-SestaMIBl and 99mTc-Tetrophosmine are highly incorporated in the tumour cells and 50% of the initial-boundactivity are released in the medium after less than 30 rain. By contrast, the uptake of 99mTc-Medronate is desively inferior and comparable to that of free perteehnectate. As regards 18F-FDG incorporation, a linear relationship between uptake and number of cells ranges fore 6x103 to lxl06. Our data also suggest that a preferential uptake of 18F-FDG occurs in the exponential phase of growth compared to the stationary phase. All tracers,, except for free pertechnectate, seem to be valid radiopharmaeeutieals for in vivo scan localization of breast eaneer. Acknowledgements- This work was partially supported by a grant-in-aid for scientific research (n° 420.198.542) from A.I.R.C.

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uptake [%1 in breast ca cells gastric ca cells ovarian ca cells

37°C 1,7 1,6 2,1

20°C 0,7 0,9 1,0

4°C 0,6 0,3 0,7

DNP:0.2 1,5 1,2 1,9

/ 1 mmol/1 1,1 0,8 0,9

In conclusion, the uptake of Tc-tetrofosmin in tumour cells seems to be dependent on energy metabolism. Further experiments with cation canal inhibitors will be clarify the role of cation canal carrier.

• Radiochemistry and Radioassays PTu885

PTu887

K.-J. Langen], K. Csapl~~, H. M/itflensiepen1, M. Holschbach2, H.-W. Mtlller-Garmerje. Inst. of Med. ~ and Nucl. Chem.2, Research Center Jfilich, Dept. of Nucl. Med.3, University. of D~Jsseldorf,Germany.

W.Y. Lin, M.N. Chert, S.J.Wang. Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

IN-VITRO ANALYSIS OF AMINO ACID TRANSPORT OF 1-125-~METHYLTYROSINE AND 1-125-O-METHYL-~x-METHYLTYROINE IN A GLIOMA CELL LINE The amino acid analogues L-3[I-123]-Iodo-c(-methyltyrosine(IMT) and L3[l-123]-Iodo-O-methyl-c~-methyltymsine (OMIMT) are currently under clinical evaluation as SPECT tracer of amino acid transport in brain tumors. Both substrates are assumed to be transported by the Ll-amino acid transport system. The aim of this study was to investigate the carrier systems involved in IMT and OMIMT transport and to compare the results to those obtained for H-3-L-methionine (MET). Glioma cells type 86-HG 39 were cultured and incubated for 60 minutes at 37°C with 1-125-1MT. 1-125-OMIMT and H-3-MET in the exponential growth phase of the cell line (day 3) and after reaching a plateau phase (day8). Experiments were repeated after specific inhibition of the Ll-amino acid transporterby 2-aminobicyclo-(2,2,1)-heptane-2-carboxylicacid (BCH). Uptake of the different tracers at growth phase compared to plateau phase was increased by the following factors: IMT 4.4 + 1.3 (n=4, p<0.02), OMIMT 3.0 + 0.1 (n=4, p<0.02), MET 3.6 + 0.8 (n=4, 13<0.01. In plateau phase cells BCH reduced uptake of all tracers by 70 - 80 %. In exponential growth phase, however, results were different. BCH reduced MET uptake again by 80 % while LMT and OMIMT uptake was reduced by only 30 %. The results indicate that the uptake of IMT and OMIMT is increased in rapidly proliferating glioma cells to the same extent as MET but other transport mechanisms than an activation of the Ll-transponer appear to be involved in the exponential growth phase of glioma cells.

CYFRA 21.1: A NEW AND USEFUL TUMOR MARKER IN DETECTING NASOPHARYNGEAL CARCINOMA: COMPARISON WITH SQUAMOUS CELL CARCINOMA ANTIGEN. Cyfra 21.1 (Cyfra) is a newly developed tumor marker which is useful in evaluating non-small cell lung carcinoma (ca), especially the squamoas cell type. The purpose of this study was to assess clinical value of Cylia for nasopharyngeal carcinoma (NPC) and compared the results with squamous cell ca antigen (SCC). Serum levels of Cyfra (CIS bio-Intea-aational, France) were measured in 111 newly diagnosed NPC and 83 other squamons cell carcinomas of head and neck (20 buecal ca, 16 hypophm3nagealca, 18 laryngeal ca, 10 palate ca, 9 lip ca, and 10 orophawageal ca ), and in 73 patients with cervical ca. In addition, 80 patients without evidence of neoplasm were included as normal controls. In the same groups of patients SCC (Abbott Laboratories, USA) was also determined. The cut-off values of Cyfra and SCC, determined at the 95th percentile of the standard Ganssian variate of controls, were 2.48 ng/ml and 1.49 ng/ml respectively. The results are tabulated as follows: Sensitivity (%) No. Cyfi'a SCC Head & Neck Ca 194 38.5 21.0 except NPC 83 33.7 22.9 NPC 111 55.9 19.8 Cervical Ca 73 42.5 64.4 The diagnostic sensitivity of Cyfra in sqtmmous cell ca of the head and the neck was superior to SCC. Especially for NPC, the sensitivity of Cyfra was much higher (55.9%) than that of SCC (19.8%). For cervical ca, however, SCC was still the better tumor marker. In conclusion, Cyfra 21.1 is a useful serum marker for patients with squamons cell ca of the head and neck, especially in NPC patients. Besides, Cyfra may be also useful in monitoring recurrence of NPC which is someUmesdifficult to detect.

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C ~3 u)

Q.

PTu886

PTu888

W.Y. Lin, M.N. Chen, S.J. Wang. Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

G.C. Zucchelli, A. Pilo, M. Ferdeghini, S. Masini, C. Prontera CNR Institute of Clinical Physiology, Pisa; Service of Nuclear Medicine, University, Pisa (Italy).

A COMPARISON BETWEEN RADIOIMMUNOASSAY AND TDX FLUORESCENCE POLARIZATION IMMUNOASSAY FOR THE ASSAY OF CYCLOSPOR]NE IN PATIENTS AFTER KIDNEY TRANSPLANTATION Radioimmanoassay (RIA) has been used for monitoring the blood levels of cyclosporine (CsA) in patientLs with renal transplantation in the past decades. However, ILIA suffers from some shortcomings such as long incubation time, calibration problems and complicated procedure. Recently, a method utilizing the fluorescent polarization immunoassay technique (FPIA) has been developed. We analyzed the blood CsA concentration in a total of 131 blood samples from 41 patients with kidney transplantation by both RL~ (Incstar) and FPIA (TDx Abbott) methods. Our data shows a good correlation of CsA measurements between FPIA and ILIA with a R squared value of 0.949. The sensitivity was 10 ug/L for RIA and 15 ug,% for FPIA. The FPIA assay showed greater precision than the RIA method. However, mean and median CsA concentrations determined by FPIA were obviously higher than those by RIA. We conclude that the FPIA method with rapid, simple-performed, reliable, and precise characteristics may become an excellent alternative to RIA method in the monitoring of CsA treatment. However, the clinician should be aware that a CsA concentration measured by FPIA method higher than previous measurements (such as RIA method) should be interpreted cautiously before dosage interventions. The discrepancy between these two assays should be taken into consideration~

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INTERLABORATORY COMPARISON OF THYROGLOBULIN MEASUREMENTS. Data collected in a multicenter coUaborative study carried out in 1995 have been analyzed to evaluate the variability of thyroglobulin (Tg) measurements. Laboratories participating in the survey (about 60) received 20 control samples sent in 2 despatches. Control samples were prepared as follows: a) 8 samples from pools of patient sera (without Tg autoantibodies) at different concentration of Tg; b) 7 samples spiking a low pool (without Tg autoantibodies) with different amounts of Tg standard (BCR, CRM 457 supplied by Cummunity Bureau of Reference, Brussel); c) 4 samples from pool of patients with Tg autoantibodies; d) 1 sample spiking a pool (containing Tg autoantibodies) with Tg standard. The between-laboratory agreement observed in the 15 control samples without anti-Tg autoantibodies was abnormally high: 40-50 CV% in samples with Tg concentration higher than 5 I.tg/L and up to 80-120 CV% in the low concentration range ( <5 lag/L). The large variability observed was mainly attributable to systematic differences between methods. These differences were likely due both to different specifities of the antibodies (polyclonals and monoclonals) and to different local kit calibrators. Results produced in spiked control samples by the most used methods were used to estimate a conversion factor from p.g/L of the different kit standard to the common standard (BCR CRM 457); using these conversion factor the results collected for pool P007 were coverted in units of the common standard; the between-lab variability decreased from 45.7 to 18.8 CV%. The total variability of results produced in control samples containing anti Tg autoantibodies was found larger than that in samples without antibodies (93-116 CV%). The different extent of cross reaction from autoantibodies in the various method/kits contribute to enlarge the between-kit differences produced by different calibrators. The interference appears very different from method to method. The precision (between-assay and between-laboratories) of the methods was found clearly unsatisfactory (49-117 CV%) in the low concentration range (<4 lag/L) and better (8-29 CV%) for samples at higher concentration (4-73 ~tg/L).

1253

0

• Radiochemistry and Radioassays PTu889

PTu891

M . C . S i q u e i r a , ] A . S i l v a Cruz, ~ O.Neves, s C e n t r e of Gastroenter°l°gy ,! Dept. of O b s t e t r i c s and G y n e c o l o g y . F a c u l t y of M e d i c i n e 2, U n i v e r s i t y H o s p i t a l of S a n t a M a r i a 3 , Lisbon, P o r t u g a l

M.Correa,J.Jimenez-Hoyuela,M.D.Fernandez*,F.Garcia-Pesquera Nuclear Medicine Service and Laboratory Department* Virgen del Rocio U. Hospital.- SEVILLE .- Spain.

Q U A N T I T A T I O N OF P L A S M A P R O S T A G L A N D I N E2 (PGE2) BY R A D I O I M M U N O A S S A Y (RIA), IN P R E G N A N T W O M E N DURING THE LABOUR The p u r p o s e of this study, was to i n v e s t i g a t e the e f f e c t of e n d o c e r v i c a l p r o s t a g l a n d i n E2 applied in form of gel for the i n d u c t i o n of labour. T h e s t u d y i n c l u d e d 26 t e r m i n a l p r e g n a n t w o m e n without pathology. Blood samples were collected bef~ re and 3 0 m i n a f t e r the a d m i n i s t r a t i o n o f e n d o c e r v i c a l PGE2 gel (0.5mg of PGE2 in 3g of gel) in t~ bes c o n t a i n i n g i0 mg of E D T A N a 2 and 5~g of l y s i n e acetylsalicilate. Red b l o o d c e l l s w e r e s e p a r a t e d f r o m p l a s m a at 4~C for 10min at 1000g. P l a s m a PGE2 was e x t r a c t e d with e t h y l a c e t a t e at p H = 3 . 5 and chr o m a t o g r a p h e d on s i l i c i c acid c o l u m n s w i t h solvent s y s t e m ( t o l u e n e : e t h y l a c e t a t e : m e t h a n o l ) (70:30 :5], w i t h m e t h a n o l as g r a d i e n t of c o n c e n t r a t i o n s in o r d e r to s e p a r a t e PGE2 from o t h e r p r o s t a g l a n d ~ n s . T h e i s o l a t e d PGE2 was d e t e r m i n e d by c o m p e t e t i ve b i n d i n g r a d i o i m m u n o a s s a y using 3H l a b e l l e d antigen (PGE2) as r a d i o t r a c e r and m o n o c l o n a l a n t i body as b i n d i n g l i g a n d in the p r e s e n c e of c o n c e n t r a t i o n s of s t a n d a r d PGE2. R e s u l t s are e x p r e s s e d as m e a n + / - S D . P l a s m a PGE2 in p r e g n a n t w o m e n g a v e the f o l l o w i n g values: B e f o r e i n d u c t i o n 3 4 7 + / - 5 1 . 6 p g / m l and a f t e r admin i s t r a t i o n of PGE2 gel 7 1 9 + / - 1 2 8 . 6 p g / m l . D i f f e r e n c e s b e t w e e n mean values of PGE2 c o n c e n t r a tions,using S t u d e n t ' s t test for p a i r e d v a r i a b l e s (Df=50, t = 1 3 . 2 2 ) , was s t a t i s t i c a l l y s i g n i f i c a n t ( p < 0 , 0 0 0 1 ) . W e c o n c l u d e that in the t e s t e d p r e g n a n t women, the c o n c e n t r a t i o n s of PGE2 in b l o o d was in c r e a s e d twice, a f t e r the a d m i n i s t r a t i o n of PGE2 gel for i n d u c t i o n of labour. Thus, this t e c h n i q u e has p r o v e d to a h i g h l y s e n s i t i v e and r e l i a b l e method for p r o s t a g l a n d i n e s t i m a t i o n .

VALUE OF BONE ALKALINE PHOSPHATASE AND OSTEOCALCIN FOR IRMA IN METASTATIC DISEASE . The efficacy of bone alkaline fhosphatase (B-ALP) isoenzyme measurement for IRMA in confirming metastatic bone lesions was compared with total alkaline phosphatase (T-ALP) and osteocalcin. 226 patients with cancer and 59 healthy adults were studied falling into following groups:Group I, 130 patients with breast cancer,54 with bone metastases confirmed by scintigraphy,Group II, 58 patients with prostatic cancer, 26 with bone metastases and group Ill, 38 patients with lung cancer,14 with bone metastases. B-ALP was assayed using a IRMA method (Tanden OSTASE, Hybritech, Liege) and serum osteocalcin was performed using a IRMA method (ELSA OST NAT, Cis bioInternational, France). Table summarizes the results.B-ALP was increased in 40.7 of group I, 76.9 % of group II and 5 7 . 1 % of group IIl, osteocalcin in 57.6 % of group II and T-ALP in 42.3 % of group Ill. T-ALP(U/L) B-ALP(ug/L) osteocalcin(ng/mL) controls 186+44 10.9+4.5 10.8+6.6 Group I non-laetastases 151+46 17.7+13.1 9.8+5.9 metastases 277+570 20.7+19.1 13.9+28.7 Group II non-metastases 159+ 27 12.1+12.2 12.3+9.9 metastases 613+881 a 44.6+34.3 b 19.0+8.3 b Group III non-metastases 221+68 17.0+13.3 10.2+4.5 metastases 228+63 44.5+39.0 b 14.O+8.4 a) p = 0.05 b) p=O.O01 Our data indicates that B-ALP assay was more sensitive than measurement of T-ALP activity and serum B-ALP and osteoealcin show different result in patients with metastatic disease.

