[] Neurology Neurology

1.3

1.1 Y. L o m e ~ a S .Vida!- Sicart, A.Cruceta, J. Pavla, J.M.Mir~, S.MaN@, F.Garcia, R.Herranz, E . R i b e r a and F.Graus. H o s p i t a l Clinic, H o s p i t a l Vall d ' H e b r 6 n and C e n t r e M e d i c i n a D i a g n ~ s t i c a . Barcelona, Spain.

~REDICTIVE

VALUE

OF

201-T}LALLIUM

SPECT

IN

THE

DIAGNOSIS

OF

PRIMARy BRAIN LYMPHOMA IN AIDS PATIENTS. C o n s e c u t i v e AIDS p a t i e n t s (p.) who a r r i v e d to our e m e r g e n c y units due to s y m p t o m a t i c b r a i n m a s s e s were i n c l u d e d in a twoy e a r p r o s p e c t i v e s t u d y to e v a l u a t e the u s e f u l n e s s of 201TI SPECT in the d i a g n o s i s of p r i m a r y b r a i n l y m p h o m a (PBL). S i x t y p. (41 males, m e a n age:36±8) were i m a g e d by CT the same day of their admission and started empiric a n t i b i o t i c t h e r a p y for t o x o p l a s m o s i s (toxo). 201TI SPECT was p e r f o r m e d i to 8 days later (mean 3,6±i,8) w i t h a t w o - h e a d e d SPECT camera (Helix,Elscint) fitted with fan-beam collimators. SPECT images were visually classified as p o s i t i v e (intracranial focal uptake) or negative, b l i n d to CT. A l e s i o n - t o - n o n l e s i o n u p t a k e ratio ( U R ) was c a l c u l a t e d r e t r o s p e c t i v e l y a c c o r d i n g w i t h CT findings. Five p. d i e d w i t h o u t b r a i n mass d i a g n o s i s and were excluded. F i f t y - s i x p. were d i v i d e d as follows: G r o u p A) 27 p.(32 lesions) bad toxo as final d i a g n o s i s (good clinical and r a d i o l o g i c a l r e s p o n s e to a n t i - t o x o treatment); g r o u p B) 6 p.(6 lesions) w i t h h i s t o l o g i c a l d i a g n o s i s of PBL; g r o u p C) 9 p.(ll lesions) w i t h p r o b a b l e PBL (no r e s p o n s e to correct a n t i t o x o t r e a t m e n t d e f i n e d by C T / M R p r o g r e s s i o n of the lesions), and g r o u p D) i0 p. with clinical diagnosis of progressive multifocal l e u k o e n c e p h a ! o p a t h y . The r e m a i n i n g 3 p. had h i s t o l o g i c a l d i a g n o s i s of rodoccoma, m y c o b a c t e r i u m x e n o p i b r a i n abscess, and a s e p t i c b r a i n abscess. In g r o u p A (mean U R = l . 2 3 ± 0 . 3 3 ) 27/32 lesions had n e g a t i v e SPECT and 5/32 had positive SPECT. In g r o u p B (mean U R = 2 . 2 3 ± 0 . 7 0 ) 6/6 lesions had p o s i t i v e SPECT. In group C (mean U R = 2 . 2 4 ± 0 . 5 8 ) ii/ii lesions had p o s i t i v e SPECT. In g r o u p D (mean U R = I . 0 7 ± 0 . 1 4 ) 10/10 lesions had n e g a t i v e SPECT. In the last 3 p., o n l y the a s e p t i c a b s c e s s was v i s u a l l y positive, s h o w i n g a UR= 2.2. S i g n i f i c a n t d i f f e r e n c e s were found w h e n c o m p a r i n g the U R b e t w e e n g r o u p s A vs B, and A vs C (p<0.0005). D e f i n i n g a v i s u a l l y p o s i t i v e SPECT or a UR=I.6 as a t h r e s h o l d to d i a g n o s e PBL, the sensitivity, e s p e c i f i c i t y and a c c u r a c y of 201T1 SPECT w e r e of 100%, 86% and 95%, r e s p e c t i v e l y . The U R of the 5 non PBL lesions w i t h v i s u a l l y p o s i t i v e SPECT r a n g e d from 1.7 to 2.2. Our r e s u l t s suggest that a v i s u a l l y n e g a t i v e 201Tl SPECT m a y e x c l u d e PBL; a p o s i t i v e SPECT w i t h UB>2.2 p o i n t s out PBL, and a p o s i t i v e S P E C T w i t h U R < 2 . 2 m a y indicate s t e r e o t a x i c b i o p s y to c o n f i r m diagnosis.

¢-

Bohuslavizki K.H., Brenner W., Tietje N., Behnke A:, Tinnemeyer S., Mester J., Clausen M., Mehdom H.M., Henze E. Clinics of Nuclear Medicine and Neurosurgery, Universitis of Kiel and Hamburg, Germany

In patients suffering from brain tumours somatostatin receptor scintigraphy using In-111-octreotide proved useful for differential diagnosis of meningeoma versus neurinoma. Usually in somatostatin receptor scintigraphy delayed imaging is performed up to 24 hours p.i. However, this procedure is time consuming and expensive. Therefore, we investigated whether 24 hour images may be omitted in patients suspected for meningeoma. Following clinical examination and standard MRI 71 patients were suspected for meningeoma in 92 localizations. Prior to surgery all patients received somatostatin receptor scintigraphy after i.v. Injection of 200 MBq In-111-octreotide, and planar whole body images were obtained 10 min, i, 4, and 24 hrs. SPECT was performed 4 and 24 hrs p.i. Resuits of somatostatin receptor scintigraphy in all lesions were evaluated with respect to both histology and time of image acquisition. In total, somatostatin receptor scintigraphy yielded 58 true positive, 20 tree negative, and 14 false negative results with the latter all below 5 ml (2.1_+0.8 ml) in volume. In 52/58 (=89.7 %) of true positive scans diagnosis could be established on 4 hour images without further information of 24 hour images. In 10 out of these 52 localizations SPECT was necessary to confirm planar findings. Only in 6 out of 58 (=10.3 %) localizations 24 hour images were imperative. These were 3 patients with intracerebral recurrences following surgery (volume <3 ml), 2 spinal meningeoma and 1 intracranial meningeoma. With regard to intracerebral meningeoma diagnosis could be established in 52•53 (=98 %). In conclusion, somatostatin receptor scintigraphy yields sufficient information using a 4 hour acquisition protocol including SPECT imaging in patients suspected for intracerebral meningeoma. Only in small meningeoma (<5 ml), spinal localizations or negative scans at 4 hours delayed images at 24 hours are necessary.

1.4

G.- J, Meyer, W. Burchert, J. van den Hoff, R. H6fs, H. Hundeshagen.

T. Kuwert, B. Woesler, C. Morgenroth, H. Lerch, M. Schfifers, S. Palkovic, P. Matheja, W. Brandau, H . Wassmann, O. Schober, Dpts. of Nuclear Medicine and Neurosurgery, WWU Miinster, Germany.

SPECIFICITY AND SENSITIVITY OF L -ll-C.METHIONINE TRAPPING FOR THE DETECTION OF LOW GRADE BRAIN TUMORS: A 2 TO 5 YEAR FOLLOW-UP STUDY. Low grade brain tumors present a large variability in clinical outcome. Accordingly their classification and follow up is difficult. This study presents results obtained in 58 patients with suspected low grade brain tumors. All patients were studied by positron emission tomography with L-11-C-methionine. Quantitative analysis was performed using the Gjedde-Patlack method. Blood samples were obtained from surface veins of heated hands in all examinations. Rate constants .of methionine trapping were determined in suspective brain regions and contralatera~mirror regions. Furthermore representative grey and white maV:erregions as well as a region in the cerebellum were analyzed. The representative regions were localized and sized according to anatomically identifiable structures down to a size of about two cm2. According to tumor/non-tumor ratios of trapping ~onstants as well as to tumor/white. matter and tumor/grey-matter ratios the patients were classified as high-grade, lowgrade, or non-tumor patients. The threshold for low grade tumor classification was fixed at a 20% above normal uptake values (> 99% confidence level). The threshold for higher grade tumor classification was set at 50% above normal uptake values. Of 58 patients studied, 10 presented brain tumors of grade 1II or higher and were excuded from the current evaluation. 19 patients presented L-11-C-methionine PET resuits, which were classified as low grade tumors. 22 patients showed no signs of low grade malignancy. 7 patients were grouped as suspect cases, with an increase of uptake ratios, which was 21%-25% above the normal average. Of 48 patients presenting no high grade tumors, 38 could be followed clinically for at least two years.(19 patients with low grade tumors, 14 patients with no signs of low grade malignancy and 5 of the suspect cases) 65% of the low grade tumors remained clinically stable, whereas 35 % developed recurrencies or higher grade malignancies. In the non-tumor group no patient developed clinical signs of malignancy during the observation time. 1 of the suspect cases (25%) developed further clinical symptoms and underwent sugery, proving a low grade tumor. Although the number of patients that could be follow over a longer period is still too small to give conclusive results it seems that L-I 1-C-raethionine PET is able to detect low grade brain tumors with a very high sensitivity and specificity of both well above 90%.

t~ ¢.. ID

IS A 4 HOUR PROTOCOL OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY SUFFICIENT IN PATIENTS SUSPECTEDFOR MENINGEOMA 9

1.2 Abteilung Nuklearmedizin und spezielle Biophysik der Medizinisehen Hochschule Hannover, D-30623 Hannover

O

i i

DIAGNOSIS OF RECURRENT GLIOMA WITH SPECT AND 1-123-c~-METHYL TYROSINE 1-123-c~-methyl tyrosine (IMT) allows to investigate amino acid transport rate in brain neoplasms. It was the aim of this study to evaluate the potential of LMT-SPECT to diagnose the recurrence of gliomas after primary therapy. Methods: Using a triple-headed SPECT camera, the cerebral uptake of IMT was determined in 27 patients on the average 22 months after surgical removal of a primary brain tumor. Eighteen patients had suffered from high-grade gliomas, nine from low-grade tumors. Four patients were examined before and after surgical revision of a presumed tumor recurrence, so a total of 31 studies were evaluated. The final diagnosis was based on prospective clinicopathological follow-up. Recurrence was diagnosed in 23 cases with marked clinical deterioration occurring on the average 3.1 months after SPECT and 6onfirmed by histopathology in 14 instances. Eight cases were free of recurrence as evidenced by unconspicious clinical follow-up ranging from 6 to 17 months after SPECT in seven cases and by clinical course and histopathology in the remaining subject. Results: Patients with recurrence had significantly higher ratios between IMT uptake in the tumor area and that in a background region than patients without recurrence (2.27 + 0.59 versus 1.47 + 0.29; p < 0.002). The best cutoff level of the IMT uptake ratio in the differentiation between recurrence and benign posttherapeutic lesion was 1.8. Using this study-specific discrimination threshold, the sensitivity and specificity of IMT-SPECT for detecting glioma recurrence were 18 (78 %) of 23 and 8 (100 %) of 8, respectively. The area under the binorreal receiver operating characteristic curve fitted to the data was 0.90 + 0.06. Conclusion: IMT-SPECT is a promising new tool in the follow-up of patients with gliomas after primary therapy.

859

01 Ll

t~ x__

O

• Neurology/Oncology 1.5

Oncology 2,1

M. Schmidt, K. Scheidhauer, C. Luyken *, G. Hildebrandt *, H. Schicha Clinic for Nuclear Medicine and * Clinic for Neurosurgery, University of Cologne, Germany

P. Shreve. R.S. Steventon, E. Deters, M.D~ Gross, R.L.Wahl. Ann Arbor Veterans Administration and University of Michigan Medical Centers, Ann Arbor, MI

SOMATOSTATIN-RECEPTOR S C I N T I G R A P H Y IN BRAIN TUMOURS The somatostatin analogue [lllIn-DTPA-D-Phel]-octreotide (In-111octreotide) allows scintigraphic visualization of somatostatin-receptor expressing tissue. While it is well known that a large variety of tissues express somatostatin-receptors the clinical value of In-111-octreotidescintigraphy in brain turnouts is still under clinical investigation. [n 83 patients with 96 brain tumours (39 meningeomas, 20 pituitary adenomas, 9 gliomas WHO grade II, 10 gliomas WHO grade IIl and IV, 7 metastases and 11 other varieties: 7 neurinomas, 1 epidermoid, 1 haemangiopericytoma, 1 osteosarcoma and 1 pseudocyste) I n - l l l octreotide-scintigraphy was performed 4 and 24 hours after i.v. injection of 110 MBq In-111-octreotide. Planar images of the head in four views with a 128 x 128 matrix as well as a SPECT (64 x 64 matrix) were acquired. 38/39 meningeomas showed an intense tracer accumulation. 5/20 pituitary adenomas were faintly visible. 15/20 pituitary adenomas did not show any tracer uptake. All grade II gliomas with an intact blood brain barrier were not detected whereas 9/10 grade III and IV gliomas/glioblastomas showed In-111-octreotide uptake. 4/7 metastases as well as the osteosarcoma and the haemangiopericytoma were judged as positive. The other varieties (7 neurinomas, 1 epidermoid, and I pseudocyste)did not show I n - l l l octreotide uptake. The results demonstrate that [l 1lin_DTPA_D_Phel]_octreotidc_scintigraphy does not allow a non-invasive tumour differentiation. However, this technique is often valuable in the differentiation between meningeomas and pituitary adenomas as well as meningeomas and neurinomas. Furthermore this technique allows the differentiation between scar tissue and recurrent meningeomas postoperatively, which has an important impact on further therapeutic planning.

1.6 A. Varrone A. Soricelli, A. Cuocolo, W. Acampa, G. Storto, G. D'Amore, P. Muto and M. Salvatore. Department of Diagnostic Imaging, University of Naples Federico II. 99mTc-TETROFOSMIN AND 99mTc-HMPAO UPTAKE IN BRAIN TUMORS BEFORE AND AFTER RADIOTHERAPY. Brain tumor response to radiotherapy is based on clinical assessment and CT or MRI findings. However, these techniques may not be able to differentiate radiation changes from tumor viability. On the other hand, 201-T1 and 99mTc-HMPAO may be helpful for this purpose. Moreover, changes of 20 l-T1 retention index in radiotherapy treated brain tumors are related to the prognosis. 99mTc-tetrofosmin (99mTc-TF) is a myocardial perfusion tracer which can be used for brain tumor imaging. The aim of this study was to assess 99mTc-HMPAO and 99mTc-TF uptake in 20 patients (10 men, mean age 62+_12 yrs) with primary (n=7) and metastatic (n=13) brain tumors. 99mTc-TF (370 MBq) and 99mTcHMPAO (740 MBq) scans were performed in the same day with a brain dedicated SPECT system (Ceraspect, DSI, USA). Patients were treated with conventional (n= 11) or sterotacticatly guided radiotherapy (n=9). Eleven patients died within 8 months after radiotherapy and were not reevaluated. The remaining 9 patients were studied before and 2-6 months after radiotherapy. 99mTc-TF Tumor/ Background (T/B) ratio and 99mTc-HMPAO Tumor/Cerebellum (T/C) ratio were calculated. In all pre-treated patients a significant relationship (r=0.82, p<0.001) between T/B and T/C ratios was found. 99mTc-HMPAO uptake around the tumor showed a more severe reduction in the majority (71%) of patients that died or did not respond to radiotherapy as compared to those responding to radiotherapy. Among 9 patients studied pre and postradiotherapy, 5 showed increased and 4 decreased or unchanged T/B ratio post-radiotherapy. Patients with increased T/B ratio showed increased T/C ratio or worse perfusion post-radiotherapy and died within 7 months or did not respond. Patients with decreased or unchanged T/B ratio responded to radiotherapy and showed TIC ratio after treatment. In conclusion, T/B and T/C ratios showed good relationship both pre- and post-radiotherapy although neither ratio seems to have prognostic value in pre-radiotherapy evaluation. Moreover, pretreatment assessment of brain perfusion and changes of T/B and T/C ratios post-radiotherapy seem to be predictors of brain tumor response to radiotherapy.

860

FDG IMAGING OF NEOPLASMS USING A DUAL HEAD SPECT CAMERA OPERATED IN COINCIDENCE MODE The purpose of this study was to investigate the performance of a dual head SPECT Anger camera operated in coincidence mode (SPECT-PET) in FDG imaging of cancer relative to conventional attenuation corrected full ring BGO detector positron emission tomography (PET). Thirty two patients with known or suspected malignant neoplasms underwent PET imaging (Siemens ECAT 931 or 921 EXACT) one hour following intravenous injection of 370 MBq (10 mCi) FDG, and then SPECT-PET (ADAC Vertex MCD) imaging 1-2 hours later. Both SPECT-PET and conventional PET images were read blindly, without anatomic imaging or clinical data available. For comparison of diagnostic performance on a lesion per lesion basis PET was considered as the gold standard. Sensitivity for a total of 117 discrete neoplastic lesions was: 15/18 (83%) for lung nodules/masses, 13/23 (58%) for mediastinal lymph nodes, 5/10 (50%) for axfllary lymph nodes, 21/27 (77%) of rib/vertebral metastases, 4/5 (90%) neoplastic lesions in the neck, and 8/34 (23%) of primary and metastatic foci in the abdomen. While neoplasm in lung nodules or lymph nodes under lcm could be detected by SPECT-PET when FDG uptake was highly elevated, lesions less than 1.5 cm were not detected reliably. Four false positive lesion diagnoses were made on SPECT-PET, but in all cases were due to erroneous location or identification of normal FDG uptake. These preliminary findings suggest FDG imaging using a modified SPECT camera in coincidence mode can detect many of the lesions detected on conventional full ring BGO detector PET, particularly in the lungs. Limited sensitivity occurred in the abdomen, and in all locations for tumor deposits generally less than 1.5 cm.

2.2 M.P. Sandler, D. Delbeke, J.A. Patton, W.H. Martin, R. Vithalani, *A. Balan, Department of Radiology, Vanderbilt University Medical Center, Nashville, TN and *Elscint, Ltd., Haifa, Israel. COMPARISON OF FDG PET AND COINCIDENCE ECT IMAGING USING A DUAL HEAD SCINTILLATION CAMERA IN PATIENTS WITH SUSPECTED MALIGNANCIES Purpose: The purpose of the study was to compare coincidence imaging obtained with a dual-head gamma camera and with a dedicated PET camera to evaluate malignancies. Methods: Fifteen patients with known or suspected malignancies underwent PET imaging (Siemens, ECAT 933) approximately 60 rain after injection of 10 mCi of FDG. Whole body imaging was performed on 13 patients and brain imaging on 2 patients. Coincidence ECT images were then acquired for 30 minutes over the region of interest using a dual head gamma camera equipped with a 3/8 inch crystal and a slit parallel hole collimators (Elscint, Varicam). The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton, and Compton/photopeak coincident counts. PET and coincidence ECT images were interpreted by 2 independent observers. Results: Thirty-three lesions ranging from 0.7 to 5 cm were detected by PET (3I hyper and 2 hypometabolic). Coincidence ECT detected 26 (78%) of these lesions. Among the 7 lesions not seen with coincidence ECT, 5 were less than 1.4 cm in size, and 2 were located centrally within the liver suffering from marked attenuation. The non-detectability of some lesions on coincidence ECT compared to PET may be explained by several factors: 1) Start of imaging time (mean +/- SD: 72+/- 18 rain for PET versus 160+/- 44 min for ECT leading to FDG decay to 6.75 mCi for PET and 3.86 mCi for ECT); 2) Limited efficiency of a 3/8 inch Nal crystal to detect 511 keV photons; 3) Suboptimal 2D reconstruction algorithm; and 4) Attenuation correction may also improve detection of centrally located lesions. Conclusion: FDG coincidence ECT imaging using a dual head gamma camera is a promising technique for oncologic imaging.

[] Oncology 2.3

2.5

.M. Bedimian, R.J. Smith, F. Benard, J. Karp and A. Alavi, U n i v e r s i t y of Pennsylvania, Division of N u c l e a r Medicine, Department of Radiology.

JM. Nuutinen, S. Leskinen, P. Lindholm, K-O. S6derstr6m, K. N~gren, U. Ruotsalainen, E. Salminen, H. Minn, Department of Oncology and Radiotherapy, Department of Pathology; Turku University Central Hospital and Turku PET Center; FINLAND

THE C L I N I C A L A D V A N T A G E S OF P O S T - I N J E C T I O N SINGLES T R A N S M I S S I O N SCANS A t t e n u a t i o n c o r r e c t e d PET provides enhanced d e t e c t i o n of tumors and their response to therapy. Unfortunately, coincidence transmission scans t y p i c a l l y last I0 m i n / p o s i t i o n and may double s c a n n i n g times. This p r e s e n t a t i o n d e s c r i b e s the clinical implementation of posti n j e c t i o n singles transmission (ST) scans on a v o l u m e imaging PET scanner. D e l a y e d emission s c a n n i n g u s i n g 370 MBq of F-18 FDG is followed by ST scans of 1.8 m i n / p o s i t i o n using a 222 MBq Cs-137 (662 keV gamma rays) point source. ST images are s e g m e n t e d into lung and soft tissue v o l u m e s and 511 keV gamma ray attenuation c o e f f i c i e n t s are applied. Twenty patients were s t u d i e d w i t h ST ii of w h o m also had coincidence t r a n s m i s s i o n studies. Most patients had various forms of cancer. The ST method results in a c c u r a t e and n o i s e l e s s attenuation correction. Imaging 60 cm of torso w i t h ST lasts only 60 m i n u t e s c o m p a r e d to 40 minutes for emission scans alone. 17 lesions were detected in the singles group as c o m p a r e d with 7 and 12 in the c o i n c i d e n c e c o r r e c t e d and emission only images respectively. Post injection ST scanning p r o v i d e s h i g h quality, high sensitivity a t t e n u a t i o n c o r r e c t e d FDG-PET images of the torso w i t h i n an acceptable p e r i o d of time making it an ideal m e t h o d for whole body tumor surveys.

[C-11]METHION1NE-PET IN PREDICTION OF MALIGNANCY GRADE AND SURVIVAL IN UNTREATED LYMPHOMAS AIM: To study whether the uptake of [C-11]methionine (MET) is associated with the histological grade of malignancy and survival in patients with untreated lymphoma. PATIENTS: 33 (55 % male) patients with lymphoma participated in the study. 27 of them were studied before the therapy and 6 before treatment for recurrent disease. 29 had non-Hodgkin's lymphoma (9 low, 11 intermediate, 9 high grade/WHO classification) and 4 had Hodgkin's disease. The median follow-up time (until death or December i996) was 21 months (range 0.5-89 mo). METHODS: An ECAT 931/08-12 PET-scanner was used for PET imaging. After transmission scan a median dose of 444 MBq of MET was injected intravenously and a dynamic scan was acquired for 40 minutes. SUV and Ki values were calculated at 30 minutes postinjection. Sephadex analysis was performed to correct for metabolites in plasma. The PET results were correlated with the clinical follow-up data. RESULTS: The median SUV was 7.0 (range 5.4-t2.4) in high, 6.2 (range 1.9-10.4) in intermediate and 5.7 (range 3.8-8.3) in low grade lymphomas. One intermediate grade lymphoma of the skin was visually negative (SUV 1.9). In Hodgkin's disease the median SUV was 7.0 (range 3.2-7.9). The median Ki values were 0.162 in high, 0.099 in intermediate, 0.078 in low grade Iymphomas and 0.149 in Hodgkin's disease, respectively. Ki and SUV values were comparable in all cases. We could demonstrate no correlation between MET uptake and survival or malignancy grade. CONCLUSIONS: We conclude that MET PET is useful for detection of lymphomas. However, MET does not distinguish high grade tumors from the other malignancy grades. MET uptake was not correlated to the survival of the patients.

2.4

2.6

A. Dimit rakopoulou-Str~, ~ ~, L.G. Strauss~, P. Schlagz, P. Hohenberger z, F. Oberdorfer 1, G. Kontaxakist, G. van Kaick~.lGerman Cancer Research Center, Heidelberg, 2Department of Surgery and Surgical Oncology, V~rchow-K]inikum, Robert-R6ssleKlinik, University of Berlin, Berlin, Germany

S. Stroobants, P. Dupont, E. Coomans, G. Verhoef*, J .Thomas**, R. Bennink, P. Zach6e*, G. Bormans, M. Bogaerts*, L. Mortelmans, Dept of Nuclear Medicine, Hematology* and Oncology**, U.Z.K.U. Leuven, Belgium

PET STUDIES WITH O-15-WATER AND F,-18-FLUOROURACIL (F-18-FU): COMPARISON OF SYSTEMIC AND REGfONAL ADMINISTRATION IN LIVER METASTASES

COMPARISON OF WHOLE-BODY FDG-PET AND GALLIUM-67 CITRATE IMAGING FOR STAGING AND THERAPY FOLLOW-UP IN LYMPHOMA PATIENTS Aim: To compare the efficacy of whole-body FDG-PET and gallium-67 citrate scanning (Ga) in the staging and therapy follow-up of lymphoma patients in relation to CT. M e t h o d s : 15 lymphoma patients (8 Hodgkin's disease (HD) and 7 non-Hodgkin's lymphoma) underwent PET, Ga and CT prior to and at the end of chemotherapy. The PET study (6'/bedpos) was performed with an ECAT 931 and started 60min p.i. (dose: 6.5 Mbq/kg). The gallium scan was started 72h p.i. (dose: I80230 Mbq). Three anterior and posterior planar images (10rain/image) were acquired with a double headed gamma camera. In each patient 14 different lymph node regions were visually scored. Results: Prior to chemotherapy, CT was positive in 56, PET in 71 and Ga in 37 regions out of 210. PET and CT were concordant in 189 regions, 18 were positive exclusively on PET (lesions < 1.5cm). Three regions were only CT positive (abdominal and cervical LN in 1 pt with HD).'AII regions positive on Ga were also positive on PET (small and/or abdominal lesions were missed on Ga). After chemotherapy (mean follow-up 5 months), 3 regions were positive on both PET and CT but negative on Ga. Progressive disease was noted in all of them. 3 regions were PET positive and CT negative: 2 relapsed (1 Ga positive) and 1 is still in complete remission (CR), but received additional radiotherapy (RT). Nine regions were only positive on CT (bulky prior to chemotherapy): 6 received additional RT and are still in CR, 3 mediastinal residual masses relapsed. On a patient based analysis, 6 pt relapsed: in 3/6 only PET suggested active disease (stable, Ga negative, residual mass on CT), in 1/6 both Ga and PET showed residual uptake (negative on CT) and 2/6 with mediastinal residual mass relapsed within one month after a negative PET and Ga. Nine pts are clinically in CR (all Ga negative): 4/9 were negative on all imaging methods, 1/9 was only PET positive and 4/9 were only CT positive ( all pts positive on PET or CT received additional RT). Conclusion: FDG-PET is more sensitive as compared to gallium scintigraphy in both staging and therapy follow-up of lymphoma patients.

Regional chemotherapy can potentially increase drug delivery at the tumor sites and has therefore been used for the therapy' of metastatic colorectal cancer. Dynamic positron emission tomography (PET} and Fluorine-18-Fluorouracil (F18-FU) was used in patients with liver metastases from colorectal cancer to examine the pharmacokinetics of the drug up to 120 rain p.i. following systemic and regional application of the same dose of FU. All patients included in the study (n=15) had a surgically implanted catheter in the gastroduodenal artery due to regional chemotherapy. Dynamic PET studies (up to 5 rain) with O-15-water were performed for the evaluation of the accessto the lesions immediately prior to the F-18-FU study using both application routes. The final evaluation includes 24 metastases obtained in 15 patients. 21/24 (87.5 %) of the lesions showed an improved access using the intraarterial approach. 20/24 (83.3 %) of the lesions demonstrated a better FU influx after regional application, Regional administration revealed higher F-18-FU concentrations with a maximum uptake of 18.75 SUV for the FU influx and a maximal uptake of 5.03 SUV for FU trapping, 8/24 (33.3 %) of the metastases demonstrated an enhanced FU trapping following the regional administration, Cluster analysis revealed a group of metastases (n=6) with a non-perfusion dependent FU transport using the systemic application. 5/6 (83.3 %) of these group of lesionsdid not show any enhancement of the F-18-FU uptake after regional application. The data gave evidence for at least one different, energy-dependent transport system, which can be saturated even after systemic application of the drug. The data show, that the main limiting factor for a therapy response is the very high and rapid etimination of the cytostatic agent out of the tumor cells. Furthermore, it was~not possible to predict the pharmacokinetics of FU after regional application using an intravenous PET-study. It may be possible using intravenous PET double tracer studiesto identify metastatic lesions having a non*perfusion dependent transport system and exclude them from a regional treatment protocol.

861

•

Cardiovascular

Cardiovascular 3.1

3.3

M. ScNifcrs I, H. Lerch I, T. Wichter 2, C.G. Rhodes 3, A.A. Lammertsma3, M. Borggrefe2, F. Hermannsen 3, O. Schober I, G. Breithardt ~, P.G. Camici 3. Depts. of Nuclear Medicine I and Cardiology, Westftilische Wilhelms-Universitgt MOnster, Germany, and MRC Cyclotron Unit 3, Hammersmith Hospital London, UK. AUTONOMIC DYSFUNCTION IN PATIENTS WITH IDIOPATHIC VENTRICULAR TACHYCARDIA: A STUDY USING PET WITH C-11CGP 12177 AND C-11-HYDROXYEPHEDRINE.

I.Balogh, A.Medveczki, T.Vecsey*, E.Bodor*, Uzsoki Str. Hospital, Nuclear Medicine Department, Cardiovascular Surgical Institute of Semmelweis Medical University*, Budapest. THE SCINTIGRAPHIC AND CLINICAL EVIDENCE OF THE PRESENCE OF REINNERVATION OF THE TRANSPLANTED HEART

with idiopathic right ventricular outflow tract tachycardia (RVO-VT) is suggested by the inducibility of ventricular tachyeardia by stress or catecholamine infusion and the therapeutic efficacy of antiadrenergic drugs. The aim of this study was to assess presynaptic catecholamine re-uptake (uptake-l) and postsynaptie ~3 adrenoceptor density (13AR) in RVO-VT patients using quantitative positron emission tomography (PET). METHODS. A group of eight RVO-VT patients (6 m, 2 f, mean age 44 _+ 1I yr) was studied with PET. Bmaxfor [3AR was derived from a C- 11-CGP 12177 (CGP) scan, the presynaptic catecholamine re-uptake was assessed by calculating the volume of distribution (Vd) for C-11-hydroxyephedrine (HED). In addition, myocardial blood flow and flow reserve was measured using oxygen-15 labelled CO2 at baseline and after administration of dipyridamole. Patient data were compared with those found in age matched groups of normal controls (HED: n = 10; CGP: n = 19; COs n = 20). RESULTS. Global mean Vd for HED was significantly lower in the RVO-VT patients (41.0 5:13.5 ml/g tissue) compared to controls (71.0 5:18.8 ml/g tissue, p < 0.002). Furthermore, global [3AR in RVO-VT patients (6.8 -+ 1.2 pmol/g tissue) was significantly reduced compared to controls (10.2 + 2.9 pmol/g tissue, p < 0.004). There were no significant differences in myocardial blood flow (0.98 5:0.14 vs. 0.97 ± 0.24 ml/min/i00g, p=ms.) and flow reserve (3.4 ± 0.4 vs. 3.1 ± 1.l, p=n.s.) between RVO-VT patients and controls. CONCLUSIONS. The findings of the present study confirm pre- and postsynaptic autonomic dysfunction in RVO-VT patients and give further insights into the underlying pathophysiology.

Our aim was to study:l) How early can be experienced any sign of reinnervation. 2) Is there any relationship between clinical and scintigraphic signs of it. For this reason we studied 8 pts with transplanted heart (mean age: 34+12 years) with 1-123 MIBG scintigraphy performing planar examination in different time (o.5.,t.,2,4 hours) after the injection of radiopharmaceutical. We used a semiquantitative analysis to measure the 1-123 MIBG uptake of the heart, characterising the extent of it with a 4 grade scale system (+ -~ ++++). Within two weeks we measured the change of the heart rate (HR) for the stimulation of Atropin (i.v.o.02 mg/kg) and Metoprolol (i.v.o.1 mg/kg). The first examination performed half year after operation and every year these examinations were repeated. The average follow up period was 45_+10 months. Within one year and between one and two years after operation we did not experience any 1123 MIBG uptake of the heart and HR response was less than 3% decrease for Metoprolol and without any change for Atropin. After two years 1-123 MIBG uptake of the heart was detected at 7/8 pts. The longer time after the transplantation was accompanied by the more extended MIBG uptake. The effect of Metoprolol was 18_+8% decrease of HR, but Atropin could not cause any effect for HR. At one pt. without MIBG uptake couldn't be found decrease of HR after the administration of Metoprolol. 1-123 MIBG uptake of the heart as the evidence of adrenergic neuron integrity means a scintigraphic sign of sympathetic reinnervation of the transplanted heart and in every cases was combined with the effect of the Metoprolol acting on sympathetic endings. Atropin taking effect on parasympathetic ending wasn't effective on HR. Thus the sympathetic reinnervation was late (after 2 years) and the scintigraphic and clinical signs of it could be registered together.

3.2

3.4

BACKGROUND AND AIM. Cardiac autonomic dysfunction in patients

J. Pech~fi, R. R n w i n e m and Z. University Hospital and Comenius School of Medicine, Div. of Nuclear 1st Dept. of Internal Medicine.

CesnakovS, University Medicine,

1 2 3 1 -M I B G SCINTIGRAPHY

MYOCARDIAL

AND 2 01 -THALLIUM IN ESSENTIAL HYPERTENSION

The increased sympathetic activity in early stage followed by structural cardiovascular changes afterward is one of the d o m i n a n t p a t h o physiological mechanisms of e s s e n t i a l hyperten sion (EH) . T h e r e f o r e the investigation of the cardiac adrenergic innervation by a n o r e p i n e p h fine analogue MIBG is of a g r e a t interest. 123I -MIBG myocardial scintigr aphy followed by 201-Thallium myocardial imaging two d a y s later was p e r f o r m e d in a total of 30 p a t i e n t s with non-treated EH (13 w e r e in s t a g e I (HI) , 1O in s t a g e II (H2) a n d 7 in s t a g e III (H3) a c c o r d i n g to W H O c r i t e r i a , n o n e h a d c o n g e s t i v e h e a r t failure) a n d 14 n o r m o t e n s i v e s (N) . T o t a l m y o c a r d i a l M I B G u p t a k e was c a l c u l a t e d f r o m p l a n a r i m a g e s as a hear t / m e d i a s t i n u m ratio (H/M) at 4 and 24 hours after injection. The medians of H / M at 4 hours in HI (1.94) and H3 (1.69) were significantly lower in c o m p a r i s o n w i t h N (2 . 12) a n d this d i f f e r e n c e was e v e n g r e a t e r after 24 hours. The medians of H3 at 4 h o u r s (1.69) and 24 h o u r s (1.48) w e r e s i g n i f i c a n t l y lower a l s o in comparison with H2 (2.01 and 1.83) . S m a l l to moderate myocardial perfusion d e f e c t s w e r e present in 46% of HI, 50% of H2 a n d 71% of H3 patients. Conclusion: There is a significant change in total myocardial MIBG uptake already in e a r l y s t a g e s of EH. T h e p r e s e n c e of c a r d i a c a d r e n e r g i c nerves' disintegration is clearly evident in late stage of EH mainly in association with exercise myocardial ischemia.

862

A.Giordano ~, S.L.Nori 2, M.Martire 3, M.L.Calcagni l, G.Meduri I, A.F~ I, B.Rossi l, L.Troncone I. Inst.of iNuclear Medicine, 2Anatomy and 3Pharmacology of the Catholic University. Rome - Italy. MIBG UPTAKE MECHANISMS IN THE HEART: IN-VITRO (SYNAPTOSOMES) AND IN-VIVO (RAT HEARTS) MODELS

While several papers deal with clinical applications, few authors studied the mechanisms of MIBG uptake in the heart. Therefore, we intended (i) to verify to what extent MIBG and norepinephrine (NE) use the same uptake mechanism; to this aim we quantified the capability of MIBG to inhibit the uptake of NE using adrenergic nerve terminals isolated from rat cerebral cortex (synaptosomes). We also(2)developed an in-vivo model to scintigraphically quantify the interference of different drugs on MIBG cardiac uptake and to study the perfusion and "innervation" of the heart in experimental LV infarction; to this aim we studied 93 wistar rats co-injected with I123MIBG and TI201 and performed 7-camera imaging with counting of excised ventricles. Results:(1) the kinetics of inhibition of NE uptake by MIBG in synaptosomes (method of Dixon) followed a competitive mechanism with a Ki value (inhibition constant) of 0.04 p_M; (2)a good MIBG/TI visualization of excised rat ventricles was obtained using 75gCi doses and dual-isotope imaging (counts interference: <10%); after challenge with reserpine MIBG count/sec at lh p.i. was similar to controls (7.8~2 vs 7.1~2; P= NS) while it was significantly lower at 4h p.i(2.5~i vs 5.8~i, P=.0001); MIBG uptake reduction after LV infarction (-27% vs controls) was significantly greater than that of T1 (-11%; P=.0001). In conclusion: (i) the in-vitro model on synaptosomes confirmed that MIBG uses the same uptake mechanism of NE with competitive inhibition in nerve terminals;(2)the in-vivo model allowed to demonstrate the feasibility of dual-isotope MIBG/T1 imaging of rat hearts, to quantify the inhibitory effect of reserpine on cardiac MIBG uptake (confirming abundant non-specific uptake early p.i. in rats) and to reveil a MIBG/TI discrepancy after LV myocardial infarction.

[] C a r d i o v a s c u l a r / O n c o l o g y

Oncology 3.5

4.1

F. Benggll, I. Matsunari, P.Barthel, G. Schmidt and M. Schwaiger. Nuklearmedizinische Klinik and I. Medizinische Klinik, Technische Universitht Miinchen, Germany

"f.M. BehrI, S. Gratz 1, P.M. Markt~ 2, M. Hfifiaer3, A. Schauer4, H. Becker2, D.L. Munz1, and W. Becker ~. Departments of Nuclear Medicine ~, Surgery2, Internal Medicine (Endocrinology) 3 and Pathology4 of the Georg-August-Udiversity of GStfingen, Germany.

MYOCARDIAL KINETICS OF 1-123-MIBG AND LUNG U P T A K E OF THALLIUM-201 EARLY AFTER A C U T E MYOCARDIAL INFARCTION

ANTI-CEA ANTIBODIES VERSUS OCTREOTIDE FOR THE DETECTION OF OCCULT AND METASTATIC MEDULLARY THYROID CANCER: ARE CEA AND SOMATOSTATIN-RECEPTOR EXPRESSION PROGNOSTIC FACTORS ?

Myocardial uptake and washout of 1-123-MIBG as well as lung uptake of T1-201 have been used to assess impairment of left ventricular performance and to predict outcome in patients with heart failure or myocardial infarction. The aim of this study was to directly compare parameters derived from planar M I B G and T1 imaging in patients after acute myocardial infarction (MI). 60 patients treated with reperfusion therapy for MI (MI pts) underwent planar M I B G - and resting Tl-imaging within 14 days of the onset. Age matched normal control groups for MIBG- and Tl-imaging each consisted of 8 individuals without heart disease. Planar imaging was performed at 30 rain and 5 h after injection of MIBG using a g a m m a camera with a large field of view (Siemens DIAC M). The heart to mediastinum ratio (H/M) in delayed images, as welt as the washout rate (WR) were calculated using ROI-technique. Within 4 days of the M I B G study, planar T1 imaging at rest was started 15-20 min after injection. The lung to heart ratio (T1-LH) was obtained in a manner similar to M I B G imaging. The MI pts had a preserved left-ventricular function (mean LVEF 5 6 . 5 + i 6 . 1 % ) . I-I/M was significantly lower in MI pts compared to normals (2.36_+0.66 vs 2.92+0.54, respectively; p<.02), while W R was increased (11.6+-7.9% vs 1.2+10.9%; p<.001). T1-LH in MI pts w a s similar to normals (0.50+0.06 vs 0.48+0.05; p=.40). Both H / M and W R correlated weakly to LVEF (r=.34, p<.01 and r=-.28, p < . 0 4 , respectively), but T1-LH did not (r=-. 1 i, p=.44). The results demonstrate increased washout and decreased heart uptake of M I B G in the MI pts as compared to normals, suggesting increased sympathetic nerve tone beside myocardial denervation even in patients with minimal impairment of left ventricular function after agressive reperfusion therapy. These findings indica'~e a high sensitivity of M I B G parameters to changes in cardiac performance. Lung uptake of Tl at rest, on the other hand, was normal and thus, seems to be less sensitive.

Frequently in medullary thyroid cancer (MTC), elevated calcitonin levels indicate metastatic disease, although conventional radiological procedures fall to localize responsible lesions. The aim of this study was to compare the sensitivity of anti-CEA MAbs versus somatostatin analogs in the staging of MTC intraindividually, as well as to assess possible correlations between the scintigraphic behavior and the patients' prognosis. A total of 26 patients with MTC was examined between 1977 and 1996:10 suffered of known, 14 of occult MTC, 2 patients were free of disease at the time of presentation. The patients were investigated with anti-CEA MAbs (labeled with 99roTe, lltln or 131I; receiving a total of 35 injections) and rain-labeled octreofide within two weeks. All patients underwent conventional radiological evaluation (ultrasonography, CT, MR/) and / or biopsy within four weeks. Clinical follow-up was obtained. All patients with known disease had elevated plasma CEA (range 6.8-345 ng/ml), whereas in 9/14 occult cases, levels were _<5 ng/ml. In patients with knovcu disease, the overaU lesion-based sensitivity was 86% for the anti-CEA MAbs, whereas octreotide was unable to target any tumor in patients with clinically aggressive disease (overall sensitivity only 47%). With octreotide, significantly higher tamor/non-tumor ratios were seen in clinically stable or slowly progressing forms, whereas anti-CEA-Mabs yielded highest uptake in rapidly progressing, aggressive disease. In all patients with occcult MTC, anti-CEA MAbs as well as octreotide were able to correctly localize at least one lesion (patient-based sensitivity virtually 100%): in postsurgically persisiting hypercalcitoninemia, cervical lymph nodes were identified as the most frequent site of disease, whereas in patients with occult disease several years after primary surgery, we found a characteristic "chimney-shaped" bilateral mediastinal lymph node involvement. For the staging of MTC, anti-CEA MAbs and octreotide seem to have a sensitivity which is superior to conventional diagnostic modalities, especially when used in combination. Better detectability with anti-CEA antibodies (higher CEA expression ?), may be associated with more aggressive forms, whereas somatostatin receptor expression at normal plasma CEA levels and weak anti-CEA MAb targeting seems to be associated with a more benign clinical course. This is hi accordance to the studies of Busnardo et al. and Mendelsoim et al. (Cancer 1984; 53:278 & 54: 657), who showed higher CEA expression to be associated with a worse prognosis, as well as to the invitro findings of Reubi et al. (Lab Invest 1991; 64: 567), who demonstrated the loss of somatostatin receptors in less differentiated MTC.

3.6

4.2

H. Lerch ~ M. Schafers 1, T. Wichtei~, C.G. Rhodes 3. A A . ~ m a 3, F. Hermansen 3, O. Sehober 1, G. Breithardt2, P.G. Camici 3. Dept. o f Nuclear Medicine t, Cardiology and Angiology2, Westfalische Will~lms-Universit~it Miinster, Germany, and MRC Cyclotron Unit 3, Hammersmith Hospital, London, U K

MHGC Kranenborg, OC Boerman, MCA de Weijert, JC Oosterwijk, E Oosterwijk, FHM Corstens Departments of Nuclear Medicine, and Urology, University Hospital Nijmegen, The Netherlands

GLOBAL REDUCTION OF CARDIAC fl-RECEPTOR DENSITY IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY Background and Aim: Regionally altered presynaptic adrenergic function was shown in patients with arrhythmogenie fight ventricular cardiomyopathy (ARVC) using I-123-MI]3G SPECT. The aim of this study was to elucidate function o f both pre- and postsynaptic activity by quantitative positron emission tomography. Methods: In 8 patients, aged 38.9_+9.5 (26-53, median 37) years, off medication, presynaptic function and postsynaptic B-receptor density were investigated by PET, C-I 1-hydroxyephedrin (HED) and C-11C G P 12177. The data were compared to age matched control groups (HED: n=l 1, CGP: n=20). In addition, myocardial blood flow and coronary reserve were measured by O-15-CO2 at baseline and after dipyridamole administration. Involvement o f left ventricle w a s excluded by electrophysiologieal study, right and left heart eatheterisation including right ventricutar endomyocardial biopsy, and coronary angiography. Results: In the patients Bm~ for C G P 12177 was lower than in the controls (5.8_+1.4 pmol/g vs. 10.2+_2,.9, p=0.0007), whereas presynaptic function w a s not significantly different (Vd H E D 61.2+~24.3 vs. 71.0_+18.8 ml/g, p=0.22). Myocardial blood flow and coronary flow reserve were normal (p=n. s.). Conclusion: Postsynaptic (13-), but not presynaptic function is globally depressed in patients with arrhytbmogenic right ventricular disease without functional or structural involvement o f the left ventricle.

RADIOIMMUNOTARGETING OF RCC TUMORS IN MICE WITH ANTIRCC X ANTI-DTPA BISPECIFIC MONOCLONAL ANTIBODIES Radiolabeled antibodies (MAbs) can target tumors selectively. However, high levels of radioactivity are observed in nontarget organs due to slow MAb clearance. High background levels may be overcome by pretargeting protocols using bispecific (bs) MAbs. We have evaluated an anti-renal cell carcinoma (RCC) x anti-DTPA bsMAb (G250xDTInl) for multistep targeting of s.c. RCC tumors in nude mice. Mice were injected i.v. with bsMAb. After 3 days mIn-DTPA was injected i.v. and 1 h later the biodistributinn of the radiolabel was determined. The targeting of I /zg ~2~I-G250xDTInl,~251-G250and anti-DTPA MAb t2~I-DTY4 was determined. Both t-~SI-G250(102.9 + 31.1%ID/g) and ~25I-G250xDTInl(27.6 -+ 6,1%ID/g) showed specific tumor uptake, in view of the 2.3 ± 0.5 %ID/g of nonspecific ~zSI-DTY4. In the tumor mln-DTPA was caught by pretargeted G250 xDTInl but not by G250 (0.40 + 0.07 vs 0.006 + 0.004 %ID/g). Subsequently, the effect of G250xDTthl protein dose (2-18 #g) was studied. High tumor uptake (30 %ID/g) was seen at 2 and 4 #g. The tumor uptake decreased at higher doses and tumor was saturated at 10-15 #g G250xDTInl. At a 100-fold molar excess mIn-DTPA the mln-DTPA tumor uptake increased with increasing bsMAb dose upto 15 ~g and decreased thereafter, again indicating saturation of the tumor at 15 #g G250xDTInl protein dose. Subsequently, at 15 #g G250xDTInI the amount of mIn-DTPA was varied (10, 100 or 250-fnid excess). At a 10-fold excess significantly higher mIn-DTPA tumor uptake was observed. No differences were observed in tumor/blood ratios at all mInDTPA doses. Using 15 Izg G250xDTInl and a 10-fold excess mln-DTPA tumor retention of mIn-DTPA was determined (1-48 h p.i.). There was good retention of mlnDTPA in the tumor, while the radiolabel cleared rapidly from the blond. Consequently, tumor/blood ratio increased with time to 500 at 24 h p.i. Shortly after mIn-DTPA injection high mln-DTPA blood levels were observed. Therefore, circulating G250 xDTInl was blocked by injection of a 0.5 to 6-fold excess [gM-DTPA-In 30 rain prior to mln-DTPA injection. Efficient blocking of circulating G250xDTInl was achieved. With a 0.5, 1 or 3-fuld excess IgM-DTPA-In no reduced mIn-DTPA tumor uptake was seen compared with the two-step approach. As a result the tumor/blood ratio of mInDTPA increased from 1.1 + 0.2 (two-step) to 24.2 ± 6.9 (three-step) 1 h p.i. In conclusion, RCC tumors can be targeted very rapidly with low background activity and high tumor/blood ratios using a three-step protocol with G250xDTInl, IgMDTPA-In and mIn-DTPA. In the near future this three-step protocol will be used for radioimmunotherapy studies using 90y. and t86Re-labeledchelates.

863

tO ,m t~ t-

t__ l

O

• Oncology/Bone 4.3

4.5

Mart!in G. Steffens. Noor E. Zegwaart-Hagemeier, Otto C. Boerman, Egbert Oosterwijk, Frans AlL Debruyne and Frans t~ Corstens. Departments of Nuclear Medicine and Urology, University Hospital Nijmegen, The Netherlands.

H. Amthauer. T. Schumacher, E. HeiNer, J. Ricke, R. Jochens, C. Stroszczynski, J. Maeurer, B. Gruenert, B. Hell, J. Bier, H. Eichstaedt Departments of Nuclear Medicine / Radiology and Oro-Maxillo-Facial Surgery, Virchow-Clinic, Humboldt-University Berlin, Germany

IMMUNOHISTOCHEMICAL ANALYSIS OF HETEROGENEITY OF 131IcG250 MONOCLONAL ANTIBODY UPTAKE IN PRIMARY RENAL CELL CARCINOMAS. In a clinical phase I protein dose escalation study with ~3~l_labeledchimeric monoclonal antibody (mAb) G250 (cG250) in patients with primary renal cell carcinoma, tumor uptake of mAb ]3~I-cG250was highly heterogeneous, lntratumoral variations in tumor uptake exceeding a factor 100 were observed, in the current study we investigated the correlation between tumor uptake and four histological parameters: antigen expression, blood vessel density, tumor viability and percentage of tumor cells within the sample. To investigate the heterogeneous uptake whole tumorslices (1 cm thick) of 5 different tumors were cut in 1 cm3 cubicles. In each of these cubicles t3tI-cG250 uptake was determined in a gamma-counter (% ID/g) and antigen expression (marine mAb G250), vessel density (mAb PAL-E), tumor viability (mAb RCK-102) and percentage of tumor cells (mAb RCK-I02) were determined immunohistochemically. Low power fields (100 x) were scored as <5 %, 5-25%, 25-50 %, 50-75 % or >75 % positive using a I0 x 10 ocular counting grid and a weighed mean was calculated for the entire section. The correlation coefficients (r2) between the uptake of 1311_cG250and each of these four parameters were determined. In two out of five tumors analyzed a correlation between 131I-cG250uptake and antigen expression was found (r2 = 0.48 and 0.59) while the other three tumors did not show such correlation (r2 < 0.23). No correlation between any other parameter and mAb cG250 uptake was found. All tumor samples with high I~][-cG250 uptake (> 0.1% ID/g) showed high antigen expression (>50 %). However, the reverse was not true: not all samples with high antigen expression displayed high uptake. These observations indicate that high antigen expression is a prerequisite for high antibody uptake. However, regional differences in antibody uptake within a tumor cannot be explained by antigen expression alone nor by tumor vascularization or percentage of viable tumor cells. In future, clinical studies time-related changes in tumor uptake will be investigated in patients with primary RCC.

PRE- AND INTRAOPERATIVE DIAGNOSIS OF HEAD AND NECK CANCER USING 99 mTc-RADIOIMMUNOSCINTIGRAPHY Purpose. This study was designed to evaluate the preliminary efficacy and diagnostic value of combined pre- and intraoperative Radioimmunoscintigraphy (RIS) as a new diagnostic method for detection of metastatic squameus cell carcinoma (SCC) in the head and neck. Methods. Ten patients (46-71 years; median 60) underwent preoperative scintigraphy (4-6 hours p.i.) and intraoperative scintimetry (22-26 hours p.i.) after injection of 2 mg monoclonal antibody to SCC (SQ 174, Biomira Inc., Canada) labeled with 800-1200 MBq 99mTc. The gamma detection probe (C-Trak, Care Wise Medical Products, Morgan Hill, CA, USA) was used to count all areas of clinically apparent primary tumor, suspected lymph node sites, great vessels and selected normal tissue in vivo. After tumor and neck dissection the tumor bed was scanned with the probe to ascertain completeness of resection and scintimetry of the excised tissue was performed ex vivo, Finally excised tissue and separately submitted radionuclide labeled lymph nodes were sent for routine pathological evaluation and compared to other diagnostic modalities (Ultrasound, CT and MRI). Results. In preoperative RIS all primary tumor sites could be confirmed, in one case with occult primary tumor a lesion in the right palatine was identified as a primary SCC. The gamma probe identified 21/24 of all histologically proven lymph node regions, compared to 17/24 with the scan, 16/24 by ultrasound, 19/24 by CT/MRI. In 4 patients false positive lymph node involvement was seen in 6 Iocalizations. In three patients the intraoperative results mirrored the preoperative and histological result properly. In three patients false negative results were obtained. In all cases, verification of primary tumor's complete resection was possible. Conclusions. We conclude that this technique allows localization of infiltrated lymph node sites and the verification of complete tumor resection. It is thus helpful in early decision making on adjuvant treatment modalities.

Bone

4.4

5.1

J.P. Vuillez. D. More, P.Y. Brichon, E Rouvier, E. Brambilla, J. Barbet, C. Brambilla. Hopital A. Michallon, CHU Grenoble and Immunotech, Marseille, France.

S. Mirzaei, P. Knoll, Th. Wenzel, K. Koriska,

TWO STEP IMMUNOSCINTIGRAPHY (IS) USING AN ANTI-CEA/ANTI-DTPA BISPECIFIC ANTIBODY AND IN-111 LABELED DI-DTPA FOR MEDIASTINAL STAGING OF NON SMALL CELL LUNG CARCINOMA (NSCLC) Mediastinal lymph nodes involvement is a very important criteria for the surgical treatment of NSCLC. Computed tomography (CT) is the best non invasive tool for assessing this involvement, but it cannot detect neopiasic lymph nodes which are less than 2 cm in size. On the other hand, lymph nodes can be enlarged without being malignant. It was previously showed that anti-CEA IS could be useful to improve the accuracy of mediastinal staging in N S C L C . However, IS had been limited by the low tumor/mediastinal tissues ratio. The so called "Affinity Enhancement System" (AES) two step method using an anti-CEA/anti-DTPA bispecific antibody and In-11 l-labeled di-DTPA (injected in a second time) has been proved to widely increase this uptake ratio. Here we report results in 10 patients with NSCLC who were considered not having a mediastinal involvement and were imaged before surgery with AES. Planar and tomographic acquisitions were done 6 and 24 hours after In-111-di-DTPA injection (5 mCi). All patients were operated. IS was positive for the primary tumor in 8 out of 10 patients. In general, contrast was much larger than with classical IS. Among these 8 patients, IS was positive for the mediastinum in 3 cases and negative in 5. All these 5 negative cases were true negative ; among the 3 positive cases, there was 1 true positive and 1 false positive (uptake in the intra-pulmonary lymphnodes, which w e r e v e r y d i f f i c u l t to d i s t i n g u i s h f r o m hilar l y m p h n o d e s scintigraphically) ; the last case remains undetermined at present, because IS showed a focus in the side opposite to the tumor, which was not p o s s i b l e to c o n t r o l d u r i n g the t h o r a c o t o m y . R e l a t e d to immunohistochemistry, specificity of uptake for CEA targeting was larger than with directly labeled anti-CEA F(ab')2. Oar results show that AES is an efficient method, which give better images than classical immunoscintigraphy. Assessment of its clinical value in NSCLC staging will require a larger group of patients.

864

H. K{ihn,

Department of Nuclear Medicine, Wilhelmineuspital Vienna, Austria

Tc-99m M E T H Y L E N E D I P H O S P H O N A T E (MDP) I M A G I N G F O R S C R E E N I N G O F T O R T U R E SURVIVORS Tc-99m MDP bone scintigraphy, particularly in case of child mistreatment, has been used to prove clinically and radiologically non detectable bone lesions. The aim of this study was to evaluate bone scintigraphy ( as a forensic test) in torture survivors who underwent corporal mistreatment within a time period of 5 years to 4 months before the nuclear medicine investigation 20 victims of l 1 countries ( 2 female, 18 male, aged 19-46 y) with a credible history of torture ( mostly in the area of skull and ribs, but also fingers or lower legs) were investigated. According to the reported degree of traumatisation they were categorized into 2 groups: group A ( n = 1 0 ) injury with hard objects ( butts, truncheons), time since the torture 6-18 months, in one case 5 years and group B ( n = 1 0 ) traumatisation with fists or kicks, time since torture 4-12 months, in one case 2 years. A pathologic uptake ofTc-99m MDP in the area of injury was found in all patients of group A, while X-ray was positive only in three. In group B, bone scans were positive in 6 patients, while X-ray was negative in all of them. Due to their social situation as refugees~ individual follow-up of these patients was not possible. However, our preliminary results suggest that bone scintigraphy is a highly sensitive unique tool to prove maltreatment - at least with hard objects - for a period of at least 1-2 y after traumatisation and is also of great value in cases of minor traumatisation.

[] B o n e

5.2

5.4

DL Hastin.qs, WHJ Wall, DE Miller, JB Hall, ME Welsh, SP Jeans, Royal Lancaster Infirmary and Christie Hospital, Manchester

P.E. Zouboulis P. Megas, D.J.Apostolopulos,E.Houstoulaki,C. Kalantzis, H. Lampiris, P.J. Vassilakos. Departments of Nuclear Medicine and Orthopedic, University Regional Hospital of Patras, Patras, Greece.

FACTORS AFFECTING THE NORMAL RANGE OF QUANTIFICATION OF SACROILIAC ,JOINT INFLAMMATION ON BONE SCANS

QUANTITATIVE SPECT ANALYSIS OF EVALUATING BIOLOGICAL FIXATION

99mTc - MDP OF THREE

UPTAKE

IN

DIFFERENT

eID

CEMENTLESS TOTAL HIP PROSTHESES. Purpose of the study: Cementless total hip replacement is followed by a tissue response which

It is well known that wide normal variations limit the value of sacroiliac joint (SIJ) quantification. Our aim was to compare methods for quantifying the sacroiliac joint (SIJ) ratio (SR) on MDP bone scans, and determine which one gave the smallest variance and best precision. 55 normal cases were studied, 19 male, 36 female with an age range of 11-81. We evaluated 4 profile methods (using the sacrum as reference) first with a profile spanning the full height of the SIJ (PF), and then centred within this, profiles of 13, 7, and 3 pixels (P13,P7,P3). Two further methods used region of interest count density, one with sacrum (RDS), one with femur (RDF) as reference. The seventh method used region totai counts (RT) with a sacrum reference. For each method the SR was (mean[Std.Dev.]) PF=1.02[0.13], P13=1.25[0.18], P7=1.26[0.19], P3=1.26[0.19], RDS=1.t1[0.14], RDF=3.32[0.99], RT=1.15[0.22]. SR was highly correlated (p>0.5) between PF,P13,P7,P3, and RDS, but RDF and RT were poorly correlated with these. The profile methods were statistically equivalent but PF had best precision, whereas RDF and RT offered poor precision. Between sexes there was no significant difference. For all methods, except RT, the SR was highly correlated with age, RDS being the most significant (p < 0.0001) and PF the secondmost (p < 0.001). We conclude that: RDF and RT are too inaccurate to be used; PF or RDS offer best precision and variance; the normal range is minimised by age matching, but not by sex matching.

closely resembles fracture healing. Biological fixation of cementless implants depends on prosthetic design factors, surgical technique and biological factors.A prospective study was scheduled in order to evaluate the influence of different prosthetic design factors in obtaining optimal biological fixation in cemantless THR, as well as to establish the potential prognostic value of quantitative SPECT analysis of 99mTC-MDP uptake in such interventions. Material and Methods: 32 patients, I1 male and 21 female, age 33-71 years, who were programmed to undergo a THR due to primary osteoarthritis, are included. 18 CLS-SpotornoProtek (SP), press fit Ti prostheses, 11 Perfecta-Orhomet (PO), proximal porous coat~1 Ti prostheses and 30stealook-Howmedica (OH), proximal porous coated with a distal centralizer Ti prostheses, were implanted. The choice of implant was made using a Computer Aided Design (CAD) technique. Patients were imaged one week before the operation and 15 days, 2, 9 and 15 months postopamtively. Quantitative meaanrements were performed with a Region Of Interest (ROI) technique. 3 ROIs were datennined for the femur, according to Gruen, and 2 for the acetabulum, according to Chamley. The measurements of the quantitative analysis of the above mentioned ROIs were performed in the coronal and transaxinl projections. Results: The preoperative scintigrams were used to exclude measurement errors, by evaluating the preoperative bone stock. For the SP prostheses, maximum concentration is measured in the femoral zone 4, following the theory of three point fixation. In 4 cases, where SP were implanted, maximum concentrations were measured in the femoral zones i, 2, 6 and 7, following the mathematicelly expected load tranfer, according to Huiskes. For the PO prostheses, maximum concentration is measured in the femoral zones l, 2, 6 and 7, whereas OH prostheses seem to follow the press fit pattern. For the acetabular zones, all three implants show maximum concentration in zone 1, with the porous coated component of PO showing more equal load distribution in the transaxial projections. The maximum concentration in each ROI, in the m2jority of cases, was measured 15 days postoperatively, followed by progressively lower concentrations up to 15 months postoperatively. Higher concentrations on the second, third or fourth postoperative scintigrams are considered a significant prognostic factor of early detection of failure to achieve initial stability, probably leading to early aseptic loosening. Conclusions: This is an ongoing clinical prospective study. Different biomechanieal properties of the implants, as well as different types of fixation for the acetabular and the femoral components are evident, through different patterns of 99mTc-MDP uptake, winch are obtained. Knowledge of biomechauleal behavior of different types of cementless implants is fundamental in evaluating seintigraphic studies of cemantless THR. Close clinical and mdiulogical patients monitoring is essential in assesing our results. Quantitative SPECT analysis of 99mTc- MDP uptake seems to offer, already from the 2rid postoperative month, an early prognostic sign for the final implant fixation.

5.3

5.5

N.Manthey. A.Tausig, T.Pfluger*, P.Knesewitsch, K.Tatsch, and K.Hahn Depts. of Nuclear Medicine and *Diagnostic Radiology, Klinikum Innenstadt, University of Munich, Germany

P.J. Ryan, K. Reddy, J. Fleetcroft. Medway Hospital, Department of Nuclear Medicine, U.K.

T c - 9 9 m - D P D SCINTIGRAPHY IN COMPAI~JSON TO W H O L E - B O D Y - M R I IN THE DIAGNOSIS OF B O N E M E T A S T A S E S : P R E L I M I N A R Y R E S U L T S

A PROSPECTIVE EVALUATION OF CLINICAL EXAMINATION, MRI SCAN, BONE SPECT AND ARTHROSCOPY FOR THE DETECTION OF MENISCAL TEARS

At modem MRI tomographs the whole body (wb) can be screened within 40 minutes. For the detection of metastases it is necessary to implement sequences with strong tissue contrast wherein tissues with long Tl-values, suppression of fat and a large field of view. Modem STIR-sequences fulfill those criteria. Aim of this ongoing study is to compare the sensitivity of wb-MRI with planar bone scintigraphy (BS) with respect to the detection of metastatic bone lesions. Methods: So far 12 patients with histologically proven breast or prostate cancer underwent planar wb Tc-99m-DPD BS and within one week a wbMRI with STIR sequences (Magnetom VISION, 1,5 T, SIEMENS). For further evaluation the wb was divided into 5 regions: skull, spine and pelvis, femora, humeri and ribs/sternum. In any of those 5 regions each separate lesion, typical for metastases in the BS, was taken into account. BS and wb-MRIs were independently read by two experienced observers. Results of both methods were compared. Results: In 6 patients no lesion was found to be typical for metastases neither in the BS nor in wbMRI. The other 6 patients Region wb-BS wb-MRI showed 65 typical metastatic Skull 3 0 lesions in BS and 88 in wbSpine 31 58 MRI. In the skull and the Femora 11 15 ribs/sternum wb-MRI did not Humeri 9 9 detect all metastases. Wb-MRI Ribs/Sternum 11 6 and BS revealed the same numbers of lesions in the humeri. In the femora and spine, wb-MRI revealed a considerably higher number of lesions suspicious for metastasis than planar BS. Conclusions: Whole body MRI seems to be at least as sensitive as routinely assessed planar bone scintigraphy in detecting skeletal metastases in the spine, femora and humeri. Because of pulsation, truncation and susceptibility artifacts wb-MRI might be less sensitive for the detection of metastases in the skull and ribs.

co |m

Recent studies have shown SPECT bone scintigraphy is valuable for the detection of meniscal tears of the knee. This has not been formally assessed in a prospective study and there is a lack of data comparing bone SPECT with other non invasive methods. 1O0 consecutive patients referred to an orthopaedic surgeon with undiagnosed knee pain were assessed by clinical examination, MRI scan, bone SPECT and arthroscopy. The MRI scan and.bone SPECT studies were reported blind to other information. Using arthroscopy as a good standard both MRI and SPECT showed high diagnostic ability for the detection of meniscal tears with respective sensitivities, specificities, positive and negative predictive accuracies being 80%, 71%, 84% and 71% for MRI and 84%, 80%, 88% and 76% for SPECT. Some meniscal tears were detected by MRI alone (nos = 5) or SPECT alone (nos = 8). We conclude SPECT bone scintigraphy is a suitable alternative to MRI or the detection of meniscal tears. The comparable diagnosis ability of SPECT bone scintigraphy implies it can be successfully used when MRI is unavailable and may be preferred where the cost of bone SPECT is significandy less.

865

m

•

Paediatrics

Paediatrics 6.1

6.3

Anderson PJ, Ranjarangan V Gordon I. Great Ormond Street Hospital for Children NHS Trust. London WC 1N 3JH

A. Boubaker, B. Meyrat, P Frey, M.F Bezy~ C. Mttller, A. Bischof Delaloye, Departments of Nuclear Medicine and Pediatric Surgery, University Hospital, Lausanne, Switzerland.

ASSESSMENT OF DRAINAGE IN PUJ OBSTRUCTION - PELVIC EXCRETION AS AN INDEX OF RENAL FUNCTION

DIURESIS RENOGRAPItY W I T H EARLY (2-3') FRUSEMIDE INJECTION.

Aim: Because of the ongoing discussion on the classical assessment of the response to a diuretic stimulus, we have developed a model called the pelvic excretion efficiency (PEE). The PEE is a mathematical description of a ratio of kidney uptake and excretion to assess drainage. Methods: 33 children with prenatal diagnosis &unilateral renal pelvic dilatation (PUJ) were treated conservatively after birth. They underwent 165 diuretic DTPA renograms up to the age of 72 months. Drainage was assessed as the response to Lasix (T 75), response to bladder emptying and a change &posture after Lasix (I'M), and the ratio of the amount of isotope in the pelvis at the end of the examination to the estimated total amount &isotope extracted from the blood by the kidney (pelvic excretion efficiency - PEE). Results: The contralateral normal kidney showed a "normal T 75" (< 5 miD.) in 67%, while the PM was "normal" (< 50%) in 75% of the renograms, the PEE was > 85% in 100% of the normal kidneys. The affected kidneys with PUJ showed an "abnormal" T 75 (>10 miD.) in 85%, while the PM was "abnormal" (> 50%) in 54% &the renograms, the PEE was < 85% in 67% ofail renograms. When the PEE was <60% both the T75 and PM were "abnormal". Conclusion: The Pelvic Excretion Efficiency, PEE, mathematically models the renal uptake and excretion. The PEE is readily undertaken and may be a more sensitive technique to assess drainage on diuretic renography.

In young children multiple venous punctures or the necessity to keep an intravenous access open for more than 20 min may sometimes be problematic. For this reason we studied the possibility to inject frusemide (0.5-1 m#k~) 2-3 min after tracer iniection (I-123-OIH 0 5 - 0 7 MBq/kg). Thins approach would not only sfiorten the procedure but also not interfere with the measurement of absolute and relative function during the first 2 rain. 44 children (34M/10F) aged 1 month to 9 years (m: 2,5 yrs) with upper urinary junction obstrucuon (UJO) were included. Among the 88 renal units (RU) 33 had UJO (including 9 severe obstructions), 16 dilatation after Surgery (D) and 39 were normal (N) according to suruery and follow-up (clinical, ultrasound). Children were encouraged to drink 15 ml/kg durin~ the 30 rain preceding the test, no bladder catheter was inserted. Respc~nse to frusemide was quantified by an elimination index (EI) defined as the 3/20 rain renal activity ratio. An EI>3 was considered normal. Children with EI<3 were subsequently imaged-in prone position. In case of improvement by this manoeuvre (PP+ ) they were con sidered as responders, whereas those with an EI
Renal Units

severe UJO I incomplete UJO t dilatation [normal Total

n

El>3

EK>3,PP+

EI
9 24 16 39 88

0 6 8 33 47

0 [8 8 6 32

9 0 0 0 9

In 22 RU (6 D, 5 incomplete UJO, 11 N), results could be compared to a previous study done under the same conditions except for frusemide which had been injected 20 rain after OIH In all these cases both tests showed identical results In our experience early injection of frusemide during 1-123-OIH renography CaD be c°nsidered as a reliable, fast and economl~c method for the assessment and follow-up &children with UJO

6.2

6.4

~,BQnnin*, E.Le Stanc*, H . L o t t m a n n °, C . L o i r a t °°, Y . A i g r a i n °, B . B o k * . Nuclear Medicine* Department, Beaujon Hospital, Clichy; Surgery ° and NephrologyO0 D e p a r t m e n t s , R.Debr4 Hospital, Paris, FRANCE.

S.Morano, G.Ciofetta, P.Caione, N.Capozza, E.Matarazzo, R.Ronchetti. Ped. Nucl.Med. Lab., II Ped. Clinic University of Rome "La Sapienza'; Urologic Surgery, Bambino Gesu' Hospital, Rome Italy. 99mTc-DMSA ABSOLUTE RENAL UPTAKE, IN CHILDREN WITH M U L T I C Y S T I C KIDNEY: CHANGES RELATED TO GROWTH. Renal cortical scan is useful in confirming the diagnosis of multicystic-displastic kidneys; the contralateral kidney function is believed to be normal, or more frequently increased by compensatory hypertrophy. The aim of this study was to investigate the functional behaviour of these c o m p e n s a t o r y kidneys, along with child growth, as judged by 9 9 m T c - D M S A absolute uptake. We reviewed all children studied in our Laboratory during the last 5 years. 54 children with confirmed diagnosis of m u l t i c y s t i c kidney (group A) were found; mean age at the time of D M S A - s c a n was 2.06 yrs., range 0.0615.75 yrs., 61% males. For comparison, 108 children, who resulted as normal DMSA-scans, were c o n s i d e r e d (group B), mean age 2.3 yrs., range 0.1-18.1 yrs., 58% males. Absolute uptake (DMSA-AU), on planar p o s t e r i o r view at 3 hours, was calculated as the fraction of injected activity, corrected by radioactive decay, body attenuation and perirenal background. In normal children (group B) we m e a s u r e d a mean DMSAAU value of 47.1% ± 6.2% and no significant correlation with age, as reported by previous studies. On the countrary, the c o n t r a l a t e r a l s to m u l t i c y s t i c kidneys showed a peculiar behaviour: the mean value in the first month after birth was 21.41% ± 9.4%, that is about half the DMSAAU of a normal 2 kidneys system; a steep increase of DMSAAU values was found during the first year of life (n = 36, r=0.028, p<0.001), ending up with the value e n c o u n t e r e d in normals; the D M S A - A U was then found to d e c r e a s e from age 1 to 18 years, down to about 30%(n=i0, r=0.65, p<0.05). In conclusion, the 9 9 m T c - D M S A cortical scan is not only useful to confirm the diagnosis of m u l t i c y s t i c kidney, but m a i n l y to monitor the functional behaviour of the contralateral kidney.

ASYMPTOMATIC HYDRONEPHROSIS (AH) IN INFANTS: ARE DIVERGING CONCLUSIONS OF WASHOUT CURVES (WOC) ANALYSIS DUE TO A LACK OF REPRODUCIBILITY ? W0C analysis has been reported to lead to diverging conclusions in AH infants. We tried to assess if t h i s c o u l d be due to a lack of reproducibility or to differences between the methods themselves.

71 consecutive infants (mean age: 3.1 months, range: 1-8.5 months) with 86 AH diagnosed before birth by ultrasound underwent a standardized renal scintigraphy (RS): adequate hydratation, 15 to 19 MBq of 99mTc-MAG3, Img/kg of furosemide. 3 sets of regions of interest (ROI) and corresponding WOC were obtained from 3 independent readings by 2 physicians. 17 parameters reported in the literature were derived from the 3X86 WOC. The agreement b e t w e e n interpretations was assessed using a Kappa (K) test. A good intra and interobserver agreement was noted for 14 of the 17 methods (K>0.7). Thus, for these methods, ROI drawing and WOC analysis are not the cause of diverging conclusions. Our study confirmed marked differences between methods: obstruction varied from 9.3 to 82.9%, no obstruction from 14 to 70.2%. The use of WOC alone to interpret RS should not be recommended for AH until a consensual interpretation method has been p r o s p e c t i v e l y evaluated. Meanwhile, other scintigraphic tools (split renal function loss between 2 consecutive RS, detailed images analysis, post-micturition or post-upright position views) have to be considered.

866

[] P a e d i a t r i c s / P h y s i c s Physics

6.5

7.1

C. V a n de Wiele, M. S i m o n s , J . V a n de Walle, Sutter, A. Raes, K. E v e r a e r t , RA. Dierckx, U n i v e r s i t y H o s p i t a l Gent, B E L G I U M 24h ABSOLUTE DMSA UPTAKE ZN CHILDREN WITH KIDNEYS IN RELATION TO AGE AND GENDER

J.

De

L. MaffiolP, M.R. Castellani', A. Spinelli', E. Adobati =, D.R.M. Negri =, V. Mongioj =, A.ChitF, S. M~nard =, E. BombardierPo

Divisions of Nuclear Medicine 1, Experimental Oncology "E "~, Health Physics ~. National Cancer Institute, Milan, Italy

NORMAL

TO d e f i n e the age a n d g e n d e r r e l a t e d n o r m a l v a l u e s of absolute 24h DMSA uptake in children with normal kidneys a retrospective study was performed. Out of 576 DMSA scintigraphies performed on c h i l d r e n between 1993 a n d 196, 136 (272 k i d n e y s ) were classified as n o r m a l b y two i n d e p e n d e n t o b s e r v e r s on the b a s i s of the p r e s e n c e of smooth cortical outlining, the absence of cortical loss a n d a r e l a t i v e uptake in the r a n g e of 45% to 55%. All 136 scintigraphies were arbitrarily divided in 8 s u b c l a s s e s (SC)according to the c h i l d r e n ' s age in m o n t h s (M) : SC I :
B I O D I S T R I B U T I O N A N D D O S I M E T R Y OF TWO MONOCLONAL A N T I B O D I E S D I R E C T E D A G A I N S T HUMAN EPITHELIAL RECEPTORS The overexpression of proto-oncogenes in response to proliferative signals is associated with cell growth and in particular with human tumor growth. We evaluated the biodistribution, pharmacokinetics and dosimetry of two monoclonal antibodies (MINT5 and MGR6) directed against the Epithelial Growth Factor Receptor (EGFR) and the oncopretein p185 (HER2, coded by c-erbB-2) respectively developed and characterized at our institute. MINT5 (IgG1) was obtained by immunization of Balb/c mice with human spinocellular carcinoma. Bivalent fragments were subsequently prepared. MGR6 (IgG2a) is the result of routine immunization with the human cell line CALU3. Both reagents were radiolabeled with 1-131 (mean specific activity = 362 MBq/mg). Under thyroid blockage conditions, 185 MBq of MINT5 were i.v. injected in 11 pts with advanced non-small cell lung cancer, and MGR6 in 9 women with bone metastases from breast cancer. Each pt. underwent serial whole body scans (at 2, 6, and 24 hrs and daily for the following 4 days). The biodistribution was evaluated with ROIs drawn over several organs. The pharmacokinetics was studied in sera collected at regular intervals. Dosimetry was estimated by the MIRD method. Neither side effects nor toxicity nor HAMA response were observed after MAb administration. The t½[~ values were: 21-50 hrs for the whole MINT5., 13-19 hrs for its fragments and 13-62 hrs for MGR6. As regards MINT5, high hepatic and splenic uptake was observed, while in the lungs at 1 hr p.i. only 14% of I.A. was detected. However, premodication with whole unlabeled MAb significantly reduced the hepatic uptake. Poor uptake was still seen in the tumor. The highest dose was delivered to the spleen. Mean dose/activity unit was 0,010 cGy/MBq for the whole body. As regards MGR6, metastases were detected in 6/9 cases. Target organs for MGR6 were heart and liver. The mean dose to the whole body was 0.02 cGy/MBq. Both MAbs are safe. The biodistribution of the MINT5 fragments is more favorable than that of the whole antibody. Premedication with cold antibody is needed to reduce the hepatic uptake. MGR6 has a good sensitivity in detecting breast cancer metastases. MGR6 and MINT5 are promising radiopharmaceuticels for the HER family.

This work has been partially supported by CNR-ACRO and AIRC grants.

6.6 ~ , Beatovi6 S, ~r.agar 1, Paunkovi6 N, Stefanovi6 A, Ajdinovi6 B, 5ano~evi6 S, Han R. Imtitute of nuclear medicine, Clinical Centre of Serbia, Belgrade, Yugoslavia. INTEROBSERVER AGREEMENT IN THE REPORTING OF 99mTc-DMSA RENAL SCINTIGRAPHY: MULTICFJq'I~C STUDY 99mTc-DMSA renal scintigraphy is nowadays considered as the sensitive method in the assessment of reduction of functional cortical mass, but the .Wae "gold standard" is not available for clinical use, The aim of the study was to evaluate the interobserver variability of the scintigraphy reports in two observer groups. Six observers from four different centres (group A), including three observers from one imtitution (group B) were asked to interpret original renal scans from 60 patients (116 kidneys). Scintigraphies were done in one centre, displayed on X ray films as analogue 300 KC images in four standard pos/tions. Seven parameters of scinfigraphy protocol were analysed with at least two responses: kidney size(l), uptake(2), outlines(3), scars(4), SOL(5), differential function(6) and conclusion(7). Among 116 kidneys, concordant results in interpretation of seven points of report, from 1 to 7, in group A was found in 62%, 42.5%, 45%, 9%, 47%, 52% and 34%, and in group B in 72%, 55%, 59%, 22%, 62%, 60% and 41%, respectively. Some improvement in concordant reporting was noted in the group of 3 observers, in comparison of group of all, statistically significant in category of scar reports (p
7.2

R.M. Dunn~, M.E. Juweid~, T.M. Behr2, R.M. Sharkey~, and D.M. Goldenberg:. Garden State Cancer Center~, Belleville, NJ, USA, and Department of Nuclear Medicine of the University of G6ttingen2, Germany. A COMPARISON OF PATIENT SPECIFIC RED MARROW/BLOOD RATIO IN MEDULLRAY THYROID CANCER PATIENTS UNDERGOING RADIOIMMUNODETECTIONAND RADIOIMMUNOTHERAPY Assuming a radiolabeled monoclonal antibody does not react with cellular components (either normal or malignant) of the marrow, the red marrow dose can be estimated from sequential blood sampling, and the whole-body contribution. However, regardless of possible interpatient differences, several investigators use "fixed" murrow-to-blood activity concentration ratios to determine the red marrow dose in all patients. In this study, we examined the feasibility of using an imaging-based method to determine the marrow-toblood activity concentration ratio, and, hence, the red marrow dose in each patient. A total of 18 patients with medullary thyroid cancers who received diagnostic doses of approximately 8 mCi of mI-labeled MN-14-F(ab)2 anticarcinnembryonic antigen antibody were studied. Planar images obtained at 3 4 hours after infasion (time of equilibrium between blood and, marrow compartments)were used to draw regions-of-interest(ROIs) around the sacrum (i.e., marrow compartment), and around the heart (i.e., blood compartment). The activity concentration 0.tCi/ml) in the sacrum and the heart were then determined. The activity concentration in the heart was also compared to that of blood obtained by counting of blood samples taken from patients. The mean sacrum/heart concentration ratio was 0.36 + 0.09, and the ratios ranged from 0.25 to 0.46 in the 18 patients studied. The mean sacrum/blood (obtained by counting blood samples) activity concentration ratio was 0.33 -+ 0.07, and the ratios ranged from 0.23 to 0.40. In conclusion, while the average marrow/blood activity concentration ratio based on the imaging method is within the commonly accepted values of 0.25 to 0.40, the range of values derived herein argues for the use of an imaging-based patient-specific marrow/blood ratio rather than a "fixed" ratio for all patients. This method provides means of improving the accuracy of the red marrow dose determination, which can lead to improved patient management. (Supported by USPHS Grants CA66906-01 and CA 39841 from the NIH).

867

co

i m

.l=a

eCD ¢n t._

m

• Physics 7.3

7.5

WA Waddinqton 2, MJ Travis I, DC Costa 2, GF Busatto l, LS Pilowskyl, - R Mulligan 2, S Gacinovic 2, J Merten~, D Terri@re 3, RW Kerwin I, P.J. E L I 2 : iInstitute of Psychiatry, London, UK. 2Institute of Nuclear Medicine, London, UK. 3V.U.B. Cyclotron, Brussels, Belgium.

• 3 GS Limouris ~, A Manetou=, A Tnkkas k, G Kelepeshis 3, J Armenia-

PRELIMINARY HUMAN DOSIMETRY LIGAND, 1 2 3 - I - 5 - I - R 9 1 1 5 0 .

FOR

THE

NOVEL

4 . 3 1 . . . . k o s , G Gmlafos ; Nuclear Medicine Dw, Aretelon Itosp, Univ Medical Faculty, Athens; 2Med Phys Unit, NIMTS Hosp, Athens 3Slate Card ac • 4 . . . . Dept, Htppokratlon Hosp, Athens; Thessalonlki Umv Medlcal Facu ty

5-HT2A

TI-201 K I N E T I C S

We h a v e p r e v i o u s l y e v a l u a t e d 1 2 3 - I - 5 - I - R 9 1 1 5 0 for human in-vivo SPET brain imaging of 5-HT2A receptors. Initial data suggests that labelled l i g a n d d i s t r i b u t e s m a i n l y in the liver, bowel and lungs w i t h b r a i n u p t a k e of 1 . 8 - 2 . 1 % i n j e c t e d dose (id). W e have i n v e s t i g a t e d the d o s i m e t r y of 123-I5-I-R91150, b a s e d on s e q u e n t i a l w h o l e b o d y i m a g i n g in t h r e e h e a l t h y m a l e v o l u n t e e r s . A bolus of 185 MBq 123I-5-R91150 was administered intravenously. Simultaneous anterior and posterior scans were p e r f o r m e d at 5, 30, 60 min., 3-5, 15, 24 and 48 (on 2 subjects) hr p o s t - i n j e c t i o n . 24 hr. u r i n e c o l l e c t i o n was o b t a i n e d for 1 subject, C o n j u g a t e i r r e g u l a r R O I ' s w e r e p l a c e d over those o r g a n s d e m o n s t r a t i n g t r a c e r uptake. T i m e - a c t i v i t y curves obtained from g e o m e t r i c m e a n ROI counts y i e l d e d o r g a n r e s i d e n c e times, a n d s t a n d a r d M I R D m e t h o d o l o g y was applied to d e t e r m i n e the total absorbed radiation dose to each o r g a n for the adult male (70kg) r e f e r e n c e model. A b s o r b e d dose to the b l a d d e r was e s t i m a t e d u s i n g an e s t a b l i s h e d d y n a m i c b l a d d e r model, for a v o i d i n g i n t e r v a l of 4 hours. E x c r e t i o n was p r i n c i p a l l y via the h e p a t o b i l i a r y system. C u m u l a t i v e u r i n a r y e x c r e t i o n was 22% id o v e r 24 hrs. M e a n e f f e c t i v e dose e q u i v a l e n t was c a l c u l a t e d as 0.037 m S v / M B q , and mean effective dose 0.036 mSv/MBq. H i g h e s t m e a n a b s o r b e d o r g a n doses (mGy/MBq) w e r e to the u p p e r large i n t e s t i n e - 0.i01, lower large i n t e s t i n e - 0.091, small i n t e s t i n e - 0.067, lungs - 0.050 and liver - 0.045. We c o n c l u d e that 123-I5 - I - R 9 1 1 5 0 has a c c e p t a b l e d o s i m e t r y for a d m i n i s t r a t i o n to h u m a n subjects.

AND

DOSIMETRY

1N

HUMAN

TESTES

TOMOSCINTIGRAPHY Following T1-201 i.v. administration for a variety of radioisolopic procedures, a substantial amount of the radiopharmaceutical is taken up b y the highly radiosensJtive testicular parenchyma. In view of this high radiosensitivity (weighting factor,Wv = 0,2) we attempted to determine the absorbed dose as well as the equivalent dose delivered to patients during myocardial tomoscintigraphy. In 11 men aged 40 to 55 yr, TI-201 myocardial perfusion studies were performed ; 4 out of them underwent reinjection. 148 M B q and 103,6 M B q was the total i.v. injected activity in cases with and without reinjection respectively. T w o balloons filled with 20 ml of water plus 230 kBq of T1-201 [phantom activity (PD)] represented the testicular phantoms (ph). Patients were completely shielded with lead aprons so that only the testes were uncovered. The testicular uptake and I"]-201 clearance were monitored for 5 days for both groups• The percentage of the injected dose (ID) in the testes (t) was calculated according to the following equation: % ID = 100 * [( cnts t - cnts bkg) / (cnts ph - cnts bkg)] * (PD / ID). A s s u m i n g that Au and A t are the cumulated activities in the body and testes respectively and StB and S t the doses to the testes per unit cumulated activity in the body (tB) and testes (t), the total testicular dose was f o u n d to range between 0,24 to 0,27 m G y / MBq of the injected activity. We conclude that since testes possess the highest tissue weighting factor and T1-201 perfusion imaging is performed routinely and in tremendous daily frequency world-wide, the strict amount of the administrative dose, reinjection including should not exceed 166,5 MBq due to radiobiological burden reasons. AFTER

MYOCARDIAL

7,4

7.6

WCAM Buijs, MG Steffens, O Boerman, E Oosterwijk, JA Siegel and FHM Corstens. University Hospital Nijmegen, The Netherlands.

T.M. Behr 1, S. Memtsoudis ~, R.D. Blumenthal 2, R.M. Duam2, R.M. Sharkey2, D.M. Goldenberg 2, and W. Becker I, Dept. of Nuclear Medicine I of the University of G6ttingen, Germany, and Garden State Cancer Center at the Center 2, Belleville, USA.

ESTIMATION OF ADMINISTRATION

ABSORBED RED OF 131-I-cG250

MARROW

DOSE

AFTER

Previously we have shown that 131-I-cG250 preferentially localizes in primary renal cell carcinoma lesions (RCC) and its metastases. In the context of a radioimmunotherapy (R/T) protocol for patients with metastasized RCC, we compared two methods to estimate the absorbed dose to the red marrow based on planar gamma camera images• Methods. Sixteen patients with primary RCC have been studied at 5 different protein dose levels ranging from 2 to 50 rag. Patients received a single intravenous infusion of 222 MBq 131-I- labelled eG250. Total body images were acquired on day 1, 2, 3, 6 arid 7 p.i.. Activity in blood and urine was monitored. The geometric mean of total body counts and ROI counts of the source organs (heart, kidneys, liver, lungs, spleen and thyroid) were calculated after correction for background, attenuation and physical decay. In method I the red marrow dose was calculated from the residence times in the source organs, the urinary bladder and the remainder of the body, using the MIRDOSE3 program. In method II the same data were used, but the red marrow was included as a source organ, assuming that the red marrow activity concentration was 25% of the blood activity concentration. The red marrow residence time is than 5.6% of the blood residence time. Results. In thirteen patients all primary tumours and known metastases were imaged. No accumulation in red marrow was observed. The mean absorbed dose in the red marrow was 0.264-0.05 mGy/MBq and 0.364-0.07 mGy/MBq for method I and method II, respectively. For bone marrow 2 Gy is considered to be the maximum tolerated dose that can be administered safely without bone marrow support. The results indicate that 7.7 and 5.6 GBq 131 -I-labelled cG250 respectively can be administered safely. In conclusion, the absorbed dose in the red marrow, calculated with method I was lower than with method IL Considering that metastases received an absorbed dose of 6.2 mGy/MBq and assuming a dose limiting bone marrow toxicity at 2 Gy, a maximum of 35 Gy can be guided to the metastases• Our estimations suggest that turnout-sterilizing levels of> 50 Gy can only be reached with bone marrow support.

868

COMPLETE VERSUS FRAGMENTED, mI- VERSUS 9°y-LABELED, ANTIBODIES FOR RADIOIMMUNOTHERAPY (RAIT) OF CEA-EXPRESSING CANCERS: INFLLrENCE OF THE DOSE RATE AND RENAL ACCRETION ON TOXICITY AND ANTI-TUMOR-EFFICACY lgG has shown high tumor uptake values, thus radiation doses, but also higher red marrow doses as compared to fragments, which, in contrast, exhibit a more rapid blood clearance and lower tumor accretion. Furthermore, fi-agments are burdened by a high renal accretion. The aim of this study was to assess which factors affect the anti-tumor effectiveness and dose-limitlng organ toxicites of nlI- and 9°Y-labeled IgG versus Fab. The maximum tolerated doses (MTD) as well as organ toxicifies of the t31I- and 90y. labeled anti-CEA antibody, MN-14 (IgG versus Fab), were determined in nude mice bearing subcutaneous human colon cancer xenografts. The mice were treated without artificial support, with inhibition of the kidney uptake of antibody fragmants by Dlysine (Behr et al., Cancer Res 1995; 55: 3825), with bone marrow transplantation (BMT) and combinations thereof Blood counts, kidney (BUN, creatinine) and liver function parameters as well as tumor growth were monitored at weekly intervals. The kidney was the first dose-limiting organ with 9°y-labeled Fab. Acute radiation nephritis occurred at injected activities _> 325 gCi (renal dose > 100 Gy), chronic nephrosis at _>250 I~Ci (> 70 Gy). The MTD without artificial support was 200 gCi. Dlysine reduced the kidney uptake by approximately 85%, but enabled a doseintensification to only 250 gCi, since the bone marrow became dose-limiting, despite marrow doses of < 5 Gy. The combination of BMT and lysine allowed for increasing the MTD to 400 ~tCi. With 9°y-IgG, as well as t31I-labeled immunoconjugates (IgG or Fab), the red marrow was the only dose-limiting organ (9°y-IgG: 100 p.Ci without [red marrow dose 9 Gy], 130 p,Ci with BMT [12 Gy]; mI-IgG: 260 gCi without [20 Gy], 350 laCi with BMT [27 GyD. The MTD of nlI-Fab without BMT was 3 mCi [4 Gy], with BMT 4 mCi [5 Cry]). At eqnitoxic doses, Fab fragments were more effective in controlling tumor growth than the respective IgG, despite lower absolute tumor doses (e.g., 20 vs. 35 Gy for 9°Y-Fab vs. -IgG), which may be due to a 5-fold higher initial dose rate of Fab as compared to IgG (e.g., for 90y: 40 vs. 8 cGy/h at 4 h p.i.). These data show that nephrotoxicity is an important issue in therapy with radiometalconjugates, but not with radioiedinated antibody fragments; it can be overcome easily by the application of basic amino acids. The improved anti-tumor effectiveness of antibody fragments as compared to IgG, but also the higher myelotoxicity at comparably lower red marrow doses, are most likely due to the higher initial dose rates observed with antibody fragments.

[] Radiopharmacy Radiopharmacy 8,1

8,3

W. Burchert, *H.Schmidt, P. Gielow, +G. Cichon, *C. BCittner, *M. Dogar, ÷M. Strauss, *M. Manns, H. Hundeshagen. Depts, of Nuclear Medicine and *Gatroentero?~ogy,Medizinische Hochschule Hannover, +Department of Molecular Medicine, Max-Planck-Institut, Berlin, Germanv

T. Leitha, C. Glaser, S. Lang, W. Millesi. Univ. Clinics of Nuclear Medicine, Maxillofacial Surgery and Pathology Vienna/AUSTRIA

SCINTIGRAPHIC THERAPY CONTROL OF LIVER DIRECTED GENE TRANSFER OF H U M A N L O W DENSITY LIPOPROTEIN RECEPTORS WITH 111-IN-LABELLED L O W DENSITY LIPOPROTEINS (LDL)

AFFECTED BY MDR OR CELL PROLIFERATION?

Familial hypercholesterolemia (FH) is associated with early death d u e to myocardial infarction. The h y p e r c h o l e s t e r o l e m i a is mainly caused by a deficiency of hepatic LDL-receptors (LDLr). A n e w therapeutic approach is the liw,~r-directed gene tranfer of LDLr. To m o n i t o r the success of the gene transfer in vivo we developed a scintigraphic procedure. Methods: LDL was isolated and subsequently labelled with nlIn. As an a n i m a l m o d e l of FH Watanabe Heritable Hyperlipidemic rabbits (WHHL) were used. Scintigraphy was p e r f o r m e d before a n d after gene transfer at different time points after injection (lh, 4h, 24 h, and later) u s i n g a g a m m a camera (Siemens ZLC 370) e q u i p p e d with a m e d i u m energy collimator. Results: Low tracer uptake in the liver was f o u n d before therapy. After g e n e transfer the liver uptake of mIn-LDL was very high. No specific liver uptake was found, if the same gene transfer procedure w a s p e r f o r m e d with Ggalactosidase instead of LDLr as a n e g a t i v e control. A s t u d y 30 days after gene transfer s h o w e d a c o n t i n u e d therapeutic effect by increased tracer a c c u m u l a t i o n over that time period. Additionally, the specific uptake of the tracer by hepatocytes was confirmed by i m m u n o h i s t o c h e m i s t r y . Conclusion: Scintigraphy with lUIn-LDL is capable to m o n i t o r n o n i n v a s i v e l y the effect of gene therapy in vivo with h i g h specificity. For future application of gene therapy in h u m a n s this procedure is expected to be of high diagnostic i m p a c t

A consensus has emerged that early imaging (within 20 min. p.i. of MIBI) has the highest diagnostic yield. Tc-99m-MIBI uptake has been associated with tumour vascularisation, invasiveness, cell proliferation and P-glycoprotein-mediated multi-drug-resistance (MDR). The aim of this study was to assess if these parameters affect tumour uptake in current imaging protocols. Material and Methods: 23 patients with recurrent squamous cell carcinoma (SCC) of the mouth floor scheduled for surgery were imaged 10 rain. p.i. with a triple head gamma camera (360 °, 3°/step SPECT, UI-1!KPAR collimators). Tumour:non-tumour tissue-(Tu/Ntu), tumour:gingiva- (Tu/Oi), tumour:salivary gland(Tu/Sa), tumour:nuchal muscle-ratios (Tu/Nu) were calculated based on the cts/pix values of ROIs in the axial slices. The expression of the MDR gene was determined histochemically from biopsies. Cell proliferation was quantitated by the histochemical analysis of the Ki-67 protein (Ki-67 index), additionally the p53 tumour suppressor gene (p53 index), a posttranslational stablizator of the cell cycle at the G1 stage, was assessed. Results: No significant differences were found for the uptake indices between MDR + and MDR - tumours. Ratios MDR + MDR Tu/Ntu 6.3 4- 7.8 6.1 4- 3.0 Tu/Gi 1.9 4- 1.2 2.0 4- 2.3 Tu/Sa 0.99 4- 0.49 0.85 4- 0.43 Tu/Nu 2.7 4- 1.3 2.7 4- 0.82 Additionally no significant correlation between MIBI uptake and the Ki67 and p53 indices was found. Conclusion: The currently applied imaging protocols for MIBI in oncology are not affected by tumour specific properties as MDR or cell proliferation in SCC of the mouth

8.2

8.4

K.Nakamura e, H.Fujii*, A.Kubo*, S.Satake**, H.Takami**, l. Sugawara***, *Keio University, Department of Radiology, **Teikyo University, Department of Surgery, ***The Research Institute of Tuberculosis, Pathology Resealch Division.

L. Aloi, C. Caraco', W.C. Eckelmanand R.D. Neumann Nuclear Medicine and PET Departments, Warren G. Magnuson Clinical Center, NIH, Bethesda, MD.

IN VIVO EVALUATION 125-LABELLED MRK-16 TC-99m-MIBI.

FDG UPTAKE AND GLUCOSE TRANSPORTER EXPRESSION IN CANCER CELL LINES The glucose analogue 2-fluoro-2-deoxyglucose (FDG) has been successfully utilized to image, stage and evaluate tumor progression. While it is generally believed that FDG uptake is directly correlated with tumor glucose metabolism, the precise molecular mechanisms behind this process are not fully understood. Several human tumors have been shown to express the glucose transporter isoform GLUT-1. To evaluate the relationship between GLUT-1 expression and FDG uptake we have studied three human cancer cell lines derived from breast, liver and an epidermoid carcinoma (T47D, HepG2 and A431 respectively) and correlated the results with the amount of GLUT- 1 mRNA and protein expression. We have previously shown that when these cells are grown as subcutaneous xenografts in nude mice, T47D cells have the highest [3H]DG uptake but the lowest amount of GLUT-1 mRNA. To evaluate FDG uptake in the absence of confounding variables (such as tumor blood flow or necrosis) we have now studied cells grown in culture. Cells were studied in different phases of growth. When cells were growing exponentially, FlOG uptake in T47D was 50% higher than in A431 and 100% higher than in HepG2. When cells were confluent, T47D cells still showed higher uptake but all three cell lines showed a reduction of -50 % in the rate of FDG uptake. Northern blot analysis of RNA extracted from exponentially growing cells showed that 8-actinnormalized levels for GLUT-1 in T47D cells were ~90% lower than in A431 and HepG2 cells. None of the other facilitative glucose transporter isoforms (GLUT 2-5) mRNAs were present at detectable levels in any of the cells. Western blot analysis showed a very small amount of immuno-detectable GLUT-1 protein in T47D compared to A431 and Hep G2 (66% and 83% lower respectively). Our results show that in this system, where direct determinations of FDG uptake by cancer cells are made, the amount of GLUT-1 present on the cell membranes is not correlated with the level of FDG uptake.

IOR

Multidrug resistance(MDR) in tumors is associated with P-glycoprotein(P-gp) expression. In vivo quantification of P-gp may allow MDR to be evaluated noninvasively prior to treatment planning. The purpose of this study is to perform in vivo quantification of P-gp in a MDR xenograft nude mouse model by using radiolabeled monoclonal antibody, MRK-16, or Tc-99m-MIBI. Mice were each xenografted with KB-3-1, human epidermoid carcinoma, or KB-G2, which was introduced mdrl gene into KB-3-1. Monoclonal antibody that targets an external epitope of P-gp, MRK-16 was labelled with 1-125 by the iodogen method. Biodistribution studies were performed with I125-MRK-160 or TC-99m-MIBI. Peak tumor uptake at 2 days post injection of 1-125-MRK-160 was significantly greater in KB-G2 compared to KB-3-1 tumors (15%ID/g vs 9%ID/g). TC-99m-MIBI localized in KB-G2 (0.42%ID/g) one hour after injection, which was remarkably lower than in KB-3-1 (0.77%ID/g). Injection of verapamil, one of MDR modulator, into the tumor increased the KB-G2 tumor uptake of Tc99m-MIBI with 1.4-fold, while no change was observed in the KB-3-1 tumor. The treatn~nt of verapamil did not affect the biodistribution of 1-125-MRK-16, except slightly increase in uptake of KB-3-1 and KB-G2 tumors. We conclude that in vivo quantification of P-gp in MDR tumors can be performed with either 1-125-MRK-16 or TC-99m-MIBI. Our findings suggest a potential clinical application for Tc-99m-MIBI in the evaluation of P-gp with regard not only to its presence but also its function.

e19

IS EARLY IMAGING OF SESTAMIBI (MIBI) IN ONCOLOGY

floor.

OF P-GLYCOPROTEIN BY MONOCLONAL ANTIBODY

co i i

869

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• Radiopharmacy/Neurology Neurology 8,5

9.1

YM. Zhang,. MA Stalteri, SJ. Mather, Department of Nuclear Medicine, St Bartholomew's Hospital, London EC 1A 7BE, UK, and Xijing Hospital, Xi'an 710032, P. R. China.

R.Benti,*A.C.Turconi,*G.Felisari,G.Marotta,C.Canzi,R.Casati,C.Sdraia ti, V.Longari, M.Gasparini, M.Castellani, °N.Bresolin, P.Gerundini. Nuclear Medicine Dept IRCCS-Ospedale Maggiore;*Neurology Dept, IRCCS-E.Medea, Bosisio Parini; °Neurology Inst.-Univ. of Milan; Italy

TECHNETIUM LABELLED C-MYC ONCOGENE mRNA ANTISENSE OLIGONUCLEOTIDE: PREPARATION AND INVITRO CHARACTERISATION. Oncogenic mRNA's are suitable targets for radiolabelled antisense oligonucleotide probes which may be used to image the oncogenic process in-vivo. A 15 mer phosphodiester oligonucleotide, complementary to the transcription initiation site of c-myc oncogene mRNA with 5'-end aminolinker (antisense, ASDNA) was synthesized. Its complementary strand (sense, S-DNA) was also synthesized with its 3'-end biotinylated. The bifunctional chelator N-hydroxysuccinimdyl hydrazinonicotinate (HYNIC, kindly provided by Prof A. Verbruggen, Leuven) was conjugated to the AS-DNA in bicarbonate buffer. Unreacted HYNIC was removed by a Sep-Pak reverse-phase column. Technetium-99m labelling was achieved by incubating the conjugated AS-DNA with pertechnetate, SnCl2 and Tricine as co-ligand at room temperature for 60 rain. Tc-99m-AS-DNA was purified by Sep-Pak column. Labelling efficiency was 60-80 % and the radiochemical purity normally higher than 95% after Sep-Pak purification when analysed by radio-HPLC. No significant activity was associated with the oligos when S-DNA, unconjugated AS-DNA, and conjugated AS-DNA without Tricine as co-ligand were labelled in the identical conditions. Tc-99m-AS-DNA was stable in solution and in fresh serum. In contrast to previous publications, no protein-binding was observed. The labelled DNA bound efficiently with its complimentary sense oligonucleotide with a sensitivity of 30 nanomolar/L as assessed by dot-blot. However no hybridisation was observed when the labelled oligonucleotide was incubated with blotted mRNA extracted from c-Myc expressing cells. In conclusion, although the Tc-99m labelled antisense oligonucleotide probe may hold potential for detecting c-myc overexpression, the specific activity must be high enough to detect the limited copies of c-myc mRNA available in vivo.

Mitochondrial Encephalomyopathies (ME) are a group of uncommon genetic diseases shared by a progressive impairment of energy production and oxidative metabolism in mitochondria. Mostly affected are tissues with high energy requests as muscles, brain and retina. Cognitive deficits are common in late ME course, but in earlier stages full Neuro-Psychological Profile (NPS) and brain perfusion SPET were not related yet. In 14 patients (mean age 46 yrs) with defined genotypes and phenotypes (11 Progessive External Ophtalmoplegia-PEO, 3 Keams-Sayre Syndrome-KSS, 1 Myoclonus Epilepsy with Ragged Red Fibers-MERRF) were evaluated general intelligence, memory functions and visuo-perceptual skills. Brain SPET was obtained with a triple-head camera 30 min after i.v. bicisate (ECD) administration (740 MBq). Focal asymmetries of rCBF were defined first by visual analysis of canto-meatal oriented sections and then assessed by semi-quantitative ROI processing. Neuro-Psychological Profile (NPS) showed =o cognitwe defects, but a significant discrepancy in non-verbal vs. verbal performances was detected; in addiction a specific decay in short term memory items was found. Magnetic Resonance (MR) showed diffuse white matter abnormalities only in 2 KSS patients. SPET revealed at least a significant ROI asymmetry (>10%) in brain cortex, basal ganglia, thalami and cerebellum in 91%, 45%, 45% and 9% of ME patients respectively. More affected in PEO group were temporal lobes (73%), basal ganglia and thalami (35%). Focal hypoperfusions in the hemispheres were bilateral, more relevant (mean 18.4% vs contralateral ROIs) and extended in KSS; in MERRF patient only the right thalamus had reduced ECD uptake. This puzzling distribution of small hypoperfused areas probably reflects the wide phenotypical variability of defective mitochondria &stribution in the brain, yet reported in other affected tissues of ME patients. Focal neuronal dysfunction seems the common result of progressive mitochondrial hypometabolism in different ME phenotypes. The related peffusion deficits in grey matter, either hypometabolic or post-deafferentation, are detectable by SPET even wlmout co-hexisting MR abnormalities. This SPET pattern is functionally related to the type of defective mnestic/attentional performances defined by NPS analysis in our ME series.

8.6

9.2

O.K.Hjelstuen, H.H.Tznnesen, G.M.M~landsmo,T.Roald, P.O.Bremer,A.Verbruggen. U n i v e r s i t y of Oslo, N o r w e g i a n R a d i u m Hospital, Oslo, Isopharma AS, K j e l l e r , N o r w a y and UZ Gasthuisberg,Leuven, B e l g i u m

A.M. Catafau, J. Kulisevsky, Ll. Bern/t, J. Pujol*, M. Estorch, A. Flotats, C. Marl, J Deus*, I. Carri6. Hospital de Sant Pau and Magnetic Resonance Centre of Pedralbes*, Barcelona, Spain.

B I O D I S T R I B U T I O N A N D R N A H Y B R I D I S A T I O N EXPERIMENTS OF A 99mTc LABELLED O L I G O D E O X Y N U C L E O T I D E (ODN) A N T I S E N S E TO THE BREAST CANCER ONCOGENE CAPL. CAPL is o v e r e x p r e s s e d in tumour m e t a s t a s i s formation. Our aim was to test the b i o d i s t r i b u t i o n of a 9 9 m T c - l a b e l l e d 20-bp ODN (GX-I), complementary to a region on exon 2 in the CAPL oncogene. GX-I and a random ODN control (CTRL) with phosphodiester backbones and 3'-MAG3 were labelled with 99mTc and purified. 99mTc-M-AG3-GX-I labelling yields were >99%, stable for >12 h as d e t e r m i n e d by ITLC and RP HPLC. B i o d i s t r i b u t i o n tests of the 99mTc labelled ODNs in groups of 4 normal mice, sacrificed 5 and 60 min after injection, demonstrate that the 99mTc-MAG3-ODNs are excreted largely through the kidneys; at 60 min, 55% of the dose of 99mTc-MAG3-GX-I and 72% of 99mTc-FLAG3-CTRL was found in the urine. H e p a t o b i l i a r y excretion at 60 min accounted for 34% and 23%. The rest of the activity was d i s t r i b u t e d in an unspecific manner. The h y b r i d i s a t i o n properties of the ODNs to transcribed CAPL R N A were tested before and after labelling with 99mTc in an assay comprising of 90 min h y b r i d i s a t i o n in a TRIS/EDTA/MgCI2/DTT solution at 25°C with RNase H treatment. Preliminary testing show that the GX-I and 99mTcMAG3-GX-I h y b r i d i s a t i o n to R N A is c l e a r l y higher than CTRL and 99mTc-MAG3-CTRL. We have d e m o n s t r a t e d the b i o d i s t r i b u t i o n of the CAPL oncogene specific ODN GX-I labelled with 99mTc via M_AG3 and that the h y b r i d i s a t i o n properties of MAG3-GX-I after labelling with 99mTc still is clearly better than the 99mTc-MAG3-CTRL.

870

Tc-99m ECD BRAIN SPET AND NEUROPSYCHOLOGICAL PROFILE IN MITOCHONDRIAL ENCEPHALOMYOPATHIES WITHOUT COGNITIVE DEFICIT

BRAIN PERFUSION SPECT IN PATIENTS WITH SUBCLINICAL HEPATIC ENCEPHALOPATHY AND MRI PALLIDAL HYPERINTENSITY.

Brain perfusion SPECT abnormalities and MRI pallidal hyperintensity may be related to the cognitive status and portalsystemic shunting of blood in patients with subclinical hepatic encephalopathy (SHE). We prospectively measured MRI globus pallidus intensity and regional cerebral 99mTc-HMPAO uptake in 13 cirrhotic patients with SHE at the time of performing a battery of standardized neuropsychological tests related to basal ganglia function and sensitive to the effects of liver disease. HMPAO uptake as an index of regional cerebral blood flow (rCBF) was evaluated by region/cerebellar ratios for orbitary frontal, prefrontal, lateral temporal, mesial temporal regions, basal ganglia, and thalamus. MRI globus pallidus signal was measured on an IR sequence (1.5T;TR/TE/TI 1,500/20/650reset) and normalized to the putamen signal. Correlation between rCBF ratios, neuropsychological tests scores and MRI pallidal signal was assessed. Poor performance on motor tasks involving speed (Purdue Pegboard test) and frontal-premotor function (Luria Graphic Alternances, Stroop test) correlated with basal ganglia (r=.57, p < .05) and mesial temporal rCBF (r=.81, p=.001), but not with the globus pallidus signal (r=.06, p=NS), rCBF ratios did not correlate with globus pallidus signal except for the thalamus (r=.60, p <.05). These results suggest that SPECT and MRI basal ganglia imaging changes reflect different aspects of neurological involvement in cirrhotic patients with SHE. Brain perfusion SPECT ratios relate to basal ganglia dysfunction, whereas MRI pallidal hyperintensity does not.

[] Neurology 9.3 MJankowski, P.Lass, T.Bandurski Medical University, Gda_6sk, Poland

BRAIN SPECT IN PATIENTS WITH LIVER CIRRHOSIS AND ENCEPHALOPATHY; DECREASED PERFUSION OF FRONTAL LOBES Cognitive impairment and dementia are frequently met in end-stage liver diseases, including liver cirrhosis. Little is known on cerebral perfusion and cerebrovascular reactivi~in those patients. We performed brain SPECT using ~ T e - H M P A O and a lriplc-head gammacamera before and 20 rain. after iv. injection of ].0 g o f acetazolamide in 26 patients with hver cirrhosis of varying duration/severity and cognitive impairment. Semiquanfltative analysis included interhemispheric asymmetries ~ d comparison of regional 9~Tc-HMPAO uptake to the eerebellar one. CT scanning, neurological and psychological assessment was perfolrned the same time. The results were compared with brain SPECT results of 10 patients with mild diffuse liver lesion and 16 healthy volunteers. Results: cerebral perfusion abnormalities were found in 24/26 patients with liver cirrhosis, presenting mostly as diffuse decrease of 99~TeHMPAO accumulation in frontal lobes (bilateral hypofrontalism), seen in 20/26 patients. The mean 99~Te-I-IMPAO frontal uptake was 80.7 + 4.7 % of eerebeUar uptake with comparison to 91.7 % + 3.2 in healthy subject. This correlated well with results of psychological tests, duration and severity of disease. Focal perfusion defects were seen in 16/26 patiens, mean asymmetry index (AI) 13.8 + 7.7 %. There was no significant differences in rCBF between the group with mild liver lesion and healthy controls. Acetazolamide augmented focal perfusion defects in cirrhotic group (mean AI rise 7g.6 + 13.9 %), revealing new perfusion defects in 7/26 pts., but did not significantly changed hypofrontalism Conclusions: our results indicate high incidence of cerebral perfusion changes in liver cirrhosis, predominantly in fi'ontal lobes, probably related to the duration and severity of illness.

9.5 S. V ~ ' m r i , H. van den B~'oe',~, P. r ~ 3 y , R.E. S~-ir~m', J.S. @ ' ~ , L.i. ~doe÷, A.J. ~ , ~ T~. O'~'iscoll* and M. Oritd~ey, !lucle~" ? ~ d i e ~ Dept., 2oyal Liv~pool Pbspi~tal, ~Brain i n j u r y Rd~]iliimtion Centre, Ra~hbone Hospital, Liverpool, +Univel~i~ of Alberia andYCross Cancer Institute, Edmc~ten, Cansda. IDENTIFICATION

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OF HYPOXIC REGIONS IN TRAUMATIC BRAIN INJURY

(TBI). The current assessment of patients with traumatic brain injury (TBI) includes magnetic resonance imaging (MRI) which identifies structural changes, single photon emission tomography (SPET) using a perfusion radienuclide tracer and neuropsychological testing (NPT). The technical limitations (such as resolution) of MRI and SPET often result in normal findings and yet NPT may be abnormal. The aim of this pilot study was to attempt to identify and characterise the extent of hypoxic injury to the brain in our group of patients with moderate to severe TBI. We hypothesised that there is a variable element of hypoxic injury in the areas with reduced perfusion seen in moderate or severe TBI, and that this can be characterised. We also wanted to test whether a normal perfusion study would exclude hypoxic injury. This hypothesis was tested using 1123 IAZA (lodoazamide) as the hypoxia tracer and 99Tcm HMPAO to assess perfusion. The oatients were grouped based on perfusien SPET into i) }~ormal SPET and MRI with abnormal NPT, 2) Abnormal SPET and MRI (Control I), S) Diffuse nenfecal abnormality on SPET (Control II) and 4) Normal volunteers. Preliminary results following the iv injection of 185 MBq of I12S IAZA and tomographic imaging 5-6 hours later showed no retention of the hypoxia tracer in the brain of a normal person; retention of hypoxic tracer in patients with normal perfusion SPET and abnormal NPT and retention of hypexic tracer in patients with abnormal perfusion SPET (areas with reduced perfusion but with possible scope for improvement as they are still viable). Conclusion: There is a possible complimentary role for hypoxia imaging together with perfusion SPET in the evaluation of patients with TBI. A normal perfusion SPET may not exclude hypoxie injury to the brain.

9.4

9.6

J.A. Miiller l, J. K. Mellies 2, T. Btiumer2, L. Wetzig 2, P. Haller 2, Departments of Nuclear Medicine t and Neurology 2, St~idtische Kliniken Osnabriick, Germany

G. Taddei, F. Nobili, E. Catsafados, L. Bazzano, G. Rosadini, G. Rodriguez, and G. Mariani. Nuclear Medicine Service, DIMI; and Neuropathopbysiology Service, DISM/CNR, University of Genoa; Genoa (Italy).

SPECT IN AUTOSOMAL DOMINANT MIGRAINE WITH LEUKOENCEPHALOPATHY (CADASIL)

9~"Te-HMPAO SPECT WITH A BRAIN-DEDICATED GAMMAC A M E R A AND Q U A N T I T A T I V E EEG ASYMMETRIES IN PATIENTS WITH ALZHEIMER'S DISEASE

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disorder, characterized by granular deposits in pericytes of penetrating cerebral vessels. Clinical features are migraine and lacunar infarctions leading to subcortical dementia. The gradual course over decades renders this disorder ideal to study disease progression and mechanisms of vascular dementia. Methods/results: We studied 12 individuals (IDs) of a three generations CADASIL family with MR] and SPECT (n=l 1). Six IDs were genetically affected, six were healthy. Four affected IDs had migraine with aura (MA), three were demented (D), two were asymptomatic (AS). All affected IDs had extensive MRI leukocncephatopathy, three of them had additional basal ganglia (BG) T2-signal-hyperintensities. SPECT with 99mTe-ECD (Neurolite®) revealed cortical- and BG-hypoperfusion matching with MRI signal-changes. Only the three IDs with BG-hypoperfusion were demented. Regional cerebral blood flow indices were as follows: n=6 affected, frontal temporal parietal BG clinical status 1 D, MA 0,72 0,75 0,83 0,75 2 D, MA 0,80 0,63 0,8i 0,76 3 D, MA 0,97 0,84 1,00 0,77 4 MA 0,89 0,68 0,91 0,92 5 AS 0,79 0,68 0,79 1,06 6 AS 0~99 0,84 0~99 0~97 n=5 healthy 0,96 0,96 1,09 1 ±0,07 :~0~11 a:0~02 ±0105 Conclusions: We demonstrate temporal hypoperfusion even in cognitively normal IDs with CADASIL. Only basal ganglia hypoperfusion results in cognitive impairment. Clinical relevance of SPECT-eortical hypoperfusion in vascular leukoencephalopathies has to be evaluated together with subcortical perfusion.

tO lima

Alzheimer's type dementia (DAT) is a primary degenerative disorder involving the whole cerebral cortex. However, neuropsychological and neurophysiological asymmetries have occasionally been reported. The relationships between such asymmetries and severity of the disease are still debated and poorly known. Nineteen DAT patients (mean age 67 yr) underwent brain 99~TcHMPAO SPECT employing a brain-dedicated gamma-camera with an annular crystal (CERASPECT, Waltham, MA), as well as quantitative electroence-phalography (qEEG) with power spectrum analysis, and Mini Mental State Examination (MMSE, as an index of the severity of disease). Mean power-weighted qEEG Frequencies (MF) from a central-posterior temporal region, a posterior temporo-parietal (TP), a hippocampal (Hi) and a thalamic (Ta) region of interest (ROI) were determined 6n the two hemispheres. SPECT data were normalized to the cerebellum and specific ROI-to-cerebellum count ratios were obtained. Asymmetries were computed for both the MF and SPECT data based on the formula: [(rV - lV)/(rV + N)/21 x 100 where r = right, l = left, and V= value (MF or ROl/cerebellum ratio). MF asymmetries were directly correlated with both TP and Hi asymmetries (p
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• Oncology Oncology 10.1

10.3

_S..Adams], R.P. BaumI, T.Stuckensen2, K. Bitter2, G. HdrI Department of Nuclear Medicines, Department of Oral and Maxillofacial Surgery ,Umverslty Medical Center, Frankfurt/Main, Germany 2

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,

.

PROSPECTIVE COMPARISON OF ISF-FDG PET WITH CONVENTIONAL IMAGING MODALITIES (CT, MR/, US) IN LYMPHONODAL STAGING OF HEAD AND NECK CANCER in head and neck squamous cell cancer (SCC) lymph node involvement is the most important prognostic factor. The aim of this study was the detection of cervical lymph node metastases by 18F-FDG PET and a prospective comparison with clinical, CT, MR[, sonographic and histopathologic findings. Methods: Fifty patients (35 men, 15 women, mean age 55.5 yrs) with histologically proven SCC were studied before treatment by FDG PET, acquired on a whole-body tomograph (ECAT Exact 47, Siemens). Prior to the PET study, patients fasted for at least 12 hours and normal blood glucose levels (<100mg%) were confirmed in all patients. 60 min after intravenous administration of 18F-FDG (mean: 374 MBq), whole-body (3 bed positions, I2-15 rain each) and regional scans (head and neck region) were performed. Transmission scans (15 rain) were obtained for attenuation correction. Standardized uptake values (SUV) were calculated for all primary tumors and nodal lesions. Conventional imaging modalities (CD) (CT, MR1, US) and clinical examinationwere performed in all patients within 1 week of the PET study. Results: Histopathology of'the resected neck specimens depicted a total of 1110 lymph nodes, 64 of which showed metastatic involvement. Sensitivity and specificity for detecting lymph node metastases (counting each single node) were higher for PET (87%, and 71%, respectively) compared with conventional radiological modalities and clinical examination (CT: 79%/65%; MR[: 76%/50%; US 70%/64%; Palpation 65%/66%). The mean SUV value of primary lesions and lymph node metastases was 4.28 (range: 3-13) and 3.42 (range: 2-9). The studies showed no correlation between FDG uptake and histological grading of the tumors. Conclusion: This prospective histopathologically controlled study confirms FDG-PET as the procedure with the highest sensitivity and specificity for detecting lymph node metastases of head and neck squamous cell cancer and has become a routine method in our University Medical Center.

L Biassor~, PK Marsden, P Tierney, EB Chevretton, M McGurk, I Fogelman, MN Maisey. "The C l i n i c a l PET C e n t r e " and E N T D e p a r t m e n t , UMDS Guy's and St Thomas" Hospitals, London UK. CORRECTED STANDARDISED UPTAKE VALUE (SUV) F O R 1 8 - F D G IN S Q U A M O U S C E L L C A R C I N O M A (SCC) O F THE H E A D A N D N E C K CORRELATES WITH HISTOLOGICAL GRADING BUT NOT WITH C L I N I C A L STAGE.

of the study was to investigate the relationship of SUV for 18-FDG with histological grading and clinical staging in patients with SCC of the head and neck. Methods: Grading was evaluated in 23 patients (27 lesions) before therapy and in 13 patients (17 lesions) after therapy. 9 lesions were classified as benign, 6 as well differentiated SCC, 17 as moderately differentiated SCC, 12 as poorly differentiated SCC. Stage was evaluated prior to therapy in 48 patient and was defined according to the American Joint Committee on Cancer. A mean activity of 270 MBq (range 155-363 MBq) of 18-FDG was injected. Emission and transmission scans were ~hen performed. Images were corrected for decay and attenuation. SUVs were calculated for the highest value pixels in each lesion and corrections were made for blood glucose level, lean body mass and partial volume effect. Results: A correlation was observed between pre-therapy SUV and grading (p=0.024,KruskalWallis test); however no significant correlation was observed when corrections for blood glucose level, lean body mass and partial volume effect were omitted (p=0.21, Kruskal-Wallis test). In the post-therapy group no correlation between SUV and grading was observed. There was no correlation of SUV with the clinical stage. C o n c l u s i o n : Our data suggest that a correlation exists between SUV and grading in pretherapy patients with head and neck SCC provided SUVs are calculated with the relevant correction factors. Aim

10.2

10.4

PP v a n Ri~kz~ C H J T e r h a a r d 2, M P M Stokkel z, G J Hordijk3. Dept. of 1 N u c l e a r Medicine, 2 Radiotherapy, 30tolaryngology, U n i v e r s i t y of Utrecht, the N e t h e r l a n d s

M. Dietlein, K. Scheidhauer, E. Voth, P. Theissen, H. Schicha, University of Cologne, Department of Nuclear Medicine.

D E T E C T I O N OF L O C A L R E C U R R E N C E A F T E R R A D I O T H E R A P Y F O R L A R Y N G E A L C A N C E R U S I N G A D U A L H E A D SPECT S C A N N E R W I T H PET C A P A B I L I T Y (FIRST EXPERIENCE)

IS MIBI-SPECT OR FDG-PET COMPETITIVE TO IODINE-131 IN DIFFERENTIATED THYROID CANCER ?

M e a s u r e m e n t of 1 8 F - F D G u p t a k e in the neck, u s i n g P o s i t r o n E m i s s i o n T o m o g r a p h y (PET) m a y be u s e f u l to d i s t i n g u i s h local r e c u r r e n c e f r o m r a d i a t i o n effects, after r a d i o t h e r a p y for l a r y n g e a l cancer. However, d e d i c a t e d PET s c a n n e r s are not w i d e l y available. W i t h a dual h e a d SPECT s c a n n e r w i t h a c o i n c i d e n c e m o d u l e (ADAC, MCD), PET s c a n n i n g of 1 8 F - F D G is possible, w i t h a spatial r e s o l u t i o n of 5 ram, c o m p a r a b l e w i t h a d e d i c a t e d PET scanner, Methods and materials: A f t e r a 12 h o u r s fast, at 45 m i n a f t e r i n t r a v e n o u s l y i n j e c t i o n of 185 M B q 1 8 F - F D G ii p a t i e n t s u n d e r w e n t imaging of the n e c k d u r i n g 25 min. Image i n t e r p r e t a t i o n was visually. D i r e c t l a r y n g o s c o p y u n d e r g e n e r a l a n e s t h e s i a was p e r f o r m e d 13 times in these p a t i e n t s . S i x p a t i e n t s (4 T2, 2 TI) h a d p r o v e n r e c u r r e n t disease. Five p a t i e n t s (2 T2, 3 Tz) s h o w e d c l i n i c a l l y local control. Results: 1 8 F - F D G PET scans w e r e p o s i t i v e in all 6 l o c a l l y r e l a p s e d cases. H i s t o p a t h o l o g i c a l e x a m i n a t i o n of the l a r y n g e c t o m y s p e c i m e n d e m o n s t r a t e d a m e a n t u m o r s i z e of 2.6 cm ( r a n g e 1.4-5 cm). In one case 1 8 F - F D G - u p t a k e w a s false p o s i t i v e in a lymph node. 1 8 F - F D G PET scans w e r e n e g a t i v e in all five l o c a l l y c o n t r o l l e d patients. Conclusion: M e a s u r e m e n t of 1 8 F - F D G w i t h M C D w a s v e r y s e n s i t i v e to d e t e c t local relapse, r e g i o n a l r e l a p s e w a s false p o s i t i v e in i/ii patients. T h e s e r e s u l t s j u s t i f y a p r o s p e c t i v e s t u d y on e a r l y d e t e c t i o n of local r e l a p s e w i t h this technique. Introduction:

872

MIBI-scintigraphy with SPECT as well as FDG-PET were compared to I-131 scintigraphy in the follow-up of differentiated thyroid cancer. In 50 consecutive patients (33 papillary, 13 follicular, 4 oncocytary cancer, primary status: pT1/2/3/4 : 3/16/9/22) a MIBI (740 MBq Tc99m) whole body scan including SPECT of neck/chest as well as a FDG-PET (CTI ECAT Exact scanner, 370 MBq F-18, in fasting state) of neck/chest were performed during hypothyreosis and before 1-131 whole body scintigraphy. Morphologic imaging was done by MRT in all and by CT without contrast media in 21 patients. All patients with recurrence or residual tumor (n = 4) showed MIBI and FDG-uptake. In those 15 patients with lymph node metastases (verified by histology (n=10) or Iodine-uptake (n=5)), 8 showed MIBIuptake and 9 FDG-uptake, but 4 patients were negative with both tests. Among 6 patients with iodine-negative lymph node metastases, 4 patients were positive with MIBI respectively FDG, but 1 patient in each group was positive with one tracer only. In lymph node metastases smaller than 1 cm, MIBI was positive in 5/9 patients, FDG in 4/9 patients. All 6 patients with small (< 1 cm) pulmonal metastatic nodules showed neither MIBI-nor FDG-uptake, but they could be diagnosed by helical-CT. The results indicate, that diagnostic 1-131 scintigraphy in hypothyreosis cannot be replaced by MIBI or FDG-PET; none of the latter was better than the other. But there is an indication for MIBI and/or FDG-PET in the case of elevated thyroglobulin in combination with a negative 1-131 scan. This holds true before a selective lymph node dissection, even in the case of morphological correlates, in order to detect additional metastases in normal sized lymph nodes. The 1 cm border of lymph nodes in the morphologic based imaging is not valid for MIBI and FDG-PET.

II Oncology/Cardiovascular 10.5

11.2

M. Dietlein K. Scheidhauer, E. Voth, P. Theissen, H. Schicha, University of Cologne, Department of Nuclear Medicine.

R. Kluge~, M. Forster~, R. Hambrechtz, W. H. Knapp~, HerzzentrumLeipzig2 and Departmentof Nuclear Medicine1. Universityof Leipzig. Germany

FDG-PET IN THE FOLLOW-UP OF DIFFERENTIATED THYROID CANCER

DIAGNOSTIC ACCURACY OF ATTENUATION CORRECTED MYOCARDIAL SPET

Metastases of the differentiated thyroid cancer may reveal an alternating uptake-pattern in the FDG-PET and in the [131I]-wholebody scintigraphy (WBS). The aim of the present study was to evaluate a diagnostic algorithm in an unselected group of patients. FDG-PET, WBS and MRI were performed in 58 consecutive patients~ pulmonal helical-CT in 25 patients. 38 patients had papillary, 15 patients follicular carcinomas and 5 patients variants of a follicular carcinoma. Primary tumor stage (pT) was pT1 in 3, pT2 in 19, pT3 in 11 and pT4 in 25 cases.

The accuracy of myocardial SPET is limited by irregular intrathoracic photon attenuation. The aim of the study was to evaluate the benefit of attenuation correction (AC) by simultaneous emission and transmission tomography for the detection of CAD. Method: 50 patients with angiographically confirmed CAD (10 patients of each group with 1-vessel-disease(1-vd) of the RCA, LCX and the LAD, with 2-vd of LCX and RCA, and with 3-vd) were investigated with and without AC. Stress studies were performed with 400 MBq Tc-99m-tetrofosmin and a dual-head camera (Vertex, ADAC Lab.) equipped with two scanning Gd-153-1ine sour&s. Images were quantified using circumferential count rate profiles and comparedto the normal range obtained from a data base of 50 patients with a likelihood of CAD < 10%. Results: I Detectionof CAD Tree identification of all stenosedvessels

To detect the complete extent of metastases the sensitivity of FDGPET was 50 %, of WBS 61%, of the combination 86%. If the offer of FDG-PET would be limited to patients with elevated thyroglobutin (Tg)-levels and negative WBS, the sensitivity of this algorithm reached 82 %. Among 21 patients with lymph node metastases, 7 patients revealed only FDG-uptake, 4 of them showed a second FDG-spot in a lymph node metastasis of normal size. None of the 8 patients with pulmonal metastases smaller than 1 cm had FDG-uptake, 5 of them had Iodine-uptake, but all had a correlate in the helical-CT. 2 patients with larger pulmonal infiltrates showed a concordant or mixture uptake-behaviour. In conclusion WBS cannot be replaced by FDG-PET. If the Tg-level is elevated and WBS negative, FDG-PET is indicated to detect lymph node metastases and is complementary to morphologic imaging. Helicai-CT is required to exclude pulmonal metastases before surgery planning. FDG-PET improves the surgicai strategy by detection of additional metastases in normal sized lymph nodes.

Cardiovascular 11.1

SIMULTANEOUS TRANSMISSION-EMISSION M Y O C A R D I A L GATED Tc99m-MIBI SPECT: EFFECT OF NON-UNIFORM ATTENUATION CORRECTION The clinical usefulness of non-uniform attenuation correction (AC) in non-gated myocardial SPECT has recently been reported. The aim of this study was to determine the effect of non-uniform AC with simultaneous transmission-emission acquisition on gated Tc99m-MIBI SPECT (GSPECT). Two-day stress/rest GSPECT was performed using a 3-head camera in 68 pts both with and without AC (STEP@ Picker). 32 males (88±14 kg) without reversibility in non-AC (NC) stress/rest were selected for further evaluation: 20 without (Group A) and 12 with (Group B) a history and ECG evidence of inferior myocardial infarction (MI). The distribution of regional myocardial uptake at rest was evaluated quantitatively with. circumferential short axis profiles for diastole (D), systole (S) and for non-gated (NG) images (sum of 8 frames/cardiac cycle) both with AC and without AC: Relative cnts (%) in basal Max. differences between relative cnts in basal circum, profiles sediments IGroup A) anterior inferior Group A Group B D S NG D S NG D S NG D S NG NC 84.7 91.2 88.6 60.0 69.2 63.4 33.1 27.4 31.4 41.1 39.1 37.3 ±6.1 85.5 ±11.2 0.001

AC 9/10 10 / 10 9 / 10 10/10 10 / 10

NC 8/10 8 / 10 10 / i0 9/10 9 / 10

AC 9/10 10 / 10 8/10 7/10 3/10

NC 6/10 7 / 10 9/10 4/10 3/10

In AC studies, extent and depth of defects in RCA- and CX-terntories exceeded those of non-corrected (NC) studies. However, the defect size in LAD-territories was smaller in AC than in NC studies due to diminished defect recognition in the basal anterior and anteroseptal wall segments. Conclusion: AC may enhance the diagnostic accuracy, of myocardial SPET when infero-posterior wall segmentsare to he evaluated. The detection of CAD of the LAD, however, does not profit from AC with the systemused.

11.3

A. Fikrle, E.-P. Ritter, D. Ltischer, S. Lourens, A.R. Haldemann, J.A. Kinser, M. Sulzer, W. Meting, Department of Nuclear Medicine, University of Berne, CH-3010 Berne, Switzerland

±8.3 ±5.4 AC 77.0 87.0 ±7.6 ±7.2 p 03109 0.069

1-vd RCA l-vd LCX 1-vd LAD 2-vd RCA+CX 3-vd

±10.1 85.6 ±7.5 0;001

±10.4 82.6 ±5.6 0.002

±8.3 76.1 ±10.6 0.1101

±9.7 ±7.9 18.5 16.8 ±5.1 ±4.1 0.001 0.002

±8.1 18.1 ±4.8 0.001

±17.0 18.7 ±5.8 0.012

±14.1 26.6 ±14.8 0.123

±10.9 24.5 ±8.0 0.008

The relative regional uptake in AC was higher in the inferior and lower m the anterior segment. The highest AC/NC difference was in D. The reduction of count rate variability with AC was greater in D than in S and more significant in Group A than in Group B. AC imaging improves the accuracy of detection of inferior wall abnormalities by reducing attenuation artefacts. The influence of AC is greater in ,,normal" pts than in pts after MI and is not of the same degree in D and in S (D>S). Therefore, the quantitative parameters (i.e. ,,wall-thickening") may be influenced differently in AC and in NC images. This is important for the interpretation of AC-GSPECT.

K. Takeda, M. Nakamura, T. Ichihara, N. Motomura, H. Sakuma, Y Nomura, N. Kato, K. Matsumura, T. Nakagawa. Department of Radiology, Mie University School of Medicine, Mie, Japan. Toshiba Medical Engineering Laboratory, Tochigi, Japan. COMPARATIVE STUDY OF LIVER-HEART ARTIFACTS IN SPECT WITH AND WITHOUT SCATTER AND ATTENUATION COMPENSATION In recent publications, using Monte Carlo simulation, several investigators showed that scatter correction is an important adjunct to attenuation compensation in reducing artifacts in cardiac SPECT images. This study evaluated liver-heart artifacts in myocardial SPECT images reconstructed with and without scatter and attenuation compensation. Methods: We compared myocardial SPECT images reconstructed from a numerical phantom against myocardium, liver, lung and spine images generated from gated MR images and from gated SPECT data of the same volunteer. We simulated Tc-99m-MIBI projection data using the three-dimensional numerical phantom with different levels of hepatic uptake of Tc-99m-MIBI. Gated SPECT projection images were acquired using the triple energy window (TEW) scatter correction method. Attenuation-uncompensated transaxial images were reconstructed from the scatter-uncompensated projection data. Attenuation-compensa[ed transaxial images were reconstructed from scatter-compensated projection data using measured attenuation maps from transmission CT images. The liver-heart artifacts in these SPECT images were compared against the simulated images. Results: Hepatic uptake of Tc-99m myocardial perfusion agents can cause an apparent reduction in the localization of activity in the inferior wall in cardiac SPECT without scatter and attenuation compensation. At very small liver-to-heart distances, activity from the liver spills over to the myocardium in SPECT with scatter and attenuation compensation. Simulations showed that the distance between the liver and the heart has a significant influence on the severity and appearance of the artifact. This spill-over artifact was reduced theoretically using spatial resolution (collimator blurring) in cardiac SPECT with scatter and attenuation compensation.

873

tO =l t~ eID ID

O. m

t~ L_

O

• Cardiovascular/Oncology 11.4

12.2

J. Pinkert, N. Eckeh, G. Wunderlich, R. Runge, S. G~ibler, J. Bredow and W.-G. Franke Dresden University of Technology, Dept. of Nuclear Medicine, Germany

I.Virgolini~ I.Szilvasi, P.Smith-Jones, P.Angelberger, and A.Kurtaran. Universities of Vienna, Austria, and Budapest, Hungary, and Departement of Radiochemistry Research Center Seibersdorf, Austria.

PREDICTIVE VALUE OF HAMA ESTIMATION AFTER INJECTION OF ANTI-MYOSIN AND ANTI-GRANULOCYTE ANTIBODY

"MAURITIUS": ANIMAL AND HUMAN BIODISTRIBUTION AND TUMOR LOCALIZATION.

Human antimouse antibody (HAMA) response can be a limiting factor for diagnostic imaging with radioactive labelled antibodies due to high uptake by the reticuloendothelial system (RES) mainly by the liver In this study we evaluate retrospectively the HAMA values of 814 pts. prior the first application of In-lIl-antimyosin and Tc-99m-antigranulocyte antibody and of 118 pts. prior to repeated application. HAMA values were determined using an one-step-enzyme-immunoassay with a sensitivity of _< 1 ng/ml HAMA in serum samples obtained at the time of first injection of antibody and prior to repeated application. According to manufacturers guidelines a cut-off of 200 ng/ml at a specificity of 95 % was used to identify elevated HAMA levels. The uptake by the RES of the liver representing an increased storage of HAMA complexes was visually assessed using a score comprising the categories ,,normal" ,,increased" and ,,high increased". Before the first application the mean HAMAvalue amounted to 19.4 :=56.9 (n = 814), 14 pts. showed primary increased levels (> 200ng/ml, false positive) with normal RES uptake. 118 pts. had one or more repeated investigations and at time of last investigation the mean HAMA level was 45.6 :=133 (n = 118). Pathologically raised HAMA values were determined in 6 pts. (all received the Tc-99m-antigranulocyte antibody) but only one of these people was scored to had an increased RES uptake. 8 pts. had increased (n=6) or high increased (n=2) RES uptake scores but the HAMA values in these pts. were estimated below the cut-off in the normal range. No impairment of scan quality was seen in case of the antimyosin antibody Although the number of studied cases was small our results suggest that a preceding HAMA estimation can not predict scan quality.

DOTA-Lanreotide or "MAURITIUS" is a novel somatostatin receptor (SSTR) ligand which recognises SSTR subtypes 2 through 5 and binds (when labelled with In-111 or Y-90) to a variety of human tumours in vitro. Animal biodistribution studies with "Y-90MAURITIUS" in rats (4 MBq, 0.16 nmole) indicated a high uptake in SSTR-positive tissues (such as adrenals 2.1% I.D., 24 h p.i.) and a low retention in normal organs (bones 0.04% I.D., muscle 0.003% I.D., 24h p.i.). The radioligand was more lipophilic than In-111DTPA-D-Phe-l-octreotide (OCT) and displayed a slightly lower retention of activity in kidneys, liver and spleen. Acute toxicity studies performed in rats showed no toxic side effects at a high dose of 10 mg/kg. Initial clinical studies were performed in 8 patients with neuroendocrine turnouts and in 4 patients with lymphomas using "In-Ill-MAURITIUS" (100 MBq; 3 nmote). No side effects were noticed after intravenous injection. The biodistribution of "1n111-MAURITIUS" was similar to In-ll 1-OCT, showing a rapid blood clearance, uptake by liver and spleen as well as a moderate kidney load. Tumours were visualised immediately after injection and were still visible at 96 h in all patients. A direct comparison with I n - I l l OCT scintigraphy (n=3) showed a significantly higher tumour uptake as well as a lower kidney and spleen burden at all time points up to three days p.i. This provides a wider therapeutic window than the current experimental I n - I l l - O C T therapy. Furthermore, due to the similar chemical properties of In and Y, "In-Ill-MAURITIUS" could be used to predict the dosimetry of "Y-90-MAURITIUS".

Oncology 12.1 F.H. Schilling 1, H. Bihl 2, O. Lang 2, M. Hofmann 2, H. Jacobsen 3, J.Treuner 1, P. Kogner4, Departments of Nuclear Medicine Stuttgart2/ Stockholm3; Olga-Hospital Stuttgart 1, Karolinska Hospital Stockholm 4

~111N-PENTETREOTIDE SCINTIGRAPHY IN NEUROBLASTOMAS: MORE THAN IMAGING ?

Objectives: 1.To evaluate relative efficacy of 1111n-pentetreotide and 1231MIBG scans for the detection of primary and metastatic neuroblastoma. 2.To assess prognostic value of l~lln-pentetreotide uptake by correlating it with the three common biological parameters with prognostic significance, i.e. amplification of N-myc oncogene, deletion of chromosome lp36 and diploid/tetraploid DNA content. Methods and Materials: Within one week ~ln-pentetreotide and 1231MIBG scans were obtained in 54 patients with neuroblastoma (11 St.I; 8 St.ll, 8 St. III, 23 St. IV and 4 St. IVS according to INSS) at diagnosis (43), PR (2), CR (0), relapse (5) and with progressive disease (4). N-myc copy number, DNA ploidy and chromosome lp36 integrity were assessed with common methods in tumor tissue of all patients. Results: In all 54 pts neuroblastoma manifestations were still present at the time of scanning.Three pts were negative in both 1111n-pentetreotide and 1231-MIBGscan. All others (51) were positive for MIBG (detection rate: 94,4%). 34/54 pts showed high uptake (detection rate: 63%) and 20/54 pts no uptake in the l~ln-pentetreotide scan. No pt with a negative 1231-MIBG scan and a positive 11'ln-pentetreotide scan was found. The detection rate of neuroblastoma with ~231-MIBGwas signifi-cantly higher lp=0 046) than withlllln-pentetreotide. A neurob astomas with a positive 23 " I-MIBG scan and a negative 1 1 1 In-pentetreotide scan revealed at least one prognostic unfavourable biological parameter (p<0.001). Conclusions: 1. ~f~ln-pentetreotide scintigraphy is less sensitive than 1231-MIBG scintigraphy for detecting neuroblastoma. 2. A highly significant correlation between MIBG-positivity / pentetreotide-negativity and unfavourable biology of neuroblastoma could be shown. ~lln-pentetreotide scintigraphy could provide additional information as an in vivo biological prognostic parameter in neuroblastoma.

874

12,3 I.Vir,qolini, M.Leimer, Y.Qiong, C.Bischof, M.Peck, T.Pangerl, D.Gludovacz, J.Lister-James, K.Kaserer, B.Niederle, F.Hamilton, P.Valent, and R.Dean. University of Vienna, Austria, and Diatide Inc. 6, New Hampshire, USA. HIGH-AFFINITY

SOMATOSTATIN

BINDING

OF

RECEPTOR

TECHNETIUM-99m-P829 TO AND VIP-

(SSTR) 2, SSTRS,

ACCEPTOR/SSTR3. Recent data suggest that receptors (R) for somatostatin (SST) are expressed on various tumor cells. High level expression of SSTR on such tumors provided the basis for the successful clinical use of radiolabeled ligands for the in vivo Iocalisation of tumor sites. We have charactedsed the in vitro binding properties of the novel SSTR-ligand Tc99m-P829, using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell lung cancer, melanomas), various tumor cell lines, and COS7 as well as CHO cells transfected with the SSTR subtypes 1, 2, 3, 4 and 5. Tc-99m-P829 bound to primary and immortal tumor cells with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 10 nM. Tc-99m-P829 also bound with high affinity to SSTR2 (tC50, 2.3 nM), SSTR5 (IC50, 1 nM) as well as to SSTR3 (IC50, 2.8 nM). Binding of Tc99m-P829 to the transfected SSTR3 was found to be displacable by unlabeled P829, SST-14 and vasoactive intestinal peptide (VIP) (IC50, 0.5-5 nM), and less effectively by Tyr-3-OCT (IC50, 5-50 nM). In contrast, the binding of Tc-99m-P829 to the transfected SSTR2 and SSTR5 could be displaced by P829, Tyr-3-OCT, but not by VIP. In summary, our data show that Tc-99m-P829 binds with high affinity to many different types of primary and immortal tumor cells. Furthermore, our data identify the SSTR2, the VIP-acceptor SSTR3 and the SSTR5 as the respective target receptors. Since these receptors are frequently expressed at high levels on pdmary tumor cells, Tc-99m-P829 appears as a promising novel peptide tracer.

[] Oncology/Bone 12.4

12.6

R. Lebtahi, G. Cadiot, N. Delahaye, M. Faraggi, L. Sarda, D. Daou, C. Peker, Y. Petegnief, M. Mignon, D. Le Guludec. HGpital Bichat, France.

0.$chillaci,°S.Angeletti,R.Danieli,°B.Annibale, v. Picardi,*G.Silecchia,°G.DelleFave,F.Scopinaro. Nucl.Med., °Gastroent., *II Surg., Univ. "La Sapienza",Rome,Italy.

THE FOLLOW UP OF NEW SITES REVEALED BY SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN PATIENTS WITH ZOLLINGER ELLISON SYNDROME. Somatostatin receptor scintigraphy (SRS) detected previously unknown endocrine tumors susceptible to modify management in 25% of patients (pts) with gastroenteropancreatic tumors in our series. The aim of this study was to evaluate the follow up (range 0.25 to 52 months) of these new sites discovered by SRS in pts with ZES with available follow up and the specificity of these findings. 85 consecutive pts with ZES without known extraabdominal metastases were included, since the management of the patients with extensive metastatic disease is not modified by the detection of additional tumors. Relevant findings were found by SRS in 27 pts (24/67pts without liver metastases and 3/18 pts with liver metastases without extrahepatic metastases). Follow-up was available in 20 (74% of pts) who presented 23 relevant findings. Nineteen (83%) relevant findings were confirmed at 3 months of follow-up; 4 (17%) were not confirmed at 30 months of follow-up. Findings located in the duodenopancreatic area (90%), the chest (100%), the bone (100%) and the liver (60%) were confirmed. Conclusion : SRS detects many abnomaLities suceptible to modify patients management in patients with ZES considered as curable by surgery. The specificity of hot spots located outside the liver is very high. In contrast, the specificity of hot spots located in the liver remains to be evaluated when other conventional imaging remains negative; a longer follow-up may be required.

12.5 E.Le Stanc*, C.Flobert**, F.Bonnin*. JL.Stievenart*, P.Ruszniewski**, B.Bok*, *Department of Nuclear Medicine, **Department of GastroEnterology, Beaujon Hospital, clichy, FRANCE. SYSTEMATIC HISTOLOGY AND SOMATOSTATINE R E C E P T O R SCINTIGRAPHY (SRS) SENSITIVITY IN GASTRO-ENTEROPANCREATIC TUMOURS (GEP). SRS sentivity has been reported to be acceptable in large series of GEP p a t i e n t s , but usually without a systematic histological study of all abnormal loci. We prospectively evaluated 15 GEP patients (i0 women, 5 men; age: 26 to 67 years, mean: 46.4): 4 carcinoids, 4 calcitoninomas (C), 1 somatostatino-ma (S), 2 C+S, 1 insulinoma and 3 other neuro-endocrine tumours (NE). Histological confrontation was obtained in each abnormality detected by pre-operative SRS, tomodensitometry and endoscopic ultrasonography. SRS views were performed 4H, 24H (and later if necessary) after injection of 150 MBq of lllIn-Octreoscan®. The mean interval between SRS and histology was 2.2 months (range: 2 days-7 months). SRS was negative in 5 patients. In the i0 others, all primary tumours and all metastatic livers (8 cases) were detected but 3 extrahepatic metastases were missed (pleura, adrenal gland, lymph node). Gathering the 15 patients, 14 of 28 tumoral localisations and one of 7 multinodular liver (MNL) escaped SRS detection. Thus, SRS sensitivity was 67% for patients, 50% for separate lesions and 86% for MNL. Tumoral NE cells were found in all SRS hyperfixation foci. In this short but well documented series sensitivity values are lower (except for MNL) than in most published series when specificity is excellent.

HIGH LEVELS HAMPER THE WITH In-lll

OF CIRCULATING SOMATOSTATIN DON'T VISUALIZATION OF SOMATOSTATINOMAS PENTETREOTIDE SCINTIGRAPHY.

Somatostatin(S)-producing tumors are very rare among gastroenteropancreatic neurondocrine neoplasms. It has been postulated that in somatostatinomas a down-regulation of S receptors after chronic exposure to high endogenous S levels may occurr, and, than, may lead to a false-negative scintigraphic result using In-lll pentetreotide (P). The aim of this study was to evaluate the usefulness of In-lll P imaging in the detection of somatostatinomas. Three patients (2 F) with elevated plasma levels of S (65-200 pg/ml) and bioptic or surgical specimens of removed tumoral tissues positive for S-like immunoreactivity were submitted to In-lll P scintigraphy. Total body planar images (at 4, 24 and 48 hours) and abdominal SPECT at 4 hours were performed. In the first patient In-ll P visualized multiple liver lesions and 4 lung/mediastinal localizations. In the second case scintigraphy detected 6 sites of focal abnormal hyperfixation: 3 in the liver and 3 in the pancreatic area. In the third patient only SPECT was able to demonstrate a single liver lesion. The detected LM were then histologically proven. In conclusion, our results show that the in vivo imaging of somatostatinomas with S receptor scintigraphy is possible, also in the presence of high levels of circulating S, and indicate that the suggested receptor downregulation does not occurr in these rare neuroendocrine tumours.

Bone 13.1 T. Erselcan* G.Kafah**, A.T.Erg0r** C.U.Medicat Faculty, Department of Nuclear Medicine* and Pediatrics**, Sivas, Turkey. NORMAL FOREARM AND VERTEBRAL BONE MINERAL DENSITY VALUES IN TURKISH CHILDREN Bone mineral density (Bmd gr/cm 2) of the lumbar spine (L1 - L4 ) in 170 (93 girls,77 boys) and forearm (Radius+Ulna) in 148 (72 girls,76 boys) healthy children was measured, between 0-16 ages, with dual energy x-ray absorptiometry(Hologic, 4500 W). Relationship between Bmd and age, weight, height and body mass index (bmi) were determined by means of regression line analysis, then pediatric Bmd normograms within 95 % CI were created according to ag e,Patients were divided into five age groups.Bmd values are " Age Forearm Bmd gr/cm z L1-L4 Bmd gr/cm 2 group (mean_+SD) (mean±SD) 0 0.191+0.03 (n=14) 1-4 0.240±0.04 (n=29) 0.391_+0.06 (n=23) 5-8 0,301_+0.03 (n=56) 0.504+0.06 (n=56) 9-12 0.347_+0.05 (n=51) 0588+0.12 (n=47) 13-16 0.440_+0.06 (n=20) 0.751_+0.12 (n=21) The best fit function in the regression analysis for mean L1-L4(L) and forearm(F) Bmd with age(A), weight(w), height(H) and bmi(B) were as follows : exponential ones; R2(LA) = 0.66, R2(FA): 0.76, R2(LH) = 0.76, R2(FH) : 0.81 (p=0.001). cubic ones; R2(LW) : 0.69, R2(FW) = 0.78, R2(LB) = 0.13, R2(FB) = 0.11 (p=0.001). However, in the presence of height and weight, partial correlation coefficient of age for L1-L4 Bmd was non-significant (r= 0.04, p=0.6) in multiple stepwise regression analysis. Hence, the best and practical predictive function of L1-L4 Bmd is ; 0.259 x height (m) + 0.005 x weight (kg) + 0.078. So, we believe that it's better if Bmd pediatric normograms will be based on height and weight,instead of age. The most important Bmd increase among the age groups were in L1-L4 in girts, aged 13 -16, and at the forearm region in 0 age group, if one considers the adult Bmd values, bone mineralisation is completed 80 % in girls and 55 % in boys atthe end of age 16. 875

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• Oncology 13.2

13.4

A P G van Driel, MF Schreuder, A van Lingen, JC Netelenbos, EFL David, JC Roos. Depts o f Endocrinology, Nuclear Medicine and Radiology, Free University Hospital, Amsterdam, The Netherlands.

B.Okudan, T.Atasever, F.G6~ii~, N.B61fikba~h V.Sepici and ]M.('int/i Department of Nuclear Medicine, Gazi lniversity Medical School Ankara,Tu rkey

L U M B A R V E R T E B R A L V O L U M E E S T I M A T I O N W I T H DXA. Measurement o f the bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA) results in areal values (g/cm2) rather than volumetric values (g/cm3). The aim o f this study was to calculate the vertebral volume using antero-posterior and lateral D X A and the following geometrical approximations: cubic, cylindrical with a circular cross section and cylindrical with an elliptical cross section. The volume obtained from CT scans formed the reference volume. The estimates were evaluated in an antropomorphic lumbar vertebral phantom and in three patients. To determine the reproducibility (expressed as the coefficient o f variance, CV) o f the volume estimates, the phantom was measured by D X A on five different days. In the phantom, the volume approximations by the cube or cylinder with circular cross-section geometry showed more than a 50% (range: 54% to 74%) overestimation, compared to the CT volume. The elliptical cylinder a p p r o a c h was very accurate: 2.1% and 1.2% for L2 and L3, respectively. The reproducibility was better than 1%. In the patients, the CT volume w a s compared only with the elliptical cylinder volume estimate. For both L2 and L3 the mean relative difference was less than 2 % (range: -1.5% to 5.7%). We conclude that the approximation o f the lumbar vertebral volume by an elliptical cylinder from antero-posterior and lateral D X A is accurate and reproducible.

13.3 C.S.Kalirai, S.Koneru, J.R.Buscombe, D.McCooI, A.J.W.Hilson, J.E.Agnew. Nuclear Medicine and Medical Physics, Royal Free Hospital and School of Medicine, London, UK CAN OBESE PATIENTS STILL BENEFIT FROM TURBO DENSITOMETRY? Modem hone density machines often give a standard (array-l-5 minute) acquisition and a faster turbo (10 second scan) for both spinal and hip hone densitometers. Whilst such turbo scans have been verified for the body mass index (BMI), it is the depth of attenuating tissue which will be the most important factor which is directly related to the girth of the patient's abdomen. This study was performed to determine if the patients girth had any significant effect on the accuracy of spinal and hip bone density using the turbo acquisition compared to the array acquisition. 32 consecutive patients (without hip prosthesis) underwent both turbo and array acquisitions of the hip and spine using an Hologic 4500W whole body densitometer. In all patients the girth was noted. There was a good correlation (ra=0.99) between the figure for bone density acquired from both modes in the hip and femur. The turbo acquisition underestimated the spinal bone density In all patients (mean difference=0.032g/m2) (p<0.05, Wilcoxon ranked sign test) but this was not related to girth (Fig 1). No such difference was found in the measurement of hip bone density Fig I Difference in bone density (turbo-array - T-A BMD) o.ca

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In conclusion girth does not appear to have any affect on the accuracy of turbo acquired bone density compared with array acquired however the turbo method underestimated spinal bone density by an average 0.032 g / m 2 and therefore cannot be recommended.

876

ASSESSMENT OF JOINT INFLAMMATION IN RHEI MATOI1) ARTHRITIS: A CORRELATIVE STUDY WITH TC-99m HI(; SCINTIGRAPHY AND CLINICAL FINDINGS Aim:This prospective trial was carried net to determine the usefillhless of Tc99m Human immmmglobnlin (HIG) scintigraphy in the assessment of the severity of joint inflammation in varimls joints Methods: Forb-three paticms (35 females. 8 males mean age: 5(1.4_+1 7 yrs) diagnosed as rhemnatoid arthritis were included in the study. The presence or absence of pain and/or swelling ~as evahlated in 18 joints according to the Rithie index Tc-99m HIG scintigrapb3 was performed 4 and 24 hr after injection of 74(1 MBq of activib,. 7 minutes of images were obtained from shoulder, elbow, wrist, hand, hip, knee. ankle and foot joints. Scans were visually ewduated by using 4 grade scoring tO:normal. 1:mild increased activity, 2:moderate increased activib. 3:severe increased activity) withont knowledge of clinical fiadmgs. ESR and CRP ~ahles ~ere also obtained. The relationship between Tc-99m HIG scan scores and clinical findings were evahtated by Spearman's and Kendall rar,k correlation Results: Correlation was found between scintigraphic grading and both pain and swelling scores in the metacarpophahmgeal (MCP) and proximal iaterphalangeal (PIP) joints(r=0.35,P< 0.05). In the knee joint, pain and scintigraphic scores were correlated (r-0.35.p<0.05) but swelling did not Scintigraphic scores of shoulder. elbow, wrist, hip. ankle and metatarsophalangeal (MTP) joints did not show correlation with pain and swelling scores. ESR and 24 hr Tc 99m HIG scan scores showed correlation m the knee. wrist. MCP and PiP joints (r=0.45. p<0.01). On the other hand CRP values and both 4 and 24 hr Tc99nl HIG scan scores showed correlation in wrist and knee joints (r={I.4t). p<0.05). There wore on signifcant difference between 4 hr. and 24 hr. Tc-99m HIG scan scores (r=0.77,p<0.05) and 24 hr. studies did not give additioaal ilfformation.Conclusinn: Tc-99m HIG scintigraphy and clinical evaluation (pain and swelling scores) shewed mild to nmderate correlation in the assessment of inflammation in MCP, PIP and knee joinls.Tc-99to HIG scans and clinical scores did not show correlation in other joints (shredder. elbow, wrist, hip. aJd
13.5 J. Malamitsi*, J. Christacopoulos**, E Dounis***, E. Giamarellou***, ~-ff~oukakis*, *Radioisotopes Department, Hippocration General Hospital, Department of Medical Physics, University of Athens, Greece; **General Hospital for Chest Diseases "Sotiria" Athens, Greece; ***Laikon Hospital, University of Athens, Greece 99mTc-CIPROFLOXACIN (INFECTON) DETECT BONE AND JOINT INFECTION

AS

A

MEANS

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Aim of the study was to evaluate 99mTc-Ciprofloxacin (INFECTON) scintigraphy as a means to detect bone and joint infection, in comparison to other scintigrapKic and radiological methods. Twenty-one patients were examined with INFECTON. One patient underwent an INFECTON study twice within 2 months. Twelve out of these 21 patients were postorthopaedic surgery. 67Ga-citrate, 99roTe-Human Polyclonal Immunoglobulin and 99mTc-MDP bone scans, conventional radiology, CT or MRI were performed on these patients who had a known or suspected bone or joint infection. Clinical, biochemical and microbiological data from cultures contributed along with the imaging techniques in deciding on the presence or absence of infection. Five out of 22 studies proved to be negative on INFECTON in agreement with the other tests performed and the clinical data. Two studies were of equivocal result but in the light of the other imaging studies and follow-up it was decided that the infection was still present and that antibiotic treatment should be continued. The remaining studies were positive which proved to be an accurate result. The patient who underwent two INFECTON studies showed only a soft tissue infection on the first study, which was absent on the second. The isolated infecting agents were Staphylococcus aureus but also Staphylococcus epidermidis, Clostridium spp., Pseudomonas aeruginosa and Bruce/la mel/tensis. From this limited series of patients, INFECTON seems to be a promising agent in detecting infection in bone and joints with a high true positive and a high true negative rate.

[] Bone/Paediatrics 14.2

13.6

Departments of Nuclear Medicine and *Pediatrics, Clinical Hospital, Spilt, **Clinical Department of Nuclear Medicine and Radiation Protection, University Hospital, Zagreb, ***Faculty of Engineering, Split, CROATIA

Nuclear Medicine and *ImmunohematologyDepLs °OrthopaedicClinic, Rizzoli Institute, Bologna. Italy 99mTc HMPAO GRANULOCYTE SCINTIGRAPHY IN KNEE ARTHROPLASTY: A RETROSPECTIVE STUDY

Paediatrics 14.1

Quantitative analysis of left-to-right cardiac shunts by the algorithm of Maltz and Treves is hampered by statistical fluctuations of the first shunt recirculation curve, which is also influenced by subsequent shunt and systemic recirculations. The least squares gamma variata fit to the first shunt recirculation curve may lead to erroneous shunt quantification. In this work, symmetry adjustment of the gamma variate function curve was used to improve the quality of gamma variate fits. The symmetry of the gamma variate function curve is adjusted to that of an experimental curve by primary variations in the parameter tz of the gamma variate. Twenty nine patients aged 1 week to 28 years (mean 14.44 years) were studied. The diagnosis of a simple left-to-right shunt was established by cardiac catheterization. Radionuclide angiocardiography was acquired at 1 frame per 0. I second. A bolas of 0.3 to 1.0 second duration was obtained by jugular and subclavian vein injections. The right pulmonary time activity curves were analyzed. The first shunt recirculatiou curve was fitted from 10% maximum on the upslope to the point on the downslope where the influence of subsequent recirculations was obvious (deflection point). An overestimation of shunt size, as compared to oximetry data, has resulted in 28/29 cases, which was explained by imperceptible influence of subsequent reeirculations on the first shunt recirculation curve. A correlation was found between the level of the deflection point, relative to the maximum of the first shunt recirculation curve, and shunt size overestimation. On the basis of this observation a graded correction of the second gamma variate fit could be done. A very good correlation of the pulmonary to systemic flow ratio with oximetry data (r=0.93, SEE=0.22, p
14.3

V.Bri~qahti MD, G.La Cava MD, G. Bernini MD, A. Tamburini MD, R. Sestini and M. Maggi MD. Az. Osp. Careggi - Nuclear Medicine Unit, Phisiopathology Dpt. University of Florence and Paedriatic Dpt. University of Florence. QUANTITATIVE 11 lln-DTPA-D(Phe}-PENTATREOTIDE IN NEUROBLASTOMA: A NEW PROGNOSTIC TOOL. This study describes a technique that increase the specificity of 111-ln-DTPA-D(Phe)pentatreotide as prognostic evaluation in patients (9) with NeuroNastoma in comparison with Polymefise Chain Reaction (PCR) results. SPECTs studies were performed; the imaging provides acquisitions at 4 hours and 24 hours after the injection (55.5 MBq). The quantitative approach was based on the region of interest ( manually designed) activity of an area of pathological uptake (ROI-T) vs, background (ROI-NT). The time course of ROI-T/ROI-NT ratios between 4hr. and 24hr. is the prognostic index for our study.

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Aim of the study_: to evaluate diagnostic accuracy of 99mTc HMPAO granulocyte scintigraphy (GS) in knee arthroplasty with suspected infection. Methods: a ren'ospective study of the 56 patients submitted to GS for suspected infection of prosthesis from 1987 to 1996. Four patients had a Kotz prosthesis after an osteosarcoma resection, 20 a monocompartment and 32 a total knee a~n:hroplasty. Final diagnosis was obtained by surgery, culture examination and longterm follow-up in cases considered uninfected. Scintigraphic images were taken after 3 and 24 hours from cell reinjection. From 1990 a scintigraphic evaluation of bone ma~Tow disu'ibution was added to the diagnostic protocol (sulphur colloid or 30 min GS images). Results: GS resulted positive in 39 patients (37 TP, 2 FP) and negative in 17 (no FN studies) showing a 100% sensitivity and 89% specificity. The only 2 FP studies were in the group not completed by a bone marrow scan. Conclusi0ns: data from this retrospective study suggest that GS may be an accurate diagnostic tool in knee athroplasty with suspected infection and guide clinical decision as previous demonstrated for hip artluoplasties.

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R. Jakl*, D. lvan~evi6**, S. Popovid**, Z. Milas***, V. (~'_apkun

A. Fumo,°A. Sudanese,°A. Toni,°L. Busanelli, A. Palermo,*C. Basile

Neuroblastoma I 9 cases 1993-1996 Florenc( SMS SMS SMS PGR EV. rnlBG TNT 4h TNT 24h TNTinc SSR2 8.09 20.5 0,78 5x106 NED +

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9 B IV 1.02 1.03 0.01 2x107 DOD + B=Boy, G=Girl, TNT4h=ROI-T/ROI-NT ratio at 4h, TNT24h=ROI-T/ROI-NT ratio at 24h, TNT inc=(TNT24h-T NT4h)/[(TNT24h+TNT4h)/2], PCR=mRNA measurements with reverse t ranscriptase-polym erase chain reaction, EV.=evolution (1-3 years), mlBG=131-1metabenzilguanidina, Hist.=Histological diagnosis, DOD= dead od disease, AWD=alive with disease, NED=non evident disease. The patients have executed also mlBG and NMR studies and were operated and histological confirmed the diagnosis of NeuroNastoma. Specific mRNA measurements quantified also the presence od SST2 receptors in the tumors. We have applied a novel approach to the study with 111-ln-pentatreotide and were able to demonstrate the specificity binding on the basis of the increase of ROIs ratios between 4hr. and 24hr. The Scintigraphy results appear correlated (R=0.692 p
D. Sobid-Saranovid. !. Jovanovid*, S. Pavlovid, N. Kozarevid, M. Dukid*. Institute of Nuclear Medicine, CCS, * Pediatric University Clinic, Belgrade, Yugoslavia

ASSESSMENT OF GLOBAL VENTRICULAR FUNCTION BY RADIONUCLIDE VENTRICULOGRAPHY IN CH][LDREN WITH DOUBLE-INLET SINGLE VENTRICLE Double-inlet single ventricle is a term used to describe univentricular atrioventricular connection in which both or common atrioventricutar valves open in single ventricutar chamber. It is almost always accompanied by L or D malposition of great arteries. Assessment of ventricular function is not possible with echocardiography or selective contrast ventriculography because of complex heart malformations and abnormal geometry of the heart. The aim of this study was to find out is it possible to assess ventricular function in double-inlet single ventricle by radionuclide ventriculography. We studied five children, 3 boys and 2 girls, mean age 11 years. Four of them had double-inlet left ventricle and one double-inlet right ventricle. Four had surgical treatment (operatio Fontan or Glenn) 6 month to 5 years before our investigation. After in vivo labeling of red blood cells with 370 MBq of 99mTc radionuclide ventriculography was performed in all patients in three projections: anterior, LAG 450 and LL 900. R-R interval was divided in 32 frames. Ejection fraction was calculated with conventional processing techniques and phase and amplitude images were assessed. In 3 patients EF was normal (62%, 52%, 50%, respectively). In 2 patients with cyanosis and hepatomegaly EF was 34% and 36%, respectively. In those two patients phase images reveal nonsynhronised, almost dyskinetic apical part of the single ventricle. Our preliminary results indicate that radionuclide ventriculography provides clinically useful quantitative information regarding global systolic function of double-inlet single ventricle. In addition, regional function of single ventricle could be evaluated by phase and amplitude images. Further clinical validation is necessary, especially in follow-up of children with double-inlet single ventricle.

877

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• Paediatrics/Physics 14.4 M.Charron, F.delRosario, S. Kocoshis, C. DiLorenzo, S. O~enstein, P. Putnam. Division of Nuclear Medicine and Gastroenterology, Children's Hospital of Pittsburgh, University of Pittsburgh, PA

Physics 15.1 C.Jeanguillaume, S.Bcgot, M.Quartuccio and P.Ballongue Bat 510 Facult6 des Sciences d'Orsay 91405 ORSAY FRANCE Hopital Henri Mondor 94010 CRETEIL FRANCE

SENSITIVITY AND SPECIFICITY OF Tc-99m-HMPAO-WHITE BLOOD CELLS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE Studies have suggested that Tc-99m-HMPAO White Blood Cell (Tc-99m-WBC) is superior to contrast radiology in the assessment of extent and activity of inflarmmatory bowel disease(IBD). Thus, we evaluated the sensitivity and specificity of Tc-99m-WBC compared with colonoseopy and biopsy for the evaluation of colonic inflammation in children. Methods: We reviewed the charts of 215 children who underwent Te-99m-WBC scan; 80 had Crohn's disease (CD), 34 had ulcerative colitis (UC), 18 had indeterminate colitis (IC), 52 had non-specific gastrointestinal complaints but no demonstratable IBD by conventional diagnostic methods (PN), and 31 were controls (NL; children who underwent Te-99mWBC scan for other medical problems). One investigator blinded to the diagnoses reviewed the scans. Results: There were 100 boys and 115 girls (average age 12 y.o.). The Tc-99m-WBC scans corresponded with histologic findings in 125/137 children. There were 9 false negatives; 3 from the CD group, 1 each from the UC and PN groups, and 4 from the IC group. All had normal laboratory tests, appeared normal at colonoscopy and had biopsies that showed mild chronic inflammation, except for 3/4 patients in the IC group who were diagnosed with autoimmune colitis and had abnormal labs. There were 3 false positives which were attributed to the presence of a fistula (i) or active bleed (2). CD UC IC NL PN Total pt with biopsy 41 22 12 31 32 137 Sensitivity 93% 95% 67% 100% 97% 93% Specificity 98% 95% 92% 100% 100% 98% Conclusion: Tc-99m-WBC is sensitive and specific for evaluating the extent of IBD, but has limitations for other causes for colitis.

COMPUTER AIDED COLLIMATION GAMMA CAMERA (CACAO) THE NEXT STAGE IN NUCLEAR MEDICINE INSTRUMENTATION Conventional parallel holes collimators produce poor resolution and poor sensitivity with gamma cameras. To overcome these drawbacks, we described previously, (1,2) a project utilizing computer aided collimation gamma cameras (CACAO in French) This method associates a position sensitive detector, a collimator with large holes (larger than the intrinsic resolution of the detector), an additional linear movement of the camera head and a dedicated reconstruction software. Information theory was used to evaluate the potential benefit brought by this method (3). A novel approach based on random walk diagrams was able to identify the information content of the acquisitions and to predict the quality of the reconstructed images. Moreover this approach which is not based on a particular algorithm, allows the operator to choose the best data acquisition protocol even if the program to treat the data does not still exist. This information evaluation identified two main factors governing the quality of SPECT images: 1) the statistical counting uncertainty and 2) the multiplex volume uncertainty. Comparison between the conventional SPECT technique and the CACAO method was performed using these criteria. CACAO has been proven to bring an important improvement in the quality of SPECT images, when the right reconstruction program will be available. A good program must not only be accurate to meet the calculated quality of the images, but also fast enough to allow practical use. A fast reconstruction program based on Fourier transform has already been developed. Examples of CACAO simulations and reconstruction images are shown. In conclusion, CACAO has the potentials to greatly improve the quality of SPECT images . 1- C. Jeanguillaume. 14th Annual IEEE EMBS Conf, Paris (France), 29 octobre/1 novembre 1992, part 5 of 7 pp. 1813-1815. 2- High sensitivity gamma camera system US Patent N ° 5 448 073 September 05, 1995. 3- C. Jeanguillaume, S. Begot, R.B.M. 1996;18:(7) 198-206 and 207-215

14.5

15.2

T.Lantto, E.Lantto,I.Anttolainen,J.-P.Kaukonen, R.Mokka, Departments of Nuclear Medicine,Pediatrics and Surgery, Pgij~it-H~ne Central Hospital, Lahti and Department of Radiology Central Finland Health Care District, Jyv/iskyl~i, Finland

L Yang, J. T. Kuikka, L. Patomg.kiand E. L~nsimies Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, FIN-70211, Kuopio, FINLAND Department of Applied Physics, Kuopio University, FIN-70211, Kuopio, FINLAND

THE USE OF COMBINED THREE-PHASE BONE AND WHITE BLOOD CELL IMAGING IN PEDIATRIC BONE INFECTIONS The value of combined three-phase bone scanning (TBS) and Tc-99mHMPAO-labelled white blood cells (LEUC) in suspected bone infections was retrospectively assessed in 55 scintigrams of 53 pediatric patients (pts); age range 1 m o - 16 y. Patients were imaged with both agents within 4 days. The abnormality of each image was graded from 0 = no abnormality to 3 = high uptake.Final diagnoses were based on radiology,puncture,biopsy, histology or bacterial culture. Bone disease was in 21 pts; osteomyelitis (OM) in 18 pts,benign bone turnout in 1 pt,stress fracture in 1 pt and fibrous dysplasia with pathologic fracture in 1 pt. Joint diasease was in 30 pts; transient synovitis (TS) in 17 pts,septic arthritis in 8 pts and rheumatoid arthritis (RA) in 5 pts. Of the other 4 pts 1 pt had soft tissue abscess, lpt had hematoma, 1 pt had acute lymphocytic leukemia and 1 pt had post traumatic low back pain. TBS was positive in all bone disorders. LEUC was negative in 3 0 M s and in 1 healed OM and in all noninfectious bone disorders. In these cases TBS gave the essential information. High LEUC activity confirmed in 5 pts and negative LEUC excluded OM in 2 pts with equivocal TBS results. Combination of the two methods gave important information in 12 pts. In joint disorders TBS and LEUC were highly positive in 5 pts with PA, LEUC activity was lower in 2 pts. In R A especially the blood-pool images of TBS showed increased activity,LEUC activity was usually low. In TS both the TBS and LEUC uptakes were negative or of low grade. In joint disorders combination of both methods gave important information in 7 pts. The combination of TBS and LEUC imaging gives marked additional information in suspected bone infections and should be used to confn-m or exclude infection.

878

A NON-UNIFORM SCATTER CORRECTION USING SINGLE ISOTOPE Tc-99m IN SIMULTANEOUS TRANSMISSION AND EMISSION TOMOGRAPHY In single photon emission tomography (SPET) images, the quantitative measurement of radioactivity in specific organ and regions of interest is extremely difficult because of the limited spatial resolution, partial volume effect, tissue attenuation and scatter. The simultaneous SPET and transmission tomography scans with dual isotopes have been reported to correct attenuation and scatter. However, there is the cross-contamination from crosstalk of transmission and emission sources. A method has been developed to acquire emission and transmission data simultaneously with single isotope scan. The transmission source has same energy spectrum as the emission source because Tc-99m is only used. The triple-headed SPET system allows for transmission and emission data to be acquired in one detector (D1) while other two detectors (D2, D3) simultaneously acquire emission data. The transmission data can be calculated by the subtraction between DI and D2 (D3) after the time decay correction. A transmission-dependent method for scatter correction was implemented with the transmission and emission data. The phantom study was performed using the cardiac and lung inserts in Jaszczak phantom cylinder. To evaluate the scatter correction method, four line sources were scanned in the same phantom. The phantom studies show that the method provides a non-uniform attenuation distribution. There is no cross-talk using single isotope Tc-99m as the transmission emission source. The results of scatter correction demonstrate a clear improvement in the quantitative accuracy of radionnclide concentration and spatial resolution. FWHMs are 0.73 cm without and 0.63 cm with scatter correction at the source-to-detector distance of 18 cm. The contrast calculated by the average counts/pixel between two regions of interest are 0.76 without and 1.24 with scatter correction. In conclusion, the results indicate that the single isotope method can overcome the cross-contamination in dual-isotope acquisition. They further support the feasibility of simultaneous SPET and transmission scan using single isotope.

• Physics 15.3

15.5

N.Manthev, A.Tausig, F.Pachmayer, R.Walser, D.Slotty, P.Knesewitsch, K.Tatsch, and K.Hahn. Dept. of Nuclear Medicine, University of Munich, Germany

D. Hellwig and C.-M. Kirsch

cO

Dept. of Nuclear Medicine, University Homburg/Saar, Germany

l m

t~ t-THE INFLUENCE OF RESTORATIVE AND SMOOTHING 3D FILTERS ON ECT MEASUREMENTS OF AN ANTHROPOMORPHIC HEART PHANTOM USING NONUNIFORMATTENUATION CORRECTION.

The aim of this study was to investigate the effect of 3D Wiener (Wnr) and Low Pass (LOP) postfiltering of ECT measurements of an anthropomorphic heart phantom (H-Phantom) using iterative reconstruction and nonuniform attenuation correction. The HORGAN COUNT-RATE Phantom is commercially avalfable and has Lung I/6 x Heart chambers for the left ventricle, lungs and I Liver [ 4/5xHeart liver which were filled with Tc-99m, according to the table above. Data were acquired with a triple head camera (PRISM 3000, Cardio Fan, Picker, Gd-153-1ine-source for the transmission projections) using activities of 0.9 up to 30 MBq within the myocardium. Thus, activities covered the range theoretically expected in the myocardium of patients (1.2-13.5 MBq) using a one-day stress (250MBq) / rest (650MBq) protocol. The raw data were iteratively reconstructed and postfiltered with Wnr and LoP filters and a 16-segment semiquantitative analysis was performed. Heart LoP Wnr The mean values of the Activity Range (mean) Range (mean) normalized counts/voxel for (MBq) (%) (%) the different segments were 30 71-100 (86) 66-100 (84) systematically greater and differed less from 100% for 15 82-100(93) 76-100(88) the LoP than for the Wnr 7.5 85-100 (92) 75-100 (87) filter. The variations of the 3.6 85-100 (91) 76-100 (87) counts/voxel between the 16 1.8 85-100 (91) 76-100 (87) segments were considerably 0.9 83-100 (91) I 74-100 (85) smaller for theLoP filter. LoP postfiltcring resulted in a more accurate reproduction of the true activity distribution within the H-Phantom. Within the activity range expected in patients using a standard one-day-protocol LoP postfiltering seems to be the preferable approach for processing-myocardial scintigrams. The results encourage to extend the study to patient investigations in order to determine the influence of LoP and Wnr filtering in the clinical setting.

ITERATIVE 3D MAXIMUM-LIKELIHOOD-RECONSTRUCTION(MLR) FOR CLINICAL SPECT STUDIES Introduction: Low target/background contrast and low accumulation of tracer in targets close to organs with high uptake are the main problems for the reconstruction of tomographic data by the commonly used filtered backprojection (FBP). Some of it may be overcome by MLR. The statistical error due to poor count rates can be reduced by the application of 3D reconstruction algorithms (3D-ALG), since information of adjacent slices is utilised. The pixel by pixel computation of detection probabilities (DP), however, is more complicated than for the 2D case. Until now the computational burden limits the clinical applicability of 3D-ALG. The aim of our work was the realisation of a 3D-ALG with considerable reduction of computation time. Method: The detection process was separated in a transverse and axial part ~---'d"~'~iteration formula of MLR was rewritten in a form applicable to 3D. Using rotational symmetries the number of DP to compute was reduced by a factor of 8, the simultaneous reconstruction of all 64 slices yields a factor of 64. The computation of DP takes care of resolution effects and allows for the implementation of camera efficiency. Attenuation correction is still to be implemented. Clinical data was acquired with dual and triple head gamma cameras (MultiSpect2 and MultiSpect3, Siemens Gammasonic). Results. Phantom studies show improved detectability of hot and cold lesions compared to FBP. Typical streak artefacts known from FBP are missing in MLR. The rigorous consideration of resolution effects in the computation of DP results in a reduction of the checkerboard effect known for MLR images at many iterations. For a single iteration step an average time of 0.2 seconds is achieved on a Pentium-S 166 MHz PC for the reconstruction of a 64x64 image from 60 projections, resulting in a total reconstruction time of 15 minutes for a complete 3D data set, if 100 iteration steps are used. Conclusions: The efficient implementation of MLR allows for its application cm ~ o r k and increases the diagnostic power of SPECT studies. Increasing lesion detectability and reducing artefacts MLR is a further step towards quantitative SPECT.

15.4

15.6

M. Baehre, F. Kamm, E. Richter

K. Cherif, YmPetegnief , D. Le Guludec, Department of Nuclear Medicine, H6pital Bichat - Paris, France.

Clinic for Radiotherapy and Nuclear Medicine, Medical University of Luebeck, Germany RESULTS OF ITERATIVE RECONSTRUCTION AND FILTERED BACK PROJECTION IN MYOCARDIAL SPECT STUDIES The problems of tomoscintigraphy with the aid of the filtered back projection (FBP), above all its tendency to artifacts, are well known. In general, iterative reconstruction methods (IT) are considered superior to FBP in SPECT and PET. However, only few studies prove and quantify this estimation. Therefore, we compared IT and FBP in myocardial SPECT. Patients and methods: 67 patients were examined after exercise and at rest with a standard protocol (74 MBq 2OlTI, 128x128 matrix, 30s per frame, step-and-shoot, 180 ° rotation, 6°). The data were reconstructed iteratively (according to Luig, absorption correction implemented) and with FBP (no absorption correction) and anonymized. Tomoscintigrams obtained were evaluated independently by 4 observers without knowledge of any clinical findings. The judgements were based on a discrete rank scale and covered 25 segments of the heart (higher ranks corresponded to more clearly delineated defects). Results: base middle apex IT- FBP IT- FBP IT- FBP ant. wall 31,0 - 32,5 19,0 - 27,5 n.s. post. wall 13,4 - 21,0 8,0 - 26,4 20,5 - 28,7 septum 26,0 - 19,8 25,7 - 19,5 24,1 - 22,9 lat. wall 2 8 , 4 - 18,6 1 8 , 0 - 11,9 t 5 , 0 - 7,6 Tab. 1: Sum of ranks in 12 of 25 segments (p < 0,01). Results at rest corresponded to those after exercise, In the anterior and posterior wall, FBP enhanced imaging of tracer defects when compared to the iterative technique. On the other hand, iteratively reconstructed tomograms showed superior recognizability of areas with decreased uptake in septum and lateral wall. Conclusion: Iteratively reconstructed myocardial SPECT studies in fact provide superior information compared to FBP. Due to missing absorption correction, FBP overestimates defects of the posterior wall and - to a lesser extent - of the anterior wall.

INFLUENCE OF RESOLUTION AND BACKGROUND ON WALL THICKNESS ESTIMATES IN TC-99m GATED MYOCARDIAL SPECT We investigated the effect of imaging conditions on the quantification of myocardial wall thickness (WT) in Tc-99m perfusion gated SPECT. The influence of partial volume effect, cavity background and count statistics was assessed on a cylindrical heart phantom with a fixed-3 cm cavity and WT varying from 0.45 to 1.75 cm. Gated SPECT studies were performed with a double-head camera equipped with a LEHR collimator (15 mm on-axis spatial resolution), in heart-centered orbiting over 180°, 8 segments/cycle, 16 views/head Different time/view were simulated. Data were reconstructed with Wiener filter and the values of FWHM, peak maximum and total wall activity were then calculated on radial count profiles from 5 short-axis slices. A minimuin average myocardial counts of 40/pixel per segment gave reproducible measured WT from one segment to the other. Below this value, only qualitative analysis should be considered. Linearity between measured FWHM (y) and tree WT (x) was found when the cavity was empty (y= 0.258 x + 1.615, R2= 0.964). The peak maximum was fairly linear for WT greater than 0.75 cm The wall activity was also linearly correlated with WT for walls greater than 0.6 cm. For cavity to wall activity ratios varying from 8 to 41%, measured WT increased from 0 to 28% without significant change in peak activity. Moreover, the observed asymmetry in profiles led to underestimate the endocardial volume up to 38%. When cavity background was substracted, WT varied inversely with a 27% decrease for the maximum cavity activity. These results suggest that linear relationships can be used to model partial volume effects on FWHM and profile maximum. On the other hand, estimates of WT are strongly altered when cavity background to waft activity ratio is higher than 15%.

879

m

t~

8

• Radiopharmacy Radiopharmacy 16.1

16.3

H. Hal! 1, C. Halldin 1, D. Guilloteau 2, C. Lundkvist 1, S. Chalon 2, P. Emend 2, J.C. Besnard2, L. Farde J, and G. SedvallL tKarolinska Instituter, Department of Clinical Neuroscience, Stockholm, Sweden, and 2INSERM U316, Laboratoire de Biophysique M6dicale et Pharmaceutique, Tours, France.

M.X. Yu ~, K.A. Bergstr6m ~, C. Halldin 2, J.T. Kuikka 1, C-G. Swahn2, K. ~errnanl~ J. Hilttmen3, J. Tiihonen 1, N. Lassen4, C. Widebeck4, L. Farde< ~Kuopio Univ. Hospital, Finland; 2Karolinska Institute, Sweden; 3MAP Medical Technol. Oy, Finland; 4Bispebjerg Hospital, Denmark.

DOPAMINE TRANSPORTERS IN THE POST-MORTEM HUMAN BRAIN. AUTORADIOGRAPHIC LOCALISATION USING [I-125]PE2I.

Previous studies of the distribution of the dopamine transporter in the human brain have been performed using compounds with relatively low selectivity like ~-CIT. Using a new, selective dopamine transporter inhibitor, N-(3 -iodoprop-2E-enyl)-2[3-carbomethoxy-3[3-(4'-methylphenyl) nortropane (PE2I), the distribution of the dopamine transporter was characterised in the normal post-mortem human brain using whole hemisphere autoradiography. PE2I was radioiodinated to high specific radioactivity (2200 Ci/mmol). PE2I has higher affinity for the dopamine transporter than [3-CIT (Ki-values 17 nM and 27 nM, respectively), and has in contrast to ~-CIT very low affinity for the serotonin and noradrenaline transporters. The autoradiograms showed very dense binding to basal ganglia (putamen, nucleus caudatus, nucleus accumbens) and less dense binding to substantia nigra. No binding was found in the cortex or cerebellum. The labelling of human dopamine transporters with [I-125]PE2I was inhibited by the addition of the dopamine transporter inhibitors GBR12909 and [3-CIT, but not with citalopram (serotonin transporter inhibitor) or maprotilin (noradrenaline transporter inhibitor). Due to the relatively high lipophilicity of the compound, it accumulated slightly in white matter. The in vitro autoradiography obtained with radiolabelled [I-125]PE2I provide detailed qualitative and quantitative information on the distribution of the dopamine transporter in the human brain. Moreover, the autoradiograms give complementary information for the interpretation of results obtained at lower resolution in humans with PET or SPECT using [C-11]PE2I and [I-123]PE2I, respectively. These in vitro data provide a strong basis for expecting [C-11]PE2I and [I-123]PE2I to behave as highly selective radioligands in vlvo.