PTu890

PTu892

M. Martin(D, G. Moorkens(2), R. Abs(2), P. Blockx(1) Departments of Nuclear Medicine(l) and Endocrinology(2), Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium.

J.M.Jimenez-Hoyuela,M.Correa,M.A.Guerrero*,R.Montes*, F.Gareia de Pesquera. Nuclear Medicine Service and Nephrology Service* Virgen d e 1 R o c i o University Hospital.- SEVILLE .- SPAIN

GROWTH HORMONE RELEASE IN CHRONIC FATIGUE.

SERUM OSTEOCALCIN AND CHRONIC RENAL FAILURE.

Chronic Fatigue Syndrome (CFS) is a complex syndrome of which etiology, presentation and management stimulate intense medical debate. Patients are often previously fit adults having an abrupt onset of severe disability, affecting both mental and physical capacity. Several organic abnormalities have been reported to be associated with CFS, e.g. viral infection, i m m u n e dysfunction, CNS abnormalities and hypothalamic-pituitary axis dysregulations. In 25 patients presenting with symptoms of chronic fatigue the growth hormone (GH) release was evaluated with and without challenge. GH serum levels were determined during sleep (samples each 15rain), during insulin tolerance test (ITT, 0.1-0.15 IU Actrapid/kg), during arginine (Arg, 30g/30min IV) and clonidine (Clon, 300p.g po) stimulation tests. Baseline Insulin Growth Factor I (IGF-I), cortisol and intact ACTH were also measured. All parameters were determined with radioassays: Pharmacia hGH RIA method, the SM-C-RIA-CT from Medgenix, ACTH kit from Nichols Institute and the GammacoatTM Cortisol from Incstar. In this group of patients we consider that the GH serum levels should at least go up to 30 g U / m l during sleep, 40 l~U/ml in ITT and to 20 g U / m l during Arg and Clon tests. The GH release during sleep was deficient in 20/25 patients with peak levels ranging from 2-30 g U / m l (median 13.5 ~tU/ml). For these 20 patients GH levels during ITT, Arg and Clon varied strongly, only 7/20 patients showed deficient GH release for all 3 tests. According to age and sex, the IGF-I levels were too low for 3/20 patients. Intact ACTH levels ranged from 3 to 37 p g / m l with a median value of 14 p g / m l (ref. range 9-52 pg/ml). Cortisol levels ranged from 46-207 n g / m l with a median value of 124 n g / m l (ref. range 50-250 ng/ml). For 20/25 patients with chronic fatigue the GH release during sleep was deficient. Results of GH release during ITT, Arg and Clon tests varied strongly, as well normal as deficient responses were observed.

1254

BONE-PHOSPHATASE IN PATIENTS WITH

The most commonly used marker to assess osteoblast function is the measurement of alkaline phosphatase enzymatic activity (ALP).We have investigated the relatioships of bone alkaline phosphatase (BALP), osteocalcin and ALP in patients with chronic renal failure (CRF). We studied 55 clinical healthy subjects and 260 patients with CRF and different bone-resorption rates: normal (group I), mildly increase (group II),high (group III) and very high (group IV).B-ALP was assayed using a IRMA method (Tanden OSTASE,Hybritech,Liege) and serum osteoealcin was performed using a IRMA method (ELSA OST NAT, Cis bioInternational, France). RESULTS. n TALP (U/L) BALP (ug/L) osteocalcin (ng/mL) controls 55 186+44 10.9+4.6 10.8+6.6 Group I 120 182+70 9.8+4.0 24.2+30.7 Group If 78 235+89 17.3+6.1 a 33.7+24.2 a Group III 32 278+120 a 23.0+6.6 a 57.8+33.1 a Group IV 30 298+138 a 36.0+19.6 a 73.3+40.9 a a) p=O.O01 BALP was increased in 23.0 % of group II, 43.7 % of group III and 60.0 % of group IV, ALP in 37.5 % of group IIl and 53.3 % of group IV and osteocalein in 47.4 % of group II, 90.6 % of group III and 93.3 % of group IV. Our data indicate that both osteocalcin and BALP give more sensitivity than ALP and as BALP is not cleared by kidney may be a valid marker of the increase in bone-turnover in patients with CRF.

• Radiochemistry and Radioassays PTu893

TOSuO01

B. GrUnert. H. Amthauer, T. Schumacher,H. Xu, J. Ricke, C. Strnszczynski, H. EichstMt Abt. f. Nuklearmedizin der Strahlenklinik und Poliklinik (Leiter: Prof.Or.Or.h.u.R.Fe]ixl, Virchow Klinikum tier Humboldt Llniversitiit zu Berlin

M.Soto, M.Tantull, P.Sanz, M . M a r t i n e z , J.Fernandez, A.Ige~o.

Nuclear Medicine Barcelona, Spain.

Department

l.Mendo,

of

P.Jordano,

Hospital

Cl~nic.

A T T E N T I O N P R O T O C O L OF N U R S E R Y IN B R A I N S P E C T IN E P I L E P S Y

SERUM OSTEOCALCIN,PTH, 25-OH-VITAMIN D AND DSTASEIN PATIENTSBEFOREAND AFTER LIVERTRANSPLANTATION The imbalance between resorption and formation of bone matrix can be determined by measuring a prominent enzymatic activity of bone forming or resorbing ceils• These assays were also used to resolve the uncertainties concerning the rate of bone turnover in patients before and after orthotapiu liver transplantation (OLD. The measurement of parathyroid hormone (PTH) was performed to determine disorders in calcium metabolism, 25-OH-vitamin D levels reflect the vitamin LI metabolism. Consecutiv measurements of serum osteocalcin, PTH, 25-OH-vitamin D and ostase levels in 74 patients before and 6 months after OLT were performed by radioimmunnassay. Serum asteocalcin levels at 6 months after OLT were increased in 74 patients after OLT (p < 0•0001). Serum estase was decreased in 70 patients after OLT (p =0.05). There were no significant changes in serum PTH levels (n=73) and 25-OH-vitamin D (n=73) 6 months after OLT (p > 0•05). Osteocalcin (nglml) before OLT 6M after OLT

PTH (pglml)

Vitamin 03 (ng/ml)

Ostase (ug/L)

5,37+-0,66

44,73_+ 3,55

23,15+9,45

34,45_+9,6B

22,24 _+1,641

38,2t _+5,fl5

21,54_+3,25

20,41 t5,81

The o b j e c t i v e of the p r e s e n t c o m u n i c a t i o n is to e m p h a s i z e the importance of n u r s e r y cares in the c o n t r o l l i n g , o b s e r v a t i o n and chase of the B r a i n SPECT in Epilepsy. We will e x p l a i n the m e t h o d o l o g y r e q u i r e d for Brain S P E C T including: A.Patient's preparation. B.Dose's p r e p a r a t i o n . C.Dose's a d m i n i s t r a t i o n . D . P o s i t i o n i n g of the p a t i e n t in the g a m m a c a m e r a . E . I m a g e s A c q u i s i t i o n and processing. The patients' t r a c k i n g and c o n t r o l l i n g process is d i v i d e d in 3 parts: Interictal S P E C T Ictal SPECT Brain SPECT w i t h a W a d a Test In the Interictal S P E C T the dose of 9 9 m T c - H M P A O is a d m i n i s t e r e d in b a s a l s c o n d i t i o n s . It makes us to l o c a t e the e p i l e p s y focus as in h y p o p e r f u s i o n areas. In the Ictal SPECT the dose of g9mTc-HMPAO is a d m i n i s t e r e d d u r i n g the e p i l e p s y crisis. This helps us locate the epilepsy focus in a hyperfusion zone. C o n c e r n i n g the Brain S P E C T w i t h a W a d a Test the d o s e of 9 9 m T c - H M P A O is a d m i n i s t e r e d a l o n g w i t h the i n t r a c a r o t i d i n j e c t i o n of the a m o b a r b i t a l . T h i s Brain SPECT is u s e d in p a t i e n t s w i t h a t e m p o r a l e p i l e p s y focus for its s u r g i c a l p o s s i b l e c o n s e q u e n c e s w i c h can a p p e a r w h e n r e m o v i n g t h e a n t e r i o r t e m p o r a l lobe.

In conclusion PTH and 25-OH-vitamin D are not very helpful in the follow up of bone metabolism after OLT. But the results suggest that serum osteocalcin and ostase are useful markers of bone turnover in these patients, at least in the early postoperative period•

C O N C L U S I O N S : The Brain S P E C T in E p i l e p s y a l l o w s us to l o c a t e the e p i l e p s y focus. The W a d a Test can h e l p us to p r e d i c t the likely p o s t s u r g i c a l c o n s e q u e n c e s . We h a v e to be aware of the t e c h n i c a l c o m p l e x i t y of this p r o c e s s and this c o m u n i c a t i o n is i n t e r e s t e d as a g u i d e for the i n v o l v e d nursery staff. F u r t h e r m o r e , as we c o n t r i b u t e to p r o v i d e the p a t i e n t w i t h g o o d i n f o r m a t i o n on t h i s process.

PTu894

TOSuO02

Lena Nyberg I, A. UIl~n 2, T. Stigbrand 2 , J. Brundell I AB Sangtec Medical, Sweden 1 Dept. o f Immunology, Ume& University Hospital, Sweden 2 SANGTEC®100 A NEW METHOD FOR MEASURING PROTEIN S i00 IN SERUM AND CSF IN PATIENTS WITH CEREBRAL IMPAIRMENT AFTER E X T R A C O R P O R E A L CIRCULATION AND MINOR HEAD INJURY. Sangtec®100 is a immunoradiometric assay based on three monoclonal antibodies binding to the Po-subunit o f the protein S- 100. S- 100 is a homo- or heterodimeric protein consisting of two subunits, c~- and 15. S-100a(c~g) and S-100b(fs13) are present in glial cells and S-100a0 (c~a) is found mainly in heart and striated muscle. We have developed an assay discriminating between the cx- and Po-subunit, and as a merit of the low detection limit (0,2 >g/l), is it possible, in a blood sample, to monitor patients obtaining CNS complications in association with ECC as well as brain damages in patients with minor head injury. The assay estimates the concentration of S-100a and S-100b, but will not capture the S-100a0. Antibody affinity (BIAcore) and western-blot studies of the monoclonal antibodies, reveals high binding specificity to the Po-subunit. The serum sample (I00 lal) is incubated with a plastic bead coated with monoclonal antibodies and the assay procedure with two incubations takes 3 h. • • • 125, • < the tracer antibody is labelled with I. The lowest measurable value is 0,2 pg/l and the between assay variation is below 10 %. The serum concentration of S-100 in healthy people is below the detection limit. Recent findings suggest that monitoring of Sangtec®100 in serum will be a valuable tool for prognosis of CNS impairment after ECC surgery and also provide information about the presence and extent of brain damage in minor head injury.

D.P. Coleman, J.M.Jones, W.D.Evans and A.R.Richards. Department of Medical Physics and Bioengineering, University Hospital of Wales, Cardiff, U.K

CAN COUNT RATE ALONE BE USED TO EXPRESS 14C-UREA BREATH TEST RESULTS ? The 14C-Urea breath test is routinely used for the detection of Helicobacter Pylori in the stomach and to monitor the success of eradication therapy. The results are currently expressed as the percentage of administered activity per mmol of exhaled CO2 at 40 rains. However the measurement process is time consuming since it involves counting samples with and without the addition of an internal 14C standard. The objective of this stud), was to compare sample count rate (CPM) before standardisation with % per mmol of CO2 in order to assess whether the former c o u l d provide a quicker but still reliable indicator of the presence of H. Pyhiri. Tests were performed on 164 patients using 92.5kBq of 14C-Urea (Amersham International PLC). Breath samples were collected into 2ml of a IM hyamine hydroxide/ethanol solution with phenolphthalein as indicator. Subsequently, 10ml of Optiphase Hisafe3 scintillation fluid (Wallac) was added and the mixture counted on a LKB Wallac liquid scintillation counter together with background samples and diluted standards. Background corrected sample count rates were calculated prior to recounting after the addition of internal standard. A significant positive correlation (r = +0.993, p < 0.001) was obtained between corrected count rate and % per mmol CO2. r = + 0.993 n= 164

7ann

o o 20n0 io~0

-.'.. J'-

o

oQ8

o.o~ ol % per mmolC02

g.12

~ 14

This strong correlation indicates consistency of delivered activity (and thus manufacturers calibration), dispensing of patient activity and standards, sample collection, quenching of patient samples and efficiency of beta counting. It indicates that sample count rate without standardisatlon can provide a quick and reliable result. 1 255

TOSuO03

TPSuO05

E.B. Koenders, R.A.M.J. Claessens, O.C. Boerman, W.J.G. Oyen, F.H.M. Corstens Departments of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.

C.Onofri, S.Fanti, A.Romeo, V.Grazia, S.Zoboli, M.Levorato, C.Corbelli, E.Cnnti, L.Martini, M.Marengo, A.DeFabritiis, 1LFranehi, N.Monetti. Dpts o f Nuclear Medicine, Angiology, Medical Physics. S.Orsola-Malpighi Hospital, Bologna, ITALY.

THE EFFECT OF THE IgG-SOURCE ON THE IN VIVO BEHAVIOR OF

CO2 BRAIN SPECT FOR ASSESSING CEREBRAL PERFUSlON RESERVE: TECHNICAL ASPECTS OF SINGLE-DAY APPROACH

Tc-99m LABELED IMMUNOGLOBULIN PREPARATIONS. Preparations of human immunoglobulin G (IgG) labeled with Tc-99m are currently used for the scintigraphic detection of infectious and inflammatory foci. In the present study we investigated the effect of the IgG-source on the in vivo behavior of this radiopharmaceutical. Four different brands of human IgG (CLB, Sandoz, Cutter, Baxter) were labeled with Tc-99m via the hydrazinonicotin (HYNIC) linker. The immunoeonjugates were analyzed on HPLC, for both the presence of high molecular weight (HWM) aggregates as weIl as for free Tc-99m. To determine the cause of the formation of the HWM aggregates the lgG was subsequently analyzed on HPLC following each step of the conjugation procedure (pH rise - conjugation - neutralization - dialysis radiolabeling). The biodistribution of each of the four Tc-99m-HYNIC-IgG preparations was determined in rats with focal S.aureus infection by T-camera imaging as well as by dissecting tissues 24 hr postinjection of the radiopharmaeeuficals. Labeling efficiency of each of the IgG-HYNIC preparations was always higher than 95 %. The Cutter and Baxter IgG-based preparations contained the least amount of HMW aggregates (11%), while the other preparations contained more than 15% HMW aggregates. Of the total HMW aggregates formation one third was caused by rising the pH to 8.2 and two third was due to the conjugation with HYNIC. With all preparations the abscess was clearly imaged, and their abscess uptake levels were similar (1.0 _+ 0.2 %ID/g). However, remarkable differences were observed in the uptake levels of several nontarget tissues. The Tc-99m-IgG preparation based on the Baxter and Cutter lgG showed a significantly lower splenic (1.0 %ID/g), hepatic (0.9 %lD/g) and renal (I.6 %ID/g) uptake at 24 hr p.i., as compared to the other two preparations (1.4 %ID/g, 1.1 %ID/g and 3.0 %ID/g, respectively). Differences in HMW aggregate content might partly explain this observation. The variations in HWM aggregate formation may partly be due to the differences in glyeosylation between the various IgG sources. These data indicate that a careful choice of the source of the nonspecific human immunoglobulin can contribute to the opimization of the imaging characteristics of Tc-99m-lgG.

Cerebral perfusion reserve can be assessed by brain SPECT and vasodilatatory stress. This study aimed at evaluating technical aspects and problems of single-day CO2 + rest brain SPECT. We studied 16 patients with internal carotid artery stenosis. Technetium99m-ECD was used as radiotracer (200-300 MBq for CO2 study and 700-900 MBq for baseline study: dose ratio=1:3.5). SPECT was carried out using a three-head camera with fanbeam collimators, matrix 128x12g, cireular orbit of 120 step, 22 see/step. Images were FBP reconstructed and realigned in ortogonal axes reoriented to bipolar line: no external markers were used but attention was paid to carefully repositioning patient. To induce vasodilation continuous inhalation of 5% CO2 gas was used, employing a flexible mouthpiece more tolerated than rigid mouthpiece or mask. The availability of a high-efficiency gammacamera allowed good quality images to be acquired even for CO2 brain SPECT, despite the low dose (CO2 SPECT mean counts per study = 1850+120 K). It was possible to complete study acquisition (CO2 + rest) of two patients in 225_+_20 min. For reconstruction we found 3D Wiener post-filtering optimal. On the basis of visual analysis, comparative realignment was good in 12 cases and satisfactory in the remaining 4. Our data demonstrate the feasibility of ECD brain SPECT with CO2 inhalation and single-day approach. The use of high-quality tomograph is necessary and several technical factors should be respected to prevent possible pitfalls (ECG monitoring during inhalation, care in dose ratio and execution timing, proper patient repositioning and appropriate reconstruction of the images).

TOSuO04

TPSuO06

M. Welling, R. I. J. Feitsma, W. Calame, E. K. J. Pauwels

~ , IH van der Sijs, G Olivier, S Anroedh, J Romijn, J Visser, EA van Royen. Academic Medical Centre, Departments of Nuclear Medicine and Pharmacy, Amsterdam, The Netherlands.

Tc-99m-LABELLED MONOCLONAL ANTIBODIES AGAINST TNF-c~ AND INTERLEUKIN-8 AS RADIOPHARMACEUTICALS FOR THE DETECTION OF BACTERIAL INFECTIONS

QUALITY

CONTROL

PROCEDURE.

OF MAG-3 BY THE SEPPAK

This study was designed to assess monoclonal antibodies directed against TNF-cx (anti-TNF) or Interleukin-8 (anti-IL-8) as a radioactive agent for the In our hospital, the uptake of renal transplants is calculated as a detection of Staphylococcus aureus or KlebsieUa pneumoniae infected fraction of the injected dose. In this study, we investigated the thighs in mice and compared with non-specific 99roTe-labelled polyclonal stability of MAG-3 until 24 hours after preparation. In addition, we human immunoglobulin. investigated the influence of different boiling times on the quality of Methods: At 5 rain or 20 h after the infection 20 pg of the 99~Tc-labelled the product by dividing the contents of bottles into fractions and antibodies were injected. At various time-intervals the accumulation of the boiling each fraction for different times ranging from 5 to 30 radiotracer in the infected thighs was assessed and expressed as a target-tominutes. non-target (T/NT) ratio.Twenty hours after injection, the binding of 99roTeThe mean labellingspercentage was 93% (range 88.9-97.9%). labelled antibodies to circulating mononuclear cells and granulocytes was The lipophilic impurity was independent of boiling times, and was on quantitated. average 2.8%(range 1.7-5%). Results: In this experimental study the 9~Tc-anti-TNF accumulated to a The hydrophilic part had a mean value of 2.4% (range 1-15.5%). higher extent (p<0.05) in S. aureus infected thighs in mice at 4 hours after The optimum heating time seemed to be 15-20 minutes.The labelling the infection (TINT ratio 4.21 __+_0.97) than 99~Tc-IgG (2.39 ± 0.76) and at did not decrease until 24 hours after preparation. one hour (2.37 - 0.26) in K. pneumoniae infected mice (p<0.03) compared with 9~Tc-IgG (1.22 _+ 0.38). At 24 hours after the inoculum of S. aureus Quality control of MAG-3 is important when the uptake of the anti-IL-8 detected the infection more intensely (2.90 _+0.13) compared with pharmaceutical is calculated as a fraction of the injected dose, as in 99~Tc-IgG (2.25 _+ 0.29, p<0.05) and after 21 hours (2~31 ± 0.40) in K. case of renal transplant studies. pneumoniae infected mice compared with 9~Tc-IgG (1.35 _+0. l 5, p<0.03). In left to right ratio calculations its effect on the background is In S. aureus and in K. pneumoniae infected mice the initial localization of uncertain, because of the behaviour of the lipophilic and hydrophilic sites of TNF-~ and IL-8 activity correlates (P<0.05) with increased binding impurities in vivo. of the 99~Tc-labelled monoclonal antibodies to mononuclear cells and at later scans with the increased binding (P<0.05) of 9~Tc-labelled monoclonal antibodies to both mononuclear cells and granulocytes. Conclusion: 99mTc-labelled monoclonal antibodies, directed against TNF-c~ and IL-8 can visualize bacterial infections in mice at distinct intervals after infection and is related to binding of the antibodies to various types of leucocytes.

1256

TPSu007

TPSu009

Britt Marie Jansson, University Hospital Lund, Department of Clinical Physiology,

L.F.L. Lu, M.M. Dalipaj, T.D. Ruddy. University of Ottawa Heart Institute at the Ottawa Civic Hospital, Ottawa, Canada

GASTRIC SCINTIGRAPHY

COMPI~RISON OF 991Te-SEST~4IBI UPTI~E DURING /~RBUT~J(INE INFUBION VERSUS EXERCIBE BTREBS. Arbutamine (ARB) h a s b e e n d e v e l o p e d for stress

Gastric scintigraphy is a most sensitive and reliable method to quantitate gastric emptying. Studies are being conducted by using a variety of techniques. They differ in patient positioning (laying, sitting, standing), recording (single or dual headed gamma camera ) and the way data are acquired (continuos serial images or intermittent registration). Food transport alter stomach shape, position and the distribution of its content and these geometrical errors should be corrected. We chose to perform the examination with the patient in upright position, using a single head gamma camera with intermittent recording in anterior and posterior projection consecutively. The patient is marked with pencil on the level of the xiphoid process as lateral as possible. A cobalt marker is placed on the ink mark at each frame. Plexiglas is placed on the screen to draw stomach region and cobalt marker that enables the same positioning on each frame. The measurement start after the patient received a standardised meal consisting of omelette. Each frame is recorded for 1 min and imaging is performed every 5 minutes during the first 30 minutes and thereafter every 15 minutes for the next 90 minutes. With this method the study is performed under physiological conditions. Intermittent recordings is well tolerated by patients. Anterior and posterior projections allow adequate geometrical corrections performed with single head gamma camera as compared with simultaneous recording with dual headed gamma camera.

testing in patients unable to exercise. Eight patients (mean age 64±10 years,7 male & 1 female) with known coronary artery disease underwent 99mTc-Sestamibi (MIBI) imaging after ARB infusion & exercise stress on separate days within a 14 day period. Approximately 700 - 800 MBq (~8 - 22 mCi) of MIBI was injected at peak ARB or exercise stress & multigated planar imaging was carried out. The 16 frames of each three gated planar views (ANT, LAO, LLAT) were added to give three separate compiled views. MIBI uptake in cts/pixel was calculated using regi~Rs of interest drawn over various cardiac & extracardiac structures. The cts/pixel were normalized to the highest MIBI dose. Peak heart rates were similar after ARB & exercise. There was So significant difference in MIBI uptake (mean±SD) in the myocardium between ARB (anterior: 662±160, inferior: 650±174 cts/pixel) & exercise (anterior: 757±211, inferior: 704±220 cts/pixel). MIBI uptake was greater after ARB for sternal and liver regions (255±71, 749±195 cts/pixel) as compared to exercise (171±34, 424±165 cts/pixel) (p < 0.02). Heart/lung & heart/liver ratios were smaller after ARE (2.58± 0.39 & 0.86± 0.19, respectively) as compared to exercise (3.22±0.30 & 1.76~0.48, respectively) (p < 0.05). Myocardial uptake of MIBI was similar after ARB versus exercise. However extracardiac uptake differed with more favourable heart/lung and heart/liver ratios after exercise stress.

TPSu008

TPSu010

Lorotte A., Fayolle S., Pelletier M., Langlet D., Lucas S., Mabire F., Grimon G., Desgrez A. ; service de m6decine nucltaire, htpital AntoineBtcl~re, AP-HP, 92141 Clamart. FRANCE

G. Bern, A.-M. Danielsson, L. Engelin, M. Finnbogason, R. Hatherly. Department of Hospital Physics, Section for Nuclear Medicine, Karolinska Hospital, S-171 76 STOCKHOLM, Sweden

PERFUSION LUNG SCAN: H O W T O F A C I L I T A T E T H E I N T E R P R E T A T I O N OF IMAGES EVOLUTION

VENTILATION AND PERFUSION LUNGSCINTIGRAPHY WITH SPECT USING A THREE-HEADED GAMMACAMERA

The department of Nuclear Medicine often performs repeated lung perfusion scan. Main concerning pathologies are acute or chronic pulmonary embolism and pulmonary arterial hypertension. The followup of these patients includes a perfusion scan at regular intervals. Acquisition is carried out through a Gammatome II. Eight projections are transmitted to a computer (NXT, Sopha Medical) and stored in a 128x128 matrix. The matrix is transfered to visualization memory. A grey scale is applied by chosing 3 parameters: minimum threshold (%), maximum threshold (%) and y function. The images are carried out through a reprograph (Formax) on films (KODAK NB 20,3x25,4cm). Numeric data are stored on optical disk (OPD). We aim at presenting you a comparative method of image visualization. We had 2 problems: how to reproduce the image aspect and how to obtain a general view of the scintigraphic evolution of the disease. Achievement: We decided to apply the same scaling to the images realized for all the tests made for the same patient. During the first scintigraphy, the technologist notes on the film the scaling parameters. These values will be applied to the images made during the next examinations. We now carry out an additional film showing 2 to 4 examinations. Each of these is represented by 4 incidences (anterior, posterior and posterior obliques, strictly made with the same angulation); these 4 incidences have been selected because they allow to visualize the highest quantity of pulmonary segments. When the patient has come more than 4 times, the nuclear doctor decides which tests will be reproduced on the film (usually the one of the day, the previous, the first, and one intermediary exam, which are imported from OPD, on the same additional film). Conclusion: We obtain a more reliable reproduction while comparing the tests supported by the same patient because all the parameters used to carry out, process the images, display and developing the films are the same. An evaluation is being made through a questionnaire among the chest specialists and the nuclear physicians.

The conventional method of lung scintigraphy involves a series of planar acquisitons for ventilation/perfusion. We routinely employ SPECT for lung examinations with the query of embohis. Ventilation is acquired using a Tc-99m DTPA aerosol (mean size 1.2 It) generated by a nebulizer (Intersurgical, Wokingham, Berkshire, UK). A total count rate over the lungs of about 1.0 kc/s is achieved in 3-5 minutes with an average of 40 MBq delivered to the patient. A S P E C T acquisition is performed with the patient supine and raised arms using a Triad XLT three-headed gammacamera (Trionix, Twinsburg, OH., USA) equipped with ultra-high resolution collimators at 90 angles for a total acquisition time of 12 min. On completion of the ventilation acquisition another SPECT study with the patient in the exact same position using identical parameters is performed after administration of 170 MBq Tc-99m MAA. A subtraction of the images acquired at the ventilation study from the later acquisiton is made, this giving rise to images principally representing the perfusion. Both studies are reconstructed and presented as transverse sections and reprojected 3D-images. The total examination time for the ventilation/perfusion study is approximately 45 min. With exception of two patients with severe rheumatoid arthritis it has been possible to perform combined ventilation/perfusion studies with SPECT as described in more than 200 patients consecutively examined since the begining in early 1994. The three-headed camera system makes it possible to maintain adequate statistics using low-sensitive ultra-high resolution collimators which improves the depiction of cold spots on which the scintigraphic diagnosis of pulmonary embolism is based. The tomographic examination also brings about an increased contrast resolution and a more detailed anatomic information presented in exactly corresponding sections of the ventilation and perfusion studies thus improving the diagnostic accuracy. The total examination time is comparable, if not shorter than for a complete conventional examination with planar technique.