DOES THE LIPOPHILIC LABELED METABOLITE OF [1-123]EPIDEPRIDE OBSTRUCT DOPAMINE D2 BRAIN IMAGING

A labeled lipophilic metabolite of [I-123]epidepride has been observed in human plasma. The aim of the study was to determine the detailed metabolite pattern of [I-123]epidepride in human plasma and furthermore to study the possible influence of the labeled lipophilic metabolite to the dopamine D2 SPET imaging. Plasma from 14 subjects at 3-510 minutes after injection of [I-123]epidepride was mixed with acetonitrile and after centrifugation the supernatant was used for gradient HPLC analysis. SPET imaging was performed with Siemens MultiSPECT3 gamma camera with fanbeam collimators. [I-123]Epidepride was metabolized rapidly and three labeled metabolites were observed of which one was more lipophilic than the unchanged [I-123]epidepride. The percentage of [I-123]epidepride and the lipophilic metabolite in plasma after 60 min injection were (34.54-7.3)% and (11.04-8.6)%, respectively. We studied also the correlation of the percentage of the lipophilic metabolite and the distribution volume of striatal radioactivity with 8 subjects. A linear regression fit showed a correlation of amount of lipophilic metabolite and distribution volume measured at 60 rain after injection (1{=-0.73, P=0.042). Whereas a correlation of amount of lipophilic metabolite and specific binding (striatum-eerebellum) was not so significant. In conclusion, the amount of the labeled lipophilic metabolite of [I-123]epidepride was normally 10-15% at all time points. It may be possible that the lipophilic metabolite has an influence on dopamine D2 brain imaging with SPET, which should be confirmed with larger population of study subjects.

16.2

16.4

S. Chalon, P. Emond, L. Garreau, Y. Frangin, *L. Mauclaire, D. Guilloteau, J.C. Besnard, INSERM U316, Univ., Tours, *Cis Bio Industrie, France.

D. Serge{. R Schliebs-~,S. Refiner~. 1 K~.mpfer~. C. DanncnbergI. W. H Knapp1, Department of Nuclear Mcdicinc~and Patd-Fbchsig-lnstitutc for Brain Research2. University of Leipzig, Germany

CHARACTERIZATION OF THE COCAINE DERIVATIVE PE2I, HIGH SPECIFIC MARKER FOR IMAGING THE DOPAMINE TRANSPORTER BY SPECT

A

Parkinson's disease is c h a r a c t e r i z e d by loss of d o p a m i n e r g i c neurons. Nuclear medicine using specific ligands for the dopamine transporter (DAT) could be very usefull to explore this d e g e n e r a t i v e process. For this, several labeled cocaine a n a l o g s have been developed, but most of them lack selectivity or have kinetic properties unsuitable to p e r f o r m a q u a n t i t a t i v e e x p l o r a t i o n at the day of injection. To improve this, we synthesized a n e w series of cocaine derivatives and selected the most s e l e c t i v e for the DAT. PE2I, N - ( 3 - i o d o p r o p 2E-enyl)-2~-carbomethoxy-3~-(4'-methylphenyl)nortropane, was o b t a i n e d with high specific activity. [125I]PE2I had high in vitro affinity for the DAT (Kd=0.09nM, B m a x = 2 8 0 f m o l / m g prot). Specific u p t a k e was observed in vivo in rats, with a maximal striatum/cerebellum ratio of 9 obtained 2 hours post-injection, a striatal fixation totally prevented b y a p r e - i n j e c t i o n of GBR 12909, and no fixation in the frontal cortex. We have also tested PE2I in a ra~ model of unilateral lesion of the n i g r o s t r i a t a l p a t h w a y with 6-OHDA. Three w e e k s after lesions, rats were IV injected with 3.7 M b q of [125I]PE2I. Two hours later, brains were removed, frozen, cut and exposed on sensitive films during 6 weeks. On the lesioned side, we o b s e r v e d a mean S t r i a t u m / f r o n t a l cortex ratio of 0.86±0.10, vs 7.20±0.91 on the intact side. This shows that PE2I is suitable to detect in vivo specific i n j u r y of d o p a m i n e r g i c cells. In addition, in vivo imaging in monkeys showed that [123I]PE2I was r a p i d l y and highly a c c u m u l a t e d in the striatum, reaching a p l a t e a u b e t w e e n 30 and 80 min post-injection. All these results demonstrated that PE2I fullfiled criteria of specificity and kinetics to be used in human SPECT studies.

880

CORTICAL IQNB BINDING AND PERFUSION AFTER DESTRUCTION OF THE CHOLINERGIC TRANSMISSION 1N AN ANIMAL MODEL

lodoquinuclidinylbcnzilatc (IQNB) is a potential ligand of muscarinic rcccptors in vivo. This study deals with the question whcther in vitro and in vivo administration of [~:SlliodoQNB in rats is able to demonstrate changes in cortical muscarinic receptor densit3 induced by inummolesion, and xxhcthcr potential effects on IQNB distribution in vivo are associated with effects on cerebral perfusion Methods: 7. 15, 30 and 90 days after specific imnmnolesion of the rat forebrain cholinergic system by ir~jectionof the immunotoxin 1921gG-saporinbrain slices (5 animals for each interval) and 5 controls were obtained for in-vitro autoradiography. Therefore, they were incubated with 003 nM (R.R)1~2511iodoQNB. For in-vivo investigations 5 immunolesioned and 5 control animals were injected with 5 MBq (R,R)-[I"~I]iodoQNB (specific activity: 30 TBq/mmol) and 800 MBq [99'=Tcl-d,I-HMPAO. Cerebral distribution of both tracers 30 d post immunolesion were imaged using double tracer autoradiography. Results: Effectiveness of immunolcsion was verficd by 70 ± 6 % reduction in acetylcholinesterase activity in the cortical target area. Impaired cholinergic transmission was paralleled by 10-15 % increase in cortical and hippocampal [~2-~I]iodoQNBbinding corresponding with a respective increment shown when in vitro autoradiography was used There was, however, no significant change in cerebral perfuslon. Conclusion: Deficits of the cholinergic transmission can be demonstrated with thc model used and by in rive administration of [l'3l]iodoQNB. The clmngcs in distribution of the radioligand are not secondaB' to local changes in cerebral perfllsion.

[] Radiopharmacy/Oncology Oncology 17.1

16.5 J. Owens, A. Tebbutt, J. Patterson, Wyper, D Hadley, G. Durant*, S.

K. Muir, D. Magar*, J. McCulloch, University of Glasgow ,Scotland, UK and *CNS, Cambridge MA, U.S.A. IHITIAL

ASHEHMENT

CHANNEL L Z G A N D I N

OF C N S 1 2 6 1

A NEW NMDA I O N

NORMAL V O L U N T E E R S

AIM: Determination of the uptake,

retention

and

metabolic fate of CNS1261(N-(l-naphthyl)-N'-(3iodophenyl)-N'-methylguanidine) in normal

subjects. METHOp_S: 123I-CNS1261 purity and with high

was

synthesised,

in high specific activity, via an electrophilic iododestannylation reaction. Subjects received an IV bolus of 123I-CNS1261 (120MBq) and SPECT scanning was performed on an SME 810 neuroscanner. Venous blood samples were analysed by ultrafiltration, precipitation and hplc. SU_~: Ultrafiltration showed no free authentic ligand at any time in plasma in contrast the acetonitrile extracts demonstrated rapid clearance of 123I-CNS1261 from the plasma (no tracer detectable at 20 min). Degradation was by deiodination with no evidence of any lipophilic metabolites. Radioactivity cleared slowly from the brain (T|~ approx. 150 min). CONCLUSION: 123I-CNS1261 is bound strongly to plasma proteins but sufficient tracer enters the brain to allow imaging by SPECT. Despite the rapid clearance from blood, brain clearance is prolonged and kinetic analysis indicates substantial tracer binding, either specific or non-specific, studies are underway in conditions thought to involve specific activation of the NMDA receptor system.

I N.Weinberg, W.A,Berg',R Pani" F. Scopinaro_G Bakale' ,L P Adler PEM Technologies,Bethesda MD, and FM Technologies, Fairfax VA, USA 'Radiol. Dept., Univ Maryland, Balto. MD, USA; "'ExpMedDept, Univ La Sapienza, Rome, ITALY; "'Nucl Med.Div.,Univ.HospitaI,Clevetand OH. USA. METHODOLOGY FOR COMBINING X-RAY AND METABOLIC IMAGES OF NONPALPABLE PRIM AR Y BREAST CANCERS Due to the high mobility of breast lesions, it can be difficult to conduct radiotracer imaging studies of nonpalpable cancers without the capability of correlating nuclear medicine images to high spatial resolution anatomic images We show how the adoption of breast compression permits coregistration of gamma-ray images performed in the same patient sitting as x-ray imaging. The methodology, which is applicable to all functional images taken with breast compression, results in a composite anatomic/functional image that is easily interpretable by clinicians Two commercial stereotacbc x-ray mammography gantries [Lorad Corp, Danbury CT, USA, and Fischer Imaging, Denver CO, USA] were each fitted with arrays of gadolinium orthosilicate crystals configured to image positron emitters with high count sensitivity [Weinberg et at, EJNM 23:804-806, 1996] After informed consent, and under protocols approved by respective institutional review boards, one patient on each gantry was injected with up to 370 MBq of 2-(F-18)-fluorodeoxyglucose intravenously. Both patients had cancers that appeared on x-ray mammograms to be less than 7 mm in diameter, Prior to the patient study, locations of four radio-opaque fiducial markers placed on a compression paddle were determined on the gamma-ray image by holding an Na-22 point source at each marker. In each patient study the patients breast was compressed with the gamma-ray imaging detectors in place for a 5 minute acquisition. After gamma ray acquisition, and without releasing compression, the gamma-ray imaging detectors were removed and a single x-ray image taken that included the cancer as well as the fiducial markers The cancers were segmented on gamma ray images by thresholding 3 standard deviations above the mean image intensity A polynomial warp transformation employing the four fiducial markers as reference points was used to overlay the x-ray image with the segmented gamma-ray image in beth cases, the composite overlaid image clearly demonstrated registration of the x-ray and gamma-ray abnormalities. Support: USPHS2R44CA58061-O2A2,5R29CA59854-4,Komen

Found.

16.6

17.2

P. Perret~ C. Ghezzi, JoP. Mathieu, C. Morin, M. Comet and D. Fagret, L a b o r a t o i r e d'Etudes des Radiopharmaceutiques - ESA CNRS 5077.

G Cook S Houston M Maisey I Fogelman. Clinical PET Centre, Guys & St Thomas' Hopitals, London UK

VALIDATION OF 6-DEOXY-6-IODO-D-GLUCOSE OF GLUCOSE TRANSPORT IN VIVO.

Detection of bone metastases in breast cancer by 18FDG PET: Differing metabolic activity in osteoblastic and osteolytic lesions.

AS A TRACER

Many diseases are associated with glucose metabolism or transport abnormalities (myocardial or cerebral ischemia, non-insulin-dependent diabetes mellitus (NIDDM), cancer). A new radioactive glucose analogue has been synthesized : [123I]-6-deoxy-6-iodo-D-clucose (6DIG) . Its biological behaviour in vitro is similar to that 3-O-methyl-D-glucose, a reference tracer of glucose transport. The aim of this study is to point out that 6DIG is able to show up pathological variations of glucose transport in in vivo models. Thus, preliminary studies has been carried out in homozygote diabetic (db/db) mice (NIDDM), e x h i b i t i n g a severe insulin resistance c h a r a c t e r i z e d by a lack of g l u c o s e uptake in p r e s e n c e of insulin due to a transport defect. Biodistributions of 6DIG (Snmoles/mouse) with (l,5UI/kg) or without exogenous insulin have been realized in d b / d b mice and in db/+ non-diabetic control mice. Results show that 6DIG as well as glucose uptake increased (by 30%) with insulin in mosL of insulino-sensltive tissues of db/+ mice. In db/db mice, insulino-resistant and hyperglycaemic with or without exogenous insulin, 6DIG uptake did not rise in p r e s e n c e of this hypoglycaemic hormon. Conclusion : 6DIG is able to show up in the heart, d i a p h r a g m e and skeletal m u s c l e of d i a b e t i c mice, a glucose transport defect and in non diabetic mice, a physiological variation (in the presence of insulin) of glucose transport. It's the first time that an iodinated analogue of glucose shows so promising results in vivo.

Bone scintigraphy is currently the method of choice in detecting bone metastases but I~FDG PET is a sensitive method for the detection of metastatic breast cancer and has advantages over more conventional nuclear medicine techniques. We have compared 18FDG PET with bone scintigraphy in patients with proven skeletal metastases and have further analysed the data depending on whether lesions were sclerotic, ]ytic or mixed and have correlated findings with patient survival. 23 women with breast cancer with confirmed bone metastases were studied with both ~gmTc MDP bone scintigraphy and 18FDG PET and a comparison made of the two modalities with regard to the number of lesions detected and to the quantitation of uptake (standardised uptake values, SUV) of ~BFDG in either osteolytic or osteobtastic metastases. Survival curves were plotted for both lytic and blastic bone metastases and also for patients with high and low accumulation of ~BFDG. Overall, ~BFDG PET detected more lesions than bone scintigraphy (mean 14.1 and 7.8 respectively, p<0.01). However, ~BFDG detected fewer osseous metastatic sites in a subgroup of patients with osteoblastic disease. Further, SUVs were progressively higher in osteoblastic, mixed and osteolytic disease (means 0.95, 3.6 and 6.6 respectively, p<0.01). Survival is reduced in patients with pure osteolytic disease compared to the remainder (p=0.04) and a trend towards lower survival was seen with high SUVs (>3.5) although this did not reach statistical significance (p=0.12). ~BFDG PET is superior to bone scintigraphy in the detection of purely osteolytic disease and the earlier detection of disease in this group of patients, who are more likely to experience complications, may have prognostic significance. In contrast, osteoblastic metastases show lower metabolic activity and are commonly undetectable. Prognosis is worse in those patients with bone metastases with higher avidity for FDG.

881

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O

• Oncology 17.3

17.5

F.Crippa, R.Agresti, M.Greco, C.Pascali, A.Bogni, C. Chiesa, V. De Sanctis, V. Delledonne, B. Salvadori, M. Leutner, D. Decise and Bombardieri - National Cancer Institute, Milan (Italy)

M. Lonneux. R. Bausart, R. Detry, F. Jamar and S. Pauwels. PET Laboratory and Dept. of Surgery, Univ. of Louvain Medical School, Brussels, Belgium.

FDG-PET IN T H E P R E S U R G I C A L S T A G I N G O F T H E A X I L L A IN B R E A S T C A N C E R We have presurgically studied 72 pts with a diagnosis of primary breast cancer. Visual analysis of attenuation-corrected PET images and standardized uptake values (SUV) of FDG uptake in carcinomas were compared with histopathologic surgical findings. The SUV distribution differences between carcinomas with and without axillary metastases were evaluated by means of statistical and ROC analyses. PET correctly classified 64 of the 72 pts; 4 false-positive and 4 false-negative PET results were found. The overall sensitivity, specificity and accuracy of PET for axillary metastases were 85%, 91% and 89%, respectively. With respect to the clinical axillary stage of the pts (TNM classification), we obtained the following results: NO pts = sensitivity 70%, specificity 92%, accuracy 86%; N l a pts = sensitivity 85.5%, specificity 100%, accuracy 95%; N l b 2 pts = sensitivity I00%, specificity 67%, accuracy 87%. The median SUV in carcinomas with axillary metastases was significantly higher than in those without (4.6 and 2.9, respectively), but there was a great SUV overlap between the two groups (interquartile ranges 2.7-7.2 and 1.9-4.5, respectively). Analysis of the ROC curve showed that with the best SUV cut-off value of 2.9, the sensitivity and specificity were 74% and 56%, respectively. In conclusion, PET showed good overall diagnostic accuracy in the detection of axillary metastases (86%) and the very high accuracy (95%) in N l a patients is of particular importance. However, falsenegative PET findings can be encountered. SUVs of breast carcinoma cannot predict the spread of the disease to the axilla even if higher values are often associated with axillary metastases.

ISOLATEDCEA ELEVATIONIN COLORECTALCANCERFOLLOW-UP: IMPACTOF 18FFLUORODEOXYGLUCOSEPOSITRONEMISSIONTOMOGRAPHY. We prospectively evaluated the sensitivity of whole body PET-FDG in the early detection of eolorectal cancer recurrence. Twenty-two consecutive asymptomatic patients were enrolled 12-42 months after initial surgery, on basis of elevated CEA levels (>5 ng/ml) detected during half-yearly follow-up examinations. Besides PET-FDG, all patients underwent a routine workup including chest X-ray, liver ultrasound, pelvis CT and colonoscopy or barium enema. PETFDG was performed without knowledge of other imaging modalities results. PET-FDG was performed in the whole-body mode, without attenuation correction, 60 min after iv injection of 370 MBq of FDG. No bladder catheter was used. Furosemide and forced iv diuresis were used to minimize bladder activity. The significance of PET abnormalities was further evaluated by additional imaging procedures (liver MR, chest CT or bone scan), guided biopsy or second look surgery. Twenty-four FDG positive sites were visualized in 19 pts: liver (n=5), lung (n=7), bone (n=2), site of initial resection (n=4) and extra-hepatic abdominal (n=6). All sites were further confirmed to be true positive recurrences. Routine imaging procedures detected 7/24 sites in 5/19 pts. Addition of chest CT, liver MRI and bone scan to usual workup permitted accurate staging in 12/19 pts (16/24 sites, missing 6/6 extrahepatic abdominal sites and non conclusive in 2/4 local recurrences). All sites detected by conventional imaging were positive on PET-FDG. Our data indicate that PET-FDG is the most accurate procedure for imaging patients with rising CEA levels following surgical treatment of colorectal cancer. Due to its high sensitivity, whole-body PET-FDG should be proposed as the first-line diagnostic and staging procedure when recurrence of colorectal cancer is suspected.

This work has been partially supported by an AIRC grant.

17.4 V. Ivan(~evic~A.Wolter, K-J. Winzer, H.-U. Aldinger, I. Reisinger, J.M. MOiler, D.L. Munz. Clinics for Nuclear Medicine and Surgery, University Hospital CharitY, Humboldt University, Berlin, Germany. IMAGING OF SUSPICIOUS BREAST LESIONS AND AXlLLARY LYMPH NODES WITH F-18-FLUORODEOXYGLUCOSE AND Tc99m-TETROFOSMIN IN PLANAR AND SPECT TECHNIQUE Since several agents seem to be suitable for scintimammography (SM), a comparative evaluation of the different methods available is needed. Hence, we prospectively investigated F-18fluorodeoxyglucose (FDG) and Tc-99m-tetrofosmin in both planar and SPECT technique in an intraindividual comparative study. Thirty-five patients with 36 tumours, clinical and/or mammographical suspicion of breast cancer and subsequent surgical proof (32 malignant, 4 benign turnouts) were included and injected with FDG (370 MBq) and tetrofosmin (750 MBq) within the last preoperative week. Lymph node metastases were verified in 11 patients. FDG and tetrofosmin imaging was started 40 rain and 5 min post injection, respectively, performing planar images in multiple views and SPECT using a dual-head gamma camera. For FDG imaging, 511 keV ultra-high energy collimators and an accordingly modified software were used. Overall sensitivities for breast cancer with planar FDG, planar tetrofosmin, FDG SPECT and tetrofosmin SPECT were 59%, 63%, 81% and 63%, respectively. Overall positive predictive values were 90%, 71%, 96% and 87%, respectively. Sensitivities for pT1 tumours (n=14) amounted to 36%, 50%, 71% and 50%, respectively, and for turnouts pT2 or larger (n=18) to 78%, 72%, 89% and 72%, respectively. The true positive/false negative values for lymph node metastases were 1/10, 2•9, 7•4, and 4/7, respectively. Because of the tow prevalence of benign lesions specificities and negative predictive values were not calculated. In conclusion, FDG SPECT has a higher sensitivity than SM with tetrofosmin for both breast cancer and lymph node metastases. Detectability of breast turnouts was size/stage dependent for all the imaging modalities investigated. Tetrofosmin SPECT did not prove superior to planar imaging except for lymph node metastases. FDG in planar technique should not be used.

882

17.6 R. HUSTINX, P. PAULUS, N. JACQUET, P. RICO. Departments of Nuclear Medicine and of Abdominal Surgery, University Hospital-Liege, Belgium. WHOLE-BODY FDG PET AS A FIRST LINE PROCEDURE FOR DETECTION AND STAGING OF RECURRENT RECTAL OR SIGMOID CARCINOMA : PRELIMINARY RESULTS.

It is now well established that FDG PET is a valuable tool to detect local recurrences of rectal carcinomas. In order to test the hypothesis that whole body FDG PET could be used as a first line procedure in the follow up of patients previously operated for rectal or sigmoid cancer, we reviewed data obtained from 34 patients in that situation. A total of 49 potential malignant sites were suspected on the basis of metabolic and/or conventional methods, distributed as follow : local sites: suspected n=16, malignant n=10; distant sites: suspected n=33; malignant n=26. These results were confirmed by histopathological examination or peroporative liver ultrasonography (n=32) or by follow up (n=17). The mean follow up was 9.3 months (min.4, maxA9). Overall, a malignancy was present in 23 pts (20 recurrences, 1 lymphoma, 1 lung cancer and 1 caecal cancer), l 1 pts investigated because of an elevation of the tumoral markers level or the presence of clinical abnormalities were free of disease. Results of whole body FDG PET were compared to those of the conventional methods (CM) , including chest X rays, CT of the thorax, abdomen and pelvis, US, MRI, and colonoscopy. Local sites: ~PET ,CM

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4TN 1

52FP

[

Distant sites: PET

21

I CM

20 patients presented a recurrence, either local, distant or both, from wich 16 were correctly detected and staged by PET (CM: 15). PET underevaluated 1 patient (CM: 1), overevaluated 2 others (CM: 2) and missed 1 recurrence (CM: 2). A recurrence was erroneously suspected by PET in 3pts, by CM in 5pts. 2 other malignancies were disclosed by PET as well as by CM. In one pt., PET correctly excluded a local relapse suspected by CT, revealed a caecal cancer but underestimated its spread. These data suggest that used as a first line procedure, whole body FDG PET could be cost effective in the follow up of patients previously operated for rectal or sigmoid carcinoma.

• Cardiovascular 18,1 Knuuti J. Hgrk6nen R, O.-P. Pitkanen, P. Nuutila, O.T. Raitakari, H. Laine, T. Takala, H. lida, J. Viikari, T. R6nnemaa. Dept. of Nuclear Medicine and Turku PET Center, Turku, Finland. CORONARY FLOW RESERVE IS REDUCED IN YOUNG ADULT TYPE 1 DIABETIC (IDDM) PATIENTS

Cardiovascular

co

18.3 R. Weise, D. Bailer, J. Holzinger, G. Notohamiprodjo, S. Betker, H. Montanus, J. Lehmann, U. Gleichmann Heart Center NRW, Bad Oeynhausen, Germany

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RELATIONSHIP BETWEEN LDL-CHOLESTEROL, CORONARY RESISTANCE AND FLOW RESERVE

The prevalence and incidence of coronary heart disease (CHD) are increased in IDDM. To investigate whether coronary vascular reactivity is impaired in young IDDM patients without diabetic complications myocardial blood flow and flow reserve were measured using positron emission tornography and ~SO-labelled water. We studied 12 nonsmoking male IDDM subjects (age 30.1_+6.6 y) and 12 healthy matched volunteers (CTRL). Subjects were similar with respect to blood pressure and serum lipid concentrations (Total, LDL- and HDL-cholesterol, trigycerides, Ape A-l, Ape B and Lp(a)) (ns. IDDM 'vs. CTRL). IDDM subjects were without microvascular complications and had normal exercise echocardiography. Myocardial blood flow was measured during euglycemic hyperinsulinemia (insulin infusion 1mU/kg/min) at baseline and after dipyridamole infusion. The baseline myocardial blood flow was similar in both groups (0.88+0.25 vs. 0.84_+0.18 mL.g~.min ~, CTRL vs. IDDM, ns.). The flow during hyperemia was lower in IDDM (3.2_+1.6 vs. 4.5_+1.4 mL.g~-min~, p=0.04). Consequently, coronary flow reserve (the ratio of flow during hyperemia and at baseline) was lower in IDDM than in CTRL (3.76+1.69 vs. 5.31_+1.86, p=0.04) and the total coronary resistance during hyperemia was higher in IDDM (53.7_+31.5 vs. 31.4_+11.6 mmHg.min.g.mL-1 p=0.03). In conclusion, coronary vascular reactivity is impaired in IDDM without microvascular comptications. This abnormality can not be explained by other known risk factors for CHD. The results imply early impairment of coronary vasomotion in IDDM patients which may represent an early precursor of future CHD.

It was the aim of the study to assess the myocardial blood flow after pharmacologic stress in 25 patients with angina pectoris (AP) and elevated LDL-cholesterol but without significant coronar artery disease (CAD) to calculate the minimal coronary resistance (CR,.a: mean arterial pressure/MBFn) and to compare these results with a reference group without CAD and both normal flow reserve (CFR) and LDL Method : Regional myocardial blood flow was measured at rest (MBt~R) and after infusion of 0.56 mg/kg dipyridamole (MBF,) using positron emission tomography (PET) and N-13 ammonia as flow tracer. Simultaneously, arterial pressure and heart rate were registered. After all data corrections myocardial and blood time activity curves were derived from regions &interest (ROI) over the myocardium and ventrical chamber and fitted using a three compartment model. Results:A reference group of 8 persons (RG) and 25 patients (P) were investigated. Study group (P): 12 males; 17 females; age: 58,3 _+ 10.1 years; LDL-chotesterol: 178 _+ 53 mg/dl; HDL: 52 _+ 22 mg/dl; LDL/HDL: 3.9 _+1.6; CRmi,: 0.46 + 0.13 mmHg/ml/min * 100g (p < 0.0l). RG : 3 males; 5 females; age: 51.5 + I2.6 years; LDLcholesterol: 142 +_ 24 mg/dl; HDL: 51 _+ 15 mg/dl; LDL/HDL: 2.96 _+ 0.87; MBF~ : 92 _+22 ml/min * 100g; MBFD: 372 _+ 75 ml/min * 100g; CR~io: 0.25 +_ 0.05 mmHg/ml/min *100g~ instantaneous coronary flow reseve (CFR - MBF,/MBFR): 4.0 _+ 1.3. A linear correlation between CR~i, and the ratio of LDL/HDL (r = 0.56; p < 0.01) was found. Conclusions:PET seems a useful non-invasive tool to assess coronary flow reserve in patients without significant CAD, angina and LDLcholesterol elevations. Clinical studies are necessary to clarit~ if LDLlowering improves coronary reserve in those patients.

18.2

18.4

M. Schmidt, P. Theissen, J. Crnac *, F. Baer *, E. Voth, H. Schicha Clinic for Nuclear Medicine and * Medical Clinic 111, University of Cologne, Germany

J. Kupfersehl~ge*1, HJ. KaiserI, L vom Dahl~, U. Buell~. Dpts. of ~NuclenrMedicineand 2Cardiology.AachenUniv. of Technology,Germany

NONINVASIVE MAGNETIC RESONANCE CORONARY A N G I O G R A P H Y - A C O M P A R I S O N W I T H CARDIAC CATHETERIZATION AND MYOCARDIAL SCINTIGRAPHY With the advent of ultrafast gradient echo sequences magnetic resonance imaging (MRI) is capable to visualize coronary arteries. However, the clinical value of this new technique has not been definitely established. We postulated that ultrafast MRI is able to image significant parts of the proximal coronary arteries and can detect haemodynamically significant stenoses as proven by myocardial scintigraphy. 20 patients (pts) (15 men, 5 women) with angiographically documented coronary artery disease (stenosis > 70%) were imaged with MRL 13 of them underwent myocardial SPECT with polarmap evaluation. MRI was performed using a k-space segmented 2D, navigator-controlled pulse sequence. Slice thickness was 5 mm with I mm overlap. From 60 proximal coronary arteries, 6 (10%) were excluded because of incomplete imaging due to patient claustrophobia. Mean length of visualized segments was 11_+4mm for the left main (LM), 32+13 mm for the left anterior descending (LAD), 13+10 mm for the left circumflex (CX) and 65+25 mm for the right coronary artery (RCA). The table shows the number of stenosis detected by magnetic resonance coronary angiography (MRCA) in comparison to angiography (Anglo):

A"

CHANGES OF REFERENCE PERFUSION VALUES FOR QUANTITATIVE MYOCARDIAL ~a~Tc-MIBI SPECT USING NON-TRANSMISSIVE ATTENUATION AND SCATTER CORRECTION (ASC) Reference data sets for myocardial peffusion values vary for the method used. The aim of the present study was to create a normal data base for exercise ~Tc-MIBI SPECT with ASC as it was developed in this laboratory~. 25 normals (17 females, 51 +14 y.) were recruited with a likelihood for CAD of 4 _+3%,a body mass in&x of 26.6 14.1 kg*ma and normal visual findings in the bicycle exercise ~Tc-MIBI SPECT (rate pressure product 28121 +7468 mmHg*mina). SPECT was performed 40 minutes after stress injection of 400 MBq ~rc-MIBI using triple-energy window acquisition, 2x180°, matrix 1282, LEHR coll., camera VERTEX, ADAC. Following filtered backprojection (Butterworth 5~ order, cutoff 0.3) with and without ASC, the left ventricular long axis was defined interactively. A vector analysis program, based on modified ECAT 6.4 software, Siemens-CTI, generated 25 regional uptake values normalised as percentage of the individual perfusion maximum. Quantification was performed twice and revealed an interobservervariability <4.3%. 25 normia

mesh

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18/24 0/0 7/11 1/2 10/11 From the 13 pts who underwent myocardiaI scintigraphy, MRCA detected haemodynamically significant stenoses as proven by scintigraphy in 9 pts. In these 9 pts MRCA corresponded to angiography. In 2 pts MRCA missed the angiographically documented stenoses. However, these stenoses were not haemodynamically significant as stress scintigraphy did not demonstrate a perfusion defect in these two pts. In only 2 pts MRCA was not able to visualize a haemodynamically significant stenosis, mainly due to incomplete vessel imaging. Thus, MRCA is able to image significant parts of the coronary arteries and appears to become a promising tool in detecting haemodynamically significant coronary artery stenosis.

The ASC gained a more homogenous accumulation by decrease (-) of apical and increase (~) of posteroseptal and basal uptake values. For clhucal use norreal data set consists of regional mean values minus 2.5 standard deviations. In conclusion, the adapted reference data base may improvequantitative interpretation of ~I'c-MIBI SPECT with ASC in posteroseptaland basal myocardium. # Schulz Gct al. (abstr.) Eur J Nucl Med 1996; 23:1049

883

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• Cardiovascular/Oncology Oncology

18.5 G. Sacchetti, A Baroli, AS. Bongo, E. Pittaluga, M Rudoni E. tnglese, Ospedaie Maggiore Novara, Dept. of Nuclear Medicine and Cardiology.

DETECTION OF MODERATE AND SEVERE CORONARY ARTERY STENOSIS WITH 99mTc-TETROFOSMIN MYOCARDIAL SPECT. The aim of this study was to determine the diagnostic accuracy of 99mTc-tetrofosmin perfusion imaging with respect to various degree of CAD. Su'ess-rest SPECT was performed on separate days in 80 pts (64M, 16F; mean age 61; 43 pts with previous myocardial infarction), within 6 mo of coronary angiography. Patients with CABG were not enrolled. Scintigraphic examinations were blindly and independently evaluated by 3 observers. A mild to severe reduction of uptake in the anterior, inferior or lateral regions was considered a marker of LAD, RCA, LCX disease. Isolated apical defects were considered not specific for individual vessels; thus 3 patients with only apical defectes were excluded from the analysis. Coronary stenosis was defined as a luminal diameter narrowing of > 50% in one or more vessels. Thirty six and 31 pts had single and multiple vessel disease respectively. Severe stenosis was defined as a proximal stenosis of > 75% or a peripheral stenosis of > 90%. Sensitivity and specificity in severeIy stenosed vessels were: 80, 65% for LAD; I00, 46% for RCX; 58, 78% for LCX territories. When considering all the significantly stenosed vessels, a decrease in sensitivity was observed (to 59% for LAD, 88% for RCA, 47% for LCX) while specificity values remained unchanged. No changes in sensitivity or specificity were observed in regions supplied by severely stenosed vessels when regions with previous myocardial infarction were excluded, whilst only a borderline decrease of sensitivity was observed in RCA and LCX territories extending the analysis to all the significant stenoses. 99mTc-tetrofosmin sensitivity for the localization of individual stenosed vessels is only moderate when all hemodynamicaiiy significant stenoses are considered, but diagnostic accuracy for severe disease of individual vessels seems appropriate for clinical decision making with the exception of a low specificity in RCA territories, probably due to inferior wall attenuation artifacts,

19.1 M. Raderer, A. Kurtaran, M Hejna, F. Vorbeck, P Angelberger, W.Scheithauer, and LVirgolini. University of Vienna, Depts of Nuclear Medicine, Internal Medicine I and Radiology, and Research Center Seibersdor£ Jz3I-VASOACTIVE INTESTINAL PEPTIDE RECEPTOR SCINTIGRAPHY IN PATIENTS WITH COLORECTAL CANCER Recent studies have shown that various gastrointestinal tumours express substantial amounts of VII' receptors, providing the basis for the use of 123I-VIP as a radioligand. We report the results obtained in 80 consecutive patients with colorectal adenocarcinomas, who underwent scanning by means of 123I-VIP (1 ~g, ~ 150 ]~lBq). Thirteen patients were free of tumour after complete resection of Dukes' C cancer, 8 patients presented with primary and 14 with locally recurrent tumours, but were free of metastases Ten patients had locally recurrent disease and liver, lung or lymph node metastases, respectively. Disease confined to organ metastases (i.e. liver, lung or lymph nodes) was present in 35 patients. The primary or recurrent turnouts ranged from 3 - 16 cm, and the size of metastases was between 1 - 13 cm in diameter. Scan results were evaluated by 2 nuclear medicine physicians independently in a blinded way, and results were then compared with CT-scans not older than 4 weeks. Seven out of 8 primary (87%) and 21/24 (82%) locally relapsing cancers were imaged with 123I-VIP. True negative VIP-scans were obtained in all 13 patients in whom the cancers had been euratively resected. MI patients with lymph node metastases showed positive VIPscans (4/4), and true positive scans were obtained in 25/28 (89%) patients with liver metastases and in 2/3 cases with lung metastases. In 4 patients with relapsing cancer, the VIP-scan indicated the presence of disease before CT, and in 2 patient the diagnosis of scar tissue instead of a local recurrence of rectal cancer as suggested by CT could be established. We conclude that 123I-VIP receptor scanning is a sensitive method for radidimaging of colorectal cancer with the potential to provide additional information to conventional radiologic methods.

18.6

19.2

J Knu~ti, R HtirkOnen, O-P Pitk~nen, OT Raitakari, P Nuutila, K Porkka, I Nuotio, H lida, T ROnnemaa, J Viikari, DeN of Nuclear Medicine and Turku PET Center, Turku Finland.

S.R. Li, C. Bischof, S. Kapiotis, Q. Yang, M. Peck, P. Angelberger, H.A. Welch, P. Valent and I. Virgolini, Depts of Nuclear Medicine, H~imatologie and Laboratory Diagnostics~ University of Vienna, and Research Center Seibersdorf, Austria. Gescllschafi for Biotechnologische Forschung mbH, Abteilung of Gene Expression,Braunschweig,Germany. SPECIFIC BINDING OF 1-123-VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)-165 TO ENDOTHELIALCELLS AND TUMOR CELLS: IMPLICATIONFOR IMAGINGVASCULARIZEDTUMORS ? VEGF may play an important role in tumor growth and metastases formation and binds to at least two tyrosine kinase receptors to mediate its activities. The binding sites for VEGF are mainly expressed on endothelial cells and may be also present on malignanttumorsand tumor cell lines. In this study, by using I123-VEGF-165, we characterized the VEGF binding sites expressed on human umbilical vein endothelial cells (HUVEC) and various human cell lines (lung fibroblast cell line, mast cell line HMC-1, basophil cell line KU812, monocyte celt line U937, humanhepatic endothetioma cell line HEP-1, human hepatoma cell line HEP-G2, human hepatoma cell line HEP-3B, Blymphocyte cell line RAJI) as well as a number of human tumors (breast cancer, melanoma, renal cell cancer, meningioma, etc.). In addition, the functional properties of 1-123-VEGF were investigated. Two classes of high affinity binding sites on the cell surface of HUVEC (Bmaxl, 1580+_325 binding sites/cell, Kdl, 8+-2 pM; Bmax2, 9500+-846 binding sites/cell, Kd2, 86+-19 pM) were revealed. High affinity binding sites for 1-123-VEGF-165 were also found on many tumor cell lines (lung fibroblast cell line, HMC1, HEP-I, HEP-G2, HEP-3B and KU812) and primary tumors (melanoma, renal cell cancer, meningioma,and breast cancer). The binding of 1-123-VEGF-165 was inhibited by unlabeled VEGF-165, but not by high concentrations of several other peptides (such as vasoactive intestinal peptide, tumor necrosis factor, somatostatin). 3-H-thymidine incorporation was dose-dependent stimulated in response to 1-123-VEGF. This study demonstrates specific binding sites for 123-I-VEGF-165 on human endothelial cells and a variety of tumor cells. We conclude that radiolabeled VEGF-165 may be useful for the in vivo localisation of vascularized tumors.

CORONARY FLOW HYPERLIPIDEMIA

RESERVE

IN

FAMILIAL

COMBINED

We have previously shown that myocardial blood flow reserve is impaired in young aduRs with familial bypercholesterolemia. We have also found that the other standard risk factors are associated with the abnormalities in flow reserve. The familial combined hyperlipidemia (FKH) has been also suggested as a strong risk factor for coronary heart disease. To investigate whether functional abnormalities in coronary vasomotion can be detected in FKH we studied 16 male young patients (age 32+3.4 y) and a matched group of 14 healthy subjects. The myocardial blood flow was measured at the basal state and during dipyddamole induced hyperemia using PET and 150-labeled water. The FKH patient group consisted of patients with hyperlipoproteinemia classes Ila, lib, IV. No difference were found in heart rate and blood pressure between the subject groups. The baseline myocardial blood flow was similar in the patients and controls (0.77+0.17 vs. 0.77+0.19 mL.g-l.min-1, respectively, ns.). A significant increase in the flow was obtained in both subject groups by dipyridamole infusion. However, the myocardial flow at maximal vasodilatation was not significantly reduced in the patients as compared to the controls (3.2+1.4 vs. 3.6+1.6 mL,g-~.min"1, ns.) Consequently, coronary flow reserve (the ratio of flow during hyperemia to flow at baseline) was similar in the patients and the in controls (4.3+2.0 vs. 4.4+1.8, ns). In contrast to the findings obtained in patients with familial hypercholesterolemia, coronary blood flow and flow reserve appear not to be reduced in young men with FKH. The results suggest FKH as a is weak risk factor for coronary functional abnormalities in young adults.

884

II Oncology

19.3 A. Kurtaran, W. Schima, M. Raderer~ Ch. M~ller, J~ Pidlich, G. Novacek, P. Angelberger, and I. Virgolini. . D e p a r t m e n t s of Nuclear Medicine, Oncology, Radiology and Gastroenterology, U n i v e r s i t y of Vienna, Austria.

Tc-99m-NEOGALACTOALBUMIN(NGA) INSULIN IN THE .MASS L E S I O N S .

DIFFERENTIAL

AND

19.5 J. Lister-James, M.N. Coel, J. Ko, Y.M. Baran, E.M. Aten. Diatide, Inc., Londonderry, NH. and The Queen's Medical Center, Honolulu, HI.

DETECTION OF NON-SMALL CELL LUNG CANCER (NSCLC) WITH Tc-99m P829: PRELIMINARY CLINICAL EXPERIENCE

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1-123-TYR-(AI4)-

DIAGNOSIS

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T c - 9 9 m - N G A is a liver imaging agent ti~at binds to hepatic-binding protein, a hepatocyte-specific receptor. We describe the imaging pattern of hepatoce!lular carcinoma (HCC) , m e t a s t a t i c liver lesions (MTS}, and focal nodular hyperplasia {FNH) using T c - 9 9 m - N G A in combination with 1-123-TyrIAI4) -insulin. In this study we investigated 45 patients with HCC, 15 patients witil MTS, and 12 patients with FNH. All HCC lesions as well as m e t a s t a t i c liver lesions were identified as cold spots immediately after i.v-injection of !.00-150 MBq/50 nmol TC-99m-NGA, while in all patients with FNH a normal or even increased acclmulation of Tc99m-NGA was observed. For the further aifferen~iation of HCC from MTS the 1-123-Tyr(Al4)-insrLlin scintigraphy is needed. In our study all HCC lesicns showed an accumulation of 1-123?yr- (AI4) -insulin (i00-15@ MBq/l]ag) , i n d i c a t i n g the presence of insulin receptors which we could demonstrate in our in vitro studies. NO significant accumulation I- 123-Tyr- (AI4 ]-insulin was observ,=~d in MTS, since NTS express no recepLors spesifiz for I-!23-Tyr-(A14)-insulin. We conclude that this dual tracer method is clinically useful and is easily to performe in the differential diagnosis of focal liver lesions.

The purpose of this study was to evaluate Tc-99m P829, a somatostatin receptor binding peptide, for the detection and localization of NSCLC. The 7 patients studied (5 males and 2 females, mean age 62.8 y) all were diagnosed with NSCLC: 2 adenocarcinoma, 2 poorly differentiated squamous cell lung cancer, 2 stage 4 NSCLC, and 1 bronchoalveolar cancer. The mean dose of Tc-99m P829 was 0.52 GBq (range 0.3-0.56 GBq) and l l g g (range 5-20gg) peptide. Planar images were obtained starting at 15 minutes and planar and SPECT images were obtained at 2 to 3.5 h post-injection. Uptake of Tc-99m P829 was seen in the primary lung tumor as early as 15 minutes post-injection in all patients. SPECT imaging was considered necessary for complete evaluation of metastases. Metastatic uptake was seen in 6 patients with confirmed mets as follows: 2 of 2 patients with nodal lung mets, 2 of 4 with brain mets, 3 of 3 with bone mets, 1 of 1 with extensive liver mets and 1 of t with abdominal mets. Of the 2 patients with false negative brain met Tc-99m P829 uptake, one patient was undergoing radiation therapy to the head, and one patient had multiple small brain mets of 5- l t mm. One patient with extensive liver mets imaged as "cold defects" with Tc-99m P829 was undergoing chemotherapy. There was 1 new finding by Tc-99m P829 of brain mets in 1 patient which was confirmed subsequently by MRI, and 1 new finding of an enlarged neck node confirmed by physical exam and follow-up CT. One patient had a new finding by Tc-99m P829 of additional uptake in the opposite lung from primary tumor which was not confirmed. In summary: the results showed Tc-99m P829 had an accuracy of 100%(7/7) for detection of primary NSCLC tumors and 82% accuracy (9/11) for detecting sites of metastatic disease. No adverse events were experienced in any of the patients. Tc-99m P829 shows promise for the detection and localization of NSCLC.

19.4

19.6

R. Larisch U, K.-W. Schulte 2, H. Vosberg I, T. Ruzicka=, H.-W. MtillerG~irtner ~,3

Department of Nuclear Medicine I and Department of Dermatology 2, University of D#sseldorf Germany," Institute of Medicine, Research Center Jiilich 3

H.C. Steinert, P. Blauenstein, R. B6m, Th. Berthold, G.K. yon Schulthess, P.A. $chubiqer. Departments of Medical Radiology and Dermatology, University Hospital, Z0rich, and the Paul Scherrer Institute, Villingen PSI, Switzerland.

D I F F E R E N T I A L I N VIVO A C C U M U L A T I O N O F 123I-IBZM IN M E L A N O T I C AND A M E L A N O T I C M E L A N O M A M E T A S T A S E S

[BR-76]-BROMODEOXYURIDINEPET IMAGING OF MALIGNANT MELANOMA: FIRST RESULTSIN PATIENTS

1231-iodobenzamide (IBZM) is a specific antagonist of dopamine D 2 receptors and has a substantial affinity for malignant melanomas. This has been attributed to specific D2 receptor binding on melanoma cells. However, IBZM binding to melanoma metastases occurs 24 hours after injection, which is much later than specific D2 binding. This points to another mechanism of IBZM binding to melanoma cells. The aim of this study was to characterize IBZM binding melanoma patients clinically and histologically to shed light on the nature of this mechanism. M e t h o d s : Twenty-one patients with proven or suspected metastases of a surgically removed malignant melanoma entered this prospective study. Whole body scans, planar scintigrams and SPECT scans were performed 2 to 5 hours after intravenous injection of 185 MBq IBZM and on the following day. Result, s: The suspected diagnosis of metastatic cancer was later confirmed in 17 patients. Twelve of these patients had a melanotic and 5 had an amelanotic subtype of the tumor. There was IBZM accumulation in the metastases of 10 of the 12 patients with melanotic melanoma and in none of the 5 patients with the amelanotic tumor type (p < 0.01; chi-squaretest). IBZM accumulation occured in none of the 11 amelanotic metastases but in 20 out of the 25 melanotic metastases (p < 0.001). The sensitivity is thus 83 per cent for the detection of melanotic melanoma metastases on a patient basis and 80 per cent on a lesion basis. No false positive IBZM accumulations occurred in our patients, C o n c l u s i o n : IBZM binds to melanotic malignant melanomas with high specificity and moderate sensitivity but not to amelanotic melanomas. Our data suggest that the tracer does not bind to membrane dopamine receptors of the tumor but is built in or closely bound to intracellular melanin.

® It is known that Bromodeo×yuridine (BrUdR) can be substituted for thymidine in DNA. The aim of this study was to evaluate [Br-76]BrUdR uptake in melanoma metastases and to analyse the radiopharmacokinetics in the blood. • Until now, seven patients (6 male, 1 female, age range 23-69 years) with known metastizing melanoma have been enrolled in the study. BrUdR was labeled with Br-76 ( t l / z = 1 6 h). For in rive studies, 25-50 MBq [Br-76]-BrUdR was injected and dynamic PET scans for (50 min were performed. At 1 h p.i. whole-b0dy PET scan with attenuation correction was acquired in all patients. Additional whole-body PET scans were obtained at 4 or 24 h p.i. in three patients. Multiple bood samples were taken until 60 min p.i.. • The maximal uptake of [Br-76]-BrUdR in metastases was reached between 15 and 25 min post injection with a ratio (TU/nonTU) of 1.5. Only metastases greater than 1.5 cm were detected, in contrast to FDG PET, four brain metastases were visualized with BrUdR PET. Analysis of blood samples showed a fast metabolism of [Br-76]BrUdR with a half life of 3 to 10 min and the formation of a highly variable amount of bromouracil. At 30 min post injection, the main form of the radioactivity was free bromide. In vitro incubation (18h) at room temperature of [Br-76]-BrUdR exhibited only the formation of bromouracil without free bromide. • [Br-76]-BrUdR is taken up in melanoma metastases. The rapid metabolism of the radiotracer might limit its potential of in rive imaging of tumor proliferation. Correlation of the imaging results with in vitro measurements of tumor proliferation are in progress.

885

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•

Infection/Inflammation

Infection/Inflammation 20.1 S.Gratz, T.H.Behr, A.Herrmann, H.Zappel 2 , W.Becker Department of Nuclear Medicine and Pediatrics 2 of the Georg August University, GOttingen, Germany

Neonates and Infants With Fever Of Unknown Origin: Sensitivity, Specifity and Diagnostic Accuracy of Immunoscintigraphy with the Antigranulocyte Antibody BW 250/183 Rationale : Fever of unknown origin (FUO) is is higher than 38,3°C, the duration of fever exceeds 3 weeks and a correct diagnosis in the first week of hospitalization is not possible At the age of neonates and infants, the right diagnosis of fever of unknown origin (FUO) many times is difficult and unsatisfactory .In this retrospective study the clinical value of 99mTc- labelled antigranulocyte antibodies was investigated. Methode :33 immunoscintigraphies were performed with an activity of 185-259 MBq ggmTc-labelled antigranuloeyte antibodies ( BW 250 / 183 ) in 30 neonates and infants ( 21 boys, 9 girls, mean age 29.4 ± 2 months), who suffered from fever of unknown origin. Immunoscintigraphy was done as wholebody images ( n=7 ) or single planar images ( n=23 ) 4h and 24h p.i. In case of children with known cardiac failure, SPECT of the thorax was performed for diagnosing endocarditis ( n=2 ). For verification, the results of the immunoscintigraphy were compared to the radiologic findings (conventional radiography = 5, MRI = 4 ), bioptical evaluations ( n=2 ) and clinical follow - up under specific therapy. Results : At 12 / 30 children (40%) the correct diagnosis of an infective focus was possible with the immunoscintigraphy. The sensitivity and specifity of diagnosing correctly infective foci was _> 95% ( n=12; nasopharyngitis=l, colitis=2, infection of the central permanent catheter tip =2, middle ear infection=l, spondylitis/discitis=3 osteomyelitis=2, umbilical infection=l). The diagnostic accuracy of single planar images (7/12; 58.3%) was superior to wholebody images (5/12; 41.7%). In the later, a correct anatomical location was not possible in one patient (paranasal sinus / tympanic cavity ). A lower specifity was found in cases of vertebral body infections, since all showed photopenic lesions (spondylitis TH12=2, L4=1). No infective focus was found with the immunoscintigraphy at 18 / 30 children ( 60% ). In this group of children, the main reason for FUO was the chronic juvenile rheumatoide arthritis with 27.7 % ( n=5 ). An exclusion of endocarditis at children with cardiac failure was possible in the case of 2 children with SPECT. In 4118 (22 % ) patients a postive location of a infective focus was neither possible with immunoseintigraphy nor with c~inica[ examinations. In this case, the fever disappeared under appropriate antibiotic therapy after few days of therapy spontaneously. Conclusions : 1.) All known bacterial foci (n=5) were correctly found with high diagnostic accuracy, sensitivity and epecifity ( colitis =2, umbilical infection =1, osteomyelitis=2 ). 2.) All the other foci (n=7) showed improvement in the follow - up after appropriate antibiotic therapy 3) The immunoscintigraphy is usefull for the diagnosis or exclusion of suspected bacterial foci.

20.3 E.Th.M. Dams 1, W.J.G. Oyen ~, O.C. Boerman ~, R.A.M.J. Claessens/, A.B. Wymenga 2, J.W.M. van der Mee/, F.H.M. Corstens ~. University Hospital Nijmegen ~ and St. Maartensklinield, Nijmegen, The Netherlands.

TECHNETIUM-99m-HYNIC-HUMAN IMMUNOGLOBULIN G FOR DETECTION OF INFECTION AND INFLAMMATION A novel method to label polyelonal human immunoglobulin G (lgG) with Tc99m via the nicotinyl hydrazine derivative has shown promising results in detection of experimental infection. In this study, Tc-99m-HYNIC-tgG was directly compared to In-111-DTPA-IgG in patients suspected of infectious or inflammatory disease. Thirty-seven patients (22 females, 15 males; mean age 54 yr, range 17-78 yr) with 39 suspected infections or inflammatory loci, were prospectively studied. After administration of 740 MBq Tc-99m-HYNIC-IgG, imaging was performed at 4 and 24 hr postinjection. To avoid cross-over activity, In-I l l-IgG was injected 24 hr after Tc-99m-IgG, and imaged at 4, 24 and 48 hr postinjection. The scintigraphic results were confirmed by microbiological, histological, radiological and clinical methods. Tc-99m-HYNIC-IgG and In-111-DTPA-IgG scintigraphy showed 100% concordancy. All 17 patients with proven infection or inflammation (19 loci, mainly localized in the locomotor system), had positive scintigraphic findings. No falsenegative seintigrams were recorded. In three patients, the scintigrams were concordantly false-positive. As a result, the sensitivity and specificity of imaging infectious or inflammatory foci with Tc-99m-HYNIC-IgG and In- 111-DTPA-IgG in these patients were 100% and 85%, respectively. Tc-99m-HYNIC-IgG scintigraphy is equally effective as In-1 l l-DTPA-IgG scintigraphy for detection of infection and inflammation. The apparent physical and logistic advantages of Tc-99m over In-111, makes Tc-99m-HYNIC-IgG a promising new radiopharmaceutical for infection/inflammation imaging.

20.2

20.4

D.M. Goldenberg, C. Pinsky., W. Wegener, B. Barron, C. Hanna, and A. Passalaqu& Garden State Cancer Ctr., Belleville, NJ; Immunomedics, Inc., Morris Plains, NJ; U of Texas Med. Sch. Houston, TX; Spartanburg Reg. Med.Ctr., Spartanburg, SC; and Children's Med.Ctr. of Akron, OH

A. Burroni D. Volterrani, P. Bertelli, A. Vella and A. Vattimo. Department of Nuclear Medicine, University of Siena, Policlinico "Le Scotte", Viale Bracci, 53100 Siena, Italy.

USE OF LEUKOSCAN ®, AN ANTI-GRANULOCYTE ANTIBODY FRAGMENT, IN THE EVALUATION OF PATIENTS WITH ACUTE NON-CLASSIC APPENDICITIS

EARLY PULMONARY PATIENTS WITH INFECTIONS.

The objective of this study was to evaluate the safety and imaging efficacy ofLeukoScan®(Immunomedics, Inc., Morris Plains, NJ), a 99mTc-labeled anti-granulocyte (NCA-90 epitope) fragment of the IMMUMN3 murine monoclonal antibody, in a group of patients with suspected acute non-classic appendicitis. The study was conducted as a multicenter, open label, clinical trial, involving 109 patients (60 females and 49 males). The patients received 10-30 mCi LeukoScan, depending on age, and were imaged at 15-30 rain, l, 2, and 4 hr p.i. Clinical diagnosis was made on the basis of laparotomy and histology (36 patients), or by followup for 7-14 daysifno surgerywas undertaken (73 patients). Safety was evaluated by recording adverse reactions, vital signs, clinical laboratory tests, and human anti-mouse antibody (HAMA) levels. Of the 109 patients, 94 were included for efficacy analyses, while 15 failed to meet all protocol criteria. The results showed that LeukoScan images had a sensitivity of 90.5% for appendicitis, a specificity of 84.9%, a positive predictive value of 63.3%, and a negative predictive value of 96.9%. Most of these imaging studies were evaluated as positive by planar images within 4 hr; some (16%) required SPECT at 4 hr. No significant adverse events were reported, and no HAMA elevations were found. It is concluded that LeukoScan is an imaging agent that accurately detects focal inflammation/infection in the setting of suspected atypical appendicitis, and is safe, well-tolerated, and has virtually no immunogenicity. A patient presenting with signs and symptoms of non-classic appendicitis and a negative LeukoSean study has a 97% predictive value of not having this acute disease. (Supported in part by Immunomedics, Inc.) 886

WBC-HMPAO-Tc99m UPTAKE I N CLINICAL MUSCULO-SKELETAL

A diffusely increased uptake of WBC-HMPAO-Tc99m in the lungs has frequently been observed in early views (lh post-injection) during routine leukocyte scanning in patients with inflammatory diseases. The aim of our study is to evaluate if this pulmonary uptake of white bl(xxi cells is a non-specific sign of active inflammation and if this finding has a correlation with the scintigraphic results and erythrocyte sedimentation rate (ESR) values. 26 patients (16 males and 10 females; mean age 56.1±18.8) with a clinical suspicion of musculo-skeletal infection were referred to our department for scintigraphic evaluation. The leukocyte scan was performed at 1 (early) and 5 (delayed) hours after i.v. injection of 370 MBq of WBC-HMPAO-Tc99m. Regions of interest tROis) were -drawn over the lungs (P), liver (L) and the lumbar tract of the spine (S) from posterior and anterior views. The geometric mean of each ROI was calculated and P/L and P/S mean ratios of count rate were obtained. These data were compared with scintigraphic results and with ESR values: a non-parametric statistical evaluation was also performed. In spite of a greater value of P/L at 1 hour revealed in the group of positive scintigraphic patients (n=15; mean=0.56) in comparison with negative patients (n=l 1; mean=0.49), no statistical difference was found between these two groups, particularly if we analyzed the P/S ratio. On the other hand, we found a considerable correlation between the early lung uptake and the ESR values (P/L ratio: p=0.035; P/S ratio: p=O.005) using the Speannan's rank correlation test. No significant correlations were found when comparing delay ratios with ESR values. Therefore we believe that the leukocyte trapping in the lungs may be considered a non-specific sign of acute inflammatory disease, as are ESR and C-reactive protein values. The early pulmonary uptake could be a phenomenon related to leukocyte margination, probably due to activation by cytokines during passage through inflammatory loci.

[] Infection/Inflammation/Physics Physics 20,5

21,1

R D Gunasekera, A Notghi & L K Harding, Physics and Nuclear Medicine Department, City Hospital Trust, Birmingham, U K.

Y. D'Asseler 12, M. Koole 12, Y. De Deenel,C. Van de Wiele ~, R. Achten ~, R.A. Dierckxl,. I. Lemahieu 2 ~University Hospital of Gent (UHG), 2 ELIS-MEDISIP university of Gent, Belgium.

CLINICAL EXPERIENCE OF WHITE CELL SCINTIGRAPHY White cell scintigraphy is extensively used in the localisation of infection and inflammation. A total of 1129 scans between 1983 and 1996 were reviewed, (422 indium and 707 technetium). There were 1014 patients within an age range of 1-93 years, mean (SD) 56 ± 20 years. Fifty five percent were referrals from other hospitals and 2% were paediatric patients. Indium labelled cells were used exclusively from 1983 to 1988 with a transition to technetium in 1991 and only 1% scans using indium from 1992 until 1996. There was a p e a k in number in 1991 and a decline thereafter, currently with an average of i00 studies per year. The majority of scans were for orthopaedic problems (49%) followed by abdominal sepsis and bowel inflammation (27%), cryptegenic fever (16%) and vascular graft and soft tissue/miscellaneous infection (8%). Technetium labelled white cells compared with indium had more positive scan findings in hip and knee prosthetic infections (35% vs 14%), cryptogenic fever (14% vs 6%), and had equal results in the diagnosis of abdominal sepsis and bowel inflammation (48% vs 46%). In suspected osteomye!itis of spine with a positive bone scan, 5% showed an increased uptake whilst 23% had cold lesions. WBC scans were less likely to be abnormal in cryptogenic fever, in contrast to >90% symptomatic patients with active inflammatory bowel disease and 44% of vascular graft infection. Gallium scans should be considered in the diagnosis of chronic infections such as TB, cryptogenic fever and chronic infections of hip and spine.

EVALUATION OF THE ACCURACY OF MRI-SPECT COREGISTRATION USING 8 DIFFERENT ALGORITHMS. The aim of this study was to assess the accuracy of coregistration using 8 different algorithms (Nuclear Diagnostics Hermes software on a Sun Ultra Sparc 2). In order to simulate clinical studies (2headed SPECT) a Hoffman brain phantom was filled with 3.5 mCi Tc-99m. For MRI (1,5 T), the phantom was filled with water, doped with Ga-DTPA for contrast enchancement. For both examinations phantom images were acquired using the clinical protocol. The images were matched using Uniformity !ndex, Count Difference, Shape Difference, Sign Change, Variance, Square Root, 2__DD and 3D Gradient as similarity measure and the Simplex minimisation method. The scaling parameters were constrained. The accuracy was evaluated using external 99mTc point sources (1.5 gCi) for SPECT and small plastic tubes in a cross configuration filled with water for MRI. The average misregistration (avg.) and its standard deviation (sd.) together with the coregistration time are listed below : UI CD SD SC V SR 2DG 3DG avg(mm) 4.6 4.3 i0.0 14.1 4.5 4.1 13.5 12.8 sd(mm) 2.9 2.5 3.7 4.7 3.0 3.1 6.4 2.9 time(s) 85 i01 81 88 185 231 45 58 Preliminary conclusions are (a) for all coregistration algorithms the needed time was clinically acceptable, (b) uniformity index, count difference, variance and square root are the most accurate for MRI-SPECT registration, while the other similarity measures give a less accurate result.

20.6

21.2

M.P. Iturralde, M.Mc Donough,Medforum Hospital Specialists in Nuclear Medicine and Otorhinolaryngology. Pretoria, South Africa.

V. Bosniakovic, Center for High Technology, CCS and Vinca Institute for Nuclear Sciences, Belgrade, Yugoslavia; ADAC Laboratories, USA.

Tc- 99M-HMPAO LABEI.!.FD LEUCOCYTES IN THE DIAGNOSIS OF C H R O N I C SINONASAL I N F L A M M A T O R Y DISEASE.

Chronic inflammatory disease of the paranasal sinuses and nasal fossae is a common and frequently underdiagnosed clinical problem which may he complicated by repeated viral and/or bacterial infections usually seen in immunocompromised patients. Progressive tissue damage in these patients is associated with daily purulent mucus production and chronic colonisation of airways showing persistent structural abnormalities on X-rays. In most cases, the diagnosis of an acute infection episode is difficult and is often based on non-specific symptoms such as fever, pain, increased nasal secretion and/or blocked nose. Using Tc-99m HMPAO labelled leucocytes we have imaged 57 patients with suspected or verified sinonasal infection to evaluate the usefulness of this scintigraphic procedure. Mixed radiolabelled WBC's (Tc-WBC) were injected i.v. Images were obtained with a gamma camera at 4 and 20 hours in most cases. Abnormal focal uptake and concentration of Tc-WBC was found in 137 paranasal sites in 38 patients and in 19 cases imaging was negative. These images were correlated with other parameters of acute infection such as, leucocytes counts, ESR, C-reactive protein, and mucus cultures as well as with CT scans and endoscopy. The best correlation was obtained with CRP which was higher in patients with a positive sinonasal scan than in negative cases. Tc-WBC imaging predicted acute infection better than CT scans. Results obtained clearly demonstrated the value of Tc-99mHMPAO labelled WBC scintigraphy in portraying acute infection in patients with chronic sinonasal airways inflammatory disease and in assessing the response and management of endoscopic surgery and/or antibiotic therapy.

THE DESIGN OF A UNIVERSAL NUCLEAR MEDICINE IMAGER The detector head is designed for a Universal Nuclear Medicine Imager (UNMI) capable of performing planar, SPECT and PET studies. The head is to be incorporated in a dual headed UNMI machine, based on position sensitive (PS) area, i.e. gamma camera type of the detectors (fitted with coincidence electronics for PET studies, without lead collimators). In order to retain planar - SPECT performances while improving (over the coincidence SPECT systems) the PET ones, the means is devised for determining depth of interaction (DOI) in a thick Nal (TI) crystal by newly designed light collimators (LC). The total 6/8"crystal thickness is divided in two halves, each 3/8" thick, by insertion of a thin (e.g. 0.03") quartz glass layer; these layers are also added to the external lower and upper (facing conventional PM tubes array, around 0.125" thick) surfaces of the crystal to fdrm the intemal LC channels, by their reflectively (specular) polished coupling surfaces. These channels (serving for DOI determination) according to the light refraction / reflection taw direct the light reflected from quartz layers (as exceeding the critical angle ) through NaI(TI) layers to the extemat LCs coupled to the lateral NaI sides; these are connected to the specific DOI determining PM tubes via quartz glass optical cables. DOI coincidence circuit, connecting conventional PS and DOI PM tubes arrays, identifies a DOI layer and shifts an, x, y, address to the particular DOI memory stuck. The UNMI design is likely to retain the spatial resolution of PS detectors for low energy, improve it (with improved efficiency) for medium energy single photon emitters, and to improve efficiency and spatial resolution in PET studies done by PS detectors using thicker NaI(TI) crystals; the latter is achieved by enabling a correction for parallax error, which in turn increases the sensitivity by widening the acceptande angle in both transverse and axial directions.

887

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= n

eID x.__

Q. m

6

[] Physics 21.3

21.5

D.G. Popescu 1 , M. Fauchet 2 , S. Askienazy 1 , and V. Sauret 2 - 1H6pital SaintAntoine, Paris, 2CIMA Compiegne, France

D. Hamilton, Department of Medical Physics, Forces Hospital, Riyadh, Saudi Arabia.

E~

MINI BETA PROBE WITH SCINTILLATING FIBRE DETECTING MtLLIMETRES TUMORS. Inlra-operative probes are small instruments which proved their efficiency in detecting tumors and helping for tumor surgery. The use of gamma rays is a limiting factor due to the poor shielding (if any) of the crystal, resulting from Compton scattering, and non specific distribution of the radioactivity. In the contrary, by using the beta rays, we overcome these disadvantages. In order to facilitate the use of beta emitters, we developped a hand-held probe for intra-operative use (patented device). This probe was designed and realised in order to fulfil two objectives : a) to offer a good handiness and b) to be easy to use with endoscopic systems. This probe is made of a two metters long scintillating fiber to detects the beta rays and to selfconduct produced light to an amplifier. This probe is light and protected for sides coming radiations. Its flexibility permits reaching hidden points. This probe is disposable. The probe is connected to specific electronics with a microprocessor for signal lreatement and information handling. A simple algorithm has been developped to reconstruct the beta energy spectrum from integral measurements at different thresholds. Five isotopes (32p, 67Ga,90y,131I]86Re) have already been tested. The probe has a efficiency which enables to distinguish in vitro simulated small tumors (few hundreds of cubic millimiters) with hundred thousands Becquerel. This, almost background free, small size, very light probe just started in vivo testings. It seems to be a very handy tool for radioguided surgery.

EVALUATION OF GENETIC ALGORITHMS RENAL SCINTIGRAPHY

Armed

IN CARDIAC AND

Artificial neural networks (ANNs) are being introduced into nuclear medicine as aids in pattern recognition. They are well suited to solving linearly non-separable problems because they use internal feature detectors to discover multiple non-linear interactions among input variables, which permits a complex partitioning of the pattern space. Correct design of the ANN architecture is often critical to the performance of the network but choosing the correct data presentation strategy, network architecture and division of data into training and testing sets relies on a certain amount of trial and error on the part of the researcher; which can be very time consuming. A new computer technique has recently become available which uses genetic algorithms to genetically engineer the optimal architecture of ANNs. A comparison of the effectiveness of manual and automatic network design has been undertaken for pattern recognition in SPET myocardial perfusion and planar renography data. The results show accuracies of 87% and 81%, respectively, for the automatic network designs compared to 92% and 77% for the manual designs. The conclusion is that genetically engineered networks are easier to produce and that they produce almost as good results as the manually architectured techniques.

21.4

21.6

P. Ryyn~inen~, S. Savolainen 1~2,J. Benczik 3, M. Kulvik 4,5, J. V~ih~italo6, M. K~irkk~iinen3, Depts of 1Phys and 3Clin Vet Sci, 41nst of Biotech, 6Lab. of Radiochem, University of Helsinki, 2Depts of Radiology and

C. Groselj, M. Kukar °, J. J. Fettich, I. Kononenko °. University Medical Centre Ljubljana, °Faculty of Computer and Information Science Ljubljana, Slovenia

SNeurology, Helsinki University Central Hospital, Finland KINETIC MODELS OF BORONOPItENYLALANINE (BPA) The planned treatment approach in boron neutron capture therapy (BNCT) in Finland will be based on the use of BPA as the boron (10B) carrier. The kinetic models of BPA are needed to optimise the starting point of the treatment: the boron concentration should be in it's maximum in the tumour during the treatment. Biodistribution of BPA was investigated in five dogs. BPA-fructose was infused intravenously (approx. 250 mg/kg) during 30 rain. Blood samples were taken during infusion, and thereafter and urine was collected. Dogs were scarified 10, 50, 75, 105 and 130 min after the end of the infusion and tissue samples from brain, kidney, liver, lungs, pancreas, periosteum, retina, spleen and testicle were collected. Compartmental analysis was used for modelling. Data available in literature was used to optimise the model for quantitative study of boron concentrations in human tissues. The derived models will be verified using the blood and tissue samples from the dogs. The exchange rates between blood, brain, depot (extravascular space) and turnout were calculated using compartmental analysis with SAAMII program. The available BPA data indicate that the four (blood, brain, tumour, depot) compartmental model characterises the kinetics of BPA in humans. The exchange rates between compartments from human data were (in min-1): from plasma to depot 0.727, to tumour 0.475, to urine bladder 0.020, and to plasma from depot 0.013 and from tumour 0.192. Excretion from urine is 0.010 minq. According to the results of first dog experiments the ratio of exchange rates equals to those derived from human data. It is concluded that four compartmental models for BPA can be used to estimate the boron concentrations in the brain and tumour in BNCT.

888

ARTIFICIAL INTELLIGENCE IMPROVES THE ACCURACY OF CORONARY ARTERY DISEASE DIAGNOSTIC METHODS Improvements and rationalisation of diagnostic procedures of coronary artery disease (CAD) are very useful. Machine Learning (ML), a subfield of Artificial Intelligence has proved to be useful in many fields of medicine. One of its advantage is, that it can use all data of particular examination, all specific data of the patient, and the results of former diagnostic procedures in interpretation of result. This is the reason, why more accurate results are often obtained this way. We applied the Naive Bayesian classifier as one of the ML methods in stepwise diagnosis of CAD. A group of 326 patients has performed cycloergometry and stress myocardial perfusion scintigraphy for diagnosis of CAD, which was confirmed or excluded by coronarography. The post-test probability for CAD after each diagnostic step was calculated in classical way and with ML method. Our results show that the mean post-test probability for CAD after cycloergometry was 0.78 for positive results and 0.42 for negative ones. Using ML it was 0.81 for positive and 0.33 for negative results. After scintigraphy the mean posttest probability was 0.75 for positive in 0.43 for negative results. With application of ML post-test probability rose to 0.90 for positive and decreased to 0.25 for negative results. CONCLUSION: In our group of patients AI method significantly improved the diagnostic accuracy for both observed investigations. In 45 pts (13.8%) at cycloergometry and in 17 pts (5.2%) at scintigraphy the post-test probability changed to values of over 0.90 or under 0.10. If we agree that the patients with post-test probability of presence of disease greater 0.90, or absence of disease lower than 0.10 do not need any further diagnostic procedures, important impact on the accuracy of the diagnosis of CAD as wetl as important savings can be achieved by using ML methods.

[] In Vitro Assays In Vitro Assays 22.1

22.3

W. Brenne[, A. Hauschitd, K.H. Bohuslavizki, G. Engel, H. Mtinig, E. Christophers, E. Henze Departments of Nuclear Medicine, Dermatology and Internal Medicine, University of Kiel, Germany

L. Giovanella, L Ceriani, *A.V.Bono, *P. Vio, G.Roncad Nuclear Medicine and *Urology, University Hospital -Varese (Italy)

C L I N I C A L I M P A C T O F S E R U M - S I 0 0 T U M O R M A R K E R IN PATIENTS WITH METASTATIC MALIGNANT MELANOMA In patients with malignant melanoma no commonly used tumor marker is available either to indicate progression of disease or to monitor therapy. Recently, a new immunoradiometric assay has been introduced detecting the g-subunit of the calcium-binding protein S 100 which is expressed by astrocytes and Schwann cells as well as by melanoma cells, while it is not found in melanoblasts and dysplastic nevi. The aim of this study, therefore, was to evaluate the clinical value of this potential tumor marker in melanoma patients. 1443 serum samples of 412 non-selected melanoma patients including all stages of disease and samples of 107 patients with benign or malignant non-melanoma skin disorders were measured by IRMA S100. Serum levels > 0.3 ng/ml were considered positive. A highly positive predictive value was revealed for distant metastases by follow-up studies up to 60 months: 1/285 stage VII patients, 6/73 stage III patients with locoregional lymph node metastases, and 41/84 patients with distant metastases (stage IV) were S 100-positive, while all 107 non-melanoma patients were true negative. 4 of 6 stage III patients progressed to stage IV within three months. Thus, S 100 was the first indication for distant metastases in these patients. In 57 stage IV patients S100 levels were measured weekly during chemo- or immunotherapy. A good correlation of S100 serum levels and response to therapy was found as confirmed by a complete staging before and after treatment: rising serum levels were measured in 29/30 patients with progressive disease and decreasing serum levels were found in all 11 patients under remission. Furthermore, S 100 values proved to have a significant impact on the overall survival time in stage IV patients with levels < 0.3 ng/ml indicating a significantly longer survival time (p < 0.001). Ill conclusion, S100 IRMA is a highly specific and even prognostic tumor marker in melanoma patients with distant metastases. Thus, it may be used for follow-up examinations in high-risk patients to indicate progression of disease and prognosis as well as for monitorihg therapeutic efficacy in stage IV patients.

CLINICAL ROLE OF FreePSA/PSA RATIO IN DIFFERENTIAL DIAGNOSIS BETWEEN CANCER AND BENIGN HYPERTROPHY OF THE PROSTATE Background Total PSA (PSA) is a well established tumor marker for evaluation and follow up of prostatic cancer (PCa).OthenNise its usefulness as cancer diagnostic tool is limited by its weak specificity with regard to benign prostate hypertrophy (BPH). In serum the major quantity of PSA is complexed with alphal-antichymotrypsin. A non-complexed form constitutes a minor fraction of serum PSA and is called free-PSA (fPSA): preliminary experiences show that the froe/total PSA ratio (PSA-R) seems to be more careful than PSA only in differential diagnosis between PCa and BPH. Aim Purpose of our work was the evaluation of the diagnostic performance of PSA-R among untreated patients with PSA between 2.5 and 20 ng/ml and histological diagnosis of PCa or BPH. Materials and methods 68 patients with PSA levels between 2.5 and 20 ng/ml and histological diagnosis of PCa (n=32) and BPH (n=36) were evaluated. We determined serum levels of PSA and FreePSA by immunoradiometdc assays (Tandem IRMA, Hybritech)and PSA-R was obtained. Results

PCa PSA (nglml) fPSA(ng/ml) PSA-R

7.30 (3.00-19.60) 0.85 (0.20-1.85) 0.12 (0.01-0.24)

BPH 7.08 (2.56-15.90) 1.00 (0.20- 4.78) 0.22 (0.07 - 0.36)

Mann.Whitney ns ns p <0.0001

Comparative analysis of the ROC curves shows that PSA-R curve area is the largest while fPSA alone has not clinical interest.The PSA-R cut-off selected on the basis of the ROC analysis is 0.16. Conclusions In prostate pathology, measurement of PSA alone allows a poor discrimination between PCa and BPH .For a PSA-R of 0.16, 66% of PCa are detected with a specificity of 90%. Even if further studies are request to define the clinical impact and cost-effectiveness of PSA-R evaluation, we underline its importance in differential diagnosis between PCa and 8PH.

22.2

22,4

S. Massaron, E. Seregni, L.Ferrari, A. Martinetti, E. Bombardieri. Istituto Nazionale per 1o Studio e la Cura dei Tumori - Milan - Italy.

E . B e r c o v i c h , S.Nuvoli, A.Scanu, A.Mocci, A.Masia, G.Spanu, C . B a g e l l a , C . P a l a , M . E . S o l i n a s , A.Marrosu, F.Fadda, A . S p a n u and G.Madeddu. Depts. of U r o l o g y and N u c l e a r Medicine. U n i v e r s i t y and G e n e r a l H o s p i t a l of Sassari. Italy.

~SERUM S100 PROTEIN DETERMINATION IN PATIENTS AFFECTED BY MALIGNANT CUTANEOUS MELANOMA The protein S100 is a 21 kD acidic dimeric calcium-binding protein, whose 13subunit is mainly found in the central nervous system and in melanocytes. The aim of this study is to evaluate the clinical significance of this subunit deterrmnatian in the management of patients with melanoma. A cohort of 360 patients entered the study, 126 were at diagnosis (stage I=94, stage II=19 and stage III=13 pts), and 234 in follow-up (169 disease-free, 16 with local recurrence, 33 with lymphnode and/or in-transit and 16 with distant metastases). The patients were followed for a period ranging from 2 to 14 years. Serum Sl00 was evaluated by an IRMA (Sangtec Medical, Bromma, Sweden) which uses two different monoclonat antibodies directed to the 13 subunit of the protein. The lower detection limit was 0.2 gg/l. The distribution of Sl00 serum levels in the normal population was detemuned in 190 healthy blood donors and 95th percentile was 0.480 p.g/l. The differences between groups were determined by means of the Mann Whitney U-test. Survival curves were calculated by the Kaplan-Meier method and the statistical significance of the observed differences was determined by the log rank test. S 100 sensitivity in patients with primary melanoma was 2.1% in stage I, 5.3% in stage II, 23.1% in stage III and 4.7% overall. We found no statistical correlation between SI00 levels and disease stage. In the 234 previously treated patients, S100 sensitivit5' was 18.7% in patients with local recurrence, 24.4% in patients with 1}azaphnode and/or in-transit metastases and 68.7% in patients with distant metastases. The S 100 specificity evaluated in patients with no evidence of disease was 97.6%. The S100 levels differed significantly among these groups. To assess the prognostic value of S 100 at diagnosis, patients were stratified using the cut-off value of 0.480 p.g/l. We found no statistical correlation between S100 basal levels and overall survival. Our study demonstrated in a large series of patients that S100 determination is of limitcd utility in patients with primal" mclanoma. Acceptable sensitivities of t ~'~ test are found only in patients with advanced disease.

T O T A L (T) A N D FREE (F) PSA L E V E L S AND F R E E / T O T A L R A T I O (F/T) IN THE D I A G N O S I S OF P R I M A R Y P R O S T A T E C A N C E R (PC} Nowadays, the c o m b i n e d use of T-PSA, F - P S A and F / T seems to give a b e t t e r d i a g n o s t i c e f f e c t i v e n e s s in r e s p e c t of only T - P S A in d i s t i n g u i s h i n g p r i m a r y PC from benign p r o s t a t i c h y p e r p l a s i a (EPH). To f u r t h e r study this p r o b l e m we s t u d i e d 293 u n t r e a t e d m a l e pts, aged 44-90 yrs: 57 PC and 236 BPH. All of these had u n d e r g o n e d i g i t a l rectal examination, t r a n s - r e c t a l US and p r o s t a t e biopsy. At the first observation, 3 PC pts w e r e in stage A-B, 32 in stage C and 22 in stage D. In all pts, both T and F - P S A w e r e a s s a y e d by s a n d w i c h IRMA (cut-off: 4.0 and 2.1 ng/ml, r e s p e c t i v e l y ) ; F/T was also c a l c u l a t e d (cut-off: 0.18). TPSA was e l e v a t e d in 52/57 PC: 42 of these w i t h v a l u e s >ll ng/ml and i0 w i t h i n the gray area (4-11 ng/~l). The r e m a i n i n g 5 had v a l u e s <4 ng/ml. F - P S A was above c u t - o f f in 36/57 cases. F/T was >0.18 in 19/57, all w i t h high T and F - P S A values, w h i l e it was <0.18 in the r e m a i n i n g 38 cases who also i n c l u d e d 10/10 pts w i t h T - P S A w i t h i n the gray area. T - P S A was above c u t - o f f in 64/236 BPH: 7 of these w i t h v a l u e s >ll ng/ml and 57 w i t h v a l u e s w i t h i n the gray area. The r e m a i n i n g 172 w e r e <4 ng/ml. F - P S A was high in 25/236 pts. F/T was >0.18 in 219/236 cases, also i n c l u d i n g 53/57 cases w i t h T - P S A in the gray area. T and F - P S A mean levels w e r e s i g n i f i c a n t l y h i g h e r and F/T lower in PC (71.84±133.40, 13.40±30.7 ng/ml and 0.17±0.14, r e s p e c t i v e l y ) c o m p a r e d to BPH (3.36±3.4, 0 . 9 4 ± 1 . 1 2 ng/ml and 0.29±0.i0, r e s p e c t i v e l y ) . F/T was also s i g n i f i c a n t l y lower in the i0 PC pts (0.12±0.03) than in the 57 BPH (0.25±0.08) w h o s e T - P S A was w i t h i n tha g r a y area. Our data s u g g e s t that F / T in r e s p e c t of o n l y T - P S A seems to d i f f e r e n t i a t e b e t t e r b e t w e e n PC and BPH. F/T u s e f u l n e s s is g r e a t e r when T - P S A levels are w i t h i n d i a g n o s t i c g r a y area, since it can reduce false p o s i t i v e results in BPH, a v o i d i n g in some cases u n n e c e s s a r y biopsy.

889

• In Vitro Assays/Neurology Neurology 22.5

23.1

L. Ferrari. E. Seregni, C. Camaghi, A. Chiti, L Bertarin, E. Bombardieri. Istituto Nazionale per Io Studio e la Cura dei Tumori - Milan - Italy.

G. Berdinq, S. Siggelkow, H. Streit, H. Kolbe, T. 8rOcke, R. Dengler, K.F. Gratz, H. Hundeshagen. Medizinische Hochschule Hannover, Abt. f. Nuklearmedizin u. Klinik f. Neurologie; Neurologische Univ.-Klinik Wien.

T U M O U R M A R K E R E V A L U A T I O N IN P A T I E N T S A F F E C T E D BY CARCINOIDS Carcinoid is a rarc ncoplasm arising from cclls with ncuroendocrinc differentiation Clinical response is usually evaluated both in terms of bulk shrinkage and modifications in tumour secretory activity. The aim of this study was to evaluate the utility of chromogranin-A (CgA), neurone-specific enolase (NSE), carcinoembr?'onic antigen (CEA) and 24-hour urine 5-Hydroxy-3-indole acetic acid (5HIAA) level measurement in the diagnosis and follow-up of patients with carcinoids. Overall, 664 determinations were performed in 100 patients. Fourteen patients were without any clinical evidence of disease and 86 had residual or metastatic tumour. Tumour markers were measured by means of immunoradiometrie (NSE, CEA, 5H1AA) or mamunoenzymatic (CgA) assays. The results of tumour marker measurements and marker specificity and sensitivity in patients with and without disease are illustrated in the following table. CgA (U/l) NSE (gg/l) CEA (fig~l) 5HIAA (mg/l 24-hour) Disease-free pts 12 7 6.4 2 7.5 (specifici~) 85.7% 100% 85.8% 100% Pts with disease 92.8 9. I 1.8 7.0 (sensitivity) 73.3% 34.3% 14.6% 41.8% .Vormal values: CgA <34.7 Ud, NSE <12.5 teg I, CEA <5.0 ~g/l. 5HIAA
IMPAIRMENT OF DOPAMINERGIC NIGROSTRIATAL NEURONS IN MULTIPLE SYSTEM ATROPHY ASSESSED WITH [1231]-13-CIT SPECT CORRELATES WITH RESPONSE TO L-DOPA Striatal dopamine transporters were investigated in 11 patients with multiple system atrophy and 11 normal controls using [12311-13-CIT SPECT. The patient group was subdivided with regard to response to L-Dopa. Response was poor in 5 and good in 6 cases. For [1231]-fl-CIT SPECT 185 MBq were injected intravenously. The acquisition was started 24 h p.i. using a Siemens Multispect threeheaded camera, equipped with medium-energy collimators. 180 frames, each with 40 sec. duration and a matrixsize of 128,128, were collected over 360 °. Reconstruction was done with a Butterworth filter (cut-off 0.55 Nyquist, order 20) and including attenuation correction according to Chang (/1=0.12cm1). Regions of interest of standardized size were drawn over caudate nucleus and putamen on either side and the occipital cortex as reference. Ratios of count densities between striatum and cortex were calculated as a semiquantitatlve measure of ligand binding to dopamine transporters. Ratios were significantly lower in patients as compared to controls (4.4±2.0 vs, 9.0±1,5, t-test p=0.0001). Furthermore, regarding L-Dopa therapy, ratios were significantly lower in cases with poor response than in those with good response (3.1 ±1.1 vs. 5.4±2.0, t-test p=0.0047). It is concluded that [12al]-3-CIT SPECT allows to detect impairment of nigrostriatai neurons in multiple system atrophy and can give prognostic information with regard to response to L-Dopa.

22.6

23.2

F. Guadaqni 1, P. Ferroni 2, R. Arcuri 1, C. Bott[ 1, S. Carlini 1, G. Del Monte 1, I. Venturo 1, G. Amadei3, A. Piazza3, O. Buonomo 3, M. Roselli 3 1Regina Elena Cancer Inst.; 2Dept. Exp. Medicine, Univ. La Sapienza; 3Dept. Surgery, Univ. Tor Vergata, Rome, Italy.

J. Booij, J. Lavalove. P. Korn, D.H. Linszen, M.E. Isra~51,E.A. van Royen. Depts. of Nuclear Medicine and Psychiatry, Academic Medical Center Amsterdam, The Netherlands.

IS CEA SERUM MEASUREMENT USEFUL IN MONITORING BREAST CANCER PATIENTS? The presence of serum CEA (Abbott CEA RIA MAb) and CA 15.3 (Centocor Inc., PA) levels was evaluated in 1014 patients with breast cancer. Among the patients, 288 (28.4%) were of premenopausal status (mean age: 44.3 _+0.6 SE), while 726 (71.6%) were of post-menopausal status (mean age: 64.3 _+ 0.7 SE). Patients were diagnosed with ductal (76.4%), Iobular (9.0%) or other (14.6%) histological types of breast cancer. 278 patients had Stage I, 446 Stage II, 137 Stage III, 8 Stage IV primary breast cancer. Moreover, 29 patients were evaluated at the time of diagnosis of local recurrence and 116 at the appearance of metastatic disease. Elevated serum CEA and CA 15.3 levels were found in 14.5% and 28.9%, respectively. The evaluation of CEA in patients with negative serum CA 15.3 levels allowed only a 6% increase of the overall sensitivity. The sensitivity of serum CEA was very low in all stages, reaching only 25% in Stage IV patients and approximately 40% in metastatic disease. In contrast, CA 15.3 reached a sensitivity of 75% in both cases. Although the number of patients with local recurrence included in the study was relatively low (n=29), it should be pointed out that 12 (41.4%) patients showed positive CA 15.3 levels, while only one patient had elevated serum CEA levels. Furthermore, the evaluation of CEA in combination with CA 15.3 levels in local recurrent disease and advanced stages of breast c a n c e r demonstrated no significant advantage. Even though CEA is one of the most widely used tumor markers for monitoring breast cancer patients, the present study demonstrated its low sensitivity and the non-complementary expression with CA 15.3. Therefore, the utility of measuring CEA in the post-surgical monitoring of breast cancer should be reconsidered.

890

IMAGING OF ENDOGENOUS DOPAMINE RELEASE BY METHYLPHENIDATE (RITALIN~) CHALLENGE USING [I-123]IBZM SPECT. A recent study suggested the ability of a bolus plus constant infusion technique with [1123]iodobenzamide (([I-123]IBZM) and SPECT to study d-amphetamine induced endogenous dopamine (DA) release by evaluation of the DA D2 receptor availability (Laruelle et al., 1995). [I-123]IBZM (a DA D2 receptor radioligand) binding is sensitive to DA release. The response of the challenged DAergic system is of interest to investigate changes associated with neuropsychiatric illnesses. However, d-amphetamine is not a registered drug in Europe. Therefore, in our study the feasibility of the constant infusion SPECT technique to image endogenous DA release, induced by the registered DA uptake blocker methylphenidate (RitalinR), was investigated in 12 healthy male volunteers (age range 21-27 y ) in a double-blind, placebo-controlled conditon. Changes in endogenous DA release were evaluated by SPECT and a bolus plus constant infusion administration schedule of [I-123]IBZM: bolus activity 68 _+4 MBq; rate of infusion 16 _+ 1 MBq/'h. Duration of the study was 300 rain. Subjects were scanned on a brain dedicated SPECT camera (Strichman 810 X). In the placebo group, the striatal and occipital activities were stable from 120 min to the end of the experiment. In the methylphenidare group, the occipital cortex activity was also stable from 120 to 300 min. Methylphenidate (0.5 mg/kg) injected at 180 rain induced, in comparison with placebo, behavioural responses and significantly (Wilcoxon Rank Sum) decreased striatal [I-123]IBZM binding. In conclusion, this study demonstrates the feasibility of using [I-123]IBZM constant infusion and SPECT to measure endogenous DA release by methylphenidate challenge and to investigate neurochemical aspects of behaviour. Laruelle M, Abi-Dargham A, Van Dyck CH, et al. SPECT imaging of striatal dopamine release after amphetamine challenge. J Nucl Med 1995; 36:t 1821190.

II Neurology 23.3 K.A. Bergstr6m~, J. Jolkkonen2, J.T. Kuikka ~, K.K. Akerman ~, H. Viinam~iki~, O. Airaksinen~, E. Lansimies ~, J. Tiihonen3. ~Kuopio University Hospital, 2AIV Institute, 3Niuvanniemi Hospital, Kuopio, Finland. FENTANYL DECREASES [~-CIT BINDING TO THE DOPAMINE TRANSPORTER

23.5 Y. Krausz, O. Bonne, Y. Gelfin, I. Aharon, B. Lerer, R. Chisin. Departments of Nuclear Medicine and Psychiatry, Hadassah University Hospital, Jerusalem, ISRAEL. BRAIN SPECT IMAGING IN HEALTHY VOLUNTEERS ON FLUOXETINE. The selective serotonin reuptake inhibitor, fluoxetine, has been

Evidence from animal studies suggest that centrally acting opiates increase synaptic dopamine (DA) concentration. However, the exact interaction between p.-opioid receptors and the DA system is. unclear. We report here an effect of fentanyI on the [I-123]13-CIT binding to the DA transporter in a female patient and in rats. A female patient with suspected depression underwent [I-123]13-CIT SPET study after intratecal injection of fentanyl for her back pain. After 2 week drug-free period, [I-123]13-CIT SPET study was repeated. In the experimental study, male Wistar rats were treated with fentanyl either subacutely for 4 days (10 gg/kg, twice a day, i.p.) or acutely (50 gg/kg, i.p.) before brain imaging. Brain planar imaging was performed at 3.5 hours after an i.v. injection of 60 MBq [I-123]13-CIT with Siemens Orbiter gamma camera with a pinhole collimator. In a female patient, [I-123][3-CIT binding in the basal ganglia was decreased by 37% during fentanyl as compared to the binding after 2 week drug-free period. Similarly in rats, acute femanyl treatment decreased [I-123]13-CIT binding to striatum by 41% as compared to that in the control rat. After subacute administration of fentanyl, [I-123][3CIT binding decreased by 5%. According to the present data, fentanyl decreases [I-I23][LCIT binding in the basal ganglia both in a human patient and in rats, Enhanced DA release which results in an increased competition between endogenous DA and [I-123]13-CIT may account for the present data. However, in vitro 13-CIT has more than 5000 fold higher affinity to the DA reuptake site than DA, which suggests that fentanyl may have a direct effect on the DA transporter. In conclusion, fentanyl was found to decrease [3-CIT binding to the DA transporter possibly by a mechanism other than enhanced dopamine release.

implicated in improvement of mood and well-being in subjects with no psychiatric abnormalities, aside from its advantage in major depressive disorders. We studied the effect of the drug on personality and mood, and on the regional cerebral blood flow (rCBF) of healthy volunteers, to determine whether the enhanced synaptic availability of serotonin has an impact on psychological aspects and brain perfusion not limited to psychopathological states. Fourteen normal subjects (8 male, age 38.5+12.9 years, range 22-63) were studied, with a capsule per day for 10 weeks: placebo (2 weeks), fluoxetine 10 mg (1 week), fluoxetine 20 mg (5 weeks) and placebo for the last 2 weeks. Subjects underwent weekly assessments by psychological tests associated with affect & anxiety, and tests associated with personality were completed at baseline and after 6 weeks of fluoxetine treatment. Tc-99mHMPAO SPECT was performed following the 2 week-placebo period and after 4 weeks of fluoxetine. Semiquantitative analysis of the SPECT study was based on ratio of mean counts/pixel of a selected ROI to mean cerebellar uptake. These ROl's were drawn on pre4ormed templates of 3 transaxial slices - at 4, 6, and 7 cm above the orbitomeatal line. When comparing the subjects before and after fluoxetine, statistical analysis showed no significant change in scores obtained by the psychological tests over the course of clinical trial. Furthermore, no significant changes were observed in rCBF of either hemisphere at any of the 3 levels examined. In conclusion, fluoxetine treatment has no substantial psychological effect in normal subjects and induces no changes in rCBF, in consistency with our previous data showing that changes in rCBF are related to alleviation of the depressive state, rather than to a direct effect of the anti-depressive treatment.

23.4

23.6

MJ Travis!,GF Busatto1,LS Pilowsky1,R Mulligan2,S Gacinovic2,P Acton2,DC Costa2,j Mertens3,D Terri~re3,pJ 1 ii Ell2,V Bigliani ,RW Kerwin . Institute of Psychiatry, London, UK. 2Institute of Nuclear Medicine, London,. UK.3V.U.B. Cyclotron, Brussels, Belgium. 5-HT2A RECEPTOR BLOCKADE IN VIVO IN SCHIZOPHRENIC PATIENTS TREATED WITH CLOZAPINE OR RISPERIDONE: SINGLE PHOTON EMISSION TOMOGRAPHY (SPET) FINDINGS

A.M. Catafau. A. Etcheberrigaray, J. Perez de los Cobos, M. Estorch, J. Guardia, A. Flotats, L1. Bernfi, C. Mari, M. Casas, I. Carri6. Hospital de Sant Pau, U.A.B., Barcelona, Spain.

5-HT2A receptors may be critical to the action of atypical antipsychotics. We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective iodine-123 labelled ligand 123I-5-I-R91150. 6 h e a l t h y volunteers (age=28±3 years, 4M/2F), 5 clozapine-treated(age=25±3 yrs, 4M/IF, dose = 470±l10mg),and 3 risperidone-treated DSM-IV schizophrenics (age=33±ll yrs, 3M, dose=8±7mg) were studied. Whole-brain SPET was performed using the brain-dedicated SME-810 system after injection of 180MBq 123I-5-I-R91150. Images were acquired from 120min onwards, when specific binding of 123I-5-I-R91150 (as assessed using c o r t e x : c e r e b e l l u m ratios) is maximal and stable. ROI templates were fitted to each scanning sequence and adjusted for brain size. C o r t e x : c e r e b e l l u m ratios were significantly lower in both clozapine and risperidone treated patients compared to c o n t r o l s in the frontal ROI (clozapine 0.85 ! 0.I0 vs control 1.38! 0.15, p< 0.001; risperidone 0.85!0.05, p<0.005) and the parietal ROI (clozapine 0.87 ! 0.09 vs control 1.43± 0.06, p<0.001, risperidone 0.89±0.04, p< 0.001). There was no difference in occupancy between the two drug treated groups. These results provide the first SPET imaging evidence that clozapine and risperidone potently block 5HT2A receptors in vivo. Further studies will allow investigation of the relationship between clinical parameters and 5-HT2A blockade.

REGIONAL CEREBRAL BLOOD FLOW CHANGES INDUCED BY NALTREXONE CHALLENGE IN ALCOHOL DEPENDENT PATIENTS. Naltrexone is an opioid antagonist that has been introduced for alcohol-dependence therapy. The biological basis of its therapeutic effect is not fully understood. To investigate the effects on regional cerebral blood flow (rCBF) of a naltrexone challenge in alcohol dependence, ten right-handed male alcoholic inpatients underwent two 99mTc-HMPAO brain SPECTs: a basal SPECT on day 10 of abstinence, and a second SPECT on day 12 of abstinence after administration of 150 mg of naltrexone. Region/cerebellar ratios for the following regions: orbitary frontal, prefrontal, lateral temporal, mesial temporal, basal ganglia and thalamus, were obtained for each hemisphere. A % of rCBF change between both SPECTs was calculated for each region as 100x(naltrexone-basal)/basal. Values from 13 brain SPECTs of age-matched normal volunteers including test-retest measurements were used for statistical comparison. Compared to controls, alcoholics showed lower rCBF in left and right prefrontal regions (87+5 and 86_+5 vs 96_+3 and 96_+4, p < .0005), but no differences in the remaining regions in the basal SPECT. After naltrexone, a significant rCBF decrease was found versus test-retest values in left basal ganglia (-5+4% vs 1_+4%, p=.005), right basal ganglia (-4+5% vs 1+3%, p=.02) and left mesial temporal region (-5_+8% vs 2-+3%, p=.02). Naltrexone challenge induces a rCBF decrease in basal ganglia and in the mesial temporal region, which are limbic structures rich in opioid receptors.

891

co

i n

0~ e-

l t~

• Oncology Oncology 24,1

24.3

P.Colarinlm. J.Bivar, L.Salgado, P.Oliveira, J.Faria, J.So~ma,J.Almeida, M.R.Vieira. Scrvi¢o de Medicine Nuclear - Instituto Portagu~ de Onenlogia F.G. Lisbon, Portugal.

C.DeCicco,G.Paganelli,M.Cremonesi,*V.Galimberti, M.Bartolomei,#G.Viale,G.Prisco,*P.Veronesi,*A.Luini and *U.Veronesi.Div. of Nuclear Medicine, *Senology and #Pathology, European Institute of 0ncology, Milan, Italy.

LYMPHOSCINTIGRAPHY (LS) IN EARLY STAGE CUTANEOUS MELANOMA: SELECTIVE LYMPEIADENECTOMY. Correct staging is crucial for management and prosnosis of patients(pts) with malignant melanoma. We described our experience with LS and intranperative gamma probe-guided selective iymphackmctmny of smtinel node (the first node of the lymphatic drainage). Methodi&Meterials: From March 1995 to December 1996 emaneons LS was performed on 33 pts (18males&f5 females). Colloidal (Re) sulphide-~c (particle size 3-15nm) was intradermally infiltrated arround biopsy excision site (30pts) or primary lesion (3pts). Multiple depots (6-8) of radiotracer (0,05 to 0,1ml/each, 613MBq, respectively) were performed. A large field-of-view syr,.em, low energy, all-purpose collimator (140-keV, 15-20% energy wuMow) were used. Scanning started immediately, serially 5-rain images were acquired until the sentinel node(s) were defined. The site of the node(s) was marked on patient's skin. A delayed 2%onr mmge was obtain to ensure that all potential lymphatic drainage sites were imaged. Selective lymphadmectmny was performed 4 to 24 hours after LS. Intradermal patent blue V injectim and a han~oid gamma probe (TecProbe 2000) assisted surgery. Results: Thirty three pts with cutaneous melanoma-stage MI, have been submitted to san~nei node biopsy. i.ocation of primary lesion were: trunk(gpts), ex~-eii~y(19pts), head and neck(5pts). In all lots LS showed lymphatic drainage: 46 lymphatic channels and 42 mvinel nodes were visualised. 41 sentinel nodes and 17 satelli~ nodes were excised. His~logical examination revealed micrometastasis in three pts. Radical lynch node dissection was carried out. Pceitive nodes had diameters of 8,10,11,12 and 23 nun, respectively. In the 30 pts with node-negative biopsies no regional nodal recurrmces were observed with a folinw-up of: M 8months(3pts), >~12menths(gpts), >~6months(10pts), ,<6months(Spts). Conclusion: Lymphoscintigraphy and hanc~old gamma probe can accurately idmtify nodal micrometastasis in patients without palpable lymph nedm.

G A M M A - P R O B E G U I D E D RESECTION OF THE SENTINEL N O D E IN B R E A S T CANCER. The p r e s e n c e of metastases in regional lymph nodes (LN) is an important p r o g n o s t i c factor in the m a n a g e m e n t of breast cancer. A x i l l a r y lymph node dissection (ALND) is still the main p r o c e d u r e for staging, in absence of reliable less invasive technique. The aim of this study was to a p p l y to b r e a s t cancer the sentinel lymph node (SN) concept, in order to develop a m e t h o d w h i c h allows a selective LN biopsy. To localize the SN a n d v e r i f y its p r e d i c t i v e value versus the remaining a x i l l a r y LN, 163 p a t i e n t s w i t h operable breast cancer underwent lymphoscintigraphy. The day b e f o r e surgery, 0.2 ml of h u m a n serum albumin m i c r o c o l l o i d s (Albures, Sorin Biomedica, Italy), labelled w i t h 5-10 M B q of T c - 9 9 m w e r e injected close to the tumor site. Images were a c q u i r e d in anterior and oblique projections at i0 m i n and 3 h and the d e t e c t e d SN were m a r k e d on the skin. A sentinel lymphadenectomy guided by a gamma detecting probe (C-Trak TM) and ALND were p e r f o r m e d in all patients. SN w e r e identified in 98% of the cases (160/163). W h e n identified, the SN a c c u r a t e l y p r e d i c t e d a x i l l a r y nodal status in 156 of 160 patients (97.5%) and in all cases (45 patients) with tumor ~1.5 cm in size. This technique seems to be p r o m i s i n g in the management of a x i l l a r y lymph node dissection, in breast cancer patients.

24,2

24.4

A.M.EI-Shirbiny, S.Yeh H.S.COdy, P.I.Borgen and S.M.Larson, Memorial Sloan-Kettering Cancer Center, Department of Nuclear Medicine and Surgery.

C.DeCicco, *M.Sideri, M.Bartolomei, *A.Maggioni, *N.Colombo, L.Leonardi, and G.Paganelli. Divisions of Nuclear Medicine and *Gynecology, European Institute of Oncology, Milan, Italy.

SCINTIGRAPHIC

IDENTIFICATION

OF

SENTINEL

LYMPH

NODE IN BREAST CARCINOMA. Sentinel lymph node biopsy (SLNB), well established in treating melanoma, may play an increasing role in the treatment of early-stage breast cancer. If proven accurate, SLNB can restrict axillary node dissection (ALND) to patients with nodal metastases, sparing node-negative patients the cost and morbidity of the procedure. Methods: In 33 patients with invasive breast cancer, SLNB followed immediately by axillary dissection was done as part of a prospective trial of intraoperative lymphatic mapping with Tc-99m sulfur colloid (SC) and isosutfan blue dye. 0.3 mCi of unfiltered Tc-99m SC in 4 cc saline was injected in the breast around tumor/ biopsy site. Lymphoscintigraphy (LSG) was done using a gamma camera with low energy high resolution collimator. Static and transmission images in the anterior and lateral views were obtained while shielding the injection site. Intraoperative peritumoral injection of 4 ce blue dye was followed by SLNB and ALND (using both blue dye and a hand-held gamma probe for node localization). Results: Sentinel nodes were found by LSG in 68% of patients (23/33), by blue dye in 73% (24/33), and by the gamma probe in 94% (31/33). Blue dye and/or the gamma probe found sentinel nodes in 97% (32/33), and the remaining patient was negative by all 3 methods. Internal mammary LN were identified in 4 cases in addition to axillary LN. Pathologically, axillary nodes were involved in 45% of patients (15/33), sentinel nodes were the only site of metastasis in 15% (5/33), and sentinel nodes werefalsely nega#ve in 12% (4/33).Cun¢lusiuns: while preoperative LSG was positive in 68% of patients, intraopera#ve radioloealization of sentinel lymph nodes succeeded in 94% of patients, increasing to 97% with the addition of blue dye. For early breast cancers, Assuming a 20-30% likelihood of axillary node involvement , the negative predictive value of SLNB is about 98%. Supported by a grantfrom the TOWfoundation.

892

LYMPHOSCINTIGRAPHY AND RADIOGUIDED BIOPSY OF THE SENTINEL NODE IN PATIENTS WITH VULVAR CANCER. Treatment of vulvar cancer has become less aggressive in the last ten years, but inguinofemoral lymphadenectomy still is a necessary procedure which carries considerable morbidity. In order to verify the feasibility of staging inguinal nodes by a biopsy of the first node draining tumor district, we studied 19 pts with vulvar cancer using lymphoscintigraphy (LS) and a gamma detecting probes (GDP). Ii MBq of Tc-99m HSA were subdermally injected surrounding the tumor (1-4 sites of injection). Images of the pelvis region in anterior and lateral projection were acquired i0 min and 2 b later. The first lymph node visualized was defined as sentinel node (SN) and its cutaneous projection marked. During surgery (the day after LS) a GDP (ScintiProbe MR100) was used to localize the SN, which was then removed and submitted as a separate pathologic specimen. Then a complete ipsilateral groin dissection in pts with T1 lateral lesions or bilateral groin dissection in those with T2 lateral or midline tumors was carried out through separate incisions, for a total of 35 groins dissected. SN biopsy was easily carried out in all pts without extensive dissection. In two groins the SN alone was positive on the final pathological specimen; in one case an other LN was found to be positive; in 16 pts all the LN were free of disease. LS and radioguided surgery proved to be easy and accurate in the detection of SN and promising in reducing the morbidity related to the complete groin dissection.

== Oncology/Cardiovascular Cardiovascular 24.5

25.1

S. Dresel, M. Weiss, M. Heckmann*, B. Rossmt~ller, B. Konz*, K. Tatsch, and K. Hahn Departments of Nuclear Medicine and *Dermatology, University of Munich, Munich, Germany

A. Cuocolo, E. Nicolai, M. Petretta, L. Pace, S. Cardei, A. Varrone, B. Triroarco, M. Salvatore. Centro per la Medicina Nucleate del CNR and I Medicina Intema, Universit5 Federico II, Napoli, Italy.

PRE- & INTRAOPERATIVE DETECT]~ON OF THE SENTINEL LYMPH NODE IN MALIGNANT MELANOMA: COMBINED LYMPHOSCINTIGRAPHY AND GAMMA PROBE GUIDANCE

CORONARY REVASCULARIZATION IMPROVES SURVIVAL AND LEFT VENTRICULAR FUNCTION IN PATIENTS WITH CHRONIC CORONARY ARTERY DISEASE AND DYSFUNCTIONAL BUT VIABLE MYOCARD1UM AT THALLIUM-201 IMAGING.

The identification of the sentinel lymph node (SLN), the first draining lymph node of the primary tumor, is crucial for both the surgical approach and the prognosis of the patient. Therefore, it is essential to reliably localize this lymph node pre- and intraoperatively. We investigated whether combined lymphoscintigraphy and gamma probe guidance may be a powerful diagnostic tool for this purpose. 18 patients with histologically proven malignant melanoma (tumor thickness >0.75mm) were preoperatively examined by ultrasound, CT, and planar scintigraphy. The latter was performed after intradermal injection of 40 MBq Tc-99m nanocolloid around the lesion (Picker Prism 2000, LEHR collimators). The first lymph node identified was marked on the skin. For intraoperative mapping, which was done immediately after scintigraphy, a handheld gamma probe (C-Trak system, Care Wise) was used. Measurements of the SLN and the adjacent lymph nodes were performed in and ex vivo complemented by measurements of the lymphatic basin after removal of the SLN. The preoperatively marked lymph node presented in all patients with the highest amount of radioactivity. Macroscopically all nodes were unsuspicious. Ultrasound and CT did not show any pathologic lymph node enlargement. Histologically in 4/18 patients metastatic involvement of the lymph node was found which was followed by wide exploration of the respective lymphatic basin with consecutive lymph node excision. Our findings clearly demonstrate that the combination of preoperative lymphoscintigraphy and intraoperative mapping with a gamma probe is a capable and powerful tool for exact localization of the SLN. Our results are in line with previously published studies, documenting metastatic involvement of lymph nodes in about 30% of high risk melanoma with unsuspicious morphological findings. In terms of costeffective patient management and planning the best surgical strategy for each individuum the diagnostic detection of the SLN represents an important factor, since extended lymph node dissection can be avoided in patients presenting with negative SLN.

24.6

25.2 J. C a s t e l l o n b e h a l f o f t h e S p a n i s h M u l t i c e n t r i c Study. Hospital General Universitari Vall BArcelona.

the most appropriate

incision.

C

t_

The role of revascularization of dysfunctional myocardium with preserved thallium-201 (T1-201) uptake in determining prognosis in patients after myocardial infarction remained to be defined. This study was designed to evaluate the effects of revascularization on survival and left ventricular (LV) function in patients with previous myocardial infarction and evidence of viable myocardium at T1-201 imagin~. Seventy-six consecutive patients with LV dysfunction related to myocardial infarction (>8 months) and evidence of viable myocardiuro at resting T1-201 tomography were followed clinically for 17+8 months. LV ejection fraction (EF) was assessed by radionuclide angiography at baseline and after one year. Thirty-nine patients were revascularized (group A) and 37 treated medically (group B). During the follow-up there were 9 cardiac deaths. Cumulative survival rate was 97% in group A and 66% in group B (p<0.01). By multivariate analysis, the extent of viable myocardium was the best predictor of cardiac death (chi-square 8.67, p<0.01) and provided additional information to clinical and LV functional data (p<0.01). The inclusion of revascularization variables improved the prognostic value of the model (global chi-square from 5.7 to 21.9, p<0.01). After one-year follow-up, LVEF improved >5% in 16 patients. The extent of viable myocardium was the best predictor of functional improvement (ehi-square 15.49, p<0.001) and provided additional information to clinical and LV functional data (p<0.01). The inclusion of revascularization variables improved the prognostic value of the model (global chi-square from 3.6 to 22.5, p<0.01). These results demonstrate that the extent of viable myocardium at T1-201 imaging is the strongest predictor of cardiac death in patients after myocardial infarction. Revascularization of dysfunctional but still viable myocardium improves survival and LVEF in such patients.

G.Paganelli, C.De Cicco, A.Luini*, #E.Cassano, #M.Pizzamiglio, M.Fiorenza, *V.Galimberti, *S. Zurrida,and *U.Veronesi Divisions of Nuclear Medicine,*Senology, #Radiology, European I n s t i t u t e of O n c o l o l o g y , Milan, Italy. RADIOGUIDED SURGERY IN NON-PALPABLE BREAST LESIONS. Clinically occult breast lesions are found with increasing frequency as a result of the widespread use of mammographic and ultrasonic screening. Several methods are used to locate suspicious occult lesions prior to excision, the most common being to introduce a hooked w i r e or to inject a p a t h of carbon particles. None of the methods are ideal however. We have developed a new localization technique c a l l e d ROLL (radioguided occult lesion localization) in which a small quantity of 99~Tclabelled human serum albumin is inoculated directly into the lesion during mammographic or ultrasonic examination. A gamma detecting probe (GDP) is then u s e d to locate the lesion as an hot spot and guide its removal during surgery. We had treated 115 patients using this technique. All patients had clinically non-palpable breast lesions identified by mammography or ultrasound as small opacities or clusters of microcalcifications. Pathological examination revealed 69 cancer lesions, 68 of which w e r e treated b y breast conserving surgery. In all cases but 2, the radiolabelled tumor was identified a n d r e m o v a l of t h e l e s i o n w a s g r e a t l y f a c i l i t a t e d b y t h e GDP. Specimens X-Ray completely contained the located lesion in all cases. Lesion removal is g r e a t l y f a c i l i t a t e d b y u s e of the g a m m a probe, w h i c h has the additional advantage that it permits accurate location of the skin projection of the radiolabelled l e s i o n a l l o w i n g the s u r g e o n to c h o o s e

C O =m

ASSESSMENT ISONITRILE MULTICENTER

OF MYOCARDIAL VIABILITY WITH AND THALLIUM-201. RESULTS TRIAL.

Viability d'Hebron.

TECHNETIUM-99m OF SPANISH

Regions with severe impaired function in patients with chronic coronary artery disease may improve contractility after coronary revascularization procedures. This multicentric trial was undertaken to assess the yield of rest technetium-99-isobutil-isonitrile (~Te-MIBI) and thallium-201 (mlTl) single photon emission tomography in the prediction of functional recovery. Methods. 116 patients (mean age 59 ±I0, 12 women) with s e v e r e impairment of regional contractility who underwent coronary artery bypass grafting (84) or ~ercutaneous coronary angioplasty (32) were studied. Rest Tc-MIBI and mITl single photon emission tomography and three wiews radionuclide ventriculography were performed before and 36 months after revascularization. Regional contractility and radiotracer uptake were evaluated in 9 left ventricular segments. R e s u l t s . No change was observed in mean left vehtricular ejection fraction pre- and post-revascularization (41.1% ± 14.5% vs 41.8% ± 15.7%). 28% of patients increased > 5 ejection fraction units, 50% did not change and in 22% of patients ejection fraction decreased >5 units. Only 34.4% of segments with severe impairment of regional contractility improved after revascularization. Using 30% uptake as lower limit of myocardial viability, sensitivity of 79% and specificity of 40% for ~ T c ~ M I B I and 80% and 46% respectively for m I T l were obtained. There was a significantly inverse relation (p=0.04) between the number of segments with less than 30% of radiotracer uptake and the probability of increasing ejection fraction after revascularization. Conclusions. No differences were observed in the sensitivity or specificity of ~ T c - M I B I and ~ITl single photon emission tomography in the prediction of functional recovery after revascularization in patients with coronary artery disease and severe impairment of regional contractility. The probability of increase ejection fraction after revascularization is inversely related to the extent of regions with less than 30% of uptake. Background.

893

m

O

•

Cardiovascular

25.3 E. Ostwald, G. Schulz, K-Ch. Koch*, J. vom Dalai*, E. Kleinhans, H.J. Kaiser, S. Verhasselt*, U. Buell. Dpts. of Nuclear Medicine and *Internal Medicine I, Aachen University of Technology, Germany IS THERE ANY THRESHOLD OF 201-THALLIUM UPTAKE AT REST TO PREDICT MYOCARDIAL VIABILITY .9 A PROSPECTIVE STUDY USING QUANTITATIVE ANALYSIS OF WALL MOTION RECOVERY Criteria of 20 l-Thallium-Chlorid (2°~TI)SPECT to estimate myocardial viability are controverse. This study searchs for regional quantitative thresholds to predict functional recovery as the ultimative target of revascularisation (RV). Study included 32 pts with advanced CAD, previous infarction and severe wall motion abnormalities in the LAD-territory, who underwent RV independently of the 2mTl viability interpretation and a second angiography 3 +I mo alter RV. In RAO levocardiography wall motion was analysed both visually and by the centerline method, expressed as standard deviations from the reference (KWM) compressed to 5 segments. SPECT was acquired 15 min and 3 h after rest injection of 100 MBq TI2m and both sets were regionally normalised to individual maximum at 15 min pi, expressed as percent uptake. The 32 pts had successful RV of the LAD (no re-stenosis >50%). Before RV, 29 of 64, thereafter 16 of 64 anterior and apical segments revealed an akinesia. wall motion 1%] =°~TI uptake RWM segments 15 rain pi 3 h pi before RV after RV A RWM recovered 13 67.2+14.5" 70.9-H4.8~ -2.45+0.69 -1.26+:1.13 1.20+1.20~ notrecov. 16 46.2+10.1 # 47.4 :t:12.9~ i -2.47 +0.64 -2.75:t0.75 -0.28+0.73 ~ mean .+SD,differences ~/~,e/~ and ~/~significantfor p < 0.01 (ANOVA,LSD) Reciever operator characteristics (ROC) of ROC'area0,878 2°~T1 uptake to predict recovery (= viable) I / : : demonstrated an optimal threshold at >70% with a positive predictive value (ppV) of 1.0, a npV of 0.70 and an accuracy of 0.76. At the ~50% uptake (= "non-viable), threshold of npV was 1.0, of ppV 0.68 and accuracy was 0.79. In conclusion, 3 h pi, in the LAD territory, a resting 2°~T1 uptake of <50% indicates scar and an uptake >70% indicates viable myocardium. In the 50 to 70 percentage range 2°tT1uptake did not predict functional recovery sufficiently.

25.5 M Faraggi, D. Karila-Cohen, R. Lebtahi, D. Czitrom, L. Sarda, E. 8rochet, P. Assayag, D. Doumit , P.G. Steg, D. Le Guludec, Services de Medecine Nucleaire et de Cardiologie, Hbpital Bichat, Paris, France. MYOCARDIALCONTRASTECHOCARDIOGRAPHYAND EARLYREST THALLIUM REVERSE REDISTRIBUTIONDEMONSTRATE SUCCESSFUL MICROVASCULAR REPERFUSION IN PATIENTS WITH ACUTE MYOCARDIALINFARCTION AND PATENTINFARCT-RELATEDARTERY,

Rest thallium reverse redistribution (RR) has been observed early after myocardial infarction, but the links between RR, acute microvascular perfusion, infarct-related artery patency and functional recovery remain unclear. We acutely and prospectively assessed microvascular perfusion by myocardial contrast echocardiography performed immediately after restoration of complete patency of the infarct-related artery in 18 patients: After intra-coronary injection of sonicated ioxaglate, a 3-grade perfusion score (16 segments) was compared to the thallium defect sizes (expressed in % of the whole myocardial bull's-eye) and to a 4-grade echocardiographic wall motion score simultaneously performed 7 and 42 days after the acute phase. On day 7, the average defect size on post-injection scans (25,4+14.9%) increased during redistribution (34.0+12.9%, p<103), indicating reverse redistribution, while this change was not observed at 6 weeks. Defect size on postinjection scans on day 7 correlated with the per'fusion score acutely obtained with myocardial contrast echocardiography (r=0.62, p<102). Poor perfusion scores were associated with larger post-injection TI defects (37.2_+13.3% vs 19.6_+12.2% in patients with high scores, p<0.05), while the relation was not significant with redistribution defects. Post injection scans on day 7 were also related to the final wall motion scores on day 42 (r=0.67, p<10-2). Conclusion: Seven days after acute myocardial infarction, reverse redistribution is observed in patients with early and complete patency of the infarct-related artery and disappears in subsequent weeks. Post-injection thallium images on day 7 mainly reflect the acute microvascular perfusion and are related to regional function on day 42. Therefore, in TIMf-3 patients, reverse redistribution is related to effective myocardial reperfusion and salvage.

25.4

25.6

V.M. Heinrichs, *G.K. Lund, J.Mester, M.Luebeck, *C.A.Nienaber, M.Clausen Department of Nuclear Medicine and *Department of Cardiology, University Hospital Eppendorf, Hamburg

U. Schricke 1, I. Matsuuari 1, U. Haase 2, J. Dirschinger 2, F. Bengel 1, C. Duvernoy 1, A. Sch6mig 2, M. Schwaiger 1. IDep. of Nuclear Medicine, 2Dep. of Cardiology, Technische Universit~.t M[tnchen, Munich, Germany

PREDICTION

OF

INFARCTION

USING

ACCELERATED TC-99M-SESTAMIBI WASHOUT IN INFARCT MYOCARDIUM AFTER SUCCESSFUL REPERFUSION

WALL

MOTION

MYOCARDIAL

RECOVERY PENFUSION

AFTER

ACUTE

MYOCARDIAL

SCINTIGRAPHY

Purpose: Spontaneous recovery of left ventricular wall motion after acute myocardial infarction (ANI) is a known phenomenon. We investigated the ability of myocardial perfusion scintigraphy to predict functional recovery. Methods: 32 patients (6 women, 26 men) after myocardial infarction and with angiographically proven successful recanalisation of the infarct related artery were investigated 9 ± 4 days after ANI. T1201 rest-/redistribution SPECT, resting Tc-99m-MIBI-SPECT and resting echocardiography were performed in each patient. Functional recovery was assessed by echocardiography 51-310 days (median 121 days) after ANI. For evaluation the left ventricle was divided into 16 segments. Only the segments corresponding to the area of raaximttm risk were analysed. Segments with a tracer uptake of more than 50% of the respective study raaxLmum were considered viable, all others nonviable. Segraents were classified akinetic, hypokinetic or normokinetic by echocardiography. Functional recovery was defined as an improvement in segmental wall motion at control echocardiography by at least one category. Results: 285 segments were evaluated. 85 of 158 akinetic (54%) and 29 of 60 hypokinetic segments(48~) exhibited functional recovery at follow up echocardiography. ~ o n g 85 transiently akinetic segments 76, 68 and 64 were scintigraphically viable by resting Ti-201, 4hredistribution TI-201 and Tc-99m-MIBI-SPECT respectively. The corresponding predictive values of scintigraphic viability are surmmrized below: segments prevalence of predictive values after ANI recovery (echo) Tl-rest Tl-red MIBI-rest hypokinetic 48% 55% 57% 54% akinetic 54% 73% 81% 84%

I[ p<0.001 I

P<0,'0011

Conclusion: Myocardial perfusion scintigraphy is a helpful predictor of wall motion recovery in akinetic segments after AMI. It has no additional value for hypokinetic segments. The highest predictive values regarding functional recovery were obtained by 4h-redistribution resting T1-201 and resting Tc-99m-MIBI-SPECT.

894

Although Tc-99m-sestamibi SPECT imaging is an accepted technique to measure infarct size and the amount of salvaged myocardium, accelerated clearance from salvaged myocardium has been reported (JNM 1996; 37: I289-1294). The aim of this study was to determine whether or not the time delay between tracer injection and imaging would alter the measmed defect size in patients with acute myocardial infarction (MI) undergoing successful primary angioplasty. 11 patients with M1 had area at risk imaging (AR) using i000 MBq Tc-99m-sestamibi before reperfusion 5+2 hr after onset of symptoms and a follow-up study 4 to 8 days later. For the second study we performed 30 min (early) and 3 hr (delayed) imaging after injection of 1000 MBq Tc-99m-sestamibi. Defect size was measured by a polar map approach using 60% of peak activity as a threshold cutoff, and was expressed as % of the left ventricle (%LV). The amount of sNvaged myocardium was defined as differences in defect size between the AR and the early images. The mean regional activity in the area at risk was calculated for each of AR, early and delayed images. Before revascularisation, the area at risk measured on average 52.7+_19.5%LV. In the follow-up study, the measured defect size decreased on early images (34.2+18.1%LV) and increased again on delayed (43.0+18.4 %LV, p<.0001) imaging. Accordingly the mean activity before revascularisation was 36,8+5.4% of peak and increased on the early follow-up images (55.0+6.8 %). In the delayed follow-up images the mean activity was again deacreased (47.6_+6.3 %, p<.0001). Conclusions: Comparison between early and delayed SPECT imaging performed 4 to 8 days after acute myocardial infarction reveals accelerated Sestamibi washout (i.e. a pattern of reverse redistribution) in the infarct region indicating that determination of defect size in these patients is time dependent.

[] Therapy Therapy 26.1 Bohuslavizld K.H., W. Brenner, S. Tinnemeyer, S. Lassmann, K. Kai-

ser, J. Mester, M. Clausen, E. Henze.

26.3 G. MOdder, R. M6dder-Reese Special Practice for Radiosynoviorthesis, 50858 Cologne/Germany

Clinics of Nuclear Medicine, Universities of Kiel and Hamburg, Germany RADIOPROTECTION OF SALIVARY GLANDS BY AMIFOSTINE IN PATIENTS TREATED WITH HIGH-DOSE RADIOIODINE

Salivary gland impairment following high-dose radioiodine treatment (HD-R1T) is a well known side effect. Since differentiated thyroid cancer (DTC) has a very good prognosis reduction of long-term side effects becomes important for the patient's quality of life. Therefore, the radioprotective effect of amifostine was investigated in patients receiving high-dose radioiodine therapy. Quantitative salivary gland scintigraphy was performed after intravenous injection of 100-120 MBq Tc-99m-pertechnetate in 17 patients with DTC prior to and 3 months after high-dose radioiodine therapy with 6 GBq I-131. Parenchymal function of salivary glands was quantified by calculating the uptake of Tc-99m-pertechnetate in percent of injected activity. Eight patients were treated with 500 mg amifostine (Ethyol®) per sqm body surface prior to radioiodine, and 9 patients served as control.

Prior to 3 months

Controls

Amifostine

Parotid gl. Submand. gl. 0.46_+0.10 0.42+-0.17 0.29_+0.12 0.27_+0.16

Parotid gl. Submand. gl. 0.43_+0.13 0.38+0.16 0.42_+0.14 0.36+_0.17

Tc-99m-pertechnetate uptake is given in detail in the above table. In 9 controls HD-RIT significantly (p<0.01) reduced pertechnetate uptake by 37 % and 3 1 % in parotid and submandibular glands, respectively. Three out of these 9 patients exhibited xerostomia grade I. In contrast, in 8 patients treated with amifostine there was no significant (p=0.878) decrease in parenchymal function following HD-RIT, and xerostomia did not occur in anyone. In conclusion, parenchymal damage in salivary glands induced by HDRIT can be reduced significantly by amifostine. This may help to increase quality of life of these patients.

RADIOSYNOVIORTHESIS IN P O L Y A R T H R O S I S O F T H E FINGERS The most frequent primary osteoarthritis is the polyarthrosis of the fingers (Rhizarthmsis, Heberden's polyarthrosis, Bouchard's polyarthrosis), often occuring systemically in connection with a primary generalized arthrosis. Rhizarthrosis is found in most cases associated with Heberden's and Bouchard's polyarthresis, but also may be isolated. With activated rhizarthresis the patients have difficulty doing a wringing motion, opening a screwcap or to hold fork (opposition, abduction and circumduction of the thumb aggravates pain). Subluxation may occur early. Destructive (erosive) polyarthosis of the DIP and PIP joints appears with unusually violent inflammatory phases, leading to ankylosis. The reactive synovitis, and thus the activation of the arthrosis, is especially intensive. Causatively discussed is an exceedingly osteodestructive reactive synovitis, an abnormal osteoaggressive synovial fluid, disturbed subchondral perfusion or aseptic necrosis of the bone. The common treatment (incl. surgical interventions) is unsatisfactory until now. Radiosynoviorthesis is well established as a therapeutic procedure in finger joint involvement in rheumatoid arthritis but yet not known for osteoarthritis of finger joints. For the first time it is reported the effect of radiosynoviorthesis (with erbium-169) in these diseases (rhizarthrosis: 130 joints, Heberden's polyarthrosis: 90 joints. Bouchard's polyarthrosis: 68 joints). Besides the clinical symptoms the soft tissue scintigrafy of the joints is significant for the indication of radiosynoviorthesis. All patients were examined systematically before and after treatment. The effect of radiosynoviorthesis depends not at least on bone destruction, but even in progressive stages there may result satisfactory effects, sometimes after re-radiesynoviorthesis. For all joints an improvement was found in 72 %.

26.2

26.4

S.H. Han, B.A. Zonnenberg, J.M.S.P. Quirijnen, J.M.H. de Klerk, A.D. van het Schip, A. van Dijk, P.P. v a n Rijk, University Hospital Utrecht, Department of Nuclear Medicine, The Netherlands.

J. Vose.D. Colcher,P. Bierman,P. Leichner,O. Akabani, K. Harrison,M. Hohenstein, S. Lesser,L. Hammershaimb,D. M Goldenberg,M Tempero, and J. Armitage.Univ. of NebraskaMed. Ctr.,Dept.of InternalMed., Pathology,,and Radiation Oncology and Immunomedics,Inc., Morris Plains, NJ, and Garden State Cancer Ctr, Belleville, NJ.

EFFICACY OF RHENIUM-186-ETIDRONATE IN BREAST CANCER PATIENTS WITH METASTATIC BONE PAIN Objectives: E f f i c a c y of R e - 1 8 6 - e t i d r o n a t e (Re) in b r e a s t c a n c e r (BC) p a t i e n t s w i t h p a i n f u l bone metastases. Patients and methods:30 patients w i t h a d v a n c e d BC s u f f e r i n g from m e t a s t a t i c bone p a i n (MBP) w e r e t r e a t e d w i t h Re u s i n g d i f f e r e n t dosages in a noncomparative, openilabel study. 24 patients were evaluable for efficacy (6 patients had incomplete data sets). Dosages varied from 1295 to 2960 MBq. E f f i c a c y was e v a l u a t e d a c c o r d i n g to the m u l t i d i m e n s i o n a l pain model using a paper-andpen diary. The diary had to be kept twice daily for 8-10 wks (2 wks b e f o r e t h r o u g h 6-8 wks a f t e r Re treatment).Response was d e t e r m i n e d u s i n g a strict d e c i s i o n rule, in w h i c h p a i n i n t e n s i t y (PI), m e d i c a t i o n i n d e x (MI), and d a i l y activities (DA) were core determinants. Response was defined as: l) r e d u c e d PI ~ 25% w h i l e MI a n d D A w e r e at least constant; or 2) reduced PI <25% in combination with i m p r o v e m e n t of MI a n d / o r D A ~ 25%, without w o r s e n i n g of e i t h e r factor. D u r a t i o n of r e s p o n s e s h o u l d a l w a y s e x c e e d a m i n i m u m of two weeks. Results: 54% (n=13) of all cases r e p o r t e d a response. The m a x i m u m follow-up period was 8 weeks. Duration of response ranged from 2 to 8 weeks (mean 5 wks). The responders (13/24) not only experienced considerable pain reduction, but in 8 patients this was also accompanied by a considerable reduction in MI (~ 25%). No clear dose-response relationship was found. Conclusions: Using strict pain assessment criteria, Re s h o w s a r e s p o n s e of 54% in the palliative treatment of MBP originating from BC.

I-I31-LL2 (ANTI-CD22) RADIOIMMUNOTHERAPY (R/T) OF REFRACTORY NON-HODGKIN'S LYMPHOMA (NHL): RESULTS OF A REPETITIVE DOSING TRIAL. Sixteen patients (pts.) with relapsed/refracto~' low or intermediate-grade NHL participated in a phase I/II trial of I-13 I-LL2 RIT. All pts., but one, failed at least 3 chemotherapy regimens and 7 had failed bone marrow transplant. Pts. had stem cells harvested for use in the event of prolonged ~'topenias. Pts. then received 2 (N=3), 4 (N=7), or 6 (N=6) biw doses of 1-131-LL2 with an initial dose of 555 MBq/m: and all subsequent doses administered based on whole body radioactivity and calculated to bring the whole body radioactivity to 555 MBq/m~. Starting with dose level 2, all pts received 20 mg unlabeled LL2 pre-RIT. Five pts. who had a partial response (PR) or stable disease (SD) and one pt. who had a CR(u) at 8 weeks and did not require use of their stem cells, received a second course at the same dose level and one pt a third course. Non-dose-limiting toxicities associated with therapy included cvtopenias requiring stem cell infusion in 3 pts. (2 pts. in cycle 1 and 1 pt. in cycle 2), hypoth? roidism in 3 pts., rash and HAMA in 1 pt., and asymptomatic HAMA in 1 pt. Responses to the therapy included CR or CR(u) in 3 pts., PR in 1 pt, SD in 2 pts., progressive disease in 8 pts. Two pts. are too early to evaluate. T~o pts. who achieved CR status were pts. with int-grade NHL who had failed dose-intensive chemotherapy and autologous stem cell transplantation. One ofthase patients continued in CR(u) for 24 months following the initiation of 1-131-LL2 therapy then relapsed in a localized bone lesion; the other continues in CR at 16+ months post-therapy. The 2nd CR(u) is currently undergoing re-treatment with I-131-LL2 and has had this response for 1+ month. The patient achieving a PR is continuing to respond 12+ months post-treatment. Biopsies of lymph nodes following treatment confirmed presence of the RIT agent and external imaging was confirmatory for targeting in 11/12 completed pts.

895

• Therapy/Endocrine 26.5

27.2

T.M. Behr ~, T. Liersch2, S. Gratz ~, R.M. Dttun ~, E. Weber 1, B. Ringe2, W. Hiddemarm4, H. Becker 2, W. Becket ~. Depts. of Nuclear Medicine ~, Surgery z, and Oncology ~ of the University ef G6ttingen, Germany, and Garden State Cancer Center ~, Belleville, USA.

D. M o k a E. Voth, K. Smolarz, A. LarenaAvellaneda, H. Schicha. Dept. of Nuclear Medicine, University of C o l o g n e and Dept. of Surgery, St. Katharinen-Hospital, Frechen, Germany

RADIOIMMUNOTHERAPY OF COLORECTAL CANCER IN MINIMAL RESIDUAL DISEASE AND IN AN ADJUVANT SETTING: PRELIMINARY RESULTS OF AN ONGOING PHASE-I/II TRIAL WITH AN ~3~I-LABELED ANTI-CEA lgG The 5-year survival of colurectal cancer patients with liver metastases is close to zero in tmresectable cases and, in case of resectability, remains still below 30%. Adjuvant chemotherapy has not been able to improve survival rates; therefore, new therapeutic strategies are warranted. The aim of this study is to evaluate, in a phase-VII trial, the toxicity and therapeutic efficacy of radioimmunotherapy in an adjuvant setting or minimal residual disease in colorectal cancer patients after resection of liver metastases. So far, 17 eolurectal cancer patients were entered in the ongoing mCi/m~-based dose escalation study with the ~x~I-labeled anti-CEA MAb, F023C5 IgGn 4 weeks after successful resection of hepatic metastases. 10/17 patients were free of disease at the time of RAIT, 7 had known minimal residual disease (lung, liver; all lesions _<2.5 cm). The patients were given single injections, starting at 50 mCi/m~. The maximum tolerated dose (MTD) is defined as the dose level where -< 1/6 patients develop myelotoxicity > grade 3. Dosimetry was calculated from imaging data according m the MIRD scheme. In patients with minimal residual disease, complexatiun between the injected MAb and circulating CEA correlated to plasma CEA levels, whereas in adjuvant settings with normal plasma CEA, no significant complexation occurred. However, enhanced hepatic clearance of the injected antibody was observed (blood tv, 12.5 _+4.9 h), correlating to postsurgically altered liver function parameters (the more elevated the liver enzymes lAP, GOT], the faster the clearance). At mean whole-body doses of 0.54 cGy/mCi and red marrow doses of 1.07 cGy/mCi, myelotoxicity seems to become the dose-limiting factor. A good correlation between red marrow doses and resulting toxicities was found; at 80 mCi/m", 2/3 patients developed grade-3 leuco- or thrombocytopenia (present dose level: 100 mCi/m~). In patients with minimal residual disease, all known lesions were targeted; tumor doses increased exponentially with decreasing tumor size (Nghest observed dose: 185 cGy/ mCi in a 0.5-cm lung lesion). O f six assessable patients with minimal residual disease, one had a partial remission, two a minor/mixed response, two experienced stabilization of previously rapidIy progressing disease. All patients showed an at least transient normalization ofsermn tumor marker levels. An enhanced hepatic clearance of anti-CEA MAbs at altered liver function parameters has been described by us earlier (Behr et al., Cancer Res 1996; 56: 1805); its pathophysiological basis remains unclear at this point. Myelotoxicity seems to be dose-limiting. Although the MTD has not yet been reached, anti-tumor effects are encouraging. Further dose escalation and longer follow-up of treated patients are ongoing.

Endocrine 27.1 C BillolPy, B. Halimi, S. Fntsch, J.D. Ram, P. Cattan, E. Sarfa'a - 5ervKes de M4,decine Nucl6.aire et de Chirurg~e CK='r~ale- H6pital Saint-Louts - PARIS- FRANCE

PREOPERATIVE

LOCALIZATION

ADENOMA

99MTc

USING

- MIBI

OF

SMALL

PARATHYROID

- SPECT.

Aim: The value of the 99mTc-MIBI scintigraphy in SPECT technique was assessed in the preoperative localization of small parathyroid adenoma (PTA). Methods: 29 c o n s e c u t i v e p a t i e n t s (i0 male, 19 female, mean age 65 ± 12 years) with the established diagnosis of primary hyperparathyroidism and non-diagnostic ultrasonography were scanned preoperatively. After a t h y r o i d e x a m i n a t i o n to e x c l u d e r a d i o n u c l i d e accumulating thyroid adenomas, p l a n a r and tomographic images were acquired 15 min. and 120 min. after i.v. injection of 740 MBq 99mTc-MIBI using a 3 head gamma camera (Picker Prism 3000). The s e n s i t i v i t y was d e f i n e d by the a b i l i t y to predict the correct side of the lesion. Results: All patients had small, solitary PTA (~ ig). Correct lateral l o c a l i z a t i o n of PTA using planar M I B I - s e i n t i g r a p h y was possible in 72 %. There was an increase in sensitivity to 96 % using the SPECT technique and the 3D display (volumerendered reprojection). Conclusion: This study indicates that tomographic 9 9 m T c - M I B I p a r a t h y r o i d s c i n t i g r a p h y is h i g h l y sensitive and specific for lateral localization of even small PTA, especially using SPECT and 3Ddisplay. This method is clinically useful because it can help to improve the efficiency of parathyroidectomy (e.g. performing only an unilateral exploration) and to decrease postoperative morbidity (laryngeal nerve injuries, hypoparathyroidism).

27.3 A. Ftotats, C. Marl, L1. Bern&, A. Ballafin*, J. Martinez-Garcia*, J. Piera, M. Estorch, A.M. Catafau, I. Card& HospiTal de Sant Pau. F. Puigvert *. Barcelona. Spain.

RESULTSOF SCINTIGRAPHYWII'H ~ T C - MIBL FADS, AND SPECF IN 59 CASES OFREOPERATIONSFORHYPERPARATHYROIDEM. AIM OF THE STUDY : Evaluate m 59 paticl~ts ([Ks)the msulls of a l~ewsdnhgraphic meth~x.t tL~l~ 99mTC-MIBI, Factor Aralys~ of D~amic 9auctures (FADS) and SPECT, Ix,fore r~rperalion for r~vmTentor tx'm-~t hypt~'paraflayro~&s;m0qlrl~. PATIENTS AND METHODS : 3he 3 types of Fatc~lt HPT were observed (30 pnn~D', 25 SCmladary,4 tertiary). 13 pls had one or several th)ax~idrodules, 1 pt had a thyroid, 4 ~ s bavehadaprev~mspartial(m2pts) or total (in 2pLs) thyroidecl~rmy. 68 sdnllgraphies were performed belore 65 rmperali~-s. 7 pts were operated c~l only 14 days after a p r e ~ u s m~successful ~ . 49 pts were cured after one surgery, in 7pls, d e ~ removal of abmrmal gleand(s) , HPT Wts'NM :in 4 of lIese pts, a ntwe rmtxvation aaowed cure, and was m'suca~ful in 2pts. In3 pts, t~oabnormal g!and was found. F i ~ , 25 to 30 one nmvate hnage acqutsllion was started at the ~ne of inlraverr~s bolus ~ec~m of 15-20 mCt of 99mTc-MIN with a pirv~le mll/mator ~ on the thyroid area. Secrandly, lateral planar v/ews (T~/)of IK
ghrds tn thethyroidareawasl~gh(865%)und tte s F ~ t y excdla* (~ 5 %). CON(IUSION : This rcw s~m~raphic method allows to ~ .~msNvity of imaging m~xMitiesin cases of tx'rs~'ut or r~x~m~t HPT with ~ s t x ~ , txvause of ¢ is V.%m'ea~; meth~.xtto d ~ t t hy[x,rf,hst~-and nwdi,x4ir~ gtaiKts.Thus, the cure rate of re~rWxaiXm~shtgh

896

99mTc-SESTAMIBI SCINTIGRAPHY FOR L O C A L I S A T I O N OF HYPERFUNCTIONAL PARATHYROID GLANDS IN SECONDARY HYPERPARATHYROIDISM. The aim of the study was to assess the feasibility of 99mTCsestamibi double phase scintigraphy for localisation of hyperftmctional parathyroid glands in patients with secondary hyperparathyroidism 99mTc-sestamibi double phase scintigraphy (740 MBq i.v., imaging at 15 and 150 min.) was performed in 16 patients (5 male and l l female, mean age of 51 _+ 14 years) prior to parathyroidectomy. All patients had hyperparathyroidism secondary to chronic renal failure and one of them had previous subobtimal surgery. Fifty-seven hyperplastic glands of 1.37 + 1.83 g weight (range 0.07-9.00 g) were resected. 99mTc-sestamibi scintigraphy correctly localised 42 of the 57 hyperplastic glands (sensitivity 74%), and correctly identified the multiglandular disease in 13 of the 15 patients(87%) with no previous surgery. The weight of the hyperplastic glands that were detected by 99mTc-sestamibi scan was higher (1.59+A.91 g, p<0.05) than that of the undetected hyperplastic glands (0.29 ~.23 g). We can conclude that localisation of secondary multiglandular parathyroid involvement is feasible with 99mTc-sestamibi double phase scintigraphy. The sensitivity of this technique is, however, affected by the parathyroid glandular weight.

[] E n d o c r i n e / R e n a l

27.4 D.J. ADostoIoDoulos, E. Houstoulaki, C. Giannakenas, C. Kalantzis, C. Markou, T. Alexandrides, J. Spiliotis, J.G. Vlachojannis, P.J. Vassilakos. Departments of Nuclear Medicine, Endocrinology, Surgery and Nephrology, University Regional Hospital of Patras, Patras, Greece. KINETIC PROPERTIES OF TC-99m TETROFOSMIN IN THYROID AND PARATHYROID GLANDS. COMPARISON WITH TC-99m SESTAMIBI.

Object: The objective of this study was to evaluate Tcggm-Tetrofosmin (TF) for parathyroid detection, focusing on the kinetic properties of this agent in the thyroid and parathyroid tissues. Kinetics of TF were directly compared to those of Tc99m-Sestamibi (MIBI) in a subgroup of patients studied with both radiopharmaceuticals. Methods: 66 preoperative pts were studied with TF (Group A); 38 with primary and 28 with tertiary hyperparathyroidism (pHPT and tHPT). A series of 30 images, 1 rain each, was dynamically acquired immediately after the injection of 550 MBq of TF. 3-4 delayed images, up to 3 hrs p.[. were also obtained. Tc99m-pertechnetate was used in order to subtract the thyroid from the early images of TF. The diagnostic efficacy of the subtraction scan (TF/PERT) was compared to that of the TF single-tracer washout technique (TFwo). The half-clearance times (T1/2) of TF from the thyroid and the enlarged parathyroid glands were calculated from the late component of the corresponding time-activity curves. A subgroup of 19 pts (Group B) were also studied with MIS[ (injected dose: 370 MBq), following the same acquisition protocol and processing as the TF studies. Results: Group A: With reference to 32 adenomatous (AD), 112 hyperplastic (HPL) and 86 normal parathyroid glands surgically identified, the sensitivity and specificity of the TF~ETR scan was 74.3% (AD: 87.5%, HPL: 70.5%) and 92% respectively. The corresponding figures of the TFwo technique were 61.8% (AD: 78.1%, HPL: 57.1%) and 75%. Evaluable kinetic results (mean T1/2+_SD) are eummarised below: THYROID P A R A T H Y R O I D Statistical Difference (p) AD 168_+80 ( n = 3 1 ) 243_+154 (n=26) <0.05 HPL 145_+62 (n=33) 149+77 (n=61) NS TOTAL 156_+72 (n=64) 176_+112(n=87) NS Group B: As far as subtraction is concerned, TF and MIBI were equally effective parathyroid detection (8/9 AD and 22/36 HPL). Compared to subtraction, the TFwo technique missed one more AD and another 6 HPL, while the MIBI single-tracer washout technique missed another 3 HPL. Evaluab]e kinetic results (mean T1/2_+SD) were as follows: n TF MIBI Statistical Difference (p) THYROID 19 191_+85 81_+38 <0,000t PARATHYROID 24 1 8 9 + 1 0 3 188-+97 NS Conclusion: Tcg9m-tetrofosmin appears suitable for parathyroid imaging, but the single-tracer washout technique is less sensitive than subtraction, particularly for the detection of hyperplastic glands, and less specific. The clearance of this agent from abnormal parathyroid glands does not seem substantially different from that of Sestamibi; in contrast, tetrofosmin has considerably slower clearance from the thyroid.

27.6 V.Vallejos, J. Nora, NT. Gonz~lez*, R. Rafecas**, A. Mufioz, A. Fern&ndez, J. MartinComin and M. Ramos. S.Medicina Nuclear, Nefrologia* and Cirugia. CSUB Hospital Principes de EspaNa. Barcelona. Spain. USEFULNESS OF PAIIATHYROID 99mTc-TETRDFOSMIN IN HYPNRPANATHYROIDISM.

SCINTIGRA2HY PATIENTS

WITH WITH

The aim of the work was to study the diagnostic value of 99mTc-Tetrofosmin (TTF) to localize anomalous parathyroid glands in patients (p) with hyperparathyroidism (HPT). We have studied 37 p: 18 with primary HPT (45-83 years, 4 males) and 19 with secondary HPT (26-72 years, 6 males), 7 of them renal graft recipients. 15/37 patients underwent surgery (ii primary HPT + 4 secondary HPT). All patients were injected with 740-925 MBq of TTF.Subsequently 15, 30 and 60 minutes images were acquired for 300 seconds using a pin-hole collimator. A thyroid scintigraphy(SC) with 99mTc04was obtained in 23 cases (72 h later) when the thyroid activity made difficult the identification of parathyroid glands. Primary HPT: 15 p showed a focal uptake, in ii the surgery demonstrated adenoma in the same localization and 4 are pending of surgery, in 3 cases the scan was normal. Secondary HPT: ii p showed a diffuse uptake in 2 or more glands, and histology confirmed hyperplasia in 4. The 6 remaining patients showed a focal uptake (tertiary HPT in renal transplantation?).The 2 cases with normal SC corresponded to true negative and the other a false negative scans. In conclusion, our results suggest that TTF may be used as a suitable tracer for preoperative localization and screening of anomalous parathyroid glands.

Renal

27.5

28.1

D. Huglo, V. Beauchat T. Prang~re, A. Bailliez, P. Ziegels, C. Proye, X. Marchandise, M. Steinling - Departments of Nuclear Medicine, and General and Endocrine Surgery, H6pital HURIEZ - CHU de Lille, 59037 Lille cedex - FRANCE

F.J. Rink, G. Meyer, K. Tatsch, K. Hahn Department of Nuclear Medicine, University of Munich, Germany

PARATHYROID IMAGING : IS DOUBLE PHASE S T U D Y P O S S I B L E W I T H 99~Tc-TETROFOSMIN ?

99mTc-MIBI is a recognised tracer for parathyroid imaging using subtraction tec~hnique or/and <> (Talllefer 1992). With this technique, 2 frames are performed 20 minutes and 2 hours after injection and abnormal parathyroid glands are better seen on the second because of faster clearance from thyroid. 99mTc-Tetrofosmin is also a potential tracer for this indication and this work has studied the thyroid and parathyroid clearances to know if double phase study is also possible with Tetrofosmin. Methods : Scans of 89 patients without thyroid disease and with primary hyperparathyroidism cured by surgery were studied. Regions of interest were drawn on 2 frames performed 20 and 120 minutes after 1V injection of 550 MBq of tracer (MIBI or Tetrofosmin), on normal thyroid tissue, abnormal parathyroid gland and background. After background subtraction and correction of the physical decay of 99mTc, results were expressed as Residual Uptake (R.U., in % : 2 h/20 min). Results (mean + standard deviation, * = p < 0.05 with Student's t test) MIBI 38 Tetrofosmin n R.U. n R.U. Uthyroid 38 4 6 + 2 2 % ~ * > 51 63 + 1 2 % ~ n s [parathyroid 37 65 _+ 38 % ~* q u~ 58 + 16 % There was no difference of duration between early and delayed frames. Conclusions : The thyroid and parathyroid clearances are significantly different with MIBI but not with Tetrofosnun. Since the faster washout from the thyroid is only seen with MIBI, Tetrofosmin cannot he used with double phase technique. In our experience, if subtraction technique is performed (99mTc/123I), sensitivities of MIBI and Tetrofosmin in parathyroid imaging are the same.

S I M U L T A N E O U S A S S E S S M E N T OF M A G 3 - AND OIHCLEARANCE: C O R R E L A T I O N B E T W E E N A SINGLE-SAMPLEAND AN EXTERNAL COUNTING M E T H O D

Due to its poor imaging properties and comparatively high radiation exposure O/H labeled with iodine-131 has been almost totally replaced by Tc99m-NAG3 in dynamic renal scintigraphy. However, in several nuclear medicine facilities it is still in use for the determination of the total renal clearance. Using a simultaneous dual tracer technique we compared the slopeclearance of Tc-99m-MAG3 measured by a single sample method with that of I- 131-OIH assessed by an external counting method. A total of 204 examinations was performed including 52 follow up studies after highdose chemotherapy with cisplatin or ifosfamid. There is a strong binominal corre40o [ I... ~ . lation between Tc-99m-MAa3-regres_ -350 " // and 1-131-OIH-clearanc~ values (r=0,92). We found a deviation of ~soo : ~'.fi • the curve from the line of sion especially in cases with a very ~250 .~o" ~';: " high ERPF. One possible explana~ " tion for that finding suggested pre20o A~ .,. viously by Russel et al. might be , t ~,: : the presence of circulating, poorly 150 /.'4 J excreted impurities from the kit;~ 100 "" [ prepared Tc-99m-MAG3. The ~50 mean ratio between the Tc-99mMAG3- and the 1-131-OIH0 ~ clearance was 0,59 + 0,09. With the exception of one patient this 0 100 200 300 400 so0 600 700 800 ratio showed only minor changes 1-131-O//-I-dearance[ral/min] in follow up studies. We conclude from our simultaneous dual tracer studies that Tc-99mMAG3 is suitable to replace 1-131-OIH not only in renal scintigraphy but also for estimating effective renal plasma flow. Possible underestimations of ERPF by the use of kit-prepared NAG3 in cases of highly normal renal tubular function might be negligible in clinical routine applications. 897

co =l e"

x_

Q. mill

t~

•

Renal

28.2

28.4

W.S.Watson, E.Donald, M.Duxbury, J.Morrison, T.Murray, G.T.McCreath, Nuclear Medicine and Radiology Departments, Southern General Hospital NHS Trust, and Regional Radionuclide Dispensary, Western Infirmary, Glasgow, Scotland.

W.S.Watson, Nuclear Medicine Department. Southern General Hospital NHS Trust, Glasgow, Scotland.

EFFECTIVE RENAL PLASMA FLOW (ERPF) DERIVED FROM SINGLE BLOOD SAMPLE FOLLOWING 99mTc-HAG3 INJECTION

SINGLE SAMPLE EFFECTIVE RENAL PLASMA FLOW (ERPF): CLINICAL ASSESSMENT OF PREDICTION FORMULAE

Single blood sample methods for ERPF determination following radio-iodinated hippuran i/v injection are well established. The introduction of 99mTc-MAG3 led to the development of methods to derive ERPF values from 99mTc-MAG3 plasma activity. Russell et al (1988) noted that the plasma activity of 99mTc-MAG3 was 0.563 times the plasma activity of radio-iodinated hippuran in samples taken 44 min post tracer injection. Therefore, (99mTc-MAG3 plasma activity/0.563) could be introduced into the single sample ERPF prediction equations developed for hippuran after the method of Tauxe et ai(1982). Single sample ERPF values were obtained for i00 patients given both 99mTc-MAG3 and 125Ihippuran with blood sampling at 44 min. The radiochemical purity of 99mTc-MAG3, the ~in vivo" red cell uptake and plasma protein binding of MAG3 were measured. There was an excellent correlation between ERPFs obtained using 99mTc-MAG3 and 125Ihippuran (r=0.92, p<0.00005);the ratio of ERPF(MAG3)/ERPF (hippuran)=l.03±0.18(mean±iSD). Red cell uptake(99mTc-MAG3)=0.6±0.4 %dose/red cell volume, plasma protein binding(99mTc-MAG3)=42i4% while 99mTc-MAG3 radiochemical purity=85i3%. Stepwise regression indicated that the ERPF(MAG3)/ERPF(hippuran) ratio was influenced by 99mTc-MAG3 plasma protein binding and radiochemical purity.

The ~gold standard" ERPF technique in nuclear medicine is the multi-sample method after iv bolus injection of radio-iodinated hippuran. This is time-consuming, and so, single sample methods were sought. Two main formulae were developed where single sample plasma activities at around 40 min post-injection were correlated with ERPF values based on multi-sampling between 5 to 60 min(Tauxe et ai(1982), Piera et ai(1997). To assess these formulae in clinical practice, venous blood samples were taken between i0 and 180 min post 125I-hippuran injection in 18 adults. Double-exponential curve fitting to the plasma sample activity-time data was performed out to 60 min and 180 min, yielding ERPF(2EX60) and ERPF(2EXI80) respectively; the latter should be the more accurate as the sample activity-time curve was better defined. Plasma activities at 40 min were inserted into the ~Tauxe" and ~Piera" formulae yielding ERPF(Tauxe48) and ERPF(Piera40). Excellent correlations were obtained between the multi-sample estimates of the present study and the single samples estimates (r-squared >93%). However, ERPF(Tauxe40)/ERPF(2EXI80)=I.18 and ERPF(Piera40)/ERPF(2EXI80)=I.12 indicated that the single sample methods overestimated our best multi-sample estimate. The ratios, ERPF(Tauxe40)/ERPF(2EX60)=I.08 and ERPF(Piera40)/ERPF(2EX60)=I.00, were closer to unity. This suggested that the sampling period chosen in the studies of Tauxe and Piera and their co-workers, i.e. 5-60 min, was too short.

28.3

28.5

A. Fuat Yapar, Levent Kabasakal, Zeynep Do~ruca, Emin ¢inta~,

M. Froissart, P. H o u i l l i e r , C. Hignette, Mk Paillard. Service de Physiologie et Radioisotopes, H6pital Broussais, and Inserm U356, Paris, France.

Cetin 0nsel. Cerrahpa~a Medical Faculty, Department of Nuclear Medicine, Istanbul, Turkey.

DETERMINATION OF RENAL AND EXTRARENAL CLEARANCES OF Tc-99m-EC Tc-99m-ethylenedicysteine has been shown to have proper pharmacokinetics in determination of ERPF. The present study was undertaken in order to determine whether there is a clinically significant extrarenal clearance of Tco99m-EC For this purpose 11 male patients, age range 15-75 years, were included to the study. None of the patients had oedema, ascites, renovascular hypertension or urinary tract obstruction. Urinary catheter was placed to all patients prior to the study. Patients were hydrated orally by 200 ml water per hour for 5 hours. A single shot of 100 Mbq of Tc-99mEC was given to the patients. After the injection 15 blood samples of 2 ml were drawn for 5 hours and collected in heparinized tubes. Urine was also collected quantitatively through the urinary catheter for the same period. Plasma and urine samples were counted in a well type gamma counter. Plasma and 5 hours urinary clearances were determined by using three-compartment analysis. Plasma clearance range was found to be 161.5 ml/min and 364.6 ml/min with a mean value of 2694±63.2 ml/min. Urinary clearance range was 147.2 ml/min and 348.7 ml/min with a mean value of 252.6±61.3 ml/min (p<0.05). Plasma clearance overestimated renal clearance of Tc-99m-EC only by 6.2±4.3%. These preliminary results suggested that although the plasma clearance was significantly higher than the urinary clearance, Plasma clearance minimally overestimates the urinary clearance of Tc-99m-EC.

898

COMPARATIVE EVALUATION FILTRATION RATE (GFR) VARIOUS TRACERS •

OF GLOMERULAR MEASUREMENTS USING

The aim of our study was to determine accuracy and precision of GFR measurements using plasma (PC) and urinary (UC) clearances of 51Cr-EDTA, 99mTc-DTPA, Inulin and creatinine. R a d i o a c t i v e tracers were administered by single bolus injection and inulin by constant infusion. 20 patients (15M, 5F, aged 22 -67,S. creat. 0.7-8.8 mg/dl) underwent simultaneous measurements. In 13, the study was repeated within a 4-week interval in steady conditions. Equivalence study results (n = 33 tests) expressed as linear function of inulin UC. Tracer 1 EDTA DTPA I n u l i n EDTA DTPA Creat. slope 1 1.121 1 . 1 4 8 1 . 0 5 2 1 . 0 5 1 0 . 9 1 8 1.336 intercept I -0.221 -1.296 2 . 2 2 5 6 . 5 0 9 6 . 7 8 9 10.353 r 1 0.981 0 . 9 7 4 0 . 9 5 3 0 . 9 3 7 0 . 9 6 0 0.928 BH: B r o c h n e r - M o r t e n s e n f o r m u l a f o r PC CP: c o n s t a n t p e r f u s i o n e q u i l i b r i u m PC ReDroducibilitv study results (n : 13 p a t i e n t s ) : s/H: c o e f f i c i e n t o f v a r i a t i o n a n d i t s s t a n d a r d dev.

~racer I n u l i n EDTA DTPA I n u l i n EDTA DTPA Creat. s/M (%)J 7.49 6.54 10.88 5.74 9.43 6.71 6.37 ± SD ~ 6.03 5.67 6.15 3.99 5.79 5.39 7.13 As confirmed by a Bland-Altman plot analysis, UC of the three injected tracers and inulin PC were quite similar. BM formula tends to overestimate low and underestimate h i g h GFR. The best results are obtained with inulin PC by the constant infusion technique. An a d a p t a t i o n of the latter method to 51Cr-EDTA should be evaluated for clinical research purposes. However radioactive tracers PC appears to be acceptable in clinical practice.

[] Renal/Physics 28.6

29.2

Ph. DECOSTRE, Nuclear Medicine, H6pitaux Civils du CPAS de Charleroi, JUMET (Belgium)

D. Hamilton, D. O'Mahony, J. Coffey, J. Murphy, O'Hare, P. Freyne, B. Walsh, D. Coakley, Armed Forces Hospital, Riyadh, Saudi Arabia and St James's Hospital, Dublin, Ireland.

PLASMA AND TOTAL STEADY STATE DISTRIBUTION VOLUME OF 99mTc-DTPA DERIVED FROM 20-MIN CAMERA RENAL STUDY AFTER BOLUS INJECTION : APPLICATION TO CORRECTION OF CARDIAC CURVE DISTORTION. The use of a cardiac curve as a plasma concentration stand-in remains controversial. With 99mTc-DTPA, whatever the cardiac region of interest, an unknown proportion of interstitial fluid activity (ECF) distorts the cardiac curve and calibration with a late plasma concentration leads to underestimation of early plasma concentration. Best ECF percentage is derived by comparing cardiac curve with central venous plasma concentrations. In 10 patients, a correction algorithm, based on properties of the peripheral organ distribution volume, PODV, in mammillary systems, gave best percentage of 34.4 _+ 13.6 (mean _+ sd) with correlation coefficients between plasma and cardiac curve of 0.65 +_0.10 and 0.99 -+ 0.04 before and after correction. This work presents an algorithm to estimate the best percentage without reference plasma samples. In open systems, after bolus injection, distribution volume, VD(t), defined as the inverse of plasma concentration diverges. In closed systems, VD(t) tends to a steady state value, VDSS. Were plasma concentration expressed in % dose retained, VDret(t) should behave as in closed systems. From PODV properties applied to 20-rain 99rnTc-DTPA renogram, a continuous excretion curve is derived, whose validity is demonstrated by comparing actual and predicted bladder contents (n=57, r=0.97). Plasma concentration is normalized to the retained dose curve to derive VDret(t). After transformation, 99mTe-DTPA distribution space comprises two compartments, plasma and ECF, with bidirectional exchange. VDret(t) monoexponentially tends toward an asymptotic plateau (VDret~) close to VDSS which is estimated at peak ECF activity. In 792 patients without edema, VDSS (% BW) is 14.2 ± 2.8 with rate constant of equilibration of 0.23 + 0.08 min"1. Validity was confirmed : a) in 15 patients by biexponential fit of a plasma curve (2 to. 180 rain) : VDSS was 14.8 + 2.9 versus 14.6 +_3.2. b) in 32 patients with GFR below 20%, small difference between values whith plasma in % injected or % retained dose tends to zero whith GFR. The Y- intercept of monoexponential fit, VDreto, is plasma volume but is overestimated due to cardiac curve distortion. In the 10 patients studied, VDret0 (% BW) is 7.4 _+ 1.5 before and 4.8 + 1.4 after correction, the latter being close to true plasma volume. The present algorithm may be used to estimate the limits for ECF correction of the extemafly recorded cardiac curve with 99mTc-DTPA. without central reference plasma samples.

COMPARISON O F A R T I F I C I A L NEURAL NETWORK AND DISCRIMINANT ANALYSIS FOR THE CLASSIFICATION OF MILD ALZHEIMER'S DISEASE USING SPET DATA.

Physics 29.1 ~ , D. Lindahl, J. Lanke, A. Lundin, J. Palmer, Departrm~nts of Clinical Physiology, Statistics, Radiology and Radiation Physics, Lund University, Lund, Sweden

N.

O

= m

C

l_

A comparison of the performance of artificial neural network and discriminant analysis for the classification of normal subjects and probable Alzheimer's disease (pAD) patients was undertaken using data extracted from four regions of interest constructed on single photon emission tomographic (SPET) cerebral perfusion images. Two studies using feed forward neural networks (FFNNs) were undertaken. The first, to determine if it were possible to classify normal subjects and pAD patients in a mixed group; comprising i0 healthy control subjects and 29 patients diagnosed as pAD varying in severity from mild established to moderate dementia. The second, to determine if the networks generated in the first study could prospectively classify 15 additional patients with very mild or mild cognitive impairment. The results were compared to those obtained with the same data using discriminant analysis (DA) and assessed on the basis of the area under receiver operating characteristics curves(/~OC). The FFNN successfully classifed all datasets in the first study, achieving an AROC of 1.00; DA achieved 0.94. When tested on data from the second study, the areas under the ROC curves varied between 0.86 and 1.00; that for DA was 0.99. It is concluded that FFNNs can discriminate pAD patients with mild to moderate dementia from control subjects using data obtained from SPET cerebral perfusion images.

29.3 J.Rudzka, K.Rudzki, S.Nowak, Silesian School of Medicine, Department of Nuclear Medicine, Katowice, Poland

PHYSICI~-NS INTERPRETING MXOCAP~DIAL SCINTIGR~S BENEFIT FROM THE ADVICE OF N E L ~ IqEq~ORKS.

APPLICATION OF ARTIFICIAL NEURAL NETWORK IN ANALYSIS OF RENAL DYNAMIC STUDIES

Artificial neural networks have been trained to detect coronary artery disease from myocardial perfusion images better than human experts using coronary angiography as gold standard. In clinical practice this type of neural networks will not take over the decision-making process from the physicians, but assist them by proposing an interpretation of the scintigrarn. The purpose of this study was to assess the influence of the neural networks on the physicians' interpretations. A population of 135 patients who had undergone both myocardial technetitun-99m-sestamibi scintigraphy and coronary angiography within 3 months was studied, q~nree experienced physicians independently classified all scintigrams regarding the presence/absence of coronary artery disease in two vascular territories using a four-grade scale. The physicians classified the scintigrams twice with and twice without the advice of artificial neural networks at different occasions. The ~oint evaluation of the three physicians showed significantly improved performance with decision support, measured as increases in the areas under the receiver operating characteristic curves from 0.65 to 0.70 (p=0.018) and from 0.79 to 0.82 (p=0.006) in the classifications of the two vascular territories. Furthermore the joint evaluation showed significantly less intra- and interobserver variability with decision support. Physicians interpreting myocardial scintigrams benefit from the advice of neural networks. These results show the high potential for neural networks as clinical decision support systems.

Our previous observations showed, that artificial neural networks (ANNs) trained with the aid of the time/activity curves may be capable to recognize some functional processes in the dynamic image series. The purpose of the present study was to test the ability of the trained ANNs to analyze the renal sequential scintigrams. ANNs containing 3 layers of processing elements were used. They were trained with mathematically generated renographic curves of different patterns (normal three-phas e renogram pattern, delayed uptake and delayed excretion pattern, renal failure pattern with measurable kidney uptake, blood-background type curve, accumulation type renogram pattern).The trained ANNs were applied for direct analysis of 30 different renographic image series. The time/activity curves were then automatically generated for each pixel of the scanned area and evaluated by the ANNs. The examined parameter was displayed as a colour X-Y map. It was found, that the trained ANNs correctly classified all the examined parameters describing the renographic pattern. Mapping the classification results permitted the visualization of the area of abnormality and its localization. In conclusion, ANNs seem to be a promising tool for evaluating sequential renal scintigraphic studies. They may be applied for extracting regions of interest (e.g. in hypofunctioning, ectopic kidney). Moreover, some pathological processes within the kidney can be displayed.

899

m

• Physics/Radiopharmacy 29.4

29.6

PE Radau, PJ Slomka, Per Julin* and GA Hurwitz. Dept. of Nuclear

H. Speckter], K. Darabi2, O. Nickelj, A. Bockisch~, J. Andreas ~ ~Dept of Nuclear Medicine Mainz, ' Dept of Neurosurgery Mainz,3 Dept of Nuclear Medicine Essen, Germany

Medicine, University of Western Ontario and London Health Sciences Centre, London, Canada. Karolinska Institute*, Dept. of Clinical Neuroscience, Huddinge University Hospital, Stockhohn, Sweden. AUTOMATED ALIGNMENT AND QUANTITATIVE ANALYSIS OF BRAIN STUDIES UTILIZING THE CLINICAL SOFTWARE BRASS

INFLUENCE OF MARKER DISPLACEMENT ON THE ACCURACY OF FIDUCIAL MARKER OR LANDMARK BASED IMAGE FUSION

To improve the interpretation of cerebral SPECT, we have developed the software program BRASS, (Brain Registration and Analysis of SPECT Studies). This software implements an automated method for alignment, sizing and quantification of images using a three-dimensional reference template and a region map. Initial tests of registration accuracy as measured on correlated MR images have been applied. The program BRASS provides automatic alignment of a study to a normal template, using a simplex-minimization technique that fits orientation, position and size (nine parameters). The sample brain template composed of 10 normal studies may be replaced with a site-specific template. Once aligned, perfusion abnormalities may be calculated on a voxel-by-voxel basis or by regions ofa pre-defined map. A map consisting of 14 areas including the cerebral cortex, basal ganglia and cerebellum has been created, which may also be easily replaced. BRASS has a single button for automatic fitting and quantification using defaults. Initial tests of brain SPECT registration accuracy with BRASS have been made using aligned 3 dimensional MP-RAGE MRI and 99m-Tc-HMPAO SPECT images in 6 controls and 6 patients with probable Alzheimer's disease (AD). The SPECT images were aligned to normal SPECT image, and these same transformations were applied to the corresponding MRI images. Eleven landmarks were found on each MRI image. For each landmark, the mean distance can be calculated between the mean position and the position on different images. The 3-dimensional distance was 5.6 +/- 2.1 mm, whereas the in-slice distance was 3.5 +/- 1. l mm. These distances are interpreted as a measure of SPECT registration accuracy and may lead to improved constraints for non-linear registration.

Aim: Fiducia] marker or anatomical landmark orientated methods are widely used for coregistration of functional to morphological image data. Theoretically 3 external or internal markers define an exact orientation in order to calculate the coordinate transformation between the two modalities. However these spots are subject to physical or user dependent displacement. Method: In order to study the effects of marker displacement on the accuracy of the coregistration we choose a computer simulation approach. The image fusion software developed in our department calculates the best linear transformation of two given sets of coordinates. These sets consist of the centers of gravity of the appearance of the fiducials or the spatial coordinates of the landmarks respectively. Starting with an exact orientation, we displaced some or all markers by 0.1 mm up to 30 mm using a Monte Carlo Method. Modelling fiducial marker data we assume a mean displacement of 3 mm, in case of anatomic landmark data 10 mm (PET) or 15 mm (SPECT). Mean, standard deviation and variance were computed. Calculating the eigenvalues of the gained matrix of covariances one gets the principal axis of the displacement ellipsoid for any spatial area. Results: To achieve a target displacement in the same order as the marker displacement, at least 6 fiducials (neurocranium; abdomen: at least 8) should be used. Using anatomical landmarks a set of more than 20 corresponding marks is necessary to achieve an acceptable target displacement. Conclusion: Inadequate placement of the fiducials (e. g. only to the face in examinations of the neurocranium) may lead to more than a ten times higher positional inaccuracy. Especially in case of using anatomical landmarks, an increase in the number of markers reduce random errors.

Radiopharmacy

29.5

30.1

Michael L. Goris 1, Orith Portnoy 1, H William Strauss I, Jerome Declerk 2 Arnaud Buzbach 3 and Nicholas Ayache2. 1) Stanford University, Stanford USA 2) 1NRIA, Sophia_Antipolis, France 3) Focus Medical, Grenoble, France.

Marion de Jcn,q, Bert Bernard, Wout Breeman, Willem Bakker, Leo Hofland, Theo Visser, Ananth Srinivasan, Eric Krenning. Depts of Nucl Med and Intern Mad Ill, Univ. Hospital Dijkzigt, Rotterdam, The Netherlands. Mallinkrodt Medical, St, Louis, USA.

Elastic transformation of scintigraphic images and the analysis of population references.

RECEPTOR BINDING AND TISSUE DISTRIBUTION IN RATS OF I n - l l 1-LABELLED DTPA-OCTAPEPTIDES.

We have investigated applications based on the ability to transform images and register them to a template. The images are scintigraphic myocardial perfusion, brain perfusion and lung ventilation perfusion SPECT images. In the three applications a complete study consists of a basal image (model) and an intervention image (object). In the case of ventilation perfusion studies, the model is the ventilation study. In the case of myocardial perfusion images, the object is the stress image. For brain studies, the intervention may be pharmacological or a particular type of activity. Model and object are generally of the same size and shape, but not in the same position and orientation, nor do they have identical distribution of densities. In a first operation the model and object are registered and matched, in a second one both are registered and matched over an organ specific template. This elastic registration method is based on the identification of surface points on the organ (segmentation), which are used to measure attraction between template and target. This attraction is satisfied first by a rigid transformation, a global affine transformation and then a local spline transformation. Surface points are defined by the absolute value of the gradients along radii originating approximately near the center of the ventricular cavity, or in orthogonal searches for lung and brain. Weight is given by distance and the underlying density. Points at the extremes of the cluster of the distribution of distances between template and target points are disregarded. All operations are performed in 3D. We were able to show that the method does not minimize density distribution differences between model, object and template. For myocardial and pulmonary studies, the resulting clinical applications are based on the ability to produce normal population average density and difference images. In cerebral studies the matching allows to evaluate population responses to interventions, which, in a single patient would not be distinguishable from noise.

We evaluated the potential of In-111*labelled somatostatin analogues: [DTPA,DPhe-l,Tyr-3]octreotide (DTPAT3OC), [DTPA,D-Tyr-1]octreo-tide (DTPAT1OC), and [DTPA,D-Phe-l,Tyr-3]octreotate (DTPAT3-TATE; Thr(ol) in octreotide replaced by Thr), as radiopharmaceuticals for in vivc detection and peptide-receptor-radionuelide-therapy (PRRT) of somatostatin receptor-positive tumours. In vitro octreotide receptor binding and rat in vivo metabolism was investigated in comparison with [In111-DTPA,D-Phe-1]octreotide (DTPAOC). Results: In vitro: all compounds showed high and specific binding for somatostatin receptors in rat cerebral cortex rnicrosomes; IC-50-values were in sub-nanomo[ar range. In vivo: 24 and 4 8 h post injection of In-111-DTPAT3OC and In-111-DTPAT3TATE, radioactivity (%ID/g) in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and turnout was significantly higher that after injection of In-111-DTPAOC. After injection of In-111DTPAT1OC, radioactivity in these tissues was significantly lower than that after injection of In-111-DTPAOC (see Table: data %lD/g, 24 and 48h p.i., mean, n>_4): Table: DTPAOC DTPAT10C DTPAT3OC DTPAT3TATE 24 h - 4 8 h 24 h -48 h 24 h -48 h 24 h -48 h Blood .003 - .O01 .003 -.001 .003 -.001 .003 -.002 Pancreas 0.69 - 0.47 O.05a-O.O4a 2,40a-1.95a 3.56a-2,00a Adrenals 1.33 - 0.59 0.09a-O.07a 5.83a-3.35a 9.87a-7.37a Pituitary 0.51 ~ 0.O5 O.03a-O.O2a 1.65a-1,68a 2.30a-1.83a Tumour 0.58 - 0.31 n,d. 0,96a-0.46a O.84a-0.56a a) P 9 0 % by 0.5 mg unlabelled octreotide, indicating specific binding to the octreotide receptors. Blockade of DTPATIOC was > 7 0 % , Conclusion: 1) Position of Tyr-residues and Thr(ol) instead of Thr in cctreotide influences metabolism. 2) Radlolabelled DTPAT3OC and DTPAT3TATE are very promising for scintigraphy and PRRT of tumours in humans.

900

[] Radiopharmacy 30.2

30.4

Stolz B, Bruns C, Hailer R, Tolcsvai L and Weckbecker G. Novartis Pharma AG, Research, CH-4002 Basel, Switzerland.

TJ,Hoffman, N.Li, C.A.Higginbotham, G.Sieckman, W.A.Volkert, H.S.Truman Mera.V.A.Hospital and University of Missouri, Research Service and Department of Radiology, Columbia, MO 65201, USA.

COMPARISON OF THE THERAPEUTIC EFFICACY OF S°Y-DOTA-TYRLOCTREOTIDE WITH CONVENTIONAL CHEMOTHERAPEUTICS IN MOUSE TUMOR MODELS

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d.,,# ¢..

~D

SPECIFIC UPTAKE AND RETENTION OF Rh-105 LABELED BOMBESIN ANALOGUES IN GRP-EXPRESSING CELLS

~D x._ Ct.

Many human tumors overexpress somatostatin receptors. For diagnostic purposes these tumors can be targeted with the In-111 labeled DTPA-DPhe Ioctreotide (OctreoScan®ll 1). We have extended this concept of receptor-targeted radionuclides to its radiotherapeutic use. A new octreotide analog (DOTA-Tyr 3octreotide) was synthesized that forms a stable chelate with the [8--emitting Y. ~Y-DOTA-Tyr3-octreotide has been shown to induce tumor shrinkage in nude mouse tumor xenografts and to cause complete tumor remission in a rat tumor model. The aim of the present work was to compare this new radiotherapeutic with the conventional chemotherapeutics doxorubicin, 5-fluorouracil and mitomycin C. Single agent studies demonstrated that doxorubicin (3 mg/kg) was ineffective in both tumor models. With 5-fluorouracil (35 mg/kg, 4 times) tumor growth suppression for one week without shrinkage was observed in the rat pancreatic AR42] xenografts. Similarly, with mitomycin C (3 mg/kg) tumor growth suppression without shrinkage was achieved for ten days in the human small cell lung cancer NCI-H69 model. In contrast to these conventional chemotherapeutics the S°Y-DOTA-Tyr3-octreotide induced tumor shrinkage by maximum 60 % in the AR42J xenografts and by approximately 30 % in the NCI-H69 xenografts. The combination with doxorubicin did not potentiate the effect of 9°g-DOTA-Tyr3-octreotide. However, the combination of S°Y-DOTATyr3-octreotide and mitomycin C doubled the extent of tumor shrinkage. Under ~his treatment condition tumor shrinkage by more than 70 % was observed, whereas with mitomycin C alone no regression in tumor volume was obtained. Conclusion: As a single agent therapy mY-DOTA-Tyr3-cctreotide was superior to conventional chemotherapeutics with regard to rumor shrinkage and tumor growth suppression. The combination of mitomycin C with 600 pCi mY-DOTATyrX-octreot de potentiated both the extent of tumor shrinkage and, as a consequence, the survival time of the nude mice.

Several human cancers express GRF receptors that bind bombesin (BBN)with high specificity and affinity making this an attractive system for development o f new radiopharmaceuticals. We are curranfly assessing Rh-105 labeled BBN conjugates as potential therapeutic agents as Rh-105 (36 hr. half-life) is a beta~ emitter that can be produced as a NCA product. Comparison of two synthetic BBN conjugates shows that separation of the Rh105-chelate (i.e., a RhCl2-[16]aneS4-macrocycle) via a 5 carbon spacer group substantially increases binding a f f ~ t y and in vivo uptake by GRP-expressing cells. Specifically the Rh-Sa-BFC conjugated directly to the N-terminal amine of Gin7 on the BBN (7-14) binding sequence (i.e. Rh-BBN-22) exhibited an ICs0 of 37.5 nM (relative to [I-125] Tyr4-BBN) using Swiss 3T3 cells. In contrast, Rh-BBN-3715-hydroearbon separation of the Rh-BFC and BBN (7-14)] exhibited an lCs0 of 4.76 nM. Biodistribution studies in normal mice performed with Rh-105-BBN-22 and BBN-37 showed that both conjugates exhibit specific localization in the pancreas (aeinar ceils express GRP receptors) with efficient clearance from the blood and other normal tissues (e.g. approx. 24% ID remains in the kidneys at 2 hr.). However, long term uptake and retention of Rh-105-BBN-37 is more than twice Rh105-BBN-22 (e.g., 1.00% ID vs 2.25% ID at 2 hr. p.i.) and pancreas/blood ratios (% ID/gm) reached 25-30 with Rh-105BBN-37. These results indicate that insertion of spacer groups between the Rh-105-BFC and the BBN-binding region will produce analogues with superior binding affinities and in vivo uptake and retention in GRP-expressing cells. Further work with Rh-105-BBN derivatives of this type are required to assess their promise as potential radiotherapeutic agents.

30,3

30.5

HR Mticke, M. B6h~, S. Froidevaux, A. Heppeler, E. Jermann. Institute of Nuclear Medicine, University Hospital Basel, Switzerland

J.C. Reubi 1, B. Waser 1, H Friess2, M. B0chler2, and J. Laissue 1 1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, and 2Department of Visceral and Transplantation Surgery, University of Berne, Switzerland.

Biodistribution of Two New DOTA-Derivatized Somatostatin Analogs in Tumor Bearing Mice.

DTPA-D-Phe(1)-Octraotide labeled with in-111 is a successful radio[igand for the imaging of somatostatin (SRIF) receptor positive tumors. It's not very useful for the labeling with other radionuclides. Aim: We undertook this study to investigate if DOTA (1,4,7,10tetraazacyclododecane-l,4,7,10-tetraacetic acid) dedvatized SRIF analogs allow specific tumor targeting with different metallic radionuclides useful for SPET, PET and therapy. Moreover we studied the influence of the replacement of Phe(3) in Octreotide by the more hydrophilic tyrosine. Results: Two conjugates were synthesized: DOTA-D-Phe(1)-Tyr(3)Octreotide (DOTATOC) and the corresponding octreotide derivative (DOTAOC). Both label well with Ca-67 (Ca-68), In-111 and Y-90. In vitro binding studies using SRIF receptor positive rat brain cortex membranes showed specific in vitro binding with Kd values of 0,45 nM (Ca-67 DOTATOC), 2,3 nM (In-111 DOTATOC) and IC(50) 3.9 nM (Y-89 DOTATOC against 1-125-tyr(3)octreotide) significantly higher than the corresponding DOTAOC derivatives (2.2 nM for Ca-67, 4.2 nM for In-111). In vivo biodistdbution studies in a tumor bearing mouse model (AR4-2J) show that all radioligands are highly specific tumor targeting radiopharmaceuticals. The 4 hrs uptake values in tumors are as follows (expressed as % inj. dose per g): Ca-67, 8.7 (0.44 = blocked animals); In-111, 12.5 (1.0); Y90, 14.4 (1.3). The uptake of In-111 DOTATOC is about a factor 3 higher than for In-111 OctreoScan. Surprisingly the corresponding DOTAOC radioligands show also a factor of 2 lower uptake in receptor positive tissues. The residence time on tumor is highest with Y-90 (= 30hi, the tumor to kidney ratio at all time points out to 48 h is highest for Ca-67 DOTATOC. Conclusion: Three very promising new SRIF receptor radioligands were evaluated. Ga-68-DOTATOC may be an optimal PET tracer, In-t11DOTATOC may be superior to In-111-OctreoScan for SPET and %90DOTATOC appears to be promising for receptor mediated radiotherapy.

l

O

NEUROTENSIN RECEPTORS: A NEW DIAGNOSTIC MARKER FOR DUCTAL PANCREATIC ADENOCARCINOMA. A high density of receptors for the regulatory peptide somatostatin in neuroendocrine tumors has recently emerged as useful diagnostic marker to localize these cancers in vivo. Such a diagnostic strategy would be highly welcome for devastating human cancers, such as exocrine pancreatic adenocarcinomas. Since this type of tumor does not express sufficient somatostatin receptors, we evaluated in vitro the receptor expression of another regulatory peptide, neurotensin, in normal and diseased pancreas. Neurotensin receptors were evaluated in vitro with receptor autoradiography using 125-monoiodo-Tyr3-neurotensin in 24 ductai pancreatic adenocarcinomas, 20 endocrine pancreatic cancers, 18 chronic pancreatitis, and 10 normal pancreas. 75% of all ductal pancreatic adenocarcinomas, in majority of differentiated form,were neurotensin receptor-positive with density values ranging from 710 to 8450 dpm/mg tissue (mean + SEM: 3158 + 638 dpm/mg tissue). The tumoral neurotensin receptors were of high affinity and specific for bioactive neurotensin since neurotensin and acetyl-neurotensin(8-13) displaced 125-I-Tyr3-neurotensin in the nanomolar range, whereas the inactive neurotensin(t-11) analog showed no binding. Endocrine pancreatic cancers did not express neurotensin receptors. No receptors were found in chronic pancreatitis or normal pancreas tissues, consisting of pancreatic acini, ducts, and islets. The selective and high expression of neurotensin receptors in ductal pancreatic adenocarcinomas represent the molecular basis for novel clinical applications, such as in vivo neurotensin receptor scintigraphy for early tumor diagnosis using a recently synthesized DTPA-linked neurotensin hexapeptide.

901

• Radiopharmacy/Neurology 30.6 D. T e r r i e r e ( 1 ) , K. C h a v a t t e ( 1 ) , D. T o u r w @ ( 2 ) , J. M e r t e n s (i).

31.2 R.

(i) V U B - C y c l o t r o n , Brussels, Belgium. (2) V.U.B. Dept. Org. C h e m . , B r u s s e l s ,

Boumon

(i),

Belgium.

RADIOSYNTHESIS AND EVALUATION OF A NEW NEUROTENSIN ANALOGUE. A POTENTIAL TUMOR F O R SPECT.

InlIITRACER

S m a l l cell l u n g carcinoma, h u m a n c o l o n c a r c i n o m a and human meningiomas show an increased amount of n e u r o t e n s i n receptors. We synthetised a new neurotensin analogue: DTPA-Arg-Arg-Pro-Tyr-IleLeu-OH or DTPA-NT(8-13). Inhibition of the b i n d i n g of H 3 - N e u r o t e n s i n to g u i n e a p i g f o r e b r a i n membranes by DTPA-NT(8-13) s h o w e d a Ki v a l u e of 3.4 nM (Ki neurotensin 3.9 nM). The radiol a b e l l i n g is a c h i e v e d in a Kit f o r m u l a t i o n (10#g DTPA-NT(8-13)). T h e l a b e l l i n g y i e l d is > 98%. P u r e n.c.a, t r a c e r is o b t a i n e d b y s e m i - p r e p . H P L C f o l l o w e d b y p r e c o n c e n t r a t i o n and r e c o v e r y f r o m a mini-column. The o v e r a l l yield is 75% w i t h a r a d i o c h e m i c a l p u r i t y of > 99% a n d a s.a. of m o r e t h a n 370 T b q / m m o l . In v i t r o b i n d i n g to H T 2 9 h u m a n c o l o n a d e n o c a r c i n o m a c e l l s w i t h N.C.A. t r a c e r a n d C.A. t r a c e r (Kit f o r m u l a t i o n ) shows two types of b i n d i n g s i t e s : one t y p e w i t h a K d of 0.45 n M a n d a B m a x of 2 f m o l / m i l j , cells, the H i g h A f f i n i t y (HA) b i n d i n g s i t e s a n d the o t h e r type w i t h a K d of 2 n M a n d a B m a x of 65 f m o l / m i l j , cells, the L o w Affinity (LA) b i n d i n g sites. I n h i b i t i o n of the L A - s i t e s b y l e v o c a b a s t i n e shows that 30% of the b i n d i n g s i t e s is of type L A a n d 70% of type HA. In v i v o (naked m i c e ) s p e c i f i c binding, inhibited b y n e u r o t e n s i n , to the c o l o n , t h e i l e u m a n d H T 2 9 t u m o r c e l l s was o b s e r v e d .