1257

¢)

o O

2:O

TPSu011

TPSu013

R.Baravelli ^- L.Ferraguti ^ - B.Marini ° - A.Perri* R Bentivoglio ^^ ^Nuclear Mediuine Dpt. S.AD~a Hospital Ferrara-Italy =Nuclear Medicine Dpt. S.Gerardo Hospital Monza-Italy ^^School of Radiology Tech. S,Anna Hospital Ferrara-Italy

K.Saito, H. M u r a t a , Division of Nuclear Tokyo, Japan

THE STABILITY O F 9 9 m T c - T E T R O F O S M I N R O O M T E M P E R A T U R E (22 °C)

QUANTITATION OF REGIONAL CEREBRAL BLOOD FLOW WITH AUTORADIOGRAPHY METHOD USING 12~I-IMP S P E C T -- REPRODUCIBILITY OF RCBF AND ITS CLINICAL USEFULNESS -Reproducibility of regional cerebral blood flow(rCBF) values obtained by the Autoradiography(ARG) method with one SPECT scan and one point arterial blood sampling at I0 m i n a f t e r 123I-N -isopropyl-p-iodoamphetamine(IMP) infusion was evaluated and its clinical usefulness was studied. The error in t h e c r o s s c a l i b r a t i o n factor between SPECT count and well type scintillation counter was 0.7~. The error in r C B F b y s a m p l i n g time difference was less than 3~. Thus, the technical error in r C B F v a l u e s was within 4~. There was a favorable correlation between the rCBF values in two separate scans measured by the ARG method in 4 patients (r=0.93),however, rCBF values measured in t h e 2 n d s c a n t e n d e d to be of a lower value. Quantitation of rCBF with the ARG method was applied to patients who had undergone carotid endarterectomy. In a c a s e w i t h r i g h t i n t e r n a l carotid occlusion and left internal carotid stenosis,left carotid endarterectomy was per-

•

LABELING AT

The stability of 99mTc-tetrofosmin labeling, a tracer for the study of the myocardial perfusion, is guarantied from the producer until 8 hours at 4 ° C of temperature. The purpose of our work was to establish the stability of labeling of tetrofosmin at room temperature. MATER~/%LS and METHODS: We effected quality controls (QC) of tetrofosmin by paper radiochromat ography (ITLC-SG) , using a mixture of two solvents ACETONE (35%) and DICHLOROMETHANE (65%) . We evaluated the percentage of labelled, hydrolized and free Technetium. The labelling efficiency was evaluated inLmediately after labeling and incubation (T0), and after a delay of 2, 4, 6 and 8 hours22* C - in vial maintened in eight (8) samples. BESmhTS : In every samples the labelling efficiency resulted mere than 95%. The stability of labeling between 2 to 8 hours do not resulted lower than 90%, the lowest limit for tbe i.v. injection of
% Bound

% Free 2,2

o

97.8

2

97.6

2.4

4

97.$

2.1

6

94.1

5.g

&

94.2

5.8

CONCT.USI~S : 99mTc-tet rofosmin keeps its labelling efficiency until 8 hours also at room temperature.

H. M a r u n o Medicine,

Toranomon

formed. In this case, no s i g n i f i c a n t d i f f e r e n c e in rCBF was o b s e r v e d by the q u a l i t a t i v e i n t e r p r e t a t i o n b e t w e e n pre- and p o s t - o p e r a t i v e IMP images. However, the i n c r e a s e in rCBF o v e r i 0 ~ was d e t e c t e d in the p o s t - o p e r a t i v e rCBF v a l u e m e a s u r e d w i t h the A R G method. R e p r o d u c i b i l i t y of rCBF w i t h the ARG m e t h o d was good. T h e r e f o r e , we t h i n k that the ARG m e t h o d is u s e f u l as a c l i n i c a l m e a n s w h i c h can be a p p l i e d to o b s e r v e a rCBF imp r o v e m e n t a f t e r the o p e r a t i o n .

TPSu012

TPSu014

S. Pr6vot 1, A. Berriolo-Riedinger1, C. Touzery l, S. Rudoni% G Matejka2, M. Cohen% Y. Cottin% G. Vaillant 2, B. Verges2, J. M. Brun% F. Brunotte ~ (1) Service de M6decine nucleaire,Centre Georges-Fran~ois Leclerc, (2) Service d'Endocrinotogie, C.HU. Bocage, DIJON - FRANCE

L. Betto, P. Zanco and G Ferlin. Nuclear Medicine - Castelfranco Veneto, Italy.

COMPARISON OF THE FREQUENCY OF USE OF MYOCARDIAL STRESS TESTS IN THE DETECTION OF ASYMPTOMATIC DIABETIC PATIENTS CORONARY ARTERY DISEASE Coronary artery disease (CAD) is a major cause of morbidity and mortality in diabetic patients. Thallium SPECT after exercise stress testing (T1) improves the non invasive approach sensitivity and specificity. Diabetic patients, however, are often unable to exercise optimally because of obesity, peripheral arteriopathy and/or associated neuropathy. They are candidates for dipyridamole stress testing (0.56 mg/kg)(T2). A standardized low-level bicycle exercise (men 40 W/4 minutes - women 30 W/4 minutes) following dipyridamole infusion (T3) is an interesting alternative which increases myocardial request and improves the contrast between myocardium and adjacent area. The aim of this work is to compare the frequency of use of the 3 stresses in 197 asymptomatic diabetics (DIA) (112 men, 85 women) versus a population of 941 non diabetic patients comparable in age (POP) (604 men, 337 women) referred for the detection of CAD.

DIA (%) POP (%) p

AGE (years) m +_SD 61.5 _+9.4 60.4 + 11.4 NS

T1 27.4 37.7 < 0.01

T2 48.7 37.6 < 0 01

T3 23 9 24.7 NS

The results show that the maximal exercise test (T1) is more frequently used in non diabetic patients. Dipyridamole infusion (T2) remains the preferred procedure for diabetics. The combined test (T3) is used in 23.9 % of cases at least in the two groups. Considering the combined test synergic effect on myocardial ischemia induction, this test should be suggested rather than dipyridamole infusion alone in asymptomatic diabetic patients.

1258

Hospital,

W H A T IS THE BEST TIMING FOR MIBI MYOCARDIAL SPECT? COMPARISON OF 15-, 60- AND 180-MINUTE SCANS. Usual acquisition time for MIBI scan is 60-75 min after injection Earlier acquisition could reduce the total time of the study, allowing advantageous,short-lasting one-day protocol,while redistribution of MIBI could significantly change the tracer uptake in delayed images.To evaluate the real impact of different acquisition times on MIBI scan 15 infarcted patients (12m,3f, aged 45-62y)were enrolled .Rest and stress SPECT acquisition was repeated 3 times: at 15, 60 and 180 minutes after MIBI injection.To reduce the interference of bowel activity, 1/2 litre of water per os was given to the patients 3 min before acquisitions.Left ventricular wall was divided into 16 segments, and, using a semiquantitative analysis, a score was assigned to each segment in each acquisition, by 3 blinded skilled observers~The extension of the perfusion defects in rest and stress images,the extension of reversible defects and the severity of stress defects were analyzed. The localization of the defects was also evaluated, dividing the ventricle into anterior and infero-posterior territories.The 15- and 180-min image parameters were then statistically correlated assuming as gold standard the 60-min results. Both 15- and 180-rain images correlated well with usual 60-min acquisition for all the examined parameters (p<0.01). The best correlation was obtained evaluating the extension of the reversible defect and the severity of the stress defect(p<0.0001).The agreement with 15min images was good in localization of the defects too (k=0.82).The results with 180-min acquisition were not so good(k=0.56): a higher number of ischemic territories were observed, with respect to 60-rain acquisition (20 vs 14, on a total of 30 examined territories),both in anterior and infero-posterior site. In conclusion our experience suggests that MIBI SPECT may be acquired earlier than usual, from 15 rain after MIBI injection, while delayed acquisition could lead to overestimation of ischemic area.

TPSu015

TPSu017

G Alvarez I_g!esias.JA Ruiz Guijarro F G Gallardo. IVIVG6mez

E. Higazi, M. Sayed', S, Heiba, A. Khalaf, H. Salman, Z. Saieh, M. Naeem, S. Brously, S. Mohanadl, N. Hayat. Dept. of Nuclear Medicine and Cardiology, Faculty of Medicine, Kuwait University and Ministry of Public Health.

CIC

-

INSTITUTO SALLUD CARLOS NADRID - SPAIN

III

LEFT VENTRICULAR FUNCTION AND MYOCARDIAL PERFUSION IMAGING ASSESSED FROM GATED Tc99TETRAFOSMIN, Tc99-tetrafosmin is a new myocardial perfusion imaging agent that is used as an alternative to conventionait T[201 imaging, it is likely that Tc994etrafosmin could provide myocardial images of better quality with less soft-tissue attenuation than T[201. Tc99-tetrafosmin perfusion imaging allows characterization of the extent of perfusion abnormalities. Electrocardiographic gating of Tc-99m--tetrafosmin provides additional ability to determine the abnormalities myocardial function Patients 30 patients (t4 men and 16 women) were studied. 'Fen patients had previous myocardial infarction. Perfusion study: Stress and rest SPECT images were acquired in one day protocol, Tc99m-tetrafosmin was injected either during peak exercise ( 22 patients) or 3 min following intravenous dipyridamole infusion (0.142 mg/kgtmin administered over 6 mill.) (8 patients) Acquisition started 15 min. after radiotracer administration. Rest study was performed 3 hours after stress images. Function study was acquired alter the rest perfusion acquisition, A planar gating image was obtained in "best septal " view. Data analysis: perfusion and function images were qualitatively evaluated In the perfusion study eight segments were analyzed. Segments were classified as fi~llows: Normal segments, fixed defect segments and reversible defect segments. Gated Tc-99mtetrafosmin images were filtered using a Wiener filter Wall thickel/ing and changes in left ventricular cavity size between systole and diastole images were considered for determining regional contractility and ventricular function. Results: 120 segments were analyzed 73% segments were normal segments, 9% were fixed defect segments, 10% were reversible segments and 8% were partially reversible segments. Only 4 patients had poor left ventricular function. Fifty for of 73 normal perfused segments had normal regional contractility and for of eight fixed defects had amnesia Conclusion: Simultaneous function and pefusion meassurement potentially increases specificity of fl~e test Functional information may be adjunctive to the results of the pe ffusion study with regard to diagnosis and prognosis.

VALIDATIONOF LATERALPOSITION QUANTITATIVE Tc-99m SESTAMIBI SPECT IMAGINGWITH CORONARY ARTERIOGRAPHY. The lateral position use for myocardial perfusion imaging can overcome the diaphragmatic attenuation problem of the routinely performed supine position. Furthermore, it is more tolerable by patients particularly female ones than prone position imaging. Sixty five studies of 50 consecutive patients (14 female) age 34:70 with suspected coronary artery disease included in this study. Following a standard exercise protocol, routine SPECT supine imaging were performed followed by a similar second lateral position acquisition. The patients were laid down on their right side and the gamma camera rotated from left posterior oblique to right anterior oblique. Quantitative analysis of both abnormal myocardium extent and severity of all images were done using commercially available GE Bull's eye program and compared to coronary arteriography data. All patients tolerated lateral position, The mean _+SD of extent and severity of abnormal pixels were as follows : Region

Supine

Extent Lateral

P

Supine

Severity Lateral

P

Anterior 27.8_+27.9 26.3_+25.0 NS 131,0!-_165.1 1465_191,1 NS Septum 12.9-+19.6 12.5+_22,8 NS 73.3_+143.1 65,95-142.0 NS Inferior 25.9&-_27.1 19.7+-27,8 <0.01 138.45:160.6 100.7_+160.7<0.001 Lateral 33.1-+31.7 23.3_+30,2 <0.005 173.7-+153.9 130.7_+189.5<0.01 Apex 17.2_+34.413.6+_26,8 NS 115.6_+247.2 62.15-134.5 <0,01 The overall CAD sensitivity and specificity as determined by coronary arteriography were 94% and 71% for lateral vs 94% and 45% for supine position, Individual vessel sensitivity and specificity was only marked for RCA 92% and 85% in lateral vs 100% and 45% in supine. We concluded that lateral position imaging can better assess CAD than traditional supine position and is suitable for males as well as females.

TPSu016

TPSu018

J.C.M. Buijs, F.J. Beekman, A.J. van Dongen and P.P. van Rijk, Department of Nuclear Medicine, University Hospital Utrecht, The Netherlands

R.S. Fieber, K. Richter, K. Tatsch, H.F. Kung*, K Hahn

EFFECT ANGLES

ASPECTS OF DOPAMINE D2 RECEPTOR AND DOPAMINE TRANSPORTER IMAGING IN PARKINSON'S DISEASE

O F M A T R I X SIZE A N D N U M B E R ON BRAIN SPECT IMAGES

OF PROJECTION

W e investigated the effect of projection matrix size and the number of projection angles during acquisition. A single slice Hoffman brain phantom containing 5 M B q 99m Technetium and a few H M P A O patient studies (injected dose 800 MBq) were evaluated. Ultra high resolution fan beam collimators mounted on a triple headed Picker Prism 3000 camera were used. The acquisition time in all cases was 25 minutes. Combinations of both 64x64 matrix (projection pixel size 7.12 ram) with 60 and 120 angles and 128x128 matrix (projection pixel size 3.56 mm) with 60 and 120 angles were considered. A Butterworth filter (order 3, cut-off frequency 0.67 cycles per cm) was used. Results of phantom data, in particular star artifacts, were evaluated by subtracting a scaled apparently noise-free phantom image from the image. For both matrix sizes, images significantly improve in the case of 120 angles: less star artifacts are seen. However, the image quality improvement by taking more angles is stronger in case of 128x128 matrix size. The effect of the fi]ter cut-off did not strongly influence these results. In conclusion, 120 projections are preferable to 60 projections, especially when smaller pixel sizes are used. This is supported by patient studies: artifacts appearing on brain surface were strongly reduced by taking more projections.

Dept. of Nuclear Medicine, University of Munich, Germany, Dept. of Pharmacology, University of Pennsylvania*, Philadelphia, USA

Functional disorders of the dopaminergic system are known to be involved in a variety of neurologic and psychiatric disorders. Since pathological changes may precede the onset of clinical symptoms by years, abnormalities detectable by imaging techniques could provide important information for the clinician. Since several years various radiotracers (e.g. 1-123 labeled IBZM, IBF or Epidepfide) are available to study the postsynaptic dopamine D2 receptor status. More recently 1-123 labeled cocaine analogues, such as B-CIT, B-CIT-FP or IPT have been developed, which permit to image the presynaptic dopamine transporter as well. We investigated patients suspected to suffer from Parkinson's disease using 1-123 IBZM (I- 123-(S)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl)methyl]-benzamide) and 1-123 IPT (I-123(N)-(3 -iodopropen-2yl)-2B-carbomethoxy-3 B-(4-chlorophenyl)tropane) SPECT to address both the pro- and postsynaptic aspect of the dopaminergic system. SPECT data were acquired 120 min after administration of 185 MBq 1-123 I B Z M and 90 min p.i. of 150 MBq 1-123 IPT using triple head camera systems (MULTISPECT 3 SIEMENS / PRISM 3000 PICKER, HR Fan beam or special 1-123 collimators, 128x128 matrix, filtered backprojection, CHANG's attenuation correction). Semiquantitative evaluation was performed by ROI technique, comparing striatal (caudate, putamen) to reference ratios. According to the underlying pathophysiology the characteristic finding observed was normal or slightly elevated IBZM binding to the postsynaptic dopamine D2 receptors combined with decreased IPT binding to the presynaptic dopamine transporter. The latter reflects the degree of nigrostriatal degeneration and was already evident in the early stage of Parkinson's disease. Imaging pre- and postsynaptic aspects of dopaminergic system allows to definitely diagnose Parkinson's disease and may be helpful in the assessment of other neurodegeneratlve disorders as well. 1259

¢n o')

o o cO

TOMo019

TOMo021

Y.Takahashi,H.Shinbata,Y.Yuyama,A.Masuhara Ehime Prefectural Central Hospital,and Ehime Prefectural Imabari Hospital,Japan. Department of Radiology.

T. Berthold, A. Buck, H. Steinert, M Ladd, C. Burger, G K yon Schulthess, K. Borbely Division of Nuclear Medicine, University Hospital, Zurich, Switzerland

THE USEFULNESS OF HIGH-SPEED CONTINUOUS REPETITIVE D A T A A C Q U I S I T I O N IN T c - 9 9 m T e t r o f o s m i n M Y O C A R D I A L SCINTIGRAPHY Since T c - 9 9 m T e t r o f o s m i n has a long r e t e n t i o n time in myocardium, and is applicable to emergency examinations because it is supplied in vials, it can be u s e d to e v a l u a t e t r e a t m e n t s i n v o l v i n g after injecting Tc-99m Tetrofosmin intravenously. The radioactivity of the r a d i o l i g a n d m a y b e d e c r e a s e d long after reperfusion causing degradation of the SPECT image. Continuous acquisition has been postulated as a method of increasing radiological counts. However, parameters for this method are not well established. To clarify the relationship between the rotation rate of the detector and image quality, we evaluated SPECT images for measurements with 1,3,6,9 and 12 rotations w i t h i n a given total data a c q u i s i t i o n time. SPECT equipment c o m p r i s e d of a G C A - 9 3 0 0 A with three detectors was used for the study. When we evaluated the results using a cylindrical phantom, the total counts tended to be dacreased with y=-0.0034x2+0.016x+l.24 r2=0.99 (step;l.00), and s t a b i l i t y of decay rate d u r i n g SPECT data a c q u i s i t i o n (changes in RI c o n c e n t r a t i o n ) was decreased which was related with y=0.024xZ-0.78x 98.14 r2=0.98. E v a l u a t i o n s using a m y o c a r d i a l phantom demonstrated that uniformity and visualization of the defective area were degraded w h e n m e a s u r e m e n t s w e r e o b t a i n e d w i t h 9 or 12 rotation. Evaluations using healthy human volunteers demonstrated the same tendencies. Furthermore, a ~ u e s t i o n n a i r e was used was to clarify patient's impression of e x a m i n a t i o n s using high-speed continuous rotation of the detector. Patient felt uneasy about the high-speed rotation of the detector since the SPECT detectors are exposed rather than concealed as is in the case of the CT detector.

TOMo020 B._~iSSOn, C. Rolf, S. M&nsson, Department Clinical Physiology, University Hospital, Lund, Sweden.

Our clinical methods are all documented according to a common structure. That makes the m e t h o d descriptions easy to read and follow. Changes in the method have to be properly documented before we can use it in routine. Thus the method descriptions are always kept up to date.

PURPOSE'. to assess the optimal acquisition time and reconstruction filter in brain metabolic mapping with 2D and 3D acquisition techniques. METHOD: five patients with cerebral glioma and five with partial epilepsy were examined using a GE PET Advance Scanner (GE Medical Systems, Milwaukee USA). PET examinations were started 30 minutes after intravenous application of 250 MBq of 18-F Fluorodeoxyg[ucose. Patient head position was fixed using fixation straps: 1 on the forehead and 2 on the chin. The medial and orbital-meatal lines were verified by laser alignment lights. A 2D emission scan was acquired for 30 minutes, followed immediately by a 3D acquisition for 30 minutes. The 2D emission scan was reconstructed for each patient using an axial Hanning filter with a cutoff of 6.0. The 3D emission scan was reconstructed for each patient using an transaxial Harming filter with a cutoff of 4.0 and a axial ramp filter with a cutoff of 8.5 (based on recommendations from GE). No axial filter is available for 2D acquisitions. Calculated attenuation correction was used for both scans. The reconstruction software used was the standard product software provided by GE, which gives 35 slices, each 4.25mm thick, coverial an axial field of view (AFOV) of 144 mm. Accurate estimation of metabolic patterns in the brain tissue within, surrounding and remote from the lesion were estimated by regions of interest representing the tumor/focus, peritumoral/pedfocal and remote tissues, contralateral mirror regions, and standard brain regions. The 2D, 3D, and data obtained from Magnetic Resonance Imaging (MRI) were compared qualitatively. RESULTS: The "anatomometabolic" mapping between PET and MRI appeared to be more valuable using the 3D technique. The anatomic structures and localization of lesions were more well-defined because of the higher resolution resulting from higher sensitivity in 3D. CONCLUSION: For the same dose and acquisition time, 3D acquisition gives superior image quality to 2D acquisition. For equivalent image quality, either dose or acquisition time may be reduced in 3D. With 250 MBq, 10 min acquisition time is sufficient. Also, the axial ramp filter is superior to the axial Harming filter in 3D.

TOMo022 of

A C C R E D I T A T I O N IN NUCLEAR MEDICINE. EXPERIENCE FROM THE POINT OF VIEW OF A TECHNOLOGIST. In 1994 our department was the first in Europe to be awarded accreditation for nuclear medicine. Our most frequent in vitro and in vivo procedures became accredited. SWEDAC, the Swedish Board for Accreditation and Conformity Assessment performed a quality assessment according to the European Standard EN 45001. The inspection covered organisation, personal competence, accuracy of instrumentation, validation of clinical methods, traceability of measurements, verification of software etc.

COMPARATIVE BRAIN PET FDG EXAMINATIONS WITH 2D AND 3D ACQUISITION TECHNIQUES

E.Clarke, A Notghi, Physics & Nuclear Medicine Dept City Hospital NHS Trust. Birmingham UK

ARE MIBI / TETROFOSMIN STUDIES A RADIATION HAZARD TO TECHNOLOGISTS?

We use a one-day MIBl/Tetrofosmin protocol for heart studies. Tomographic rest images (250 MBq) are acquired in the morning. Pharmacological and/or physical stress are given after approximately 4 hours with a further 750 MBq of MIBI/Tetrofosmin. Exercise images are then acquired. 380 of these studies were performed in 1995, a 248% increase from 1994. This increased demand means up to 15 studies performed per week and technologists were concerned about continual exposure to 1000 MBq per study. Radiation doses were therefore measured using a digital pocket dosemeter during rest, exercise and stress administration. Results

mean

n

Rest Imaging

1.0 gSv

18

Exercise Imaging

2.5 gSv

18

Stress Administration

2.0 gSv

16

Total per study: 5.5 laSv

Before we are allowed to perform an accredited investigation by our own we need a ~license ~ from our manager. This is mainly based on experience. This "license" also includes the technologists weekly testing of equipment. To work in an accredited department cannot be learnt by reading a book. One has to learn by experience and adapt for a new way of thinking. This may take some time but it is necessary.

1260

If one technologist had performed the complete heart studies for 1995 their dose would have been 2 mSv, well wilhin the dose limits for those who are not pregnant. However following ALARP principles, stress administration now occurs in a larger specially equipped area and technologists encouraged to maintain their distance from the patient where possible. MIBVfetrofosmin heart studies are not a cause for concern but the radiation dose to technologist 5.5 gSv is higher than the average value for other studies (1.5 ~Sv) measured in the department.

TOMo023

TOMo025

M.E. Kooy, A. Sinon, J.A.K. Blokland, Department of Diagnostic Radiology and Nuclear Medicine, Leiden University Hospital

H Greuter, JMPA Eijndhoven, AJ Wilhelm, W den Hollander, GJJ Teule, A van Lingen. Nuclear Medicine, Free University Hospital, Amsterdam, The Netherlands

STEP MODE VERSUS CONTINUOUS MODE ACQUISITION ON THE TOSH/BA GCA 7200 DI GAMMA CAMERA. To obtain a good quality SPECT study a high amount of radioactivity must be used, or lung ar..quisitiontimes must be applied. The actual duration of a stepped SPECT study consists of the acquisition time per projection plus the time required for rotating the gantry between each step. On the Toshiba GCA 7200 di the rotation time including Robocontour~ movement may take as lung as I 1 minutes for a 120 steps 360° rotation. This is a significant part of the total acquisition duration. When continuous acquisition mode is used this time may be used to reduce the total acquisition duration, or increase the count density in each projection. But, the continuous rotating detector will introduce smoothing and so, toss of resolution. In this study we investigated the resolution and image quality during continuous rotation acquisition mode versus stepped acquisition mode. A Jaszczak phantom filled with 450 MBq 9~Tc solution was imaged in the same position, first in continuous and in step mode. Projections were acquired at 3°, 4° and 6° (120, 90 and 60 projections). Total acquisition duration and the number of projections were equal in both situations. Reconstruction parameters and attenuation eorreetion were equal too. A thick slice (29 mm) was reconstructed through the rods section, thin slices (2.9 ram) were reconstructed through the balls. The resolution and the image quality were visually assessedfrom the slices printed on film. Each member of a panel of six experts individually sorted the films in order of first increasing resolution and secondly increasing overall quality. Six points were assigned to the best scoring film, 1 point to the lowest. All scores were added together giving a total score for each acquisition method. This analysis revealed that the best resolution and image quality was obtained when continuous mode acquisition with the smallest projection angles was used. When larger acquisition angles were applied stepped acquisition mode was better. We conclude that continuous mode acquisition can be used to obtain better quality images in the same total acquisition time as in step mode acquisition, or equal image quality can be obtained in a remarkably shorter total acquisition duration.

TOMo024 L.F.Metello*. M. Malef*, J.J. Pedroso de Lima** *C.H. "New Paul Brien",D.A.D.R.I., Bruxelles - Belgique **I.B.I.L.I.- Fac. de Med., Univ. de Coimbra - Portugal S T A N D A R D I Z A T I O N ON NUCLEAR M E D I C I N E PROCEDURES: an u r g e n t n e e d w i t h s o m e risks to a v o i d . There is definitely no doubt about an urgent need to standardize nuclear medicine procedures, meaning this absolutely not that nuclear medicine technologists should became static repetitive routine workers. As technologists, it seems quite important to adopt a nonstatic behaviour, keeping and maintaining ourselves aware of all those, often small, details that can interfere on the final results of a day-to-day work. The work here presented consists of a collection of different "tips", mostly developed and/or practised in normal working departments, with an utility, that has been clearly demonstrated, to improve different aspects of the daily routine. For instance, it is showed that there is interest on the use of potassium perchlorate on all kind of examinations where "in vivo" RBCs labelling efficiency is a crucial point. Effectively, if potassium perchlorate is used, (orally administered at the same time of the stannous pyrophosphate injection), in order to blocate the thyroid gland and the gastric mucosa, the labelling efficiency can be increased from almost 50%, comparing with values obtained in the same situations, but without the use of potassium perchlorate. Being of extreme simplicity to perform, its costs, in funds as in occupational time, are quite negligeable, but the final results are notorious. It seems quite likely that improving final imaging quality must be the main purpose of most the technics and/or strategies to be described, but patient's access, confort and handling, radioprotection and professional safety (as well as patient's and environmental's, when clinically related) are also our concern. There is here no ambition to exhaust the subject, but rather to contribute to better, more functional, easier and safer working conditions, sharing "tips" and demonstrating how professionally important is to keep an open-minded attitude, away of routine directed situations.

A COMPREHENSIVE QUALITY CONTROL TEST FOR DOSE CALIBRATORS. For the daily routine of nuclear medicine it is of paramount importance that dose calibrators (DC) are accurate in measuring the activity of a radionuclide to be administered o f a radionuclide. DC readings are hampered by variations in source geometry and volume. In this study we examined a new parameter Qdc, based on the ratio of specific activities, which is expected to be independent on variations in source size and shapeas well as its position in the DC.. Methods. The new parameter represents the average ratio of the specific activity of a bulk activity (in 60 ml) and the specific activity of samples in syringes of different capacities and filled at different levels. This parameter was measured for a relatively new and an old DC, and for different radionuclides (Tc-99m, Ti-201, Ga-76) Results. The following results were obtained for both DC's and Tc-99m: For different volumes in test tubes, positioned within 15 cm of the DC bottom, the Qdc varied less than 5%. For syringes from 2 to 10 ml, the variation was less than 2%. For concentrations between 50 and 500 MBq per 60 ml, a subtle decrease in variability of 0.5% per 100 MBq/ml was observed. For TI-201 and Ga-67 similar results were obtained. The measurement of the Qdc takes approximately 1 hour. Conclusion. The new parameter Qdc summarizes the combined effects of different source positions and volumes. It is measured reproducibly and very well suited for regular quality control testing

TOMo026 D. Crombez, G. Bormans, T.J. de Groot, L. Mortelmans, A. Verbmggen Laboratory of Radiopharmaeeutlcal Chemistry, F.F.W., K.U.Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuverg Belgium