Neurology 31.1 H.M.L. |ansen. D. Decoo, A.T. Willemsen, E. Achten, K. Strijckmans, J. Debruyne, J. Sambre, J.M. Minderhoud, J. Korf and J. De Reuck. Co-regish'ation of PET and M R / i n different courses of MS using Cobalt (C0)55 as a Calcium (Ca)-tracer. Multiple Sclerosis (MS) is an auto-mrmune central nervous system (CNS) inflammation resulting in multifocal demyelination and axonal loss. At this moment, M R / i s the most accurate paraclinical test in MS to monitor disease activity, allthough poorly correlated with clinical impairment. PET using Co-55 as a Ca-tracer m a y visualize Co-transport across t h e neuronal membrane , Ca-mediated inflammatory processes and passive leakage through a breach in the bloodbrain barrier. Co-registration of MRI and Co-PET m a y actually allow identification of clinically active lesions. Methods: MRI and Co-PET were performed as described elsewhere (1). Eased on a statistic parametric mapping (SPM-95)-software package, MRI and Co-PET were supetKmposed using a carbondioxyde (CO2)-PET as an intermediate. A semi-automated technique was used to count the MSlesions above a preset treshold-value related to the mean average Couptake. Distribution-patterns in grey and white matter were studied in t h e different MS-courses. Lesions on both modalities were compared in h i g h resolution mode. We included four groups of eight MS-patients w i t h relapsing-remitting (RR), primary progressive (PP), progressive relapsing (PR) and secondary progressive (SP) course-labels and eight h e a l t h y volunteers. Severity of illness in MS was assessed in terms of impairment using Kurtzke's Expanded Disability Status Scale (EDSS) and Scripp's Neurological Rating Scale (NRS). Results: Co-PET displayed focal uptake throughout the MS-brain, both in the grey and white matter. All four patientgroups (as compared to controlls) demonstrated a more inhomogeneous distribution of Co-spots with a tendency to show clustering, most evident in RR- and PR-MS. SPM*analysis revealed an essentially different distribution pattern of MS-spots on MR/ and Co-PET, allowing every MRI-lesion to be retrieved as a Co-PET lesion. Any relation w i t h clinical parameters will be assessed when follow-up scores are a v a i l a b l e . Conclusions: (Merging of) Co-PET and MR/ m a y eventually form complementary tools for identifying clinically relevant lesions, thus providing a more reliable secondary outcome measure in MS. (1) Jansen H, Willemsen A, Sinnige L, et al. Cobalt-55 PET in relapsingprogressive multiple sclerosis.J. NeuroL Sci. 1995 ; 132 ; 139-145

902

A. Ott¢, K. Wachter, T.M. Ettiin, Th. Stratz, U. Kischka, S. H0gefle, E.U. Nitzsche, .L Mttller-Brand. Div. of Nuclear Medicine University Hospitals Basel and Freiburg, Rehabilitation Clinic Rheinfelden, Switzerland NEW ASPECTS OF FIBROMYALGIA AND THE LATE WHIPLASH SYNDROME - A CONTROLLED BRAIN SPET STUDY Background: Brain SPET findings in the late whiplash syndrome are well known and have been confirmed by PET. Until now unrecognized, remains the question whether there are diferences in brain abnormalities between patients with late whiplash syndrome (LWS) who are 100 % on job and those who are not able to work, but were before the trauma. Second, the LWS has several similarities to fibromyaigia (FM), and insurances now often pretend that LWS patients have FM without causal relation to the accident Therefore, the similarities - or differences - between LWS and FM not only have a pathophysiologieal interest, but also some practical importance. Methods: Using Tc-99m-bicisate (ECD) high resolution SPET, four patient groups (in total n=59) were investigated: Group 1 (n=ll): patients with 100 % on job LWS (aged 33±7 years); group 2 (n=28): patients with unable to work LWS (aged 42±13 years); group 3 (n=10): patients with therapy responding FM (aged 52±6 years); group 4 (n=10): patients with therapy non*responding FM (aged 48±7 years). 15 healthy controls (aged37± 12 years) supplied the control group. Standardized regions-of-interest (ROIs) were determined in 3 adjacent slices (6.33 mm) in the frontal, parietal, temporal, parieto-oocipital (PO) cortex, in the cerebellum, brain stem, basal ganglia and thalamus. Then, the peffusion index (Pl=ROl/global uptake at the basal ganglia level) was calculated. R e s u l t s : In both, group 1 and2, there was a significant hypoperfusion in the bilateral PO region as compared to the control group (P<0.01, Mann Whitney U test). However, no statistical difference between group 1 and 2 could be seen in all regions, especially in the vulnerable PO zone (P>>O.05). In addition, group 3 and 4 did not differ statistically from the control group, especially in the brain stem (P>>0.05) as described by Costa et al., 1995, or PO (P>>O.05). C o n c l u s i o n s : This study breaks ground in three major aspects of the FM-LWS discussion: First, PO hypopaffusion in the LWS can be seen irrespective of the ability to work. Second, FM and LWS patients can easily be separated. Third, brain stem hypopaffusion in FM could not be verifiedin our patient group, irrespective of the answer to treatment.

31.3 S.Asenbaum, M.Stamenkovic, S.Schindler, W.Pirker, T.Br~cke, Departments of Neurology, Psychiatry and Nuclear Medicine, University of Vienna, W~hringer G~rtel 18-20, A-1090 Vienna, Austria [l~31]5-ClT A N D S P E C T DOPAMINE TRANSPORTERS

INDICATE ELEVATED STRIATAL IN T O U R E T T E ' S S Y N D R O M

In Tourette's syndrom (TS) an involvement of the dopaminergic system is supposed. The aim of the present study was therefore to investigate the striatal dopamine (DA) transporters in vivo using the cocaine derivative 5-CIT, labelled with [123I]. Methods: We compared the striatal [123I]5-CIT binding of 13 healthy volunteers (7 male; ages 26-75 y) and 20 patients with TS (13 male; ages 14-53 y). TS was diagnosed according to DSM-IV. Half of the patients had never received neuroleptic treatment, in the others any therapy was stopped at least one week before the investigation. For semiquantification regions of interest (KOI) were drawn manually over the cerebellum, the whole striatum and the putamen and caudate nucleus separately. A ratio (striatum/ cerebellum-l), reflecting specific over nondisplace = able binding, was calculated as well as the putamen/ caudate ratio. Percent deviation of [123I]5-CIT binding to age-expected control values was assessed additionally for each patient. Results: Patients with TS revealed a higher ratio (striatum/cerebellum-l) than controls (9.8 vs 7.4, F=20.7, p<.0001), which was also significantly higher than ageLexpected values (+16%, F=9.5, p<.C04). However in 8/20 patients the ratio fell within the normal control range (mean + 2s.d.). The ratio putamen/caudate did net differ between the groups. No correlations existed between striatal [123I]5-CIT binding and clinical measures or previous therapy. Conclusion: The findings support the hypothesis of an involvement of the dopaminergic system in TS demonstrating higher striatal DA transporter density in the majority of the patients with TS.

II Neurology/Oncology 31.4

31.6

J.C.Dickson, R.T.Staff, H.G.Gemmell, F.I.McKiddie~ P.M.Duff, S.E.Wilcock, F.W.Smith, Department of Biomedical Physics and Bioengineering, University of Aberdeen, Aberdeen, UK A LONGITUDINAL STUDY OF 99mTc F~MPAO-SPET SCANS OF DIVING SUBJECTS WHO HAVE EXPERIENCED DECOMPRESSION ILLNESS There has been uncertainty as to whether 99mTc HMPAO-SPET is useful in the management of decompression illness (DCI). The aim of this study was to identify whether the appearance of a rCBF image of a diver changes with time, and to investigate a number of other factors which could influence such scans. Twenty DCI subjects who had had an initial scan days after their incident of DCI, were called back for a repeat scan between 2 and 27 months post-DCI. An ROC experiment was performed with two mid-brain transaxial slices from these studies and from 20 non-diving control subjects. Observers were asked to identify how certain they were that cerebral involvement of DCI had occurred. We have shown previously that a DCI rCBF brain image has a globally patchy appearance. In general it appeared easier to identify DCI from the repeat scans than from initial scans (areas under the ROC curve of 0.729 and 0.625 respectively). A histogram of change in ROC response with time interval between scans showed a peak at between 8-11 months post-DCI. An analysis of diving type and practice also showed a difference in the appearance of images up to 8 months post-DCI, with the responses of sports divers being significantly different from those of the commercial divers (p=0.001). In conclusion, the sensitivity of a rCBF image to identify DCI is dependent on the time post-DCI when the scan is performed.

K. Borbely*, M. Kordas*, I. Nyary* National Institute of Neurosurgery, Budapest, Hungary

31,5

CSF SPECT AND BRAIN PERFUSION HYDROCEPHALUS SURGERY

SPECT

tO

i m

Ventficular enlargement as registered by CT/MRI might be neurologically stable or progressive in nature. In order to determine the role of Tc-99m-DTPA SPECT cisternography combined with Tc-99m-Neurospect/HMPAO SPECT brain perfusion procedures in the preoperative evaluation of patients with hydrocephalus thirty consecutive studies were carried out in cases where patient management was of concern. The results of radionuclide studies were correlated with CT, MRI, and clinical findings. In twenty one cases the hydrocephalus appeared to be communicating, whereas in nine cases it was occlusive. In three cases there was a contradiction between the findings of the CT/MRI and radionuclide studies. The results of SPECT studies correlated well with clinical data. Twenty five ventriculoperitoneal shunt implantations were carried out on the basis of radionuclide studies. Five patients were not operated upon due to compensated cerebrospinal fluid dynamics and normal brain perfusion. Subsequent patients care demonstrated a positive correlation between radionuelide patterns and clinical findings. The sensitivity and specificity of cistemography SPECT is higher than that of CT/MRI in differentiating between communicating versus occlusive forms of hydrocephalus, as well as evaluation of functional changes of cerebrospinal fluid (CSF) space In cases where evidence of increased intracraniai pressure does not exist, functional data are highly useful for the timing of surgery. The combination of CSF SPECT and BRAIN perfusion SPECT studies seems to be of high importance in management of patients with hydrocephalus.

Oncology 32.1

P.Lass, M.Koseda, A.Wilkowska, G.Romanowicz, P.Lyczak, M.Hebanowski, K.Mizan, T.Bandurski, R.Junik, M.Stfpiefi, J.M.Slomihski Medical Universities Gdahsk and Poznah, Poland

H. W o l f , B. Frieling, W . B r e n n e r , S. T i n n e m e y e r , E. H e n z e Clinic of Nuclear Medicine, Christian-Albrechts-University of Kiel, G e r m a n y

BRAIN SPECT IN SYSTEMIC LUPUS ERYTHEMATOSUS AND RELATED DISEASES; INVERSED EFFECT OF ACETAZOLAMIDE TEST Systemic lupus erythematosus (SLE) and related diseases are frequently accompanied by psychonenrologieal symptoms and signs. Little is known on cerebral perfusion and cerebrovascular reactivity in those patients. We performed brain SPECT using ~Te-EIMPAO before and 20 min. after iv. injection of 1.0 g of acetazolamide with a triple-head Multispect-3 gammacamera (Siemens) in 80 patients: 62 patients with (SLE), 10 with Sjoegren's syndrome, 8 with systemic sclerosis. 32 patients were psychoneurologically asymptomatic, 20 bad focal neurologic signs, 20 persistent headache, in 18 depressive syndrome was seen. Neurological, psychological, imunological assessment and MR/ scanning was performed the same time. The comparative SPECT data-base were 16 healthy volunteers. Results: cerebral perfnsion asymmetries were found in 56/62 (90 %) patients with SLE, all symptomatic and 24/30 asymptomatic; 8/10 patients with Sjoegren's syndrome, and 3/8 patients with systemic sclerosis. Diffuse hypoperfusion of both frontal lobes was seen in 64 % of SLE and $0 % of Sjoegren's syndrome patients. Acetazolamide increased cerebral perfnsion asymmetry in 36/80 patients, no influence was seen in 6/80 pts., the improvement of regional 9~I'e-HMPAO uptake in 38/80 patients. Acetazolamide response was normal in systemic sclerosis patients. Mill scans were abnormal only in 16 patients. Conclusions: our results indicate high incidence of cerebral perfusion changes in autoimmunological diseases, including asymptomatic patients. An unexpected finding was paradoxically inversed effect of acetazolamide, seen in n half of patients.

UPTAKE OF TC-99M-SESTAMIBI, TC-99M-TETROFOSMIN AND T C - 9 9 M - F U R I F O S M I N IN SENSITIVE A N D M U L T I - D R U G RESISTANT CARCINOMA CELLS Tc-99m-labelled sestamibi, tetrofosmin and furifosmin ( Q I 2 ) are lipophilic cationic complexes, which are widely used as myocardial perfusion tracers. They have also shown potential ability in the detection of various tumours. The purpose o f this study was to compare their uptake in sensitive and multidrug-resistant (mdr) cell lines of breast, pancreatic and gastric carcinoma. The mdr positive cell lines have been proven to express Pgp 170, a transport protein responsible for cellular efflux of antitumour drugs. Adherent cells were incubated for 1 h with 10 kBq of tracer. The results are expressed as an accumulation ratio of total cell uptake (after subr stracting nonspecific binding) over total radioactivity and normalized to one million cells. The uptake values in % are given in the table (mean + s.d.; n = lOi

cell line kindof tumor Pgp Te-sestamibi Tc-tetrofosmin Tc-furifosmir D120P MCF7 D257 P D257 RDB DI 81 P D 181 RDB

breastca breast c~ gastric ca] gastric ca + pancreatic ca pancreatic c~ +

t~ e-

STUDIES IN

1.42+0.17 t 0.95+0.12 1.72-+0.09 1.32-+0.10 2.97 _+0.23 1.30 -+0.11 0.32 -+0.03 0.05 -+0.01 1.30 -+0.09 0.65 + 0.05 0.31 + 0.03 0.24 + 0.02

0.51 -+0.05 1.14_+0.11 1.00 _+0.09 0.08 _+0.02 0.32 -+0.03 0.20 + 0.02

In all sensitive carcinoma cell lines Tc-sestamibi showed the highest cellular uptake, followed by Tc-tetrofosmin and Tc-furifosmin. In comparison the uptake in the mdr cell lines was significantly lower. The u.ptake was increased by addition of verapamil, a k n o w n Pgp reversmg agent (not shown in the table). In conclusion, Tc-99m-sestamibi showed the best in vitro uptake in these tumour cell lines. All, Tc-99m-sestamibi, Tc-99m-tetrofosmin and Tc-99m-furifosmin, seem to be Pgp transport substrates capable of functional imaging of the typical mdr phenotype.

903

ID m

t~

• Oncology 32.2

32.4

J L Moretti, M Duran Cordobes, V de Beco, J Vergote, F Benazzouz, N Safi, S Piperno-Neumann, J C Kouyoumdjian. EA 449 UFR L. de Vinci Paris 13 et H. Mondor Paris 12.

L. Kostakog!% D. Guc, P. l(arath, U. Giindiiz, A. Kars, M. Hayran, C. Bekdik, E. Kansu. Hacettepe University Medical Faculty, and Middle East Technical University, Ankara, Turkey

GLUTATHIONE MODULATION OF SESTAMIBI TC 99m (MIBI) UPTAKE IN HUMAN CELL LINES OVEREXPRESSING M U L T I D R U G RESISTANCE RELATED PROTEIN (MRP). MRP 190kD is a membrane protein involved in resistance of tumor cells to chemotherapy. Its function is mediated either by a direct m e c h a n i s m or indirect one after reduction of the ligand b y glutathione (GSH). MIBI uptake is dependent upon multidrug resistance phenotype as for Pgp 170kD. We performed this study to assess the role of MRP a n d the mediation of GSH in MIBI efflux. Different human cell lines Pgp (-) were selected upon M R P phenotype [sensitive ( s e ) resistance (re)] : A549 (re) (MRP+) lung adenocarcinoma and H69 (re) (MRP+++)* and H69 ( s e ) small cell lung cancer lines, MCF7 (se) breast cancer line and KB 3.1 (se) mouth squamous cell cancer line. MIBI uptake into the cells was determined after 90 minutes of incubation at 37°C with or without a 24 hours pretreatment by buthionine sulfoxime (BSO, 25 piN) a GSH depletor. Reduced glutathione (GSH) cellular content was measured by using Ellman's reagent. O u r data demonstrate that 1/Glutathione depletion provoked an increase of MIBI uptake in s e n s i t i v e cells. 2/In MRP resistant cells, glutathione depletion induced a tremendous decrease of M I B I efflux related to the level of protein expression. In conclusion, MIBI efflux by MRP seems to b e related to the indirect mediation of GSH. KB3.1 H69 MCF7 A549 H69Ar se se se re+ Ire ++ MIBI uptake 12.1 25.9 13.9 2.8 0.7 before BSO±(sd) (0.6) (3.6) (1.9) (0.2) (0.5) MIBI uptake 31.1 31.9 40.1 9.1 4.3 after BSO±(sd) (4.5) (3.5) (3.7) (0.5) (0.6) Courtesy of *Susan Cole Canada. Grant ARC. Yonne 89 and 93 Cancer leagues, MIDY Foundation. Cell

lines

ASSOCIATION OF THE DEGREE OF TC-99M-SESTAMIBI (MIBI) ACCUMULATION WITH P-GLYCOPROTEIN EXPRESSION IN PATIENTS WITH LUNG CANCER: COMPARISON OF THE RESULTS WITH IMMUNOHISTOCHEMISTRY AND RT-PCR. In a prospective audy we correlated the magNtude of MIB! accumulatien with the expression of P-glycoprotein (P-gp) in Imnor (Ira) tissues detected by tmmunohistochemistry and RT-PCR in patients (pts) with lung cancer. Twenty pts underwent M/BI imaging and bronchoscopic biopsy prior to chemo- or radiotherapy (10 SCLC, 10 epidermoid cancer). The interval between biopsy and imaging varied from two to seven days. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-I, developed against the internal epitope of P-gp. RT-PCR analysis was performed following extraction of mRNA of the tumor. Tin/background (tm/bkg) ratios were correlated with the presence of P-gp expression detected by RT-PCR and/or immunohistochemistry. There was complete agreement between RT-PCR and immunohistochemistry (~-/o100). Six patients had P-gp positivity in their tins. There was inverse correlation between P-gp positivity and magnitude of MIBI accumulation in the lm when those with necrosis excluded from the group. Tm/bkg ratios for P-gp"-" and P-gp"+" patients were 2.20+0.28 and 1.80+0.34, res~ctively, (p=0.014). There was necrosis in 5 tumors detected by either CT or histology. There was statistical difference in tm/bkg ratios between necrotic tms and those without necrosis when tins with P-gp positivity excluded (p<0.01). In summary, the current data strongly suggest that although the magnitude of MIBI accumulation has a strong correlation with the presence of P-gp expression, caution should be exercised when interpreting scans of patients with necrotic lms.

32.3

32.5

L. Kostakoglu, D. Gii~, H. Canpmar, E. Alper, A. Kars, M. I4.ayran, C. Bekdik, E. Kansu. Hacettepe University Medical Faculty, Ankara, Turkey and Uludag University Medical Faculty, Bursa, Turkey.

W.Yu.Ussov, Yu.E.Riannel, E.M.Slonimskaya, L I Musabaeva, H.V.Sivirinova, V.NKorsunskii, S.A.Velichko, Tomsk Institute of Oncology, Siberia and Institute of Biophysics, Moscow RUSSIA 99mTe-MIBI SPECT IS S U P E R I O R TO MRI IN D E T E C T I O N OF W I D E S P R E A D OF METASTASES IN B R E A S T C A N C E R

DETERMINATION OF P-GLYCOPROTEIN USING Tc-99m-MIBI IN PATIENTS WITH HEMATOLOGIC MALIGNANCY: COMPARISON OF THE RESULTS WITH FLOW CYTOMETRIC ANALYSES. We undertook a study to evaluate the relationship between the degree of Tc99m-MIBI (MIBI) uptake and the level of P-gp in comparison with flow cytometric results in patients with hematologic malignancy. A total of 18 tissues (16 patients) were evaluated. Eleven patients were included in the study at the time of initial diagnosis and 5 during relapse after therapy. Two patients evaluated prior to therapy had repeat studies after therapy. The patients' ages ranged from 22 to 50 (mean+SD:35+9.8). Following MIBI imaging, bone marrow aspiration or peripheral blood was obtained for flow cytometric analysis. Flow cytometry was performed using two different antibodies, one developed against the external (UIC2), the other developed against the internal (JSB-1) epitope of P-gp. Alter injection of 15 mCi of MIBI, whole-body and pelvic spot images were acquired using a dualhead gamma camera and LEHR collimator. The uptake in the bone marrow was evaluated against the background (nearest sofr tissue) by both qualitative (scoring system) and quantitative (tm/bkg ratios) analyses. There was an inverse correlation between the levels of P-gp and MIBI imaging results using both qualitative (scoring system) and quantitative (tmfokg ratios) analyses. We performed two different analyses by setting the cut-off point for P-gp positivity at 1. >10% and, 2. >_25%P-gp. Both qualitative and quantitative mean values of MIBI analyses were statistically different from one another for P-gp "+" and P-gp "-" patient groups (p=0.0085, p=0.016 and p=0.0011, p=0.0007, respectively). The specificity at the %10 level (100%) and the sensitivity at the 25% level (100%) were the highest. This finding suggested that the higher the P-gp expression the higher the sensitivity of MIBI imaging. As a result, functional imaging agent MIBI could non-invasively detect the presence of P-gp. However, the expression of P-gp should be above a certain threshold level for the detection of P-gp by MIBI imaging. These preliminary results should be supported by other studies with expanded number of patients.

904

Although co-use of mammography, scintimammography, needle biopsy and ultrasound provides sensitivity in detection of primary node of breast cancer close to 100%, diagnosis of lymphatic metastases (mets) remains unresolved 99mTc-MIBI SPECT has been discussed as efficient tool for revealing mets. We have compared 99~Tc-MIBI SPECT with chest MtLI in 36 ladies with breast cancer of T1-3 N1-3 M0-1 stages in aspect of detection of mets in ROIs assigned to four axillar, supra- & infraclavicular, upper and lower parasternal areas. 99mTc-MIBI SPECT was performed using 740 MBq of the agent and 1 cm attenuation-corrected slices were reconstructed from 64-128 planar scans recorded over anterior thorax view (180 ° of rotation). Three-dimensional T1, T2, and proton density MRI scans were obtained in a day after 99mTc-MIBI study using 0.2 T system and digitally superimposed over SPECT images. Local accumulation of 99mTc-MIBI was analysed basing on anatomic distribution of lymph nodes and was reported as pathologic if separated visually from background and was > 1.25 if quantified as [NoduleBackground] ratio of 99~Tc-MIBI uptake per voxel (background taken over lung). In all such cases fine needle biopsy when successful technically revealed mets (112 locations in 36 pats). MRI was negative or controversial in 43 locations of these 112. The biggest discrepancy occured in parasternal (21 location) mets. 99mTc-MIBI SPECT revealed the primary node of cancer in 35 of 36 patients whereas MRI did in 33. In I6 patients the 99mTc-MIBI SPECT data led to extension of radiotherapy designed earlier. Concomitantly, in 6 patients whole-body 99mTc-M1BI scans detected distant mets (13 locations in total). Therefore we conclude 99mTc-MIBI SPECT is clinically useful, more sensitive, more economic and more available if compared to MRI technique of detection of metastatic widespread of breast cancer

[] O n c o l o g y / C a r d i o v a s c u l a r

33.2

32.6 S. Severi, E. Leonardi*, E. Lorenzi, M. Bonzanini*, Brancato °, M. Romano ^, M. Camerani.

B.

Nuclear Medicine, Radiology °, Pathology*, Radiotheraphy ^ S.Chiara Hospital - Trento - Italy T H E 99MTC MIBI BREAST C A N C E R C O N C E N T R A T I O N IN M A M M O S C I N T I G R A P H Y (MSMIBI): R E L A T I O N W I T H T U M O U R C E L L U L A R I T Y AND MITOTIC INDEX (MI). In order to evaluate if MSMIBI concentration in breast tumours may be related to biological characteristics such as cellular density and mitotic proliferative index, we studied 32 highly marnmographic suspected lesions who subsequently underwent an open biopsy. Materials and methods: before surgery we injected intravenously, in every patients,740 MBq of MIBI, after 15 minutes we acquired 6 static views (2 anteriors, 2 laterals and 2 anterior oblique), 2000 Kcounts each. The cellularity was evaluated on the histological sections by morphometrical analysis: for each case an automatic measurement of the mean percentage of cellular / acellular areas ratio was performed using color image analysis. The MI was studied in each case, by counting in a semiquantitative way, the number of nuclei immunostained with MIB-1 (a monoclonal antibody reacting with cells in cellular cycle different from GO). MI less than 10% was classified as low (1MI), MI between 10 and 20%, intermediate (iMI) and MI more than 20% high (hMI). 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 showed a diameter less than 12 mm and 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%. Of the 6 FN cases 3 were 1MI, 2 iMI and 1 hMI. Interestingly of the 24 TP cases only 4 were IMI, 9 iMI and 1lhMI. Conclusions: The MSMIBI has an high sensitivity in tumour detection that is strictly related to the tumour size and may be improved in highly cellular cancer expecially for lesions with a diameter similar to the gamma camera resolution. Otherways the clear MI difference between FN and TP cases seems to indicate that this parameter is well related to MIBI tumours concentration.

W.S. Richter. R. Aurisch, B. Kettner, S. Fischer, D.L. Munz. Clinic for Nuclear Medicine, Charite, Humboldt University Berlin, Germany

33.1

COMPARISON BETWEEN TECHNET1UM-99m SESTAMIBI AND TETROFOSMIN TOMOGRAPHY 1N THE DIAGNOSIS AND LOCALIZATION OF CORONARY ARTERY DISEASE. Recent studies suggest that both exercise-rest Tc-99m sestamibi and Tc99m tetrofosmin cardiac tomography have high diagnostic accuracy for detecting coronary artery disease (CAD). However, only few data are available comparing Tc-99m sestamibi and Tc-99m tetrofosmin cardiac tomography in the same patients. This study was designed to directly compare the results of Tc-99m sestamibi and Tc-99m tetrofosmin in patients with suspected CAD. Within one week 32 consecutive patients (27 men, mean age 51+9 years) underwent one-day exercise-rest Tc-99m sestamibi and Tc-99m tetrofosmin tnmography (370 MBq iv at peak exercise and 1110 MBq iv at rest 4 hours later for both tracers). Regional distribution of Tc-99m sestamibi and Tc-99m tetrofosmin was quantitatively measured in corresponding segments. At coronary angiography, 7 patients had normal coronary vessels, 11 patients onevessel and 14 patients multivessel CAD (->50% diameter stenosis). The quality of images judged visually was comparable with the two tracers. The calculated heart to lung (2.9+0.5 vs 2.7-+0.5, P=NS) and heart to liver (1.2-+0.4 vs 1.2-+0.4, P=NS) ratios for Tc-99m sestamibi and Tc99m tetrofosmin were similar. Overall sensitivity, specificity and diagnostic accuracy for the identification of patients with CAD were 92%, 71% and 88% for Tc-99m sestamibi and 96%, 86% and 94% for Tc-99m tetrofosmin, respectiveiy (all p=NS). Sensitivity, specificity and diagnostic accuracy for the detection of individual stenosed coronary vessels were 70%, 86% and 78% for Tc-99m sestamibi and 72%, 92% (p<0.05 vs Tc-99m sestamibi) and 82% for Tc-99m tetrofosmin, respectively. The quantitative severity of perfusion defects and defect size were similar for the two tracers. In conclusion, one-day exercise-rest Tc-99m sestamibi and Tc-99m tetrofosmin quantitative tomography provide similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.

e,-

KINETICS OF Te-99m Q12 (FURIFOSMIN) IN PATIENTS SUBMITTED FOR ROUTINE MYOCARDIAL SPECT Tc-99m Q12 (furifosmin) is a new radiopharmaceuticat for myocardial perfusion imaging. The aim of this study was to examine the kinetics of Tc-99m Q12 in patients submitted for routine myocardial scintigraphy. In 13 patients (9m, 4 fm, aged 59.3+11.9 yr.) whole body scans were acquired 39+26 min, 118+42 rain, and 218+27 min after injection of 320-380 MBq Tc99m Q12 at rest (n=7) or at maximum stress (n=8). In 12 patients (10 m, 2 fm, aged 55.8+9.3 yr.) myocardial SPECT examinations were performed 13+11 min, 94+20 min and 178+14 min after i.v. injection of Tc-99m Q12 and compared with TI-201 SPECT at rest. Global myocardial activity showed an exercise-independent washout of 12.5+5.7% per hour between the 1st and the 2nd whole body scan and of 8.3+1.1% /h between the 2nd and the 3rd. Heart-to-liver and heart-to-lung ratios increased over time from 0.79+0.29 to 1.47+0.14 and from 1.67+0.16 to 1.96+0.26, respectively. Estimated myocardial Tc99m Q12 uptake was 1.72+0.47% I.D. Differences in segmental Tc-99m Q12 activity between the three SPECT acquisitions could be found in 26.2% of the 84 segments. A fill-in of defects as well as a segmental washout were registered. Consequently, classification of segments as ischemic depended to a relevant degree on the time intervall between Tc-99m Q12 injection and imaging. A tracer washout was observed more often after dipyridamote as compared with bicycle exercise (p<0.005). Myocardial activity of Tc-99m Q12 is not stable over time. For myocardial imaging, acquisitions early after injection are to be recommended.

Cardiovascular A. Cuocolo L. Pace, P. Sullo, E. Nicolai, S. Cardei, W. Acampa, A. Varrone, M. Salvatore. Centro per la Medicina Nucleare det CNR, Universith Federico II, Napoli, Italy.

e-. o |l

33.4 SFanti, M.Dondi, P.L.Guidalotti, G.Fagioli, C.Corbelli, NMonetti. Nuclear MedicineDpts, PolielinicoS.Orsola-Malpighi,Bologna; Ospedale Maggiore, Bologna;Ospeda]eper gli Infermi,Faenza;Italia. MYOCARDIAL SPECT WITH TRANSMISSION-EMISSION ATTENUATION CORRECTION: IMPACT ON FALSE POSITIVE RATE IN PATIENTS AT LOW-RISK OF CAD. We aimed at evaluating the results of myocardial SPECT with transmissionemission attenuationcorrectionin a populationat low risk of CAD. We studied 95 consecutivepatientsat low probabilityof CAD (< 5%), from the subjects referred for stress+rest myocardial SPECT. Studies were carried out using 99mTclabelled myocardial peffusion radiopharmaceuticals (Sestamibi and Tetrofosmine) and acquired employing a three-head camera equipped with a commercially available transmission/emission device. We reconstructed two series of tomographic images, attenuationcorrected (AC) and non attenuation corrected (NAC), that were analysed by segmentalanalysis, using a qualitative 5-point score (0=normal; 4=no uptake). For single patient evaluation we considered as false positive all studies with 2 or more segments scored _>2. Results of total score calculationfor each myocardialwalt are detailedin'tab.l. TABLEI After attenuation s~essNAC restNAC s~essAC restAC correction we found a ANTER 34 27 44 37 significant decrease in APEX 68 59 1!2 97 INFER 201 148 78 72 total score of the inferior SEPT 111 94 67 58 and septal wails (p<0.05). LATER 49 38 40 31 We also observed a mild increase in total score of apex and anterior wall, though the change did not reach statistical significance (p=ns). The false positive rate was reduced by application of attenuation correction from 24% (23/95) for NAC studies to 5% (5/95) for AC studies. Our findings indicate that nonuniformattenuationwithin the chest significantly affect myocardial SPECT results in patients at tow risk of CAD. Application of attenuationcorrection may reduce the number of false positive studies, with a relevantimpacton specificity.

905

o. l

x_

O

• Cardiovascular/Lungs 33.5 R Miiller-Suur,L E Strandberg, and L Mesko. Departments of clinical physiology ,hospital physics and internal medicine Karolinska Institute Danderyds Hospita/Danderyd Sweden ADENOSIN IS SUPERIOR TO EXERCISE FOR STRESS SESTAMlBI TOMOGRAPHY IN CAD PATIENTS TREATED WITH BETA BLOCKERS: A QUANTITATIVE SPECT ANALYSIS Myocardial perfusion was assessed in CAD patients (post infarction with significant angiographic stenoses) with ongoing beta blocker therapy (n=16). A quantitative analysis of 99mTc-Sestamibi computed tomography (SPECT) with a special soft ware (Cequal) was used both during a pharmacological stress with adenosin (140ug/min.kg) combined with a light leg exercise and symtom limited maximal bicycle exercise. During bicycle stress test 83-+10% of maximal heart rate was reached compared to 63-+9% during adenosin (P<0.001). Also the blood pressure was higher during bicycle test compared with adenosin (181-+ 25 vs 153+_30 mmHg, P<0.001) respectively. None of the patients showed AVblock. Only mild noncardiae adverse effects were seen during adenosin. Quantitative bulls eye analysis showed the following results: 6 patients did not fullfill soft ware criteria for reversibility in either test. The remaining 10 patients showed significant larger defects during adenosin stress ( extent score 173-+2] vs 139-+23,P<0.04) and more pronouneed reversibility ( reversibility score 77-+17 vs 42-+ 18, P<0.02) than during bicycle stress. Also the severity of reversibility was higher in the subgroup during adenosin vs exercise ( [68_+45 vs 90_+45, P< 0.05). In three of the ten patients no reversibility was observed by the computer analysis during bicycle test.Visual analysis of all data supported these computer analysis findings. CONCLUSION: pharmaeological stress testing with adenosine in CAD patients with beta blocker therapy is superior to the traditional exercise test and should be the strategy of choice for myocardial peffusion scintigraphy in these patients.

Lungs 34.1 D.M. Howarth, P.A. Thomas, L.W. Allen, L.Lan. Dep. of Nuclear Medicine, John Hunter Hospital Newcastle, NSW Australia.

AN OUTCOME STUDY OF PATIENTS REFERRED FOR VENTILATION AND PERFUSION LUNG SCINTIGRAPHY FOR THE DIAGNOSIS OF PULMONARY EMBOLUS. Despite extensive evaluation of lung scintigraphy in the diagnosis of pulmonary embolus there remains a paucity of outcome data. The aim of this study was to determine the role of hmg scintigraphy in the management of pulmonary embolus. Between June 1994 and July 1995 patients were imaged using Tc-99m technegas and Tc-99m MAA and followed-up in December 1996 by contact with each patient's local medical practitioner and review of hospital medical records. Of a total of 832 patients there were 178 deaths (90% unrelated to pulmonary embolus or its treatment). Lost to follow-up were 179 patients. Median patient age was 67 years. The respective probabilities for pulmonary embolus (modified PIOPED) were: high 17% (85% coumadin treated), and normal 2.9% (untreated). Poor outcome was defined as thrombotic events or unexplained sudden death in the releated patients and bleeding complications in the anticoagulated patients. A 96% negative predictive value was found for patients with normal or low probability lung scintigraphy indicating that this result is highly predictive of a good outcome. However, the positive predictive value was only 7% indicating that a moderate or high probability lung scintigraphy result is not predictive of a poor outcome. Similarly, when a high probability result alone was used the respective negative and positive predictive values were 95% and 10%. When bad outcome in untreated patients was defined as thrombosis or thrombo-embolic events the respective negative and positive predictive values were 98% and 12%. Thus, using modified PIOPED classification lung scintigraphy is a useful predictor of a good outcome but not of poor outcome.

33.6

34.2

K.K. Balan, S. Vinjamuri, W. Inglis and M. Critchley, Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool L7 8XP U.K.

M.J. ~ , J.A. Varggs (I), V. Peir6, N. Novoa (2), C. Salas (3), M. Alonso, J. Ortiz Berrocal. ~ icss of Nuclear Mmiicine, (i) Interhal M~dicine, (2) lhoracic Shmcjery, (3) Pathology. Clinica Riert~ de Hierro. Mgdrid. Spain.

IS THERE AN INCREASED RISK OF BRONCHOSPASM IN PATIENTS WITH CHRONIC OBSTRUCTIVE AIRWAYS DISEASE (COAD) DURING ADENOSINE STRESS MYOCARDIAL SCINTIGRAPHY? Adenosine cardiac stress is widely used as an alternative to exercise testing and is often accompanied by dyspnoea. Although known asthmatics are excluded from this test because of the danger of bronchospasm, there is incomplete information regarding the role of factors such as chronic obstructive airways disease (COAD) and tobae6o smoking. 122 consecutive patients (M 75, F 47: Median age 60 years; range 31-83 years) undergoing myocardial scintigraphy and pharmacological stress testing with intravenous infusion of adenosine also had volume-flow spirometry (Vitalograph Compact; Vitalograph Ltd., U.K.) before, during and after the test. The indices assessed were forced expiratory volume in one second (FEVI), its ratio to the forced vital capacity (FVC) and peak expiratory flow rate (PEFR). Results: 63 (52%) patients who reported dyspnoea during the study did not demonstrate any evidence of airways resistance. Patients with COAD (n = 36; 30%) showed a significantly lower PEFR and FEVI compared to those without COAD (P< 0.006, P< O.OS respectively) before and during the test but there was no demonstrable deterioration in these parameters after adenosine stress. Similarly, patients with a history of tobacco abuse (n = 74; 61%) and lower resting FEVI but normal PEFR and FEVI/FVC compared to those subjects without this problem, did not show any alteration in respiratory function. Conclusions: i. COAD is not a contraindication to adenosine stress test. 2. Tobacco somkers do not appear to be at increased risk for bronchospasm during adenosine stress test and S. Dyspnoea during adenosine stress is not associated with any appreciable bronchial resistance.

906

~ : To assess the use o f 9 ~ - t e ~ f ~ (~) in ~ solitary ~ulm:nary nodules and the possible relaticrship betw~n tptake and mltidrug resistance @{R). ~ ~ : Lung masses were assessed in 59 patients, plaomr s~@es were acquired i0 and 60 min after iv adninistration of 99@rc-TF (20 KCi), and s~HEr images at ram 70. Image processing for patholcgic study included quantitative study of pints of interest, lhe percentage of cells expressing HIR was assessed by flew cytcmstry (F~CSort c ~ e r and Lysys II progra% Bect@q-Dickinscn). ~ : ~iree patients p ~ t e d 2 different lesicns. There were 49 n~lignant and 13 b~ign lesicns. Malignant lesicns included 16 ~ ~ @~C), 27 squamsus c s r c ~ (SC), i tnJifferentiated large-cell tumor (LC), 2 m~tastases of cslorectal AC, 2 hrcndisl carcinoid tumsrs and i Ks]iqpant fibrous histiocytc~a. Cnly b r c ~ tulors presented tptak~(see follcwlng table).

Histolcgic type

Mean tmor/healthy tissue (Hr) Pange turor/H~

(16) 9+/7-

i.68f0.27

1.17-2.40

SC (27) 2@/7-

1.68/O.40

1.35-2.24

LC (I) I+

1.60

Pesults of the study of HlR expression in the lesicns were as follcws: Histology ;C AC AC ST SC ST B-celA Aspg (differ) I (m~d) (msd) (poor) ~nsd) (~oor) (well) (2) icma

~

/Hr o

Neg

i.48

i.79

2.37

I.48

Neg

Neg

Neg

32%

25%

8%

2%

8%

43%

2-11%

19%

~ : In b r c ~ carmer, 99~IFc-TF uptak~ is not related to the histolcgic type or degree of diff~tiaticn. Cytm~tric study reveals a relatic~ip hetwe~ MER expressicn and TF t ~ that does not appear to exist in b~nign lesicns. This study was partially f ~ by a grant from the Ftmdacidn IA]R.

[] Lungs/Therapy 34.3

34.5

P. O l i v i e r , P. H a o u z i , P.Y. M a r i e , J. S i a t , N. Q u i r i , T. A r s e n a , N. D a v i d , N. H a s s a n , J. B o r e l l y , G. K a r c h e r , A. B e r t r a n d . C H U - N a n c y , F r a n c e .

H W Gray, R G Bessent, J H McKillop Department of Nuclear Medicine Royal Infirmary Glasgow

PREOPERATIVE PERFUSION LUNG SCANNING IN P A T I E N T S WITH BRONCHOGENIC CARCINOMA. REST OR EXERCISE ? One of the m a i n c r i t e r i a to o p e r a t e p a t i e n t w i t h lung carcinoma is based on prediction of postopeerative FEVI (volume expired in the f i r s t second, P r e F E V I ) . P r e F E V 1 is r o u t i n e l y c a l c u l a t e d as the p r o d u c t of the p r e o p e r a t i v e FEVI by the p o r t i o n of total pulmonary blood flow of the expected remaining lung tissue, determined from lung scintigraphy. This parameter is however poorly correlated with the short term morbidity and m o r t a l i t y f o l l o w i n g lung r e s e c t i o n . We a s s u m e d that this low predictibility of p u l m o n a r y tolerance before lung resection c o u l d be e x p l a i n e d b y the lack of p r e c i s e e v a l u a t i o n of the c o n t r i b u t i o n of the r e m o v e d t i s s u e to gas e x c h a n g e w h e n the s u b j e c t needs to i n c r e a s e its p u l m o n a r y blood flow. The question was whether resting scanning gives a reasonable approximation of the repartition of pulmonary blood flow, when gas exchange rate i n c r e a s e s . Thus, L u n g s c a n n i n g was p e r f o r m e d on 20 p a t i e n t s w i t h l u n g cancer, b o t h at rest and at the end of a r a m p - l i k e c y c l o e r g o m e t e r exercise. 2 mCi macroaggregated albumin particles were injected a f t e r e x e r c i s e and i0 mCi, a f t e r one h o u r recovery. The lung w i t h c a r c i n o m a d i s p l a y e d a s i g n i f i c a n t and' s y s t e m a t i c r e d u c t i o n of the p e r f u s i o n (-8,5~6%) of total blood flow. As a group, distribution of p u l m o n a r y b l o o d f l o w was not a f f e c t e d by e x e r c i s e (43±7% vs 4 1 i 9 / V O 2 = 9 8 2 ± 2 9 0 m l ) however patient by patient ananysis showed that in 2 patients a dramatic redistribution (up to 20%) of flow towards the n o r m a l lung was o b s e r v e d w h i l e 2 o t h e r p a t i e n t s presented an opposit r e s p o n s e . In conclusion, resting perfusion lung scanning doesn't give n e c e s s a r i l y a p r e c i s e idea of p u l m o n a r y b l o o d flow d i s t r i b u t i o n d u r i n g m u s c u l a r a c t i v i t y w h i c h m u s t be t a k e n into a c c o u n t to p r e d i c t p u l m o n a r y tolerance in a d a y life s i t u a t i o n .

C O

im

C

Evaluation of Diagnostic Odds in Lung Scan Reporting° A questionnaire was sent to 217 consultants in Scotland to assess their understanding of VQ scan reports in a numerical odds scale. In question i, the physician was asked to select a diagnosis between "PE highly likely" and "PE highly unlikely" (5 point scale) for each of nine lung scan reports expressed as diagnostic odds between i00:I against and 20:1 for PE. The results revealed a broad understanding of the concept of diagnostic od~s. In the remaining questions, the physicians were given two case histories, one with low and the other with a medium pre test probability of PE. They were asked their management of each patient given a "Normal", "Low probability" or "Indeterminate" verbal lung scan report or a "100:1 against" or "i0:i against" or "i:i evens" diagnostic odds report for PE. Management decisions offered ranged from full heparinisation to elimination of PE from consideration. Results showed that physicians used the "normal VQ" and "i00:i against" PE reports in a similar fashion, as also the "low probability of PE" and "i0:i against PE", reports. With the "indeterminate" and odds of "I:i evens" however, there was a clear preference for diagnosis of PE in the odds compared to the verbal format. We conclude that one advantage of using a numerical format for lung scan reporting may be a greater ~wareness of the risk of PE in patients with indeterminate VQ scans.

34.4

Therapy 35.1

G.Ciofetta, F.Midulla, S.Morano, A.Carli, M.Cafaro, R. Di Berti, R. Ronchetti. II Ped. Clinic, Nuclear Medicine Lab. ,I University of Rome, Italy.

SZM C l a r k e , C H o e f n a g e l , M Fischer,JF Chatal, v Lewington,L Troncone,M R Vieira,S Nilsson European Association of N u c l e a r M e d i c i n e C o m m i t t e e on R a d i o n u c l i d e Therapy

THE VALUE OF GASTRIC SIGNAL MONITORING IN THE RADIOACTIVE AEROSOL STUDIES OF LUNG MUCOCILIARY CLEARANCE,IN CHILDREN Peripheral radio-aerosol deposition is required for good quality ventilation (V) imaging; mucociliary clearance (MC) instead needs proximal bronchial deposition; obtaining both in format ions in the same patients is usually done in two different days. The purpose of this study was to device a method to get the (V) scan and an index of (MC) within 1 hour. 30 children affected by recurrent bronchitis were studied, as follows: 99mTcAlbumin-Colloid (AC) small particles (3.9 + 1.2 micron) were administered by aerosol. Sequential imaging was performed for 30 mins. ; activity/time plots were obtained for peripheral, proximal lung zones and the gastrointestinal region. Resulting lung-curves were almost flat, indicating stable signal distribution in most patients (21/30); gastric signal remained stable only in few cases (8/30 patients), affected by severe mucociliary abnormalities (5/8 Kart agener 's Syndrome, 3/8 s e v e r e bronchiectasis) ; the remaining 22 patients showed a "progressive gastric uptake", in spite of their bronchial plots stable plateau. The gastric-uptake rate (gK) compared very strictly (r= 0.912, p<0.001) with the (MC) data obtained in 13/30 patients, who had a repeated study with larger particles (5.98+1.38 microns). Our gastricuptake-rate (gK) was also in better agreement with the severity of ultra-structural ciliary abnormalities, found at electron microscopy. Gastric-uptake is likely due to the even small amount of particles depositing in t h e proximal airways, lung plots remaining stable, influenced by the abundant signal coming from the v e r y peripherally deposited particles. We recommend the use of small particles radioaerosols and gastric monitoring in children: both (V) and (MC) data are obtainable, with minimal patient discomfort and cooperation.

EANM SURVEY EUROPE

OF

RADIONUCLIDE

THERAPY

PRACTICE

IN

T h e w i d e v a r i e t y of p r a c t i c e a c r o s s E u r o p e in the f i e l d of r a d i o n u c l i d e t h e r a p y is w e l l r e c o g n i s e d . 23 c o u n t r i e s h a v e b e e n s u r v e y e d to d e t e r m i n e the n u m b e r of r a d i o n u c l i d e therapy centres,the number of t h e r a p y b e d s , t h e n u m b e r of p a t i e n t s t r e a t e d by radionuclide t h e r a p y a n d the i n d i c a t i o n s a n d t o t a l a m o u n t o~ a d m i n i s t e r e d a c t i v i t y in the y e a r 1995. D a t a h a v e b e e n r e c e i v e d f r o m 20 c o u n t r i e s w h o s e populations total 509million. 654 therapy centres w i t h 1 4 9 2 d e d i c a t e d b e d s t r e a t e d 81 132 p a t i e n t s in 1995. W h i l s t G e r m a n y h a s the h i g h e s t n u m b e r of b e d s (791) and t r e a t e d t h e m o s t p a t i e n t s (31 8 0 0 ) , the UK h a s the m o s t t h e r a p y c e n t r e s (129). 7 counties with populations less than I0 m i l l i o n w e r e s u r v e y e d w i t h A u s t r i a h a v i n g the m o s t b e d s (58) a n d t r e a t i n g 2 300 p a t i e n t s a n d I r e l a n d the least (4) t r e a t i n g 15 p a t i e n t s . The most commonly treated conditions were b e n i g n t h y r o i d d i s e a s e and CA t h y r o i d with more t h a n 88 5 0 0 G B q of 1 3 1 I o d i n e u s e d . The implications of t h e s e d a t a are p r o f o u n d if r e g u l a t i o n s for the a d m i n i s t r a t i o n of r a d i o nuclide therapy are changed.

907

m

O

• Therapy 35.2

35.4

J. Pinkert~. W-G. Franke', V. Haing2, U. Neumarm2, R. Hliscs~, L.Oehme~and A Kiilmel Dresden Universityof Technology, Depts. of Nuclear MedicineI and Radiology~, Germany

S. Srivastava. H. Atkins, G. Krishnamurthy*, G. Meinken, F. Swailem*, L. Mausner, T. Walsh*. Medical Department, Brookhaven National Laboratory, Upton, NY, and *VA Medical Center, Tucson, AZ.

ENHANCED TUMOR UPTAKE IN INTRAARTERIAL APPLICATION

1-13I-MIBG TREATMENT BY

SAFETY AND EFFICACY OF T1N-117m DTPA IN PATIENTS TREATED FOR PALLIATION OF METASTATIC BONE PAIN.

Iodine-131 MIBG therapy by intravenous injection is well established for treatment of pheochrnmoc~oma, neuroblastoma, or carcinoid tumors e.g. But this treatment is at most cases palliative due to poor tumor uptake. In this stu@ we evaluated the clinical value of intraarterially (ia.) infused I-131 MIBG in 6 patients with inoperable progressive APUDOMAs (5 carcinoid tumors and 1 paraganglioma) applied via superselective arterial catheter (one patient with two treatments). All pts underwent clinical and lab examinations, contrast enhanced CT scans and angiographies. For measurement of tumor uptake and dosimctric calculations one day before the i.a. treatment a dose of 350 MBq 1-13I MIBG was given intravenously and a whole body scan and SPECT for quantification of tumor uptake was done before the i.a.-eatheter was introduced. The tissue suppliedby the catheterised artery was determined by i.a. injection of Tc-99m MAA 4000 MBq MIBG were infused i.a. within 30 min. The infusion was monitored by planar sequence scintigraphy in 5 pts. SPECT and whole body scans were performed after 24 h, 48 h and 96 h (4 pts. with additional scans). Tumor uptake was determined in comparisonwith an external standard from SPECT and wholebody scans. The increase of tumor uptake 24 h after ia. application was estimated at 186 % +124 in the areas supplied by the catheterised artery (19 lesions evaluated in the 6 pts.). No significant enhancement was found in metastases with other arterial supply. 60 % of the uptake at 24 h was already reached 30 rain after i.a. infusion. Time course measurements from tumor region showed an increasing storage of MIBG compared with background during i.a. infusion but not in pts. with i.v.-application as also demonstrated by PATLAK-plot. A regression of tumor size showed 2/6 pts. Tumor related symptoms like pain and flush were reduced in 3/6 pts We conclude from our ongoingstudy that i.a. MIBG treatment is verb_.'promising in therapy of APUDOMAs with only minor side effects

purpose: We analyzed and compared with other agents, the hematological parameters and other factors related to the safety and efficacy of Sn- 117m DTPA for the treatment of metastatic bone pain. Methods: Data from a dose escalation trial in 47 patients using 2.6, 5.3, 6.6, 8.5, and 10.6 MBq/kg doses of Sn-117m DTPA were analyzed. The administered Sn-117m activity per kg, and the calculated marrow doses, were correlated with % and absolute decreases in WBC and platetet counts, % pain response, and the time of onset of pain relief. Response was also correlated with the extent of bone metastases using total Sn117m uptake into bone and the bone index. Results: In 39 patients with complete data sets, the average maximum % drop in WBC and platelets, respectively, was 26±16 and 23±18. No correlation was found with the administered activity or the calculated marrow dose. Comparable literature values (JNM 37:31P;244;1996) for standard dose levels of St-89 C12 (n=l 7), Re-186 HEDP (n=l 2), and Sm153 EDTMP (n=9), respectively, are: 37±13 and 39±24; 35±16 and 43±12; and 45±21 and 56±15 (p<0.05 for all comparisons). Of 39 patients, 2 patients experienced grade 2 and 1 patient experienced grade 3 WBC toxicity, but no patients showed platelet toxicity. Time of onset of relief was modestly correlated with marrow dose, administered Snl17m activity, and the bone index (r= -0.66, -0.59, and -0.49, respectively). Onset of pain relief was noted at 5±3d with doses >6.6 MBq/kg (n=20), and at 19±15d with doses <5.3 MBq/kg (n=10), p=<0.05. Conclusions. At 2.6-10.6 MBq/kg doses, Sn-ll7m shows less hematological toxicity than other bone pain palliation agents (p<0.05). Overall pain response (75%) is similar to other agents, and is not correlated with the tin-I 17m dose. The time of onset of pain relief was shorter at higher doses (p<0.05). Work supported by US DOE, Contract No. DE-AC02-76CH00016, and by Diatide, Inc.

35.3

35.5

P.P.M. Kooij, W.H. Bakker, D.J. Kwekkeboom, H.E. van der Pluijm, M. Behe, N. Macke, E.P. Krenning. Departments of Nuclear Medicine University Hospital Dijkzigt, Rotterdam,The Netherlandsand UniversityHospital Basel, Switzerland.

G.Paganelli, C.Grana, M.Chinol, M.Cremonesi, C.De Cicco, * F . D e Braud, M . M a g g i o l o a n d **A.G. S i c c a r d i . Div. Nucl. Med., *Oncol., European Institute of Oncolology,**DIBIT H S. R a f f a e l e , Milan, Italy.

COMPARISON OF BIODISTRIBUTIONIN HUMANS OF A NEW CHELATED SOMATOSTATINANALOGUE FOR RAUIONUCLIDE THERAPY, [DOTA-D-PHE-I-TYR-3]-OGTREOTIUE,AND [DTPA-D-PHE-I]0CTREOTIDE. A new chelated somatostatinanalogue, [DOTA-D-Phe-l-Tyr-3]-eetre0tide(DOTATOC), was developed for future use in peptide receptor radlonuclide therapy (PERT) with Y-90. In vitro, DOTATOG had a binding affinity for the somatostatinreceptor in the subnanomolarrange. Eight patients were injected with 190-210 MBq In-III-DOTATOG.Two patients had HUN-I, two had MEN-If, one had operated MTC, one not operated HTC, one had carcinoid syndrome and one had a pancreaticislet cell tumor. None had any sideeffects. Blood was sampled at iO, 20, 40, 60, 90, and 120 min, and 4, 8, and 24 h pi. Urine was collected in 3 h and later 6 h periods up to 24 h pi. Feces was collected during the first 48 h pi. Five patients were injected with 200-220 MBq [In-lll-DTPA-D-Phe-l]-oetreotide {In-III-OG) within 6 weeks of ln-III-DOTATOCscanning, and urine and feces were collected following the same protocol. All tumors that were identifiedwith InIII-0C imaging were also visible with In-ILI-DOTATOG imaging. No additional tumors were identified with In-III-DOTATOG imaging. Compared to In-lll-0C, uptake in the tumors was about twice as high with In-III-DOTATOC.Uptake of radioactivity in these five patients in various organs 24 h pi, expressed as percentage of injecteddose, was as follows:

ANTIBODY GUIDED THREE-STEP RADIOTHERAPY WITH 90y_ B I O T I N IN G L I O M A P A T I E N T S A 3 - s t e p t h e r a p y t r i a l u s i n g anti t e n a s e i n M o A b s a n d the a v i d i n b i o t i n s y s t e m w a s a p p l i e d to 45 p a t i e n t s , with histological diagnosis of g r a d e III a n d IV malignant glioma. All patients had measurable disease refractory to o t h e r t h e r a p i e s , assessed by CT or MRI. Tumor pretargeting was performed i n j e c t i n g i.v. 35 m g / m 2 of b i o t i n y l a t e d anti-tenascin M o A b BC4 (let step) followed, a f t e r 36 h, b y 30 m g of a v i d i n a n d 50 mg of s t r e p t a v i d i n (2ns step). 1824 h later, 1-2 m g of Y - 9 0 - D O T A - B i o t i n were injected i.v. (3rd step). T r e a t m e n t w a s w e l l t o l e r a t e d a n d no a c u t e t o x i c i t y w a s o b s e r v e d u s i n g Y - 9 0 d o s e s of 1.48 up to 2.96 G B q / s q m . T h e d o s e d e l i v e r e d to the t u m o r r a n g e d f r o m 8 to 25 Gy w h e r e a s the d o s e to n o r m a l b r a i n a n d b o n e m a r r o w w e r e in a r a n g e of 0 . 3 - 1 . 1 G y and 0.6-1.4 Gy respectively. Responses to the treatment, measured b y CT or MRI w e r e e v a l u a t e d according to W H O criteria. Tumor regression was o b s e r v e d in 8 out of 39 p t s four m o n t h s a f t e r RIT. A n o n e y e a r f o l l o w - u p is n o w a v a i l a b l e for 28 p t s a n d w e f o u n d an o b j e c t i v e response in 5/28 pts, including one complete remission, two partial responses, one m i n o r r e s p o n s e , one s t a b l e d i s e a s e , w h i l e in the o t h e r 23 pts the d i s e a s e p r o g r e s s e d . The overall median survival of the 32 p t s w i t h glioblastoma multiforme was 15.5 months. In the o t h e r p t s w i t h a n a p l a s t i c glioma, the s u r v i v a l r a t e e x c e e d e d 36.6 m o n t h s . This n e w t h e r a p e u t i c m o d a l i t y has shown to be safe and tumor regression in p a t i e n t s w i t h d i s e a s e in r e l a p s e w a s o b s e r v e d .

Liver In-III-DOTATOC In-lll-0C

1.4 2.2

Spleen Kidneys Pituitary 2.4 2.4

5.2 5.4

0.021 0.010

In-III-DOTATOC was cleared from the blood rapidly, 15% of the injected dose being present 1 h pi, and 0.4% being present 24 h pi. Urinary excretion,almost exclusively of the intact peptide, was 85% 24 h pi. Excretion into the feces was less than i%. These data did not differ significantlyfrom those for In-lll-0C in the same patients. Conclusions: i) In-III-DOTATOGshows a higher uptake in somatostatin receptor positive organs and tumors in vivo comparedto In-LII-OG; 2) The biedistribution is comparableto that of In-lll-0C except for the lower liver uptake; 3) Given these favourablecharacteristics,the developmentof Y-90-DOTATOCfor PERT seems promising.

908

[] 35.6 Perkins AC, Hughes ODM, Frier M, Bishop MC, Price MR, Denton G, Wastie ML, Rutherford R and Schubiger PA. University Hospital and City Hospital, Nottingham, UK and Paul Scherrer Inst., Switzerland. INTRAVESICAL ADMINISTRATION OF Cu-67-595 MAB: A POTENTIAL THERAPEUTIC CONJUGATE FOR SUPERFICIAL BLADDER CANCER The intravesical administration of radioimmunoconjugates provides an attractive approach for the therapy of superficial bladder cancer. We have radiolabelted the anti-mucin antibody 595 with Cu-67 using a 14N4 macrocycle and evaluated its potential as a radiotherapeutic conjugate. 14 patients with tumours identified by preoperative radiology underwent intravesical administration of Cu-67-595 antibody (500~g/20MBq). After one hour the activity was drained and the btadder washed out. Tumour uptake was assessed by imaging 1 hour post washout and by the assay of activity in turnout and normal urothelium. Imaging correctly demonstrated tumour in t l of 13 patients with tumour confirmed by cystoscopy. No uptake was seen in one patient with cystitis and no tumour. The mean uptake, % injected dose per gram was 0.056%+0.048% in tumour and 0.0082%+_0.0086% in normal tissue (p<0.001). The mean T:NT ratio was 14:1 with higher uptake in higher grade tumours (G2,3). No radioactivity was detected in blood and there was no evidence of HAMA in serum taken from patients These initial studies confirm good accumulation of this antibody conjugate in superficial bladder tumours and indicate the feasibility for a course of multiple treatments. We are now undertaking extended imaging studies to determine the dosimetry for an anticipated therapeutic trial.

Gastroenterology 36.1 M. Pap6s, T. Tak~cs, L. Tr6n, G. Farkas, E. Ambrus, J. Lonovics, L. Csernay, L. P~vics Albert Szent-Gy6rgyi Medical Universky, Department of Nuclear Medicine, 1st Department of Medicine, Department of Surgery, Szeged, DOTE PET Centre Debrecen, Hungary THE POSSIBLE PLACE OF FDG-PET INVESTIGATIONS IN THE DIFFERENTIAL DIAGNOSIS OF FOCAL PANCREATIC LESIONS Eleven patients with focal pancreatic lesions were investigated. Atypical abdominal pain and weight loss were the main symptoms in all patients; 2 of them had chronic pancreatitis in his history. Acute pancreatitis was excluded on the basis of a non-elevated serum amylase level. In all patients, the CA 19-9 level was measured, and abdominal ultrasound (US) and CT and ERCP investigations were performed. Following these diagnostic procedures, FDG-PET investigations were also applied. The final diagnosis was verified by surgery in 8 patients and on the basis of 6-month clinical follow-up in 3 cases. The values of the different diagnostic modalities were analysed retrospectively. Malignant lesions were found in 4 cases (adenocarcinoma in 3 and apudoma in one). Elevated CA 19-9 levels were measured in all of these cases. CT and US were informative for malignant disease in only one patient (liver metastaseses were detected). ERCP was unsuccessful in 2 patients, whereas in the remainding 2 cases it could not clearly differentiate between malignant and benign disease. FDG-PET revealed a malignant focal pancreatic lesion in all of these patients. Seven focal cases of pancreatic disease proved to be benign. An elevated CA 19-9 level was measured in 3 of them. CT and US localized the focal lesion in all of them, but these methods were ineffective in the differential diagnosis. ERCP was negative in only one of the 7 patients. Six negative FDG-PET results were in agreement with the surgery findings or with the clinical follow-up. In one case, however, PET proved to be false-positive. Conclusion: FDG-PET is an effective tool for differentiation between malignant and benign focal pancreatic lesions. Our results suggest that in cases with focal panceatic lesions detected by CT or US, and with simultaneously elevted CA 19-9 level, FDG-PET is the next step in the diagnostic strategy.

Therapy/Gastroenterology

36.2 I. Banzo, C. Gutierrez-Mm_ndiguchia, I. Blanco, I. Uriarte, NK. Vallina, R. Quirce, JM. Carril SERVICI0 DE MEDICINA NUCLEAR HOSPITAL DNIVERSITARIO MARQUFS DE VALDECILLA SANTANDER. ESPAI?~ HEPATOBILIAK~ S C I N T I G ~ 4 Y I ~ ~ Pd~AT~D TO T-%~JB~ IN OK'FrZYlDPIC ~

DZA~NOSZS OF BILE

TRANSPLANIg._~C~ (OLT) Bile leak (BL) is a postoperative ccmplication of OLT. In the biliary anastcmssis as a choledochscholedochostcmy (CC) over a T-tube (~T), BL may be produced after Tr removal or migration. Frc~ Nov 91 to Dec 96, 151 patients (pts) underwent 170 OLT in cur hespital. We have ~ u a t e d the usefulness of hepatobiliary s c i n t i ~ h y (HBS) for the diagnosis of BL in 22 pts (mean age 42, range 18-57) who develcped ~ pain after intentional removal (20 pts) or spontaneous migration, deteunir~ted by cholangicgrapby, (2 pts) of the TT. HBS was performed between 5 &nd 120 hotu~s frcm the onset of ahdaminal pain using 185 MBq of 99rain Mebrofenin. Supine anterior images were acquired during the first minute (rain) after injection, every 5 rain for 30 min, at 60 and 120 rain or later if necessary. HBS imaging of BL was defined by the visualization of activity outside the biliary system. In 15 pts a final diagnosis of BL was established by surgery (I0 pts), ~IRCP (4 pts), and aspirative punction of US collection (I pt). In the other 7 pts BL was excluded by clinical follow-up (5 pts) and by ERCP (2 pts). HBS %-as positive in 14 of 15 pts with BL, shc~%g an int1~eritcneal BL in 5 and a subhepatic BL in 9. In 6 of these 9 pts HBS location of BL was related to liquid collections seen on US. ~CP was pe-~o~ in 8 pts and papilotcmy in 6 pts. Papilotc~ reached to the closture of BL in 4 pts. Ten pts were cperated c~: 5 repair of bile duct, 2 CC rea~mstc~Dsis, 2 CC conversion to RDux-en-Y, and I replacement of TI'. HBS was noxTnal i n one pt with US bilcma and alxkn~nal abscess. In the 7 pts without BL HBS shswed a normal transit of activity. Whilst TT is into the CC, diagnosis of BL is feasible by cholangiography. Once TT is rera]ved, HBS studies the status of biliazy anastc~Dsis, helps to diagnosis of BL, and provides infornmtion about the cc~nunication between US collections and the biliary system.

36.3 L. Madfiesy, H.V. Middelfart, P. Matzen, P. Funch-Jensen and Lo Hojgaard*, Depts. of Medical and Surgical Gastroenterology and Clinical Physiology/Nuclear Medicine*, Hvidowe Hospital, University of Copenhagen, Denmark. CHOLECYSTOKININ-AUGMENTED QUANTITATIVE HEPATOBILIARY SCINTIGRAPHY AND SPHINCTER OF ODDI MANOMETRY IN PATIENTS WITH SUSPECTED SPHINCTER OF ODDI DYSK1NESIA - IS IT A REAL PROVOCATION TEST? Introduction: Endoscopic sphincter of Oddi (SO) manometry (ESOM) and quantitative hepatobiliary scintigraphy (QHBS) are accepted methods for the diagnosis of SO dysfunction (SOD). Cholecystokinm (CCK) or its analogue caerulein (CE) augmentation was suggestedas a stress test during QHBS, which may improvethe sensitivity, since a subgroup of patients with SOD may present with paradoxical SO contraction originally described by ESOM. The aim of this study was to compare the results of CCK-augmentedQI-IBSto ESOM Patients and methods: 16 patients (PTs) with postcholecystectomy syndrome were investigated. QI-IBSwas performed in every PT, ESOM was accomplished in 10 PTs up till now. From the 60. rain of QHBS and at the second part of ESOM 5 ng/bwkg/min CE (Takus) was administered for 10 min in each PT. Time to peak activity (Tmax) as well as hatftime of excretion (T1/2) of the liver parenchyma (LP), hepatic hilum (HH), common bile duct (CBD), hilum-toduodenum transit time (HDTT), and also average SO basal pressure (ABP), maximal BP (MBP), amplitude and peristalsis of the phasic contractions (PCs) were determined by QHBS and ESOM, respectively. The T1/2 for the CBD, the ABP and the MBP were calculated for both before and during CE administration. Results: On the basis of the results of ESOM the final diagnosiswas SOD in 5 of 10 PTs. Delayed biliary drainage with slower CBD emptying was demonstrated by QHBS in 7 of 16 PTs. Tmax for the LP and HI-I,and also HDTT showed good linear correlation with MBP (r : 0.76, 0.89, 0.76). The T1/2 for the CBD was significantly decreased after CE administration both in the group of PTs with normal and abnormal bile transit (from 19.3+4.0 and 63.4_+25.8 to 12.2_+4.0 and t3.l_+5.6 rain, respectively), therefore the differences between the two groups were masked after CE ABP and MBP were also significantly decreased after CE, and the PCs were stopped. During CE administration all PTs experienced some abdominal discomfortor pain regardlessof the presenceor absenceof SOD. Conclusions: QHBS and ESOM are comparable methods to examine functional disorders of the SO. CCK-augmentatiouduring QI-IBScould not be regarded as a provocation test, but it may be useful to study the relaxato~ functionof the SO.

909

• Gastroenterology/Renal 36.4

Renal 37.1

R. Aurisch, R. Michael, D. Gerber, D.L. Munz Clinic of Nuclear Medicine, Charit6 Hospital, Humboldt University Berlin, Germany.

C. V a n de Wiele, Y. D'Asseler, M. Koole, J. De Sutter, C. De Saedeleer, RA. Dierckx, University H o s p i t a l Gent, B E L G I U M

VISUALIZATION OF THORACIC DUCT LEAKAGE BY SCINTIGRAPHY AFTER ORAL INGESTION OF 1-123-1PPA

INFLUENCE OF TIME INTERVAL AND CHOICE OF BACKGROUND ON TC-99M DTPA DIFFERENTIAL RENAL FUNCTION USING DOUBLE BACKGROUND CORRECTION

There are some reports in the literature on the scintigraphic visualization of the thoracic duct following oral ingestion of labeled long-chain fatty acids. We used this method to locate leakages caused by complications of surgery or congenital malformations. Patients: Until now we examined 3 pts: # 1 a 52-year-old male with chyloascites after resection of the esophagus and removal of abdominal lymph nodes; # 2 a 62year-old male with lymph fistula after neck dissection due to tumor of the tongue; # 3 a 12-year-oldmale with congenital lymph malformation with chylothorax. Methods: Oral application of about 400 MBq l- 123-IPPA through a gastric tube. Planar scans using a large field camera after 1, 2, 4, 6 and 8 hours and additional SPECT studies when leakage-related hot spots were suggested. Results: The scintigraphy of pt # 1 showed a hot spot in the right upper abdomen best visible 6 h. Later on this clear demarcation disappeared by prevailing of the activity within the chyloascites. The leakage could be closed by re-laparatomy, conforming that the leak was exactly located scintigraphically. In pt # 2 the lymph origin of liquid of the fistula in the neck region could be proved. The leakage was clearly visible after 4 hours and located near the left vein angles.The operative intervention was successful. In the pt # 3 with right chylothorax we did not found the expected 1-123 activity in the right hemithorax, where a permanent drainage was necessary. On the contrary, there was a distinct pathologic activity pool in the left hemithorax as from I20 rain. p.appl., indicating the lymph transport from the intestinal region to the venous system in a atypical way. Therefore, the lymphatic liquid of the right hemithorax did not derive from the intestinum and hence fatty acid restricted diet was not longer necessary.

To d e t e r m i n e the influence of time interval and the choice of background on Tc-99m DTPA d i f f e r e n t i a l renal function (DRF} as e s t i m a t e d b y a double background correction ( area-surface method + Rutland-Patlak plot) using Tc-99m 24h DMSA differential DRF as g o ' I d standard, a prospective study was performed. At present, 13 p a t i e n t s (7 men or boys and 6 women or girls, m e a n age 25.5 years, range 0.1-64 years) with r e l a t i v e 24h DMSA values outside the 45-55% range have b e e n included. In all patients, using a surface method, DTPA DRF was d e t e r m i n e d between 60-180 sec (tl), 60-160 sec (t2) and 120-180 sec (t3) using perirenal (P)-, suprarenal (S) and infrarenal (1) ROIs. The mean and standard deviation of the d i f f e r e n c e s m e a s u r e d b e t w e e n DNSA DRF and DTPA DRF of the right kidney were r e s p e c t i v e l y : -1.9 (SD : 7.3) for Ptl, -2.1 (SD: 7.5)for Pt2, -2.0 (SD .. 7.5) for Pt3, 0.i (SD: i0) for Stl, -1.3 (SD: 9.3) for St2, 5.4 (SD: 7.4) for St3, -0.8 (SD: 4.6) for Itl, -0.8 (SD: 5.1) for It2 and -0.3 ( S D : 4.1) for It3. In 8 out of 13 patients, suprarenal ROIs resulted in negative Y-intercepts as well as v i s u a l incorrect slope fitting of the Patlak p l o t for the right kidney regardless of the time interval used. This m a y be due to o v e r c o r r e c t i o n by intravascular hepatic background activity resulting in higher statistical fluctuations e s p e c i a l l y in the early plot points. The s m a l l e r mean differences and standard deviations found using infrarenal ROIs as compared to p e r i r e n a l ROIs suggest the former may be preferable to perirenal ROIs for the determination of d i f f e r e n t i a l renal function.

Conclusions: Oral application of I-123-labeled fatty acids (IPPA) can yield results with important clinical impact. The method is simple and safe, but a sequence of scans is necessary to find out the individual time interval between application and the most meaningful scan.

36.5 S. De Botton, D. Huglo, V. Canva-Detcambre, J.-F. Colombel, V. Beauchat, P. Ziegels, T. Prang6re, M. Steinling, X. Marchandise, B. Wallaert - Departments of Nuclear Medicine, Gastro-enterology and Pneumology - CHU de Lille, 59037 Lille cedex - FRANCE S I M U L T A N E O U S D E T E R M I N A T I O N OF P U L M O N A R Y A N D I N T E S T I N A L P E R M E A B I L I T I E S (PP AND IP) IN P A T I E N T S WITH ALCOHOLIC LIVER CIRRHOSIS In patients with alcoholic liver cirrhosis (ALe), the normality of IP has been established but PP has not been often studied. The aim of this prospective study was to evaluated IP and PP in patients with ALC. Methods : 35 patients (age 32-62) with biopsy proven ALC, were included (mean grade B in Child's classification). None had previous history of pulmonary disease and all had normal CT scan. Lung function test and bronchoalveolar lavage (BAL) were also performed. Healthy volunteers (11 for PP and 14 for IP) acted as controls. Patients and volunteers were non smokers and did not intake alcohol at least 1 week before studies. PP was assessed using 99mTc-DTPA aerosol. After 2 min breathing in supine position, 60 s frames were acquired for 20 rain. Tv2 (rain) and Residual Activity (RA in %) were obtained from exponential fitting over the first 10 min of right pulmonary clearance curves. IP was concurrently evaluated from 24 h urinary excretion of 51Cr-EDTA expressed as a percentage of the total oral dose. Results (mean + sd) : patients with A L e Wilcoxon test Controls PP : Tv2 (min) 65.9 +32.2 p < 0.05 85.2 + 20.8 PP : RA at 10 min (%) 87.1+6.7 p < 0.002 92.8+2.6 IP : % 51Cr-EDTA 2.39 + 2.20 ns 1.74 + 0.81 IP was not significantly increased in patients with ALe. PP was significantly increased in patients with ALC versus controls. PP (RA) was significantly correlated (p < 0.05) to the total number of cells in BAL (r = -0.379) and to the number oflymphocytes (r = -0.351). Conclusion : In patients with ALC, PP is increased with normal IP. This increased PP is correlated to the number of cells and lymphocytes in BAU This fact might reflect abnormalities of macrophages functions and/or increased number of lymphocytes.

910

37.2 S. Ekberg, S. Olsson, M. Stenstr6m, G. Granerus*, Department of Medicine and Care, Division of Radiation Physics and *Division of Clinical Physiology, Section of Nuclear Medicine, Link6ping University, Sweden. A COMPARISON BETWEEN TWO SOFTWARES FOR THE QUANTIFICATION OF 9 9 m T c - M A G 3 RENAL STUDIES. For the purpose of quality assurance a commercial renal software package- QuantEM (SP1) developed by Emory University Atlanta, and sold by General Electric - was compared to an in house developed and validated software (SP2). 34 patients with high prevalence of unilateral renal disease were included in the cornparison. The two software protocols were applied to each patient study, allowing the use of the same kidney ROls but slightly different background ROIs. Split function was calculated from integral counts (SPI) and slope values (SP2). Camera based clearance was obtained by renal uptake in relation to administered dose (SPI) and uptake rate in relation to plasma concentration (SP2). During acquisition a more narrow energy window ( 17%, 2% offset) than stipulated by the QuantEM method (20%) was chosen. The single sample plasma clearance technique described by Taylor as reference for the absolute clearance measurements was used in 22 cases. The mean difference in side distribution between SPI and SP2 (right kidney in percent of right and left kidneys) was 0.8 percentage units (SD 1.2) and in estimation of absolute clearance of MAG3 40 ml/min (SD 46 ml/min). Cornpared to the reference method, SPI overestimated absolute clearance with mean 53 ml/min (SD 45 ml/min) and SP2 with mean 13 ml/min (SD 55 ml/min). Thus, there was a close agreement between the results of the two softwares for calculation of side distribution. On the other hand absolute clearance (gamma camera based clearance) differed substantially. Among the differences between the two protocols especially the importance of energy window, background ROI and algorithm has to be further evaluated.

[] Renal 37.3

37.5

H.Seymen Birinci, S,0nal, Y,Menda,P.Demirkale, S.Cantez IstanDul Medical Faculty, Department of Nuclear Medicine Capa-Istanbul

SH. EL-HADDAD,A. HEGAZI, and A. EL-TAWIL

Medicine, Cairo University

4-J

C EVALUATION OF POST-F~eWL RI~NAL SEQCALAE USING QUANTITATIVE RADIONUCLIDE STUDIES Studies using 131I-0IH and 99mTc_ DTPA done p r e ~ i a t e

post-, i

and 3 months post- ESWL. No significant changes of total renal ERPF and GFR could be detected Treated kidneys GFR,GFR% I~RPF,% ERPF and tmax showed no significant changes after ESWL except for a transient significant impprovement of their T I/2 (p<0.04):that occurred irsnediately after ESWL. Gontralateral kidneys showed only transient statistically significant improvement of both% GFR and T I/2 (p 0.02 and 0.004 respectively). Regional evaluation of the stone bearing Zones revealed transient significant deterioration of their regional I~{PF ([3<0.03) We found that shocks<3500 caused transient significant improvement of treated side ERPF, whereas>3500 shocks caused the reverse(p 0.05). Moreover power index(number of shocks x KV) 5500( caused deterioration of their GFR that persisted up to 3 months (p 0.03). Follow-up for these cases after 5 years is done.

37.4

37.6

O. Fehmi Yardi Levent Kabasakal, Kerim SOnmezo~lu, Haluk B. Sayman, Ebru Alkan, Ilhami Uslu, Cetin 0nsel. Cerrahpa~a Medical Faculty, Department of Nuclear Medicine, istanbul Turkey.

B:Baggio, G.Gambaro, D.Casara. G.Saladini, C.I)afermou, F.Veriato, A.Budakovic. General Hospital and University of Padova and CNR Centle on Ageing of Padova, Italy.

COMPARISON OF Tc-99m-DMSA AND CORTICAL PHASE SUMMED IMAGES OF Tc-99m-EC IN EVALUATION OF SPLIT RENAL FUNCTION AND RENAL CORTICAL DISEASES

PvIPAIILMENT OF" RENAl, }IAEMOI)YNAMICS IN IX)NGTERM CIGARETTF, SMOKERS

DMSA is the agent of choice in detection of renal cortical defects. Due to use of anterior and posterior images DMSA is also considered to be superior to renal tubular agents in calculating split renal function. However, high radiation dose is the major disadvantage of DMSA, particularly in paediatric patient population. In the present study we compared DMSA and cortical phase summed images of Tc-99m-EC in detection of renal cortical defects and calculation of split renal function. For this purpose 37 patients were included to the study with an age range of 23 days and 68 years. DMSA was given 50 I,tCi/kg and the images were obtained at 4 hours and 24 hours after injection in anterior, posterior and two lateral projections. Dynamic Tc-99m-EC images were obtained for 30 rain and cortical phase images were created by summing the first 60-180 see images. The split renal function obtained by DMSA and Tc-99m-EC showed excellent correlation when all the patients were compared (r=0.97). When we compared the patients with hydronephrotic kidneys the correlation was inferior (n=25, r=0.84). When we include ouly the patients with hypoplastic kidneys the correlation between the two agents was also high (n=12, r=0.90). The cortical images of Tc-99m-EC was divided into three regions and by 2 observers. The results are compared with the DMSA images which showed excellent agreement. This study suggested that split renal function calculated with Tc-99m-EC may be unreliable especially in hydronephrotic kidneys. However, cortical images of Tc-99m-EC is of value in evaluation of renal cortical defects.

| i

Nuclear Medicine, and Urology Departments Faculty of

REEVALUATION OF INTERMEDIATE F+20 DIURESIS RENOGRAPHY WITH F-15 DIURESIS RENOGRAPHY To reduce the number of intermediate results in classical diuresis renography (F+20) diuretic administration prior to tracer injection (F -15) has been proposed. The purpose of this study was to reevaluate intermediate F+20 with F-15 diuresis renographies.MET}{ODS:F-15 diuresis renographies were performed to 10 intermediate F+20 renographies.To maximize the diuresis, 15 mg/kg saline were given intravenously at least 30 min before the injection of Tc 99m DTPA and continued until the end of the study at a rate of 200 ml/kg/24h. The patients were asked to void before the study. Catheterization was performed to children younger than 7 years old. The patients were placed in supine position over a gamma camera interfaced to a Microdelta computer. Clearance half times (TI/2) were calculated which measured the time taken to clear half of the activity present in the renal pelvis after the injection of diuretic from renogram curves.When the response remained intermediate (TI/2 15-20 min ), F-}5 diuresis renography was performed. RESULTS=Four of i0 intermediate F+20 diuresis renographies remained intermediate, 2 became normal and 4 became obstructed after F-15.CONCLUSION:F-15 seems as a good choice to r e d u c e the number of intermediate results of F+20.

C O

The objective of this study was to determine the effect of long-tern1 cigarette smoking on renal haemodynamics. 30 subjects who had no vascular disease risk factor other than cigarette smoking and 24 non smokers,age and gender nlatched, controls were studied. Patients underwent complete laboratory evaluation and vascular ultrasonography and Doppler analysis.Renal haemodynanlic function" was determined by 99m Tc-MAG3 tubular extraction and 99m TcDTPA glomerular filtralion, hi addition plasma endothelin-I levels were measured. Smokers had a significant reduction of plasma flow ( 199 vs. 256 ntL'min,p<0.001 ),a normal GFR mad an increased filtration fraction ( 5 l% vs 37%,p<0.005 ) in comparison with comrols. The haemodynamic disfunction was associated with an increasing in plasma endothelin-I levels ( 2l vs 25 pmol/l,p<0.(101 ). In conclusion,these results suggest that long-term cigarette smoking induces a significant impact on renal thncdon,probably mediated by vasoactive hormone alteration.

911

O

• Physics Physics 38.1

38.3

M.A. Lodge and P.K. Marsden, Guy's and St. Thomas' Clinical PET Centre, Division of RadiologicaI Sciences, UMDS, London

M. Rentschler, J. Kotzerke, G. Glatting, R. Weller, S. N. Reske, Universit~t UIm, Abteilung Nuklearmedizin, Germany.

A CLINICAL EVALUATION OF THE QUANTITATIVE ACCURACY OF SIMULTANEOUS EMISSION / TRANSMISSION SCANNING IN WHOLE-BODY PET In 2D PET, sinogram windowing of rotating rod sources provides the opportunity for simultaneous emission / transmission (SET) scanning which, in turn, facilitates the acquisition of attenuation-corrected wholebody images within a practical time-frame. We present the results of a clinical investigation of the extent to which SET data compares to separately acquired measurements in terms of quantitative accuracy. 15 patients were studied on an ECAT 951R tomograph with a dynamic acquisition protocol which lasted for 15 minutes per bed-position in both emission and SET modes. As pre-injection transmission scans are often impractical for clinical use, the standard against which SET was compared was a 15 minute post-injection transmission scan,,derived from the SET acquisition, and the separate 15 minute emission scan. Data acquisition commenced 75 minutes after administration of 350 MBq of FDG; 50 MBq transmission sources were employed; corrections for rod dwell and transmission spillover were applied to the SET data; measured attenuation correction was performed; ordered-subsets EM (1 iteration, 16 subsets) reconstruction was used for the SET data; FBP was used for the separate data. ROI analysis of muscle uptake showed a strong correlation between the quantitative values obtained from the SET acquisitions and the separately acquired standard (r=0.98 (I5 rains); r=0.95 (7.5 rains)). Muscle values agreed closely (y=0.97x+intercept) although an offset, probably due to scatter, meant that typical values were overestimated by 9%. Although redistribution of the tracer in the 30 minute period between emission and SET acquisitions biased tumour analysis in favour of the later scan, the SET data were also highly correlated with the standard (r=0.99 (15 mins); r=0.97 (7.5 mins)). We conclude that, even for short acquisition times, SET can be used to produce quantitative information which correlates closely with separate measurements.

DETECTABILITY OF SMALL STRUCTURES COMPARISON BETWEEN 2DAND 3D TECHNIQUE

38.2

Purpose: Our goal was to determine quantitatively the detectability of small structures in dependance on both, object size and object to background activity ratio by using the 2D- and 3D-acquisition technique in Positron-Emission-Tomography (PET). Methods: A Plexiglas cylinder (diameter 20 cm, start activity 0.037 MBq/ml F-18) containing 6 line sources (diameters from 1 to 6 mm, start activity 37 MBq/ml N-13) was placed in a PET-scanner (ECAT EXACT HR +, FWHM 4.3 to 5.5mm). Dynamic measurements were performed in 2D and 3D mode over 4 hrs in each case. Due to the different half-lifes of F-18 and N-13, object to background activity ratios varied in a time dependent fashion. The image data were reconstructed with a Hanning filter using measured attenuation correction. The object to background ratios were determined employing the ROI technique. To decide if an elevation of the object to background ratio was significant, the Students t-test was applied (5%). Results: For both acquisition techniques, object detectability is marked by an object to background ratio of at least 1.6. In the 2D mode, this ratio is obtained in objects ranging in diameter between 1 or 2 mm for a "true" activity ratio of 35. Objects measuring 3, 4, 5 or 6mm are detectable with ,,true" activity ratios of 28, 10, 8 and 4, respectively. Using the 3D acquisition mode, the required "true" activity ratio for object detection is by a factor of 1.5-1.8 smaller as compared to that necessary for the 2D technique. Conclusion: Compared to the 2D-PET, the gain in sensitivity of 3DPET allows detection of structures being smaller by a factor of ~ 1.3 with the same 'true' object to background activitiy ratio. Moreover, objects with the same size are detectable with 3D technique if the "true" activity ratio is smaller by a factor of 1.5-1.8 as compared to the 2D acqusition mode.

38.4 M Peneder, C. Burqer, A. Buck, Division of Nuclear Medicine, University Hospital, Zurich, Switzerland

NON INVASIVE QUANTIFICATION OF REGIONAL CEREBRAL BLOODFLOW USING POSITRON EMISSION TOMOGRAPHY - VERIFICATION OF A NEW METHOD

Purpose: Several methods have been proposed to quantify the regional cerebral bloodflow (rCBF) by means of positron emission tomegraphy (PET) and H2~O. In general they require both dynamic PET data and the instantaneous tracer concentration in blood. The latter is obtained by arterial puncture, blood withdrawel and activity counting during the scan. This blood sampling, however, involves patient discomfort and risks, and is tedious to perform in practice. A non-invasive method for rCBF assessment obviating the need for blood sampling was proposed by Watabe et al. in late 1996 [Watabe, H., et al. Noninvasive Quantification of rCBF Using Positron Emission Tomography, J Cereb Blood Flew Metab 16:311-319]. It is based on the definition of two cerebral regions - a ,,low-flow"and a ,,high-flow" region. By comparing the time-activity curves (TAC) of these regions their flows (f~, f2) and distribution volumes (Vdl, Va2) can be estimated. Then, the TAC from each pixel can be compared to that of the low-flow region and its flow and distribution volume estimated, whereby the previously obtained parameter values (fl, Vdl, Vd2)are contained in the calculation prescription. In an attempt to quantify the PET data of a physiological stimulation study it was found that the initial step of parameter calculation is critical for the rCBF outcome, and that the calculation is highly unstable. An investigation was therefore done on the factors influencing the method's accuracy and on potential improvements. Methods: Several analytical procedures have been developed. They allow to derive a closed-form solution for the pm:ameter pre-calculation rather than the iterativefitting originally proposed. Furthermore they provide a means to study the bias introduced by the inherent coupling of the parameters and by the choice of the regions. The PET measurements were done with eight healthy persons at conditions simulating different altitudes (reduction of oxygen partial pressure in the breathing air; the part of the lowered partial oxygen pressure was replaced by nitrogen). The results of the rCBF calculation were compared with an established method [Alpert et al., 1984] using the arterial input curve. Results: 1) The approach does not support four individual parameters, but only three parameter fractions. Therefore one parameter must always be fixed by the user. This parameter enters proportionally into the pixel-wise rCBF calculation. 2) The parameter estimation and the ensuing rCBF calculation is highly dependent on the shape of the high-flowTAC. }n practical situations even negative parameters may result. A small variation of theTAC tail may easily produce 30% difference in the bloodflow values. 3) The rCBF values calculated using the non-invasivemethod are highly correlatedwith those calculated with the invasive reference method, with correlation cofficients 0.90<_r_<0.97.The regression slope, however, ranged from 0.7 to 1.3, depending on the choice of the region and on the measurement data. Conclusions: The proposed method is highly sensitive to the preprocessing step and hence prone to biased rCBF values. As it requires the external definition of one parameter, it does not allow stand-alone quantification of rCBF. An individual non-invasivecalibrationfor this parameterwould be needed.

912

USING PET: ACQUISITION

P. Schmidlin, J. Zaers, D. Newport*, L.E. Adam, G. Brix, M.E. Bellemann, W.J. Lorenz, Deutsches Krebsforschungszentrum Heidelberg, Germany, a n d * CTI Inc., K n o x v i l l e , Tn, USA. FIRST RESULTS ~BTAINED WITH THE FOURIER REBINNING ALGORITHM IN C O M B I N A T I O N WITH FAST ITERATIVE RECONSTRUCTION The F o u r i e r R e b i n n i n g (FORE) a l g o r i t h m b y M. Defrise (Inverse Problems ii, 983-994, 1995) allows processing of 3D P E T r e c o r d s ,by twodimensional reconstruction, using the full information of the 3D data. Recently, a v e r s i o n of this a l g o r i t h m w a s i m p l e m e n t e d in our ECAT EXACT HR + PET. Our fast HighOverrelaxation Single-Projection (HOSP) iteralive r e c o n s t r u c t i o n was attached, to p e r f o r m 2D-processing of the FORE output. Overrelaxation parameters were extracted from a series of patient records, in order to optimize convergence. From these data a t y p i c a l s e q u e n c e of o v e r r e l a x a t i o n parameters w a s d e r i v e d w h i c h n o w m a y b e u s e d for o t h e r p a t i e n t data. T h e r e c o n s t r u c t i o n of 63 s l i c e s n e e d s a b o u t 15 to 20 m i n u t e s . A s l i c e is r e a d y after 8 steps. First tests revealed imaging p r o p e r t i e s c l e a r l y s u p e r i o r to c o n v e n t i o n a l 2D or 3D p r o c e s s i n g . The resolution was examined u s i n g 64Cu p o i n t sources. Provisional evaluations d i d not s h o w a loss of r e s o l u t i o n due to rebinning. We p l a n to c o n t i n u e the e v a l u a t i o n of FORE, e s p e c i a l l y w i t h r e s p e c t to r a d i a l a n d axial resolution, a n d to n o i s e and artefact propagation.

[] Physics/Radiopharmacy Radiopharmacy 38.5

39.1

A. Hoekstra P.P. van Rijk, University Hospital Utrecht, Department of Nuclear Medicine, Heidelberglaan I00, 3584 CX Utrecht, The Netherlands.

J.T. Patt l, G. Westera I, J.E. Spang: and P.A. Schubiger2

ACCEPTANCE

N-[C-11]METHYLHOMOEPIBATIDINE: RAD1OSYNTHESIS AND BIODISTRIBUTION IN MICE

tO |n

/Div. Nuclear medicme. University Hospital Zarich. 2Dept. of Radiopharmacie. Paul Scherrer institut. Villigen. Switzerland. 4-a

ELECTRONICS

T~STS

OF

AND

511-keV

GAMMACAMERAS COLLIMATOR

WITH

COINCIDENCE

FOR

FLUORINE-18.

Recently two dual head garamacameras were installed in our department. One system (ADAC, VERTEX) has detectors with 3/8 inch thick crystals and equipped with 5!l-keV collimators. The other system (ADAC, MCD) has detectors with 5/8 inch thick crystals and coincidence electronics designed for the detection of both, in coincidence emitted, 511-key photons. The cameras can be used for both regular nuclear medicine procedures and F-18-DG studies. Methods: Acceptance tests were performed according to the NEMA method of measurement for both cameras. The performance of the cameras was also tested for fluorine-18 using the following phantoms. i. A line source filled with F-18. 2. A S P E C T phantom with the following compartments: uniformity, cold lesion-, linearity- and hot-lesion inserts. 3. A Deluxe SPECT phantom with solid spheres and solid rods. Phantoms were measured with the 511-keV collimator system as well as with the coincidence system. Results: Both cameras satisfied the NSMA-specifications as given by the manufacturer. The measurements of the VERTEX system with the 511-keV collimator show ring artefacts, a detectable cold lesion of 22.4 mm and a hot lesion of 14.3 ram. The fluorine-18 measurements with the MCD system show no ring artefacts, a detectable cold lesion of 9.2 mm, a hot lesion of 5.9 ram and good linearity. Conclusion: The results of the system with the coincidence electronics is superior to those of the camera with 511-keV collimators.

Epibatidine and some of its derivatives show a high affinity to ot4132and e.7 nicotinic acetylcholine receptor subtypes in tile brain. Tile high toxicity of these ligands may cause problems for hunlan application. We have labelled tile analogue 613-(2-Chlom5-pyridinyI)-8-azabicyclo[3.2.1joctane (homoepibatidine) to provide a less toxic tracer for nicot01ic receptors m tile CNS Tile racemie homoepibatidine precursor was reacted with [C-11]methyliodide in DMF at 120 °C for 10 minutes. Purification was performed over a Nucleosil 50-7 column with dichloromelhane/nmthanol/triethylalnine (85/15/0.001) (v/v/v) as mobile phase. Quality eootro[ x~as carried out over a SupelcosiI LC-ABZ HPLC column with acetonitrile (41) %) and buffer solution pH 7 (60 %). The specific activity was in the range 180 to 400 GBq/gmol tEeS). Tile radioehelnical purity, was better than 99 %. In vitro studies ill whole rat brain homogenate showed, that receptor binding of N-[C-I l lmeth~ lhomoepibatid0m was inhibited by preincubation with (:t:)epibatidine or (-tnicolmc The biodistribution of N-[C-lllmethylhomoepibatidine was mvestigaled m li2nlalc ICR-micc The anlounl of carrier injected in one animal was adjusted to be in tilt range o01 to oo 15 btg/kg body weight. Uptake of tile compound was highest m brain, except for liver and kidneys: % of the injected dose/g after 5 rain (mean of 3 animals): brain 12. I-+08. eye 3.0:~0 6. blood 16±0.3. liver 14.2±2.0, kidneys 177±7.6. spleen 1(I.9±4.2. lungs 7.3±1,8. heart 330.2. stomach 2.7±i.0, Gllrael 4 9 ± 0 6 nlusclc 2.3±0.7. The figure shows the time course of brain and blood activit3 20

~ l l -- brain ~ S - - blood

~15

~° :g s

~ " ~ . ;

t;

2'0incubationaotime [mirl].o

5o

~o

Tilt N-nleth3iated homoepibatidiue derivative passed the blood brain barrier and showed a high brain uptake. A sntooth decrease of the total brain activity was found for this injeelcd dose N-[C-I l Fn~ethslhomoepibatidine is a prmnising PET-ligand for nACh teccpu/is in the blain

38.6

39.2

R.J.Ott, R.Veugen, N.A.Flower, D.Visvikis, A R e a d e r , P h y s i c s D e p a r t m e n t , I n s t i t u t e of C a n c e r R e s e a r c h , S u t t o n , Surrey, UK.

C. Loc'hl, IVl. Bottlaenderl, M. Kassiou 2, J.L. Musachio3, E.D. London 2, R.F. Dannals 3, B. Mazi6rel, 1-Service Hospitalier Frdd~.ric Joliet, CEA, Orsay, France, 2-Brain hnaging Center, NIDA, Baltimore, USA, 3-The Johns Hopkins Medical Institutions, Baltimore, USA.

3D SCATTER

EVALUATION OF A Br-76 A N A L O G OF EPIBATID1NE FOR PET IMAGING OF NICOTINIC A C E T Y L C H O L I N E RECEPTORS

CORRECTION

FOR LARGE-AREA

PET CAMERAS

Positron volume images (PVIs) are p r o d u c e d b y o u r large--area p o s i t r o n c a m e r a ( M a r s d e n et al, PMB 34: i043-i062,1989) via a 3D backprojection-filtering method. A method of scatter correction t h a t c a n be a p p l i e d to 3D backprojections would be useful as 2D projections a r e n o t c r e a t e d w i t h this m e t h o d . Image scatter characteristics have been i n v e s t i g a t e d u s i n g p o i n t s o u r c e m e a s u r e m e n t s in air and in a range of tissue-equivalent phantoms. Scatter is shown to b e a slowlyv a r y i n g f u n c t i o n of the a x i a l a n d r a d i a l s o u r c e position and is object-size dependent as expected. The integrated scatter fraction v a r i e s f r o m 32% to 65% in o b j e c t s of i 0 - 2 7 c m d i a m e t e r . F r o m t h e s e m e a s u r e m e n t s an a l g o r i t h m has been developed which directly relates s c a t t e r a n d a t t e n u a t i o n f r a c t i o n s at a n y p o i n t in a t i s s u e e q u i v a l e n t object. 3D i m a g e - s p a c e scatter distributions have been produced using this algorithm plus an exponential scatter r e s p o n s e f u n c t i o n o b t a i n e d f r o m the d i f f e r e n c e b e t w e e n p o i n t s p r e a d f u n c t i o n s (PSFs) m e a s u r e d in air and water. Convolution of this distribution with an in-air PSF produces a backprojected scatter image which can be subtracted from the original data backprojection prior to 3D deconvolution. Images of a tissue-equivalent phantom containing 'cold lesions' show that scatter correction enhances 'lesion' contrast and improves lesion recovery coefficients. The m e t h o d is a p p l i c a b l e to PVI in g e n e r a l .

Post-morton studies of brain from patients who died of Alzheimer's disease have revealed a reduction in cortical and hippocampal nicotinic acetylcholine receptors (nAChRs). In the search for tracers which would allow h7 rive quantitation of nAChR concentration, epibatidine, (exo-7-azabicyclo-2-(2chloro-5-pyridyl)-[2.2.1]heptane has been labeled with C-11, F-18 and 1-123. ]n order to study the in rive behaviour of the bruno analog, BrPH, and to charaeterise its pharmacological properties, we have labeled epibatidine with Br-76 (T1/2 = 16.2 h). [Br-76]BrPH was prepared by using a Cu + assisted bromodeiodination exchange. The tracer purified by RP-HPLC was obtained in 40% radiochemiizal yield with specific radioactivity 20 GBq/gmoh In biodistribution and autoradiographic studies in rats, the regional distribution paralleled the neuroanatomicaI localisatiou of nAChRs. Two hours post injection, the highest concentration in the brain was found in thalamus (4 % ID/g). PET imaging of [Br-76]BrPH in baboon (24 MBq, 1.7 nmole, i.v.) demonstrated a rapid and high uptake in the brain (5% ID). Peak uptake (0.05 % ID/mL) occurred at 30-40 rain for the thalamus. The half-lives of [Br-76]BrPH clearance from thalamus, frontal cortex and cerebellum were 6.5, 2.9 and 0.5 h, respectively. Due to the constant washout in the cerebellum, the thalamus to cerebellum ratio was 7 at 3 h after injection. Subcutaneous injection of cytisine (1 mg/kg), 3 h p.i. of [Br-76]BrPH, reduced the radioactivity concentration in thalamus, cortex and cerebellum by 58, 50 and 27% respectively, at 4 h. Metabolite analysis using radio-TLC showed that at 30 rain and 2h, 60 and 40% of the radioactivity represented unchanged [Br-76]-BrPH in plasma. These preliminary results suggest that [Br-76]BrPH has the potential to be developed as a useful PET radiotracer for imaging nAChRs in brain.

913

C

L_

C~ m

8

• Radiopharmacy 39.3

39.5

C. Lundkvistl, C. Halldin ~, V.W. Pike 2, H. Olsson ~, P. Karlsson ~, J.A. McCarron 2, C.-G. Swahn 1, H. Hall 1, H. WikstrOm3, M. Mensonidas3 and L. Farde I. IKarolinska Institutet, Department of Clinical Neuroscieuce, Stockholm, Sweden, 2MRC, Hammersmith Hospital, London, U.K. and 3University of Groningen, The Netherlands.

S. Srivastava, K. Kolsky, G. Meinken, V. Joshi, R. Mease, and L. Mausner. Medical Dept., Brookhaven National Laboratory, Upton, NY.

IS [CARBONYL-C-11]DESMETHYL-WAY-100635 (DWAY) A PREFERABLE RADIOLIGAND FOR QUANTITATION OF 5-HT1A RECEPTORS? [Carbonyl-C-11]WAY-100635 has recently been shown to be a highly suitable radioligand for PET imaging of the 5-HT1A receptor in human brain. Metabolite studies measured in plasma have indicated that there may be small amounts of the analogue DWAY which may be a problem since DWAY is expected to be a potent and selective ligand for 5-HT1A receptors and may enter the brain. DWAY was labelled with carbon-11 in the carbonyl position by the reaction of the descyclohexanecarbonyl compound (which was prepared in a 3-step synthesis) with [carbonyl-C11]cyclohexanecarbonyl chloride. DWAY was obtained in acylation yields up to 90% and purified with reverse-phase HPLC. Radiochemically pure DWAY with a specific radioactivity of 1600-5300 Ci/mmol was obtained. Human post-mortem autoradiography with DWAY demonstrated binding in areas known to have a high density of 5-HT1A receptors. After i.v. injection of DWAY in a Cynomolgus monkey radioactivity accumulated rapidly in the monkey brain (5.7% of injected dose at 5 rain). There was a high accumulation of radioactivity in neocortical regons with a frontal cortex to cerebellum ratio of 6 after 60 min. Raphe nuclei retained a medium level of radioactivity throughout the experiment with a ratio to cerebellum of about 3. Transient equilibrium in the cortical regions was obtained at about 60 rain. A pretreatment experiment with WAY-100635 (0.5 mg/kg) 25 rain before radioligand injection reduced the radioactivity in neocortex and raphe nuclei to the level of cerebellum. Blood samples were taken to measure the percentage of radioactivity in monkey plasma represented by unchanged radioligand and radioactive metabolites Radioactive metabolites appeared rapidly but were all more polar than unchanged DWAY which represented 52% of the radioactivity at 4 min and 20% at 55 rain. In conclusion, DWAY shows excellent radioligand behaviour, modelling studies are needed to see if DWAY is preferable to [carbonyl-C-ll]WAY-100635 for quantitation of 5-HTIA receptors in humans.

COBALT-55 LABELED ANTIBODY IMMUNOSCINTIGRAPHY USING PET.

CONJUGATES

FOR

Purpose: To enhance the diagnostic usefulness of radiobioconjugates through PET imaging, we have developed Co-55 [t½ 17.5 h; [~+m~×1500 keV, 77%; y 511 keV (152%), 477 keV (16%), 931 keV (73%)] as a PET label for MAbs, and investigated its production, imaging properties, labeling chemistry and bindistribution in mice. Methods and Results: High-purity, no-carrier-added (NCA) Co-55 was produced using the Fe-56 (p,n) reaction at a proton energy of 28 MeV. A typical 4 h irradiation produced 10.2 mCi Co-55/g Fe. Radiochemical separation (90% recovery, total time -5h) was accomplished using MIBK solvent extraction followed by gradient elution with HCI on an anion exchange column. Images of a modified Jaszczak phantom filled with Co55 EDTA solution showed a satisfactory resolution, very comparable to that from F-18. The previously developed bifimctional chelating agent 4isothiocyanato cyclohexyl EDTA (4-ICE) produced Co-55 immunoconjugates of an anti-CEA F(ab')z MAb with high labeling yields (>90%), high serum stability (95% at 4 d), and 80ii0% immunoreactivity retention. In nude mice xenografted with LS-174T human tumor cells, tumor (T) uptakes (% ID per g) of the Co-55-4-ICE conjugate (and DTPA-DA conjugate, used for comparison) at 24 h and 48 h, respectively, were as follows: 4-ICE, 25.2 and 17.7; DTPA-DA, 9.0 and 4.9, The tumor to blood (B), liver (L), and kidney (K) ratios at 24 h and 48 h, respectively, were: 4-ICE, T/B 4.4 and 9.3, T/L 4.3 and 5.1, T/K 3.6 and 4.5; DTPA-DA, T/B 3.2 and 5.4, T/L 1.3 and 1.1, T/K 2.1 and 1.6. Conclusion: Our results demonstrate that high-purity NCA Co-55 can be produced in sufficient quantities and that Co-55 tabeled bioconjugates using the semi-rigid ligand 4-ICE produce biodistributions that are favorable for PET imaging with labeled MAbs/peptides. Work done under U.S. DOE, Contract No. DE-AC02-76CH00016.

39.4

39.6

M.Bergstr~m, L. Lu, F. Wu, K.-J. Fasth, V. Tolmachev a n d B. L & n g s t r O m , Uppsala University P E T Centre, U n i v e r s i t y H o s p i t a l , U p p s a l a , S w e d e n

A. Eigtved, P.Larsen, M.Jensen, B.Foder, S.Holm, A.K.Hansen, P.Iversen, L.Friberg. Dept. of Clinical Physiology & Nuclear Medicine and Dept. of Urology, Rigshospitalet and Deot. of Experimental Medicine, University of Comenhagen Copenhagen, Denmark. 16beta-FI8-FLUORO-5alfa-DIHYDRO-TESTOSTERONE (18F-DHT) hS AN ANDROGEN RECEPTOR LIGAND FOR PET STUDIES OF THE PROS?ATE. Dihydrotestosterone has been labelled with fluorine-18 for the purpose of studying the androgen receptor binding with PET (Bonasera et al, JNM 1996 37:1009-1015). We examined the androgen receotor distribution and density in the prostate of two monkeys, two healthy human volunteers and three patients with locally advanced prostate cancer. Methods: 200-300 MBq (monkeys 50-70 MBq) 18F-DHT was injected i.v. and dynamic acquisition covering the pelvic region was performed for 90-120 minutes followed by a subsequent whole-body scan (7 minutes per actual field of view) with a GE Advance or a GE 4096 PET scanner (GE Medical Systems, Milwaukee, WI). Arterial and venous blood samples were drawn during the dynamic scan. A urine bladder catheter secured a low uptake in the bladder. The radioactivity of the blood samples was measured in a well counter, and Thin Layer Chromotography (TLC) was carried out for metabolite analysis. Results: We saw a rapid and prolonged vascular filling and a gradual increase in prostate uptake was seen peaking in 15-25 min. oost injection. The normals and the monkeys had a mean prostate to non-target (muscle tissue) ratio of 1.6 and i.i respectively. The mean ratio for the prostate cancer was 2.6. Conclusion: 18F-DHT seems to be a useful_ ligand well suited for studies of androgen receptors in the orostate. In an ongoing study we use this method to investigate the androgen receotor occuoancy in prostate cancer natients during anti-androgen therapy.

ANIMAL STUDIES FOR THE VALIDATION OF 76BRBROMODEOXYURIDINE AS A TRACER FOR CELL PROLIFERATION To evaluate if in vivo uptake of 76Brbromedeoxyuridine would represent DNA-synthesis and thereby allow a non-invasive measurement of proliferation potential with PET, 76Brbromodeoxlcuridine w a s i n j e c t e d into rats. A f t e r 2-32 h o u r s t h e y w e r e s a c r i f i c e d a n d o r g a n s t a k e n out for m e a s u r e m e n t of r a d i o a c t i v i t y a n d f r a c t i o n incorporated into DNA. In a second set of experiments the rats were pretreated with hydroxyurea. Two mini pigs were studied with PET for i0 h o u r s following the i n j e c t i o n of 7 6 B r bremodeoxyuridine. F o r c e d d i u r e s i s w a s a p p l i e d to reduce free 76Br-bromide. Organ and blood radioactivity concentration was recorded with time. In rats, h i g h a m o u n t s of r a d i o a c t i v i t y w a s s e e n in blood, lungs, s p l e e n a n d intestines, u n r e l a t e d to DNA-incorporation. With hydroxyurea p r e t r e a t m e n t m a r k e d d e c r e a s e s w e r e f o u n d o n l y in spleen and intestines, with the inhibition correlating well with DNA-fraction. The noninhibited part correlated well with the d i s t r i b u t i o n of f r e e 7 6 - B r - b r o m i d e . In the pigs, t h e h i g h e s t u p t a k e w a s n o t e d in the red bone marrow, i n t e s t i n e s a n d spleen. D i u r e s i s i n d u c e d a s i g n i f i c a n t r e d u c t i o n in b l o o d a n d n o n p r o l i f e r a t i n g tissues. Conclusions: 76Br-bromodeoxyuridine can be used for t h e a s s e s s m e n t of p r o l i f e r a t i o n in vivo, b u t only after correction for a s i g n i f i c a n t extra cellular 76Br-bromide contribution.

914

[] Neurology Neurology

40.1

40.3

H. Stevens. H.M.L. Jansen, M. Lemmerling, B.M. de Jong, A.T.M. Willemsen, J. De Reuck, J. Korf. University Hospital Groningen, NI. and University Hospital Ghent, B.

D.G. Pavei, M. Dujovny, S. Brint, Q. Lin, P. Saxons, V. lbanez. Univ. of Illinois Medical Center, Chicago, Illinois and Laboratory of Neurosciences, NIA/NIH, Bethesda, Maryland.

55Co-PET in cerebral ischemla in relation to bloodflow, oxygen metabolism and Gd-MRI. Background: Several studies indicate the feasibility of Co-isotopes (55Co and 57Co) in imaging of neuronal damage in stroke, multiple sclerose, cerebral tumours and trauma. These studies show that Co-isotopes allow visualization of brain pathology related to inflammatory processes, reactive gliosis and to cell death. Till now it is not clear if the 55C0 accumulation occurs in the core of infarction or in the penumbra. Therefore we compared in the present stu~iy 55Co-PET with functional parameters such as cerebral bloodflow (rCBF) using C1502, oxygen metabolism (rCMRO2) using 1502 and cerebral bloodvolume (CBV) using C150 in PET and with the anatomical parameter Gd-MRI. Patient and Methods: Twenty- one patients (8 men; 13 women) age 37 to 80 (mean 66) with middle cerebral artery (inca) stroke, as proven by CT or MRI, were examined with 55Co-PET (0.5- 1.0 mCi 55COC12),C1502-, 1502- and C150-PET in one session 0-30 days after stroke-onset. Regions of Infarction were defined where rCMRO2 was below 65% and rCBF below <45% of the respective contralateral value and were superimposed on the cobalt scan. To compare the Cobalt uptake with the Gd-MR[ a co-registration progr~nnwas used to realign the MRI-images to the bloodflow images. Results: Seven patients showed a positive Co-PET scan and were used for further analysis. Comparing the Co-uptake with oxygen metabolism and bloodflow it showed that Co accumulates in areas with a diminished oxygen metabolism and is not dependent from bloedflow. Comparing the Co-uptake with the Gd-MRI we found Co-uptake in a part of the Gd enhanced brain tissue with a tendency to be located peripherally or outside the Gd demarcated brain tissue. Conclusion: The results of the present study suggest that Co-accumulates independent of bloodbrain barrier breakdown in infarcted tissue with a rather preserved flow. Acknowledsement: This work was supported by UCB, a grant (GGN 22.2741)from the Dutch Tech~.ologyFoundation (STW) and a grant from (92.305) the Netherlands Heart Foundation.

IMPROVED DETECTION O F D I A M O X INDUCED C H A N G E S BY USING STATISTIC P A R A M E T R I C M A P P I N G O F BRAIN SPECT IMAGES.

40.2

40.4

W.Yu.Ussov, A.M.Chcrniavsky, M.P.Plotnikov, Irene Yu. V.M.Shipulin. Tomsk Medical Research Centre, Siberia, Russia

the regional CBF.

Methods and results After informed consent was obtained six patients (one female and five male) were entered into this study. CO was assessed by the Stewart-Hamilton method with a gamma-camera in LAO45 position using Tc-99m labeled erythrocytes. After CO measurement whole body scanning was performed. Tc-99m HMPAO (740 MSq) was then intravenously administered. Five minutes after administration of Tc-99m HMPAO we performed another whole body scanning to assess the distribution of Tc99m HMPAO between the brain and the body of the Patient. Finally, SPECT scanning of the brain is performed. Global CBF is calculated as lroUows: C=(D/I~e'%'rVER). Where C (proportion of CO entering the brain), D (measured proportion of injectec~ close that is r Ioc hemical purity ot Tc-99m HMPAO )=087 retained in the brain), L (ad" . , e"'s' (frachon ' of injected Tc-99m HMPAO remaining unconverted at T)=0.89 V (fraction of Tc-99m HMPAO that remains in the blood before entering the brain =0.96, E (unidirectional extraction efficiency for brain =0.72, R (fraction of primary Tc-99m HMPAO complex entering the brain that is retained)=0.68 as descnbed by Neirinckx et al. We calculate rCBF by dividing the activity in the ROI by that of the whole brain multiplied by the global CBF. We were able to obtain CO by means of a Swan-Ganz catheter in patient nr. 1 (5780-6368 ml/mln). Patient nr. CardiacOutput ml/min Glebal CBF ml/min

1 6180 900

2 5976 957

3 8712 1237

4 7591 949

5 9350 1307

6 5410 541

Conclusion rCBF quantification with SPECT and Tc-99m HMPAO is possible and can simply be applied in a clinical setting. Validation of this method by comparison with other establisned methods such as rCBF measurement with PET must be performed in the future.

e(D ID

The extent and direction o f changes induced on brain SPECT images by the administration of Diamox (D) is often difficult to evaluate. We have previously demonstrated that Statistic Parametric Mapping can be used in the evaluation of repeated brain SPECT acquisitions. In this report the effect of Diamox is evaluated. Method: following 128x128 SPECT image acquisitions on a triple head camera (Prism 3000) with fanbeam collimator and 128x128 matrix, a reconstruction with subsequent oblique reorientation yielded a cubic voxe[ of variable size averaging 2.2 mm. The SPECT results were displayed in the form of relative value color coded surface maps as well as in standard color coded orthogonal slices. 17 paired (D) studies were used and the entire brain volume submitted to the SPM-95 analysis for each paired study, in conjunction with a group of 14 reference pairs. A special program subsequently displays the results on 26 Talairach normalized slices, in color, according to the level o f a Z value scale. Results. Abnormality maps, i.e., relative decrease post (D), were obtained for each o f the 17 pairs as well as separate maps indicating those areas with relative rCBF increase. Each map is associated with a specific statistical significance for each area displayed. The SPM maps, compared to the standard displays, were shown to identify all known post (D) changes but in addition enabled also an unequivocal evaluation of the extent of abnormality, detected additional abnormal areas (especially in the deep structures) and separated clearly the areas with normal response. Conclusion: The use of SPM improves and facilitates the evaluation of the changes induced by Diamox, and an intuitive, meaningful display o f results can also be obtained.

J van Peski, RJ Meijer, D Hasan, WH Bakker, PJ Koudstaal, and EP Krenning from the Departments of Neurology and Nuclear Medicine, University Hospital Rotterdam, The Netherlands

QUANTITATIVE MEASUREMENT OF RCBF WITH TC-99M HMPAO Introduction Recently, Matsuda, et al. reported a method to approximate rCBF with Tc99m HMPAO by calculating the Brain Perfusion Index (BPl=(100xkxf0x ROlao,asize):(ROIbraJnSizel/ and compare the results with rCBF obtained by cominuous inhalation Xe-133 SPECT imaging. A major weakness of this study is that the SPl does not correct for changes in d=stnoution of blood flow between brain and remaining parts of the body: if systemic vascular resistance drops and thus systemic blood flow increases, activity in the brain will dropproportionally even when cerebral blood flow remains unchanged. Cerebral Xs-133 SPECT imaging is subiected to error since the slow diffusible Xe-133, in contrast to Tc-99m HMPAO is mcomp=etely extracted at high flow rates. The 81 keV emission of Xe-133 results in a substantial adsorption by the calvarium and in Compton interference. Moreover, the inhalation technique applying Xe-133 gas has never been cross-tested against other accepted methods in an animal model such as iodo-[C-14]antipyrine. Neinnckx, et aLpubUshed in an appendix of an article (1988), handling the retention mechanism of Tc-99m HMPAO, that the proportion of cardiac output (CO) entering the brain (global CBF) can be calculated. Thus, after CO is measured, one can calculate the actual global CBF. We developed a new method to assess

eo |i

Shvera,

Q U A N T I F I C A T I O N OF CEREBRAL ISCHEM1C D A M A G E IN S T R O K E IN UNITS OF P E R M E A B I L I T Y - S U R F A C E P R O D U C T : P R O G N O S T I C R O L E F O R URGENT C A R O T I D SURGERY Brain 99mTc-HMPAO SPECT has been shown to be of prognostic value for functional recovery from cerebral ischemia in stroke. Here we have tested ability of local cerebral permeability-surface (PS) product calculated for 99mTc-HMPAO to be a predictor of irreversible damage of the brain. This is a retrospective study employed 3-years old data from 25 patients with stroke due to internal carotid artery occlusion in whom the 99mTc-HMPAO study was performed at admission net later than in 9 h after onset of manifest stroke symptoms. Patients underwent surgically successful urgent carotid endarterectomy (CE). Radionuclide protocol comprised dynamic study of cerebral uptake of 99mTc-HMPAO with subsequent quantitative brain SPECT. Blood clearance curve was obtained simultaneously from arterialized venous blood samples. The permeability-surface product, which represents virtual volume of blood cleared through regional capillary bed was calculated as PS=-rCBF ln(1-E) from classic Crone-Renkin eqn. Cv = Ca, e "PS/F where E=(Ca - Cv)/Ca and rCBF is local blood flow. Regional E was calculated as asymptote of brain regional retention function h(t)=F -1 {F[A(t)]/F[Ca(t)]}, A-local radioactivity, F - Fourier transforms, rCBF thus was obtained as ratio A/[E*~Ca(t)dt]. PS distribution over cerebral surface at admission was compared with newly acquired CT and MRI scans as markers of anatomic damage caused by stroke. Values of PS in control group were over 38 ml/min/100 g in all vascular regions of brain (in average 40.2 sd 3.8 ml/min/100 g). In all regions where PS product in acute carotid occlusion was over 34 ml/min/100 g no evidence of cortical damage were observed and full neurotogic recovery was obvious. In patients in whom in any of occlusion-dependent regions values of PS failed below 30 ml/min/100 g, urgent CE led to further deterioration of neurologic condition and cystic degeneration seen on MRI scans. Thus we conclude cerebral 99mTc-HMPAO PS index provides prognostic separation of patients in w h o m reestablishment of carotid blood flow could improve neurologic symptoms and revitalise viable cerebral tissue.

915

m I.--

O

• Neurology/Oncology Oncology 40.5

41.1

H Barthel. S. Hesse. J. Berrouschot*, D. Sclmeider*, WH. Knapp, Departments of Nuclear Medicine and *Neurology, University of Leipzig, Germany

H. Azaloux*, J. L. More~ti, J. C. Kouyoumdjian, Boisseron*.*CHU Fort de France, Martinique et 449 UFR L. de Vinci Bobigny Paris 13.

DIFFERENTIATION BETWEEN REVERSIBLE CEREBRAL ISCHEMIA AND ACUTE STROKE USING Te-99m-ECD SPECT Prognosis and adequate therapeutic decisions in acute stroke (< 6h after onset of symptoms) are difficult This present study deals with the question whether early SPECT can differentiate between reversible cerebral isehemia and ischemic stroke. 61 patients (24 £ 37 m, age: 57 J- 12 y, no stroke history) with acute ischemia in medial cerebral artery territories underwent Tc-99m-ECD-SPECT (400 600 MBq, brain dedicated camera: Ceraspect (DSI)) within 6h after onset of symptoms. Patients had neurological deficits (Scandinavian Stroke Scale (SSS) < 40 pt) at the time of injection of the radiopharmaceutical. SPECT data were auah,sed visually (local activity deficit in symptomatic hemisphere: "yes" or "no") and semiquantitatively: (1) deficit defined with irregular ROIs using contour detection program: volume and depth (count rate, related to injected dose) of deficit. (2) 88 ROIs in 5 transverse and 3 coronal slices, assaranetr3' index between count density of corresponding contralateral ROIs, asymmetry > 15 % = "abnormal". Neurologic state was evaluated using S S S after 24h and after 5d, CT was carried out immediately and after 5d Results: 18 patients were symptom-free after 24h (group A), in 43 patients symptoms persisted and areas of hypodensity were found in CT (group B). Visual SPECT analysis: only 1 of the 18 patients of group A revealed local activity deficits, however, 40 of the 43 patients of group B. ROI analysis of SPECT data resulted in 3 4- 4 (m.v 4- SD) abnormal areas in patients of group A and 17 4- 8 abnormal areas in group B (p < 0.001). In group B there was a negative correlation between deficit volume and SSS ld and 5d post event (r = -0.54 and -0.59: p < 0.001) and between number of ROIs with activity deficit and SSS ld and 5d post event (r = -0.57 and -0.54; p < 0.001) It is concluded that early SPECT in acute stroke can differentiate between evolving cerebral infarction and reversible ischemic episodes: In case of evolving infarction quantitative early SPECT is able to predict clinical outcome with considerable reliability.

SESTAMIBI Tc 99m (MIBI) SCINTIGRAPHY C A N C E R COMPARED TO P R O N O S T I C FACTORS.

IN

D. EA

BREAST

MIBI is highly sensitive for the detection of breast malignancy in patients with palpable breast masses. This study was undertaken to evaluate whether positive scintigraphic malignant lesions exhibited selective patterns of clinical and biological prognostic factors as do TNM Stage, lymph nodes , Scarf Bloom Richardson (SBR) g r a d i n g , Oestrogen ( O R ) and Progesterone ( P R ) receptors, plasmatic and cytosolic CA 15.3. 59 female p a t i e n t s aged 37-76 years with malignant tumors were referred for MIBI scintigraphy. All seintiscans were interpreted by 3 different trained physicians. Blood samples were obtained for plama CA 15.3 a n d frozen samples from excised tumors were p u l v e r i s e d and assayed for CA 15.3 and for OR and PR receptors. Among the 59 scintiscans, 44 were M I B I + (GI) and 15 MIBI- (GI). The results are e x p r e s s e d in percent in each group and displayed in the following table. MIBI

breast

scintigraphy

"~5~""5?"'~'Y~'~Y~

....~ ' ~ " ' ~ T " " ? ' g j Grading

SBR

....~ g ¥ " [ g ~ 7 " ~ T ~ = ~

............ :.................................................... ........................................................................................

II

G1 +

i !

G2 -

~ ~ .............. i ........... ~"~ ................ V ~ .............. ~........... ~'~ ................

(%)

91

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

g ~ .............. i ........... ~ ~ ................

[

100

Plasmatic positive C A 1 5 . 3 (%) 27 i 13 Our data indicate that the different parameters failed to discriminate the two groups of patients. The disease free survival after one year f o l l o w - u p of all the patients indicated that MIBI status was not correlated to prognosis. In conclusion our data confirmed that MIBI scintigraphy results have no prognostic value in breast cancer.

40.6

41.2

J. Darcourt, O. Migneco, M.H. Mahagne, J. P. Fournier, F. Bertrand, F. Bussi~re. Nuclear Medicine and Emergency Departments. Nice University Hospital.

R. Tiling, R. Linke, H. Sommer, M. Pechmann, K. Gebauer, K. Tatsch, and K. Hahn. Departments of Nuclear Medicine and Gynecology, Ludwig-Maximilians-University of Munich, Germany

EARLY 99mTe-ECD BRAIN SPECT AND N E U R O L O G I C A L RECOVERY AFTER STROKE We prospectively tested the hypothesis that peffusion brain SPECT abnormalities, measured few hours after stroke onset, could help to predict spontaneous neurological recovery. Twenty one patients, mean age 76 (range 57-91) were studied in average 7 hours (range 4-13) after a middle cerebral artery stroke, using 1000 MBq of 99mTc-ECD and a triple head camera (Prism 3000, Picker) equipped with UHR fan beam collimators (120 128x128 projections of 55 sec; FWHM=8mm). Neurological deficit was measured upon patient admission (O1) and after 3 months (03 : for 18 patients) using the Orgogozo neurological scale (normal = 100 ; range 100-0) and an evolution index (EI) was calculated (EI=O3 - O1 / 100 - O1). Patients functional status was also measured at 3 months using the Rankin score (R3 :for 20 patients)(normal = 0 ; range 0-6). SPECT images were analysed semi-quantitatively in order to evaluate the relative extent of severely reduced CBF (below 25% of maximum) supposed to represent infarcted tissue and moderately reduced CBF (between 25 and 60% of maximum) supposed to correspond to the ~ SPECT penumbra >>. Results show that the initial neurological deficit (O1) is not correlated with the evolution index EI. The total extent of SPECT abnormalities significantly correlates with the 3 neurological parameters O1, EI and R3 (p<0.02). However, the best correlations with neurological recovery (El) and 3 month status (R3) are observed with the relative extend of previously defined penumbra (p<0.01). This parameter does not correlate with the early neurological deficit (O1). Therefore, early 99mTc-ECD brain SPECT may help to predict each patient's potential recovery by evaluating the relative extend of penumbra and infarction and to select candidates for therapeutic trials.

916

SCINT1MAMMOGRAPHY WITH SESTAMIBI FOR DETECTION OF BREAST CARCINOMA: DIAGNOSTIC ACCURACY OF PLANAR, SPECT, AND COMBINED DATA EVALUATION T h e p u r p o s e of this study was to compare the results of planar and SPECT scintimammography (SMM) for the diagnosis of breast cancer. In addition our goal was to determine whether SPECT reconstructed with iterative algorithms (ISA) or with filtered back projection (FBP) provides more accurate data. 174 consecutive patients with unclear physical examination and/or mammography underwent SMM. From this group, those pts who had histopathologlcally confirmed diagnoses (n=113) were selected for this study. E a c h p t underwent planar lateral and anterior breast imaging as well as SPECT following the injection of 740 MBq Tc-99m sestamibi. SPECT data were reconstructed using both ISA and FBP. Planar SMM, ISA-SPECT, and FBP-SPECT were evaluated separately and combined. The results are summarized in the table below. All ISA-SPECT studies Sensitivity Specificity were of diagnostic quality, whereas FBP-SPECT was conPlanar SMM 80% 83% sidered non-diagnostic in 14 pts ISA-SPECT 71% 70% who had to be excluded from FBP-SPECT 69% 66% statistical calculation. In the Planar SMM 85% 72% combined approach cases with +ISA-SPECT non-di.agnostlc FBP-SPECT Planar SMM 81% 70% were mterpreted according to +FBP-SPECT their planar classification. Three carcinomas indeterminate on planar SMM were correctly identified by combined planar SMM plus ISA-SPECT. ISA-SPECT and FBP-SPECT provided additional information to planar SMM with respect to localization of sestamibi uptake, tumor extent improved diagnostic certainty and detection of axdlary nodes in 40 and 14 pts, respective y. Reconstruction with ISA rather than FBP may be considered as the preferable approach to process SPECT data of scintimammograms. Combined with planar SMM, ISA-SPECT can slightly improve sensitivity and provides important additional information to planar scans. Therefore, ISA-SPECT should complement planar SMM if the latter reveals positive and in particular indeterminate findings.

[] Oncology 4113

41.5

D. Francois, J. Hermans, F. Bodart, P. Merlo, Ch. Boudart, JM.Boudart, M. Beauduin, Department o f Nuclear Medicine, JP Fauconnier, Department o f Gynecology, Ch. Six, Department o f Surgery, A. Schmitz, department o f anatomopathology, H6pital de Jolimont, Belgium.

RT D h ~ JB Bomanji, W Waddington, J Wheetan, J Pringle, R Souhami, PJ ElL Institute of Nuclear Medicine and Dept of Oncology, Middlesex Hospital, London.

VISUAL AND QUANTITATIVE ANALYSIS OF 9 9 M T c - M I B I MALIGNANTANDBENIGNBREASTLESIONS.

UPTAKE IN

99MTc-M1BI is k n o w n to be taken up and retained in malignant breast lesions. However, benign lesions may also show some MIBI uptake. The ai_mmo f this study is to find out the best visual criteria to detect cancer lesions and to determine if quantitation could improve the results. Methods : 75 consecutive w o m e n with breast lesions were studied preoperatively. Ten min after IV inj. o f 20mCi 99mTc-MIBI, left: lat, fight lat and anter, planar images & t h e breasts were acquired for 10 min in the prone position. The visual score was : gradel (G1) : no abnormal uptake; G2 : mild and irregular uptake; G3 • moderate and well-delineated uptake; G4 " intense, circular, well-delineated uptake. A ratio pathol./normal (P/N) was caculated by dividing the mean counts in a ROI drawn on the lesion by the mean counts in an equivalent ROI near the lesion. Final diagnosis was given by the histology o f the lesion Results : visual analysis : fibrocystic disease. fibroadenoma adenosis papillomatosis cancer

G1 13 7 1 3

G2 1 I

G3 1 4

2

G4 2 4 1 35

Considering G3 and G4 positive for malignancy, the sensitivity is 92%, the specificity 66%, the positive and negative predictive values 76% and 88%, the accuracy 80%. The index P/N is not significantly different in the benign and the malignant groups (1.7±0.3 vs 2.0±0.6 respectively, p=0.07), and it could not help to improve the visual results. Conclusion " Visual analysis o f the intensity and the shape o f the MIBI uptake allows an accurate discrimination between benign and malignant breast lesions and allows to detect benign lesions with high cellular proliferation justifying a biopsy. Quantitatien did not improve the results.

CORRELATION OF SERIAL AND QUANTITATIVE THALLIUM SCANS WITH HISTOLOGICAL RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN OSTEOSARCOMA. - METHODOLOGICAL ASPECTS AND PRELIMINARY RESULTS

Adjuvant chemotherapyprior to surgery is part of standard managementof Osteosarcoma. The most reliable method of judging response to chemotherapyis howeverretrospectiveie histological analysis of the surgical specimen for tumor necrosis. This precludes any proaetivemeasuresearly in the course of treatment. We have prospectivelyevaluatedthe role of serial Thallium-201 scintigraphyin identifying non respondersearly in the course of treatment. To date, 17 patients have been scanned,at diagnosis, after every cycle of chemotherapy,and preoperatively. Static, whole body, and tomographicimages were acquired at various time points, from 5 minutes m 2 hours post injection, towardsdefining semi quantitativeindices and optimum imagingtimes. Tumour to backgroundratios (T/B), and tumour uptake as a percentageof whole body activity were derived. Preliminarydata shows that T/B ratios fall over a 2hr period (average decrease of = 24%). Comparisonbetween serial changes (from baseline to preoperativescans) on the 5,35 and 110 minute T/B ratios show good correlation (r>0.9). This implies that the time point of imagingis net crucial as long as the same time windowis repeatedon serial scans. Of the I7 patients scanned, i5 have been operated and histologicalanalysis for percentage tumor uecrosis is currently available for 10. Patients were classified as responders or non respondersbased on histologicalcriteriaof whetherthere was >90% or <90% necrosisin the resected tumor. A decrement in the above indices of >25% within the first two cycles and >50% at the preoperativescan were the scintigraphiccriteria taken to indicate a favourable response. Basedon the above scintigraphiccriteria, 2/3 histologicalrespondersand 6/7 non responders could be identified within 2 cycles of chemotherapy. In non responders SPECT delineated "sanctuary"areas of tumour better than planar images. To our knowledgethis is the first report of a rigorousprospectivethallium scanningprotocol in osteosareomaevaluating every cycle of chemotherapy. Results are preliminary but demonstratethe potentialof this technique.

41.4

41.6

~

J' Taki, N. Tonami, N. Asada, H. Tsuchiya, K. Tomita, of Nuclear Medicine and Orthopedics, K a n a z a w a University, Kanazawa, J a p a n

M.Gasparini. L.S. Maffioli,* L. Devizzi,* M. Castellani, A. Bruno, V. Longari, R. Benti, E. Bombardieri, P. Gerundini. Nuclear Medicine Department Ospedale Maggiore, IRCCS - Milano *lstituto Nazionale dei Tumori Milano- Italy

T H A L L I U M - 2 0 1 S C I N T I G R A P H Y IN P R E D I C T I O N O F RESPONSE TO C H E M O T H E R A P Y IN B O N E A N D SOFT TISSUE TUMORS

THE VALUE OF GALLIUM SCAN AS A PROGNOSTIC FACTOR IN PATIENTS WITH NON-HODGKIN LYMPHOMA: A LONG TERM FOLLOW UP. In patients with non-Hodgkin lymphoma (NHL) the use of gallium scintigraphy (Ga-67) compared to conventional staging and restaging techniques is still controversial. In particular in a combined modality treatment with chemotherapy and radiotherapy, its role in detecting active disease after treatment may be of particular interesting in planning the subsequent therapeutic strategy. In order to evaluate the ability of Ga-67 to define residual disease we have perspectively investigated 33 NHL's patient and we studied if the positivity of the scan during chemotherapy eouId predict the clinical outcome. All patients with histologically diffuse large cell lymphoma were investigated, 48-72 hours after the i.v. injection of 185-259 MBq of Ga-67. The imaging included whole body acquisition, anterior and posterior planar views of thorax, abdomen and pelvis and in many eases SPET acquisition. Patient evaluation included physical examination, laboratory assessment with complete blood count and chemistries, biopsies, complete radiographic baseline studies including chest X-rays, CT scan, magnetic resonance, ultrasonography and lymphography. To be scored as a complete remission (CR), patients were judged to have no measurable disease. All patients were studied at the staging and prior to following cycles 4 ° to 6 ° of intensive chemotherapy for a total of 73 scintigraphy. The patients were divided in two groups in relation to the positivity or negativity of Ga-67 after the 4 ° or 6 ° cycle of therapy. In the first group 14 of 33 patients (42%) showed persistent uptake of gallium after the fourth cycle of therapy. Of these, 8 (61%) have died, 2 were considered in partial remission (PR) and 4 were in CR. The CR was reach after the 6 ° cycle of chemoterapy. The follow up of this group of patients was 26.7 months (range 745). In the second group 19 patients resulted negative after the 4 ° cycle of CT. Of these 16/19 (84.2%) are alive without evidence of disease and 3 have died for relapsed of disease. The mean follow up was 36.0 months (range of 16-48 months). A statistical analysis of the association between Ga-67 result after 4-6 cycles of chemotherapy and survival was performed using the log-rank test; there was a statistically significat association between scan result and survival (p=.00125). Gallium 67 imaging seems to be an excellent indicator of residual viable tumor: a positive scan halfway through therapy can predict for a poor prognosis.

s

The purpose of this study was to assess the ability of T1 scintigraphy in mid-course o f c h e m o t h e r a p y to predict the final t u m o r response to chemotherapy in m a l i g n a n t bone and soft tissue tumors. Twenty-three patients were studied with T1. There were 16 men a n d 7 w o m e n (age range, 9 to 74 years; average age, 37.6+22.9 years). Planar scintigraphy was p e r f o r m e d at 15 rain after injection of 111 M B q o f T1 before chemotherapy, after the second and/or the third chemotherapy, and after the final c h e m o t h e r a p y before operation. T1 uptake ratio was calculated by dividing the count density o f the lesion by that o f the contralateral normal area. % reduction of Tl uptake ratio calculated by [100 x (pre-post) / pre] was c o m p a r e d between mid-course o f c h e m o t h e r a p y and after final chemotherapy and also compared to histologic response. In patients with histologically complete response (n=7), more than 15 % reduction of T1 uptake ratio (34.8+_28.2 %) was obtained after second chemotherapy, more than 50 % (67.4+-13.3 %) after third, and more than 53 % (67.0-2--12.4 %) after final chemotherapy. In patients with histologically no change ( n = l l ) , less than -5 % reduction o f T1 uptake ratio (-12.9-2_11.8 %) was obtained after second chemotherapy, less than 25 % (-0.8+_20.6 %) after third, and less than 17 % (-1.1+16.6 %) after final chemotherapy. In patients with histologically partial response (n=5), % reduction ranged from 31 to 40 % (35.8+-6.4 %) after second chemotherapy, from 6 to 63 % (41.6+_.25.1%) after third, and f r o m 57 to 62 % (59.4+3.9 %) after final c h e m o t h e r a p y , which overlapped with c o m p l e t e response or no c h a n g e group, Thus, it is c o n c l u d e d that T1 study in mid-course o f c h e m o t h e r a p y can predict the final response to chemotherapy. If T1 uptake ratio is r e d u c e d m o r e than 10 % after second chemotherapy or more than 40 % after the third, the chemotherapy should be continued, and if T1 uptake ratio is reduced less than 0 % after second chemotherapy or less than 30 % after the third, the chemotherapy should be ceased a n d other treatments including change of the drugs, additional radiation a n d prompt operation should be considered. Serial T1 scintigraphy is a useful method for the early evaluation of chemotherapy.

917

• Gastroenterology Gastroenterology 42.1 42.3 A. Holz~pfel, G. Stacher, H. Bergmann. A. Bestetti, F. Carola, L. Tagliabue, A. Del Sole, C. Di Leo, C. Conciato*, _G. Minear, _ Depts. of Nuclear Medicine and of Biomedical Engineering & B. Marasini*, GL. Tarolo Physics and Psychophysioloqy Unit at the Dept. of Surgery, Istituto di Scienze Radiologiche and Istituto di Scienze Biomediche University of Vienna, and LBI of Nuclear Medicine, Vienna, Austria. H. San Paolo - Universita degli Studi di Milano, Milan, Italy

ESOPHAGEAL SCINTIGRAPHY WITH A SEMISOLID MEAL: USEFUL TEST TO DISCRIMINATE ESOPHAGEAL DYSMOTILITY 1N PATIENTS WITH SYSTEMIC SCLEROSIS AND PATIENTS WITH RAYNAUD' PHENOMENON Aim: to discriminate patients with Raynaud's phenomenon from patients with systemic sclerosis (SSc) by esophageal scintigraphy with a semisolid meal. Methods: we enrolled 13 patients with clinical and serologic diagnosis of Raynaud's phenomenon (2M, 1IF, mean age+SD 44_+13) and 9 patients with clinical and serologic diagnosis of systemic sclerosis (9F, mean age 55_+13). After an overnight fast all subjects underwent esophageal scintigraphy, using a semisolid orally ingested bolus labelled with 50 MBq of 99mTc-sulfur colloid. Esophageal transit time and emptying time were assessed with the patients in the upright (sitting) and in the supine position. Results: the esophageal transit time and emptying time, evaluated in both position, were significantly higher in patients with systemic sclerosis compared to Raynaud's patients ones (table).

SSc Raynaud P

Upright emptying (S) transit (S) 225_+135 19.2_+10 82_+69 8.4_+4.3 <0.01 <0.01

Supine emptying (S) transit (S) 379_+32 20.3_+8 131_+116 8.6_+2.3 <0.0001 <0.001

Clinical scores regarding to dysphagia and acid regurgitation were not significantly different between these two patients groups. Conclusions: esophageal scintigraphy seems to better discriminate patients with Raynaud's phenomenon from patients with systemic sclerosis than clinical indexes.

STUDYING GASTRIC EMPTYING OF A SEMISOLID MEAL SCINTIGRAPHICALLY: IS CORRECTION FOR TISSUE A T T E N U A T I O N NECESSARY? Purpose: TO investigate whether in scintigraphic studies of gastric emptying of a semi-solid meal a correction for tissue attenuation is necessary. Material and Methods: Studies were carried out on the recordings performed in patients with fast, normal and slow emptying of a standard meal labelled with 72 MBq 99m-Tc sulfur colloid. The patient's stomach was imaged dynamically for the 53 min following meal ingestion using an anteriorly located single-headed g a m m a camera with the patient's torso and the camera's detector head tilted 30 ° . Upon completion of recording, a left lateral image was made with 57-Co markers attached along the contour of the abdomen. Regions of interest (ROI) for the anterior view were created including the entire stomach, the oral half and the aboral half of the stomach, as well as a background ROI. A binary-edge ROI containing the stomach was created for the lateral view, The latter was used to calculate line attenuation correction factors according to the method given by P.J. Collins (Gut, 1983, 24, ii17-i125). Timeactivity curves were generated for attenuation corrected and uncorrected data. From the unfitted curves, percentages of meal emptied from the stomach over time were calculated. Results: After ingestion, the meal was transported quickly to the aboral part of the stomach, from where it was emptyied at a more or less constant rate. Time-activity curves derived from corrected and uncorrected data were very similar and the fraction of radioactivity remaining in the stomach at 50 min after the start of recording (RR50) differed only little, ranging from 0 to 9 %; in ii patients the RR50s differed < 3 %. Although the differences were greater in patients with fast emptying, paired ~ tests demonstrated that the differences were significant neither for the patients with normal and slow nor for those with fast emptying . Conclusions: The results show that in the patients with fast, normal, and slow gastric emptying alike, tissue attenuation was of only minor impact on the time-activity curves as well as the RR50S. For clinical purposes, when using a semi-solid test meal, correction for tissue attenuation seems not necessary.

42.2

42,4

P e r k i n s A C , K o n g M-F, Frier M, B l a c k s h a w PE, King P, M a c d o n a l d IA, Tattersall RB. University Hospital, Nottingham, UK

H.Giannngpoulou,S.D.Ladas#, P.Tassios#, E.Houssianakou S.Raptis#, M.Kesse-Elia. Dept. of Nuclear Medicine and #Gastroenterology Unit-Second Dpt.Of Internal Medicine Athens University, Evangelismos Hospital,Athens ,Greece THREE-DAY OCTREOTIDE-ASSISTED HELICOBACTER PYLORI ERADICATION TRIPLE THERAPY AFFECTS GASTRIC EMPTYING OF SOLIDS. Introduction: Since orally administered antibiotics for H.pylori eradication therapy exert their effect by local diffusion into the gastric mueosa, gastric emptying affects antibiotic-mucosa contact time.The aim of this study was to assess the effect of delayed gastric emptying provoked by octreotide co-administration, on the efficacy of the short H.pylori eradication therapy for peptic ulcer disease. Method:26 symptomatic H.pylori positive patients with active duodenal (n=20). or gastric(n=6) were studied. All patients reeieved a three day course of octreotide (0.1g subcutaneously t.d.s.), amoxicilline and metronidasole (500mg orally q.d.s.) and colloid bismouth subcitrata(CBS) (240mg b.d.). CBS treatment was continued for another four days. Endoscopy with antral biopsies for CLO-test, culture and crash tissue smears were performed on admission to the study at 4, 8 weeks and six months post treatment. The gastric emptying rate for liquids and solids was measured in 7 patients before and on the second day of octreotide treatment, simultaneously for solid meal consisting of scrumbled eggs labelled with 500 pCi of Tc-99m colloid and liquid meal - orange juice labelled with 100 t~Ci In-111 DTPA. Results :There was no significant difference in the gastric emptying rate of liquids before and during the octreotide treatment. The gastric emtying rate of solids (Tll2) was 2.3 (1.7-2.8 median range) and 6.0 (3.5-6.0) hours respectively (p<0.001). Median 24-hour gastric PH was 4.3(0.3-4.9) in 10 patients. 24/26 (92.3%) ulcers were completely healed at four weeks and remained healed at eight weeks. All 24 patients were asympotmatic at six months. In 19/24 patients who accepted to have endoscopy at six months, ulcers remained healed, but the H.pylori eradication rate dropped to 68.4%. Conelusions:l.OctreoUde significantly delays gastric emptying of solids in all patients and increases 24-hour median gastric PH above 4 in 50% of the patients. 2.A three day octreotide-assisted H.pylori eradication triple therapy is highly effective to maintain a peptic ulcer in remission at six-month follow-up.

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

AND NORMAL

The comparison of gastric emptying results between different centres is difficult due to wide variations in methods. Following a review of gastrointestinal markers [1] we set out to establish a standard method for clinical studies. To determine the normal range we have examined gastric emptying of a solid and liquid meal in 10 normal male subjects (age 23.6 _+ 3.4 years). Reproducibility was assessed by repeating the study for each subject. After an overnight fast subjects ate a meal consisting of a pancake labelled with 3MBq Tc-ggm-ion exchange resin and a milkshake containing 0.33MBq In-111-DTPA, providing 400kcal (57% carbohydrate, 30% fat and 13% protein). Anterior and posterior gamma camera images were recorded every 20 min for 3 hours. The mean T50 for solid and liquid emptying was 128.9_+7.2 min and 33.1_+4.3 rain respectively. There was no significant difference between T50 of the repeat studies (p=0.061 solid, p=0.459 liquid). The mean +SD of the differences between repeat T50 measurements were 14.9+21.97 min (solid) and 5.1+19.74 min (liquid). This data demonstrates that the method has good reproducibility and has allowed the construction of a template showing the normal range _+2SD to simplify the presentation and interpretation of the results of patient investigations.

1. Frier M and Perkins AC. Radiopharmaceuticals and the gastrointestinal tract. EJNM 1994;21:1234-1242.

918

[] Gastroenterology/Miscellaneous 42.5 R. Linke, K. Tatsch, W. Mtinzing, C. Folwaczny*, M. Meier +, O. Schnell , K. Hahn. Departments of Nuclear Medicine and Internal Medicine*, Klinikum Innenstadt, University of Munich and Diabetes Research Institute*, Schwabing City Hospital, Munich, Germany A S S E S S M E N T O F G A S T R I C P E R I S T A L S I S IN P A T I E N T S B E F O R E AND U N D E R P R O K I N E T I C T H E R A P Y In a variety of disorders gastric peristalsis may be compromised, which secondarily results in impaired gastric emptying. In such cases specific prokinetic therapy may be helpful. Aim of our study was to evaluate whether quantitative analysis of gastric peristalsis may be a useful tool to document the effects of prokinetic therapy. For this purpose 2 entitles of pts with well characterized disorders of gastric function (diabetes mellitus [DM] and progressive systemic sclerosis [PSS]) were studied. In 16 pts (9 DM, 7 PSS) and 15 controls gastric emptying was determined after ingestion of a semiliquid test meal (400 ml oatmeal, 30 ° LAO, 40 min). In addition from a short time interval (10.-17. rain) condensed images (140 frames, 3 sec/frame) were established using the latter to evaluate the amplitude of gastric contractions by Fourier analysis. Pts were studied twice, under baseline conditions and after 4 weeks under prokinetic therapy with 3 x 10 mg cisapride (Propulsin®). Amplitude

Controls 28-+8

DM PSS Total baseline 8-+ 3 15-+11 ll-+ 8* (%) cisapride 12 -+ 8 23 -+ 5 17 -+ 9 *° Empt.-rate 2.4 -+ 0.3 baseline 1.6 -+ 1.0 1.9 -+ 0.7 1.7 -+ 0.9* (%/min) cisapridc 1.7 -+ 0.7 2.3 -+ 0.8 2.0 -+ 0.8 * p < 0.01 compared to controls; o P < 0.05 compared to baseline Under baseline conditions pts with DM and PSS showed significantly reduced gastric peristalsis and emptying as compared to controls. After 4 weeks of treatment with cisapride in both groups gastric contraction amplitudes showed a significant increase, which was associated with a remarkable improvement of gastric emptying. Our data indicate that the effects of prokinetic therapy may be specifically assessed with scintigraphic analyses of gastric peristalsis. Therefore, evaluation of the latter may not only be considered as a simple, non invasive method to primarily diagnose an impairment of gastric function in patients with DM and PSS but also to objectively monitor the respective changes under specific therapy.

Miscellaneous 43.1 L Lauer, P. Sieg*, M. Baehre, E. Richter

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O

, m

Clinic of Radiotherapy and Nuclear Medicine, * Clinic of Oral and MaxilTofacial Surgery, Medical University of Luebeck, Germany

ell)

LONG TERM FOLLOW-UP OF SUBMANDIBULAR GLAND TRANSFER FOR XEROPHTHALMIA WITH SALIVARY GLAND SCINTIGRAPHY Microvascular submandibular salivary gland transplantation is a new therapeutic solution for patients with severe xerophthalmia. Up to now, 20 patients who underwent this kind of surgery have been examined using salivary gland scintigraphy (SGS). The aim of the study was to investigate gland viabilitiy and function in the early and late postoperative stages. Methods: 20 patients (25 transplanted glands) were examined 1 week (lw) (21 scintigraphies), 3 months (3m) (20) and some 6 months (6m) (8)_and 1 year (ly) (10) following surgery. After applying 50 MBq ~mTc-Pertechnetate, a sequential scintigraphy of 60 minutes (1 frame/ min) was performed in bilateral views (128x128 matrix, zoom 1,3, Picker 2000 XP). Additionally this was followed by static acquisition in anterior view (10,min/image, 256x256 matrix) until 7 hours after injection or until a secretion into the eye was visible. 40 studies with viable glands could be analysed semiquantitatively. ROI were drawn for the transplanted gland (T), for a background region (BG), for the parotid gland (P) and - if still existing - for the ipsilateral submandibular gland (S). Results: 19/25 transplanted glands showed a significant tracer accumulation in the first SGS t w or 3m following surgery. Except for 1 case exhibiting a markedly reduced activity of all salivary glands, this matched with the observed clinical evaluation of transplant viability or necrosis. Secretion of saliva into the eye was demonstrable in all cases, but in 10 cases only after 3m and in 2 after 6 m ROI-Analysis showed a significant decrease of the T/P ratio between l w and 3m. No further decrease was found at 6m and ly. The ratios T/BG and T/S did not decrease with time. Conclusion: Salivary gland scintigraphy can be used to reliably assess viability and function of the transplanted gland. Also the secretion into the eye can also be determined. In long-term follow-up up to 1 year the transplanted glands did not show significant decrease of function.

42.6

43.2

M.Fj/ill.inGg,M.Castedal, E.BjOmsson,J.Gr6tarsd6ttir, H.Abrahamsson. Depts of Gastroenterology, Nuclear Medicine, and Radiation Physics, Sahlgrenska University Hospital, G6teborg, Sweden.

i. G6~kara 3. Karsho~hi, T. Ozpa~a~'l. Hipokrat Laboratories, ~i~li Etfal Hospital and Okrneydam Hospital, lstanbul, Turkey.

MMC-ASSOCIATED DUODENOGASTRIC REFLUX Aim of the study: To decide the composition of the alkalinising substances that neutralise the contents of the stomach during the duodeno-gastric reflux in phase III of the migrating motor complex (MMC). By using a dubbeI-isotope tectmique it was possible to distinguish between duodenal contents coming from the bile ducts and duodenal contents coming from the duodenum itself. Methods: Ten healthy volunteers were subject to antro-duodeno-jejunal manometry with a catheter making it possible to decide the direction of each duodenal contraction. Through a separate catheter, DTPA-In-111, "0.5 MINt/rain, was deposited continously directly in the duodenumduring 15 rain of phase II of the MMC. A second infusion of DTPA-In-111 was done during phase III. By giving 25 MBqTc-99m IODIDA as a bolus injection followed by infusion of 0.25 MBq/minduring2h it was possible to decide the contribution of bile tothe contentsof the duodenum.Dynamic registration with a gamma camera was done. Based on different ROIs, time-activity curves were generated. Results: Duodenal motility of phase II was dominated by antegrade peristalsis and propulsion of duodenal- and bile tracer to the jejunum. Phase III of the MMC was dominated in its later portion by retrograde duodenal peristalsis with simultaneous increase of DTPA-In-111 in the stomach. During the retroperistalsis in phase III the secretion of Tc--99mIODIDA to the dudenumwas stopped and instead there was a marked increase of Tc99m IODIDA in the gallbladder. During the subsequent phase I (motor silence) DTPA-In-lll was retained in the stomach until phase II ( motor activity) when the stomach again started to empty. Conclusion: In phase II of the MMC there is propulsion of duodenal contents and antegrade duodenal motility, while in phase III there is duodenogastric reflux. Admixture of bile is effectively hindered by divertion of bile to the gallbladder, most probably by phase III associated contraction of the sfincter of Oddi.

t~

THE COMP.GRISON OF SPET AND PINHOLE PLANAR SCINTIGRAPHY FINDINGS AT THE DETERMINATION OF HYDROXYAPATITE ORBITAL IMPLANT VASCULARIZATION The success of Te99m MDP three phased facial scintigraphy at the determination of the vasculanzation of hydroxyapadte orbital implant was presented before . The potential usefi.flness of SPET at this area was investigatedon this study. Six pafiants (4 males, aged 15-29)with hydroxyapatite orbital implants inserted 6 months ago, were included to the study. After the completion of three phased scinfigraphy and pinhole planar imagmg; a 180 degree of pinhole BPET acquisition, starting fi-om 45 degree posterolateral of the implant which is positioned at the center of the camera field of view, was obtained in e~h patient SPET and pinhole planar images of the implant were validated at the basis of the activity level, activity uniformity and the shape. Higher, equal or lower implant activity levels in comparison to nasal bone were accepted as (+++), (++), and (+) respectively. Homogenous implant activity and implant activity with defects were accepted as umform and nonuniform respectively. Scinhgraphicshape of implant activity was interpreted as circular or noneircular. .Nt the implants with (+++) or (++) activity level, circular shape and uniform acfivitypattem are accepted as normovasculartzed ; and suitable for drillingof the implant for eye prosthesis insertion. It was fbund that SPET showed falsely increased activity level in 2 out of 6 cases, from (--+) to(+++); and, caused falsely increased uniform activity and noncircular shape patterns in 2 out of 6 cases and 4 out of 6 cases respectively. This results showed that the vasculanzafion evaluation of the implant by SPET is not better than pinhole planar scintigraphy and may cause mistake. Planar pinhole scinfigraphy should be the preferable method to SPET with its more reliability,easier applicabilityand lower price.

919

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Miscellaneous

43.3

43.5 A.T.Khairy, A.Elyan

and H.F.Azmy

Ain S ~ r s i t y Hospitals, Cairo, Egypt . (Depts. of Diagnostic Radiology and Obeste[rics ) HYSTEROSALPINGOSCINTIGRAPHY (HSS) VERSUS HYSTEROSALPINGOGRAPHY (HSG) IN STUDYING FALLOPIAN TUBES IN PATIENTS WITH INFERTILITY. To compare HSS and HSG in assessing the Fallopian tubes 70 patients with infertility (primary in 41, secondary in 29) were examined by both bests. Their mean age was 29 +6 years. For HSS 57 HBq Te-99m HSA micraspheres was applied in posterior vaginal fornix. Images were taken every 15 min. for sn hour, then at 2 and 5 hrs when needed. The total number of examined tubes was 139, as one patient had underwent unilateral salpingectomy. Laparaseopy was done in 15 patients and serum levels of FSH and oestrogen were determined in 14 patients. Among the 139 tubes~ 64 were patent (46%) and 6 were blocked (4.4%) by both imaging tests. In 67 tubes (48.2Z) however, HSS revealed functional blockage despite pateney of tubal lumen by HSG. In 2 tubes only (I.4~) HSS gave a false impression of tubal patency despite blocked lumen by HSG. There was no significant relationship between NSS and HSG (P>O.05). HSS showed highly significant relationship with laparescopie findings (P<0.004) and with serum hormones (P0.05). It is concluded that NSS is useful in infertile patients with normal HSG as it csn detect functional blockage of the Fallopian tubes despite their anatomical patency.

C.Cittanti P.Colamussi, M.Giganti, C.Bolzati, LUccelli, A.Piffanelli Department of Clinical and Experimental Medicine - Section of Nuclear Medicine - University of Ferrara - Italy

99mTc-MIBI LEG SCINTIGRAPHY FOR NON .INVASIVE ASSESSMENT OE PROPIONYL-L-CARNIT1NE INDUCED CHANGES IN SKELETAL MUSCLE METABOLISM Camitine derivatives, such as propionyl-L-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). It has been postulated that PLC may exert its action through: 1) metabolic mechanisms, such as the optimization of both oxidative phosphorilation efficiency and pimvate utilization: 2) an antiradical effect, probably by chelating the iron required for the generation of hydroxyl radicals. Moreover, its activity does not appear to be related to any modification of regional blood flow. The aim of the study was to ascertain whether 99mTc-MIBI leg scintigraphy may be a useful tool in the evaluation of changes induced in skeletal muscle metabolism by PLC chronic therapy or not. Twenty patients with clinical and instrumental evidence of PAOD (Fontaine stage II) where randomly assigned to a 3-month period of therapy with either PLC (3g/die p.o.) or placebo. Rest 99mTc-MlBI leg scintigraphy and Echo-Doppler sonography were performed on all subjects immediately before and at completion of the treatment period. Regions of interest, drown on scintigraphic images around each thigh and calf segment, were normalised to total-body activity counts derived from an analogic fiveminutes whole-body scan obtaining an index of regional fractional uptake (rFUI). At the end of protocol the following results were observed in patients who underwent PLC administration: a) a significant increase in both thight and calf 99mTc-MIBI uptake in comparison with baseline values (p<0.001) [thighs: 0.34+0.08 vs. 0.40_+0.08; calves: 0.20_+0.05 vs. 0.23+-0.06]; b) considering rFUI ratio values (post-therapy/pre-therapy), a significant increase in 99mTc-MIBI uptake in thigh and calf was observed in PLC-treated patients as compared, by an unpaired t-test analysis, with the placebo group [thighs: 1.20_+0.21 vs. 1.03_+0.09; calves: 1.19_+0.26 vs. 0.94_+0.22]; c) the absence of statistically significant modification of Doppler blood flow indices of inferior limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of 99mTc-MIBI was demonstrated without apparent dependence on regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics.

43.4

43.6

_Waqieh Sh., Ybustafa T. & Radwan A. Cairo University, Departr~nts of Nuclear YedicJl~ and Andrology.

Anders Rvdht. Ole Suhr~, ,~ke Danielsson%Sven-Ola Hietala~, Katrine Riklund Ahlstr6m~, Mark B. Pepys2 and Philip N. Hawkins%Depts of Diagn. Radiology and Internal MedicineE,University Hospital of Northern Sweden, Ume£ Sweden and Immunological Medicine Unit2, Dept of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK SERUM AMYLOID P COMPONENT SCINTIGRAPHY IN FAMILIAL AMYLOIDOTIC POLYNEUROPATHY

VALUE OF R A D I ~ VrNI//XIRAZ4Y WITH INIRAV~IX2S VASCOILA2DR SIRESS TSb-T IN DIAGN3SIS OF IMPUISN~. g~rpose: To evaluate radicrmclide phallcgraphy usir~ i n ~ papaverin stress test in patients with impDtenoe. Met_hods: 30 patients with ir~cotenoe (13 pyscbmc~]ic, 12 artericg~r/c 4 ver~g~r/c and 7 combined) as well as 5 ccntrols ware subjected to Tc-99m labeled RBC's quantitative dynmnic phallography with intra~ injecticn of 90 mj ~ after i0 rain frzm the begir/ng of the study which ccl]tJ/]ued for i hsur. Results were interpreted qualitatively to identify type of ctmve whether A, B or i n t ~ a t e (A: increase curve steegress after vascdilator injection with s e c ~ pulses of increased activity- B: generally romx]ed curve with insignificant change in the shape of the curve after vasodilator injecticn- intezmediate: absemt s e o ~ pulsaticns with rise in curve slcpe aft@r vascdilator injection) . Quantitative indices in the form of pencgram index (PI) ~ vasodilator respcmse index (VRI) wmre calculated. Results: cut of the 13 patients with ~ c impotenoe, ii s ~ type A curve similar to that of ,the 5 controls. Only 2 patients ~ intermgdiate type of curve. 7he mean values of PI & VRI for this group were 1.36 and 1.01 respectively. These figures were o:mpaz-~ble to th:6~ of the fine controls. All patients wit/] arterioger/c impotence shswg~ type B cdrve with a rfean PI and VRI of 0.44 and 0.37 respectively. Both indices varied significantly hetwee_n the two patient groups. Two patients with ~ c impotence interragdiate type of curve, the ~ 2 patients and the 7 osmbined showed type B curve. 2~e quantitative indices of the the latter 2 ~ ~P_re c~pat-able to thoee with arterioge/lic impotence. Cbncluaicn: quantitative phallography using intravenous papaverin test is a very useful ncn invasive ncn hazardnus screening test for patients with impoterce and can differentiate accurately between ~mhcc3~r/c and vasculcgP//c ir~otence The latter group needs further investigation by mDre ccmplex and znvasive techniques.

920

Familial amyloid polyneuropathy (FAP) is a fatal neuropathic hereditary amyloidosis. Orthntnpic liver transplantation halts the production of mutated transthyretin, and the clinical progression of the disease. Effective tools to monitor and evaluate the patients' clinical status and amyloid load before and after transplantation are urgently required. The aim of the present study was to evaluate the application of serum amyloid protein (SAP) scintigraphy on patients with FAP for estimation of amyloid deposits before and after liver transplantation. Purified human SAP labelled with ~23Iwas given intravenously to 25 patients with biopsy-proven or suspected systemic amyloidosis. Imaging was performed in each individual 24 hours after administration of the radiolabelled protein. SAP accumulation of L23Iwas found in all biopsy proven FAP patients before transplantation. In two of the patients with FAP a pronounced regression of the amyleid load was observed after transplantation, whereas a moderate decreased activity was observed in 2 patients and no regression in 4. Scintigraphy after the injection of ~23ISAP is a non-invasive useful method to diagnose and evaluate the pattern of amyloid deposits in various organs. It is also a valuable tool to monitor regression of amyloid deposits posUransplantation.

[] Quality Assurance Quality Assurance

44.1

44.3

1A. Ahonen, 2T. Lantto, 3E. Vanninen, 4j. Heikkinen. ~Div of Nuclear Med, Oulu University Hospital, 2Dept of Clin Lab, P&ijb.t-H&me Central Hospital, 3Dept of Clin Phys and Nucl Med, Kuopio University Hospital, 4Div of Nucl Med, Mikkeli Central Hospital, Finland

D. S. C. Marshall & P. ]. Ryan Medway Hospital, Giltingham, UK. Department of Nuclear Medicine

Quality assurance of bone and lung scan reports

| m

VERIFICATION OF ATTENUATION CORRECTION USED IN THALLIUM MYOCARDIAL SCINTIGRAPHY Phantom studies with additional attenuatingmaterial were acquired during the commissioningof the attenuation correction facility of our dual headedVertex gamma camera. Simultaneousemissionand transmissionimagescan be collected using a moving energywindow set to 100 keV to acquire the transmissiondata from the opposing 153 gadoliniumline source, whilst the remainderof the head is acquiringthe 20t thallium emissionimage. The phantom usedwas a Data Spectrum cardiac phantomwith a single defect moved into the anterior, lateral, inferior and septal positionswithin a perspextorso phantom with 3 additional tissue equivalent bolus bagsplacedanteriorly on the left and right chest and in the left lateral position.

The aim of the study was to evaluate the quality of reports in Finland and to improve especially interpretation to more quantitative and distinct direction and to harmonize report structures. The Quality Assurance (OA) program was organized with the help of Labquality Ltd, the Finnish organiser of external quality assessment schemes. The QA program w a s divided into two parts. The first retrospective part consisted 10 already reported routine scans, which were sent to experts. The second ongoing prospective part consists 10 scans Scanswere reported by a singleexperiencedobserver,blinded to the attenuation correction status and defect position. The number, size and position of chosen by experts; scans have been sent to gamma imaging units. defect(s), contrast and smoothnessof the imageswere reported. The number of 17 gamma imaging laboratories participated in the retrospective part. single pixei slicesover which defect(s) were seen is given below~ In March 1996 all laboratories were asked to send the first five consecutive bone and lung scan images and reports of January to Where 2 numbers are given, the first is the true defect and the second is a false defect. Labquality Ltd. Images and reports were anonymously circulated to TRUE WITH AT'iN CORRN WITHOUT AT'IN CORRN three nuclear medicine experts, who gave score from 0 (very poor) to 3 (excellent) from each image report. Overall quality, description and defect position Short Vert Long Horiz Long Short Vert Long Horiz Long interpretation were judged separately. Experts created specified ANTERIOR 6 3 4 7 6 5 arguments / recommendations for the structure of a good report. 5 5 3 6+3 7 3+3 Average scores of general quality (incl bone and lung reports) were LATERAL 4 3 3 3+4 3+4 3+3 2.2-+0.4 for overall quality, 2.3-+0.3 for descriptive part and 2,2-+0,4 for INFERIOR SEPTAL 7.+2 4 3 3+6 4+5 7 interpretation part. In 4 laboratories average scores for overall quality did not reach satisfactory level (score <2). Average scores for bone Remits: Falsedefects were only reported in the Anterior position and arose scintigraphy were 2.2-+0.4, 2.3±0.3 and 2.1_+0.5 and for lung mainly from uncorrected attenuation. scintigraphy 2.3+0.3, 2.3_+0.3, respectively. Surprisingly, the quality of The best filter was established as the Butterworth with a 0.4 cut-off. The ADAC attenuation correction facility correctly removes the effects of interpretation of the bone images was worse than the lung images. In some laboratories the reports showed need of external quality anterior attenuation, assurance of nuclear medicine reports. Further goals of this study were to harmonize and clarify reports in the future and to give assistance to computerized, automatic reporting systems.

44.2

44.4

J.Heikkinen 1, J.T. Knikka2, A. Ahonen3 and P. Rautio4 1Dept of Nucl Med. Mikkeli Central Hospital, 2 Dept of Clin Phys and Nucl Med, Kuopio University Hospital, 3Dept of Nucl Med, Oulu University Hospital, 4Dept of Clin Phys, North Karelia Central Hospital, Finland

M.J Woods, J.D.Keightley, C.J.Scott, M.Ciocanel Centre for ionising Radiation and Acoustics National Physical L a b o r a t o r y Teddington, Middlesex TWII 0LW, United Kingdom

M U L T I C E N T E R EVALUATION OF M Y O C A R D I A L PERFUSION SPECT IMAGING: A P H A N T O M STUDY

QUALITY OF RADIONUCLIDE CALIBRATOR MEASUREMENTS IN UK HOSPITALS

The aim of the study was to evaluate the quality of myocardial perfusion SPECT imaging in Finnish nuclear medicine laboratories. Nineteen laboratories participated in the study. Physicist visited all laboratories and filled the same myocardial phantom with routinely used radioactive solution (Tc-99m or TI-201) simulating clinical stress and rest conditions. Cardiac insert included three reversible defects (simulating ischemia): 3.0 x 3.0"x 1.4 cm 3 septal (90 % recovery at rest), 3.0 x 2.0 x 1.4 cm 3 posterobasal (full recovery) and 2.0 x 2.0 x 1.4 cm 3 lateral (full recovery). There were also two fixed defects (simulating infarct): 3.0 x 2.0 x t .4 cm 3 posteroapical and 1.0 x 1.0 x 0.6 cm 3 apical. The phantom was similarly imaged as a myocardial perfusion patient. Reconstruction, printing and interpretation were also performed according to clinical routine in each center. All image sets were anonymously evaluated by three nuclear medicine specialists. They gave score from one (worst) to five (best) according to how well they saw knox~a defects and what was the informative appearance of the image set. Points were also given to interpretations from 0 to 8 according to how well laboratories detected defects in their reports. Quantitative parameters were also calculated from digital images by comparing 14 regions of interest between stress and rest. Average scores by experts were 3.6 + 0.8 for all image sets and 3.2 + 0.5 for thallium and 3.9 _+ 0.6 for technetium tracers. Average points of the interpretations were 5.6 _+2.1, 4.4 _+ 1.7 and 6.5 _+ 1.7 and the points given from quantitations were 9.5 + 1.3, 9.0 + 0.4 and 9.9 _+ 1.5, respectively. Results of the technetium studies were clearly better than those of the thallium. Too many interpreters (36 %) did not detect lateral 2.0 x 2.0 x 1.4 cm 3 defect. Overall quality was satisfactory but also proposals for improvements of myocardial imaging still remained.

cO

The administration of radiopharmaceuticals both for diagnostic and therapeutic purposes requires the activity of the administered dose to be determined accurately. The instrument which provides these measurements in the most economic and accurate manner is the radionuclide calibrator. As such, the radionuclide calibrator plays a critical role in nuclear medicine and it is important that its use and calibration are part of a robust quality assurance system. A irk recommended protocol designed to achieve these ends has been available since 1992 and many hospital departments have incorporated this into their procedures. Whether or not these procedures are effective may be tested in a number of ways but intercomparison exercises are a suitable avenue. Since 1980 the accuracy of activity measurements of seven radionuclides have been tested by intercomparisons, three (67Ga, 123I and lllIn) in the last two years. The results of these exercises have highlighted some particular, and potentially serious, problems as well as providing an indication of the overall quality of measurements. These results are p r e ~ e n t e d and the implications for nuclear medicine in the UK are discussed.

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• Quality Assurance/Neurology Neurology 44.5

45.2

W.F.D Sampson ~, A.S. Houston I, R. Noslin 2, ~Royal Hospital Haslar, Department of Nuclear Medicine and ~Kings C o l l e g e London, Department of Physics.

A NEW U S E R - F R I E N D L Y RENAL DYNAMIC ASSESSING GFR MEASUREMENT FROM IMAGES

PHANTOM FOR RADIONUCLIDE

J.T.Kuikka, J. Tiihonen, J. Karhu, U. Lepola, K.A. Bergstr6m, P. R~is~en Kuopio University Hospital, Niuvanniemi Hospital and Psychiatric Research Clinic of Kuopio, FIN-70210 Kuopio, Finland FRACTAL ANALYSIS UPTAKE SITES

OF

STRIATAL

DOPAMINE

RE-

A prototype renal dynamic p h a n t o m for assessing GFR m e a s u r e m e n t has been described previously. Several problems existed w i t h this phantom, the principal d r a w b a c k being its cumbersome nature. A new phantom, w h i c h has been designed and built, overcomes many of these problems including ease of use. The new p h a n t o m comprises four compartments: plasma r e p r e s e n t e d by water into which 99mTcpertechnetate is injected; interstitial fluid represented by w a t e r into w h i c h the activity passes; p a r e n c h y m a represented by resin and tin colloid serving as a filter; and collecting system represented by resin and partially overlaying the parenchyma as viewed by the gamma camera. The kidney and plasma compartments are separated from the interstitial compartment by a rigid porous diaphragm. A peristaltic pump is used to pull the filtrate through the kidney at variable rates w h i c h can be m e a s u r e d at the outset. The activity is held up in the parenchyma and released at a given time by altering the pH of the plasma with sodium hydroxide. It then passes though the collecting system and out of the phantom. D y n a m i c images may be obtained using a gamma camera, GFR calculated using a suitable method and this c o m p a r e d with the m e a s u r e d rate. The new p h a n t o m is portable and of much superior design to the original. It may be used to evaluate d i f f e r e n t GFR methods on a variety of gamma camera systems.

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of sub-regions in the organ/tissue studied, This resolution-dependent variance can be described by the fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy, righthanded volunteers (age range: 20-75 years) with high-resolution [n3I]~-CIT SPET. The subjects had no history of psychiatric or neurological illness or drug or alcohol abuse. The mean fractal dimension was 1.15 -+ 0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension = 1.00) but much less than complete randomness (dimension = 1.50). There was a gender difference, females had higher heterogeneity both in the left and right striatum than that of males. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio being 1.19 _+0.15; p < 0.001). In conclusion, the dopamine transporter favors higher heterogeneity in the left side of the living human brain. A gender difference in heterogeneity is consistent with females having finer control of motor behavior than males. Application of fractals for the interpretation of PET and SPET images can be used to the characterization of brain function.

45.1

45.3

J.T.Kuikka, J. Tiihonen, K.A. Bergstr6m, K. Akerman, P. R~is~nen Kuopio University Hospital, FIN-70210 Kuopio, Niuvanniemi Hospital, FIN-70240 Kuopio, Finland.

W. Pirker. S. Asenbaum, G. Bencsits, P, Angelberger*, L. Deecke, I. Podreka, T. Brticke Departments of Neurology and Nuclear Medicine, University of Vienna, (*)ForschungszentrumSeibersdorf, Austria

STRIATAL SPET IMAGING WITH [I-123]EPIDEPRIDE AND [I-123113-CIT IN HEALTHY MALES

SPECT IMAGING OF THE PRE- AND POSTSYNAPTIC SIDE OF THE DOPAMINERGIC SYSTEM IN ATYPICAL PARKINSONISM

The anatomical distribution of striatal dopamine D2 post- and presynaptic receptors in humans can be studied with [I-123]epidepride and [I-123][3-CIT. We compared findings of the regional striatal uptakes of these two tracers in healthy males. Twenty three males were imaged with [I-I23][3-CIT SPET and 8 other age-matched males with [I-123]epidepride SPET. Transaxial slices were reconstructed and slices were consecutively summarized and 3 of them in which the basal ganglia was best visible were taken for further analysis. Thirty six irregular regions of interest/striatum were semi-automatically drawn using a lower threshold of 60 % of the maximal striatal count density. The global uptakes were calculated for the head of the caudatus and for the putamen. A fractal analysis was applied to estimate striatal heterogeneity of the regional uptakes. Results were that [I-123]epidepride scans showed higher uptakes in the putamen than in the head of the caudatus, whereas the findings of [I-123][3-CIT scans were opposite. In addition, the fractal analysis revealed higher striatal heterogeneity with [I-123]epidepride than that of [I-123][3-CIT (Table). Ligand epidepride [3-CIT

Fractal Dimension Right Left 1.06+-0.05 1.09+-0.07 1.17+0,08 1.16_+0.07

Intercept (%) Right Left 14.9-+5.4 14.5_+4.9 8.2+3.0 9.8+3.1

Results suggest that striatal findings of [I-123]epidepride and of [I-123][3-CIT scans in healthy males are completely different.

922

Previous studies have shown that IBZM-SPECT is useful for the differential diagnosis of Parkinson's disease (PD) and atypical parkinsonian syndromes such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). To evaluate if other available SPECT [igands could improve differentiation of atypical parkinsonism from PD we performed SPECT studies of the pre- and postsynaptic side of the dopaminergic system in 15 patients with MSA, 4 patients with PSP, 3 patients with CBD and 3 groups of normal subjects using [123I] [3-CIT as a label of dopamine transporters and the D2 receptor ligands [1231] IBZM and/or [123I] epidepride. Parkinsonian symptomatology in all patient groups was staged H&Y 4 (mean). All patients fullfilled current criteria of clinical probable disease. A vascular etiology was excluded in all patients with CT and/or MRI. The SPECT studies were performed with a triple head camera. Ratios striatum/referenee region -1 reflecting specific/nondisplaceable binding, putamen/caudate ratios and leftright asymmetry indices were used as SPECT outcome measures. All patient groups showed significantly reduced striatal [3-CIT binding (MSA: 3.4+0.9, p<0.005; PSP: 3.3+1.1, p<0.005; CBD: 4.6+0.8, p<0.005; controls: 7.4.+1.2). Decreased putamen/caudate ratios and increased asymmetry were found in MSA, PSP and CBD, however both parameters were similarly altered in a group of 10 previously studied PD patients in H&Y stage 4. IBZM binding was significantly reduced in MSA (MSA: 0.39-+0.07; controls 0.64.+0.08; p<0.005). Binding in 2 PSP and 2 CBD patients studied with IBZM was below the range of controls. Striatal epidepride binding was significantly reduced in PSP patients (PSP: 9.9_+2.2; controls: 19.0_+6.3; p<0.05). In MSA the reduction of epidepride binding did not reach the level of significance (12.8-+4.3). II1 conclusion IBZM appears to be the most useful SPECT tracer for the differential diagnosis of atypical parkinsonism and PD. 13-CIT-SPECTenabled visualization of the presynaptic dopaminergic lesion in all MSA, PSP and CBD patients but it does not seem to be possible to differentiate atypical parkinsonian syndromes and Parkinson's disease with this ligand.

[] Neurology/Oncology 45.4

45.6

D.C. Costa, Z. Walker, S. Gacinovic, A.G.M. Janssen, R.W.H. Walker, C.L.E. Katona, UCL Medical School, London, UK; Amersham Cygne, Eindhoven, The Netherlands and Thq Royal Hospitals NHS Trust London, UK.

K. Tatsch, G.D. Borasio, R. Linke, S. Dresel, V. Schlamp, J. Schwarz, P.D. Mozley*, and K. Hahn Departments of Nuclear Medicine and Neurology, University of Munich, Germany, and Dept. of Radiology*, University of Pennsylvania, USA

"IN VIVO" DEMONSTRATION OF DOPAM1NE TRANSPORTER LOSS IN DEMENTIA WITH LEWY BODIES: AN FP-CIT / SPET STUDY. In this study we investigated "in vivo" the integrity of the pre-synaptic dopamine transporter in the striatum of 22 subjects: 5 Dementia with Lewy Bodies (DLB), 6 Alzheimer's disease (AD), 6 drag-naive Parkinson's disease (PD) and 5 normal volunteers (NV). Single photon emission tomography (SPET) with !he SME 810 was carried out 3.5 to 4.5 hours post-injection (i.v.) of 110-185 MBq of [123I]-2B-carbometoxy-3g-(4iodophenyI)-N-(3-fhioropropyl)nortropane (FP-CIT). Circular regions of interest were employed to calculate the average FP-CIT uptake in the caudate nucleus (CN), rostral (A) and caudal (P) putamen (Put) using the occipital cortex and cerebellum as reference to obtain radioactivity ratios for both hemispheres (right - R and left - L). Analysis of variance (ANOVA) was performed using StatView 4.5. The DLB and AD groups were older (76.2"+8.3 and 74.5+8.3) than NV (61.2-+i 1.2) and PD (64.3+11.1). PD were more disabled than DLB with Hoehn and Yahr of respectively 2.08_+0.59 (range 1.5 - 3.0) and 1.20+-0.98 (range 0.5 - 2.5). Mini Mental State examination (MMSE) showed the DLB to be more demented (11.8/30) than AD (24.8/30) and PD (27.2/30). All NV had high MMSE scores (29.6/30). The uptake results showed no difference between NV and AD in CN andPut. Both DLB and PD had significantly lower uptake than NV and AD in the CN and Put. Although not statistically different, PD had slightly higher CN than DLB (5.49-R and 5.92-L vs. 4.72-R and 4.76-L). The opposite results were obtained in the caudal putamen, as shown in the table (mea1~lSD): DLB PD NV AD R A Put 3.65+_1.23 3.67_+1.33 6.01_+1.09 6.22+_1.31 L A Put 4.05+_1.08 4.02-+1.26 5.98_+1.08 6.58-+1.03 R P Put 3.20_+0.86 2.43+0.57 5.10+0.91 4.44-+1.09 L P Put 3.43-+0.74 3.04-+0.45 5.18-+0.80 4.98"+1.52 This is the first "in vivo" study to demonstrate marked reduction of the pre-synaptic dopamine transporter in the striatum of DLB, and its integrity in AD. In addition it depicts a trend for more affected CN and less affected P Put in DLB than PD. Larger samples are necessary to test the hypothesis that FP-CIT and SPET will be able to differentiate between DLB and PD.

AMYOTROPHIC LATERAL SCLEROSIS: EVIDENCE FOR D O P A M I N E R G I C D E F I C I T A S S E S S E D W I T H IPT S P E T

Amyotrophic lateral sclerosis (ALS) is a chronic disease involving primarily motor neurons from the cortex, brainstem and spinal cord. Recent neuropathological studies have suggested that dopaminergic cells in the substantia nigra may also be affected in ALS. Purpose of this study was to investigate in vivo, whether ALS patients present with nigrostriatal dopaminergic deficits detectable by IPT SPET. IPT is a cocain analog which selectively binds to the presynaptic dopamine transporter. SPET scans of the brain were performed in 18 ALS pts (bulbar onset n=8, arm/leg onset n=10) and 8 age matched controls. Images were acquired 90-120 rain p.i. of 160 MBq of [I-123]lPT (N-(3-iodopropen-2yl)-2B-carbomethoxy-313-(4-chlorophenyl) tropane) using a triple head camera (PRISM 3000, Picker) equipped with HR-fan beam collimators. For semiquantitative evaluation of specific IPT binding'transverse slices corrected for attenuation were used to calculate ratios between striatum (S), caudate (C), putamen (P), and a reference region (R). Specific uptake of IPT was diminished in 12/18 ALS pts. Striatal IPT binding was moderately but significantly reduced in the ALS group as compared to conN [S-RI/R [C-R]/R [P-R]/R P/C trols (p<0.01). The Controls 8 7.3+1.2 8.6-+1.3 6.5+-1.2 0.75 reduction of IPT ALSpatients 18 5.6+1.1 6.8-+1.4 4.8"+1.1 0.71 binding was similar Arm/leg onset 10 5.8+1.2 6.9-+1.5 4.9-+1.3 0.71 . Bulbar onset 8 5.5-+1.0 6.6-+1.2 4.6-+0.9 0.71 an pts with bulbar onset and those with arm/leg onset. Preserved P/C-ratios suggest that putamen and caudate are affected to a similar extent. There was no correlation between striatal IPT uptake and the age of the pts or the duration of the disease. In concordance with neuropathological studies we observed a dopaminergic deficit in a remarkable subset (approx. 2/3) of patients with ALS. Therefore, imaging of the dopamine transporter with IPT SPET may be helpful to further explore the subclinical affection of nigrostriatai dopaminergic neurons in ALS and also to study related overlap syndromes with extrapyramidal involvement (e.g. ALS-Parkinson-dementia complex).

Oncology

45.5

46.1

K. Tatsch J. Schwarz, R. Linke, S. Dresel, P.D. Mozley*, J. Scherer #, R.S. Fieber, and K. Hahn. Depts. of Nuclear Medicine and Neurology, University of Munich, State Mental Hospital Haar#, Munich, Germany; Department of Radiology*, University of Pennsylvania, Philadelphia, USA

A. Dimitrakoooulou-Strauss 1, L.G. Strauss~, F. Gutzler 2, F. Oberdorfer~, G. Irn~artinger I, G. Kontaxakis~, G. van Kaick~ German Cancer Research Center, Heidelberg, 2Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany

EVIDENCE FOR COMORBIDITY OF SCHIZOPHRENIA A N D P A R K I N S O N ' S D I S E A S E IN P A T I E N T S W I T H REDUCED DOPAMINE TRANSPORTER BINDING

Comorbidity of schizophrenia and Parkinson's disease (PD) is unlikely since schizophrenia may be related to an excess of dopamine in mesolimbic/-cortical dopaminergic systems whereas PD is characterized by a loss of dopamine in mesostriatat/-limbic dopaminergic pathways. However, there is an entity of schizophrenics presenting with progressive parkinsonism. Diagnosis of PD is very difficult in such pts as they are usually treated with neuroleptics. In those cases comorbidity of PD codid be proven by a dopaminergic deficit evaluated by imaging the presynaptic dopamine transporter with cocain analogs like IPT. SPET scans of the brain were performed in 2 schizophrenics (61, 43 yrs, clozapine) with parkinsonism, 4 schizophrenics without signs of PD, 6 age matched controls, and 22 pts with PD (Hoehn & Yahr stage II-IV). Images were acquired 90-120 min p.i. of 160 MBq of [I-123]IPT (N-(3iodopropen-2-yl)-2g-carbomethoxy-3g-(4-chlorophenyl) tropane) using a triple head camera (PRISM 3000, Picker) with HR fan beam collimators. Transverse slices corrected for attenuation were used to calculate IPT binding ratios between caudate (C), putamen (P), and a reference region (R). Specific IPT uptake in Schizo/PD-pts revealed patterns characteristic for [C-R]/R [P-R]/R P/C PD: IPT binding was markedly Controls 8.4"+1.2 7.3-+1.1 0.87 reduced, the putameu was more Schizo 7.9"+1.1 7.5-+1.2 0.96 affected than the caudate and Schizo/PD #1 4.4 1.4 0.31 there was a marked asymmetry Schizo/PD #2 5.4 2.3 0.41 with lower striatal IPT uptake PD 5.8"+2.3 1.8_+0.9 0.32 contralateral to the more affected body side. Schizophrenics without signs of PD showed normal ratios. Our findings indicate that assessment of the dopamine transporter with IPT SPET may be a powerful tool to prove nigrostriatal dopaminergic deficits in schizophrenics suffering from coexisting PD. Even though this combination may be rare it has to be verified since pts will benefit from dopaminergic therapy despite a chance of worsening psychiatric symptoms. Evidence for comorbidity of schizophrenia and PD as supported by our data further challenges the dopamine hypothesis of schizophrenia.