SHORTER SYNTHESIS OF [18FIFDG BY DEHYDRATION OF [18F]FLUORIDE ON AN ION EXCHANGE MEMBRANE Current 18FDG production procedures involve the nucleophilic substitution of 18F-fluoride (18F) on tetraacetylmannose triflat¢ (!). This reaction is performed in AcN either in the presence of kryptofix 2.2.2 (K222) or Bu4NH4-carbonate or on a quaternary 4aminopyridinium resin. In a traditional FDG production, irradiated [180]H20 is passed over an anion exchange membrane (AEM) that retains 1BE which is subsequently displaced by rinsing with an aqueous K2CO3/K222 solution. This solution is transferred to an FDG synthesis module in which the H20 is evaporated. Before addition of !, the last traces of H 2 0 are removed by two additions of AcN and subsequent azeotropic distillation of the AcNH20 mixture. The I-I20 removal requires about 13 min. With the purpose to shorten the synthesis time we have investigated the possibility to elute 18F- with an AcN solution of K2CO3/K222 and to use this solution as such for the reaction with 1_. As K2CO3 does not dissolve in a solution of K222 in anhydrous acetonitdle, K222 and K2CO3 were dissolved in 1 ml of H 2 0 and lyophilised. The lyophilisate was reconstituted with anhydrous AcN and this solution was used to elute 18F from the AEM (BioRad AGlx8, o 4 mm). Although the AEM displacement yield was low (20%), it was possible to use the solution as such for the synthesis of 18FDG with acceptable yields (30%, decay corrected). Additional experiments were conducted in which the AEM was rinsed with an AcN-H20 (95:5) solution of K2CO3/K222. With this solution, the recovery of 18F from the AEM was excellent (>90%) and the eluate was successfully used to synthesise 18FDG (yield 50%, decay corrected). Small amounts of water seem to be necessary for an efficient displacement of 18F from the AEM and do not impede nucleophilic substitution yields. 1261

TOMe027

TOMe029

G.Hansson G.Olsson, Department of Clinical Physiology, University Hospital Lund, Sweden

C. Boonen, H. Vanbiltoen, G. Bormans, A. Verbruggen Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U.Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuven, Belgium

INFLUENCE OF THE BODY MOTION ON THE DMSA RENAL SCINTIGRAM Body motion during examination causes artefacts on DMSA renal scintigraphy that may cause misinterpretation. The aim of the study was to evaluate the significance of body motion on DMSA interpretation. Patients and methods: Thirty children, aged one month to eight years were examined. Renal scintigraphy was performed 3 h after iv injection of 2 MBq Tc-DMSA per kg body weight, with the child lying supine immobilised by vacuum pillow. Static DMSA scintigraphy was performed as dynamic acquisition, one minute per frame during 10 minutes (15 min on children below 8 kg). Data were collected in a 256x256 matrix, zoom 2,5. Region of interest over each kidney was defined automatically by computer, on the isocount level contour at 20 %. Each frame that moved out of the estimated contour on the first image was transferred manually to estimated location. Thereafter all frames were summed to one static image. Kidney length and width were measured on the isocount level on corrected and original image. Statistical significance were calculated by Student's paired t-test. Results: Only in one patient was the difference in length/width between uncorrected and corrected images 4 ram. In 4 patients the differences were 3 mm and in the rest of the patients the differences were 2 mm or less. The differences in length/width, between corrected and uncorrected images were not statistically significant. Separate renal function was not affected by movements. Conclusion: In general, movements are small and do not change the results significantly but it is important to use dynamic acquisition that makes it possible to correct for large movements that may cause misinterpretation.

TOMe028 I. Hamilton, D Marshall, A Jeffries, P.J. Ryan Nuclear Medicine Department, Hedway Hospital Windmill Road, Gillingham, Kent ME7 5NY

RADIOCHEMICAL PURITY OF 99mTc-BICISATE (99mTe-L,LECD) PREPARED FROM A FRACTIONATED NEUROLITE KIT According to the reconstitution instructions of the Neurolite labelling kit, the content of vial B (containing the ligand) has to be dissolved in 3 ml of saline of which 1 ml is added to vial A (containing 1 ml of phosphate buffer) to which previously 2 ml eluate has been added. This implies that 2 out of 3 ml of the ligand solution (vial B) are not used. We have investigated the radiochemical purity (RCP) of 99mTc-bicisate preparations reconstituted from fractions of the residual 2 ml ligand solution after storage in a freezer. The residual 2 ml bicisate solution was divided in 3 portions of 0.5 ml (150 lag ECD) and 2 portions of 0.25 ml (75 gg ECD) which were immediately frozen in liquid nitrogen and stored at -20°C up to t week before labelling. The 0.25 ml and 0.5 mt portions of the bicisate solution were thawed and a mixture of 30 or 100 mCi (only for 0.5 ml portion) of 99mTcO4 in 2 ml saline and 1 ml of phosphate buffer pH 7.5 was added. RCP was assessed at several time points post labelling (25', 40', 60', 4h, 6h) with both 2 strip TLC (ITLC acetone; ITLC 20% saline) and gradient RP-HPLC. For the 0.5 ml .portions a RCP >95% was attained within 25' after labelling, irrespective of the amount of 99mTcO4 added. RCP of the 0.25 ml portions however was only 90% at 25' post labelling, but attained >95% at 40' post labelling. 99mTcO4 was the main contaminant. RCP of all preparations remained >95% up to 6h post labelling. The results demonstrate that residual bicisate solutions of Neurolite kits can be labelled efficiently after fractionation and storage in a freezer. The procedure only requires the availability of injectable phosphate buffer pH=7.5. Quality control after labelling is also strictly necessary. Further experiments with regard to the stability of the fractionated ligand solution as a function of freezer storage time are in progress.

TOTu030 E. Wandke, S. Marnitz, U. Dopichaj-Menge, Ch. Neumann, H. Siewert, V. Ivancevic, and D.L. Munz. Clinic for Nuclear Medicine, Charit6, Humboldt University, Berlin, Germany

IS DIURETIC RF.NO@R~PHY WORTE'WETLE IN INF~.NTS AND NEONATES? The increasing use of maternal ultra sonography has led to the increased detection of asymptomatic hydronephrosis in neonates. Diuretic renegraphy can be used to evaluate these patients but its reliability has been questioned due to the relatively immature kidney function giving a poor response to diuresis and also poor reproducibility. Diuretic renograms performed on 23 children under I year of age with perinatal hydronephrosls on ultrasound, were reviewed. All patients had a normal micturating cystogram. Renograms were performed using 99Tc m MAG 3 and minimum dose of of 20 MBq, followed by 0.25 mgm/kg lasix 15-20 minutes following injection. There were 24 hydronephretic kidneys. In 15 children aged <6 months lkidneys = 16), there was a brisk response to lasi× T½ washout <10 minutes) in 5, a slower response (T½ 10-20 minutes) in 3, a poor response (T½ >20 minutes) in 8. In 8 children aged 6-12 months (8 kidneys) the respective values were 6, I and I. In 5 patients a repeat study after I year was performed with no change in their T½ washout times. We therefore conclude that a brisk response to frusemide can be demonstrated in diuretic renography in infants under I year old with good reproducibility.

1262

PRONE Tc-99m SESTAMIBI-SCINTIMAMMOGRAPHY ON A DEDICATED PATIENT TABLE The diagnostic performance of scintimammography with Tc99m Sestamibi (SM) can be improved by prone patient position with pendent breasts. We thus investigated the practicability and attenuation characteristics of a carbon table with a 20x35cm breast window designed especially for prone SM by phantom measurements and in 60 patients. Planar images and SPECT were performed with a dual-head gamma camera. For the phantom measurements we used a 2x750 ml breast phantom (BP) filled with 12 MBq/I and a 2.3 cm spherical tumour phantom (TP) filled with 80 MBq/I of a Tc-99m solution. BP was placed in the window with the TP positioned laterally, centrally, and medially within the BP. All measurements were done triplicate in the ~ateral view with and without the side strat of the table being between the detector and the tumour. Applying ROI technique, tumour/background ratios (TB) were calculated. The ratios of the TB-with-strat over TB-without-strat amounted to 0.90+0.05, 0.88_+0.01, and 0.92_+0.02 (mean+sd) for the lateral, central, and medial position of the TP, respectively. 37/60 patients complained about pressure by the lower rim of the breast window and 15/60 patients reported pain. However, the complaints did not make an abortion of the investigation necessary Jn any case. In conclusion, the dedicated table is suitable for prone SM. However, the lower rim of the breast window has to be modified for a more comfortable patient positioning. The attenuation of the side strat has to be corrected for, if a semiquantitation of tumour uptake is to be performed in the lateral view.

TOTu031

TOTu033

L. Leidekker, R.A. Vald6s Olmos, C.A. Hoefnagel.The Netherlands Cancer Institute, Department of Nuclear Medicine, Plesmanlaan 121, 1066 CX Amsterdam, NL

A. Lagerwaard, MMC Tiel-van Buul, J. Greve, E A van Royen. Academic Medical Centre, Department of Nuclear Medicine, Amsterdam, The Netherlands.

USE AND I M P A C T O F S P E C T IN A C A N C E R C E N T R E .

Evaluation of renal u p t a k e of DMSA in oncologic p e d i a t r i c patients treated with chemotherapy.

During the past five years the Department of Nuclear Medicine of the Netherlands Cancer Institute in Amsterdam, has changed from a department with a limited use of available SPECT equipment to a department with sophisticated use of S P E C T . In Oncology there is an increasing demand of SPECT procedures. Apart from an overalt increase of the number of planar procedures, at the Netherlands Cancer Institute, SPECT procedures have proportionally increased even more, and currently include : - examinations in which SPECT is performed as the main test, e.g. brain, head and neck tumours, lungperfusion and -ventilation. - SPECT complementary to planar imaging, e.g. bone (spine), lymphoma, heart, neural crest tumours (post MIBG therapy). The clinical and departmental impact and relevance of investigations done only by planar imaging, a combination of planar and SPECT imaging, or only with SPECT procedures in the oncological environment will be discussed. Although SPECT-procedures constitute approximately 10 % of the total number of Nuclear Medicine procedures, the impact of SPECT on the workload is considerable in relation to the total volume of the Nuclear Medicine procedures, since factors such as set-up time, acquisition-time, processing-time and Quality Control of SPECT procedures take longer than conventional planar scintigraphy. The implications for departmental management, logistics and financial consequences will be underlined.

TOTuO32 W.J.M.van den Broek F.H.M.Corstens. Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands

RADIATION SAFETY AND HYGIENE DURING TREATMENT OF CHILDREN WITH HIGH DOSE 1311-MIBG High dose 1311-MIBG is a novel therapy for disseminated neuroblastoma. ChiIdren are r~ursed in special therapy ur~its. Since the children obviously need extensive care, radiation safety measures for patients and staff were evaluated. During the past t w o years 8 children (1-9 years old) with neuroblastoma were admitted to undergo high dose~311-MIBG therapy for 6-10 days per treatment. The administered dose was either 3.7 or 7 . 4 GBq ~3~1 per treatment. Patients underwent 1 - 10 treatments. The radiation doses received by the parents of the patients and the medical staff were determined. The isolation room was furnished as a children's room (toys, TV, VCR, etc.). The parents of these children were hospitalized on the same ward and took care of their child themselves during the isolation. The nurses of the ward were responsible for the medical care. A filmbadge dosimeter as well as a digital personal dose-rate meter (Stephen 6000) registered continuously the external radiation. The filmbadge dosimeter was worn by the parents during at least 14 days after the administration. The digital dose-rate meter was set such that it gave an audible signal when a dose rate of 100 mSv/h was exceeded. Every time a person went into the isolation unit the administered external radiation was registered to detect when and h o w much radiation was received. The cumulative doses of the parents ranged from 0 . 2 9 - 3 . 9 6 mSv per treatment and were dependent on illness and age of the child. Highest doses were received during the second day of treatment. Nurses and nuclear technologists received doses less than 0 . 1 5 mSv per treatment. In conclusion, participation of parents in children's care reduces the radiation burden of the staff. The external radiation dose of parents can be kept in reasonable limits by adding a digital personal dose-rate meter.

Dimercapto succinyl acid (DMSA) is absorbed in renal tubular cells. The tubular function can thus be measured by Tc-99m DMSA scintigraphy. The Academic Medical Centre, Amsterdam includes a large Children Oncology Department in which approximately 50% of all Dutch children with cancer are treated (400 new patients ~per year). Chemotherapy schemes often contain the pharmaceutical Ifosfamide, which may damage the renal function, especially the tubular cells. In all children, treated with chemotherapy including Ifosfamide, the tubular function is followed-up by Tc-99m DMSA-uptake scintigraphy. If the Tc99m DMSA uptake decreases, the dose of Ifosfamide is adjusted. For logistic reasons, a half hour before administration of the radiopharmaceutical, a Venflon R is given to the child in the outpatient pediatric department. Between 10 and 40 MBq is administered intravenously, dependent on age and weight. The syringe is measured before and after injection and the remaining activity is subtracted from the original dose. Exactly two hours post injection, anterior and posterior views of the kidneys are obtained with a standard dose of Tc-99m of maximally one-fifth of the patient's dose in a syringe lying on the abdomen of the patient. The Tc-99m DMSA-uptake is measured in each kidney using the geometric mean of counts in the kidneys and the true administered activity expressed in counts (related to the measured geometric mean of counts from the standard dose on the abdomen). In this presentation, based on the cases of three children treated with Ifosfamide, the relation between the Tc-99m DMSA-uptake (i.e. the tubular function of the kidneys) and the dose of Ifosfamide will be shown.

TPTu034 J.M.Jones, J.H.Pearce, W.D.Evans and A.R.Richards, Department of Medical Physics & Bioengineering, University Hospital of Wales, Cardiff, U.K.

STABILISED 99mTcHMPAO FOR WHITE CELL LABELLING The Central Radionuclide Dispensury at the University Hospital of Wales supplies radiopharmaceuticals to 12 gamma cameras in g different hospitals in South-East Wales. Provision is made for labelling 99Tcm autuiogous white cells using HMPAO on a peripatetic basis. The requirement of a short time interval between HMPAO reconstitution and addition to white cells effectively means that one vial of the agent must be used for each patient thus increasing the cost of the procedure. Previous studies have shown that addition of stabiliser (COC12.6H20) to 99mTcHMPAO for brain perfusiou imaging maintains it's integrity after subdivision for up to 5hrs. The objective of this study was to investigate the suitability of the stabilised radiopharmaceutical for white cell labelling. A vial of HMPAO (Amersham International plc) was reconstituted with stahilising agent and sufficient activity of 99mTcO4 for three separate white cell labelling procedures at 0, 1 and 3 hours post reeonstitutien with freshly drawn blood from the same volunteer in each case. Another vial of HMPAO was reconstituted but without stabiliser for comparison. The radiochemical composition of the 99mTcHMPAO was tested prior to each cell labelling using a thin-layer/paper chromatography system; primary lipophilic complex was expressed as a percentage. Cell labelling efficiency was calculated and elution of activity from labelled cells was measured 1 hour post preparation. The results are shown in the table:-

Primary Lipophilic % Labelling efficiency% Elution activity %

No Stabiliser 0hr 82 43 12

0hr 81 49 9

With Stabiliser lhr 81 51 9

t/)

_t o

3hr 77 52 9

Addition of slabilising agent appears to have no significant effect on any of the measurements for up to three hours after reconstitution. This suggests that stabilised HMPAO may be used to improve the flexibility and cost-effectivenessof white cell labelling, although in vivo studies are required to assess the viability of cells labelled by this procedure. 1263

_tO

TPTu035

TPTu037

N Oudheusden, MMC Tiel-van Buul, JBA Habraken, R. Wesche, EA van Royen. Academic Medical Centre, Departments of Nuclear Medicine and Endocrinology, Amsterdam, The Netherlands.