POSITRON EMISSION TOMOGRAPHY (PET) WITH C-11-ETHANOL AND F18-DEOXYGLUCOSE (FDG) IN HEPATOCELLULAR CARCINOMAS (HCC) FOR THERAPY MANAGEMENT. PET is a noninvasive method for the study of solid tumor perfusion, metabolism and interaction with different therapeutic agents. We used PET in patients with nonresectable hepatocellular carcinomas scheduled for intratumoral ethanol therapy. One aim of the study was the investigation of the kinetics during intratumoral ethanol treatment. Furthermore, FDG follow-up studies were performed to assess early effects immediately after therapy in the tumor and the surrounding liver tissue. The ongoing study study includes 9 patients with child A cirrhosis and HCC (UICC stage III-IVA; tumor size 3-6 cm). Dynamic PET studies (60 min) with FDG were performed prior to therapy (day 0), one day after treatment (day 2), and one week after therapy (day8). C-11-Ethanol (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. Seven out of nine tumors demonstrated a high C-11-uptake shortly after the end of the ethanol injection followed by constant C-11-ethanol concentrations during the rest study period of 45 minutes. The PET data demonstrated no significant elimination of the (211-ethanol in 7/9 tumors during the acquisition time. The surrounding normal liver parenchyma showed a very low £-11-uptake in these patient s. We noted in two cases a rapid decrease of the C-11-ethanot concentration dueto a puncture of a tumor vein. In another case the surrounding liver parenchyma demonstrated significant C-11-uptake in the early phase following intratumoral injection of the drug due to repositioning of the needle. The time activity curves of the liver gave evidence of a slow but steady increase of the tracer uptake with time in three patients. A possible explanation of that is a low ethanol elimination out of the tumor cells. The evaluation of the FDG data demonstrated a liver equivalent uptake in 8/9 tumors (welt and moderate differentiated HCC), which were poorly delineated against the normal liver parenchyma prior to therapy. One moderately differentiated HCC showed an increased FDG metabolism, The tumors were bypometabolic in the center with a rim-like FDG-accumulation at day 2 and day 8 in 7/9 patients. We noted no FDG-uptake in the tumor periphery in the two cases with the rapid ethanol decrease following therapy. £T-follow-up studies four weeks after the first ethanol therapy showed no significant change of the tumor volume. PET with C-11-ethanol may be useful for the prediction of intratumoral ethanol therapy, since only tumors with a stow elimination of the drug are likely to respond to therapy. The increased FDG-uptake in the tumor periphery may be caused by repair mechanisms and is a good prognostic criterion for a palliative effect.

923

cO iim effJ x._

Q. m

O

• Oncology 46.2

46.4

S. Stroobants, O.S. Hoekstra*, P. Dupont, J. Vansteenkiste, E. Coomans P. De Leyn, J. Verschakelen, M. Demedts, L. Mortelmans. U.Z. KU Leuven, Belgium and VU Amsterdam*, The Netherlands.

O. Cremerius, p. Effert, G. Adam, M. gimny, R. G~nther, G. Jakse, U. BUll, Departments of Nuclear Medicine, Urology and Diagnostic Radiology, University Hospital, Aachen, Germany

M E D I A S T I N A L STAGING IN NSCLC: C O M P A R I S O N OF DIFFERENT ACQUISITION AND RECONSTRUCTION PROTOCOLS. Aim: To obtain an efficient PET protocol for mediastinal staging in nonsmall cell lung cancer (NSCLC) by evaluating different acquisition and reconstruction methods. Methods: 33 pts with NSCLC underwent a PET scan 1 week before surgery. A transmission scan (Tx) was acquired prior to IV injection of 500 MBq FDG followed by a 60' dynamic study over the upper chest, a static emission (10', 10cm more caudally) and a whole body (WB) scan (4'/bedpos), was performed. 3 sets of images were reconstructed using filtered back-projection (FBP) and iterative reconstruction: (1) summed images (10') between 50'-70' p.i., corrected for dose, decay and attenuation (SUV); (2) combination of (1) and dynamic data; (3) WB images. Images were visually scored by 2 independent readers. Lesions were localized according to the Naruke map. Hot spots on SUV images were projected onto Tx for lesion localisation (overlay). Pathology was the gold standard. Results: The overall accuracy in detecting the correct nodal stage (21 NO, 3 N1, 7 N2, 2 N3) was 90% and similar for all methods. N-stage was incorrect in 3 pts: 1 with hilar LN adherent to the tumor was classified as NO; microscopic N2-disease was missed in I pt; mislocalisation of a hilar LN wrongly classified the pt as N2. On a lesion based analysis, 4 LN were missed with all methods: 1 microscopic invasion and 3 LN adherent to the tumor. Another hilar LN was only missed on WB using FBP due to streak-artifacts. False positive uptake was noted only on the SUV images in 2 regions: 1 due to prolonged blood pool activity, becoming true negative with dynamic data. Inaccurate localisation was a problem in 4 LN: 2 were incorrect with all methods, 2 others were only correct using overlay. Discussion: iterative reconstruction results in better image quality compared to FBP, especially in WB imaging. The efficacy in detection of metastatic LN is similar for WB and SUV images. Localisation of lesions however is more accurate with the use of the reconstructed Tx. Problems of blood pool activity can be solved using either dynamic information or delayed acquisition. Conclusion: in routine clinical practice an iteratively reconstructed, delayed WB, followed by a transmission scan for localisation of LN, is the method of choice for staging NSCLC.

CELL CANCER

18-FDG PET AND CT FOR THERAPy CONTROL OF METASTATIC GER~ AFTER CHEMOTHERAPY

Metastatic germ cell cancer may be cured either by salvage-chemotherapy and/or -surgery even if complete remission is not achieved by first-line therapy. Today many patients undergo diagnostic "second-look" surgery because detection or exclusion of viable tumor in residual masses by morphology-orientated imaging methodeu and tumor markers is not reliable. We evaluated PET using 18-FDG to assess viable residual tumor in 22 patients (ii ueminoma, Ii nonseminoma) after chemotherapy. 29 PET scans were performed 14-375 (median 60) days after completion of therapy. PET results were compared to CT performed parallel to PET (median 56 days after therapy). Validation was based either on histology of secondary surgery (n=9) or clinical follow-up of 6-57 month (n=20). Viable tumor was suspected, where focal abnormal FDG uptake was present. CT findings of complete or partial remission were regarded negative, stable disease or progression positive for residual tumor. PET was found to be false negative in 2/9 scans (CT 3/9) and false positive in 2/20 (CT 9/20). Both PET false negatives were in nonueminoma patients (one differentiated teratoma at secondary surgery), both false positives in focal inflarmnations. FDG uptake was higher in eeminoma (SUV 7.2-7.5) than in nonseminoma (SUV 1.4-3.4), the difference was statistically significant (p<0.05).

[

SeneitivitTspecificity~A ...... Y

PET 0.78 ns CT 0.67 ns ns/ns: not significant;

1

0.90 s |0.86 s 0.55 s |0.59 s s/s: p<0.025 (Chi-square-test)

We conclude that PET is significantly more accurate than CT for therapy control of metastatic germ cell cancer and may alter management of these patients in the future.

46.3

46.5

M. Zimn71, W. Schreeder2, S. Welters2, U. Cremerius 1, W. Ruth2, U. Buell 1. Depts. of 1Nuclear Medicine and 2Gynecology; Aachen University of Technology Aachen, Germany

M. Gysen, S. Stroobants, P. Dupont, M. Stas, I. De Wever, L. Mortelmans. N u c l e a r M e d i c i n e and Surgical Oncology, Gasthuisberg, Leuven, Belgium.

F-18-FDG-PET TO DIAGNOSE AND TO STAGE OVARIAN CANCER. PRELIMINARY RESULTS. Aim of the study was to evaluate F-18-FDG-PET for diagnosis and staging of ovarian cancer. Methods: PET studies of abdomen and pelvis were performed in 30 pts., suspected of having primary (n=19) or recurrent ovarian (n=ll) cancer, after i.v. administration of 224 MBq F-18-FDG (mean). All pts. were in a fasting state. To reduce urogenital radioactivity the bladder was catheterized and diuresis was forced with 500ml NaC1 and 20mg furosemide. The field of view reached from the dome of the liver to the pubic region. Data were corrected for attenuation and reconstructed iteratively. Three views were evaluated both visually and quantitatively by using the "standardised uptake value (SUV)". The findings were validated by argery/histology/c3¢~ogy. Results primary-tumor (T) / peritonealrecurrence (R) carcinomatosis(PC) tree+ 20 14 true6 4 false+ 1 1 false3 3 PET was false+ for T in a case of salpingoophoritis, false- in two low malignant potential carcinoma (LMP) and in one low grade granulosa ceil tumor. PET detected 10 out of 10 recurrences. 2 out of 3 false- findings concerning PC occurred in cases with microscopic disease. 1 of 3 in apt. with small nodular PC and adipositas permagna. Quantitative analysis revealed an SUV of 8.5+4.5 (range 2.517.6) for ovarian carcinoma including LMP and of 3.6+2.7 (range 1.3-9.3) for benign tumors including inflammatory disease (p<0.05). SUVin LMP was 2.5 and 4.6, respectively. SUV in salpingoophoritis 9.3. Conclusion: 18-FDG-PET is a suitable imaging modality in the diagnosis of recurrent ovarian cancer and is helpful to assess PC. The method is of limited profit in differentiating inflammatory disease from malignant tumors and LMP from benign masses, respectively. Quantitative analysis reveals a clear threshold between malignant and benign tumors only"if LMP and inflammatory disease are excluded. Therefore, SUV does not provide additional diagnostic accuracy compared to visual analysis.

924

U.Z.

CLINICAL VALUE OF WHOLE-BODY FDG-PET IN RECURRENT MALIGNANT MELANOMA. AIM: The aim of the study is to assess the performance of whole-body FDG PET (WB-PET) as a single diagnostic procedure compared to conventional staging procedures in patients with recurrent malignant melanoma. METHODS: 30 patients with a history of malignant melanoma and clinical evidence of recurrent disease were retrospectively analyzed. All patients underwent a conventional diagnostic work-up and an additional WB-PET, performed on an ECAT 931/8/12 scanner (5 min/bedposition), starting 60 min after intravenous injection of -+ 500 MBq FDG. WB-PET findings were compared to conventional diagnostic work-up using histological results, additional imaging or clinical follow up as reference. RESULTS: On WB-PET 101 lesions suspected of malignancy were identified, compared to 59 lesions on conventional imaging. Concordance was found in 51 lesions, whereas 50 lesions were only seen on WB-PET. 36/50 Lesions were found to be true positive based on histological data (4/50), additional imaging modalities (10/50) or clinical follow up (22/50). False positive results were seen in 9/50 lesions (increased uptake was seen in abdominal lesions, muscle and lung hill). 5/50 lesions are still indeterminate after a mean follow up of 6 months. Conventional diagnostic work-up showed 8 lesions that were not seen on WB-PET. 6/8 lesions were confirmed as metastases ( 1 adrenal, 2 bone, 1 lung, 1 brain and 1 subcutaneous lesion), 2/8 were false positive and confirmed histologically (I subcutaneous lesion) or by clinical follow up (1 enlarged lymph node). In 16 out of 30 patients the WB-PET-findings led to a change in therapy. CONCLUSION : WB-FDG-PET, as a single diagnostic procedure, provides an accurate tool in the staging of recurrent malignant melanoma resulting in a clear change of therapeutical strategy in 50% of the patients.

[] O n c o l o g y / C a r d i o v a s c u l a r

46.6 S. Adams±, R.P Baum t, P.M. Schumm-Dr~iger 2, K. Usadela, G. H6r I Department of Nuclear Medicine 1, Department of Internal Medicine2 University &Frankfurt Medical Ctenter, Frankfurt/Main, Germany IMAGING OF NEUROENDOCRINE TUMORS WITH 1SF-FDG PET, attIN-SOMATOSTATIN RECEPTOR AND 99mTC-V-DMSA SCINTIGRAPHY Neuroendocrine tumors tend to grow slowly and are difficult to detect. [tllIn-DTPA-D-Phel]-pentetreotide and 99mTc-V-DMSA scintigraphy has been shown to localize neuroendocrine tumors not detected by conventional imaging modalities. The a i m of this study was to compare metabolic behavior (FDG PET) of neuroendocrine tumors with somatostatin receptor scintigraphy (SS-R) [GEP tumors] and double-radionuclide sclntigraphy (SS-R and 99mTc-V-DMSA=DNS) [MTC] in detecting metastatic nodal spread. Methods: 13 patients with metastasizing neuroendocrine tumors (carcinoids n=4, insulinomas n=2, MTC n= 7) and elevated tumor markers (carcinoids: 5-HIAA; insufinomas: insulin mad C-peptide; MTC: hCT and CEA) were studied. Prior to PET all patients with GEP tumors underwent SS-R. DNS Was performed in all patients with MTC. PET studies were acquired on a whole-body tomograph (ECAT Exact 47, Siemens). Prior to the PET study, patients fasted for at least 12 hours and normal blood glucose levels (<100mg%) were confirmed in all patients. 60 min after intravenous administration of lSF-FDG (mean: 374 MBq) a whole-body (3-5 bed positions, 12-15 m~n each) and regional scan (thorax or abdomen) were performed. Transmission scans (15 rain) were obtained for attenuation correction. Results: 3 GEP tumor patients with low proliferative activity showed no metastatic lesions wheras SS-R demonstrated multiple lymp node and liver metastases. 3 patients with medium and high proliferative activity showed increased metabolic activity and SS-R was completely normal ("flipflop phenomenon"). In patients with recurrent MTC and increasing CEA levels (hCT levels elevated but not increasing) DNS detected only 3 lesions (99mTcV-DMSA positive) in 2 patients, whereas PET demonstrated one putmonal, 3 bone, 20 medlastinal, 10 locoregional and 2 liver metastases. All lesions were confirmed by surgery or follow-up. Conclusion: PET imaging of neuronendocrine tumors reveals increased glucose metabolism only in GEP tumors with high proliferative activity and in metastasizing MTC. Therefore SS-R or DNS should be performed prior to a PET study.

47.2 M. L0beck, R. Buchert, H. Nfigete1, H.M. Stubbet, B. Schl0ter, W. Beyer, J. Mester, C. Fuchs, C. Nienaber2, W, R6diged, M. Clausen Departments of Nuclear Medicine, 1Cardiac Surgery and 2Cardiology, University Hospital Eppendorf, Hamburg, Germany

PROGNOSTIC ASSESSMENT BY PET/[F-18]FDG OF PATIENTS WITH CAD AND SEVERE LVD PRIOR TO CABG. A retrospective analysis of the medical records of 241 subjects with CAD and severe LVD admitted to the hospital for CABG was carried out to evaluate the prognostic value of the preoperative use of PET/[F-18]FDG. 153 patients had undergone clinical, angiographic, and PET/[F-18]FDG assessment prior to CABG, whereas 88 had undergone clinical and angiographic assessment only. Among the 153 patients, 110 (Group A) had been operated because of the evidence of hibernating tissue by PET/[F-18]FDG, and 43 had not undergone surgery because of the lack of evidence of hibernating tissue. Of the 88 patients who had not undergone a PET/[F-18]FDG study, 2 were excluded from surgery because of non-graftable coronary vessels, whereas 86 (Group B) were operated. Subpopulations A and B were comparable for their preoperative conditions. Outcome was as follows: exitus within 30 days of surgery was 1% in group A, and 20% in group B (p<0.0001). The perioperative use of ventricular assist device, of intra-aortic balloon pump and of inotropic drugs, was significantly higher among patients of group B that those of group A. The 5 years survival rate of the operated patients after discharge from hospital was not different between groups A and B. PET/[F-18]FDG appears to be crucial for the prognostic assessment of perioperative risk of mortality and morbidity in patients with severe LVD waiting to undergo CABG.

olD

F-18-DEOXYGLUCOSE-PET AND Tc-99m-MIBI-SPECT FOR DOCUMENTATION OF THE EFFECT OF TRANSMYOCARDIAL LASER REVASCULARISATION IN THERAPY REFRACTORY CORONARY HEART DISEASE

The transmyocardia[laser revascularization(TMR) is a new methodfor the treatmentof end stagecoronaryheartdiseasewithoutalternativetherapy options. The method, presentlyin the phaseof clinicaltesting, has an estimated porioperativemortalityof 5-10%. The effectivityof transmyocardial channels placedby TMR (about 1 channel/cm2)is underdiscussion. The aim of this prospectivestudyis the investigationof longterm effects of TMR on the myocardialperfusionand viabilityconsideringthe clinical status and hemodynamicdata. Method: The studyprotocolincludescardiaccatheterization,spiroergometry, echocardiography,dynamicF-18-FDG-PETunderstandardizedinfusion of glucoseand insulin, Tc-99m-MIBI-SPECTat rest and under dipyridamole stress (0.6 mg/kg), each shortlybeforeand 6 monthsafter TMR. Parametric imagesof the metabolicrate of glucosewerecomputedusingthe GjeddePatiakapproach.The resultswere evaluatedby a 9-segmentmodel. Relative changes in perfusionand glucoseconsumptionwere calculatedsegmentally with respectto the septa[maximum. Patients: 18 of 33 consecutiveTMR patients(mean age: 63+8 years) underwent the baselineand follow up tests accordingto the protocol. Results: The over all metabolicrateof glucoseafter TMR was reducedby 21% (meanof all segments).3 patients had a globalincreaseof the metabolic rate. Duringfollow up, a slight increasein the restingperfusionwas observedin 6 of 162 segmentsin 6 patients,a decreasein 26 segments in 13 patients(amongthem 18 segmentsin the posteriorwall). Normalizationof the perfusionof severelyhypoperfusedsegmentscould not be demonstrated. In patientswith unchangedor slightly improvedMIBI/FDGfindingsthe LVEF decreasedafter TMR by 2.4%, in patientswith enlargeddefectsize by 15.7% (mean). Conclusion;The subjective,in somecases definitiveimprovementof the clinical status in about80% of patientsafter TMR (CCS-score:2.1 vs 3.3) could not be confirmed by PET/SPECTinvestigationof myocardialmetabolism and peffusion. This observationagreeswith the hemodynamicresults.

Cardiovascular 47.1 Lucianani G, Landoni C, Paolini G, Galli L, Zuccari M, Di Credico G, Rossetti C, Pelenghi S, Grossi A, Striano G, Fazio F. INB-CNR, University of Milan, HS Raffaele, Milan, Italy

co |l

47.3 J.J. Bax, J.H. Cornel*, F.C. Visser**, P.M. Fioretti#, C.A. Visser**. Leiden, *Alkmaar, **Amsterdam, #Rotterdam, The Netherlands.

FDG SPECT TO PREDICT RECOVERY OF LEFT VENTRICULAR EJECTION FRACTION AFTER REVASCULARIZATION.

"[he aim of this study was to evaluate the use of F18-fluorodeoxyglucose (FDG) and single photon emission computed tomography (SPECT) to predict impmvement of left ventricular ejection fraction (LVEF) after revascularization. Patients (n=22) with poor LVEF (<30%l were studied with FDG SPECT (to assess glucose utilization) and early thallium-20l SPECT (to assess perfusion). The SPECT studies were analyzed using polar maps (that were divided in 13 segments). In these 13 segments regional contractile function was assessed by resting echocardiography. Dysfunctional ~egments showing either normal perfusion or hypoperfusion with increased FDG uptake were considered viable. LVEF was assessed before and 3 months after revascularization by echocardiography or radionuclide ventriculograpby. A patient was considered viable (likely to improve in LVEF) when 3 or more segments with contractile dysfunction on echo were viable on FDG/TI-201 SPECT. Results: 14 patients had 3 or more viable, dysfunctional segments on FDG/T1-201 SPECT and 8 patients had 2 or less viable, dysfunctional segments. Both groups had comparable LVEFs before the revascularization (25_+6% versus 24_+6%, NS). In the patients with 3 or more viable segments the LVEF improved significantly to 32_+6% after revascularization. In the patients with 2 or less viable segments the LVEF remained unchanged (25_+6% after revaseularization). Considering an improvement of LVEF >5% significant, FDG/TI-201 SPECT correctly identified I2/12 (100%) of the patients that improved in LVEF as viable, whereas 8/10 (80%) patients that did not improve in LVEF were identified as nonviable. Conclusion: The data demonstrate that FDG/TI-201 SPECT is useful in the selection of patients with a poor LVEF who may benefit (in terms of improvement of LVEF) from revascularization.

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• Cardiovascular/Therapy 47.4

47.6

E. Voth, F.M. Baer 1, H.J. Deutsch1, C.A. Schneider1, M. Horst 2, R. Wagner3, K. Wienhard3, U. Sechtem 1, H. Schicha Depts. of Nuclear Medicine, 1Cardiology, 2Cardiac Surgery, University of Cologne, 3MPI for Neurological Research, Cologne,

A. Bruno, *A. Finzi, M. Castellani, G. Marotta, *G. Call, *L. Preti, M. Gasparini, V. Longari, R. Matheoud, R.Casati, P.Gerundini. Nuclear Medicine and*Cardtology Departments, IRCCS - Ospedale Maggiore, Milan, Italy

Optimally performed i.e. by an experienced scientist and in TEE technique, dobutamine-echocardiography is a method qualified to judge residual viability of infarcted, aldnetic myocardial segments. Dobutamine-TEE offers therefore an alternative to FDG-PET concerning this purpose.

SPECT WITH TL-201, Te-99m TETROFOSMIN AND SESTAMIBI IN THE IMAGING DETECTION OF HYBERNATING MYOCARDIUM AFTER MYOCARDIAL INFARCTION. Imaging detection of post-AM] hybemating myocardium (HM) includes T1201 (Tl) Rest-Redistribution (RR) and low-dose Dobutamine-Echo (DE) tests. Tc-99m Tetrofosmin (TF) and Tc-99m Sestamibi (MIB1) usefulness, still controversial for this topic, was investigated and compared with T1 late redistribution and/or DE kinetic response. 28 pts. (20 males, mean age 60.5, range 37-74) with recent AMI (<6 months) and severe (>75%) stenosls of the infarct-related artery were studied by DE test, RR, MIBI and TF rest SPECT images. Percentage uptake of both Tc-agents was different in 127 akinetic (score 3) vs 90 hypokinetic (score 2) segments on basal echo (TF 56+_19.3 vs 73.3+17.2%, MIBI 54+t7.6 vs 71+16.2%), as well-a~observed after RR analysis (61+16.1 vs 77+15.1% in redistribution studies). Considering 39 segments with complete (3-2 to 1 score) and 19 with incomplete kinetic improvement (3 to 2 score), Tc-agents (TF: 70 +-I6 vs 59.+17%, MIBI: 68_+18 vs 56+18%) ad TI (74_+15vs 68 +14%) uptake was significantly higher if DE recovery was partial. 19/127 (15%) and 12/120 (10%) of akynetic segments had normal TF and MIBI uptake at rest (>80% of maximum uptake in the same SPECT section) in 5 and 4 pts. respectively. In these normoperfused segments, despite a positive DE response, no usefixlimprovement of perfiasion is expected after revascularization, supporting a reduction of DE predictive value for perfusion recovery. Conversely Tl redistribution was absent in 40/58 hypo-akinetic segments with positive DE, suggesting a reduced sensitivity of RR for viability. ]n 58/448 segments (13%) DE and RR tests agreed for IIM; the r uptake ofTl~ MIBI and TF is reported. DE response TI rest T1red. %upt TF rest%upt MIBkest%upt compl. 3 to 1 6 9 + 1 4 . 7 72+15.8 64_+17.8 60+22.8 incompl.3to 2 68_+14.4 67_+14.2 59_+17.1 56+_18.2 compl.2to 1 80_+15.6 81_+14.2 77+15.7 76_+15.1 Tc-99m agents vs RR obtains a better visualization of hypoperthsel myocardium close to normoperfused wall at rest, more comparable with DE and basal echo ~amre,s. However ti~ ~ malc~DE a~t w.xfusion scores obtained with either of radioWaecrtested is still suboptimal in our series. HM detection with both To-agents SPECT is similar in hypokinetic areas, whereas in akinetic areas a slightly better TF uptake was found. SPECT with Tl-201, Tc-99m Tetrofosmin and Tc-99m Sestamibi versus Dobutamine Echo for imaging detection of hybemating myocardium after myocardial infarction.

47.5

Therapy 48.1

FUNCTIONAL RECOVERY AFTER SUCCESSFUL CORONARY REVASCULARISATION: PREDICTIVE VALUE OF F-18-FDG PET AND LOW-DOSE D O B U T A M 1 TRANSESOPHAGEAL ECHOCARDIOGRAPHY In order to evaluate the predictive value concerning functional recovery, 121 patients with chronic myocardial infarction (infarct age -> 4 months) and akinetic infarct region by ventficulography were studied by F-18-FDG positron emission tomography (FDG-PET) and multiplane transesophageal echocardiography (TEE) at rest and during dobutamine infusion (5, 10 gg/kg/min). 42 of these patients were followed up with TEE 3-6 months after successful revascularisation (20 PTCA, 22 CABG). Corresponding FDG-PET and TEE tomograms were compared using a 26 segment model. Segments with an FDGuptake of >50% of maximum and a dobutamine-inducible contractile reserve were judged vital. TEE wall motion analysis after revascularisation served as reference standard. Before the intervention 30/42 patients (71%) had infarcted segments with an FDG accumulation >50%, 25/42 (59%) segments with a dobutamine-inducible contractile reserve. FDG-PET and dobutamine-TEE judged infarct related vitality concordantly in 36/42 cases (86%). After revasculafisation there was retum of wallthickening in the infarcted area in 26/42 patients (62%). From these data the following predictive values were calculated: FDG-PET Dobutamine-TEE

l pos. pred. value] neg. pred. value 83 % 92 % 92 % 88 %

I

Accuracy 86 % 90 %

E.Prvulovich, J.Bomanji, * D.Holdright, D.Costa, PJ. Ell. Institute of Nuclear Medicine and* Department of Cardiology, University College London Medical

School, UK. A COMPARISON OF THALLIUM-201 AND F-18 FDG SPET IN THE ASSESSMENT OF PATIENTS FOR CORONARY REVASCULARISATION The aim of this study was to compare conventional stress-redistribution (RD) Thallium-201 (T1), rest-RD T1 and 18 F-Fluorodeoxyglucose (FDG) single photon emission tomography (SPET) in the assessment of patients (pts) for coronary revascularisation. We studied 33 pts with dyspnoea from coronary artery disease (left ventricular ejection fraction < 45%) and history of prior infarction under consideration for coronary revascularisation. Early rest T1 images were acquired 20 minutes post injection (pi) and both sets of delayed T1 images at 3-4 hours pi. FDG images were acquired one hour pi using a Maxxus gamma camera equipped with high energy collimators. Thirteen of 33 (39%) of stress-RD TI studies showed only fixed perfusion defects (TI uptake < 50% maximum); 20 studies (61%) showed a combination of fixed and mild reversible perfusion defects. The results of stress-RD and rest-RD T1 studies were similar in 29 of 33 (88%) pts; the extent of defect reversibility shown by rest-RD TI imaging exceeded that of stress-RD TI imaging in 4 pts. In nine patients there was FDG uptake > 50% of maximum within fixed perfusion defects (inferolatex?al in one pt and inferior in 8 pts) suggesting myocardial viability. Our data suggest that stress-RD T1 imaging is unnecessary in pts with dyspnoea from coronary artery disease under consideration for coronary revascularisation; rest-RD T1 studies will identify pts who have defect reversibility. Although FDG SPET appears to identify additional areas of viable myocardium which might benefit from coronary revascularisation our results should be viewed with caution. The location of FDG uptake predominantly to fixed inferior defects suggests that our findings may result from the limited attenuation of high energy (511 keV) FDG gamma rays rather than myocardial viability.

926

T.M. Behfl, V. Vougioukas ~, S. Memtsoudis 1, S. Gratz 1, K. Nebendsh] ~, H. Schmidberger 2, W. Becker I. Departments of Nuclear Medicine I and Radiation Oncology 2 of the Georg-August-University of G6ttingen, Germany. THERAPEUTIC EFFICACY AND DOSE-LIMITING TOXICITY OF AUGER ELECTRON VERSUS CONVENTIONAL BETA EMITTERS IN RADIOIMMUNOTHERAPY OF COLORECTAL CANCER WITH INTERNALIZING ANTIBODIES Clinically, radioimmunotherapy with conventional It-emitters (e.g., ~3~I, 90y) has shown only limited success in the therapy of solid rumors. Recent clinical data suggested higher anti-tumor efficacy of internalizing monoclonal antibodies (MAbs) at lower toxicity when labeled with Auger-electron- (e.g., ~25I)as compared to f3-emitters (.e.g., Welt et aI., J Clin Oncol 1996; 14:1787). The aim of this study was to compare the anti-tumor efficacy and toxicity of the IzsI- and 131I-labeled intemalizi[ng MAb, 171A, to conventional chemotherapy with 5-fluorouracil/leucovorin (5-FU/LV) in a human colon cancer model in nude mice. The biodistribution of radioiodinated 17-1A was studied at different protein doses in nude mice, bearing subcutaneous human colon cancer xenografts. For therapy, mice were injected either with unlabeled, 125I- or I31I-labeled 17-1A (IgGza) at the protein dose which gave highest tumor/non-minor ratios, or were admihistered 5-FU/LV. Control groups were left untreated. The maximum tolerated dose (MTD) of each agent was determined. Myelotoxicity (blood counts) and minor growth was monitored. Bone marrow transplantation (BMT) was performed to allow for dose-intensification. Highest minor/blood ratios were observed at a protein dose of 200 gg. The MTDs of ~3~I- and 12sI-17-1A without artificial support were 300 gCi and 3 mCi, respectively. Myehitoxicity was dose-limiting. BMT enabled an increase of the MTD to 400 pCi of ~31i.labeled 17-1A, whereas the MTD of 12sI-17-1A with BMT has not been reached at 5 mCL The MTD inthe chemotherapy group was 0.6 mg 5-FU / 1.8 mg LV given at 5 subsequent days. Whereas no effects were seen with cold 17-1A and the effects of 5FU/LV were minimal, tumor growth was retarded significantly with J3~I-17-1A. With 125I-label however, partial remissions (i.e., >_50% reduction of minor volume) occurred at 3 mCi, and even complete remissions at 5 mCi. Tumor doses needed to acheive comparable anti-minor effects were half as high with tz~I-17-1A as with 131I-label. In contrast, no significant difference was observed in the therapeutic efficacy of an t~Iversus ~zSI-labeled, non-internalizing ~lnti-CEAantibody at equitoxic doses. These data suggest the superiority of Auger-electron emitters, such as I25I, at equitoxic doses as compared to chemotherapy or to therapy with conventional [?,-emitters. The lower toxicity of Auger emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing rumor tissue, but not in the stem cells of the red marrow). Further studies, preclinical as well as clinical, are ongoing.

II Therapy

48.2

48.4

S Gratz ~, D. Gtbel 2 T M . B e h r ~ A.Herrmann ~ Weber ~, R.M. Dunn 3, ~ e r t 2, W.Becker Departement of Nuclear Medicine, Orthopedics 2 of the Georg August University, G6ttingen and Garden State Cancer Center at the Center for Molecular Medicine and Immunology 3 , Bellevilte, N J, USA

S H. Cunningham, ILl. Mairs, T E, Wheldon, P. Welsh, G.Valdyanathan, M. R. Zalutsky, Radiation Oncology and Clinical Physics Depts, Glasgow University and Radiology Dept, Duke University, North Carolina.

Radiosynoviorthesis with Rh~X-sulphate, ErlU-citrate and YS°--citrate for radiation synovectomy: First Doaimetric Data.

RADIOTOXICITY TO NEUROBLASTOMA CELLS AND SPHEROIDS OF BETA-, ALPHA- AND AUGER ELECTRON-EMITTING CONJUGATES OF BENZYLGUANIDINE

e-

Radiolabelled metaiodobenzylguanidine (MIBG) is selectively taken up by tumours of neuroendocrine origin, where its cellular localismion is believed to be cytoplasmic. The radiopharmaceutical ~3~I-MIBGis now widely used in the treatment of neuroblastuma but other radioconjugates of benzyl gnanidine have been little studied. We have investigated the cytotoxic efficacy of beta, alpha and Auger electron emitting radioconjugates in treating neuroblastoma cells grown in monolayer or spheroid culture.Using a no-carrier-added synthesis route we produced 123I-, 125I-, 131I- and 21tAt- labelled benzylguanidines and compared their m vitro toxicity to the neuroblastoma cell line SK-NBE(2C) grown in monolayers and spheroid culture. The Auger electron emitting conjugates ([123I]MIBG and [1251]MIBG) and the,alpha emitting conjugate ([211At]MABG) were highly toxic to monolayers and small spheroids whilst the beta emitting conjugate [t31I]MIBG was relatively ineffective.The Auger emitters were more effective than expected ff the cellular localisation of MIBG is cytoplasmic. As dosimetrically predicted however, [21IAt[MABG was found to be extremely potent both in terms of concentration of radioactivity or number of atoms / mi administered. In contrast, the Auger electron emitter conjugates were ineffective in the treatment of larger spheroids whilst the beta emitter showed greater efficacy. These findings suggest that short range emitters would be well suited to the treatment of circulating turnout cells or small clumps whilst beta emitters would be superior in the treatment of subelininical metastases or macroscopic turnouts. These experimental results provide support for a clinical strategy of combinations ('cocktails') of radioconjugates in targeted radiotherapy.

x__

Rationale: Aim of this prospective study was to calculate the effective absorbed dose after using Rhea-sulphate, Erl~-citrate and Yg°-citrate for radiosynoviorthesis ( RSO ). Methode: At 20 Patients with known rheumatoid Arthritis ( n=19 ) and eacroileitis ( n=l ) a radiosynoviorthesis ( RSO ) was done ( n=36) after a previously effected examination of all joints: shoulder ( n=8 ), hand( n= 4 ), fingers ( n=7 ), elbow ( n=3 ), hip ( n=l ), knee ( n=6 ) and the upper ( n=6 ) or lower ankle joint ( n=l ). The activity applied to the middle sized joints of the hand the ellbow, the upper and'lower ankle joint was 74 MBq Rhl~-sulphate and 111 MBq Rh18%sulphate to the bigger joints of the shoulder and the hip. 185 MBq yg0_ citrate was applied to the knee and 37 MBq Er~Sg-citrate to the small finger joints. The application of the radionuelide into the bigger joints was effected under supervision by image converter examination after previous intraarticular instillation of TriamcoEonhe×acetonid. Dosimetric datas (n=20) were elaborated by using planar quantification following the MIRD scheme. The activity of the arthritis / synovitis was controlled by a blood pool ecintigraphy after injection of 370 MBq Sg~TC-MDP before and 5 months after the RSO (oomplet follow up n=12). For semiquantitative measurements the ROI technique with identical sized ROl's was applied.Results: After (n=23) application of Rhl~-sulphate the mean radiation absorbed dose to the wholebody was 5.3z~2..73 cGy, liver 10.0±8.05 cGy, spleen 20.3~2.87 cGy, kidneys 9.38+11.35 cGy and at the injected joints of the shoulder 249.6+~46.1 Gy, hand 375.8+158.1 Gy, elbow 53.37+_29.93 Gy, upper/lower ankle 176,76+101.13 Gy. In (n=7) cases, where a obligate fixation of the joint was not possible, the dose applied to the lymph node masses (n=25) was 2593±5380 Gy (max. 189 Gy) and to single lymph nodules 14,67±11,2 Gy (max. 63 Gy). In cases of obligate fixation, lymph nodulescould not be detected. After (n=7) Erl~-citrate the dose applied to the wholebody was 0.411 cGy, lymph nodules 2.3 Gy, small finger jonts 816 Gy and after (n= 6) Y~°-citrate respectively to the wholebody 15.5 cGy, liver 26.5 eGy, spleen 11.9 cGy, kidneys 67 cGy and knee 338 Gy. Die effective equivalent mean dose to all patients was 8.31:53,2 cSv/mCi, whereas in cases of fixation the mean value was significantly lower with 6.45-+3.43 cSv/mCi. The mean reduction of the ~9~Tc-MDP blood pool uptake was in the 1. month 40.75%, in the 2. month 48 %, in the 5, month 48% at bigger joints and respectively 63.25 % at smaller finger joints compared to the beginning. Conclusions: 1.) A significant higher radiation absorbed dose to the lymph nodules has to be exspected in case of no joint fixation. A fixation of the joint has to be obligatorily demanded, 2.) The radiation absorbed dose in case of radiosynoviorthesis to the wholebody is as high as in case of radiotherapy with l ~3~of benign thyroid diseases.

48.3

T. E. Wheldon, R_ J. Mairs, N. O'Rourke, A. Barrett, Departments of Clinical Physics and Radiation theology, Glasgow University and Western Infirmary.

RADIOBIOLOGICAL MODELLING OF ALTERNATIVE STRATEGIES FOR TARGETED RADIOTHERAPY OF LYMPHOMA Radionuclide therapy of non-Hudgldn lymphoma (NHL) using I31I-conjugated anti-B 1 monocloual antibody is being clinically evaluated in several centtes. The results to date show promise that targeted radiotherapy could be curative for some NHL patients likely to relapse on conventional treatment protocols. Treatment strategies in present use include high dose myeloablative radionuclide administration followed by autologous bone marrow rescue (Seattle strategy) and several schemes for non-ablative therapy using lower single or fractiuaated doses of radionuclide. We have evaluated alternative strategies for targeted radiotherapy of lymphoma by computer simulation of cell kill and tumour curability achieved by radionuclide treatment, alone or in combination with total body irradiation (TBI). The model studies include Monte Carlo simulation of differing lymphorna radiosensitivies in a patient population and incorporate differing absorption of 131t disintegration energy in tumours or microtumours of differing size. Simniations included single or divided doses of 131I-antibodyas sole treatment and also combined modality strategy treatments in which varying levels of ~3~Iactivity were combined with external beam TBI to remain within radiation tolerances of critical normal organs. The model parameters were varied in a series of treatment simulations to evaluate the efficacy of alternative strategies in eradicating disseminated lymphoma comprised of macroscopic and microscopic tumours and circulating single cells. The model studies strongly suggest the benefits of combined modality treatment in a wide range of situations. We conclude that moderate dose levels of 13]I-antibodycombined with TBI and marrow or stem cell rescue may be the optimal strategy for curative treatment of selected NHL patients and that clinical evaluation of this strategy is now appropriate.

48.5

R.M. Du.rmI, M.E. Juweid 1, T.M. Behr2, J.A. Siege/I , R.M. Sharkey~, and D.M. Goldenberg ~. Garden State Cancer Center a, Belleville, NJ, USA, and Department of Nuclear Medicine of the University of G6ttingen2, Germany. DOSIMETRIC POTENTIAL OF MINIMAL RESIDUAL AND MICROMETASTATIC DISEASE USING RADIOLABELED ANTIBODIES The highest prospects for radioimmunotherapy (RAIT) are thought to be in the context of minimal residual and micrometastatic disease (down to mmrange). We hypothesized that such small lesions may not be detectable with conventional nuclear medicine imaging methods (including SPECT), yet they could receive a substantial radiation absorbed dose as a consequence of RAIT. In order to simulate the in vivo conditions, approximately 1.15 gCi of ~3tI were absorbed onto a 2-ram-diameter bead, and placed into a 1200 cm ~ liver phantom filled with water, containing 3 mCi of 131I.The activity concentration of the bead was 287.5 gCi/cm3 as compared to 2.5 ~Ci/cm 3 for the liver phantom (i.e., a ratio of 115:1). The 287.5 p.Ci/cm3 corresponds to an uptake value of 0.3 % of the injected dose per gramm (%ID/g) obtained at 24 - 48 hours after infusion of 100 mCi of ]3tI-labeled IgG, which is well in the range of the 0.001 - 1%ID/g reported with 13~I-labeled monoclonal antibodies (e.g., Siegel et al., Cancer Res. 1990; 50: 1039-1042; Behr et aL, J. Nucl. Meal. 1997; 38: in press). The radiation absorbed dose to the bead from the beta component emissions of ~3~Iwas calculated assuming a hypothetical effective half-life of 48 hours, usually found in our clinical studies. The phantom was imaged with the bead placed in the center by both, planar and SPECT methods. The 2mm-bead could not be visualized by either method, despite the relatively high activity concentration and lesion-to-background ratio. The estimated radiation absorbed dose was -5400 cGy using absorbed fractions based on Berger's point kernels. In conclusion, these data indicate that relatively high absorbed doses can be delivered to small tumor lesions, although they may not be detectable by the conventional gamma camera. Hence, the potential for radioimmunotherapy in an adjuvant setting and minimal residual disease should not be overlooked. We utilized t3tI since it is the most commonly used radionuclide for radioimmunotherapy; however, other radionuclides with shorter path length beta particles may prove more suitable in adjuvant settings or minimal residual disease. (Supported in part by USPHS Grant CA 39841 from the NII-I).

927

co im

¢n

O. m

• Therapy/Endocrine 48.6

49.2

RJ Mairs, A Nestmsteh-Riz,WJ Angerson, PD Stantoih JR Reeves, R Rampling, J Owens and TE Wheldon. Depamnents of Radiation Oneology, Clinical Physics & Surgety,Universityof Glasgow

~. 7:':::hat~, P. Bucsky, Th. Parlowsky, Chr. Reiners. Clinic for Nuclear Medicine, University of W0.rzburg and Clinic for Pediatrics, University of Ltibeck, Germany.

THE IMPLICATIONSOF PROLIFERATIVEHETEROGENEITY FOR THE DESIGN OF DNA-TARGETED RADIOTHERAPY:DIFFERENTIAL CYTOTOXICITY OF ALTERNATIVERADIOIODOANALOGUES OF IUDR TO HUMAN GLIOMA CELLS IN MONOLAYER OR SPHEROID CULTURE. Radioiodinatediedodcoxyufidine(IUdR) is a novel, cycle-specificagent which has potentialfor the treatmentof residualmalignant glioma after surgery. Since only cells in S phase will incorporate IUdR into DNA, a major limitation to this therapy is likely to be proliferative heterogeneity of the turnout cell population. Using a chinogenlcend point, we have compared the toxicitiesof three radioiodeanalognesof IUdR - [~zh]lUdR, [l~IlIUdR and [ml]lUdR - to the human glioma cell line UVW, cultured as raonolayers in exponential and plateau phase of growth and as multicellnlarspheroids. Monolayerstreated in exponentialgrowth phase were most efficiendy~ by [1251]lUdR(effectiveDo = 2.36 kBq m14), while [tZVl]IUdR and [131I]IUdRwere less effectiveeradicators of clonogens (effectiveDo = 9.75 and 18.9 kBq ml-l respectively). Plateauphase monolayercultureswere marginallymore susceptibleto treatment with [lz3I]IUdRand [lZ~l]lUdR(40% clonogenicsurvival) than [~II]IUdR (60% clonogenicsurvival). In contrast, colonyformation from cells derived from glioma spheroids after incubationwith activity concentrationsgreater than 40 kBq lol4 or" radiopharmaceuticalwas inhibited to a greater extent by [1311]IUdRthan by [I~I]IUdR or [lZ~l]IUdR:clonogenicsurcival values were 13°/~ 45% and 28% respectively. It is concluded that IUdR conjugates of the Auger electron emitters ~23Iand ~zsIkilled only cells which were in S phase during the period of incubation with radioplmrmacentical,whereas the superior toxicity to clonogenic cells in spheroids of [~311]IUdRwas due to cm~-fire i8-irradiatiorL [I~I]IUdR was more to,de than [lnl]IUdR when compared on the basis of administered activity. However, in terms of number of molecules of radiolabelled drug, [mI]IUdR was many thnes more effeaive than [lZ~l]IUdR.These findings suggest that [~3q]lUdRor combinalionsof [~3q]IUdRand [~Z~l]lVdRmay be more effectivethan [lnl]lUdR alone for the treatmentof residualglioma.

CHARACTERISTICS OF DIFFERENTIATED THYROID CANCER IN CHILDREN AND ADOLESCENTS WITH RESPECT TO AGE, SEX AND HISTOLOGY B a c k g r o u n d . Because of its rarity there have been only a few detailed studies on differentiated thyroid cancer (DTC) in children. The present study was undertaken to assess the characteristics of DTC with respect to age, sex and histology in children and adolescents. M e t h o d s . In a questionnaire based survey, data of 114 children and adolescents (318y), followed after treatment for DTC (78% papillary, 22% follicular type) between 1980 and 1993 in 65 clinical institutions in Germany was analysed. Characteristics of 80 females and 34 males were evaluated and the influence of age, sex, histology, multicentric tumor, tumor stage and lymph node on distant metastases was tested using multivariate discriminant analysis. Between group comparison was performed using student t-test and chi-square test. Correlation between incidence and age was assessed by linear regression analysis. R e s u l t s . The overall incidence of thyroid cancer in females was higher than in males with a peak of female/male ratio at puberty. The incidence of DTC correlated with age in females < I 6 y (r=0.84, P=0.0006), which was more pronounced in females with papillary thyroid cancer (PTC) (r=0.83, P=0.006) but not with follicular thyroid cancer (FTC) (r=0.20, P=0.16). FTC was associated with less advanced disease (p=0.009), less lymph node involvement (P=0.007) and lower rate of metastases (P=0.02) as compared to PTC. Males tend to have a higher risk for metastases. However, statistical analysis failed just to reach the significance level (P=0.08). Multivariate analysis revealed tumor stage as the only powerful factor (P=0.02) associating with distant metastases. C o n c l u s i o n s , 1. Due to a higher frequency in females at puberty PTC seems to be influenced by sex-hormones. 2. Childhood thyroid cancer is frequently associated with lymph node involvement , distant metastases and extrathyroidal tumor infiltration, which is more pronounced in children with PTC. 3. The most powerful factor influencing the risk for distant metastases in children is the advanced tumor stage.

Endocrine

49.1

E.V. Epchtein_n, Institute of Endocrinology Metabolism, Kiev, Ukraine.

49.3

and

THYROID CANCER IN CHILDREN OF UKRAINE (tO-YEAR FOLLOW-UP) Among the remote after-effects of the Chernobyl accident, one may cite hyperthyroidism, autoimmune thyroiditis, benign and malignant thyroid tumors in children. Our investigations have shown that wiShin 10 years after Chernobyl, hypothyroidism and autoimmune thyroiditis in children who were exposed to radiation have not manifested. However, starting from 1990 the number of thyroid cancers in Ukraine increases in children. If for 5 years before the accident (1981-1985) the number of thyroid cancers for 100.000 children population made 0,04-0,06, in last years (1991-1995) it makes up in Ukraine 0,39-0,43. This index is significantly higher in 5 regions which have been most affected as a result of the Chernobyl accident: Chernigov region: 1,84; Kiev region: 1,43; Zhitomir region: 1,22; Cherkassy region: 0,92; Rovno region:O,55. For the post-Chernobyl period near 800 persons in all, who were aged 0-18 years at the moment of the accident, have been operated for a thyroid cancer. In this connection, a particular attention must be payed to a timely diagnosis providing a yearly examination of subjects residing in "contaminated" areas, which includes examination by an endocrinologist, ultrasound investigation of thyroid gland, and, in case of thyroid nodules, fine needle aspiration biopsy of these nodules followed by cytologic and, if necessary, immunocytologic analysis.

928

THYROGLOBULIN, LOW DOSE 1-131 AND TC-99m TETROFOSMIN WBS IN THE FOLLOW UP OF DTC: A DIRECT COMPARISON UNDER ENDOGENOUS TSH STIMULATION Hans Juerqen Gal~owitsch, Peter Mikosch, Ewald Kresnik, Iris Gomez and Peter Lind Department of Nuclear Medicine and Special Endocrinology, Austria

LKH Klagenfurt,

Thyroglebulin, determined under endogenous TSH-stimuIation after withdrawa; of Lthyroxin therapy (off-T4) has proved to be the most sensitive method for evaluation of patients with recurrent malignancy or distant metastases This study employs a comparative approach between Iow dose 1-131 scan and the previousIy reported high sensitive Tc-99m tetrofosmin WBS using Tg - off -T4 as a base of comparison.Patients and Methods: 58 consecutive patients of our foflow-up programm with thyroid carcinoma primary ablated with thyroidectomy and radioiodine therapy were examined after L-thyroxine - withdrawal over three to four weeks with 1-131 (185 MBq) and Tc-99m Tetrofosmin WBS and Tg-determination (off-T4) within 5 days. Patients with a Tg level above 0.5 ngtml, were defined as group A (n=29). Group B (n=2g) comprised patients who had a Tg ~evel (off-T4) below O 5 ng/mL Results: 1-13"i revealed only 19 out of 44 tumor sites (43.18 %). Additionally, 3 remnants could be demonstrated. Sensitivity showed decreasing values for local recurrences (4/7 - 57.1%), bone lesions (7/13 - 53.85%), mediastinal (2/4 - 50 %), lung parenchymal (3/7 - 42.85%), lymph node (2/9 - 222) metastases. Whole body scintigraphy with Tc-99m tetrofosmin revealed a total of 41out of 44 malignant lesions (93.18 %). Sensitivity was superior for bone metastases (13/13 100 %), for lung parenchymal metastases (9/9 - 100 %), mediastinum (4/4 - 100 %) and lymph nodes (9/9 - 100 %). Local recurrences cou)d be detected in 6/7 patients (85.7 %) and thyroid remnants in two cases (2/11 - "18.2%) One liver metastasis could not be detected because of physiological tracer distribution of Tc-£9m tetrofosmin Thyroglobulin - off-T4 detected malignant recurrence or metastases in 18/19 patients (94.7 %) when using a cut-off of 3 ng/ml, and 84.2 % (16/19 patients) with a cut-off of 10 ng/ml. Specificity is calculated with 7'1.8 % when using a cut off Qf 0.5 ng/ml, 89.7 % with a cut-off of 3 ng/ml and 100 % with a cut-off of 10 ng/ml. Conclusion: Scintigraphy with Tc-99m tetrofosmin showed clear advantages concerning sensitivity in most metastatic lesions when compared with low-dose 1-131 scan. Despite a slight lower specificity, Tc-99m tetrofosmin WBS has therefore proved to be a usefool tool in the asessment of metastatic lesions in DTC.

[] E n d o c r i n e / H a e m a t o l o g y -

Oncology

Haematology - Oncology 50.1

49.4 J.N@mec, R.Bflek, P.Vl~ek, P.Chyfr~, V.Zamrazil Clinic of N u c l e a r Medicine, 2nd School of M e d i c i n e C h a r l e s ' U n i v e r s i t y RepublPraha"icInsfit°te of E n d o c r i n o logy, Praha, Czech

C. Stroszczynski, H. Amthauer, N. Hosten, H Oellinger, R. Jechens, J. Ricke, H. Eichstaedt, R. Felix

co im

Department of Nuclear Medicine and Radiology, Virchow-Clinic, Humboldt-University of Berlin, Germany

e,, THE P R O G N O S T I C VALUE OF MA T H Y R O G L O B U L I N LEVELS CANCER

INITIAL H Y P O T H Y R O I D PLASIN D I F F E R E N T I A T E D THYROIO

MONITORING OF MALIGNANT LYMPHOMA OF THE BONE: COMPARISON OF GA-67-SPECT AND MRI

The purpose of the study is to e v a l u a t e the s u r v i v a l rates in d i f f e r e n t i a t e d f h y r o i d c a n c e r s based on i n i t i a l h y p o t h y r o i d plasma t h y r o g l o b u l i n levels. Plasma t h y r o g l o b u l i n was m e a s u r e d by own r a d i o i m u n o a s s a y at the first e n c o u n t e r with differ e n t i a t e d t h y r o i d c a n c e r s in h y p o t h y r o i d i s m following radical t h y r o i d s u r g e r y and/or f o l l o w i n g radioiodine t h y r o i d ablation. C u m m u l a f i v e s u r v i v a l rates were m e a s u r e d in nine groups a c c o r d i n g to rising initial t h y r o g l o b u l i n levels. M e a s u r e m e n t s were p e r f o r m e d in ] lO1 patients. If was found that the survival rates decreased continually a o c o r d i n g s to i n i t i a l plasma f h y r o g l o b u l i n levels, the lowest m o r t a l i t y was found in p a t i e n t s with low plasma t h y r o g l o b u l i n , where s u r v i v a l rates were more than 0.80 for 15 years. P a t i e n t s with modestly e n h a n c e d plasma t h y r o g l o b u l i n levels showed s u r v i v a l rates of a b o u t 0.70 in 15 years while the p a t i e n t s with high intial plasma t h y r o g l o b u l i n levels had s u r v i v a l rates of about 0.4 in 15 years. M u l t i f a c t o r i a l study showed that plasma thyroglobulin level together with age at diagnosis and the p r e s e n c e of d i s t a n t m e t a s t a t i c lesions at d i a g n o s i s were the most i m p o r t a n t n e g a t i v e prog n o s t i c factors.

Introduction: Malignant lymphoma of bone is uncommon and, hence presents diagnostic and therapeutic problems. Therapy management depends on classification which usually is done in four groups: 1. primary, 2. multifocal without nodal and/or soft tissue involvement, 3. multifocal with nodal and/or soft tissue involvement, 4. bone infiltration > 6 months after diagnosis. We analyzed the accurancy of Ga-67-SPECT in comparison to MRI for the monitoring of therapy response. Methods: 12 patients (21-68 years, median 43) underwent pre- and posttherapeutic Ga-67-SPECT, bone scintigraphy and MRI. Ga-scintigraphy was performed 48 hours after injection of 120-217 MBq Ga-67-citrate, SPECTreconstruction was done in cases of involvement of spine or pelvis. MRI was done with an 1.5 tesIa MR imager. Contrast media Gd-DTPA as a bolus 0,2 mmol/kg was administrated, dynamic and post-contrast images were aquired. All clinical results, laboratory investigations, diagnostic images and histological findings were used as a gold standard. Results: Ill defined lesions (n:7) of primary bone lymphema all has been detected by Ga-scintigraphy and MRI. After first line therapy, dynamic MRI correlates well with tumor size and remission status. Ga-scintigraphy identified properly residual activity in 3/3 lesions. In case of secondary involvement of the bone (17 lesions), sensitivity of Ga-scintigraphy was moderate (!2/17 true positive), while MRI detected all lesions of the examined regions. After first line therapy, signal intensity ofthe lesions correlates with clinical remission status. Conclusions: In cases of primary lymphema of the bone, Ga-scintigraphy and MRI are valuable diagnostic tools for therapy monitoring. After Ioca]isation of secondary involvement of the skeletal system with scintigraphic methods, MRI mirrores therapy response properly.

49.5

50.2

T.M. Behr, T. HomByounfar, S. Gratz, A. Herrmatm, E. Kruck, I. Schreivogel, and W. Becker. Department of Nuclear Medicine of the Georg-Augnst-Unlversity of G6ttingen, Germany.

F Nejmeddine, M Raphael, A. Martin, L Guillevin, JL Moretti, N Caillat-Vlgnero~. Nuclear Medicine, Haematology, Histopathology and Internal Medicine Departments, H6pital Avicenne, Bobigny, FRAN~.

IS THE ANALYSIS OF ENDOGENOUS THYROID HORMONE SYNTHESIS MORE SENSITIVE 1N DETECTING (MICRO-)METASTASES OF DIFFERENTEATED THYROID CANCER THAN THE DETERMINATION OF THYROGLOBULIN AND 131IWHOLE-BODY SCANNING ? The determination of serum thyroglobulin (Tg) levels and Na~;lI whole-body scanning are, together with clinical examination and other radiological procedttres (ultrasonography, CT, MRI) the gold standard in the follow-up of differentiated thyroid cancer (DTC) patients. The aim of this study was to assess whether the chromatographic analysis of the endogenous synthesis of thyroid hormones may be more sensitive in detecting tumor recurrences or (miero-)metastatic disease than these standard procedures. A total of 50 patients with DTC (25 papillary, 20 follicular, 3 Hfi~Ne cell, and 2 anaplastic cancers) were given 2-300 mCi Na~31I for diagnosis or therapy (all TSH _>40 gU/ml)= Whole-body scanning was performed over 72-168 h after 131I administration. Serum Tg levels were determined (normal values in athyroid patients _< 1.0 ng/dl). Additionally, the patients' serum was analyzed for the presence of 131I-TJT~ at 48-72 h after ~3tI administration: briefly, thyroid hormones were liberated from protein-Waading by 8-anilino-l-naphtalane sulfonic acid. The serum was analyzed chromatographically on a gel filtration column. Elution of radioiodinated proteins and unbound I was performed with PBS, thyroid hormones were eluted with TBG from normal donors' sera. Concordantiy positive results between the three diagnostic procedures (i.e., Tg, whole-body scans, and chromatography) were found in 27 patients, concordantly negative in 10 patients. From the 13 patients with discordant results, chromatography was the only positive method in 8 patients (2 of them of HitO.Ne cell histology). In one case, chromatography and Tg (1.2 ng/dl) were positive, in 2 cases were chromatography and scans positive at normal Yg values (0.6 and 0.9 ng/di, respectively), whereas in 2 cases scans and chromatography were (obviously false-)negative at pathological Tg levels (6.6 and 8.2 ng/dl, respectively). One of them became chromatographically positive at higher activities (100 instead of 2 mCi), the other case was an anaplastic cancer. In three of those patients, who were only chromatographically positive, "seroconversion" was demonstrated four to six months after therapeutic radioiodine administration (with activities ranging from 80 to 200 mCi). . . . The chromatographic assessment of 1 3 1 I-T3fr4 synthesis seems to be more. sensltlve in detecting micrometastases of DTC than the determination of serum Tg levels and whole-body scanning. Preserved ability to synthetize thyroid hormones was demonstrated in scintigraphically negative Hfirthle cell cancers as well. The only falsenegative case of tttis study may be due to Tg synthesis without iodine incorporation.

GALLIUM-67 IMAGING OF NON-HODGKIN' S LYMPHOMAS (NHL), CORRELATION BETWEEN HISTOPATHOLOGIC FINDINGS AND TRANSFERRIN RECEPTOR EXPRESSION. The aim of the study was to establish a relation between the Ga 67 uptake in different NHL and the intensity of the transferrin receptors (TfR/CDTI) expression on the tumoral cells. Seventy patients (pts) suffering from NHL have been included in this prospective study (40 males, 30 females, age range : 18-85). A histopathologic and J/mmnophenotypic analysis were performed according to the REAL classification. An evaluation of the TfR/CD71 expression was completed, in 31 pts among the 70, on frozen biopsies with 2 monoclonal antibodies. Imaging was performed within 48 hours after the injection of 0.6 MBq per kg body weight of Ga-67-citrate and analyzed by 2 readers blinded to the clinical data and to the results of the other imaging modalities. Tracer uptake was assessed in a region of interest drawn on the tumor (T) and in an area of same surface in the soft-tissue background (BGD). The ratio [(T-BGD)/BGD] was determined for each patient. Results : i)There is a highly significant relation between evaluation of the TfR/CD71 expression performed on the 31 frozen biopsies and the Ga-67 uptake ratio determined in the same pts. A strong expression of TfR ont he tumor cells is correlated with a high uptake of Ga-67 in the tumor (p < 0.0002). 2)Througt the 8 groups of the REAL clasification, the range of the Ga-67 upake ratio we obtained was 0-5. N~_L with a high grade of malignancy showed a strong. TfR expression on their cells and a Ga-67 uptake ratio strictly greater than 2. This study confirms Ga-67 as a very sensitive imaging agent in the evaluation of NHL and highlights Ga-67 as a specific molecular tracer for prognosis elements in the course of lymphomas.

929

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• Haematology- Oncology 50.3

50.5

R.W. Lipp, W.J. Schnedl, F. Aglas, G. Ranner, G. Hoefler, G. Leb, and H. Sill. Departments of Internal Medicine and Radiology, Institute of Pathology, KarI-Franzens-University Graz, Austria.

M. Pap6s, Z. Borbtnyi, L. Trdn, A, Cserh~iti, Marten, G. Varga, L. Csernay, L. P~ivics

BONE MARROW INVOLVEMENT IN PATIENTS WITH NONHODGKIN'S LYMPHOMA DEMONSTRATED BY IN-111OCTREOTIDE SCINTIGRAPHY.

E. Ambrus,

I.

Albert Szent-Gytrgyi Medical University, Department of Nuclear Medicine, 2nd Department of Medicine, Department of Radiology Szeged, DOTE PET Centre Debrecen, Hungary THE POSSIBLE ROLE OF FDG-PET AND MIBI-SPECT INVESTIGATIONS IN THE RESTAGING OF P A T I E N T S W I T H M A L I G N A N T L Y M P H O M A S AFTER THERAPY

Depending on different recording modalities, In-lll-[DTPA-D-Phe-1]octreotide scintigraphy shows sensitivities between 57 and 87% for the demonstration of non-Hodgkin's lymphoma (NHL) without evidence of bone marrow involvement (BMI). The study intended to demonstrate BMI by an adapted method simultaneously increasing the sensitivity of lesion detection. Ten selected patients presenting with histologically proven NHL (8 low and 2 high grade) and with 50 to 100% BMI were included into the study. Long-time SPECT (60 sec per frame, 3 ° interval) of neck/thorax and abdomen/pelvis was recorded with a double head gamma camera 4 hours after i.v. administration of 20 gg octreotide labeled with 191-360 MBq (mean 254) In-I 11. Three to 7 days later, SPECT of the same regions (15 sec per frame, 3 ° interval) was recorded 4 hours after i.v. administration of 0.5-1 mg monoclonal antigranulocyte antibody (Mab 250/183) labeled with 361-595 MBq (mean 454) Tc-99m to show bone marrow distribution. Three dimensional image reconstruction served for the interpretation of results. The In-lll-octreotide scan of one patient with high grade NHL (100% BMI) showed multifocal BMI (cranial bones, spine, pelvis and femur) correlating with cold lesions in the anti-granniocyte scan. The antigranulocyte scan of a second patient (low grade, 90% BMI) showed a cold focal lesion in the ninth thoracic vertebra, not corroborated by the In-111octreotide scan. The In-111-octreotide scans showed extramedullary lesion sites in these 2 and in another 5 patients (70%). The lesion related sensitivity (10 patients) was 60% above and 30% below the diaphragm resulting in a total sensitivity of 48%. There was no false positive result, the smallest lesion correctly identified by scintigraphy had a diameter of 1 cm, the largest lesion missed measured 3.5 cm. In conclusion, In-111-octreotide scintigraphy visualized in bone marrow the presence of lymphoma ceils only when these were tightly packed to loci expressing high densities of somatostatin receptors. Loosely distributed lymphoma cells within bone marrow escaped detection but the used method increased the sensitivity for extramedullary lymphoma detection.

In 14 patients (9 with Hodgkin disease (HD) and 5 with high-grade non-Hodgkin lymphoma (NHL)), 16 FDG-PET and MIBI-SPECT investigations were carried out (2 were repeated investigations in different clinical stages of the disease). The CT findings suggested a residual tumour mass in all of the patients. FDG-PET investigations (multiple scans) of the suspected regions were carried out following administration of 225-518 MBq F18-FDG. Early and late planar and SPECT studies were also applied, using 720-804 MBq of Tc99mMIBI. The reconstructed slices were evaluated visually by three nuclear medicine specialists. FDG-PET revealed an active tumour mass in 15 of the i6 cases, localized in 34 of the 36 suspected regions. Four occult lesions were also detected by PET. A pathological MIBI uptake, however, was found in only 10 cases in 14 regions. Repeated treatment was indicated one month after the investigations, on the basis of the clinical and laboratory activity signs of the disease (more than 10% weight loss, nightsweat, fever, enhanced blood sedimentation rate and elevated LDH level). Of the 10 cases who required second-line therapy, 9 gave a positive MIBISPECT. Of the 6 patients who showed no activity signs, 5 had previously furnished a negative MIBI-SPECT. Second-line therapy was effective (more than 50% reduction of tumour mass on CT or chest X-ray) in 5 patients, whereas 5 cases proved to be nonresponders. Conclusions: FDG-PET and MIBI-SPECT revealed different biological features of HD and NHL. A positive MIBI-SPECT result predicts the later activation of the lymphomas and the need for second-line therapy.

50.4

50.6

B.M. Dohmen, M. StkIer, R. Lietzenmayer, M. Mitiler-Berg, W. Brugger, L. Kanz, R. Bares. Departments of Nuclear Medicine and Internal Medicine II, Eberhard-Karls-University, Tfibingen, Germany.

H Younq, M Deenamode, D Glass, D Swirsky, AM Peters. Department of Imaging and Haematology, Hammersmith Hospital, London, UK.

FDG-PET FOR CLASSIFICATION OF RESIDUAL OR RECURRENT TUMOR 1N HODGKIN'S DISEASE OR HIGH-GRADE NON-HODGKINLYMPHOMA.

WHOLE BODY PET IMAGING OF ERYTHROPOIESIS WITH 52FE-TRANSFERRIN AND A 3D PET SCANNER, THE ECAT ART 52-Fe-transferrin imaging may provide information on the distribution of erythropoietic tissue, complementing in vitro ferrokinetic measurements with 59-Fe-transferrin. 52-Fe-transferrin is a positron emitter and the injected activity is limited to 7Mbq by dosimetry. Single photon imaging results in low quality images due to high photon energy (511keY) and low photon flux. The ECAT ART, a low cost, partial ring, rotating, fully 3D PET camera with a sensitivity of 11400 cps/kBq/ml, was evaluated for imaging 52-Fe-transferrin. 12 subjects with a range of erythropoietic disorders had whole body scans, 16 hours post injection of 52-Fe-transferrin (5-7MBq). Reduced marrow uptake with extramedullary erythropoiesis in the spleen correlated with disease progression in myelofibrosis (n=3). Marrow expansion was seen in sickle cell anaemia (n=l), increased iron utilisation (n=2) and atypical handling of iron (n=l) demonstrated from vitro ferrokinetic studies. High iron uptake was demonstrated in the liver with aplastic anaemia (n=l). Normal distribution was demonstrated in simple iron deficiency (n=2) and normal ferrokinetics (~=i). In conclusion, 3D whole body PET with the ECAT ART produces images of sufficient statistical quality to accurately localise intra and extra medullary erythropoiesis with 52-Fe-transferrin.

Purpose: Differentiation between residual/recurrent vital tumor and scar or inflammatory tissue is a common problem in treatment control of patients with malignant lymphoma. The diagnostic reliability of morphological criteria like tumor size or shape, investigated by ultrasonography, CT or MRI is limited. Therefore FDG-PET was evaluated for detection of viable lymphoma tissue in morphologically suspicious lymphatic nodes. Methods.33 patients with residual lymphoma (n=lt) or suspected tumor recurrence (n=lT) of either Hodgkin's-disease (n=15) or of high-grade NHL (n=18) were enrolled in the study. Static attenuation corrected PET scans of morphologically suspicious lesions were obtained after i.v. injection of 350 MBq [F-18]-FDG. Focally increased FDG-uptake was used as sign of malignancy. Findings were validated by histology (n=lt) or clinical follow-up (n=17). Results: FDG-PET was correct in 13 out of 16 patients with residual Iymphoma masses (6 TP, 7 TN). Two patients with false negative findings relapsed 2 resp. 5 month after the negative PET-scan. One false positive result was obtained 8 weeks after radiotherapy. Recurrent tumors were correctly classified in 15 or 17 patients (14 TP, 1 TN). False positive results were due to a histologically proven lymphatic byperplasia and a case of sarcoidosis. Thus, FDG-PET showed a 91% sensitivity and 73% specificity. Positive and negative predictive value were 87% and 80%. Conclusion." FDG-PET appears to be a sensitive technique for the diagnosis of residual as well as recurrent malignant lymphoma. Inflammatory disease can cause false positive results, which can possibly be avoided by use of more selective tracers like [C-11]-thymidlne. Small tumor cell clusters in residual tumors, leading to relapse after a longer disease-free interval, can be missed.

930

[] P h y s i c s Physics 51.1

W.-G.Franke, R.Freyer*, T.Schmitt*, L.Oehme, M.Paukert* Department of Nuclear Medicine and *Institute of Biomedical Engineering, Dresden Unversity of Technology SPECT VOLUME QUANTITATION USING A HYBRID TWO STEP SEGMENTATION SCHEME

The first step in quantitative evaluation of single photon emission computed tomography images is the determination of the functional volume of a region (organ, anatomical structure,lesion). Volume quantitation in SPECT data is usually performed by counting the voxels inside the borders of a 3D region and multiplying the sum by the elementary voxel volume. The border determination is performed by image segmentation mostly based on interactive drawing of ROI ore semiautomatic clustering or edge detection methods. The image quality properties of SPECT render this process more difficult in any case. In our proposed quantitation scheme (hybrid two step procedure) we substitute the crisp segmentation (object voxel y/n) by a consideration of sub-voxel volumes in the object border region. The objects to be evaluated are assumed to consist of a kernel and a shell region. The kernel voxels contribute completely and with high reliability to the object volume and are determined in the first step by a 3D clustering method. The contribution of the shell voxels is partially and uncertainly. A fuzzy model was found to be suitable for describing this uncertainty. The input of the fuzzy shell model is given by a set of 3D image signal properties corresponding with surface information e.g. the grey value gradient. Depending on the membership of these local properties to characteristic fuzzy sets and based on fuzzy rules the partial object volume of each shell voxel is calculated in the second step. Both fuzzy rules and membership functions were optimized for phantom studies and clinical studies (thyroid, myocard) of various image quality. The quantitation results (3-5 % deviation in phantom studies) were shown to be of higher accuracy than from crisp segmentation methods using only edge detection, thresholding or interactive ROI drawing.

51.2 JJ Sychra, MJ Blend. U n i v e r s i t y of Illinois Hospital, C h i c a g o

SPECT IMAGING OF METASTATIC PROSTATE CANCER: A COMPUTER METHOD FOR TUMOR DETECTION Current imaging procedures such as CT and MRI are insensitive to the early spread of prostate cancer to regional lymph nodes. W h o l e body and S P E C T imaging with the radio labeled monoclonal antibody C a p r o m a b Pendetide (In-111 MoAb 7E11 -C5.3 or CYT-356) has been shown to dramatically increase the detection of early spread of disease in prostate cancer patients. However, I n m M o A b - C Y T - 3 5 6 can be seen in tumor tissue (including perivascular nodes) as well as in the vascular system. This makes metastatic tumor detection difficult especially if involved nodes are located in close vicinity of blood vessels. S P E C T acquisition of T c 9~n-labeled red blood cells obtained at the same time as I n m - M o A b imaging can define the vascular system, and can be used to suppress the vascular component in In m M o A b based images to aid in the detection of metastatic disease. W e have developed a three-pronged approach to the detection of metastatic prostate tumors, based on single simultaneous I n m M o A b and T c ~m S P E C T acquisitions. It eliminates the registration problem, reduces the time required for a patient to lie still for imaging, increases imaging system throughput, and patient scheduling is simplified. T h e first part of the method is based on dynamic subtraction of the T c ~ n (vascular) component from the In TM image and is supplemented by cluster and projection analyses of the 2-D histogram of InTM and Tc~ voxel intensities. Successful testing on twenty patients has yielded 59% more of suspicious lesions than the routine clinical evaluation of the I n m M o A b images alone, and has lead to a reversal of negative diagnosis in three cases. Future version of this method will include a Compton scatter correction, statistical analysis of significance of the dynamic differences of In m and T c 9sin images, S P E C T / M R / C T image fusion, and dosimetric analysis.

51.3 C. Burqer§§, K. Mikolajczyk~, M. Szabatin~, P. Rudnicki ~ §~Divisionof Nuclear Medicine;UniversityHospital, Zurich, Switzerland §Institute of Precision and Biomed. Engineering, Warsaw Univ. of Technology, Poland

A JAVASOFTWAREENVIRONMENTFOR QUANTITATIVEPOST-PROCESSINGOF BRAINPET DATA Purpose: Brain PET is a discipline with a high level of research activities. There are two major domains which have resulted in workable models: Kinetic models can transform adequately measured data into quantitative images of brain function. The advantage of obtaining pedusion, blood volume of glucose turnover rather than mere counts is obvious. Spatial normalization techniques allow to elastically transform individual brain images into the stereotactic coordiante space. The use of normalized images has several advantages. For instance, images of a study population can be to derive a normal distribution (,,normals database") against which an individual patient's image can be pixel-wise compared. The objective of the present project is to combine these techniques in a comprehensive, portable software package in order to make the relevant research achievements accessible for clinical use. Methods: The functionality is structured into three main modules. (1) A pixel-wise modeling tool supports input of sampled blood data and dynamic PET Data. The initial models include calculation of glucose turnover (Patlak), brain perfusion (invasive and non-invasive approach), and blood volume. Blood data may be pre-processedto decenvolvedispersion effects. (2) A spatial normalization ton performs eIastic transformation into the stereotactic Talairach space. The transformation can be calculatedwith one dataset (eg. transmission images), and be applied to another set (eg. functional images). (3) A volume-of-interest(VOI) tool allowing define 3-dimensional VOIs and apply them to image data. The main intent is to set up a database of VOIs in the Talairach space in order to run standard VOI analyses on normalized images. The three tools are able to exchange information. For instance, time-activity curves from standardized regions can be supplied to the modelling tool by calculating the normalization transform, applying it to the dynamic data, and summing the counts within a standard ROI taken from the database. Aiming at maximal software portability, WWW-standards were chosen as the implementation platform: JAVA is the programming language, and definition/display of ROIs is based on VRML. Data portability is ensured by supporting image input/output with DICOM3.0 and flat fiIe formats. Results: An initial version of the pixel-wisemodelling tool has been completed. It demonstrates that rapid software development is possible in JAVA. However, due to the short lifetime of JAVA, the developer faces several difficulties: cross-platform portability is not yet complete regarding file I/O and user interface; garbage collection becomes a problem for memory-intensiveapplications; a performance penalty, although not severe when a just-in-time-compiler. Conclusions: A complex and camputationally demanding application has been realized in JAVA within 6 months. The approach chosen brings pixel-wise kinetic modeling as the first of a suite of functional brain image processing modules into everybody's reach. Acknowledqement: This work is supported by the Swiss National Science Foundation, Program for Cooperation with CEEC/NIS, Project 7PLPJO48289.

51.4 WCAM Buiis, JA Siegel and FHM Corstens, Department of Nuclear Medicine, University Hospital Nijmegen, Tile Netherlands,

ESTIMATION OF ABSOLUTE ORGAN ACTIVITY USING FIVE DIFFERENT METHODS OF BACKGROUND CORRECTION: A PHANTOM STUDY. For the purpose of patient-based dosimetry in radioimmunotherapy, estimation of absolute organ uptake is necessary. The methods used preferably should be accurate as well as easy to perform in routine clinical practice. One of the major sources of uncertainties in quantification of organ activity from planar images is the activity present in tissue surrounding the target. Method. To validate the estimated organ activity as a function of contrast, a cylindrical phantom with a diameter of I8.5 cm was filled with 5.6 litre water to simulate the abdomen of a patient. Two other cylinders of 150 ml each were filled with approximately 19 MBq of 99mTc to simulate kidneys and were positioned in the abdomen phantom. The phantom was imaged with a dual headed camera with the kidneys placed at posterior depths of 1, 5 and 10 cm. Activity was then added to the major cylinder resulting in kidney:background ratios of 10:1,5:1, and 2: I. The phantom was imaged at the three kidney depths for all linage contrasts. The conjugate geometric mean method was used to quantify activity. Five methods for background correction were applied: 1. no correction; 2. routine background correction; 3. Kojima method (background corrected for organ thickness and depth); 4. Thomas method (analytical solution); 5. Bulls method (background corrected for organ and total body thickness). Results. The accuracy of these methods can be given as % difference from measured activity in left kidney: for method 1 the % difference ranged from + 1% with infinite contrast to +4t 1% for the contrast 2:1 case. For method 2 these figures are -1% to -80%, for lnethod 3 from +10% to -18%, for method 4 from -3% to +119% and for method 5 from -4% to +39%. In conclusion, even though quantitlative SPECT is the most rigorously correct method for activity quantification in conditions of low image contrast, planar scintigraphy can be accurately applied if appropriate attention is paid to background correction. The planar technique can result in accurate activity estimates using very simple methods (methods 3 and 5).

931

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• Physics/Radiopharmacy Radiopharmacy 51.5

52.1

O. Nickel, H. Speckter, J. Andreas, Dept. of Nuclear Medicine, Johannes Gutenberg-University Mainz, Germany

S. Srivastava, K. Kolsky, V. Joshi, M. Sweet, G. Meinken, L. Mausner. Medical Department, Brookhaven National Laboratory, Upton, NY.

THE USE OF ANATOMICAL 3D ROI TEMPLATES FOR BRAIN SPECT QUANTIFICATION Aim of study: The quantification of brain SPECT requires a standardization of the regions of interest as well as an exact definition of their position in space relative to a standardized coordinate system. We developed a method, which allows an exact matching of 3D ROI templates to the individual brain anatomy, independent of external markers or additional CT or MR tomograms. Method: We define, in analogy to the coordinate system of Talalrach, a proportional system, which is given by the brain "long axis" and borderpoints of the outer cortex. The long axis is defined from a 2-3cm thick mediosagittal slice by an algorithm, which finds the longest distance between the frontal and occipital cortex. Relative to this coordinate system we defined 3D ROI templates for measuring SPECT countrates. We constructed 2 sets of templates: One set divides the whole brain into 74 geometrical sectors; it is suitable for the relative quantification of brain perfusion studies. The other set is adapted to the anatomical structures and is suited for the quantification of brain receptors. Results: The method was usable on all examinations, which we tested in our department (HMPAO, IBZM and Iomazenil) and resulted in a reliable standardized reorientation of the brain tomograms. The adaptation of the ROI templates to the individual brain requires small shifts of ROls, which are done interactively. In follow-up studies this has to be done only once, the ROI dataset can then be applied without interaction to the following examinations. Conclusions: The method allows a standardized semiquantitative measurement of tracers in the brain. It is a requirement for a comparison with a normals database, to get a reliable quantitative information about brain perfusion or receptor kinetics.

Medicine,

St.

Principal Component Based Parathyroid Gland Detection

Principal components in conjunction with MIBI imaging have been applied to the detection of parathyroid glands in primary and tertiary hyperparathyroidism. A set of principal components are derived from within a ROI defined over the pertechnetate thyroid gland. For each pixel fully contained within the ROl,the counts from all the pixels in a 5 x 5 neighbourhood are combined into a feature vector which may be thought of as being attached to that central pixel. We calculate for the projection of the data from the MIBIPertechnetate thyroid onto the principal components derived from the Pertechnetate thyroid a standard (Mahalanobis) distance from the mean which is distributed as a chi-square with degrees of freedom equal to the number of principal components used. In this work 7 principal components were used accounting on average for over 97% of the variance in the data set. The analysis is repeated separately for both the thyroid and neck regions as these regions possess different underlying textures and the final results formed from a combination of these two sets of results. This approach to parathyroid gland detection has advantages over conventional subtraction imaging in that image normalization is not required and a quantitative statistical measure of significance of detection is returned. An increased robustness with respect to image misregistration is also seen in clinical practice. The method has a potential wide range of applications for change detection in other areas of nuclear medicine.

932

Purpose: We have optimized the production at BNL of Sc-47 (tV2 3.35 d; 13m~441 keV, 68%, 601 keV, 32%; 7 159 keV, 68%) and investigated the labeling chemistry and biodistribution of Sc-47 labeled immunoconjugates. Methods and Results: Sc-47 was produced using the 47TiO2 (n,p)47Sc fast neutron reaction (specific activity 0.3-30 GBq/gg). Radiochemical processing was optimized to reduce production cost, to improve chemical purity, and to optimize subsequent protein labeling reactions. An antiCEA F(ab')2 MAb was used to study the stability and biodistribution of the radioconjugates. Four chelating agents were used: 4isothiocyanatocyclohexyi EDTA (4-ICE); mono-NHS ester of DOTA (DOTA-NHS); 2-(p-SCN-Bz)-6 methyl DTPA (IB4MDTPA - courtesy of O. Gansow, NIH); and the conventional DTPA dianhydride (DTPADA). Labeling yields (average of 3 ligands per MAb) were between 7595%, and stability in serum measured out to 96 h was >95% for all preparations, except for DTPA-DA (83%). Immunoreactivity ranged between 70-80%. HPLC-purified fractions were administered i.v. into human tumor (LS-174T cells) xenografted nude mice (n=5 for each data point) to study biodistribution (% ID per g). 4-ICE, DOTA-NHS and 1B4M-DTPA all showed high tumor uptake at 48 h (32.2, 34.7, 27.9). Kidney uptake of 4-ICE was higher than DOTA-NHS or 1B4MDTPA (15.4, 7.0, 7.0) but the uptake into liver was higher for DOTA-NHS than 4-ICE or 1B4MDTPA (9.4, 5.8, 5.6). The DTPA-DA conjugate that had lower serum stability also gave poor tumor uptake (12.4), and high kidney (14.8) and liver (17.1) uptakes. Conclusion: We have developed the large-scale, cost-effective reactor production of high-purity no-carrier-added Sc-47, and demonstrated its potential for labeling antibodies for radioimmunotherapy. Similar chemistry can be used for labeling peptides and other bioactive molecules. Work done under US DOE, Contract #DE-AC02-76CH00016.

52.2

51.6 M. J. Carroll, KE.Britton. Dept of Nuclear Bartholomew's Hospital, London, England.

DEVELOPMENT OF SCANDIUM-47 AS A 13-/7 THERAPEUTIC LABEL FOR ANTIBODIES AND PEPTIDES.

P.Bouzioti, A.D.Varvarigou, S.C. Archimandritis, M.Papadopoulosand E. Chiotellis NC.SR.'Demokritus', Inst. Of Radiodiagnostics, Aghia Paraskevi 15310 P..O.Box 60228 GREECE PREPARATION AND EXPERIMENTAL EVALUATION OF A SERIES OF SAMARIUM-153 COMPLEXES

In the present study we have prepared a series of polyacetate and polyphosphonate ethylenediamine derivatives and we have investigated their ability to tag Samarium153. The radionuclide was producedby six hours irradiation of non-enriched Sm-152 in a 5.0 MeV reactor, at a flux of 1.3-1.5 x 1013rdcm2 sec and was identified by y spectroscopy. The amines investigated were the following: Comp. I. EthyleneDiamine TetramethylenePhosphonic Acid (EDTMP) Comp. II TetraazaCyclododecaneTetramethylenePhosphonic Acid (DOTP) Comp. III. Ethylene Diamine-[( N,N'Dimethylene-DiphosphonicAcid)(N,N'Dimethylene- DiaceticAcid)] (EDDADP) Comp. IV. Tetraaza CychidodecaneTetramethylene Acetic Acid (DOTA) Synthesis was accomplished according to literature procedures. Compound I, which is reported in the literature as yielding the most well established Samarium-153 radiopharmaceutical for pain palliation from bone metastases, has been prepared as reference. All the compounds synthesized were identified by elemental analysis, IR and 1H-NMR spectroscopy. For the labelling, a solution of 153SmC13was added to a neutral or alkaline solution of the ligand and the final pH was adjusted to 7.0-7.5. The yield of labelling and the stability of the complexes formed were examined by chromatographic techniques. In vivo biodistribution of the radiolabelled Samarium complexes was evaluated in mice, with particular focusing on blood clearance, urine elimination and bone uptake. Chromagraphic findings indicated high yield of labelling (> 97%) and great in vitro stability of the radiolabelled species, both in refrigerator and at room temperature, up to 4 days after the preparation. Biodistribution results demonstrated that Sm-153 forms stable phosphonate and acetate derivatives, eliminated exclusivelythrough the renal system. Low to zero liver uptake showed that no colloids were formed in vivo, with any of the complexes investigated. Samarium phosphonates (Comp. I and III) presented significant skeletal localization. Bone values (% dose/organ) depended on ligand structure and were about 30 for Comp. I and 20 for Comp. II1. Samarium acetates ( Comp. II and IV) did not localize at any particular organ or tissue. Animal studies have shown that, among the Samarium complexes evaluated, lS3Sm-EDTMP presented the most interesting biodistribution, in mice. Comparative 1H-NMR and crystallographic studies of the above chelates are in progress, in order to find out their exact structure and be able to design new Samarium-153 agents.

m Radiopharmacy

52.3 C. Van de Wiele, B. De J. Philipp6, C. Dhooge H o s p i t a l Gent, B E L G I U M

PgP RELATED NEUROBLASTOMA

Moerloose, J P . V a n Haelst, RA. Dierckx, University

Tc-99m M~BI CELL LINES

UPTAKE

IN

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

co

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co

HUMAN

A standardized in vivo assessment of Pgpe x p r e s s i o n p r i o r to c h e m o t h e r a p y initiation could p r o v i d e important information concerning the r o l e of Pgp in neutroblastoma and its relation to c l i n i c a l o u t c o m e . T h e r e f o r e , we e x a m i n e d the u p t a k e c h a r a c t e r i s t i c e of T c - 9 9 m MIBI in the a b s e n c e or presence of i00 ~M verapamil,a known P-gp inhibitor, in 3 human neuroblastoma cell lines (GI-M-EN, SK-N-FI and SK-N-SH) with known P-gp expression and function as determined by immunocytochemistry and flow cytometry. A d d i t i o n a l l y , T c - 9 9 m MIBI r e t e n t i o n was d e t e r m i n e d in a P-gp p o s i t i v e and P-gp n e g a t i v e cell line (SK-N-FI and GI-M-EN). Serial T c - 9 9 m MIBI u p t a k e s (in the p r e s e n c e or a b s e n c e of i00 ~M v e r a p a m i l ) were determined at fixed periods of time by measuring the radioactivity retained in P e t r i dishes after w a s h i n g w i t h ice cold HBSS, using a ganumaprobe at fixed distance. Tc-99m MIBI r e t e n t i o n was m e a s u r e d after 30 m i n u t e s e f f l u x . Tc99m MIBI u p t a k e by cell lines o v e r e x p r e s s i n g P-gp (SK-N-FI and SK-N-SH) was found to be lower than the u p t a k e by the P-gp n e g a t i v e cell line G I - M - E N , and increased significantly when verapamil was added to the cell suspension. The accumulation ratios were 0.35, 3.04 and 2.49 for GI-M-EN, SK-NFI and S K - N - S H r e s p e c t i v e l y . The r e t e n t i o n ratio was 0.28 for GI-M-EN and 3.74 for SK-N-FI.In conclusion, T c - 9 9 m MIBI can be u s e d to d e t e r m i n e the P-gp status of n e u r o b l a s t s in vitro.

THE POTENTIAL OF INTERLEUKIN-1, ITS RECEPTOR ANTAGONIST AND A CHEMOTACTIC PEPTIDE FOR IMAGING OF INFECTION. A COMPARATIVE STUDY, There has been a growing interest in the development of small receptor binding agents as radiepharmaceuticals for imaging of infection and inflammation. Interleukin-1 and chemotactic peptides are such promising agents. In the present study, the potential of two forms of interleukin-1 (IL-le~ and ILIB), the interleukin-1 receptor antagonist (IL-lra) and the synthetic chemotactic peptide, N-formyl-methionyMeucyl-phenylalanyMysine (fMLFK) for imaging of infection and inflammation were directly compared in a rabbit model of infection. Human recombinant IL-lc~, IL-I~, IL-I ra and fMLFK were radiolabelcd with 1-123 according to the Bolton-Hunter method. Twenty-four hours after induction of Escherichia call abscesses in the left thigh muscle, rabbits were i.v. injected with 0.5 mCi '~-3I-IL-lc< Ez3I-IL-18, '23I-IL-lra or J~31-fMLFK. Gamma camera images were obtained at 5 rain, 1, 4, 8 or 20 hr p.i. Biodistribution was determined at 20 hr p.i. The in vitro receptor binding capacity of all radiopharmaceuticals was preserved after the labeling procedure. Although all radiopharmaceuticals rapidly cleared from the blood, at 20 hr p.i., blood levels of =z3I-fMLFK (0.0009 + 0.0001) were significantly lower titan of the other studied agents (p < 0.03). The abscesses could be clearIy visualized with all agents from 4 hour p.i. onwards. After 20 hr, the highest abscess-to-contralateral muscle ratios were obtained with 123I-IL-1B, i.e. 36.0 ± 6.3 versus 18.7 ± 5.4, 18.1 +_ 2.3 and 29.9 _+ 7.0 for respectively ':3I-tL-lcq ~231-IL-lra and '23I-fMLFK. The abscess uptake of ~nI1L-II~ (0.01 ± 0.002) was significantly higher than of E23I-IL-lra (0.006 ± 0.0005) and 123I-fMLFK (0.003 _+ 0.0007)(p<0.05). In conclusion, all studied agents localized in the infectious focus. The potential of radiolabeled IL- 11~for imaging of infection is better than of the other agents: higher absolute uptake in the infection and higher abscess-to-contralateral muscle ratios were obtained. The observation of localization of radiolabeled ILIra was important since this protein can be administered to humans without any side-effects.

52.4

52.6

O.C. Boerman W.J.G. Oyen, G. Storm, L. Corvo, F.H.M. Corstens. Department of Nuclear Medicine, University Hospital Nijmegen and Department of Pharmaceutics, University of Utrecht, The Netherlands.

S.Gratz, T.Behr, A.Herrmann, L.Tarditi 3, R.Franceschini 3, B.Rhodes 4, E.Weber KM.StL~rmer~, W.Becker Department of Nuclear Medicine and Department of Trauma, Plastic and Reconstructive Surgery 2 of the University of G6ttingen, FRG, SORIN Biomedica a, Saluggia, Italia and RHOMED 4, Albuquerque, New Mexiko, USA

LIPOSOMES LABELED WITH Tc-99m TO IMAGE EXPERIMENTAL ARTHRITIS. Liposomes coated with polyethylene glycol (PEG) can be used to visualize infectious and inflammatory loci in soft tissue. The hydrophilic PEG-tails cause the formation of a water mantle around the liposomes, reducing their recognition by maerophages. As a result their residence time in the circulation is enhanced and their localization in inflammatory loci is improved. In the present study the ability of PEG-tiposomes to image arthritis was tested and compared to non-PEG liposomes in a rat model. Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labeled with Tc-99m: (i) non-PEG-liposomes, (ii) PEG-liposomes or (iii) nonspecific human polydonal IgG. Liposomal formulations were labeled using HMPAO-Tc-99m for transport over the lipid bilayer. The complex was trapped within the liposomes due to reduction of the complex by encapsulated glutathion. For each of the radiopharmaceuticals the in viva distribution of the radiolabel was monitored both scimigraphically (0-24 hr) as well as by counting the dissected tissues at 2, 8 and 24 hr p.i. The pharmacokinetics of the radiopharmaceuticals differed markedly; halflife in the blood: PEG-liposomes (18 h) > 99mTc-IgG (3 h) > non-PEG liposomes (1 h). The inflamed focus was visualized with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood; inflamed joint uptake: PEG liposomes (1.15 %ID/g) > 99mTc-IgG (0.35 %ID/g) > eon-PEG-liposomes (0.05 %ID/g). Quantitative analysis of the images revealed that the inflamed ankle-to-background ratio was highest with the PEG-liposomes (7.5 at 24 hr p.i.), while with the other two agents this ratio did nat exceed 4. In conclusion, this study shows that 99roTe-labeled PEG-liposomes can be used to visualize arthritis. Enhanced label uptake in the inflamed joint and enhanced target-to-background ratios can be obtained with PEG-liposomes due to their enhanced circulatory half-life. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the sitespecific delivery of anti-rheumatic drugs.

Tc99r"-LABELLED ANTI-SSEA-1 IgM ANTIGRANULOCYTE ANTIBODY : Biodistribution, dosimetry and affinity. Rationale: Aim of this study was to evaluate first kinetic data and the radiation absorbed doses to the organs of this new 99mTc-labelled antiSSEA-1 antigranulocyte antibody.Patients and methods: 17 patients with proven infectious loci were examined with 555 MBq 99mTc SSEA-1 murine monoclonai antibody (RHOMED, USA, SORIN, ITALIA). Whole body images with the antibody were performed 1h, 4h and 24h p.i. Blood sampling was done at 5, 15, 30, 45 and 60 rain. after the antibody injection for performing a discontinous Percoll~/plasma gradient evaluation for the determination of the recovery, for performing a scatchard plot for the affinity determination of SSEA-1 and for the white blood cell control. In order to determine the cell bound fraction of the radiolabelled antibody at various time points, the activity in the supematant and in the pellet was measured. The radiation absorbed doses were calculated by using the MIRD concept. Results: The activity present on granulocytes was found to be 5, 15, 30 and 45 min. p.i. respectivelly 33.5%, 30.6%, 21.3% and go%. The affinity constant of the ~ m Tc labelled IgM SSEA-1 antibody ( Leuko - 1 ) was calculated to be K a = 1.6 x 10 ~2 I / mot. The peripheral leukocyte count after mab injection showed a temporary decrease of the white blood cells in the first 15 minutes of about 2148% without any clinical symptoms and any changes in the vital signs at this time. From the cell bound, the binding of the anti SSEA-1 to granulocytes was found to be 90% until lh p.i. The cell bound constant was measured to be 40%. The dose rate measured in coy / mCi delivered to the wholebody was 1.1 x 1 0 2, liver 6.5 x 10-,2 spleen 2.4 x 10-,1 both kidneys 5.9 x 1 0 2, lung j1.2 x 10-,2 ovaries 9.4 x t0",3 testes 3 5.9 x 10-3 and thyroid 7.9 x 10-.The effective dose was 1,97x10-.2 Conclusions : The rapid blood activity clearence and the good target/background ratio, the high affinity constant, the easy handling and the tow radiation exposure make this new antibody a promising in vivo labelling agent of granulocytes.

933

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• Neurology Neurology 53.1

53.3

M.O Habert l, E. Landr~ ~, F. Chassoux t, A.M. Bernard 2, A. Biraben 3, A. Francois-Joubert 4, P. Kahane 4, M. Zanca s, P. Coubes 5, L. Minotti 4' K. Benah.6. iSte-AnneHosp. Pans. 2E. Marqffls . Hosp,3Pontchafllou • Hosp. Rennes. A. MichallonHosp, Grenoble.sG. de ChauliacHosp, MontpelIier.6R. Debr4Hosp, Paris.France.

F.J. Setoain, P. Lome~a, S. A r r o y o , J. Pavia, A. C a t a f a u , J . RumiA ~, S. V i d a l S i c a r ~ a n d J . S e t o a i n . S e r v . de M e d i c i n a N u c l e a r , N e u r o l o g i a ~ a n d N e u r o c i r u g i a ~. H o s p i t a l c l f n i c de B a r c e l o n a . Spain.

A MULTICENTER STUDY OF 99mTc-ECD SPECT IN PATIENTS WITH DRUG-RESISTANT PARTIAL EPILEPSY : CORRELATION WITH STEREO-EEG (SEEG) - PRELIMINARY RESULTS. The aim of this study is to determine the value - in terms of localization of the epileptogenic zone (EZ) - of SPECT with 99mTc-ECD in the presurgical check-up of adult patients with refractory temporal or extratemporal (ET) epilepsy, on the basis of SEEG data and/or clinical evolution after cortectomy. The selection criteria superpose to the indications of the surgery. All patients undergo a workup including clinical and neuropsychologicaI examinations, video-EEG, MRI and interictal SPECT. An ictal SPECT is made either during the pre-SEEG check-up with a concomitant scalp EEG, or during SEEG recording of spontaneous or electrically induced seizures (EIS). In order to obtain a common anatomical reference system for SEEG and SPECT data, SPECT slices were reorientated according to AC-PC line I. To date, 74 pts had ictaI SPECT, 37/74 having completed SEEG, 10/74 had cortectomy without previous SEEG. Different ictal SPECT patterns were observed: 1) MTC+LTC hyperperfusion in seizures originating from MTC; 2) temporal hypoperfusion in cases of MTC EIS; 3) <> of interictally hypoperfused regions which were part of EZ; 4) various patterns of hyperperfusion in LTC, FTC or ET seizures; 5) non conclusive or normal. Pattern 1 has already largely been described. Patterns 2 and 3 are Iikely to be related to the different nature of EIS (shorter and involving smaller volume) and to the choice of 99mTc-ECD as the tracer. Few data have yet been provided in pattern 4 seizures. Although comparison between SPECT and SEEG information raise some methodological difficulties, such correlations allow an analysis of the timing of tracer injection in comparison with onset and propagation seizure, therefore, a better understanding of the significance of ictal SPECT alterations. i p. Veraet al. Eur J NuclMed (1996)23:871-877.

ICTAL/POSTICTAL ~=TC-HMPAO BRAIN SPECT IN EPILEPSY The aim of the study was to assess the uzility of interictal and peri-ictal (ictal - postictal)'~}°~Tc-HMPAO SPECT in patients with medically intractable epilepsy. Material and methods: Interictal and peri-ictal brain SPECTs were carried out on 37 of 86 patients that were admitted to the presurgical evaluation of medically refractory seizures. The seizure focus was determined by ictal video-EEG studies. 24 patients suffered from temporal lobe epilepsy (TLE) and 13 had extratemporal seizures (ETE). The ETE were localized in frontal lobe (i0), parietal lobe (2) and one patient presented hypothalamic gelastic seizures. Interictal brain SPECT were performed on all patients with 740 MBq of ~ T c HMPAO. Ictal SPECT were carried out on 14 patients and the remaining 23 patients had early postictal SPECT. Peri ictal SPECT were performed with 555-740 MBq of ~gmTc-HMPAO. Image acquisition was performed in a DualHead gamma camera system with Fanm-beam collimators. Results : Interictal brain SPECT showed hypoperfusion in the seizure foci in 16/37 patients (58% on TLE and 15% on ETE). Ictal SPECT showed focal hyperperfusion in the seizure foci in 13/14 patients (i00% on TLE and 75% on ETE, where wrong localization was observed in a frontal seizure). Finally, early postictal SPECT correctly localized the seizure foci in 12/23 patients (71% in TLE 10/14 and 22% in ETE 2/10). Conclusions : Interictal brain SPECT may be useful in the localization of the seizure foci in patients with temporal lobe seizures. The ictal SPECT (in patients with TLE and ETE) and the postictal SPECT (in those with TLE) provide high sensitivity for the localization of seizure foci. We consider that it should be used in the presurgical evaluation of patients with intractable complex partial seizures.

53.2

53.4

T. K u w e r t I, P. M a t h e j a I, S .R.G. S t o d i e c k 2, B. D i e h l 2, K. W o l f ~, M. S c h ~ f e r s I, K. S c h g f e r s I, H. L e r c h I, E.B. R i n g e l s t e i n 2, O. S c h o b e r I. Depts. of N u c l e a r M e d i c i n e I a n d N e u r o l o g y 2, W W U M~nster, Germany. F R E Q U E N C Y O F GABAA R E C E P T O R D E N S I T Y R E D U C T I O N I N NEWLY DIAGNOSED AND CHRONIC COMPLEX-PARTIAL SEIZURES. AIM. Epileptogenic foci e x h i b i t d e c r e a s e d GABAA receptor density. The a i m of our s t u d y was to compare patients with newly diagnosed complex partial seizures (CPS) to t h o s e w i t h c h r o n i c CPS w i t h r e g a r d to the i n c i d e n c e of focal r e d u c t i o n s of t e m p o r a l GABAA r e c e p t o r density. METHODS. Relative GABAA receptor density was assessed with 1-123-iomazenil and a triple-headed S P E C T c a m e r a in 72 p a t i e n t s w i t h c r y p t o g e n i c CPS. 38 p a t i e n t s h a d n e w l y d i a g n o s e d CPS (Group I; age 35.5 ± 14.3 yrs), 34 c h r o n i c CPS (Group II; age 38.0 ± 13.7 yrs). The m e a n d u r a t i o n of s e i z u r e s was in G r o u p I 2.0 ± 2.6 years (median: 0.8) a n d in G r o u p II 12.9 ± 8.9 years (median: 12.0). Tracer uptake was q u a n t i f i e d in four t e m p o r a l r e g i o n s c o v e r i n g the w h o l e t e m p o r a l lobe. I n d i c e s of asymmetry (ASY) were calculated for these r e g i o n s a n d the p a t i e n t s " v a l u e s c o m p a r e d to 95 % confidence intervals determined in 13 c o n t r o l s u b j e c t s (age 31.7 ± 13.5 yrs). RESULTS. A significant temporal asymmetry of GABAA receptor density was found in 11/38 patients (29%) of G r o u p I a n d in 11/34 p a t i e n t s (32%) of G r o u p II. This d i f f e r e n c e in f r e q u e n c y was not s i g n i f i c a n t (p > 0.05). CONCLUSIONS. Foci of decreased GABAA receptor d e n s i t y can be d e t e c t e d at the onset of CPS w i t h similar frequency as in chronic CPS. This suggests that they are central to the pathogenesis of this disorder and not just secondary phenomena caused by excitatory cell d e a t h t r i g g e r e d by r e p e a t e d seizures.

J.T.Kuikka, J. Tiihonen, J. Karhu, U. Lepola, K.A. Bergstr0m, P. R~s~inen Kuopio University Hospital, Niuvanniemi Hospital and Psychiatric Research Clinic of Kuopio, FIN-70210 Kuopio, Finland

934

FRACTAL ANALYSIS OF CEREBRAL BENZODIAZEPINE RECEPTOR UPTAKE IN PATIENTS WITH GENERALIZED ANXIETY DISORDER Functional brain imaging studies have shown several abnormalities in experiencing and controlling of fear and anxiety. However, inconsistencies in the location and direction of blood flow and benzodiazepine receptor uptake changes were observed. Regional perfusion and receptor uptake variability exits even in healthy brain. Fractal analysis of this variability between healthy controls and patients might improve the reliability of findings on a such disorder. We studied 10 drug-naive female patients with generalized anxiety disorder (GAD) and 10 age- and gender-matched healthy controls with high-resolution SPECT using a specific benzodiazepine receptor ligand [123I]NNC 13-824l. Blindly analyzed results showed that the uptake was decreased (p<0.05) in the left temporal pole in patients with GAD when compared with controls. The fractal dimension of the left hemispheric uptake in patients with GAD was significantly higher than that of controls (1.28 _+ 0.09 and 1.17 + 0.07, respectively), whereas the intercept decreased by 43 +- 23 % reflecting more homogeneous, cerebral benzodiazepine receptor density in patients with GAD than in controls. The results suggest that in patients with GAD the most affective hemisphere is left, and the benzodiazepine receptor density becomes more homogeneous and cannot maintain necessary heterogeneity needed in daily life. The adaptive advantages of the normal benzodiazepine receptor density are not available in an inherently unpredictable environment in patients with GAD.

[] Neurology/Oncology 53.5

54.2

J.T.Kuikka, J. Tiihonen, J. Karhu, K.A. Bergstr/Sm, P. R~.s~nen, M. Eronen Kuopio University Hospital, FIN-70210 Kuopio, Niuvanniemi Hospital, FIN-70240 Kuopio, Finland.

J.Th.Loch~, P.Lind*, K.Seybold, I.F61des**,G.A.Jan.oki** Kantonsspital Aaran (Switzerland), *Landeskrankenhaus Klagenfurt (Austria), **Korvin Hospital, Budapest (Hungary)

F R A C T A L ANALYSIS OF STRIATAL DOPAMINE TRANSP O R T E R DENSITY IN ALCOHOLICS We recently observed that striatal dopamine transporter density (DAT) is markedly lower in non-violent aIcoholJcs (type 1) than in healthy controls, whereas violent alcoholics (type 2) had slightly higher DAT density than controls. We further performed a fractaI analysis to measure the heterogeneity of the regional striatal [~23I]13CIT uptake in 21 age- and gender-matched healthy controls, in 10 type 1 alcoholics and in 21 type 2 alcoholics. SPET scan was taken 21-23 hours after injection of 185 MBq of [~23I]J3-CIT. Tmnsaxial slices were reconstructed and thirty six regions of interest were semi-automatically drawn to the striatum. Linear least-squares regression lines were fitted for the logarithm of the relative dispersiorL (= standard deviation of the counts/mean counts) versus the logarithm of the number of sub-regions. The slopes (fractal dimension) and the intercepts of the fits were calculated. Type 2 alcoholics had higher striatal DAT heterogeneity when compared with controls and type 1 alcoholics. Another marked finding in young habitually violent offenders was the absence of normal left-to-right asymmetry seen in other subjects. There was also a marked association (r - -0.75, p < 0.02) between the mean heterogeneity of left striatum and the mean number of committed homicides, This high negative correlation reflects that committing of violent crimes decreases markedly among habitual offenders when they reach age of 40-50 years. Normalization of the left-to-right heterogeneity ratio associated with the decreased violent behavior may reflect a late neurobiological maturation among habitually violent offenders.

CLINICAL S!GNIFICANCE OF BONE MARROW IMMUNOSCINTIGRAPHY (BMS) IN TUWIORPATIENTS WITH ABNORMALBONE SCAN. This report of a prospective three-center study evaluates the diagnostic potential of a newly designed one-step kit for Tc-99m labeling of an antigranulocytes antibody (mab-47, NCA-95). The preparation and pharmakokinetics have been described elsewhere (Eur J Nucl Med 23, 1064, 1996). 555 MBq Tc-99m, 120-250 btg antibody were injected intravenously and scans performed after 2-4 hrs p.i Wholebody bone marrow scans (BMS) and MDP-bone scans (BS) were performed within a few days delay in 96 patients with suspected tumerous metastases using LFOV gamma cameras and routine imaging methods. Patients with cancer of breast (43), prostate (19), bronchus (11), kidneys (7), intestinal tract (3), miscellaneous tumors (13) were included. For searching out distribution abnormalities of both tracers the evaluation of the scans was made by a stepwise comparison of 24 predefined body regions. Discordant results were confirmed as metastatic or benign based on X-ray, CT, MRI, biopsy or follow up B S Out of a total of 2304 evaluated regions 276 (12%) showed concordant positive and 1889 (82%) concordant negative results. The remaining 139 (6%) discordant findings resulted from 93 abnormal BS and 46 from atypical BMS. Skeletal metastases were confirmed in only 32/93 (34%) of abnormal BS, whereas metastatic BM invasion was found in 34/46 (74%) cases. Therefore, the predictive values of a positive test were 83% for MDP scans and 96% for BMS, whereas the predictive values for a negative test were almost equal (98,2% v s 98,3%) No significant HAMA response have been found in these patients with malignant disease. Thus BMS can improve specificity of abnormal BS and is particularly useful in excluding metastases. The new kit is suitable for a quick and accurate diagnostic routine. Key words: Bone marrow immunoscintigraphy, mab-47

Oncoiogy 54.1 A. Dimitrakogoulou4;traus~i ~, L.G. Strauss~, M. $chwarzbach 2, E Willeke 2, F. Oberdoffer ~, G. Mechtersheimer 3, G. Irngartinger1, G. van Kaick~.~German Cancer Research Center, Heidelberg, ZDepartment of Internal Medicine, University of Heidelberg, 3Institute of Pathology, University of Heidelberg, Heidelberg, Germany

BIOLOGICAL CHARACTERIZATION AND MULTIDRUG RESISTANCE (MDR) IN SOFT TISSUE SARCOMAS USING PET AND SPET. The management of patients with primary and recurrent soft tissue sarcomas demands functional methods to differentiate viable tumor tissue and to detect the tumor extension. Furthermore, in patients with large primary tumors preoperative chemotherapy has been used with divergent results for reduction of the tumor volume. A major problem in this case is the early assessment of the response to chemotherapy. An in vivo assessment of the multidrug resistance (MDR) is required to indJviduaJize and optimize chemotherapy. PET and SPET were used in 5 patients with suspected recurrent soft tissue tumors (4 recurrent liposarcomas, one malignant schwannoma), and in 3 patients with a primary tumor (two liposarcomas, one synovial sarcoma). Dynamic PET multitracer studies were performed with O-15-water (tissue perfusion), C-11-aminoisobutyric acid (AI8, alaNne4ike transport of amino ac'~ds), and F-18-DeoxTglucose (FDG, tumor viability). Dynamic PET studies were performed over 8 minutes (8"1 min) using O15-water, for 30minutes (5"1 rain, 5*2 rain, 3*5 rain) for C-11-AIB and for 60 minutes (5"1 rain, 5*2 min, 9*5 rain) for FDG. Planar acquisitions as well as SPETstudies were performed after the intravenous injection of Tc-99m-Sestamibi at the s a m e day prior to t h e PET study to assess the MDR, since Sestamibi is supposed to be a substrate for the P-glycoprotein. All malignant lesions showed an increased uptake of all four tracers. One patient with a lesion classified as tumor recurrency in MRI. due to Gd-DTPA enhancement showed a low uptake of all three tracers in PET and was classified as a scar tissue. This patient did not underwent surgery and the result was confirmed through the clinical follow-up data. Large lesions demonstrated a very inhomogenous uptake with enhanced values in the rim of the lesions and a low uptake in the central parts due to necrosis, hemorrhage etc,. The FDG-uptake variied between 1.9 and 4.6 SUV for the tumors (60 min p.i) with a ratio tumor/muscle (T/M) variing between 1.88 and 4,18. The perfusion values varied between 1.8 and 3.8 SUV (5 rain p.i.) and the ratio T/M between 2.25 and 4.35. The AIB-uptake variied between 1.5 and 3.3 SUV (30 min p.i.) and the ratio T/M between 0.9 and 1.2. Furthermore, it is planned to examine the MIBI-uptake to the expression of the Pgp in the resected tumor material.

54.3

K. Schomiicker, M.I. Gaidouk, T. Fischer (a), H. L6hr (b), S. Salditt, S. Liebenhoff, and H. Schicha. Clinic of Nuclear Medicine University of Cologne, Germany, Department of Nuclear Medicine, University of G6ttingen (a), Germany, and St. Hildegardis-Hospital, Cologne (b),

Germany.

BIOKINETICS OF Yb-169- AND Y-90-PORPHYRINE COMPLEXES Aim." The tendency of porphyrins (primarily haematoporphyrin derivatives (HPD) or photofrin II (PII)) to accumulate in malignant tumors has been widely used, in recent years, to develop promising, new fluorescent diagnostic techniques and photodynamic therapy (PST)methods. Our aim was to insert radioactive isotopes of Yb and Y into selected porphyrines, and to study their biodistribution. Methods: Carrier-added radioactive isotopes were used for the incorporation of Y-90 and Yb-169 into the porphyrine complexes (tetraphenyl-porphyrin sulfonate TPPS (-porphyrine I), meso-tetra-(pcarboxyphenyl)-porphyrin TCPP (=porphyrin II) and 2,4-di(methoxyethyl)-deuteroporphyrin DMDP (=porphyrin III). Experiments were performed on mamma-carcinoma-bearing mice, The activity of the organs was determined, 3 to 23 h after i.v. injection, with a NaI(TI) gamma counter. Results: Three Yb-169-porphyrine complexes and one Y-90-porphyrine complex could be synthesized in non-carrier-free form. The best results were obtained with the TCPP complexes: Complex Yb- 169-TCPP Y-90-TCPP

Tumor/muscle 20_+4 23-+4

Tumor/blood 15_+3 [ 9-+2

Tumor/liver 3_+1 2_+0.5

[

I

Conclusion: The synthesized radioactive metal-porphyrine complexes could become interesting candidates for tumor scintigraphy, and perhaps therapy, once technical problems in their synthesis and purification have been solved. The tumor model also needs to be improved.

935

co |m t-

o~ 1:1. m

• Oncology/Cardiovascular 54.4

54.6

J.D.Lucas, H.D.Apthorp, M.J.O'Doherty, J.C.H.Wong, D. Sandrock, V. Ivancevic, W.-S. Richter, R. Aurisch, I. Reisinger, and D.L. J.B.Bingham, P.H.McKee, C.D.M.Fletcher, M.A.Smith. Munz. Clinic for Nuclear Medicine, CharitY, H u m b o l d t University Berlin, Departments of Orthopaedics and Clinical PET G e r m a n y . Centre, UMDS and Guys and St Thomas" Hospital Trust, London SEI 7EH. INTRAOPERATIVE TUMOR LOCALIZATION - SIMULATION USING A PORTABLE

EVALUATION OF THE ROLE OF FDG PET IN THE FOLLOW UP P H A N T O M MANAGEMENT OF SOFT TISSUE SARCOMAS. A retrospective study was performed to evaluate the ability of FDG PET to identify local recurrent tumour and the development of distant metastases in the lung and at other sites following surgical excision of soft tissue sarcomas. The control criteria for the identificatio~ of local disease and lung metastases were; clinical examination, histological diagnosis of biopsy tissue when indicated, and MRI and CT scans respectively. The comparisons in 62 patients, median age 52 years, with 15 histological types of soft tissue sarcomas are reported. The patient follow up time from diagnosis to last imaging investigation or death was a median of 2 years and 5 months. 71 comparisons for the detection of local disease were available. The median time between the FDG PET and the control assessment was zero i.e.the same day. The sensitivity and specificity of FDG PET was 80% and 94.7% respectively, there being 13 true positives and 3 false negatives. All of the false negatives were correctly identified by MRI. 70 comparisons were available for the identification of lung metastases. The median time between the FDG PET scan and the control assessment was 1 day. The sensitivity and specificity of FDG PET was 86.7% and 100% respectively, there being 13 true positives and 2 false negatives. In addition 13 other sites of metastases were identified in 8 patients of which FDG PET identified 12 of these sites. FDG PET does identify both local and distant tumour recurrence as a one step procedure.

IN A PROBE

BREAST

After surgery of nonpalpable breast tumors intraoperative sonography and Xray-mammography are used for detection/exclusion of residual tumor tissue. Aim of this study was to evaluate the diagnostic efficacy of a portable probe in a breast phantom. A breast phantom (cube, length 11 cm, filling volume 750 ml) was filled with Tc-99m pertechnetate solution (6 MBqfl). A tumor phantom (sphere, diameter 1.8 cm, volume 3.05 ml, 30 MBq/I) was placed inside the breast phantom at 1, 5, and 10 cm distance from the surface simulating realistic in vivo situations. Using a cesium iodide crystal probe (collimation with a diameter of 8 mm at 10 mm length; TECPROBE 2000, Stratec, Birkenfeld, Germany), the following measurements (5 fold each, acquisition time, 4 s) were done: i) at the level of the tumor phantom and laterally thereof at 1.5 and 5 cm distance; ii) after emptying of 2/3 of the tumor phantom (simulating 1 ml remaining residual tumor) at the same probe position as under i). Finally, the residual tumor phantom was placed at 1, 5, and 10 cm distance from the breast phantom's surface. Five trained physicians tried to localize and mark blinded and inde-pendently the tumor phantom on the covered surface of the breast phantom. Close to the surface (I cm), the tumor phantom (with 193.0 +1- 4.5 eps) could be discriminated from near (118.4 +1- 6.5 cps) and far breast phantom regions (20.6 +1- 1.8 cps; p < 0.001), while at a distance of 10 cm from the surface only a small but significant difference was measured (120.4 +/- 3.3 vs, 103.4 +/- 6.2 vs. 20.0 +1- 3.2 cps; p < 0.01). The residual (1 ml) tumor phantom was to be delineated clearly at the surface (148.6 +1- 8.1 vs. 122.0 +/- 4.2; p < 0.001), at a distance of 5 cm slightly significantly (115.9 +/- 5.5 vs. 103,8 +/- 1.1 cps; p < 0.01), and at a distance of 10 cm not significantly from neighboring regions (96.5 +/- 6.7 vs. 95.8 +/- 5.7 cps; p > 0.05). The blinded localization was possible close to the surface with a 10,6 +/- 8.0 mm deviation from the ,,true" position, at a distance of 5 cm with 12.1 +/- 12.6 ram, and at a distance of 10 cm not possible (error 54.2 +/- 13.9 mm). Conclusion: Tumor localization using a portable probe in a breast phantom is possible close to the surface. With increasing distance from the surface, however, the error reaches a point which makes the acceptance of the system in the surgical theater unlikely.

Cardiovascular 54.5

55.1

P. Paulus. S. Henry, R. Hustinx, P. Rigo. Nuclear Medicine, University Hospital, Li6ge, Belgium

V Caveliers, I Pansar, F De Geeter, A Bossuyt, PR Franken. Free University Brussels (AZ VUB), Department of Nuclear Medicine, Brussels, Belgium.

IMPROVED HEAD AND NECK FDG-PET IMAGING USING SEGMENTED ATTENUATION CORRECTION

EFFECT OF GLUCOSE LOADING ON THE BIODISTRIBUTION AND METABOLISM OF BMIPP INTRA-1NDIVIDUAL COMPARISON IN HEALTHY VOLUNTEERS.

FDG-PET imaging has been shown useful to detect recurrences and lymph node extension in patients with head and neck carcinomas. Precise anatomic references are however frequently lacking to localise the pathologic findings. In this study we have assessed the ability of transmission image segmentation to define the airways and air cavities and to use these borders as landmark for lesion identification. 10 patients have been studied using a UGM 240 H Penn Pet (Quest) equipped with a rotating Cs-137 transmission source. Image acquisition is performed 60 to 90 minutes after IV injection of 6 mC FDG. Two partially overlapping emission steps are collected for 12 minutes (total field of view 19.2 cm) followed by three 6.4 cm transmission fields of 90 seconds (total acquisition time : less than 30 minutes). Transmission data are reconstructed using iterative reconstruction. A segmentation algorithm defines density values corresponding to air, tissue and table density. Emission images are then reconstmcted using filtered back projection and a wiener filter. Attenuation correction is performed using the body contours and correction values based on the known rather than the measured attenuation data. The currently available program allowed visualisation of the full airways in 8 of the 10 patients. In the others motion or insufficient data did not provide enough contrast to visualise the larynx. Use of segmentation visualise the airways and greatly improves disease localisation. This should, together with bony structures, provide landmarks for image interpretation and image fusion.

936

1-123 BMIPP has been proposed as an alternative to F-18 FDG to assess myocardial viability with SPET It is unclear whether the biodistribution and metabolism of BMIPP can be altered by circulating energy substrates as it is for FDG. Therefore, 6 healthy volunteers were investigated within one week interval: a) after 12 hours fasting; b) 60 min. after 75 gr. oral glucose loading and a standard 2500 kJ meal. Following intravenous injection of 154 MBq 1-123 BMIPP, heart-liver dynamic images, total body and myocardial SPET studies were obtained with a 2-head gamma camera for 240 rain. Venous blood samples were taken at 2, 5, 10, 15, 20, 30, 60, 90, 240 min. and 24 hours for blood clearance measurement and HPLC-analysis. Blood glucose and insulin increased from 4.74 mmol/L to 7.94 mmol/L and 9.07 mU/1 to 114.2 mU/1 respectively while NEFA decreased from 076 mmol/L to 0.08 mmol/L after glucose loading. All imaging studies demonstrated a slight increase in heart and liver activity after glucose loading and SPET showed a small increase of the myocardial/blood pool ratio 60 min after tracer injection, heart activity averaged 3.95-+0 31%ID under fasting conditions and 4 15+ 0.36 %ID after glucose loading. No difference was found in the plasma disappearance curve of BMIPP but less formation of the end metabolite, PIPA, was observed after glucose loading. We conclude that in healthy volunteers B M ~ P oxidation is slightly reduced during glucose loading which results in a longer retention of the tracer in the myocardium and a slower clearance of its metabolites in the blood.

II Cardiovascular 55.2

55.4

DS Lee, SN Yoon, WW Lee, YJ Kim, JH Park*, J-K Chung, MC Lee, C-S Koh. Departments of Nuclear Medicine and Radiology*. Seoul National University Hospital, Seoul, Korea.

M. Spadafora, P. Miletto, M.L.De Rimini, R. Golia, G. Mazzarella, G. Mazzella, L. Mansi °, A Cuocolo*, G. Rosato. S.G. Moscati Hospital, Avellino; Faculty of Medicine, 2nd University ° and Federico II University* of Naples; Italy.

INSULIN R E S I S T A N C E IN REMOTE M Y O C A R D I U M AND WHOLE BODY USING H Y P E R I N S U L I N E M I C EUGLYCEMIC INSULIN CLA~=P AND F-18FDG PET IN CANINE M Y O C A R D I A L INFARCTION MODEL This study was p e r f o r m e d to follow insulin resistance(IR) of remote normal m y o c a r d i u m and of whole body after m y o c a r d i a l infarction in experimental canine (n-8) closed chest myocardial infarction model. Branch of left anterior d e s c e n d i n g ~rtery or left circumflex artery was o c c l u d e d with gelfoam. Infarct size was s e m i - q u a n t i t a t e d as large, m o d e r a t e and small using p e r f u s i e n SPECT. Whole body IR was a s s e s s e d by whole body glucose disposal rate using h y p e r i n s u l i n e m i c euglycemic insulin clamp(IC). IR of remote myocardium was assessed with F-18-FDG PET q u a n t i t a t i o n of glucose m e t a b o l i c rate using IC or not(no IC). M e a s u r e m e n t s were repeated until the IR d i s a p p e a r e d or the animal died. Before intervention at baseline, myocardial glucose metabolic rate(IC) was 0.6-1.1 ~mole/min/g and whole body glucose disposal rate was 6.39.1 mg/kg/min. Glucose m e t a b o l i c rate d e c r e a s e d in remote myocardium(0.54±0.17~mole/min/g) during acute phase of myocardial infarction. It was related with increased plasma free fatty acid(r -0.79) and with d e c r e a s e d whole body glucose d i s p o s a l ( 4 . 9 8 ± l . 6 2 m g / k g / m i n ; r=0.75). Dogs having much d e c r e a s e d m e t a b o l i c rate(IC) did not reveal m y o c a r d i u m but blood pool in baseline state(no IC) during acute phase. Decrease Of metabolic rate of remote m y o c a r d i u m and whole body were related with infarct size. In conclusion, acute m y o c a r d i a l infarction per se evoked insulin resistance in normal m y o c a r d i u m as well as in whole body and this could be p r o v e d by F-18-FDG PET during insulin clamp.

t-" TRIMETAZIDINE (TMZ) IMPROVES MYOCARDIAL UPTAKE 99m-Tc TETROFOSMIN (TF) IN HYPOPERFUSED REGIONS.

OF

Myocardial uptake of TF in vivo may be determined by a combination of flow and metabolic status of the myocytes. The accumulation of TF by the mitochondda is related to their ability to transduce metabolic energy into electronegative membrane potential. TMZ represents an original anti-ischemic drug that decreases the oxidative damage to mitochondria and protects heart against the ischemic damage to mitochondrial respiration (1) with direct cytoprotective effect since neither systemic hemo-dynamics nor coronary blood flow are altered by the compound. Aim of the study was to evaluate the effects of TMZ on TF uptake in hypoperfused myocardial segments (seg). Sixteen patients without complete reversibility on previous stress-rest SPET studies, underwent two rest SPET with TF (555 MBq/study) before and after one week of TMZ therapy (60 mg/die). No change in clinical and,instrumental features was observed within the 7 days of treatment. TF uptake was evaluated in 22 seg/patient Quantitative analysis of 76 seg, having _<50% of the maximal uptake, showed a significant increase of tracer uptake after TMZ (+8.9 %, p<0.001), Of these seg, 16 (21%) showed an increase of tracer uptake >10% after treatment. No significant (p>0.05) differences were observed in normally perfused seg. ]-he results of the present study demonstrate that TMZ therapy may enhance the uptake of TF in hypoperfused areas. Since neither systemic hemodynamics nor coronary blood flow are altered by TMZ, we supposed that the increase of the tracer is mainly related to improved metabolic status of myocytes, according with a direct cytoprotective effect of the drug. Moreover our data suggests the use of SPECT TF imaging with ]-MZ as a new method to improve the detection of viable myocardium. References 1. Veitch K, Maisin L, Hue L. Trimetazidine effects on the damage to mitochondrial functions caused by ischemia and reperfusion. Am J Cardioi 1995;76:25B-3OB.

55.3

55.5

W.S. Richter, S. Beckmann, R. Aurisch, M. Schartl, D.L. Munz. Clinics for Nuclear Medicine (Char±t6) and Cardiology (VirchowKlinikum), Humboldt University Berlin, Germany

M.0nle, S.inamr, M.T.Kitap(;I, A.(~engel, R.Yak;m, H.D6rtlemez. Gazi University Medical Faculty, Dept of Nuclear Medicine and Cardiology, Ankara, Turkey

MYOCARDIAL FATTY ACID METABOLISM IS IMPAIRED IN SEGMENTS WITH REVERSE REDISTRIBUTION

I N D I U M - I l l ANTIMYOSIN ANTIBODY UPTAKE DETERMINES L-CARNITINE-INDUCED PROTECTIVE EFFECTS ON ACTIVE MYOCYTE DAMAGE IN ADVANCED STAGE DILATED CARDIOMYOPATHY

The aim of this study was to assess fatty acid metabolism in segments showing reverse redistribution in TI-201 scintigraphy. In 12 patients (11 m, lf, age: 54±12 yrs) myocardial SPECT with TI-201 (exercise - 4h redistribution - 24h late redistribution/ reinjection) and 1-123-1odophenylpentadecanoic acid (IPPA) were performed after acute myocardial infarction (AMI) with reperfusion (PTCA or lysis). For quantitative analysis, relative uptake [%] was calculated in 24 left ventricular segments in each patient. A total of 288 segments was analyzed. 14 segments showed evidence of reverse redistribution (difference between TI uptake at rest and during exercise at least 10%). Results are summarized in the table: I TI (ex) TI (4h) TI (late) IPPA rev. red. 80+14% * 66+14% 80+11% * 67+15% normal 91±6% 91±7% 93+5% * 89+7% scar 63+15% * 63+14% * 65+14% 68+15% rev. red. - reverse redistribution; TI (ex) - TI uptake during exercise; TI (4h) TI uptake at 4h redistribution; TI (late) - TI uptake at 24h redistribution/ reinjection * - significantly different from the corresponding IPPA uptake In patients after AMI with reperfusion, segments with reverse redistribution are characterized not only by an accelerated TI201 loss but also a disturbance of fatty acid metabolism.

C O

Iil~l

This prospective study aimed whether L-carnitine, as a protective drug of cellular oxidative metabolism, improves the structure and function of damaged myocardium in pts with dilated cardiomyopathy at advanced stage. Seventeen pts (14 M, 3 F, age:58.4_+13.3yrs, NYHA functional class:3-4) unden~nt In-111 ant±myosin scintigraphy, cardiac catheterization and redionuclide ventdculography before and after the treatment for six months. Nine pts received L-carnitine (2 gdday) plus supportive therapy including 'digitalis, diuretic, vasodilator' (CARN-group, 8 M, 1 F) and rest eight pts ware treated with supportive therapy alone (CONT-group, 6 M, 2 F). Four pts died after the first examination (2 pts in CARN, 2 pts in CONT, .25-2 months later) and no other death occurred to date (follow-up: 6-17 months). There was no significant difference between age, NYHA class, ant±myosin uptake (AMU), end-diastolic pressure (EDP) and ejection fraction rates (EFR) at initial (Age: .59±12.8 vs 57.7±14.7; NYHA:3.33±.5 vs 3.38_+.5; AMU:1.75±.32 vs 1.58_+.18; EDP:18.75_+8.28 vs 19.17_+10.65; EFR:23.62_+8.26 vs 23.71_+6.9 in CARN and CONT, respectively). NYHA class was reduced and the significantly decreased AMU was observed by camitine treatment while supportive therapy alone did not affect both parameters (t~NYHA:l.29±.76 vs .38-+.74, AAMU:.25±.20 vs -0.02 ±.06, respectively, p<.05). EFRs were also increased ~ter L-camitine, but this change did not reach significance statistically (~EFR:7+8.99 vs 4+7.14 compared to CONT). A strong correlation was observed between AMU at initial scan and ,~,MU (r=.8946, 1>=.022). In died pts, significantly higher EDP (26.25±3.86 vs 16-+8.83, p<.05), lower EFR (18.25±2.75 vs 25.64±7.62, p<.05) and lower AMU (1.50-+.05 vs 1.68:h.30) ware found compared to that of alive. In conclusion, initial antimyosin uptake and the changes in AMU and EFR were the major determinants of therapeutic response to L-carnitine, which parameters showed the best correlation with the change in NYHA functional class. It appears that L--camitine has protective effects on reversibly damaged myocytes on dilated cardiomyopathy. On the other hand, low AMU may also be an indicator of poor prognosis in addition to low EFR or high EDP in these pts.

937

(/)

m

• Cardiovascular/Therapy 55.6

56.2

V. Prassopoulos, J. Lekakis, J. Nanas, M. Dimopoulos, N. Agapitos, Ch. Palaistides, P. Kostamis, S. Slamatelopoules, S. Moulopoulos. Dep! of Nuc/ear Medicine and C/in/ca/ Therapeutics '~lex~ndra" gfliversib/ Hospital, Athens, Greoce.

I.Ro M c D o u q a l l , S t a n f o r d H e a l t h Services, D i v i s i o n of N u c l e a r M e d i c i n e

ANTIMYOSIN SCINTIGRAPHY IS USEFUL IN DETECTING CARDIAC AMYLOIDOSIS Cardiac amyloidosis is one of the most likely causes of restrictive cardiomyopathy lhe diagnosis of which may be missed during life. We investigated prospectively the diagnostic value of antimyosin scanning in detecting cardiac amyleidosis. Methods: Seven patients with biopsy confirmed primary or myelomarelated amyloidosis with myocardial involvement were studied (3 women, 4 men, age 56+9 years). Congestive heart failure was present in 4 patients; all patients had left ventricular thickening on echocardiogram. Six patients with long standing hypertension and left ventricular hypertrophy on echocardiogram served as controls (2 women, 4 men, age 544-11years, ns). In-111-antimyosinscintigraphy was performed 48 hours after intravenous injection of 2mCi In-tll-antimyosin. Planar imaging was performed and a heart to lung (H/L) ratio was calculated. A H/L >1.6was considered abnormal. Results: All control patients had a normal antimyosin study (H/L range 1.3 to 1.6, mean 1.43_+0.1).All amyleidosis patients presented abnormal scanning (H/L range 2.1 to 3.2, mean 2.5+0.4, p<0.001). Diffuse uptake was present in all amyloidosis patients. Patients with amyloidosis and heart failure had higher H/L (2.76+0.30) compared to patients without heart failure (2.174.0.06,p<0.05). in conclusion, diffuse antimyosin myocardial uptake in patients with left ventricular thickening is suggestive of amyloid heart disease, in contrast to patients with left venlricular hypertrophy due to hypertension. In patients with known amyloidosis and a positive anlimyosin scanning, endomyocardial biopsy to detect amyloid heart disease could be ommitted.

74 M B q 1-131 S E L D O M C A U S E S S T U N N I N G O R U N D E R E S T I M A T I O N OF THE E X T E N T O F D I F F E R E N T I A T E D THYROID CANCER Purpose: To d e t e r m i n e if 74 M B q 1 - 1 3 1 is an a p p r o p r i a t e d o s e for w h o l e - b o d y scan. D i a g n o s t i c d o s e s of 370 M B q for e v a l u a t i n g the e x t e n t of d i f f e r e n t i a t e d t h y r o i d c a n c e r h a d b e e n s h o w n to d e m o n s t r a t e m o r e l e s i o n s t h a n 74 MBq. H o w e v e r , 370 M B q has b e e n d e s c r i b e d to s t u n t h y r o i d so t h a t t h e r a p e u t i c 1 - 1 3 1 is not t a k e n up in a b o u t 80% of patients. M e t h o d s : 154 d i a g n o s t i c w h o l e - b o d y s c a n s 2-3 d a y s a f t e r 74 M B q 1-131 h a v e b e e n c o m p a r e d w i t h p o s t - t r e a t m e n t scans. All w e r e m a d e w i t h w h o l e - b o d y g a m m a c a m e r a (most w i t h S i e m e n s dual h e a d e d scanner). 73% w e r e in women, 27% in men, of age r a n g e 6-86 y e a r s (mean 39.7). T h e r a p e u t i c 1-131 w a s p r e s c r i b e d w i t h i n 24 h o u r s of the d i a g n o s t i c scan in 69%, and t h e p o s t - t r e a t m e n t scan m a d e a f t e r an a v e r a g e of 8.4 days. 34% r e c e i v e d i,i00 MBq, a n d 62% b e t w e e n 3,700 to 7,400 M B q of 1-131. R e s u l t s : In 2 (1.5%), t h e r e w a s less u p t a k e on the p o s t - t r e a t m e n t scan. In 14 (9%), m o r e l e s i o n s w e r e s e e n on the p o s t - t r e a t m e n t scan. M o r e n o d e s w e r e n o t e d in 8; t h i s did not i n c r e a s e t h e s t a g e of the d i s e a s e . N e w u p t a k e w a s n o t e d in the l u n g s in 5 and n o d e s in 1 on the p o s t - t r e a t m e n t s c a n (4%). C o n c l u s i o n : 74 M B q 1-131 s e l d o m c a u s e s s t u n n i n g ( p o s s i b l y in 1.5%) and s e l d o m u n d e r e s t i m a t e s the e x t e n t of d i s e a s e (4%). It is an a p p r o p r i a t e d i a g n o s t i c dose.

Therapy

56.1

56.3

M.E. Dottorini, L. Pedrazzini, G. Lomuscio, A. V/gnat/, L. Colombo. Ospedale di Circolo -Busto Arsizio - Italy - Department of Nuclear Medicine.

G.T. Krishnamurthy, F.M. Swailem, S.C. Srivastava*, T. K. Walsh. Nuclear Medicine/Diagnostic Service, V.A. Medical Center and Dept of Radiology University of Arizona, Tucson. AZ, and Brookhaven National Laboratory, Upton, NY*

CLINICAL SIGNIFICANCE OF THYROID STUNNING BY 131-I DIAGNOSTIC DOSES ON 131-I THYROID REMNANT ABLATION: A RETROSPECTIVE STUDY ON 108 DIFFERENTIATEDTHYROID CANCER(DTC) PATIENTS.

R A D I A T I O N E X P O S U R E TO F E L L O W PATIENT, NURSE, AND S P O U S E F R O M P A T I E N T S G I V E N T1N-117m D T P A F O R P A L L I A T I O N O F M E T A S T A T I C B O N E PAIN

The aims of this study were: 1) to evaluate clinical significance of thyroid stunning by diagnostic doses (180 MBq) of 131-I on 131-I thyroid remnant ablation; 2) to investigate which other factors may be important to predict whether 131-I ablation was successful. Patients: We retrospectively evaluated 108 consecutive DTC patients treated in 1995 only for thyroid tissue remnant ablation. Eighty-two patients were treated without prior exposure to diagnostic doses of 131-I (Group A) and twenty-six 2448 hours after 180 MBq 131-I whole body scan (WBS)(Group B). The two groups were comparable for TNM, Tg and TSH at the time of first treatment, but the remnants were slightly larger in Group A (p:0.02). Therapeutic doses of 131-I were 3.6i-0.3 GBq (Group A) and 3.7±0.1 GBq (Group B). Results: Success of 131-I ablation was assessed by 131-I WBS 8 months (median) after the first treatment (see Table). Grou 2rid 131-I treatment 8.5% 19.2% N.S. 2rid 131-I WBS: no uptake 82.9% 80.8% 2nd 131-I WBS: positive 12.2% 11,5% N,S. 2nd 131-I WBS: strongly positive 4.9% 7.7% Mean Tg decrease (ng/mL) 11.5±32.2 5.1±11.2 N.S. We then evaluated by a logistic model to examine whether some factors (number of prior thyroid surgical interventions, surgery team, TNM, TSH, Tg and amount of thyroid remnants) were important in predicting successful 131-I ablation: only serum Tg level at the time of the first treatment was inversely correlated with success of 131-I ablation (p:0.01). Conclusions: 1) thyroid stunning may cause a reduction of successful 3.7 GBq 131-I ablation of thyroid remnants, but differences are small and not statistically significant; 2) serum Tg level after surgery is the most important factor predicting successful 131-I ablation in DTC patients. 13l-I WBS need not be performed routinely prior 131-I ablation, but can be used in selected cases, when localization of 131-I-avid tissue is important to plan subsequent 131-I therapy.

938

Purpose: Tin-117m DTPA, a potential new agent for palliation of metastatic bone pain has a physical half life of 13.6 days and emits a gamma photon (159 keV, 86% abundance) in addition to conversion electrons. This project was undertaken to measure radiation exposure levels to personnel who come in contact with treated patient to enable providing proper radiation safety guidelines. Methods: Radiation exposure levels from Tin-117m DTPA to other patients (n- 6) 2 meters away in the same room or across the wall in the next room, to nurses (n=12) caring for the patient, and to the spouse (n=10) sharing bed at home after hospital discharge, were measured by direct reading pocket dosimeters and Siemens EPD2 digital dosimeters. The spouse radiation exposure was measured daily for 60 days and cumulative radiation was calculated for 10 physical half lives (136 days) from a normal/sad 20 mCi (740 MBq)Tin-117m DTPA. Results: During the first three days of therapy, radiation exposure to the next patient in the same room or across the wall in the next room was 1.8#Sv/h. Nurse exposure was 0.4/~Sv/h. The spouse sharing the bed with the patient a week after the dose was exposed to 0.02roSy/day (0.83#Sv/hr)during the 2nd and 3rd week. Spouse cumulative exposure for 10 half lives was 0.8 mSv Conclusion: Fellow patient, nurse and spouse radiation exposure levels are all well within USNRC limit (5mR/hr or 50~Sv/hr) enabling doses up to 30 mCi (1110 MBq) Tin-117m DTPA to be given on an inpatient or outpatient basis with out requiring any addkional measures that may increase the cost of radionuclide therapy for bone pain palliation.

[] Therapy/Cost Effectiveness 56.4 Pirich C, Schwameis E, Radauer M, Flores J, Wanivenhaus A, Trattnig S, Sinzinger H Departments of Nuclear Medicine , Orthopedics and Radiology, MR Institute, University of Vienna,

56.6

EFFECTS OF RADIATION SYNOVECTOMY ON ARTICULAR CARTILAGE AND SYNOVIAL VOLUME AS EVIDENCED BY MR-IMAGING Dysprosium-165 offers promising physical properties for radiation synovectomy. We carried out a MR study in i0 patients with chronic synovitis to investigate the effects of radiation synovectomy on synovial volume, enhancement and articular cartilage. MR imaging was performed before, 1 week and 7-16 months after radiation synovectomy. Examinations were performed on a 1.5 Tesla MR-Unit (Magneton, SP 63, Siemens, Erlangen, Germany) using a circular polarised knee coil. The following sequences were applied:a sagittal T lweighted spin-echo sequence and a T lweighted 3D gradient echo sequence with frequency selective fat saturation. Results demonstrated a reduction in synovial volume and enhancement related to the decrease in local inflammatory activity in all patients. The absence of damage to the articular cartilage by radiation synovectomy could be proven by MR imaging as well. The morphological changes in the synovia without any effect on articular cartilage confirm the clinical results of radiation synovectomy for chronic synovitis.

FEASIBILITY AND EFFECTIVENESS RADIOIMMUNOTHERAPY WITH I-131 ANTITENASCIN MABS.

P.Riva*, A.Arista°, G.Franceschi*, N.Riva~, M.Casi*, AM.Cremonini ° G.Guiducci °, G.Moscatelli*, and HMacke ^. *Nuclear Medicine Dept. and Ist.Oncologico Romagnolo; °Neurosurgery Dept. "M.Bufalini" Hospital -Cesena (Italy) ^lnst of Nuclear Medicine Basel (Switzerland) OF AND

N.V.S. ~ s ,

During past six years 62 pat. with glioblastoma, unden,vent one or more injections (up to 6) of 1-131 (mean dose MBq 1809.3) conjugated anti-Tenascin BC-2 and BC°4 MAbs. Radioimmunotherapy (RIT) was given as additional treatment after surgery,external radiotherapy and chemotherapy. The infusions of the radiopharmaceutical were carried out through an indwelling catheter surgically inserted into the postoperative cavity. No significant untoward consequences were encountered. The most important clinical results were the favourable prolongation of the median survival (23 months versus 12 attainable with traditional cares) and of the disease free period (12 months versus 5). The objective response was composed of 9 PR,3 CR and 20 NED (Not Evidence of Disease in cases who underwent RIT when their lesions were minimal). The response rate (PR+CR+NED) resulted 51.6%. In the group of cases who had the treatment when their tumour burden was very reduced, the median survival was 26 months and the response rate resulted 70%. More recently a phase I study by utilising Y-90 instead of 1-131, was carried out. A BC2-DTPA-Y-90 conjugate was employed. This compound showed a satisfactory labelling efficacy (>95%); the immunoreactivity after the radiochemical procedure was retained (>80%). 12 patients with advanced and no more curable tumours received Iocoregionally escalating doses (185, 370, 555, 740 MBq) of BC2-DTPA-Y-90.3 cases were treated at each incremental level. The infusion of quite large amounts of Y-90 did not cause early nor late local or systemic adverse outcomes. The radiation dose delivered to the turnout proved to be 68.8 cGy/MBq (versus 13.5 cGy with 1-131). The length of patients' hospitalisation was 3 days (versus 10 days with 1-131). The radioprotection of the medical staff was much easier with respect to the use of 1-131. The biodistribution of BC2-DTPA-Y-90 was assessed by means of consecutive total body scintigraphies which were performed by using the Y-90 bremsstrahlung emission. A very high accretion of MAb was recorded only in the place corresponding to the neoplastic tissue and not at all in the rest of the body.The radioactivity was completely absent in the blood and in the urine. (Work supported by National Research Council Program (ITALY): Clinical Applications of Oncotogy Research, subproject n.8, by AIRC: Italian Association on Cancer Research and by Cassa di Risparmio di Cesena).

57.1 Marinho, M.R.C. Nobre, I.J. E . T . R o c h a , J.C. M e n e g ~ e t t i .

Coelho, M.I.C.C. Radioisotx~pes frc~

the Heart Institute, Social Cardiology and Center of Nuclear Msdicine L]IM-43, Uni%.arsity of S~o Paulo, Brazil SAMARIUM- 153-EDTMP FOR PAIN PALLIATION P A T I E N T S W I T H R H E U M A T O I D ARTHRITIS.

IN

Samaritlm-153-EDTMP (Sm) is a beta emitter used for treating bone pain. We p o s t u l a t e d that rheumatoid arthritis being a disease w h i c h presents pain and osteoblastic activity as an integral part of its pathological features would benefit from the t h e r a p e u t i c use of Sm. We conducted a d o u b l e - b l i n d placebo controlled study in 19 patients with rheumatoid arthritis (18F, IM}. Eleven patients, mean age 60 ± 17, range 35 to 85 years received ImCi/kg of Sm by intravenous injection and 8 (all females), mean age 65 ± 14 range 42 to 82 years received saline intravenously (placebo). Pain response after treatment was assessed daii~ by the patients themselves, weekly by interview and on the 2 n and 8 th week a physical examination was carried OUt. Pain was rated using a visual analogue scale. Haematological blood samples were taken w e e k l y during 8 weeks. Results are shown in the following table.

Treatment (n=!l) Placebo (n=8)

Pain response >50% <50% 8/ii 3/11 (73%) (27%) 4/8 4/8 (50%) (50%)

Nadir Leukocytes/mm ~ 3,673 6,763

counts Platelets/rm~ ~ 82,902 p<0.001 192,125 p
There was a significant improvement on the baseline pain in the treatment group. However we did observe a 50% report of improvement in the placebo group. This result is slightly above of the expected. We speculate that the poor social-economic condition of the patients (better medical assistance) might be responsible for the difference detected. In the blood counts profile m e d i a n baseline platelet counts was 244,000/n~m ~ and 2 0 6 , 6 2 5 / ~ m 3 for patients receiving treatment and placebo group respectively. The observed reduction was 66% in the treatment and 7% in the placebo group. M e d i a n baseline leukocyte counts was 8,709/mm 3 (treatment) and 7,525/mm 3 (placebo). There was a reduction of 57% in the treatment group and of 10% in the placebo group. Our results indicate that patients with pain due to chronic rheumatoid arthritis may benefit from the use of Sm153-EDTMP as an alternative to withdraw temporarily intmunossupresive or non hormonal a n t i - i n f l a m m a t o r y medication.

.i,,a

LOCO-REGIONAL Y-98 LABELLED

Cost Effectiveness 56,5

C O

| u

Gugiatti A., Rossetti C., Lucianani G.. Grimaldi A . , , Landoni C., Borgonovi E., Fazio F. INB-CNR, University of Milan, Institute H S Raffaele, CeRGAS University L.Bocconi, Milan Italy COST-EFFECTIVENESS OF D I F F E R E N T IMAGING TECHNIQUES FOR THE A S S E S S M E N T OF M Y O C A R D I A L VIABILITY IN ITALY PET with F18-FDG has been recently included among the reimboursable procedures by the national health care system (NHS) in Italy. Aim of this analysis was to compare the costeffectiveness in Italy of PET with F18-FDG, echodobutamine and SPET with TI201 rest redistribution for the assessment of myocardial viability. We have utilized an algorithm to obtain a decision tree. The input informations were: the epidemiology of CAD patients to be evaluated for residual myocardial viability, the treatment protocols with the relative life expectancy, the diagnostic accuracy of the different techniques as indicated by the literature and the costs of diagnostic and therapeutic procedures as reimboursed by the NHS in Italy: PET= 1,300 US $, echodobutamine= 160 US $, TI201 rest redistribution= 350 US $. As result, a decision tree has been obtained for the three d i f f e r e n t d i a g n o s t i c p r o c e d u r e s considering the expectancy of life with the different approaches and the related costs. The results indicate that PET F18-FDG is the most effective procedure in terms of life expectancy (6.5 yrs vs 6.0 yrs with echodobutamine and 5.8 yrs with SPET TI201). The cost per added year of life considering the conventional diagnostic and interventional protocols is 2,800 US $ with PET F18-FDG, with echodobutamine 3,000 US $ and with SPET TI201 3,500 US $. On this basis PET with F18-FDG appears to be a cost-effective tool for clinical evaluation of myocardial viability.

939

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Cost Effectiveness/Hypertension - Captopril

57.2

57.4

S.R. Underwood, B. Godman,S. Salyani,J. Ogle, P.J.Ell. EuropeanAssociationof Nuclear Medicine, Association of Radiopharmaceutical Producers of Europe, European Nuclear Medicine Equipment Suppliers,AD Little Ltd

ED Williams, R Blair, Regional Medical Physics Department, Sunderland and Newcastle General Hospitals, UK

ECONOMICSOFMYOCARDIALPERFUSIONIMAGINGIN EUROPE-THEEMPIRESTUDY

CAN PERFORMANCE AGAINST SERVICE QUALITY STANDARDS IN NUCLEAR MEDICINE BE IMPROVED BY MONITORING?

Physiciansuse myocardialperfusion imaging (MPI)to a variableextent in patients presenting with possiblecoronaryartery disease(CAD). There are few clinical data on the most costeffective strategy although computer models predict that routine use of MPI is costeffective. We have studied 400 patients presenting to 8 hospitals for the diagnosis of CAD. The hospitals were regular users or non-users of MPI with one of each in 4 countries (F, D, I, UK). Information was gathered retrospectively on presentation, investigations, complications,and clinical management,and patients were followed up 2 years in order to assess outcome. Pre- and post test probabilities of CAD were computed for diagnostic tests and each test was also assigned as diagnostic or part or management. Diagnostic strategies defined were h Ex-ECG/angio, 2: Ex-ECG/MPI/angio, 3: MPI/angio, 4 anglo. Primary outcome measureswere the cost and accuracyof diagnosis,the cost of subsequent management, and clinical outcome. Secondarymeasures included prognostic power at diagnosis, normal angiography rate, and rate of angiography not followed by revascularisation. Mean diagnostic costs per patient were: strategy [: £356, 2: £284, 3: £317, 4:£1079

(P<0.00 I). Mean diagnostic cost in the MPI user centres was £397 and in the non-users £526 (P<0.001). Meanprobabilityof the presenceor CAD when the final clinical diagnosis was CAD present were, strategy l: 0.88, 2: 0.90, 3: 0.95, 4: I.O0, and when CAD was absent, h 0.22, 2: 0.13, 3: 0.12, 4:0.04 (P<0.0 I). Mean 2 year managementcosts (CAD present/absent) were: strategy h £3725/£195, 2: £3232/£235, 3: £3324/£286, 4: £4584/£362. Prognostic power at diagnosis was higher (P=0.001) and normal coronary angiography rate was lower (28% vs 43%, P=0.01) in the scintigraphic centres and strategies. Numbers of cardiac events over 2 years did not differ between strategy or centre, but only 14% of patientsin the scintigraphy usercentres reported continuingcardiac problems at 2 years, compared with 45% in the non-users.

To provide an a s s e s s m e n t of service quality in the nuclear medicine services provided by 1 3 hospitals in our locality, standard p a r a m e t e r s w e r e developed in c o n s u l t a t i o n w i t h all the participating hospital d e p a r t m e n t s . These standards specify for e x a m p l e t h a t all urgent investigations be c o m p l e t e d w i t h i n one w o r k i n g day after request, and t h a t 9 0 % of p r o c e d u r e s should start w i t h i n 20 minutes of a p p o i n t m e n t time. Over a period of three years the m e t h o d s used for collecting data have been refined and d e v e l o p e d , generally progressing f r o m estimates and sample m e a s u r e m e n t s , to c o m p u t e r - b a s e d monitoring of all procedures. The results of monitoring have been shared on an a n o n y m o u s basis b e t w e e n the participating hospitals. Reviewing data since 1 9 9 3 , the m a j o r i t y of service quality targets have been met, and there is evidence of i m p r o v e m e n t in p e r f o r m a n c e in several of the hospitals. It is concluded t h a t peer pressure can be e f f e c t i v e in raising service quality standards.

We concludethat investigativestrategiesusing MPI are cheaperand at leastequallyeffective compared with strategiesthat do not use MPI, both for cost of diagnosisand for overall 2 year managementcosts. Patient outcome is similar.

Hypertension

- Captopril

57.3

58,1

R.Giubbini, A.Terzi, P. Rossini, E.Milan. Nuclear Medicine Dpt., Spedali Civili. Brescia (Italy).

Oj_.U~ur, i. Peksoy, B. Caner, S. ~ekirge, F. Balkancl, E, Lay Ergtin and C. Bekdik. Hacettepe University Faculty of Medicine, Ankara, TURKEY.

COST-EFFECTIVENESS OF Tc-99m-SESTAMIBI SPECT IN THE DETECTION OF RESTENOSIS AFTER PTCA. The detection of restenosis after primary successful PTCA is an emerging problem due to the increasing number of procedures performed every year. Both the evaluation of symptoms and ECG stress testing give equivocal results in many patients. Therefore there is the need for catheterization in order to evaluate short and long term results. Stress imaging is considered an alternative method to catheterization, in a previous study of our group (JNM 1996;37:1300-5) we found 89% sensitivity and 78% specificity in the detection of restenosis in a cohort of consecutive pts with inconclusive ECG stress tests. We applied these values to two diagnostic strategies: catheterization in all pts (model 1) vs stressrest Tc-99-Sestamibi SPECT in all pts followed by catheterization in SPECT positive subjects (model 2). in our country the reimbursement for uncomplicated coronary angiogram is equivalent to 1743 ECU and for a Sestamibi SPECT to 296 ECU. The cost per pt of model one is 1743 ECU, hypothesizing a 2% complication rate during catheterization, which determines a reimbursement surplus. The prevalence of positive SPECT in post-PTCA pts referring to our lab is 55%. Therefore the cost per pt of model 2, hypothesizing the same complication rate in pts undergoing catheterization, is 1245 ECU per pt. The saving per pt is therefore 498 ECU, which corresponds on an annual basis activity in our Lab to a saving of 78684 ECU for our National Health Service. Furthermore the application of model 2 allows the complication rate of catheterization to be contained at 1%. On the other hand the clinical limitation of model 2 is related to the occurrence of a 6% false negative rate in the entire population. However, whether the detection of restenosis in the presence of normal perfusion is clinically relevant in terms of decision making towards a second PTCA procedure, is questionable. In conclusion Tc-99m-Sestamibi SPECT is a cost-effective diagnostic tool when applied in the detection of restenosis after PTCA.

940

R E S U L T S OF A 2 Y E A R P R O S P E C T I V E S T U D Y TO ASSESS E F F I C A C Y AND M E T H O D O L O G Y OF T c - 9 9 m - E C CAPTOPRIL SCINTIGRAPHY In this report, the overall results of a 2 year prospective study is presented. The potential usefulness of EC captopril scintigraphy was evaluated in 72 pts. All of the patients had renal angiographic correlation within 2 months following scintigraphy. In a random fashion, the same day (n=33) and the two-day (n=39) EC captopril renography protocols were used. For the same day protocol, the baseline study was done first with a lower dose of EC injection (74 MBq). Four hour later, captopril study was performed using 296 MBq EC dose 1 hour after the oral administration of 50 mg of captopril. For the two-day protocol, baseline and captopril scintigraphies were performed following the injection of 185 MBq of EC, on separate days (72 hour apart from each other). 40 mg of furosemide was immediately injected after EC injection. Visual evidence of increasing parenchymal retention and/ or quantitative worsening in renographic grade were accepted as diagnostic parameters to detect renovascnlar hypertension (RVH). Captopril scintigraphy was considered as true positive if it could detect 50 % or more stenosis in renal arteries or its branches. Using these criteria out of 72 patients (143 kidneys), EC captopril scintigraphy detected renal artery stenosis in 20 patients [22 kidneys (3 bilateral, 2 unilateral segmental, 15 unilateral involvement)]. EC captopril scintigraphy could not detect one of the kidney with decreased renal function in a bilaterally involved patient. We observed false positive results in a patient v ith periarteritis nodosa. Angiography (+) Angiography (-) Two-day scinti graphy (+) 10 Two-day scintigraphy (-) 67 Same-day scintigraphy (+) 12 2 Same-dayscintigraphy(-) i l 51 Conclusions: l -Overall sensitivity, specificity and accuracy of EC captopril seintigraphy to detect renal artery stenosis found to be 95 % (22/23), 98 % (118/120) and 97 % respectively. 2- Both the same day and the two day protocol can be used effectively to detect RVH.

[] H y p e r t e n s i o n - C a p t o p r i l

58.2

58.4

E. Fommei, L. Mezzasalma and the MulficenlxeStudy Group. Institute of Clinical Physiology, Hypertension Unit, University of Pisa, Italy.

Magri G.C., Pizzocaro C., Rossini P., Rampini S., Tortorici C.* Nuclear Medicine Dpt, Civic Hospital of Brescia; *Nephrology Dpt - University of Brescia Brescia (Italy)

DETECTION OF RENOVASCULAR HYPERTENSION BY CAPTOPRIL RENOGRAPHY WITH MAG3: A MULTICENTRE STUDY. A multicentre study was undertaken among nine centres to assess the validity of 99mTc-mercaptoacetyltriglycine (MAG3) for the diagnosis of renovascular hypertension by captopril renography. Participants: F. Arzilli, Pisa, Italy; JC Conesa, Barcelona, Spain; E. Dubovski, Birmingham, Alabama, USA; M. Myslivec6k, Olomouc, Czech Republic; A. Prigent, Paris, France; A. Serefoglou, Athens, Greece; C. Tainturier, Suresnes, France; E. Vanninen, Kuopio, Finland; CG Zhang, Taiyuan Shanxi, China. Data from 153 hypertensive patients were collected. Patients were selected according to clinical criteria for renovascular hypertension. Data forms included vital statistics, laboratory examinations, drug treatment and the results of renal angiography, revascularization and clinical follow up. Baseline and post-captopril scintigraphy were evaluated according to both inspective renographic analysis and quantitative parameters. Out of the 153 patients. 72 had normal renal arteries (NRA), 23 had <70% renal artery stenosis (RAS), 58 had ->70%RAg. NRA patients (meank+SD):age 43_+13 yrs, s. creatinine 89_+14maGI/L, blood pressure 164_+20/103_+13mmHg; <70% RAS patients (meam++gD):age 52#_16yrs, s. creatiuine 115+61 maGI/L, blood pressure 170±25/101_+19mmHg; _>70%RAS patients (mear~+SD): age 54_+16yrs, s. creatinine 121+56 mmol/L, blood pressure 166-+22/99±15mmHg. Here we report scthtigraphic results in a comparison with arteriographic diagnosis in patients with normal renal function and without other nephropathies. On post-captopril analysis, renographic curves were abnormal in 90% of _>70% RAS patients and, respectively, normal in 89% of NRA patients. Among the quantitative parameters, only the retention index (20rain activity/peak activity) yelded consistent results, being _>40%in 81% of ~>70% RAS patients and, respectively, negative in 79% of NRA patients. Out of the patients with <70% RAS only a minority presented positive results for significant RAS by either inspective or quantitative analysis. These preliminary results demonstrate the clinical validity of captopril renography with MAG3, indicating high levels of sensitivity and specificity of the tecnique for the detection of significant renal artery stenosis.

e-

o

ii

CAPTOPRIL RENAL SCINTIGRAPHY (CRS): WHEN THE BASELINE STUDY (B.) IS NEEDED?

In two recent position papers both I day, (B.+CRS) (1D) and 2 day,( CRS first; B only if indicated) (2D) protocols are considered to be effective in screening patients with suspected renal artery stenosis undergoing angiography; 1D protocol may result more expensive because each patient requires 2 studies, while 2D requires prolonged discontinuation of anti-hypertensive drugs. Aim of this study was to assess the diagnostic value of CRS alone and the usefulness of the B. to reach the final diagnosis. !17 consecutive CRS performed between 1995 and 1996 were reviewed. In 70 Pts a CRS only was performed; because of a normal resultt, B. was not performed. In 47 Pts B. and CRS both were performed. Both CRS and B. were performed by using a tubular tracer (P-~sOIH or Tc99mMAG3)and standard acquisition criteria. Pts classified "negative" by CRS at visual analysis (64.9%) don't require further radionuclide evaluation, as well as those considered "positive" (8.5%), therefore 13. can change the management of only 12 Pts (26%). A score analysis, according to the foUowing criteria: 0) Normal; 1) Minor abnormalities, with 5min 60 all The results of CRS alone obtained 0 22 11 33 by using the previous described 1 0 3 3 criteria and dividing the study 2 1 3 4 group according to pts age (group 1 <60 yrs and group 2 >60 3 0 3 3 yrs) are summarized in table. 4 2 2 4 However, Pts with score 0 plus 3 all 25 22 47 or 4, in whom angiography is bold = B. useful raccomanded, don't have further benefit adding B.. B. can change the final result only in 1/25 pts in group 1 and in 6/22 in group 2. Conclusion The 2D protocol CRS seems to be the best approach ian Pts <60 years old while in older Pts a previous B. study (1D) may be a better choice.

58.3

58.5

JL Larnpreave, P Dominguez, M Rengel*, C Trampal, L Inchausti*, A Bittini, MP Madariaga, I Almoguera. Nuclear Medicine and Nephrology* Departments Hospital Universitario Gregorio Marafidn. Complutense University of Madrid Madrid. SPAIN

K. Liepe ~ A. Seemann 2 p Gross 2 W.-O Franke ~, J. Kropp i Depts of 1Nuclear Medicine, 2 Internal Medicine, Dresden University of Technology, Germany

RENOVASCULAR HYPERTENSION (RH) IN KIDNEY TRANSPLANTED PATIENTS ASSESSED WITH CAPTOPRIL RENOGRAPHY, DOPPLER (US) AND ARTER1OGRAPHY. The aim of this study was to assess the diagnostic usefulness of angiotensin-converting enzyme inhibitor renography (CR) in kidney transplanted patients, evaluating the possible role of this procedure in onekidney one-clip model, which is theoretically less renin-dependent and more volume dependent than other Gnldblatt models. Materials: Eleven transplanted patients with clinical suspicion of RH underwent a CR 1 h. after a 50 mg oral dose of captopril. Blood tension was monitored before and after captopril intake and oral hydration was performed Whenever the result indicated possible RH, the patient was retested one month later in basal conditions. Both studies were performed with furosemide (F=0 rain) in order to avoid possible false positive results secondary to tracer retention and were evaluated by 2 experts blind to the clinical data of the patients. Doppler ultrasound and arteriography were also performed before surgical treatment was accomplished Results: All the six positive (6/6) patients for CR were considered as true positives (no false positives), corroborated by US (6/6) and arteriography (4/6). A significant reduction after surgical intervention in tension values and number of drugs necessary to control it were considered as the best indicators of the presence of previous RH in these patients Only 2 have not yet been operated despite positive CR, US and clinical data (they still remain highly hypertense), because of an unclear arteriography (2/6), although they will be soon submitted to angioplasty. Among the 5 patients with negative CR, 3 were also negative on US and arteriography (true negatives) and 2 were false negatives (FN). One of the FN had a polar branch stenosis. Conclusion: Angiotensin-converting enzyme inhibitor renography is useful in the diagnosis of renovascular hypertension in transplanted patients, supporting the hypothesis of its renin-dependency

C O M P A R I S O N O F L O S A R T A N AND C A P T O P R I L DIAGNOSIS O F R E N O V A S C U L A R H Y P E R T E N S I O N

IN T I l E

Radionuclide renography (RNR) with ACE inhibition plays an important role in the diagnosis of renovascuIar hypertension (RVH). Captopril induces a blockade of angiotensin II, associated with an accumulation of kinines. The vasodilative effect of kinines may weaken the effect of captopril. Our position hypothesis was, that the non-peptide angiotensin II receptor antagonist losartan may overcome this limitation. In a preliminary study we evaluated 18 patients (pts) (10 female, 8 male, mean age 63 years) with suspected RVH. Tc-99m-DTPA-renography was performed before and during Losartan (50 rag) and Captopril (50 rag) The visual and quantitative evaluation of RaNR was compared with the results of angiography and the plasma renin activity. In addition, we calculated the glomerular filtration rate of 5 pts. Of !8 pts with angiographies 16 showed renal artery stenoses (RAS)- 10 high with 2 bilateraI RAS, 3 middle and 3 low grade. The results of the RNR was positive for RVH in 10 (5 pts during losartan, 7 pts during captopril). 8/10 pts with high grade RAS were positive in RNR (4 pts during losartan, 6 pts during captopril). The two other pts with positive RNR showed one middle and one low grade RAS. We obtained the same positive result by effect of loasartan and captopril in only two cases. In 6 pts RNR was negative despite a positive angiography. In two pts with bilateral renal artery stenoses, renography was positive only unilaterally. The calcuIation of glomerular filtration rate and the plasma renin activity showed no additional information. I n c o n c l u s i o n : In our preliminary study, RNR during Losartan showed no higher sensitivity to diagnosis RVH compared to RNR during Captopril.

941

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• Telenuclear Medicine Telenuclear Medicine 59.1 E. J. R. Somer, R. D. Badawi, J. L. Hearns, P. J. Liepins, Guy's and St Thomas' Clinical PET Centre, Division of Radiological Sciences, UMDS. A DICOM COMPATIBLE REPORTING PACKAGE

INTERNET REMOTE FOR NUCLEAR MEDICINE

The components required for remote have long existed in isolation but of internet browser, image viewer, proves to be a simple but effective

image reporting the combination and database package.

We have developed a system in which Interfile data is automatically converted to a DICOM compatible format from which relevant details are extracted and inserted into a standard mSQL database. The format conversion software has been tested with standard ADAC, Park Medical and Nuclear Diagnostics Interfile and a multimodal capacity is being developed. Clinical staff may connect to the service over an ISDN link or through a commercial Internet Service Provider. A search engine with a web interface queries the database and returns a list of patient studies matching the search criteria. When selected the image data is downloaded with a partially filled report form. Osiris, a freeware medical image viewer which supports DICOM formats is used as a browser helper application. Report submission is either over the internet or via fax. Security is provided by the Secure Socket Layer protocol which allows encryption, server and client authentification and message integrity checking.

59.3 S. Askienaz/, D. Gambini2, M. Spector< CI. de Labrioile-Vaylet~, L Barritault2 - ~CHU Saint-Antoine, 2CHU Necker, 3Universite Paris V, Paris, France A TELEMEDICINE NETWORK DEDICATED TO PATIENTS IMAGES. Paris hospital administration (APHP) rules 50 hospitals and 30000 beds. Each hospital has its own network, and all hospitals are linked through an interhospital network. These networks are mainly used for administrative purpose but some patients data (biology) may be accessed through the intrahospital network. We thought that we could use this network in order to transmit data between the Nuclear Medicine (NM) department and the prescribing physicians jointly with the images reports. A link between NM and the Xray department (MRI and CT) using DICOM 3 have also been established in order to perform inter modality comparison. Interfile and PCX files can also be transmitted. A software permitting a limited display (color scaling, windowing, zoom and cine) of different sources has been developped and runs on any PC, under Windows (3.1 or higher). Each machine can be either client or server. Data transmission (using TCPIP protocol) starts by a <> compression and decompression is performed at the reception site. Patients data are sent to, or searched into dedicated mailboxes situated in each machine. The same structure is applied between different hospitals (but there only one machine permitts the interconnection between the different hospitals in order to increase security of the data). This interhospital transmission is used in two situations : a) transmission of patients data to ask for an expertise of a dedicated physician ; b) evaluation of a patient's situation before sending the patient to a dedicated department in an other hospital. Up to now, 6 hospitals are linked, and another one is on the way to be connected. We are starting to build teaching files for trainies in NM. that could be accessed this way from the different places.

The system is currently under trial and will be expanded to allow collaborative reporting between different departments within the hospital and between different hospital sites.

59,2

59.4

Rocchisani J.M., Moretti J-L CHU de Bobigny, Paris XIII. France.

Y. Suzuki* and M Nakamura**. Tokai University Medical School. Depam`tlent of

A WEB MEDICINE

INTERFACE TO DEPARTEMENTAL PICTURE DATABASES

Radiology* and Biomedical Engineering**. lsehara. Japan.

NUCLEAR

Digital archiving of images in a Nuclear Medicine department allows to reuse original data for reporting ,in the follow-up of patients and for clinical studies. We have developped an interface using World wide Web (Web) tools for an easy access to pictures databases of our department. Picture coming from various source of acquisition are stored on the disks of workstations and permanently on WORM optical disks. Databases are maintained on a dedicated workstation containing patient and picture informations. A public domain Web server has been implemented with appropriate security.on that station. From any computer of our local network, the user may address requests to the server by hypertext markup langage (HTML) forms through a client software (browser).The server then runs common gateway interface softwares that access to databases informations or data, and return results in HTML format to the browser. So the user may explore databases, find an information by key-words search, and retrieve images that are displayed by the browser after a on the fly format conversion. Remote access through the Net is possible for authorized physicians. Web tools provide a convient access to picture databases of a Nuclear Medicine department with inexpensive and computer-independant softwares. In the future, we will add other functionalities of this emerging technology to allow remote processing and a multimedia management of patient examinations.

942

A WORLD-WIDE

WEB SERVER FOR NUCLEAR MEDICINE TEACHING

FILES. The World-Widc-Web(WWW) is becoming a useful tool for the nuclear medichie commullit3,'. The WWW provides oppolmnities for ~idely distributing educational materials such as teaching files. In this paper, we like to introdnce the unclear medicine teaching files constructed on our WWW . sever(URL: nlfsmed.u-tokai.ac.jp) Each case is composed of the following components: 11 a brief description of clinical history, ptlysical findings and laborator3 data. 2) Key images of nuclear medicine and other imaging modalities ~ith description of tile findings. 3) Diagnosis and comments about the case with emphasis on the images of nuclear medicine. Our digital teaching file images and text are composed m Hyper Text Markup Language(HTML). These teaching files are accessed using WWW client sofm'are such as Netscapc Navigator and In`temet Explorer. TwentTfive cases of diseases common among Japanese ha~.'c been uploaded alld art effort to increase nmnber of cases is still continued. The eases cover a uide field of nuclear medicine: cardioloD', bone and ,ioint. pulmonology, urology, gastroenterology and hepatoloD. ondocrinolog3, and ontology. In the 3 years since its creation, our teaching files have been accessed b3 the clients of the 75 different foreign countries and the total access counts reached about 70.000 at the end ofjannar3. 1997. The top 5 foreign countries in order of access number are USA. Canada. Korea. Unttcd Kingdom and Australia. Digital teaching files on WWW sexer have several advantages mcr their film-based connterparLs. Network access permits use at multiple sites, both an nistitution and across nndtiple institutiofts. We can have a discussion abmlt each case or mmge ver3 couvenientl 3 regardles~ hine and distance ~ia Internel. It uill gread> contribute to promote the international colhlbomtion among tile personnel ill nnclear medicine. It is uunecessa O to rearrange the cases al'ter using. Loss of teaching file cases is prevented. The space and nmnpower necessa D' to nlailRain tile files can be smed,

[] Telenuclear Medicine/Radiopharmacy 60.2 G. Brauers,

59.5 T. S&a, L. Csernay, L. Pfivics

C. M. Archer, J. F. Burke; R&D, A m e r s h a m I n t e r n a t i o n a l , UK.

Healthcare

Albert Szent-GyOrgyi Medical University, Department of Nuclear Medicine, Szeged, Hungary QUALITY CONTROL OF NUCLEAR MEDICINE TRANSFER VIA A COMPUTER NETWORK

IMAGE

The significance of the possible loss of information during image transfer via a computer network was tested by using static (256x256 matrix; 700 000 and 2 million counts) and whole-body images (512x 1024 matrix; 700 000 and 2 million counts) of a transmission bone phantom with 23 built-in lesions with different contrast ratio, and SPECT images of a Jaszczak total performance phantom (128x128 matrix; 90 images; 360 degrees rotation; 3 million and 30 million counts). A hard copy was produced on X-ray film by using a video imager (primary image [1]). Digital images were converted into DICOM format and transferred via the computer network to Silicon Graphics high-performance viewing stations (transferred image [2]). X-ray films were redigitalized by using a 12-bit film scanner, and transferred to the viewing stations for subsequent display (redigitalized transferred image [3]). The detectability of the phantom lesions on the three different types of images was scored from 1 to 4 (l=definitely negative, 2=uncertain, 3=suspected positive, 4=definitely positive) by three nuclear medicine specialists. The detectability of the lesions according to the primary and transferred images was analysed by means of the Receiver Operation Characteristic (ROC) curves. There was no significant difference between the ROC areas (0.934±0.02 for standard video images of the original data [1], 0.937±0.03 for the display after the network transfer of the original data [2], and 0.931±0.02 for the display after the network transfer of the scanned images [3]). It is concluded that there is no significant difference between the medical information quality of standard video images and computer displays generated after the network transport of original data and that after the scanning of original X-ray films.

THE CHEMICAL CHARACTERISATION IMAGING AGENT 99mTc-HL91

OF

THE

TUMOUR

The imaging agent 99mTc-HL91 is currently in phase I clinical trials for the d e t e c t i o n of h y p o x i c tumours. W h i l e this c o m p l e x is k n o w n in the l i t e r a t u r e , the c h e m i c a l n a t u r e of 9 9 m T c - H L 9 1 was not f u l l y e s t a b l i s h e d . Synthesis on the c a r r i e r level, 99Tc, h a d s h o w n that 99Tc-Pn(AO)2 c o n t a i n s a m o n o - o x o t e c h n e t i u m core w h i l e 99TcPent(AO)2 is a d i - o x o t e c h n e t i u m c o m p l e x .

l

I

O~H~O

99Tc-Pn(AO)2 lipophilic

I

I

O~H~O

99Tc-HL91 ?

[ I O~H/O 99Tc-Pent(AO)2 hydrophilic

NMR and UV/vis Our investigations using IR, s p e c t r o s c o p y and X - r a y c r y s t a l l o g r a p h y show that in solution, the 9 9 T c - H L 9 1 c o m p l e x can a d o p t b o t h the p e n t a - c o o r d i n a t e d m o n o - o x o f o r m and a h e x a coordinated form. The interconversion is v e r y facile and is s o l v e n t d e p e n d e n t . T h i s m a y be imp o r t a n t for the m e c h a n i s m of u p t a k e of 9 9 m T c - H L 9 1 since the m o n o - o x o s p e c i e s is l i p o p h i l i c and the di-oxo species is h y d r o p h i l i c . Electrochemical i n v e s t i g a t i o n shows that the b i o r e d u c i b i l i t y of 99Tc-HL9i is t e c h n e t i u m - e s s e n t i a l .

Radiopharmacy 60.1 $.M.Okaivi, C.M. Angelov, R.G. Cavell, /Ll.B. McEwan, M.R. Suresh. Faculty of Pharmacy. Dept. of Chemistry. University of Alberta, and Cross Cancer Institute, Edm~?nton,Alberta, Canada

60.3

LABELLINGOF PHOSPHORUS-NIIROQENBASED BIFUNCTIONALUGANDS. A variety of phosphorus-nitrogen(P-N) based compoundsare being synthesized which has the capability to form a complex with radioac'dve metal ion together with linked to a bioactive peptide. Further advantage of such bifunctional ligands is the ability to selectively react with 99mTc or 186/188-Re in a +7 oxidation state and in the absence of reducing agents. We hope the P-N ligands will behave as potential bifunctional ligands to conjugate them with bioactive peptide for the diagnosis of cancer. We approach the synthesis of the iminophosphorane ligands through the reaction of silylaminophosphine[, TzNPRz(T=SiMe3). The P-N ligands which are derived from the applications of these silylaminophosphine reactions with a diversity of organic substrates, have the a~bilityto attach 99m-Tc and 186/18g-Re by means of a covalent bo,d.

99mTc-LABELLED ANTI-FIBRONECTIN "SINGLE-CHAIN" Fv (scFv) CGS-l-cys: CHARACTERIZATION O F THE R A D I O P H A R M A C E U T I C A L FOR U S E IN H U M A N S A N D P H A S E I I M M U N O S C I N T I G R A P H Y TRIAL. H i g h - a f f i n i t y r e c o m b i n a n t a n t i b o d i e s as w e l l as their scFv fragments are now available from p h a g e d i s p l a y l i b r a r i e s . T h e scFv f r a g m e n t s h a v e a m o r e r a p i d c l e a r a n c e and are less i m m u n o g e n i c than complete antibodies. Furthermore, these f r a g m e n t s can be t a g g e d w i t h C - t e r m i n a l p e p t i d e tags w h i c h do not i m p a i r a n t i g e n b i n d i n g and represent a convenient functionalization site for a n u m b e r of a p p l i c a t i o n s u c h as r a d i o n u c l i d e labelling. We have labelled a cysteine-tagged recombinant s c F v d i r e c t e d a g a i n s t E D - B d o m a i n of f i b r o n e c t i n (CGS-l-cys) w i t h 9 9 m T c in o r d e r to c a r r y out scintigraphic studies of III/IV grade astrocytoma a n d b r e a s t cancer. A n o t h e r c y s t e i n e tagged recombinant scFv directed against lysozyme (Hy-HEL-10) was also labelled with 9 9 m T c to be u s e d as n e g a t i v e control. These radiopharmaceuticals w e r e s u b m i t t e d to q u a l i t y controls for chemical purity, "in vitro" stability, immunoreactivity, presence of pyrogens, sterility and absence of acute t o x i c i t y in rats. All t h e p e r f o r m e d t e s t s s h o w e d s u i t a• b l e . f e.a t u r e s | for . immunoscintigraphic a p p l l c a t l o n s in humans. A n l m a l s t u d i e s on C G S - I cys tumor targeting and biodistribution were also performed. A very favourable tumor/background ratio was obtained.

R.?Z R2PNTz + ZQX

~

/ +P---_NT2~ R X

~

]R-Mo,~o~,~o

] Z= NMe2,NEt2,CN, etc R~p--QZ]Q=CH2,CO,CH2CO,etc iX= ClorBr

Labelling with 99mTc is achieved either in the presence of reducing agent or by direct addition of 99mTc to the P-N ligand. Stability in plasma was examined by incubating the labelled P-N ligands with plasma at 37°C for tgh.The radio-TLC indicates that for some of the P-N ligands a single 99mTc-species is formed by simply mixing the P-N compound with 99mTc and, it is presumed that in these types of P-N complexes, 99mTc remains in a high oxidation state. However, P-N complexes produced under non-reducing labelling conditions exhibited somewhat unpredictable behaviour in terms of labelling efficiency. In comparison, P-N complexes formed in the presence of stannous tartrute are usually more stable and reproducible. In coclusion, P-N compoundsstudied have the ability to label with 99mTc, when labelling is performed with and without a suitable reducing agent. Moreover, P-N complexes showed a high stability when incubated with plasma. A more detailed evaluation of the P-N compoundsis in progress in order to determine their full potential as useful bifunctional ligands.

M. L ~ t o r e l , D . Neri2,L. Zardi3,B. ~ l l a 3, F. Ponzol,. l~il,A.P. Iurilli I, A. PaI~,G. S ~ i n a t o 4 , A . Centi ColellaI. iDept, of Experim. Med. and 42nd Clin. of Obst. Gynec., Ist U]~v. of Rome;2~4iss Fed.lnst. of Technology, Zurich;~at. Inst. for Cancer Research, Genua.

943

cO .m t~ e"

L-

O. m

t~

O

• Radiopharmacy/Neurology 60.4 N.Vanlid-Razumenid Lj.Vuksanovid and *J.Joksimovi~ Vin6a Institute o f Nuclear Sciences, P.O.Box 522, 11001 B E L G R A D E , *Institute for Biological Research, B E L G R A D E , Yugoslavia A N A L Y S I S OF P R O T E I N BINDING OF T c - R A D I O P H A R M A C E U T I CALS IN R E L A T I O N S H I P W I T H SPECIFIC B I O L O C A L I S A T I O N Organo-specificity o f 99mTc-radiophalrnaceuticals is influenced b y their physico-chemical characteristics and by their interaction with transport proteins in h u m a n blood as well. The interaction with transport proteins was examined on a series o f 13 radiopharmaceuticals (99mTccomplexes o f the following ligands): H M P A O for brain scintigraphy; GH, P A H I D A , M A G 3 , and D T P A for kidney imaging; PYP, MDP, and DPD skeletal imaging agents; E H I D A and I O D I D A hepatobiliary agents; P H Y T A T E for liver imaging, as well as both complexes o f DMSA: renal imaging agent Tc/III/-DMSA, and tumorotropic agent Tc/V/-DMSA. Interaction o f 99mTc-complexes with blood proteins was investigated from two aspects: total protein binding, and specificity o f binding to certain classes o f proteins. T O T A L P R O T E I N BINDING. After in vitro labelling o f h u m a n sera with 99mTc-radiopharmaceuticals, total protein binding was determined by three procedures: (1) protein precipitation b y trichloro-acetic or perchlm-ic acid; (2) dialysis o f labelled sera through membrane with M W cut-off 12,000 Da, in cold physiological saline; (3) ultrafiltration through Centricon-10 filters (Amicon product).The highest binding % was found with renal agents - complexes o f D M S A and GH, then hepatobilJary agents and 99mTc-PYP. S E L E C T I V E B I N D I N G for individual protein classes was analysed b y agarose gel electrophoresis. Sera obtained from blood o f patients w h o received 99mTc-agents for scintigraphy were subjected to electrophoresis. The following specific binding was found:cq-antitrypsin is the main transport protein for DPD, H M P A O , renal D M S A , GH, DTPA, P A H I D A , and EHIDA; albumin for Tc/V/-DMSA, and MDP; transferrin for IODIDA and P H Y T A T E ; etz-globulin for M A G 3 . Some agents were b o u n d for two protein classes like PYP, renal D M S A , and PAH1DA. Some relationships between protein binding and biolooalisation were noted for two 9 9 m T c - D M S A complexes and three skeletal agents.

60.6 K. Mang'era, C. Boonen, P. Adriaens, A. Verbmggen Laboratory ofRadiopharmaneuticalChemistry, F.F.W.K.U. Leuven, 3000 Leuven, Belgium *99roTe-COMPLEX OF L-CYSTEINYLACETYLDIGLYCINE (CAG2) AND ITS DIETHYL ESTER: SYNTHESIS AND BIOLOGICAL BEHAVIOUR 99mTe-L,L-ethylene dicysteine (99mTc-L,L-EC) and 99mTc-mercaptoacetyl tfiglycine (99mTc-MAG3) are in clinical use for renal function studies. In mice, 69% of injected 99mTc-MAG3 is excreted in urine by 10 min and 90% by 30 min post injection (pi.). For 99mTc-L,L-EC, the values are 74% and 95%, respectively. The 99mTc-complex ofL, L-ECD (diethyl ester ofL, L-EC) is taken up and retained in brain and is in clinical use as a regional blood flow tracer. The oxo-Tc-glycine sequence in 99mTc-MAG3 and 99mTc-L,L-EC is thought to be responsible for recognition at renal tubules and for high urinary excretion. LCAG2 can be considered as a hybrid of L,L-EC (the cysteinyl portion of LCAG2) and MAG3 (the acetyldiglycine portion). 99mTc-L-CAG2 would therefore contain two oxo-Tc-glyeine sequences that are representative of the oxo-Tc-glycine sequence of Tc-L,L-EC and that of Tc-MAG3. L-CAG2 was synthesised. 99mTc-tabelling gave o two peaks on HPLC (isomer A and B; presumably ,_._(/ diastereomers). In mice, 35% of 99mTc-L-CAG2(A) ~ i : , : : : ~ : ~ ' ~ / ! is excreted in urine by 10 rain, and 54% by 30 min "] p.i. 99mTc-L-CAG2(A) shows higher hepatobiliary k,,^ ::~'"~0 excretion and slower blood clearance than 99roTe"........ MAG3 or 99mTc-L,L-EC. Isomer B shows even Te-CAG2 i i ~ slower urinary excretion (7% and 18% at 10 and 30 rain p.i., respectively). However, renal uptake and retention was pronounced (47% at 10 min and 57% at 30 rain p.i). Although (s)low urinary excretion precludes possible use of 99mTc-L-CAG2 (A or B) as renal function tracers, high renal uptake and retention of 99mTc-LCAG2(B) could be useful for study of functional renal mass and the complex will be studied further in baboon. The results show that presence of an oxo-Tcsequence(s) does not necessarily assure high urinary excretion. 99mTc-L-CAG2-diethyl ester also yielded two isomers. However, none of the isomers showed significant brain uptake in mice at 2 min, 10 min or 30 rain p.i.

Neurology 60.5

61.1

M. Eisenhut, U. Titsch, A. Mohammed, S. Wagner, Department of Nuclear Medicine, University of Heidelberg, Germany

J.L. Baulieu, F. Tranquart, D. Guilloteau, S. Chalon, S. Akoka, F. Gold, J. Laugier, J.C. Besnard, E. Saliba INSERM U 316 37044 Tours France.