A.Chodoeva. G.G.Me[nikova, A.Z.Zurdinov, Z.Sh.Sharshenalieva. Sector of Radiobiology and Departament of Pharmacology. Kyrghyz Medical Institute. Kvrghvzstan.

T I l E C A L C U L A T I O N OF S C I N T I G R A P I I l C T I I Y R O I D VOLUME - A COMPARISON BETWEEN METHODS

Patients with hyperthyroidismcan be treated with NaI- 131. Indications are: Graves disease (GD) in which pharmaceutical treatment failed, toxic multinodular goiter (TMG), and toxic uninodular disease. I- 131 therapy is also be indicated in patients with sporadic non-toxic goiter (SNG) in which the enlarged thyroid gives mechanical or estheticai complaints. In our hospital, the therapeutic dose of I-131 is calculated using the 24-hour thyroid uptake and the scintigraphically measured thyroid volume. Data of 40 patients were evaluated, 31 women and 9 men, mean age 52 y., range 18-76 y. Eighteen patients had GD, 12 patients SNG, and 10 patients TMG.Anterior and lateral views were obtained. For measurement of the uptake, a ROI was manually drawn around the thyroid using a lower threshold of 0%, whereas for the volume calculation, the ROI was based on a lower threshold of 20%. In this study, the thyroid volume, calculated as anterior surface x lateral diameter (method I; lateral image was needed) was compared with the "Doehring calculation method" (method II; surface in pixels x correction factor for estimated depth x correction factor for matrix size), in which the lateral image was not needed. The thyroid volume, estimated by ultrasonography, was used as the reference standard. Mean calculated volumes of the ps are shown in the table. I - LT 0

II - LT 0

I - LT 20

II - LT 20

Echo

GD

238 ml

146 ml

49 rnl

26 ml

23 ml

SNG

327 ml

204 ml

61 ml

37 ml

69 ml

TMG 284 ml 182 ml 64 ml 36 rnl 48 ml We conclude that in patients with Graves Disease, the calculation of thyroid volume using the formula anterior surface x lateral diameter leads to an overestimation of volume by a factor 2, while the Doehring method shows agreement with the sonographicallymeasured volumes. In sporadic non-toxic goiter, this was opposite, and for TMG, the "truth" layed in the middle. The ROI used for measurement of the uptake, cannot be used for calculation of the thyroid volume.

THE INFLUENCE OF A RADIOPROTECTIVE AGENT ON LIPID PEROXIDE OXIDATION. The aim of our research was to study the influence of the sodium salt of munocarboxycellulose (NaMCC) on biochemiluminescention of the blood serum. The experiment was conducted on 126 rats. Water suspension of NaMCC was introduced per os in the doses: 300; 600; 900 mg/kg every day during 3 months. Chemiluminescention of the animal's blood serum was measured on the KGDA-0.1 plant every month. The results of the experiment revealed the following picture: the introduction of NaMCC during the 1st month caused the increase of chemiluminescention intensity by 109-i32 % in comparison with control values. At the end of the 2nd month a decrease of intensity to 37.4-57% in comparison with control figures was observed. During the 3rd month of the experiment the change of chemiluminescention intensivity, but more approached to the values of the control series was also noted. Chemiluminescention is a flare appearing because of formation of vacant radicals during the lipid peroxide oxidation (LPO) process. The LPO depends on some factors such as UVradiation of hydroperoxides and the content of radionuclides and ions of polyvalent metals in the body. Consequently, the intensivity o f the chemiluminescention flare may act as indirect evaluation of specific activity of the radioprotective preparation. Our study demonstrates that the chemiluminescention intensivity of the blood serum depends on the length of the NaMCC introduction period and may be used in evaluation the content of radionuclides and trace metals in the organism.

TPTu036

TPTu038

J.P. Straatman P. Wanet, A. Sand, K. v.d. Kerkhof, D. v. Lonkhuizen, A. Spolspoel ; Department of Nuclear Medicine, H.-Family Hospital, Reet, Belgium.

G.L.Marzocchi, A.Borghi, V.Gnudi, F.Mirandola, D.Stabellini, G.Lucchi, C.Salvatore, A.Palermo. Nuclear Medicine Dept. H. M a g g i o r e - Bologna (ITALY)

M E A S U R E M E N T OF CR-51 A C T I V I T Y IN BLOOD SAMPLES USING A G A M M A C A M E R A WITH PIN-HOLE COLLIMATOR. Cr-51 activity in blood samples (e.g. EDTA k i d n e y clearance, red cell volumetry, red cell survival) is u s u a l l y c o u n t e d in a gammacounter. However for technical or practical c o n s i d e r a t i o n using a gammacamera with pin-hole collimator might be favorable. In order to test the s e n s i t i v i t y and linearity of the gammacamera, dilutions were made r a n g i n g from 37 kBq downto 290 Bq comparable to doses used in clinical setting (7.4 kBq/kg to 50kBq/kg) . Standard g e o m e t r y was o b t a i n e d by using an insert in the pin-hole collimator (i0 cc syringe). G a l l i u m maps were used for h o m o g e n e i t y and linearity correction. Linearity and sensitivity were excellent in the full testing range w i t h R 2 of 0.9995 and correlated well w i t h values obtained from a wellcounter. Similar results were o b t a i n e d for T c - 9 9 m and three different s i n g l e - h e a d e d gamma cameras. Conclusion: A gamma camera with pin-hole collimator is as efficient as a g a m m a c o u n t e r in clinical practice.

1264

MULTIFRACTIONING OF A SINGLE VIAL OF HM-PAO FOR GRANULOCYTE LABELLING: METHOD EVALUATION. The e m p l o y m e n t of 99mTc-HMPAO as a tracer for leucocyte labelling is supplanting almost c o m p l e t e l y the use of the mixtures of the 11 ] In. Using pure granulocyte fractions it is used a small number of cells as regards the conventional preparations. If a linear relationship b e t w e e n number of present cells in the preparation and labelling yield exists, then is possible that is necessary a small quantify of Tc-HMPAO for get the same results in terms of labeling eficiency a n d it is therefore possible the e m p l o y m e n t of a vial for more studies. CHOSEN OF THE RADIOISOTOPE Our experience has c o n d u c t e d us to a diversified choice b e t w e e n the t w o radioisotopes: In-Oxine a n d Tc-HMPAO, essentially on the base to the clinical question. It is used 111 In-oxine granulocytes in the evaluation of site, activity a n d complications of the Crohn's disease followed by the measure of the fecal excretion, and in all the cases where one suspects an inflammatory focus in which the renal radioactivity or bladder, present w h e n the Tc-HMPAO is used, it could hinder his recognition. In all the other cases, included the study of the ulcerous UCR, where, w h a t w e w h a n t to study is the evaluation of the extension of the illness, w e use the granulocyte marked with Tc-HMPAO. METHOD A vial of HM-PAO comes reconstituted with 10 ml of physiological solution and divided in 6 fractions of 2 ml that they c o m e preserved to - 20° C. To the m o m e n t of the employment, the single dose comes defrost a n d it been adds up 0.3ml of a solution obtained diluting a vial of phyrophosfate so that the concentration of Stannous Chloride is of 0.66 microgr/ml. At this time w e a d d up 740 Mbq of 99mTc 0 4 - v a c u u m packed. CONCLUSIONS The results obtained in vitro a n d in vivo confirm the possibility to use every time the m e t h o d proposed without any loss of diagnostic quality.

TPTu039

TPTu041

G.L. Marzocch!, D. Stabellini, F. Mirandola, I. Adversi, A. Palermo, Salvatore C., Nuclear Medicine Dept. H. Maggiore - Bologna (ITALY)

D. Crombez, G. Borrn.arts, A. Verbruggen

INTRINSIC AND EXTRINSIC UNIFORMITY CORRECTION MAP APPLIED TO THE SPET.COMPARISON AND EVALUATION OF RESULTS. This study has been performed in order to verl~ the possible change of sensitivity obtainable with the use of intrinsic vs. extrinsic correction maps in SPETacquisition. We acquired, with a single rectangular head LFOV Gamma Camera Sopha model DSX, two uniformity correction floods using, for the intrinsic map, a spot source of about 15 Mbq of Tc 99m placed at 5 LFOV of distance from the head without collimator and, for the extrinsic map, a DLP (Dynamic Line Phantom), set for FLOOD function, endowed with a 370 MBq linear homogeneous source..,J~e line source travels about 12 times across the field of view at a Constant moderate speed. The Gamma Camera head is equipped with UHR collimator Inormally used for the SPET). Both the acquisitions are performed with automatic stop at 30 Mcts (like from protocol furnished from the firm). The SPET acquisitions, applying alternatively the two uniformity correction maps, are performed using, like source, an ECT phantom with cold bars of various diameters (10, 12, 15, 18 and 25mm), normally used for the resolution tests. With the present paper, we wish to emphasize possible differences after reconstruction of the examination. Our results show that, in spite of the greater effort required to perform the acquisition of the extrinsic flood does not correspond a likewise sensitivity increase of the spatial resolution of the system.

Laboratory of Radiopharmaceutical Chemistry, F.F.W., KU.Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuven, Belgium RATIONAL APPROACH TO A VALID TLC LIMIT TEST FOR KRYPTOFIX IN I$FDG PREPARATIONS WITH DIFFERENT SPECIFIC RADIOACTIVE CONCENTRATIONS A common procedure for the preparation of 18FDG is a nucleophilic substitution of 18F-fluoride on tetraacetylmannose triflate in acetonitrile in the presence of the aminopolyether Kryptofix 2.2.2 (K222). During the subsequent work-up, the amount of K222 and other potential impurities has to be reduced to a sufficient low level to allow the IV injection of the 18FDG preparation (S) in patients. The maximum volume (Vm) of S required for a single dose may vary largely (0.5 to >25 ml), depending on the specific radioactive concentration, which in turn depends on the batch volume, synthesis yield and time elapsed after production. Therefore, the limit for impurities in 18FDG cannot be defined as a fixed concentration, but as a fixed amount (Lm) in Vm. If Lm is 500 p.g for K222, the limit concentration of I<222 is 1 mg/ml if Vm=0.5ml and 20 ~tg/ml if Vm=25 ml. For this reason, a different approach of TLC procedure and reference solution (Ref) is required than for conventional drugs. We have solved this problem by adjusting the concentration of K222 in Ref in accordance with Vm. Thus the limit test for K222 in S is performed using a Ref with a K222 concentration equal to 0.500/Vm mg/mI, Vm being the max volume of that particular 18FDG solution that may be injected. If equal volumes of S and Ref are applied separately on the TLC plate, the spot of K222 in the TLC of _S should not be more intense than in that of Ref. This guarantees that less than 500 gg K222 will be administered in a single patient dose. To avoid sensitivity problems for diluted solutions (V>20 ml), the volume applied on TLC is 2 gl if Vm<10 m], 4 p_l if 1020ml.

TPTu040

TPTu042

A. Lind.h, H. Brundin, M. Brunnberg, S. Ekberg, M. Stenstr6m, Department of Clinical Physiology, University hospital, Link6ping, Sweden.

L.Larsen,B.Dondera, The National University Hospital, Department of Clinical Physiology N u c l e a r Medicine, Rigshospitalet, Denmark.

WORKING PRACTISE IN HOTLAB USING ISOLATORS SUPPLIED WITH GLOVE PORT.

R A D I O A C T I V E LABELLING OF G R A N U L O C Y T E S T H R O M B O C Y T E S WITH lllIn-Cl3.

Relate to new policies for preparation of radiopharmaca in Sweden w e proceed to handing all dispensing, from elution to prepared syringe in isolators equipped with glove port. Today w e have two isolators delivered from Dan-LAF. The isolators are modified to clarify radiation protection demands in accordance with the recommendations of the National Radiation Protection Board. The isolators are shielded with 6 mm lead all round and a 16 mm lead-glass window. It is equipped with a HEPA filter, 99.997% to meet performance criteria for aseptic operation. Tc-99m elution is transferred into the isolator, after activity measurement, via a transfer chamber. The weight of the elution is measured inside the isolator on a balance connected to a computer for automatic registration. The computer program gets information from the patient booking schedule and all volumes for the daffy kit and syringe preparation are then calculated. As a final check, the first syringe of each kit is measured in a ionisation • chamber. The absorbed dose level to the personnel has decreased after w e introduced isolators in hotlab. This is due to the all round lead shielded isolators as well as w e use a balance instead of ionisation chambers (we do not have to remove the syringe lead shield).W e daffy handling 25 G B q Tc-99m and each week 11-201, 1-123,In-111 and Cr-51.

and

AND

The purpose of this a b s t r a c t is to describe the procedures required for labelling, granulocytes and thrombocytes and the scanning techniques necessary to visualise the uptake of these agents. Indium-lll chloride (lll-In-Ci-3), Mallinckrodt, The Netherlands, is labelled with tropolone to form a lipophilic complex. Autologous granulocytes and thrombocytes are isolated. The complex is taken up by the cells. The labelling process is performed in vitro and special attention is given to aseptic techniques. Scintigraphy is performed on a large fieldview gamma camera(medium energy collimator) 224 hours after injection. lllIn-labelled thrombocytes have been used to show damage of the endothelial tissue in a stripped vein in the legs of in-situ by-pass arterial surgery= lllIn-labelled granulocytes are used to localise inflammatory processes in bones and other sites in the body. To further clarify an infectious process in bone, an additional scanning agent 99mTc-HMDP, Mallinckrodt, is used and the dual energy peaks of the isotopes can be utilised in performing simultaneous imaging.