Tc-99m MELANOMA IMAGING AGENTS: SYNTHESES AND BIODISTRIBUTION OF Tc-99m BENZAMIDE COMPLEXES

DOPAMINE D2 RECEPTOR IBZM-SPECT 1N THE ANOXOISCHEMIC HUMAN NEONATE

The clinical value of dopamine D2 receptor (RD2) SPECT in adult and child is now well established. However very few is known about RD2 availability and pathological modification in the newborn. In a previous work (Eur J Nuc Med 21:487-489) we observed a significant decrease of RD2 availability after anoxo-ischemia in the newborn rat. The aim of the present study was to assess the falsability of RD2 SPECT i'n human newborn and to look for a possible change after anoxo-ischemic stress. After parent informed consent, five one week old newborns (39-40 week age gestational) who suffered from anoxo-ischemia at bcarth were included : mild hypoxic-ischemic encephalopathy (HIE) (Sarnat 1) n=2, moderate HIE # x xt x2 5 CH NH-CH;-C(CH3);-SH NH-CH2-C(CH3)2-SH with seizure (Sarnat 2) n=3. SPECT was performed one hour after a 35 MBq IBZM I.V. injection, using a Ceraspect* camera and a 30 minute 7 CH NH-CH~-CH~-SH NH-CH~-CH~-SH acquisition. Brain NMR imaging was performed on the same day to allow 8 CH NH-CO-CH2-SBz NH-CO-CH~-SBz anatomical locating. The patients were maintened in a dedicated incubator 10 CH O-(CH~)4-CH(CH~-NH-CH~-C(CH~)~-SH)a H and the heart rate and pO2 were monitored over the period of imaging. The 14 CH CO-N((CH~)~NH-CHz-C(CH3)2-SH)CH2-C(CH3h-SH H scintigraphic reconstructed brain slices were visually analysed and the ratio 16 CH SH H between the mean activity in the basal ganglia and cerebellum (S/C) was 18 N NHNH~ H calculated. No modification of the vital signs was observed during the acquisition time. Sn2÷was used as reducing agent and compounds 16 and 18 were complexed in the In all cases IBZM uptake was observed in the head of caudate and in the presence of coligands (HSCH2CH2)2Sand tricine, respectively. Among the 9~Tc computamen as delinated by NMR. In infants with mild HIE IBZM uptake was plexes tested so far, complex 18 showed the highest melanoma uptake and was retained symmetrical (S/C = 2.4 - 3.1).In infants with moderate HIE a unilateral in the tumor longer than in most non-target tissues of C57B16 mice. This finding decrease in 1BZM uptake was noted, despite no evidence of basal ganglia indicates specific binding. Although the results did not yet meet those values which lesions at MRI (S/C = 1 - 1.5 vs 2.8 - 3.2 controlateral). In one infant with were obtained with the radioiodinated congeners improvements are expected by the extended cerebral lesions a diffuse decrease in IBZM uptake was noted (S/C currently pursued systematic search for an optimum ~ T c ligand structure. = 1 - 1.3 for right and left). In conclusion, these results indicate that: 1. RD2 are present and available %ID/g Melanoma/Non-Target Tissue for radioligand binding as soon as the first post-natal week. 2. It is possible Compl. Melanoma Blood Lung Liver Muscle Brain to perform RD2 imaging in the neonates using IBZM SPECT. 3. Hypoxia lh/6h lh/6h lh/6h Ih/6h lh/6h lh[6h ischemia at hearth could be responsible for striatal RD2 loss or maturation 8 0.18/0.12 0.9/4.4 0.4/2.4 0.1/0.2 10.6/21.9 24.1/71.1 disturbance underlying extrapyramidal motor dysfunction. 10 0.64/0.36 1.5/1.5 0.6/0.7 0.1/0.1 4.3/4.6 25.5/23.4 14 . 0.68/. . . . . . 0.6/. . . . . 0.5/.... 0 . 1 / - 3.6/. . . . . 14.3/....... 18 1.60/0.84 2.9/1.3 1.7/1.2 0.7/0.6 7.3/5.3 34.8/30.1

Various 1-123 labeled N-(2-diethylaminoethyl)benzamide derivatives have been successfully applied for the imaging of human melanoma metastases. Due to availability problems and high cost the replacement of 1-123 by Tc-99m appears to be a challenging synthesis goal. Therefore, a series of stable Tc-99m o ( complex structures were selected and combined with x2~ that benzamide structure element which proved to be NH~ - I N ~ optimal, N-(2-diethylaminoethyl)benzamide. The following ligands have been synthesized:

944

II Neurology 61.2

61.4

L O Kapucu. E. Ko~. M UnJ0. A Zenciroglu. K Gtictb'ener. Y. Atala.,, and Eric van Royen. Gazi University and Sami Ulus Children Hospital, AnkaraTurkey' and Academic Medical Center. &msterdam-The Netherlands

BernaOkudan.,N ahideGiik¢ora,! TukErgiin,N e~eKa rabac ak, Tamer Atasever,I~vtlclm Giieiiyener,Ferhunde Oktem. Department of Nuclear Medicine, (;azi University Medical Sehn.l, Ankara,Turkey T H E EVALUATION BASELINE AND IJNGt'INTI(~ A(TFIYATION BRAIN SPECT IN DYSLEXIA

DOPAMINE D2 RECEPTOR IMAGING WITH 1-123 IBZM BRAIN SPECT IN CHILDREN WITH HYPOXIC-ISCHEMIC BRAIN INJURY

Purpose: The purpose of this study was to evaluate the striatal dopamine D2 receptor density in infants with perinatal h}~0oxic-ischemic brain injury (HIBI) using 1-123 IBZM brain SPECT and to correlate the findings with the severity of HIBI and neurologic outcome Material and Methods: Twenty infants who were diagnosed to have perinatal HIBI x~cre included in this study. "['hey were classified as ha~dng mild (n:6). moderate (n:10) or severe (n:4) HIBI according to their neurologic findings at birth using the criteria of Samat and Samat. Neurologic outcome of these infants was detem~ined by means of serial neurologic examinations and Denver developmental screening test: ten infants recovered x~lthout ans deficit and the remaining 10 were affected to a degree va~'ing from mild motor impairment to cerebral palsy All 20 infants were examined using 1-123 [BZM brain SPECT at tbe mean age of 78_+2.3 months Transaxial slices were obtained 2 hours follox~qng iv.injection of 300 vCi (i 1 1 MBq) 1-123 IBZM m~d the activity' ratios of striatal to occipital cortex (ST/OC) were calculated. Results: The mean (ST/OC) ratios in patients with mild. moderate and severe HIBI (1219±0.078. 1.097±0069 and 0813±0.14. respectively) x~ere significantly' different from each other (p=0 001) The infants who recovered from HIBI vdthout any neurologic deficit had higher mean ST/OC than the others ( 1.184_+001 vs 0.969_+0 16, p=0.002). Conclusion: The results of this study show that in infants with hypoxicischemic brain fl!iury striatal D2 receptor densit.~ decreases as the sexerit? of injui) increases The D2 receptor densit3 is higher in infants who recover without neurologic deficits as compared to those who are affected neurologically Dopaminc D2 receptor intaging can be used to assess the sexerity of hypoxic-ischemic brain injury in children

c-

Baseline and acti;ation regional cerebral blood flo,a lrCBF) SPECT ~as carried out in 10 cases with dyslexia (ll/ean age+SD: 1 I(,±24 yrs. 8 male. 2 female, 7 right handed. 2 mixed. I left banded ) and It) age matched controls were also performed brain perfllsion study to dciernlille differences in cortical fimction Brain SPECT studies uere performed 515 nun after the ix' injcclioll of Tc99m HMPAO using a rotaiiug P.'.oheaded gamina carnera with a high rcsohltion lov, CUEr'g} collimator.During baseline SPECT. control subjects did nol dispta) aoy significant difference between the righl and left henlispheric conical regions for any gixen area (p>0tlS). Hog,ever. in d}s[exic SUI~iEClS.

relatb,rely lower rCBF t~as obser',ed at baseline in left lemporal lobe compared Io the contrahneraI side and Im~er rCBF ~as obscrxcd al right occipital cortical region COluparedIo the left (p lead Io a

new question for delermioation of role of this area m Icxical flmction

61.3

61.5

1A.Ahonen ' 2 Dahlstr6m, 2I. Moilanen, ~P. Tomiainen, ~J. Heikkil~i. 1Division of Nuclear Medicine, University Hospital of Oulu and ZDepartment of Child Psychiatry, University Hospital of Oulu, Kajaanintie 50, FIN-90220 OULU, FINLAND.

A. Burroni, D. Volterrani, P. Bcrtelli, A. Vella and A. Vattimo. Department of Nuclear Medicine, University of Siena, Policlinico "Le Scotte", Viale Bracci, 53100 Siena, Italy.

BRAIN SEROTONIN TRANSPORTERS IN DEPRESSIVE CHILDREN Very, little is known about amount and distribution of brain receptor in children. There are only few publications handling brain receptor imaging in children. For ethical reasons radioactive tracer cannot be injected into normal children and therefore receptor reference values for children are not available, which is causing difficulties in interpretation of results. We have investigated 17 children with neuropsychiatric disorders using 123-~-CIT ([123-I]2~-carbometoxy-3!g-(4-iodophenyl)tropane[123I]2[8-CIT) for imaging of brain dopamine and serotonin transporters. The first scans were taken one and four hours (serotonin transporter density). Transaxial slices oriented in orbito-meatal tOM) line were reconstructed and the following regions were drawn for measurements of serotonin receptors: medial prefrontal cortex (MFC), frontal white matter (FWM), thalamic area (Th), middle-brain (MB) and occipital white matter (OWM). Following serotonin transporter indexes were calculated: MFC/FWM, Th/FWM, MB/FWM, MFC/OWH, TI'gOWH and MB/OWH. Diagnosis were based on clinical examination and on structural diagnostic interview C-SSAGA. In addition to this, Child's Behavior Checklist according to Achenbach were filled in by childrens parents, teachers and the children themselves. The thalamic serotonin transporter density index 4 hours after injection was significantly lower (p<0.01) in 11 depressive children with multifactorial courses (inc. 9 conduct disorders) or in pure depression (n=2) compared to a group consisting of 4 sole conduct disorder, one normal child and one child with autistic features. The highest serotonin level was measured in this autistic child. Our preliminary results are promising. However, neuropsychologieal tests must be completed and more children imaged before any definitive conclusions can be drawn.

QUANTITATIVE EVALUATION OF BRAIN PERFUSION WITH ECD-Tc99rn SPET IN RETT SYNDROME Rctt syndrome (RS) is a rare early-onset progressive neurological disorder witnessed in children, exclusively in females. The clinical manifestations are deceleration of head growth, impaired communicabiin 3, loss of manual skill and speech, stereotypies, mental deterioration leading to dementia, epilepsy, bruxism and scoliosis. The pathogencsis is still unknown. The disease has four clinical stages based on the extent of mental deterioration. The aim of this study was to establish a relationship between rCBF assessed with Tc99m-ECD SPET and the clinical manifestation and progression of the disease. We performed the study on I8 girls (aged 3 to 19 years; mean 10.5+5.3) displaying the classical form of RS and we c,)mpared their data with that of an ~age-matched reference group of 9 normal children. All RS girls underwent a detailed clinical examination, a brain MRI and an EEG invesligatkm. A quantitative analysis of rCBF was performed calculating a perfuskm index (Pl=cortex/cerebellum) in each lobe. A statistically significant (p=.00(B) global reduction of CBF was found in the group of RS girls (P1=0.99_+0.10) when conrpared with the reference group (PI=1.23_+0.12). Moreover, a great difference was also observed between the control group and stage IV (p=.0009) and between the c(mtrol group and stage III RS girls (p=.0034). The areas with greatest CBF reduction were the frontal and temtx~ro-parietal regions in concordance with diffuse EEG alterations. No significant right-to-left asymmetry was found to recur in the cortex. MRI revealed only mild to moderate cerebral atrophy in 5 patients and ventricular asymmetry in 2. Reduced CBF in patients with normal brain MR1 may indicate that SPET analysis reveals a functional alteration such as reduced blood supply before morphological damage is appreciable. Our data confirms that RS is a diffuse and non-focal or non-side neurological disorder. Tc99mECD SPET seems to be sensitive in revealing diffuse brain blood flow abnormalities closely related to EEG alterations, even when MRI patterns are normal. Morexn'er, brain blood flow reduction is related to the clinical progression of the disea~.

945

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8

• Neurology/Cardiovascular 61.6

62.2

I Gordon, B Lask, R Bryant-Waugh, D Christie, and S Timimi. Great Ormond Street Hospital for Children NHS Trust. London WC1N 3JH

R.F. Carretta, F.L. Weiland, P. Vande Streek, R.W. Dann, K.S. Madsen, E.M. Aten. Sutter Roseville Medical Center, Roseville, CA., Diatide, Inc. Londonderry, NH and The Multicenter Trial Sites.

A POSSIBLE BIOLOGICAL SUBSTRATE UNDERLYING ANOREXIA NERVOSA. Aims: The aetiology of anorexia nervosa is not well understood, but is likely to be multifactorial. Despite considerable research, the biological contribution is yet to be identified. The aim was to investigated the possibility of an underlying biological substrate as one of the comer stones in the pathogenesis of anorexia nervosa. Methods and Results: 15 children, age 8 - 16 years who all fulfilled DSM IV criteria for anorexia nervosa and had a ratio of weight/beight of <80% agreed to undergo regional cerebral blood flow studies (rCBF) using single photon emission computerised tomography (SPECT). Thirteen had unilateral temporal lobe hypoperfusion, 8 on the left side and 5 on the right. The abnormality persisted in the three out of 4 girls who have had a follow up scan after weight restoration. Discussion: This is the first report of reduced regional cerebral blood flow in childhood onset anorexia nervosa, and suggests an underlying primary functional abnormality. Changes in rCBF which are purely due to starvation would likely be global and symmetrical. The reduced rCBF seen may be primary especially that it was unilateral and in three of four children with follow up studies who had regained their weight, the changes were persistent. The current understanding of anorexia nervosa is that of a hypothalamic pituitary gonadal abnormality. The hypothalamus also forms an integral part of the limbic system where direct connections exist between the hippocampal formation and the amygdala of the temporal lobe and the hypothalamus. These timings give weight to the hypothesis that there is an imbalance of the limbic system. This imbalance may be the primary biological abnormality that has been triggered by external factors so resulting in anorexia nervosa.

Cardiovascular 62,1 C. Hossein-Foucher1, A. Millaire2, P. de Groote2, X. MarchandiseI. t Department of Nuclear Medicine ; 2 Department of Cardiology C ; CHR&U Lille, France. RADIOLABELLED ANTIMYOSIN ANTIBODIES IN THE DIAGNOSIS OF ACUTE MYOCARDITIS : PRELIMINARY RESULTS. The usefulness of indium-Ill antimyosin scintigraphy (AMS) in diagnosing myocarditis has been generally investigated in biopsy proven cases which are often severe myocarditis.Very few data are available concerning the use of AMS in patients with mild or moderate myocarditis diagnosed without endomyocardial biopsy. In our study, myocarditis was suspected when a body of arguments was present including data from clinical examination (fever, viral context, chest pain, pericardia[ rub), ECG (acute ST segment elevation or T wave inversion with further complete recovery), biological tests (inflammation, viral titers) and 2-D echo (pericardial effusion or segmental wall motion abnormality). 18 patients were investigated (13 males, 5 females, age 37 + 17 years). AMS was performed 48 hours after the injection of 74 MBq of Indium 111 antimyosin monoclonal antibodies and compared with a rest thallium scan. ROIs were drawn to calculate a myocardial/pulmonary uptake ratio. Coronary artery disease was excluded by coronary angiography (n=5) or thallium scan. In 11 patients, the diagnosis of myocarditis (or myopericarditis) was considered as definite when creatine kinase MB was significantly increased in blood. The 7 other patients presented isolated peficarditis (n = 4) or other cardiac disease (1 stable valve heart disease and 2 supra ventricular arrhythmias). ROC curves were established to determine the best uptake ratio to diagnose myocarditis. A ratio of 1.55 was the best compromise between sensitivity and specificity (91% and 100 % respectively). When positive, the uptake was most often localized (80 %) than diffuse. In conclusion, our results suggest that antimyosin cardiac scintigraphy is an accurate test in diagnosing myocarditis in a clinical series of patients,

946

ACTIVATED PLATELET TECHTIDE TM Tc-99m P280: SAFETY AND EFFICACY FOR THE DETECTION AND LOCALIZATION OF ACUTE DEEP VENOUS THROMBOSIS (DVT). Tc-99m P280 is a platelet GPllb/llla receptor binding radiopharmaceutical. The goal of this work was to evaluate the safety and efficacy of Tc-99m P280 for the detection and localization of acute DVT. In a multicenter trial conducted at 14 sites, 135 patients presenting within i0 days of the onset of symptoms of acute DVT were imaged following intravenous administration of 0.37-1.3 GBq (mean 0.78 GBq) Tc-99m P280 containing 20-100 ug P280 peptide. Lower extremity images were obtained at 10-90 min post injection. The results were read by the investigators and by 3 independent blinded reviewers, and were compared to a censored final institutional diagnosis (CFI). The CFI was independent of the Tc-99m P280 study and was based on a primary confirmatory procedure conducted within 36 hr of Tc-99m P280, secondary procedures and clinical signs. The confirmatory procedure, which was ultrasound in 126 patients, was not read blind and was n o ~ validated. The results from the 118 evaluable studies showed an agreement rate, sensitivity and specificity of 81.4%, 81.3% and 81.5% according to the investigators and 57.3%, 56.0% and 61.7% by the blind reviewers. The blinded reviewers had no knowledge of the patients' medical history or clinical signs and the results underscore the value of these factors in arriving at a correct diagnosis. The Tc-99m P280 result changed the CFI from DVT to no DVT in 9 patients, from no DVT to DVT in 3 patients and changed the localization of the DVT in 1 patient. No serious adverse events were associated with Tc-99m P280 administration. The results demonstrate the potential of Tc-99m P280 for the safe and effective detection and localization of acute DVT. -

62.3 Van01i G., Rossetti C., Carpinelli A., Savi A., D'Angelo A., Crippa L., Deutsch E., Knight H., I_ucignani G., Fazio F. INBCNR, University of Milan, Institute H S. Raffaele, Milan, Italy. Mallinckrodt Medical, St Louis, MO FRESH THROMBUS IMAGING IN HUMANS WITH A NEW Tc99m-LABELED PEPTIDOMIMETIC We have evaluated a new labeled molecule consisting of an N3S-chelate chemically linked to a peptidomimetic moiety which has high affinity for the Gpllb/llla receptor expressed on activated platelets. This prototype is easily prepared from an instant kit and 99m-pertechnetate with radiochemical purity >95%, and is stable for up to 6 hr. Studies in normal volunteers show rapid blood clearance (T/2 = 11.46 +__ 4.1 rain) and extensive liver uptake (31.7+ 1.6% i.d. 30 rain p.i.). The aim of this work was to assess the labeled compound for imaging fresh thrombi in humans. We studied ten patients (4 males, 6 females, mean age = 60 +_ 11 yr) with diagnosis of deep vein thrombosis based on pain of one lower limb, plasmatic fibrin degradation products (D-Dimer) >2.3 ug/ml, and positive compression with ultrasonography examination. The labeled compound (15-20 mCi) was administered intravenously to each patient within 2 hr of enrollment. Whole body images were acquired at 30 and 60 rain p.i. Activity ratios between affected and contralateral limb were calculated. No adverse reactions were observed. Tracer accumulation was in aH cases consistent with diagnosis. Affected/contralateral limb activity ratios w e r e 1.89 _+ 0.50 at 30 rain and 1.94 + 0.55 at 60 rain (in normals= 0.98 + 0.004 and 0.99 + 0.005 respectively). These results indicate that this class of 99inTo compounds has potential for the imaging of fresh thrombi.

Cardiovascular/Radiation Protection 62.4 E.M. Aten, J. Lister-James, K.S. Madsen, R.W. Dann, D.T. Wallace and R.T. Dean. Diatide, Inc., Londonderry, NH and The Multicenter Trial Sites. ACTIVATED PLATELET TECHTIDE T M Tc-99m P280: EVIDENCE FOR HIGHER AGREEMENT RATE (WITH ULTRASOUND) USING A FULL VIAL DOSE Tc-99m P280 is a platelet GPIIbfiIIa receptor binding radiopharmaceutical for imaging deep vein thrombosis (DVT). The goal of this work was to determine whether the ability of Tc-99m P280 to detect and localize DVT was dependent upon the injected dose of P280 peptide. In a Phase 2 study, 27 patients having DVT confirmed by ultrasound (US) received 20, 50 or 100 gg peptide (0.2, 0.5 and 1 x full vial dose) labelled with 185,370 or 740 MBq Tc-99m. A 3-person blinded read of the Tc-99m P280 scans showed copositivity with US of 59.3%, 66.7% and 88.9% for the ascending peptide doses. The corresponding results based on the un-blinded study-site evaluations were 88.9%, 77.8% and 100%. In a Phase 3 study, t 18 patients presenting within I0 days of the onset of symptoms of DVT were imaged using 370-740 MBq Tc-99m P280. 94 patients received <70gg and 24 patients received >70gg peptide. The Tc-99m P280 scans were read by 3 blinded reviewers and compared to the institutional diagnoses (95% of patients had US). The agreement rate, copositivity and conegativity for doses >70gg was 69.4%, 68.3% and 75.0% versus 54.3%, 52.6% and 59.4% respectively for doses <70~tg. Although statistically significant (p<0.05) for only one bIinded reader, the trend observed in the Phase 2 study was confirmed. In conclusion, these results indicate that the agreement rate of Tc99m P280 with US for the detection and localization of DVT is higher when a full vial dose is administered.

ADVERSE OUTCOME ASSOCIATED WITH HIGH RESTING LEFT VENTRICULAR EJECTION FRACTION IN OLDER PATIENTS: A CLINICAL OUTCOME STUDY. High resting left ventncular ejection fraction (EF) is sometimes characterized as supranormal, but older patients (pts) with a very high EF often do not have "normal" hearts. To assess the prognostic implications of this latter observation, follow-up was reviewed for 900 consecutive clinical pts age _>50who had resting Tc-99m-labeled red blood cell radionuctide ventriculography studies with normal EF (_>50%) performed from 1987-1991. All-cause mortality was examined for pts grouped by age and EF using KaplamMeier curves. 506 pts (56%) died during follow-up; mean duration of follow-up among survivors was 6.5 years. One-year (1YS), 3-year (3YS), and 5-year survival probabilities (5YS) for the various groups were as follows. EF (%)

I Aqe (yr)

# Pts

1YS

3YS

5YS

50-59

i 50-59.9

76

0.907

0.692

0.'567

60-69.9

249

0.831

0.676

0.542

->70

141

0.879

0.69I

0.541

50-59.9

52

0.942

0.885

0.766

60-69.9

185

0.807

0.653

0.520

_>70

93

0.817

0.575

0.408

50-59.9

10

0.700

0.700

0.600

j 60-69.9

69

0.797

0.604

0.458

60-69

->70

i

_>70 i 25 I 0.680 0.555 0.394 There was no significant difference in survival among the 3 age groups for EF 50-59%. Survival for pts <60 with EF 60-69% was better than for all other groups (p60 in age, there was a progressive decrease in 1-5YS with increasing EF. Poorest prognosis was for pts aged _>70with EF>_70%. In pts ->60 Years old, high EF may be associated with an adverse Iongterm prognosis. In particular, EF_>70% should be reported as "normal" with caution.

Radiation

62.5 G. Manca, C.R. Bellina, G. Parenti*, M. Grosso, G. Boni, R. De Caterina**, W. Bernini**, S. Vargiu, and R. Bianchi. Division of Nuclear Medicine (Dept. Oncol), *Department o f Neurosciences University of Pisa, 'Institute of Clinical Physiology;' CNR, Pisa. SCINTIGRAPHY WITH I N - i l l AUTOLOGOUS LABELED PLATELET FOR THE DIAGNOSIS OF "HIGH RISK" CAROTID ATHEROSCLEROTIC LESIONS The most commonly used criterion for selecting patients (pts) with atherosclerotic lesions of the carotid artery and high risk for stroke is currently the estimation of carotid stenosis by angiography. However, this technique does not allow to evaluate the thrombotic and embolic potentiality of the atherosclerotic plaque, which is a useful information for risk stratification and surgical management of pts with high-grade carotid stenosis. The aim of this study was to compare In-Ill labeled platelet scintigraphy and other noninvasive diagnostic tools with the histology of the atherosclerotic plaque in pts with carotid stenosis and high risk for stroke. Nine pts (7 males and 2 females, age range 48-74 yrs) with carotid stenosis >70% (detected by digital subtraction angiography) underwent carotid doppler ultrasound, transcranial doppler for "emboli detection" and autologous indium-ill labeled platelet scintigraphy with blood pool subtraction. All pts were then operated and the results of the diagnostic tests were related to the histological findings (thrombosis and/or plaque haemorrliage}. Six pts with thrombosis and/or plaque haemorrhage were positive on radiolabeled platelet scintigraphy. In the remaining three patients with fibrotic plaque, no uptake was detected. No significant correlation was found between hystological findings and the results of the other noninvasive diagnostic tests. In our patient group, Indium-1 I1 labeled platelet scintigraphy shows the highest positive and negative predictive value for detection of the thrombotic and embolic potentiality of the plaque compared with other techniques.

¢-

62.6

Protection

63.1 S F Barrington, A G Kettle, P J Hountford, W H Thomson, S Batchelor, D N Burrell, R J Farrell, M J O'Doherty, L K Harding, UK Radioiodine Dose Study Group, Nuclear Medicine, Kent and Canterbury Hospital. RADIATION EXPOSURE OF CRITICAL GROUPS A F T E R 1-131 FOR THYROTOXICOSIS Methods to limin the radiation exposure from patients receiving radioiodine therapy are under scrutiny. Recent US guidelines limit the dose received by members of the public to ImSv and family members to 5mSv. Changes to European Com~vLunity guidelines are anticipated. Current methods vary widely with some countries requiring hospital isolation. In the UK 800MBq 1-131 may be administered to outpatients. Data are required for the actual dose received from radioiodine patients to formulate guidelines. We report interim results of a study to m e a s u r e the dose received by patients families after 1-131 therapy in 5 UK centres. Advice was given to restrict close contact for 5-25 days depending on 1-131 activity and the age of the patients' children. Partners accompanying patients for treatment recorded travel doses with electronic personal dosimeters. All family members were given LiF thermoluminescent dosimeters(TLDs) to wear on both wrists. Data were obtained from 31 adults and 70 children. A c t i v i t y of 1-131 a d m i n i s t e r e d was 195-604 MBq. Travel doses m e a s u r e d 42 5 2 ( m e a n 4 9 ) u S v in one hour. TLDs worn for 647(mean 24)days recorded <5.3mSv in all adults. 68/70 children received
947

O

= B

c-

o. m

O

•

Radiation Protection

63.2

63.4

W. Esclmer_, H.W. Hillger, U. Wellner, H. Schicha Clinic for Nuclear Medicine, University of Cologne, Germany

I. Pe~uelas, JM. Marti-Climent, R. Calvo, JA. Richter. PET-CUN Center, Department of Nuclear Medicine, University Hospital School of Medicine, Pamplona, Spain.

RADIATION EXPOSURE FROM INHALATION OF IODINE EXHALED BY RADIOIODINE THERAPY PATIENTS

A SIMPLE SET-UP FOR HAND-DOSE REDUCTION PREPARATION AND INJECTION OF [O-15]WATER.

I

IN

THE

Conclusion: An upper limit of 250 MBq on the activity of the RT patient at the time of discharge from hospital is justified. With that limit, the effective dose to persons living with the patient will certainly not exceed 1 mSv.

Dose drawing and injection of [150]water for PET studies results in considerable hand doses to laboratory technicians and nurses due to the high activities used for such studies. We have designed a simple and cost-effective setup and evaluated its efficacy by measuring the dose received in the hands of laboratory technicians during [150]water dose drawing. In this set-up, the [iSO]water batch is directly transferred under argon flow from the synthesis unit (IDA) to an activimeter placed in a manipulation hot cell, and by over and underpressure-based fluid transfer and three-way valve operation, a syringe placed in a 5 cm Pb container is automatically filled with the desired activity of [150]water through an sterility filter. The diminished manipulation of the syringe results in a highly significant reduction of the dose received not only by laboratory technicians but also by nurses. Dose measuring with a calibrated direct reading Geiger counter firmly tied to the hand back of the operator, produced values as low as 15.1 ± 7 ~Sv (mean ± st. dev) per procedure for a [O15]water activity of 3.9 ± 2.1 GBq at the beginning of the procedure, while the activity at the time of injection was between 1.3 and 1.5 GBq. The system has demonstrated to be not only efficient in hand dose reduction, but also simple, useful, cost-effective and easy to use.

63.3 M. Marti-Climent, I. Pe~uelas, R. Calvo, JA. Richter. PET-CUN Center, Department of Nuclear Medicine, University Hospital School of Medicine, Pamplona, Spain.

63.5 E. Havlik ~ A. Kurtaran 2, P. Schaffarich ~, P. Smith-Jones2, B. Niederle 3, I. Virgolini2, H. Bergmalm ~, JDepartment of Biomedical Engineering and Physics, ~L.Boltzmann-Institute of Nuclear Medicine, 2Dept. of Nuclear Medicine, 3Dept. of General Snrge~, University of Vienna, Austria

Purpose: To investigate the radiation exposure to relatives of radioiodine therapy (RT) patients due to iodine activity exhaled by the patient and inhaled by the family member. The investigation was aimed at determining the maximum exposure to members of the public with the proposed upper limit of 250 MBq on the activity of the RT patient at the time of discharge from hospital. Method: In n = 10 volunteers (all spouses of RT patients) we measured whole body (WB) iodine activity 2-3 days after discharge of the patient. A WB counter with 4 NaI detectors was used for these measurements. Iodide concentration in urine was also determined. The measured values were compared with calculations based on our model of iodine kinetics, taking into account administered and discharge activity, time spent together, room air volume and air throughput. Results: All measured exposures were below 50 pSv effective dose equivalent (mean 8.0, SD 11.2, min 0.2, max 31.8 pSv). Computed exposures were somewhat higher and varied more (mean 13.4, SD 25.5, min 0.2, max 85.2 gSv). Thus some model parameters will have to be readjusted.

RADIATION PERSONNEL

DOSE

TO

POSITRON

EMISSION

TOMOGRAPHY

Positron emission tomography technologists and nurses were monitored with personnel and area thermoluminescent dosimeters (TLD). Methods: The average dose was based on the TLD dose accumulated over studies conducted over eight 1-month interval. The average dose per study, for the 416 PET examinations performed, was 414 MBq. Laboratory technologists were involved in dose drawing, hot laboratory management and basic cyclotron maintenance, while nurses were dedicated to patient care and dose injection. Dose injection was done using 5 cm Pb lead syringe shielding, while dose drawing was done without syringe protection. Area dosimetry was performed using ten TLD dosimeters distributed in possible hot points around the PET installation. Results: Average dose per study (zSv/study) was: ]Shallow Deep Fingers] Technologists 7.4 4.7 256 Nurses 6.1 5.7 33 Average area dose around the installation was found to be less than 0.15 mSv/month, except for the patient preparation room, scanner room and near the transfer line from cyclotron to hot laboratory that were 0.91, 0.60 and 0.48 mSv/month respectively. Conclusion: The technologists received more dose than nurses, specially to fingers, due to dose drawing.

948

R A D I A T I O N D O S E RATES N E A R PATIENrFS U N D E R G O I N G H IIn.DTPA.D.PHE_ 1 - O C T R E O T I D E S C I N T I G R A P H Y Radiation exposures near patients undergoing l[lln_DTPA_D.Phe. IOctreotide ( r a i n - O C T ) scintigraphy were estimated because of radiation protection considerations. Dose rates were measured at distances of 0.5m, l m and 2 m from t h e surface of 16 patients who h a d received intravenous injections of 130 _+ 30 M B q r a i n - O C T ® (OctreoScan ,Mallinckrodt Medical B.V., Petten), using calibrated portable dose rate detectors (Berthold LB 133®), at 10 minutes, b e t w e e n 1 and 5 hours and 24 hours after administration of the tracer. The initial dose rates were 10.7/xSv/h at 0.5 m, 3.4 #Sv/h at I m and I. I #Sv/h at 2 m distance from the patients, respectively. T h e m e a n effective half-life was estimated to be 8.5 hours. By integration of the time course of t h e dose rates the radiation doses were calculated and t h e possible exposure to other persons were estimated: T h e m a x i m u m dose to persons in t h e waiting area (attendents or other patients) was 47 #Sv, to family m e m b e r s 22 ;zSv, to nurses in a ward 16 ixSv and to neighbour patients in a ward 37 #Sv. O u r results d e m o n s t r a t e t h a t the calculated m a x i m u m radiation exposures to personnel, family m e m b e r s a n d other patients are far below the limits for not-professionally exposed persons set by radiation protection regulations.

63.6

P2

HL Sharma and A M Smith. Department o f Medical Biophysics, University of Manchester, Oxford Rd, Manchester, UK.

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

U P T A K E A N D L O C A L I Z A T I O N OF R A D I O P H A R M A C E U T I C A L S IN M O U S E OVARIES The number o f reproductive germ cells in female m a m m a l i a n species is finite (3,000-5,000 for mouse and 300,000 for human) and, if once destroyed, cannot be replenished. Experiments using external irradiation o f the mouse have shown that primordial oocytes are more radiation sensitive than developing oocytes. In the same model, it has been shown that A u g e r emitting radionuclides have a greater R B E compared to their [3--emitting counterparts. Despite this, we have found little information on the ovarian uptake o f radionuclides and their distribution within this organ. Using the extensively investigated mouse model, we measured the ovarian uptake o f various radiopharmaceuticals relevant to nuclear medicine: Tc-99m labelled MDP, M A G 3 and DTPA, TI-201, Ga-67, 1131, I n - l l l , Fe-59 and In-ll4m. The data was acquired at lh, 4h and 24h post injection with 4-5 animals per time point. The percentage uptake o f injected dose per gram o f tissue (% i.d./g) and whole organ were calculated for each radiopharmaceutical. Autoradiographs were obtained from ovarian sections using In-114m. Generally, all the Tc-99m labelled pharmaceuticals showed low concentrations in the ovaries: 0.25 for MAG3, 0.81 for D T P A and 1.26 for MDP. The respective concentrations for 1-131, Ga-67, TI-201, In-111, and In-114m were: 1.08, 4.15, 6.28, 6.85, and 7.30. The highest concentration o f 9.54 was seen with Fe-59 (all % i.d./g at lh). Autoradiographs o f the ovarian sections with In-l14m clearly showed that the radionuclide was specifically localized in i) the cytoplasmic region o f the growing follicles ii) the epithelium o f the ovaries and iii) the inner epithelial lining o f the oviduct. Some growing follicles showed a very high grain density compared to others, suggesting a wide variation in their radiation exposure.

THALLIUM-201 REST-REDISTRIBUTION TO OUTCOME AFTER REVASCULARIZATION.

P1

P3

J . S o a r e s J[., M . C . P . G i o r g i , L . F . M o r e i r a , E . B o c e h i , F . Bacal,N.Stolf,M.Izaki,F.V.Salis,R.Abe,G.G.Cerri,J. C.Meneghetti. Heart Institute-Department 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 Sao P a u l o - Brazil.

Roy S, Cottin Y, Guy F, La[ande A, Touzery C, Walker PM, Louis P, Wolf JE. Brunotte F Service de M6decine NucIdaire, Centre G.F.Leclerc, Dijon, France. Service de Cardiologie, CHU Dijon, France.

LEFT VENTRICULAR EJECTION FRACTION BY RADIONUCLIDE VENTRICULOGRAPHY (RN) AS A P R O G N O S T I C INDEX IN P A R T I A L L E F T V E N T R I C U L E C T O M Y .

COMPARISON BETWEEN MYOCARDIAL THALLIUM UPTAKE AND W A L L THICKNESS MEASURED ]BY MR[ IN POST-MYOCARDIAL INFARCTION PATIENTS.

Partial left v e n t r i c u l e c t o m y (PLV) - Batista's operation is a new surgical procedure for treatment of severe congestive heart failure (CHF) in o r d e r to i m p r o v e p a t i e n t ' s survival. The technique consists on p a r t i a l resection of the left v e n t r i c u l a r (LV) lateral wall to d i m i n i s h v e n t r i c u l a r v o l u m e a n d c o r r e c t its g e o m e t r y . In o r d e r to e v a l u a t e the r e s u l t s of this s u r g e r y we have s t u d i e d 23 pts (18 male; m e a n age 48 years) with CHF, NYHA functional class III and IV, s u b m i t t e d to P L V plus m i t r a l v a l v o p l a s t y . All pts u n d e r w e n t RN. L V E F w a s o b t a i n e d b e f o r e and a b o u t 22 days after intervention. There was a significant increase in LVEF: 0.19 ~ 0.05 (pre surgery) to 0.23 ± 0.07 (post surgery). Clinical evolution 6 months after surgery showed 69.5% (16/23) s u r v i v a l (Group I) and 30.5% (7/23) mortality (Group II). Pre and p o s t - s u r g e r y LVEF was r e s p e c t i v e l y : 0.19 ± 0.05, 0.26 + 0.06 (Group I) and 0.19 ~ 0.06, 0.18 Z 0.05 (Group II). T h e r e was a s i g n i f i c a n t d i f f e r e n c e in p o s t - s u r g e r y I V E F b e t w e e n g r o u p s I a n d II (p=0.01). These results indicate that surgery improved LVEF. The changes in LVEF permitted to d i s c r i m i n a t e two g r o u p s w i t h d i f f e r e n t p r o g n o s i s : the i n c r e m e n t of L V E F c o r r e l a t e d w e l l w i t h b e t t e r survival while the d e c r e a s e of L V E F c o r r e l a t e d with poor prognosis. Our d a t a s u g g e s t t h a t RN p l a y s an i m p o r t a n t role in the p r o g n o s i s of t h e s e pts.

Myocardial 2°1TI SPECT is currently used for the evaluation of viability after myocardial infarction. By showing the myocardial mass and its contraction, MRI wall thickness measurements also reflect viability. The purpose of this study was to evaluate the relation between the TI uptake after reinjection using myocardial SPECT and the wall thickness measured by MRI, M e t h o d : We studied forty-nine patients (mean age=59±18 years) after myocardial infarction, They underwent stress-redistribution-reinjectio~a 2°~Tl myocardial SPECT. The myocardium was divided into 13 segments which were classified visually as normal (group 1), reduced on stress image but with redistribution or reinjection (group 2), severely reduced, without redistribution or reinjection (group 3). TI uptake for each segment was also quantified as tl'~e percentage of maximal activity. Patients also underwent MR imaging with 1,5T MR imager using breath-hold cine MRI. End-diastolic (DWT) and undsystolic wail thicknesses (SWT) were measured using a eenterline method on each short-axis slice, and were grouped into 13 segments to allow the comparison with SPECT data. Wall thickening (~5WT) was expressed as SWT-DWT. Results : A significant correlation was found between TI t[ptake at stress, redistribution, reinjection and DWT, SWT and AWT (p<10~).The strongest correlation was found when comparing ZxWTand uptake at reinjection(Re). Re (%) DWT(mm) SWT(mm) AWT(mm) ]Group 1 (N=280) 89=13 8.8±2.5 11.6:k3.2 2.8±1.7 Group 2 (N-196) 75±12' 8.4±2.7 10.4±3.6" 2.[±!.7" Group3(N=16I) 57±15 $~ I 6.4±3.053 7.6-3.6 $~ 1.1--1,2s~ *p
PREDICT

FUNCTIONAL

We evaluated the accuracy of thallium-201 (TI-201) rest-redistribution SPECT to predict improvement of regional and global LV function after revascularization. The relation between the amount of viable tissue and the improvement of LVEF after the revascularization was also assessed. 31 patients with chronic coronary artery disease, scheduled for revascularization, were studied. A resting echo was performed to identify regional dyssynergy. The echo data were analyzed using a 13-segment model and each segment was scored on a 4-point scale, ranging from 0=normal to 3 =dyskinetic. On the same day, the patients underwent T1-201 imaging (10 rain and 3 4 hr delayed images were acquired) to identify viable myocardium within the dysfunctional regions. To analyze the T1-201 data, the following viability criteria were used: 1.normal TI-201 uptake, 2.mild fixed reduction of TI-201 uptake on the 3 4 hour image and 3.significant redistribution of TI~201. Improvement of regional and global LV function were assessed by echocardiography/radionuclide ventrianlograpby, performed before and 3 months after revascularization. Criteria for improvement were: improvement of segmental wall motion by 1 point or more (regional) and improvement of LVEF >5% (global). Results: 156 dysfunctional segments were identified: 57 segments improved in function and 99 remained unchanged. T1201 imaging identified correctly 54 segments that recovered function (sensitivity 95 %) and 53 segments that did not recover function (specificity 54%). Eight patients had more than 3 viable segments on TI-201 imaging; in these patients the LVEF improved from 31.8_+11.9% before to 41.6_+1h7%, P<0.05 after the revascularization. In the 23 patients with 3 or less dysfunctional, viable segments the LVEF remained unchanged (45.6_+12.6% versus 45.8+12.9%, NS). Finally, a linear relation existed between the number of viable segments on T1-201 imaging and the improvement in LVEF: y=l.36*x-l.7, r=0.70, P<0.0I. Conclusion: T1-201 restredistribution seems to overestimate improvement of regional function, but appears accurate in the selection of patients who are likely to improve in global LV function. The improvement of LVEF is linearly related to the amount of viable tissue on T1201 rest-redistribution.

tO IM t~ e-

tD x.__

949

tD O

P4 A.Bottega J. SoaresJr .F.H.Hironaka,D Pamplona,W.A.Chalela,M.C. P.Giorgi ,M. lzaki ,A.C.{.. Munhoz ,G.G.Cerri, d.C.Meneghetti. Heart Institute,Department of Nuclear Medicine.University of Sao

P6 W. Burchert, *H.G. Wolpers, J. van den Hoff, R. W e i n h a r d t , , G.J. Meyer, *P.R. LichtIen, H. H u n d e s h a g e n . Departments of Nuclear Medicil~e and *Cardiology, MediziniscEe Hochschule Hm~nover,Germany

Paulo-BraziJ

DOBUTAMINE RADIONUCLIDE VENTRICULOGRAPHY IN THE DETECTION OF MYOCARDIAL VIABILITY AFTER TtlROMBOLYSIS. The aim of our study was to assess the accuracy of dobutamine (DB) stress radionuclide ventriculography (RV) in predicting improvement of the left vemricular regional function very early after acute myocardial infarction(AMI) treated with thrombolysis We studied 29 pts ( 25 male, mean ago 55 years ) after the prime episode ofAMI. MI of them were in NYHA functional class I RV was performed on baseline and during I0 ug/Kg/min DB infusion 3 to 14 days after AMI treated with thrombolysis. Rest RV was repeated after 3 months. Improvement of infarcted region ejection fraction (EF) was observed in l0 pts (Group l) after DB infusion. In 19 pts the EF did not increase after DB infusion (Group It). After 3 mohths, 8 of 10 pts of Group I showed improvement of the infarcted region EF (sensitivity = 72.7%), whereas no improvement of the infarcted region EF was observed in 16 pts of the Group II (specificity 88.8%). The following table shows the rest infarcted region EF(IREF), the increment of infarcted region EF(MREF) during DB infusion and after 3 months: GROUP Rest IREF AIREFDB AIREF 3too. G I 0.33_+0. I 1' 0.07_+0.06** 0.12_+0 14.* G Il 0.34_+0. I2 0.0 I_+0.04 0.01_+0.13 *pNS vs G2 **p < 0.05 vs G2 The improvement of infarcted region EF very early after thrombolysis during DB infusion in low doses correlated with late improvement of regional function Our results showed that DB stress RV identified myocardial viability after thrombolysis with high accuracy(82.7%).

Positron emission tomography (PET) with a perfusion tracer and isF-tluorodeoxyglucose (FDG) is the standard procedure to assess tissue viability after myocardial infarction. H o w e v e r , dependence of tracer uptake on metabolic state, long scan times, and m o v e m e n t artifacts are disadvantages of this procedure. To overcome these Emitatiorts we used HC-acetate (ACT) for a s s e s s m e n t of perfusion and oxidative metabolism in order to evaluate myocardial viability. Methods: Thirty patients (55+18y.) witE chronic myocardial infarctions (42_+11% ejection fraction) were investigated before and 7_+5 m o n t h s after revascularizatio;t with PET (ACT, FDG; Siemens-ECAT 951). Moreover, regional wall motion was assessed by coronary angiography. Results: 60 of 155 preoperatively dysfunctional segments i m p r o v e d and showed a corresponding increase in regional myocardial blood flow (MBF). Significant differences of MBP at rest were found between n o r m a l m y o c a r d i u m , reversible segments, and irreversible injured segments in the baseline s t u d y (1.04_+0.27 vs. 0.7i_+0.18 vs. 0.43-+0.18 m l / m l / m i n ) . Only irreversible injured m y o c a r d i u m showed a reduction of oxidative metabolism. The predictive accuracy was similar to that of FDG and superior to oxidative metabolism or f l o w / m e t a b o ] i s m mismatch. Conclusion: A single ~C-acetatePET allows tire definition of irreversible injured m y o c a r d i u m as accurate as a combined p e r f u s i o n / F D G study requiring less than half the investigation time.

P5

P7

L Bontemps, M. Nazzi, M. Gabaln, Y. Sayegh, G. Dayoub, 13. Jegaden, R. Itti, Cardiological Hospital, Department of Nuclear Medicine, 69003 Lyon, France.

T. Athanaseulis, J. Nanas, D. Halzifetiadis, D. KentoyannJs, G.E Alexopoulos, P. Kostamis.

QUANTIFICATION OF PERFUSION, VIABILITY AND CONTRACTION IN PATIENTS WITH IMPAIRED LEFT VENTRICULAR FUNCTION, BEFORE AND AFTER SURGICAL REVASCULARIZATION When functional improvement is the primary goal of coronary artery bypass grafting (CABG) in patients with impaired left ventricular function, a combined radionuclide evaluation of perfusion, viability and contraction in the pre-operative state should be able to predict the outcome of CABG. A consecutive population of 30 patients (26 males and 4 females with ages ranging from 39 years to 79 years) has been prospectively studied in this context (left ventricular ejection fraction LVEF < 40%) a few days before surgery and one to two years after CABG. A previous history of myocardial infarction was present in 24 cases. Using a quantification software (P. Rigo, Liege) thallium uptake defects at stress and after redistribution have been measured pre- and post-operatively, as a percentage of the total myocardium, by taking into account both the extend and the severity of the defects, on a polar map constructed from tomographic long-axis radial slices. At the same time LVEF was measured using blood pool labelling and planar imaging. Improvement in cardiac ejection is demonstrated by a significant increase of LVEF from 28.2% +/- 8.5% (pre-CABG, mean +/- standard deviation) to 35.8% +/- 7.3% (post CABG). In the same time stress thallium uptake defects decreased from 34.8% +/- 13.8% to 25.5% +/- 10.8% whereas resting defects remained allmost stable (27.5% +/- 10.9% vs 25.7% +/9.9%). A significant ischemia characterized as a stross/redistribudon defect variation higher than 5% was present in 16 patients before CABG and remained present in 7 cases after CABG, but also <, which was not present in the pre-operative state, appeared in 9 cases post CABG. There is in fact no significant correlation between the improvement in LVEF and the reduction of the ischemic component of defects, hut some inverse correlation exists between the severity of the fixed defects (non viable parts) and the functional improvements. Therefore it may be concluded that existence of viable myocardium is the major determinant for a favourable outcome of CABG and that ischemia, although important for improvement of symptoms or quality of life, is less concerned when the contractile function has to be improved. 950

MYOCARDIAL VIABILITY ASSESSED BY ~IC-ACETATE-PET

Depts of Nuclear Medic/fe and Therapeutics "Alexandra" UniversityNosp#al, Athens, Greece. EARLY AND LATE Tcggm-TETROFOSMIN IMAGES IN PATTENrs WITH RECENT MYOCARDIAL INFARCTION. COMPARISON WITH THN_LIUM RESTREDISTRIBUTIONIMAGESI The objectives were: 1) to determine whether Tc99m4etrofosmin (Tc-TE) heart washout rate is regionally different in patients with recent myocardial infarction (MI) and 2) to compare early and late Tc-TE imageswith thallium rest-redistributionimages (RR-TL). We studied14thrombolyzedacute MI patients wilh high patency grade of the infarct related coronary arlery, one week post MI. All patients were injectedwith 555 MBq Tc-TE at resl and early and late sped images were obtained40 rain and 3 hours post injection. RR-TL images was performed in 7/14 patients. One month post MI a follow up Tc-TE study was performed in four patients. The left ventricle was divided ,/to 20 segments. Relative uptake in each segment was characterized, accordingto Lhe maximal activity found in each study, as normal: 70-100% of max, mildly decreased: 50-70%, moderately decreased:30-50% and severelydecreased:0-30%. GJmparison of early and late Tc-TE images showed that 14/21 segments with early mN perfusiondefect (PD) changedto moderale PD in late image. Likewise, 3/21 mild PD changed to severe PD, 12/31 moderate PD changed to severe and 6/187 normal segments changed to mild PD. Forty one segments with severe PD remained unchanged. All normal segments (181/187)that were not correspondedto the infarct related artery remained unchanged. RR-TL images revealed reverse redistribution phenomenonin '/8/50 affected segments, The relative Tc-TE uptake was also reduced between early and late image in all of these segments. In the follow up Tc-TE study of the four patients, 9/15 segmentsthat demonstratedreductionof the relative uptake in the initial study remainedunchangedin the late image, Conclusion, Preliminary results indicate that 1) Tc99m-tetrofosmin washout rate is faster than normal in some affected myocardial regions in thrombolyzedpatients with recent MI and this phenomenonis spontaneouslydecreased over one month of follow up, possibly corresponded to viabb stunned myocardium. 2) Myocardbl regions that demonstratethalliumreverse redistributionphenomenonalso demonstratefaster than normal Tc99m-tetrofosminwashout rate implyingthe same generatingmechanism.

P8 A. Bentmp, G. Claus* H.J. Otto, H. Klein* Department for Nuclear Medicine and Cardiology * University of Magdeburg, FRG

PIO ll.M. Moustala, A. Fawzy, Sh. El-Tobgl and M. Abd~l-Ghani l)epamnents of Nuclear Medicine* and Cardiolo~% Cairo Universib:, EK','pl

ASSESSMENT OF PERFUSION AND WALL MOTION WITH GATED SPECT IN THE DIAGNOSIS OF CARDIOMYOPATHY

TttALLIUM-REINJEC rlO~-NTG AS PREDIC'fOR O1.' MYOCARDIAL VIABILI.FT

The study included 85 patients with myocardial infarction ranging between 1,5 - 96 months with at !~ast one perlhsion defect on exercise T1-

Echocardiography is superior to conventional myocardial perfusion imaging for the investigation ofventricular dysfunction, yet often fails to identify the underlying cause Coronary- and left heart angiography may cause volume overload in pts with poor cardiac function. In ishemic heart failure, regional perfusion and contractility are diminished whereas in primary DCM, wall motility is disturbed without matching perfusion deficit. We studied the diagnostic value o£gated SPECT as a non-invasive tool in the differentiation between coronary artery disease (CAD) and dilated cardiomyopathy (DCM) in pts with heart failure Methods: 30 pts. with diminished left ventricular function (echocardiography) and dyspnea NYHA lI-III and 10controls without cardiac failure were included. Gated SPECT was carded out after i v injection of 14 mCi Tc99m-Sestamibi at rest. Analysis of regional perfusion was obtained and myocardial count increase rate between end-diastolic and end-systolic frames was related to wall thickening in 16 myocardial segments All patients and controls underwent coronary angiography within 2-60 days after nuclear testing. Results: In I8 pts with prima~ DCM, global perfusion/wall-thickening ratio amounted to 60 -+ 0 9 whereas in 12 pts with CAD, in poststenotic myocardial areas a significant lower ratio was found ( 4 0 _+ 0.8, p<0.01) In controls, global ratio was 1.5 _+ 01 and allowed discrimination against both groups with heart failure (p<0.01). Conslusion: Simultaneous assessment of perfusion and wall motion with gated SPECT and Sestamibi may prove to be useful in the differential diagnosis of heart failure and avoid coronary angiography in pts. with non-ischemic ventricular dysfunction.

201 using a dose of 111 MBq (3 mCi). Stress and redistdbution images /oUowcd 24 hours later by reinjection 1 mCi TI with images at one hour. Four hours later 2nd rck,!jcction dose of 1 mCi TI-201 wilh l0 mg sublingual nitroglycerine (NTG) with a 4th set of images at one hour. Each set of images was divided into 25 segments with 4 points scoring system aecordhlg to the degree ol myocardial uptake for calculation of extent and severity of pcrfusion defects.The total segments studied ~,;crc 2125 segments with 892 (42%) normal and 1233 (58%) hypop, crl&sed segments. On redistribution 283 of the sco~nents (23%) showe, d complete improvement.

Fudher improvement on reinjcetion

in 360 se~nents

(37.9°,0) and 33(} scglncnts (56.9%) on rcinjcetion-N'['O with signilicant statlstical diftcrcncc between both g;oups (P:z0.il09).Thc

mean severib"

hldcx was 41 ,_. 23, 3I 2 23, 17 + 14 and i3 2 i7 ha stress, redistribution, rciqicclion and rciltieclion-NTG respcclivcly wilh slatistical ,sigfdlicant difference bcm'ccn the different ~:,ups.

Vdhcrcas Ihc meal1 cxlcnt index

was 57 - 34, 45 2 34, 28 L- 34 and 21 _* 33 in the same ~'oups with nt~ significant changes between reinieclion and rcinjcetion-NTG.

to

| m

Ta conclude: 3"1-21)1 reinjcction-NTG lead to additional improvcmen| compared to rcittjcction in assessment of myocardial viabilib,.

¢-

L-

P9

Pll

L. Sarda, C. Nguyen, D. Vilain, R. Lebtahi, N. Delahaye, F. Salmon, D. Daou, M. Faraggi, D. Le Guludec. Hepital Bichat, Paris, France.

A. Dobbeleir, A.S, Hamb~e and P.R. Franken. Middelheim General Hospital, Antwerp and Free University (VUB) Brussels, Belgium.

O INTEREST OF IN111-ANTIMYOSIN-ANTIBODY (AMA) AND REST THALLIUM IMAGING IN PATIENTS WITH PRESENTATION OF ACUTE CORONARY SYNDROME AND NORMAL CORONARY ANGIOGRAMS, Patients with clinical and EKG presentation of acute coronary syndrome having normal coronary angiograms are not rare. The prevalence of myocarditis in this population is not known. 22 consecutive pts admitted to intensive care unit for recent onset of intense prolonged or repetitive chest pain, associated with ST-T changes or recent Q waves on the EKG, and with normal coronary angiograms, were investigated. 2D-echocardiography for wall motion study, and coupled AMA/rest thallium (TI) imaging to look up for myocytes necrosis and potential myocardial scar, were performed. Planar thoracic images (anterior, LAO 40 and 70°) were obtained 48h after IV injection of In111-AMA (92 MBq). Significant uptake was considered for an heart to lung ratio (HLR) over 1.8. Then, 111 MBq of TI were injected, and a dual isotope rest SPECT acquisition was performed. Results: in 5/22 pts (23%), AMA and TI scintigraphy were negative. In 8/22 pts (36%; G1), diffuse significant AMA uptake (HLR=2.27+0.13) with normal TI scan assessed the diagnosis of myocardifis. Half G1 pts had global LV dysfunction, while half had only regional wall motion abnormalities. 9/22 pts (41%, G2) demonstrated significant segmental AMA uptake (HLR=2.15+0.08), with normal TI scan. 3 of them had normal LV function; global LV hypokinesia was found in 1, while only regional wall motion abnormalities were present in the other 5. The location of regional dysfunction and segmental AMA uptake were matched, but their extent differed (larger in AMA). In G2 pts, the diagnosis of segmental myocarditis was highly probable in the presence of normal TI scan and of complete functional recovery on echocardiography after 6 months. Conclusions: 1/On the basis of AMA and TI scintigraphy, 36% of pts with presentation of acute coronary syndrome and normal coronary angiograms had diffuse myocarditis, and 41% had high probability of segmental myocarditis. 2/The presence of only regional wall motion abnormalities does not exclude the diagnosis of myocarditis.

HYBRID CODED POLAR MAPS AND EXTENT REPRODUCIBILITY OF MYOCARDIAL VIABILITY USING Tc99m-sestaMIBI AND 1123-BMIPP. Disagreement exists concerning the thresholds for perfusion separating normal myocardium, jeopardized tissue and scar. Since mismatching between flow and metabolism in regions with decreased perfusion constitutes a hallmark of viability, we illustrated the combined assessment of flow (MIBI) and metabolism (BMIPP) for different levels of MIBI uptake using hybrid coded polar maps. Rest MIBI and BMIPP SPECT were performed within 3 days, the studies were scatter corrected, reconstructed and polar maps created. Combining the MIB,I and BMIPP data, nine new polar maps were created, using different levels of perfusion as thresholds for normal and scar tissue. Normal tissue defined as a perfusion of at least 50, 60 or 70 % of the mean normal local uptake was represented in red. Scar tissue defined as MIBI uptake of less than 20, 30 or 40 % represented in blue. In between, MIBI was compared to BMIPP to evaluate the possible presence and degree of mismatching. Green was used for matched regions, i.e. BMIPP within 10 % of MIBI uptake, yellow was used for mismatching between 10 and 20 %, and orange for BMIPP > 20% lesser than MIBI. For quantitative assessment of viable tissue, a correction bullseye was created representing the contribution of each pixel related to the total myocardial surface, taking into account the bullseye display deformation and contribution of each slice to the total myocardial volume. From the viability and surface correction polar maps the relative extent of normal, necrotic and viable tissue were calculated globally as well as for each coronary artery territory. Reprocessing the data completely, the reproducibility of this method was analyzed using the 60% lower normal and 30% upper necrotic limits in 15 patients with post infarction LV-dysfunction. Mean intra and interobserver extent differences were 0.25% (SD 2.01) and -0.92% (SD 2.60) for the whole ventricle. LAD, LCX and RCA intraobserver values were 1.65% (SD 2,93), -1.56% (SD 3.60) and -1.24% (SD 2.84). Interobserver values were respectively 1.54% (SD 3.32), -0.52% (SD 3.40) and -0.34% (SD 4.14). Using 2 SD interobserver differences as minimum extent for presence of viable tissue 8 of the 15 patients showed viability: 3 in LAD, 1 in LCX, 2 LAD and RCA, 2 LCX and RCA.

951

P12

P17

Z. Petrasinovic, M. Ostojic, B. Beleslin, A. Djordjevic-Dikic, R. Babic, G. Stankovic, S. Stojkovic, J. Stepanovic, M. Nedeljkovic, I. Nedeljkovic, S. Pavlovic, N. Kozarevic, V. Obradovic. Institute for Cardiovascular diseases, Belgrade, YU

L. S a l ~ , J. Thur6czy*, G y A. d~noki, K. Bodd Department of Applied Radioisotopes, National "F.JC." Research Institute for Radiobiology and Radiohygiene *University of Veterinary Sclence, Budapest, Hungary

DYPIRIDAMOLE RADIONUCLIDE VENTRICULOGRAPHY VERSUS DYPIRIDAMOLE STRESS ECHOCARDIOGRAPHY FOR ASSESSMENT OF MYOCARDIAL VIABILITY The purpose of the study was to compare diagnostic value of low dose dypiridamole radionuclide ventriculography (DYPLRNV) and low dose dypiridamole echncardiography (DYPI-ECHO) for the prediction of functional recovery of viable myocardium in the medium term follow up. Twenty patients (18 male; 515<10 years) with previous myocardial infarction and resting wall motion dyssynergy were studied before angioplasty of infarct related artery, by RNV and ECHO at rest, as well as during drug infusion (0,28 mcg/kg/min over 2min). RNV as well as ECHO was repeated at rest, 12 weeks after successful angioplasty. Five percent increase of regional ejection fraction (REF) by RNV was used as criterion for functional improvement of infarcted regions. By ECHO, viability was defined as improvement of wall thickening or contractile improvement of grade one or more, utilizing wall motion score index (WMSI). Out of 180 examined (20x9) segments by RNV, 51 were dyssynergic and they had abnormal REF (29M10%). Out of these 51 segments functional improvement was documented in 33 on low DYPI. Sensitivity for predicting functional recovery after 12 weeks follow up was 63%, and specificity was 77%. WMSI assessed by ECHO was 1.353<0.22, 1.165<0.20 and 1.13~<0.14 for rest, low DYPI and rest follow up, respectively (p<0.05). Sensitivity of low DYPI-ECHO for predicting functional recover), was 80%, and the specificity was 90% (p=ns vs low DYPI-RNV). In conclusion, both techniques, RNV and ECHO are comparable diagnostic predictors of myocardial viability in medium term tbllow up.

QUAigTITATIVE T H Y R O I D S C I N T I G R A P H Y IN DOGS O u r g o a l s were to c o m p a r e the m o r p h o l o g i c a l (size, h o m o g e n i t y , e c t o p i c l o b e s ) a n d f u n c t i o n a l data (thyroid/background, thyroid/salivary gland ROI rates; 20 minutes thyroid uptake) of euthyroid, hypothyroid, h y p e r t h y r o i d and dogs with thyroid malignancies. S i x t y four dogs were e x a m i n e d a l t o g e t h e r after i n t r a v e n o u s l y a d m i n i s t e r e d 5-10 M B q / b w k g ~mTCp e r t e c h n e t a t e w i t h a large f i e l d of v i e w gamma c a m e r a (Picker, D y n a 9010). A n a e s t h e t i z e d dogs were layed in a v e n D r a l recumbency and 20 minutes dynamic study was performed immediate!ly after injection. Thereafter v e n t r a l and left lateral s t a t i c p i c t u r e s were t a k e n a n d p r e d o s e - p o s t d o s e a c t i v i t y were also c o u n t e d to c a l c u l a t e i n j e c t e d doses. ROIs were d r a w n a r o u n d the t h y r o i d lobes, s a l i v a r y glands and a background regio in the n e c k and 20 m i n u t e s t h y r o i d u p t a k e was c a l c u l a t e d . All the a b o v e q u a n t i t a t i v e data i n c l u d i n g t h y r o i d sizes were statistically evaluated (unpaired S t u d e n t ' s t-test). Thyroid/background, t h y r o i d / s a l i v a r y g l a n d ROI r a t i o s a n d 20 m i n u t e s o r g a n u p t a k e of the hypo and hyperthyroid dogs were statistically different (p<0.005) from the euthyroids. We c o u l d not find any c o r r e l a t i o n b e t w e e n t h y r o i d s i z e s and function. Q u a n t i t a t i v e t h y r o i d s c i n t i g r a p h y a l s o in dogs seems to be useful to d i s t i n g u i s h between n o r m a l and a b n o r m a l t h y r o i d f u n c t i o n h o w e v e r detectable morphological differencies areuncommon.

P14

P18

L.Bokeriya, M.Toumanian, 2.Prokhorovitch, M.Litvinov, D.Koledinsky, S.Bondarenko, M.Zelenikin. Independent PET-group, Moscow; B a k u l e v C a r d i o - v a s c u l a r S u r g e r y Centerr R u s s i a n A c a d e m y of M e d i c a l Sciences.

~:'- }:_'.2T OF LYMPH NODE INVOLVEMENT ON PROGNOSIS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER. Mfirtl M, Farahati J, Reiners Chr. Clinic for Nuclear Medicine, University Hospital Wiirzburg, Germany. B A C K G R O U N D . The prognostic effect of lymph node involvement in patients with differentiated thyroid cancer (DTC) remains still controversial. The goal of our study was to clarify the prognostic impact of lymph node involvement in patients with DTC with respect to tumor stage.METHODS. A total of 422 patients (46 +/- 13 years of age) with papillary thyroid cancer (PTC) (297 females and 125 males) and 174 patients (52 +/- 13 years of age) with follicular thyroid cancer (FTC) (116 females and 58 males) treated and followed between 1980 and ] 995 in our clinic were the subject of the present investigation. Standard treatment comprised total thyroidectomy (except in patients with papillary microcarcinoma), ablative radioiodine therapy and thyroid-sthnulating hormone-suppressive therapy with levothyroxine. Between group comparison was carried out by chi-square test. Survival was evaluawas evaluated by Kaplan-Meier life table analysis.

POTENTIALITIES OF POSITRON EMISSION TOMOGRAPHY FOR EVALUATION OF MYOCARDIAL STATUS IN CHILDREN WITH TETRALOGY OF FALLOT

Purpose: to e x a m i n e m y o c a r d i a l status in c h i l d r e n w i t h t e t r a l o g y of Fallot w i t h p o s i t r o n e m i s s i o n t o m o g r a p h y (PET). Methods: PET studies of the heart were c a r r i e d out in 36 patients: 12 c h i l d r e n a g e d from 1 to 4 years b e f o r e (group l)and 23 child r e n a g e d f r o m 4 to 14 years a f t e r (group 2) r a d i c a l c o r r e c t i o n of disease. C l i n i c a l status in g r o u p 1 was c o n s i d e r e d as severe, in g r o u p 2 - s a t i s f a c t o r y . The p a t i e n t s in group 2 w e r e d i v i d e d into s u b g r o u p s (sg), d e p e n d i n g on h e m o dynamics specifity, revealed with ACG and EchoCG. In sg 1 (5 patients) h e m o d y n a m i c s was close to norm, m o d e r a t e h e m o d y n a m i c d i s o r d e r s were o b s e r v e d in sg 2 (I0 patients) and m a r k e d d i s o r d e r s - in sg 3. M y o c a r d i a l p e r f u s i o n was assessed with ammonium at rest and after d i p i r i d a m o l u m load. G l u c o ! y s i s a c t i v i t y was ass e s s e d w i t h FDG at rest and a f t e r g l u c o s e load. Results: The a n a l y s i s of results o b t a i n e d s h o w e d that s e r i o u s m y o c a r d i a l i n j u r i e s c o u l d o c c u r e in e a r l y age, m o r e e x p r e s s e d in left v e n t r i c l e and m o r e s i g n i f i c a n t in c h i l d r e n w i t h m a r k e d he m o d y n a m i c disorders. In remote p e r i o d the m y o c a r d i a l lesions were n o t e d in all child r e n e v e n w i t h s a t i s f a c t o r y state. T h e r e was n o t e d the d i r e c t d e p e n d e n c e b e t w e e n s e v e r i t y of m y o c a r d i a l lesions and d e g r e e of r e s i d u a l h e m o d y n a m i c disorders, that s h o w e d the i m p o r t a n c e of a d e q u a t e d i s e a s e ' s c o r r e c t i o n . C o n c l u s i o n : PET is e f f e c t i v e for a s s e s s m e n t of m y o c a r d i a l status in c h i l d r e n a f t e r r a d i c a l c o r r e c t i o n of diseases.

952

i~T1-3 NO

PTC ofpts. (n=422) Death No. FTC ofpts. (n=165) Death No. 298 1 124 1 pT1-3 N1 36 1 8 1 pT1-3 Nx 10 0 9 2 pT4 NO 32 1 12 3 pT4 N1 35 7 8 5 pT4 Nx 11 0 4 1 RESULTS. Mortality in patients with advanced DTC stage pT4 (17/102=16.7%) was significantly higher than those in stages pT1-3 (6/485=1.2%) (P=0.001). Co-correlation of lymph node involvement resulted in a higher mortality, which is more pronounced in patients with advanced disease (P=0.002). In agreement, survival analyses revealed reduced life expectancy in lymph node positive patients with DTC and perithyroidal tumor in'fi tration compared to those w th N0status (P=0.000001). Further analyses in patients with DTC stage pT4 disclosed this effect to be more pronounced in patients with PTC (P=0.02) than those with FTC (P=0.09). C O N C L U S I O N S . Lymph node involvement affects inversely the survival in patients with advanced PTC. In contrast, life expectancy in patients with FTC (all tumor stages) or PTC (tumor stages pT1-3) is not remarkably influenced by lymph node involvement.

P19

P21

B.E.Prat~, S.L.Hyer, H.A.Flower, A. V.R.McCready, C.L.Harmer Thyroid Unit Royal M a r s d e n Hospital

DIFFERENTIAL DIAGNOSIS OF COMPARISON OF THYROID SCANS CLINICAL INFORV~ATION

A!-Saadi,

THYROTOXICOSIS(PET & US) WITH

The amount of radioiodine given to treat thyrocoxicosis will depend on the aeriology of :he disease, with Graves' disease usually treated with lower activities of radioiodine than nodular goitre. Homogenous uptake on an isotope scan is indicative of Graves' disease, together with other clinical findings. The aim of this study was to compare 63 PET images from 55 patients with the clinical diagnosis made prior to PET imaging. The PET images were scored from 1= homogenous uptake to 5= multinodular. 70% of those patients who were diagnosed in the clinic as having Graves' scored mainly 1 and 2. The other 30% had hypo and/or h y p e r f u n c t i o n i n g nodules. In contrast, of the group diagnosed as having nodular goitre by ultrasound or Tc99m scintigrapy, 40% did not demonstrate any distinct nodularity on PET. These results demonstrate that appearances of nodules on high resolution ultrasound may be providing misleading information. As the efficacy of radioiodine therapy is partly determined by the distribution of the isotope, prior scanning with PET is of value in determining what dose of radioiodine needs to be given.

G. Ahenvoerde. H. Lerch, T. Kuwert, M Sch~ffers, P. Matheja, O. Schober, Dept of Nuclear Medicine, Westfiilische WilhelmsUniversit~tt Munster, Germany. FDG-PET IN PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA, ELEVATED SERUM THYROGLOBULIN LEVELS, AND NEGATIVE IODINE SCANS

Background and Aim: In patients with differentiated thyroid carcinoma, elevated serum levels of tbyroglobulin (bTg) in case of otherwise negative diagnostic procedures including 1-13 l-iodine scan is a rare, but significant diagnostic problem. We aimed to investigate whether F-18-FDG-PET is capable to detect metastatic lesions in these patients. Method: Ten patients (age 46~:13 years, 4 male, 6 female, 7 papillary, 3 follicular carcinoma) were investigated by whole body FDG-PET. The serum hTg levels were in the range of 1.5-206 ng/ml (64-~=76 ng/m], median 20 ng/ml). All but one FDG-PET were performed in the state of hypothyroidism (TSH 67±41 laU/ml). Xrays of the chest were performed in all, x-ray computed tomography (CT) and magnetic resonance imaging (MRT) of the neck and chest in 3 and 2 patients, respectively. Results: In 4 patients FDG-PET revealed focal elevation of glucose metabolism The hTg levels of the FDG-PET in these patients were t09±77 ng/mt (range 22-206 ng/ml, median 104 ng/ml). In the group of patients with negative FDG-PET hTg levels were 35e65 ng/ml (range 1.5-167 ng/mI, median 10 ng/ml, p=0.05). In all patients (n=3) with hTg levels below 20 ng/ml FDG-PET was unremarkable. Conclusion: These first results show that in patients with elevated thyroglobulin levels >20 ng/ml and otherwise negative diagnostic procedures, FDG-PET may be helpful to detect metastatic lesions in thyroid cancer.

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,= P 2(? D.PopGjorcheva, V.Bogdanova, N.Simova, S.Miceva-Ristevska, S.Loparska Institute of Pathophysiology and Nuclear Medicine, Medical Faculty, Skopje, MACEDONIA LEFT VENTRICULAR FUNCTION IN HYPOTHYROID PATIENTS, BEFORE AND AFTER TREATMENT, ASSESSED BY RADIONUCLIDE VENTRICULOGRAPHY Using the method of radionuclide ventriculography (RNV), we have examined left ventricular (LV) function in 22 control (C) and 35 hypothyroid patients at rest, before and after treatment. We have analyzed following LV performances: ejection fraction (EF), ejection and filling period (EP, FP), peak emptyng and peak fillling rata (PER, PFR) and time to PER and PFR normalized for the EP and FP (TPER/EP and TPFR/FP). The hypothyroid state was characterized by a significantly Jower values of EF (0.59 vs. 0.68 in C, p<0.00t), PER (- 2.25 EDV/s vs. - 3.07 EDV/s in C, p<0.001) and PFR (2.04 EDV/s vs. 3.03 EDV/s in C, p<0.001), significantly longer EP (0.35 sec vs. 0.30 sec in C, p<0.001) and higher TPER/EP ratio (0.48 vs. 0.39 in C, p<0.0OS). There were no changes in FP and TPFR/FP. After treatznent the alterations in EF, PER, TPER/EP ware completely reversible, since only partial reversibility in PFR and no change in EP were obtained when the patients were euthyroid. Thus, LV function is decreased significantly in hypothyroidism. Cardieinhibitory effect of thyroid hormone deficit in hypothyroidism is present as in patients younger as in patients older than 50 years. In older hypothyroid patients, possibly due to coexisting cardiac and metabolic changes, LV hypofunction is more profound than in younger and the changes in cardiac function are not quite reversible after treatment. Change in LV function appears very soon after the thyroid dysfunction begins (within two months persisting hypothyroidism), but alterations in some LV performances are more stressed in long-lasting hypothyroidism.

P 22 K. Hamar_, H. Bender, F. Grfinwald, E. Klemm, C. Menzel, A. Schomburg, H. Palmedo, P. Willkomm, T. Bultmann, and H.J. Biersaek. Department of Nuclear Medicine, University oft}onn, Germany

RECURRENCE RATE OF SURGICALLY TREATED NODULAR GOITER: THE IMPACT OF BASAL TSH In European countries, the most common treatment of non-toxic goiter is homone therapy and/or surgery. Nevertheless, it is not yet clear whether further therapy (e.g. hormone substitution) is necessary in order to reduce incidence of recurrence. The aim of the study was to assess the impact of basal TSH-levels on the recurrence rate at'~ersurgical therapy. Over a period of 11.8 years, 343 patients were postoperatively followed. Characteristics were as follows: m:f = 71/272, (20.7 %):(79.3 %); mean age was 39.5 (6.0 to 83.0) years. The following surgical procedures were performed: thyroidectomy N=7 (2.0 %), bilateral subtotal thyroidectomy N=264 (77 %), enucleation N=13 (3.8 %), and hemithyroidectomy N=59 (17.2 %), respectively. Thyroid hormone levels (TH), basal TSH and postsurgical treatment with levothyroxine were evaluated. Recurrence was defined as (1) nodules (ultrasound), and (2) total volume >18 ml (women) >25 m1 (men), respectively. Only patients without clinical symptoms, normal sonograpby (no nodules and no increased volume) and suppressed (<0.3 U/l) or normal (0.34U/I) TSH-levels were included. According to basal TSH, 3 groups were defined: group I: suppressed basal TSH (TSH< 0.3 U/l), group II: basal TSH between 0.3 and 1.0 U/l, and group III: basal TSH > 1.0 and < 4 U/I . The recurrence rate in group I was 8/134 (6.0 %), in group II 35/98 (35.7 %) and in group IlI 49/111 (44.1%). Statistically sigmficant differences were established between the three groups employing the chi square test: I versus II and III: p<0.01 ; II versus III: p<0.04 . Our data indicate, that the postsurgical recurrence rate is related to the basal TSH level. We conclude that TSH is an important factor in the development of a recurrence in nodular goiter. Thus, postsurgieal treatment with thyroid hormones require sufficient doses in order to suppress basal TSH.

953

L

Ill

d.J

¢n O O.

P 23 M.A.Muros. A.Rodriguez, M.D.Martfnez del VaNe, A.Ramfrez, M.G6mez, &Bravo*, I.Maleno**, J.M.Llamas. Nuclear Medicine, Nephrology* a~d Pathology** Departs. '~/irgen de las Nieves" Hospital. Granada. Spain. PRESURGICAL LOCALIZATION OF PARATHYROID ENLARGEMENT IN SECUNDARY HYPERPARATHYROIDISM: EXPERIENCE WITH 99M-TC-SESTAMIBI SCINTIGRAPHY PURPOSE: Aim of this study was to determine the sensitivity of double-phase 99m-Tc-SESTAMIBI scintigraphy for the detection of abnormal parathyroid glands in patients with secundary hyperparathyroidism and to identify the factors affecting detection. NIETHOD: 14 patients (8 males and 6 females) with biochemical proof of secundary hyperparathyroidism were referred for doublephase 99m-Tc-SESTAMIBI scintigraphy. The interpretation of parathyroid imaging was compared with findings at surgery and also correlated with ultrasound results, gland histology and volume. RESULTS: The 14 patients were found at surgery to have 36 enlarged glands. Sensitivity was defined as the percentage of the positive Iocalizations and was 72.2% (26 of 36) for 99m-TcSESTAMIBI scintigraphy and 55.5% (20 of 36) for ultrasound. Surgical accuracy ie the percentage of patients accurately and completely described was 57.1% (8 of 14) for 99m-Tc-SESTAMIBI scintigraphy and 42.8% (6 of 14) for ultrasound (US). Sensitivity Surgical accuracy ......................................................

No. of glands = 36 No. of patientes = 14 MIBI 72.2% (26136) MIBI 57.1% (8/14) US 55.5% (20136) US 42.8% (6/14) With respect to the detection of anormal glands, the mean volume of the glands detected by 99m-Tc-SESTAMIBI scintigraphy was 2.89 cm3 and the mean volume of glands not detected was 0.23 cm3. CONCLUSIONS: Our results in terms of sensitivity are in keeping with the data published for the double-phase 99m-Tc-SESTAMIBI scintigraphy. Sensitivity gives a good idea of the performance of a method but is no representative of the true contribution of the technique for the surgeon. Double-phase 99m-Tc-SESTAMIBI scintigraphy is more efficient (scored best in sensitivity and surgical accuracy) than ultrasound for the presurgical detection of abnormal parathyroid glands in patients with secundary hyperparathyroidism.

P 25 M. Kibar, T. Tetiker, A. Tutus, $ YiJce, M. Reyhan, M. Sert, Departments of Nuclear Medicine and Endocrinology, Gukurova University Faculty of Medicine, Adana, TURKEy

DOUBLE PHASE Tc-99m-TETROFOSMIN SCINTIGRAPHY I N THE DETECTION AND LOCALIZATION OF PARATHYROID ADENOMAS: A COMPARATIVE STUDY WITH TECHNETIUM99M-SESTAMIBI SCINTIGRAPHy

Tc-99m-tetrofosmin has recently been used as a new agent for myocardial perfusion imaging, We aimed to determine the diagnomc value of parathyroid scintigraphy using Tc-99m-tetrofosmin in the preoperative detection and localization of parathyroid lesions, and to compare the scintigraphic findings with those of Te-99m-sestamibi scintigraphy. Sixteen pati~ts with histologically proven parathyroid adenomas were examined. Parathyroid scintigraphy was performed using Tc-99msestamibi and Tc-99m-tetrofosmin within a time interval of 2-5 days. Tc99m-tetrofosmin seintigraphy was performed if delayed Tc-99m-sestamibi scint/graphy showed a focal hot lesion. For these two agents, the same imaging equipments and protocols were used. Diffuse uptake in the thyroid gland was observed with both agents approximately up to 60 rain post injection. Using delayed static images, both Tc-99m-sestamibi and Tc99m-tetrofosmin correctly identified and localized all of the parathyroid adenomas. On visual evaluation, the image quality (contrast) of Tc-99msestamibi images was slightly better than Tc-99m-tetrofosmin images. The retention half-times of Tc-99m-tetrofosmin and Tc-99m-sestamibi that calculated in the parathyroid adenomas of the six patients ranged 0.6 h to 1.4 h and 0.7 h to 1.6 h, respectively. Although our patient group is very ~mall, there wa~ no statistically significant d/fference between the retention rates of these two agents in the parathyroid adenomas. We believe that the good image quality and easily preparation will make Tc-99m-tetrofosmin a good ahemative agent to Te-99m-sestamibi for parathyroid scinfigraphy in routinely use,

P 24

P 26

B. O. Helal, D. Le Guillouzic, H, Gouya, F. Archambaud, A. Prigent Department of Nuclear Medicine. 94275 Kremlin Bicetre France.

M.Duet*, ('.Ajzcnberg**, S.Benelhadj*, A.Warnct**, ().Mundler*, H6pital Lariboisit?re * Department of Nuclear Medicine, **Departmentt of Internal Medicine

RELATIVE WASHOUT OF TECHNETIUM-99mTETROFOSMIN IN PARATHYROID ADENOMA AND THYROID TISSUE Since its introduction by Coakley et al in 1989, 99mTc-sestamibi has been used for .parathyroid scinti~raphy using either a double phase technique or 9pmTc-sestamibi /~2-~I thyroid subtraction technique. Similarly, 99mTc-tetrofosmin, an equivalent myocardial perfusion imaging agent, has been proposed and recent reports have claimed a good sensitivity for parathyroid localization. To assess whether the dual-phase technique is an accurate imaging protocole for adenoma localization, we estimate the 99mTc-tetrofosmin clearance from normal thyroid tissue and parathyroid adenoma. Scintigraphy was performed 15 min, 90 min and 3 hours after IV injection of 555 - 740 MBq 99mTc-tetrofosmin in 9 patients (5 females, 4 males) with bioehemically proven hyperparathyroidism. Seven patients had a single parathyroid adenoma (one with a multnodular goiter) and one patient had two parathyroid adenomas. Regions of interest were drawn over the parathyroid adenoma and the normal thyroid gland. Parathyroid adenoma / normal thyroid ratio was determinated for each acquisition. In order to avoid superposition of the two different tissues, only ectopic parathyroid adenomas were included. The ratio was unchanged between the early (15 mini and the delayed (90 min and 3 hours) images. So, there is no significant difference in the washout of parathyroid adenoma and normal thyroid tissue. In conclusion, the similar clearances of 99mTc-tetrofosmin of parathyroid adenoma and normal thyroid tissue could give false negative results when the adenoma is located in the thyroid, especially in the presence of multinodular goiter and in smaller intrathyroidal parathyroid tumor. Consequently, the dual-phase technique could be less sensitive than the subtraction technique,

954

S n M A I ON IA I'lN RECEPTOR IMAGING (SR[) IN PiTUrFARY TUMOURS : IN rERES'I (U.' t SO~,fAFOSTATIN RECE['TOR DENSrrV iNDEX TO PREDICT TUMOUR SUR[NKAGE

19 pts with pituitary adenomas (8 GIf-, 3 TSH-, I gonadotrophin secreting and 7 non functioning adenomas) underwent SR[ with t 11 [n_DTPA_D.Phe l_ octreotidc. Only pts with positive SRI, defined by an uptake index (U1) calculated as the ratio of pituitary activity to a same size hemispheric area activity superior to 2 were treated long term by octreotide. Eleven out of the 19 pts had a significant turnout shrinkage [V+] (by at least 20% of the size before octreotide therapy). Turnout shrinkage was compared to a new index which evaluates somatostatin receptor density (1)1), determined as the ratio of U[ to tumoral volume in cm 3, obtained by, nmhiplying the largest transverse, vertical and anteroposter[or diameters on MRI All pts with a signifflcant shrinkage had a DI > 0.30. Seven pts with no slmnkage [V-] had a DI < 0.30. The last one (DI = 0.36) was treated by the lower dose of octreotide (150 mcg/d). DI 4,0 i

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We conclude that to predict tumour shrinkage by octreotide therapy in pts with pituitary tumors positive SR1 determined by UI superior to 2 is not suffisant and DI superior lo 0.30 would be an effective index.

P 27

P 29

B i d z i 6 s k i J . , B o n i c k i W . , K r 6 1 i c k i L. Dep. of N e u r o s u r g e r y , D e p . of N u c l e a r Medicine Medical School of Warsaw, W a r s a w Poland

P.Theissen, S. Kaldewey, E. Voth, D. Moka, H.Schicha Clinic for Nuclear Medicine, University of Cologne, Germany

SOMATOSTATIN ADENOMA5

RECEPTOR

SCINTIGRAPHY

IN P I T U I T A R Y

The aim of this work was to e v a l u a t e a role of s o m a t o s t a t i n receptor s c i n t i g r a p h y in p a t i e n t s w i t h p i t u i t a r y adenomas lllIn-OcreoScan ( N a l l i n c k r o d t ) was used. Injected a c t i v i t y a m o u n t e d about 180 MBq. Planar and/or 5PECT s c i n t i g r a p h y was p e r f o r m e d 2,4 and 24 ha. after a p l i c a t i o n of r a d i o t r a c e r . In all cases hormonal c h a r a c t e r i s t i c , MRI as well as h i s t o p a t h o logical e x a m i n a t i o n s were a v a i l a b l e . Type

of a d e n o m a

No

GH p r o d u c i n g adenoma GH p r o d u c i n g adenoma after r a d i o t h e r a p y Prolactinoma A C T H p r o d u c i n g adenoma Multihormonal H o r m o n a l l y silent

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22

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R e s u l t s of s c i n t i g r a p h i c e x a m i n a t i o n s i n f l u e n c e d on the theraphy strategy.

in most

cases

In c o n c l u s i o n , 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 is a p o w e r f u l l diagnostic method,which can i n f l u e n c e on the t r e a t m e n t of the patients.

EFFECT OF RADIO IODINE THERAPY ON METABOLIC CHANGES OF THE SKELETAL MUSCLE IN SUBCLINICAL HYPERTHYROIDISM The skeletal muscle is one of the most important target organs of the thyroid hormons. By phosphorous (P-31) magnetic resonance spectroscopy (MRS) it could be shown for the first time in-vivo that the phosphorous energy metabolism of the skeletal muscle is affected in subclinical hyperthyroidism, To funher confirm these metabolic changes which were similar to those in overt hyperthyroidism and to study the influence of therapy, a MRS follow-up was performed after radio iodine therapy. 15 patients (pts) with subclinical hyperthyroidism (TSH _< 0.1 glE/mI) because of nodular goiter underwent a P-31-MRS of the calf muscle before and after radio iodine therapy (RIT). The second MRS was performed at an interval of 3 months after RIT. 24 healthy volunteers were also examined by MRS for comparison. MRS was done with an external standard solution (K2HPO4) as reference to quantify the concentrations of creatine phosphate (PCr), inorganic phosphate and B-ATP. The mean TSH value after RtT increased to 1.6 + 117 glE/ml (paired t-test p = 0.0002). In 13 pts the TSH reached values between0.7 and 2.9 glE/ml. In 2 pts TSH remained low (0.I resp. 0.2 glE/ml) after RIT. The table shows the mean values of the metabobtes during MRS follow-up in the pts and compared to the volunteers: PCr [mmol/kg] B-ATP [mmol/kg] P i [mmol/kg] Volunteers 28.5+2.6 5.8+ 1.1 4.6_+ 1.3 ' Pts (subclinical 18.2_+3.5 4.7_+1.4 4.5_+ 1.1 hyperthyr,) Pts (2"J MRS after RIT) 25.7 _+3.6 5.1 _+ 1.7 4.3 _+ t .3 The paired t-test showed significant increase of the PCr (p = 0.0009) and a tendency towards higher values of the B-ATP (p = 0.055), but no post-therapeutical difference of Pi. The significant difference of the PCr between pts before RIT and volunteers (p = 0.0005) disappeared at 2n° MRS (p = 0.129). In those 2 pts without clear TSH increase after RIT the PCr remained low also. The recent results confirm the MRS measurements with changes of the muscle metabolism in subclinical hyperthyroidism and show that those are reversible after successful therapy (RIT). Moreover, the opinion can be supported that at least symptomatic pts with subclinical hyperthyroidism do need adequate therapy,

P 28

P 30

N. Berqstr~m, C. Juhlin, T. Bonasera, L. Lu, E. B e r g s t r 6 m , C. Backlin, A. Sundin, P. L i d s t r b m a n d B. L&ngstrbm. Uppsala University PET Centre, U n i v e r s i t y H o s p i t a l , Uppsala, S w e d e n

B. Klemenz, H. Wieler, K.P. Kaiser

IIC-METOMIDATE ADRENAL TUNOURS

BINDING IN V I T R O

TO AND

ADRENAL IN V I V O

CORTEX

e-

Dept. o f Nuclear Medicine, Bundeswehrzentralkrankenhaus Koblen%

o

Germany

AND

The purpose was to d e v e l o p a PET tracer for adrenal cortex tumours. For this reason the labelling procedure was developed for IlCmetomidate, a h i g h l y p o t e n t i n h i b i t o r of l l b e t a hydroxylase. Frozen sections of a d r e n a l s from rat, p i g a n d humans, as w e l l as h u m a n a d r e n a l c o r t e x t u m o u r s a n d v a r i o u s o r g a n s f r o m rat a n d p i g w e r e u s e d in f r o z e n s e c t i o n a u t o r a d i o g r a p h y to a s s e s s b i n d i n g of l l C - m e t o m i d a t e . The binding in the tumours was correlated with immunohistochemical demonstration of llbetahydroxylase. S e v e n p a t i e n t s w i t h a d r e n a l masses, the majority being incidentalomas were investigated with PET and llC-metomidate, All patients were then operated a n d the h i s t o l o g y c o m p a r e d w i t h the PET findings. All sections of adrenal cortex and adrenal a d e n o m a s s h o w e d h i g h binding, In the t u m o u r s the binding correlated well with llbeta-hydroxylase staining. E x c e p t for some b i n d i n g in liver, all o t h e r o r g a n s l a c k e d s i g n i f i c a n t binding. In all patients with processes derived from adrenal cortex, including two cancers, one a d e n o m a a n d o n e d y s p l a s i a as w e l l as the n o r m a l a d r e n a l s w e r e w e l l v i s u a l i s e d w i t h a h i g h uptake. O n e cyst, one p h e o c h r o m o c y t o m a a n d one m e t a s t a s i s l a c k e d uptake. In c o n c l u s i o n , PET w i t h l l C - m e t o m i d a t e s e e m s to have excellent in vivo properties for the c h a r a c t e r i s a t i o n of processes d e r i v e d from the a d r e n a l cortex.

tO

mm

IS C O L O R - C O D E D D O P P L E R S O N O G R A P H Y (CCDS) USEFUL IN T H E D I F F E R E N T I A L D I A G N O S I S OF N O D U L A R GOITER ? The incidence o f functional autonomous adenomas, detected in every second nodular goiter by scintigraphic methods, is very high in an iodine deficient area. The color-coded Doppler sonography (CCDS) as a diagnostic tool controversially.

in

differentiating

thyroid

nodules

is

discussed

The aim o f this prospective and randomized study was to investigate the value o f CCDS in 200 patients with nodular thyroid alterations compared with 99m-Technetiurn-(Tc)-scintigraphy. Ultrasound regular B-mode and CCDS was performed with a Picker CS 9600 (color flow m a p p i n g - m o d e [CFM-mode]; 5 M H z , pulse repitition frequency" [PRY]: 1,5 kHz, filter: medium, artefact suppression: 2 [of 3], packet size: medium) after clinical investigation o f the thyroid and prior to scintigraphy (37 M B q Tc-99m-Pertechnetate i.v., Gamma-camera: Picker CX 250 compact). Autonomous adenomas were detected in 22.5% o f all patients, and 44.5% o f the thyroid nodules showed increased vascularity. There was no correlation between nodular vascularity and thyroid 99m-To uptake (TeTU). In contrast to this we could demonstrate a significant correlation between vascularity and the diameter o f the nodule (p< 0.0001). The

results are discussed in the context o f method specific limitations o f ultrasound examinations. In conclusion our results confirm that CCDS has no great importance in the differentiation o f thyroid nodules. Scintigraphy remains the diagnostic method o f choice to assess the topographic thyroid function.

955

P 31

P 33

S. Rasmussen, H. Dige-Petersen, R. Fiege, (Glostrup Hospital), N. Knudsen, H. Perrild, T. Jergensen, E. Christiansen, (Bispebjerg Hospital). Copenhagen, Denmark

S. Mechlis-Frish, Z. Bar-Sever, R. Hardoff, E. Lubin, Department of Nuclear Medicine and Thyroid Clinic Rabin Medical Center, Beilinson Campus, Tel Aviv University, Israel

THE PREVALENCE OF FOCAL THYROID STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN A POPULATION WITH BORDERLINE IODINE DEFICIENCY Aim: To investigate the prevalence of thyroid structural abnormalities by ultrasonography (US)and 99mTc-scintigraphy (99mTc) in a borderline iodine deficient population (88gg/24 hour). Methods: In 1993-94 a random sample of 4156 persons was invited to participate in a population survey. The group was equally distributed in ~ g e s 41, 51, 61 and 71. 2656 persons, 1333 M and 1323 F participated. The thyroid gland was examined by US and participants with solitary solid or dominant nodules (SSN) exceeding 1 cm or goiter (>40g) were further investigated by 99mTc (200 persons). Biochemistry included thyroid function and anti-TP0. After 2 years 43 persons with SSN were reexamined (US and 99mTc). Results: Multinodular structure as defined by US was present in 612 (23%), 65 (2.4%) had cold SSN, 12(0.5%) had SSN with 99mTc uptake, 6 (0.2%) had simple cysts, leaving 1961 (73.8%) with a normal gland. SSN appeared with the same frequency for both sexes and in all age groups. Heavy smokers had a higher prevalence (p<0.05). Multinodular structure was most common in women (p<0.05)and increased with age in both sexes (P<0.0001). Anti-TPO>200 was associated with multinodular structure (p<0.02). 2 years follow-up showed 39 nodules unchanged, 3 had diminished, 1 had increased. Conclusion:In a general population with low iodine intake, structural abnormalities in the thyroid gland are common. Cold SSN do not change in size in a 2 years follow-up period.

P 32 W.-G. Franke, K. Z~Sphel, G. Wunderlich, A. Ktihne, J. Kropp, K. Augustin, Dept. of Nuclear Medicine, Dresden University, Germany. C L I N I C A L V A L U E OF A N T I - T G P O IN A U T O I M M U N E THYROID DISEASE - A NEW THYROID AUTOANTIBODY? Rationale: Anti-TGPO is a bispecific antibody binding to thyroglobulin (TG) as well as thyroid peroxidase (TPO). It is thought to be different from anti-TG and anti-TPO and is supposed to be raised in some patients (pts) with autoimmune thyroid disease. We paid particular attention to Hashimoto's thyroiditis, a condition comparatively difficult to diagnose. Material and Method: We investigated 205 pts suffering from Graves' disease (81), Hashimoto's thyroiditis (36), toxic nodular goiter (50), differentiated thyroid carcinoma (10, partly with paraneoplastic thyroiditis), and non-classified autoimmune thyroid disease (28). We used an immunoradiometric assay (IRMA) from B.R.A.H.M.S. Diagnostica, Berlin. Results: 185/205 pts (90 %) had raised titers of anti-TG as well as antiTPO, in 20 pts only one autoantibody was raised. Anti-TGPO was found in 85/205 pts (42 %). If anti-TGPO was raised then anti-TG was always raised, too. This was, however, not true vice versa. We found raised antiTGPO titers in 47 % of pts with Hashimoto's, 49 % of pts with Graves', 40 % of pts with non-classified autoimmune thyroid disease, but only in 11% of pts with toxic nodular goiter. In pts with thyroid carcinoma antiTGPO was only found if there was histological evidence of paraneoplastic autoimmune thyroiditis. We re-examined 16/36 pts with Hashimoto's thyroiditis after 1 year: 7 pts had retained their raised anti-TGPO, 7 pts showed no anti-TGPO on both occasions, and 2 pts had ,,lost" their previously raised anti-TGPO on follow-up. Conclusions: Anti-TGPO seems to be a thyroid autoantibody of its own. A single anti-TGPO determination does not allow differentiation of various forms of autoimmune thyroid disease. Diagnostic value in Hashi moto's tbyroiditis was not higher for anti-TGPO, as compared to established parameters (anti-TG, anti-TPO). Follow-up anti-TGPO determinations in Hashimoto's did not contribute any further information so far. "

956

DIAGNOSTIC VALUE OF EARLY AND LATE TC-99M SESTAMIBI IMAGINfJ 1N THE EVALUATION OF NON FUNCTIONING THYROID NODULES The aim of this study is to learn if early and late Tc-99m MIBI seintigraphy can help determine the nature of thyroid nodules that are cold on Tc-q9m pertechnetate scans. Thirty seven patients (34 females, 3 males; age 26-85 years, mean 54 years) with cold thyroid nodules on Tc-99m scans underwent early and late M)BI studies (10 and 120 minutes post injection, respectively). MIBI uptake in the nodules was graded 0 when no uptake was observed, I when uptake was less than in the surrounding gland, 2 when it was similar to the uptake in the gland and 3 when it was increased compared to the surrounding gland. All patients had fine needle aspiration and 9 had the nodules removed surgically. Of the 37 nodules, 10 were highly cellular ( 4 papillary carcinomas and 6 adenomas) and 27 were poorly cellular (26 colloid goiter and 1 hemorl-hagic cyst). When uptake in the nodule was increased on early images (grade 3) and either remained unchanged or slightly decreased on late images (1o grade 2), the sensitivity and specificity for highly cellular lesions was 90% and 88% respectively. This pattern was observed in 12 patients including all patients with carcinomas and 5 of 6 patients with adenomas, it could not distinguish between benign and malignant lesions. Twenty three patients had late uptake less than the surrounding gland (,grades 0 and 1) irrespective to their early uptake. This panem was 81% sensitive and 90% specific (PPV 95%) for poorly cellular lesions. In conclusion, patterns of early and late MIBI uptake can help distinguish between highly and poorly cellular cold thyroid nodules. While poorly cellular lesions are usually benign, ,'911BIscintigraphy could not differentiate between benign and maiigjlant conditions in highly cellular lesions.

P 34 ~JiA. Verhaegen. W.£G. Oyen, A.R.~AE Hermus, W.13/L van den Brock, FI~ Corstens. Departments of Nuclear Medicine and Endocrinology, University Hospital Nijmegen, The Netherlands.

THERAPEUTIC EFFECT AND TOXICITY OF HIGH CUMULATIVE DOSES 1-131 FOR TREATMENT OF METASTATIC DIFFERENTIATED THYROID CARCINOMA. In order to evaluate the therapeutic effect and toxicity of high cumulative doses of 1-131 for treatment of metastatic, differentiated thyroid carcinoma, all patients who were treated in the period 1986-1997 with high doses t-131 (> 20 GBq) were retrospectively analyzed. Twelve patients (4M, 8F; 2 papillary, 10 follicular carcinoma; mean age at thyroidectomy 61 yr, range 26-68 yr) were treated in on average 4.9 cycles with a mean total 1-131 dose of 32 GBq (range 20-45 GBq). Regression of disease was defined as a decrease of the size and/or number of lesions as seen on imaging modalities and no rise of tbyroglobu[in levels. Bone marrow toxicity was evaluated by peripheral blood cell counts (platelets < 100x109/I, leukocytes <3x 109/1). In 6/12 patients (5 follicular, 1 papillary carcinoma) regression, but no cure, was observed after an average of 4.9 cycles with a mean total dose of 32 GBq 1131 (range 20-39 GBq). In 4/12 patients (3 follicular, 1 papillary carcinoma), stable disease was observed after an average of 4.8 cycles with a mean total dose of 30 GBq I- 131 (range 26-45 GBq). Despite 7 treatments with a total dose of 37 GBq 1-131, progression was seen in 2/12 patients (1 follicular, 1 papillary carcinoma). Transient thrombocytopenia was observed in 2 patients. In I patient transient, mild leukocytopenia was observed. In 2 patients, cryopreservation of peripheral hematopoetic stemcells was attempted, but there was an insufficient yield of CD44-positive cells. In this study, administration of high cumulative 1-131 doses for metastatic differentiated thyroid carcinoma did not result in cure, but in - 80% of patients regression or stable disease was achieved. Clinically significant bone marrow depression was not observed. I.ransient thrombo- or leukocytopenia can expected at doses > 30 GBq I-131. Harvest of peripheral hematopoetie stemeells seems to be negatively influenced by prior high-dose 1-13 l treatment.

P 35 D,J. Apostolop_oulos, E: Houstoulaki, T. Skouras, C. Giannakenas, C. Kalantzis, A. Mastorakou, V. Kyriazopoulou, C. Tepetes, P.J. Vassilakos. Departments of Nuclear Medicine, Eindocrinologyand Surgery, University Regional Hospital of Patras, Patras, Greece. COMPARISON OF TC-99m TETROFOSMIN AND TL-201 FOR PARATHYROID DETECTION. SCiNT1GRAPHIC AND TISSUE UPTAKE STUDIES. Object: Apart from myocardial perfusion imaging, other applications of Tc99mTetrofosmin (TF) are currently under investigation. In this study, the diagnostic efficacy of tetrofosmin/pertechnetate subtraction scintigraphy (TE/TC) was compared to that of the conventional thallium/technetium scan (TL/TF) for parathyroid detection. Tissue uptake studies of both TL and TF were undertaken in a subgroup of patients. Methods'. 27 preoperative pt$ with primary and 20 with tertiary hyperparathyroidism due to end stage renal failure (pHPT and tHPT) were involved, f5 pts had had previous neck surgery. 110 MBq of TL were injected first; images of the neck and mediastinum were acquired 10 min later. 550 MBq of TF were then administered and a dynamic series of 30 frames (t rain each) was obtained, using a pinhole collimator. Tc99mpertechnetate was used to delineate the thyroid, iniected either 3 hrs post TF administration, or on a separate day. A cumulative image of TF, generated from the summation of 11t~-30th frames was involved in the subtraction procedure in a subgroup of 12 pts (8 with pHTP and 4 with tHPT), a further dose of 20 MBq of TL and 20 MBq of TF were given at the time of operation, approximately 15 min before the blood supply interruption of the first abnormal parathyroid identified. The removed gland(s), as welt as a small piece of the thyroid were counted in a well-type scintillation detector against a dose standard. Results: Comparative results of TLJTC and TF/TC scans for the detection of histologically confirmed adenomatous tAD) and hyperplastic (HPL) parathyroid glands were as follows: TIJTC (+) TL/TC t-) Statistical TUTC (+) TF/TC (+) TF/TC (-) TF/TC(+) Difference (p) AD 16/23 (69.6%) 20/23 (87.0%) 0 4 0.13 HPL 36776 (47.4%) 57/76 (75.0%) t 22 <0.0001 TOTAL 52/99 (52.5%) 77/99 (77.8%) 1 26 <0.0000 The smaltest gland detected by TL/TC and TF/TC weighed 390rag and 180mg respectively. The specificity of the two methods was 84.6% (55/65) and 92.3% (60/65) respectively. Tissue uptake studies in 8 solitary AD and 10 secondary HPL yielded the following results: TL (mean±SO) TF(mean±SD) Statfstical Difference (P) Thyroida[ Uptake (%Dose/g) 0,025±0.011 0,012±0.006 <0,01 ParathyrNdal Uptake (%Dose/g) 0.039±0.010 0.032±0.007 <0.05 Parathyroid/Thyroid ratio 1.870±0.975 3,316±1,190 <0.001 Conclusion: Tetrofosmin/pertechnetate subtraction ecintigraphy is superior to the conventional thalfium/technetium scan for parathyroid detection, particularly in cases of parathyroid hyperplasia. The uptake of thallium per gram of both thyroid and p,arathyroid tissues is higher than that of tetrofosmin, but the former agent shows considerably lower parathyroid to thyroid relative concentration.

P 37 M, Castellani, V, Longafi, E. Reschini, *A. Paracchi, G. Marotta, R Benti, P Gemndini. Dept of Nuclear Medicine, Ospedale Maggiore IRCCS, and *Dept of Endocrinology, Ospedale Fatebenefratelli, Milan. ROLE OF MIBI SCINTIGRAPHY IN THE DECISION MAKING OF SURGERY IN PRIMARY HYPERPARATHYROIDISM Ultrasonography (US) is the most common imaging tool to detect an enlargement of parathyroid glands. Nevertheless, the use of scintigraphy in the assessment ofhyperfunctioning parathyroid glands has been increasing. Aim of the study is to assess the value of scintigraphy in comparison with US in the diagnosis of primary hyperparathyroidism and in the clinical decision making of the patient. Eighty-one pts with a complete biochemical (PTH, Ca and P), anstrumental (US and "dual phase" MIBI scintigraphy) pattern and 6 months minimum follow up, were considered. Thirty-one of these pts (11 f; mean age 59) with a mean PTH value of 22.84 ± 20.68 pmol/L (normal range 1.2-5.6 pmol/L) Ca 2.92 ± 0.29 mmol/L (2.2-2.5 mmol/L) and P 0.75 _ 0.21 mmol/L (0.8-1.4 retool/L), underwent surgery. Parathyroid adenomas in 24 cases (minimum weight 250 mg) andhyperplasia in 2 were found. In the 5 negative cases at surgery the PTH value remained high. Twenty-eight abnormal parathyroidglands were surgically removed. Sensitivity (Se), specificity (Spy. positive (Ppv) and negative (Npv) predictive values of US and scintigraphy are summarized in the table. The values are calculated assuming 124 explored glands (4 glands for each of 31 operated pts). TP I TN [ FP [ FN J Se % [ Sp % ] P ~ US 20 96 0 8 71.4 100 100 [ 92.3 I MIBI I 93 I 3 I 3 I 89.2 ] 96.8 I 89.2 I 96.8~ TP=true positive; TN=true negative; FP=false positive; FN=false negative The group not surgically treated (50 pts; f 45; mean age 59) had PTH and Ca serum levels (13.7 pmol/L ± 10.1 and 2.65 retool/L, ± 0.26) significantly lower than the operated group (p<0.05). Only 4/50 cases had the scintigraphy positive and 14/50 pts had US indicative for a parathyroid gland enlargement. Our data suggest that the high sensitivity o f MtBI "dual phase" seintigraphy carl improve the detection of hyperfunctioningparathyroid glands. Moreover, despite the high US specificity, the decision of the clinician to address a patient to surgery seems more dependent on a positive scintigraphy than on a positive US.

to im e., if) i._

O.. P 36 L. Pinkas, P. Hagag*, H Kais**, A. Halevy**, M Weiss**, L. Mindlin, T. H o m e . institute of N u c l e a r Medicine, E n d o c r i n o l o g y and * * D e p a r t m e n t of S u r g e r y "B", Assay Harofeh Medical Center, Tel A v i v University, Israel

L O C A L I Z A T I O N OF P A R A T H Y R O I D L E S I O N S IN C L I N I C A L L Y PROVEN PRIMARY HYPERPARATHYROIDISM T c - 9 9 m sestamibi (MIBI) is recently used for p r e o p e r a t i v e localization of p a r a t h y r o i d a d e n o m a s . W e investigated the relationship b e t w e e n M I B I p a r a t h y r o i d scintigraphy and clinicalbiochemical d a t a for primary hyperparathyroidism. The results of M I B I imaging w e r e c o m p a r e d with 2°~TI/~mTc subtraction m e t h o d and the results of s u b s e q u e n t operations. Study: A total of 59 patients were included in our prospective study. In all cases, parathyroid images w e r e carried out by d o u b l e - p h a s e T c - 9 9 m M I B I scan followed b y 2°rTl/SsmTC subtraction study, and at least o n e other imaging t e c h n i q u e including ultrasonography, CT scan or MRI. The count-ratio p a r a t h y r o i d / t h y r o i d w a s calculated from the ROI d r a w n on the M I B I scan. Full biochemical e v a l u a t i o n of the patients was performed. In 19 s u b s e q u e n t l y o p e r a t e d patients, the imaging resuJts were compared to the surgicaJ findings. Results: M I B I scan correctly localized 16 of 19 parathyroid !esions. The sensitivity was 84%, h i g h e r than the sensitivity that was o b t a i n e d from 2°~TI/ssr"Tc scintigraphy (73.3%) and u l t r a s o n o g r a p h y (69%). No false positive image was obtained. In two cases with minimal multiglandular parathyroid hyperplasia, the M I B I scan w a s negative. T h e r e w a s a strong correlation b e t w e e n the results of M I B I scan scintigraphy and PTH levels. Conclusion: W e think that the Tc-99m M I B I scan is a sensitive m e t h o d a n d should be included in the p r e o p e r a t i v e evaluation of the patients with primary h y p e r p a r a t h y r o i d i s m . O u r results s h o w poor MFBI imaging results in cases with mild PTH.

P 38 LI. 13erna A. Flotats, M. Puig-Domingo, J. Piera, X. Matias-Gum, A. Caix~s, M. Estorch, A. Catafau, C. Mad, I. Carri6. /[o.~pilal de A~n[ l'al~. Barcelona. Spain.

Te-99m-MIBI IN THE LOCALIZATION OI7 PARATltYROID ABNORMAL GLANDS IN PATIENTS PRESENTING WITH PRIMARY HYPERPARATHYROIDISM. We perlbrmed double-phase Tc-99m-MlB[ scintigraphy in 70 patients, 19 men and 51 women, mean age of 57 ~: 13 years, presenting with primal' hyperparathyroidism. LaboratQ~, tests showed a PTH of 24. l i 25.3 pmol/L (nl: 1.5 - 6.7) and a calcium serum level of 2.80 ~ 0.22 mmol/L (nl: 2.14 2.54). Four of them had been unsuccessfullyoperated. Images were obtained 15 and 150 minutes after injection of 720 MBq ofTc-99m-MIBl. CT-Scan, ultrason%~aphy (US), and TI-20 Eq'c-99m subtraction scintigraphy were also carried out. Subsequent surgery removed 67 adenomas (2,59 ± 5.84 g), 6 hyperplasfic glands (0.34 ± 0.26 g), and ] carcinoma of 8.20 g. Tc-99m-MlB[ scintigraphy was able to localize correctly 70 out of 74 lesions: 65/67 adenornas, 4/6 hyperp]astic glands and [/I carcinoma. Sensitivity tbr adenomas was 97%, with a global sensitivity of 94%, and a positive predictive value of 97%. There were 2 false positive results in nodular goiter due to Hashimoto's tyroiditis, and 4 false negative results (2 adenomas and 2 hyperplastic glands). Tc-99m-MIBI scintigraphy detected the abnormal tissue in all patients who had undergone unsuccessful previous surge.ry. The sensitivity, of CT-Scan, US, and TI-201/Tc-99m subtraction scintigraphy was 40% 53% and 62% respectively. PTH {4 ± 1.51 pmoFL) and calcium (2.)3 ± 0.22 retool/L) postoperative serum levels showed curation of all patients. We conclude that Tc-99m-MlBI scintigraphy is the method of choice to localize abnormal parathyroid tissue in patients presenting with primal" hyperparathyroidism.

957

ll) O D,.

P 43

P 41 I. Skiba-Choifiska. F. Rogowski, E. Jaroszewicz, A. Citko, D. Jurgilewicz, T. Budlewski, B. Kiersnowska-Rogowska. Departments of Nuclear Medicine and Hematology, Medical Academy, Biatystok, Poland CHANGES OF ALVEOLAR-CAPILLARY BARIER PERMEABILITY IN THE COURSE OF ARDS IN RAT DURING THE TREATMENT WITH MONOCLONAL ANTIBODIES TO CHOSEN ADHESION MOLECULES.

The aim of study was to investigate the influence of immunoneutraIization of immunoglobulin CD54 alone and together with: integrins CD1 la or CDI8 in the course of rat ARDS--Iike lung injury induced by i.v.injection of lipopolisaccharide (LPS) and platetet activating factor (PAF). Five groups of experimental Wistar rats were studied: I - control (n=6), II - LPS+PAF (n=6), III - LPS+PAF +mAb to CD54 (n=3), ~V - LPS+PAF+ mAb to CDI8+ mAb to CD54 (n=4), V- LPS+PAF+ mAb to CD1 la+mAb to CD54 (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 rain before LPS+PAF (Sigma, USA) administration. One hour before killing, in the third hour of experiment the rats were given the mixture of autologous leukocytes (WBC) labelled with Tc-99m-HrnPAO (IZINTA, Hungary) and erytrocytes (RBC) tagged with Cr-51 (Polatom,Poland) and bovine serum albumin J-125-BSA (ICN,USA). The alveolar-capillary barier permeability was determined by: calculatiun of wet-todry (W/D) weight ratio and normalized dry lung weight (DLW), J-125-albumin leakage, accumulation of Tc-99m leukocytes in the lung and the red blood cells extravasation (Cr-51-RBC). Obtained results showed significant increase W/D ratio (x=5.6) in group II, only slight increase in group Itl, and almost unchanged in groups 1V and V iB comparison to control W/D (x=4.8). The highest values of DLW were seen in group II but near to control in the others (especially in group IV). Albumine space was highest in the group II and lowest in the group IV, but accumulation of leucocytes remained unchanged. Fraction of blood remaining in lungs had similar value in all groups. In conclusions: changes of parametres of alveolar-capillary permeability measured with the use of radioisotope methods are useful to confirm ARDSlike rat lung injury after LPS+PAF and therapeutic effects of immunoneutralization of chosen adhesion molecules. Monoclonal antibodies to CD54 and to CD18 administered together are the best to prevent the injury of alveolar-capillary barier in the study model of experimental ARDS.

G. (~-apft, H. Durak, T. ~amsarl, S. ~appak ~ahin, Y. Yenigerio~llu,(~. Ulker, M. Ba~ar, E. S. U(}an Departments of Nuclear Medicine, Nepbrology and Chest Disease bokuz Ey]Oi University, izmir, Turkey EFFECT OF HAEMODIALYSlS ON PULMONARY EPITHELIAL PERMEABILITY It has been known that there are changes in arterial blood gases and CO diffusion capacity during haemodialysis (HD) in patients on chronic haemodlalysis programme. This study aims to investigate the effects of HO on the permeability

of pulmonary epithelial membrane

using Tcg9m DTPA inhalation scintigraphy before and after HD. Fourteen patients (7 female, 7 male) with the mean age of 4.27 were included Mean period of HD was 28 months. Hemophane membrane and HOO3 dialysate were used for HD. Subjects breathed 40 mCi of Tc9gm DTPA for 3 mintltes. In supine

position with their back

against a gamma camera. Posterior lung images were obtained for every 1 minute for 30 minutes. Regions of interest were drawn around the periphery of the ~ungs. Time activity curves were obtained with decay correction for Tc99m. Clearance half time was calculated by placing monoexponential fit on the curves. Moreover, hemoglobie, leucocyte, PO2, PCo2, HCO3 values were measured before and after HD. pulmonary function tests (PFT) were performed for each case.

Before HD A~er HD

Right lun 9 51±15

Left lun@ 62±26

Total lun 8 57±17

POz mmH 8 92±14

PCo2 mmH 9 39±19

HCOa mmollH 21±12

7.35

55±2

57±18

56±18

94±14

38±24

24±97

7.48

p>O.O5

p>0.O5

p>O.O5

p>O.O5

p<0.05

p<0.05

p>O.O5

pH

There was a significant increase ir~ HCO~ and pH values. Clearance half times of both lungs before and after HD were similar. This suggests that baemodialysis does not have any effect on pulmonary alveolar permeability. The lack of any significant change in pFT and the expected hypoxemia after HD may support this implication. The lack of hypoxemia may be attributed to the more sophisticated machines, biologioaliy compatible membranes and HCO~ dialysate.

P 42

P 44

N,Kanzaki, T.Akita, R.Soda, K.Takahashi, T.Hayabara, K.Sato, ~S.Kurata, M.Kibata, Y.Hiraki. Department of Radiology, National Minami Okayama Hospital, Japan

K.Melis*, H.Slabbynek**, J.Kunnen *~*, D.Coolen**, L.Mortelmans***, J.Vandevivere*. General H o s p i t a l Middelheim, D e p a r t m e n t s of N u c l e a r Medicine*, P n e u m o l o g y * * and Radiology***, Antwerp, Belgium.

INFLUENCE

OF

AGE

AND

1-123-MIBG B E H A V I O U R

G E N D E R ON 81m K R Y P T O N V E N T I L A T I O N / T C - 9 9 m M A A P E R F U S I O N S C I N T I G R A P H Y IN THE D I A G N O S I S OF P U L M O N A R Y EMBOLISM.

IN N O R M A L L U N G

1-123 MIBG is a biochemical marker which can be used to monitor pulmonary norepinephrine(NE)metabolism.The purpose of this study was to investigate pulmonary

1-123 MIBG behaviour in relation to

age and gender in 26 subjects. Subjects and methods: The subjects were 17 healthy volunteers and 9 patients with no cardiac or pulmonary disorders (age range 24 to 88 yr, mean 47.7 yr; 14 M, 12 F). 1-123 MIBG (111 MBq) planar images were

obtained 15 rain (early) and 3 h (delayed)

Aim of the studv : to assess the a c c u r a c y of the use of 81m K r y p t o n as the v e n t i l a t i o n a g e n t i n s t e a d of the usua l l y u s e d X e n o n 133 performing the v e n t i l a t i o n - p e r f u s i o n s c i n t i g r a p h y (V/Q scan). Patients and m e t h o d s : over a two year p e r i o d we perform e d a ZlmKr v e n t i l a t i o n / 9 9 m T c M3kA p e r f u s i o n s c i n t i g r a p h y in 592 p a t i e n t s w i t h the clinical s u s p i c i o n of p u l m o n a r y embolism. We u s e d the r e v i s e d PIOPED criteria but j o i n e d the l o w , v e r y low and normal p r o b a b i l i t i e s (prob). W i t h i n two days all p a t i e n t s had a chest X ray (CXR) and in 74 patient s a p u l m o n a r y a n g i o g r a p h y (A/lgio) was performed. Results

after 1-123 MIBG Anglo+

Anglo-

NoAngio

lung-to-mediastinum ratio (LMR) on early and delayed images, and

High

22

3

28

29

24

55

the lung clearance rate (LCR) was calculated from both ilnages. Results: Neither early nor delayed LMR showed a correlation with

Interm

13

20

87

89

61

120

i

IS

403

251

168

419

age, but there was a significant inverse correlation between LCR and

Total

36

38

518

342

250

592

was observed between subjects who were > 60 years (mean LCR 21.0+5.7, range 13.5- 25.4) and those who were < 40 years (mean LCR

V/Qscan

sons

High

69

41

92

97

32.2_+4.3, range 25.3-39.6, p=0.0136). No significant

High/Int

97

82

39

52

injection. Pulmonary uptake of 1-123 MIBG

was quantified by the

V/Qscan

L/VL/N

CXB+

CXR-

Total

age (~-0.565, p=0.0026, mean LCR 29.0+6.3, range 13.5-40). Separation

differences were

observed between male and female subjects. Conclusion" 1-123 MIBG behaviour may reflect a physiological decrease with aging influence

in the function

of

pulmonary NE

pulmonary NE metabolic function using 1-123 MIBG.

958

metabolism. The

of age has to be taken into account when

assessing

(%)

sensPIOPED

spec

(%)

specPI0PED

S e n s i t i v i t y and s p e c i f i c i t y were comparable to the PIOPED results. The i n t e r p r e t a t i o n of the V / Q s c a n h o w e v e r did not change u s i n g the result of the c h e s t X ray. C o n c l u s i o n : V/Q s c i n t i g r a p h y using Krypton as the vent i l a t i o n agent is accurate in the diagnosis of p u l m o n a r y embolism.

P 45

P 47 do~o,G Costa,g Sousa,A Domenech J Lima Hospitais da Universidade de Coimbra, Portugal

B. Kettner, R. Aurisch, D. Sandrock, V. Ivancevic, I. Reisinger, P. Waurick*, R. Ewert*, and D.L. Munz. Clinic of Nuclear Medicine, Charit6, Humboldt University Berlin, *German Heart Center Berlin, Berlin, Germany.

GA-67 AND SACE IN SARCOIDOSIS. A COMPARATIVE STUDY

BENEFIT OF COMBINED VENTILATION/INHALATION/PERFUSION SCINTIGRAPHY IN PATIENTS WITH LUNG TRANSPLANTS

Faria

Aim: With this work we compare the results obtained with GA-67 scintigraphy and serum Angiotensin-l-Converting Enzyme (SACE) in activity evaluation of Sarcoidosis. Patients: We have retrospectively evaluated 165 studies in 113 patients, 93 female aged 43.4 (SDI 15.5) and 72 male aged 34.6 (SDI 12.2) years, either during initial diagnostic or follow-up and disease activation. In about 88% of cases there was pulmonary involvement and in 12% also other localisation's were found, e.g. salivary glands, eyes, liver~ spleen and joints. All of them had simultaneous GA-67 scan and SACE, and diagnosis has been established on the basis of clinical findings, radiological studies and laboratory tools including bronchoalveolar lavage (BAL) and biopsy. Method: GA-67 citrate (74-111 Mbq) was injected and planar or whole-body images were obtained at 72 hr. An half-quantitative assessment was used to evaluate activity in lungs and other organs, considering liver and soft tissue uptake as reference. Results: GA-67 studies have been positive in 121 (73.3%) and negative in 44 (26.7%) of patients. SACE has been positive in 105 (63.6%) and negative in 60 (36.4%) of cases. Concordant GA-67 and SACE were found positive in 90(54.5%) and negative in 29(17.6%) of patients. The predictive positive values obtained were 74.4% for GA-67 and 85.7% for SACE. Negative predictive values were 65.9% for GA67 and 48.3% for SACE. Conclusion: In our study GA-67 scan had better sensitivity but lesser specificity than SACE. In Sarcoidosis evaluation both studies should be useful.

Aim of this prospective study was to determine patterns of ventilation, inhalation, and perfusion in patients undergoing lung (Itx) or heart and lung transplantation (hltx). In 36 patients (t4 hltx, 22 Itx, 18 women, 18 men, aged 13 - 56 years, mean +/- SD, 37 +1- 15 years) 37 investigations of the pulmonary system were performed: clinical investigations (bronchoscopy and lung function) vs. scintigraphy (ventilation, inhalation, and perfusion scintigraphy; static images, 200 MBq Xenon-133, 20-30 MBq Tc-99m Venticoll ®, 150 MBq Tc-99m MAA). Overall, 185 single studies (10 perfusion studies missing) were compared. All studies in a single patient were done within 24 hours and judged by two independent observers as normal or abnormal (unequivocal judging of all studies). Results: Scintigraphy (Inhalation/Ventilation)

normal abnormal

Clinical investigation normal abnormal 12 3 4 18

30 studies yielded concordant results in terms of pulmonary function testJbronchoscopy vs. scintigraphic studies. Mismatches were found in 7 cases. Especially inhalative immunosuppression could be controlled by ventilation and inhalation because of a higher sensitivity as compared to bronchoscopy concerning aerosol distribution. Additionally, perfusion scintigraphy revealed information about perfusion distribution not achievable by other noninvasive methods. In 1 patient, only the perfusion scan disclosed a pulmonary stenosis not known before, leading to reintervention. In conclusion, scintigraphic approaches yield clinically important functional information at least in a subpopulation of patients with lung transplants. These data are not warranted by conventional clinical methods.

cO am

4--1

¢¢ e(D L-

O. P 46

P 48

R Wollmer, E. Piitulainen, J. Areberg, M. Linddn, S. Eriksson, S. Matlsson. Dcpts. of Clinical Physiology, Lung Medicine, Medicine and Radiation Physics. Mahn6 University Hospital, Maim0, Sweden.

R. Hastinx P. Paulus, J. Foidart, T. Bu~y, D. Cataldo, P. Rigo. Department of Nuclear Medicine, University Hospita]- Liege, Belgium.

TOTAL BODY PROTEIN MEASURED BY 1N VIVO NEUTRON ACTIVATION IN PATIENTS WITI{ EMPHYSEMA The association between chronic obstructive pulmnr~ary disease and weight loss is well known. Since malnutrition appears to indicate poor prognosis, early deteelion may be impollant for direcling treatment. The aim of this study w~'; to evaluate measurements of lolal body protein as .'m early indicator of Inahlutrilion ill palicnts with emphysema and to relate total body protein to anthropometric variables, lung function and muscle strength. The study group coosislod of 20 patients. The crilcria lor inclusion were a clinical diagnosis of emphysema ,'rod a forced expiraloJ7 volume <50 ~ nl predicted. Body weight was not considered. 18 normal subjects served as controls. Total body protein (reflecting mainly muscle mass) was measured by in vivo neutron activation analysis of niuogen. The patients were scanned over a collimated neutron beam li-om a :5"-Cfsource, The prompt gamma rays resulting from the t4N(n,)%~N reaction were detected with four large Nal(Tl) detectors. In mmingy with body m ~ s index (BMI), protein mass index (PMI) w~s calcuhned as total body protein per height squared. Respiraku7 muscle strength was measured as maximal inspiratory and expiratory pressure (Plm~~ and PE , respeclivcly). The groups were similar in age and height. Body weight mid BMI were not significantly lower in patients than in controls. Me,'m total body protein and PMI ware lower in the patients than in the controls (10.7_+2.4 kg vs 12.7_+2.1 kg, p<0.01 and 3.6_+0.5 kg/m 2 vs 4.3_+0.4 kg/m: p<0.001, respectively). Pl ~ and P E were lower in patients than in controls (86_+33 cml L_O vs 111+29 emil.O, p<0.05 and 116_+31 cmll,O vs 148_+44 cmll._O, p<0.05, respectively. Mez.~urement of total body protein may be a sensitive indicator of nuU-itional status in patients with emphysema. We suggerst that reduced total body protein and PMI in patients with emphysema arc early signs of malnutrition and muscle wasting.

s_

O EFFICACY OF TC99M 1'829, A RADIOLABELLED SOMATOSTATIN ANALOG, IN VISUALISING MEDIASTINAL SPREAD OF NON-SMALL CELL LUNG CANCER.

The technetium labelled somatostatin analog P829 is at present under evaluation for its efficacy in neuro-endocrine tumour localisatien. The finding of uptake of this radiophurmaceutical in a non-small cell lung cancer (nSCLC) lesion has prompted us to start a pilot study of its efficacy in visualising mediastinal spread of nSCLC by P829-SPECT (P829) as compared to FluorlS-FDG (PET) in the same patients. Until now 6 patients have been entered in the study, on the basis of pasitive findings in the PET procedure. In the staging presented here metastases other than pleural or pulmonary have not been considered. Patient group Age/sex/histology Loealisation of TNM stage by: primary lesion CT PET P829 69/M/adenocarc. R middle lobe T3N3M0 same same 50/F/adenoearc, L. sup. lobe T3N3M0 same same 71/M/squamous ceil L. lower lobe T4N3M0 same same 69/M/squamous cell R. sup. lobe T2N2M0 T2N3M1 T2N3MI 50/F/squamous cell R. middle lobe T4NIM0 same same 76/M/squamous cell R. lower lobe T3N3MI T3N2MI T3N3MI Neither PET nor P829 can establish the exact size of the primary lesion nor can P829 visualise marginal mediastinal infiltration. The T staging is taken from the CT results. Listing of individual lesions visualised by PET versus P829: Tot. Primary Ipsilat Contralat. Subelavicular Pleura Lung lesion mediast, mediast lymphnedes (contralat.) PET 42 6 11 I2 4 8 1 P829 38 6 9 10 4 g 1 The difference in lesions visualised is entirely due to the fact that PET allows spatial resolution of small lesions grouped together, which are seen as one lesion by P829. P829 images made at 30 rain. to 1 hr. post injection were inferior (due to higher background activity) to 3 to 4 hr. images. This finding, the level of uptake and the rather sharp delineation of the lesions support a specific uptake mechanism. However, at this time we have not shown definitively that this is dun to binding to somatostatin receptors. The target to background ratio for PET is superior to Pg29. No assessment of P829 false positive rate was made. More studies are needed, but the diagnostic quality of P829 imaging is such that, when FDG is not available, P829 seems to be a justifiable alternative.

959

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J. Kropp*, M. Andreeff*,L. Oehme*,S. Schenong**.Y. Prescher**,J. Pinkert*, W.G. Franke*, W.G. Daniel**. Depts. of *Nucl. Med., **Cardiology,Technical

E.Poiseau*, C.Roue**, F.Bonnin*, JL.Stievenart*, M.Fournier**, B.Bok*. * D e p a r t m e n t of N u c l e a r Medicine, **Department of Pneumology, BEAUJON Hospital, Clichy. FRANCE.

University of Dresden; Germany

DIAGNOSIS OF PULMONARY EMBOLISM USING V/Q SCINTIGRAPHY AND GATED SPECT. Planar pulmonary scintigraphy is limited to diagnose subsegmemal pulmo- nary embolism (LE) which is improved by "normal" SPECT (nSPECT) acquisition but still hampered by movement artifacts. Gated SPECT (gSPET) might be helpful (dual head, 64x64 matrix, 64 views, 8 time-bins, 15 breath cycles per view) to overcome this limitation. The cyclic movement of a sphere (in coincidence with a trigger pulse) in a body shaped phantom containing an appropriate activity (negative contras0 was used for simulation studies. In patients (pts) gSPET ~vas realized by the registration of the temperature difference of the in- and exheald air from which gating was derived. The gated phantom studies showed a significant increase of resolution and contrast compared with nSPET readed by visual analysis. In 36 pts suffering from deep vein thrombosis (proven by duplex sonography) V/Q scintigraphy was performed using Tc-99m-labeled Technegas and MAA using n- and gSPET immediately before and 10 days after initialization of two different therapy regimes (standard or low-molecular-weight heparin; early versus late mobilization). All scans were blindly readed by two experienced physicians. Interobserver agreement was 82% and 94% tbr nSPECT and gSPECT, respectively. Initially 58 % of pts had LE. 55 % of pts showed no clinical change. In the two groups with different therapies improvement of LE was diagnosed in both in 6 (17 %) pts whereas in 2 pts (5.5 %) a worsening was found. We conclude, that by gated pulmonary SPECT there is an improvement of spatial resolution and contrast which leads to a more reliable diagnosis of pulmonary embolism in V/Q scintigraphy.

EXERCISE-REST LUNG PERFUSION (LP) TOMOSCINTIGRAPHY IN PATIENTS WITH SEVERE EMPHYSEMA (SE) . Lung volume reduction surgery (LVRS) may improve exercise tolerance in SE patients by expansion of compressed functional lung tissue. Preoperative rest LP scintigraphy has been widely performed. The aim of this preliminary study was to assess if complementary functional informations can be derived from exercise LP studies. Six SE patients (IF/5M; age range: 32-70 years) underwent 2 LP scintigraphies after intravenous injection of 200 MBq of 99mTc-macroaggregates: the first after a standard 6 min walking test, and a second one 2 days later after a i0 min lying rest. Usual planar views and SPECT acquisitions were recorded using a single head gammacamera. Exercise and rest LP SPECT transaxial and coronal views were visually compared by 2 independent senior nuclear medicine physicians. Post-exercice SPECT were well tolerated in these SE patients. No d i f f e r e n c e s were noted in 2 patients SPECT images. P o s t - e x e r c i c e regional perfusion changes were only observed in severely diseased tissues. Increased (3 patients) or decreased (i patient) lung perfusion areas were only observed with SPECT. Post-exercise i m p r o v e d LP may be r e l a t e d to persistence of relatively preserved functional lung tissue in severely diseased parenchyma. Would these changes be linked to improved post-LVRS exercise tolerance, comparison between exercise and rest LP may help in s c r e e n i n g p a t i e n t s candidates for LVRS.

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Elisa Botelho. Lima Baatos, R.Menesee, O.Soares, I.Cotta, J.Gomes Duarte IPO-FG Porto-PORTUGAL Servk;o de Medicina Nuclear

M.Szentesi, P.R@ti, E.Piroska, S.Takfics. National Institute of

99m-Tc-TETRAFOSMIN MAMMOSCINTIGRAPHY: A COMPARATIVE STUDY WITH MAMMOGRAPHY AND HISTOPATHOLOGY

MIBI and tetrafosmin labelled with technetium-99m are perfusion tracers commonly used in Nuclear Cardiology. They have also been proved to be useful in diagnostic work-up for patients with several malignancies.

We had studied tetrafosmin in patients with breast patology. Mammography is the most sensitive technique for detecting non-palpable breast lesions, but it has a low speficity and positive predictive value,which causes a lot of unnecessary biopsies.

103 patients, classified by mammography as low,intermediate or high probability of malignancy, pedormed mammoscintigraphy 10 minutes after injection of 600 MBq Tc-99m-tetrafosmin.Lateral views of both breasts were obtained as well as anterior view for visualization of axillary region. 53 patients had breast cancer, histologically proven, 38 of them were true positive by mammoscintigraphy. The other 50 had benign lesions.In two (one fibroadenoma and on phyloide tumor), mammoscintigraphywas false positive.

The eensitivity(SS), specificity(SP), PPV and NPV were 71,7%, g6%, 95% and 76% respectively.

These values were also studied for each of the radiologicalgroups.

We believe the role of mammoscintigraphy is justified because of its great SP and PPV Supported by Comiss~.o da Investiga£;&oem Cuidados de Sat)de

960

R h e u m a t o l o g y and Physiotherapy. Budapest. H U N G A R Y .

T H E E F F E C T I V E N E S S OF R A D I O S Y N O V I O R T H E S I S A T RA CHRONIC SYNOVITIS AFTER 5 YEAR PERIOD

205 Patients in different departments of NIRP have been treated by Yttrium-90 radiosynoviorthesis/Y-90 RS/ since I st January 1985. Evaluation was based on the criteria described by M011erRau and Sch0tte, and on our own point system. Local activity was measured with dynamic knee-joint scintigraphy. At 115 RA patients the effectiveness of the stadium /st/ of disorder / Steinbrocker st./, of the local X-ray phase and that of general and local activity of the illness was examined. In the first four years excellent and good results were recorded in 80% after years effectiveness declined to 67%.Effectiveness was significantly influenced by the Steinbrocker st. of disorder and local X-ray st., activity. Conclusion:Y-90 RS is an effective way of treating chronic kneejoint synovitis. Treatment must be done in Steinbrocker st. l-II, local st. I-II.

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M.Besta~no, R PaIumbo, A.Marinelli, F.Paoletti, G.Pedroli, P.Puppo, AReitano, S.Viaggi and A.Piffanelli Writing committee of Italian Associatior~Nuclear Medicine (AIMN) Study Group on Radionuclide Therapy

I. B. T ys~n_, s A. V. Heal, M. Reck. James A. Haley VA Medical Center, Nuclear Medicine Service. University of South Florida College of Medicine, Dept. Radiology.

TREATMENT WITH BONE-SEEKING RAD1OPHARMACEUTICALSOF PAINFUL BONE METASTASIS FROM PROSTATE CANCER: AN EXPERIENCE OF 500 PATIENTS OF AN ITALIAN MULTICENTER 1LEGISTER(NUCLEARLINK)*. Since I996 a study group of AIMN has started a national multicenter, observational data-bank project on patients with bone metastatic prostate cancer eligible for radioanclide therapy (RNT), collecting longitudinal information after 89-Sr-Cl (n °= 51l) or 186-Re-HEDP (n ° . 78) courses. METHODS: At baseline consecutive patients ~ r e observed according to a wellassessed protocol (scintigra~, radiography, laboratou, and clinical exams as Karnofsky Index). Follow-up data available for 68.8% of the cases, included an assessment of pain evolution based upon clinical evaluation or RNT efficacy (VAS scale, rate and severity of pain by an additional scoring system, analgesics use modifications). Flare phenomenon and plateletsAVBC changes were also recorded. Quality control and progressive filing of the data were performed by a computerized information system (Link Italia, MO-I) RESULTS: Among 500 patients (mean age 69 y) registered at entry visit, 87% on 89-Sr (mean dose: 146 Mbq) and 13% on 186-Re (mean dose: 1291 Mbq) courses were respectively addressed; t5.7% of patients experienced additional RNT. A three months post-assessment showed "good-excellent" response to RNT (reduction in painful sensation and/or use of analgesics) in 54.3% and in 59.2% of 89-Sr and 186-Rc treated patients respectively. Relationships between "poor responders" to RNT and presence of negative prognostic factors (such as additional non skeletal metastasis) were also investigated. Further prospective data collected in a 1 year period, could implement the statistical significance of the multicenter study for improving health management with RNT in CA prostatemetastatic patients. * A.Arena (FI), GP.Atzei(Roma), F.Banfi (MI), A.Berbellini(Me), C Capirci (RO), G.L Cartia (VC), E.Cattamzzi (UD), E.Di Diego (CH), M.E Dottorini (VA), A.Favero(TO), L Feggi (FE), M.Gasparini (MI), MN.Giatmoni (CA), M Gradam (PS), M.G.Grassi(MI), A.Maneschi(MS), D.Mascia (GR), N.Molea (LU), S,Piccolo (NA), A.Pinte (Terni), C.Pizzocaro(BS), M Povolato (TS), V.Rossi (AR), R.Sciuto (Roma), A.Soricelli (NA), A.Toraldo (CZ), P.Toraldo (PG), P.Vanoli(VA),E.Vezzani(PT), G.Villa(GE), G.Virotta(BG), R.Zoccola(AL),P.L Zorat (TV):

BONE MARROW DISTRIBUTION STUDIES IN THE CLINICAL EVALUATION IN STRONTIUM-89 BONE PAIN PALLIATION THERAPY Prostate cancer now has surpassed lung cancer as the leading cancer among men. Whereas in the past most men died of another illness, many of the aging male population will experience the morbidity of prostate cancer - its protracted infirmity and propensity to metastasize to the skeleton, where it may cause uncontrollable pain. Strontium-89, although effective in the palliation of bone pain from prostatic cancer, has been reported to be associated with some toxicity, primarily hematological, with depression of white ceils, platelets and bone marrow, resuking in patient death or difficult recovery. The purpose of this study is to determine if: 1) the measured bone marrow distribution profile can be predictive of excessive bone marrow suppression; 2) the measured bone marrow distribution profiles can be predictive of an unfavorable response in the patient's outcome; and 3) earlier administration of Sgsr therapy as the primary therapy can delay or suppress new pain sites or metastatic progression without toxic effects. A total of 24 patients, who underwent 89Sr bone pain palliation from metastatic prostatic carcinoma, were evaluated pre- and post-therapy with bone and bone marrow scans, whole body profile scans, hematology and chemistry profiles, and patient questioning. Patients were grouped by pain reliefreports. ~I~ose reporting complete pain refiefhad a mean life post therapy of417 days while those with incomplete pain relief had a mean life of 89 days. Although most patients reported benefit, foUow-up blood element counts indicated persistent anemia and bone marrow depression, but less severe and good recovery in the complete pain relief group, All patients showed shifts in bone marrow distribution, with ashifl to head and thorax in patients with a good outcome. There is insufficient data for early treatment evaluation. Keywords: Strontium-89, Prostate, Pain Palliation

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P Madaria~9, I Almoguera, O Ve~azo, A A l o n s o ~, ML M a r t i n e z , C . T r a m p a l , J L Lampreave,P Dominguez, A . B i t t i n i , j M P6rez V ~ z q u e z Departments of Nuclear Medicine and Oncoiogy*.Hospital General G.Marafi6n Madrid

S.K.Shukla a'b, C.Cipriani a, G,Atzei a, G.Argir6 a, S.Boemi a, R.Cusumano c, A.Aeeoncia e, G.S.Limouris d, K.Schom~cker e a) Serv. Med. Nuel., Ospedale S. Eugenio,Roma; b) CNR,Roma; c) Dep. Urol., Aurelia Mosp., Roma,Italy; d) Nucl.Ned.Sec0, Athens Univ.,Greece; e) NueL.Med.Dep., KSIn Univ.,Germany

TREATMENT OF SYMPTOMATIC BONE B R E A S T C A R C I N O M A U S I N G Sr-89.

SR-89 CHLORIDE AND CITRATOYTTRATE-gO IN THE TREATMENT OF ADVANCED PROSTATE CANCER PATIENTS (APCP)

METASTASES

OF

The p u r p o s e was to d e m o n s t r a t e the u s e of Sr 89 in women with breast cancer and bone pain r e f r a c t o r y to c o n v e n t i o n a l t r e a t m e n t s M a t e z i a l s iSince A u g o u s t 1993 till J u n e 1996, we administered 148 MBq (4mCi)of Sr-89 i.v injection to 32 w o m e n with breast cancer and r e f r a c t o r y p a i n to o p i o i d a n a l g e s i c s . All of t h e m h a d s k e l e t a l m e t a s t a s e s seen in b o n e s c i n t i g r a p h y White cell count was > 3 X 1 0 -3 HI a n d p l a t e l e t count w a s > I 5 0 X ! 0 ~ ~i K a r n o f s k y index, severity of p a i n a n d a n a l g e s i c r e q u i r e m e n t s w e r e e v a l u a t e d at baseline and 3 and 6 months after Sr-89 administration. Re~!ts :Seven cases were lost to follow up because they didin't come to the evaluation, l e a v i n g 25 p a t i e n t s . One of t h e m d i e d 2 m o n t h s after treatment, We c o n s i d e r e d a V E R Y E F F E C T I V E response a reduction in p a i n a n d / o r analgesia need between 80-100% ;EFFECTIVE between 20-80% and NO R E S P O N S E 0-20%. R e s p o n s e to p a i n :8 cases (33%) v e r y e f f e c t i v e , 9 cases(37%)effective,and 7 cases(30%) n o response. Response to analgesia requirements:8 patients (33%)very effective,8 patients (33%) effective a n d 8 p a t i e n t s (33%) no response. C o n c l u s i o n :In our experience, a pain and analgesic response rates of 70% and 66% respectively makes the t r e a t m e n t with St-89 a u s e f u l a l t e r n a t i v e therapy, w i t h o u t a l m o s t sideeffects in the palliation of painful osseus m e t a s t a s e s f r o m b r e a s t carcinoma.

C O

i m

C

L

The purpose of the present study has been to find an advanced prostate cancer-affine radiopharmaceutical for the systemic therapy of APCP who no more respond to hormone therapy, radiotherapy, chemotherapy or immunotherapy; and have intense pain. We have treated 70 APCP by i.v. injection of !48 MBq Sr-89 chloride (metastron) and 32 patients with 90 MBq citratoyttrate-90 solution containing both cationic and anionic species of Y-90 in the solution. Total-body distribution of both radionuelides is studied by Bremsstrahlung imaging at different intervals p.i. The bone metastasis pain palliation with St-89 is generally slow, not appreciably felt before 15 days, and lasts for about three months. With citratoyttrate-90, the pain palliation is very rapid and felt al~eady nearly three hours p.i. I% lasts only for about i0 days, necessitating another dose of citratoyttrate-90. Sr-89 treated patients need reduced dose of the analgesics, while the patients treated with citratoyttrate90 had no need of it. Y-90 patients quickly regained their normal way of life, Sr-89 is firmly bound to the painful bone lesion and it could be imaged for more than 4 months p,l., even when its pain palliation effect has disappeared. We are investigating the reason for this strange hebaviour of Sr-89 in vivo. Citratoyttrate-90, concentrating both in the primary and secondary lesions, has curative action in APCP. Platelet depression is more frequntly observed in Y-90 treated patients. We are tryin~ to avoid thls disadvantage of citratoyttrate-90. Our results show this due to very interesting chemistry of Y-90 in aqueous solution.

961

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F. Giammarile, P.Chauvot, C. Desuzinges. Nuclear Medicine Department, Centre L~on B~rard, Lyon (F).

H Palmedo, S Guhlke, A Beets*, J~ Sartor, F.F. Knapp*, J. Bogatzky and HJ. Biersack. Department of Nuclear Medicine, University Bonn, Germany, *Nuclear Medicine Group, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN, USA.

BONE PAIN PALLIATION WITH STRONTIUM-85 THERAPY: FIRST EVALUATIONS IN 59 PATIENTS. Aim: In this retrospective study, we evaluated the efficacy of Strontium-85 for the palliation of metastatic bone pain 85Sr, formerly used for bone scan detection, decays by electron capture with gamma emission of 514 keV, and physical half-life of 64 days. The associated X emissions of 10 to 15 keV allow an effective internal radiotherapy, with a maximum dose delivered to target within a range of 10 nun. Methods: Between 1977 and 1992, 119 doses of 85Sr chloride (mean activity 340 MBq) were administered to 108 patients (52 prostate, 41 breast and 15 other cancers) with hyperaIgic generalized bone metastases. Results: 85Sr bone scans were obtained up to 8 weeks after injection, in order to document isotope biodistfibution and to estimate absorbed doses. Dosimetry calculations demonstrated tumor to normal bone uptake ratios up to 5:1. Survival times, pain scale and blood values were recorded. Although global hematological toxicity of the treatment was low, one patient (with pronounced marrow involvement) presented a fatal myelodepression at the 4th month. At 12 weeks, 714% of patients presented significant benefit from treatment, and 50.4% became free of pain. Beneficial effects lasted from 1 to 20 months (mean 3.3). The data analysis showed no evidence of a significant dose-response relationship. Average dose of the first 65 treatments was 405 MBq and response rate 71.0% The average dose of the subsequent 54 treatments was lower (250 MBq), with the same clinical results (72.2% of response rate). The higher symptomatic improvement was obtained in patients treated at an early stage of metastatic skeletal disease and in prostate patients. Conclusion: Systemic radionuclide therapy using 85Sr is a feasible, effective and well tolerated palliative treatment in patients with refractory bone pain. We attained at least the same response rate as that reported with bone-seeking beta-emitting radionuclides such as 89Sr. However, no significant dose-response relationshp was evident.

Rhenium-188 (Re-188) has a high energy beta radiation (2.11 MeV, T~:2=17h) and is available from the tungsten-188/rhenium-188 generator. The option of very cost effective radiolabeling with Re-188 and the physical characteristics suitable for therapy led us to investigate Re-188-HEDP as a compound for pain palliation in patients with disseminated bone metastases We used a clinical-scale generator (74 GBq) which was weekly checked for sterility and apyrogenicity. Laboratory and animal studies have shown that carrier-added (c.a.) Re-188 HEDP behaved different from no-carrier-added (n.c.a.) Re-188 HEDP which did not accumulate significantly in bone but in soft tissue. Therefore c.a Re188-HEDP (same level as in Re-186-HEDP) was used in the patient studies 4 patients (prostate cancers) with painful disseminated bone metastases received a single injection of 1.11 GBq Re-188-HEDP. The bone marrow dose was calculated to be 0.56 mSv/MBq. Early (3 h pJ.) and late (24 h p i.) whole body imaging with a standard gamma camera (HEMR coil) showed significant accumulation in osseous metastases which was identical to the Tc-99m DPD scan. The ratio of bone metastasis to normal bone was up to 10. Clinically, no adverse event due to the Re-lgS-HEDP injection could be documented. Biochemical parameters and blood counts (thrombocytes, leukocytes) did not show significant alterations These preliminary data suggest that human studies should be continued and that a higher dose can be used to investigate the full effect of Re-lg8-HEDP on pain palliation

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Z.IBI$, N.0.KO¢0K, N.¢ANAK¢I*, G.ZRBAY, A. AKIN Ankara University Medical School Nuclear and Anesthesiology* Dept. Ankara/TURKIYE

G.ARAS, Medicine

R E S U L T S O F T R E A T M E N T O F P A I N F U L BONE M E T A S T A S E S R e - 1 8 6 H E D P IN 4 P A T I E N T S W I T H R E C T U M C A N C E R

WITH

Palliation of pain from multifocal bone metastases in patients (pts) with carcinoma is a serious problem. The aim of this preliminary study was to evaluate the effect of Re 186 HEDP on the reduction of pain and its side effects. M a t e r i a l , m e t h o d : 4 pts (2 male,2 female) with rectum cancer and multiple bone metastases were included in study. 3 pts were treated with single injections of 1295 MBq Re 186 HEDP and i pt with doubl injections. Inclusion criteria were scintigraphic evidence of multiple bone metastases, bone pain localized in the area of higher uptake and resistance to usual pain relasing treatments, adequate hematologic and renal function. A scanning system and different questionnaire for daily and weekly were used for assesment of pain and analgesia. The performance status was assesed by the Karnofsky index. P,esults:Pain relief was observed as complet in 1 pt and as partial in 2 pts in 1-3 weeks and continued 7-9 weeks. 1 pt shewed no answer. A flare reaction was not observed. Slightly decreased thrombocytes (16±7%), leucocytes (22±12%), AP (20±8%) levels were measured after the therapy compairing with pretherapy levels. Conclusion:The high ratio (75%) of good responses indicates that Re 186 HEDP is an efective agent in the treatment metastatic bone pain in rectum cancer and can be used safely.

962

RE-188-HEDP FOR PAIN PALLIATION METASTASES: FIRST CLINICAL RESULTS.

OF

BONE

Research at ORNL supported by DOE under contract DE-AC05-960R22464 with Lockheed Martin Energy Research Corporation.

M . W i n d e r e n 2, K . B r e i s t o l ~, H . M . O r m s t a d 3,O. K . H j e l s t u e n 3 B .Andreassen~, P. O. Bremer3, @. Fodstad2. ~Dept. of Nucl. Med. a n d 2Tumor B i o l . , T h e N o r w e g i a n R a d i u m H o s p i t a l , Oslo, 3 I s o p h a r m a AS, Kjeller, Norway. 1 5 3 S m - M D P R A D I O N U C L I D E T R E A T M E N T OF S K E L E T A L METASTASES FROM MT-I BREAST CANCER CELLS AFTER I N T R A C A R D I A L I N O C U L A T I O N IN N U D E RATS. MT 1 h u m a n b r e a s t c a n c e r c e l l s g i v e s m e t a s t a s e s to b o n e w h e n i n j e c t e d in the h e a r t of a t h y m i c n u d e rats, a n d the p r e s e n t s t u d y was p e r f o r m e d in o r d e r to v a l i d a t e the t h e r a p e u t i c agent 1 5 3 S m - M D P a g a i n s t s k e l e t a l m e t a s t a s e s . G r o u p s of 5 a t h y m i c nude rats, 4 w e e k s of age w e r e i n j e c t e d w i t h ix106 cells in the left v e n t r i c u l a two days b e f o r e i n t r a v e n o u s t r e a t m e n t w i t h 50 or 200 M B q / k g of ! 5 3 S m or left as u n t r e a t e d c o n t r o l s . MDP, 88 mg, was l a b e l l e d w i t h 1.7 G B q 1 5 3 S m at p H I0/60°C/30 min. A l a b e l l i n g y i e l d of >97% w a s obtained, w i t h a s t a b i l i t y of >92% o v e r 24 hours. F r o m 13 m i n to 2 h a f t e r i n j e c t i o n of 1 5 3 S m - M D P the tibial bone u p t a k e i n c r e a s e d 1.5 times a n d f r o m 2 to 24 h 15 times, m e a s u r e d b y g a m m a counting. R a d i o a c t i v i t y in the l i v e r was s t a b l e a n d a slight i n c r e a s e in the lungs w a s o b s e r v e d , p o s s i b l y due to l i b e r a t e d 153Sm. A n i m a l s w e r e k i l l e d due to d e v e l o p m e n t of b o n e m e t a s t a s e s 20.5, 25.0 a n d 31.6 days a f t e r cell i n o c u l a t i o n in the ctr, 1 5 3 S m - M D P 50 a n d 200 M B q / k g groups, resp. In the 200 M B q / k g 1 5 3 S m - M D P g r o u p we o b s e r v e d 1 / 5 1 1 o n g t i m e s u r v i v o r (>60d) . The t u m o u r m o d e l w i l l be u s e d for f u t h e r evalua t i o n of t r e a t m e n t of b o n e m e t a s t a s e s i n c l u d i n g radionuclide therapy. Different stages from c i r c u l a t i n g c e l l s to m a n i f e s t b o n e tumour, i.e. at the m i c r o - m e t a s t a t i c level, w i l l be evaluated.

P 63

P 65

N.V.S. M a r i n h o , I.J. Coelho, L.F.C. Roman, E.T. Ro cha, J.C. M e n e g h e t t i , M . I . C . C . G u i m a r ~ e s . R a d i o i s o t o p e s f r o m the H e a r t I n s t i t u t e a n d C e n t e r of N u c l e a r M e d i c i n e L I M - 4 3 r U n i v e r s i t y of S~o Paulo, B r a z i l

A.Segarra*; S.RulI*; A.G_Utriila**; J.M.Llamas. Nuclear Medicine, Rehabilitation* and Rheumatology** Departs. "Virgen de las Nieves" Hospital. Granada. Spain.

SAMARIUM- 153-EDTMP SKELETAL UPTAKE COMPARISON BETWEEN SCINTILLATION INTERNAL DOSIMETRY DATA.

CALCULATION: CAMERA AND

Radiation dosimetry is important for assessing the efficacy and toxicity of radionuclide therapy. However, to estimate the radiation absorbed dose using the MIRD formalism requires specialized staff not always available on a clinical environment. The aim of this study was to use the scintillation camera for calculating the skeletal uptake of Sm-153-EDTMP in order to compare with the data generated from internal dosimetry method. Eleven studies were carried out in 8 patients (SM and 3F) with metastatic prostate cancer and arthritis (3). All the patients underwent whole body scintigraphy, anterior and posterior projections, 6 hours after IV injection of Sm-153-EDTMB (37 MBq/kg). A calibrated syringe, with a known Sm-153-EDTMP activity was also imaged. A relation between counts and activity was established and the percentage of Sm-153-EDTMP uptake in the skeleton was derived. For internal dosimetry method, urine samples were collected hourly over 6 hours starting immediately after injection. The results of the comparison were the following: % of ID uptake in the skeleton Scintillation camera Internal dosimetry method (mean ± SD) (mean ± SD) 67.47 ± 12.13 70.93 ± 19.02 In this group of patients the values obtained for the scintillation camera were 4.9% smaller when compared to the ones obtained from the internal dosimetry method (p=ns).From these preliminary results we concluded that this difference might be due to geometric and detector sensitivity differences. Nevertheless, the scintillation camera san still provide an approximated result. In cases, in which it would be not possible to perform the internal dosimetry method, the scintillation camera could be used as a guide to identify the patients that will require a more strict follow-up from the haematological point of view.

J.M.Lbpez-Ruiz; A.RodlS~uez: M.A.Muros; M.D.Martinez de] Valle;

EFFECTIVENESS OF RADIOISOTOPIC SYNOVIORTHESIS IN THE TREATMENT OF INFLAMATORY ARTHROPATHY. OBJETIVES: Evaluation of the radioisotopic synoviorthesis effectiveness in the treatment of patients with different inflamatory arthropathies. STUDY GROUP. Twenty patients have been studied (8 male; average age 36.2 years -range:20-60) afected by: Seropositive Arthritis (n=5) and Seronegative Arthritis, n=15 (Psoriatic Arthritis, n=7) . In 7 patients the disease was monoarticular and in 13 poliarticular. All patients were in the I-II Radiologycal Stage of the American Rheumatism Associations. In all cases the conventional medical treatment failed. METHOD: lntra-articularl injection of the radionuclide. In the KNEES (n=16): 90-Y; 370 MBq, and in the WRIST (n=4): 186-Re; 185 MBq.The patients were clinically evaluated at 1, 6, 12 and 24 months of the treatment, with special attention to the evolution of rain, inflamation and effusion of the articulation. ~,ESULTS: Are shown in th~ TI~I)I~,I; l

NOT SUFFERING FROM

lm.

6m. I 12 m.

24 m.

INFLAMMATION PAIN,EFFUSION

95%

55%

40%

50%

PAIN,EFFUSION

95%

75%

60%

[ 61%

PAIN

95%

75%

60%

[ 66.6% I

I

EFFUSION 95% 95% , 80% 66.6% The results are of special interest after 24 m. CONCLUSSIONS: The radioistopic sinoviorthesis is a useful technique in the treatment of patients without response to the conventional treatment. In our experience it is possible to reach a 50% of clinical remissions two years after the treatment.

C O im 4~

C x_

P 64 I D o r m e h l : , W L o u w 2, F S c h n e e w e i s s ~, U C a r l 4, G S c h m i t t 4. ~AEC I n s t i t u t e f o r L i f e S c i e n c e s , U n i v e r s i t y of P r e t o r i a , ~ A t o m i c E n e r g y C o r p . , P e l i n d a b a , 3 I n s t i t u t e f o r M e d i c i n e , Jfilich, 4Clinic for Radiotherapy, U n i v . of D U s s e l d o r f . PROGRESSIVELY REDUCED Sm-153-EDTMP UPTAKE IN NORMAL BONE AFTER MULTIPLE APPLICATIONS. A NONHUMAN PRIMATE STUDY. Re-application of Sm-153-EDTMP for maintained palliation of m e t a s t a t i c b o n e p a i n in p a t i e n t s was f o u n d to be p r o g r e s s i v e l y less effective. Does EDTMP exert a blocking function, limiting a c c e s s to b o n e t i s s u e o n r e - a p p l i c a t i o n ? This investigation concerns the pharmacokinetics and bone localisation of S m - 1 5 3 - E D T M P in the normal baboon during three successive applicat i o n s (6 w e e k i n t e r v a l s ) e a c h w i t h t w o d i f f e r e n t concentrations of E D T M P (0.7 E D T M P m g / k g , n o r m a l ; a n d 1.4 E D T M P m g / k g ) . T w o g r o u p s of s i x b a b o o n s w e r e used, o n e f o r e a c h c o n c e n t r a t i o n . Scintig r a p h y i n c l u d e d a t w o h o u r d y n a m i c s t u d y (i m i n frames) following iii MBq Sm-153 EDTMP i.v. S £ a t i c i m a g e s (4 min) f o l l o w e d h o u r l y at 2 t i l l 5 hrs. T i m e - a c t i v i t y c u r v e s w e r e o b t a i n e d f o r the heart, kidney and liver, and relative b o n e to b a c k g r o u n d u p t a k e f r o m the s t a t i c i m a g e s . Blood and urine clearance curves were obtained. Compar i s o n s w e r e d r a w n ( S t u d e n t ' s t - t e s t ) b e t w e e n successive applications, and between the two concentrations. Partial blocking appears with the lower EDTMP concentration, significant after the third application (P<0.05) . T h e f i r s t a p p l i c a t i o n of the high concentration i n d i c a t e s l o w e r u p t a k e in t h e b o n e t h a n t h e l o w e r one, p o i n t i n g to b l o c k i n g by the high concentration, h o w e v e r n o t w i t h subsequent re-applications. Re-application of t h e high EDTMP-concentration c o u l d r e d u c e l e v e l s of serum calcium, increase parathyroid hormone level, triggering osteoblastic activity and bone remodelling, thus partially off-setting blocking w h i c h w a s h e n c e c l e a r e r at t h e l o w c o n c e n t r a t i o n .

L_

P 66 S. Sophocleous. Nuclear Medicine Center AYIOS THERISSOS. Nicosia - Cyprus

O RADIOSYNOVIORTHESIS. FIRST EXPIRIENCE IN CYPRUS PRELIMENARY RESULTS Treatment of inflammatory synovitis (e.g. rheumatoid arthritis and other arthropathies) with radiopharmaceuticals is well established in central Europe. In small peripheral countries like Cyprus there are many (not only logistic) problems to solve and resentmens to overcome before this method can be established. Method In order to select the patients for the correct indication for radiosynoviortliesis obligatory apparative diagnostics are ultrasound and soft tissue scintigraphy of the joints. The mandatory strict intraarticular injection of the radiopliarmaceutical is performed trader CT control. Three radiopharmaceuticals were employed aliways in constant dosage. Ytrium-90 for the treatment of knees, Erbium-169 for the treatment of wrist joints and Rhenium- 186 for the treatment of thumb joints. Results Over 6 months 17 patients had radiation synovectomy treatment (9 male, 8 female). The mean age was 66 (35-80) years. 13 knees, 2 wrist joints and 2 thumb joints were treated)Very good improvement (pain, mobility) is found in 60 % of all patients. Conclusion For the definitive assessment of the resuks in those patients a total period of maximum 4 years may be necessary. 963

P 67 S.J. Wang, M.N. Chen, B.T. Hseih, Z.T. Tsai, G. Ting, and *F.F Knapp, Jr. *Oak Ridge National Laboratory, TN. Taichung Veterans General Hospital and 1Institute of Nuclear Energy Research (INER), Taiwan.

THE EFFICACY OF INTRATUMORAL INJECTION RHENIUM-188 AMINEX INTO THE HEPATOMA OF RATS.

OF

Selective radionuclide therapy using intrahepatic arterial injection has been proved to be an effective treatment of hepatoma. However, this technique requires extremely selective catheterization, which is highly dependent on operator's skill and equipment. In addition, the common existence of arterio-venous shunts in hepatoma is also a considerable problem. This obstacle has been overcome by direct intratumoral injection. In this study, we evaluate the efficacy of intratumoral injection of Re-188 Aminex (BioRad co., U S A ) into the hepatoma of rats. Animal model was established by direct implantation of N1-S1 hepatoma cell line (ATCC, Maryland, U S A . ) into the liver in Sprague Dawiey rats. Two weeks after implantation, 37 MBq of Re188 Aminex ( mean size=15_+ 5 um) in a volume of 0.1 ml were injected into the center of the tumor directly in three rats. The tumor size was evaluated by sonography before and 1 week after treatment. The results are tabulated as follows: maximal tumor size ifl transverse section Before Tx 1 wk after Tx Rat No. 1 14.5x22.8 mm 13.0x14.4 mm Rat No. 2 20.1x36.3 mm 9.5x10.6 mm Rat No. 3 15.1x21.2 mm 14.6x16.1 mm Whole body gamma images at 1, 4 and 24 hours shows well localization of radioactivity in the tumor and no definite radioactivity is identified outside the tumor. Our preliminary study suggests that intratumoral injection of Re-188 Amine)< may be used as an effective method for the treatment of unresectable hepatoma.

P 68 S.J. Wang, W.Y. Lin, M.N. Ghen, B.T. Hseih, Z.T. Tsai, S.P. Wey, G. Ting, and *F.F. Knapp, Jr. *Oak Ridge National Laboratory, TN. Taiohung Veterans General Hospital and Institute of Nuclear Energy Research (INER), Taiwan. RHENIUM-188 AMINEX: A NEW RADIATION SYNOVECTOMY AGENT. Radiation synovectomy is efficacious in controlling the symptoms of rheumatoid arthritis. However, the procedure is not widely used because of concerns about leakage of radioactivity from the treated joints. The leakage can be minimized by selecting the desired size of the particle. In this study, we labelled aminex (15 4-5 u) with Re-188 and analyzed the biodistribution following intra-articular injection in rabbits with antigen-induced arthritis to assess its applicability for radiation synovectomy. Twelve male rabbits were slaughtered at 1, 24, and 48 hours after injection of 3.7 MBq of Re-188 Aminex. Samples of different organs were obtained and counted to calculate the tissue concentration. The results are tabulated as follows: Time Concentration of variant o r g a n s ~ e d dose/9 or m~.___ (hr} LN liver lung spleeenkidney muscle bone blood urine 1 0.0038 0.0040 0.0042 0.0032 0.0028 0.0032 0.0066 00011 0.0036 24 0.0069 0.0045 0.0043 0.0028 0.0039 00035 0.0068 0.0008 0.0046 48 0.0027 0.0023 0.0027 0.0020 0.0031 0.0021 0.0035 0.0009 0.0018 *LN: lymphnode Our data revealed very low radioactivity in all organs at different times, which suggest the leakage of radiotracer from the knee was negligible. Our preliminary resutls indicated that Re-188 aminex could be an potential radiopharmaceutical for radiation synovectomy.

964

P 71 E. Busemann-Sokole L.J.M. Rijks, M. Stabin, K. de Bruin, A G M Janssen, E.A. van Royen, Academic Medical Centre, Department of Nuclear Medicine, Amsterdam, NL; Radiation Internal Dose Informat on Center, Oak Ridge, TN, USA; Amersham Cygne BV, Eindhoven University of Technology, Eindhoven, NL. RADIATION DOSIMETRY OF THE ESTROGEN RECEPTOR RADIOLIGAND Z-[I-123]M1VE USED IN BREAST CANCER IMAGING. Iodine- 123-1abelled cis- 1113-methoxy-17c~-iodovinylestradiol (Z-[1-123 ] MIVE) is a radioligand used in estrogen receptor imaging of breast cancer. Its radiation dosimetry was investigated in 5 healthy females. Approximately 150 MBq Z-[I-123]MIVE (SA 185 TBq/mmol) was intravenously administered. In 4 of the subjects the thyroid was blocked. Conjugate posterior and anterior whole body imaging was performed at I. 2, 4, 6, and 24 hr p.i.. Urine was collected up to 24 hr for calculation of urinary excretion and to predict fecal excretion. Blood samples were taken up to 24 hr p.i.. The geometric mean counts were calculated from regions over the thyroid, heart, brain, breasts, and liver, and the percentage of the administered activity was calculated from the geometric mean counts of the whole body image of 1 hr. The resulting data were fit to a multicompartmental model and time-activity curves were generated The MIRD method was applied to calculate the absorbed radiation doses. The images showed rapid bepato-biliary excretion and increasing bowel activity with time. This gave tavourable imaging conditions for the thoracic region, but imaging of the abdominal region was impeded. Diffuse accumulation of activity was seen in normal breast tissue. The breast-to-nonspecific uptake ratio increased over time Z-[I-123]MIVE was cleared through the renal system and the gastrointestinal tract. Predicted mean excretion at 50 hr pi. was 58% ~: 14% (SD) in urine and 31% ± 19% in feces. In the subject without thyroid block, the thyroid was the most critical organ, receiving 0.33 mGy/MBq This thyroid dose added significantly to the effective dose equivalent Otherwise, the excretory organs received the highest absorbed doses. The lower and upper large intestinal walls received 0.11 and 0.098 mGy/MBq, respectively, the urinary bladder wall 0.090 mGy/MBq, the gallbladder wall 0.087 mGy/IVIBq, and the small intestine 0.043 mGy/MBq The average effective dose equivalent of Z-[I-123]MIVE was estimated to be 0.033 mSv/MBq. In conclusion, administration of 150 MBq of Z-[I-123]MIVE results in an acceptable radiation dose (5 mSv effective dose equivalent).

P 72 A.M. Palmer. Radiopharmacy Unlt, United Bristol Healthcare NHS Trust, Bristol General Hospital, Bristol, United Kingdom, BSI 6SY. COMPARISON OF AND TECHNETIUM

PLACENTAL TRANSFER OF RADIOIODINE IN G U I N E A PIGS A N D MICE. Apart from

a few case reports there are no published data on the placental transfer, and consequent risk to the fetus, of radiopharmaceuticals in humans. Experimental data necessarily relies on animal models. The choice of model often depends on availability, cost or convenience. Placental structure is important when assessing the extent to which experimental results can be extrapolated to humans. In this study the placental transfer of two radiopharmaceuticals is compared in two animal models with different placental structures. Materials and Methods: Sodium (131) Iodide and Sodium (99m) Pertechnetate was administered to separate groups of pregnant guinea pigs and mice in early and late stages of gestation, corresponding to the first and third trimesters of the human pregnancy. At intervals, groups of animals from each set were sacrificed by anaesthetic overdose. The specific activity in fetuses and placentas was determined. Results: The peak fetal uptake of technetium in mice was 1% ( 8.2% in placenta) after 3 hours in early pregnancy and 2.8% (0.7% in placenta) after 0.5 hour in late pregnancy. Peak fetal uptake in guinea pigs was 1.4% (0.8% in placenta) at 2 hours in early pregnancy and 3.9% (1% in placenta) at 2 hours in late pregnancy. For radioiodine peak fetal uptake in mice was 1% (@.2% in placenta) in early pregnancy and 7.4% (1.4% in placenta) in late pregnancy. In guinea pigs the uptakes were 2.4% (1.2% in placenta) in early pregnancy and 8.9% (1% in placenta) in late pregnancy. Conclusion: These data suggest that the differences in placental s t r u c t u r e between these two models has little effect on gross transfer of pertechnetate or iodine.

P 73

P 75

S. Fenche[, J. Kotzerke, K. Grillenberger, S.N. Reske. Dept. of Nuclear Medicine, University Hospital of UIm, Germany

A.M. Palmer, M. Saunders & A.W. Preece. Radiopharmacy Unit, United Bristol Hea!thcare Trust and Biophysics Unit, U n i v e r s i t y of Bristol, Bristol, U.K.

PHARMACODYNAMICS OF TC-99M-PERTECHNETATE AND RE-188PERRHENATE AFTER ORAL APPLICATION OF PERCHLORATE Re-188-Perrhenate is a beta and gamma emitter. It was proposed for intravascular brachytherapy using a ballon-katheter. Rupture of the ballon is a rare but fatale complication. The whole body distribution of Perrhenate after intravascular application is similar to Tc-99m-Pertechnetate which means that the thyroid is the critical organ. To reduce the radiation burden for the thyroid after a ballon rupture, Perchlorate can be given as a competitive antagonist. But exact pharmacodynamic data of Perchlorate are not available. Therefore, we investigated the thyroid activity after oral application of Perchlorate using Pertechnetate (20 pts.) and Perrhenate (1 pat.) in patients who underwent routine thyroid scintigraphy preparing radioiodine therapy. In 9 patients Tc-uptake was measured 15 mins after i.v. injection of Pertechnetate. Then 2 mL Perchlorate were given orally and Tc-Uptake was measured again 30 rains after Perchlorate application. In 11 patients we acquired a dynamic study of 45 mins with oral application of 2mL Perchlorate 15 mins after Tc-99m-injection of 85 MBq +10%. Tc-99m-Pertechnetate-Uptake was 2.7 -+ 2.6% (range 0.4 - 9.4) at 15 rains and 0.34 -+ 0.35% (range 0.0 - 1,5) at 45 mins. The ratio of the late to the early Tc-Uptake was 0,14 + 0,07 (range 0.00 - 0.25). From the dynamic data the half time of activity wash out (T1/2) was estimated as 7.95 +1.98 rains (range 5,9 - 11). In 1 patient we acquired a dynamic study of 45 rains after i.v, injection of 85 MBq Re-188-Perrhenate in an identical protocol. The Perrhenate-Uptake was 0.4% at 15 rains p,i. and 0,2% 30 mins after Perchlorate. T1/2 after Perchlorate application was 6.3 min. In conclusion, Perchlorate can be used to reduce radiation burden after thyroid scintigraphy with a fast effect after oral application. The reduction of thyroid activity yields approximately 85% within 30 mins. The same strategy is feasible after the unintentional application of Perrhenate.

ALTERATION OF ANAESTHETIC.

BIODISTRIBUTION

OF

R;d]IOIODINE

BY

During studies on the biodistribution of radiopharmaceuticals, unexpected distribution changes were n o t i c e d at early time points after administration under anaesthesia. As radioiodinated p h a r m a c e u t i c a l s are increasingly being used i n t r a - o p e r a t i v e l y to localise tumour mass for excision any a l t e r a t i o n in distribution under anaesthesia could be c l i n i c a l l y relevant. This study was undertaken to study this effect. a n d M e t h o d s : Sodium {i-131) Iodide was administered by tail vein injection to three groups of eighteen adult female mice. One group was not anaesthetised, one r e c e i v e d Halothane (4% in Nitrous oxide) and one received Ketamine (100mg/kg). From each group three mice were sacrificed by anaesthetic overdose at each of six time points up to, and including, four hours. The specific activity in each of the major organs was determined.

Materials

The b i o d i s t r i b u t i o n of radioiodine under Halothane anaesthesia was m a r k e d l y different to that obtained either without anaesthetic or with Ketamine. A reduction in thyroid uptake was p a r t i c u l a r l y striking. Results:

C O

=m

The mechanism for this alteration in b i o d i s t r i b u t i o n is so far unknown but could have relevance for the use of radiolabelled pharmaceuticals used intra-operatively.

A.M. Palmer. Radiopharmac~ B r i s t o l , U.K.

L_

P 76

P 74

M. Unit, BSI

Bristol

General

Hospital,

6SY

PLACENTAL TRANSFER OF GALLIUM (67) CITRATE IN GUINEA PIGS Methods: 21 Pregnant guinea pigs between 3

months and 1 yr of age were studied. At 7-8 weeks gestation (equivalent to the third trimester in humans) the animals were anaesthetised by inhalation of a mixture of 70% nitrous oxide, 25% oxygen and 5% carbon containing 4% Halothane :H:. Gallium (67) Citrate (IMBq in 0.5ml) was administered into the right side of the heart by intracardiac injection. The animals were allowed to recover consciousness and placed in individual cages until required. Blood sampling was performed at appropriate intervals under anaesthetic. At intervals up to ten hours, g r o u p s of three animals were sacrificed by Halothane overdose. The weight and radioactive concentration of the major maternal organs and fetuses were determined and the fetal radiation dose from radioactive material in the maternal organs, placenta, amniotic fluid, and fetal body itself was calculated. The calculations were based on the MIRD equations and assumed that biodistribution of gallium in the human is similar to that in the guinea pig. Results: Biodistribution of Ga-67 in the maternal organs was similar to that expected in the human. Placental and fetal uptake peaked at around five hours after administration of gallium to the mother with a m a x i m u m of 2.8% of the injected dose accumulating in the fetus. The total radiation dose to the fetus is estimated to be 0.24 mGy per MBq administered to the mother based on the physical half-life of the radionuclide. Using an effective half-life of 4.3 hours, as determined experimentally in the guinea pig, reduces this estimated dose to 3.7 X i0 -~ mGy/MBq injected.

Saunders, A.M. Palmer and A.W. Preece, Research Unit, Bristol Oncology Centre and R a d i o p h a r m a c y Unit, Bristol General Hospital. Bristol BSI 6SY, U n i t e d Kingdom. FETAL BIODISTRIBUTION OF ADMINISTERED DURING PREGNANCY

TECHNETIUM-99M

A l t h o u g h it is p o l i c y to avoid a d m i n i s t r a t i o n of radiopharmaceuticals (RPx) to a pregnant woman, there are occasions when this is desirable on clinical grounds. There are few data on their placental transfer and the consequent fetal risk, although previous work has shown that some radionuclides readily cross the placenta and accumulate in the fetus. Data on fetal b i o d i s t r i b u t i o n will make it p o s s i b l e to evaluate which procedures are safe and avoid u n n e c e s s a r y radiation exposure of the fetus while avoiding the inappropriate restriction of the use of n u c l e a r medicine procedures during pregnancy. A guinea pig model has been used to m e a s u r e the placental transfer, and maternal and fetal biodistribution, of sodium (99m) pertechnetate which is used as the label for an extensive range of commonly used RPx. The biodistribution of pertechnetate in maternal and fetal tissues at varying stages of p r e g n a n c y has been studied. M a t e r n a l b i o d i s t r i b u t i o n was as expected from literature and clinical data. Fetal biodistribution demonstrated high levels of p e r t e c h n e t a t e uptake in the fetal thyroid (about 2%/gm of injected dose) and also, to a lesser extent, in the placenta. B i o d i s t r i b u t i o n in other organs followed a p a t t e r n similar to that seen in the mother. The results have been used to estimate the potential radiation £ose to the fetus following a d m i n i s t r a t i o n or ingestion of the radioactive material by the mother. These data c o n f i r m that p e r t e c h n e t a t e can pass across the placenta and localises p r e f e r e n t i a l l y in specific tissues which m a y have significance for fetal d o s i m e t r y with organs, such as the thyroid in particular, being at risk. 965

4-a

O

P 77

P 79

A Manetou 1, GS Limouris'- ; i Med Phys Unit, N1MTS Hosp, Athens . . . Nuclear Medicine Dlv, Areteion Hosp, Univ Medical Faculty, Athens

M. Saunders, A.M. Palmer and A.W. Preece, B ~ py s ~ Research Unit, Bristol Oncology Centre and ~Radiopharmacy Unit, Bristol General Hospital, Bristol BSI 6SY, United Kingdom.

A FIRST O R D E R APPROXIMATION OF T H E T U M O R A B S O R B E D DOSE USING Tc-99m MDP PRIOR TO Sr-89 THERAPEUTIC APPLICATION

PLACENT2~L TRANSFER AND FET~%L DISTRIBUTION OF FE-59 This study investigated the placental transfer of ferrous (Fe-59) citrate in order to evaluate the potential risk to fetal health from enviror~ental radionuclides ingested by pregnant women. This is a subject about which nuclear medicine personnel may expect to receive requests for advice following publicised nuclear incidents. Radioactive iron is one of a number of radionuclides which can contaminate the food chain as well as water supplies. Few data are available about placental transfer and uptake into specific fetal tissues. Our previous work has demonstrated that there is active fetal accumulation of some nuclides such as 1331-I and 85-Sr leading to fetal radiation doses much higher than might have been predicted. The pregnant guinea pig has been used as the model as it has a placental structure nearest to that of the human, with a period of gestation of a convenient duration and fetal maturity allowing biodistribution measurement. These early studies with Fe-59 have concentrated on intra-cardiac single bolus administration of Fe-59 in order to obtain biodistribution data at different stages of pregnancy. Later we will investigate the effect of chronic low level dosing of the isotope. Preliminary data suggest that there is specific uptake of Fe-59 in erythrocyte containing tissues. Significant uptake was seen in maternal blood, erythrocytes, spleen and femur bone-marrow. Activity detected in maternal urine or bile was very low. In the fetus, uptake of Fe-59 was detected in blood, erythrocytes, spleen, bonemarrow and liver, with moderate levels in the placenta. These data suggest that there may be a significant dose to certain fetal organs, in particular the bone-marrow which affects risk estimates for childhood leukaemia.

Background: A first order approximation of the tumor absorbed dose prior to treatment with Sr-89 was attempted in three patients treated for metastasized prostate carcinoma. Material and Methods : All patients underwent bone scanning with Tc-99m MDP, two days before the administration of Sr-89 and a number of sequential quantitative images were obtained over the first 8 hours after Tc-99m MDP injection. The collected data were used to derive an individualized Sr-89 time retention curve. Dosimetric estimations were subsequently based on the model described by ICRP Pbl.30 (1979). In the present study a simplified model for the kinetics of both Sr-89 and Tc-99m MDP was assumed. Results: Normal adult data on time retention of the two radiopharmaceuticals in the whole skeleton were combined together and a linear relationship was derived between the time required for the same percentage uptake of the two radiopharmaceuticals after single injection. The same relationship was assumed to hold for metastatic sites. The ratio of the estimated absorbed dose in the principal metastases of the three patients over the absorbed dose in normal bone of the same type and volume were found to be 2.4, 1.4 and 1.7. Conclusion: A first order approximation of the absorbed dose by the skeleton is provided by the proposed method, before the therapeutic application of Sr-89 Chloride using a diagnostic Tc-99m MDP bone scan. The method is useful, simple, inexpensive and can be routinely performed.

P 78

P 80

J.R. Jourdain, F. Vitaux, A, Petiet, N. colasLinhart, B. Bok, Medical School X. Bichat (Paris 7), Department of Biophysics and Montfermeil Hospital, Department of Isotopes.

Sauret V, Saunders M, Palmer A.M, & Preece A.W. Biophysics -Rese~ Unit, Bristol Oncology Centre, and Radiopharmacy Unit, Bristol General Hospital, Bristol BSI 6SY, England.

EARLY PHARMACOKINETICS OF PERTECHNETATE AFTER INTRAGASTRIC IN THE RAT.

'TRANSFER OF 99mTC-PERTECHNETATE ACROSS THE HLR4AN PERFUSED PLACENTA I N VITRO. Current human dosimetric calculations are based on the assumption of p a s s i v e transfer, and a homogenous distribution of activity within the foetus, or calculating the dose to the uterus or ovaries assuming no transfer.Much of the direct evidence that radiopharmaceuticals cross the placental barrier and accumulate to some extent in the foetus comes from animal studies. It is difficult to evaluate the extent to which such data can be extrapolated to humans. We have used the in vitro perfused human post-partum placenta model based on the isolated cotyledon. This represents the closest in vitro approximation to the dynamics of the placenta in vivo and has been assessed and validated in physiological terms. Placentas are obtained following normal spontaneous delivery or elective caesarean where there is no indication of placenta damage. Creatinine transfer is used as an internal control to provide a withinexperiment index of the efficiency of perfusion. Transfer of 99mTc occurs rapidly, certainly within 30seconds, and activity on the fetal side of the placenta continues to rise for about 1 hr. A concentration equilibrium exists such that maternal activity is higher than fetal, although the placenta retains significant activity. Using this model allows us to assess whether transfer though the human placenta is qualitatively similar to that in animal models, albeit that the perfused placenta allows us to measure transfer only after parturition when some degree of physiological change may have already occurred. Nevertheless, combined with animal foetal biodistribution measurements, the data will allow much better estimates of foetal radiation dose than hitherto possible.

TECHNETIUM-99 ADMINISTRATION

Technetium-99 (~- emitter, T = 2.1.i05 yrs) is not only the radioactive daughter of Tc-99m, but also a component of nuclear wastes. Therefore, concentrations have been increasing regularly in the environment. Uptake kinetics and disposition of Tc-99 in target organs (skin, kidneys and thyroid) are essential to evaluate the eventual chemical and radiotoxicity of this metal and to better u n d e r s t a n d its mechanisms both in nuclear medicine and environmental research. Five ng per kg of Tc-(99+99m) (18.5 MBq) were administered to 60 Wistar male rats. Animals were sacrificed from 5 minutes to 72 hours after intragastric administration. For each animal, the activity of different tissues (skin, kidneys, thyroid, blood) was measured and, various parameters were calculated : half-life (absorption Tl/2a and elimination Tl/2e) and mean residence time (MRT). After oral administration, 99TCO4is quickly absorbed within the skin (Tl/2a = 27.3 min) and thyroid (Tl/2a = 16.9 min). A long retention period of this metal is observed in the rat skin (Tl/2e = 4.1d ; MRT = 5.6d), thyroid (Tl/2e = 2.6d ; MRT = 5.1d) and kidneys (Tl/2e = 2.6d ; MRT = 4.0d). The use of technetium-99m label is very convenient for short term studies, but another marker such as technetium-95m becomes n e c e s s a r y for long-term investigations.

966

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Ma~garida Rod rigues, E. Havlik, B. A. Peskar, H. Sinzinger, Department of Nuclear Medicine, University of Vienna, W~ihringer G/irtel 18-20, Vienna, Austria.

M. Robinson, F. Vitaux*, A. Petiet, P. Voisin**, N. Colas-Linhart. Medical School X. Bichat, Biophysics Department, Paris, *Montfermeil Hospital, Department of Isotopes and **IPSN-CEA, Fontenay aux Roses.

PROSTAGLANDINS AS BIOCHEMICAL MARKERS OF RADIATION INJURY TO THE SALIVARY GLANDS AFTER 13~I.THERAPY? Because safivary glands, as well as thyroid tissue, are able to concentrate radioiodine, the treatment of thyroid diseases with '3~I may have secondary effects on salivary gland function which seriously affect the quality of life such as sialoadenitis and xerostomia, among others. Many investigators have shown that safivary secretion is stimulated by prostaglandins (PG). In this study we evaluate, whether '3]I-therapy influences the levels of PG in saliva, PG being thus potential markers for radiation injury to the salivary glands. 17 patients (12 females, 5 males; 38-69 years old) who had previously received ]~I (4-120 mCi 2 to 3 months earlier) for treatment of hyperthyroidism (12 patients) or differentiated thyroid cancer (5 patients) and 27 healthy volunteers (15 females, 12 males; 40-60 years old) were studied. 5/17 patients and 10/27 volunteers were smokers. After rinsing the mouth stimulated whole saliva was collected while the patient were chewing, using a standardized protocol. PG (6-oxo-PGF1~., bicyclo-PGEm, TXB~, PGFz~) in saliva were measured using R/A. Significantly (p<0.001) lower levels of 6-oxo-PGFl~, bicyclo-PGEm and PGF2~ and higher levels of TXB2 were found in the group of patients in comparison with the group of controls. These variations were greater in the measurements of 6-oxo-PGF~ and in those patients who received ->15 mCi as well as in those who were smokers. No significant differences were found between the two sexes. This study demonstrated that salivary gland uptake of 131I affects significantly PG in saliva. They may thus potentially be used in the future as biochemical markers of acute radiation injury to the salivary glands in patients treated with ~3aI. The usefulness of exogenous PG administration to patients, in particular smokers, who received ~3~I-therapy needs to be evaluated in further studies.

UNSTABLE CHROMOSOMAL ABERRATIONS IN LYMPHOCYTES INDUCED IN VITRO AND IN VIVO DOSE OF TECHNETIUM-99m.

HUMAN BY LOW

In Nuclear Medicine, radiation doses after administration of technetium-99m (99mTc) labeled pharmaceuticals are usually considered of no radiobiological consequence. Therefore, very few biodosimetric studies have been undertaken. The aim of the study was to verify potential 99mTc irradiation consequences using biological dosimetry through conventional chromosomes aberration analysis. An in vitro dose-effect curve of 99mTc was established using external irradiation of whole blood delivered by 99mTc labeled microspheres. Four hundred metaphase cells were scored for each point dose (0 ; 10 -4 ; 10 -2 ; i0 -I ; 5.10 -1 and 1 Gy). This irradiation was validated as homogeneous as the distribution of aberrations (dicentrics and rings) followed a Poisson distribution. The curve obtained for chromosomal aberration frequencies could be considered as linear. The yield of chromosomal aberration was between 10 -2 and I0 -I Gy. Blood samples were taken from 9 patients before and after a standard 99mTc-oxydronate (99mTc-HDP) injection for imaging benign bone disease. Blood estimated dose was about 4.8 mGy. As predicted by our experimental curve no chromosomal damage was found 3 hours post-injection blood samples. However, it's necessary to study large samples of metaphases to confirm these results.

C O

| i

C O O L_

P 82 Abstract withdrawn by authors

P 84 N. Colas-Linhart, J.R. Jourdain, F. Bonnin, E. Hindie, M. Robinson, C. Vaylet, A. Petiet, B. Bok, Medical school X. Bichat (Paris 7), Department of Biophysics. TRACK MICROAUTORADIOGRAPHY OF 99mTc-TECHNETIUM RADIOPHARMACEUTICALS (99mTc-R) : ANIMAL EXAMPLES AND POTENTIAL INTEREST IN DOSIMETRY AT THE CELLULAR LEVEL. Microautoradiography (MAR) is of utmost importance for biodistribution and pharmacokinetic studies at a microscopic level of 99mTc-R. The detection of tracks obtained from 99mTc high energy (>i00 keY) internal conversion electrons within a thick nuclear emulsion have been the basis of track-MAR. A visible track (5 consecutive grains) is highly specific, contrary to the usual grain method. The spatial resolution is about I0 micrometers. This technique has been applied first to labeled cells (lymphocytes and polymorphonuclear cells) showing that the number of detected desintegrations may markedly vary (range 1 to 1,000) from a labeled cell to another. Track-MAR was extended to slices of tissue and showed an elective but very heterogeneous uptake of Kupffer cells on liver slices. Quite all organs may be studied if 99mTc-R is not diffusible after uptake. Several examples are shown in rats: lungs (99mTc-microspheres within capillaries), kidneys (99mTc-dimercaptosuccinic acid in the cortex), skin (pertechnetate). The spatial resolution is not sufficient to assess 99mTc-R subcellular localisation, but a semi-quantitative assessment of the cell uptake heterogeneities may provide an improved insight in the estimation of the actual radiation dose delivered by 99mTc-R.

967

O

,4,,,I

O

P 85

P 87

R. Sobnack, C.C. Nimmon, K.E. Britton, Saint Bartholomew's Hospital, Department of Nuclear Medicine.

S. Savolainen in, ~ y n ~ i n e n i, T. Korppi-Tommola2, H. Huhmar?, M. Kallio 3, J. Hiltunen 4, HJ. Aronen 2, IDept of Phys, University of Helsinki, Depts of 2Radiology and 3Neurology, Helsinki University Central Hospital, 4MAP Medical Technologies Ltd., Finland

RANDOM ERRORS DUE TO PHOTON STATISTICS IN BONE MINERAL DENSITOMETRY USING DUAL PHOTON AND DUAL ENERGY X-RAY ABSORPTION.

KINETICS OF 111-In-LABELED BLEOMYCIN

The effect of random errors on bone mineral density (BMD) measurements caused by uncertainty in the emission rate of photons from the source used has been examined. This led to an estimate for the best precision with which such measurements can be made on either a dual photon absorption or dual energy X-ray absorption system for a wide range of conditions. In addition, the baseline BMD error associated with the soft tissue surrounding the bone was calculated and used to develop a new concept of m i n i m u m detectable BMD. By considering the magnitude of such random errors and their effect on measuring BMD changes, it was also possible to propose the m a x i m u m frequency of measurements on either the lumbar spine or the femoral neck for assessing bone losses in individual patients using e criterion of m i n i m u m expected percentage lost. Actual measurements on patients and phantoms indicated overall precision values which were roughly five times the idealised values due to photon statistics alone. Thus manufacturers should identify and eliminate or, at least, greatly reduce the additional sources of error if the photon absorption method is to remain a competitive technique for bone densitometry.

Biodistribution of lllIndabelled bleomycin (IlIln-BLMC) in 22 patients with brain tumours was investigated. I111n_BLMC was injected intravenously (165+-30 MBq, specific activity approx. 100 MBq/mg of IIIIn-BLMC). Blood samples (from 12 to 17) were taken during 50 hours and urine was collected during one day after the injection. The tumour samples from seven patients were collected at the operation. As the tracer enters directly into the intravascular plasma volume the inletoutlet detection theorem for bolus injection can be applied. The mean transit time in plasma pool equals to the derivative of the plasma curve at zero moment (14+-2 min (n=12)). The mean sojourn time (including the recirculatinting molecules) was detected as the area/height value of the plasma clearance curve (I.8_+0.2 h (12)). The mean transit time in total body equals to the abscissa of the point of gravity of the plasma clearance curve (12.5_+l.3 h (12)). The mean half-life in the urine was determined as the inverse of the regression coefficient of the semilogarithm of activity-time curve (3.5+.0.6 h (t2)). The exchange rates between plasma, turnout and depot (extravascular space) were calculated using compartmental analysis with SAAMII program. The excretion rate from the plasma was 0.022±0.009 min l (15) and the exchange rates between compartments were (in rain -l, n=15): from plasma to depot 0.012_+0.006, depot to plasma 0.001±0.001, and from plasma to tumour 1.040±0.488, tumour to plasma 0.357±0.137. It is concluded that a three compartmental model is sufficient to describe the kinetics of I ItIn-BLMC and that transfer coefficient between compartments are sensitive parameters reflecting biodistrubution of I 1I In-labelled bleomycin.

P 86

P 88

Department of Nuclear Medicine, Department of Clinical Physics, Western Infirmary, Glasgow, Scotland, UK.

O. Sipilg 1'~, P. Nikkinen i, H. Pohjonen L, V.-P. Poutanen l, A. Visa z, S. Savolainen ~, T. Katila 1'2, K. Liewendah? ~-Helsinki University of Technology, 02150 Espoo, 2Helsinki University Central Hospital, 00290 Helsinki, Finland

V A R I A T I O N OF SPATIAL RESOLUTION WITH GAMMA RAY ENERGY.

SIMULATION STUDIES FOR EVALUATION OF REGISTRATION ERROR IN BRAIN SPET AND MR IMAGES

G , A. Wright,

J. Prosser, A. A. Bolster.

Gamma camera manufacturers specify the performance of their cameras in accordance with the NEMA specification. Spatial resolution is therefore almost exclusively quoted for Te-99m only. ha our institution there is currently considerable interest in post therapy I- 131 mlBG and In111 pentatreotide Planar & SPECT imaging. Therefore we required information about the resolution of our gamma camera (Dual headed Picker Prism 2000) system, at these higher energies, in a realistic imaging environment using the appropriate collimator. To investigate the variation in resolution with energy the planar system spatial resolution was measured using a line source placed in various depths of scatter for four radionuclides (T1-201, Tc-99m, In- 111, 1-131) representing a wide spread of energies. The SPECT system spatial resolution was also measured for the same 4 radionuclides, using a Data Spectmrn phantom with triple line insert Example FWHMs for Tc-99m and I- 131 are shown below (in lnm) Planar Resolution (ram) Depth of scatter (mm) Tc-99m 1-131 0 4.7 52;1.6 202 15.1 SPECT Tc-99m 1-131 [ [_~dial Resolution (mm) [central line] 11. l 19.8 _] In conclusion, spatial resolution in scatter, both planar and SPECT, deteriorates si~alficantly at high energies which is of relevance for clinical studies using certain radiopharmaceuticals

968

Simulation studies were performed to evaluate the significance of different error sources in a clinical registration procedure for brain SPET and MRI based on the use of external markers. The transformation is computed using a noniterative least squares method. The 6 external markers usually used for patient studies contain Tc-99m (0.2 MBq) and coconut butter (50 #1). Tile error model for simulations was first verified by phantom experiments using a 3D brain phantom (JB003, Nuclemed N.V./S.A., Belgimn). The phantom was imaged with Picker SX300 single-head and 3000XP triple-head gamma cameras and with 1.0 T and 1.5 T Siemens Magnetom MRI devices. Tile mean root-mean-squared (RMS) residual of the locations of three internal test markers after registration varied from 5.2±1.3 m m to 3.1+1.0 mm depending on the imaging equipment and parameters and the number of external markers (4-13) used in registration. In the simulations it was found that about 2 mm of the residuals of the test markers in phantom experiments were due to the locating error of the markers. When including a resolution error (7-10 mm for SPET, 2 mm for MRI) in the test markers, the mean RMS residual after registration was slightly smaller than the resolution error. This was due to small random locating error of the external markers. The registration error was site-dependent being minimal near the centre of mass of the external markerK Relative to the spatial resolution of SPET images the accuracy of registration is not the limiting factor in region of interest analysis of registered images provided that the design and attachment of the marker system are appropriate.

P 89

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I. Szilv~isi J Varga', Z. Nagy, K. Buga, J. K~rnyei" Haynal University, Dept. of Nuclear Medicine, Budapest, Medical University of Debrecen, Dept. of Nuclear Medicine', Inst. oflsotopes, Budapest"

JM Jimenez-Hoyu~!Q, M Barbarisi, McClellan, LI Araujo. Univ. of Medical Center, Div. of Nuclear Cardiology, Philadelphia, PA. U S A

CORRELATION OF OIH AND Tc-99m-EC CLEARANCE. CAN ERPF BE MEASURED BY EC USING SINGLE BLOOD SAMPLE?

Tc-99m-ethylenedicysteinate (EC) is a promising new agent for dynamic renal scintigraphy. Its high-quality gammacamera images are useful to visualize renal parenchyma and urilmry tract in patients with impaired renal .function. Only a few number of papers about the renal clearance (Cl) values of Tc-99m-EC have been published. In the present study a direct comparison of the clearance of I-131-OIH and Tc-99n-EC was performed in 14 normal volunteers using simultaneous single-shot injection of both agents and compartmental analysis based on multiple blood sampling. Six samples were taken during 60 minutes. Distribution volumes of both radiopharmaceuticals were determined. Correlation of clearance values were evaluated by regression analysis. Results: CI(OIH) = 0.8262 x CI(EC) - 25.23 with a regression coefficient: 0.9587. Optimal timing for withdrawal of blood has been found to be between 30 and 35 minutes after i.v. injection of EC. Our data show that Tc-99m-EC clearance values calculated using single blood sampling are reliable for determining ERPF. Further studies are needed in patients with impaired renal function. Key words: ERPF, Tc-99m-EC

A Alavi, JR Pennsylvania Medicine and

EFFECT OF ATTENUATION CORRECTED SPECT IMAGING IN THE ASSESSMENT OF LATERAL WALL PERFUSION DEFECTS Attenuation corrected (AC) i m a g e s h a v e b e e n s h o w n to improve uniformity and thus may improve the assessment of regional per±us±on defects. To a s s e s s t h e e f f e c t o f A C on l a t e r a l w a l l p e r ± u s ± o n d e f e c t s we q u a n t i t a t i v e l y anaiized the myocardial per±us±on images (MPI) of 33 patients with catheterization proven circumflex CAD. Tc-99m sestamibi SPECT stress MPI were acquired on a tripled headed camera with Gd-153 source for simultaneous transmission and emission imaging. Images were reconstructed using a iterative algorithm with (AC) and without AC (IT) and r e s l i m e d in t h e s h o r t a x i s p l a n e . Regional count density was measured w i t h a t o t a l of 32 R O I ' s p e r p a t i e n t p l a c e d on t h e apex, m i d - a p e x , m i d - b a s e a n d base slices. ROI values were normalized to the highest 10% for each patient. Values for the anterolateral and lateral segments were compared with and without AC. In a d d i t i o n , the number of ROI's <80% were calculated as an i n d e x o f d e f e c t size. A student T test was used to assess differences. R e s u l t s a r e s h o w n as m e a n s a n d sd: ANTERO-LATERAL LATERAL AC No AC p ~ AC No AC p S apex .76±.Ii .91±.13 .001 .72±.!6 .80±.14 .o01 m i d ep .85±.16 .95±.17 .001 .74±.17 .78±.17 .001 mid ba .86±.19 .95±.19 .001 .72±.20 .76±.21 .01 base .86±.20 .90± 20 .01 .71±.20 .74±.22 .09 The anterolateral and lateral count density is l o w e r w i t h AC, w i t h a d e c r e a s i n g difference from apex to base. The number of ROI's below an 80% threshold in t h e c i r c u m f l e x artery territory was 1 2 6 w i t h A C vs 84 w i t h n o AC. C o n c l u s i o n s : MPI with attenuation correction results in significantly g r e a t e r s e v e r i t y a n d s i z e of l a t e r a l wall defects,

eo

= m

e-

ID x._

O. P 90

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J. L j n ~ e n , A. Kuronen, J. Stepanek* and S. Savolainen+, Dept of" Physics, Helsinki University (POB 9, FIN-00014 Helsinki University), *Paul Scherrer Institut, tHelsinki University Central Hospital

J. Castel!, C. Santana Boado, J. Candell Hiera, S. Aguad~Brnix, A. Garcla-Burillo, T. Canela, J.M. Oonz~lez, J. Cortadellas, D. Ortega, J. Soler-Soler. Hospital General U n i v e r s i t a r i Vall d'Hebron.

MODELLING ABSORBED DOSE IN IDEAL CELL CLUSTERS

DIAGNOSTIC IN MEN

The therapeutic effect of radionuclides used in radioiminunotherapy (RIT) depends strongly on the cellular level geometry, and the microscopic activity distribution. A program for modelling absorbed electron dose in ceil clusters was developed. The program was used to compare the therapeutic effects of 1 ] IIn, 113In and 114In. It uses electron dose kernels calculated with the EGS4/PRESTA Monte Carlo code. The source was assumed to be a sphere or a spherical shell of diameters of 12 (tumor) and 30 (normal cell) btm Small energy Auger and CosterKronig electrons (E
L

ACCURACY

OF WmTC-ISONITRILE

SPET

IN WOMEN AND

Background. Noninvasive diagnosis of coronary artery disease in women has some limitations as 2 higher percentage of false positive results as well a a lower prevalence of disease can be observed in a female population. In this study we aimed to evaluate the diagnostic accuracy of ~Tc-isonitrile single photon emission tomography (SPET} in women and men, in the group of patients with proven coronary artery disease by coronary angiography (select minority) and in all patients in whom non invasive test (silent majority) has been performed. Methods, Seven hundred and two consecutive patients without previous myocardial infarction were studied with ~ T c isonitrile SPET. 163 patients had coronary anqiography (select minority) while 539 did not (silent majority). Diagnostic accuracy of the test was calculated for the select minority. Then, sensitivity and specificity of the silent majority were recalculated according to Diamond et al. criteria. Results. Prevalence of coronary artery disease (32% vs 80%, p = O.OOOl} and peak O: consumption achieved in exercise test (watts, exercise duration) were lower in women. The probability of positive results of a T c isonitrile SPET was also lower in women (34% vs 85%). The sensitivity of ~Tc-isonitrile in women of the select minority was lower (85% vs 93%, p = 0.Ol) whereas there was no significant difference for specificity (91% vs 89%).After correcting the results for the silent majority there were no significant differences in sensitivity (87% vs 88%) and specificity (91% vs 96%) between women and men. Conclusions. The sensitivity of ~Tc-isonitrile in women was lower than in men whep only the select minority was considered. When the silent majority was taken into account (correction of selection bias) sensitivity and specificity results did not differ significantly between sexes.

969

O a.

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R, Aurisch, G. Appel, I. Reisinger, U. Bauer, G. Appel, F.X. Kleber, D.L. Munz Clinic of Nuclear Medicine and Medical Clinic, Charit6 Hospital, HumboldtUniversity Berlin, Germany

H Everaert, C Vanhove, *JJ Hamil, PR Franken. Free University Brussels (AZ VUB), Brussels, Belgium and *Siemens Medical Systems, Hoffman Estates, IL, USA.

RADIONUCLIDE VENTRICULOGRAPHY IN YOUNG ADULTS WITH TRANSPOSITION OF GREAT ARTERIES (TGA) AFTER ATRIAL SENNING-CORRECTION

GATED MYOCARDIAL PERFUSION SPET STUDIES USING A 3-HEAD CAMERA EQUIPPED WITH CARDIOFOCAL COLLIMATORS

In patients (pts) with TGA the aorta is connected to the right and the pulmonary artery to the left ventricle, the operative correction establishes the right ventricle as the systemic ventricle. Its performance is, therefore, thought to be crucial for prognosis.

Cardiofocal collimators (CFC) are more sensitive than parallel-hole collimators (PHC) of the same resolution because the rays converge in the center of the field of view. Because distortion may occur when the heart is not properly centered, the reconstruction algorithm has recently been modified in order to enhance the central field of view. In this study, ECG-gated myocardial perfusion SPET images obtained with CFC and PHC were compared in 20 patients with a history of myocardial infarction. Myocardial perfusion SPET images gated in 8 time bins were recorded 60 min after injection of 740 MBq 99mTc-tetrofosmin. The 3-head camera was equipped with CFC and PHC and studies were acquired in an at random sequence. Acquisition parameters were 96 projections 360 degree, 32 stops, 40 sec / stop with PHC and 20 sec / stop with CFC in order to obtain similar count densities. The extent (EXT) and severity (SEV) of the perfusion defects were quantified on polar maps using the non-gated data. Left ventricular end-diastolic volume (EDV) and ejection fraction (LVEF) were calculated on the gated data using the Cedars-Sinai Quant program. Mean differences (+sd) and coefficients of correlation (r) are summerized in the Table.

Patients: 12 pts ( 9 m, 3 f), aged 17-25 years, with NYHA I (n= 4) or NYHA 11

(n=8), who underwent atrial repair of simple TGA using the SENNING operation between 1979 and 1982, were evaluated 13 - 16 years after operation. Methods: Radionuclide ventriculography (first pass and equilibrium study) was performed at rest and during stepwise exercise test for determination of cardiac output (CO), pulmonary transit time (PTT) and left and right ventricular ejection fraction (LVEF, RVEF). Results: All I2 pts demonstrated a normal CO ( mean 4,6 +/- SD 1,4 l/min) and mild prolonged PTT (mean 7,9 +/- SD 2,1 s). The global EF at rest also was normal: LVEF 62,6 %, RVEF 59,4 %. However, differences were observed between pts with NYHA I and NYHA II under stress conditions both for RVEF and LVEF: NYHA 1 NYHA 11 rest stress rest stress LVEF (%) 65,5 75,2 61,1 57,6 RVEF (%) 58,5 64,7 59,9 56,5 Discussion and Conclusions: In pts with NYHA II the decrease of EF of the

systemic right ventricle under stress conditions corresponds with reduced cardiopulmonary exercise tolerance and reduced oxygen uptake and can be regarded as a tendency towards insufficiency. Therefore radionuclide ventriculography and exercise studies are qualified for early diagnosis of systemic ventricle dysfunction in pts with TGA.

EXT (%) SEV (%) EDV (ml) LVEF (%)

PHC (mean + sd)

PHC-CFC (mean diff. _+sd)

40.1 _+ 19.7 28.7 + 13.7 144 +_ 74 43.4 +_ 11.6

-2.05 -+ 8.05 0.65 4- 4.51 0.80 + 9.05 1.10 -+ 4.61

r= rr= r-

0.912 0.954 0.993 0.939

p= p= p= p=

NS NS NS NS

We conclude that identical quantitative information on both perfusion and function can be derived from gated-SPET myocardial perfusion studies obtained with CFC compared to PHC. The larger sensitivity of the CFC however allows to reduce the acquisition time substantially.

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M. Kibar~ Z. Do~ruca, L. Kaba~akal, G: Btiyiikdereli, A. U~al, M Jan, ~. Onsel, Departmearts of Nuclear Medicine and Cardiology, (;uloxrova Univ. Faculty of Medicine, Adana, and Department of Nuclear Medicine, Istanbul Univ. Cerrahpa,fa Medical Faculty, Ittanbul, TURKEY

A. Fikrle. D. L6scher, M. Fleisch, S. Lourens, A. R. Haldemann, J. A. Kinser, M. Sulzer, W. Mering Inselspital, University of Berne, CH-3010 Berne, Switzerland

GA TED TECHNETIUM-99ra TETROFOSMIN SPECT IN DIFFERENTIA TION ARTIFA CT FROM INFARCT Soft-tissue attenuation artifacts generally appear as fixed perfusion defects that mimic infarct in routinely use. The purpose of the present study wa~ to evaluate the usefulness of gated Te-99m-tetrnfosmin SPECT in differentiation of inferior and anterior wall attenuation artifacts fi'om myocardial infarction, and compare qualitatively assessed perfusion abnormalities in simultaneously obtained nongated and gated SPECT. In 23 of the 48 patients, 34 (14%) segments showing fixed defect were detected in the nongated ¢tress/re~'t images. Of these fixed defects, 22 (65%) demonCtrated abnormal wall motion and/or thickening in the gated mess images. Twenty-one of there 22 legrnents (95.4%) had ECG and/or angiographical evidence of prior MI. In the other one segment, angingraphy and ECG findings did not correlate with scintigraphic findings to localize the lesion site. In this segment, scintigraphy showed a fixed defect in inferior wall, while angiography and ECG was showing the evidence of anterior wall disease. However, of the 34 fixed defects, 12 (35%) showed normal wall motion and/or thickening. Of these segments, 11 (92%) had normal ECG and coronary angiography results. But, in the remaining one segmenL wall motion and/or thickehing analysis failed to detect the inferior MI. In the evaluation of individual segnent in respect to fixed or reperfused le~ions on nongated stress/rest images, the sensitivity and specificity of apical, anterior, lateral, septal and inferior walls were 86%-97%, 83%83%, 50%-92%, 78°o0-100% and 80%-64%, respectively. In the gated images, apical, lateral and septal values remained similar, while the values of anterior and inferior walls were changing as 7500o-100% and 8000o-86%, respectively. For the detection of regional defect in the nongated SPECT images, the overall sensitivity and specificity were 77%-89%, but in the gated SPECT images, these values were 75%-95%, respectively. In conclusion, gated Tc-99m tetrofosmin SPECT imaging increases the study specificity in detection of coronary artery disease by differentiating infarct from az't/fact which causes of false positivity.

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COMPARISON OF LEFT VENTRICULAR EJECTION FRACTION (EF) ASSESSED BY GATED Tc-99m MIBI SPECT (GSPECT) AFTER EXERCISE AND AFTER DIPYRIDAMOLE (DPD) The aim of this study was to compare the post-stress EF(S-EF) and the rest EF(R-EF) assessed by GSPECT using (i)exercise stress(Ex) and (ii)DPD. We performed a 2-day stress/rest protocol in 375 pts. The EF ~vas obtained by GSPECT performed 30 rain. after stress MIBI-inj. [266 pts after Ex, 109 pts after DPD (0.84 mg/kg)] and on the following day, 60 rain. after MIBI-inj. at rest. The EF determination was performed using 3D-Perfusion/Motion Map TM Picker Software. The pts were divided in 4 groups: A= normal stress and rest scintigrams without myocardial infarction (MI); B =pts>3 months after MI with a fixed defect without reversibility; C=pts after MI with both a fixed defect and reversibility; D=pts with evidence of stress/rest reversibility without MI. Within D, the DPD pts were subdivided: pts with and without ECG evidence of ischaemia. Of the 375 pts, contrast left ventriculography (CVG) was performed in 57 within 2 weeks of the scintigraphic study. The correlation coefficient CVG-EF vs. S-EF was 0.81, CVG-EF vs. R-EF 0.87. The results (EF in%) are tabulated: DIPYRIDAMOLE (n=109) EXERCISE (n=266) Group n 125 A 57 B 56 C 28 D

S-EF

R-EF

p

61±4 59+4 <0,05 4 5 ± 1 1 48±10 n.s. 47+9 56±7

51±8 60±5

<0.05 <0.05

n 50 18 21 20

S-EF R-EF 58+7 59+6 41±1240+14 40±1144+12 53±5 55±6

p n.s. n.s. <0.05 n.s.

[D (ECG ne~.) 13 55±6 55±7 n.s. 7 50+4 54+_5 <0.05 D (ECG pos.) The S-EF is not always the same as the R-EF. In ,,normal" pts S-EF after Ex was significantly higher than R-EF, but after DPD no significant difference was found. In groups with stress/rest reversibility, me S-EF after Ex was significantly lower than R-EF, but after DPD only in pts with ECG evidence of iscbaemia. The estimation of EF with GSPECT reveals good correlation with CVG, although it systematically underestimates the EF. GSPECT provides useful information regarding myocardial function after stress and at rest permitting simultaneous assessment of myocardial perfusion and function.

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J. Wells, D. Marshall, P. Ryan. Medway Hospital, Department of Nuclear Medicine, U.K.

P I T F A L L OF T c - 9 9 m TETROFOSMIN LUNG UPTAKE A S S E S S M E N T A N D H O W TO A V O I D IT: C O M P A R I S O N W I T H THALLIUM-201 AND Tc-99m SESTAMIBI MYOCARDIAL SPECT STUDIES. S.I. H e i b a , G. Ziada, E. H i g a z y a n d M, Saleh. U n i v e r s i t y of K u w a i t , KUWAIT

A N E V A L U A T I O N OF A T T E N U A T I O N CORRECTION FOR STRESS T H A L L I U M SPECT M Y O C A R D I A L PERFUSION IMAGING Thirty consecutive patients with known or suspected ischaemic

heart disease, 18 male, 12 female of average age, 61 were investigated by SPECT thallium perfusion scintgraphy using a stress redistribution protocol. Simultaneous emission and transmission studies were acquired on the A D A C vertex and reconstructed data was analysed with and without attenuation correction by a single experienced observer blinded to the attenuation correction status. Mid cavity transaxial and long axis slices were divided into 16 segments reported as normal, ischaemia or fixed defects. Each major coronary artery territory was also classified as normal, ischaemia or fixed defect. There was disagreement in classification of 13% of segments with more normal segments following attenuation correction. There was disagreement in the classification of arterial territories in 8 / 3 0 LAD, 6 / 3 0 RCA and 3 / 3 0 CX. Interfering bowel activity was noted in 6 non attenuation corrected studiesand 12 attenuation corrected studies. We conclude that attenuation correction in clinical practice produces significant alteration in scan findings particularly in the LAD and RCA artery territories with a reduction in fixed and ischaemic defects. There is however an increase in the number o f studies with interfering bowel activity.

L u n g u p t a k e evaluation during routine Tc-99m tetrofosmin (tetrofosmin) myocardial SPECT studies may be hindered by the remarkable chest muscles uptake particularly post exercise. This study was conducted to investigate this observation and analyze the various components of chest activity that may add to the actual lung uptake. Methods: Routine 2 days exercise myocardial perfusion SPECT studies were performed by 28 subjects (group i) using Tc-99m eestamibi (MIBI) and 31 subjects (group 2) using tetrofosmin, and compared to thallium-201 (thallium) exercise studies done by 28 subjects (group 3). All subjects were males with < 5% clinical likelihood of CAD, normal exercise ECG and perfusion images. Chest to heart count ratios (CHR) were calculated from the anterior projection data of the SPECT images and were further assessed and eubclassified into lung, anterior chest and posterior chest to heart count ratios (LHR, AHR and PHR respectively) from the left anterior oblique (LAO) projection data. Results: In the post exercise images, tetrofosmin CHR (0.35 ± 0.07) was higher than thallium {0.27 ± 0.05, p <0.0001) and MIBI (0.29 ± 0.07, p <0.005) ones. Both tetrofosmin AHR and PHR were significantly raised than equivalent thallium and MIBI ratios. Nonetheless, there were no significant differences in the LHR between any of the 3 radiopharma-ceuticals. In the rest images, all ratios of tetrofosmin were not different from those of thallium and MIBI ones except PHR (0.39 ± 0.06) that was again higher than thallium (0.34 ± 0.04, p <0.005) and MIBI (0.32 ± 0.09, p <0.01) ratios. Additionally, no notable difference was found between any of the thallium and MIBI ratios neither in stress nor in rest images. C o m c l u s i o n : Tetrofosmin lung uptake with exercise should be interpreted with caution as chest muscle uptake is higher than similar MIBI and thallium studies. Alternatively, lung uptake is more accurately evaluated from the LAO projection where count contribution from chest muscle activity is much decreased.

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R.K. Halkar:,M. Jones, J.R. Gait, G.P. Camarano, and A.T. Taylor, VAMC (Atlanta) and Emory University Hospital, Atlanta, Georgia.

D. Daou, R. Lebtahi, Y. Petegnief, M. Faraggi, L. Sarda, D. Le Guludec. Nuclear Medicine Dept, H6pital Bichat, Paris, France.

C O im C

O EFFECT OF BREAST ATTENUATION ON LEFT VENTRICULAR EJECTION FRACTION (LVEF) ASSESSMENT BY GATED BLOOD POOL STUDY (GBPS) GBPS is routinely used to monitor chemotoxicity in cancer patients. The literature shows five times more men than women have been used as subjects in publications that validate LVEF assessment by GBPS. The effect of breast attenuation on GBPS has not been documented. The purpose of this study was to assess the effect of breast attenuation in GBPS using computer simulation. GBPS of 37 male patients (assuming no breast attenuation) of varying LVEF (11-70%) were used. The left breast was simulated using a filter mask that attenuated 30% of the counts. LVEF was calculated using automatic processing without any attenuation, with attenuation filter mask partially covering the left ventricle (LV) to the distal 1/3 and completely covering the LV. A change of more than 5% point in measured LVEF from the original (without attenuator mask) GBPS study was considered to be significant. Using this criteria attenuation partially covering the LV caused significant increase in LVEF in 12 of the 37 patients, but attenuation fulty covering the LV caused changes only in 5 of the 37 patients (Chi-square test P =<0.05). Partially covering attenuation caused significant change in LVEF in 4 out of 21 patients with original GBPS of <45%, and 8 out of 16 in patients with original GBPS of >45% (Fisher's Exact test P=<0.05). Attenuation completely covering the heart caused a "hale" around the heart mimicking pericardial effusJon. In conclusion, breast attenuation in GBPS may significantly effect the measurementof LVEF when the attenuator (breast) covers the LV partially and the LVEF is >45%.

ANGIOSCINTIGRAPHY (RNA) IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC): ONE (H1) AND THREE (H3) HARMONICS FOURIER PHASE ANALYSIS VERSUS FACTOR ANALYSIS. The diagnostic value of RNA in the evaluation of ARVC has been previously reported. The aim of our study was to compare the value of different modalities &image analysis for the detection and localization of right ventricular wall abnormalities: HI versus H3 Fourier phase distribution analysis, and Fourier phase analysis versus Factor analysis. 14 patients with confirmed ARVC were evaluated: studies were done in the right anterior oblique (RAO), best septaI left anterior oblique (LAO) and left lateral (LL) views with 16 frames/cycle and 600 Kcounts/frame. As compared to H1, H3 analysis increases the diagnostic certainty in 21/42 (50%) of views and H3 was definitely abnormal in 3/42 (7%) of views with normal H1. Fourier phase analysis as compared to Factor analysis, detected abnormalities in the RV outflow tract in respectively 11/12 versus 6/12 pts presenting with outflow ARVC abnormalities, 12/13 pts versus 8/13 pts in the inferior wall, and 5/12 pts versus 9/12 pts in the RV apex.

H1 Fourier H3 Fourier Factor analysis 11/14 pts 12/14 pts 11/14 pts 11/14 pts 12/14 *pts 7/14" pts 8/14 pts 9/14 pts 6/14 pts 30/42 views 33/42 *views 24/42 *views *:p<0.05 Thus, H3 as compared to H1 increases the diagnostic value for ARVC. Fourier analysis seems more valuable for the detection of outflow tract and inferior wall abnormalities while Factor analysis seems relevant for the RV apex. The combination of Fourier and Factor analysis seems useful in the detection and localization of ARVC. LAO RAO LL LAO+RAO+LL

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J.A.K. Blokland W. de Vos, B.L.F. Van Eck - Smit, E.K.J. Pauwels, Leiden University Medical Centre, Department of Radiology, Division of Nuclear Medicine, The Netherlands

J.Pavfa, D.Ros*, M.SoI&, A.Muxf, R.Herranz Nuclear Medicine Department. Hospital Clfnic i Provincial of Barcelona. *Lab. Biophysics and Bioengineering. Fac Medicine, Univ. Barcelona. Spain

TRIPLE ENERGY WINDOW SCATTER CORRECTION: THE CLINICAL EFFICAY

BULL'S EYE PHASE ANALYSIS IN GATED-SPET PERFUSION STUDIES

The inclusion of scattered photons during SPECT acquisition of myocardial perfusion studies may prevent an accurate assessment of the perfusion. The triple energy window scatter correction method (TEW) may solve this problem by estimation of the scatter contribution and subtraction of this contribution from the acquisition data. In general TEW will result in improved image contrast but will also reduce the signal-to-noise ratio. In this study we investigated the influence of TEW on the detection of peffusion defects in patients. Myocardial peffusion was studied 30 patients after TI-201 injection during stress and rest conditions. SPECT image data was acquired applying a 20% main energy window and 7% sub-windows to enable the estimation of the scatter contribution. All studies were analysed after normal processing of the data, as well as after applying TEW. Data were visually analysed from the computer screen showing the short, horizontal and vertical long axis slices of the stress and reinjection studies simultaneously, as well as the bulls-eye display. Each myocardial segment was scored by an experienced nuclear medicine physician using a 4 point scale ranging from 0 (absolutely abnormal) to 3 (absolutely normal). The results of the scatter corrected data were compared to those obtained from the non-corrected data. A relevant change in score was defined as an increase or a decrease of 2 points or more. Also the quality of each study was scored as poor, acceptable, or good. Comparing the scatter corrected data with the non-corrected data it turned out that TEW revealed 11 additional defects in the stress studies of 8 patients and 15 additional defects in 12 rest studies which all were normal without TEW. Small changes were seen in 20 myocardial segments on stress studies and in 38 segments in rest studies. When the quality of the non-corrected images was acceptable or better then the resulting images after TEW were also acceptable. We conclude that TEW improves image contrast, revealing more defects on myocardial perfusion images.

Left ventricle bull's eye (BE) images obtained by using a spherical coordinates system depend on the origin and the orientation of the axes. Usually the origin is taken in the centre of the ventricular cavity and the axes follow the direction of the cardiac axes. As the position of the centre and the direction of the cardiac axes change throughout the cardiac cycle, the coordinates system must be different in each instant. Thus, a realignment process between each set of reconstructed perfusion images is necessary. The realignment algorithm was implemented by matching a coordinates system to the left ventricle in two specific instants of the cardiac cycle, end-diastole (ED) and end-systole (ES). The coordinates system in ED was obtained by fitting an' ellipsoid to the medium myocardial surface. The origin of the coordinates system in ES was obtained as in ED. The directions of the cardiac axes in ES were obtained by minimization of the function f = 2-r, r being the correlation coefficient between the perfusion BEs in ED and ES. The correlation coefficient is a useful parameter because it is invariant in a possible linear change of activity in ES versus ED. A downhill simplex algorithm was used in the minimization process. The coordinates systems in the remaining instants of the cardiac cycle were obtained by interpolation between ED and ES. Once a coordinates system was matched to the left ventricle in each instant of the cardiac cycle, BE images of thickness, radius and perfusion were obtained. Then, a first Harmonic Fourier analysis was carried out, allowing an efficient compression of the most relevant information of the cardiac cycle. This work has been supported in part by the CICYT(SAF96/O062)

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B.L.F. van Eck-Smit, A. Dirksz, J.A.K. Bloklandj E.E. van der Wail. Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine. Leiden, Netherlands

H. Schirrmeister, M. Rentschler, C.Diederichs, J. Kotzerke, S. N. Reske. Department of Nuclear Medicine ,University of UIm, Germany

GATED SPECT RADIONUCLIDE ANGIOGRAPHY: WHAT IS THE GAIN?

COMPARISON OF lsF-PET AND 99r~Tc-MDP-BONE SCANS IN PATIENTS WITH CANCER

Introduction: Gated planar radionuclide angiography (pI-RNA) is a well established technique for the assessment of left ventricular (LV) function. The semi-automated method of analysis shows good intra-observer and inter-observer variability (<2%). Variations in background activity and superimposition of adjacent structures influences LV measurements and hampers the assessment of regional wall motion. Application of SPECT may overcome these shortcomings. Purpose of the study: to determine whether gated SPECT RNA (sp-RNA) would improve the detection of regional wall motion abnormalities without reducing the accuracy of LV measurements. Methods: In 18 patients sp-RNA was performed after completion of routine 15RNA. Twelve patients were treated with cardiotoxic agents, 5 patients were known with a previous myocardial infarction, 1 patient was known with dilated cardiomyopathy. For sp-RNA a 3-head gamma camera was used (360 °, 60 projections, 1 min./projection). Reconstruction data were filtered with a 0.25 Butterworthfilter. No attenuation correction was applied. Short, horizontal long, and vertical long axes were reconstructed from 2 pixel thick transversal slices. SPECT EF's were assessed by applying a 35% threshold to a region containing the LV. On pI-RNA and sp-RNA studies regional wall motion (normal, hypo-, a- or dyskinesia) was visually assessed in 9 myocardial segments. For the assessment of intra- and inter observer variability sp-RNA EF measurements were performed twice by the same observer and once by a second observer. Results: On pI-RNA wall motion abnormalities were observed in 12 segments. On s-RNA 15 sgm were considered abnormal. In 9 sgm abnormalities were considered more severe on sp-RNA than on pI-RNA. In the 12 patients treated with cardiotoxic agents no wall motion abnormalities were observed. There was a linear relationship between pI-RNA and sp-RNA EF measurements (y=x+5,8; r=0,83; SEE=8,0). The intra-, and inter-observer variabilities were 1,9% ± 2,8 and 3,2% ± 2,9% respectively. Conclusion: sp-RNA is an accurate method for the assessment of LV function. The gain of SPECT in RNA is the improved detection of regional wall motion abnormalities without reducing the accuracy of LV measurements.

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Purpose: We compared 18F-PET and planar bone scintigraphy regarding to frequency , morphology and location of benign and metastatic bone disease. Patients and Methods: 28 patients with carcinoma (8 breast, 7 prostate, 13 thyroid) were studied with 99mTc-MDP and 18F PET using a gamma camera (Siemens Bodyscan) and a positron-emission-tomograph (Siemens/CTI ECAT Exact HR+ ) MRT, CT and iodine whole body scans (patients with thyroid cancer) were used as "golden standard" to differ metastatic from benign lesions. Results: Prospective analysis showed 4,5-fold more abnormalities in the spine on PET-images (49 benign, 11 metastatic) than conventional bone scans (7 benign 6 metastatic). With PET 50 percent of the metastases occured as lytic lesions surrounded by an increased rim of activity. Benign changes in the spine never appeared with the described morphology. Both, benign and malign spinal lesions in MDP bone scans occured as regions with enhanced uptake. In peripher regions. PET showed as many lesions (16 benign, 5 metastatic) as in MDP bone scans (15 benign, 5 metastatic). Conclusion: Our findings suggest that 18F-PET is useful to evaluate the skeleton and is more sensitive in detection and more specific in the judgement of spinal abnormalities in comparison to 99mTc-MDP bohe scans.

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34.. Kibar, A. Tutus, O. Denli, T. Sarpel, A. Acar, M. Ercan, Departments

T. Erselcan 1, F.Candan 2, S.Saruhan3,T.Ayga3, C.U.Medical Faculty, Department of Nuclear Medicine 1, Internal Medicine 2 and Dietetics 3, Sivas, Turkey.

of Nuclear Medicine, Dermatology-, and Physical Therapy, Cakureva University Faculty of Medicine, Adana, Yqrkiye TECHNETIUM-99M CITRATE SCINTIGRAPHY VERSUS BONE SCINTIGRAPHY IN THE EVALUATION OF PSORIATIC ARTHROPATHY

The aim of this stuff/was to determine the diagnostic value of Tc-99m citrate scintigraphy in the evaluation of inflammatory activity in joints of psoriatic patients. Twenty-one patients (mean age: 42.9 _+12.3 years) with known or suspected psoriatic arthropathy were included in the study. All patients underwent conventional bone scintigraphy (Tc-99m MDP) and Tc-99m citrate scintigraphy with a 2 days interval Vi~uaI and quantitative analysis of the tracer uptake in each joint was performed on the both scintigraphie~. In 716 jnint~ without current clinically active inflammation but with or without previous inflammation (grade 0), an increased Tc-99m MDP uptake wa~ observed (1.72 ± 0.57), whereas no increased Tc-99m citrate uptake was observed (1.11 _+0.17). Some 106 joints with mild pain or ~welling (grade 1) exhibited increased Te-99m MDP uptake (2.77 ± I. 1; p<0.001 versus grade 0) and increased Tc-99m citrate uptake (1.35 _+ 0.31; p<0.001 versus grade 0), while 18 joints with moderate to severe pain or swelling (grade 2) also exhibited increased Tc-99m MDP uptake (3.27 + 1.75; p<0.001 versus grade 0 and NS versus grade 1) mad increased Tc-99m citrate uptake (1.70 _+0.52; p<0.001 versus grade 0 and grade 1). In visual evaluation, all of the clinically actively involvedjoints (grade 1 and grade 2) showed increased uptake by both the two agents. However, 62 and 24 of 716 joints (grade 0) which were not clinically actively involved were also detected by Tc-99m MDP and Tc-99m citrate scintigraphy, respectively. In conclusion, Tc-99m citrate scintigraphy distinguish betweenjoints with and without active/m']ammation, and even inflammation severity in patients with psoriatic arthropathy. Whereas bone scintigraphy only di~Jnguish betwe~a joints with or without active inflammation, but do not inflarrunation severity. Thus, we concluded that Tc-99m citrate scinfigraphy is a useful method in the evaluation of psoriatic ar*du-oparhy.

P 109 J.Pinkert 1. R. Pinkert 2, M. Andreeff ~, D. Sendler 2 and W -G.Frankc a, Technical University Dresden, Depts. of Nuclear Medicine ~ and Oral and Maxillo-Facial Surgery~ EVALUATION OF HEALING AFTER INSERTION OF COLLAGEN COATED TITANIUM J A W IMPLANTS W I T H BONE SPECT A uncomplicated take after insertion of titanium implants in the jaw is limited by the open healing in the gingiva region. To achieve a close fixation of the connective tissue with the titanium implant a biocompatible surface like connective tissue is needed. Coating with hydroxyapatite was hot successful. Aim of our study was to evaluate healing after insertion of commercially produced titanium implants (FRIALITH-2) coated with a newly developed collagen surface. Five minipigs with 10 implants in the lower jaw &each minipig were studied with bone SPECT. Bone SPECT with Tc-99m-HMDP was performed after 4 weeks, 3 and 6 months after insertion of implants using a dual head camera equipped with low energy high resolution collimators (90 frames at a 128x128 matrix). After iterative reconstruction coronal and transversal slices were reconstructed. The regional uptake in the implant region was semiquantitatively estimated using ROI and compared with a reference region in the upper jaw. Already 4 weeks after implantation only a small increased uptake in the implant region was seen and semiquantitatively demonstrated by the ratio implant region / upper jaw 1.36 ±0.2. The control studies showed no local elevated uptake after 3 and 6 months. The fast reduction of local uptake in the implant region representing a normalisation of bone metabolism support the hypothesis of a quick and uncomplicated healing when the new material was used also supported by histological examination of implants after 6 months. These results suggest that the new developed collagen coated titanium implants have favourable characteristics for uncomplicated healing. These results must be verified in man. In case of collagen coated jaw implants a elevated bone metabolism after 3 months may indicate a pathological healing.

HOW MUCH DEXA CONTRIBUTES TO THE BODY COMPOSITION ANALYSIS IN CLINICAL ROUTINE, AS COMPARED TO THE CONVENTIONAL CHEAPER METHODS• The purpose of this study was to compare results of the body composition analysis (BCA) of two conventional methods, namely skin fold thickness (SF) and bioelectrical impedance (BIA), by dual energy X-ray absorptiometry (DEXA) in clinical practice. According to their body mass index [BMI: weight(kg)/height2(m)], total of 36 patients (26 women, 10 men) were divided into two groups (GrA = bmi< 25 ;GrB=bmi>25). All patients, free of systemic diseases and overnight fasted, were subjected to the measurements of skinfolds at four standart sites ( biceps, triceps, suprailiac, sub-scapular), whole body BIA at 500 ~A and 50 kHZ ( Bodystat 1500 ) and whole body DEXA scan ( Hologic 4500 W), performed in the same morning. Fat mass (FM) and lean mass (LM) in percentages of total body weight were obtained directly from the manifacturer's ready reports, and calculated from the age and gender spesific regression equations of four sites SF. Differences in measure ments were evaluated by ANQVA and linear regression analysis. Results of measurements ~ mean +_SD Age ' BMI FM FM I FM LM LM I LM !(year) kgtm2 dexa bia I SF dexa bia I SF GrA ~28.4 22•7 29.3 23 4 25 4 70.7 76.6 746 n:12 I_+8.8 ._-1.0 _-7.1 _+6.6 3583 _+7.1 +66 _+53 GrB 40.9 •34•9 42 3 37•3 577 62•7 632 n=24 ±15.4 _+5.7 -+7.7 ±81 _+7.5 -+.7.7 -+8.1 _+75 No significant difference was found among three measurements in GrA. Only LM in SF method slightly differs from dexa in GrB (p=0.04). Regres.coeffic.(R 2) for FM and LM; dexa-bia:0.86, dexaSF:0.83 in GrA, and 0.73, 0.58 in GrB, respectively (p=0.001). Besides regional body studies, we think that conventional meths. are quite sufficient for the BCA in routine clinical follow up.

Plll T. Erselcan* A.T.Erg0r** C.UMedical Faculty, Department of Nuclear Medicine* and Pediatrics**, Sivas, Turkey. DIAGNOSTIC VALUE OF BONE MINERAL DENSITY MEASUREMENT BY DEXA IN 0 - AGE GROUP PATIENTS WITH RICKETS In this study, it has been investigated as to whether measurement of bone mineral density (BMD gr/cm 2 ) in the forearm bones of 0age group children with rickets may probably serve as a more quantitative follow-up of the disease. For this purpose the BMD in the forearm bones of 14 patients (mean ± SD ;age 7 ± 2.08 months, weight 7.82 ± 1.13 kg, height 66.14 ± 3.50 cm) with clinically, radiologically and biochemically diagnosed to have rickets and 14 healthy children (mean ± SD ; age 6.46 := 3.50 months, weight 7.13 ±1.65 kg, height 67.64 ±10.26 cm) has been measured by Dexa method (Hologic, 4500 W). No significant difference was found between the patient and control groups in age, height and weight (p=0.53, 0.30, 0.19 respectively, Mann Whitney U Test). Forearm BMD (mean ± SD) in the patient group was determined to be 0.180 ± 0.02 and that in the control group as 0.190 :~ 0.03 gr/cm 2 . Statistically, no significant difference was observed in between the two groups (p=0.12). No significant difference was also determined in the total area and bone mineral content (BMC). in patient group: area= 6.t4 ~1.09 cm 2, BMC=l.12 ± 0.26 gr, in the control group: area= 6.10 ± 0.91 cm 2 , BMC = 1.17 ± 0.22 gr. In conclusion, 1 - as no significant decrease was determined in the BMC besides the BMD, the bone matrix anomaly has been considered to be the determining factor in rickets physiopathoiogy and, 2 - no clinical benefits from measurement of forearm BMD may be derived in the diagnosis of rickets and follow-up of treatment in 0 - age group children.

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Le.0 G. Flores II, Shigeki Nagamachi, Seishi Jinnouchi, Takashi Ohnishi, Hiroshi Nakahara, Shigemi Futami and Katsushi Watanabe. Department of Radiology Miyazaki Medical College, 5200 Ohaza, Kihara, Kiyotake, Miyazaki, Japan 889-16

T. Baso~lu, N. Ank, C. Co,~kun, T. Kandemir M. ~ahin, i. Bernay , B. Adam , Departments of Nuclear Medicine, Nephrology and Biochemistry, Ondokuz May=s University Hospital, Samsun - TURKEY

RELATIONSHIP OF EXTRAOSSEOUS ACCUMULATION IN BONE SCINTIGRAPHY AND HISTOPATHOLOGY We evaluated the relationship of Tc-99m HMDP extraosseous accumulations (EOA), histopathology and various laboratory findings. In 155 of 4824 patients EOA were noted. In 163 EOA, 33.7% were found in the abdomen, 27.6% in chest, 22.7% in extremities, 9.8% in the pelvic area and 6.1% in the head and neck area. About 80% of EOA were due to malignant process, 11% due to benign process and in 9% diagnosis was unconfirmed. In the abdomen, 36.6% of the EOA were due to hepatocellular carcinoma and intestine carcinoma. In the chest, 46.7% of EOA were due to breast carcinoma. In the extremities, 28.7% of the EOA was due to sarcoma. In 83 of patients with EOA, the WBC count, serum Hb, serum Hct, platelet count, serum Ca, P, Fe and unsaturated iron binding capacity were noted. The WBC was elevated in patients with malignant process. The serum hemoglobin was below normal in benign and malignant process both in males and females. All other laboratory findings were within normal limits. EOA therefore is more frequently associated with malignant process and is often accompanied by leukocytosis and serum hemoglobulinemia.

QUANTITATIVE BONE SCINIIGRAPHY AND X-RAY ABSORPTIOMETRY AS COMPLEMENTARY METHODS IN MONITORING MEDICAL TREATMENT OF RENAL OSTEODYSTROPHYIN HAEMODIALYStSPATIENTS The aim of our study was to compare the scintigraphic and bone mineral density (BMD) measurements to the biochemical parameters such as parathyroid hormone (PTH) and alkaline phosphatase(AP) during a medical treatment of renal osteodystrophy in uremic patients on chronic hemodialysis. 5 patients with secondary hyperparathyroidism were selected for intravenous caIcitriol treatment. The duration of treatment was 12 months in all patients .Because of hyperphosphatemia or increased calcium X phosphorus product ,the dose greater than 1 #g could not be achieved in participating subjects. Renal bone disease was confirmed in all patients by whole body scans prior to therapy .Quantitative pin hole bone scintigraphy ( bone/soft tissue ratio, B/S) and dual energy x-ray absorptiometry were performed in all five patients for both femoral neck , trochanter and diaphysis before and after therapy. Right/left average values were taken for the analysis. No significant changes in all measured parameters could be determined ( p > 0.05). This was probably due to the inability to achieve meaningful doses of intravenous calcitriol because of Hyperphosphatemia .The Pearson correlation matrix of the different methods of measurement showed : AP PTH BMD * B/S * Before 1,00 0.94 0.30 0.63 AP After 1.00 0.90 - 0.03 0.56 Before -1.00 0.23 0.83 PTH After -1.00 - 0.20 0.86 Before -1.00 0.35 BMD * After -1.00 - 0.17 • = Femoral Diaphysis Values Scintigraphic measurements of Bone / Soft tissue activity ratios were significantly better correlated with PTH and AP values than the BMD values. Best results were obtained for femoral diaphysis. These interesting findings justify further comparative investigations in larger populations to find out which of the two methods reflects better the bone resorption activity in uremic patients.

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B.F. Lee, Y.F. Huang, Jin-Chung Liu, Hsin-Su Yu,

R.M. Aiqner, C. Ruda*, G.F. Fueger, H. K~rcher ~ K a r l - F r a n z e n s University, D e p a r t m e n t of Radiology, Division of N u c l e a r Medicine, *Department of M a x i l l o - Facial- Surgery, Graz, A u s t r i a

Kaohsiung Medical College Hospital, Department of Nuclear Medicine ODMPARATIVE STUDY OF Tc(V)-99m-DMS AND CgiLLIUM-67 IN THE

COMBINED TECHNETIUM-99M-MDP AND TECHNETIUM-99MTETROFOSMIN SCINTIGRAPHY IN THE FOLLOW-UP OF MICROVASCULAR ANASTOMOSED FLAPS

ASSESSMENT OF BONE AND JOINT INFECTIONS Accurate noninvasive diagnosis of bone and joint infections remains a vexing clinical problem. The aim of the study is to investigate the diagnostic value of Tc(V) -99m-DMS in combination with TC-99m-MDP bone scan to localize bone and joint infections co~pared with Ga-67 and bone scan. Twenty patients referred for investigation of bone and joint infections were studied. In all patients, bone scan was initially obtained. Subsequently, comparative scans with Tc(V)-99m-DMS and Ga-67 were carried

out

within one week interval. Microbiological and clinical findings were considered to be proof of the presence of bone and joint infections. Whole-body images were acquired 4 hr aftter the injection of 555 MBq of Tc(V)-99m DMS and 48 hr following the injection of iii MBq of Ga-67. Tc(V)-99m-DMS correctly identified presence, location and extent of the suspected bone and joint infections that were corresponding to the findings of Ga-67 and bone scan. Side effects after the DMS administration were not observed. Tc(V)-99m-DMS is a new and safe radiopharmaceutical

In r e c o n s t r u c t i o n surgery the e v a l u a t i o n of the p e r f u s i o n and v i a b i l i t y of the m u s c l e s and b o n e s in the p o s t - o p e r a t i v e p e r i o d is m o s t i m p o r t a n t in patients. C o m b i n e d Tc 9 9 m - t e t r o f o s m i n a n d Tc-99mM D P s c i n t i g r a p h y was a p p l i e d for e a r l y differ e n t i a t i o n b e t w e e n u n c o m p l i c a t e d and c o m p l i c a t e d h e a l i n g p r o c e s s after m i c r o v a s c u l a r a n a s t o m o s e d flaps. Eight p a t i e n t s w i t h cancer of the h e a d a n d neck were investigated post-operatively. Upon i n t r a v e n o u s i n j e c t i o n of t e t r o f o s m i n at the f i f t h day p o s t operatively, r a d i o n u c l i d e a n g i o g r a p h y was p e r f o r m e d . Static images (planar and SPECT) w e r e d o n e i0 m i n u t e s and 30 m i n u t e s p o s t i n j e c t i o n (p.i.) .Two days later threephase MDPs c i n t i g r a p h y was done. Planar and S P E C T images w e r e d o n e 3 hrs p . i . . T h e r e l a t i v e u p t a k e r a t i o s w e r e obtained. A n u n c o m p l i c a t e d h e a l i n g p r o c e s s was o b s e r v e d in 5 patients, localized m~#cular n e c r o s i s was v i s u a l i z e d in 2 patients, l ~ l i z e d (avascular) e a r l y bone n e c r o s i s was s e e ~ in 1 patient. The c o m b i n e d use of f u r i f o s m i n and MDPs c i n t i g r a p h y f a c i l i t a t e d the early d i a g n o s i s of p o s t o p e r a t i v e c o m p l i c a t i o n s after m i c r o v a s c u l a r a n a s t o m o s e d flaps w h e r e a s c o m p u t e d t o m o g r a p h y or m a g n e t i c r e s o n a n c e i m a g i n g w e r e not a p p l i c a b l e resp. n o n - r e v e a l i n g .

for the investigation of bone and joint infections and can be easily prepared in every nuclear medicine department.

974

Key words reconstruction tetrofosmin,

surgery,

bone

scintigraphy,

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D. Huglo, M. Arnould, V. Beauchat, D. Fron, M Steinling, B. Herbaux, X Marchandise - Department of Nuclear Medicine and Paediatric Surgery, H~Spital HURIEZ - CHU de Lille, 59037 Lille cedex FRANCE

J.B. Cwikla, J.R.Buscombe, D.S.Thakrar, NJ.Goddard, A.J.W.Hilson Nuclear Medicine, PSK 2, Otwock, Poland, and Nuclear Medicine and Orthopaedics. Roval Free Hospital and School of Medicine, London, UK

CONTRIBUTION OF INTRA-OPERATIVE RADIODETECTION IN SURGERY OF OSTEOID OSTEOMA The aim of this study was to evaluate the usefulness of intra-operative radiodetection of osteoid osteoma in modifying the reconstructive surgery" and in improving the quality of exeresis. Patients : Since 1986, 23 radioguided surgeries were performed in 22 children (14 males, 8 females) with a mean age of 11.3 years (3.8-17.7). The tumour was tibial (8), fibular (3), femoral (7), spinal (2 lumbar and 1 cervical), sacral (1) or scapular (1). In 2 cases, it was a recurrence 4 and 1l months after the first surgery (without radiodetection). A child had had 2 locations 23 months apart. Methods : A day before surgery, 7 MBq/kg of 99mTc-HDP were intravenously injected and usual frames performed if necessary. Before exeresis, the surgeon measured bone activity in different locations with a sterilised probe (semiconductor Cadmium Telluride 25 mm2 x 1 ram) to research the maximum corresponding to nidus and normal bone uptake. After exeresis, measurements are systematically performed on excised piece(s) and in the cavity to obtain significant decrease of initial activity. Results : 22 osteoid osteomas were found on histological examinations. In the first 3 cases, osteosynthesis and bone graft were performed after large exeresis. Afterwards, intra-operative radiodetection had allowed smaller resections and only plaster immobilization in 4 cases and no complementary treatment in other patients. In all cases, pain related to nidus had disappeared. In one case with osteosynthesis and bone graft, a stress fracture occurred i4 months later. There was no recurrence. Conclusions : The intra-operative radiodetection of osteoid osteoma appears a technique easy and efficient and with this technique, the reconstructive surgery and the complementary treatment can be decreased.

SUPERIOR BONE SCINTIGRAPHY OF THE UNIPLANAR COLLIMATED SPECT

FEET USING

This study was performed to assess the utility of bone SPECT in the feet using a new commercially available uniplanar ban beam collimator originally designed for cardiac imaging. 18 patients with symptoms or signs of probable skeletal pathology in either the foot or ankle were imaged using a two headed gamma camera fitted with uniplanar fan beam collimators. All patients were imaged 2.5-4 hours after administration of 500-750MBq Tc-99m MDP. The SPECT acquisition was performed in a 128x128 matrix, giving a pixel size of 2.00-2.30 mm depending on the radius or orbit. Images were displayed as transaxial, coronal and sagittal slices and a three dimensional volume rendered image and displayed for reading by three readers blind to the clinical results. Sites of abnormal uptake on the foot SPECT scan were then compared with the site of known or suspected pathology and in 17 patients with planar radiology. SPECT images produced using the uniplanar fan beam collimators were of good quality in all patients with all three readers finding localisation easiest on the sagittal and three-dimensional images. In 10 patients abnormalities were found which could explain the patient's symptoms or signs and at the site expected from the patient's clinical history. In 5 patients there were abnormalities on the bone scan in the ipsilateral foot but at a different site. 2 patients had contralateral abnormal uptake to side suggested by the clinical history and no abnormality in the bones if the foot with symptoms. One patient had bilateral degenerative disease. Planar radiology was normal or unhelpful in 13 of the 17 patients in which it was performed SPECT imaging of the feet is possible and provides accurate localisation of abnormal uptake when performed using uni-polar fan beam collimators with a standard acquisition times of 15 minutes for a double headed gamma camera.

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P 119

G. MariaN, C. Motta, G. Taddei, G. Villa, R. Costa, C. Maragliano, R. Gatti. Nuclear Medicine Service, DIMI, University of Genoa, and "G. Gaslini" Children's Hospital; Genoa (Italy).

stefan Gratz ~, Georg K6ster;, Thomas Behr 1, Horst Peter K0hler2. Dirk Hedrich 2, Rolf Vosshenrich 3, Eckhardt Grabbe3, Hans-Georg Willert ~, and Wolfgang Becker 1 Departments of Nuclear Medicine, Orthopedics and Radiology, Georg August University of G6ttingen, Germany

COMPARISON OF 99mTc-SESTAMIBI AND '~gmTc-TETRO-FOSMIN FOR THE SCINTIGRAPH1C IMAGING OF LIPID DEPOSITS IN THE BONE MARROW OF PATIENTS WITH GAUCHER'S DISEASE. We have previously reported the favourable results obtained with direct scintigraphic imaging of lipid deposits in the bone marrow of patients with Gaucher's disease employing ~Tc-Sestamibi (99"Tc-MIBI) v e r s u s the earlier procedure based on inhalation of the lipid-soluble gas ~Xe. Although the exact mechanism of 99"q'c-MIBI localization in the lipid Gaucher infiltrates is not known, it is thought to reflect factors linked to the level of disease activity (cellular density and metabolic activation). The present study is part of an ongoing investigation involving a total of 25 patients with Gaucher's disease, in whom scintigraphy with 99"TcMIBI is being evaluated both to detect lipid deposits in the bone marrow and to assess the efficacy of substitutive therapy with the defective enzyme, Ceredase, in reducing such deposits. In a subgroup of the study population above, scintigmphic imaging of bone marrow Gaucher deposits was performed first with ')~mTc-MIB1then repeated, 48 hr later, with the myocardial perfusion agent, '~'>mTe-Tetrofosmin (99"q'c-TF). Upon i.v. bolus injection of the tracers, a dynamic acquisition over the knees was recorded for 30 rain, followed by static acquisitions at 30 rain and 2 hr. Target-to-background ratios were then estimated for the static acquisitions, taking the medial mid-region of the thigh muscles as the background. Uptake of the two radiopharmaceuticals at the affected sites was detectable few min after i.v. injection, and led to clear scintigmphic imaging of bone marrow involvement by the lipid Gaucher infiltrates for both tracers. Early (30 rain) target-to-background ratios (whose values reflected the varying degree of bone marrow involvement in the individual patients) were higher for 99mTc-MIBIthan for 99mTc-TF(from +2.5% to +56.6% A). At the 2-hr imag~ing99mTc-MIBIstill maintained higher targetto-background ratios than "Tc-TF (from +2.1 to +32.2 a), although wash-out from the affected sites was slightly faster for 99"q'c-MIBI than for 99"Tc-TF. These results indicate the superiority of 99"Tc-MIBI over 99mTc-TF for the scintigraphic imaging of lipid deposits in the bone marrow of patients with Gaucher's disease.

Radionuclide Arthrography in suspected Rotator Cuff Rupture Rationale: In the past scintigraphic arthrography in comparison with contrast adhrography has shown far better results in patients with suspected hip protheses loosening, because of the lower viscosity of the radionuclides. In this study, a radionuclide arthmgraphy of the shoulder joint was performed in 19 patients with suspected rotator cuff ruptures. The scintigraphic results were compared with ultrasound (n=19). radiologic arthrography.(n=19) and endoscopy (n=13) of the shoulder joint.The efficacy of the procedure was evaluated, Methods: After intravenous injection of 300 MBq ~9=Tc methylene diphosphonate (MDP) bone scintigraphy for landmarking of the shoulder was imaged. Afterwards, scintigraphic arthrography was performed in 9 patients as combined contrast and radionuclide arthmgraphy, whereas in 10 patients the radionuclide was injected in the rotator cuff only via ultrasound and contrast arthrography followed several days after. The radiographic contrast medium was mixed with ~mTc micmcoltoid (ALBURES 400 pCi / 5ml) and in case of ultrasound conducted instillation, the microcolloid was mixed with local anesthetic. After completion of the radiographic arthrography(n=9)or ultrasound (n=10) conducted instillation, nuclear arthrography was performed 30 minutes later, and scintigraphic images with a small field of view gamma camera were recorded. Images were interpreted by superposition of the 99mTc microcolloid images and the corresponding 99mTc - MDP image. Findings at endoscopical surgery (n=13), which was performed only in patients with suspected rupturing of the rotator cuff, were used as the gold standard. ResultS: The total number of rotator cuff ruptures found with the radionuclide arthrography was 9. In cases of complete rotator cuff rupture (n=5), nuclear arthmgraphy performed equal to radiographic arthrography in 4 patients and in case of incomplete rupture (n=4), 3/4 results were consistant, A difference was seen in patients with capsulitis, calcification and rotator cuffs, that have been already revised in the past. Conclusion: Nuclear a}'thrography is a sensitive technique for detection of rotator cuff ruptures. Because of the lower viscosity of the radionuclide, small ruptures can be easily detected, offering additional value over radiographic arthrography and ultrasound, especially for evaluation of incomplete cuff rupture& Radiographic arthrography remains necessary not only for the evaluation of the inflamed degenerations of the shoulder joint but also for detailed evaluation of osseous structures. 975

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G.Rubini, G.Di Giovine, A.Desiate*, V.Milano*, F.Lauriero, D. Rubini, A.D'Addabbo. Dept. of Nuclear Medicine an~ Inst. of *Odontostom~tology and Maxillo-Facial Surgery - University of Bari, Italy

M._Reinharx~, U. Ross 2, E. Moser t ~) Dept. o f Nuclear Medicine and 2) Dept. o f Oto-Rhino-Laryngology, Albert-Ludwigs-University, Freiburg i.Br., Germany

COMI~ARI S O N BETWEEN 99mTc-MDP EVALUATE ARTHROPATHY OF THE JOINT.

M O N I T O R I N G S O D I U M - F L U O R I D E T H E R A P Y OF ACTIVE OTOSCLEROSIS WITH TYMPANO-COCHLEAR-SC1NTIGRAPHY

SCAN AND MR TO TEMPOROMANDIBULAR

The aim of the study was to correlate the results of 99mTc-F~3P scan and MR in pts. with Temporo-Mandibular Joint (TMJ) arthropathy with that of MR and monitor efficacy of splint stabilisation treatment. 16 pts. with temporomandibular articulation disorders (pain, clicking and/or crepitus, functional limitation of opening) were studied. MR and 99nTfc-MDP scan of TMJ was performed on two consecutive days. MR showed signs of monolateral Avascular Necrosis (AVN) of a condyle (in 4/10 pts) and bilateral signs of arthrosis (A) in 12 pts. (marginal osteophytosis of the mandibular condyle, deformation-luxation of the meniscus). 99mTc-~D? scan of TMJ identified monolateral hyperactivity in 4 pts. with AVN. In the remaining 12 pts with A increased bilateral uptake was noted, more evident on one side. The index of 99mTo-MDP TMJ uptake (TMUI) was calculated comparing the ATM ROI counts with those of the chin ROI. This index was calculated also in 15 normals. TMUI was 2.4+0,6 (P<0,001) in AVN, 1.6_+0,44 (P<0,001) in A and 1_+0.09 in normals, respectively. The second 99mTc-MDP scan after i0_+0.8 months treatment with splint stabilisation showed a reduction in the activity and normalisation of TMUI in 14/16 pts. who correctly followed treatment, while in 2 (i AVN, 1 A), who did not, TMUI and hyperfixation were unchanged. Scintigraphie study of ATM permitted identification of the more functionally con~oromised side and monitoring over time of the evolution of arthropathy in response to splint treatment.

Metabolic changes o f the bony labyrinth are o f particular interest in patients with suspected otosclerosis in order to detect the active state o f the disease prior to an intended surgical or medicamental treatment. Active otosclerotic loci can be accurately detected by means of Tympano-Cochlear-Scintigraphy (TCS). TCS was performed in 40 subjects 2.5 h after i.v. injection o f 700 MBq 9~Tc-DPD using one-pinhole technique over I 0 minutes on each side. Semiquantitative evaluation was done by forming a ratio o f the labyrinthine ROI releated to the clivus ROI. M e a n activity ratios o f patients with active otosclerosis were significantly higher than that o f normal controls: normal (N=20) 0.58+/-0.17 (mean +/- SD.), active fenestral otosclerosis (N=10) 1.53+/-0.38 and 2.75+/-0.80 in active capsular otosclerosis (N=I0). TCS could not differentiate between inactive cases and normal controls. Ten patients with active otosclerosis were treated over 1 to 3 years with sodium-fluoride. Follow-up studies showed a slight but not significant decrease & t h e activity ratios, whereas audiometry and CT showed no change o f the pretherapeutic findings. TCS is a useful technique to assess metabolic changes of; the bony labyrinth. Semiquantitative evaluation is necessary for follow-up studies.

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D. A. Yi~ksel .Z. Burak, G. Erenel, H. Ozsoy, E. Ta~kiran, D. Ta~klran Ege University Faculty of Medicine, Department of Nuclear Medicine

I. Gtz-akara N. Edis, H. trice, M. Mulazuno~,lu,K. Kepkep, T.Ozpagaca. Cliulcs of Nuclear Medicine and Gynecology & Obstetrics, Okmeydam Hospital Turkey

EARLY DIAGNOSIS OF OSTEOARTRITIS DUE TO PARTIAL MENISECTOMY WITH TC-99m MDP BONE SCINTIGRAPHY Osteoartritis (OA) secondary to partial menisectomy (PM) is a complication showing late clinical and radiological evidences. Its early diagnosis is difficult. The measurement of degradation products of proteoglycans (PDP) in synovial fluid may be a possible marker of early stage of OA. The aim of this study was to determine the early findings of OA after PM by using Tc-99m MDP scintigraphy that shows the osseous homeostasis and provides important indirect information about the articular cartilage. 20 patients who were followed up for an average 22.3 months were included. Average age and malelfemale ratio were 33.9 years and 14M/6F respectively. They had normal x-ray. The surgical diagnosis of patients were 4 lateral(L)(25%), 11 medial(M) (55%) and 5 medial plus lateral(ML)(25%) meniscal lesions. Ten patients had mild clinical sign. The controls were included 8 healthy knees. All patients were evaluated clinically by physical examination, functional score and activity scale. The measurements of PDP were done by using dimethyl methyl-methylen blue. 20 mCi Tc-99m MDP two phase bone scan and SPECT were applied to all patients. The PDP levels of patients were significantly higher than controls. In the blood pool images; 4 diffuse(D), 4 M, 1 L and 1 patellofemoral(PF) region demonstrated increased activity concordant with late static images. In the late static phase ; 10 M, 4 L, 8 ML and 17 PF regions showed increased activity , whereas 11 D, 14 M, 3 L, 17 ML and 29 PF increased activities were diagnosed in the SPECT. 14 non-operated opposite knees had mild to moderate activities. There was a significant correlation between scintigraphic findings and PDP levels. In conclusion; these findings suggested that Tc-99m MDP bone scintigraphy is a sensitive and non-invasive modality in the early diagnosis of osseous homeostatic changes due to PM. These data may be especially useful in directing appropriate therapy in the early presentation.

976

THE IMPORTANCE OF Tc-99m HMPAO LEUKOCYTE SCINTIGRAPHY IN THE DIAGNOSIS OF PELVIC INFLAMMATORY DISEASE Diagnosis of pelvic inflammatory disease (PID) is not easy in every case. In order to evaluate weather Tc-99m labeled autologous leukocyte scintigraphy could be used in the diagnosis of PID, this study was planned. Twenty Imae patients prediagnosed as PID with their physical exam, laboratory (sedimentation, urine analysis, hemogram, C-reactive protein cervicovagmal cullxtre) and ultrasonography findings were included to the study. Eighty cc blood with ACD was withdrawn ; Leukocytes were separated and labeled with Tc-99m HMPAO prepared as 1 vial HMPAO for three samples. A half hour, 2 hours and sometimes 24 hours after the reinjection oflabeled leukocytcs, planar anterior scintigraphies were obtained in an ADAC Pegasus Genesis gamma camera Lvstem equipped with LEGP collimator. For the analysis of scintigrams a small ROI on tile centrum of upper Os ileum and a same size ROI on the PID suspected periutenne area were selected. The ratios of the periutegne ROI eount~ to the Os ileum ROI counts were determined. The ratio equal or more than 2 was accepted as positive, file ratio less than 2 was accepted as negative for PID. All patients were sent to laparosenpy; and definitive diagnosis of PID were established using Hagel criteria. Tc-99rn HMPAO scintigraphy assessed correctly 8 out of 11 patients with PID, and t5 out of 16 patients with non PID . Scintigraphy was false positive in 3 patients and false negative in I patient. The sensitivity specificity, positive predictive value , negative predictive value and accuracy of Tc-99m HMPAO scintigraphy for the detection of PID was 0.72, 0.93, 0.88, 0.83, 0.81 respectively. Findings showed Te-99m autologous leukocyte sc~ntigraphy ks a diagnostic method sensitive enough for detection of PID; though this method should be used especially for the differential diagnosis of PID.

P 126

P 124 Z Darlas* S. Leclercq**, M.H. Rosas** M. Pegoix**, J.E. Film#nt*,

D. Agostini*, 3".1t. Aubriot**, G. Bouvard*" Departments of Nuclear Medicine* and of Orthopaedics**, CHU, Caen , France INTEREST OF COUPLING TC99M-SULFUR COLLOIDS TO TC99M-HMPAO LEUCOCYTES SCINTIGRAPHIES IN DETECTING BONE INFECTION

B.De~irmenci, , O Kdm;, G.~apa, A. K.~!rak, O. Akpmar, H. Halil~olar, H. Durak, A. Akko~lu. Dokuz Eyl0i University, Depts of Nuclear Medicine and Chest Disease, iZMJR/TURKEY

Tc-99m TETROFOSMiN SCINTIGRAPHY AS A INDICATOR OF ACTIVE PULMONARY TUBERCULOSIS

Purpose: Scintigraphic identification of abnormal labeled leucoc~es in skeletal

infectious foci is complicated by normal bone marrow distribution of leukocytes, and depends on the presence of leukocyte activity in the absence of colloid uptake. The aim of this study is to evaluate the impact of couplmg Leukocytes(A) and Colloid (B) scintigraphies (sc) in detecting bone infection Methods:

(1)Patients: 74 pts, 97 sc, divided into two groups with regard to the scintigraphic technics: I(A) only]: 35sc; [(A)&(B) coupled]: 62 sc. Suspected prosthetic infection: 48 pts, 68 sc. Suspected osteitis: 26pts, 29sc. (ll)Scintigraphies: (A): 99mTc-HMPAO-Leukocvtes: planar localized scans (15mn), 3-4 hours after injection ofautologous leukocytes labeled with 250-300 MBq of 99mTc-HMPAO; (B): 99mTc-Colloids: same scans as upper, 30 mn after rejection of sulfur colloids labeled with 180-200MBq of 99mTc. Delay between (A) and (B): 48 hours.Device:gamma-camera Elscint Apex SP6; collimator APC-4RS low energy-high resolution. (Ill)Final diagnosis of sepsis : based on bacteriological and histological criteria after surgical biopsies and/or clinical, biological and radiological follow-up. (IF)Comparison between the two groups: Prevalence (/5"), Sensitivity (Se), Specificity (Sp), Accuracy (Ac).Sigmficance tests: Khi 2, Fisher exact test. Results: lPr (%) Se (%) Sp (%) Ac (%) [(A) only I 48.5(17/35) 88 (15/17) 78 (14/18) 83 (29/35) [(A)&(B)coupled] 3 2 (20/62) 90 (18/20) 95 (40/42) 93.5(58/62) P value

0.11

0.63

0.06

0.16

False negatives in the two groups (2/35 & 2/62) correspond to sepsis with no sigmficative concentration of leukocytes.False positives in the group N°2 (2/62) correspond to soft tissue foci falsely identified as bone sepsis. Conclusion: In detectmg bone infection, 99mTc-HMPAO-Leukocytes tmagmg is

a highly sensitive method, and has its specificity, improved when it is coupled to 99mTc-Colloid scintigraphy, especially by reducing false positives.

For detection of active pulmonary tuberculosis (APT) may be difficult on clinical and radiological basis, the new, non-invasive and easy applicable methods are needed. In this study, we aimed to investigate the role of Tc-99m tetrofosmin scintigraphy on delineating APT. Twenty-seven patients (pts) with APT proven by sputum smears and cultures, and 6 pts with inactive tuberculosis OPT) were included in this study. Mean age was 42.6-+16.1. Anterior and posterior thorax images of 10 minutes duration were acquired 20 and 60 minutes after the injection of 370 MBq Tc-9gm tetrofosmin. Images were evaluated visually and semiquantitatively by two-blinded nuclear medicine physicians Visual grading was made as follows:(-): no uptake, (+): activity is equal to sternoc!eidomastoid muscle uptake (SMU), (++): activity is greater than SMU and (+++): activity is equal to cardiac muscle uptake. Regions of interest (ROl's) were drawn on lesion (L) and adjacent normal lung area (NL). The mean count values of ROl's were obtained and UNL ratios were calculated. Results: Visual grading ATP lots ITP pts 6 + 4 ++ 23 +++ At semiquantitative evaluations, the difference between active and inactive tuberculosis was statistically significant (p < 0,02) (Mann-Whitney U). The sensitivity and specifity of this method was found to be 73 % and 83 % , respectively. If 1.3 (average value of active pts) was accepted as the threshold value, tt is concluded that there is considerable Tc-99m tetrofosmin uptake in pulmonary tuberculosis which is most probably related to disease activity, Tc-99m tetrofesmin scintigraphy can be used in the detection and follow-up of active pulmonary tuberculosis.

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C1 P 125 K. C a s i e r , C. V a n de University

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P 127 J. V e r s i j p t , R. V a n h o l d e r , Wiele, M. S i m o n s , R. A. D i e r c k x , Hospital Gent, Belgium.

99m-Tc - HMPAO labelled white blood cell scanninq for the detection of i n f e c t i o n in End-Staqe Renal Disease End-stage renal disease (ESRD) is characterised by a status of acquired i~nunodeficiency ~with decreased granulocyte chemotaxis. Theoretically this may affect the sensitivity of 99m-Tc-HMPAO labelled ~ C - s c i n t i g r a p h y . With this regard a retrospective study (1990-1996) was performed including 33 patients with ESRD (17 men and 16 women, mean age 58, range: 18-79 yrs) referred for exploration of infection (42 episodes). Underlying primary renal diseases were: chronic interstitial nephritis (n, number of patients = ii), polycystic renal disease (n=7), chronic glomerulonephritis (n=6), diabetic nephropathy (n=5) and miscellaneous (n=4). Antibiotic treatment with a mean duration of 9 days (range: 1 26 d) was given prior to scanning in 35 infection episodes. Sensitivity and specificity of 99m-Tc-HMPAO labelled pure granulocyte scintigraphy (555 Mbq) was determined using the final clinical diagnosis (cultures in 67% or other technical investigations in 33%) as gold standard. Sensitivity, specificity, positive predictive and negative predictive values were respectively 61%, 67%, 91% and 22%. Hypothetically the low sensitivity found in ESRD may be attributed to the known decreased chemotaxis, the chronic character and the site of infection, the use of antibiotics prior to scantling, peritoneal dilution and the use of immunosuppressive therapy. In conclusion, this retrospective 99m-Tc-HMPAO labelled granulocyte study confirms the theoretically expected low sensitivity for the detection of infectious foci in ESRD.

C. Turan, A. Tutus, biT. Ercan, M . K ~ g ~ k a y d l n Erciyes U n i v e r s i t y School of M e d i c i n e and H a c e t t e p e U n i v e r s i t y School of M e d i c i n e . Departments of Pediatric Surgery and Nuclear Medicine, Turkey. EVALUATION OF Tc-99m CITRATE FOR SCINTIGRAPHIC VISUALIZATION OF ACUTE APPENDICITIS IN RABBITS

A p p e n d i c e a l ! i g a t i o n was m a d e t h r o u g h a midline incision in the study group (n=8) to e v a l u a t e Tc 99m c i t r a t e as agents .for the visualization of acute apendicitis. Sham operation without appendiceal !igation was made in the control group (n=7). Twenty-four hours later, l mCi (37 MBq) Tc 99m c i t r a t e was £njected into auricial vein in both the rabbit groups. Three hours later, static images of the rabbits were o b t a i n e d w i t h a g a m m a camera. T h e r e w e r e p o s i t i v e images in 7 rabbits of the study group while there was no positive image in the control group. Appendicitis was histologically confirmed in all the e x p e r i m e n t a l g r o u p s of the study. Our results show that Tc 99m citrate is a useful agent for v i s u a l i z a t i o n of acute apendicitis with the following advantages: a higher diagnostic value, faster and e a s i e r m e t h o d for in-house preparation, low cost and b e i n g e x o r e t e d m a i n l y t h r o u g h the k i d n e y s and having a faster blood clearance.

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A. Klisarova H. Bohchelian, L. Koeva, G. Tranulov Department of Nuclear Medicine, Clinic of Endocrinology, Medical University, Varna, Bulgaria

M. Schreekenberqer!, E. Gouzoulis-Mayfrank 2, O. Sabri 1, Ch. Arning 1, H.J, Kaiser ~, G. Wagenknecht ~, H. Sass 2, U. Buell 1. Departments of Nuclear Medicine I and Psychiatry=, Aachen University of Technology, Aachen, Germany.

Tc-99m-LABELLED ANTIGRANULOCYTE ANTIBODY IN COMBINATION WITH Tc-99m-METHYLENE DIPHOSPHO NATE BONE SCINTIGRAPHY IN DIABETICS WITH OSTEOMYELITIS

E F F E C T S O F ,,ECSTACY" O N C E R E B R A L G L U C O S E METABOLISM: A PET A C T I V A T I O N STUDY DURING EXPERIMENTAL PSYCHOSIS

The aim of the study was to evaluate the diagnostic value of immunoscintigraphy with Tc-99m-labelled antigranulocyte antibody in combinatior~ with Tc-99m-MDP bone scanning for detection of osteomyelitis in diabetics The study group comprised of 15 patients with non-insulin dependent /Type II/ diabetes, foot ulceration and suspection of osteomyelitis. Patient clinical characteristics were as follows: mean age-53,7+6,1 years, sex ratio (M/F) - 8/7. All patients were subjected to a clinical examination, radiography, investigation of doppler ankle/arm systolic blood pressure. Pre- and postprandial blood glucose level and H b A l c were analysed. All patients underwent bone scintigraphy with 370 MBq Tc-99m-MDP three hours after injection in 3 projections followed in positive cases by labelled antigranulocyte antibody scanning. Immunoscintigraphy was performed 4 and 24 hours after administration of 740 MBq Tc-99m-MAB BW 250/183. Bone scan and immunoscintigraphic images were compared and defined as positive or negative for osteomyelitis. The final diagnosis was established by clinical follow-up or bacteriological cultures. Osteomyetitis was confirmed in five cases. The estimated diagnostic value of the applied method was sensitivity 92%, specificity 94%, accuracy 92%. The application of immunoscintigraphy with Tc-99m-labelled antigranulocyte antibody in combination with Tc-99m-MDP bone scanning is an efficient method for precise diagnosis of osteomyelitis in diabetics.

Purpose: Little is known about the acute effects of the designer drug "Ecstacy" (3,4-methylenedinxymethamphetamine, MDMA) on in-vivo cerebral glucose metabolism (MRGlu) in humans. It was the aim of this study to investigate the influence of the "Ecstacy"-analogon MDE (3,4methylenedioxyethamphetamine) on MRGlu during unspecific and specific cognitive activation. Methods: 10 healthy volunteers received orally either 2 mg/kg MDE (n=5) or placebo (n=5) in a randomised double-blind study. Two FDG-PET scans per subject were performed on separate days 2 hours after drug administration: 1. word repetition (unspecific activation) and 2. word association (specific activation). After absolute quantification of MRGlu (Sokoloff), 47 regions of interest (23 ROIs per hemisphere and 1 brain stem ROI) were defined on cerebral 3D-flash MRI images of each subject for regional quantification. PET/MRI images were overiayed and subtraction images specific minus unspecific activation were calculated. Results: Word association versus repetition showed under placebo an increased MRGlu in the left prefrontal codex (+7.2%) and in the left insula (+9.0%); p<0.05, WUcoxon-test. MDE versus placebo yielded a considerable decrease of MRGlu in the bilateral prefrontal codices (left: -12.1%, right: 11.6%), in the left insula (-18.6%), left amygdala and parahippocampal gyrus (-10.4%), and in the left superior temporal lobe (-14.6%); p<0.05, Utest. The global MRGlu was slightly increased under MDE administration (+7.2%, not significant). Conclusion: Acute experimental psychosis under MDE reveals a significant decrease of MRGlu in the bilateral prefrontal (association) codices. The lefthemispheric increase of MRGlu during word association as a specific cognitive activation is almost completely compensated under MDE administration. Approved by the local ethical committeeand the Federal PharmaceuticalCommission. Supportedby DeutscheForschungsgemeinschaft(GO 717 / I-l)

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E. Entok, F. Alata~, N. Asian, M. Metinta~, 1. Ak, N. ()zdemir, E. Vardareli. O s m a n g a z i University Medical Faculty, Departments of Nuclear Medicine and Chest Disease, Eski~ehir, Turkey

34. Kibar, A. Avck A. Tutus, M. Reyhan, F. Sezgm, A. Noyart,

THE BONE SCANNING M A L I G N A N T DISEASE

TECHNETIUM-99m-ETHYL CYSTEINATE DIMER SPECT BRAIN IMAGING I N TOURETTE'S DISORDER

IN

THE

EVALUATION

OF

Whole-body bone scanning has an important role in diagnosis and management of malignant disease. In this study it was aimed to show regional distribution of bone metastases (BM) and relationship among the biochemical markers such as Calcium (Ca+*), ALP and PSA. 74 patients who had lung Ca with BM (Group la), 40 patients without BM (Group Ib), 50 patients who had breast Ca with BM (Group lla), 16 patients without BM (Group Ilb) and 36 patients who had prostate Ca with BM (Group Ilia), 15 patients without BM (Group lllb) were included in the study. Regional BM were seen most frequently 46.9% in ribs, 16.8% in thoracal vertebras, 9°,/0 in limbs, 8.3% in pelvis of 618 lesions in Group Ia, 33.2°/0 in ribs, 18.3% in thoracal vertebras, 14% in lomber vertebras, 11.2% in pelvis of 322 lesions in Group lla, 39.5% in ribs, 15.1% in thoracal vertebras, 13.8% in pelvis, 9.4 in limbs of 385 lesions in Group Ilia. There was not significant difference in the blood Ca*+ levels bet;veen the patients with and without BM. The level of ALP of the patients with lung, breast and prostate Ca with BM had higher than that of patients witi~out BM (p<0.001, p<0.05, p<0 05). Apart form these findings the PSA levels of the patients in Group Ilia were significantly higher than levels of those in Group lllb (p<0,05). These results show that rib and thoracal vertebra metastases are observed frequently, whereas limbs and pelvic BM are seen less frequently. While blood C a " levels do not have an important role in the determining BM, high ALP and PSA levels thought they are not so guiding, are important in terms of its suggesting the BM.

978

Departments of Nuclear Medicine, Child Psychiatry and Child Nephrology, eukurova University Faculty of Medicine, Adana, TURKEY

Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) is a new cerebral blood flow imaging agent. In this study, we aimed to determine if there were any significant differences in patterns of regional cerebral perfusion between patients with Tourette's Disorder (TD) and a group of normal controls using Tc-99m-ECD SPECT. The patient group consisted of 19 fight-banded children (four girls and 15 boys) all met DSMSV criteria for TD Their ages ranged from 7 to 14 years (mean _+ SD age, 10.9 _+ 2.4 years). Nine right-handed healthy children, ages ranged from 9 to 14 years (11.5 _+ 1.6 fears) as a control group were also studied. For quantitative analysis, regular regions of interests were placed manually in 15 regions on coronal and transaxial slices. Because of the reliability of measurements, we chose the visual cortex as a reference region. The values are significantly lower for the patient group hi left caudate (p<0.05), cingulum (p<0.0l), right cerebellum (p<0.05), left dorsolateral prefrontal (p<0.0l) and left orbitofrontal (p<0.05) area. There was no strong correlation between the severity of motor tics and the blood flow in all regions. The strongest inverse correlations for blood flow were with depression scores. The strongest correlation with the Child Depression Inventory (CDI) scores were found between right anteromedial temporal (r = -0.57) and le~ posteromedial temporal (r = -0.54) regions. The strongest positive correlation was between severity of vocal tics and midcerebellar region (r - +0.27). The Maudsley Obsessional-Compulsive Questionnaire scores have negative correlation with all blood flow values, but not as high as CDI scores. The strongest correlate regions were left anteromedial temporal (r = -0.50) and right posteromedial temporai (r = -0.49) regions. Patients with coprotalia had significantly lower blood flow in right dor;olateral prefrontal region. In conclusion, we have demonstrated that there is a difference of perfusion of certain brain regions in patients with TD using Tc-99m-ECD SPECT.

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A. Tutu~ M. Kibar, S. Sofuo~lu, AS. G6niil. Erciyes University School of Medicine, ~ukurova University School of Medicine. Departments of Nuclear Medicine and Psychiatry, Turkey.

B. De.qirmenci, K. Alptekin, H. Durak, A. KOse, S. Krrag, E. Derebek, E. Ozbilek, B. Klwrclk. Dokuz Eyl(JI 0niversity, Depts of Nuclear Medicine and Psychiatry, IZMIR,TURKEY.

A Tc-99m HMPAO BRAIN SPECT STUDY IN ADOLESCENT PATIENTS WITH MAJOR DEPRESSIVE DISORDER

We have not encountered any brain SPECT study performed in adolescent depressed patients. Therefore. we used Tc-99m HMPAO brain SPECT in adolescent patients with major depressive disorder (MDD) to examine possible changes in cerebral perfusion and possible association between perfusion indices and clinical variables similar to those of adult patients. Fourteen adolescent outpatients (mean_+SDage:13.11_+1.43 years) fulfilling the DSM-IV criteria for MDD and 7 age-matched healthy control subjects (mean_+SDage: 13.80_+I.60 years) were included in the study. Tc-99m HMPAO brain SPECT was performed twice in the patient group and once in the control group. The first SPECT investigation was performed on nonmedicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion index (PI) was calculated as the ratio of regional cortical activity to whole brain activity. We found significant differences between the values of PIs of the untreated depressed patients and those of the controls indicating relatively reduced perfusion in anterofrontal, left temporal and right temporal areas. No significant differences were found between the remitted depressed patients and those of the controls in PI values. Our study suggests that adolescent patients with MDD may have rCBF deficits in frontal and temporal regions compared to normal subjects similarly in adult depressed population. The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests that they may be state-dependent markers for adolescent MDD.

P 134 P.J. Shah, A. Ogilvie, G.M. Goodwin, K.P. Ebmeier. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EHI0 5HF

Tc-99m HMPAO BRAIN PERFUSlON SPECT IN DRUG-NAIVE OBSESSIVE COMPULSIVE PATIENTS WITHOUT DEPRESSION The purpose of the study was to evaluate brain perfusion SPECT in drug-naive obsessive compulsive patients without depression (DNOCD). Nine patients (5 female, 4 male; mean age:30.8_+9.7) and six controls (3 female, 2 male;mean age:37.5_+6.4) who had no neuropsychiatric ilnesses were included in this study. " Yale- Brown Obsessive Compulsive Scale" (YBOCS) and "Hamilton Rating Scale" (HRS)values were obtained. HRS values were less than 16, the mean YBOCS value was 24+8. Brain perfusion SPECT imaging was performed with a triple-head gamma camera equipped with lowenergy high resolution collimators, 20-60 minutes after 924 MBq of Tc99m-HMPAO injection. Metz filter (FWHM: 11 ram) was used for filtering. Motion and attenuation corrections were made. The transaxial, sagitta] and coronal slices were obtained parallel to orbitomeatal line. Regions of interest (ROI's) were drawn first on right hemisphere (15 ROl's) and then mirrored ROl's were placed on the left hemisphere. ROl's were drawn for cerebellum and cingulate one for each (total= 32 ROl's). Mean count values per pixel were obtained. ROl's / cerebellum ratios were calculated. At visual evaluation, hyperperfusion was observed on left frontotemporal cortex in 4 patients (pts), on basal ganglia in 8 pts (2 left-2 right thalamus, 3 left-1 right nucleus caudatus), on bilateral orbito-frontal cortex in 2 pts, on cingulate cortex in 1 pt. Hypoperfusion was seen on bilateral posterior parietal cortex in 2 pts, on left frontal cortex in 2 pts, on left parietotemporal cortex in 2 pts and on right thalamus in 1 pt. At semiquantitative evaluation, hyperperfusion on right thalamus, left frontotemporal and bilateral orbitofrontal was statistically significant (p _<0.05)(Mann Witney U). A strong positive correlation between YBOCS values and regional brain perfusion alterations was observed (r: 0.08, p: 0.012). In the present study, variable brain perfusion alterations were found in DNQCD. This study may suggest that the basal ganglia hyperactivity for the pathogenesis of OCD. Basal ganglia hyperactivity may lead to frontal hyperactivity through the thalamic and pallaidal connections.

P 136 R. Larisch~ A. Ktimke2, F. Kehren3, W. Gaebel2, H.-W. Mtiller-G~rtner1'3 Department o f Nuelear Medicine j and Department o f Psychiatr/, University o f Dfisseldorf Germany," Institute o f Medicine, Research Center Jiilich 3

CLINICAL AND PSYCHOMETRIC CORRELATES OF DOPAMINE D2 BINDING IN DEPRESSION AS MEASURED BY 123I-IBZM.

STRIATAL ASYMMETRY OF DOPAMINE D= RECEPTOR BINDING IN MAJOR DEPRESSION

A~_~; TO test the hypotheses that depressed patients had reduced dopamine function as measured by 123IIBZM binding compared to controls, and that measured dopamine function would correlate with objective measures of psychomotor speed. Method; 15 depressed patients with major depression and 15 age and sex matched controls were examined with a clinical and neuropsychological test battery and high resolution IBZM-SPET. Estimated specific binding was computed by averaging striatum to whole slice ratios over 8-10 scans acquired from 70 minutes post injection. ResultB~ Using whole slice as reference, right striatal uptake ratios were 1.68 (SD: 0.08) for patients and 1.62 (SD: 0.07) for controls (MannWhitney U-test, p = 0.03). Left uptake ratios were 1.66 (SD: 0.08) for patients and 1.63 (SD: 0.09) for controls (p = 0.23). There were correlations between IBZM binding in right and left striatum and measures of reaction time (right: rho= 0.59, 95% c.i.: 0.18-0.83. left: rho= 0.60, 95%-c.i.: 0.190.83) and verbal fluency (right: rho= -0.56, -0.81 to -0.13. left: rho= -0.52, -0.80 to -0.09). Conclusion@; IBZM binding was higher in the right striatum in depressed patients and, within this group, was correlated on both sides with impaired psychomotor speed. Increased IBZM binding in striatum probably reflected reduced dopamine function, whether due to reduced release of dopamine, or secondary up-regulation of receptors. This may be trait or state related, an issue that needs to be addressed with longitudinal studies.

Abnormal patterns of cerebral hemispheric asymmetry have been implicated in the pathophysiology of several neuro-psychiatric diseases. Several investigators have suggested that major depressive patients show dysfunction of the nondominant cerebral hemisphere. Additionally, among others, we have shown that the dopaminergic system is involved in this disease. The aim of this study was to compare hemispheric lateralization of dopamine D2 receptor binding of major depressive patients and normal controls. Methods: Nineteen patients fulfilling DSM-IV criteria for major depression and 19 normal controls were investigated with the specific dopamine D2 receptor antagonist ~23I-iodobenzamide (IBZM), using single photon emission computed tomography. A ratio of right-to-left striatal IBZM binding was calculated. After this measurement a treatment with a selective serotonin re-uptake inhibitor (SSRI) was initiated in the patient group. Results: Sixteen of the 19 controls exhibited a ratio with higher values on the right side whereas only 1I of the 19 patients had higher D2 receptor binding on the right side. The difference of the ratios between patients and controls was significant in t-test (p < 0.05). One-way ANOVA showed that this difference was mainly due to a significant difference beween the control group and those patients who did not respond to the antidepressive treatment with an adequate improvement of mood (p < 0.05 after Bonferrohi correction). Conclusion: Right-toleft asymmetry of dopamine D2| receptor binding is usually present in normal controls with higher values on the right side and seems to be disturbed in major depressive disorder. Especially those patients who do not respond to SSRI exhibit this disturbance. This might be a valuable biological parameter for clinical psychiatry.

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P 137 2

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H. Else~, I. Gerdsen, M. Henze-, H. Pleines;, S. Haisch2, A. Linke2, P. Georgi1Depts. of Nuclear Medicinei and Psychihtry;, University of Heidelberg, Germany

S. Yang, N.J. Peng. Department of Medicine, Long Chiang Veterans Hospital and Kaohsiung Veterans General Hospital, National YangMing University School of Medicine, Taiwan.

SPECT STUDY OF REGIONAL CEREBRAL PERFUSION IN PATIENTS WITH DEPRESSION AND DEMENTIA SEMIQUANTITATIVEDATAANALYSISOF BENZOD1AZEP1NERECEPTOR DISTRIBUTION1N sCHIzoPHRENIA, A STUDY WITH 123I-JOMAZENIL-SPECT Background." There has been growing evidence from post mortem and SPECT studies that gabaergic tr~smission is impaired in schizophrenia and other neuropsyehiatrie disorders. However, quantification of receptor density using SPECT might vary according to the reference region. Goal: The aim of the present study was to investigate benzodiazepine receptor distribution in schizophrenic subjects in relation to psychometric data and to compare receptor density by using three different reference regions. Methods: 11 schizophrenic patients (mean age 28,4 + 4,9) were diagnosed according to DSM IV criteria. Patients with substance abuse and neurological disorders were excluded. Psychopathological symptoms were assesed on the BPRS, SAPS, SANS and SCS rating scales. In addition, neuropsychologieal data (D2; WCST) and neurological soft signs (NSS) were evaluated. Under resting conditions in a dimed room 132,9 MBq 123-I-Jomazenil were intravenously given. Subjects were scanned 10 and 120 minutes post injection using a dual head gamma camera system (ME-collimator, 64 frames, 64x64 Matrix, 35 see/frame, zoom 3,2). Images were reconstructed by filtered backprojection. Whole-body scans were performed after 10 and 160 minutes and plasmaclearance measured within 30 and 120 minutes p.i. Images were analized by a semiqantitative approach on 6 slices each with ten ROI's. comparing total slice, white matter and cerebellum as reference regions. Results." The plasma-clearance correspondedto a monoexponentialfunction (blt=84,Sminutes). Laterality effects (index >10%) were observed mainly for the frontal and temporaI lobe (83%) but differences up to 5% were observed depending on the reference regions selected. Some ROl's in iomazenil-SPECT showed significant correlation to psychatric scaling values. Conclusion: Our results are in concordance with the present model of schizophrenia.

Some patients of late life depression with cognitive deficits are severe enough to meet the criteria of dementia. Such patients may resolve with appropriate treatment. Recent studies have demonstrated that depressed patients frequently exhibit abnormalities of brain perfusion. The purpose of this study is to differentiate the depression from dementia using Tc-99m HMPAO brain SPECT. Forty two patients who met the criteria of major depression (25) without psychotic feature and the score of the Hamilton depression rating scale more than 18 and dementia (17) with cognitive function test in DSM-III R were included in this study. Twenty five normal controls were also done for comparison. Brain SPECT images were created at 1 hour after intravenous administration of 555 MBq (15 mCi) Tc-99m HMPAO. Semiquantitative regional cerebral blood flow (rCBF) were performed on inferior frontal, superior frontal, temporal, parietal and occipital cortex in each patient. The patients with dementia showed lower rCBF over temporal cortex than those from depressed patients and normal controls (p< 0.01). The cognitive function impairment correlated well to the reduction of rCBF over the temporal cortex. Depressed patients had lower rCBF over inferior and superior frontal cortex than those from the patients with dementia and normal controls (p< 0.01). Our preliminary results suggest that Tc-99m HMPAO brain SPECT be valuable to differentiate patients with major depression and dementia using semiquantitative method.

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F PASQUIER, I LAVENUE, B JACOB, F LEBERT, C LAMY, H PETIT, M STEINLING Memory Disorders Unit ; Institut of Nuclear Medicine. Universitary Hospital of Lille ; 59037 LILLE Codex ; FRANCE

E Safaie Semnani, F Nobili*, A Di Marco*, G Taddei, G Mariani, and G Rodriguez*. Nuclear Medicine Service, DIMI, and *Section of Neuropathophysiology, DISM, University of Genoa; Genoa, Italy.

RELEVANCE OF HMPAO-99mTe BRAIN SPECT STUDY IN A MEMORY CLINIC : A 4 YEARS EXPERIENCE Relevance of SPECT as diagnostic tool is controversial in relation with the various patterns observed within several types of Neurodegenrative Diseases (ND). The aim of this study was to determinate the benefit of SPECT in a Memory Clinic. HmPAO SPECT was performed in 271 outpatients. Final diagnosis was established by a staff of neurologists for Alzheimer, Vascular, FrontoTemporal or Diffuse Lewy Body Dementia (respectively : AD, VD, FTD, DLBD) according to NINCDS-ADRDA, AIREN, Lund and Manchester groups criteria, Hughes criteria. HmPAO SPECT were obtained 15 rain alter iv injection of 555 MBq using a Tomomatic 564. Visual assessement of HmPAO decrease was performed by 3 independant observer in frontal, posterior and subcortical regions on normalized SPECT images. The benefit of SPECT was computed using the Baysian's probabilities leading to the a posteriori probability with the knowledge of the a priori probability (probabilily = P). Curves of the a posteriori P were fitted for each possible comparison for ND by step of 0.05 for the a priori value. So, and for example, the a posteriori P for one particular patient to have AD with a posterior cortical defect is 45 %, for an a priori value of 20 % if the differentiel diagnosis is between AD and FTD. But the benefit is equal to zero if the diagnosis is between AD and VD with the same SPECT pattern. So SPECT is an available tool for diagnosis between some NDD by the way of the computation of the a posteriori values This way needs however a large database.

980

LONGITUDINAL REGIONAL CEREBRAL BLOOD FLOW STUDIES IN PATIENTS WITH ALZHEIMER'S D I S E A S E . The purpose of this longitudinal study was to evaluate the follow-up data of patients with Alzheimer's disease (AD), based on sequential regional cerebral blood flow measurements (rCBF). The rCBF data were correlated in each patient with the clinical evaluation of mental state. Out of a group of 78 patients with probable AD, 29 with mild AD (12 men and 17 women, mean age 66.1 years) were followed-up for a mean period of 15 months after the first combined assessment. The mean Global Deterioration Scale (GDS, equal to 1 in age-matched control subjects) was 3.6 at enrollment and 4.4 at the first follow-up examination. In addition, nine patients underwent a third evaluation 2.5 years after the baseline evaluation (mean GDS = 4.7), while 4 patients had a fourth examination at the 3.7 year follow-up (mean GDS = 5.4), and finally 3 patients underwent a fifth evaluation 4.3 years after enrollment (mean GDS = 5.4). Results of baseline rCBF measurement (t33Xe inhalation method with 32 fixed detectors, ISI) were compared with those from 29 age-matched healthy controls: all patients showed hypopeffusion in the temporopafietal cortex of at least one hemisphere. The rCBF in the associative frontal cortex was chosen to follow an initially spared area. Two patients were excluded from follow-up due to relevant ensuing systemic pathology. In 21 patients, progression of Alzheimer's disease severity matched rCBF reduction in both temporoparientaI regions (13 cases), or in either the left (5 cases), or right (3 cases) temporoparietal region. In four patients with more severe disease, an rCBF decline was observed also in the right (3 cases) or in both (I case) frontal regions. In one patient the rCBF decline also involved other regions besides the temporopariental and frontal cortex, while in one patient there was a diffuse rCB F reduction. The overall results obtained in this study indicate that progressive rCBF reduction is mainly found in temporoparietal regions, asymmetrically in a subgroup of patients, while progressive frontal rCBF decline is observed in more severe cases. In conclusion, quantitative rCBF based on '33Xe is a simple, valuable examination to monitor the progression of cerebral damage in patients with Alzheimer's disease.

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P 143

C DAEMS-MONPEURT, F PASQUIER, F LEBERT, A DUHAMEL, H PETIT, M STEINLING. Neurological Department ; Statistical ; and Functionnal Brain Imaging Units ; C.H.R.U DE L I L L E ; 59037 Lille Cedex ; FRANCE ALZHEIMER'S DISEASE AND HMPAO SPECT : CLUSTER ANALYSIS AND NEUROPSYCHOLOGICAL CORRELATIONS. The heterogeneity of Alzheimer's Disease (AD) is well established. For Functionnal Brain Imaging the assessment of this heterogenity is the most often subjective. The aim of this study was to search for cerebral uptake clusters in AD and to seek for relations between them and neuropsychological or behavioural symptoms. Tc99m-HMPAO SPECT was performed in 71 consecutive outpatients with probable AD (NINCDSADRDA). SPECT was performed using a dedicated Brain SPECT system, 15 minutes after iv administration of freeshly prepared HmPAO-Tc99m Nine pairs of ROI were determined at a level of 5 cm above the orbitomeatal line. Relative tracer uptake was expressed as the ratio for Re1 counts to mean cerebellar activity. Fiveteen neurospychological items were determined from a psychological assessment. A semi-structured interview withe the patient and a caregiver and a questionnaire were used to rate 15 behavioural disorders. Cluster analysis, Kruskall Wallis and Fischer exact tests were performed. As a whole, uptake indices were decreased in lateral, frontal and posterior areas. Determined from this mean profile, five main clusters were found. There was no difference between the clusters of age, sex, education, age at onset, and duration of the disease. Cluster 1 (n=25) was similar to the mean profile. Cluster 2 (n=lS) was characterized by relative higher anterior indices ; Cluster 3 (n=l 1) by lower indices except for left frontal regions ; Cluster 4 (n=9) by substantial higher indices except for left frontal regions, and Cluster 5 (n=7) by decreased subcortical uptake indices. Some links between these clusters and neuropsychological and behavioural items were found : MlVIS, DRS, temporal orientation, praxis, calculation were better in cluster 4 ; apathy was more frequent in cluster 4, and emotionalism was more frequent in cluster 2 and 3. These data emphasized the heterogeneity of AD, with several main syndromes grouping together behavioural, neuropsychological symptoms and SPECT profiles

V LEDUC (1), P LECOUFFE (2), L DEFEBVRE (1), F PASQUIER (l), A DESTEE (1), M STEINLING (2) Departments of Neurology (l) and Nuclear Medicine (2) C.tLR.U de Lille ; 59037 L I L L E FRANCE COMPARISON OF HMPAO-TC SPECT STUDY IN PARKINSON'S DISEASE, ALZHEIMER'S DISEASE AND DIFFUSE LEWY BODY DISEASE. Diffuse Lewy Body Disease (DLBD) typically associates a parkinsonian syndrome and a cortical dementia and despite clinical diagnosis criteria now well recognized, its clinical diagnosis sometimes arises great difficulties. Indeed, the clinical spectrum shares common points with Idiopathic Parkinson's Disease (IPD) and Alsheimer's Disease (AD). Our purpose was to compare HMPAO-TC SPECT data between IPD patients, AD patients and DLBD patients. The first group consisted in I9 patients with probable IPD (according to Hughes criteria), the second group in 19 patients with probable AD (according to the NINCDS-ADRDA criteria) and the third group in 14 patients with probable DLBD (according to Byrne's and Mc Keith's criteria). The mean age and disease duration didn't differ between the 3 groups and the mean MMS didn't differ between the AD and the DLBD group. SPECT was performed with a dedicated fast rotating SPECT system after iv. administration of 555 Mbq of freeshly prepared 99mTc-HMPAO. HMPAO uptake was measered in 10 pairs of Regions of Interest (Re1) drawn on a slice located 6 cm above the orbito-meatal plane. Tracer uptake was expressed as cortical/mean cerebellar activity ratios. Statiscal analysis was performed with a Mann and Withney test. Between IPD and DLBD patients, a significant difference in the tracer uptake (lower in DLBD) appeared for the bilateral temporo parietal left (TP) temporo occipital and occipital areas (TPO). Between IPD patients and AD patients, the difference reached significance in TP and TPO ROI (lower in AD). Between AD patients and DLBD patients, the tracer uptake was significantly lower in the frontal regions DLBD patients. So in conditions, of difficult differential diagnosis between either IPD and DLBD, or AD and DLBD, HMPAO-TC SPECT study appears to be a contributive support to the clinical diagnosis.

P 142

P 144

E, Saylt, G.G Yener, H Durak, ~ Faddo~lu, T Ertay, G Qapa, B. Keskin. Departments of Nuctear Medicine and Neurology, Dokuz Eyful University. izmir, TURKEY

BASAL

AND ACTIVATiONAL Tc99m HMPAO ALZHEIMER'S DISEASE

BRAIN SPECl- IN

Early diagnosis in Alzheimer's disease (AD) is important for administration of new treatments The purpose of this study was to differentiate mild/moderately demented AD patients from normal controls by means of activational brain SPECT and to investigate the correlation between regional cerebral blood flow end dementia severity. Activational brain SPECT was performed 1 week after basal brain SPECT in 12 mild/moderate AD patients according to NINCDS-ARDRA criteria (mean age = 68 + 8 years) and in 7 healthy, age - matched, volunteered controls (mean age = 65 ± 5 years ). In order to activate the parietal cortex, activation was performed by subtracting serial 5's from 100, 2 minutes before and after the I.V administration of 925 MBq Tc99m HMPAO. Using a three headed gamma camera (General Electric, Neurocam) equipped with high resolution collimators, 128 images of 35 seconds duration in 64 x 64 matrix were obtained over 380 degrees. Region to whole brain ratios (B / WB) were calculated in 2 pixel thick 3 consecutive slices above the orbitomeatal line, Activation percentage was calculated as follows : B / WB (activation) - B / WB (basal)

Activation

%=

x 100 B / W B (basal)

Activation anterior parietal (%) posterior parietal (%) Right anterior parietal (%) Right posterior parieta (%) Left Left

AD 5_+18Patients 6 + 24 2 _+21 6 _+ 24

%

Norma113±13controls 10 _+20 16 ± 16 11 ± 21

No statistical difference was achieved between AD patients and normal controls The correlation coefficient between MMSE score and activation percentage was r= 634 in normal controls and r= . 315 in AD patients for the left anterior parietal cortex; and r= .505 in normal controls and r= . 276 in AD patients for the right anterior parietal cortex Parietat cortex activation was seen in 44 % of AD patients and 79 % of normal controls. Activatienal brain SPECT may be promising to differentiate mild/ moderate AD patients from normal controls but can net be used as a strict criteria.

cO

= l

e-

19 ffl I9 L

S.M. Gogoleva*P, B. Croisile °, C. Houzard °, B. Philippon°,O. Hibert°, R. Itti °, L. Cinotti*°. °HOpital P. Wertbeimer, *CERMEP, LYON, FRANCE, PSakha University, YAKOUTSK, C.I.S. DESCRIPTIVE WRITING IN PATIENTS WITH ALZHEIMER DISEASE: CORRELATION OF NEUROPSYCHOLOGICAL AND CEREBRAL BLOOD FLOW SPECT DATA Neuropsychological tests (NTs) are the most widely accepted assessment of patients suspect of Alzheimer Disease (AD). Alterations in the written description of an image appeared to be an early and sensitive indicator of AD. Furthermore, SPECT cerebral blood flow (CBF) studies showed characteristic regional abnormalities in AD. In this study, we tried to establish correlations between current NTs, written parameters (description of the Cookie Theft picture) and CBF in a population of AD patients. We selected I0 patients having a diagnostic of mild to moderate AD (MMSE = 20.2 -+ 5.1). NTs were: MMSE, Blessed A, Aphasia Battery, BNT, verbal fluency, limb praxis, forward span, backward span, figure copy, immediate recall of the figure, immediate recall of a story. Written variables were: text length (words, clauses), information items, grammatical, semantic and spelling errors. Relative CBF values were obtained from transverse SPECT scintigrams using HMPAO-Tc99m. Regions of interest (ROI) were manually drawn to match to anatomical lobe conformation, and asymetry indices were computed. Correlations were then computed between tests and L/R asymetry on SPECT images. Significant correlations were found between asyrnetries and usual NTs in temporal lobes with: Aphasia Battery (p<0.01), BNT (p<0.0l), story recall (p<0.05); in anterior frontal lobes with: MMSE (p<0.05), direct span (p<0.05); posterior frontal lobes with: Aphasia Battery (p<0.05), BNT (p<0.01 ), story recall (p<0.01 ). For written variables, grammatical errors were correlated with anterior frontal (p<0.03); semantic errors with anterior and posterior frontal (p<0,02), and temporal asymetries (p<0,05). Previous studies showed an early degradation of written semantic errors in AD. Indeed, our results showed that they were correlated with both frontal and temporal asymetries as were also oral language tests. However, written grammatical errors, occurring more lately in the course of the disease, are only linked to anterior frontal asymetries, similarly to attentional capacities and disease severity. This work draw attention towards different functional networks determining specific writing abilities which arc sequentialIy aftiected in the course of AD.

981

19 O

a

P 145

P 147

E. Klemm. *D. Brechtelsbauer, **W. Koehler, *H. Urbaeh, ****A. Piotrowki, F. Grfinwald, **D, B. Linke, ***C. E. Elger, **J. Schramm, *H. Sehild, H.-J. Biersack. Departments of Nuclear Medic~ne, *Radiology, **Neurosurgery, and

***Epileptology, University of Bonn, D-53105 Bonn, Germany, and ****Department of Nuclear Medicine and Magnetic Resonance, Warsaw State Hospital, PL-03285 Warsaw

UNILATERAL HEMISPHERE AMOBARBITAL I D E N T I F I E D BY

FUNCTIONAL

INACTIVATION OF

ONE

(WADA TEST): CORRELATION OF DISTRIBUTION IN THE HIPPOCAMPUS H I G H R E S O L U T I O N 99mTc-HMPAO S P E C T

AND A N G I O G R A P H Y To predict hemispheric dominance of language and memory in the presurgical management of patients with complex partial seizures, functional short time inactivation of one hemisphere by means of intracarotidal injection of amobarbitalhas been introduced. Memory deficits during the W A D A test are attributed to anesthesia of the hippocampus which is both supplied by the anterior choroidal artery (AChA) and by branches of the posterior cerebral artery (PCA) and related structures. To evaluate hemispheric amobarbital distribution, we performed 104 WADA tests (both hemispheres separately or one hemisphere) in 66 patients (mean age 30.6 years, range 8.1 - 55.5 years). Following the routine angiography and an additional an~iographv of the internal carotid . the same procedure as ~ r the X~VADA test, 1 mC1• ~m T c artery (1CA) using HMPAO was injected in the ipsilateral ICA along with 200 mg amobarbital. SPECT was performed using a high resolution dedicated brain g a m m a camera (ASPECT, FWHM 6 - 8 mm). Solely uncus and at least partially the hippocampal head were imaged in 93 out of 104 cases. In 10 out of 11 cases with non-visualization a lesion within the hippocampus was identified. The whole hlppocampus was visualized only in patients with fetal origin of the PCA (hypoplasia of the P1 segment N = 13). If the PCA was opacified only .poorly or shortly by angiography, no tracer was accumulated within the h~ppocampal body or taft. We conclude that high resolution SPECT after intraarterial injection of ~9~Tc-HMPAO can visualize the hippocampus with high accuracy depending on its vascular supply. Thus it is an important tool to estimate the importance of mnestic deficits in patients prior to surgical removal of temporal lobe structures during unilateral functional anesthesia of the ipsilateral hemisphere. Our findings confirm the results of in vivo studies concerning the varying perfusion of the hippocampus by branches of the AChA andthe PCA.

and R.S.Liu.

Taipei Veterans General Hospital, National Yang-Ming U n i v e r s i t y S c h o o l of M e d i c i n e , and N a t i o n a l D e f e n s e M e d i c a l Center, Taipei, Taiwan. ARE THE P R O L A C T I N E L E V A T I O N AND CHANGES OF R E G I O N A L CEREBRAL BLOOD FLOW R E L E V A N T TO SEIZURES? P r o l a c t i n (PRL) e l e v a t i o n s have been noted following g e n e r a l i z e d t e n i c - c l o n i c complex partial seizure and simple partial seizure. A p o s t i c t a l (PC) serum PRL e l e v a t i o n can be used c l i n i c a l l y to aid in d i f f e r e n t i a t i n g e p i l e p t i c from p s e u d o e p i l e p t i c seizures . The goal of this study is to assess the c o r r e l a t i o n b e t w e e n the changes of regional cerebral blood flow (rCBF) and serum PRL secretion following seizures. Fifty patients (34 males, 16 females; Age ranged : 10-47 years, m e a n : 2 8 yrs) w i t h i n t r a c t a b l e complex partial seizure were included. All were e v a l u a t e d by clinical features, interictal (IC)-EEG, 24 hr v i d e o - E E G monitoring, individual IC and PC PRL determinations, IC and PC T c - 9 9 m H M P A O SPECT, and m a g n e t i c resonance imaging, preoperatively. The PC PRL levels were o b t a i n e d w i t h i n 12 min after seizure onset. The PC HMPAO SPECT was p e r f o r m e d w i t h i n 60 min after seizures. The p a t i e n t s were d i v i d e d into two groups a c c o r d i n g to the p o s t i c t a l changes of rCBF by visual interpretation. T h i r t y - s e v e n patients had increased rCBF after seizure onset (Gr,A) and the r e m a i n i n g 13 p a t i e n t s had no changes of rCBF after seizure onset as compared w i t h the IC images (Gr.B). PRL e l e v a t i o n s in G r . A were 68.7 ± 89.5 ng/ml (mean ± 2 s.d.) and those in Gr.B were 41.7 ~ 48.5 ng/ml

.

Significant d i f f e r e n c e of PRL e l e v a t i o n was found b e t w e e n G r . A and Gr.B by Fisher'e exact test

(p < 0.05).

In c o n c l u s i o n , the p r o l a c t i n secretion following the seizure a t t a c k is p o s i t i v e l y related with the changes of rCBF after seizure onset. Neuronal a c t i v a t i o n a c c o m p a n i e d with postictal or ictal increment of rCBF may deplete m o r e PRL than those without change of rCBF after seizure.

982

Te-99rn-HMPAO SPET IN DEMENTIA OF ALZHEIMER TYPE (DAT) IS THERE A ROLE FOR MEDIAL TEMPORAL LOBE QUANTIFICATION'.'

Morphological changes in DAT are known to affect medial temporal lobes (MTL) predominantly. Cerebral perfimion imaging is knm~n to highlight deficils m temporal and parielal areas. Quantitative data related to perfilsios of MTL in patienls wdh DAT are scarce. The aim of this slud3 ',','as 1o clari[v the diagnostic potential of MTL quanfificalion in pcrfusion SPET compared Mth that of tcmporoparietal pcrfnsion Melhads: Ill0 paticnls (52 males. 48 females). 20 ~ilhout (Gr 1). 37 '~ith probable DAT (Gr. 111) and 43 with mild (possiblc DAT. Gr. II) cognitive dysfimction (classification according to NINDS-ADRDA) x~ere included Baseline study ~illl 50(I MBq Te-99m-HMPAO was performed I hour after i.~ iljeclion using a double-head camera (Vertex °. ADAC Lab) Transversal sliccs were reconstmcled: (I) parallcl to the sslcus ccrebri lalcralis and (2) along tl~c CA-CP line (Talairach) = commissnra antcrior - commissura posterior For activity quantification ROls ~ere defined: (It 2 ROIs in the medial temporal (MTL) and (2) 2 ROls in Ihc lemporoparictal lobes (TP) and 4 cercbellar ROIs Then. ralios between MTL / tenlporopariclal and ccrebellar counts (mean value of 4 ROIs) were dctcrauncd. Results: Bolh (I) MTL and (2) temporoparielal acli~ily ratios are significantl3 rcduccd in patients of Gr. II and Gr Ill There is. lmwmcr, a more significant group separation nsmg the activity ratio MTL / cerebellum. This increase in separatiofl applies for boll~

II Gr. l
p / Gr 1

816±48

(n=43>

II Gr.

Ill (n=37)

71.3 i 9 . 4

592:t:79

<0.t)01

<0.001

slice ( 1)

p / Gr. lI
P 148

P 146 L.S. Chu, S.M.Yu, C.H.Yiu, M.S.Su,

K. Hohdorf. J. Halpick. C. Dannenberg. A Secse, S. Berlin. W H Knapp Department of Nuclear Medicine. University of Leipzig. Germany

D. ~. Lee, J.S. Lee, H-C. Song, J.W. Kim, C. Kwark, J.M. Jeong, K.S. Park ÷, J E. Chung, M.C. Lee, and C-S. Koh. [lepartments of Nuclear Medicine and Biomedical E n g i n e e r i n g +, Seoul National U n i v e r s i t y Hospital, Seoul, Korea b[AGNOSIS OF ICTAL HYPERPERFUSION USING PARAMETRIC D I F F E R E N C E IMAGES OF ICTAL AND INTERICTAL SPECT As Lnterictal SPECT could aid ictal SPECT to localize e p i l e p t o g e n i c zones to present baseline state, robust a l g o r i t h m to disclose and d i s p l a y the difference of ictal and interictal p e r f u s i o n would facilitate finding areas of ictal hyperperfusion. We studied ictal and interictal brain SPECT scans of 32 patients having temporal and neocortical epilepsy. We deve].oped parametric image of normalized difference bc!tween ictal and interictal SPECT after s e m i - a u t o m a t i c total count normalization, boundary extraction and s u p e r i m p o s i t i o n - s u b t r a c t i o n . Two of us i n t e r p r e t e d pair of[ ictal and interictal images v i s u a l l y and l o c a l i z e d h y p e r p e r f u s e d zones, and then, on those p a r a m e t r i c images, defined significant clusters of difference in a b l i n d e d fashion. Visual diagnosis of pair images found e p i l e p t o g e n i c zones correctly in 2i patients among total 32(66%). We found hyperperfused clusters in 20 of these 21 patients. H y p e p e r f u s e d cluster were found in 5 more patients using d i f f e r e n c e image, 4 of which were correct compared with ictal EEG or invasive studies. In 2 patients, d i f f e r e n c e image suggested one among m u l t i p l e culprit zones, one of which was correct. Parametric difference image improved d e t e c t i o n rate to 78',~. We conclude that n o r m a l i z e d difference image could aid to the pair of ictal and interictal SPECT by giving q u a n t i t a t i v e v i s u a l i z a t i o n of the ictal h y p e r p e r f u s i o n and improve the localization of e p i l e p t o g e n i c zones.

P 149

P 151

DS Lee, H-C Song~ SG Lee*, JM Jeong, J-K Chung, MC Lee, C-S Koh. Departments of Nuclear Medicine and Neurology*. Seoul National University Hospital, Seoul, Korea

DS Lee, SK Kim, SK Lee*, J-K Chung, MC Lee, C-S Koh. Departments of Nuclear Medicine and Neurologv*. Seoul National University Hospital, Seoul Korea

DIFFERENTIATION OF CRYPTOGENIC LATERAL FROM MESIAL TEMPORAL LOBE EPILEPSY USING REGIONAL ASYMMETRIC INDEX OF F-18-FDG PET. We tried to find the possibility of utilization of F18-FDG PET to differentiate lateral(neocortical) from mesia! temporal lobe epilepsy(TLE) if we adopted quantitative comparison of regional metabolic activities using asymmetric index. We studied 22 pathologically proven mesial TLE(group C in Figure), and 27 lateral TLE patients. Lateral TLE patients were normal on MR(cryptogenic: 15: group A) or had structural lesions(12: group S). Asynzmetric index(AI} was calculated as (ipsilaterel -contralateral) / (ipsiiateral +contra!ateral) x200. AI of medial lobe of cryptogenic lateral TLE was net decreased(-4.6±6.2, >0.05} and AI of lateral lobe was decreased(-13.6±8.9). AI of medial and lateral lobes of mesial TLE was decreased(-3.4!7.7 and -16.5±8.9, respectively). AI of medial lobe of lesional lateral TLE was 7.3±9.1(p<0.05 compared with mesial TLE). It was evident that lateral lobe of lesional lateral TLE had metabolic defect or decrease(AI: -21.4±10.4). While we could not find difference of metabolic activity in lateral temporal lobes between cryptogenic lateral TLE and mesial TLE patients, the difference of metabolic activity was significant in @roupA GroupB GroupC

FREQUENCIES AND IMPLICATIONS OF DISCORDANT FINDINGS OF INTERICTAL SPECT AND ICTAL SPECT IN PATIENTS WITH INTRACTABLE EPILEPSY. Interictal SPECT could be used at best as a reference ±mage to ictal SPECT, and cause sometimes confusion if it had given unexplained discordant findings from ictal SPECT. We investigated implications of discordant findings which occurred in 26 among 268 which found their epileptogenie zones using ictal EEG and/or operative outcome. Sensitivity of interictal SPECT was only 36%. .Among these 268, 69 patients had no structural lesions on MR, 14 of whom had decreased perfusion on interictal SPECT(8 true's and 6 false's(adjacent or contralatera!~). Structural lesion were found in 199 on MR, 103 of whom had decreased perfusion(89 true's and 14 false's). Among 26 having discordant cases, i0 interictai SPECT were proved wrong after operation and/or invaaive EEG and the other 16 were on speculation using PET and ietal EEG. Ictal hyperperfusion was observed in 14 patients in
revealed by AI quantitation. An AI value larqer than -i0 (cutoff: AI) predicted positively for lateral TLE(PPV:80%)

and

Med

Lat

Med

Lal

Med

Lat

negatively for mesia! TLE(NPV:77%). Asyrmmetry of metabolic activity in medial and not in lateral lobe of temporal lobe could give hints about whether the epileptogenic zones were mesial or lateral.

P 150 C. Buchoi~.uel, M. Sapienza, P. Costa, T. Watanabe, C.L. Jorge, R.M.Valerio, EM.T.Yacubian. Centro de Medicina Nuclear (LIM-43), S&o Paulo University Medical School, Brazil.

CLINICAL VALUE OF ICTAL/INTERICTAL BRAIN SPECT IMAGING IN EXTRATEMPORAL EPILEPSY. Preliminary Results. The purpose of this study was to evaluate the value of ictal/interictal brain SPECT in patients with e×tratemporal epilepsy. Fifteen patients with extratemporal epilepsy (8 with frontal lobe and 7 with posterior cortex origin) had ictal and interictal injections of I-IMPAOTc99m. The ictaI injections were performed under continuous video-EEG monitoring, with the images being acquired no more than 2 hours after injection. Focal hyperperfusion superimposed to the suspected lesion on MR] was observed in 6/8 patients with frontal lobe epilepsy (5 focal cortical dysplasias and 1 gliosis). However, these 5 cases with cortical dysplasia had had normal or falsely localized interictal SPECT studies. In this group, 5 patients underwent to surgery and all are seizure-free since then. Hyperperfusion over the lesion or the maximum irritative zone was also demonstrated in 4/7 patients with posterior cortex seizure onset. In 2 others, hyperperfusion was found as a possible propagation signal at the ipsilateral hemisphere (1 at the temporal lobe and 1 at the caudate nucleus). In this group, the interictal SPECT contributed to the definition of the epileptugenic zone, showing h3qgoperfusion in 4 and hyperperfusion in 2 patients. Again, surgery was carried out in 5 patients with successful result in all of them. In all these 15 extratemporal patients, the interictal and ictal EEG did not correlate precisely with MRI, SPECT and histological localizations. In conclusion, ietal SPECT is a very useful functional method for localization or lateralization of the epileptogenic zone in extratemporal epilepsy. However, interictal SPECT seems to have limited clinical value, specially in the evaluation of small frontal cortical dysplasias.

P 152

C O

mm

C"

L

C. H o p p e * , I. T u x h o r n °, MS. K e r d a r °, A. E b n e r °, H. H o l t h a u s e n °, U. B u s c h s i e w e k e * , Dept. of Nuclear Medicine, Ev. J o h a n n e s Hospital* and Epilepsy C e n t e r B e t h e l Q, B i e l e f e l d . Germany ICTAL AND INTERICTAL SPECT FINDINGS IN C H I L D R E N WITH EXTRATEMPORAL EPILEPSY The presurgical localization o f s e i z u r e f o c u s is especially difficult in e x t r a t e m p o r a l epilepsy. Aim: Investigation of noninvasiv S P E C T as a n ictal and interictal diagnostic method compared to o p t i m i z e d MRI imaging and intensive video-EEG. Method:51 children ( 0 , 5 - 1 6 yr) w e r e s t u d i e d in a presurgical protocol, 21 i n t e r i c t a l a n d 34 i c t a l . I0 p a t i e n t s received 9 9 m T c - ~ M P A O , 45 p a t i e n t s 99mTc-ECD. Scanning was performed on SIEMENS DIACA~SPECT-camera with a high resolution collimator. Results: 9/21 interictal examineted patients and 16/34 ictal patients showed a complete congruence o f S P E C T , M R I a n d E E G f i n d i n g s . In 3 / 2 1 i n t e r i c t a l and 9/34 ictal patients showed congruent findings o n l y w i t h M R I o r o n l y w i t h EEG. In 1 i c t a l patient SPECT showed additional i n f o r m a t i o n . In a l l w e f o u n d in 76% o f p a t i e n t s w i t h i c t a l a n d in 5?% o f p a t i e n t s with interictal examination a complete or partial congruence of all findings or additional information b y S P E C T . 75% w i t h a f o c a l cortical dysplasia (FCD) d e m o n s t r a t e d complete and well localized areas of increased perfusion congruent to the cortical abnormality on M R I . T h e seizure focus was successfully resected in 8 patients w i t h F C D . I n 41% o f c h i l d r e n without MRI lesion SPECT was helpful in f o c u s s e a r c h , Conclusion: Ictal SPECT can be a valuable additional element in p r e s u r g i c a l diagnosis in patients with extratemporal epilepsy, particu l a r l y in p a t i e n t s with focal cortical dysplasia.

983

O

P 153 P.Zidi=tski, P.Lass, P.Sloniewski Medical University, Gdafisk, Poland THE REMOTE CEREBROVASCULAR CIRCULATION SEQUELAE OF SUBARACHNOID HAEMORRHAGE ASSESSED BY BRAIN SPECT WITH ACETAZOLAM]DE TEST The aim oftbe study was to assess the regional cerebral brain flow (rCBF) in patients operated because of ruptured intracraniul aneurysm. Patients and methods: we assessed the regional cerebral blood flow and regional perfusion reserve in u period above 1 yr. after the operation by means of brain SPECT in 30 patients operated because of raptured intracranial aneurysm. The scanning was repeated 2 days later, after i.v. injeetinn of 1.0 g of acetazolamide. We correlated the clinical state expressed by GOS scale, initial Hunt-Hess score and regional perfusion reserve. Results: rCBF deficits in the vascular beds involved by extravasated blood were found in 19/30 pts. (63 %). After acetazelamide, hipoperfusion assessed by asymmetry index (AI) doubled (102 % increase). Simultaneously, we found well defined rCBF defects in those sites, where brain tissue was retracted during the operation (26/30 pts 86.6 %). Assymetry index varied between 6.6 - 18.1% (mean 10.61%). After acetazolamide asymmetry index was decreased by mean &98 %. Conclusions: our results indicate the remote cerebral perfusion defects and cerebral perfusion reserve changes after subarachnoid hemorrhage. They may also be the result of longlasting brain tissue compression during the operation.

P 155 D. Moka, K. Smolarz, E. Voth, H. Schicha Dept. of Nuclear Medicine, University of Cologne, Germany.

INFLUENCE OF CARBIMAZOLE ON THE EFFECTIVE HALF-LIFE AND THE RADIOIODINE UPTAKE UNDER THERAPEUTIC RADIOIODINE APPLICATION IN PATIENTS WITH GRAVES" DISEASE Aim: Although a radioiodine treatment (RIT) in thyreotoxic patients receiving antithyroid drugs (ATD) leads, in comparison to nonpretreated patients, to higher treatment failure rates, it is sometimes necessary in patients with concomitant diseases. Aim of this study was to optimize the RIT in these patients. Methods: The influence of the ATD was investigated in 70 patients with shortened effective half-lives of 131-1. In 35 patients the ATD was discontinued on the third day after RIT (group B1 and B2). The progress of the RIT and of a second treatment, which was still needed in 15 patients (B2), was compared to 15 patients under continuous ATD (group A) and to 20 patients where ATD was discontinued 2 days prior to RIT (group C). Results: 2-3 days after discontinuation of the ATD the effective half-life of 131-1 and 131-I-uptake rose significantly: in group B1 from 3.5 _+ 0.2 to 6.3 + 0.2 days. In group C the uptake and the half-life were 61.4 + 2.1%, 5.5 + 0.3 days. In all the patients where a second therapy dose was still necessary (B2) the uptake was significantly higher in those where the ATD were discontinued in comparison to the patients still taking ATD (A). The 131-I-uptake rose after the discontinuation of the ATD in the case of a second RIT, while decreasing significantly in patients with a continuing ATD therapy. Conclusion: Therapy of choice is a washout period of ATD of 2 days before RIT (group C). The required therapy dose then is lower and the rate of outcome success is similar in all groups. Both effective half-life and 131-I-uptake do still qualify as parameters to guide an apparently insufficient RIT whilst the patients are on the therapy ward. The use may allow to reach a sufficient thyroid dose even without a second therapy.

984

P 156 M.R. Castellani, L. Maffioli, M. Resnick, E. Seregni, A. Chiti, E. Bombardieri. D#vision of Nuclear Medicine, National Cancer Institute, Milan, Italy R E S U L T S A N D M A J O R M Y E L O T O X I C I T Y O F 1-131 T H E R A P Y I N DIFFERENTIATED THYROID CARCINOMA From Oct 1987 to Dec 1990, 195 pts with differentiated thyroid carcinoma were referred to us to receive 1-131, for ablation of thyroid remnants or for treatment of metastases, after total thyroidectomy. During the 6-10 yrs of follow-up, all the pts were treated with l-thyroxine and, in some cases, with external radiotherapy on bone metastases (mts). 117 pts (82 papillary (PTC) and 35 follicular (FTC) tumors) were considered evaluable: 78 pts were excluded for inadequate follow-up or lack of iodine uptake. 37-5.55 GBq of I-131 per cycle was administered, to a maximum of 55.5 GBq. The 82 pts (53 F, 29 M) ~ith PTC (14-80 yrs old), were studied for 6100+ months (mths) of follow-up (mean 62.2 mths) and the 35 pts with FTC (23 F, 13 M; 20-76 yrs old), for 2-92+ mths (mean 50.3 mths). Results: 45/82 pts with PTC and 11/35 pts with FTC, were treated for ablation of thyroid remnant of locally advanced tumor :t: thyreoglobuline elevation: 55/56 remained free of disease (mean duration 59.4 mths); one pt (FTC), probably with local residual tumor, recurred 26 mths later, after 4 cycles of therapy (22.2 GBq). In 37/82 PTC pts treated for functioning mrs (respectively 16 lymph node; 16 lung, 4 bone and 1 bone and lung), the following results have been obtained: 27/37 complete remission (CR) (73%) (94% lymph-node; 64.7% lung, 40% bone) ~ith a mean duration of 52.87 mths (range 42-72m), (mean act 13.74 GBq); 9/37 partial remission >50% (PR) (24.3%) (mean duration 47.3 mths; mean act. = 17.27 GBq); lpt with bones mts remained stable for 48 mths (44.4 GBq administered). In 24/35 FTC pts with functioning rots (2 lymph nodes, 3 lungs, 12 bone, 4 bones and lungs and 3 multiple rots) we obtained: CR in 6 pts (25%), respectively in 2/2 pts with lymph node rots, (mean duration: 58.5 mths), in 2/12 with bone rots (mean duration: 33.5 mths; mean act. 38.85 GBq) and in 2/4 pts with lungs and bones mts (lasting 49.5 mths; mean act. 19.42 GBq). A PR was obtained in 7 pts(29%), respectively in 1/3 pts ~ith lung mts. (lasting 48 mths) in 5/12 pts with bone mrs (mean duration: 56.8 mths, mean act 43.29 GBq) and in 1/4 pts ~ith both lung and bone rots, lasting 45 mths. The disease remained stable, respectively in 2/3 pts with lungs mts (for 30 mths), in 5/12 pts with bone rots (mean time=61 mths), and in 3pts with multiple rots (bone, lung,soft tissues and liver)(mean time 26.3 mths). Toxicity: lpt with lung and disseminated bone mts died 2 mths after the first therapy for agranulocytosis; another patient retreated after 60 months for bone progression, developed a myelodisplasia (cumulative act 44.4 GBq) and died; another pt developed a promieloc'ytic leakaemia after the administered activity of 49.95 GBq.

P 157 C. LoewenthaL M. Pedrosa, A. Fonseca, M. Henriques, M. Vieira, [nstituto Portugu~s de Oncologia Francisco Gentil, Centro de Lisboa, E. Prof. Lima Basto 1093 Lisboa Codex, Portugal A RETROSPECTIVE EVALUATION OF PATIENTS TREATED WITH H I G H CUMMULATIVE DOSE RADIOIODINE THERAPY From our pool of seveial hundred differentiated %'roid carcinoma patients {pts) undergoing radioiodine therapy, we selected those who have attained doses in excess of 30 GBq, and analyzed the pei~aining data retrospectively. Our primary objective was to identi~' possible secmtdary effects of such high doses of radioiodin~(13 II) We also analyzed the role 1311 tllerapy played m the evolution of the disease Our population consists of 24 pts (19 female, 5 male; mean age at diagnosis of 49.7 yrs (21-72)), 15 with papillary and 9 with follicular thyroid cancer. Twenty patients presented with cervical inasses, whereas in 4 pts, diagnosis became apparent after a primary bone metastasis. Radioiodine therapy was instituted in all patients after total thyroidectomy (in either 1850 or 2590 MBq doses) and was continued because of either metastases (cervical, lung, bone) or high thyroglobulin levels, in doses which varied between 3811 and 4181 MBq. The follow-up period ranged from 5 to 25 yrs and the number of therapies varied from 8 to 19, with a mean of 11 therapies. We found in this group of pts a higher than normal incidence of the follicular variant. We observed a high percentage ofpts with long-standing thyroid disease before the definitive diagnosis of thyroid cancer, namely 4 patients with multinodular goiter. Also, the histological diagnosis was difficult to determine in 8 patients, whose tumors were previously classified under another type, usually medullary thyroid carcinoma. O f the pts studied, one was lost to followup after 11 therapies, 6 are deceased and 17 are still being followed-up in our outpatient clinic. We compared the complete blood counts (CBCs) from the time of the f'trst therapy with the latest CBCs and found only 5 cases of mild anemia. We did find one case of acute Imyelogenous leukemia after 13 therapies. No other cases of severe hematological abnormalities were detected. Second cancers were detected in 2 other pts, a basal cell carcinoma and an endometrial carcinoma. At the present time, there is no evidence of other neoplastic disease in any of the pts.

P 158

P 160

F c~n RB()N* M II[U-I~ O CASELLES**P eUlmL* S ZERIX)UD*.I BERRY= H REGIS=, ~ d-7"~6decineNucleaireCHU FOU1.OUSE[,bkNO[Ell.** U~ite de Ph?siqu¢CENTRECLA1D/US REGAlD

C. Loewentha[, A.T. Fonseca, M.R.Vieira, Institute Portugu~s de Oncologia Francisco GentiM.isbna, Servi9o de Medicina Nuclear

IOUII)LSE

]ODINIi 13J TREA'I'.kllv.NU"OF WELL D[t-I:ERt{NCLa_TEDTHYROID CARCINO.'vl4IN PATIENT ON DIAl ASIS I:ORCIIRONIC RFAAL FAIIIiRI2. [Nq'RO])[ CI tON ; To our knowledge, there are few documented cases N" iodine-13 l treatment lot ,,','ell difl~renciated thyroid earcinoma in patient on hemodialysis therapy. Questions about th)roidal icxline-131 dose and contamination of material from dialysis equipment remain unanswered. XIATIiRLM£ AND MIZIIODS

:

A 56 3,'ears old female patient was treated with 3700 MBq

(tOf~nCi) of t31[ lbr a well diflkmenciated thyroid carcinoma after completed thyroid resection (1311 uptake at 24 hours = 3%). This patient was on thrice-weeNy maintenance hemodialysis therapy lot chronic renal failure. Bleed samples were dra,,,,n from the patient after the 1311 therapy initiation over a period of 5 days. Dialyses were made at day 3 and 5 after icvdine administration. Thyroidal iodine activity was evaluated on calibrated scintigmphic data. Dose rate at 1 meter from the whole body and disposable material from the dialysis equipment has been monitored using a gamma camera and a Ge'fger Mailer detector. RE,St't.TS : We have observed a mean whole body dose rate at 9mRad/h and a circulating acd',ity of 1,8% of the administered dose until the first dialysis, It reduced the whole body dose rate to 60% and the circulating activity to 78%. In comparison with other organs (pamtides, submandibular glands), the thyroidal iodine biological hall" life was high (77,66h). The thyroidal iodine clearance by the dialysis was less imlx)rtant than for other organs. Dialysis equipment dose rate was less than lmRad/h (X)NCLUStON : We conclude that iodine therapy can be done without significant c~.mtamination of the dialysis equipement. According to the litterature, the thyrdidal iodine hall" life is significantly lower in comparison with normal euthyroid patients, but the circulating acti;ity must be be taken into account to evaluate the deposited dose in the thyroid. Moreover, dialysis could be done earlier to decrease the absorbed dose by extra

EVALUATION OF SALIVARY GLAND LESIONS IN D I F F E R E N T I A T E D THYROID C A R C I N O M A PATIENTS TREATED WITH RADIOIODINE Patients (pts) treated with high doses of radioiodinc (131 I) f0; differentiated thyroid carcinmna (DTC) connnordy complain of xerostomia. In the present study, vve evaluated changes in function of the nlajor salivary glands as observed on salivary scintigraphy in a small group of DTC pts created with 131 [ at our Institution ill the last five years. We studied 31 pts (6 nrerh 25 women), with ages ranging between 20 and 72 years. Nine of these pts performed a salivary scintigraphy after their first 1311 therapy, whereas the majority (22 pts) were studied after two or more therapies. The total administered activities ranged from [813 MBq to 47 GBq (49 to 1259,5 mCi). Salivary gland scintigraphy was performed on a GE 400T Gama-Camara, alter i.v. administration o f 185 MBq (5 mCi) 99mTc-pertechnetate. Twenty minutes into the study, lemon juice was given to produce an excretory phase. We divided the functional alterations observed on scintigraphy according to the number and type of gland affected and classified salivary function according to a four-grade scale (Grade 0: no evidence of salivary gland lesion; Grade I: mild lesion, corresponding to a slight reduction in amplitude of the time/activity curves; Grade ll: moderate lesion, or greater reduction in the amplitude o f the curves and/or changes in excretory function; and Grade Ilk severe lesion, or total absense of uptake). We detected functional deficits in 26 (84%) o f the 31 pts studied, with evidence o f damage to 43 parotid glands and 18 submandibular glands. In the group of patients studied after their first radioiodine therapy, 4 out of 9 (44%) patients were shown to have abnormal salivary scintigraphy. In the group studied after two or more therapies, no normal exams were found. We conclude, in this preliminary study, that the global incidence o f salivary gland lesions is high and that there seems to be evidence for an increased incidence of lesions with higher cummulative doses o f 131 I. In our group of pts, the parotid glands were more commonly affected than the submandibular glands. Further studies will be needed to validate these conclusions.

cO

| m

e,-

thy roidal tissues.

o. P 159

P 161

G a l o f r ~ P, G u t i ~ r r e z S ~, Carbonell E*, sim6 M, Rosa I, Creus A =, M a r c o s R ~. Servei de M e d i c i n a Nuclear, H o s p i t a l s Vall d ' H e b r o n ; G r u p de Mutag~nesi, C. Biol~giques, U n i v e r s i t a t Aut~noma*. Barcelona, Spain.

B_. Melter , M. Baehre, I. Lauer, E. Richter

E V A L U A T I O N OF THE G E N O T O X I C RISK A S S O C I A T E D TO 131-I THERAPY. A STUDY O N THYROID C A N C E R PATIENTS BY USING THE M I C R O N U C L E U S TEST. 131-I is c o m m o n l y u s e d to treat h y p e r t h y r o i d i s m and thyroid c a n c e r patients. A q u e s t i o n that remains open is the p o s s i b l e s e c o n d a r y harmful effects that this t h e r a p y can i n d u c e on the p a t i e n t ' s health, m a i n l y t a k i n g into account the g e n o t o x i c p o t e n t i a l of radioiodine. To add further i n f o r m a t i o n on this subjectf here we present the results o b t a i n e d in a f o l l o w - u p study carried out with thyroid c a n c e r p a t i e n t s r e c e i v i n g 131INa as adjuvant t h e r a p y after total thyroidectomy. To d e t e c t s e c o n d a r y c y t o g e n e t i c effects, we have evaluated the micronuclei (MN) frequency in peripheral blood l y m p h o c y t e s ° It must be pointed out that MN have recently been recomended as a valuable endpoint to detect genotoxicity. Two d i f f e r e p t groups have been studied: A) 56 being a n a l y s e d d u r i n g the annual check-up, w h o m received the last t h e r a p e u t i c a l dose from 1 to 6 years before, and B) 39 p a t i e n t s from w h i c h four blood samples were taken over time: p r e v i o u s to the treatment and one week, six months and one y e a r after the treatment. A l t h o u g h the m e a n f r e q u e n c y of b i n u c l e a t e d cells with MN (BNMN) in group A does not differ s i g n i f i c a n t l y from the v a l u e s o b t a i n e d in a concurrent control of 70 donors (25.89 vs 23.99), those patients r e c e i v i n g the last dose d u r i n g t h e three previous years show s i g n i f i c a n t increases w i t h r e s p e c t to those that received r a d i o i o d i n e 3-6 years b e f o r e (29.52 vs 22.00). W i t h reference to the results found in group B, our data indicate that the frequency of B N M N i n c r e a s e s s i g n i f i c a n t l y one w e e k after the treatment (31.10 vs 15.97) and this high frequency still remains in the s a m p l e obtained six months later (28.57), following a d e c r e a s e (25.91) in the sample o b t a i n e d a year after, a l t h o u g h until now, o n l y 12 patients have b e e n scored in this last sample. T h e s e r e s u l t s indicate that 131-I t r e a t m e n t increases the level of c y t o g e n e t i c damage, detected in p e r i p h e r a l blood l y m p h o c y t e s , these a l t e r a t i o n s r e m a i n i n g for at least one y e a r a f t e r treatment.

x.__

ll)

Clinic of Radiotherapy and Nuclear Medicine, Med. University of Luebeck, Germany

O

n

Urinary iodine excretion: A potential indicator for delayed cell death after radioiodine therapy? The thyroidal iodine content is well known from x-ray fluorescence analysis. After radioiodine therapy (RIT), it can be expected that the iodine stored in thyrocytes is released in relation to the aim volume as a consequence of tissue conversion. Therefore, we investigated the course of iodine excretion in the urine after radioiodine therapy in a prospective study. Patients and Methods: In 2 1 4 patients with benign thyroid diseases urinary iodine excretion (UIE), calculated as pg I/g creatinine, was determined before, under and after RIT. The aim volume was determined by ultrasound and thyroid scintigraphy. Therapeutic activities were planned individually. Median values of UIE (M) at each determination time were calculated. For statistic evaluation, the paired Wilcoxon test was used. Results from heterogeneous groups were submitted to the nonparametric Mann-Whitney test. Results: No significant changes of UIE were found during the radioiodine uptake test so that the mean test UIE (roT, M = 100 pg I/g croat.) could be calculated. When compared with mT, UIE was significantly higher under therapy ( M = 190 /~g I/g creat., p < 0 . 0 0 0 1 ) and 6 months (M = 1 5 1 /Jg I/g creat., p < 0 . 0 0 0 1 ) after therapy. The increase of UIE correlated with the aim volume (p < 0 . 0 5 ) . Projections about the correlation between the range of the lmeasured values and the iodine stored in thyrocyts confirmed our results. Conclusion: Radioiodine therapy increases urinary iodine excretion for months. These effects seem to reflect the decline of thyrocytes after RIT. Consequences for therapeutic approaches and treatment modalities have to be discussed. 985

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S. Me]!eP, S. Chittenden a, R. McCready a, J. Kohler t, M. Tristam t, V. Lewington t, T. Hilditch °, T. Wheldon °, A. Barrett". Departments of Paediatric Oncology and Nuclear Medicine at Royal Marsden Hospital a, Sutton, General Hospital, Southampton t and Western Infirmary, Glasgow ° .

M Tristam, J S Fleming, V J Lewington, M A Zivanovic and S L Johns, NUCLEAR MEDICINE, SOUTHAMPTON UNIVERSITY HOSPITALS NHS TRUST

131-1 mlBG THERAPY COMBINED WITH CHEMOTHERAPY FOR NEWLY DIAGNOSED STAGE 4 NEUROBLASTOMA: A UKCCSG PHASE I / II PILOT STUDY.

TUMOUR

131-1 mIBG therapy has been employed for more than 10 years in the treatment of neuroblastoma and it has been shown to be an effective and well tolerated therapy. A previous UKCCSG phase I / II study of mIBG therapy in neuroblastoma patients, who had previously undergone intensive chemotherapy, showed e response rate of 33% and established a maximum tolerated whole body dose (MTWBD) of 2.0 Gy. The current UKCCSG pilot study of.combined chemotherapy and mlBG therapy aims to establish the MTWBD in de n o v o patients. A method has been devised to estimate the activity required to deliver a particular whole body dose from subsequent therapy by performing the dosimetric study at the same time as the initial 123-1 mlBG diagnostic scan. The dosimetry is performed under simulated therapy conditions of hydration and requires only e ceiling-mounted radiation detector in an area of low radiation background. In order to optimise therapy, we aimed to deliver a single fraction of 131-1 mlBG at an activity calculated to deliver a WB dose of 1.5 Gy prior to chemotherapy. To date 5 de novo patients over the age of 2 years with poor prognosis stage 4 neuroblastoma have been treated with 131-1 mlBG: 3 patients within 10 days of diagnosis and prior to starting chemotherapy and 2 patients within 3 weeks of the first chemotherapy on the OPEC/OJEC protocol. The actual WB doses received by the 5 patients ranged from 0.89 - 1.45 Gy. Myelosuppression was the only observed toxicity and has been closely correlated with the WB dose received, regardless of the degree of marrow infiltration at diagnosis. When mlBG is combined with chemotherapy in de novo stage 4 neuroblastoma patients, we found the dominant toxicity to be neutropenia, in contrast to the dominant thrombocytopenia seen when mlBG has been used as a single modelity in patients heavily pre-treated with chemotherapy. The WB dose delivered by a given activity of 131-1 mlBG predicts the degree of subsequent neutropenia, which is the critical end dose-limiting consideration when mlBG therapy is used in combination with chemotherapy, in order not to compromise the subsequent treatment of newly-diagnosed patients. The method of dose calculation by simulation with a pre-therapy 123-1 mlBG dosimetric study is sufficiently accurate for clinical purposes, but tends to underestimate the WB dose subsequently received from 131-1 m[BG therapy. We hope to overcome the logistic constraints which at present make it difficult to administer mlBG therapy prior to chemotherapy in preparation for a phase III UK study.

DOSIMETRY

IN M I B G

THERAPy:

A

CASE STUDY

Am eight year old girl with stage IV neuroblastoma was treated with ii GBq of radioiodinated M I B G (meta-iodobenzylguanidine), as part of Phase I Pilot Study of combined chemotherapy and targeted radionuclide therapy. A d m i n i s t e r e d activity was prescribed on the basis of diagnostic retention measurements and was aimed to deliver a 1.5 Gy whole body dose. Sequential SPECT studies were acquired before and after treatment and were quantified to assess tumour volume and activity. Tumour dose was evaluated using the standard MIRD formalism. During fifteen days following the administration of radionuclide, tumour volume decreased threefold, from 120 to 40 milliliters. This was attributed to the combined effect of radio- and chemotherapy. When residual tumour was excised six months later, pathology reports confirmed the accurate assessment of its volume. . Tumour dose was estimated at 50 Gy. While the dose accumulates with time, the dose-rate decreases from 0.5 Gy per hour on day one to 0.03 Gy per hour ten days later. At this level, low dose-rate effects, due to repopulation and repair, might reduce the efficacy of treatment. Howe~er, since over 95% of the dose is delivered during the first week, the effect is negligible. This example illustrates feasibility of accurate tumour dosimetry. While the validity of MIRD approach is questioned, especially at subcellular level, it remains a useful method of assessment of risk and benefit of radionuclide therapies.

P 163

P 165

~ , L. Golberg, Cross Cancer Institute, Nuclear Medicine, Department of Oncologic Imaging, Edmonton, AB, Canada

Marion de Jon,q, Willem Bakker, Eric Krenning, Wout Breeman, Marcel vd Pluijm, Bert Bernard, Thee Visser, Eduard Jermann, Martin B(~he, Pia Powell, Helmut R M&cke. Dept of Nuclear Medicine, Dept of Internal Medicine III, University Hospital Dijkzigt, Rotterdam, The Netherlands. Department of Nuclear Medicine, Kantonspital Basel, Basel, Switzerland.

1-131 mIBG THERAPY--A CRITICAL LITERATURE REVIEW. 1-131 mIBG was first reported in 1983 as a potential therapy in patients with some neuroendocrine tumors. We have evaluated the literature available on the therapeutic use of mIBG using MEDLINE. Sixty-eight papers related to mIBG therapy were identified. Each was reviewed for authorship, data overlap, evidence of protocolization, entry and exclusion criteria; formal assessments a n d definitions of response, rationale and statement of administered dose, definitions and assessments of toxicity and study objectives. This review has yielded the following results: Twenty journals were represented; 24 papers were contributed by 3 groups. Patient selection criteria were identified in less than 15 papers and there was evidence of a treatment protocol in 9; 22 papers represented case reports. In 15 papers a rationale for the administered dose was glven; the administered doses ranged from 30600 mCi per administration and up to 2,300 mCi were glven as cumulative doses. Standard criteria for toxicity were used in 22 papers. Definitions of response were given in 29 papers evaluating patients' tumor volume and in 5 papers assessing clinical response. These data suggest an immaturity in the nuclear medicine literature with the development, conduct and planning of clinical trials. This immaturity is postulated as limiting the evolution of the discipline, limiting acceptance of data by the oncology community and the opportunity to develop multi centre and multi disciplinary protocols.

986

RECEPTOR BINDING AND BIODISTRIBUTION OF Y-90- AND In-111-(DOTA,D-Phe1,Tyr-3]OCTREOTIDE, PROMISING FOR RADIONUCLIDE THERAPY. We evaluated the potential of radiolabelled [DOTA,D-Phe-l,Tyr-3]octreotide (DOTATOC) as radiopharmaceutical for in rive detection and peptide-raceptor-radionuclide-therapy (PRRT) of somatostatin receptor-positive tumours. In vitro octreotide receptor binding of In-111-DOTATOC and rat in vivo metabolism of Y90- and In-11 I-labelled DOTATOC was investigated in comparison with [In-111DTPA,D-Phe-1]octreotide (In-111-DTPAOC). Results: In-111-DOTATOC had a similar affinity as octreotide for its receptor in rat cerebral cortex microsomes. In vivo: 4, 24 and 48 h post injection of Y-90- or In-1 t 1-DOTATOC, radioactivity (%lD/g) in the octreotide receptor-expressing tissues pancreas, pituitary, adrenals and tumour was a factor of 2-6 that after injection of In-111-DTPAOC (Table data 24 h p.i., mean ± SEM, n_>6): In-111-DTPA In-111 -DOTA Y-90-DOTA Blood 0.003 ± 0.00 0.002 _+ 0.00 0.0008 _+ 0.000ab Kidneys 1.91 ± 0.11 2.32 -+ 0.13a 1.40 _+ 0.O5b Liver 0.05 _+ O.O0 0,05 ± 0.00 0.06 _+ 0.O1 Pancreas 0.69 _+ 0.06 1.70 ± 0.13a 1.97 ± O,17a Spleen 0.03 _+ 0.00 0.04 +_ 0.00 0.07 ± 0.O2a5 Adrenals 1.33 -+ 0.10 3.19 ± 0.27a 6.76 + O.27ab Pituitary 0.51 ± 0.01 1.22 _+ O.03a 2.79 ± O.21ab Femur 0.O3 ± O.00 0.05 ± O.01a 0.08 ± O.03a Tumour 0.58 ± 0,08 1.12 ± 0.11a 1.63 ± O.2ab a) P
P 166

P 168

T.M. Behr I, S. Memtsoudis ~, R.D. Blumenthal 2, R.M. Dunn 2, K. Nebendahi l, R.M. Sharkey2, D.M. Goldenberg 2, W. Becker ~. Dept. of Nuclear Medicine I of the University of G~ttingen, Germany, and Garden State Cancer Center 2, Belleville, N J, USA.

T.M. BeN. ~, E. Holler 2, B. Wrrmarm~, R.M. Sharkey 4, R.M. Dunn 4, W. Hiddemaml 3, H.J. Kolb '~, D.M. Goldenberg 4, W. Becker t. Depts. of Nuclear Medicine I and Oncology ~, GeorgAugust-University of Gtittingen (FRG), Dept. of Oocology-', Ludwig-Maximilian-University of Munich (FRG), and Garden State Cancer Center 4, Belleville, NJ (USA).

RADIOIMMUNOTHERAPY OF COLORECTAL CANCER IN MINIMAL RESIDUAL DISEASE AND IN AN ADJUVANT SETTING: EVALUATION OF 131I- AND 9°y-LABELED IgG AND FRAGMENTS VERSUS STANDARD CHEMOTHERAPY WITH 5-FLUOROURACIL / LEUCOVORIN IN A NUDE MOUSE MODEL

CD22 AS TARGET MOLECULE FOR RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY WITH THE MONOCLONAL ANTIBODY LL2 IN ACUTE LYMPHATIC LEUKEMIA AND WALDENSTR()M'S MACROGLOBULINEMIA

At the time of surgery, occult (micro-)metastases are present in more than 50% of colorectal cancer patients. Frequently, adjuvant chemotherapy is unable to prevent tumor recurrence. Therefore, innovative therapeutic strategies are needed. The aim of this study was to compare the therapeutic efficacy of radioimmunotherapy (IgG vs. Fab, ~3xIvs. 9ay) to standard chemotherapy in a (micro-)metastatic animal model. Multiple pnlmona2¢ metastases of the human colon cancer cell line, GW-39, were induced in nude mice by intravenous injection of a i0% minor cell suspension, as has been described earlier (Sharkey et al., J Natl Cancer Inst 1991; 83: 627). Whereas control groups were left untreated, therapy was initiated on day 1, 3, 7, 14, or 2I after tumor inoculation with the high-affiinty (K~=1091/mnl) monoclonal anti-CEA antibody, MN-14 (IgG or Fab, labeled with ult or 9Oy), or chemotherapy (5-FU/leucovorin) at their respective maximurn tolerated doses (MTD). The renal accretion of 9°y-Fab was reduced by the administration of D-lysine, as has been described earlier (BEN" et at., Cancer Res 1995; 55: 3825). Weight and survival of the mice were monitored at weekly intervals; animals surviving 7 months were sacrificed for histology. The untreated controls died from rapidly progressing pulmonary metastases at 5 - 7 weeks alter minor inoculation. The lifespan of animals treated with 5-FU/LV was prolonged for only 2-4 weeks, depending upon the time-point of the treatment initiation (the earlier the longer). At their MTD, 131I-IgG and -Fab (260 gCi / 3 mCi) led, also histologically, to an approximately 90% cure rate when given 1 or 3 days after tumor inoculation, whereas 9°Y-IgG at its MTD (100 p.Ci) was curative in only 60%. In 1week-old ~unors, 13~I-Fab was superior (80% cures) to 131I-IgG(45%) or the respective 9°Y-labeled immunoconjugate (IgG and Fab, both 10%). Although prolonging life in 2week-old tumors, tatI-IgG was unable to achieve cures, whereas 131I-Fab was still sucessful in 35%. In 3-weak-old tumors, 131I-or 9°y-IgG, even at their MTD with bone marrow transplantation, prolonged life for only 3-4 weeks, whereas 9°Y-Fab (MTD with D-Iysine 400 gCi) still allowed long-term survival in 20% of animals. These data suggest that, hi minimal residual disease, radioimmunotherapy may be superior to conventional chemotherapy. Fab fragments seem to be superior to complete IgG, probably due to their higher diffusion capacity and more homogenous tumor uptake. The superiority of 13~I in treating smaller metastases and of 90y in more advanced cases is consistent with the path length of the respective 13-particles.

CD22 is a 135-kD glycoprotein of the immtmoglobulin superfemily which is expressed on B lymphocytes. It has been used successfully as target molecule for radioimmunodetection (RAID) and -therapy (RAIT) of B-cell Non-Hodgkin's lymphoma with the monoclonal antiCD22 Mab, LL2 (e.g., Goldenberg DM et al., .Z Clin. OncoL 1991, 9: 548). Since CD22 is highly expressed on most blasts in acute lymphatic leukemia of B-ceil origin and on the malignant lymphocytes of macroglobulinemia as well, we studied the potential of LL2 for detection and therapy of these two hematological malignancies in two pilot cases. A 43-year-old male suffered from macroglobuimemia, first diagnosed 4 years earlier. The igM produced by the malignant clone cross-reacted with a ganglioside of peripheral neurons, causing severe and progressive sensomotoric neuropathy. Several bone marrow biopsies as well as a splenectomy were not able to demonstrate the presence of a malignant clone responsible for the IgM production. A localized tumor was suspected, but was not detected by any radiological procedure. Thus, the patient underwent RAID with 9~Tc-LL2 Fab'. The second patient was a 2g-year-old male who had common acute lymphatic leucemia (c-ALL) for 8 years. He had failed 6 high-dose chemotherapy regimens with allogenie bone marrow or stem cell transplantations from his HLA-compatible brother. He had also failed two immtmotherapeutic approaches with bispecific routine antibodies, which had caused high titers of HAMA. The patient was treated with high-dose radioirunmnotherapy with. mI-labeled humanized LL2 IgG in myeloablative intention with stem cell support. Although all diagnostic procedures had failed in the macroglobulinemia patient, 99~TcLL2 Faro' showed excelient targeting of widespread parailiac, mediastinal, axillary and cervical lymph node involvement (size < 1 cm !) as well as a patchy uptake all over the patient's bone marrow as a sign of generalized minor infiltration, precluding any localized treatment approach, such as external beam irradition. The c-ALL patient underwent a diagnostic study with humanized LL2 (50 mg of protein, 8 mCi mI) in order to assess tumor targeting and dosimetry, and was treated, based on its result, with 258 mCi hLL2 at the same protein dose. Strong uptake occurred in the patient's bone marrow as well as several extrarnedullary tumor sites (lymph nodes, spleen, muscular infiltration of the thigh). At a marrow dose of 30 Gy (whole-body 3.5 Gy, lung 12 Gy), the patient went into complete remission and bone marrow aplasia within two days. Reingraltment of the red marrow took place rapidly. The patient experienced a complete remission lasting for 6+ weeks. Relapsed ALL and Waldenstrrm's macroglobulinemia seem to be suitable targets for a radioimmunotherapeutic approach with the anti-CD22 monoclonal antibody, LL2. Future studies will show whether high-dose RAIT with heterologous stem cell support may be able to induce longer-lasting remissions or even be curative in these hematologic malignancies.

cO im e-

ll) L. P 167 T.M. Behr 1, E. Wulst I, S. Gratz ~, S. Radetzky j, K. Nebendahl I, F. Raue2, W. Becker !. Department of Nuclear Medicine of the Georg-August-UniversityI, Ghttingen, and Department of Endocrinology 2 of the University of Heidelberg, Germany. RADIOIMMUNOTHERAPY OF MEDULLARY THYROID CANCER: EXPERIMENTAL COMPARISON TO CHEMOTHERAPY AND PRELIMINARY RESULTS OF AN ONGOING PHASE-I/II CLINICAL RADIOIMMUNOTHERAPY TRIAL Therapeutic options are limited in advanced metastatic medullary thyroid cancer (MTC). Whereas a variety of chemotherapeutic regimens could achieve only limited success (response rates _<30%), more recently, radioimmunotherapy (RAIT) with radiolabeled anti-CEA antibodies has shown promising results. The aim of tins study was to compare, in an animal model, the therapeutic efficacy of RAIT to "standard" chemotherapy, as well as to evaluate the clinical use of RAIT in patients with metastatic MTC. Nude mice, bearing subcutaneous xenografts of the human MTC cell line TT, were treated either with different chemotherapy regimens (doxorubicin alone or combined with cisplatinum, or a 5-FU/dacarbazine/streptozotocin scheme) or were injected with the 13~l-labeled anti-CEA monoclonal antibody, F023C5 (IgGi subtype). Control groups were left untreated. The maximum tolerated dose (MTD) of each agent was determined. Toxicity and tumor growth were monitored at weekly intervals. Bone marrow transplantation (BMT) was performed in order to enable dose-intensification. Five patients with metastatic MTC have been euroled so far at our institution in an ongoing clinical phaseI/II RAIT dose escalation trial with the 131I-labeled anti-CEA antibody, F023C5. From the chemotherapeutic schemes tested, doxorubicin monotberapy was most effective; combination with other agents did not result in an increased anti-tumor efficacy, but in more severe toxicity. Whereas chemotherapy, regardless of the regimen used, was unable to induce complete remissions if administered below the respective MTD, complete remissions lasting up to 6 weeks were seen with RAIT already at injected activities of 60% of the MTD. Response rotes were strongly dependent upon the tmnor size at the time of the initiation of therapy (the smaller the tumors the higher the response rate), which is in accordance to an exponential increase in tumor uptake, thus radiation dose, with decreasing tumor size. BMT-assisted dose-intensification led to further increased anti-tumor effficacy. As in the animal model, side-effects of clinical RAIT were restricted to transient myelotoxicity. Three of four assessable patients showed evidence of anti4umor effects lasting up to 8+ months. The animal model, as developed by us, seems to be useful for the preclinical testing of therapeutic agents for the systemic treatment of iWfC, reflecting the actual clinical situation (response rates, toxicity) fairly well. Experimentally as well as clinically, at equitoxic doses, RAIT with radiolabeled anti-CEA antibodies seems to be superior to chemotherapy of metastatic MTC. Combination of RAIT and chemotherapy may further increase the therapeutic efficacy. (Supportedin part by Henning Berlin GmbH).

L

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I11

A.Chacarova, ~ E.Petkova Department of Radiotherapy & Department of Nuclear Medicine* National O n c o l o g y Center, Sofia, B u l g a r i a

O

THE PALLIATIVE EFFECT OF RAD1OPHOSPHOROUS TREATMENT IN PATIENTS WITH METASTATIC BONE DISEASE

P-32 was used for palliative treatment of painful metastatic bone disease. 93 patients(pts), m e a n a g e 67, r a n g e 48 - 76, entered the study: 78 w e r e w i t h breast c a n c e r and 15 w e r e with prostate cancer. W h o l e b o d y b o n e scintigraphy w a s carried out b e f o r e and after r a d i o p h o s p h o r o u s treatment, u s i n g 9 9 m T c M D P (555 M B q ) . A l l ~ts w e r e w i t h adequate h a e m a t o l o g y i c a l function ( W B C > 3 . 5 x l 0 / 1 and P L T > 140x10~/1). T h e s e pts w e r e treated w i t h d o s e s starting at 37 M B q and i n c r e a s i n g to 222 M B q at 30 - 60 d a y s intervals. In 7 8 % o f cases, P - 3 2 t h e r a p y resulted in a s y m p t o m a t i c pain reduction, w i t h d u r a t i o n o f r e s p o n s e 3 - 6 m o n t h s , at t h e c o s t o f n o s i g n i f i c a n t side effects. A f t e r treatment o b j e c t i v e r e s p o n s e w a s obtaind on hone scintigraphy. Alkaline phosphatase levels s h o w e d a significant decrease in treated ptso S e r u m P S A and C A 15-3 v a l u e s w e r e reduced in 3 5 % and 4 7 % respectively. In conclusion m a x i m u m a d m i n i s t e r e d dose o f P - 3 2 (222 M B q ) w e r e e f f e c t i v e f o r the palliative t r e a t m e n t in 7 8 % o f pts with painful bone m e t a s t a s e s for 3-6 months.

987

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R. Herranz F. Ports, A. Garcfa, S. Vidal-Sicart, C. Conill ~, JJ Grau 2, J. Alcover 3, D. Fuster, J. Setoain. Nuclear Medicine, Radiation Oncology (I), Oncoloj,:v (2) and Urology (3) Depal"tments, Hospital Cl{nic. UniversiO,of Barcelona. Barcelona, Spain.

M.-D. Desrue~, C. Morin, C. Ghezzi, M. Comet, Laboratoire d'Etudes des Radiopharmaeeutiques ESA CNRS 5077, Grenoble (France).

RETREATMENT WITH Sr-89 FOR PALLIATION OF PAIN FROM BONE METASTASES IN PROSTATE AND BREAST CARCINOMA

BIOLOGICAL EVALUATION OF AN IODINE-123 LABELLED .ANALOGUE OF MALTOSE FOR IN VIVO STUDIES OF GLUCOSE TRANSPORTERS.

In conclusion, if required, retreatment with Sr-89 can be administered safely and with the same efficacy as after the first dose.

The mammalian facilitative transport of glucose across the plasma membrane is carried out by a family of membrane proteins known as the glucose transporters (GluT). Alterations of Glut membrane distribution have been involved in the pathogenesis of altered metabolic states such as diabetes, neurodegenerative disorders and tumors. As part of a development of SPECT radioligands for in vivo quantitative measurement of glucose transporters, an iodine-123 labelled analogue of Maltose (6'-Deoxy-6'-iodo-D-Maltose named MI) was prepared. To test the interaction of MI with different glucose transporters (GluT1 and GluT4), kinetic, inhibition and competition experimgnts were c o n d u c t e d in human erythrocytes, primary culture of n e o n a t a l rat cardiomyocytes and erythrocyte membrane preparations. The inhibinion studies showed that MI was an inhibitor of the uptake of 2-Deoxy-D-Glucose by erythrocytes. Ins cellular binding was decreased by cytochalasine B (CB), a potent glucose transport inhibitor. Competition studies indicated that the binding of tritiated CB to erythrocyte membrane preparations was decreased in presence of MI. in conclusion, the biological behaviour of MI is similar of Maltose, which has been known to interact with Glut without being transported ; so, the introduction of iodine, on the left side of nhe sugar, does not suppress recognition by zhe transporter. These preliminary results suggest that MI is a potential candidate as an in vivo imaging agent of glucose transporter density.

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A.Teb~utt, J.Owens, A. McGregor, S. Magar*, G. Durant* and J.McCulloch. University. of Glasgow, Scotland, UK. and *CNS, cambridge, MA., U.S.A.

R.E. Stringer, L.I. Wiebe*, A.J. McEwan ° and P.J. Maltby, Radiopbarmacy, Royal Liverpool and Broadgreen University Hospitals, Liverpool, U.K., ~Jniversity o f - A l b e r t a and °Cross Cancer Institute, Edmonton, Canada.

DEVELOPMENT

A SIMPLE ~ FCR PURIFICATION AhD PREPARATICN OF 1-123 IC[X)AZAMYCIN ARABINOSIDE (IAZA) FOR PATIENT USE.

The aim of this study was to evaluate the effectiveness of retreatment with Strontium-89 chloride (Sr-89) for the palliation of metastatic bone pain. From a group of 76 patients who were treated with Sr-89, 16 patients (12 males with prostate carcinoma, 4 females with breast cancer) received a second dose of 148 MBq of Sr-89 some months after the first one (mean 7 months, range 3-12). Inclusion criteria were: multiple bone metastases on bone scintigraphy, bone pain localized in the areas of higher uptake, positive response after the first dose of Sr-89 but reappearance of pain, and adequate hematologic profile.The Karnofsky performance status (K) was assessed and pain (P) and analgesia (A) were scored on scales of 9 and 5 points, respectively. The efficacy of Sr-89 was evaluated after three months of treament. Three levels of response were considered: good - increase of K and decrease in P (equal to or higher than 4) or A (equal to or higher than l); partial - increase of K and decrease in P (2 or 3 points) without changes in A; no response - no variation or deterioration. Results: After the second dose of Sr-89, the response was good in 63% of the patients and partial in 37%. Clinical response after the first and second close did not show statistically significant differences, 8 patients showing good response and one partial response after both doses, 5 patients had good response after the first dose and partial after the second and the remaining 2 patients had partial response after the first dose and good response after the second.

OF

CM8-1261

A

NOVEL

MMDA

LIGAED Rationale The aim of our study was to develop a radioiodinated SPECT agent to investigate glutamate (NMDA) receptor activation in cerebral ischaemia. Utility of the previous agent (I-MK-801) is limited due to its high non-specific binding. N'-(3-[125-I]iodophenyl)N'-methyl-N-(l-Naphthyl) guanidine (CNS-1261) a novel tracer with reduced lipophilicity has been synthesised and tested.

Synthesis Synthesis of the tributylstannyl precursor was achieved in Ii % overall yield. Preparation of the radioiodinated [125I]-CNS-1261 was performed by iododestannylation using peracetic acid as the oxidant and the radiochemical yield was 95 %. [125-I]-CNS-1261 was obtained in 60 % overall yield after HPLC purification.

sioloav Lipophilicity as determined by LogD was lower for [125I]-CNS-1261(2.19) than for [125I]-MK801(3.9). Initial uptake of [125I]-CNS-1261 in normal rat brain reflects cerebral blood flow. For [125I]-CNS-1261 at 120 min p.i. the ratio of uptake in hippocampus (an area rich in NMDA receptors) relative to cerebellum (a non specific region) was twice that of [125I]-MK801. [125I]-CNS-1261 was cleared rapidly from rat plasma tl/2 = 2.17±0.44 min, however at 120 min p.i. all radioactivity in the brain was authentic [125I]-CNS-1261.

988

PURPOSE: 1-123 IAZA is a new agent for imaging hypcy~a. The published method for purification and preparation of patient dose involves preparative HPLC and solvent evaporation. This is time-ccnstmdng, costly, and prohibitive for departments without specialized equipment. We have developed a simple, rapid, cost effective method which does not require specialized

~ t ~I'nX3Dd: Crude 1-123 IAZA is suspended in i00 ~i of 70% ethanol. This is diluted to 0.6 ml in water. This solution is applied to a Waters Sep-Pak Plus C18 cartridge, previously conditioned with I0 ml 100% ethanol. The cartridge is eluted with i0 ml water, followed by 3 ml 100% ethanol. The ethanol fraction is diluted to 20 ml with normal saline and passed through a 0.2 ~m~ filter for the final inject/on preparation. RESULTS: Analysis of the fractions using HPLC shows >99% 1-123 IAZA in the ethanol fraction, with free 1-123 iodide eluting in the water fraction. Other labelled i~purities remain on the cartridge. Purification and preparation of patient dose takes only I0 min. CX3NCLUSIGNS: This method is very simple and cost effective giving a considerable time-saving over the previously published method, allowing earlier injection of patients. This method w~uld enable departments without access to specialized equipment to perform studies using 1-123 IAZA.

P 176

P 174 T. Nikula, J. Hiltunen, A Savonen MAP Medical Technologies Oy, Tikkakoski,

•

Finland

3

J. Vfih~talol~S.-L. Karonen2, M. Suommen, M. Kulvik 2'4, S. Savolainen 2 ILabs. of Radiochemistry and 3Organic Chem., 4Inst. of Biotechnology, University of Helsinld, 2Helsinki University Central Hospital

THE IMPROVED NEURORECEPTOR IODINE-123

PROCESS FOR AGENTS USING

LARGER SCALL LABELING ALKYLTIN PRECURSOR ,AND

SYNTHESIS OF 4-BORONO-2-[I-125]IODO-PHENYLALANINE, NEW TRACER FOR BORON NEUTRON CAPTURE THERAPY

A

During the last five years several new 1-123 labeled compounds primarily for examination of brain receptors have been proposed. Common preparation scheme employes the trimethyl precursor and iodine-123 labeling by cloramine-T method. We have developed the large scale production process for higher quality 1-123products, Zor reduction radiation risks for personnel, to avoid toxic organic waste as well as to get higher yields production. To avoid a violent evaporation of free iodine and methyliodide, the labeling condition was changed much milder condition by buffering the solution to pH 4.5 to 6. The labeling efficiency was increased remarkably. The labeled product is purified from precursor and free iodide by using HPLC. The mobile phase contains typically asetonitrile or other toxic solvents, which are unsuitable for in vivo use. We avoided extra manipulation by changing the HPLC eluent to non-toxic solvent (EtOH :phosphoric acid). This tremendously increased the overall yields, preparation time and radiation exposure for personnel. Following table shows labeling yields with improved process vs. conventional (iodine-123 > 5 GBq) with various neuroreceptor ligands. ligand i conventional improved

~-CZT

65

90

Epidepride NNC 13 8241

70 52

91 85

P 175 F . Dumont, G. Slegers and Department of Radiopharmacy, Ghent, Ghent, Belgium.

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy that is used for the treatment of patients with malignant gliomas. The clinically prevailing boron carrier compound is 4-boronophenylalanine (BPA). The success of a radiofluorinated analog of BPA in PET has raised the question whether BPA analogs can be radiolabelled using 1-125 for basic in v i t r o - and i n v i v o -research and I-123 for SPET. For the incorporation of a radioiodine 0-125) in BPA two solid oxidation agents were used: Iodogen® and solid lactoperoxidase (lactosorbent). A novel technique using free electrophilic iodine produced by lactosorbent was found to be suitable, Radioiodinated products were separated and identified by reverse phase HPLC using UV and radioactivity detector. A stable analog of an iodinated BPA was synthetized and the product will be identified by NMR and mass spectrometry. Direct eleetrophilic radioiodinating method using Iodogen® as an oxidating agent gave >90% yield of 4 -[I-125]iodo-phenylalanine. Direct electrophilic radioiodinating method for lactosorbent as oxidating agent gave four different radioiodinated products. The novel technique using free electrophilic radioiodine gave a new product less than 5%. The product was identified as 4-borono-2-[I-125]iodo-phenylalanine. The dihydroxyboryl group, -B(OH)2, in aromatic molecules is electron withdrawing and deactivates direct electrophilic labelling; it is a good leaving group in certain conditions like the described Iodogen® -method• However, a radioiodinated analog of BPA (4-borono-2-[I-125]iodophenylalanine) can be synthetized using free electrophilic iodine and purified from by-products using reverse phase HPLC.

e=om d.-'

olD ¢n tD x_ e,,

P 177 RA. Dierckx. University of

S Y N H E S I S OF 7 - C H L O R O - 5 - [ I - 1 2 3 1 - I O D O K Y N U R E N I C ACID: A P O S S I B L E S p E C T T R A C E R F O R I N V I V O IMAGING OF N-METHYL-D-ASPARTATE RECEPTORS Excessive stimulation of the receptor sensitive to N-methyl-D-aspartate (NMDA) could cause neuronal death in cerebral ischemia, epilepsy and Alzheimer disease. The NMDA receptor is unique amongst ligand gated ion channel receptors. In addition to the glutamate recognition site, it contains a recognition site for glycine, which must also be occcupied by an agonist for receptor activation. Several types of compounds have been synthesized and evaluated for their NMDA/glycine antagonism and optimisation of the kynurenic acid type led to the 7-chloro5-iodokynurenic acid with an ICSO-value (vs. [H-3]glycine)of 0.032 ~M. We report the radioactive synthesis of 7-chloro-5-[I-123]iodokynurenic acid as a possible tracer for the NMDA receptor. The compound is synthesised starting from a mixture of 5bromo-7-chloroand 7-bromo-5chlorokynurenic acid, in the presence of Cu(II), reducing and complexing agents and 1-123. An optimisation of the reaction parameters is carried out and under the best conditions a radiochemical yield of 80-85 % is found. The radiotracer is separated and purified using reversed phase high performance liquid chromatography and obtained in a sterile solution, suitable for injection. Biodistribution studies will be carried out.

J. Hiltunen, J.T. Kuikka, P. R~isgnen, T. Nikula, K.A. Bergstr6m, K. Akerman, C. Halldin, E.Vanninen, J. Tiihonen MAP Medical Technologies Inc. Tikkakoski, Kuopio University Hospital and Niuvanniemi Hospital, Kuopio, Finland; Karolinska Institute, Stockholm, Sweden. PREPARATION OF 1-123 LABELLED EPIDEPRIDE AND INITIAL EXPERIENCES 1N IMAGING STRIATAL AND EXTRASTRIATAL DOPAMINE D2 RECEPTORS IN ALCOHOLICS

Iodine-123 labelled epidepride ([I-123]EPI) is a highly specific radioligand for imaging striatal and extrastriatal dopamine D2 receptors in the living human brain. We report multilevel preparation of [I-123]EPI and initial imaging experiences. Routine clinical SPET imaging requires [I-123]EPI preparation of multi GBq level for several doses simultaneously. To overcome radiation induced deiodination and other radioactivity losses in the process we have further developed the preparation from previous published work, e.g. by changing the HPLC purification system to ethanol/phosphoric acid as an eluent. The collected [I-123]EPI fraction was directly constituted to injectable solution without evaporation step. The overall radiochemical yield increased from 70 % to 91%. The radiochemical purity was > 98 %. We studied 3 type 1 alcoholics (mean age of 39 years) and 8 ageand gender-matched healthy controls (mean age of 40 years). High resolution SPET imaging was performed 45 rain (extrastriatal) and 3 hours (striataI) after injection of tracer. Temporal pole and basal ganglia were regions of interest. Cerebellum served as a reference region. Temporal pole-to-cerebellum ratio (extrastriatal) at 45 rain was 2.63 -+ 0.34 (mean _+ SD) in healthy controls and 2.46 _+ 0.25 in alcoholics. Striatum-to-cerebellum ratios at 3 hours were 7.94 + 1.45 and 6.77 .%+1.61, respectively. These tentative results suggest that in type 1 alcoholics both striatal and extrastriatal dopamine D2 receptor density is decreased. 989

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B. Joharmsen, S. Kirsch, R. Jankowsky, B. Noll, H. Spies, M. Dinkelborg, C.S. Hilger, W. Semmler, Forschungszentrum Rossendorf,, Schering AG Berlin and Institut fiir Diagnostikforschung Berlin, Germany

R. J. Deeth ~, G. Brauers*, A. C. King*; ~Inorganic Computational Chemistry Group, University of Warwick, Coventry, UK; *Healthcare R&D, A m e r s h a m International, UK.

STUCTURAL STUDIES ON TECHNETIUM COORDINATION ABILITY OF CYSTEINE-CONTAINING PEPTIDES

COMPUTER MODELLING OF TECHNETIUM AMINE OXIME COMPLEXES: INSIGHTS INTO SPECIAL BEHAVIOUR OF TCHL91.

In 99mTc labelling of specific peptides, 99mTc has to be introduced at a position of the peptide molecule which would tolerate inclusion of the label without adversely affecting the receptor or other specific binding. Although for direct labelling of peptides Tc-binding sequences remote from the receptor-binding sequence have been successfully introduced, the coordination mode of such peptides is still poorly understood. The aim of our studies was i) to clarify for simple N,S-donor building blocks, such as cysteine derivatives, how the ligands bind Tc(V) and ii) to determine in solution the coordination mode of a 99Tc-labelled endothelin derivative, containing the sequence -Cys-Gly-Cys-, which is a potential agent for imaging atherusclerosis. X-ray absorption spectroscopy proved to be a valuable tool in obtaining direct structural information from the noncrystalline material and solution species. The performed studies have shed more light on the subtle interplay of the donor groups of the ligand, including the hitherto uncommon occurrence of both a deprotonated and a neutral nitrogen donor group in bis-bidentate S,N oxometal(V) complexes. EXAFS analysis of the 99Tc-labelled Cys-containing endothelin derivative revealed that coordination of the [TcO] > core is restricted to the sequence -CysGly-Cys-. Under the labelling condition used (ligand exchange reaction with Tc(V) gluconate), the preferred coordination by the cysteinyl thiol group surprisingly prevents involvement of any donor atom other than sulphur, thus forming purely S-coordinate 1:2 complexes in form of two isomers•

The 99mTc complex of the ligand HL91 [: Bn(AO)~] is currently under clinical evaluation for the detection of hypoxic tumours. While the closely related 99Tc complexes with the ligands Pn(AO)2 and Pent(AO)2 which have, respectively, one less and one more carbon in the alkyl N N bridge have been structurally characterised, the chemistry of OH OH 99Tc-HL91 has not ,been fully eludicated. Therefore ab initio t1[,.93. = l~(AO)a Density Functional Theory (DET) was used to calculate fully optimised geometries for the mono-oxo and di-oxo Tc complexes of the three ligands. The DFT results are in excellent agreement with the experimentally determined structures. The relative DFT energies are also consistent in that the complex with the lowest energy corresponds to that isolated in the solid state. To explore the factors responsible for the solution behaviour of 99Tc-HL91 the DFT calculations were extended to different potential forms. The computations demonstrate that there is virtually no interaction between a mono-oxo TcHL91 complex and a solvent water molecule. The calculations also show that for Tc-HL91 there is little energetic difference between dioxo and oxo-hydroxy coordination of Tc.

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B. Nock, C. Tsoukalas, T. Maina, I. Pirmettis, M. Papadopoulos, It• Spies,* B. Johannsen* and E. Chiotellis. I/R-RP, NCSR "Demokritos", 15310 Athens-Greece; *Forschungszentrum Rossendorf, D-01314 Dresden-Germany COMPARATIVE STABILITY VERSUS CYSTEINE OF MIXED LIGAND 99roTe COMPLEXES CONTAINING MONOTHIOLS OF DIFFERING NUCLEOPHILICITY Our work over the past few years has been focused on the design and evaluation of novel chelating systems suitable for oxorhenium and/or oxotechnetium that may lead to useful radioagents. Several 99mTc mixed ligand complexes carrying the SNS/S or the SNN/S donor atom set have shown promising biological properties for future application. The in vivo stability and thereby the biological properties of these complexes is greatly dependent on the electronic and lipophilic character of the monothiol. We report here on the comparative resistance to cysteine substitution of two parallel series of 99mTcO{[Et2NCH2CH2N(CH2CH2S)2](p-RPhS)} and 99mTco[(Et2NCH2CH2NCH2CH2S) (p-RPhS)] complexes, wherein the phenyl monothiolate coligand is substituted in the p-position by R: -NH~ (electron donating group), -H and -NO2 (electron withdrawing group). The electronic influence on cysteine substitution rate can thus be investigated. All above complexes are prepared at tracer level using glucoheptonate as transfer ligand and are purified by organic extraction and HPLC. Their structure has been previously resolved by comparison with authentic samples. The 99mTc complexes are stable in solution in the absence of thiol for long periods of time. Competition experiments with cysteine are performed in aqueous medium at pH 7.4 and using two different cysteine concentrations, 10 mM and 1 raM, by incubation at 37°C. Aliquots of the incubate withdrawn at 0, 15, 30, 60, 120 min and 24 h time intervals are subjected to HPLC analysis. A RP C18 column is eluted by TEAP buffer pH 7.4/EtOH gradient system, whereby all radioactive ingredients are well separated. All complexes are attacked by cysteine under the above conditions forming • m~xtures of intermediates, that with time lead to total loss of the original 9 9 m Tc compounds. Relative resistance to cysteine substitution is directly proportional to monothiol nucleophilicity in both series of complexes: -NH2 > -H >-NO 2. Since the free thiol content - mainly cysteine and its derivatives - varries in vivo, mixed ligand sytems as the above can be used for directing and trapping 99mTc in tissues of choice by finely monitoring stability via the monothiol.