1265

_o

=o

tO

TPTu043

TPTu045

H. Durak~ B. De(lirmenci, F B~rekyemez, O. Beyamth, i Evren. Department of Nuclear Medicine, Dokuz EyliJl University School of Medicine, izmir, Turkey.

F . L . K i n n a i r d , A.D.Hall, V . R . M c C r e a d y D e p a r t m e n t of N u c l e a r Medicine, The Royal M a r s d e n N.H.S. Trust, Sutton, Surrey, U.K.

EFFECT OF COUNT RATE VARIATIONS OF DETECTORS ON THE REGIONAL COUNTS ON TRANSAXlAL SLICES IN A TRIPLE DETECTOR GAMMA CAMERA Total of 10 phantom SPECT studies in 10 consecutive weeks were performed following the routine weekly quality control procedures in a triple detector gamma kamera (Neurocam, GE). 20 mCi Tc 99m pertechnetate in water was placed in a refillable cylinderic phantom and 64 frames of 35 seconds duration in 64X64 matrix were obtained using all three detectors(Triple Detector Study:TDS) and only one detector(One Detector Study: ODS).lmages were processed using a Butterworth filter(cut off value 0.45, power factor 10). Two pixel transaxial slices were obtained and free regions of interest (ROI) were placed on the right(R) and left(L) antero laterai(AL), right and left lateraI(L) and posterior(P) part of the transaxial slices and on the whole transaxial slice to calculate the region/whole slice ratios using the mean counts in the ROIs. Total counts in the first and last planar images acquired with every detector in TDS and in the first and last planar image acquired with one detector in ODS were used to calculate the count change within each detector(CCW) and between consecutive detectors(CCB). First Second Third One (%) Detector Detector Detector Detector CCW 2.1_+1.0 1.6_+0.5 2.1+_ 0.5 2.4-+2.5 CCB 6.3_+1.5 -9.6-+0.9 10.2_+1.3 CCB range 4.3 to 9.5 -8.6 to-11.1 8.4 to 13.2 RAL LAL RL LL P TDS 0.95-+0.08 0,99_+0.09 1.02_+0,05 1.0~--+0.08 1.02_+0.06 ODS 0.98-+0.06 1.00-+0.07 1.01-+0.05 1.02_+0.07 1.03_+0.06 Right anterolateral region showed a relatively lower count rate, but this did not reach a statistical significance. It's concluded that, caution shoud be observed in patient studies because variation in detector sensitivies may further decrease the low count rates in brain disorders.

I M P R O V I N G THE Q U A L I T Y O F I N F O R M A T I O N G I V E N TO THE P A R E N T S OF C H I L D R E N U N D E R G O I N G N U C L E A R MEDICINE INVESTIGATIONS

S. Str6mberq,

P. Nikkinen,

S-L.

Karonen, D i v i s i o n of N u c l e a r Medicine, H e l s i n k i U n i v e r s i t y C e n t r a l H o s p i t a l Laboratory, F i n l a n d Q U A L I T Y C O N T R O L OF B O N E - S E E K I N G R e - 1 8 8 - L A B E L L E D COMPOUNDS USING A GAMMA CAMERA Re-188 is a g e n e r a t o r (W-188 / Re-188) p r o d u c e d h i g h e n e r g y ~-emitter s u i t a b l e for r a d i o n u c l i d e therapy. It has a h a l f - l i f e of 16.9 hrs a n d a m a x i m u m p - e n e r g y of 2.2 M e V (range ll mm). W e have l a b e l l e d p h o s p h o n a t e compounds (HDP, DPD) u s i n g Re-188. Samples w e r e a n a l y z e d after 5, 10, 30, 60, 180 and 1320 m i n incubation. The l a b e l l i n g efficiency, the amount of free p e r r h e n a t e and r e d u c e d Re has b e e n c o n t r o l l e d w i t h thin layer c h r o m a t o g r a p h y (TLC) u s i n g s o d i u m acetate (Na-Ac) and m e t h y l e t h y l k e t o n e (MEK) as solvents. The c h r o m a t o g r a p h y plates were a n a l y z e d u s i n g a g a m m a camera (Picker P r i s m 3000 XP). The gamma e n e r g y p e a k (155 keV; 15 %) was r e c o r d e d and m o v e m e n t s on T L C p l a t e s w e r e a n a l y z e d u s i n g r e c t a n g u l a r ROIs. Our results indicate that R e - 1 8 8 - p h o s p h o n a t e s r e m a i n in v i t r o stable at least for 22 hours and the l a b e l l i n g e f f i c i e n c y is h i g h e r than 92 %. T h e s e R e - 1 8 8 - p h o s p h o n a t e s m a y also be u s e d for treatment of m e t a s t a t i c skeletal d i s e a s e and their d i s t r i b u t i o n can be c o n t r o l l e d u s i n g g a m m a camera as well as the q u a l i t y of l a b e l l e d compounds.

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One set of l e a f l e t s o u t l i n e s the n u c l e a r m e d i c i n e p r o c e d u r e , and d e t a i l s the p r e p a r a t i o n for the child, t o g e t h e r w i t h a d v i c e on r e d u c i n g the p a i n and t r a u m a a s s o c i a t e d w i t h venepuncture. The s e c o n d set gives m o r e i n f o r m a t i o n a b o u t the p a r t i c u l a r study, and are o n l y m a d e a v a i l a b l e w i t h i n the d e p a r t m e n t . T h e s e are s p e c i f i c a l l y d e s i g n e d for p a r e n t s to w o r k t h r o u g h w i t h t h e i r child, a n d i n c o r p o r a t e s u i t a b l e g r a p h i c a l e l e m e n t s to aid this process. The p r e s e n t a t i o n of i n f o r m a t i o n in a n o v e l format on s e p a r a t e o c c a s i o n s has b e e n a success, r e s u l t i n g in a m e a s u r a b l e i n c r e a s e in the n u m b e r of p a r e n t s who felt a d e q u a t e l y i n f o r m e d about the p r o c e d u r e p r i o r to its c o m m e n c e m e n t .

TPTu046

TPTu044 K.J.A. Kairemo,

Paediatric nuclear medicine poses difficulties r e l a t i n g to the p r o v i s i o n of i n f o r m a t i o n s u i t a b l e for b o t h the p a t i e n t and t h e i r p a r e n t s . In a d d i t i o n to the w i d e r e d u c a t i o n a l issues, it is i m p o r t a n t that p a r e n t s of c h i l d r e n u n d e r g o i n g such s t u d i e s are a d e q u a t e l y informed, such that they m a y h e l p the h e a l t h care p r o f e s s i o n a l s r e d u c e b o t h the short and long t e r m t r a u m a of the i n v e s t i g a t i o n . T w o sets of l e a f l e t s have b e e n produced, w h i c h p r e s e n t to p a r e n t s the i n f o r m a t i o n n e c e s s a r y for t h e m to p r e p a r e their c h i l d for the n u c l e a r m e d i c i n e study.

S van Balen, B Hoving, GW Sloof, M van Loon, GJJ Teule, A van Lingen Nuclear Medicine, Free University Hospital, Amsterdam, The Netherlands

DETERMINATION OF THE ACTIVITY RATIO IN A MIXTURE OF TI-201 AND 1-123: A PHANTOM STUDY Simultaneous registration of myocardial perfusion (Tl-201) and metabolism (I-123 fatty acids) is advantageous with respect to separate acquisitions: patient comfort, short acquisition times and the absence ofrepositioning artifacts~ We investigated in phantoms with a mixture of TI-201 and 1-123 how the ratio of the activities can be estimated. The major problem is the overlap in the energy spectra of these two radionuclides. Methods. First it was determined for both radionuclides separately whether the low energy (LE= 70 keV 20% window) counts form a measure for the absolute activity. For the determination of the activity ratio in a mixture, an additional second energy window was used (HE= 159 keV, 20%). With simple phantoms it was verified that a linear combination existed between the activity ratio as the dependent and both LE and HE counts as the independent variables. This was determined in dual isotope planar images obtained from petri dishes with a thin layer of the mixture, with and without attenuation, as well as from dual isotope SPECT acquisitions of a myocardial phantom in a thoracic container. Results. For both TI-201 and 1-123 a clear linear relation existed between activity and LE counts. The counts obtained from the dual isotope planar images revealed that from the linear combination of LE and HE counts the activity ratio could be determined with an accuracy of 10%. The dual isotope SPECT acquisitions obtained from the myocardial phantom yielded an accuracy of 15%. Conclusion. Despite overlap in energy spectra of TI-201 and I-123 in a mixture, the linear combination of LE and HE counts facilitates the determination of the activity ratio of the two radionuclides, with an acceptable accuracy. This may constitute the creation of functional images depicting the relationship between perfusion and metabolism in the myocardium.

TPTu047

TPTu049

T. Ertay*. H.Durak*, O.Kut*, (,;.Pekqetin**,E.Demirta~*, B.Uysal*, A.Gttre** Dokuz Eyliil University School of Medicine Department of Nuclear Medicine* and Experimental Research Center** EFFECT OF COLD GALLIUM AND COLD CITRATE ON THE BIODISTRIBUTION OF Tc-99m CITRATE AND Ga-67 CITRATE tN RATS The aim of this study was to compare the biodistribution of Ga-67 citrate to Tc-99m citrate in rats and to see how biedistribution is influenced following the administration of cold gallium and cold citrate. The imaging times were 10. min. and 2. hour for Tc-99m citrate and 2., 24. and 48. hour for Ga-67 citrate.Regions of interest were drawn around the oropharyrLx, lung, liver, kidney, bladder and the following organ/whole body ratios were obtained as the percentage of whole body counts. ColdGallium ColdCitrate ColdCitrate Ga-67Citrate Tc-99mCitrate Oa-67Citrate Ga~7Citrate Tc-99mCitrate 48.hour 2.hour 48.hour 4g.hour 2. hour Oropharynx Lung Liver Kidney Bladder

3.4 1.6 22.7 1 1

1.3 2.5 51.5 0.5 1.1

4 8.6 19.5 1.2 1.3

5.5 10.7 17.8 1.3 1.6

0.7 1.5 67.3 0.1 0.1

On Ga-67 citrate images both cold gallium and cold sodium citrate mildly decreased the liver activity and increased the oropharynx, lung, kidney and bladder activity. On Tc-99m citrate images cold sodium citrate significantly increased the liver activity, decreased the orophaynx, lung, kidney and bladder activity. Our results showed that the biodistribution of Ga-67 citrate and Tc-99m citrate and the effect of their cold forms on the biodistdbution of radioactive forms were different. But the effects of cold gallium and cold sodium citrate were similar on the biodistribution of Ga-67 citrate. Our results suggest that Tc-99m citrate may use the biodistribution pathways of Ga67 citrate though additional mechanisms may also be involved.

M.G6ransson, B.Jansson, S.Richter and L.Svensson, Central Isotope Department, Hospital Pharmacy and Department of Hospital Physics, Huddinge University Hospital, S- 141 86 Huddinge, Sweden. EXPERIENCES FROM A QUALITY ASSURANCE PROGRAM IN A N U C L E A R M E D I C I N E D E P A R T M E N T . Obtaining quality data is a vital component of the total imaging procedure, but no matter how strict you follow the protocol, it happens every now and then that you end up with an artifact. For inexplicable reasons the images do not turn out the way you expected. METHODS

In our department we monitored about 200 patients, children with acute pyelonephriitis (APN), by means of DMSA scans. Here we found artifacts like big variations of back-ground noise, periodically. In CBF studies with exarnetazim we found high uptake of the radionuclide around the scalp and quite high uptake of unbound TcO 4- in the thyreoid gland. These artifacts appeared irregularly and less frequently. In order to investigate the reasons for these altered radiotracer biodistribution patterns we used a QA program, based upon different parameters from the radiopharmacy operation and collection parameters from the patient study. These variables were collected in a data base for retrospective analysis. Parameters used in both studies were details of the radiopharmaceutical preparation, time elapsed between preparation, administration and examination, patient's age, ratio back-ground/targetorgan. In the DMSA study preparations from three different manufacturers were used and only normal kidneys were used as reference material. In the CBF study we also collected data on concurrent drugs. SUMMARY The results from this QA program solved our problems as far as the DMSA study is concerned. In the CBF study the results were not as clear-cut Although only one of the studies gave guiding results we are very pleased with this kind of QA program. Since the collected parameters are part of the examination we do not experience the QA as a burden.

TPTu048 I. Becker~ H. Eisenblatt, R. Walser, F Wagner*, G. Hofmann**, K Tatsch, K. Hahn Departments of Nuclear Medicine and Surgery*, University of Munich, and BG Unfallklinik Mumau**, Germany 3-PHASE B O N E S C I N T I G R A P H Y AND S P E C T IN P A T I E N T S AFTER ALLOGENIC VASC~ED FEMUR TRANSPLANTATION The transplantation of vascularized femur grafts combined with immunosuppression is a new technique, which our surgeons carried out for the first time. Compared to other diagnostic modalities (angiography, duplex sonography, biopsy) bone scintigraphy seems to be the preferable diagnostic tool to evaluate perfusion and viability of the vasculatized femur grafts. We present 3-phase bone and SPECT scans of patients who underwent this specific procedure. So far we studied 3 males (21-45 yrs) on the second, 7th and 30th day after femur transplantation with 3-phase bone scans (Siemens BODYSCAN) and SPECT (Siemens MULTISPECT 3). The first phase (blood flow) was started with the bolus-injection of 500-600 MBq Tc-99m - DPD (dynamic study, 128x128 matrix, 30 frames, 2 s/frame, LEHR-collimator). The acquisition of the second phase was done one minute after injection (static image, 128 x 128 matrix, 1 frame, 2 rain/frame). Wholebody bone scans (15 cm/min, 384 x 1024 matrix, LEHR-collimator) and SPECT (360 °, 128x128 matrix, 40 steps, 30 s/step, LEHR-collimators, filtered backprojection, butterworth filter) were performed 3- 4 hours post injection. Good perfusion without significant asymmetry between the transplant and the normal contralateral limb in late scans indicated a course without complications (n=l). In contrast, rejection (n=l) or thrombosis (n=l) was associated with decreased perfusion and markedly reduced bone metabolism. Because of enhanced soft tissue uptake in the early postoperative phase SPECT provided more reliable data on graft viability than late planar scans. This poster demonstrates the diagnostic value of 3-phase bone scans combined with SPECT in the postoperative monitoring of patients with allogenic vascularized femur grafts.

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