R. Casati, F~R. Colombo,~Y. TorrentefA. DeLiso, R. Benti,*A. Duatti, °L. Uccelli, N. Bresolim A. Bruno, A. Piffanelli, P. GerundTn~. IRCCS-Ospedale Maggiore, Milan; *University of Bologna, University of Milan, °University of Ferrara, Italy.

990

MURINE MYOBLASTS LABELING BY Tc-99m COMPLEXES FOR MURINE B1ODISTRIBUTION STUDIES. The a~fity of five different Tc-99m monocationic or neutral complexes for a line of murine myoblasts (GS) was preliminary tested by incubataon at 37°C with 10UG8 cells ahquots (Table 1). Ceils were soon centrifuged, separated and resuspended in PBS medium. The procedure was repeated after 2, 4 and 24 hours. Radioactive content was measured in the obtained cellular pellets and supernatants as well as cell viability (Trypan Blue staining and microscopic counting). Table 1 Incubated I Retained % Released % Viability% I Complex (mCi) 30rain 60min I 2h 4h 24h I 2h 4h 24h MIBI 5.2 i 0.83 - 0.97 i / / / :. 70 - 62 - 28 I?eir3i%sm]n ........... 3 ~ ..........7 - ~ 3 ~ - : - ~ 1 7 i U ! ' - 7 ........... ~............. 7 T " ~ U ' " g g " ' ~ Y ' " [~M#~6"~ ..........~.~ ............... i ~ ~ 2 " : - ~ i T ~ ' ~ % ~ " 7 ~ ; 4 " i ' ' - ~ " / ; ~ ' " ~ U T ' W T 7 N'E~ ................... i ..........~ ~ ................f g V T " < U i ' ~ i S : U - 5 2 3 : / ~ j ; g i " - / - : " g ~ 7 7 " ]

1 .....

NOEt higher retention,' low wash-outand acceptable v{ability. "in vitro" suggested its use for G8 cells "in vivo" biodistributlon assessment m a murine model af muscular dystrophy (MDX) and control mice. Muscular and extramuscular retention of NOEt labelled myoblasts (expressed as %dose/g of tissue in table 2) was obtaioed at 1 or 3 hours aker intra-aortic adminislration (mean 103 pC1 in 5.5x10+ cells) in 20 animals. In more damaged MDX muscles, as diaphragm and myocardium, the retention of labelled mjob!ast_s was significantly lower (p<0.02) than in normal mice, but not in splanclmlc organs. Muscular retention increased from 1 to 3 h in controls, but lesser m MDX. Reduced myoblasts viability (<60%) increased significantly pulmonary retention in both groups as well as hepatic uptake. Table2 diaphragm I thigh I myocardium] liver ] kidneys ] lh 3h Ih 3h lh 3h lh 3h lh 3h Contros 24 33 065 077 3 38 [ 76 { 4 6 i 5 . 8 i 1 2 . 5

//~/~ ..........i i ; 8 i i;i i6:a~i-6:~<6;~i<6i6;0 '~!i~;0ia5!~ :<~

"ln vitro" Tc-99m labelling ofmyoblasts seems a promising .procedure to obtain, a proper assessment of short term cells biodisnibution in murme muscular ana exWamuscular structures. The higher labelling efficiency ofNOEt vs the other Tc-complexes tested is possibly related to the seleclave labeUm~ of ymb!e myoblasts, high affinity for surface proteins of the cell memorane ano sumcken,uy low wash-out due to metabolization. Further studies in larger mammahans should allow proper imaging of cells biodistribution.

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R.E. Strinqer, I. O'Neil* and P.J. Maltby, Radiopharmacy, Royal Liverpool and Broadgreen university Hospitals, Liverpool, U.K., and *Department of Cheslistry, university of Liverpool, U.K.

T Murray__,_ K McKellar, J Owens and W Watson. Radionuclide Dispensary, Department of Clinical Physics and Bio-Engineering, Western Infirmary, Glasgow.

99mTc-~ ESTIM~ EXT~CnON

DICYSTEI~E ( 9 ~ ) :

THE RADIOCH~ICAL (SPE)

PURITY

A RAPID ~

FOR

USING SOLID PHASE

I:'/RPQSE= ~ i c u s l y , estimating radioch~mical purity (RCP) of 99mTo-EC involved using either a cumbinaticn of ~wo TiC ~ or HPLC both of which are tlmeccnsuning. We have developed a rapid, sh~ple SPE method to estimate RCP using an ic~-exchange cartridge (Waters Sep-Pak Aocell Plus QMA). ~THODS. The SPE cartridge was equilibrated with i0 ml 0.01N HCI. A 0.05 ml sample of 99m~k~C was diluted to 0.5 ml with 0.01N HCI and applied to the cartridge. The cartridge %ms eluted with 7 ml 0.01N HC1, followed by i0 ml 0.9% NaCI. The activities of the two eluates and of the cartridge were estimated in a dose calibrator. HPLC ~as also carried out on each 99m~c-EC preparation RESULTS: 99mTo-EC eluted in the first fraction, pertechnetate in the second fraction and reducedhydrolysed tschneti~ was retained on the cartridge. The results obtained by SPE were ~=imred with results cbta/ned by HPLC. For ~ ranging from 31.4% to 99.2% (n=17) there was very high correlation between the two methods (r=0.99). The SPE method was found to be re~ible and was successful with 99mTc-EC produced from our ' i n - h o u s e ' preparation and also with a

ommarcial product. CCNCLUSICNS~" This SPE method is sb~Dle, rapid and robust.

99mTc-MAG3

RADIOCEEMICAL

PURITY

TESTING:

The aims were: (i) To determine if there are differences in the radiochemical purity (RCP) of 99mTc-MAG3 using different methods of analysis. (ii) To verify recent recommendations to use glass bottled saline in the preparation of 99mTc-MAG3. The RCP of 99mTc-MAG3 was determined using HPLC, TLC and solid phase extraction methods as previously described. TLC relied on a two strip method with analysis based on the use of electronic autoradiography. The solid phase extract method utilised Sep-pak disposable cartridges. Statistical analysis was performed using non-parametric methods. No significant difference in the RCP of MAG3 was observed when HPLC and TLC were compared with mean(±s.d.) of 98.14%(±0.91) versus 98.25%(±0.64). However, results between HPLC and the solid phase extract methods were highly significant (p<0.001) with mean(±s.d.) of 96.75%(±1.40) versus 85.98%(±5.14). Examination of the Sep-pak fractions using both HPLC and TLC showed the presence of unexpected radioactive impurities which may explain the discrepancy between the chromatography and the extraction methods. With regard to the second aim of this study, a significant improvement (p=0.013) in RCP of 99mTcMAG3 was noted (HPLC method) when the kit was prepared using glass bottled saline instead of saline from plastic bags with a mean(±s.d) of 97.85%(±1.64) compared to 96.93%(±1.61). It is possible that components(s) leached from saline plastic containers interfere with the radiolabelling process. This finding confirms the manufacturer's new reconm~ndation for preparation of the kit.

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etl) (n Q.

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1, B.NoII2, St.NolI2 , H.SpiesZ , W.-G.Frankel , B.JohannsenZ Clinic and Policlinic of Nuclear Medicine, Technology University of Dresden, 2Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Centre Rossendorf, Germany

N. Dezutter, T. de Groot, H. Vanbilloen, A. Verbruggen.

STUDIES OF IN VIVO LABELLING OF NUCLEIC ACIDS WITH 99mTc COMPLEXES. FIRST RESULTS: UPTAKE IN CULTURED CELLS 99mTc labelled nucleobases are expected to be precursors for in vivo radioactive labelling of DNA. This offers the possibility for visualization of tumours developing in surroundings of non-dividing tissue as e.g. brain. The aim of the study was to achieve uptake of 99mTc complexes of dedvatized nucleic acid precursors, especially mercaptoamide functionalized uracil derivatives, into proliferating cells. The 99mTc complexes were prepared by ligand exchange on 99mTc(V) gluconate both as mixed ligand complexes according to the "3+1 principle" and as complexes formed by (MAGi, chelators coupled to nucleobases. Uptake of 7 selected compounds into the crude cytosolic and nuclear fractions of cultured V79 cells was checked. Pulse labelling for 4 hrs showed cellular uptake of some compounds. Best results were about 20% cellular uptake, and thereof up to 40% in the nuclear fraction. The corresponding results with aHTdR controls were 20% and 75% respectively. Postincubation experiments showed an increase of the percent 99mTc radioactivity in the nuclear fraction by a factor of 2. This means integration of the complex in the nucleus from the pool present in the cytosot after the initial incubation. No radioactivity was released into the postincubation medium. The results are encouraging, making evident that complex compounds of this kind can be taken up into the cell nucleus.

t._

~D

Laboratory of Radiopharmaceutical Chemistry, F.F.W., K.U. Leuven and Nuclear Medicine, UZ Gasthuisberg, B-3000 Leuven, Belgium.

MONOAMINE-MONOAMIDE BIS(THIOL) LIGANDS: SYNTHESIS, LABELLING WITH Tc- 99m AND BIOLOGICAL EVALUATION. In this study, we synthesized and determined the biodistribution of two Tc-99mmonoamine-monoamide bis(thiol) complexes (Tc-99m-MAMA's). MAMA = HS-CHz-CI-h-NH-CO-CFh-NH-CI-h-CI-h-SH NAA-MAMA = HS-CI-h-CH2-NH-CO-CH2-N(CI-h-COOH)-CI-D-CH2-SH Both bifunctiunal chelators can be conjugated with biologically active molecules, either via direct N-alkylation of MAMA-Tn or, for the latter compound, via the formation of an amide bond between the carboxylic group and an amine group of the biologically active molecule. S,S'-bis-trityl-MAMA (MAMA-Try) was prepared from commercially available eysteamine. After reaction of S-tritylcysteamine with bromoacetyl bromide, the primary bromide was reacted subsequently with S-tritylcysteamine to provide MAMA-Tn. N-Alkylation of MAMA-Tr2 with tert-butyl bromoacetate yielded N-(acetic acid-t-butyl ester)-MAMA-Tr2. Next, they were deprotected with trifluoroacetic acid and triethylsilane in dichloromethane. The resulting MAMA and NAA-MAMA were labelled with Tc-99m at pH 12 by addition of Tc-99mpertechnetate solution in the presence of starmous ions (yield > 80 %). The reaction mixtures were analysed by RP-HPLC. Both chromatograms showed a single main peak. The biological behaviour of the HPLC-isolated Tc-99m-MAMA and Tc-99mNAA-MAMA was studied in mice. Tc-99m-MAMA is mainly cleared from the blood by the hepatobiliary system (27.8% I.D. 10 min p.i. and 30.8% I.D. 30 min p.i.) and to a lesser extent by the urinary, system (11.4% I.D. 10 min p.i. and 25.4% I.D. 30 min p.i.). Uptake in brain (0.29% I.D. 10 rain p.i. and 0.15% I.D. 30 min p.i.) suggests that Tc-99m-MAMA is a neutral complex that can cross the blood-brain barrier. Tc-99m-NAA-MAMA is mainly cleared from the blood via the urinary system (57.9% of I.D. i0 min and 68.8% of I.D. 30 rain) but to a lesser extent via the hepatobiliary system (22.8% of I.D. 10 min p.i. and 18.1% of I.D. 30 min p.i.). Migration towards the anode suggests that Tc-99m-NAAMAMA is negatively charged at pH 7.4 and explains the negligible amount of radioactivity in the brain.

991

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I1

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S.C. Chern~, C.Y. Cheng, W.L. Lieu, K. Hsu, W.S. l]uang, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.

H.Palmedo, H. J. Biersack, S. Lastoria, J. Maublant, E. Prats, P Bourgeois, P. Rigo, A.J.W. Hilson. A Bischof-Delaloye and H E . Stegner for the Multicenter Trial Group. EANM 001.

UPTAKE OF TECHNETIUM-99m HEXAMETHYLPROPYLENEAMINE OXIME LABELED LEUKOCYTES IN EXPERIMENTAL ADULT RESPIRATORY DISTRESS SYNDROME. Adult respiratory distress syndrome (ARDS) is an often fatal pulmonary disorder for which thare are currently no reliable methods of early diagnosis. The potential usefulness of technelium-99m hexamethylprepylene amine oxime (Tc-99m HMPAO) !abeled leukocytes in the detection of ARDS was uuder taken in lids study, hnaging with Tc-99m HMPAO labeled leukoeytes were carried out in 10 canines with Escherichia coil endotoxin and phorbol myristate acetate-induced ARDS, and in 8 nomm[ control canines. Dynanfic images at 1 frame/rain were obtained for 60 rain. The lung-to-spleen (L/S) ratios of radioactivily of tl~e60-rain images were calculated. The pulmonaW ant W pressure (PAP), wet to dry lung weight (W/D) ratio and albumin concentration of lavage fluid (ALB) of both experimental ,and control canines were also measured. ARDS was proved by lung biopsies in all ARDS canines. Anmng the ARDS-induced canines, 80% showed apparent increased radionptake in bilateral pulmonary lobes, over the control grmlp in fl)e 60-rain image. The L/S ratio was significantly increased in the ARDS group compared to that of file control group [1.20+ 0.2 (Mean+--SD) vs. 11.29 ± (I.04; p<0.001]. The L/S ratios also showed significm~tlypositive correlation with the corresponding PAP values, W/D ratios and ALB 0=0.93, (1.87, 0.75 and p<0.01, 0.01 and 0.05 respectively). Negative scans (20%) in the current study might be due to insufficient induction ef ARDS. Our findings suggest that imaging of Tc-99m HMPAO labeled leukecytes is helpful in evaluating lhe severity of pulmonary damage in experimental ARDS, and may be useful in detecting clinically suspected ARDS.

V A L U E OF TC-99m MIBI IN THE DIAGNOSIS OF P R I M A R Y B R E A S T CANCER: R E S U L T S O F THE P R O S P E C T I V E E U R O P E A N M U L T I C E N T E R TRIAL. The aim of the trial was to determine diagnostic accuracy of Tc-99m MIBI in the detection of primary breast cancer and to verify its potential rote in the diagnostic work-up of breast cancer. 246 patients with a suspicious breast mass or a suspicious mammogram have been included in this trial. 5 min and 60 min (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min p.i. one anterior image was acquired for 10 min. Institutional and blind read results were correlated to core laboratory histopathology results obtained during excisional biopsy. Diagnostic accuracy for the detection of breast cancer was calculated per breast and per lesion There was no statistical difference for both groups. The accuracy of Tc-99m MIBI was depending on the quality of images:

All Scans Sensitivity Palpable 86% Non-Palpable 63% Overall 80%

Specificity 70% 81% 73%

High Image Quality Sensitivity Specificity 92% 70% 50% 96% 87% 78%

Sensitivity and specificity of mammography was 91% and 42%, respectively, and did not depend on the tumor size. In 60% of the false negative mammograms, Tc-99m MIBI was able to diagnose breast cancer (true positive). The density of breast tissue did not influence the diagnostic accuracy of scintimammography. High quality imaging with Tc-99m MIBI has a high diagnostic accuracy for the detection of primary breast cancer and can contribute significantly to the clinical work-up of patients with suspected breast cancer

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A. Martinetti, E. Seregni, L. Mariani, L. Ferrari, M.R. Castellam, E. Bombardieri. Istituto Nazionale per In Studio e la Cura dei Tumori - Milan - Italy.

R. Pijpcr~5, D. Krag¶, P. Borgstein +, H. Greuter, G. Teule, S. Meijer,,.. Dpts of Nuclear Medicine and Surgical Oncology~:, Ziekenhuis van de Vrije Universiteit, Amsterdam, The Netherlands. Dpt of Surgical Oncology~, University of Vermont, USA.

BONE METABOLISM SERUM MARKERS AND BONE SCAN IN THE FOLLOW-UP OF BREAST C A N C E R PATIENTS Bone scintigraphy plays a major role in the diagnosis and follow-up of bone metastases. The clinical utility of new biochemical markers of bone metabolism has been recently investigated in various bone diseases, ha our study we have assessed the role of various bone metabolism markers in comparison win bone scan in the follow-up of breast cancer patients. We studied 150 patients, 33 (22%) of whom had metastatic bone lesions. IRMAs were used for the evaluation of osteocalcin (BGP), bone alkaline phosphatase (BAP), C-terminal propeptide of Type I procollagen (PICP) and C-terminal crosslinked telopeptide of Type I collagen (ICTP). Multivariate regression analysis demonstrated that menopausal status (p=0.007) and metastatic bone lesions (p=0.001) affected bone marker levels. However, we found a high degree of overlapping in the marker distribution for scan-positive and negative patients as reported in the table. 5th%-ile 50th%-ile 95th%-ile 2.3 6.5 20.6 BGP (gg/l) Scan negative pts 0.8 6.0 38.5 Scan positive pts 5.1 9.7 17.1 BAP (Izg/l) Scan negative pts 4.6 14.9 25.2 Scan positive pts 72.7 101.9 165.1 PICP (gg/1) Scan negative pts 66.0 119.4 234.4 Scan positive pts 1.3 2.2 4.4 ICTP (gg/l) Scan negative pts 1.7 2.6 10.5 Scan positive pts Sensitivity, specificity, positive and negative predictive values were assessed by discrimmant analysis using logistic regression models in which bone scan outcome represented the dichotomous response and markers, taken singly or jointly, were considered as the predictors. The best discrimination was achieved with BAP (c=0.689), closely followed by ICTP (c=0.659). The association of BAP and ICTP gave a slight improvement (c=0.737) over the use of the two markers separately. I lowcver, the scasitivit3 of all tIl~c markers ~as remarkably lov,, :,.c~: at very low threshold levels (e.g. with the specificity set at 60%, the sensitivity of BAP was 21%). In conclusion, our study demonstrated that these markers cannot replace bone scan during breast cancer follow-up. Partiallysupportedby.qIRCProject.

992

I N F L U E N C E OF THE APPLIED T R A C E R ON N O D A L U P T A K E IN S E N T I N E L NODE BIOPSY 1N M E L A N O M A

Sentinel node (SN) biopsy is a new staging technique in melanoma to select patients (pts) who are most likely to benefit from regional lymph node dissection. We evaluated 16 pts with histologically proven melanoma, after injection of 20 MBq of Tc-99m-colloidal albumin (Nanocoll@, CA, n=8 pts, 10 basins) or Tc-99m-sulphur colloid (ANSulfur Colloid@, SC, n=8 pts, 8 basins). Both groups were comparable concerning Iocalisation of the primary tumor and tumor thickness. Dynamic scintigraphy (20 x 1 rain) was performed directly following injection of the tracer adjacent to the biopsy scar and 2 hours later (static: 1 x 3 rain). The SNs were biopsied with gamma probe guidance and weighed Absolute traceruptake, expressed as percentage of injected dose (average +SD), was estimated in a well counter. During dynamic scintigraphy, lymphatic channels were seen significantly more often (p<0.05) in the NC group (10/10 basins) compared to the SC group (4/8 basins). The number ofvisualised feel per basin was higher in the NC group (1 9±1.3 versus 1.1±0.6) compared to the SC group (p=0.1). Absolute uptake in in the NC group (1.02±0.4%) was clearly higher (p<0.0005) than in the SC group (0.27±0.34%). The difference in uptake did not influence the operative succes rate which was 100% in both groups. Conclusions: (1) Both tracers perform equally well with respect to success rate in biopsy. (2) However, tracemptake in the SN with NC is significantly higher and improves flexibility in time delay between injection and operation. (3) When dynamic scintigraphy is performed, NC seems to be preferable. (4) Using SC, higher tracer doses may be necessary to compensate for the lower uptake in the sentinel node. (5) Uptake of NC in more lymph nodes carries a slightly increased risk of sampling nonSNs in addition to SNs although, with the combination of scintigraphy and gamma probe, differentiation is usually simple.

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J.D.Lucas, M.A.Lodge, PoK.Marsden, M . J . O ' D o h e r t y , A, O~e, U. Roelcke, S. HOgerte,E.U. Nitzsche, K.L. Leenders,J. MUller~ B.F.Cronin, P.H.Mckee, MoA.Smith. Depts of Brand. Div. of Nuclear Medicine University Hospitals Basel and Freiburg; O r t h o p a e d i c s and C l i n i c a ~ PET Centre, UMDS and G u y s PET Program, Paul Scherrerlnstitute Vitligen, Switzerland a n d St T h o m a s " H o s p i t a l Trust, L o n d o n SEI 7EH. D E T E R M I N A T I O N OF THE A B S O L U T E M E T A B O L I C R A T E A N D THE VARIATION IN SUV O V E R T I M E F O R SOFT T I S S U E M A S S E S U S I N G F D G PET. T h e a b s o l u t e m e t a b o l i c r a t e and the v a r i a t i o n of the Standard Uptake Value (SUV) over a 6 hour p e r i o d w e r e d e t e r m i n e d for s o f t t i s s u e m a s s e s in 9 p a t i e n t s u s i n g 1 8 F D G PET. P a t i e n t s u n d e r w e n t l o c a l i z e d FDG P E T scans of t h e i r masses prior to biopsy. The scanning protocol i n c l u d e d 3 s c a n s o v e r a 6 h o u r period. An initial d y n a m i c 2 h o u r scan w i t h a r t e r i a l s a m p l i n g a l l o w e d a c c u r a t e d e t e r m i n a t i o n of the m e t a b o l i c rate of the m a s s e s u s i n g a 3 c o m p a r t m e n t model. 2 further static scans at 4 and 6 hours post injection a l l o w e d the t i s s u e u p t a k e c u r v e at later t i m e s to be e x a m i n e d . 9 p a t i e n t s w i t h soft t i s s u e m a s s e s w e r e studied, 5 m a l e s a n d 4 females, m e d i a n age 53 y e a r s (range 35 to 83 y e a r s ) . The h i s t o l o g i c a l d i a g n o s e s w e r e of b e n i g n m a s s e s in 6 patients, soft t i s s u e s a r c o m a in 2, a n d 1 G i a n t Cell t u m o u r of soft tissue. The tissue uptake curves for benign and malignant tumours fell into two d i s t i n c t c a t e g o r i e s . The m e d i a n s of the m a x i m u m SUV v a l u e s for b e n i g n and malignant t u m o u r s w e r e 3.9 a n d 22.2 r e s p e c t i v e l y a n d w e r e o b t a i n e d at m e d i a n p o s t i n j e c t i o n t i m e s of 60 a n d 255 m i n u t e s r e s p e c t i v e l y . The differences b e t w e e n the t w o t u m o u r g r o u p s of b o t h the m a x i m u m S U V a n d the p o s t i n j e c t i o n t i m e s at w h i c h the maximum SUV was obtained were significant(Mann W h i t n e y U t e s t p<0.05). P r e l i m i n a r y e x a m i n a t i o n of the rate constant for t h e dephosphorylation of ISFDG-6-P indicates that this is significantly h i g h e r f o r b e n i g n t h a n for m a l i g n a n t lesions.

REVISITING CROSSED CEREBELLAR DIASCHISIS IN GLIOMAS: A FDG AND MEFHIONINE PET STUDY Cerebral gliomas may cause a reduction of glucose metabolism in the cerebellum contralateml to the tumor side (crossed cerebellar diaschisis, CCD). We investigated whether CCD is related to tumor localisation, histological grade, and tumor biochemistry. M e t h o d s : Cerebellar glucose metabolism was measured in 51 glioma patients and 15 healthy control subjects using positron emission tomography and F-18fluorodeoxyglucose (FDG). CCD was quantitated by calculating an asymmetry index of cerebellar glucose metabolism. Further, the tumor uptake of FDG and C-11-methionine (MEW) was also assessed, and was expressed as ratio of normalized tracer uptake in t/tmor over contmlateral cortex (T/C). R e s u l t s : Frontal lobe tumors were associated with highest asymmetry index values of cerebellar glucose metabolism. In tumors of the parietal or temporal lobe, this asymmetry was less marked or absent. For all localisations, cerebellarasymmetry was on average higher in malignant than in low-grade gliomas. T/C ratios of tracer uptake were higher in malignant than in low-grade gliomas, but were not correlated with the asymmetry of cerebellar glucose metabolism. Conclusions. Our data indicate that the magnitude of CCD is mainly determined by tumor localisation and grade. The absent correlation between CCD and tumor biochemistry may indirectly indicate that CCD is also related to tumor size. These findings raise the question whether CCD provides a measure of expansion or progression particularly in low-grade tumors of the frontal lobe. Background:

t=O m t~ ¢ID L-

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C.IVI. Pinsky, N. Petrelli, A. Serafini, H. Pinsky, L.D. Hammershaimb and D.M. Goldenberg. Immunomedics, Inc., Morris Plains, NJ; Roswell Park Cancer Inst., Buffalo, NY; University of Miami, FL; and Garden State Cancer Center, Belleville, NJ, USA.

¢. Mainolfi, S. Maurea, C. Alaia, P. Varrella, C. Imparato, R. Roma, G. Abate, L. Bazzicalupo, M. Salvatore. Medicina Nucleate e Ematologia, Istituto Nazionale dei Tumori; Centro per ra Medicina Nucleare del CNR, Universit& Fededco II, Napoli, Italy

MULTIPLE INJECTIONS OF CEA-SCAN ~ 1N THE MANAGEMENT OF PATIENTS WITH CARCINOMA OF THE COLON OR RECTUM CEA-Scan ~ is a Fab' fragment of a murine anti-CEA monoclonaI antibody formulated for direct labeling with Tc-99m. It has been approved for imaging patients with colorectal cancer. This study was conducted to evaluate the safety and efficacy of multiple injections of CEA-Scan ®, Of 37 patients studied, 23 were male and 14 were female, ranging in age from 31-77 years. Most patients had Dukes' C or D colorectal cancer, and had known or occult disease recurrence. All except nine patients had elevated serum CEA levels. Thirty-seven patients had two injections of CEA-Scan®; two patients received three injections. Of 33 patients evaluable for imaging efficacy (with 35 injections), CEAScan ~ correctly detected lesions following 13 of 22 injections and absence of disease in 8 of 13 injections, for an accuracy of 21/35 (60%). The positive predictive value (PPV) was 13/I 8 (72%) while sensitivity and specificity were 59% and 62%, respectively, somewhat lower but consistent with the results obtained in larger studies after the injection of the first dose. Only one adverse event (eesinophilia) was judged as at least possibly related to CEA-Sean '*, with no deaths or drop-outs. Hematology and serum chemistry changes were clinically insignificant. None of 32 patients developed elevated HAMA titers in the F(ab'): fragment assay, so it can be concluded with 95% confidence that the true incidence of HAMA induction after 2 injections of CEA-Scan ® is less than 10%. These results in 37 patients who received at least 2 injections of CEA-Scan*' provide evidence that it is safe and effective in imaging patients with known or occult colorectal cancer. These data weuId suggest that at least two injections of CEA-Scan ~ can be given to patients with colorectal cancer safely, with reasonable imaging efficacy.

FOLLOW-UP EVALUATION OF PATIENTS WITH LYMPHOMA USING F-18 FDG PET: COMPARfSON WITH CONVENTIONAL IMAGING TECHNIQUES The diagnostic assessment of patients (pts) with lymphoma during follow-up after treatment is routinely performed using clinical examination and imaging studies such as ultrasound, standard X-ray, CT, gallium-67 and MR. In this study, we compared the results of positron emission tomography (PET) with fluorine18 (F-18) deoxyglucose (FDG) with those of other radiolegical studies in 32 pts (18 M, 14 F) with lymphoma (13 Hodgkin and 19 non-Hodgkin) evaluated before and after treatment procedures (radio- and/or chemotherapy or surgery). Wholebody PET with F-18 FDG (370 MBq iv) was performed in fasting conditions. FDG images were qualitatively evaluated and considered abnormal when lesion tracer uptake was greater than Nood pool as well as baekgroud activities. Before treatment, a total of 79 tumor lesions (47 nodal, 32 extra-nodal) was detected on the basis of clinical examination and radiological studies. Nodal tumor sites consisted of neck (n=16), axilla (n=l), mediastinum (n=17), abdominal (n=6) and pelvis (n=5) lymph nodal locations as well as spleen involvement (n=2). Extranodal lesions consisted of ocular soft tissue (n=2), thyroid (n=l), oral cavity (n=l), lung (n=5), stomach (n=3), gut (n=3), pancreas (n=2), testis (n=l), ovary (n=l) and skeletal (n=13) tumor sites. All lesions showed increased FDG uptake on PET imaging. After treatment, changes of lesion size were evaluated on radiological scans as normal, reduced, unchanged or increased. Similarly, changes of lesion FDG activity were classified as normal, reduced, persistent or increased activity. After treatment, concordant results between PET and radiological studies were observed in the majority (78%) of tumor lesions; in padicular, disease regression and stable disease were found in 45 and 17 tumor sites, respectively. However, discordant results were obtained in the remaining 17 (22%) lymphoma lesions. Of these, 9 lesions had normal FDG activity but still radiological abnormalities suggesting treatment efficacy associated to persistent fibrotic changes. Conversely, 8 lesions still showed abnormal FDG uptake, but normal radiological scans suggesting residual disease undetectable by conventional studies. In addition, whole-body PET detected 2 new lesions in 2 different pts. In conclusion, the results of this study suggest that whole-body PET imaging is able to more accurately assess treatment effects in pts with tymphoma compared to conventional imaging techniques.

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c. Mainolfi, S. Maurea, P. Varrella, C. Alaia, C. Imparato, A. Lacagnina, V. De Rosa, M. Ziviel]o, L. Bazziealupo, M. Salvatore. Medicina Nucleate e Radiodiagnostica, Istituto Nazionale dei Tumori; Centre per la Medicina Nucleare del CNR, UniversitY,Federico II, Napoli, Italy

R. Pijpers, P. Borgstein~, H. Greuter, G. Teule, S. Meijer.~. Departments of Nuclear Medicine, and Surgical Ontology::]:.Ziekenhuis van de Vrije Universiteit, Amsterdam, The Netherlands.

CHARACTERIZATION OF SOLITARY PULMONARY NODULES AND STAGING OF LUNG CANCER USING F-18 FDG PET: COMPARISONWITH CT The characterization of solitary pulmonary nodule (SPN) and staging of lung carcinoma (Ca) are relevant in clinical oncology. In this study, we report our experience regarding the potential of positron emission tomography (PET) with fluorine-18 (F-18) deoxyglucose (FDG) in 90 patients (pts) of which 24 with SPN (3 granulomas, 3 hamartochendromas, 2 flogosis, 1 earcinoid, 4 epidermoid Ca, 6 adenoCa and 5 metastases) and 66 pts with lung tumors (40 epidermoid Ca, 22 adenoCa, 2 small cell Ca and 2 metastases). All pts underwent chest computed tomsgraphy (CT) and PET with F-18 FDG (370 MBq iv, chest and whole-body imaging). The size of tumor sites (primary, lymph node and distant metastases) was obtained on the basis of CT findings. FDG images were qualitatively evaluated and considered abnormal when lesion tracer uptake was greater than blood pool as well as backgroud activities. Pts with SPN were divided into two groups on the basis of benign (n=9) or malignant (n=15) lesions. No FDG uptake was observed in benign SPN; conversely, a significantly increased FDG activity was found in malignant SPN. However, no difference in lesion size between benign and malignant SPN was observed (1.7-+0.7 vs 2.0_+0,7 cm). Pts with primary lung Ca (n=74) were classified according to mediastinal lymph node involvement on CT (N): NO (n=34), N2 (n=30), N3 (n=10). In these pts, concordant results between CT and PET were found in the majority (82%) of cases; however, 5 pts NO on CT were N2 or N3 on PET. Furthermore, 8 pts N2 on CT were N3 on PET. Finally, in 9 (12%) of the pts with primary lung Ca whole-body PET imaging showed the presence of distant metastases with increased FDG activity. Thus, the results of this study suggest that FDG PET imaging allows to characterize SPN and to accurately stage pts with primary lung Ca. In particular, increased FDG uptake in malignant SPN is suggestive of high glucose tumor metabolism and is able to differentiate these lesions from benign SPN. Furthermore, abnormal FDG activity in normal mediastinal lymph node on CT reflects the presence of metastatic involvement. Whole-body PET allows to identify the presence of distant metastases. Therefore, whole-body PET imaging shows a relevant clinical role in pts with SPN as well as in those with proven lung cancer.

INFLUENCE OF NODAL METASTASIS ON ABSOLUTE TRACER UPTAKE IN SENTINEL NODE BIOPSY IN BREAST CANCER.

Sentinel node (SN) biopsy in breast cancer is a regional staging technique which has the potential to render axillary lymph node dissection (ALND) superfluous in the majority of patients (pts). We evaluated traceruptake in SNs in 23 consecutive pts, with palpable breast cancer, who were operated 23+3 hours after peritumoral injection of 40 MBq of Tc-99m-colloidal albumin in 4 ml saline. One pt was excluded because of a preoperative suspected palpable axillary lymph node. In this pt, the palpable node was replaced by turnout while another nearby node contained tracer. Scintigraphy was performed 2 and 18 hours after injection to estimate number of SNs and nonSNs. If more equally intense axillary loci were visualised (8 pts), both were considered to be SNs. Following ALND, the SNs were excised from the ALND specimen with gamma probe guidance and weighed. Traceruptake was estimated in a well counter and expressed as percentage of injected dose. Thirty SNs and 16 nonSNs were retrieved. Traceruptake (average ±SD, median) in SNs (0.56±0.83%, 0.28) was significantly higher (P<0.05) compared to non SNs (0.19±0.39%, 0.06). The uptake in 8 metastatic SNs (0.91--1.0%, 0.44) was higher than in 22 normal SNs (0.42:~0.74%, 0.28), though not significantly (P=0.23). In one pt the biopsy specimen contained 2 lymph nodes. A micrometastasis was found in the smaller and least radioactive one, possibly as a consequence &diverging afferent lymphatic channels. Conclusions: (1) SNs show a high variation in traceruptake. (2) If net completely replaced by turnout, traceruptake in the SN is not influenced negatively by metastatic tissue. (3) Accurate clinical preoperative staging is necessary to trace pts with palpable lymph nodes in whom the SN procedure might become irreliable.

P 197

P 199

S. Hoegerle, E.U.Nitzsche, A. Einert, F. J~ngling, A. Imdahl, A. Otte, E. Moser. N u c l e a r Medicine, Diagnostic Radiology and Surgical Oncology, Univ. of Freiburg, G e r m a n y

~.Spanu, F.Ginesu,A.Farris,M.E.Solinas,G.Deiola,C.Bagella, P.Pirina, G.C.Ginesu, S.Nuvoli, P.Solinas and G. Madeddu. Institutes of Nuclear Medicine, Respiratory Diseases and ©ncology. University of Sassari.ltaly.

IMPROVED WHOLE BODY CANCER IMAGING C O M B I N A T I O N OF F-18 DG AND F-18 I O N PET

THE R O L E OF T c - 9 9 m TETROFOSMIN (T) SPECT MEDIASTINAL LZMPH NODE METASTASIS DETECTION L U N G C A N C E R (LC)

Background: This p r o s p e c t i v e

BY

b l i n d e d s t u d y was designed to a n s w e r the q u e s t i o n whether the c o m b i n e d F-18 DG a n d F-18 i o n PET e n a b l e s an improvement in d i a g n o s t i c PET c a n c e r imaging. M e t h o d s : F o l l o w i n g a 12 hours f a s t i n g p e r i o d 20 patients (PAT) u n d e r w e n t PET imaging 90 m i n a f t e r i n j e c t i o n of 300 M B q F-18 DG a n d i00 M B q F-18 ion. Image i n t e r p r e t a t i o n w a s p e r f o r m e d by three b l i n d e d experienced i n v e s t i g a t o r s . All PET r e s u l t s w e r e c o r r e l a t e d w i t h the r e s u l t s of the sum of all imaging m o d a l i t i e s used. Results: In all 20 PAT a g o o d i l l u s t r a t i o n of the s k e l e t o n was a c h i e v e d . E v e n a n a t o m i c a l d e t a i l s s u c h as vertebral arches, spinal c a n a l a n d i l i o s a c r a l articulation were clearly depicted. A l l soft tissue cancer lesions have been localized e x a c t l y as c o n f i r m e d by CT or M R I r e s p e c t i v e l y . 16 s k e l e t a l lesions were s u s p e c t e d to r e p r e s e n t bony metastatic disease b y PET. However, 3 lesions t u r n e d out to r e p r e s e n t degenerative disease. C o n c l u s i o n s : C o m b i n e d F-18 DG and F-18 ion w h o l e b o d y PET i m a g i n g is w e l l s u i t e d for simultaneous i m a g i n g of m e t a b o l i c a l l y active soft tissue cancer lesions a n d the skeleton. The method enables a better diagnostic efficiency because of its simple feasibility, the i l l u s t r a t i o n of a n a t o m i c a l r e f e r e n c e p o i n t s and simultaneous detection of potential bony m e t a s t a t i c disease.

994

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To e v a l u a t e T-SPECT as a d i a g n o s t i c tool to detect mediastinal involvement in LC pts, we s t u d i e d 87 p r i m a r y lung c a n c e r (PLC) pts, 83 M a n d 4 F, a g e d 45 to 82 yrs: 46 s q u a m o u s cell, 6 undifferentiated, 21 adenocarcinomas, 2 carcinoid, 4 SCLC and 8 u n k n o w n o r i g i n c a r c i n o m a s . We also o b s e r v e d 12 s e c o n d a r y lung c a r c i n o m a s (SLC). In all pts, SPECT chest images were a c q u i r e d 15 min. after 740 M B q T i.v. i n j e c t i o n and c o m p a r e d w i t h X - R a y and CT scan and a l s o related to bronchoscopy and biopsy for mediastinal involvement. Lymph node metastases w e r e d e f i n i t i v e l y i d e n t i f i e d in 46 PLC and in 5 SLC pts and T - S P E C T was p o s i t i v e in 35/46 and in 4/5 in a c c o r d a n c e with CT. T-SPECT was true p o s i t i v e in f u r t h e r 9 PLC and in 1 SLC pts w i t h n e g a t i v e CT, w h i l e T was false n e g a t i v e in the r e m a i n i n g 2 CT p o s i t i v e PLC pts, one w i t h a 1 cm lymph node. In 5/7 PLC pts with positive mediastinal T-SPECT and CT images at first" observation, both texts were concordant in monitoring lesion progression (2 cases) or regression (3 cases) after radio and/or chemotherapy; in the r e m a i n i n g 2 progression pts only T-SPECT showed a more marked lymph node involvement. Tc-99m Tetrofosmin SPECT seems useful to detect mediastinal lymph node met a s t a s e s in LC pts, s h o w i n g m o r e e l e v a t e d v a l u e s of s e n s i t i v i t y (96.1%) t h a n CT (80.4%) in our pts. M o r e o v e r , T - S P E C T c o u l d p l a y an i m p o r t a n t role in e v a l u a t i n g tumor r e s p o n s e to treatment.

P 200 S.N.NOVI~OV, S.V.Kanayev, L.A.Jukova. Institute of Ontology, Department of Radiation Oncology and N u c l e a r Medicine.

S C I N T I G R A P H I C SIGNS OF BONE MILRROW INVOLVEMENT IN PATIENTS W I T H M A L I G N A N T LYMPHOMAS. PURPOSE: To evaluate scintigraphic signs of bone m a r r o w invasion by Hodgkin's disease (HD) and n o n - H o d g k i n lymphomas (NHL). MATERIALS A N D METHODS: Whole body bone m a r r o w (BM) s c i n t i g r a p h y was p e r f o r m e d in 316 patients with HD and 87 - with NHL. A n t e r i o r and p o s t e r i o r images were obtained on UAPEX-SP6" ECT unit ("ELSCINT') 45-90 min after i/v injection of 10-20 M B q / k g of Tc99m-colloids ("Coren" Russia). All but 3 m e t a s t a t i c lesions diagnosed by BM s c i n t i g r a p h y were confirmed by biopsy, Xray or m a g n e t i c resonance imaging. RESULTS: 81 patients had scintigraphic signs of BM involvement: 65 - by HD and 16 - by NHL. Focal defects were m e n t i o n e d in 57/65 cases of BM invasion by HD and in 5/16 - by NHL. Twelve patients (8 with HD and 4 - with NHL) had extensive BM involvement: in 5 cases m a n i f e s t e d by diffusely d e c r e a s e d tracer uptake in the skeleton and in 7 cases - by multifocal BM lesions. All 7 hot spots were d e t e c t e d in patients with NHL and were typical for BM lesions with bone d e s t r u c t i o n and extensive infiltration of soft tissues. Peripheral expansion of tracer uptake was not associated with BM invasion neither by HD nor by NHL (p>0,1). CONCLUSION: Scintigraphic signs of BM invasion ~n patients with HD and NHL are different.

P 202 Edit Ambrus, IAszl6 P~vics, Adam Kuncz, Erika V6r6s, L~iszl6 Balkay, Mikl6s Emil, Lajos Tr6n, MiMly Bodosi, L~iszl6 Csernay Albert Szent-Gy6rgyi Medical University

COMPARATIVE STUDY WITH FDG-PET AND MIBI-SPECT IN BRAIN TUMOURS FDG-PET studies permit an assessment of the degree of brain tumour malignancy and a distinction between brain damage due to radiation and tumour recurrence. MIBI-SPECT also affords promising results in this field. The aim of this work was to compare the diagnostic value of MIBI-SPECT with that of FDG-PET in the identification of primary or recurrent brain tumours. Both SPECT and PET examinations were carried out within a week in 16 patients (13 males, 3 females, mean age: 35 years, range: 9-61 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 grades I-IV. The SPECT and PET images were analysed visually and semiquantitatively. Seven tumours proved on histology to be gliomas of grades III-IV. In 7 of the investigated 16 patients, an enhanced MIBI uptake was visualized at the site of the brain tumour. In these 7, 3 were primary and 4 were recurrences of gliomas of grades HIIV. In 5 of the MIBI-positive patients, the FDG uptake was also observed to be increased by PET. In the tumours (primary or recurrent), neither MIBI nor FDG revealed a pathologically increased uptake in gliomas grades I-II. 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)]. It is concluded that MIBI-SPECT is a valuable and simple tool for evaluation of the biological characteristics of brain tumours.

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t9 O. P 201 T.Pangerl, Peck.Radosavjlevic, K.Kaserer, B.Niederle, A.Gangl and LVirgolini, Department of Nuclear Medicine, University of Vienna, Austria. SOMATOSTATIN (SST) AND VIP RECEPTOR SUBTYPE GENE EXPRESSION IN HUMAN TUMORS Somatostatin-14 inhibits hormone secretion and tumor growth, whereas VIP acts as a cytokine. In recent years, five human SST (hSSTR1-5) and two VIP receptor subtypes (VIP1-2) have been characterized and cloned. In this study, hSSTR1-5 and hVIP1-2 mRNA transcripts from 39 tumor tissues, a variety of normal tissues as well as from 7 tumor cell lines were investigated. For hybridization, purified inserts (cDNA), from each SSTR and VIPR subtype have been used. In 6 of 8 colonic adenocarcinomas only the hSSTR3 was expressed at a considerably high level. Furthermore, in 7 of 10 breast tumors, in 5 of 5 pheochremo-cytomas, and in 3 of 3 pancreatic adenocarcinoma cell lines the hSSTR3 was the subtype which was most highest expressed. The minority of tumor entities expressed mainly hSSTR2, hSSTR4 or hSSTR5, whereas in all tumors hSSTR3 was present. Expression of pHVlPR (VIPR1) was found in melanomas, colonic adenocarcinomas and pancreatic call lines, whereas pHIVR8c (VIP2) was lacking in almost all tumors. Compared to the expression of SSTR3, the VlPR1 expression was not remarkable. We conclude that hSSTR3 is the most frequent receptor and is expressed on almost all human tumors. This ,,universal" tumor receptor seems to be involved in a variety of pathological processes related to oncology. In nuclear medicine, a SSTR3-specific radioligand is warranted for diagnosis and therapy.

P 203 A. Varrone A. Soricelli, A. Cuocolo, G. Storto, G. D'Amore, A. Postiglione, M. Salvatore. Depagxnents of Diagnostic Imaging and Clinical and Experimental Medicine, University of Naples Federico II. EVALUATION OF 99mTc-TETROFOSMIN AND 201-THALLIUM UPTAKE IN INTRACRANIAL TUMORS WITH SPECT 201-Thallium (201-TI) has been widely used for the assessment and grading of intracraniai tumors, due to its ability to accumulate within tumor cells. 99mTc-tetrofosmin has been recently introduced for myocardial perfusion imaging and in vitro studies demonstrated that its uptake depends upon plasma membrane potential and mithocondrial activity. The aim of this study was to evaluate the feasibility of using 99mTc-tetmfosmin for brain tumors imaging and to compare its uptake with that of 201-T1. Twenty-four consecutive patients with histologically verified intracraniaI masses were studied with a brain dedicated SPECT system (Ceraspet, DSI, USA). In a first group of 7 patients (group A, 3M, 4F, 53+10 yrs), three scans at 20, 40 and 120 rain were performed to assess the timing for best acquisition of 99mTc-tetrofosmin. In a second group of 19 patients (group B, 9M, 10F, 57+13 yrs) two sequential 201-T1 (74-148 MBq i.v.) and 99mTc-tetrofosmin (740-925 MBq i.v.) studies were performed 20 rain after tracer injection. A visual analysis on reconstructed images of both 201-TI and 99mTc-tetrofosmin studies was performed, assessing the contrast of the lesions to the background and the definition of the tumor's margins. For semiquantitative analysis elliptical ROIs on the tumor site (Tumor ROI) and irregular ROIs on the whole contralateral hemisphere (Background ROI) were drawn. The Tumor/Background (T/B) ratio was calculated for each lesion. In group A, no significant difference in the T/B ratio among 20, 40 and 120 min post-injection studies was observed. In group B, the quality of reconstructed images with 99mTc-tetmfosmin, judged visually, was superior to that of 201-TI in 47% of all studies, and was comparable Jn the remaining 53%. A significant relationship between 20!-T1 and 99mTc-tetrofosmJn T/B ratio (r=0.75, p<0.01) was found. T/B ratio of 99mTc-tetrofosmin was significantly higher than that of 201-TI (23.3_+21.5 vs 6.1+2.9, p<0.005). 99mTc-tetrofosmin is a suitable radiotracer for imaging intracranial lesions with SPECT. Compared to 201-TI, it allows a better definition of tumor margins mad a higher contrast between neoplastic and normal brain tissue.

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P 204 A Staudenherz B Fazeny, Ch. Marosi, T. Leitha, University Clinics of Nuclear Medicine and Internal Medicine, University Vienna - AUSTRIA

99mTe-SESTAMIBI SCINTIGRAPHY IN GLIOBLASTOMA R E C U R R E N C E S : DOES IT R E V E A L M O R E THAN JUST THE IMPAIRED BLOOD-BRAIN BARRIER

P 207 A Hertel, G v Hoist, G Seipp, G Marquardt*, P Hernaiz-Driever**, RP Baum, A Niesen, S Adams, R. Lorenz*, G H6r Departments Nuclear Medicine, Neurosurgery*, Pediatrics** Universit&tsklinikum der Johann Wolfgang Goethe-UniversitAt Frankfurt/Main, FRG

LONG TIME SURVIVAL OF BRAIN TUMOR PATIENTS: COMPARISON OF THALLIUM AND HISTOLOGICAL GRADING

99mTc sestamibi (MIBI) has been successfully applied in recurrent glioblastoma and was reported to be superior to CT/MRI. In contrast to other maIignancies in which the degree of vascularisation, malignancy, viability and multi-drug resistance are the decisive factors for MIBI uptake, the integrity of the blood-brain barrier (BBB) plays a crucial role for uptake in brain tumours. The aim of this study was to evaluate the incremental diagnostic information of MIBI as tumour-avid radiopharmaceutical in comparison to 99mTcpertechnetate (99mTC) as sole indicator for the integrity & t h e BBB. 9 patients with confirmed recurrent glioblastoma were included. MIBI SPET was performed I0 min. p.i. of 555 MBq 99mTCsestamibi i.v. with a triple-headed gamma camera equipped with Lq-IRPAR collimators over 360 ° (3°/step) and stored in a 1282 matrix. Identical acquisition parameters were used for 99~Tc pertechnetate SPET, which was acquired 3 hr. p.i. of 740 MBq 99mTc i,v.. Standard uptake values (SUV) were calculated from attenuation corrected transaxial slices. Additionally tumour/plexus-, tumour/nasopharynx- and tumour/parotis-ratios were assessed in both studies. No statistically significant differences were found for the mean SUV of tumour tissue with MIBI (3.69E-03 + 7.15E-04) and 99mTc (4.87E-03 _+ 2.23E-03; p = 0245) and for the turnout/nasopharynx- and tumour/parotis-ratios. Only the tumour/plexus-ratio was significantly lower for MIBI than for 99mTc (p = 0.033). In conclusion, our data indicate that MIBI scintigraphy in brain tumours at l0 min. p.i reveals no additional visual information over the conventional 99mTc-pertechnetate brain scan and tracer retention primarily reflects BBB integrity.

Brain tumors exhibit a bad prognosis which is mostly correctly described by histological grading according to WHO citeria. Nevertheless, in some cases, extraordinary courses contrary to expected survival are observed. Aim of our prospective study was to follow brain tumor patients whose primary brain tumor had been imaged with thallium-SPECT prior to therapy. Patients, methods: 20 adult patients with primary brain tumors (WHO I,I1: 7, Ill,IV: 13) imaged 1988 (n=15) and 1993/1994 (n=5) were followed up for survival. All pts underwent surgery and all tumors were classified histologically. 10 were alive and 10 died of their brain tumor. Maximum survival was 2475 days. Thallium scans were performed on a sophy SPECT camera 30 minutes after injection of 74 MBq TI-201. A Thallium-index was calculated from slices containing maximum tumor activity (1216ram thickness) and represented tumor to non-tumor ROIs (from the contralateral hemisphere). Results: Mean survival of WHO I,II tumors was 592 days and contrary to expectation 1206 days in WHO Ill,IV tumors. Here most tumors were grade III (n=9). if one used the mean thallium-index of 1.75 as a threshold, the figures reversed: Mean survival was 1208 for TI-index <1.75 and 666 for TI-index >1.75. Correlation between TI-index and survival was r=-0.3, whereas with WHO grading it was 0.02 (p<0.01). With TI-index <1.75 9/12 were alive, with TI-index >1.75 1/8 were alive. The same figures for WHO I,I1:3/7 alive, Ill,IV: 7/13 alive. Discussion: Functional imaging with Thallium can in some cases better demonstrate prognosis prior to primary therapy than histological grading after surgery. As this is in accordance with other reports, especially using PET tracers, prospective studies are necessary to test different therapy management based on functional metabolic brain tumor imaging.

P 206 B. Gruenert, H. Amthauer, T. Schumacher, B. Bauer, H. Eichstaedt

P 208 P. Paulus. A. Sambon, R. Hustinx, M.N. Serville, P. Moreau, P. Rigo. Nuclear Medicine, University Hospital, Liege, Belgium.

Departments of Nuclear Medicine and of Neurology, Clinic Neubrandenburg; Departmentof NuclearMedicine,Virchow-Clinic,Humboldt-Universityof Berlin, Germany

TL-201 SPECT IN DIAGNOSIS AND FOLLOW-UP OF PATIENTS WITH MALIGNANT BRAIN TUMORS Introduction: Over the past decade the use of CT, MRI and PET has shown a fast and steady progress in diagnosis of malignant brain tumors. The follow-up of patients after surgery, radiation, and/or chemotherapy has still often been inconclusive for evaluating brain tumor burden. We evaluated the role of TI-201 single photon emission computerized tomography (SPECT) in diagnosis, differential diagnosis and especially in follow-up of patients with malignant brain tumors. Methods: 46 patients (28 to 74 years; median: 47) with brain tumor were studied. The SPECT imaging were initiated 5 min (early image) and 4 hours (delayed image) after injection with 60-88 MBq of 201TI-chloride. For a semiquantitative analysis, we used the ratio of delayed count density to the early count density of the tumor (Td/Te) and the ratio of tumor to normal brain tissue (T/B). Results: 201TI scintigrams showed abnormal accumulation in 38/46 (82,6%) of patients with malignant tumors. 2/8 low-grade (grade 1 and 2) astrocytic tumors showed TI-201 accumulation up to a T/B ratio of 2.6. High grade (grade 3 and 4) astrocytic tumors showed TI-201 accumulation ratio between 2.2 and 13.0. Differential diagnosis of oligodendrogliomas, astrocytic tumors and meningiomas was not possible. In the follow-up of 19 patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing TI-201 accumulations. Ratios were also higher in patients with recurrent tumors than those with necrotic lesions (5.5 + 1.4 and 1.5 + 0.74). Conclusions: These results suggest that 201TI-SPECT may prove helpful to determine the malignancy of brain tumors and to differentiate recurrence from necrosis after therapeutic procedures in combination with CT and MRI. Further investigations should focus the benefit and costs analyses in comparison to PET and MR spectroscopy in differentiating recurrent malignancy from radiafion-induced necrosis. Moreover, a larger group of patients is needed to gain higher significance of our results.

996

USE OF POSITRON EMISSION TOMOGRAPHY WITH 18FDG IN PATIENTS WITH HEAD AND NECK CANCERS. CLINICAL USEFULNESS TO RECURRENCES DETECTION AND STAGING OF LYMPH NODE INVOLVEMENT. At initial presentation of head and neck cancers, lymph node involvement appears to be the most important prognostic factor which affect patients survival rate. Later, detection of potentially curable recurrences remains the most important clinical challenge despite improvements of spiral CT and MRI. The purpose of this study is to evaluate the clinical usefulness of FDG-PET in the detection of lymph node involvement and recurrences in 37 patients with biopsy-proven cancers. 25 patients were studied before therapy (staging) and 12 patients were evaluated for recurrent disease (recurrence). All patients were operated and in all, clinical data, CT and FDG-PET results were corrclated with the histopathologieal findings. Results : - Staging : All primary tumors were detected in 25 patients, of which 10 showed 13~ph nodes involvement at histopathological examination. In one case, FDG-PET identified one controlateral lymph node not previously shown by the standard staging data. We deplore 5 false negative results (microscopic lymph nodes involvements) and 2 false positive (granulomatous diseases). - Recurrences : 12 patients evaluated for recurrent disease were correctly identified in 11/12 cases. FDG-PET was the only imaging technique to identify local recurrence in 2 cases and lymph node involvement in 2 other cases. We deplore 1 false positive result in a patient with recurrent epiglottic tumor in whom a significant uptake in a reactional lymph node was noted. Conclusion : FDG-PET is a uscful diagnostic modality in detecting recurrent tumors and to precise the lymph node staging.

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P.L. JaqeK, E.J.F. Franssen, W. Kool, W. Vaalburg and D.A. Piers. Dept of Nuclear Medicine, University Hospital Groningen, The Netherlands.

Y.KawaL E. Tsukamom~ H. Abe, K. Kishmo, T.Kohya, N.Tamaki. Hokko Cardiovascular Hospital and Hokkaido University School of Medicine, Sapporo, Japan.

E V A L U A T I O N OF T U M O R I M A G I N G U S I N G L - 3 - [ I - 1 2 3 ] - I O D O ALPHA-METHYL-TYROSINE IN N O N B R A I N T U M O R S

C-ll-labeled amino acids have successfully been used for metabolic imaging of tumors using PET. L-3-[I-123]-iodoalpha-methyl-tyrosine (I-123-IMT) is a modified amino acid. It is reported to be avidly taken up in brain tumors reflecting amino acid transport and is suitable for SPECT. To determine its potential use in non-brain tumors we injected 300-450 MBq !-I23-IMT in 17 patients with different tumors (5 breast cancer, 4 lung tumors of which 1 benign~ 2 liver carcinoid, 4 soft tissue tumors of which 1 benign as well as 2 primary brain tumors). Tumor size ranged from i - 12 cm. Imaging was repeated after radiotherapy in 2 patients with breast cancer. Histology was obtained in all cases. Dynamic scans of the tumor area were acquired during the first 30 minutes after injection, followed by SPECT or total body scanning, which was repeated after 3 hrs. Plasma samples were analyzed for 1-123-IMT, free iodine123 and other metabolites. All tumors were visualized, except for 2 carcinoid liver metastases. Tumor to background (T/B) ratios ranged from 1.4 - 3.8 on the early planar and from 1.3 - 6.2 on the early SPECT images. Tumor uptake peaked in the first hour and had diminished in nearly all cases 3 hrs p.i. T/B ratios in a benign bone inflammatory process and a focal pulmonary vasculitis were less than 1.2 (planar) and 1.9 (SPECT) and could be differentiated from uptake in all malignant non brain tumors. 1-123-iMT was rapidly cleared from the plasma (3.2%±0.6(sd) %I.D./I at i0 min p.i.). One hour p.i. 18 ± 6% of plasma radioactivity consisted of free 1-123, amounting to less than 1% of I.D. There were no other metabolites. Normal distribution consists of some uptake in brain, liver, spleen, muscles, pancreatic region, intestinal structures and massive uptake and excretion in kidneys and bladder. We conclude that 1-123-IMT has potential as a metabolic tracer also in tumors outside the brain.

CAN BMtPP IDENTIFY AREAS AT RISK IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION ? BMIPP, a new iodinated fatty acid analog, can probe fatty acid uptake and metabolism in the myocardium. Previous studies indicated that BMIPP can reflect ischemic memory as areas of reduced tracer uptake despite normal perfusion. To assess whether the fatty acid imaging can delineate areas at risk in patients with acute MI following successful revascularization, BMIPP findings at one week post MI were compared to perfusion imaging obtained before and after revascularization therapy. Thirty-four patients with acute MI underwent tetrofosmin SPECT before (TF0) and one week (TF1) after successful PTCA therapy at rest. BMIPP SPECT was also performed at rest under fasting state at one week (BM1) post MI. The defect scores of each tracer were graded by 4-point grading system (0 as normal to 3 as defect) in 14 myocardial segments. The areas of BMIPP abnormality were identical to those of TF0 abnormality in 31/34 cases(91%). The BM1 score (13 -+8) was similar to the TF0 score (14 -+ 7), while it was larger than the TF 1 score (9 +- 7) (P<. 0001). In addition, a high correlation was obtained between BM1 and TF0 scores (BMl=3.24+0.75*TF0, R=0.75, p<. 0001). These data indicate that the BMIPP defects at one week post MI can identify areas at risk similarly as TF perfusion defects in the acute phase. This may be due to the impairment of fatty acide uptake and metabolism reflecting prior severe ischemic insult which persists a few weeks after recovery- of perfusion in acute phase of M!.

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P 210

P 213

C.Y. Chang1, C. M. Cheng% M.Y. Liu2. Departments of Nuclear Medicine I and Surgery2, Tri-Service General Hospital ; National Defense Medical Center, Taipei, Taiwan, R.O.C.

N. D a n c h i n , V. D i d i e r , P.Y. M a r i e , M. A n g i o i , P. O l i v i e r , N. D a v i d , N. H a s s a n , N. Q u i r i , T. A r s e n a , G. K a r c h e r , A. B e r t r a n d . C H U - N a n c y , F r a n c e .

DIFFERENTIAL DIAGNOSIS BETWEEN RECURRENCE OF MALIGNANT GLIOMA AND RADIATION NECROSIS BY TL201/TC-99M DTPA SPECT. Deteriorating clinical status after high-dose radiation therapy for malignant gliomas may result from tumor recurrence or radiation necrosis. Conventional imaging modalities cannot distinguish reliably these two conditions. In this current study, a total of 16 patients, 10 patients with recurrent malignant glioma (Group I) and 6 patients with radiation necrosis (Group [I), underwent both T1201 and Tc-99m DTPA brain SPECT. The brain SPECT w e r e performed 5 min after administration of 2 mCi of T1-201 and 20 rain after administration of 20 mCi of Tc-99rn DTPA respectively, Count ratios of a lesion to normal brain (L/N) were calculated from the rectangular ROI for quantitative analysis. The L / N ratios in this current study showed: ,. Brain SPECT GroupI(n=lO) GrouP1.9+II0.7(n=6) p
VERY LONG TERM PROGNOSTIC VALUE OF EQUILIBRIUM RADIONUCLIDE LEFT VENTRICULAR EJECTION FRACTION AFTER ACUTE MYOCARDIAL INFARCTION T h e s h o r t a n d m e d i u m t e r m p r o g n o s t i c v a l u e of l e f t ventrieular ejection fraction (LVEF) after myocardial infarction (MI) is w e l l e s t a b l i s h e d . The a i m of t h e p r e s e n t s t u d y w a s to d e t e r m i n e prognostic indicators in p a t i e n t s f o l l o w e d for > 15 y e a r s a f t e r an e p i s o d e of MI. A consecutive s e r i e s of 92 p a t i e n t s (54±10 y e a r s ) with 99mTc equilibrium LV angiography within 2 w e e k s of an a c u t e HI in 1 9 7 8 - 1 9 7 9 and initially treated medically were included. The infarct territ o r y w a s a n t e r i o r in 4 1 % a n d i n f e r i o r in 55 %. Inhospital complications w e r e c o n g e s t i v e h e a r t failure in 36 %, s u p r a - v e n t r i c u l a r a r r h y t h m i a s in 24 % and pericarditis in 13 %. C o r o n a r y a n g i o g r a p h y w a s p e r f o r m e d in 52 % of the p a t i e n t s . U s i n g C o x m u l t i v a r i a t e a n a l y s i s , 9 9 m T c - L V E F w a s the s o l e b e s t i n d e p e n d e n t p r e d i c t o r of d e a t h , a n d w a s an i n d e p e n d e n t predictor of r e i n f a r c t i o n . In p a t i e n t s w i t h c o r o n a r y a n g i o g r a p h y , 9 9 m T c - L V E F < 40 % a n d n u m b e r of v e s s e l - d i s e a s e w e r e the 2 i n d e p e n d e n t predictors of t o t a l c a r d i a c e v e n t s i n c l u d i n g m y o cardial revascularization. Kaplan-Meier survivalat 16 y e a r s w a s 29 % for p a t i e n t s w i t h 9 9 m T c - L V E F < 40 % vs 60 % for t h o s e w i t h 9 9 m T c - L V E F > 40 % (p < 0.01). S u r v i v a l c u r v e s of p a t i e n t s w i t h L V E F of 4150 % a n d L V E F > 50 % w e r e t o t a l l y s u p e r i m p o s e d . Radionuclide determination of L V E F early after myocardial infarction remains a potent prognostic indicator when considering a v e r y l o n g t e r m of f o l l o w - u p (> 15 y e a r s ) . B e l o w a t h r e s h o l d v a l u e of 40 %, the o u t c o m e is d e f i n i t e l y p o o r e r .

997

O n

P 214 M. Reinhardt, A. Habinger*, M. Beu, W. A. Scherbaum*, H. Vosberg, H.-W. M,",ller-G~rtner Department of Nuclear Medicine and *Diabetes Research Institute, Heinrich-Heine-University DL~sseldorf

P 216 V. Prassopoulos,J. Lekakis,J. Nanas,G. Alexopoulos,Z. Margari,A. Rapt/, P. Kostamis, S. Slamalelopoulos,S. Moulopoulos.Dept of Nuc/ear Medicine and C/in/cat Yheraped/cs "Alexandra"Universi~ Hospital, Athens, Greece,

QUANTIFICATION OF GLUCOSE TRANSPORT AND PHOSPHORYLATION IN MUSCLE BY FDG-PET

CARDIAC H23 METAIODOBENZYLGUANIDINEUPTAKE IN PREDICTING EARLYAND LATEMORTALITYIN CONGESTIVEHEARTFAILURE

The skeletal muscle is the major organ for glucose utilization under insulin stimulated conditions. In pathologic conditions like type tl diabetes the muscular glucose metabolism is disturbed and leads to a decreased sensitivity of the patient to insulin. Reduced concentrations ef Glucose-6-phosphate (G-6-P) in the skeletal muscle of diabetic patients were found applying NMR spectroscopy. A FDG-PET study showed reduced phosphorylation rates in diabetics (Kelly et al., 1996). We developed a measurement protocol for the quantification of glucose transport and phosphorylation in the skeletal muscle by FDG-PET applying the three compartment model of FDG metabolism. The sampling of the tissue and input data was optimized. Special interest was paid on the influence of the fractional blood volume on the fit results. Six patients with type I[ diabetes and four nondiabetic volunteers were studied to validate the protocol. We found a significant correlation of global glucose utilization measured during an eugtycemic hyperinsulinemic clamp with regional muscular glucose utilization as measured by FDG-PET (R2=0.87). The rate constant for phosphorylation was significantly correlated with regional (R2=0.87) and global glucose utilization (R2=0.86). Diabetics had lower phosphorylation rates than control persons. We conclude that the developed protocol is suitable for determination of rate constants in skeletal muscle. First results indicate that the intracellular phosphorylation is the disturbed metabolic step in insulin resistance and is correlated to the degree of global glucose tolerance.

It has been previously shown that adrenergic cardiac denervation assessed by H23-Metaiodobenzyiguanidine(MiBG) may identify patients (pls) with congestiveheartfailure (CHF)at highriskfor earlycardiacdeath. Methods.To examineif cardiacdenervationin CHF pts is a predictorof late mortality,we analyzeddatafrom 50 CHF pls witha 3-4,5year follow-up(age 52_+12years, 45 men, 5 women,26 pls idiopathicdilated cardiomyopathy,19 pts ischemiccardiomyopathy,5 pts valvularheartdisease).The followingparameters were assessed initially: Cardiac 1-123 MIBG uptake assessed as heart to mediastinumratio (H/M), ejectiontraction(EF), NYHAclass, pulmonarycapillary wedgepressure,rightatrialand pulmonaryarterypressures.Mortalitywas defined as early(<6 months)or late. Results. Eighteenpts were alive at the end of the follow-up period (Mortality64%, early mortality24%). Age, sex, right atrial, pulmonaryartery or pulmonarycapillarywedge pressurewere not predictorsof survival. Regarding early mortalilyMIBGuptakewas the only strongprediclor(p=0',01),while EF was of borderlinesignificance(p=0.07).MIBGH/M<1.2couldpredictearlymortalitywith sensitivity 50% and specificity89%. EF and the presenced idiopathicdilated cardiomyopathywere lhe best predictorsfor late survival (EF p=0.001, Dilated cardiomyopalhyp=0.01)while MIBGuptake and NYHAclass were of borderline significance(MIBGp=0.059,NYHAp=0.O6).EF <20%couldpredictlate mortality with sensitivity 78% and specificity 67%. MIBG H/M<1,2 could not predict late mortality. The group of CHF pts with dilated cardiomyopathyand EF>20% presentedexcellenlsurvivalrate (85%). In conclusion,MIBGuptakeis the best predictorof earlydeathin CHFpls but it is of minorsignificancein predictinglate mortality.EF is the bestpredictorof late mortalityin CliP pts.

P 215

P 217

L. van der Loan, W.~ G. (3yen. A.A.Z Verhofstad, E.C.ZH. Tan, P.Z C. Kapitein, Z Hendriks, F.H.M~ Corstens, R.ZA. Goris.

IJ.B.Bader, iD.Hellwig, 2M.M/.iller, 2H.P.StolI, 2A.Heisel, zC.Ozbek, 2H.Schieffer and IC.-M.Kirsch, iDepts, of Nuclear Medicine and 2Cardiology University Homburg/Saar-Germany

Departments of Surgery, Nuclear Medicine, and Pathology, University Hospital Nijmegen, The Netherlands. Tc-99m-HYNIC-IgG FOR EVALUATION OF SOFT-TISSUE DAMAGE CAUSED BY OXYGEN-DERIVED FREE RADICALS (ODFR). ODFR play a key role in many inflammatory diseases. However, in most models it is difficult to study the isolated effect of ODFR, since multiple abnormalities are induced. We developed a rat model for evaluation of focal effects of ODFR only. The ODFR-donor TBOOH is infused in the left superficial epigastric artery at the orifice of the femoral artery without concurrent ischemia of the limb. The limb abnormalities developing over an 24 hr. infusion period and subsequent repair, the influence of granulocyte depletion and free radical scavenging were studied by clinical evaluation and histology. For scintigraphic evaluation, Tc-99m-HYNIC-IgG was chosen given its "high uptake in inflammatory feel, high in-vivo stability, and convenient labeling procedure. Over the 24 hr. infusion period, the infused foot showed increasing signs of inflammation-like abnormalities. The affected -to-normal Tc-99m-IgG ratio was four-old higher than that in saline-infused control rats (p<0.001). Histologically, progressive muscle cell degeneration, granulocyte infiltration and vascular wall damage is observed. When the rats are made neutropenic before TBOOH infusion, the ensuing vascular injury is less severe, reflected by the lower Tc99m-IgG ratios (p<0.05). This indicates that the granulocytes have additional toxic effects on the infiltrated tissue. When non-neutrnpenic rats are evaluated over a period of 6 weeks after infusion, Tc-99m-lgG ratios gradually normalized, while clinical and histological abnormalities subsided. This repair can be facilitated and enhanced by injecting the ODFR-scavenging drug n-acetyl-cysteine (NAC): scintigraphic affected-to-normal foot ratios were initially two-fold lower in NAC-treated rats compared to untreated controls (p<0.0l). Moreover the scintigrams normalized within one week compared to 4-6 weeks in untreated rats. In conclusion, ODFR produce inflammation-like abnormalities. Tc-99mHYNIC-IgG scintigraphy allows quantitative, non-invasive monitoring of natural course and therapeutic interventions, given its concordance with clinical and histological methods.

998

CARDIAC IMAGING OF PERFUSION INNERVATION BY ~'3J-MIBG/99mTC-MIBI SCHEDULED FOR IMPLANTATION OF DEFIBRILLATOR (ICD)

AND SYMPATHETIC SPECT IN PATIENTS AN INTRA CARDIAC

Aim of the study: The coincidence between sympathetic myocardial dysfunction and severe ventricular arryhthmias may play a key role identifying patients (pts.) at increased risk for sudden cardiac death. To confirm this hypothesis we analysed the ratio between sympathetic innervation and perfusion by 123j MIBG/99mTc MIBI SPECT in pts. after cardiopulmonary resucitation due to malignant ventricular arryhthmias. An acute myocardial infraction (m.i.) was excluded, whereas all pts. of the study g~ had an m.i. in their history. 6 pts. with a cardiac disease excluded served as a control group. Methods: 10 pts. who survived a malignant ventricular tachyarrythmia scheduled for implantation of an Intra-Cardiac Defibrillator (ICD)- were included in this study. To visualise the sympathetic innervation, each patient underwent a 3600 SPECT study approximately 5h. after i.v. application of 250 MBq 123j MIBG. To distinguish disturbances of myocardial perfusion from adrenergic innervation a MIBI SPECT was 30 rain. after i.v. injection of 450 MBq 99mTc MIBI performed. Qualitative analysis of the perfusion/innervation-ratio was performed, comparing corresponding sectors of all short axis slices. Results: 2 pts. had severe sectorial defects in the MIBG study along with perfusion images. In the remaining 8 pts. congruent matching defects in infarcted areas were found. In addition severe defects of sympathetic innervation in areas of normal perfusion were registered. Within the control group defects eould'nt be observed. Conclusions: In all cases of ventricular arrythmias a severe mismatch between symp~ innervation and cardiac perfusion was demonstrated. The occurrence of severe ventricular arrythmias is associated with this pathological innervation/perfusion pattern. These results demonstrate the prognostic value of the method, identifying pts. at risk.

P 218 L, bumbreras~; I Cam62, C. Puentes3; B. Femfindez~; M Estorch2; J. Ruiz3; A. Flotats2; A. Posada3 and JJM Sampere~.

(1) Hospital Universitarto. Granada: (2) Hospital de Sant Pau, Barcelona; (3) Hospital Carlos Haya, Mdlaga .(Spain)

P 220

C.Aprile, G.Merlini, R.Saponaro, G.Cannizzaro, G.Calsamiglia, EAnesi, P.Garini, Fond." S.Maugeri" IRCCS and S. Matteo Hosp. IRCCS -Pavia, Italy APROTININ 99m Tc AND CARDIAC AMYLOIDOSIS

EVALUATION OF CARDIAC SYMPATHETIC INNERVATION IN PATIENTS WITH CORONARY ARTERY DISEASE. Objectives: This multicenter study in patients vdth CAD (Coronary Artery disease) was tmdertaken to evaluate cardiac s3~apathetic irmervation in necrotic mad ischaemic territories using metaiodobenzylgnanidine (MIBG) SPET imaging.

Methods: n=58 patients with CAD were divided into three groups: A: Myocardial infarction (MI) (n= 13); B: Myocardial ischacmia without MI (n=20); C: Myocardial infarction with post-infarction ischaemia (n=25). We compared the myocardial distribution of 123-I-MIBG and 99m-Te-tetrafosmin (I day stress-rest protocol). Vertical and horizontal long-axis images at the mid-left ventricle were selected for quantitative analysis, and a total of 16 regions of interes were determined.. Tracer uptake in each roi was scored using a 2-point scale. The total score was calculated adding the defect scores for each image. We also calculated the percent of maximal activity of the tracer in each vascular territory. Heart to Mediastinum (H/M) ratios of MIBG were calculated from anterior planar images acquired at 15m and 3h. Results: The extent and intensity of uptake of both tracers correlated in the three groups (r> 0.709; p< 0.000). The extend of defects was larger with MIBG than with perfusion tracers in the three groups (9.45 ± 3.08 vs 6.26 ± 3.06, p<.0000). More serious MIBG defects were observed in patients with painful CAD, without differences between the coronary territories (p-na.s.), The ischaemic area was also more extent in the painful patients. H/M ratio was significantly lower in patients with painful CAD (15m: 1.82 vs 1.66; p<0,007; 3h: 1.64 vs 1.82; p<0.011). When MIBG uptake was corrected for perfusion abnormalities at stress and rest, the diagnostic value for detection of angina increases (p< 0,005). These results suggests that sympathetic innervation of heart is highly sensitive to ischaemia. The extent of denervated myocardium (MIBG defect) suggests that there are ischaeimasareas unexplored with perfusion tracers. The presence of residual but viable nerves can explain the presence of pain,

Amyloidosis is an emerging problem whose real incidence is largely underestimated and cardiac involvement represents the most unfavourable prognostic factor. Herein we report our experience in the detection of heart involvement employing 99m Tc Aprotinin in 71 pts (92 studies) with primary amyloidosis (66 AL,5 AF). Scan was performed in the anterior and LAO view 90 min after iv injection of about 700 Mbq. Cardiac uptake of variable degree was observed in 32 pts: in 7 of them the scintigraphic findings were corroborated by histology, while in the remaining they were confirmed by clinical evolution. The following points are worth mentioning: O three positive scans were observed in subjects without clinical or instrumental (echo & ECG) evidence of involvement; O on the other hand, in 3/17 pts with high probability of disease, but without organ failure, the scan ruled out the involvement; O among 19 pts with suspected involvement, the disease was confirmed in 10 and ruled out in 9; O all the pts with high probability/clear evidence of disease accompanied by CHF had positive scan; ~) Deaths attributable to cardiac causes were observed only in pts with positive scan. These results confirm our previous observations and seem to indicate Tc-Aprotinin as a suitable and early indicator of amyloid deposits, while the classical electro and echographic findings are rather indicators of organ failure.

P 221

A.C. Otto ~, H. Naud62, A. van Aswegen~', M.G. L6tter ~, D.J.R. du Toit ~, M.G. Nel ~, Department of Nuclear Medicine ~, Department of Biophysics2, University of the Orange Free State, Bloemfontein, South Africa.

E.Derebek~ G. (~apa, H.Durak, O.Ergene, O.Kozan, E.Ozbilek, D.Kaya, B.De~irmenci. Dokuz Eyl01 University Hospital, izmir,Turkey.

12aI - BMIPP is a modified branched fatty acid analogue with a relative slow clearance from the heart which renders it more suitable to study myocardial fatty acid metabolism and myocardial viability. Myocardial fatty acid uptake is regulated by a variety of factors including concentrations of'potential substrates, cardiac workload and possible ischaemia. Since these factors could be altered by exercise the purpose of this study was to compare ~23I - BMIPP uptake at rest and with exercise in ten healthy volunteers. 1~I - BMIPP (185 MBq) was administered intravenously followed by planar and tomographic imaging with a dual headed scintillation camera. A geometrical mean method including the triple energy scatter correction technique was used to quantify myocardial uptake using the planar images. The mean uptake with respect to the administered dose for the rest and exercise studies were 4.62 + 0,98% and 3.02 _+ 0,58% respectively. The mean difference was 1.60 =t= 0.83% and the 95% confidence interval was 1.00% - 2.19%. This indicates that 123I -BMIPP is sensitive to the metabolic changes caused by exercise intervention to reduce global myocardial uptake significantly.

INFUSION

l

t,-'

t._

P 219

THE UPTAKE OF 1~I-BMIPP IN THE N O R M A L H E A R T W I T H EXERCISE.

=

C O

VERSUS

TETROFOSMIN

IN

BOLUS

THE

INJECTION

OF

DETECTION OF

Tc-99m

VIABLE

MYOCARDIUM.

Although the quantitative Tc-99m labeled perfusion imaging using bolus technique is proposed in the detection of viable myocardium, results are controversial. We compared bolus (B) and infusion (lnf) techniques in the detection of viable myocardium, using Tc-99m tetrofosmin (TF). 15 patients with suspected viability (more than 75% stenosis and severely hypokinetic / akinetic / dyskinetic segments) enrolled in the study. Using 2-day protocol, rest B (25 mCi) and rest inf (25 mCi, 1-hour inf in 0.9% saline sol) TF SPECT imaging were performed. Abnormal segments on angiography were evaluated quantitatively (percentage of max activity), dividing left ventricle into 9 segments. More than 50% uptake was accepted as viability criterion. All of 20 akinetic and dyskinetic segments were non-viable in both tecniques (100% concordance, B uptake=38+7, Inf Uptake=35+9). Whereas, there was 82% concordance in 17 severely hypokinetic segments regarding viability. All of 3 discordant segments were viable only with Inf technique, which was confirmed with postrevascularization follow-up. Moreover, in 14 hypokinetic segments which was concordant regarding viability, uptake values were higher in inf images (B uptake=40+7, Inf Uptake=44+_5, p<0.05). In conclusion, our preliminary results suggest that TF Inf SPECT may be more accurate technique than bolus injection in the detection of viable myocardium.

999

O

P 222

P 224

J Prosser

A Ng,

W Martin,

Department Infirmary,

of M e d i c a l Scotland.

A Rankin,

Cardiology,

IMPAIRED RIGHT VENTRICULAR WITH WOLFF PARKINSON WHITE

I Hutton.

Glasgow

Royal

M.G. Kou~elou, S. Psyhari, G.N. Theodorakis, E. Livanis, A. Karoussou, A. Kouzoumi, D.T. Kremastinos, Nuclear Medicine Dept and 2 nd Dept of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece

F U N C T I O N IN P A T I E N T S SYNDROME. CARDIAC DENERVATION AFTER RADIOFREQUENCY OF SUPRAVENTRICULAR TACHYCARDIAS

ABLATION

Gated radionuclide ventriculography (RNVG) a l l o w s a c c u r a t e a s s e s s m e n t of left a n d right v e n t r i c u l a r function. T h i s s t u d y c o m p a r e d right and left v e n t r i c u l a r f u n c t i o n in p a t i e n t s w i t h Wolff-Parkinson-White (WPW) s y n d r o m e a n d a c o n t r o l group. T w e n t y two W P W p a t i e n t s u n d e r w e n t R N V G p r i o r to r a d i o - f r e q u e n c y c a t h e t e r ablation. A f u r t h e r 18 p a t i e n t s , n o r m a l on r o u t i n e assessment, were selected from patients studied b y RNVG. Left a n d right v e n t r i c u l a r e j e c t i o n fractions were calculated using a previously v a l i d a t e d manual, s i n g l e ROI t e c h n i q u e . No d i f f e r e n c e in left v e n t r i c u l a r f u n c t i o n b e t w e e n the two g r o u p s was o b s e r v e d ; m e a n L V E F w a s 43.4% (S.D=9.4) for W P W p a t i e n t s a n d 44.6% (~6.1) for p a t i e n t s in the n o r m a l group. However, there w a s a s i g n i f i c a n t d i f f e r e n c e in r i g h t ventrieular function; m e a n R V E F = 31.4% (±8.4) for W P W p a t i e n t s and 43.9% (±6.5) for n o r m a l patients, (P<0.0001); 14 W P W p a t i e n t s h a d s i g n i f i c a n t l y i m p a i r e d R V function. At p r e s e n t 6 patients have undergone repeat RNVG following s u c c e s s f u l a b l a t i o n - m e a n R V E F p r e R F A = 29.5% (±6.25) a n d 3 4 . 5 4 % (±8.21) p o s t RFA. Four p a t i e n t s d e m o n s t r a t e d an i m p r o v e m e n t in RVEF, a l t h o u g h the g r o u p m e a n r e m a i n s s i g n i f i c a n t l y lower t h a n the n o r m a l group. R V f u n c t i o n in W P W s y n d r o m e is s i g n i f i c a n t l y r e d u c e d f r o m n o r m a l levels, i m p r o v i n g p o s t a b l a t i o n b u t still r e m a i n i n g impaired. The u n d e r l y i n g m e c h a n i s m for this i m p a i r m e n t of right v e n t r i c u l a r f u n c t i o n r e m a i n s unclear.

Previous studies have suggested that parasympathetic denervation could occur after radiofrequency ablation in certain subgroups of patients (pts), with potentially late arrythmogenic complications. The subjects of this study were 31 consecutive pts aged 25-40 years old, without structural heart disease, who underwent radiofrequency ablation (RFA) of AV nodal slow pathway and posteroseptal and left lateral accessory pathways, because of symptomatic recurrent reentrant tachycardias. All pts had time and frequency domain analysis of heart rate variability (HRV) and metaiodobenzylguanidine (I123 MIBG) scintigraphy 2-7 days before and after the procedure. Compared with preablation values time and frequency domain analysis after ablation revealed a significant reduction in HRV expressed as SDNN, SDANN, SD, LF, TP in groups of pts who underwent AV nodal and posteroseptal pathway ablation. Significant I123 MIBG map defects, indicating efferent sympathetic denervation were also found in the same groups of pts. None of the above changes of BRV and I123 MIBG scintigraphy were seen in the group of pts who undergone ablation of left lateral accessory pathways. RFA in the anterior, mid and posterior regions of the low intraatrial septum may disrupt sympathetic subendocardial fibres located in these regions causing sympathetic denervation of the sinus node.

P 223

P 225

M.G. Koutelou, E. Livanis, P. Flevari, G.N. Theodorakis, A. Kouzoumi, B. Bakogianni, A. Karoussou, D.T. Kremastinos, Nuclear Medicine Dept and 2 nd Dept of Cardiology, Onassis Cardiac Surgery Centp!, Athens, Greece ASSESSMENT OF DENERVATED BUT VIABLE MYOCARDIUM IN PATIENTS WITH MYOCARDIAL INFARCTION - BY MYOCARDIAL IMAGING WITH II23-MIBG AND TL-201 REST-REINJECTION STUDY Previous studies have revealed that the sympathetic nervous system is more vulnerable to ischemia than the myocardium itself. Thus, our study assessed sympathetic function in viable infarcted areas of the myocardium following the onset of myocardial infarction (MI). Eleven patients (pts) (all male) underwent 1-123-MIBG and rest-reinjection Thallium imaging 3-10 days post Ml. All pts received thrombolysis in the infarcted area. In 9 pts was observed redistribution and 2 pts had normal Thallium scans, but none of them had normal MIBG studies and the MIBG defects were larger than the Thallium defects. All pts underwent coronary angiography at the same admission and echo study and had coronary artery disease and wall motion hypokinesis. In all cases with regional wall motion hypokinesis, sympathetic innervation was impaired. Thus, the proposal that the redistribution of Th201 indicates myocardial viability suggests that the area with redistribution of T1-201 decreases the sympathetic function innervation. These findings indicate that denervation occurs in viable myocardium despite the viability demonstrated by rest-reinjection T1-201 imaging. These results suggest that adrenergic dysfunction may be induced by prolonged myocardial ischemia and was persist even though myocardial viability is retained because of thrombolysis.

1000

B. A j d i n ~ R. Spaid, S. Markovid, M. Perovanovid. Medical Military Academy, Institute of Nuclear Medicine Belgrade, Yugoslavia CAPTOPRILRADIONUCLIDETEST IN RENOVASCULARHYPERTENSION EVALUATIONQUANTITATIVEPARAMETERS USING R O C CURVE ANALYSIS

Captopril induced changes of the time to peak activity (T-max), the time to half of peak activity (T/2), the relative renal function index (RRFI), derived from renal time/activity curves, and the post/pro ratio (PPR), which as defined as ratio between postcaptopril peak/end ratio and precaptopril peak/end ratio calculated from the parenchymal time/activity curve, were evaluated as a diagnostic parameter of renovascular hypertension using receiver operating characteristic (ROC) curve analysis. The increase of the T-max and T/2 caused by captopril assesed in 26 patients (11 with renal artery stenosis, 15 without). Decrease of the RRFI assesed in 28 patients (13 with renal artery stenosis, 15 without), and PPR calculated in 22 patients (9 with renal artery stenosis, 13 without). All patients were hypertensive with normal renal function and renal artery stenosis was proved or excluded by renal arteriography. Best results were achieved using PPR and the increase T-max (accuracy" 86%). Worst results were achieved using the decrease of RRFI (accuracy 68%), wieh is probably result of the application of different radiopharmaceuticals (DTPA, OIH, MAG3).

UO

025

0.5

075

P 226

P 230

M. Kibar, A. Tutus, S. Payday, M. ReyhaIL Departments of Nuclear

L. Burroni, F. Chierichetti*, P. Bertelli, D. Voltermni, A. Vella, A. Vattimo and G. Ferlin* Dept. of Nuclear Medicine, Umversity of Siena and *PET-Centre, Dept. of Nuclear Medicine, Castelfranco Veneto Hospital, Italy.

Medicine and Neghrology, (~ukurova University Faculty of Medicine, Adana, TURKEY. CAPTOPRIL-ENHANCED Tc-99m-N,N-ETHYLENE DICYSTEINE RENAL SCINTIGRAPHY I N PATIENTS WITH SUSPECTED RENOVASCULAR HYPERTENSION: A COMPARATIVE STUDY WITH Tc-99M-MA G3

This prospectave study aimed to evaluate the clinical usefulness of captopril-enhaneed teclmetium-99m-N,N-ethylenedicy~teine(99~Tc-EC), a new renal tubular tracer agenL renal ~cintigraphy in patients with ~uspected renovar,cular hypert~ion and to compare thi~ agent with ~TeMAG3. Fifteen patients were ~udied with baseline and captopril-enhaneed (25-50 mg captopril) ~'~Tc-EC (80 to 100 MBq) and ~'~Tc-MAG3 (100 to 120 MBq) renal scintigraphy for detecting renal artery ~tenosis. In each patient, the icintigraphic images and time/activity curves were evaluated, and various semiquantitative parameters (T~, T~a and retention index (RI)) calculated~ Final diagnosis of renal artery stenosi~ was achieved through angiegraphy, doppler examination or outcome criteria (blood pre~iure respor~e to therapy). Of the patients, 2 had potitive eaptopril test (renovascularhyper~er~ion(RVH)) with both ~=Te-EC and 99~Tc-MAG3, and comfirmed by angiography. The other~ (n=13) had negative captoprit test, and these pafienti (e~sential hypertension (EH)) had also normal doppler examination. In the patients with EI-Lsemiquantitative parameters for ~Tc-MAG3 and ~Tc-EC were; before captopril T ~ 6.23 rain and 6.21 mitt, T~r2_ 7.8 rain and 7.1 rain, and ILl 36.4% and 37.8%, respectively; after captopril T ~ 5.8 nun and 5.7 rain, T~2 7.8 min and 7.3 rain, and RI 36% and 35.8%, respectively. In the patients with RVH for ~Tc-MAG3 and ~'~Te-EC they were; before captopfil T , , 6.5 vain and 6.6 ~ T~a 19 rain and 16 ram, and R1 48% and 51%, respecnvely; after captopril, T ~ 10.3 rain and 10.5 min, T~,~.not reached for the both, and ILl 82% and 83%, respectively. These results indicate that this new agent has excellent imaging properties similar to99~Tc-MAG3, and can be used safely for the eaptopr/l test in patients with suspected renovascular hypertension.

THERAPY-RESISTANT EPILEPSY IN CHILDHOOD: A COMPARISON BETWEEN INTERICTAL Tc99m-ECD BRAIN SPET AND F18-FDG PET Therapy-resistant epilepsy represents a diagnostic and therapeutical challenge in pediatric neurology and an accurate localization of the focus is required, since surgical treatment is available. MR] and EEG often fail to show any brain abnormalities or its precise localization, respectively. FI8-FDG PET can be considered the technique of choice for the evaluation of this neurological disorder; SPET is less expensive and more widely used than PET and Tc99m-ECD is an effective tracer for diagnostic assessment in epilepsy. The aim of this study was to e~.aiuate the accuracy of Tc99m-ECD SPET in comparison with F18FDG PET in a little group of children with therapy-resistant epilepsy and to compare scintigraphic findings with data from clinical examination, MRI and EEG. Six children (2 boys and 4 girls, aged 23 months to I2 years) were examined: 4 of them presented Complex Partial Seizure and 2 Generalized Tonic-Clonic Seizure. All underwent EEG monitoring, MRI, Tc99m-ECD brain SPET and F18-FDG brain PET. In all children SPET and PET revealed brain blood flow and metabolic abnormalities, respectively: in 5/6 patients PET confirmed the lesion in the same territories revealed by SPET. In the reimander patient PET showed more lesions than SPET and the seizure focus. MR1 revealed a structural lesion only in one patient, confirming PET and SPET results. EEG findings were positive in all children but this techique was less accurate in localizing seizure loci than PET and SPET. These data confirm that brain SPET is considerably sensitive in detecting peffusion abnormalities even if PET must be considered the technique of choice for the evaluation of metabolic disorders in epilepsy. We may conclude that functional brain imaging is necessary in ~lew of surgical treatment, especially when MRI pattern is inconclusive.

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l . K o s t a d i n o v a , A . S i m e o n o v a , C l i n i c a l C e n t r e of ~u-~9---~e--dlcine and Radiotherapy, SofiaBulgaria

B. De~irmenei, S. Miral, _(3.Gapa, H. Durak, L. Iyilikgi, Z. Aydm, S. Klra~;, H. Ellidokuz, A. Baykara. Dokuz Eyltil Oniversity, Depts of Nuclear Medicine and Pediatric Psychiatry, IZMIR, TURKEY

COMPARATIVE STUDY ON THE A P P L I C A T I O N OF CAPTOPRIL AND ASPIRIN DURING DYNA/~IC R E N A L SCINTIGRAPHY FOR THE DIAGNOSIS OF PATIENTS WITH RENOVASCULAR HYPERTENTION/RVH/ it is known that Captopril test is applied as a non-invasive screening method for the diagnosis of RVH.Its disadvantage is that during the basal study, ACE-inhibitors must be discontinued. As an alternative approach, which overcomes this, a test with aspirin was proposed. The aim of the study was to undertake a comparative investigation for the diagnostic application of aspirin /20 mg/kg/ and captopril /5Omg/ in patients with angiographically proven RVH. A dynamic renal scintigraphy was done with 99mTc-NAG3/74-111MBq/ on 16 patients with unilateral significant stenosis of the renal artery and iO controls, as well. The obtained results were evaluated with qualitative and quantitative criteria-Tmax, TI/2, devided renal function and retention index. We found that in 7 of the patients /44%/, the changes were more marked after captopril intake and the rest 9 patients/56%/ were more influenced after aspirin intake. The overall sensitivity of Captopril test was 81,3% and the sensitivity of Aspirin test was 93,8%. As a conclusion - because of the higher sensitivity and the possibility of the application of Aspirin test during treatment with ACE-inhibitors, it is preferable method to differentiate RVH from essential hypertension. When there are some contraindications for its use but strong clinical suspicion for the disease, then Captopril test must be applied.

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Tc-99m HMPAO BRAIN SPECT IN AUTISTIC CHILDREN Autism is an early and severe developmental disorder characterized by deficit in verbal and nonverbal language, social skills, cognitive functioning and abnormal repertoire of behaviours. The neurobiological mechanism of this disorder is not well understood. The purpose of the study was to evaluate regional brain perfusion alterations in autistic children (AC). Six AC (5 boys, 1 girl; mean age: 7.2-+ 2.1) defined by DSM-III-R criteria and age-matched three children (2 boy, I girl) as a control group were included in this study. Images were obtained with triple - head gamma camera equipped with high resolution collimators. 370-444 MBq of Tc99m HMPAO was injected at least 15 minutes prior to anesthesia. During the injection phase, the children were in their usual state of bebaviour. Metz filter (FWHM: 11 ram) was used for filtering. Motion and attenuation corrections were made. The transaxial, sagittal and coronal slices were obtained parallel to orbitomeatal line. Regions of interest (ROI's) were drawn first on right hemisphere (12 ROI's) and then mirrored ROl's were placed on the left hemisphere. One ROI was drawn on cerebellum (total= 25 ROI's). Mean count values per pixel were obtained. ROI's / cerebellum ratios were calculated by using mean counts per pixeh Hypoperfusion was seen on bilateral frontal cortex in 2 AC, on right parietal and temporal cortices in 4 AC and on left parietal cortex in 2 AC. Hypoperfusion on right temporal and parietal cortices was statistically significant (p _<0.05) when comparing the controls. This study suggest that the temporal and parietal cortices have abnormal regional cerebral perfusion in autism.

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K.Liewendahl, S-L.Vanhanen, P.Nikkinem J. Launes, H. Heiskala, R. Raininko, P. Santavuori. Helsinki University Central Hospital, Division of Nuclear Medicine, Departments of Child Neurology, Neurology and Radiology, 00290 Helsinki, Finland. BRAIN PERFUSION ABNORMALITIES IN NEURONAL LIPOFUSCINOSIS

INDIRECT RADIONUCIIDE CYSTOGRAPHV VERSUS CONTRAST VOIDING CYSTOGRAFHY IN D I A G N O S I S OF VESICOUHETE~A~ P~FLUX M Vlajkovi~. M Popovid H N a d o v a n o v i 6 ~ Sla~kovid Department of Hunlear Medicine,~adiolcgy and Pediatric ~urgery. Clinical Center, Ni~

Perfusion was studied with the Te-99m-HMPAO SPECT method in 19 patients aged 14 mo to 11 yrs with infantile neuronal ceroid-lipofuscinosis (INCL), 21 patients aged 8 to 28 yrs with juvenile neuronal ceroidlipofuscinosis (JNCL) and 5 patients aged 3 to 7 yrs with JanskyBielschowsky variant disease (JBVD). SPECT studies were performed with a Picker SX 300 1-detector or a Picker Prism 3000 XP 3-detector camera. The typical findings at an early stage of INCL were bilateral prefrontal, posterior temporoparietal and occipital hypoperfusion, whereas reduction in cerebellar perfusion appeared later. Typical findings at a late stage were severe global cerebral and cerebellar hypoperfusion and relatively well preserved perfusion in the basal ganglia, thalami, midbrain, brainstem and cerebellar nuclei. There was generally a good correlation between SPECT and MRI findings, except for the preservation of perfusion in the atrophic deep gray matter structures. In JNCL cortical hypoperfusion foci were detected in patients with disease manifestations for over a year but no typical distribution of hypoperfusion could be identified. In JBVD typical findings were severe bilateral temporo-oceipital hypoperfusion and cerebellar hypoperfusion already a few years after disease onset. In JNCL and JBVD did SPECT reveal hypoperfusion also in areas normal on CT. Conclusions: INCL and JBVD were associated with a quite characteristic brain hypoperfusion pattern resembling, at a late stage, that of neonatal perfusion, whereas no typical pattern was detected in JNCL. MRI was diagnostically more informative than SPECT in INCL because of signal intensity changes observed in deep gray-matter structures already before onset of symptoms. The maintenance of perfusion and therefore of vital cardiovascular, respiratory and neuro-endocrine functions in the midbrain and bralnstem explains the relatively prolonged survival in NCL patients even with clinically complete decerebration.

The aim of this study wa~ to compare the findings ez indlrect radlenucllde cystog~aphy (IRNCG) and contrast voiding eistography (CVU) in detection of -em~mours~era! r e f l ~ (VUR) in c h i l d r e n A total of 178 children (956 nephr~ureteric unitm - i{U) with recurrent urinary tract infection have been Investlgated by indirect radionuclide cystograDhY and contrast voiding oy~togrephy in the period less then one month In order tu compare t~e method~, CVU finding~ (International Study Ciasslflca~ion of Reflux) grade II and III, as well as grade IV and V were combined according IRNCG clae~ifio~tion of reflux ~rade II and III, respectively The re~ult~ were a~ f e l l o w ~ CVU iENCG O ~ !i-!~I IV~_V total 0£ NU 0 2~8 ~ 2 O 268 I 2 20 8 O 30 II i ¢ 13 O 18 IIl ~ 0 i6 ~2 40 T o t e ! o f NU 263 32 39 22 356 Sensitivity ( 8 ~ ) . positive predictlve value (94X) and negative predictive value (96%) were very high for indirect redionuolide cyetography compared to the ~alues for contxamt voiding cy~tmgraph V 94%~ 90X and ~9%, rm~pectlveiy. The accuracy of IRNCG (95Z) and CVU (95%) were e q u a l Sufficiently high sensitivity, positive and neg~tivm predi~ix,e values as yell a~ eecuracy~ make indirect radiozluclide oyetography a~ reliable nonlnvaelve sccrlnlng te~t ~or VUR detection In children with urinary tract infection.

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C. V a n de Wiele, S. De Man, J. De Sutter, J. V a n de Walle, M. Simons, RA Dierckx. U n i v e r s i t y H o s p i t a l Gent, B E L G I U M

H. Griffiths, J.R. MacKenzie, Royal Hospital for Sick Children, Glasgow

REPRODUCIBILITY CHILDREN

OF

24H

ABSOLUTE

DMSA

UPTAKE

IN

The aim of this study was to determine the reproducibility (precision) of D M S A 24h a b s o l u t e kidney uptake measurements. Eleven children (aged b e t w e e n 14 a n d 129 months) r e f e r r e d b e t w e e n 1992 and 1996 for e v a l u a t i o n of k i d n e y f u n c t i o n in w h o m absolute 24h DMSA uptake measurements were performed on 2 (n, number of patients 9, s u b g r o u p i) or 4 o c c a s i o n s (n =2, s u b g r o u p 2) w e r e included in the study. The mean time interval between succesive examinations was 10.5 months (range 2-40 m o n t h s ) . During this time, clinical status, t r e a t m e n t and k i d n e y m o r p h o l o g y as j u d g e d by D M S A s c i n t i g r a p h y remained unaltered. For d a t a a n a l y s i s , the d i f f e r e n c e b e t w e e n the first and t h e second measurement (subgroup I) or the m e a n of the d i f f e r e n c e of the 4 m e a s u r e m e n t s w i t h the m e a n of the 4 m e a s u r e m e n t s (subgroup 2) w e r e e x p r e s s e d as a p e r c e n t a g e of the m e a n v a l u e of the 2 ( s u b g r o u p i) a n d 4 s u c c e s i v e ( s u b g r o u p 2) m e a s u r e m e n t s . The mean of these differences ( ~A) represents the s y s t e m a t i c bias b e t w e e n the 2 or 4 m e a s u r e m e n t s , the s t a n d a r d d e v i a t i o n of these d i f f e r e n c e s (SD : A) r e p r e s e n t s the p r e c i s i o n of the t e c h n i q u e . For total 24h D M S A u p t a k e ~A was 2.0% (SD A : 8.9%). In ten cases, the d i f f e r e n c e was less than 1 0 . 5 % a n d in the r e m a i n i n g p a t i e n t 23.5%. For left a n d r i g h t r e n a l 24h D M S A uptake, ~A and SD A were respectively -0.8% , SD : 12.9%, and 3.5% , SD : 12.1%. T h e l o w e r r e p r o d u c i b i l i t y of left and r i g h t renal DMSA uptake may be attributable to differences in repositioning between succesive examinations. The f i n d i n g s presented suggest 24h absolute renal DMSA uptake measurements are reproducible and h e n c e m a y be u s e f u l l as an i n d e x of s e p a r a t e and g l o b a l renal function.

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A COMPARISON BEIWEENDIRECT AND INDIRECT RADIONUCLIDE CYZTOGRAMS Recent guidelines on imaging of children with UTI produced by the British Paediatric Association have suggested that an indirect radionuclide cystogram (IRNC) is an unsatisfactory technique for the detection of reflux and clinicians in this hospital have also been questioning the accuracy of the procedure. A retrospective study comparing IRNC and DRNC (direct radionuclide cystogram) in the same child has been carried out. 47 DRNC examinations were booked in 45 children during the last 5 years. Catheterisation could not be performed in 3 children and 13 of the children did not have an IRNC. Both examinations were performed in 31 children usually several months apart. 13 children had no reflux on IRNC and DRNC. 2 children had reflux on both procedures. In 4 children the IRNC was normal and the children had reflux on DRNC. ii IRNC suggested reflux or were equivocal due to high residual counts in the kidneys and ureters or failure to pass adequate amounts of urine; and in 3 of these children the DRNC was normal and in 8 reflux was confirmed. In one boy who had an initial normal DRNC the study demonstrated reflux at the time of a second study. Although the numbers are small the study shows that in our department an IRNC is a satisfactory means of demonstrating reflux in the majority of cases and the DRNC should be reserved for children in whom the IBNC was inconclusive.

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B. Banerjee, K. Chauhan, V. Reece Tameside & Glossop Acute Services NHS Trust, Department of Nuclear Medicine, Tameside General Hospital, Ashton-Under-Lyne, U.K.

Wudel E ~ , Stroedter L ~, Biewald W ~, Koppenhagen K z , Nuclear Medicine ~ . Paediatric Surgery ~. Free University Bar]in. University Hospital B. Franklin. Hindenburgdamm D-12200 Berlin.

I5 THERE ANY ADVANTAGE IN COMBINING ULTRASOUNO WITH gBTem - D~SA SCINTIGRAPHY IN PAEDIATRIC URINARY TRACT INFECTION In a number of centres, childhood urinary tract infection (UTI) is routinely investigated by combined m . . renal ultrasonography and 98Tc - OMSA sclntlgraphy. It has been well documented that 89Tc m - DMSA is the best available imaging modality, to date, for detection of renal changes in childhood UTI, while ultrasonic features of acute pyelonephritis is often difficult to detect. The purpose of this study was to evaluate whether there is any advantage in combining ultrasonography with 89Tc m- DMSA scintigraphy in the assessment of childhood UTI. A total of 180 children with proven UTI were studied by combined BgTc m- OMSA scintigraphy and renal sonography. Ultrasonic examinations were carried out with high resolution equipment by experienced sonologists. Ultrasound and 99Tc -OMSA studies were critically analysed and the findings recorded. 8oth ultrasound and gBTcm-OMSA scintigrephy were found to be normal in 127 children (71%) and abnormal in 22 children (12%). In 27 children (IS%) 99Tcm-oMSA scintigraphy exhibited abnormality in one or both kidneys but oltrasonography failed to detect any abnormality in these children. In 4 children with ultrasound, parenchymal changes of acute pyelonephritis was suspected but with 98Tcm-OMSA ssintigraphy no focal abnormality was detected. Further follow up of these 4 children failed to substantiate any renal abnormality. We, therefore, conclude that ultrassnography of kidneys is unlikely to provide any significant additional " " h y, in information over and above BBTc m -DMSA sclntlgrap the evaluation of childhood UTI.

THE URETERAL PERISTALSIS BILATERAL MEGALO-URETER

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IN THE FOLLOW-UP OF CHILDREN WITH

AiM: In the follow-up of 9 children suffering from a bilateral megalo-ureter (and a history of an urethral valve) wlth symptoms of increasing obstruction we observed a correlation between the grade Of recovery after urinary drainage through an ureterocutaneostomy (UCut) and the later result after moving the ureter back by uretereeystoneostomy (UCy). METHOD: TC-99m-MAG3 dynamic scintigraphy (5-10 MBq/kg, <120) with 2-set-frames for 41 min, 20 min furosemid iv. Zoomed scans for more ~aws of pixel (>15) in the image for the significance Of any detected wave. Age (median) i a (] month - 6 a). Follow-up 4 a (2-6 a)_ Examinations CA) before UCut, (B) la after UCut, (C) >=la UCy, Parameter: partial function PF%, visual grade of uretersl peristalsis UP (1<2..<5), renogram O'Reilly OR (l>3a>3b>2), ureterogram J (5>..>1) after a modification of Jamar [JNM 1992;32:738], half-life. RESULT: (A)==>>(B): improvement of renal and ureteric drainage, differences in PF <5% (7/9), OR from 3b/2 to i/3a in 11/18 renal units, UP <3 to >3 in 6/18 , J nearly the same izke OR. (B)==>>(C]: differences in PF <5% (5/9), 510% (4/9 pats.), OR from I/3a to I/3a: 9/18, to 3b/2 in 9/18, UP c0nst. 9/18, worsening 9/18, J from 1/3 to 1/3 10/18, to 2 7/18. Prognosis: Under the conditions of PF>=50% and UP>3 in the state (B) the probability of OR 1 or 3A in state (C) is 75%. Under the conditions of PF<50% and UP<3 in the state (B] the probabliity of OR 3b/2 in state (C) is 50%, The same values are valid for UP>=3 in (B) with OR i/3a. CONCLUSION: We observed that a good visable peristalsis correlates with a better prognosis than a difficult detectable ureteral action. After 6-12 month of the ureteroeutaneostomy the peristalsis must be good visab!e, then the prognosis of the conservation of renal function after ureterocystoneostomy is better, the later result remains doubtful because of the disease of both kidneys. KEYWORDS: ureteral peristalsis, magaureter, prognosis, children

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B. Ljuna, reg nurse, Clinical Physiology, Sweden.

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P 237 R. Sixt, Dept Pediatric SU/Ostra, G6teborg,

RENOGRAPHY IN CHILDREN A MULTICENTRE SURVEY OF PROCEDURES. Aim: To c o l l e c t i n f o r m a t i o n about pediatric renog r a p h y p r o t o c o l s u s e d b y m e m b e r s of the P e d i a t r i c I n t e r e s t G r o u p w i t h i n EANM. Methods: A questionnaire covering methodological a n d n u r s i n g a s p e c t s of r e n o g r a p h y w a s d i s t r i b u t e d to 28 c e n t r e s in E u r o p e . 14 c e n t r e s r e t u r n e d 552 c o m p l e t e d forms. Results excerpt: Common indications w e r e UTI, VUR, p o s t - o p e r a t i v e control, antenatal malformat i o n s or n e u r o l o g i c a l disorders. The m e a n a g e of t h e c h i l d r e n was 4,8 yrs (6 d a y s 22 y r s ) . 7 1 % w e r e s t u d i e d on an o u t - p a t i e n t b a s i s . 97 % w e r e g i v e n e x t r a f l u i d b e f o r e the e x a m i n a t i o n (14 % iv), w i t h a d o s a g e r a n g i n g f r o m 2-20 m l / k g B W g i v e n d u r i n g 2 0 - 6 0 m i n u t e s b e f o r e the s t u d y . 12 of 14 c e n t r e s u s e d MAG3, 2 u s e d 1-123 H i p p u r a n . The d o s a g e c l e a r l y d i f f e r s b e t w e e n c e n t r e s . Less t h a n 1 % of the s t u d i e s w e r e d i f f i c u l t to i n t e r p r e t for t e c h n i c a l r e a s o n s . written information about the examination was distributed in 48 % of the cases. In all, 147 c h i l d r e n f r o m t w o c e n t r e s r e c e i v e d local a n e s t h e t i c c r e m e p r i o r to v e n e p u n c t u r e . 59 % of the v e n e p u n c t u r e s were done by a doctor. Furosemide was g i v e n in 40 % of the cases and, of those, 39 % h a d a n e x t r a v e n e p u n c t u r e for t h e i n j e c t i o n of F u r o s e m i d e . Conclusion: There are considerable procedure differences between centres.The collected informat i o n m a y f o r m a b a s i s for d i s c u s s i n g quality assessment of r e n o g r a p h y a n d m a y a l s o p r o m o t e conformation of p r o c e d u r e s . -

Z, Burak, O. BilkaY, R. Edna, Z. Balkan, D. Efe, H. Ozklhct, Ege University, Dept.of Nuclear Medicine, TURKEY

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COMPARISON OF PARENCHYMAL TRANSIT TIME (PTT) AND DIURESIS RENOGRAPHY (DR) IN CHILDREN WITH SUSPECTED UPPER URINARY TRACT OBSTRUCTION PTT may be used in the diagnosis of obstructive pathology in a dilated renal pelvis. The aim of this study was to compare mean parenchymal transit time (MPTT) parameters with Tc99m MAG3 DR in children with upper urinary tract obstruction (UUTO). Until now, 14 children (28 kidney units) between 1-12 ages with suspected UUTO were studied. According to DR, 21 kidney units showing non-obstructive (NOD) or obstructive dilatation (OD) and 7 kidneys with normal (NL) renogram patterns were studied with PTT analysis. From each dynamic study, MPTT, Whole kidney transit time (WKTT) and parenchymal transit time index (PTTI) parameters were calculated. 4 functional images of MTT were also generated, in DR, 7 renal units were NL, 8 were NOD, 8 showed partial obstruction (PO) and 7 were totally obstructed (TO). NL NOD MPTT 2.2±0.1 3.71±0.2" WKTT 2.7+0.2 5.65±0.6 PTTI 1.04±0.01 1.59±0.08 (*): p_<0,001, (**): p_<0.003

PO 5.97±0.8** 9,7+1 2,72±0.9

TO 11.3_+1.1 13.3-+0.6 3.88-+0.3*

There was a significant difference between Tc99m MAG3 MPTT of NOD group and PO and TO groups as well as PO and TO kidneys. PTTI of TO renal units were sign. different when compared to all other groups. The results were concordant with time-to-peak and differential function parameters. Functional images demonstrated focally increased MPTT in 4 kidneys with PO. In conclusion, in this study we suggest that MPTT and PTTI are safe and non invasive parameters especially in differentiating PO from TO in suspected UUTO. MPTT determination increases diagnostic specificity when combined with DR.

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N.J. Peng, Y.H. Chiou, C.G. Kwok, G.H. Jao, J.Y. Men, D.G. Tsay, R.S. Liu, H.W. Strauss. Department of Nuclear Medicine, Kaohsiung and Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taiwan, and Stanford University Medical Center, Stanford, CA.

M. Charron, F. DelRosario, S. Kocoshis. Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA

COMPARISON BETWEEN 1800 AND 3600 ACQUISITION IN TC-99m DMSA RENAL SPECT As result of a high percentage of hypoactive upper poles of kidneys in Tc-99m DMSA SPECT (JNM 1996; 37:1346-9), we conducted a prospective study using 1800 technique compared with 3600 to avoid the tissue attenuation. Anterior 1800 , posterior 1800 and 3600 renal SPECT images were obtained simultaneously using dual head camera. Forty subjects without renal diseases were included in the study. The total counts of the raw data in the anterior 180°, posterior 1800 and 360 o were calculated. Small regions of interest were drawn over the outer cortex of upper and lower renal poles on coronal and reoriented sagittal slices. Quantitative evaluation of the upper and lower poles activity was done on the same frames in all three acquisition methods. The results were shown in the following table. upper/lower pole anterior 1800 left 0.76+0.11 right 0.85 + 0.23 total counts 1.6 x 106 + 4.3 x 105

posterior 1800 0.91+0.15 1.00 + 0. t5 1.9 x l06 _+ 5.7 x 105

full 3600 0.84+0.13 0.94 + 0.18 3.5 x 106 _+. 9.9 x 105

Comparison of the total renal counts between the anterior and posterior 1800 raw data demonstrated reduced counts in anterior 1800 data collection ( p< 0.01). The upper to lower pole ratio in the posterior 1800 renal SPECT images increased significantly in comparison to full 3600 renal SPECT images (p< 0.01) and anterior 1800 SPECT images (p< 0.01). The hypoactive upper pole caused by the attenuation effect can be corrected by posterior 1800 technique. Our results suggest that the posterior 1800 sampling technique can avoid the problem of hypoactive upper pole and less time consuming.

COMPARISON OF THE SENSITIVITY OF EARLY VERSUS DELAYED IMAGING WITH 99mTc-HMPAO-WBC IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE PURPOSE: To establish the difference in sensitivity of early imaging at 30 minutes post injection of 99mTc-HMPAOWBC versus delayed imaging at 2-3 hours for depiction of active inflammation in children with inflammatory bowel disease. MATERIAL AND METHODS: We reviewed the charts of 220 children who had early (30 minute) and delayed (2-3 hr) imaging performed for evaluation of inflammatory bowel disease. There were 107 boys and 113 girls (average age of 12 years old and median of 13 years old). The bowel was divided in 8 segments (with the total for all patients being 1760) graded on a scale of 0 to 6 (with references point in the iliac crest and liver). Any grade,> =i is abnormal. The uptake in each segment was summed. RESUTLS: One hundred and twenty two studies were abnormal (55%). The average uptake in the early images group was 5.1+-0.41 and in the late images group was 9.3+-0.64. The Friedman nonparametric test of comparison of rank was significant at the 0.001 level. One hundred and five patients had abnormal studies of 30 minutes (88%), thus an additional 12% of patients were abnormal on the late images only. When the uptake was analyzed segment by segment, 62 patients (52%) had segments positive only on the late scans. CONCLUSION: Sensitivity of the 99mTc-HMPAO-WBC can be significantly improved when late imaging is performed.

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A.Jim~nez-Heffernan, A,C.Rebollo, C.Herrera and J.Acosta*. Hospital Juan Ram6n Jim~nez, Nuclear Medicine and Pediatric* Services. Huelva. SPAIN.

A.Viqnati , MP.Cattaneo", F.Rusconi ^, R.Padoan ^, L.Mazzucchelli, L.Pedrazzini, G.Lomuscio, ME.Dottorini, L.Colombo, C.Pototsching". Nuclear Medicine and "Pediatric Depts of 0spedale Busto Arsizio; ^Pediatric Clinic I, University of Milan, Italy

PINHOLE AND QUANTIFIED PLANAR DMSA IMAGING IN PEDIATRIC URINARy T~ACT INFECTION. TC-DMSA imaging is a sensitive test in the workup of children with urinary tract infection (UTI)_ We studied i16 children combining pinhole and computer registered planar images. Findings were related to age, sex, history of UTI and vesico-ureteric reflux (VUR). The series comprises 67 boys and 49 girls with first known UTI (48) or a history or recurrent UTI (68). Ages ranged between 16 days and 14 years (mean:4,1 y). Children were imaged 3.5 hours after the injection of TCDMSA (body surface adjusted dose, minimum 37 MBq). 300K counts pinhole views were acquired in posterior and both posterior oblique projections, as well as 500K count computer registered anterior and posterior planar views, 70% of boys with first UTI (36) were infants and 54% of girls with recurrent UTI (37) were >Sy old. Images were normal, with function in normal limits (45-50%) in 44 boys and 26 girls. Recurrent or initial ITU was evenly distributed (38 vs 32) and VUR waspresent in 51% of them. Abnormalities suggesting cortical lesions, shrunken kidneys Or diffuse p a r e n c h y ~ l defects were observed in 29 children: 23 with unilateral and 6 with bilateral involvement. VUR was present in 95% of patients with unilateral DMSA abnormalities and in all six with bilateral defects. Patients with unilateral or bilateral DMSA defects included 12 boys and 17 girls; 20% of the boys were under 1 year of age and 41% of the girls were older than 5 years. DMSA images were considered equivocal in 17 patients with mild cortical flattening, mostly involving the left upper pole (splenic impression). In addition to the global usefulness of DMSA scintigraphy in children with UTI, our findings confirm the higher proportion of abnormal images in infant boys and older girls and the almost invariable presence of VUR in children with abnormal images, especially those with bilateral defects. Image interpretation is greatly aided by the routine obtention of pinhole views, which offer excellent resolution without any significant loss in specificity. Quantification of differential function is simple and provides an additional parameter in the workup of these children.

1004

SCINTIGRAPHIC ASSESSMENT OF MUCOCILIARY CLEARANCE IN CHILDREN WITH RECURRENT RESPIRATORY INFECTIONS. Fourteen children (age 3-16 years) with recurrent respiratory infections and the possible diagnosis of ciliary dyskinesia were submitted to 1 hr dynamic scan of the thorax immediately after inhalation of ultrasonically generated Tc-99m albumin colloid aerosol. A 24 hr image was acquired to evaluate the radioactivity trapped in nonciliated airways. Two pts had situs viscerum inversus. A visual analysis w~s performed on cinescintigraphy and a score was given considering the following features: the decrease of counts on lung images; the redistribution of radioactivity towards the carina and the transport of radioactivity in the trachea. Quantitative indeces were calculated at the beginning (T0) and at the end (TI) of the dynamic scan: mucociliary clearance index (CI) was obtained as the ratio between T0-TI count decrease and T0 counts in the ciliated airways: ciliated airways deposition index (CDI) and alveolar deposition index (ADI) describe the percentage of TO lung radioactivity at time T1 in ciliatsd and nonciliated airways, respectively. The mean indeces of the two lungs were considered, CI showed good correlation with the visual score (r=0.87, p<0.01) but no correlation with both CDI and ADI. Moreover, no correlation was found between the visual score and CDI or ADI. The three pts with score=0 had CI<18%; all pts (9) with score>=2 had CI>33%. Two pts had score=l: one had CI=27% and poor redistribution towards the carina; the other had CI=1696 and good transport of radioactivity in the trachea. In conclusion visual analysis together with CI seem to be a reliable tool to evaluate mucoeiliary function, In pts with borderline CI (18
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I. M ~ a i o v f i . M. Vivodova, S. Kova~ov& J. Kau~itz, R. S y r i a , K Hus~ovfi, J.. Pu~ka-

H.H.Abu-Judeh, S.Naddaf, S.Aleksic*, J.Masdeu, H.Elzeflawy, S. Billick, and H,M,Abdel-

~ov! D. Sgnova, A. Moyzesovfi,E. Kaizerovfi,M Horni~ovfi D~artment ~ Nue~ar Me~cin~ D~a~ment qf Pe~a~ic Oncolo~, MeScal Facu~ Univers~ ~ Komensky ~Elisabeth Oneo~gieal ~ i t u ~ BRA TISLAVA, Slovak R~ublic -,COMPARA TII/E STUD Y OF MIBG SCINTIGRAPHY AND THREE PHASE BONE SCAN IN CHILDREN WITH NEUROBLASTOMA In 63 c h i l d r e n (aged b e t w e e n 2 month a n d 16 year) with neuroblastoma wholebody scintigraphy with 131I or 1231-metajodobenzylguanidine and wholebody bone scintigraphy with 99mTc-Medronate (A~ersham) was performed. The s c i n t i g r a p h y with 1311-MIBG was m a d e 24 a n d 48 hours after administration a n d 4 a n d 24 h o u r s a f t e r achninistration of 1 2 3 I - M I B G . Because some difficulties with interpretation of b o n e s c a n r e s u l t s in c h i l d r e n w i t h n e u r o b l a s t o m a a n d sometimes lower accurancy was f o u n d as r e s u l t of M I B G scintigraphy, we p e r f o r m e d in 32 p a t i e n t s also perfusion (three phase) b o n e s c a n of t h e s e l e c t r e g i o n of i n t e r e s t (mostly the r e g i o n of p e l v i s , l o w e r lumb a r a n d u p p e r f e m o r a l part). The p e r f u s i o n b o n e s c a n was m a d e w i t h the s c i n t i l l a t i o n c a m e r a D i g i t r a c 7500 (Siemens) a n d the o t h e r s p o t a n d whole-body s c i n t i g r a p h y w a s m a d e w i t h the s a m e one or D S X or D S T cameras(Sopha Medical Vision). In 63% t h e r e was a g r e e m e n t of c l a s s i c b o n e s o a n a n d M I B G a n d i n 92% p a t i e n t s an a g r e e m e n t of M I B G a n d perfusion (arterial a n d v e n o u s phase) was found. All patients were clinically investigated a n d controlled by pediatric oncologists. Laboratory investigations including v a l u e of N S E (neuronspecific enolasel w e r e a l s o p e r f o r m e d . Conclusion: B e c a u s e of v e r y c l o s e a g r e e m e n t b e t w e e n r e s u l t s of M I B G s c i n t i g r a p h y a n d the p e r f u s i o n p h a s e of bone scintigraphy in p a t i e n t s with neuroblastoma (92%), we r e c o m e n d for f o l l o w up of the d i s e a s e activity the three phase scintigraphy of p e l v i c region, or o t h e r s e l e c t l o c a l i z a t i o n as a r o u t i n e c o m p l e m e n tary method.

Davem. St Vincent'sHospital,NY Med. College,and *NYUMeal.Center,NY, NY. SPECT BRAIN PERFUSION (BP) IN MILD / MODERATE TRAUMATIC BRAIN I N J U R Y (TBI)

We aim to present the largest series of BP changes post mild/moderate TBI This is a retrospective analysis of 360 SPECT BP studies of which 228 met the criteria of only mild/moderateTBI without any significant PMH. SPECT BP Imaging was done 2 hrs, 1 hr following the injection of 20 m e i of either Tc-99m HMPAO or Tc-99m ECD respectively, using the triple-head gamma camera. All studies were acquired and processed in the same manner. Images were displayed 2 pixels thick in the transaxial, sagittal, and coronal sections, 10 color scale adjusted for 100% max. uptake in the cerebellum. Any region of <70 % in the cerebral cortex and basal ganglia, or < 50% in the medial temporal was considered abnormal. All studies were read without knowledge of any clinical or radiological information. Of the 228 studies (135M, 93F), age 11-88 (mean 40.8 yrs), 176 studies were read as abnormal. In the abnormal studies: Etiology: fall 19%; blow 36%, and MVA 45%. Complaints: headache 59%; dizziness 29%; memory problems 76%; generalized weakness 23%; concentration difficulties 1 i%; visual complaints 10%, sleep disorders 10%; balance problems 6%. LOC was reported in 53%, 16% had no LOC, the status of the rest was not reported. BP changes were either focal or diffuse Abnormal/Total

Total Group 176•228

MVA 79/98

Time Interval SPECT&TBI

<3 mo

>3 mo

< 3 mo

>3 mo

NO LOC 28141 <3 rno

No. of abn. studies

79II76

971176

41179

38/79

15/28

13/28

Basal Ganglia (BG) abn.

47(59%)

49(51%)

23(56%)

14(37%)

9(60)

508%)

33(34%)

>3 mo

Frontal lobes abnormalities

37(47%)

20(49%)

12(32%)

8(53%)

5(38%)

Temporal lobes abnormalities

19(24%) 24(25%)

l 1(27%)

11(29%)

3(20%)

2(15%)

Parietal abnormalities

[I(14%)

8(8%)

6(15%)

4(11%)

3(20%)

1(8%)

DSTH

12(I5%)

23(24%)

5(12%)

16(42%)

3(20%)

3(23%)

Conclusion:(1) BG hypoperfusion is the most common finding contrary to previous reports of frontal and temporal lobes. (2) More abnormalities are detected with early imaging following the accident. (3) DSTH is most common with MVA. (4) BP changes can occur in the absence of LOC.

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R. A. Hurwitz, A Sidd~qui, H. Wellman, Indiana University Medical Center, Indianapolis, Indiana, U.S.A.

JL Lampreave, V Molina, M Desco*, A Bittini, P Dominguez, I Almoguera, JL Carreras. Servicios de Medicina NucIear y Medicina y Cirugia Experimental*. Hospital Gregorio Marafidn. Complutense University of Madrid. Spain.

T H E F O N T A N O P E R A T I O N : E F F E C T OF T I M E ON VENTRICULAR FUNCTION.

Right atrial-pulmonary artery anastomosis (Fontan) is the surgical procedure of choice for many cyanotic heart lesions with unusual anatomy. The present study is the first to examine the progression of ventricular function after Fontan. Since radionuclide angiocardio-graphy is not dependent on anatomic models, it was used to estimate pre-operative and post-operative ventricular ejection fraction (VEF) in 18 pts. Serial postoperative studies were also performed on 18 pts (I 0 with anatomic left ventricles). The interval between studies was 1-i5 yrs (mean 4.2). VEF fell from a pro-operative value of 0.58 + 0. l 2 to 0.46 + 0.12 (19< 0.01) post-operatively. Group mean VEF for all 18 pts was not statistically different between repeat postoperative studies (0.49 to 0.15 vs 0.50 + 0.11, p = 0.2). However, VEF fell > 0.10 in 4 pts and > 0.05 in 2 others. Follow-up VEF rose in only 2 of 5 pts initially studied early after surgery. Neither anatomic type of ventricle nor age at Fontan surgery was statistically related to final VEF or change between studies. Though pre-operative VEF had no correlation with final VEF, there was an inverse relationship between pro-operative VEF and change in VEF between repeat post-operative studies (p < 0.03). Results suggest that after Fontan: 1) VEF often decreases post-operatively; 2) VEF falls in at least 25% of patients undergoing serial post-operative evaluation and 3) deleterious changes do not correlate with low preoperative function, age at surgery, or anatomic type of ventricle. Thus ventricular function should be assessed periodically in all patients after Fontan surgery, to guide possible early or prophylactic treatment.

EVALUATION OF THE 99mTc-HM]?AO SPECT PATTERN IN TOURETTE'S SYNDROME: A STUDY WITH TREATMENT AND AFTER NEUROLEPTIC WITHDRAWAL. The aim of this study was to assess the brain perfusion pattern in a group of GUles de la Tourette's syndrome patients (GTS) evaluated with and without treatment separately. Methods: A group of 13 normal controls and 15 GTS patients were studied with 99mTc-HMPAO brain perfusion SPECT. Thirteen GTS underwent both scans: brain SPECT was performed first without treatment in 11 patients, because they were initially submitted without treatment, and re-tested after 3.5 months while back on neuroleptics. Oppositely, 4 GTS were studied first with treatment and re-tested only after 4 weeks of progressive neuroleptic withdrawal. A semiquantitative automatic and manual analysis of the images was carried out A multivariate analysis of variance (T2 Hotelling test) was performed to compare normal-to-GTS perfusion, and a Wilcoxon signed ranks test was applied to assess the perfusion changes with treatment. Results: Decreased perfusion in both temporal lobes and anterior medial regions of both frontal lobes could be observed when compared with controls. After treatment, a perfusion increase in the mentioned frontal regions and in the left medial temporal cortex was found. Conclusions: GTS could be characterized by a neural hypoactivity of the circuit linking these hypoperfused regions. Neuroleptic treatment could decrease the hyperactivity of the dopaminergic system, leading to an improvement of the clinical symptoms and re-perfusion of some previously hypoperfused regions.

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Erkan Vardareli*, ~flkri~ Torun **, liknur A k *, Emre Entok *, Departments of Nuclear Medicine* and Neurology** Osmangazi Universi~ TURKEY

M-Reinhardt ~, K Schmidtke 2, T. Krause t, E. Moser t ~) Dept. of Nuclear Medicine and z) Dept. of Neurology, Albert-Ludwigs-University, Freiburg i.Br., Germany

CEREBRAL A N D INFARCTION

CEREBELLAR

DL4SCHISIS I N B R A I N S T E M

contralateral cerebral hypoperfusion is a well documented phenomenon in patients suffering from cerebral or cerebellar infarction. There have been a few case reports of brain stem infarction and remote hypoperfusion. We describe the SPET perfusion pattems observed in l0 selected patients with pure, unilateral brain stem infarction and 10 control subjects. Brain perfusion SPET was performed after 30 rain. an I.V. injection of 25 mCi Tc-99m HMPAO. Images were obtained with a circular-field-ofview rotating gamma camera (GE 400 AC/T), fitted with a high resolution, low-energy parallel-hole collimator. Sixty-four views were collected using a computer (GE 4000i) with a 64x64 acquisition matrix and 1.33 zoom factor for 30 see./each, over 360 degrees. Transaxial, sagittal, coronal and oblique slices parallel to the orbitomeatal line were reconstructed raw data with backprojection technique using Ramp-Harming filter. For the semiquantitative analysis, regular regions of interest (ROts) of 4x4 pixels were used and asymmetry indices were calculated to obtain side-to-side perfusion differences. SPET findings were correlated to the location of the infarcted area on MR[. Significant perfusion asymmetries were found in 7 patients. Six of 7 patients with pontin infarction showed ipsilateraI, whereas the other one showed contralateral fronto-temporo-parieatal hypoperfusion. Additional hypoactivity was seen in contralateral or ipsilateral thalamus and basal ganglia in some cases. As a conclusion, the remote perfusion deficits in brain stem stroke depend on the lesion site, and umy occur both supra- and infra-tentorially. In addition to the cortical diaschisis, the perfusion changes in thalamus and basal ganglia may also be seen in patients with brain stem infarction. We suggest that all the ascendant and descendant pathways which are damaged by brain stem infarction may play a role in the pathogenesis of diaschisis. Contralateral cerebeUar or

CEREBRAL PEP.FUSION DURING AND AFTER TRANSIENT GLOBAL AMNESIA - FINDINGS WITH 9~'Tc HMPAO SPECT Transient Global Amnesia (TGA) is characterized by sudden onset of anterograde amnesia and variable retrograde amnesia. Annual incidence is 3 per 100,000 and clinical resolution occurs within one to 24 hours. The etiology of TGA is unknown and brain perfusion scintigraphy or PET seems to be the only diagnostic procedure to demonstrate changes during the attack. ~Tc-HMPAO SPECT was performed in 21 subjects: in 6 consecutive patients during the acute phase of TGA and in 15 matched healthy subjects who served as controls. Four of the 6 six patients received a control study after recovery. SPECT images were semiquantitatively analysed in 14 regions of interest. Uni- or bilateral ictal hypoperfusien of the temporo-basal region was found in four patients. Variable hypoperfusion of further cortical areas was seen in five patients. Two patients who exhibited the most marked cortical hypopeffusion also presented with striatal and thalamic hypoperfusion. All these changes normalized in the follow-up studies. It remains unclear whether hypoperfusion during TGA represents a primary feature or a sequel of regional brain hypometabolism. Since hypoperfusion is not confined to the temporo-basal region or to the territory of the posterior cerebral artery, it is suggested that the origin of TGA-releated changes is situated at the level of subcortical structures which project diffusely to the cerebral cortex.

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R. Ouirce,C .Gutierrez -Mendiguch~a, I .Blanco, I .Uriarte, A. Montero, A.Hern~ndez, JA.Amado, JM.Carril SERVICIO DE MEDICINA NUCLEAR HOSPITAL UNIVERSITARIO M,VALDECILLA. S A N T A N D E R . ES P A N A

J. Fischer, P. Klinge-Xhemajli*, W. Burchert, H. Hundeshagen, Abteilung fLir Nuklearmedizin, *Neurochirurgische Klinik, Medizinische Hochschule Hannover, Germany

MDRPH0-Ft~CTIC~AL CC~RELATIC~ IN THE SUBCLINICAL PI~FUSIC~ AHNOI~I%LITIF_S D ~ BY 9 9 n ~ c - ~ P ~ 3 SPECT I N PATI~TfS WITH DIABETES MELLITUS AhD NO HISTCRY OF C~R~gROVASCDLAR DISEASE TO evalute the morpho-functional correlation in the subclinical abnormalities of brain blood perfusion detected by 99mTC-HMPAO SPECT in patients with Diabetes Mellitus (DM) and no history of cerebrovascular disease, we performed structttral studies to 30 diabetic patients (DP) with abnormal brain perfusion 99mTc-~4PAO SPELT {13 type I and 1"7 type If), with a mean age and a mean time interval from diagnosis of DM of 40--+7 and 17_+7 years in type I and 58_+7 and 16_+7 years in type II DP. 20 of the 30 DP showed secondary conlolications related with the DM. 5 showed chronic hypertension(HT) and 6 microalbuminuria (MCA). 27 DP were evaluated by MRI, i by CT and 2 by both CT and MRI. Results: i0 of the 30 DP (33%) showed structural abnormalities (SA). In one of the i0 they were due to head trauma and in other to brain tunour. In the remaining 8 DP lesions secondary to cerebral ischemia were found: lacunar lesions located in the white capsula. Also, in 2 of the 8 there were two large and focal infarts. The i0 DP showed pronounced cerebral atrophy. There was not correlation between the SA and type of DM. The i0 DP with SA showed any secondary diabetic complication, althought there was not evidence of a higest incidence of HT or MCA in them. Conclusions: Brain perfusion 99n[fc-HMPAO SPECT is more sensitive than the structural imaging techniques to detect abnormalities of brain blood per fusion in DP with no history of cefebrovascular disease. 33% of the patients with abnormal perfusion showed structural abnormalities.

1006

VALIDATING PROGNOSIS OF SHUNT-THERAPY IN NORMAL PRESSURE HYDROCEPHALUS WITH 15-O-H20-PET-STUDIES OF CEREBRAL BLOOD FLOW

A complete pathophysiological explanation of normal pressure hydrocephalus (NPH) with its clinical triad of gait disturbance, mental dysfunction and incontinence combined with a ventricular enlargement is still pending. Based on the impression of concomitant cerebrovascular disease (CVD) given by pathology and clinical observation we quantify cerebral blood flow (CBF) and its significance for verifying treatment and prognosis. In 22 adult patients (mean 70 years) being treated with a ventriculo-peritoneal shunt CBF was measured by PET using 15-O-H20 before and one week after implantation. 16 patients were invastigated again in mean 7 month postoperative. After intravenous bolus-injection of 3.7 GBq 15-OH20 tissue activity was measured dynamically over 5 minutes. CBF was computed by a 1-compartement model approach using the activity concentration of brain tissue and arterial blood. After standardized orientation of the patient's data set ROIs in 4 transversal slices for the territories of the ACA, MCA, PCA and in decided cerebral regions were defined. The mean CBF of all patients was decreasing during the course of the first half year. Comparing with the clinical outcome surprisingly low CBF values (< 40 ml flow/100ml tissue/min) were found by patients with good or very good clinical improvement, whereas patients with missing or low clinical improvement showed higher CBF-values. Correlations of clinical outcome and changes in the territories of ACA, MCA, PCA as well as in other cerebral regions were not found. It seems that in patients with normal pressure hydrocephalus the clinical outcome correspondes with preoperative global CBF values. CBF studies prior to shunting seems to permit prognosis and possibly serves for surge~t indication. This has to be verifyed by a larger number of patients.

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K Borbely*L. Lazar*, M. Kordas*,J. Martos*,I. Nyary*,P. Bazso** * Natonal Institute of Neurosurgery, ** International Medical Center, Budapest, Hungary

~F.

CLINICAL ASPECTS OF SPECT CISTERNOGRAPHY Purpose: to assess the diagnostic value of Tc-99m-DTPA SPECT cisternography in the pathologhyof the cerebrospinal fluid (CSF) space. Twenty nine patients were selected in cases where neither CT nor MRI scans provided conclusive diagnostics. Ten patients with hydrocephalus, eight with CSF rhinorrhea,six with CSF cysts, and fourwith a combination of hydrocephalusand CSF cystswereexamined. The results of radionuclide studies were correlzted with CT, MRI, and clinical findingsfor eachpatient In sevencasesthe hydrocephalusappeared to be communicatingwhereasin three casesit was noncommunicating. In fivecasesof rhinorrheathe results correlated stronglywith findings obtained from surgical data. In three cases of normal cisternographyno rhinorrheawas observed clinically since the examinations.The CSF cystsappearedto be wall-communicatingin two cases, and poorly communicatingin three cases and noncommunicatingin one case. In cases of the combination of hydrocephalusand CSF cysts surgerywas not performedin one case, a shuntwas performedin two cases and in one casea Y-shapedshuntwas implantedon the basis&the obtained data by CSF SPECT. Conclusion: The CSF SPECT proved to be very sensitivein differentiating communicating versus noncommunicatingforms of hydrocephalus. The method is very helpfulfor timingof shuntimplantationdue to its functional nature. The diagnosticvalueof SPECT cisternograpyis higherthan that of CT/MRIin evaluationof rhinorrhea. The method provedto be veryuseful in presurgiealevaluation of CSF cysts. The functional data determine and differentiate the communicationof CSF cysts,and therapyemployed.

$!a~, N. Prentice, A. Ryman, G.M. Goodwin, K.P. Ebmeier MRC Brain Metabolism Ugit, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EHI0 5HF, SCOTLAND STATISTICAL PARAMETRIC M A P P I N G (SPM) IN THE ANALYSIS OF SPECT AND MR IMAGES Study Aims Our aims were i) to determine the degree to which SPM statistic maps derived from MR and SPECT images complement each other in the differential diagnosis of elderly depression (ED) and Alzheimer's disease (AD) ii) to. assess the effect on SPM statistic maps of deriving spatial n o r m a l i s a t i o n components from the (high resolution) M R image then applying them to the SPECT image. M ~ t h o d s S t a n d a r d TI-weighted MR and highresolution HMPAO SPECT images were acquired from 12 early-onset (EOED), 9 late-onset (LOED) elderly depressed and Ii AD subjects. Gray m a t t e r segments were generated from the M R images. SPECT and MR segments were spatially normalised, smoothed then analysed using SPM. ~sult~ Significant, but different, perfusion patterns and gray matter reductions were noted in the AD group compared to both EOED and LOED in both the M R and SPECT statistic images. There was also an interaction in the SPM of SPECT images n o r m a l i s e d with and without MR t r a n s f o r m a t i o n components. C o n c l u s i o n s We have demonstrated the utility of SPM in the analysis of both MR and SEECT images from the same subjects. The advantages and disadvantages of using parallel MR information in improving the spatial normalisation of SPECT images will be discussed.

P 257

M u h a m m a d Babar I m r a n R. Kawashima, K. Sato, S. K i n o m u r a , H. Ito, S. Ono, S. Yoshioka, H. Fukuda. COMPARISON OF GROUP MEAN IMAGES OF ALZHEIMER'S PATIENTS AND AGE MATCHED NORMAL SUBJECTS: A Tc99m HMPAO STUDY USING IMAGE REGISTRATION. The p u r p o s e of this study was to compute and c o m p a r e g r o u p m e a n rCBF images o f patients o f A l z h e i m e r ' s disease and age matched control subjects after t r a n s f o r m a t i o n of the individual images to standard size and shape. Eleven patients of Alzheimer's disease (age 70 +__7) and twelve age matched n o r m a l subjects (age 68 + 7) participated in this study. T c - 9 9 m H M P A O b r a i n S P E C T and X-ray CT scans were acquired. S P E C T images were normalized to average activity of 100 counts /pixel. Realigned brain SPECT images o f both g r o u p s were used to generate m e a n and standard deviation images based on voxel values. Mean images o f both g r o u p s were compared applying student t test on voxel by voxel basis. X-ray CT of individual subjects were evaluated by c o m p u t e r p r o g r a m for brain atrophy. Significant difference of RI uptake was present in s u p e r i o r parietal lobule, cingulate g y m s , temporal lobe, p a r a h i p p o c a m p u s , right middle frontal lobe, left s u p e r i o r frontal g y m s and left inferior frontal g y m s (P < 0.05). Mean of brain atrophy index for patients and n o r m a l subjects were 0.853 + 0.042 and 0.933 +_ 0.017, respectively. We conclude that use of standardization procedure enhances the confidence of findings and voxel based g r o u p comparisons b e c o m e easy and m o r e accurate.

P 259 A Steinmetz, I Cranston, MN Maisey, J Bingham, S Bardngton, K Curran. Clinical PET Centre, United Medical and Dental Schools of Guy's and St Thomas's Hospitals London, UK. IMPROVED IDENTIFICATION OF NORMAL ANATOMIC ELEMENTS ON FDG BRAIN PET BY CO-REGISTRATION WITH MRI Aim: The present study evaluated the use of co-registration of FDG brain PET with MRI in order to identify the normal brain anatomy on PET scans. Methods: Brain PET was performed on normal volunteers 30 minutes after i.v. injection of 250 MBq of 18FDG. PET sinograms were reconstructed in 3.3 mm slices. Tl-weighted brain MRI.was performed thereafter in 3-D acquisition mode and reconstructed in 2 turn transverse slices. The reconstructed PET and MRI volumes were scaled and registered with the aid of XVlR program developed by the Radiological Sciences' Image Processing Group of our centre. The registered PET and MRI volumes were resliced to standard transverse, ceronal and sagittal planes by using the standard PET reporting software (Siemens-CTI, Knoxville, TN). Modified transverse planes, parallel to the long axis of the temporal lobes were also obtained. Results: MRI resolves a sulcus of the brain as signal free gap between two facing grey matter layers. In contrast PET has more limited spatial resolution and therefore the same sulcus and the two facing cortical grey matter layers appear blurred in one single, accentuated line of uptake (when sliced longitudinally) or an indentation of the cortical grey matter towards the white matter (when sliced transversally). Applying this principle the important sulci of the brain (central, parieto-occipital, calcarine, cingulate, supedor temporal sulci) could be recognised even on non-registered PET scans. Other structures as amygdala, hypothalamus, colliculi, dentate nuclei were Iocalised, but could not be identified reliably without the aid of the co-registered MRI. Conclusions: Coregistration of a mainly functional imaging modality to a more structural one (SPECT or PET vs CT or MRI ) has been reported to be beneficial in characterisation certain known turnouts or other lesions. Coregistration of brain PET with MRI makes possible the direct identification of an increased number of anatomic structures in the brain. Besides its role as a good teaching tool we feel ceregistration could be an aid in brain research enabling more accurate placement of sampling areas on brain PET thus improving the accuracy of the analysis of the regional brain uptake.

1007

tO =m t"

L_

O

I:k

P 260

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v. Ivan6evi6, A. Alavi, E. Souder, PD. Mozley, R.E. Gut, F. Benard, A H Sadek. Clinic for Nuclear Medicine, Charite, Humboldt University, Berlin, Germany and Division of Nuclear Medicine, University of Pennsylvania, Philadelphia, USA.

Chia-Hung Kao, Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

ASYMMETRY OF REGIONAL CEREBRAL GLUCOSE METABOLISM IN HEALTHY VOLUNTEERS: A DIAGNOSTIC PROBLEM? In routine visual analysis of regional cerebral glucose metabolism (RGM) as measured by FDG PET, the range of normal variations in right-to-left asymmetry has to be known. We analyzed F-18-FDG PET scans of 127 right-handed healthy volunteers (age range 19-83 years) acquired in a PENN PET H 240 scanner. RGM was assessed qualitatively in the three planes 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 frequency of asymmetric findings in the three planes did not differ significantly. Except for the lateral (20%-34%) and inferior aspects (12%-16%) of the temporal lobes, the temporal poles (10%20%), visual cortex (10%-12%), and putamen (13%-16%), the prevalence of asymmetric uptake was < 10%. The most symmetrically visualized areas were the frontal, parietal, occipital lobes, and the cerebellum. Wernicke's areas were visualized more often in the left, and the frontal eye fields and angular gyri in the right hemisphere. RGM was consistently higher in the right than in the left lateral aspect of the temporal lobes (p<0.001). Similarly, the right frontal eye fields revealed higher glucose metabolism than the left (p<0.01), while the angular gyri were visualized more intensely on the right side in the coronal planes only (p<0.05). In conclusion, physiological asymmetry in certain brain regions may be a problem in the visual analysis of RGM by FDG PET.

P 261 Leo G. Flores II, Seishi Jinnouchi, Shigeki Nagamachi, Shigemi Futami, Hiroshi Nakahara, Takashi Ohnishi and Katsushi Watanabe. Department of Radiology Miyazaki Medical College, 5200 Ohaza, Kihara, Kiyotake, Miyazaki, Japan 889-16 DELAYED TECHNETIUM-99M-ECD SPECT OF THE BRAIN: VALIDATED BY BOTH PHANTOM AND CLINICAL STUDIES We evaluated the sequential retention of Tc-99m-ECD by phantom and clinical studies. A total of 13 cases, 4 normal volunteers and 9 patients various diagnosis but with minimal clinical and radiologic findings were included in the study. For both studies, images were taken 10 and 30 min., 1, 2, 3 and 6 hrs and were reconstructed using the same method. Activity in various locations were corrected according time decay of technetium. Correlation of mean counts and retention rate with time were analyzed. There was no significant difference in the mean counts of normal volunteer and pathological patients. With time, retention rate decreased more rapidly in frontal and parietal lobes while at slower rate in temporal and occipital lobes. There was minimal change in retention rate in basal ganglia and cerebellum while increase was noted in the thalamus. For the phantom study, water filled spherical phantom was used. There was linearity in decrease of counts with time (r=0.997) and no significant difference was noted in counts at the central and peripheral areas in the phantom (p=0.66). In conclusion, the retention rate in the brain is not uniform. This difference in retention rate could not be attributed to reconstruction parameters nor is it influenced significantly by location of ROI.

1008

TC-99M HMPAO BRAIN SPECT COMBINING FAN-BEAM COLLIMATOR W1TH SURFACE THREE-DIMENSIONAL DISPLAY IN ACUI~ CARBON MONOXIDE POISONING. Acute carbon monoxide (CO) poisoning is a frequent and often fatal ev~t. 10% to 40% survivors will suffer permanent neuropsychiatry complications which cannot b¢ predicted in the acute phase from clinical, EEG, and brain CT scan findings. Tc-99m HIvIPAO brain/mages has been used to assess regional cerebral blood flow (rCBF) and detect different nearological and psychiatric diseases. Methods: Tan patients (3 feraales, 7 males, aged t6- 29 years) with acute CO poisoning and no past neurologm disordem were ~rolled in this study. After oxygen lzeatment, all patients had normal blood COHb values and none of the 10 patients had neurologie signs of toxicity. Then, all the 10 patients were investigated by Tc-99m H M P A O brain nnagesincluding fanbemu SPECT and surface 3D display. Meanwhile, 6 of the I0 patients also received brain CT scan studies to compare. Results: Only 2 of the 10 patients had normal findings of both fan-beam SPECT and surface 3D display. Fan-beam SPECT of brains demonstrated unilateral or bilateral hypoactivity of basal ganglia in 6 patients. Surface 3D display of brains revealed local hypoactivity anomalies in the brain cortex in 7 patients and the most commonly involved area was the parietallobe, Six patients with abnormal findings of fan-beam SPECT or 3D display had normal findings of brain CT scans. In addition, the patients with higher values of C O H b and more severe neurologic signs at admission seem to have a higher incidence of abnormal Tc-99m H M P A O brain image findings. Conclusions: This stud),suggests that, in compari~n with traditional b m m imaging Tc-99m H M P A O brain images of fan-beam SPECT combining with surface 3D display can be a bettertool to find early regional cerebral anomalies in acute C O poisoned patients.

P 263 K.M.Kim, J.S.Lee, C.Kwark, D.S.Lee, J-K.Chung, M.C.Lee, C-S.Koh, and Y.J.Kim*, Seoul National University Hospital, Department of Nuclear Medicinel;Hanyang University, Department of Physics*, Seoul, Korea MODIFIED APPROACH FOR THE QUANTITATION OF CEREBRAL METABOLIC RATE OF GLUCOSE WITHOUT BLOOD SAMPLING IN F-18 FDG DYNAMIC BRAIN PET The kinetic analysis of cerebral metabolic rate of glucose(CMRglu) has been done using the dynamic PET scans and blood sampling as an input function. We have designed an Brain PET imaging protocol for the kinetic analysis of CMRglu, where the input function is directly delineated from the time activity curve(TAC) of intracarotid artery. Immediately following the intravenous injection of F-18 FDG(2.8-16mCi), dynamic PET scans were acquired near the neck region for 37 min. The CMRglu values were calculated pixel-by-pixel using the Patlak graphical analysis. Also the standardized uptake values(SUVs) were calculated for the equivalent image pixels using the body weight normalization, where cerebral SUVs could be assumed insensitive to the plasma glucose level. Correlations between CMRglu values and SUVs were calculated for whole brain regions of interest. The input functions from TAC of intracarotid artery revealed smooth bolus injection sufficient for the kinetic model, and CMRglu values correlated with the SUVs(r=0.52~0.87), depending on the cerebral regions of interest. The lower correlation came from the regions of cerebellar and inferotemporal levels. We conclude that CMRglu could be estimated from the metabolic parametric images using the imagederived input function without blood sampling and independent counting of blood activity, which is invasive and might be inaccurate due to the separate conversion of m e a s u r e d activities to input function.

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P 267

R Blair, EO Williams, Regional Medical Physics Department, Newcastle and Sunderland General Hospitals. UK

I.HM. van Helvoog_~,JJ.N. Visser, E. Busemarm Sokole, Academic Medical Centre, Department of Nuclear Medicine, Amsterdam, the Netherlands.

INTERCOMPARISON OF RADIONUCLIDE CALIBRATORS USING STANDARDISED SOURCES - A LARGE SCALE INTER-HOSPITAL PROGRAMME. For quality control of radionuclide calibrators, it is recommended that they be compared with reference instruments traceable to national standards on a regular basis. A programme has been established, based on use of a secondary standard reference ionisation chamber, to permit annual cross-calibration of all 30 radionuclide calibrators in the 1 3 nuclear medicine departments in our locality, iodine-131 and Tc-99m are included in all intercomparisons, and other radionuclides were added where appropriate. These have included Thallium-201, Phosphorus-32, Iodine-123 and Strontium-89. Results from the first three years operation of the service have been reviewed, with the following conclusions. The mean observed difference between hospital equipment and the reference instrument was less than _+3%, showing that conformity with recommended standards has generally been achieve& Where there was larger variation in results, the source of the problems could often be diagnosed: these most commonly related to damage or modification to the source positioning devices. Regular visits by the operator of the scheme also enabled the methods of record keeping to be examined and advice given on demonstration of compliance with standards.

THE USEFULNESS OF A TOTAL PERFORMANCE PHANTOM IN ROUTINE SPECT QUALITY ASSURANCE Total performance phantoms are recommended as part of the quality assurance program of SPECT systems. The Jaszczak phantom (with cold spheres and rods) is often recommended for a cheek of uniformity and contrast. We have investigated the usefulness of this phantom for routine quality control checks of our Siemens MultiSPECT3 system. A jig was constructed for reproducible positioning of the phantom free in air. The protocol of the American Association of Phycisists in Medicine described by LS. Graham et al in Medical Physics, 1995, was adopted: low energy high resolution collimator, 15% energy window, < 25k counts per second, 20 cm radius of rotation, 64x64 matrix, 500k counts for the first projection. Data were acquired for each detector head separately and all heads together. Reconstruction was performed using different smoothing filters and attenuation correction. Non-uniformity was visually assessed within the set of transverse slices by noting the presence and extent of ring artefacts. Integral uniformity was determined in uniform slices not containing spheres or rods. The contrast of the cold spheres was quantified. The precision of the measurements was determined in 10 consecutive studies. SPECT performance was monitored by imaging the phantom each week. The effects of non-uniformity were investigated by using asymmetric energy windows to produce diffuse non-uniformity, and by attaching thin copper strips to the collimators to produce localized non-uniformity. Resultant artefacts in SPECT images were compared with non-uniformity in the planar flood-field images. Quantitative analysis was influenced by statistical noise and filters chosen. The effects of introducing non-uniformity proved to be mainly useful in learning to recognize artefacts of single and multiple heads, and to correlate SPECT non-uniformity with planar non-uniformity. Monitoring system performance with visual assessment was useful to confirm that there were no significant artifacts present. A monthly QC check using the Jaszczak phantom is now part of our SPECT QC programme. With a fixed set-up, standard data acquisition and reconstruction protocol, and visual assessment this QC test is quick and simple.

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.= P 266

L

P 268

S . ~ p k a n , I. Evren, H.. Durak, E. Derebek, Department of

Nuclear Medicine Dokuz eylLil University. izmir, TURKEY

EFFECT OF DECREASED IMAGING TIME ON THE LESION

DETECTION: A COMPERATIVE CARDIACPHANTOM STUDY USING CARDiOFOCAL AND LOW ENERGY ALL PURPOSE COLLIMATORS A 2 cm lesion was created in the cardiac phantom and two sets of SPECT studies were performed with cardiofocal collimator (CF), and low energy all purpose (LEAP) collimators using a two-head detector SPECT system (Siemens Multispect 2). One detector was used for imaging. SPECT was performed with 1 mCi (High dose) and 1OOgCi (Low dose) TI - 201 in the phantom. 71 images of 20 sec., 15 sec., 10 sec., 5 sec., 3 sec., 2 sec. and 1 sec duration were obtained in 64x64 matrix in t80 ° Shapp - Logan - Harming filter was used with a cut off value of 0.8 sec. Short axis slices were visually evaluated and the detectibility of the lesion was graded as 0= No lesion, 1= Slightly, 2= Good, 3= Excellent. Appearance of the lesion 20 sec. images were not found superior to 15 sec., and 10 sec. images when CF was used. In high dose slices, CF did not seem superior to LEAP, but in low dose slices CF was found superior to LEAP for every imaging time. Even in low dose and 1 sec. images the homogenity of the image is maintaned big CF while heteregenous appearance of the slices can be observed in frame times less than 5 sec. by LEAP. It seems that CF is superior to LEAP in cardiac studies by enabling shorter imaging times.

U. Dopichaj-Men,qe, A.Wolter, V. Ivan'.eric', D.L. Munz. Clinic for Nuclear Medicine, University Hospital CharitY, Humboldt University, Berlin, Germany.

SELECTION OF THE MOST SUITABLE RECONSTRUCTION FILTER FOR BREAST IMAGING WITH F-18-FLUORODEOXYGLUCOSE SPECT The aim of our study was to determine the most suitable reconstruction filter for filtered backprojection of F-18fluorodeoxyglucose (FDG) SPECT in the imaging of breast cancer. The most suitable fiiter should represent a trade-off between reconstruction artefacts on the one hand and overfiltering on the other. Thus, an acceptably homogeneous background with high

target-to-background ratios and the least possible loss of resolution are desired. SPECT studies were acquired in a 64 word matrix and 64 projections of 60 s each using a dual-head gamma camera. Seven different reconstruction filters were evaluated: Ramp, Low Pass, Shepp-Logan, Shepp-Logan-Hanning, Generalized Hanning, Parzen, and Butterw~rth. Four data sets of patients with various pathological findings and a normal data set were analysed, in all the data sets a reconstruction without filtering was performed first. After choosing a representative transaxial slice per patient study a total of 101 reconstructions with all the filters described and varying filter parameters was performed. The reconstructed slices were evaluated visually by three observers independently and for each of the 7 filters the best reconstruction was selected. All the data sets and slices were reconstructed with each of the 7 most suitable filters and comparatively analysed in the transaxial, coronal, and sagittal planes. Following the observers' concordant analyses a Low Pass (cutoff 0.7), Shepp-Logan (cut-off 0.4), and a Generalized Hanning (cut-off 0.5, alpha 1) fulfilled the criteria requested best without displaying visually significant differences among each other.

1009

(D 0~

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P 269 Y.Takahashi, H.Shinbata, M.Abe, A.Masuhara Ehime Prefectural Central Hospital, and Ehime Prefectural Imabari Hospital, Japan Department of Radiology. EFFICACY OF TEW SCATTER COMPENSATION METHOD IN In-lll Antimyosin Fab, TI-201CI DUAL ISOTOPE SPECT (CONTINUOUS MODE)

P 271 U. Dopichaj-Menge. L. Geworski, D. L. Munz. Clinic for Nuclear Medicine, University Hospital CharitY, Humboldt University, Berlin, Germany.

INFLUENCE OF SCAN SPEED ON LESION DETECTABILITY IN WHOLE BODY SCANNING

In-lll Antimyosin Fab is characterized as the ability to positively image disordered site of myocardial infarction at subacute stadium as well as an acute stadium and also myocarditis. Diagnostic a c c u r a c y can be i n c r e a s e d by s i m u l t a n e o u s l y administerin~ TI-201CI and performing dual isotope SPECT and fuslonimage (SPECT-SPECT).Forimprovement in image by simultaneously a d m i n i s t e r i n g dual isotope and reduction of scatter fraction, Tri~le Energy Window (TEW) method was applied to examlne parameters,etc, in the relevant method. As a system,GCA-7200A/DI(Toshiba),dual head gamma camera was used for the study. M e d i u m energy general purpose collimator for In-ill was attached to one side of the detector and low energy high resolution collimator for TI-201 on the other side to collect each nuclide. The peak energy in collecting was decided and limited to 71keV for TI-201, 245keY for In-lll, taking account of crosstalk. As a basic examination, the main window of this method was changed into 17-26% and the subwindow into 2-10% respectively to study image. Sub window is peculiar to TEW method, however, window widths was extended and the rate of the s u b w i n d o w to the main w i n d o w was correlated; y=4.17x+2.67,r=0.99 for Ti-201,y=2.11x+0.33,r=0.99 for In-lll. At the same t i m e , f o l l o w i n g was reco@nized;reduction of statistical noise in count withln the window, less noise, stabilization of scatter image itself, excellent image and improvement in visualization of In-ill and T1-201 image. It is considered that extended main window and subwindow would be suitable in TEW method when the count can not be sufficiently obtained because of the limited time of routine tests.

The aim of our study was to determine the influence of different scan speeds in whole body acquisitions (WB) on lesion detectability using different lesion/background (L/BG) activity concentrations A cylindrical IEC phantom with 6 spheres ( 0 10.0, 12.8, 17.9, 22.8, 27.9, and 37.0 mm) filled with Tc-99m pertechnetate solution of varying concentrations was measured. L/BG concentrations of 1:20, 1:10, 1:5, and 1:2 were used. Scan speeds amounted to 12, 10, 7, 5, and 3 cm/min. In addition, acquisitions with BG = 0 were performed. Static images (matrix 256x256; 5 min) served as a reference. All scans were done with a dual-head gamma camera (matrix 256x1024, HR collimator). Whole body views were evaluated visually by 10 observers independently. Results and conclusions: The scan speed had no influence on lesion detectability in the highest L/BG concentration of 1:20. Using LIBG of 1:10 or 1:5 there was a minor information loss starting at a scan speed faster than 10 cm/min. In these cases whole body acquisitions with scan speeds between 7 and 12 cm/min are recommended. If the L/BG concentration is low (1:2), a scan speed of about 7 cm/min is accectable. However, in this situation acquiring multiple spot images should be considered.

P 270

P 272

E.Nilsson, P.Bostroem, C.Liljedahl, T.Wennbom, A.Pettersson, U.Garske, S.Nilsson, JE Westlin Nuclear Oncology, Akademiska Sjukhuset, University Hospital, S-751 85 Uppsala, Sweden

E.B.Koenders. M.J.A.M.Franssen, A.M.Th.Boerbooms, W.C.A.M.Buijs, J.A.M.Lernmens, F.H.M.Corstens. Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands.

QUALITY

ASSURANCE

OF BONE SCINTIGRAPHY

In our department, spot wise imaging is considered to be superior to whole body scanning. Most of our patients have malignant lesions in the skeleton. Many of them have pain and a long investigation time causes discomfort to the patient. In order to improve diagnostic information in identifying lesions in the skeleton, within a tolerable time limit, this study was designed. METHOD. In order to increase the quality of the bone scan, we compared different total counts for each projection and evaluated different angled projections over thorax and pelvis. RESULTS/CONCLUSION. After evaluation of the studies, it was decided that the administered activity had to be elevated from 400 to 600 MBq 99Tcm HDP and that the number of counts could be increased, especially in images over the thorax. A standard study was decided to be increased from 12 to 14 different projections. We found that by administering 600 MBq and by improving the investigation technique, better and more robust scintigraphies could be performed without prolonging the investigational time. Additional information was found by increasing the number of projections. This is especially important when consecutive images of the same patient are assessed, FUTURE PROSPECTIVE. In order to find additional information of diagnostic significance, the influence of drugs with known interferance on bone metabolism, is to be investigated in a prospective study.

1010

THE EFFECT OF RADIOGRAPHIC CONTRAST MEDIUM IN RADIATION SYNOVECTOMY ON TIIE STABILITY OF YTTRIUM-90 COLLOID. A radiation synovectomy is carried out by intra-articular injection of Yttrium90 citrate colloid in the knee-joint To ensure that the injection is given in the jointspace an arthography can be performed. Radiographic contrast media may contain chelating agents such as EDTA. Such chelates may solubilize the radionuclide from the colloid complex, and alter the biodistribution. Possibly formed Yttrium-EDTA complexes migrate into the bloodstream, and subsequently clear via the kidneys. This theoretical possibility was examined by using radiographic contrast medium with and without EDTA. As a control, another group received saline instead of contrast medium. 15 Patients with a chronic persistent arthritis of one knee joint were randomly divided into three treatment groups of 5 patients. Before treatment with 185 Mbq Yttrium-90 citrate colloid, 5 patients were injected with 1 ml Omnipaque (0.1 mg EDTA), 5 patients received 1 ml Uregrafin (no chelating agents) and 5 patients 12 ml saline as a sham procedure. Following the injection of the Y90-colloid, the urine from each patient was collected during 48 hours. The radioactivity in the urine was measured and expressed as a percent of the injected dosage. Cumulative urinary excretion of Yttrium-90 was between 2 and 3% of the injected dosage. No significant differences were found between the patient groups. In this study, we have shown that the presence of a radiographic contrast medium with a chelating agent has no influence on the stability of the Y~rium-90 citrate colloid during radiation synovectomy.

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P 275

M.A. Jaarsma, S.W. Kooii, A. van Lingen, P. Lips, J.C. Roos. Departments Nuclear Medicine and Endocrinology, Free University Hospital, Amsterdam, The Netherlands.

M.Kat~, L.Par, B.Poharc, G.~mid, *D.Pi~ot HOSPITAL CELJE, * HOSPITAL IZOLA, SLOVENIA

L U M B A R SPINE DXA: R E L A T I O N B E T W E E N SITES AND SCORES. With dual energy X-ray absorptiemetry (DXA) the bone mineral density (BMD) of lumbar vertebrae is measured. An individual BMD value is age and sexe matched with a normal population. This results in a Z-score, expressing the number of standard deviations (SD) which the BMD differs from the normal mean. Standard diagnostic practice is to evaluate the Z-score of the lumbar segment L1 to L4 (Z14). Alternatively, the T-score is evaluated, which expresses the deviation from the peak BMD (T14). To investigate the changes in Z- and T-scores for different lumbar sites, we studied prospectively 1go consecutive patients (pts) referred for routine DXA. This sample size was dictated by the statistical criterion to establish at least 5% significance with the detection of differences of 20% of the SD of the normal population (Z-score unit). Z l 4 and T I 4 scores were compared with scores of separate vertebrae and combinations. Comparisons were performed by 2-sided paired Student's t-tests and gain (i.e. change to more abnormal) was expressed as the percentage of pts that had a score <-1, but Z 14>-1 or T 14>-l. Loss (i.e. change to less abnormal) was the percentage ofpts that had a score >-1, but ZI4<-I or TI4<-1. The mean difference (MDIF) and sd (SDDIF) were summarized together with the statistical significance (p) and the %gain and %loss: Z24 Z34 Z4 Z2 ZI T4 T2 TI MDIF -0.04 -0.12 -0.22 0.13 0.22 -0.28 0.15 0.34 SDD1F 0.13 0.28 0.49 0.37 0.50 0.48 0.37 0.49 p 5E-3 3E-5 2E-5 8E-4 2E-5 IE-7 1E-4 1E-9 %gain 1 4 9 3 0 6 O 0 %loss I l 2 4 6 2 5 9 The results showed that both the Z- and T-score of L4 resulted in the highest gain whereas L1 showed the highest loss. L3 showed no significantly different Z- and T-scores. Measurement of the segment L2-L4 is probably as informative as LI-L4. Whether measurement should be restricted by L4 (and reduce radiation burden and acquisition time) needs further investigation in a larger population.

TECHNICAL ASPECTS OF SCINTIGKAPHY WITH Tc,-99m SESTAMIBI IN DETECTION OF PULMONARY CARCINOMA AND ITS BONE AND BRAIN METASTASES

Te-99m Sestarnibi is videly used in myocardial pcrfusion imaging Rec,enfly it is used also for minor detection. Preparation of Tc-99m Sestamibi: Sodium Pertechnetate Tc-99m in approximately 1 - 3 mt is added into the kit vial. The vial is placed in a boiling water for 10 minutes and than removed to the room temperature for 15 minutes. Radiochemical purity of Tc-99m Sestamibi is checked with Redio-TLC-Method. We use radiopharmaceutical if the radiochemical purity is more than 90 %. Patient weighting 70 kg is intravenously injected with 740 MBq. Injected dose is weight dependent. 5 minutes after i.v. injection of Sestamibi 8 % of radiophamlaceutical is in the blood pool. Aqusinon is started 15 - 30 rain. after injection with Toshiba gamma camera GCA - 90I A. Whole body image is taken, eventually SPECT of thorax and head. Whole body with Tc-99m Sestamibi: Matrix size: 256 x 1024; ES: 99mTc 140 Key 20 %; scan speed: 20.0 era/rain, enlarge: x: I. - 2ram / lp, y: I. - 2ram / lp.

SPECT of thorax with Tc-99m Sestamibi: Matrix size: 64 x 64; ES: 99roTe 140 Key 20 %; step desree 6/360; acq time: 20 s/step; enlarge: x: 1. - 8ram/lp, y: 1. - 8ram / lp. SPECT of head with Tc-99m Sestamibi: Matrix size: 64 x 64; ES: 99mTc 140 Key 20 %; stop degree 6/360; aeq. Time: 15 s / stop; enlarge: x: 1.5 - 5.33 mm / lp, y: 1.5 - 5.33 mm / lp. With optimal radiopharmaeeutieal preparation and technical procedure daring the aqusition and data procesing we can reliably diagnose pulmonary carcinoma and its bone and brain metastases.

t" O |m C t~ Q,, L

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P 274 O. 01ker, G. Qapa, E. Demirta~, E. Ozbilek, H. Durak, M.Gary Sayed, Dokuz EylQI University Faculty of Medicine, Department of Nuclear Medicine and Nuclear Medicine Institute University of Findlay YOGURT AS AN ALTERNATIVE TO S C R A M B L E D E G G S F O R T H E EVALUATION OF THE SOLID GASTRIC EMPTYING

Many factors such as clinical conditions, technical considerations (attenuation correction, dietary composition of the tracer,etc.) can cause alterations in gastric emptying rates. The aim of this study was to search if the gastric emptying rate differs between standard Tc-99m tin colloid labeled scrambled egg and Tc-99m tin colloid labeled yogurt (preferred diet). We also searched for the difference of the gastric emptying rates between duodenal ulcer patients and normal controls. Yogurt was preferred by 76% of 68 patients who were referred to our department. Six volunteers and 7 duodenal ulcer patients were involved. First the standard Tc-99m tin colloid labeled scrambled egg (Dose:l mCi, average wt.:61.8 gr) and 1 week later Tc-99m tin colloid labeled yogurt (Dose:l mCi; average wt.:59.9 gr) gastric emptying studies were performed under the same conditions. The gastric emptying rates of volunteers for scrambled eggs and yogurt were 54.2 and 52.2 min, respectively. No statistical difference was found between the emptying rates of scrambles eggs and yogurt. We also could not find any difference between the emptying rates of duodenal ulcer patients for both methods. As the result; meals for gastric emptying studies can be adapted according to the taste of different nations.

O. KUtLT. Ertay, H. Durak, ~. Pek~etin*,H. Karaar~'an, A.Gare*, Department of Nuclear Medicine and Experimental Research Center

O

Dokuz Eyl01 University. Izmir, TURKEY THE COMPARISON OF Tc 99m RHENIUM SULPHIDE AND Tc 99m-HIG IN STERILE AND INFECTED ABSCESS

The aim of this study was to compare the Tc 99m-RHENIUM SULPHIDE (Tc 99m-RE) and Tc 99m-HIG uptake in sterile and infected abscess. Sterile abscess using staphilococcus aureus ATCC 29213 in one extremity of rats. After visual inspection of abscess formation, imaging was performed with Tc 99m-(RE) and Tc 99m-HIG at 1.,4. and 24. hours. Regions of interest were drawn on the abscess (A), on the contrlateral extremity (C) and on the wholebody (WB). 9 rats were studies. Mean counts were used to calculate. Results are in the table: me. 99m (Re) A/VVB CNVB

STERILEA BSCESS

INFECTED ABSCESS

1. HOUR 4. HOUR

1. HOUR 4. HOUR

0,71+0.21 0,72±0.13 0,62+0.12 0.66+0,14

0.48-+0,10 0.50-+0.66 0.53-+0.09 0.51±0.04

STERILE

Tc 99m-HIG AfWB C/WB

ABSCESS

1, HOUR 4. HOUR 3.2::t:0.63 2.8-+0.89 1.7+-0.36 1.4+0.43

INFECTED ABSCESS

1. HOUR 4. HOUR 2.8"*'0.75 3.4+1.2 1.92+0.361.364--0.52

in sterile and infected abscess no uptake was observed for Tc99m-(RE). Tc 99m-HIG showed increased uptake in both sterile and infected abscess. It seemed that increasing uptake at 4. hour images and a A/WB ratio more than 3.7 could lead to a reasonable diagnostic accuracy for infected abscess. For the result, Tc 99m-HIG is a valuable agent in abscess imaging. In addition we suggest that it may be usefull for the differantiation between infection and inflamation.

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P 279

G.A. Pool, L. Kristensen, C.A. Hoefnagel, R.A. Vald6s Olmos. The Netherlands Cancer Institute, Department of Nuclear Medicine.

lan Jones, Derby City General Hospital NNS Trust Nuclear Medicine Department

Lymphoscintigraphy as guide in oncological treatment.

A COMPARISON OF THE RADIATION DOSE RECEIVED BY NUCLEAR MEDICINE STAFF FROM THALLIUM-2DI AND TECHNETIUM LABELLED SESTAHIBI DURING MYOCARDIAL PERFUSION INVESTIGATIONS.

At the Netherlands Cancer Institute 99mTc-nanocolloYd lymphoscintigraphy plays an important role to support the treatment of malignancies. To obtain optimal diagnostic results the following acquisition protocols for lymph node scintigraphy have been developed at the nuclear medicine department. All investigations are made with ADAC dual head gammacamera's, LEHR collimator, window: 140 KeV, 20%, static acquisition time 5 min. 1, Internal mammary chain (IM, 370 investigations/year, MEGP coll.). Determination of position and lateralisation of the internal mammary chain nodes for use in radiotherapy (RT) planning.. Abdominal intramuscular injection of 60 MBq. Static images 2 and 4 hours p.i. with 57Co markers to define the RT field and distance of the chain from the midstemal line. 2. Lymph drainage of the extremities (EL, 30/year). Locating dermal lymph pooling and collaterals in the extremities after axillary or inguinal lymph node resection in order to guide manual or electro stimulated physiotherapy. Subcutaneous injection of 60 MBq in the extremity. Anterior and posterior total body 1 and 4 hour p.i. 3. Sentinel node(s) (SN, 100/year). To locate the first draining node(s) in melanoma and carcinomas of penis, vulva and breast in order to guide selective lymph node surgery. Peritumoral or intratumoral (breast) injection of 60 MBq. Dynamic anterior and lateral studies (60 images, 20 sec/image) directly after injection. 30 min and 2 hour p.i. static anterior and lateral images and a partial total body (only after 2 h) are made. All static images are acquired with a $7Co flood to obtain bodycontouring. In breast carcinoma late images could be necessary as well as lateral views in prone position (hanging breast). We conclude that with these protocols excellent images are obtained which give accurate (>95%) location (IM and SN) of the lymph nodes, important for radiotherapy and surgical treatment. In the lymph drainage of the extremities (EL), imaging could play an important role in the treatment of oedema b y physiotherapy. A further improvement could be the determination of the lymph node depth by use of SPECT.

ABSIRACI

201T1 myocardial perfusion scintigraphy is recognised as a useful clinical procedure for the evaluation of patients wiih coronary artery disease. The introduction of Tc99m-Sestamibi has not only improved image characteristics but also reduced patient absorbed doses. The affect of this change on nuclear medicine staff doses had not been investigated. This study Found that in changing From T1201 to Tc99m-Sestamibi the Effsetive Dose EquivalenI (EDE) for patients was reduced by a factor of about 3 and thaC lhis was balanced by an equivalent increase in staff dose.

P 278

P 280

C. O'Connor, F. Barker, Y. Byrne Nuclear Medicine Department and School of Therapeutic Radiography, St. Luke's and St. Anne's Hospital and Dublin University Trinity College, Dublin, Ireland.

~

RADIATION DOSES FROM NUCLEAR MEDICINE IMAGING PATIENTS TO NON-NUCLEAR MEDICINE PERSONNEL - IS THERE CAUSE FOR ALAP~ ? In our institution it is the practice, as far as possible tc perform other procedures, such as ultrasound, prior to Nuc. Medicine injections and to defer other non-urgent procedures to another day. It is not uncommon for some patients to have travelled considerable distances, often involving journey times of up to 5 hours, to attend and in these circumstances it may not be reasonable to expect the patient to return on another day. However concern has been expressed by nursing and radiography staff in other departments about the radiation exposure which they may receive from these patients. Dose rates in/U,Sv/h were measured with a Mini Instruments 900 series monitor immediately after injection of 500-600MB% 99mTcHDP at distances of 0.I, 0.3 and l.Om from the anterior trunk of the patients at waist level. These measurements were repeated 3 - 4 hours later when the patients returned for bone imaging. Results: Distance 0 hours 3 - 4 hours 0. i m O. 3 m 1.0 m

12 - 7 0 ~ S ~ / h 8 - 35 1.5 - 7 "

5 - 20/~Sv/h 5 i0 " 1.5 - 3 "

Times likely to be spent at 0.3 m were obtained for radiotherapy simulation, xray, treatment and chemotherapy. The longest reported time was 45 minutes (for chemotherapy). At the maximum recorded dose rate this would give 52.5/~Sv. The same staff member would need to be involved with 19 patients immediately after a bone scan injection to receive an additional 1 mSv. The corresponding figures at 3-4 hrs. would be 2 0 ~ S v and 50 patients. If our previously stated practice is adhered to, occasional patients should not present cause for concern. (All staff in our institution are designated workers).

1012

J.M.Jones I W D . E v a n s I A.Tweddel 2. ' '. , ' and Bioengmeenng . , • l and Nuclear Departments of Medmal Phystcs Cardiology 2 University Hospital of Wales, Cardiff

Nuclear Cardiology: Pre - Investigation information required by patients; determined by a survey conducted on 100 patient volunteers At the University Hospital of Wales, Cardiff, the Nuclear Cardiology Department performs up to three diagnostic investigations on 20 patients per weel,-. At present the information given to patients has been determined by what we assume is required. Judgir~g by the number of telephone queries and questions posed by the attending patients we felt that the information sent to the patient with their appointment was both incomplete and confusing. To address this situation the patients were given the opportunity to state what information they felt would be informative, helpful and reassuring whilst complying with statutory requirements. To this end a questionnaire/survey was devised to obtain a consensus

of pa:ient opinion as to what should be included in th~ information brochure. The questionaire was completed during the patients' visit :o the department which presented an opportunity for them tc exl;ress opinions which could be added to the information aq:ii-ed b y m,c~:~ of the questionaire. Preliminary analysis of the completed questionaires irxticate that the information imparted needs to be structured in such a way that the attending patients can easily follow and understand what is required of them during their visit. The information should be categorised into:- a) explanation of test, b) instructions as to diet and i~escribed medication, c) degree of discomfort, d) information reg~r :ling the radioactivity The revised information brochure will be monitored closely ¢o see if it meetz the needs of both patients and staff

P 281

P 283

C.Lil'e.leddahLE.Nilsson, P.Bostroelm U.Oarske, T.Weunbom, A.Pettersson, S.Nitsson, JE.Westfin, Department of Oncology, section of Nuclear Oncology, Akademiska Sjukhuset, University Hospital, S-751 85 Uppsala, Sweden

~ MeteUo*, M F Bote)ho**, J J. P~droso de Lima** * H S H. Br-,xe))es Be)giq-~e **!B!!l-FaC d e M e d , U n k , deCoimbra P0~uga!

A MULTIUSE NUCLEAR MEDICINE DATA BASE QUALITY ASSURANCE OF PRE-TREATMENT FOR PATIENT UNDERGOING 1311 MIBG SCINT1GRAPHY Introduction: The 1311 MIBG scintigraphy is often disturbed by unspecific faeces uptake and activity in the thyroid gland. Furthermore, various drugs can interfere with the 131I MIBG uptake in the tumour. In the present study, the aim was to assure that the patient was properly prepared in order to achieve an optimal investigation quality. Method: A written information about the purpose of the scintigrapby was designed and sent to the admitting ward in advance. This was complemented with a list of drugs, known to interfere with the specific 131I MIBG uptake. Along with this information a checklist was sent for each patient in order to confirm that the prescriptions were fulfilled regarding laxation, blocking of the thyroid gland and discontinuation of the interfering drugs. The checklist was signed by the nurse in charge and returned to our department the day before planned administration. A double check of the list was then performed at our department. Results: By informing the stafat the ward and by using the checklist, no essential preparation was missed and the quality of the studies improved.

The current state of a Data Base covering all the fields of Nuclear Medicine is presented in this work. This is an international and multidisciDlinary effort that consists in collecting, treating, correlating and storing all informations that might be useful in Nuclear Medicine. It is directed to people interested and/or active in Nuclear Medicine, such as students, technologists and clinicians (with a special attention to generalists) who search for precise information in the subiect, probably correlated with their own fields of activity. The information is as complete as possible and goes from technical to clinical. The different radiopharmaceuticals usable in each case, the main steps of the technical orocedures, the apropriate clualitv control and commented clinical images are available. We are busy trying to build a source of information with interactions and links between the different subjects, integrating a bulk of knowledge useful from students to Nuclear Medicine experts. The data base is built using as basic software the "File Maker Pro 3" program on a Power Macintosh, being intended to be used on a multiplatform basis. The conversion to a more powerful data base in a near future is also projected. This data base is developed as an open tool, having in mind that it will be an never-ended process, continuously edited or actualised with new data. The CD-ROM wi!l be the support of choice for the final product.

C O |m 4~

C

~L P 282

P 284

H L u o t o l i n n a - L y b e c k , I. Laltlne., Raija Eskola, Turku U n i v e r s i t y hospital, Department of Nuclear Medicine"

H B H ~ , S. HellerstrOm, M. Malmgren, S. Ekberg*, M.Stenstr6m*, P. S&fstrOm, Department of M e d i c i n e and Care, Division of Physiology, S e c t i o n of N u c l e a r M e d i c i n e and *Division of Radiation Physics, LinkOping University, Sweden.

C O O P E R A T I O N P R O J E C T FOR THE D E V E L O P M E N T OF PATIENT CARE Q U A L I T Y The cooperation project m e n t l o n ~ in the title is part of the qualitymonitor training in which those that are responsible for the project take part. Our project group has chosen for an example patient group a group of cancer patients Who bed to visit the Oncol ical Ambulato Department, the Department of Nuclear Medicine ~ d ~_i Department o~ Radiology before their threatment can begin and hopefully in the same day. The research comprises 30 patients. Four questionnaires were made by the responsible persons for the gathering of informstlon on the possible problem areas; careThemalnserv~ceUrpose of the project is to develop the quality of patient The aim is to find out - how long patients have to queu in order to get into the hospital in these departments for ~examlnations - how long patients have to stay in different research points and how much the examinations were late from the scedule - what the patients think about the sez-~ice they have received - the amount of radioactivity emitted in different points by patients that have received a radioactive dose - the best possible flow of patients between thm three units mantloned above Different stages of the research Since ~he arrival of a patlent's a ~ i s e i o n note," a ~ p o c l a l follow upform on queuing is being filled in. All the appointments for tests and researches are made on behalf of the patient and a speclal file is opened into which the patient's papers connected with the quality project aret~elaced. R i g h t ~rom patient's arrival to the policllnlc starts also the fillln in of a form the purpose of whlch is to follow hOW much time is use~ during the pro~ess. In every point of activity the patient's srrlvals and departures are registered in the form. A special form for collecting customer feedback is handed to the patient in an envelope. In thew~ichatient's file there is also a follow-uup form on radioactive doses are measured at the oncologlcal ambulatory department during a doctor's consultation, at the Department of Nuclear Medicine when giving the radioactive dose and durlsg the researh as well as at the Department of Radiology during the ul~a sound examlnatlon or mammography study. The present stats of the research

(march 1997) and the results

On I0 March 1997 the material of 18 caaes are collected. The whole corpus should be there by the end of March. The material will be processed and the wi~Ire oft prepared durlng the spring and summer of 1997. The results yield information on welting times and the critical points where the patients have tO wait long; in connection with this we try to make the flowchart of the whole process as simple and flexible as possible. We want to know how long patients are willing to walt and what they think about our services and what they wish. We also follow the amount of radiation emitted by the patients at the different phases of the process; this is relevant information when we search for the best possible flowchart for the process and Lowest possible radiation for the personal.

EXPERIENCE SCINTIGRAPHIC

OF A REPORT

NON SYSTEM

X-RAY

FILM

A few years ago we decided to exchange our old X - r a y film develop machine. At this time, all our gamma-cameras, processing computers, imaging visualisations and report system were connected in a in house network. We found it naturally to c o n n e c t e d laser p r i n t e r s for image hard copy rather than a new film developing machine. It gave us o p p o r t u n i t y to invent a new report system, all paper based, with positive effect of the environment as well as our h o s p i t a l s economy. The printers are one black/white 1200 dpi laser printer and one colour printer. Our routine are as follows. After the examination, we printout the image. The physician use the paper copy as well as the monitor image for diagnose purpose. The physician report are written directly in the computer system. The report are then linked with the d e p a r t m e n t name and address, e x a m i n a t i o n name, p a t i e n t name and specific number, the e x a m i n a t i o n image, in some cases diagrams or result figures as well as physician report. A n u m b e r of c h e c k points are c o m b i n e d in the procedure to guarantee safety. We have detect a number of positive aspects from our n e w report system. Due to the feed back p o s s i b i l i t y for the technologist, an education moment can be introduced. The remitting physician can compare the report with the image which gives a better understanding. All examination data and reports are saved on disk w h i c h makes comparison with early examinations easier.

1013

O

P 285

P 288

C. Kolligs, S. Ft~rst, C. Kmschke, J. Stollfuss, S. Ziegler, M. Schwalger Department of Nuclear Medicine, Technische Universit~t Mfinchen, Klinikum rechts der Isar, Munich, Germany

JM Jimenez-Hovuela, JR McClellan, M Barbarisi, A Alavi, LI A r a u j o . Univ. of P e n n s y l v a n i a M e d i c a l Center, D i v of N u c l e a r M e d i c i n e a n d C a r d i o l o g y , Philadelphia, PA. U S A

Assessment of Global Myocardial Function using Gated FI8fluorodeoxyglucose Positron Emission Tomographie. G a t e d P o s i t r o n E m i s s i o n T o m o g r a p h y (PET) u s i n g F18f l u o r o d e o x y g l u c o s e (FDG) offers the potential for simultaneous assessment of myocardial viability and regional or global functional parameters. However, standard protocols for gated Positron Emission Tomography are not widely established and to our knowledge there is no commercially available software suitable for the analysis of global ejection fraction or regional wall motion. We evaluated the feasibility of a simple gated protocol in 4 patients referred for a routine viability study using 8 frame acquisition with phased forward framing. The acquisition was started 60 min. after injection of approximately 370 MBq F18-FDG. Acquisition time was 30 min. using 8 time frames with an ECG threshold of 20%. Endsystolic (ES) and enddiastolic (ED) time frames were visually determined from transverse cine images and ES/ED short axis slices were reconstructed. Global ejection fraction was calculated on a pixel basis using manually drawn endocardial borders on ES and ED short axis images. Non-gated (summed) images were also reconstructed from gated datasets and compared to static imaging performed prior to the gated study 45-60 min. after FDG injection. We found similar image quality comparing the summed images from gated datasets with those of static acquisition. The ES and ED count rates using an acquisition time of 30 rain. were high enough to provide good image quality and to allow manual calculation of ejection fractions. Left ventricular ejection fractions ranged from 24-58% with a mean value of 41_+11% which agreed well with clinical data (mean EF 38+13). We conclude that ECGgated Positron Emission Tomography using 8 frame acquisition is feasible in clinical routine The acquisition time could be further reduced by starting at 45 rain. post injection without additional static imaging. Thus, further software development for the analysis of regional and global myocardial function is desirable to make gated PET useful in a clinical setting.

NO G E N D E R D I F F E R E N C E S OF SPECT T C - 9 9 M S E S T A M I B I MYOCARDIAL PERFUSION IMAGES WITH ATTENUATION CORRECTION. T i s s u e a t t e n u a t i o n is d e p e n d e n t on v a r i a t i o n s in b o d y h a b i t u s w i t h s i g n i f i c a n t g e n d e r differences. Attenuation correction (AC) a n d n e w a c q u i s i t i o n and reconstruction procedures m a y i m p r o v e the a c c u r a c y of S P E C T imaging. We e v a l u a t e d r e g i o n a l Tc-99m sestamibi myocardial distribution and assessed gender differences for 180 °- d e g r e e s filtered b a c k p r o j e c t i o n (180), 360 °- i t e r a t i v e reconstruction w i t h no AC (It) a n d It w i t h AC images in 39 p a t i e n t s (20 women) w i t h no c o r o n a r y disease .Studies were acquired using a triple h e a d e d P i c k e r 3000XP c a m e r a w i t h a Gd-153 source for simultaneous transmission and emission imaging. In e a c h p a t i e n t regional counts were a n a l y z e d u s i n g a t o t a l of 24 R O I ' s p l a c e d on 3 short axis slices (apex, m i d cavity, b a s e ) i n the 3 sets of i m a g e s (180, It a n d AC) . ROI d a t a w e r e n o r m a l i z e d to the m e a n v a l u e a n d the n o r m a l i z e d counts for the a n t e r i o r (An), inferior (In), septum a n d l a t e r a l walls w e r e c o m p a r e d for males(F) and females(M) .Results are e x p r e s s e d as means±sd. Regional differences between males and females were a s s e s s e d w i t h the student T test. Results: An 180 In 180 An It In It An AC In AC F .86+.07 .98+.09 1.03+.06 .96+.07 1.02±.05 .99+.04 M .93±.07 .88+.06 1.07±.08 .89+.05 1.01+.06 .99+.07 p_< .0001 .0001 .004 .0001 NS NS There are no significant differences in the septum and l a t e r a l w a l l w i t h all m e t h o d s . C o n c l u s i o n s : Acquisition w i t h 1800- r e s u l t e d in the g r e a t e s t g e n d e r d i f f e r e n c e s in the a n t e r i o r a n d i n f e r i o r walls . Iterative reconstruction with no AC p a r t i a l l y i m p r o v e d the u n i f o r m i t y but o n l y w i t h attenuation correction images w i t h no g e n d e r d i f f e r e n c e s w e r e obtained.

P 287

P 289

T. Sharir, S. L i v s c h i t z , B. R a b i n o w i t z , P. C h o u r a q u i . Sheba Medical C e n t e r a n d T e l A v i v U n i v e r s i t y , Israel.

H.L Verberne. J.H. Habraken, P. Slomka*,J.J. Pick, E.A. van Royen. Departmentof Nuclear Medicineanddepartmentof Cardiology,AcademicalMedical Center, Amsterdam,the Netherlands. * Department of Nuclear Medicine,VictoriaHospital, Ontario,Canada.

ANTI-ANGINAL DRUGS REDUCE SENSITIVITY OF DIPYRIDAMOLE TI-201 SPECT MYOCARDIAL PERFUSION IMAGING B e t a - b l o c k e r s (BB), n i t r a t e s (N) a n d c a l c i u m channel b l o c k e r s (CCB) are n o t u s u a l l y w i t h d r a w n p r i o r to d i p y r i d a m o l e s u b m a x i m a l exercise stress-rest TI-201 myocardial perfusion imaging (D-SPECT). T o e v a l u a t e the effect of these drugs on perfusion defects, 26 p a t i e n t s underwent D-SPECT with (SPECT I) a n d w i t h o u t (SPECT 2) a n t i - a n g i n a l t r e a t m e n t . T w e n t y - o n e p a t i e n t s r e c e i v e d CCB, 19 N, a n d 8 BB. C o r o n a r y a n g i o g r a p h y w a s p e r f o r m e d in 18 of the p a t i e n t s . T h e results (mean ± SD) of the q u a n t i t a t i v e a n a l y s i s of stress defect s i z e f r o m p o l a r maps, are as follows: LAD LCX RCA Total (%) SPECT I 25±21 56±35 36±27 33±12 SPECT 2 17±15 4 8 ± 3 6 21±20 25±14 p 0.003 0.03 0.008 0.0006 D e f e c t s i z e at r e s t w a s s i m i l a r in all t e r r i t o r i e s . S e n s i t i v i t i e s for d e t e c t i o n of c o r o n a r y d i s e a s e in LAD, L C X and RCA t e r r i t o r i e s w e r e h i g h e r for SPECT I t h a n SPECT 2 - 93%, 79%, a n d 100% vs 64%, 50% a n d 70%, r e s p e c t i v e l y . In c o n c l u s i o n a n t i - a n g i n a l d r u g s d e c r e a s e s i z e of r e v e r s i b l e d e f e c t s and r e d u c e s e n s i t i v i t y for d e t e c t i o n of c o r o n a r y d i s e a s e in i n d i v i d u a l v e s s e l t e r r i t o r i e s , in p a t i e n t s undergoing dipyridamole submaximal exercise T 1 - 2 0 1 S P E C T imaging.

1014

EVALUATION OF QUANTITATIVE 99MTCMIBIMYOCARDIALPERFUSION SCINTIGRAPHY USING INTEROBSERVERVARIABILITY. Background: Many attemptshave been made to developa quantitativepackagefor myocardialperfusiouscintigraphy.These programswere limitedby to manyoperator depend steps. Recentlya softwareprogram,PERFITR(NuclearDiagnostics),became availablefunctioningwith a minimumof operator dependendprocedures.PERFIT ~ fines and compares patient studies with a 3D averagedmodel heart, made of ~"Tc MIBI SPECT from volunteerswith a low likelihoodof coronaryarterydisease (CAD). Aim: Evaluationof PERF1Ta using interobservervariabilitybetween3 experienced observers, a panel and the results as obtainedby PERFIT R Methods: 43 patients, 36 with one-vesselCAD and 7 controls underwent99~q'cMIBI SPECT stress and rest. The panel and the 3 observers were blindedto patienthistory. Acquisition and reconstructionwere uniform.Reconstructedimages(coronal,saggital, tranversalslices) were offeredfor judgement Observers were asked to analysethe images using a 5 point gradingsystem,stress and rest separetly.Three categorieswere evaluated: severityof perfusiondefect, size of perfusiondefectand classificationof coronaryartery correspondingto the defect.PERFIT Rresults were transformedto the same 5 point grading system.Interobservervariabilitywas calculatedwith kappa (k) for coronaryarteryand weightedkappa (wk) for severityand size (+-SE). Results: The kappa values betweenthe 3 observersand the panel for severity,size of defect and coronaryartery on the stress imageswere in the rangeof: 0.65-0.75, 0.61-0.70 and 0.63-0.80 repecdvely.For rest imagesthe ranges were'.0.40-0.64, 0.30-0.56 and 0.360.61 respectively.

Panel vs PERFIT R

severity(wk)

size (wk)

stress

0.48_+0.12

0.30_+0.13

coronary artery (k) 0.58~0.10

rest

0.41_+0.14

0.31+_0.13

0..40+-0.11

Conclusions:PERFiT R has a moderateto fair agreementwith myocardialperfusion scintigraphyas visuallyanalyzedby a panel of three experiencedobservers.

P 290 W.S. Richter, R. Aurisch, S. Fischer, B. Kettner, D.L. Munz. Clinic for Nuclear Medicine, Charit6, Humboldt University Berlin, Germany PLASMA CLEARANCE OF FURIFOSMIN (Tc-99m Q12): COMPARISON WITH Tc-99m SESTAMIBI Furifosmin (Tc-99m Q12) is now available for myocardial perfusion imaging. Comparable to Tc-99m sestamibi, furifosmin is a cationic and lipophilic radiopharmaceutical. The aim of this study was to compare the plasma clearance of both tracers. Venous blood sampling was performed until 150 min p.i. in 10 patients (6m, 4f, aged 59.9+13.2 y) after furifosmin and in 15 patients (1 lm, 4f, aged 55.1+8.2 y) after sestamibi. The plasma clearance of both radiopharmaceuticals was bi-exponential. The half-lives of the fast and slow clearance component of furifosmin were 2.0±0.8 min and 129±24 min, respectively. The corresponding values for sestamibi were 1.6±0.5 min (n.s.) and 86+21 min (p<0.001), respectively. The plasma clearance of both substances could be described by an open 2-compartment model (central compartment,plasma; disposition compartment, intracellular space of all body cells; elimination compartment, kidneys and liver). Pharmacokinetic constants for cellular influx were comparable for both tracers (furifosmin, 0.31+0.11/min; sestamibi, 0.25±0.08/min; n.s.). However, the relation of cellular efflux:influx was higher for furifosmin (0.16 vs. 0.09; p<0.03). The plasma clearances of Tc-99m furifosmin and Tc-99m sestamibi are different. More transmembraneous exchange has to be expected for furifosmin. This behaviour may exert considerable influence on redistribution and wash-out phenomena in myocardial SPECT when using furifosmin.

P 292 G.Cannizzaro, G,Calsamiglia,°M.Previtali, °L.Lanzarini, C.Aprile. Dept. of Cardiology and Nuclear Medicine Serv., - "S.Maugeri" Foundation - Montescano - Pavia; ° Dept.of Cardiology-University of Pavia - Italy -. EXERCISE T H A L L I U M 201 SPECT AND DOBUTAMINEA T R O P I N E STRESS E C H O F O R THE DIAGNOSIS OF M Y O C A R D I A L I S C H E M I A AFTER T H R O M B O L Y S E D M.L Purpose: to compare the diagnostic accuracy of exercise Thallium 201 SPECT (TI-SPECT) and dobutamine-atropine stress echo (DB-E) for diagnosis of post infarction myocardial ischemia. Material and Methods: 43 consecutive male pts. with a first M1 treated with thrombolysis ( age 56 + 10 yrs.,57% anterior Nil, 79% with Q wave) were studied within 20 days from MI with TI-SPECT (stressredistribution-reinjection technique) and with DB-E (5-40 gg/kg/min + 1 mg atropine). An ischemic response was defined as: 1) T1-SPECT: stress induced, partially or totally reversible perfusion defect; 2) DB-E: new or worsening wall motion asynergy in the infarct zone. Results: DB-E TI-SPECT I? value lschemia in infarct zone 31/43 (72%) 31/43 (72%) n.s. > 50% infarct related artery stenosis

Sensitivity Specificity Diagnostic accuracy Ischemia at distance

30/38 ( 79% ) 3/5 ( 60% ) 33/43 ( 77% ) 5/43 ( 12% )

29/38 ( 76% ) 3/5 ( 60% ) 32/43 (74%) 8/43 ( I9% )

n.s. n.s, n.s,

Multivessel disease

Sensitivity 4/9 ( 44% ) 5/9 ( 55% ) n.s. Specificity 33/34 ( 97% ) 31/34 ( 91% ) n.s. Diagnostic accuracy 37/43 ( 86% ) 36/43 ( 84% ) n.s. Concordance between tests was 67% for ischemia in the infarct zone and 88% for ischemia at distance. Conclusions: in a population of pts. with a first M] treated with thrombolysis T1-SPECT and DB-E detect myocardial ischemia in the infarct zone in > 2/3 pts. The two tests show a similar sensitivity and specificity for diagnosis of critical stenosis of the infarct related artery and of multivessel disease.

C O =m C t._

O.. P 291 R. Jochens, T. Parsch, T. Schumacher, U. Engert, H. Amthauer, H Bertram, W. Zendel, L. Tambeur, R. Hetzer, H. Eichstaedt Department of Nuclear Medicine and Imaging Cardiology, Virchow-Clinic,

Humboldt-Universityof Berlin, GermanHeartCenter, Berlin, Germany FOLLOW-UP STUDIES OF MYOCARDIAL PERFUSION IN PATIENTS BEFORE AND AFTER TRANSMYOCARDIAL LASER REVASCULARIZATION (TMLR) Purpose of the study was to evaluate the myocardial perfusion in patients before and three months after TMLR by means of TL-201 scintigraphy. Methods: 42 patients (6 f., 36 m.) were investigated with TI-201 SPECT before and three months after TMLR. Images were obtained with a single-headcamera (Elscint) after stress and three hours later after administration of 100 MBq (90-110 MBq) TI-201. A visual analysis of the images was done by three investigators; in addition a semiquantitative analysis of the segmental (apikal, anterior, lateral, inferior, septal) perfusion was performed. For TMLR in all patients the Heart Laser (800 W) was used. 5-55 (mean 30 channels) channels were applied. Results: A clinical improvement three months after TMLR w a s observed in about 45 % of patients, 45 % showed equal symptoms and in 10 % the clinical status worsened. Concerning visual analysis of the TI-201 SPECT 14 % of the patients shewed an improved myocardial perfusion after TMLR, in 72 % the perfusion was comparable and in 14 % there was a decrease visualized. The semiquantitetive analysis of the myocardial-segments showed no signifikant improvement of the lasered regions in comparison to the non-lasered septal segment. No significant change of TI-201 pulmonary-uptake during stress as an indirect scintigraphic parameter of left ventricular function was found (43,6 % before, 44,8 % after TMLR). Conclusion: Although a clinical improvement in 45 % of the patients was recognized no significant change of myocardial perfusion could be seen in 201TI myocardial SPECT three months after TMLR.

P 293 ~3,~Koutelo~, S. Mavrogeni, A. Kouzoumi, D.V. Cokkinos. Nuclear Medicine Department, 1~t Cardiology Department Onassis Cardiac Surgery Center, Athens, Greece

RELATION OF ST DEPRESSION DURING ADENOSINE THALLIUM IMAGING TO EXTENT OF CORONARY ARTERY DISEASE AND ITS PROGNOSTIC SIGNIFICANCE This study attempted to determine the relation between ST depression and seintigraphic isehemia during adenosine infusion (140~g/kg/min for 6 mimites) in patients with coronary artery disease (CAD). We studied 86 patients (pts), 70 male and 16 female. 18 pts with 3-, 22 pts with 2- and 46 pts with 1-vessel disease (VD). 75 pts (87%) had abnormal SPECT thallium images and 29 pts (34%) had ST depression. The ECG response showed markedly ST depression ~ 2 m m ) in 8 pts (9.3%). The pts having ST depression _>2ram were older (79i-_9 years) than those without ST depression 60"2-6 years and ->3 risk factor for CAD. 14 pts (48%) of those with ST depression had 3VD, 7 pts (24%) 2 VD, 7 pts (24%) and 1 pt had normal coronary arteries with history of previous myocardial infarction (MI) and 21% from those without ST depression had 3VD, 37% 2VD and 42 IVD. From p~s with ST depression 76% had extensive ischemia (->3 reversible defects) an 46% from those without ST depression ->3 reversible defects: In a follow up of 6 months to 3 years after adenosine testing 24 cardiac events occurred: I cardiac death, 1 nonfatal MI, 3 admissions for unstable angina and 19 revascularizations. Thus ST depression during adenosine relates to extensive CAD and it predicts future cardiac events and provides information to that obtained from clinical variables and the results of adenosine perfusion images.

1015

O 13.

P 294 L.Samoilenko, E.Sayutina, A.Samko, Y.Matchin, I.Perstukov, G.Soboleva, Y.Karpov, V . S e r g i e n k o Cardiology R e s e a r c h Center, Moscow, Russia

A C E T H Y L C H O L I N E (ACH) EXERSISE 99mTc-MIBI TEST IN DETECTION OF MYOCARDIAL ISCHAEMIA DUE TO ENDOTHELIAL D Y S F U N C T I O N

P 296 M.Hakimi, W.Burchert ,T. Aybek*,J.van den Heft, J.Graff*, G-J. Meyer, H.Oster*, H. Hundeshagen, Department of Nuclear Medicine of the Medizinische Hoehschule Hannover and Department of Heart Surgery of the Herzzentrum Rotenburg a. d. Fulda* QUANTITATIVE ASSESSMENT OF MYOCARDIAL BLOOD FLOW BY 13-NH3 PET IN PATIENTS AFTER TRANSMYOCARDIAL LASER REVASCULARIZATION

Impaired endothelium - dependent vascular responses of arteries are known to be an early event in atherogenesis, Endothelial dysfunction (ED) occurs in men with risk factors for coronary artery disease (CAD), before anatomical evidence of plaque formation in the arteries appears. Our study aimed to assess value of stress 99mTc-MIBI SPECT myocardial perfusion imaging for detection of ED. The 9 patients (pts) mean age 40±8 with chest pain & risk factors for CAD (arterial hypertension, hypercholesterolaemia, smoking) were studied. Of 9 pts 7 had angiographically normal left coronary artery (LAD) & 2 were found to have LAD stenosis < 50%.Increasing concentrations of Ach (5xI0-~M, 5xI0-~M,5xI0-SN) were sequentially infused into left coronary artery.99mTc-MiBI was injected simultaneously with the last dose Ach or when evidence of vasospasm appeared. SPECT myocardial perfusion imaging was perfomed within 1 hour.All pts underwent stress 99mTc-MIBI SPECT within 7 days. Results: Ach induced paradoxical constriction of LAD in 5 pts resulted to perfusio~ defects on scintigrams. 4 pts of 5 had identical defects both in intracoronary Ach & stress test images. Our preliminary finding suggest that impaired endothelium - dependent vascular responses of coronary arteries may contribute to episodes of myocardial ischaemia in pts with chest pain & risk factories for CAD.

Transmyocardial revascularization with laser (TMR) appears a promising therapy to linder angina pectoris and to increase myocardial perfusion in patients with severe symptomatic coronary artery disease refractory to interventional or medical treatments. It is believed that the laser shots induce subendocardial channeIs with potentially anglogenesis. To verify this assumption myocardial blood flow and glucose metabolism were measured in 20 patients (18 m/2f, age 62 -+7) before, and 3, 6, 9 and 12 month after TMR. Pre-TMR (61%) patients were in the NYHA class III und (39%) in class IV. We used a Siemens ECAT 951 PET-Scanner. Rest and stress studies were performed with 1,1GBq 13-(N)-ammonia and followed by a viability study with 370 MBq 18-(F)-FDG. For the stress test we used 140 /.tg/kg/min Adenosin in 12 stable patients with angina class 3-4 CCS. For data analysis area conserving polar maps were used. The blood flow at rest (RBF) increased in 25% of lasered segments (LS) versus 20% in non lasered (NL) myocardium, remained unchangend in 45% LS versus 40% in NL areas, decreased in 30% LS versus 40% NL. The coronary flow reserve (CFR) increased in 17% LS versus 41,6% NL, remained unchangend in 66% LS versus 50% NL and decreased in 17% LS versus 8,4% NL. In the whole left ventricle the myocardial blood flow (RBF and CFR) increased in 40% of the patients, remained constant in 55% and decreased in 5%. After TMR 76-90% of patients were in class 1-II NYHA and 10-30% in class III-IV. Our results suggest that TMR improves the clinical status much more than the myocardial Perfusion.

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R.T. Dhawan, K. Benson, G. Roussakis, A.K. Kapur, K. Latus, D.J. Pennell, S.R. Underwood. Royal Brompton Hospital, Department of Nuclear Medicine, London, UK

O.Schillaci,°B.Lagana',V.Picardi,R.Danieli, R.Tavolaro,F.Monteleone,P.Cannas,°R.Gentile,F. Scopinaro. Nucl. M e d and Med. Clin., Univ. "La Sapienza",Rome, Italy.

ABNORMALMYOCARDIALPERFUSION SCINTIGRAPHYIN PATIENTSWITH CHRONIC AIRWAYSDISEASESTRESSEDBY DOBUTAMINE

EVALUATION OF MYOCARDIAL PERFUSION IN A S Y M P Y O M A T I C P A T I E N T S (PTS) W I T H S Y S T E M I C L U P U S E R Y T H E M A T O S U S (SLE) U S I N G T c - 9 9 m M I B I (M) S P E C T .

Dobutamine is an established stress agent for myocardial perfusion imaging, and the technique has a high specificity for detecting coronary artery disease in most clinical settings, except in patients with left bundle branch block. Following the finding of a septal perfusion defect in a patient with chronic airways disease and normal coronary arteries, we have reviewed 57 consecutive dobutamine studies in patients with chronic airways disease. The findings were compared with a control group who did not have chronic airways disease, who were stressed by adenosine, and who were matched for age, sex and clinical indication for the study. Forty six (81%) study patients had abnormal tomographic images compared with 28 (49°/o) controls (P < 0.001). Of these, 41 (89%) study patients had septal defects compared with 9 (32%) controls (P < 0.0000I). The septal defects were isolated in 26 study patients (63O/o) compared with 0 controls (P < 0.001). The isolated septal defects were mild in the study group in 54%, moderate in 46%, and severe in none. This increased frequency of septal defects seen with dobutamine in patients with chronic airways disease suggests that mechanisms other than coronary artery disease may provoke defects. Lung disease may lead to raised right heart pressures and hence abnormal septal motion. At rest, partial volume effect may therefore cause an apparent abnormality which may be accentuated by inotropic stress. In addition, subendocardial ischaemia may be produced by increased wall stress with dobutamine. While these observations require angiographic validation, they suggest that mild and moderate septal defects in patients with obstructive airways disease stressed with dobutamine should not necessarily be attributed to coronary artery disease.

1016

In pts with SLE the involvement of cardiovascular system is the third leading cause of death, but few data have been r e p o r t e d on the evaluation of myocardial (myo) p e r f u s i o n (p) in this autoimmune disease. To this aim 16 SLE pts (14 F, age range: 21-49 years) were studied with M SPECT. All of them had no sign or symptoms of heart disease, and were submitted to M SPECT at rest and after dipyridamole infusion (0.56 mg/kg over 4'). The scintigraphic data were quantitatively analyzed. Segmental p abnormalities were d e t e c t e d in ii pts (68%). Two pts h a d reversible defects, 5 pts h a d persistent defects and 4 pts had b o t h reversible and persistent defects. All these ii pts had p defects in the anterior/septal segments, 1 also in the inferior segments and another one also in the inferior and lateral segments. A significative correlation was found between scintigraphic outcome and impairment of cardiac autonomic function evaluated b y heart rate variability (HRV; r:0.7, p<0.05). Coronary angiography were performed in 7 pts with positive M SPECT, and showed normal epicardial vessels in all the cases. In conclusion, our p r e l i m i n a r y results indicate a h i g h incidence of myo perfusion abnormalities in asymptomatic pts with SLE. Further studies are required to determine if these findings are m a i n l y due to small-vessel disease, and to better define the correlation w i t h HRV alterations.

P 298 B. Brouant, P.Y. Marie, N. David, P. Olivier, T. Arsena, N. Quiri, N. Hassan, M. Angio2, G. Karchef, N. Danchin, A. Bertrand. CHU-Nancy, France. BETA-BLOCKERS PROTECT AGAINST THE PROGNOSIS IMPAIREMENT RELATED TO THE EXERCISE ISCHENIA EVIDENCED ON TI201-SPECT Antianginal medications, and especially N-blockers, limit the exercise ischemia evidenced by scintigraphy in p a t i e n t s w i t h coronary a r t e r y disease (CAD). This study was aimed at determining whether the administration of antianginal medications might also change the prognosis impact of exercise ischemia previously detected by TI201-SPECT. We included 352 pts with CAD, who had exercise TI201-SPECT and coronary angiography, and who were initially treated medically. Survival Cox models were applied in pts who had no change in antianginal medications between SPECT and further follow-up (GI, n:136), and in those for w h o m N-blocking (GII, n=79) or only non-N-blocking antianginal medications (GIII, n=l13) were subsequently added for follow-up. During a mean 5±2 years of follow-up, 45 pts had cardiac death or myocardial infarction. Variables reflecting necrosis (irreversible defect extent, LV ejection fraction) and those from coronary angiography, provided similar prognostic informations in the 3 groups. By contrast, the SPECT variable reflecting ischemia (reversible defect extent), which provided comparable prognostic informations in GI (p:.005) and GIII (p=.004), loses its prognostic significance (p=.54) because of a marked risk overestimation in GII (lower relative risk compared with GI and GIII, both p<.05). In patients with CAD, the worsening of prognosis, which is related to the exercise ischemia evidenced on TI201-SPECT, is lowered by the subsequent administration of ~-blockers but not by that of other antianginal medications.

P 300

A.Bentrup, D.Hartung, C.Lucke*, HJ Otto, JA Schmidt* Dept. for Nuclear Medicine and Angiology* University of Magdeburg, Germany EFFECTS OF PROSTAGLANDIN THERAPY 1N PERIPHERAL ARTERY OCCLUSIVE DISEASE (PAOD) CAN BE PREDICTED WITH TC 99M-SESTAMIBI PERFUSION SCINTIGRAPHY Objectives: In semi-invasive angiology, pharmacological treatment with prostaglandin E2 analogon (PGE) has become a widely used method to avoid chimrgical intervention. Changes of leg perfusion however are inaccurately measured with conventional angiological techniques. Tc99m Sestamibi perfusion scintigraphy can quantitatively estimate the augmentation of blood supply to lower limbs. The aim of this study was to identify pts. who may derive benefit from PGE treatment. Methods: In 20 consecutive patients with PAOD IIb-IV post occlusive reactive hyperemia and perfusion were measured before, during and aIter a 14 day course ofi.a.v or i.v infusion of PGE. Dynamic and static images &lower limbs were obtained 5 rain and 3 h after ishemia and i.v. injection of 10 mCi Tc99m-Sestamibi. Count rates were measured in regions of interest including the entire lower legs. Results: Ratio &maximum blood flow and resting flow before therapy correlated significantly with doppler pressure (p<0.0005), venous occlusion pletysmography (VOP) (p<0.005) and clinical findings (p<0.05). Time to maximum count increase (MCI) and MCIbad a significant correlation with time to peak flow (PF) and PF in VOP throughout therapy (p<0.075). After therapy, MCI showed a positive correlation with changes in clinical score and walking distance (p<0.05). Conclusion: Tc99m-Sestamibi scintigraphy is superior to conventional angiological techniques by measuring changes ofperfusion in muscular microcirculation. Our results indicate that early identification of responders resp. non-responders is possible.

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,,I,.,I

C t~ Q..

P 299

M. Fara&gj, G. Montalescot, L. Sarda, J.F. Heintz, R. Lebtahi, N. Oelahaye, D. Doumit, D. Thomas, D. Le Guludec, Services de Medecine Nucleaire et de Cardioiogie, HCpital Bichat et Pitie-Salpetriere, Paris, France. SPONTANEOUS REDUCTION IN REST THALLIUM DEFECT SIZE DURING THE CHRONICPHASEOF MYOCARDIALINFARCTIONIS RELATEDTO LV FUNCTION IMPROVEMENT AND TO THE TIMI-GRADE FLOW OF THE INFARCT-RELATED ARTERY.

We prospectively studied the spontaneous changes in rest-redistribution thallium (TI) defect-size during 6 months in 52 patients with previous myocardial infarction investigated from 3 weeks to 72 months (mean 5 + 15 months) after the acute phase. A rest TI-SPECT and a radionuclide determination of the left ventricular ejection fraction (LVEF) were performed on inclusion and repeated at 6 months. TI defect-size (expressed as a % of the whole myocardium evaluated on a buffs-eye polar map) and TI uptake in the infarcted area (expressed as a % of the normal area counts) were compared to the data obtained from simultaneous coronary angiography. According to the patency of the infarct-related artery, patients were divided in Group I (patent coronary artery, n=31) and Group II (occluded artery, n=21). For the overall population, defect size decreased from 28.2_+17.2% to 24.9+19.3%(p=0.01), while, in this area, thallium uptake increased from 62.9-+13.7% to 66.9-+15.6% (p<10~). In Group I patients only, the reduction in the size of the thallium defect was significantly related to the improvement in LVEF (F-0.41, p=0.02, n=31). The only predictive factor evidenced by a multivariate regression analysis was the TIMI-grade coronary flow (p<0.008) but neither the age of myocardial infarction, nor a previous history of coronary revascularization. A significant inverse relation was found between the reduction in defect size and the percentage of coronary artery stenosis (r=-0.37, p=0.04, n=31), particularly for patients with anterior M[ (r=--0.51, p=0.04, n=17). TIMI 3 patients reduced their defect size (changes:-5A±7.0%, n=27) while the others increased this defect size (changes:+11.0_+14.4%, n=4, p<103). No significant relations were found for Group II patients. Conclusion: in patients with patent infarct-related artery, spontaneous recovery in TI-defect may occur late after the acute phase and is related to functional improvement and to the coronary flow of the infarct-related artery.

P 301

D. R. Jangid, M. L. Bhatia, N.Trehan Escorts Heart lnstititue & Research Center, New Delhi-25. INDIA RESTING QS-aVL PATTERN ON A BASELINE 12LEAD E.C.G IS PREDICTOR OF A FALSE-POSITIVE TREAD-MILL TEST ? : SCINTIGRAPHIC ELUCIDATIONS INTRODUCTIONi QS in augmented unipolar lead aVL (QS aVL) of a baseline ECG has been identified by us as a marker of false positive electocardiographic tread-mill test (T.M.T.) for coronary artery disease / Ischaemic heart disease (IHD). METHOD: 68 consequtive asymptomatic patients with baseline 'QS-aVL' and significantly positive T.M.T. (1.5-4.5 mm STdepression) by Bruce protocol, were subjected to tomographic (SPECT) 201-Thallium Stress-Redistribution myocardial perfusion scintigraphy (SR-TMPS) using 3mCi (111 MBq) of radioactivity. RESULTS: (See table) Of the 68 patients, 64 (94%) showed normal SR-TMPS (myocardial perfusion indices (P.I.) >85%). 2 patients showed mild ischaemia (septum; inferolateral wall), while the remaining 2 patients (apicoinferior wall) showed equivocal results. Status

P.I. (%)

# of Pts.

%

Normal Equivocal Ischaemia

85-100 80-85 60-85

64 2 2

94 3 3

CONCUSION: Presence of a baseline 'QS-aVL' pattern on E.C.G. in an asymptomatic patient showing significant ischaemic response (even deep ST depression) on T.M.T. would indicate a false positive test for IHD.

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P 302

P 304

JM Freire, M Pajares, R Nieto*, D Becerra*, E Otero, L Lumbreras*, FJ Senise, JJ M-Ser~pere*. University Hospital Cadiz, Granada* Spain.

J. Kotzerk_e, M. Kochs, C. Langhammer, A. Betz, C.A. Guhlmann, M. H6her, V. Hombach, S.N. Reske. Dept. of Nuclear Medicine and Cardiology, University Hospital of Ulm, Germany

DIAGNOSIS AND LOCALIZATION OF CAD USING 99mTcTETROFOSMIN IN PATIENTS WITH PRIOR MYOCARDIAL INFARCTION Our objetive was to evaluate the influence of prior myocardial infarction (MI) on the sensitivity (S) and specificity (SP) of 99mTe-tetrofosmin myocardial imaging in the identification of significant coronary stenosis. SPECT 99mTo Tetrofosmin one-day stress-rest imaging protocol were performed in 115 patients (89M, 26F) who had undergone diagnostic coronary angiography. Sixtythree patients (pt] showing prior myocardial infarction. There were 20 pt with no coronary artery disease [CAD); 43 pt with one-vessel (~70% diameter narrowing as significant stenosis), 29 pt with two-vessels and 23 pt with three-vessels disease. Myocardial SPECT data were evaluated visually using a five segment five score system (0: normal to 4: absent uptake). The Sensitivity for CAD detection were 100% in patients with and whitout prior MI. We observed diferences (p=0.O3) in the detection of significant stenosis between patients with MI (S:90%) and patients without MI (S: 80%). Concerning localization of individual coronary artery (n=345), the following values were obtaining: ALL WITH NI WITHOUT NI LAD 90% 93%(38/41) 86%(25/29) n.s. SENSITIVITY 80% 77%(17/22] 83%(19/23) n.s. SPECIFICITY LCX 73% 82%(23/28) 54% (7/13) n.s. SENSITIVITY 95% 97%(34/35) 92%(36/39) n.s. SPECIFICITY RCA 90% 93%(38/41) 82%(14/17) n.s. SENSITIVITY 89% 86%(19/22) 91%(32/35) n.s. SPECIFICITY We conclude that 99mTc-Tetrofosmin SPECT is a reliable method in detecting significant coronary stenosis in patients post myocardial infarction.

PROGNOSTIC VALUE OF TC-99M-SESTAMIBI-SPECT AFTER MYOCARDIAL INFARCTION - A 3 YEAR FOLLOW-UP STUDY The prognostic value of thallium-201 scintigraphy is well known. The natural course after a normal Tc-99m-sestamibi (MIBI) myocardial scintigraphy enrols a normal risk of 1%/year for a cardiac event (hard and soft event). However, there are no data available for risk stratification after myocardial infarction using MIBI. Out of 626 myocardial scintigraphies between 6/91 and 6/92 at the university of UIm, 153 patients have had a documented infarction. 115 of them had angiography and MIBI SPECT suintigraphy within two weeks. From 111 of them clinical information could be received after an interval of up to three years. We investigated whether the scintigraphic results (ischemia, fixed defect) were correlated with the frequency of cardiac events. Three goups (44/26/41) were investigated at different times after infarction (2-4 weeks/1-6 months/>6 months) using either dipyridamole or exercise stress test in standard technique. Interview was done 9-12/95 regarding hard events (heart death, non fatal infarction) or soft events (PTCA or ACVB >3 months after scintigraphy, hospitalisation for angina). In 111 patients we revealed fixed defects, periinfarction isohemia, and ischemia in non-infarcted areas in 30, 39, and 42 persons, respectively. The comparison with the clinical course is summarized in the following table. hard ev. soft ev. NAD E fixed defect 4 2 24 30 periinf-ischemia 5 7 27 39 non-inf ischemia 5 9 28 42 After myocardial infarction ischemia could be detected in a high percentage after different delay using MIBI, However, cardiac events were not correlated with the detection of ischemia but appeared also in patients with fixed defects in 6 out of 30, This seems to be completely different from the use of thallium201 for risk stratification after infarction and might be explained by the different kinetics of both radiotracers, The finding of a fixed defect after myocardial infarction using MIBI is not related to a better prognosis compared with the detection of ischemia.

P 303

P 305

C A n a ~ n o s t o p o u l o s , D J Pennell, J Francis, K S e r u p - H a n s e n , G Davies, S R U n d e r w o o d , R o y a l Brompton Hospital, Department of Nuclear Medicine.

M. Unlfi, B. Turgut, H. Temiz, M . T . Kitap~l, M . L . Alkan. Gazi University Medical Faculty. Departments of Nuclear Medicine and Cardiology. Ankara - TURKEY DOBUTAMINE Tc-99m FUR1FOSMIN SPECT IN THE DETECTION OF CORONARY ARTERY DISEASE: DIAGNOSTIC VALUE OF SAME DAY, REST- STRESS PROTOCOL. The purpose of this study was to evaluate the efficacy and diagnostic value of Tc-99m Furifosmin myocardial perfusion SPECT in the detection of the coronal)' artery disease (CAD), using same day, rest-dobutamine stress protocol. 25 patients (8 female, 17 male, mean age: 53.04±8.56) with suspected corona~' artery" disease, who had limitations to perform treadmill exercise were included in this stud}'. All patients had coronary angiography (CA) within two weeks. 10 mCi (370 MBq) Tc-99m Furifosmin was injected at rest conditions. Sixty minutes after the rest injection, rest SPECT study was performed. Sixty minutes after the rest SPECT acquisition, following dobutamine infusion (5ggr/kg/minmax. 40 ggr/kg/min) 20 mCi (740 MBq) Tc-99m Furifosmin stress dose was injected at peak stress. Stress SPECT acquisition was performed 60 minutes afLer stress injection. Heart to adjacent organ activity ratios were calculated on the anterior planar images, acquired just before SPECT imaging. SPECT data were evaluated visually from short axis and vertical long axis slices, using 20 segment, 5 point scoring system (0:normal. l:mildly reduced. 2:moderately reduced, 3:severely reduced, and 4:absent uptake). A significant increase in heart rate (pre:71.4+_13.7. post: 129.2+12.5. p<.005), systolic blood pressure (pre: 133 4+25.6, post: 163.4_+18.8, PDP: 172.5_+40.9) and no serious side effects were observed aider dobutamine infusion. There was no significant difference in heart to adjacent organ ratios (Heart/Lung ratio were 2.24-+0.26 at rest and 2.18+0.31 at stress. Heart/Liver ratio were 1.16+0.26 at rest and 1 29_+0.22 at stress) for stress and rest. Stress defects were observed in 38% of the investigated segments: showing 21% fixed defects and 17% reversible ischemia in rest study. According to CA results; significant stenosis (>50%) were detected in 12 LAD, 7 LCx, and 1 l RCA territories. The sensitivity, specificity and accuracy of restdobutamine stress Tc-99m Furifosmin SPECT study were; LAD: 90%, 85%, 88%. LCx: 87%, 94%, 92% and RCA: 74%, 86%, 80% and overall: 84%, 89%~ 86%. respectively. In conclusion, same day, rest-dobutamine stress Tc-99m Furilbsmin SPECT protocol is a sensitive and efficient alternative technique in the detection of CAD, showing good correlation with CA results, especially in patients who have limitations to perform treadmill exercise.

ADENOSINE AND ARBUTAMINE MYOCARDIAL PERFUSION IMAGING

COMPARED

DURING

We have compared adenosine and arbutamine "stress" during thallium-201 myocardial p e r f u s i o n i m a g i n g (MPI) in o r d e r to assess the c o m p a r a t i v e v a l u e of the n e w e r agent. We s t u d i e d 23 c o n s e c u t i v e p a t i e n t s r e f e r r e d for MPI, and each p a t i e n t h a d two studies (18 male, mean age 62 years, 5 with previous myocardial infarction). U p t a k e scores w e r e a s s i g n e d to each of 9 segments, and the extent and s e v e r i t y of d e f e c t s w e r e m e a s u r e d u s i n g a p o l a r plot. Haemodynamic changes were greater with arbutamine (double p r o d u c t increase 76% vs 51%, p = 0 . 0 0 3 ) . S y m p t o m s w e r e e x p e r i e n c e d by 21 p a t i e n t s w i t h a r b u t a m i n e and 16 w i t h a d e n o s i n e (p>0.0S). T h e r e was no s i g n i f i c a n t d i f f e r e n c e in the n u m b e r of p a t i e n t s who w e r e c l a s s i f i e d as n o r m a l or a b n o r m a l by the two agents. Overall agreement for classification of d e f e c t s as r e v e r s i b l e f i x e d or m i x e d was g o o d (K=0.71). Segmental agreement for stress scores was also good (K=0.77). M e a n size of stress d e f e c t was larger w i t h a d e n o s i n e (83±52 p i x e l s vs 65±48 pixels, p<0.O5), but s e v e r i t y and r e v e r s i b i l i t y w e r e s i m i l a r (p>0.05) . Thus, there is good a g r e e m e n t between the t e c h n i q u e s and the o b s e r v e d d i f f e r e n c e s are not c l i n i c a l l y significant.

1018

P 306 Sabahat Inan=r,TuOrul Okay, Can Ozer, Mustafa Kahraman, Haz~m Dinc~erand Yaman Zodutuna. Baymdlr Medical Center, Departments of Nuclear Medicine, Cardiology and Cardiovascular Surgery, Ankara, Turkey.

P 308

DECISION MAKING WITH MYOCARDIAL PERFUSION SPECT: THE CARDIOLOGIST'S PERSPECTIVE IN A PRIVATE HOSPITAL

ADDITIVE VALUE OF LUNG TO HEART RATIO AND STRESS LEFT VENTRICULAR DILATION IN THE DIAGNOSIS OF MULTIVESSEL CORONARY ARTERY DISEASE (CAD).

The interpretation by cardiologists of myocardial perfusion SPECT results was retrospectively analysed in order to define the role of nuclear cardiology in patient management in a pdvate hospital. A total of 223 patients (70 F, 153 M) were evaluated from May 1996 to Feb 1997. In respect to the patient condition and clinical question to be answered, treadmill exorcise (197 pts), pharmacological stress (22 pts) or rest (4 pts) myocardial perfusion SPECT were performed using sestamibi (168 pts), tetrofosmin (36 pts) or thallium-201 (19 pts). The study included 148 pts with no known CAD (intermediate likelihood of CAD, 66.4%), 32 pts with CAD who were evaluated to decide therapeutic approach (7 pts post-myocardial infarction and 25 pts pestcatheterization, 14.3%), 34 pts in follow-up after PTCA (14 10ts,6.3%) or CABG (20 pts, 9%) and 9 pts on long-term medical treatment (4%). The normality, abnormality and equivocal rates of SPECT were 84.5% (125/148), 10.1% (15/148) and 5.4% (5/148) in the intermediate likelihood group and only 11 cases were referred for cathetedzatien (7.8%). Of 32 pts with CAD, revascularization was performed in 22 pts who had severe residual ischaemia or viable tissue (22/32, 68.7%) and rest 10 pts were treated medically (mild perfusion abnormality- 9 pts-, fix perfusion defect-1 pt-). In the pts who have been revesculadzed previously, 9 pts had normal myocardial perfusion, 3 10ts had fix perfusion defect, 10 pts showed mild perfusion abnormality and 12 pts had significant ischaemia. Only 1 pt with mild abnormality and 7 pts with significant ischaemia underwent coronary angiegraphy to decide further revesculadzation procedure. In pts on long-term medical trea~merd, CAD was stable in 7 pts (mild per'fusionabnormality- 6 pts- and fix defect-1 pt-) but 2 pts who had severe ischaemia underwent PTCA. Coronary angiegraphy results were available in 40 pts. The test sensitivity was 97%. Sensitivity (%) and specificity (%) were 95/99, 79/99 and 85/100 for LAD, CX and RCA territories, respectively. These results showed that the diagnosis, follow-up and dsk stratification constitute major indications of myocardial perfusion SPECT in our hospital. Patients who had significant ischaemia in their scans were mostly referred for cathatedzation and revesculerization (42/50, 84%). The test was found to help clinician come to a decision on the presence or absence of CAD, progression or regression of disease and prediction of cardiac risk in the majority of lots and affect cardiologists' decision in routine practice in a broad spectrum of lotswith known or suspected CAD.

D. Daou, R. Lebtahi, M. Faraggi, L. Sarda, C. Coaguila, F. Salmon, C. Peker, N. Delahaye, D. Le Guludec. Nuclear Medicine Dept, H6pital Bichat, Paris, France.

TI-20l-but not Tc-99m tracers- allows the detection of indirect signs suggestive ofmultivessel CAD (stress left ventricular dilation (LVD) and increased lung to heart (L/H) ratio). The aim of our study was to evaluate the diagnostic value of scintigraphic muhivessel CAD criteria (direct signs: extent of perfusion defect, and indirect signs). This was done on consecutive patients having a symptom-limited exercise either alone (E, n=314) or associated with dipyridamole (E+D, n=182) TI-201 SPECT and a coronary angiogram within 3 months without supervening acute cardiac event. Patients were classified as 1-vessel (RC, LCx, LAD), 2-vessel or 3-vessel CAD (>50% diameter stenosis). Perfusion defects were suggestive of multivessel disease when _>2 vascular territories were involved. LVD was evaluated by visually comparing the stress and rest anterior projection of SPECT acquisition. L/H ratio was calculated on the anterior projection of stress SPECT acquisition and normalized to heart rate (abnormal if 22sd of normal patients). Results are in number ofpts (% ofpts) : R C or LCx LAD 2V or 3V Multivessel E 1/45 (2)*0 24/59 (41)° 97/210 (46)° perfusion defect E+D 1/21 (5)* 14/27 (52) 63/134 (47)° criteria (direct) £otal (E, E+D' 2/66 (3)*0 38/86 (44)° 160/344 (47) 3 scintigraphic E 7/45 (16)*o 40/59 (68)° 130/210 (62) multivessel criteria E+D 5/21 (24)* 19/27 (70) 87/t34 (65)° (d rect+ind rect) Total (E, E+B 12/66 (18)* 59/86 (69)° 218/344 (63) *: p<0.001 vs LAD and 2V or 3V; o: p<0.05 between direct and both direct+indirect signs. Conclusions: l. Indirect scintigraphic criteria highly improved the diagnosis of MVD compared to the analysis of perfusion defect only. 2. Scintigraphic results of pts with LAD stenosis are similar to those with 2 or 3V-disease. 3. Symptom-limited exercise or combined test are not different for this purpose.

t,-

O

= l

,41

t~ ¢(/) ll)

CL x._

P 307

P 309

C. Decker, M. Orlick, T. Mende, Department of Nuclear Medicine of Martin-Luther-University Halle-Wittenberg

T. Leitha H. Bailer, M. Gwechenberger, M. Pmckmayer, A Staudenherz, G Kronik; University Clinic Nuclear Medicine, Vienna, Krankenhaus Krems/Donau, AUSTRIA

EFFECTS OF NON-UNIFORM ATTENUATION CORRECTION ON MYOCARDIAL SPECT-FINDINGS IN PATIENTS WITH AND WITHOUT PERFUSION DEFECTS Thoracical photon attenuation is a source of adifacts in cardiac SPECT. Aim of the present study was to assess the effects of nonhomogeneous attenuation correction by simultaneous transmission/emission tomography on myocardial perfusion images, especially concerning patients with defects of the teflventricular inferior wall. 20 controls and 20 patients with angiographically proved CAD (anterior and inferior wall infarction in 10 cases each) were examined by a triple-head camera (Prism 3000, Picker, Cardio-Fan, Gd123 line source) according to a one-day protocol (250+750 MBq Tc99m-Tetrofosmin). The raw data was processed by both filtered back projection (NAC) and iterative reconstruction (AC). Normalized count rates of eight equal segments in representative medial and basal short axis slices of the rest study (including an apical ROI) were calculated. We found significant increases of the relative myocardial uptake in attenuation - corrected images in the inferior (p<0.001), inferolateral (p<0.001) and inferoseplal (p=0.01) segments. The ratio of lateral - to - inferior relative count rate significantly decreased (1.24+0.25 in NAC to 0.8+0.16 in AC; p=0.005). In patients with anterior wall infarction no significant differences of the relative myocardial uptake between NAC and AC studies were verified. Significant lower relative myocardial count rates in inferior segments of patients with inferior wall infarction in NAC-studies resulted in an overestimation of perfusion defect severity. The non-uniform attenuation correction in cardiac SPECT allows a more accurate assessment of myocardial perfusion concerning normal and pathological findings of leflventricular inferior wall.

ROC ANALYSIS OF THREE PEREUSION DISPLAY OPTIONS FOR ECG-GATED PERFUSION SPECT IN SEVERE CAD The simultaneous computation and display of wall motion and perfusion patterns in a single 3D ventricular model would considerably ease the assessment of ECG-gated 99mTcsestamibi SPECT, yet the effect on the accuracy of allocating regional perfusion has not been validated, yet. Methods and results: 3D perfusion mapping (3D PeffusionfMotion Map Software) was compared to the visual assessment of ungated tomographic slices and polar perfusion mapping (Cedars-Sinai PTQ) by correlation analysis and receiver operating characteristics (ROC) analysis at different cut-offlevels for coronary stenoses in 50 patients (11 Single,22 two-, 16 threewessel 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 display options were comparable 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 proximal anterior and in the distal lateral wall. Polar mapping showed a balanced but inferior regional performance. Conclusion: 3D Perfusion mapping provides comparable information to conventional display options with the highest diagnostic strength in severe stenoses.

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T.C. Yen and C.H. Kao, Departments of Nuclear Medicine, Taipei and Taichung Veterans General Hospitals, Taiwan.

A. Ramirez, A. Garcia-Mcndoza, J.P. Diaz, MA. Muros, M.D. Martinez del Val[c. A. Rodriguez, M. Urefia, JM. Llamas. Sc~ieio de Medicina Nuclear. Hospital "'Virgen de las Nieves'~. Granada. Spain

DIFFERENTIATION OF PSYCHOGENIC AND VASCULOGENIC IMPOTENCE WITH TECHNETIUM-99M LABELLED RBC ERECTION PENOORAM,

SPECIALIZATION IN RAD1OPHARMACY IN SPAIN. CURRENT AND NEW FUTURE PERSPECTIVES IN THE CONTEXT OF THE EUROPEAN UNION Specialization studies for the title of pharmacy specialist have been regulated in Spain since 1982. A Ro)al Decree (2708/1982) recognised the speeiali~, of Radiopharmacy within the secondgroup of specialties that do not require hospital training. The training period for this group of specialities is laid dm~n as being for no more than three )'ears. The Instigating Commission for radiopharmacy was formed in Jane 1990 and training of these specialists began in 1993. Selection for training is via a points system based on a national test of knowledge and the candidate's academic record. The two-year training programme is given in Spanish health institutions, with the radiopharmacy residents (trainees) incorporated into a nuclear medicine team under the responsibility of a tutor proposed by the head of the care unit and designated by the institution management. In the most recent programme eight places were offered in eight teaching units accredited for radiopharmacy training. Entry, to this regulated training programme is only open to pharmacy and chemical science graduates. The Instigating Commission for this speciality approved an official programme that defined the speciality and set out its objectives. The aim of this training plan is to prepare future radiopharmacy specialists to fulfil the functions established in the Ro)al Decree (479/1993) that regulates radiopharmacy drags for human

In this study, we use the Tc-99m labelled RBC erection penogram (rcRBC penogram) coupled with intmcavemusal injection of PGE1 to evaluate the penile hemodyrmmic changes during tumescence. As expected, the method is useful to differentiate orgamc from pysehogenic impotence, and arteriogenic from venogenie impotence. Methods: Thirty-four patients with psychogenic impotence, 23 patients with arteriogenic impotence, and 27 patients with venogenic impotence were included in the study. A Tc-99m labelled RBC erection penogram (Tc-RBC penogram) was performed on each patient after intracavemosal injection of prostaglandin E1 (PGE1). Several parameters calculated from the time-radioactivity curve of the Te-RBC penogram were used to evaluate hemodynamie changes of the penis. They included (1) the arterial phase: slope and time to peak (TTP); and (2) the venous phase: washout index (WOI). Results: During the arterial phase, the patients with psychogenic and venegenic impotence had higher slope and shorter TTP than those of patients with arteriogenic impotence (P < 0.01). During the venous phase, the patients with psychogenic and arteriogenic impotence had a lower WOI than that of patients with venogenie impotence (P < 0.01). Conclusions: The Te-RBC erection penogram is a simple, less invasive, and valuable screening test from a selected population with three distinct classes to identify vasculogenie impotence from pyschogenie impotence, and to differentiate arteriogenic from venogenic impotence in our study.

P 312 R Blair, AC Knight, and ED Williams, Regional Medical Physics Department, Newcastle and Sunderland General Hospitals, UK THE USE OF LARGE-SCALE SURVEYS OF PATIENT SATISFACTION IN NUCLEAR MEDICINE TO MONITOR AND IMPROVE SERVICE QUALITY An isolated survey of patient satisfaction may have limited value, but comparisons between those obtained in different hospitals and at different times can give more information and enable changes to be stimulated and monitored. We developed a survey form and used it at 11 different hospitals (which all provide a general nuclear medicine service) for 150 outpatients at each. There were significant variations between hospitals in several components of the responses. Potentially improving actions were proposed at relevant hospitals. Two years later, the survey was repeated to detect any changes. Also, the sensitivity of the questionnaire was increased by re-writing some of the questions to give a' range of responses rather than mainly yes/no type answers. To enable comparison with the previous survey, half the forms used were in the original format and half in the new format. The results obtained using the two types of questionnaire were generally directly comparable. Where direct comparisons could be made, improvements over the earlier survey in the level of satisfaction were found in many hospitals and over many subject areas, and could be ascribed to the actions taken by staff after the first survey. An additional benefit of the large scale surveys was that the opinion of sub-categories of patients e.g. those having a particular investigation, could also be assessed.

use.

In the near future a Royal Decree vdll be signed regulating the granting of the title of specialist in radiopharmaeyo and an associated Ministerial Order will specify the conditions required of professionals who already practise in this field and who wish to gain the official title of the speciality. An examination will be offered to those whom the Qualifying Commission judges not to have .¢ met the requisite conditions, but who consider themselves to have sufficient theoretical and practical knowledge to warrant the title of specialist in radiopharmacy. There has been a major advance in Spain in the last fe~' years through the incorporation of European Union norms on radiopharmacy into national legislation and the development of training programmes in this area. Unresolved issues include establishingthe functions of the radiopharmacist within the staffing structure of the National Health Sen,ice and achieving the recognition of radiopharmacy units within the same.

P 314 K., Ennow ~, N. Vinberg 2, i National Institute o f Radiation Hygiene, National Board o f Health and

zIsotope-Pharmacy,Danish Medicine Agency, Copenhagen,Denmark RADIATIONPROTECTIONAND THE RADIOPHARMACEUTICALSAFETYOF TC-99m ELUATES. IS IT POSSIBLETO RECONCILETHE REQUIREMENTS? The National Institute of Radiation Hygiene (National Board of Health) and the Isotope-Pharmacy (Danish Medicines Agency) have a long record of collaboration in issuing recommendations to Danish hospitals using radiopharmaceuticals. Some of the recommendations have been published, e.g. as Nordic Guidelines on preparation and control of radiopharmaceuticals in 1989. A new EC Cotmcil Directive laying down basic safety standard for radiation protection has been issued in June 1996. This directive incorporates lower dose limits which has inaugurated revisions of regulations and recommendations. For users of technetium generators this implies lower dose-rates limits arid the shielding has to be increased, which could make the preparation and handling of the eluates so cumbersome that the safety of the radiopharmaceuticals could be jeopardised, We have, therefore, issued a completely revised Code of Practice on the location and handling of technetium generators in hospitals as a joint recommendation from the Isotope-Pharmacy and the National Institute Radiation Hygiene. The CoP will be available in English [1]. In the Code of Practice we have given detailed advice on how to solve the problem of combining a high standard in radiation hygiene with the maintaining of a high degree of radinpharmaceutical safety. The CoP will be presented with illustrative examples. [ 1]"Location and Handling of Technetium Generators in Hospitals." Code of Practice from The National Institute of Radiation Hygiene and The Isotope-Pharmacy, Copenhagen 1997.

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E.Heldmann,S.Gudmundsson,B.Lilja,J.Wadstein,Malm~ U n i v e r s i t y Hospital, Department of N u c l e a r Medicine,Nalm6,Sweden.

P.F.Rambaldi, V.Tontodonato, R.Acampora, P.Puntieri, N. Di Martino, M.Vatti , L.Mansi - Institute of Radiological Sciences - Institute of Reumathology - Institute of Oesophageal Surgery - II University of Naples - Italy.

THE EFFECT OF FATBLOCKER RESORPTION IN H U M A N

LII2

ON

ANIMAL

PAT

The aim of this study was to analyse the fatbinding capacity of Fatblocker LII2 (a chitosan biopolymer) using animal fat. Twelve volunteers, age 40-58, 1 man and ii women, underwent a crossover double-blind study. Capsules with the active substance or placebo were given alternatively. The volunteers were fasting for at least 12 hours before the test. A 14C-triolein (glycerol tri[l-14C Joleate)breath test was used to measure the fat uptake. Initially 8 capsules Fatblocker LII2, each containing 240 mg active substance, or placebo were given w i t h water. A f t e r 5 minutes a piece of sugar m a r k e d with 14C-triolein was given and immediately after that 50 ml of cream, containing 40% fat. Breath tests were p e r f o r m e d after i, 2, 3, 4, 5, 6 and 24 hours. The volunteers were fasting during the first 4 hours of the test. After that they received a standardised meal, containing 3 pieces of white bread w i t h jam and a cup of coffee or tea. Subjects with Fatblocker showed reduced uptake compared w i t h placebo. The greatest reduction occurred after 5 hours. In the whole group the reduction in animal fat uptake with Fatblocker during the 6 hours was approximately 13% with great individual variations.

A QUANTITATIVE METHOD TO EVALUATE OESOPHAGEAL TRANSIT WITH RADIONUCLIDES: COMPARISON WITH MANOMETRY IN SYSTEMIC SCLEROSIS. The aim of this study was to evaluate the oesophageal involvement in systemic sclerosis (SSc) using a new radionuclide technique in comparison with manometry techniques. Methods: Thirty women with SSc (age range 17-76 years, mean 53) and l0 normal have been included in the study. Oesophageal transit studies were performed with I8MBq of Tc99m in 5cc of water in orthostatism and in supine position; a further evaluation was performed with a semisolid bolus (10cc whipped egg albumen) in orthostatism. All data have been mathematically processed by dedicated software (S/W) developed by us. This S/W extracts and elaborate the transit curves on the basis of a single swallow dynamic acquisition and an automatic score is calculated. To achieve these quantitative results the Transit Fraction (JF) and two geometrical momentum coeflScients, Mean Time Transit (MTT) and Time Bolus Length (TBL), have been calculated. Results: Analysing mean values of parameters obtained with 3 bolus, 5 patients resulted normal at qualitative and quantitative evaluation (TF>0.8, MTT<10, TBL<10), 15 had mild-moderate oesophageal involvement (0.5I0, TBL>10), ant 10 severe (TF<0.5, in this group MTT and TBL is not evaluated). Discussion: The oesophageal involvement was more evident in clinostatic position. Results are correlate with clinical evaluation and manometry but radionuclides are more sensitive than manometry in patients with mild - moderate oesophageal disease.

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K.Uchivama, Y.Niio, H.Shinohara, S.Hasebe, M.Obuchi. K.Takizawa, M.Honda and Y.Kuniyasu, Department of Radiology , Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227, Japan

A.T. Akbunar E. Alper, N. Konuk, B. Erkal, F. Yamgac, Uludag University, School of Medicine, Department of Nuclear Medicine, Bursa, TURKEY

O

PROPOSAL ON A NEW LI VER FUNCTION TEST(LI VER VOLUME INDEX) WITH Tc-99m-DT PA-GALACTOSYL HUMAN SERUM ALBUMIN(Tc-99m-GSA). The conventional hepatic receptor binding parameters ; LHL 15(hepatic uptake index), HH 15(clearance index), Ku values from Patlak's plot method and l-compartment analysis, were compared with a new parameter : Liver Volume Index(LVI), which was obtained by a formula (SPECT whole liver counts/total injection counts corrected) on the usefulness as a liver function test. A total of 156 patients were studied. They were consisted of 88 patients with hepatocellular carcinoma and liver cirrhosis or chronic hepatitis, 24 of liver cirrhosis, 19 of chronic hepatitis, 14 of acute hepatitis including 4 fulminant hepatitis and 11 normal subjects. A bolus of Tc-99m-GSA(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 × 128 on this study. Using these early phase data, the conventional parameters were calculated and the new parameter was obtained from late phase(20-35 rain) data. The LVI was correlated with the conventional parameters and biochemical data of the liver function. The correlation of LVI and laboratory data on liver function tests was relatively well with ICGR I5(r=0.648), KICG(r=0.625), LCAT(r=0.536), and Albumin and LDH(r=0.52). The LVt were correlated well with other conventional parameters ; HH 15(r=0.756), LHL 15(r=0.762), Ku value of 1compartment analysis(r=0.72) and Patlak's plot method(r=O,654). Also, the values of LVI were significantly discernible among the groups of various liver diseases. In conclusion: The LVI is a new sensitive and promising parameter for evaluating the prognosis and severity in various liver injuries. It can be obtained independently from the ROI size of the heart, ,as a objective and reproducible parameter which contains 3-D information.

A SIMPLE METHOD TO INCREASE THE DIAGNOSTIC EFFICIENCY OF GASTROESOPHAGEAL SCINTIGRAPHY USING KNEE-CHEST POSITION

The incidence and severity of gastroesophageal reflux (GER) is well known to be changed with patient posture. Scintigraphic imaging, however, is routinely carried out with the patient lying in supine position, because current gamma camera designs do not allow altering the patient table freely. In order to overcome this difficulty and to increase the diagnostic sensitivity of scintigraphy, we used a different patient positioning. 27 adult patients with suspected GER disease were included in the study (M: 7, F:17, mean age 475±11.5). Each patient underwent two dynamic acquisitions After the ingestion of 700 ml of apple juice mixed with Tc-99m phytate colloid, the patient was placed in the supine position (SP), and serial 10 second images for a total of 450 sec were recorded from the anterior projection. Valsalva maneuvers and abdominal pressure (up to 120 mmHg) were applied. Right after the completion of the study, the patient was asked to assume knee-chest (KC) position. Patient was then imaged with the same time parameters with the posterior imaging projection, adjusting the camera head parallel to tile patient's back. Valsalva maneuver was applied once during each KC study. Thus, whole study for each patient required only 15 minutes. Images were analysed qualitatively by three observers. While GER was positive only in 9/27 (33%) patients using SP, 20/27 (74%) patients were detected to have GER with KC position. No reflux was detected in seven patients using both positions, In 5/9 patients, the number of reflux episodes were higher in KC position compared to SP The study implies that knee-chest position increases the diagnostic efficiency of GER scintigraphy.

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M. Luebeck. K.A. Gawad 1, D. Bumann, S.B. Hosch% C. Fuchs, J.R. Izbicki 1, J. Mester, M Clausen, K.F. Gratz2 Depts. of Nuclear Medicine and 1Surgery, UKE University of Hamburg & 2Dept, of Nuclear Medicine, MHH University of Hannover, Germany

SCINTIGRAPHIC ASSESSMENT OF THE GASTRIC TUBE MOTILITY AFTER ESOPHAGECTOMY: A PROSPECTIVE RANDOMIZED COMPARISON OF RETROSTERNAL VERSUS POSTERIOR MEDIASTINAL RECONSTRUCTION IN CANCER THERAPY The restitution and preservation of a regular food passage is the most important therapeutic goal in patients with esophageal cancer, since dysphagia is the leading symptom. Therefore the replacementof the esophagus by a gastric tube is required either retrosternallyor in the posterior mediastinum. Aim of the study is the scintigraphic comparison of both surgical approaches in terms of the clearance function of the gastric tube and the clinical outcome. 26 patients with esophageal carcinoma (stage T1 -T3, N0-N1) were included in the study. 19 lots. underwent abdomino-thoracicand 7 pts. transhiatal esophagectomy. According to randomization reconstruction was performed retrosternally (RS) in 14 cases and in the posterior mediastinum (PM) in 12 cases. Median age: 59 (41-75) y in the RS and 61 (44-74) y in the PM group. Methods: Clearance function was assessed 3 months postoperatively by dynamic scintigraphy (60x0.5s, 28x7.5s) swallowing one liquid bolus (t 5MBq Tc-99m-DTPA/15ml) and two solid boll (15MBq Tc-99m-Chelex/2ml) in supine position. Relative tracer retention after 15, 30 and 60 s was calculated using equally sized ROIs for the upper, middle and lower gastric tube. Subjective swallowing problems were recorded by a standardized questionnaire. Results: The table shows the retention after 30 s and the significance level p % retention[ RS liquid upper 1/3 4.3_+4.9 middle 1/3 37.6+19.8 lower 1/3 42.1_+24.3 tota 83.9_+7.7

PM liquid p RS solid 5.3+3,2 n.s. 16.0-+22.5 18.4_+12.5 <0.0051 40.5_+27,5 / 26.1_+10.2 n.s. I 14.5_+12.5 49.7_+14.0 <0,005[ 70.7_+22.2

PM sofid p 10.5-+12.7 n.s. 26.7_+17.0 n.s. 16.5_+14,1 n,s. 53.9_+12.7 <0.05

42% of RS and 27% of PM patients described swallowing complaints (n.s.). Conclusions: Scintigraphy shows a significant delay of gastric tube clearance in patients with retrosternal versus posterior mediastinal reconstruction according to the somewhat higher frequency of dysphagia in this group. Though objective functional benefit by the posterior pathway is demonstrated surgical problems, restricted radiotherapy etc. have to be considered as well,

P 320 Marotta G., Bonavina L.*, Voltini F., Pagani M.*, Antoniazzi L.*, Benti R., Bruno A., Castellani M., Reschini E., Gemndini P. Department of Nuclear Medicine and *Dept of General and Oncologic Surgery, IRCCS-Ospedale Maggiore, University of Milan, Italy RADIONUCLIDE PHARINGOESOPHAGEAL TRANSIT STUDY BEFORE AND AFTER TRANSORAL ZENKER'S DIVERTICULUM-ESOPHAGOSTOMY. Scintigraphic imaging of a radio-labelled bolus is a widely accepted method to evaluate esophageal transit time. Aim of the work was to evaluate the esophageal motility by means of the radionuclide pharingo-esophageal transit study (RPETS) before and after the surgical treatment of Zenker's diverticulum (ZDE), via endosurgical stapling of the diverticular wall. The effect of "upright and supine" positions during the examination was also considered. For each position, 14 patients (mean age 63 yrs) were imaged after a single swallow of orange juice (5-10 ml) containing 18-37 Mbq of Tc99m sulphur colloid 1-30 days before and 3-80 days after ZDE. Sequential images were collected for 10'(early phase: 120 frames for 1'; late phase: 108 frames for 9'). Time activity curves were generated by drawing several ROIs on the oropharynx, entire esophagus, proximal, middle and distal thirds of the esophagus. From the curve analysis, the time necessary to clear 50% (T50) and 75% (T75) of the maximal activity for all ROIs and the percentage retention of radioactivity (%R) at 1' and 10' were calculated. Mean values are reported in the table. PROXIMAL UPRIGHT SUPINE ~SOPHAGUS before ZDE after ZDE before ZDE after ZDE 1"50 (sec) 14.3 0.6 14.6 3.0 F75 (sec) 26.5 1.3 27.8 7.8 %R 1' 16.1 1.8 16.8 2.3 %R 10' 11.5 1.1 7.9 0.6 For both positions, the paired t-test demonstrated a significant improvement (p<0.04) after ZDE in the proximal esophagus; no significant differences were observed in the middle and distal thirds. RPETS in upright position can assess short term improvement of early bolus clearance after ZDE. As expected, clinostatic RPETS allows proper analysis of stasis relief in late imaging phase. In conclusion, transoral ZDE significantly improves both symptoms and quantitative parameters of esophageal function.

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M. Charron, S. Kocoshis, F. DelRosario, C. DiLorenzo, S. Orenstein, P. Putnam. Division Of Nuclear Medicine and Gastroenterology, Children's Hospital of Pittsburgh, University of Pittsburgh COLONOSCOPY VERSUS TECHNETIUM-LABELED WHITE BLOOD CELLS IN PATIENTS WITH CROHN'S DISEASE Stricture, spasm, and other technical factors often preclude the performance of total colonoscopy and ileoseopy in patients with suspected Crohn's Disease (CD). Because contrast radiography may be normal in early CD, an alternative technique for assessing terminal ileal inflammation would be valuable in guiding clinical decision making. Thus, we evaluated the sensitivity and specificity of WBC-Tc99m compared with colonoscopy for identifying terminal ileal and colonic disease in pediatric patients with CD who had undergone colonscopy within a few days of the scan. Of the 215 patients evaluated to date with WBCTc99m, 80 had documented Crohn's Disease. In 40, total colonoscopy had been performed within a few days of the scan. In 37 patients, the WBC-Tc99m scan findings matched the biopsy result of the colonescopy; in 18 of these 37 patients the endoscopist could not eannulate the terminal ileum. The WBC-Tc99m underestimated the intensity of colonic inflammation in 2 patients, and in 1 patient false positive accumulation was noted at an anastomosis site. The sensitivity of the WBC-Te99m scan is thus 95% and the specificity 97% compared with colonoscopy. Conclusion: WBC-Tc99m is a valuable complement to contrast radiography, endoscopy and biopsy for pediatric CD patients. When total eolonoscopy or ileoscopy cannot be satisfactorily completed and when contrast radiography is negative or equivocal, scintigraphy can reliable confirm the presence of ileitis or right sided colitis.

P 322 H o l z h a m m e r M a r i o n D e c r i s t o f o r o Clemens, G e o r g

Riccabona University f o r N u c l e a r Medicine, I n n s b r u c k , A u s t r i a DOSE TO THE H A N D S OF P E R S O N A L WORKING IN A NUCLEAR MEDICINE R A D I O C H E M I C A L L A B O R A T O R Y The dose to the fingers of technologists working in a radiochemical lavatory can be comparatively high. Fingering dosimeters on TLD- basis have the disadvantage of measuring only a accumulative dose and the p#ocessing for readout takes some time. We therefore sought for adequate possibilities to display the actual dose which could assist in finding bad handling or working habits. Equipment: Stephen 6000 Series Dosemeter that was fixed to the right hand palm using an elastic band. Mode: rate ( mSv ) and dose rate ( mSv/h ), audible rate alarm set to 0,3 mSv/h. The monitored activities included; labeling procedures using 99m-Tc, 123-1, 18-F, replacing Tc-generators, unpacking radioactive consignments. Each measurement was defined as hand-dose. Different groups of employees (technologist, physicians, radiopharmacist) were observed over severn weeks. Result 1. The hand exposure from laborious labeling procedures were roughly twice as high as simple procedures 2. A five to ten-fold higher radiation dose was measured when handling high- and medium-energy Isotopes (13tq or 18-F) compared with handling 99m-Tic 3. As expected hand dosis correlated with the total amount of activity and with processing time. 4. Applying syringe-shielding led to a reduction of hand dosis by roughly 50%. 5. The variation of hand exposure among the team was not significant 6. Due to on-line indication of radiation exposure, ,,bad handling" practices were immediately detected and avoided.

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M.H.Bourquigno@), S.Askienazy (2), P.Bourguet (3), B.Aubert (4) and the "Medical Radioactive Waste" working group de la Direction G~n~rale de la Sant& (~)OPRI, Le Vesinet, {2)Saint-Antoine, Paris, (3/Eugene Marquis, Rennes, (4)IGA, Villejuif- France

W.Y. Lin, S.J. Wang, Department of Nuclear Medicine, Taichtmg Veterans General Hospital.

THE PROPER HANDLING OF MEDICAL RADIOACTIVE WASTE : A PROPOSAL. The volume of medical radioactive waste is growing in parallel with the number of nuclear medicine diagnostic examinations (NME) and therapeutic procedures. Since the potential contamination of the environment by radioactive waste is a sensitive issue for the public, the future development of nuclear medicine requires to enforce the proper handling of radioactive waste. The proposed strategy is three fold : 1- to keep track of the radioactivity at all times in order to collect all radioactive waste, 2- to store it for decay and 3then to follow the regular process of non radioactive waste. In case of biological products which are potentially septic and must be quickly processed (within 2 days in France), an appropriate antiseptic treatment can be achieved while shredding contaminated materials. In practice, the proper handling of medic~tl radioactive waste requires to identify all pathways of radioactive materials. 1- Within the nuclear medicine department, the strategy can be easily implemented, 2- A similar procedure can be applied for radioactive waste resulting from patients, in whom NME was performed, and are hospitalized in any hospital; in this case, controls of radioactivity need to be performed in the waste pathway of the hospital. 3- For patients returning home after radionuclide therapy, radioactivity could be extracted from urines through appropriate and selective filtering and the filter would then return to the nuclear medicine department. The procedure of radioactive waste handling described in this abstract is being examined in France for consensus, and already received the support of the {~ Medical Radioactive Waste ~ working group de la Direction G6n6rale de la Sant6 (France). It has the major advantage of not only decreasing significantly the releases of radioactivity in the environment, below the exemption tresholds for releases, but also to bring a solution to the elimination of long half life radionuclides, and of alpha and beta emitters. This proposal also intends to open within the nuclear medicine community a debate on medical radioactive waste management in preparation of a new legislation.

VALUE OF GALLIUM-67 SCINTIGRAPHY IN MONITORING THE DISEASE ACTIVITY OF LUPUS NEPHRITIS Evaluating the activity of lupus nephritis is very important for therapeutic decisions. The purpose of this study was to evaluate the relationship between gallium uptake m the kidneys and the results in renal biopsy and to evaluate the potential values of gallium seintigraphy as an alternative to renal biopsy in monitoring the disease activity of lupus nephritis. We evaluated the delayed 48-hour renal uptake of gallium in 32 patients of lupus nephritis according to the classification of the World Health Organization, the activity index (AI), and the chronic index (CI). The results are tabulated as follows: Ga-67 Scan No. A.I. C.I. WHO Classification Negative 15 5.1 ±3.2 4A±3.4 4.3-+'1.1 Positive

17

10.1 ±4.1

3.9±2.8

4.2±0.7

Our data showed the AI was significantly higher in the patients whose gallium scan were positive VS those whose gallium scan were negative (P=0.0007 by a student's t test). In contrast, change in the gallium uptake was not related to the CI and WHO classification (p= 0.68 and p=0.79 respectively). In addition, of the 16 patients with AI _~ 9 points, 13 (81.25%) patients had positive gallium scans while only 3 (18.7%) patients had positive scans in patients with AI < 9 points. In patients with AI > 11 points, all patients (100%) showed positive gallium scans. In conclusion, renal imaging with gallium has a high correlation to AI, which means gallium images has a close relationship to the disease activity of lupus nephritis. We suggestthat gallium scintigraphy may be as an useful alternative to renal biopsy in monitoring the disease activity in patients with lupus nephritis.

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3L_lqu ~ak 1, M. Myslive~ek1, A. Utikalova2 , P. ~irfi~ek3 Department of Nuclear Medicine 1 and Department of Urology2, University Hospital, Olomouc, Regional Hospital3, Bitovec, Czech Republic

A. Boneu c1~,C. Corone c~, F. Giammarild 3~,J. Lumbroso ~'~,I. Reschd ~ Nuclear Medicine Departments, Cancer Centers, Toulouse ~1), Saint-Cloud c2),Lyon (~, VillejuiP ~, Nantes ~ (F);

A REVIEW OF RADIATION DOSES TO CHILDREN UNDERGOING X-RAY AND NUCLEAR MEDICINE EXAMINATIONS OF THE UROGENITAL TRACT The published doses to children from 99mTc-DMSA (DMSA), 99mTcDTPA (DTPA), 99mTc-MAG3 (MAG) studies, direct (DRC) and indirect (IRC) radionuclide cystography, micturating cystourethrography (MCU) and intravenous urography (IVU) are critically selected and revised to give a comprehensive review. Organ absorbed doses and effective doses from X-ray procedures published for different age categories (e.g. 0 - 1, 2 - 5 and 6 - 15 yea~) are interpolated to be comparable with radionuclide examinations data usually related to the ages of 0, 1, 5, 10 and 15 years. Assuming routinely administered activities of radiopharmaceuticals and typical number of exposures per X-ray examination, the effective dose, dose to gonads and the dose to the most highly irradiated organ as a function of age are presented graphically for each type of examination considered. Regardless of age the effective dose to children undergoing DRC is approximately two orders of magnitude lower than that due to MCU. The effective doses to children under 5 yr of age from IVU, MCU, DMSA, MAG and DTPA are similar, being below 2 mSv; organ doses as well as effective dose from X-ray examinations increase with patient age (the opposite is true for CT examinations) and in older children they tend to be higher than those from radionuclide studies. The dose to gonads behaves similar to the effective dose. The dose to the bladder wall from Xray examinations in children under 5 years of age is more than one order of magnitude lower than that from DTPA, DMSA and MAG studies. A variation in reported X-ray patient doses appears to be approximately one order of magnitude higher than that for radionuclide procedures. Our review makes possibIe both approximate estimate of exposure needed to assess radiation risk and identification of published erroneous, unsufficiently explained or incomplete information on radiation exposure.

BONE SCINTIGRAPHY IN PROSTATE CARCINOMA: A FRENCH NATIONAL INQUIRY A national inquiry has been performed in France about bone scan in prostatic carcinoma. The aim of the study was to define methods of performing examinations, criteria of analysis of imaging results and indications of radionuclide imagin8 in initial evaluation and posttherapeutic follow-up of the disease. A questionnaire was sent to all French Nuclear Medicine Departments. Although 70% of the Nuclear Medicine Departments replied, this study is based on about 50% of the answers. In France, 10% of all bone scintigraphies are performed in patients with prostatic cancer. It is worth noting that the examination is not systematically performed. Replies are given and recommendations are proposed in order to improve image quality, optimize interpretation and rationalize prescription of bone scintigraphy in case of prostatic carcinoma. In particular, in the initial evaluation of the disease, bone scintigraphy is mainly recommended while in the post-therapeutic follow-up this examination should be performed only when PSA values increase, before a potential new treatment.

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G. Boni, M. Grosso, M. Ferdeghini, C.R. BelIina, G. Manca, B. Alberti, C. Malvezzi, and R. Bianchi. Division of Nuclear Medicine, Department of Oncology, University of Pisa.

C,_$OLER*, P. BEAUCHESNE ~, J. BRUNON ~, F. DUBOIS*. * - Dept of Nuclear Medicine, HOpital Bellevue, CHU Saint-Etienne, France. ** - Dept of Neurosurgery, H~pital Bellevue, CHU Saint-Etienne, France.

IN-111 OCTREOTIDE, TC-99M SESTAMIBI AND 1-131 SCINTIGRAPHY IN METASTASES OF DIFFERENTIATED THYROID CARCINOMA Recently, scintigraphic demonstrations of somatostatin receptors in differentiated thyroid carcinoma (DTC) have been obtained with In-I 11 Octreotide. The aim of this study was to confirm the presence of somatostatin receptors in metastases of DTC and compare In-I 11 Octreotide (OS), Tc-99m SESTAMIBI (SM) and 1-131 scintigraphy (I-131 WBS) in the same patients (pts). Ten pts (5 men and 5 women, age range 26-84 yrs) with distant metastases (8 lung, 26 bone, 4 neck or mediastin) of DTC (4 papillary, 2 follicular, 2 Hiirthle cell and 2 insular) and high Tg levels were studied with OS and SM during suppressive therapy with L-T4. OS was performed 4 and 24 hrs after iv injection of 148 MBq of In-lll Octreotide. SM images were recorded 30 rain after iv injection of 500 Mbq of Tc-99m SESTAMIBI. All pts underwent a diagnostic 1-131 WBS (185 MBq) 4-6 weeks after L-T4 withdrawal. A post-therapeutic 1-131 WBS was performed in 8 out 10 pts only because of the absence of 1-I31 uptake in metastases of Hiirthle cell carcinoma. OS and SM were positive in 8 out 10 pts. 19/26 bone, 6/8 lung and 4/4 lymph node metastases were detected with OS. A slightly better sensitivity (22/26 bone foci) was obtained with SM. OS and SM were positive in 2/2 insular, 2/2 Httrthle cell, 1/2 follicular and three poor differentiated papillary carcinomas. Finally, two l- 131 positive nodular lung metastases of well differentiated papillary carcinoma were negative on OS and SM. In conclusion our data suggest that: a) OS can detect somatostatin receptors in metastases of DTC; b) slightly better results were obtained with SM; c) OS and SM may be useful for detection of distant metastases in pts with high Tg serum levels and negative I-131 WBS.

THE CONTRIBUTION OF 99'nTc-MIBI SPECT FOR THE DETECTION OF RECURRENT GLIOMAS AFTER TREATMENT FAILURE IN PATIENTS TREATED FOR MALIGNANT GLIOMAS : A RETROSPECTIVE STUDY ON 36 PATIENTS. 99mTc-MIBI, an alternative radiopharmaceutical for myocardial perfusion study has been proposed for use as a tumor imaging agent, including breast cancer, lung cancer, lymphomas and brain tumors. After the routine radiation therapy, deteriorating clinical status or treatment failure may be due by the radiation changes of reccurent tumor. However, CT and MRI offer imperfect discrimination of tumor viability and radionecrosis. For attempting to resolve that dramatical problem we have undertaken a study to evaluate the role of sg~I'c-MIBI brain SPECT to distinguish tumor recurrence from radiation necrosis. Thirty six patients with clinical deterioration were studies prospectively (34 grade 4 and 2 grade 3), a tomoscintigraphy was performed 15 mn after intravenous injection of 1110 Mbq (30 mCi) of 99m-I'c-MIBl. The acquisition of images was obtained from a dual headed gammacamera using fan beam collimator. Transverse, coronal and sagittal views ware reconstructed. We demonstrated a MIBI uptake for 33 patients with grade 3 and 4 gliomas. MIBI uptake was correlated to tumor recurrence ; the fatal evolution occured secondary rapidly. For the 3 remaining patients, no MIBI uptake was found, their evolution could be consider as free-d[sease time. According to the preliminary results, sensibility and 9s~:m...ificity of 99mTc-MIBI brain SPECT seem to be high. We think that m-I'c-MIBI brain SPECT seems to be excellent to discriminate tumor recurrence from radionecrosis and a good predictor for survival of patients when treatment failure occured.

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T. Leitha C Glaser, W. Millesi, S. hang, C Nasel, M Pmckmayer, W. Backfrieder, F Kainberger. University Clinics of Nuclear Medicine, Maxillofacial Surgery, Radiology, Pathology and Department of Biomedical Engineering and Physics, Vienna/AUSTRIA

T.A.D.Smith, J.Titley, S.A. Eccles, W. Court and V.R. McCready, Dept of Nuclear Medicine, Royal Marsden Hospital, Sutton, Surrey SM2 5PT UK

IMAGE OVERLAY OF BONE AND SESTAMIBI SPECT IN PRIMARY AND RECURRENT HEAD NECK TUMORS (HNT) We prospectively investigated I95 patients with the c[inicaLsuspicion for HNT The final histological diagnoses were 94 primary & 53 recurrent squamous-ceI[ carcinomas (SCC), 2 primary & 7 recurrent adenoid-cystic carcinomas (ACC), 6 NIt-lymphomas, 4 distant metastases, 7 other malignancies, l0 inflammatory and 12 other non malignant conditions. Methods: Both, bone (600 MBq Tc-99m-DPD) and Sestamibi (600 MBq Tc-99m-MIBl) SPECT were performed within 7 days under identical conditions (triple headed gamma-camera, UHRPAR collimators, 3D-postfiltering) and judged independently and after superimposition. The findings were compared to the results of biopsy, surgery and CT/MR]. Results: The overall sensitivity/specificity of MIBI was 92%/78% for tumor detection and 92%/96% for the identification of lymph node involvement (CT: 79%/66% resp 89%/78%). In the subgroup of recurrent SCC the sensitivity/specificity for tumor detection was 97%/71% for MIBI vs. 77%/61% for CT. In addition, MIBI differentiated between inflammatory and malignant changes in all but one case with recurrent SCC. Image overlay with bone scintigraphy is essential for the topographical orientation and the differentiation between regional bone involvement and inflammatory changes The differential diagnosis between inflammatory and neoplastic lymph node involvement is enhanced by image overlay with the C T Conclusion: Image overlay of MIBI and bone SPECT is a useful imaging approach in the differential diagnosis of HNT and has become routine practice in our institution

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THE AND

RELATIONSHIP BETWEEN THE PROLIFERATION OF

DEOXYGLUCOSE TUMOUR CELLS

UPTAKE

The clinical role of FDG will be depend on which feature of m a l i g n a n c y is most r e l a t e d to its uptake. Generally the uptake is thought to be more r e l a t e d to c e l l u l a r i t y than to p r o l i f e r a t i v e status. This s t u d y e x a m i n e d the r e l a t i o n s h i p between deoxyglucose (DOG) uptake and proliferation by c o m p a r i n g its u p t a k e by breast tumour cells grown in the presence of serum with cells starved of serum for 24 hours. MCF7 breast tumour cells were seeded in 25 cm 2 tissue culture flasks in 4ml of Dulbecco's MEM medium supplemented with 10% FCS. Comparisons of 3H-DOG uptake and S phase fraction (Spf) were made between cells deprived of serum (S) for 24 hours and and those maintained with serum on days 4, 5 and 7 post-seeding. 3H-DOG uptake was determined by the addition of 4uCu of 3H-DOG for 30 min 1 hour after the a d d i t i o n of fresh medium. After washing with PBS cells were trypsinized and 3H uptake, cell number and S-phase fraction (Spf) determined. Serum withdrawal was associated with decreased Spf on days 4 and 5 (dy4:S+,31.5±3.5, S-, 21.3±2.0; dy5:S+, 31.8±1.6 S-, 19~2.2). DOG uptake: day 4, 8 1 6 0 ± 6 5 0 D P M / m i l l i o n cells in S+ cells and 4 4 9 0 ~ 3 8 0 in S- cells; day 5, 6490±160 in S+ and 4080±500 in S- cells. On day 7 Spf was 18~0.8 in S+ and 15.5~2 in S-. DOG uptake 6930±150 in S+ and 5960~370 in S-. Conclusion: In contrast to othex studies this work suggests an association between DOG uptake and proliferation.

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A. Chetatmeau.1, J.Y. Douillard t, E. Barbet I, J. Herpstz, G. Wynant2, M.G. Hanna2, I. Resche 1, S. Simpsonz, J.F. Chatal 1. t Nuclear Medicine Department, Regional Cancer Center, Nantes, FRANCE; 2Perimmtme Inc, Rockville, U.S.A.

K. Schomficker, H. L6hr (a), D. Moka, A. Scharl (b), K. Scheidhauer, S. Liebenhoff, S. Salditt, and H. Schicha. Departments of Nuclear Medicine and Obstet & Gyn (b), University of Cologne, and St. HildegardisHospital, Cologne, Germany (a).

RADIOLkiMU,~IOSCINTIGRAPHY OF OCCb%T COLORECU?AL CANCER ',%qTI-I 99~I'c-LABELED HUMAN MONOCLONAL ANWIBODY IN PATIENTS WITH .NEGATIVE A B D O ~ N A L AND PELVIC CT

In 12 patients (mean-age 60 years) colorectal cancer recurrence was suspected by a rise in serum CEA and by clinical signs (2 cases). Within 2 weeks before prospective radioimmunoscinti~aphy, each patient had a negative CT evaluation of the abdomen and pelvis. Tumor targeting was performed using 10 mg human IgG 88BV59 monoclonal antibody labeled with teclmetium-99m (1110 to 1330 MBco. Planar scinti~aphy and SPECI? acquisitions were obtained 14 to 20 hours after infusion, and in one case. a late SPECT 2 days after infusion was also performed. Human and-human antibody (HAHA) concentration was determined before infusion, then 1 and 3 months after infusion. The final diagnosis was confirmed histologically within 4 weeks post-infusion in 8 patients. Radioirnmunoscintigraphy results were 5 true positives, 1 true negative, 1 false positive (peritoneal eareinomatosis suspected but not proven by laparotoray) and 1 false negative (liver metastasis). During 1 year follow-up, one patient with pelvic positive radioimmunoscintigraphy who at first refused surgery had endoscopy at 11 months which confirmed anastomnfic recurrence. In the three patients with negative radioimmunoscintigraphy and no surgery, hepatic (2 cases) and pulmonary (1 case) metastases were detected by CT several months after radioimmtmoscintigraphy. No patient developed human anti-human antibody. These results thus confirm the interestof using ~'~£e-labeled human monoclonal antibody 88BV59 to localize colorec~ cancer recurrence in patients with negative CT and rising serum CEA.

COMPARISON OF Tc-99m-MIBI, Tc-99m-TETROFOSMIN, Tc99m-Q-12 AND TI-201: BIOKINETICS ON TUMOR-BEARING MICE.

Purpose of the study: Radioactive tracers originally introduced for heart scintigraphy, such as Tc-99m-MIBI, Tc-99m-tetrofosmin, Tc-99m-Q-12 (furifosmin) are being used increasingly for tumor imaging. We therefore decided to compare the biokinetics of these radiopharmaeeuticals in tumorbearing mice. Methods: DBA/2N-mice (male, 25 g), with a tumor (0.5 g, CaD2mamma-carcinoma) transplanted in the right limb, served as an animal model. The percentages of applied radioactivity per g (%/g) tissue in blood, liver spleen, kidney, muscle, femur, heart, lung, GIT, and the excretion with the urine were determined 0.5 h, 1 h, 5 h, 12 h and 24 h after i.v. application of the different radiopharmacenticals. Results: TI-201 showed tumor/blood ratios of approx. 11 + 1.5 with a tumor-accumulation of 3.5_+1.0 %/g 5 h p.i. and 24 h p.i. We found lower tumor enrichments with the Tc-99m complexes at all time points investigated. The following values were obtained 24 h p.i.: MIBI: 0.45-+0.1%@ Q-12: 0.21_+ 0.08 %/g, tetrofosmin: 0.14_+0.07%/g. The corresponding rumor/blood ratios were as follows: MIBI: 18.5_+2.1, Q-12: 1.4_+0.8, tetrofosmin: 1.5-4-0.5. The liver excretion showed little variation within the technetium complexes, but was most marked in the case of Q-12, levels falling from 14.1_+1.2 %/g (0.5 h p.i.) to 0.66ri-0.2 %/g (24 h p.i.). The liver accumulation decreased with TI-20I from 5.3_+1.2 %/g (0.5 h p.i.) to 2.5_+0.8 %/g (24 h p.i.). Conclusions: The highest tumor/background ratios were obtained with Tc-99m-MIBI, even exceeding those for TI-201. The results therefore suggest that Tc-99m-MIBI is the most suitable agent for tumor scintigraphy and for detection of "multi-drag resistance" (MDR). More investigations on other tumor types and species are needed to confirm this conclusion.

¢| lO

eID if)

ID k,, L

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A.C. Kole, B.E.C. Plaat, H.J. Hoekstra, W.M. Molenaar, W. Vaalburg. PET Center, Departments of Pathology and Surgical Oncology, Groningen University Hospital, Groningen, the Netherlands PRQTEIN SYNTHESIS RATE MEASURED WITH L-[1-11C]TYROSINE PET AND HISTOPATHOLQGICAL FINDINGS The aim of the study was to compare the in vivo protein synthesis rate (PSR) measured with PET using L-[1-11C]-tyrosine (TYR) with the in vitro reflections of biological activity of soft tissue sarcoma (STS): mitotic rate and number of proliferating cells. Estimating the grade of malignancy, in which mitotic index plays a major role, is considered to be the golden standard in evaluating STS. In 22 patients with untreated STS the PSR was measured using TYR-PET. Doses of 370 MBq TYR were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera and included arterial cannulation for blood sampling. Afterwards, all patients underwent surgery and in the resected specimen or biopsy the number of mitosis was counted and tumors were graded. Proliferative activity was assessed by immuno-histochemical detection of the Ki-67 nuclear antigen using MIB-1 monoclonal antibody and by visualizing nuclear organizer regions using a silver-staining method (AgNOR). A significant correlation (p<0.05) was found between PSR and mitotic rate and between PSR and MIB-1. No correlation was found between PSR and AgNOR. These results indicate that TYR-PET could be helpful in assessing the mitotic and proliferative activity of STS, and could therefore be used to estimate the malignancy grade in patients with STS in vivo.

M.Lapela, S.Leskinen, P.Lindholm, J.Nuutinen. Turku University, Department of Oncology and Radiotherapy, FIN-20520 Turku, Finland.

DETECTION

ID

OF RELAPSE

IN LYMPHOMA

WITH

FDG

PET

Early detection of relapse in lymphoma is essential for successfull salvage therapy. In this study, positron emission tomography (PET) with F18-fluorodeoxyglucose (FDG) was evaluated in identification of viable lymphoma tissue in clinically problematic cases. We studied 15 pts (median age, 56 yrs; seven females) with previously treated malignant lymphoma who were suspected to have relapse but the diagnosis was not easily done by histology (5 pts, no biopsy could not be easily taken because of the location of the deposits, i0 pts, initial biopsy revealed only benign tissue). Following injection of 8.0 mCi of FDG, emission data was acquired with ECAT 931/08. The PET image was visually compared with CT image, clinical examination and transmission image, and the FDG uptake was measured as standardized uptake value (SUV) of the tracer. The disease status was subsequently confirmed by histology, cytology and/or follow-up so that ten out of 15 pts turned out to have disease relapse. In the PET study, more FDG was accumulated in the suspected tissues in patients shown to have active lymphoma than in patients who were concluded to be in remission. There were no overlap of SUVs between these two groups; the median S~V was 11.6 in malignant and 3.0 in benign lesion (p=0.002, Mann-Whitney). We can conclude that FDG PET may offer a complementary method in the evaluation of suspected relapse of malignant lymphoma even in clinically problematic cases. Quantitation of FDG uptake assists to correctly distinguish between malignant and benign lesions.

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K. Raffelt_, D. Moka*, R. Leidel*, F. S(JUentrop, J. Hahn, H. Schicha* Dept. II of Inorg. and Anal. Chemistry and *Dept. of Nucl. Med. University of Cologne, Germany. EFFECT OF THYROID CANCER AND RENAL CELL CARCINOMA ON THE PHOSPHOLIPIDCONCENTRATIONOF HUMAN BLOOD PLASMA

Z. Wygoda, J. Roskosz, D. Sciegli~ska, M. Wiench, E. Gubala, J. Wloch, B. Jarz~b Centre of Oncology MSC Institute, Gliwice, Poland

We detected six different PLs: phosphatidylethanolamine (PE), sphingomyelin (SM), 1- and 2-acyl-lyso-phosphatidylcholines (LPC1, LPC2), phosphatidylinositol (PI) and phosphatidyleholine (PC). TC and RCC lead to lower PL concentrations compared to control plasma. Patients with TC have significantly lower PE, SM and PC, patients with RCC have lower LPC1 than controls. These results show the suitability of our method to prove very characteristic changes of PL metabolism in patients with various cancerous diseases.

EARLY DIAGNOSIS OF PRIY~Y AND RECURRENT MEDULLARY THYROID CARCINOMA Early diagnosis of medullary thyroid carcinoma (MTC) comprises molecular diagnostics of R E T protooncogene mutations and serum basal and stimulated calcitonin ( C T ) estimation. Nuclear imaging procedures play a substantial role in postoperative monitoring of patients. Pentavalent 99mTc-DMSA is a tracer of choice, 131-I-MIBG is considered as another of nuclear imaging and in the therapy of nonoperable recurrences. In the present study we analyse 21 patients with MTC in whom persistent or recurrent CT serum rise (CIS IRMA) was stated after surgery. Three patients were diagnosed as MEN 2A and in two patients mutation of RET protooncogene in codon 634 was stated). 99mTc(V)-DMSA revealed pathologic loci in i0 cases (48%). In 4 patients 131-I-MIBG uptake was stated and 131-I-MIBG therapy was introduced, confirmed by post-therapy scan in 3 of them. Molecular diagnostics of RET protooncogene mutations revealed three unknown cases of MRN 2A in 19 investigation relatives. DNA was isolated from leukocytes and PCR analysis was performed with CfoI and RsaI restriction enzymes. RET protooncogene diagnostics gives substantial improvement of the early diagnosis of medullary thyroid carcinoma.

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N. Elahi, L. Kostakoghi, H. Canpmar, D. Uzal, M. Hayran, M. Nabaie, C.F. Bekdik, E, Kansu. Hacettepe University Medical Faculty, Ankara, Turkey.

A. Dimit rakogoulnuJ;t rau~ 1, LG. Strauss~, W. Tilgen z, F. Oberdorfer ~, P. Mantaka ~, G. Kontaxakis t, G. van Kaickl.~German Cancer Research Center, Heidelberg, =Department of Dermatology, University of Heidclberg, Heidelberg, Germany

Alterations in cell growth and membrane synthesis can be detected by phospholipid (PL) measurement using high resolution magnetic resonance spectroscopy (HR MRS). The purpose of this investigation was to specify differences in PL metabolism between selected malign diseases in comparison to controls. ~P spectra of blood plasma were recorded on a Bruker 300 MHz HR MR spectrometer using ~H broad-band decoupling. In order to get well resolved quantitative PL signals we added natrium cholate and phosphatidic acid to the plasma. We examined 16 patients with thyroid cancer (TC) in preparation to a radioiodine therapy with known tumour residual tissue and compared the results with those of a control group of 17 hypothyroid patients in remission. Furthermore we compared the PL concentrations in plasma of 8 patients with renal cell carcinoma (RCC) to those of 8 healthy volunteers. PL in ~tmol/1blood plasma: PE I SM**

TC [~remission

I LPC1

* p < 0.05, ** p < 0.005 I PI I PC** I

[91±8 1416± 221294 ± 20166 ~ 8 11747±102 115±10 513±13 336±20 79±5

2226±118 I 330 I 144 I

CORRELATION OF THE FINDINGS OF TL-201 AND Tc-99mSESTAMIB1 (MIBI) SPECT WITH FLOW CYTOMETRIC PARAMETERS IN PATIENTS WITH ASTROCYTIC TUMORS.

PET WITH F-18-DIHYDROXYPHENYLALANIN WITH MALIGNANT MELANOMAS.

Our objective was to correlate the findings of TI-201 and MIBI SPECT with cell cycle kinetics studied by flow cytometry in patients (!0ts) with astrocytic tumors including both low grade (LGA) and high grade (HGA) gliomas. Our study group consisted of 23 pts 11 of whom were diagnosed with LGA and 12 with HGA. SPECT was performed after the injection of 111 MBq of T1-201 and 555 MBq of MIBI on two separate days using a dualhead gamma camera. Tumor/Scalp (T/S) ratios were obtained on consecutive transverse slices containing the entire volume of tumor. Paraffin-embedded specimens were deparaffinized and analyzed for DNA ploidy and proliferative index by flow cytometry for determining the malignant potential of each tumor. For the definition of each group, we determined a cut-off value of<10 for proliferative index and <2 for T/S ratios for the group with LGA and >10 for proliferative index and >2 for T/S ratios for the group with HGA. There was a significant difference in both T1-201 and MIBI T/S ratios between LGA and HGA (p<0.0001, p=0.0001, respectively). For both agents using the above cut-off values determined for LGA and HGA; a. there was a strong correlation between the magnitude of T/S ratios and proliferative index (100%), b. there was moderate correlation between T/S ratios and DNA ploidy (TI-20h %58+16.1; MIBI: % 55.5+16.9). We conclude that both TI-201 and MIBI SPECT proved equally valuable in predicting malignant potential of astrocytic tumors. Further studies are underway to correlate patient prognosis with both cell cycle kinetics and T1201/MIBI SPECT findings.

PET-FDG demonstrates a high sensitivity in the diagnosis of almost all tumor types. Although, further tracers are necessary to increase the specificity of the method. We used PET with F-18-DOPA in patients with metastases of malignant melanomas, since DOPA is metabolized to Dopaquinone and is therefore a precursor of melanin. The study includes five patients with pretreated malignant metastatic melanomas. All patients were studied twice at two different days within one week. Dynamic PET multitracer studies with O-15-water (tissue perfusion) and F-18-Deoxyglucose (FDG, tumor viability) were performed at the first study and F-18-DOPA was applied at the second study. The perfusion series were acquired as a sequence of 8 minutes, the FDG-series of 60 rain and the F-18-DOPA of 120 min, For the quantitative evaluation we used ROIs and SUV. Furthermore, the transport konstants kl and k2 were evaluated for the perfusion series and the DOPA series using a two compartment model and the median uptake in a larger vessel was used for the input function. Parametric images of the influx and efflux of the tracer were reconstructed. For the analysis of the FDG series we used the graphical Patlak analysis. The preliminary evaluation includes 7 lesions; 4 liver metastases and 3 subcutaneous metastases. The FDG-scans showed an increased FDG metabolism in all subcutaneous metastases and in 2/4 fiver metastases. The DOPA-uptake was less than the FDG-uptake in 4/7 lesions (2 subcutaneous, 2 liver metastases). 1]7 lesion (liver metastasis) demonstrated a similar FDG-uptake and 2/7 lesions (liver metastases) showed a higher F-tS-DOPA uptake in comparison to F-18-FDG. Both lesions showing a higher DOPA accumulation (metastases: 2.85 and 4.96 SUV; liver: 1.95 SU~/) were treated with a combined immunochemotherapy and could not be delineated on the FDG scans (metastases: 2.45 and 1.94 SUV accordingly; liver: 2:47 SUV). A comparison of the transport constants for the (31S-water and the F-18-DOPA showed no statistically significant|y correlation between these parameters. This means, that the DOPA-uptake is not perfusion dependent. These preliminary results demonstrate, that F-18-DOPA is a promising tracer for the melanoma diagnosis and may help to increase specificity of PET and therapy management in patients with treated metastases.

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I t Valkema, M.G. Romijn, C.H.J. van Eijck, A.E.M. Reijs, J. van Peski, P.P.M. Kooij, E.P. Krenning. Departments of Nuclear Medicine and Surgery, University Hospital, Rotterdam, The Netherlands.

E.Bombardieri 1, A.Chiti!. S.Fanti2, B.Bellanova 2, P.Tomassetti 2, A.Romeo 2, A. Spinelli t, G. Savelli ~, E. Seregni ~, N Monetti 2. Istituto

FLUORINE-18-DEOXYGLUCOSE SPET FOR THE DETECTION OF PANCREATIC CANCER, AND PRELIMINARY COMPARISON WITH GAMMA CAMERA COINCIDENCE DETECTION. Aim: We studied the feasibility of 18-FDG SPET for the detection of primary, metastatic, and recurrent pancreatic cancer. We made a preliminary comparison with gamma camera positron coincidence detection (PCD). Patients and methods: A 3-head SPET camera (Picker Prism 3000) was fitted with ultra-high energy collimators. 24 patients (pts) with primary pancreatic cancer (23 adenocarcinoma, 1 neuroendocrine tumor), 7 pts with benign lesions and 5 pts with recurrence of adenocarcinoma were investigated 45 rain. after injection of 185 MBq 18-FDG. Acquisition was obtained in continuous mode, 4 x 8 min, 360 ° divided in 120 angles, followed by prefiltering (low-pass) and reconstruction. In 29 patients dual isotope acquisition was performed using 55 MBq of Tc-99m-colloid to identify the liver. The SPET results were evaluated without prior knowledge of the results of conventional imaging, or histology. Visual grading was used: no increased uptake, grade 0; equivocal, grade 1; moderate, grade 2; intense, grade 3. Grade 3 lesions were considered "malignant". In all patients histology was used as gold standard. One pt (adenocarcinoma) had additional PCD directly following SPET (2-head PCD camera, Picker 2000 XP), and 2 additional pts (no histology yet) were scanned with PCD only. Results: Image quality was variable, in 5 pts it was poor due to a low count rate. In most cases the corresponding Tc-99m-colloid images were helpful in localizing lesions. In 18 of 24 pts with primary malignancy grade 3 uptake was seen (sensitivity 75%). 3/24 pts had grade 2, and 3/24 had grade 0 or 1 uptake. Grade 3 uptake was not seen in any of the 7 pts with benign lesions, 2/7 pts had grade 2, and 5/7 pts had grade 0 or 1 uptake. In 2/5 pts with recurrence, grade 3 lesions were noted, in 2/5 grade 2. Only 1 of 11 pts with liver metastases had grade 3 liver lesions, corresponding with cold defects on concurrent Tc-99m-colloid SPET. In 1 of 9 pts with lymph node metastases grade 3 uptake was seen. A solitary grade 3 pancreatic lesion was much clearer delineated with PCD than with SPET, with a lesion/background contrast ratio of 3.8 with SPET and 6.4 with PCD. The 2 pts scanned with only PCD had no positive lesions. Conclusion: The image quality of 18-FDG SPET in the current setting is less than the quality known of PET, with lower lesion to background contrast. Many primary lesions were detected, however, but many liver and lymph node metastases were not. PCD has much better image quality than SPET, which makes it a promising technique for oncologic 18-FDG imaging.

Nazionale Tumori, Milano and S. Orsola-MalpighiH, Bologna; Italy SOMATOSTATIN RECEPTOR IMAGING (SRI), COMPUTED TOMOGRAPHY (TC) AND ULTRASOUND (US) IN THE CLINICAL MANAGEMENT OF NEUROENDOCRINE GASTRO-ENTERO-PANCREATIC TUMORS (GEl') The aim of this study was to evaluate the sensitivity of different imaging modalities in detecting primary GEPs and metastases from GEPs. Methods. We studied 120 pts with suspected or demonstrated GEP. SRI was performed after i.v. injection of 200-250 MBq of 11 lInpentetreotide. Planar images (whole-body and accessorial views) and SPET were acquired 4 and 24 hours after tracer injection. In 18 pts the presence of a GEP was excluded, thus we evaluated 102 pts (mean age 53.2 yrs; range 19-81 yrs; 55 males, 47 females). Tumor sites were: stomach (n=ll), pancreas (n=32), biliary tract (n=2), small intestine (n=33), large intestine (n=10), liver metastases (rots) from unknown primary (n=13), diffuse metastatic involvement from unknown primary (n=l). A pathological diagnosis was obtained in 88 pts. Forty one pts were in staging, 61 in follow-up. Results. Our results were as follows: SKI CT US Other Primary tumor (%) 30/45 (67) 18/42 (43) 15/38 (39) 10/24 (42) Liver rots (%) 53/59 (90) 45/55 (82) 42/48 (88) 17/25 (70) Bone rots 8/10 5/6 Other mts (%) 29/32 (88) 15/26 (58) 13/27 (48) 9/15 (60) Moreover, SRI detected previously unknown lesions in 32 pts (31%) and in 25 pts (24%) the therapeutic schedule was significantly modified after SRI. In all other cases SRI proved to be useful in supporting the findings other methods. Conclusions. High quality SPET images were essential to detect small lesions and to obtain these results. Our study confirmed SRI to be the most sensitive diagnostic procedure for GEP; it could be used as the first-choice examination in these tumors.

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P 342 J.D.Lucas, M.J.O'Doherty, B.F.Cronin, P.K.Marsden, P.H.McKee, M.A.Smith. D e p t s of O r t h o p a e d i c s and C l i n i c a l PET Centre, U M D S and G u y s and St Thomas" H o s p i t a l Trust, L o n d o n SEI 7EH.

M J Garcia Velloso, C Gamez, J Alcalde, I A z i n o v i c , V Paloma, J Arbizu, J Richter. Servicio de Medicina Nuclear. Clinica Universitaria. U n i v e r s i d a d de Navarra. Pamplona. Spain.

A P R O S P E C T I V E E V A L U A T I O N OF A N D S A R C O M A S U S I N G FDG PET.

POSITRON EMISSION TOMOGRAPHY HEAD AND NECK TUMORS

40

SOFT

TISSUE

MASSES

A p r o s p e c t i v e a s s e s s m e n t of 40 p a t i e n t s w i t h soft tissue masses using FDG PET was performed to establish if FDG PET is a b l e to differentiate b e n i g n f r o m m a l i g n a n t m a s s e s b o t h q u a l i t a t i v e l y and quantitatively. Patients presenting with a mass t h a t w a s t h o u g h t to be m a l i g n a n t b o t h c l i n i c a l l y a n d o n MRI scan, u n d e r w e n t a FDG PET scan w i t h localised views of the mass prior to biopsy. Q u a n t i t a t i v e a s s e s s m e n t w a s m a d e by the c a l c u l a t i o n of the S t a n d a r d U p t a k e V a l u e (SUV) at 1 h o u r w i t h c o r r e c t i o n for the p a r t i a l v o l u m e e f f e c t and the p a t i e n t ' s b l o o d g l u c o s e level. 40 p a t i e n t s h a v e b e e n studied, 23 m a l e s and 17 females with a median age of 52 years. H i s t o l o g i c a l d i a g n o s i s w a s of soft t i s s u e s a r c o m a in 20 p a t i e n t s , of w h i c h 4 were low grade, 1 intermediate grade and 15 h i g h grade. Benign t u m o u r s w e r e p r e s e n t in 19 p a t i e n t s w i t h 1 c a s e of d e e p sepsis. Q u a l i t a t i v e l y , 35 of the m a s s e s w e r e i d e n t i f i e d and 24 r e p o r t e d as b e i n g m a l i g n a n t , ii of t h e m a s s e s w e r e r e p o r t e d as b e i n g b e n i g n or low g r a d e sarcomas. 5 masses, all benign, f a i l e d to t a k e u p FDG. Q u a n t i t a t i v e a s s e s s m e n t u s i n g SUV v a l u e c a l c u l a t i o n s h o w e d a m e a n v a l u e for b e n i g n t u m o u r s of 1.9 (median 1.4) and a m e a n v a l u e of 8.8 (median 7.7) for the m a l i g n a n t tumours, t h e r e b e i n g a s i g n i f i c a n t d i f f e r e n c e b e t w e e n the two t u m o u r t y p e s ( M a n n - W h i t n e y U t e s t p<<0.Ol). U s i n g an SUV v a l u e of g r e a t e r t h a n 2.0 to d e f i n e m a s s e s as b e i n g m a l i g n a n t , a s e n s i t i v i t y of 90% w i t h a S p e c i f i c i t y of 65% w a s d e m o n s t r a t e d . FDG P E T d o e s i d e n t i f y soft t i s s u e s a r c o m a s and has a high quantitative sensitivity for the d i f f e r e n t i a t i o n of b e n i g n m a s s e s f r o m soft t i s s u e sarcomas.

WITH

[18F]FDG

IN

The purpose of this study was to evaluate the clinical utility of PET-[18F]FDG imaging in staging and d i a g n o s i n g recurrency in head and neck tumors. PET-[18F]FDG imaging was performed 45 minutes after 370 M B q of [18F]FDG a d m i n i s t r a t i o n in 27 patients, 22 males and 5 females, being squamous-cell carcinoma the m o s t common tumor (19 patients, 70%). H i s t o p a t h o l o g i c analysis compared positive lymph nodes and recurrent tumor with findings on TAC, MRI and PET images. Results: In 7 patients with newly diagnosed tumors PET imaging accurately detected metastatic cervical lymph nodes in 6 cases and was true negative in one, while TAC or MRI failed to detect 2 tumors involving the nasopharynx and oral cavity. In 20 patients suspected from early recurrent malignancy PET imaging accurately detected ii cases (S=92%), was true negative in 6 cases (E= 86%) false positive in one patient with infection and equivocal in 2 patients. TAC or MRI identified accurately 6 cases (S=50%) and there were 6 true negatives (E=67%), but in 5 patients the results were equivocal and there were 3 false negatives. Combining the information from TAC, MRI and PET imaging 17 cases positives (S=94%) and 7 cases negatives (E=87,5%) were accurately diagnosed, remaining equivocal scans in 2 patients and a false positive in a patient with infection. Conclusion: PET-[18F]FDG imaging is highly effective in detecting m e t a s t a t i c cervical lymph nodes and in evaluating patients for recurrent head and neck tumors.

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J VergQte~ J.L Moretti, A Garnier-Suillerot* EA 449 et *laboratoire de Physico-chimie Biomoleculaire et Cellulaire, Universit@ Paris Ncrd, Bobigny, FRANCE.

H.W.D.Yeung, H.Macapinlac, D.Kelsen, M.Bains, R.D.Finn, S.M.Larson. Memorial Sloan-Kettering Cancer Center, New York, NY

Tc99m-MIBI EXCHANGE PARAMETERS BY RESISTANCE PROTEINS (Pgp AND N~qP).

FDG-PET IN PATIENTS WITH CANCER OF ESOPHAGUS Purpose: To evaluate the clinical utility of FDG-PET in patients with cancer(CA) of esophagus. Methods: All patients (13M/5F; mean age 58, range 32-73) with CA esophagus referred for FDG-PET in 1996 were studied. The clinical indications were pre-operative staging (6), evaluation of possible recurrence (6), and follow up evaluation after therapy (6). All patients were instructed to fast for at least 6 hours. Whole body PET images were acquired on a GE Advance scanner (35 image planes, 4.25ram/slice, 15cm AFOV) 45 minutes to 1 hour after the intravenous injection of 370 MBq of F-18-FDG. Emission PET images were acquired in the 2D mode, 6 minutes per bed position with 2 to 6 bed positions, followed by 8 minutes transmission scans at selected sites. Both the emission and attenuation corrected images were evaluated visually by consensus by 2 experienced readers. A final diagnosis was reached in 14 patients at 25 sites by histology (12 patients) or clinical follow-up of over 6 months (2 patients). Results : FDG-PET scan was true positive (TP) in 13 sites, true negative in 9 sites, false positive (FP) in 2 sites and false negative (FN) in 1 site, with a sensitivity of 93%, specificity of 82%, and accuracy of 88%. The false positives were a case of chronic post-operative cutaneous fistula, and a focal FDG accumulation at the anrto-pulmonary window with SUV of 2.3. The only incidence of false negative was a lymph node at the greater curvature of the stomach which was also not detected on CT. tn 5 patients FDG-PET helped clarify equivocal CT findings, and in one patient PET scan showed new findings unexpected by clinical follow up. Conclusion: In our experience, FDG-PET is highly accurate in preoperative staging, demonstration of suspected recurrence or therapeutic follow up of patients with esophageal cancer. (Supported in part by DOE #DE-FG0286ER60407 and the Gerschel Foundation)

MEMBRANE MULTIDRUG

The overexpression of two membranes glycoproteins, Pgp 170 kD (~DR) and NgP 190 kD is a major cause of resistance to chemotherapeutic agents in the treatment of human cancers. 99mTC-MIBI is known to be a Pgp substrate. We studied the kinetics of uptake and efflux of Tc99mMIBI in sensitive (MRP-) and resistant (MRP+) lung cancer GLC4* cell lines and in sensitive (I~)R-) and resistant (MDR+) K562 leukaemia cell lines. We determined for each cell line the percentage of Tc99mMIBI uptake, the.passive influx coefficient k+, the passive efflux coefficient k- and the active efflux coefficient ka of the resistant cell lines. Tc99m-MIBI uptake was very low in GLC4 (MRP+) compared to sensitive cells (re/se = 1/13) demonstrating that MRP extrudes Tc99m-MIBI. We have then conpared the efficiency of active efflux. We observed that the GLC4 (MRP+) ka value (0,85.10-11 + 0,2 s-I. (cell/ml)-I) is con~parable with the K562 (MDR+) ka value (1,2.10-11 + 0,2 s-I. (cell/ml)-l). This suggests that both transporters efficiencies to wash out Tc99ra-MIBI are similar in spite of a different suspected mechanism of its transport. *With the courtesy of H.Broxterman (Holland). Grants of MIDY Foundation and ARC.

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A.J.B. McEwan I, Z. Catz I, C. Morin I, L.I. Wiebe 2, ZCross Cancer Institute, Nuclear Medicine, Dept of Oncologic Imaging; 2University of Alberta, Faculty of Pharmacy, Edmonton, AB, Canada

M.Imbriaco, SDJ.Yeh, H.Yeung, OMawlawi, J.Healey, A.Huvos, SM.Larson. Memorial Sloan-Kettering Cancer Center, New York,NY.

H Y P O X I A IMAGING IN P A T I E N T S WITH BREAST CANCER. Hypoxia in tumors is b e l i e v e d of importance in radioresistance and may be a major factor in treatment failure. We have previously shown 1-123 Iodoazomycin arabinoside (IAZA) to image hypoxia in squamous carcinoma of the head and neck with an inverse correlation of IAZA avidity (hypoxia) and radiation therapy failure. In excess of 50% of b r e a s t cancers are b e l i e v e d to be hypoxic; in this pilot study we have compared IAZA and Tc-99m MIBI imaging to evaluate hypoxic status in 8 patients with primary breast cancer p r i o r to therapy. Imaging was performed immediately and .18-24 hours after the injection of 370 MBq of IAZA. Immediately after completion of the delayed image, 800 MBq of Tc-99m MIBI were injected and images acquired at 15 minutes post injection. All images were a c q u i r e d on a GE 400 AC gamma camera interfaced to a Picker Odyssey Computer with the patient prone on a scintimammographic table. IAZA images were acquired for 600 secs/image and MIBI for 300 sec/image. All patients showed p o s i t i v e MIBI images. In 6/8 patients the breast cancer showed uptake of IAZA as focal uptake in a distribution which tended to be smaller than the MIBI uptake distribution. These data confirm our earlier findings of hypoxia in tumors and demonstrates our ability to functionally define tumor status.

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TL-201 SCINTIGRAPHY FOR EVALUATION OF TUMOR RESPONSE TO PREOPERATIVE CHEMOTHERAPY IN PATIENTS WITH OSTEOSARCOMA. The degree of tumor necrosis following preoperative chemotherapy is likely to be an indicator of the prognosis for patients with primary osteosarcoma. This study was undertaken to evaluate the efficacy of Thallium-201 (T1-201) scintigraphy in assessing response to chemotherapy in patients with osteosarcoma and to correlate the findings with the degree of tumor necrosis assessed histologically. Twenty-four patients with biopsy proven osteosarcoma underwent TI-201 imaging before and immediately after preoperative chemotherapy. The maximum pixel counts taken over the tumor divided by that of a background region yielded a tumor to background ratio. The percent change in the tumor to background ratio before and after chemotherapy, defined as alteration ratio, was correlated with the percent tumor necrosis. The percent tumor necrosis was classified into 4 grades: grade l = < 50% necrosis, grade 2 = 50-89% necrosis; grade 3 = 90-99% necrosis; grade 4 = 100% necrosis. Three patients with grade 1 histological response showed an alteration ratio of 31%±4 (mean~+SD); Three patients with grade 2 response showed an alteration ratio of 76%+9; Nine patients with grade 3 response showed an alteration ratio of 84%±11; Nine patients with grade 4 response showed an alteration ratio of 96%+5; These ratios correlated well with the histologic grades (p<0.001, analysis of variance). The results of this study suggest that TI-201 scintigraphy is a powerful tool in the evaluation of tumor response to chemotherapy in patients with osteosarcoma.

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H.Macapinlac, H.W.D.Yeung, R.D.Finn, J. Humm, J. Zweit*, R. Robbins, S.M.Larson. Memorial Sloan Kettering Cancer Center, New York, NY, U.S.A.,and *Royal Marsden Hospital, U.K.

*C.St~fanesc~,*V.Rueu,~M.Rusu,~-~M.Meigr~gn,~a,~,C.Badiu, ~-~F.Stefanache,*Med.Univ.,Nucl.Med.Dept.,Iasi,Romania, ~°~C.H.U. H.gondor, Nucl.Med.Dept.. Creteil, France, ~a-*Med. Univ., Dept. of Dermatology, Iasi, Romania

IMAGING OF THYROID CANCER WITH I-i31 SPECT, 1-124 PET and FDG PET. ]'he sodium iodide symporter for iodine and glycolysis are two important biochemical processes which can be studied quantitatively in human thyroid cancer. Grunwald (EJNM 1996:23:3;p.312-319) proposed that the degree of differentiation of tumor affected the relative uptake of iodine versus FDG in these patients using semiquantitative methods (I-131). In order to improve quantiative comparisons of iodine transport and glycolysis we studied 4 patients with surgically documented thyroid cancer with I-131 SPECT, I-124 PET and FDG PET. All 4 were subsequently treated with 1-131. The imaging findings are shown: PTS

FDG PET

]- 124 PET

l- 131 SPECT

(+)bones& lung (+)bone&(+/-)lung (+)bones,(+/-)lung (faint) in chest (+)bronchialnodes (+)bronchialnodes (+) neck and lung (faint)in lung (-) in lung (+) neckand lung (+) neckand lung (+) neckand lung DQ 1-124 PET imaging offers improved sensitivity in comparison to 1131 SPECT for detecting metastatic thryoid cancer. Patients with well differentiated tumors had greater uptake of I-124 in comparison to FDG. Conversely, poorly differentiated tumors showed more FDG uptake than 1-124. In conclusion, quantitative PET imaging supports the general concept that histologic differentiation influences the relative uptake of both FDG and I-124. CG NL FT

(Supported in Part by DOE#DE-FG02-86ER60407 and the Gerschel Foundation)

99mTc MIBI IN NEUROFIBROMATOSIS IMAGING DIAGNOBIS The aim of this study was to investigate the characteristics of 99mTo MIBI uptake in neurofibromatosis and its diagnostic usefulness. ~ethod: 33 patients diagnosed with type I neurofibromatosis were investigated. For each patient a whole body scan was realized I0 minutes after i.v. administration of a 0.3 mCi/kg 99mToMIBI dose; this was followed by static images. The 99mTcMIBI uptake was quantified using an index defined like the counte/pixel ratio between two interest regions: the tumour and an homologous normal one (I-MIBI). Our r e s u l t s show positive images in 16 cases; for same patient not all the known lesions have 99mTcMIBI uptake. There was a correlation between the radiotracer uptake and the lesion histology: positive images were found in the case of plexiform neurofibromas (5 cases), median nerve nodular neurofibromas (2 oases), intraspinal neurofibromas (3 cases), acoustic neurinoma (i case). In terms of I MIBI values, two categories of positive images can be distinguished: low values, in the cases mentioned above, and high values (up to 4 times grater than the lowest one) in 3 cases showing malignant histological transformation (2 optic nerve gliomas, a peripheral sarcoma). In 4 cases the evident image corresponded to a local recidiva and in 2 patients unknown neurofibromas sites were discovered. Neither the pigmented skin lesions,nor the superficial dermal lesions had not positiv~ images (with one exception, a giant lesion, were the radiotracer uptake, with low I-MIBI, was probably in relation with the high vascular component). In conclusion, 99mTc MIBI scintigraphy may be usefull in the evolutive evaluation of neurofibromatosis.

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Chia-Hung Ka_o_o,Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung Taiwan.

O. Alonso,O) M, Martinez, (2) L. Delgado,(3) G. Lago, °) C. B~zT~no,(2) F. Mut,°) M. Nfifiez, (~) A. Garc4s,(3) J. Prlario, (3) I Muse,(s) and E. Touya,(t) Departments of Nuclear Medicine, (I) Dermatolog3x2) and Clinical Ontology,(~) Clinical Hospital of the University of Uruguay, Montevideo, Uruguay.

TC-99M MIBI CHEST IMAGES FOR SMALL CELL L L ~ G CANCERS: RELATIONSHIP TO PATIENTS) PROGNOSES AND RESPONSES OF CHEMOTHERAPY.

Tc-99m MIBI SCINTIGRAPHY FOR NODAL STAGING OF PRIMARY MALIGNANT MELANOMA AND EVALUATION OF RECURRENT DISEASE.

The purpose of this preliminary study was retrospectively to evaluate the relationship between patients ~ chemotherapy response and survival time wihh technetium-99m methoxyisobutylisonitrile (Tc-99m MIBF) uptake in small cell hmg cancers (SCLC), which represents whether multidrug resistance (mdr) - mediated 170-kDa P-glycoprotein (PgP) in malignancies is present or not. Methods: Before chemotherapy (cisplatin 25rag and etoposide 125my qd for 3 days every course), 15 male patients (ages: 54 - 64 years) with SCLC were included in this study to accept Tc-99m MIBI chest images, including SPECT and planar, for qualitative and quantitative assessment of the existence of PgP in SCLC. Results: 80% (12/15) SCLC could be detected by Tc-99rn MIBI chest SPECT relied on visual mterpretation. In 12/15 (80%) cases, Tc-99m MIBI chest SPECT can correctly predict (which represent either positive SPECT with good response or negative SPECT with poor response) the results of chemotherapy response. The correlation between tumor uptake ratios which was obtained by planar images (total cotmts m the ROI over tumor + total counts in the same size of the ROI over the contralatera[ normal lung) and survival days (from SCLC dia~m-losisto patient death) is positive and good (R = 0.91 ). Conclusions: Tc-99m MIBI chest images is important to understand mdr-PgP expression in SCLC for prediction of patients * prognosis and chemotherapy response.

The purpose of this study was to evaluate the clinical value ofTe-99m MIBt scintigraphy for nodal staging of patients with primary malignant melanoma (MM) and for the diagnosis of recurrent disease in patients with a history of a surgically excised MM. Consequently, we studied 58 patients: 17 with histologically proven primary MM (AJCC stages I-III, group A), 9 patients with proven or suspected recurrent disease (group B), and 32 patients in fol/ow-up with no evidence of disease (group C). Planar images of regional lymph nodes were acquired 10 minutes post injection of 740 MBq of Tc-99m MIBI in group A. The injection site was carefully chosen depending on the topography of the primary lesion. A wholebody acquisition was performed in all groups and additional planar views were obtained on selected cases. In group A , we found regional node uptake in 4/17 patients that were fmally diagnosed as metastases by cytology/histology. Only one patient from this group had a palpable lymph mass at the time of the study. In group B, the following metastatic sites were found: skin (4), lung (5), brain (2), non regional lymph nodes (4), bone (2), liver (1). All lesions except the liver metastasis, showed intense MIBI uptake. In group C (patients in complete remission) MIBI scintigraphy was normal in 28/32 patients. However, the technique detected in 4 patients abnormal uptake loci: lymph nodes (3), lung (1) and skin (1). These lesions were further c o , r e e d by cytology/histology and conventional imaging techniques. In conclusion, our resuks suggest that Tc-99m MIBI scintigraphy could be a valuable tool in the primary staging of MM patients and in the diagnosis of recurrences during follow-up.

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C. Soler*, P. Beauchesne**, F. Dubois*, J. Brunon** * - Dept of Nuclear Medicine, H6pital Bellevue, CHU Saint-Etienne, Fra, ** - DepI of Neurosurgery, H6pital Bellevue, CHU Saint-Etienne, France,

C. Soler* MD, P. Beauchesne MD, B. Perpoint MD, N. Prevot MD, J.N. Talabard MD, F. Dubois MD. *- Dept of Nuclear Medicine, CHU Saint-Etienne, H6pital Bellevue, France.

THE ROLE OF 99'~'Tc-MIBIBRAIN SPECT FOR FOLLOW UP OF PATIENTS WITH HIGH GRADE GLIOMAS TREATED BY A RAD!OCHEMOTHERAPY ASSOCIATION. A PROSPECTIVESTUDY ON 22 PATIENTS. s°mTc-MIBIbrain SPECT is well known to be interesting for ~iscriminate tumor recurrence from radionecrosis in patients harboring grade 3-4 gliomas when the treatment failure accured. In order to specify the role of ~mTc-MIBI brain SPECT for follow-up of these patients, we have decided to undertake a prospective study. So, after gaining their informed consent, 22 patientswere included in protocol, all patients harboring a high grade glioma (grade 3 or 4 as Daumas-Duport grading), for 13 patients a total nr partial surgical resection was performed and sterentactic biopsy was realized for 9 patients. All patients underwent a radiochemotheraa,p_y association. The quality of surgical resection was appreciated by ~"Tc-MIBI brain SPECT and Computerized Tomography (CT) in first 72 hours, and for all patients the follow up by ~Tc-MIBI brain SPECT and CT have started at the end of radiotherapy and 2 courses of chemotherapy and were repeated --:qtwo months until death of patients. The results are : * ~'mTc-MIBI brain SPECT as more specific and sensible than CT for evaluating residual tumor after surgery (first 72 hours), * Volumes and index ratio of tumor are excellent for predicting efficacity of treatment and they are correlated with clinical evolution of patients. * For patientswith complete resection, we noted that SgmTc-MIBIbrain SPECT was positive on post-treatmentcontrol as well as CT brain. * According to the dramatic evolution of malignant gliemas in spite of existing therapy, 9~Te-MIBI brain SPECT showed in many patients a <(silent ~ residual tumor. In the light of our preliminary results, we think that ~mTc-MIBI brain SPECT seems to be excellent for follgw-up of patients treated for malignant gliomas. Perhaps, this tomoscintigraphy will help us to understand more accurate this dramatical disease.

DETECTION OF LYMPH NODES AND VISCERAL METASTASES OF THE BREAST CANCER : A NEW ROLE FOR THE 99~Tc-SESTAMIBI SC1NTIGRAPHY AND TOMOSCINTIGRAPHY. Aim : The goal of this study was to shown the possible interest of 99mTc-Sestamibi (MIBI) scintigraphy for the detection of breast cancer metastases. Materials and Methods : 27 female patients with lymph nodes, bones, or lungs suspected breast cancer metastases were studied with 99~Tc-MIBI scintigraphy or tomos.~intigraphyin comparison with X Ray study, 99mTc-HMDPbone scan, CT or MRI. A dual large field of view gamma-camera equipped with high resolution and low energy collimators was used. Results : A 99mTc-MIBIuptake was found for 17 patients. 99~Tc -MIBI uptake was correlated to breast cancer metastases proved by anatomopathological study. For I0 patients no 99mTc-MIBIuptake was found according with others imaging modalities for 6 patients. On the other hand, for 4 patients without MIBI uptake, CT, MRI or 99=Tc-lqA,IDPbone scan revealed one or more breast canccL'metastases according with histopathological evaluation. For 4 patients showing a discordance between 99=Tc-MIBIscintigraphy and others imaging modalities, a drug resistance in relation with an over selection of the natural detoxificatfun process involing P-Glycoprotein could be suspected. Indeed, Piwnica-Worms has found that 99= Tc-MIBI is a transport substance recognized by P-Glycoprutein, wich is an energy-dependent drug effiux pump, meaning that accumulation of MIBI in MDR cells is decreased. lnfortunatly an immunohistochelical evaluation could not be done. But, the clinical evolution was rapidly fatal and seemed to confirm that hypothesis. In conclusion, 99mTc-MIBI scintigraphy seems to be interesting during follow up of breast carcinoma, on the one hand for the detection of metastases, and, on the other hand, in future 99mTc-MIBI scintigraphy could be used for the detection of the PGlycoprotein.

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R. Lebtahi, G. Cadiot, J.P. Marmuse, C, Vissuzaine, L, Sarda, D. Daou, N. Delahaye, M, Mignon, D, Le Guludec. HSp. Bichat, Paris, France.

_H. Moustafa*; A. Zaher**; H. Farag** and I. Ezzat**. Nuclear Medicine Departments in Kasr E1 Aini * and Cancer Institute**, Cairo Universit3". ASSESSMENT OF TREATMENT RESPONSE & TUMOUR VIABILITY USING T1201, Tc-I~flBI AND Tc-MDP IN BON~ ;,5"D SOrT TISSt,T SARCOMA

VALUE OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN THE DETECTION OF GASTRINOMA: COMPARISON WITH SURGICAL DATA. We prospectively evaluated the ability of Somatostatin receptor scintigraphy (SRS) to detect gastrinoma compared to surgical and histological findings. Twenty nine consecutive patients (pts) with sporadic Zollinger Ellison syndrome, considered curable by surgery after preoperative imaging techniques (endoscopy, US, CT, endoscopic US and SRS) were studied. Thirty nine gastrinoma were found in 26/29 pts: they were located in the duodenum exclusively (n=9 pts), in lymph nodes exclusively (n=10 pts) or in both sites (n=7 pts). In one pt, 1 liver metastases was also resected. Abdominal US and CT were positive in 3 cases. Endoscopic US was positive in I9/26 (73%) and SRS was positive in 19/26 pts (73%), the combination of both techniques lead to a sensitivity of 90%. SRS was the only positive preoperative technique in 6/26 pts (23%). In 3 pts, no tumor was found: in one pt, SRS and EUS were considered falsely positive; in this pt, preoperative and post-operative SRS showed the same 2 hot spots, suggesting that at least 2 gastrinoma were missed by laparotomy. In the second pt, all preoperative investigations were negative, but biology remained positive after surgery. In the third pt, EUS and SRS were both falsely positive and showed an accessory spleen mimiking a neuroendoorine tumor. We concluded that the association of endoscopic US and SRS enhanced the global sensitivity of all preoperative imaging techniques, which thus reached 88%, a percentage only obtained in these sites with invasive techniques. Added to the previously demonstrated ability of SRS to detect liver or extra-abdominal metastases and modify clinical management, our results suggest that SRS should be performed when curative surgery is indicated.

1030

Fil~.' five patients with bone and soft tissue sarcoma (B&STS) were in'raged following IX.' injection of 5 mCi of 7"1-201.20 mCi of Tc-~EBI and 20 mCi Tc-MDP in 3 separate days. Images were analyzed qtmntilatively and qualitatitively with calculation of L/N ratio and a cut off level of L/N ratio > 1.9 was considered positive for viable tumour. In the untreated group (23 patients, the mean L/N ratios for blood pool (BP), delayed bone scan (DBS), TI-201 and Tc-MIBI were 4.5, 7.1. 5.1 and 4.2 respectively. Ten patients were assessed after 3-6 cycles of chemotherapy by same imaging techniques and results were correlated with percentage of necrosis histopathologically. Good responder (6 patients) with turnout necrosis > 90% had 1.67, 2.32, 1.26 and 1.03 mean uptake ratios for BP, DBS, T1201 and Tc-MIBI respectively. Wherea~ bad responders with necrosis < 90% had high mean uptake ratios of 3.8g, 6.37, 3.5 and 1.97 in the same images respectively. The follow up group (32 patients) included 3 subgroups: (A) Controlled group with no evidence of recurrence with normal uptake ratio of 1.14, 1.61, 0.84 and 0.83 for BP, DBS, T1-201, TcMIBI respectively, (13) 11 patients with recurrent viable tumour with mean uptake ratios of 2.43, 2.62, 2.02 and 2.07 respectively, (C) 5 patients with additional infection with mean ratios of 1.91, 2.89, 1.78 and 1.83 in the same order. The serLsitivity and specificity of T1-201 were (82%~ 86%), Tc-MJBI (91%, 86%), BP (91%, 67%) and DBS (49.5%, 24%) respectively. To conclude: Both 2"1-201 and Tc-M]BI should replace Tc-MDP to monitor response to preoperative chemotherapy and detect viable turnouts.

P 361

P 359 H. Moastal
A prospective stud), of 60 post tt~,roidectomy patients underwent 100 studies to compare the efficiency of addition of Tc-99m-MIBI, 71-201 to 1131 whole body scanning (WBS)in the follow up of differentiated thyroid cancer. Their age ranged 16-67 years with 41 females and 29 males.' The group included 45 papillat3,, 28 fbllioular and 2 h0rthl.e cell carcinoma. Forty. lxvo scans were performed before 1-131 ablative therapy and 58 scans were performed after 1-131 ablative therapy. The presence of local or metastatic cancer were diagnosed on clinical, biochemical, radio'logic and/or histopathologic finding. In preablative group, 1-131 WBS was better in evaltmtinn of extent of residual thyroid tissue in evaluation of extent of residual thyroid tissue in the neck with similar results in early Tc99m-~vflBI and T1-201 scans at 20 minutes, whereas there was no uptake in residual thyroid tissue in late scans at 2 hours in Tc-99m-MIBI and "11-201 with better accumulation in metastatic cervical lymph nodes in 6 scans with one false positive scan. In post ablative group, Tc-99m-IVllBI and T1-201 detected additional 4 positive cervical lymph nodes and 3 metastatic'lung lesions compared to negative 1-131 scan. Whereas they were negative in one recurent lesion in thyroid and cervical lymph nodes and one roegastalic lung lesion. To conclude, the addition of Tc-99m-MIBI or TI-201 offer high diagnostic yield in the follow up of differentiated thyroid cancer in both pro- and post-ablative groups with no need for withdrawal of homaonal therapy',

M. Myslive~ek i, P. Koranda I, M. Hartlov~ 2, N. He fman z, V. Hu~tk I, M. Du~kovA 3 Depts. of Nuclear Medicine l, Radiology 2, and Pathology 3, University Hospital Olomouc, Czech Republic TECHNETID~-99m-MIBI SCINTIM/dqHOGRAPHY FOR DIAGNOSIS OF BREAST LESIONS. COMPARISON WITH CONTRAST-ENHANCED ~I. The aim of the study was to compare the diagnostic accuracy of scintimammography ( S M ) using 99~c-MIBI in the diagnostic workup of patients suspicious for breast t~mors with that of contrast-enhanced ~iRI. Methods: Seventy patients with indeterminate ma~ograms underwent preoperative prone planar and SPECT SM and pre- and postcontrast-enhanced MRI. Quantitatively determined signal increase after application of Gd-DTPA was compared with visually scored sestamibi uptake, and diagnoses of both methods were correlated with the final histopathologic results. ~esults: Overall sensitivity, specificity, positive and negative predictive values (PPV, NPV) of SM for diagnosing breast cancer were 80%, 91%, 83% and 89%, respectively. MRI provided sensitivity 68% only, specificity 80%, PPV and NPV 65% and 82%, respectively. Conclusions: Due to its considerably higher sensitivity, specificity, PPV and NPV in comparison with contrast-enhanced MRI in our group of patients, SM rather than HRI may be suitable to differentiate malignant and benign breast lesions and to reduce the number of breast biopsies which yield benign results. Thus, this method may be suggested as the preferable tool in the diagnostic workup of patients with indeterminate mammographic findings.

P 362

,H.~ang,

L B i a s s o n i , B Panizza, I Fogelman, M Gleeson. Dept of S u r g e r g and " T h e Clinical PET C e n t r e " UMDS Guy's and St Thomas' Hospitals, London UK.

Evaluation of Nedtastinal Netastases in Patients with Lung Cancers Using To-ggm-MIB1 SPELT: Co~trJson with LT s c a n

Tu'~19m-NIHl SPECT has been studied to evaluate the mediastinal lymph node metastases, however u few dates directly compared with surgical r e s u l t s , its role has not been d e f i n i t e l y In this study, ~ d i r e c t l y compared the resuHs of

established. To-99m-MIBI

SI~CI" and cr with surgical results for evaluating the medtastinal lymph node metastases ~n 32 patients (25 N,7 F, mean nge=58+14 ) with lung cancers (14 epidermoid, 10 adenooaruinome, $ small call lung cancer).

Before surgical operation, all patients

underwent

the Tv-~OrMIBI SPECI ( 740 ~ q , iv ) and LT chest scan, I~IHI SPl~Cr ned Cf images were qualitatively analyzed, then their results were ooslpared with pathological findings. ]'he results were l i s t e d in the table. ....................................................... C T NIBI SPELT .

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S~-; ;C;--

Pts NO. 10 5 13 4 ..................................................

(TP: true positive, FP= false positive, TN:true negative, FN= f a l s e negative). The result shewed the NIBI SPELT has better s l ~ 3 i f l o i t y ($7g) tiara CT scan (87g). ]'his study dee~us%rates that NISI SPELT is accurate and effective t~l in evaluating the mediastinal metastases in patients with lung oaee~r. In particular, the NIHI SPELT seeme

to be better than LT scan, hut the further study Is needed.

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P 360 J.X.Zhmeg, ~[. LI. Dept. of Nuclear Nedioine, Rui Jin Hospital, Shanghai, P. R. CHINA

C O

=m

PRELIMINARY EXPERIENCE WITH 18-FDG PET SCANNING IN PAR/%GANGLIOMAS O F T H E H E R D A N D NECK. him:evaluation of FDG in patients with paragangliomas of t h e h e a d a n d neck. M e t h o d s : 9 p a t i e n t s (5 m a l e s a n d 4 females) w i t h ii l e s i o n s (9 g l o m u s j u g u l a r e a n d 2 c a r o t i d b o d y t u m o u r s ) were studied; age ranged f r o m 35 to 81 y e a r s (median 66); 2 patients were untreated at t h e t i m e o f t h e scan, 7 p a t i e n t s h a d b e e n p r e v i o u s l y t r e a t e d (2 h a d surgery, 3 r a d i o t h e r a p y , 2 s u r g e r y and radiotherapy). PET i m a g i n g was p e r f o r m e d w i t h t h e w h o l e b o d y t o m o g r a p h S i e m e n s E C A T 951R. 250 MBq of FDG were injected in a previously established line in the antecubital fosse. Emission and transmission scans w e r e p e r f o r m e d . R e s u l t s : P E T F D G s h o w e d c o r r e c t l y all 3 l e s i o n s demonstrated by CT/MRI in the 2 untreated patients (SUV range 8.05-13.67). In the p o s t t h e r a p y g r o u p PET F D G w a s p o s i t i v e in 4 k n o w n lesions, all d e m o n s t r a t e d by MRI (SUV r a n g e 4.695.59); F D G s h o w e d 2 n e w l e s i o n s a n d w a s n e g a t i v e in o n e d i s e a s e - f r e e patient; in o n e p a t i e n t P E T w a s h e l p f u l in d i f f e r e n t i a t i n g i n f e c t i o n ( a b s c e s s in t h e neck, drained, w h e r e S U V was 3.13) f r o m r e s i d u a l d i s e a s e a f t e r s u r g e r y (SUV 7.34); in o n e p a t i e n t w i t h recurrent d i s e a s e PET w a s n e g a t i v e . T h e r e w e r e i0/Ii t r u e positives, 1 t r u e n e g a t i v e , 1 false negative. Conclusion: PET F D G s e e m s to offer another potentially useful approach to f u n c t i o n a l l y i m a g i n g of t h e s e u n c o m m o n tumours.

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P 363

P 365

I. Garry, S. B/key, N. Sinyam/n and J. Sayfan', Fla~mek Med/cal Center, Afula, Israel

A NEW SCINTIGRAPHIC COMBINATION FOR THE EARLY DIAGNOSIS AND EVALUATION OF PRIMARY MAMMARY CARCINOMA AND ITS AXILLAKY LYMPHATIC SPREAD The aim of ttm study Lsto hm-oduce a new c o m b h ~ s c ~ g , ' a t ~ c method (COMB) for the early diagnosis and evaluation o f primar]

mammary carcinoma at~ ~ ~

~ c

s~ead. Om preaimmry

mmlts are presented here. Tw~mty-five women with palpable breast nmss were evaluated by a combiaafi-on of Tc-MIBl scan, anti-CEA m o . o c k . ~ ,.nfil~ sca~t(MoAb)~ ~ l y m p ~ (LYM). ~ resultswere c~m~q~m-edwid~ findh~gs a~ physi~:~d~:~ulm~r~ .~.~ry remks of this study are mmmafiz~ i , the foilowi~ table:

Sp:c~

-I7='I= I -I=' -

60~

95%

95~

65"% [ 95=/.

60%

95%

A c c o t f f ~ to txtr rea~ts, MIBI study was f o ~ to be tl~ most smsitire and MoAb study was tl~ m0st spedfi¢ for the wahafion of wimary lesiom~ Subctaaneous l y m p ~ g r a p h y was found to be the most ~=rMtk~ and MIBI saJdy the most slmcifie for tt~ e v a h ~ o n of mdlla~ lymph node spread. The combimatkm of the three studies raised both se~tivity ~md spedficity of the study for the diagnosis of primary and m e ~ u a i c ~ lesions up to 95%. This study is now in progress to assess th~ value of this method in much highe~ numbe~ o f pafiemts

P 364 A.C, Kole, J. de Vries, W. Vaalburg. PET Center and Department of Surgical Oncology, Groningen University Hospital, Groningen, the Netherlands

I. Uriarte, R. Quirce, C. Gut i~rre z-Mendiguchia, A. Montero, A.Vega, I.Banzo,NK.Vallina, JM.Carril. S~IgVICIO DE MEDICINA NUCLEAR HOSPITAL UNIVERSITARIO M.VALDECILLA. SANTANDER. ESPA~A. ROLE OF M I B I - S C ~ IN THE D ~ I S OF NC~PALPABLE LESIC~S WITH ISOLATED MICROCALCIFICATIC[qS C~ MAM~0GRAPHY

Microcalcifications may be the only suspicions ~aphicaly sign of malignancy in the breast, but it involves a high number of false positive and therefore an indesirable numher of unnecessary biopsies. To evaluate the contribution of s c i n t i ~ a p h y with 99mTe-MIBI (MIBI-Sg~) to reduce the number of unnecessary biopsies in this patients we performed a prospective study in 29 patients with non palpable breast lesions in whom biopsy was indicated by microcaleification pattern on mammography (MS) . According to the MS signs the probability of malignancy ~ms: high (HP) in 6 patients, intermediate (IP) in 16 and low (LP) in 7. An abnormality rate from 0 (absolutely normal) to 4 (very abnormal) was given to each MIBI-SMM, only 0 was considered normal, and the results were cot%oared with the final histologic diagnosis.There were ii malignant and 18 bening lesions. RESULTS: The overall results show that ii of the 18 benign lesions were MIBI negative and i0 of the Ii malignant were MIBI positive (8=91%). The only i benign lesion in the HP group was MIBI negative, and 4 of 5 malignant were MIBI positive. In the 17 benign lesions in the IP and LP groups together I0 were MIBI negative (E=59%) and the 6 malignant were MIBI positive (S=I00%) . The PPV and NPV for the IP + LP groups were: 40% and 100% respectivily. CONCLUSION: According to this results, the use of MIBI-SMM may he optimized when is applied to non palpable lesions presenting with microcalcifications of intermediate and low probability of malignancy in MS, allowing the reduction of 59% of unnecessary biopsies.

P 366 C. Gutierrez -Mendiguchia, I .Uriarte, R. Quirce, A.Hernandez, A.Vega, JM.Carril SERVICIO DE MEDICINA NUCLEAR HOSPITAL UNIVERSITARIO MARQUES DE VALDECILLA

mmT~Dm. RESPONSE TO CHEMOTHERAPY MEASURED WITH L-[1-11C]TYROSINE AND POSITRON EMISSION TOMOGRAPHY. Because chemotherapy kills cells at a fixed time point in their cell cycle, an exponentional decrease of tumor metabolism is expected when monitoring therapy with PET. Possibly, patients who respond well have a faster decreasing metabolism than non-responders. In order to obtain more information about the effect-curve of chemotherapy, the amino acid uptake during therapy was monitored using L-[1-11C]-tyrosine (TYR) with PET in a patient with breast cancer receiving six courses of chemotherapy. The patient, who had advanced breast carcinoma, was scanned before therapy and on thºe seventh day after each course using a Siemens ECAT 951/31 camera. Standardized uptake values (SUVs) based on lean body mass were calculated from a twenty minute static scan starting 20 minutes after injection of 370 MBq TYR. Images were corrected for attenuation. After completion of chemotherapy radical mastectomy revealed fibretic tissue with scattered viable tumor ceils at the primary tumor site. This was regarded as a good but not complete response. Uptake of TYR in the tumor decreased linearly during chemotherapy, although the first effect could only be established after two courses. Maximum and average SUVs gave the same results. These results indicate that 2,0 ~ --e-- COlltra[ateral T ~ --o.-. . . . 9e chemotherapy has a linear rather 15 -o-- maximum than an exponential effect. Predicting therapy-outcome with
1032

A.Montero,

ESPA~A

99n~c-MIBI S C CORRELATIC~ ~ D ~ I S AND ~ C

~ THE A L

IN NC~ PALPABLE LESI(I~-S. UPTAKE I N T ~ I T Y , HISTOLOGICAL PROBABILITY OF M A L I ( ~ t ~ Y

To optimize the use of scintimamaography with 99mTcMIBI (SMM-MIBI) in in the diagnosis of nc~ palpable lesions, we performed a prospective study in 79 patie/its with biopsy indicated by manmography (MG), 38 were benign (B) and 41 malignant (M). According to the MS signs the probability of malignancy was: high (HP) in 28 patients, 4 B and 24 M; intermediate (IP) in 31, 18 B and 13 M; low (LP) in 20, 16 B and 4 M. S~94-MIBI was performed i0' after the intravenous injection of 740 MBq of 99mTc-MIBI in the opposite arm to the breast afected, acquiring prone lateral and AP views during !0' with a HR collimator. SMM-MIBI was evaluated by three observers without know the histological diagnosis (HI)) and MS results. An abnormality rating from 0 (no uptake) to 4 (highest uptake) was given and co~oared with MS and HD. Results: 18 of the 38 B (47%) showed no uptake, and none showed uptake higher than 3. 26 of the 41 M (63%) showed uptake higher than i and no uptake in 3 (7%). According to the MS probability of malignancy, with independence of the HI], we found that in the PIP group 68% showed uptake higher than i and 32% higher than 2; in the IP 58% were lower than 3 and 32% showed no uptake; in the LP 80% were lower than 2 and 25% showed no uptake. When the HD was also considered, we found that in the B lesions 100% in the HP, 50% in the IP and 31% in the LP did not show uptake. However,in the M lesions the rate was higher than 1 in 78% in the HP, 38% in the IP and 50% in LP with no false negative values in this group. Conclusions: The extreme values of the abnormality rating corresponded with the HI], but there was an overlapping for rates i and 2. Despite the different prevalences there does not seem to be a correlation betweerl the MS signs and the intensity of uptake in $594.

P 367

P 369

S- V i d a l - S i c a r t A. Muxi, F. Pons, R. Herranz, C. Laterza, F. Novell', M. Trias*, J. Setoain. N u c l e a r Medicine and Surgery* Departments. Hospital Clinic. University of Barcelona. Barcelona, Spain.

U. Uysal, L. Kostakolg~, D. Uzal, M. Hayran, N. Elahi, C.F. Bekdik. Hacettepe University Medical Faculty, Department of Nuclear Medicine, Ankara, Turkey.

RADIOIMMUNOGUIDED SURGERY OF COLORECTAL CARCINOMA WITH A lll-In LABELLED ANTI-TAG-72 MONOCLONAL ANTIBODY

MONITORING WITH T1-201, Tc-99m-SESTAM1BI IN PATIENTS WITH SUPRATENTORIAL GLIOMAS (STG):CORRELATION WITH PROGNOSIS.

Aim: The goal of this study was to evaluate the u s e f u l n e s s of r a d i o i m m u n o s c i n t i g r a p h y (RIS) and r a d i o i m m u n o g u i d e d surgery (RIGS) in localizing colorectal tumoral tissue. M a t e r i a l and Methods: Twenty eight patients (19 males and 9 females), mean age of 65 ~ 12 years, were studied. N i n e t e e n p r e s e n t e d a p r i m a r y tumour and I0 were suspected of recurrence. Preoperative diagnosis was made in all cases acording to hospital protocol. One mg of Monoclonal a n t i b o d y (MoAb) CYT-103 labelled with 148-185 MBq of lll-In was injected. RIS p l a n a r and SPECT images were p e r f o r m e d at 48 and 72 hours p o s t i n j e c t i o n and RIGS between 76 and 96 h after dose administration. A systematic s c r e e n i n g with the probe was p e r f o r m e d on aorta, liver, small bowel, colon, rectum and all suspicious areas by triplicate. After tumour resection, the tumour bed was scanned to a s c e r t a i n complete resection. We considered as p a t h o l o g i c a l an index tumor to b a c k g r o u n d greater than 1.5. Results: RIS: In p r i m a r y tumors we found i0 TP and 8 FN. All the recurrences were TP (n = I0). RIGS: In p r i m a r y tumors we found 15 TP and 3 FN. In r e c u r r e n c e s 8 TP and 2 FN were observed. RIGS c h a n g e d the traditional surgical procedure in two cases with small tumor deposits. There were statistical differences b e t w e e n counts in normal tissue versus tumoral tissue. Conclusions: RIGS, as a c o m p l e m e n t a r y technique to RIS, is p a r t i c u l a r l y useful in recurrences and could help the surgeon in the r e s e c t i o n of small tumour deposits which are difficult to localize.

Our aim was to ascertain the prognostic value of TI-201 and Tc-99mSestamibi (MIBI) as compared with that of CT/MRI and histologic grading in patients (pts) with STG. Sixteen post-surgical patients (mean ageiSD: 38.5+14.8) underwent consecutive TI-201 and MIBI prior to therapy, 1, 3, and 6 months posttherapy. The gold standard for the presence of residual disease was the 18to 24-month clinical follow-up and repeat CT/MRI studies. A total of 128 SPECT studies were correlated with concomitant CT/MRI studies. Tumor/background if/B) ratios were obtained on re-oriented transverse slices on consecutive SPECT studies of each patient. T/B ratios were used as indices with which the patient prognoses were correlated. The results were as follows; 1. the median "171-201and MIBI indices in patients who expired or had disease progression (n=8) were sigmficantly higher than those who had disease regression (n=8) (p<0,05). 2. in the prediction of patient prognosis; a) 1- and 3-month TI-201 and MIBI studies were superior to CT/MRI, b) in pre-therapy studies there was a trend for TI-201 T/B ratios to be superior to histologic grading (p=0,0~25) in determining the clinical behavior of the tumor, 3. the earliest and most sensitivetime for predicting prognosis was 1 to 3 months following therapy for both TI-20I and MIBI studies. In summary, the TI-201 and MIB1 indices proved useful for predicting prognosis of patients with STG as early as 1 to 3 montl~ after the completion of therapy.

P 368

P 370

I. Gart~, S. Bikov, N. Binyamis and J. Sayfan~ Haemek Medical Center, Afula; Israel

A NEW SCINTIGRAPHIC COMBINATION FOR THE EARLY DIAGNOSIS AND EVALUATION OF PRIMARY MAMMARY CARCINOMA AND ITS AXILLARY LYMPHATIC SPREAD The aim of this study is to introduce a new combined scintigraphic method (COMB) for the early diagnosis and evaluation of primary mammary carcinoma and its axillary lymphatic spread. Our preliminary results are presented here. Twenty-five women with palpable breast mass were evaluated by a combination of Tc-MIBl scan, anti-CEA monoctonal antibod scan(MoAb) and subcutaneous lymphoscintigraphy (LYM) The results were compared with findings at physical examination, mammography (MAM), surgery and histopathology The preliminary results of this study are summarized in the following table: Primary MAM [MIBI IMoAb Scnsit 90% 95% 60% Spccif 60% 80% 95%

Lymphatic COMB MoAb ]MtBI ,LYM [ C O ~ 95% 80% 85% 90% 95% 95% 65% 95% 60% 95SZ~

According to our results, MIBI study was found to be the most sensitive and MoAb study was the most specific for the evaluation of primary lesions. Subcutaneous lymphoscintigraphy was found to be the most sensitive and MIBI study the most specific for the evaluation of axillary lymph node spread, The combination of the three studies raised both sensitivity and specificity of the study for the diagnosis of primary and metastatic axillary lesions up to 95%, This study is now in progress to assess the value of this method in much higher numbers of patients,

O

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C

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P.HeJ~, S.Mayer, M.Schwaiger, R.SenekowitschSchmidtke Nuklearmedizinische Klinik der Technischen U n i v e r s i t A t N~nchen, Munich, G e r m a n y THE R A T E OF M E T A B O L I S M OF M E T H I O N I N E (MET) L Y M P H O M A C E L L S IS N O T L I M I T E D BY T R A N S P O R T

IN

C - l l - l a b e l l e d Met is u s e d for t u m o u r i m a g i n g a n d t h e r a p y m o n i t o r i n g b y PET. The u p t a k e of Met as well as its i n c o r p o r a t i o n into the T C A - i n s o ! u b l e fraction in treated and untreated cells were investigated in vitro in order to determine w h e t h e r t r a n s p o r t is r a t e - l i m i t i n g in the r a t e of m e t a b o l i s m of Met. BHL-4 cells, g r o w n in RPMI 1640 w i t h 1 m g / l Glc, were treated with vincristine (0,02 #g/l; alkaloid) for 4 hours. 20 h o u r s a f t e r t r e a t m e n t the cells w e r e i n c u b a t e d w i t h H - 3 - M e t (185kBq/ml) in combination with various unlabelled Met-conc e n t r a t i o n s (5-60 mg/i) at 37°C for 30 min. A f t e r s t o p p i n g the i n c u b a t i o n w i t h i c e - c o l d PBS, half of the s a m p l e s w e r e w a s h e d 3 times w i t h PBS. The macromolecules of the remaining samples were precipitated in i c e - c o l d 10% TCA. The p e l l e t s w e r e d i s s o l v e d i n 0 , 1 N N a O H + 1% SDS and the r a d i o a c t i v i t y was d e t e r m i n e d in a l i q u i d - s c i n t i l l a t i o n c o u n t e r . The r e s u l t s w e r e c a l c u l a t e d in nmol Met p e r 105 cells. The a m o u n t of Met in the T C A - i n s o l u b l e f r a c t i o n was n e a r l y c o n s t a n t o v e r all M e t - c o n c e n t r a t i o n s . In a d d i t i o n a l i n e a r c o r r e l a t i o n of M e t - u p t a k e to the M e t - c o n c e n t r a t i o n in the m e d i u m was found. Therefore, no saturation of Met-transport was m e a s u r e d up to 60 mg/l Met. C o m p a r e d to u n t r e a t e d c e l l s we f o u n d a s i g n i f i cant d e c r e a s e in the M e t - u p t a k e and in the TCAi n s o l u b l e f r a c t i o n in v i n c r i s t i n e - t r e a t e d cells. in c o n t r a s t to FDG t h e s e r e s u l t s s u g g e s t that the rate of Met m e t a b o l i s m d o e s not d e p e n d on the Met supply and transport.

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O

P 371 A. Dimitrakoooulou-Strauss', L.G. Strauss', H. Goldschmidt~, E Oberdorfer~, J. Kriesten', G. Kontaxakis', G. van Kaick'.tGerman Cancer Research Center, Heidelberg, =Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany

PET WITH C-11-AMINOISOBUTYRIC ACID (AIB) FOR DIAGNOSTICS AND THERAPY MANAGEMENT OF ONCOLOGICAL PATIENTS. The relevance of the use of amino acids in oncological patients is still an open question. We used a synthetic amino-acid, C-11-AIB, which reflects the "Alanine. like transport" (A-type) and has the advantage of a clear C-11-signal, since no metabolism occurs. We applied C-11-AIB in 15 patients (pts) with recurrent lymphomas (10 pts with Hodgkin's and 5 pts with Non-Hodgkin's lymphomas), in 10 pts with colorectal recurrencies, in 6 pts with hepatocellular carcinomas and 6 pt~ with brain tumors. Furthermore, we performed all studies as multitracer studies using the sequential application of O-15-water, C-11-AIB and F-18-FDG in order to gain the optimal information for the interpretation of the AIB-signaL Dynamic PET studies were performed over 30 rain (5"1 rain, 5*2 rain, 3*5 min) with 370-444 MBq C-11-AIB. ROIs were used to calculate time.activity curves for the tumor, the normal tissue, and the aorta. Parametric images of the influx and elflux of the AIB were caFculated using a two compartment model. For the input function we used the ROI data of a large vesse{ (median value of three vessel ROIs). The transport constants kl and k2 were calculated pi×et by pixeL The same model was used for the evaluation of the perfusion studies. The influx constant was calculated for FDG on the basis of the graphical Patlak analys!s. The AIB-uptake was in all tumor lesions low as compared to FDG. All tumor lesions w e r e positive for FDG. The highest tracer accumulation was observed for FDG as compared to the perfusion and the A-type amino acid transport (AIB). We observed two false positive results with FDG in surgically confirmed abscesses. Both lesions were negative in the AIB scans. AIB-scans were helpful for the differentiation of recurrent brain tumors treated with radiation therapy and in colorectal recurrencies. In contrast, malignant lymphomas demonstrated a low AIB-uptake independent from the histological subtype. Hepatocellular carcinomas demonstrated a liver equivalent AIB-uptake and coutd not be delineated. We noted no significant correlation between the amino acid influx (kl for AIB) and the FDG influx constant, while a low correlation existed between the influx of O-15-water and AIB (~=0.6). Comparable results were observed for k2 of O-IS-water and hie (r=0.54). The results show, that combined AIB studies can help to characterize tumor biology and are promising for the improvement of cancer treatment planing.

P 372 L.G. Strauss', L Schad', A. Dimitrakopoutou-Strauss', M. Knopp', J. Debus2, F. Oberdorfer', G. van Kaick~.'German Cancer Research Center, Heidelberg, 2Department of Radiation Therapy, University of Heidelberg, Heidelberg, Germany

P 375

D.Dey, LJ Hahn, PJ SIomka*, RK Kloiber. University of Calgary and Foothills Hospital, Calgary, Canada, *London Health Sciences Centre, University of Western Ontario, London, Canada.

COMPARISON OF X RAY AND TRANSMISSION COMPUTED TOMOGRAPHY ATTENUATION MAPS IN QUANTITATIVE CARDIAC SPET. In this study we compare the use of X ray CT and radionuelide TCT (Transmission Computed Tomography) attenuation maps in quantitative cardiac SPET. Tc-99m SPET images of an anthropomorphic cardiac phantom with uniformly distributed myocardial activity were obtained with a single-headed gamma camera [15 sec/fr, 120 fr over 360 degrees, pixelsize 4.75 ram]. Following decay of emission activity, TCT images of the phantom were obtained in the same orientation as SPET by using an uncollimared Tc99m flood source and a collimated single-headed gamma camera [20 mCi, 15 sec/fr, 120 fr over 360 degrees]. The attenuation coeffcient for water at the effective energy of the X-ray CT scanner ( E c T ) was found by measuring the half-value-layer for water. CT attenuation maps for Izl0 keV were obtained by scaling X ray CT maps at EOT with the ratio of attenuation coefficient of water at ECT to that at 140 keV. CT attenuation maps were registered to ~he TCT (and uniform SPET) images using a threedimensional automated registration method. Three additional sets of Tc-99m SPET -and- TCT images of the phantom were acquired using a 1t ml infero~basal defect; the specific activity ratio of the defect with the rest of the myocardium was 25%, 50% and 75%. For each SPET measurement, as reference for registration, TCT images were acquired in the same orientation as SPET. The original CT and TCT attenuation maps were registered to the TCT images corresponding to each defect. SPET images were eorreeted for scatter (dual energy subtraction) and for attenuation using Iterative Ordered Subset Expectation Maximization (OSEM) reconstruction with CT and TCT attenuation maps. The volume of each defect was calculated by difference-based region growing. Compared with filtered backprojection oniy (FBP), there is an improved accuracy in calculated defect volume with attenuation compensation using either CT or TCT map, but not in the average specific activity. While CT attenuation maps give more accurate calculated defect volumes, the differences in both defect volume and average specific activity between CT and TCT are less than 10%. We conclude that while CT attenuation maps give better quantitative results. TCT attenuatlon maps are acceptable and can be used.

P 376

D.A. Weber, S. Loncaric*, DK Shclton. University of CaliforniaDavis Medical Center,Sacramento, CA,

*University of Zagreb, ClinicalHospitalRebro, Zagreb, H R V T H E CROSS-TALK C O R R E C T I O N F O R D U A L R A D I O N U C L I D E

PET WITH F-18-FDG AND O-15-WATER AND GD-DTPA MRI IN PATIENTS WITH BRAIN TUMORS RECEIVING RADIOTHERAPY. The early diagnostics of viable tumor tissue in patients with brain tumors receiving radiotherapy is still a problem. The reported results using contrast enhanced MRI studies are not conclusive. We used PET with F-18-FDG and O-15-water as welt as MRI with Gd-DTPA in patients with treated brain tumors. Aim of the ongoing study is the comparison of the kinetics of the Gd-DTPAto the tissue perfusion and the regional FDG metabolism. The correlative assessment of the PET and MRI studies necessitates common land marks. Viable as well as necrotic tumor tissue must be idenfied and associated with morphological 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 Gd-DTPA, (parameter: TR=170 ms, TE=5 ms, FL=900, RFOVffi160*270mmz, MA=128"25~, TH=5 ms, 15 sections, acquisition time 22 sec). Double tracer PET studies were performed with O-15-water (1550-3600 MBq, 8"1 rain images) and F-18~FDG (240-360 MBq, 19 images, 60 rain). 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-IS-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 hypcand hypermetabolic areas, which were associated with hypo- and hyperintense regions in MRI. Therefore, FDG uptake correlated to the Gd-DTPAenhancement in the tumor region. The quantitative 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. There was no correlation between the Gd-DTPA kinetics and the tissue perfusion as measured by O15-water in the tumor region. In conclusion, Gd-DTPAseems to correlate with the FDG-uptake in the tumor area and is not perfusion-dependent in comparison to O-IS-water.

1034

IMAGING. Dual radionuclide i m a g i n g a l l o w s simultaneous e m i s s i o n and transmission imaging, viewing of paired tracers during the same clinical and physiologic state and eliminate problems in image coregistration incurred in comparing images from sequential studies. However, the crosstalk components (XC) present in one or both energy windows (EWs) in dual radionuclide study influence the detectability of cold defects and can lead to overestimate areas of hyperperfusion. Energy spectra, and planar and SPECT images were obtained for a point source placed at various depths in a water fiUed cylinder, a brain phantom with and without lesions, and a heart phantom. The brain phantom contained 10 lesions that range in size from 1 to 12 cm 2. The correction paxmneters determined from simulations and experimental studies were evaluated clinically for simultaneous imaging of Tc-99m and TI-201, and Tc-99m and Xe-133. For each radionuclide, images in 16 energy windows were recorded. These included: 1) 15 and 20% energy windows (EWs) centered over the Tc-99m (140keV) photopeak 2) 20 and 30% EWs at 70 keV and 15 and 20% EWs at 167 keV, 3) 20 and 30% EWs at 81 keV, 4) eight EWs, 5 keV wide, equally spaced between 90 and 130 keV.

Since tbe spatialand energy distributionof the Tc-99m crosstalkphotons in 171and Xe windows differfrom the spatialand energy distributionsof photopeak photons, Tc-photopcak images can not be used to obtain good estimate of the crosstalk component. The eight 5 keV E W were summed,

varying the number and the startingenergy in order to determine the energy window thatgives the bestestimate of the cross-talkcomponent, The point spread functions for crosstalk and scatter-correctionwindow measured at different positions in phantoms were used to determine the blurring function (2D Gaussian filter) that should be applied to scattercorrection window prior to crossmlk correction in order to account for small differences in spatial distribution of the photons in two windows. Cold defects of 10 to 60% with Xe and T1 were seen as 3 to 45% defects due to cross-talk from Tc. The study shows that large changes in lesion conmast and detectability due to Tc-crosstalk can be corrected using a third EW in dual radionnclide imaging of Tc-Xe and Tc-TI.

P 377 H. Harke., H. Fricke, J. van den Heft, W. Burchert, B.O. Knoop, H. Hundeshagen, Abteilung Nuklearmedizin und Spez Biophysik, Medizinische Hochschule Hannover, Germany

P 379 M. J. Guy, I. A. Castellano-Smith, D. Visvikis, M. A. Flower, G. D. Flux, R. J. Ott Joint Department of Physics, Institute of Cancer R e s e a r c h and Royal M a r s d e n NHS Trust, Sutton, U K

COMPARISON OF AN EXACT ITERATIVE EM-ML-ALGORITHM AND A COMMERCIAL FBP WITH ITERATIVE PRE-RECONSTRUCTION ATTENUATION CORRECTION.

IMPROVED A T T E N U A T I O N C O R R E C T I O N FOR ECT U S I N G C O N V E N T I O N A L CT: THE DUAL ENERGY D E T E C T PROCESS

For a three-headed SPEGT system (Siemens Gammasonics, Hoffman Estates, Illinois) with two high resolution parallel hole and an asymmetric fanbeam collimator we have developed an iterative EM-ML reconstruction algorithm including attenuation and scatter correction based on measured transmission data (SIRA). The commercial reconstruction algorithm is based on correcting projections before performing a FBP. In comparing forward calculated and measured projections a correction is applied iterative to the projections (IPC). Acquisitions were performed simultaneously with Tc-99m and TI-201. The respective transmission scans were obtained with Am-24I. To examine the effect of attenuation the phantom geometry has to be asymmetric. We used an asymmetric body phantom with rods (5cm diameter) of different absorbing materials and an asymmetric body phantom with Jaszczak heart insert. Furthermore we compared patient acquisitions with standard cardiac perfusion acquisition protocol. Transmission maps of the asymmetric body phantom with rods were generated out of the crosstalk-corrected transmission data with the SIRA and the IPC algorithm with different numbers of iterations, The SIRA algorithm generates a nearly undistorted p-maps compared to the p-maps with different artifacts of the IPC method. The reconstructed emission transverse slices show just small enhancements for the IPC algorithm but a very good geometrical shape and activity distribution for the SIRA algorithm. A regional activity analysis quantifies those results. Reconstructed images of the heart phantom and patient data are shown in a 3D display as a very sensitive tool for detecting small activity differences. The results show that only an exact iterative reconstruction algorithm can correct attenuation artifacts caused from asymmetric absorbers.

Accurate attenuation correction is a vital component of a n y q u a n t i t a t i v e E m i s s i o n CT (ECT) study, e s p e c i a l l y 131I m I B G SPECT w h e r e accurate a c t i v i t y c o n c e n t r a t i o n m e a s u r e m e n t s are required. In this case, conventional CT is often .used to obtain an a t t e n u a t i o n map, w h i c h is then scaled to the 131I e m i s s i o n energy (364keV). Scaling inaccuracies due to the i n c r e a s e d p h o t o e l e c t r i c component of the a t t e n u a t i o n coefficients of bone at CT energies lead to an overestimate of activity. Dual E n e r g y CT is m o r e a c c u r a t e but must be j u s t i f i e d against i n c r e a s e d cost and dose to the patient. We p r o p o s e a m e t h o d (Dual E n e r g y Transmission Estimation CT or DETZCT) of obtaining two a t t e n u a t i o n maps from a single CT scan u s i n g a conventional CT s c a n n e r operating at 120 and 140 kVp for alternate slices. The m i s s i n g slices of each m a p are r e c o n s t r u c t e d u s i n g cubic spline interpolation. The effect of the x - r a y b e a m s p e c t r u m has b e e n i n v e s t i g a t e d b y simulated scaling u s i n g the CT spectra a n d b y a p h a n t o m study. A s s u m i n g a perfect detector, segmented abdominal CT data predicts a mean activity o v e r e s t i m a t e of 2±3% for DETECT c o m p a r e d to 6±3% for the best single e n e r g y (120 kVp) CT m e t h o d w h e n scaled to 364 keV. These p r e l i m i n a r y results suggest that DETECT can offer reliable a t t e n u a t i o n c o r r e c t i o n for ECT w i t h no dose or user penalty.

t|O m

ell) L

Q. P 378

P 380

G. El Fakhri ~, I. Buvad, M. P~ltgrini~, P. Aimeicla"~, H. Benali', B. Bcndriem2, R. Di Paola ~. : U66 INSERM, Paris and 2 SHFJ, Orsay.

J. Patton, A. Satran, M. Stoner, M. Coppas, and M. Sandier, Vanderbilt University Medical Center, Section of Nuclear Medicine

,,l=l

cO

O P R O P A G A T I O N OF E R R O R S DUE TO SCATTER CORRECTION IN C A R D I A C SPECT RECONSTRUCTION: A MONTE CARLO STUDY Using Monte Carlo simulations, we studied how the errors in the projections due to imperfect scatter correction propagate during SPECT reconstruction and ~fect absolute quantification in cardiac imaging. Method: a SPECT acquisition of a c~diac phantom was simulated using the SimSel Monte Carlo code. The phantom included equivalent materials forsoft tissue, lungs, liver, spine and a left ventricle (LV) with a 10 mm wall thickness. Uniform 99mTc LV activity (7.7 10.2 MBq/ml) and liver activity (4.6 10 2 MBq/ml) were considea-ed. 64 projections were simulated over 360°. The 20% window images (I20) were calculated, as well as the projections corrected for scatter usiug the Jaszczak subtraction (JS) and a method based on factor analysis (FA). SPECT reconstructions were performed using l) filtered backprojectinn (Harm filter, fc= 0.9 cm~) without (FI3P) and with a non-uniform second order Chang altenuation correction (FBPC); 2) an iterative regularized backprojection method based on minimal residuals including a non-uniform attenuation correction (RBP). To study the error propagation in the LV region, a 2089 voxel LV ROI was drawn on the original volume and projected to obtain the corresponding projection ROIs. Results: the mean percent errors (MPE) between estimated and actual primary counts in the projection ROls are shown in lable 1, as well as those between the values reconstructed from the primary prt2iections ,'rod l?om the scatter corrected projections (for a fixed reconstruction scheme) in the LV ROI. The MPE between the bull's eye plots calctllated from the scatter corrected images and the primary pholon images are given in table 2.

I20 JS FA 120 JS FA 62 ± 14 14 ± 5 13 ± 6 23± 6 5±2 -4+4 17±5 6+5 -6_+5 23± 6 6± I -4±3 17±4 6±4 -6±4 23_+ 9 7±2 -2±4 16±4 8±3 -5 ::t 3 Table l Table 2 Taking the bull's eye plots calculated from the /me simulated activity as the reference, the MPE in absolute quantification was close to -90% for all images reconstructed using FBP. For FBPC (respectively RBP) reconstructions, the MPE were -20% (-19%) using primary projections, -7% (-6%), -15% (-13%) and -25% (-24%) using I20, IS and FA projections respectively. As partial volume effect (PVE) was not compensated for, the error in absolute quantification was greater with scatter.free images than with I20 images since the scatter counts in the latter partially balanced the activity underestimation due to PVE. 'Ihe PVE can be expected to result in a 25..40% reduction of estimated activity for a 10 mm wall (Buvat et al, J Nucl Med, 38: 324-329, 1997), consistent with the activity underestimation observed using either primary or scatter corrected projections. Conclusion: the errors due to imperfect scatter corrections get significantly reduced afleareconstruction. To improve absolute quantification in cardiac SPECT, scatter correction must be combined not only with attenuation correction, but a/so with PVE correction. projection ROI LV ROI FBP LVROIFBPC LV ROI RBP

NEW HIGH ENERGY COLLIMATORS OPTIMIZED FOR DISA CARDIAC SPECT USING A DUAL HEAD (90 ° GEOMETRY) SCINTILLATION CAMERA WITH 5/8 INCH CRYSTALS Dual isotope, single acquisition (DISA) 180 ° SPECT is an established procedure for simultaneously mapping distributions of Tc-99m-MIBI and (F-18)DG in the heart following a rest or stress perfusion, rest metabolism protocol. In order to take advantage of a new dual head, variable geometry scintillation camera with 5/'8 inch (15.875 mm) thick crystals, new high energy collimators have been fabricated. These collimators have improved spatial resolution (11.8 vs 14.1 mm FWHM of LSF at 10 cm in airat 511 keV and 8.4 vs 10.8 mm at 140 keV) when compared to those previously used, and a more uniform response with depth at 511 keV (106% increase in resolution from 0 to 20 cm versus 151%) and essentially the same at 140 keV (135% versus 138%). The resolution of the new collimators at 140 keV is the same as that for the low energy, high resolution collimator. The planar sensitivity of the new collimators was decreased (60 vs 93 cpm/pCi at 511 keV and 59.6 vs 107 cpm/pCi at 140 keV). However, increasing the crystal thickness to 5/8 inch resulted in a 100% increase in planar sensitivity at 511 keV and 10.1% at 140 keV. Positioning the two detector heads in a 90 ° geometry for a 180 ° acquisition results in an additional increase of 100% in sensitivity for both energies. The net gain in sensitivity is 158% for F-18 and 23% for Tc-99m. No degradation in collimated spatial resolution was observed with the thicker crystals. These changes have improved the diagnostic quality of DISA SPECT studies of the myocardium and should improve the quality/accuracy of gated SPECT and geometric ejection fraction determinations.

1035

P 381 I.Juvells 1,C.Falcbn2,J,Pavia 3,D.Ros 2 1Lab. Optics. Fae. Physics, 2 Lab. Biophysics and Bioengineering. Fac Medicine, Univ. Barcelona, 3Nuclear Medicine Department Hospital Clinic i Provincial of Barcelona. Spain ASSESSMENT OF THE IMAGE QUALITY IN ORDERED SUBSETS SPET RECONSTRUCTION

P 383 D.A. Weber. M. Ivanovic, and D.K. Shehon, J. Xu University of California Davis Medical Center, Sacramento, CA.

IMAGE REGISTRATION IMPROVES ACCURACY OF THE INTERNAL CAROTID ARTERY BALLOON TEST OCCLUSION Image registrationof serial S P E C T Tc-99m H M P A O

brain images

The original MLE-EM reconstruction algorithm requires a high number of iterations to provide acceptable images. A modified algorithm using selected subsets of projections has been reported by Hudson. This algorithm accelerates the original EM in a factor proportional to the number of subsets used. The aim of this work is to quantify the quality of the images as a function of the num-ber of subsets in order to assess the limitations of the algorithm. Simulated and real projections were obtained from a cylindrical phantom containing solid cylinders. Sixty projections with 200 kc in total and 1, 2, 5, 10, 20, 30 subsets were used. A projectorbackprojector pair including a uniform attenuation map and the spatially variant collimator detector response were used. The maximum value of the correlation coefficient between the theoretical and reconstructed images was 0.95 for 1, 2, 5, 10 subsets. This value decreased to 0.94 and 0.92 for 20 and 30 subsets. The number of iterations for which these values were achieved was 20, 10, 4, 1, 1 and 1 respectively. These results and those derived from other functions of merit show that the number of subsets cannot increase arbitrarily. When the number of iterations drops to 1, an increase in the number of subsets impairs the image quality. Finally, it should be pointed out that the maximum value of the correlation coefficient for 2 subsets is similar to the one that was obtained by using an acceleration factor of 2 in the successive substitutions algorithm and in an accelerated additive algorithm. No further factors were investigated owing to instabilities of the classic algorithms. This work has been supported in part by the CICYT (SAF96/0062)

collected pre- and post- balloon test occlusion (BTO) of the internal carotid artery (ICA) was investigated to evaluate the influence of registration on the quantitative accuracy of estimating relative perfusion within the area of the middle cerebral arterydistribution. The image registration technique applied was experimentally validated to provide a SPECT registration accuracy of <1 pixel for transverse plane translations and rotations and for sagittal plane rotation limited to <6 ° for 128x128x64 images with a pixel spacing of 2.5 mm/pixel. Ten patients being worked up for neurosurgical procedures in the treatment of neoplastic lesions by permanent ICA occlusion were administered 925 Mbq of Tc-99m HMPAO intravenously on two occasions for a baseline and post BTO. Registered MR and CT images were used to develop the ROIs for the SPECT images and ROIs were symmetrically placed over the left and fight middle cerebral artery distribution on the registered and unregistered serial SPECT images to provide an assay of compromised collateral circulation. The observations were: the contralateral ratios in unregistered images showed changes of: <5% in 2/10 patients and 814% in 8/10 patients. Differences in slice selection and ROI positioning varied this ratio by as much as 5%. Repeat calculations on registered images using ROIs defined on MR or CT showed changes of: <5% in 6/10 patients, 5-8% in 2/10 patients and >10 % in 2/10 patients. Alterations in uptake ratios <5% indicate that collateral circulation is intact and the ICA can be sacrificed without the risk of stroke. These findings show that image registration provide the means to objectively improve the accuracy and reproducibility of the ICA BTO study in nuclear medicine and image registration should be considered for improving the accuracy and reproducibility of other nuclear medicine procedures that require ROI analyses of serial images.

P 382

P 384

P.Almeida* ,M.J.Ribeiro**, M.Bottlaender*, O.de Dreuille*, C.Loc'h*, B.Mazi6re* and B.Bendriem*, *SHFJ-CEA,Orsay(FR), *S.Biofisica-FMC(PT) Q U A N T I T A T I V E K I N E T I C S OF 1 2 3 I - E P I D E P R I D E IN B A B O O N BRAIN MEASURED WITH ATTENUATION CORRECTED SPECT The p u r p o s e of this study was to e v a l u a t e the p o t e n t i a l of a t t e n u a t i o n c o r r e c t i o n (AC) in SPECT to q u a n t i t a t i v e l y m e a s u r e the k i n e t i c s of 123IEpidepride(EPI), a doparninergic D2 receptor ligand. 0.4 G B q of 123I-EPI were iv i n j e c t e d in a baboon after a 2 day treatment with lugol. E m i s s i o n (E) a n d t r a n s m i s s i o n (T) m e a s u r e m e n t s (M) were acquired on a dual-headed system with v a r i a b l e h e a d angulation. The p r o t o c o l was: 12 EM (20 m i n each, heads at 180 °) s t a r t i n g 5 m i n pi f o l l o w e d b y one TM (24 m i n h e a d s at 90o). T M were o b t a i n e d w i t h 2 s l i d i n g line sources of 153Gd (2.8 GBq). The (AC)-SPECT was c a l i b r a t e d u s i n g a 14.8 cm c y l i n d e r u n i f o r m l y filled w i t h a 123I s o l u t i o n of k n o w n r a d i o a c t i v i t y concentration. A striatal model (RSD) in a b r a i n s h a p e d p h a n t o m s u r r o u n d e d b y a skull {bone e q u i v a l e n t material) was also imaged u n d e r the same c o n d i t i o n s r e s u l t i n g in a 90% r e c o v e r y of a c t i v i t y concentration. The AC and non-AC kinetics in b a b o o n striatum (STR) and cerebellum (CRB) are shown in the figure. U s i n g (AC), the c o n c e n t r a t i o n values w e r e m u l t i p l i e d b y 2.5 and 2 in STR a n d CRB r e s p e c t i v e l y at 4 h pi. The % i n j e c t e d d o s e / 1 0 0 ml w e r e then 6 in the STR and 0.7 in the CRB. At that time, AC i n c r e a s e d r_..=,,~)=) S T R / C R B ratio from 7 to 9 a°°°~~ _ ~ I showing that AC affects ~l~"~.-[~~"--*14-sm~ differently the two ~-ca,~ structures. Scatter and ~-sm~ Point Spread Function ~ ~ w ~ ' l corrections are n o w u n d e r ]~-~-~'~.{~I development to further "% ~ I~ ,~ ~ ~ e n h a n c e the q u a n t i f i c a t i o n .

1036

~ , J. Machac, Division of Nuclear Medicine The Mount Sinai Medical Center, New York, NY, USA

EVALUATION OF A NEW THREE-WINDOW TRANSFORMATION CROSS-TALK CORRECTION METHOD FOR SIMULTANEOUS DUAL-ISOTOPE IMAGING A new transformation cross-talkcorrection method for simultaneous dual-isotope S P E C T imaging which utilizesinformation from three energy windows was presented and testedin a simultaneous F-18/Tc9 9 m cardiac phantom study. The method is combination of the previously reported "three-window technique" and transformation eross-talk correctionmethod. The transformation method takes into account the differentspatialdistributionsof the primary and scatter eross-talkphotons in the differentenergy windows. In addition to the cross-talk correction,the restorationfilterswere also applied to the resulting, corrected images. The contrast between the leftventricle cavity (LVC) and the myocardium was used in transaxialslicesas a paran~ter to evaluateresultsof the dual-isotopecorrectionmcthod with restoration. The contrast improvement in the dual-isotope corrected images in both energy windows i.e.,Tc-99m primary window (140 kcV) and F-18 primary window (511 keV), was significant.The corrected 511 kcV dual-isotope image had the contrast of 0.74 vs. 0.60, which was the value in the non-correcteddual-isotopeimage. For dual-isotope 140 keV Wansaxial slice,the contrastimproved from 0.78 to 0.92 after correction. Due to the restoration the contrast in the corrected dual-isotope images were even better than in the corresponding uncorrected single-isotopeimages. In conclusion, the presented three-window transformationdual-isotopecorrectionmethod with restorationimproves significantlythe qualityof the simultaneous

F- 18/rc-99m SPECT imaging.

P 385

P 387

D Ros,J Pavia*,M.Espinosa,F.J.Setoain*,CFalc6n, FJ.Lomer~a*. Lab. Biophysics and Bioengineering. Fac Medicine, Univ. Barcelona, *Nuclear Medicine Department. Hospital Clinic i Provincial of Barcelona. Spain

S. Walrand, L. van Elmbt and S. Pauwels. Department of Nuclear Medicine, University of Louvain Medical School, Brussels, Belgium.

ITERATIVE ALGORITHMS FOR THE REGISTRATION OF 99mTcHMPAO BRA~rq SPET STUDIES

COMPARATIVE EVALUATION OF 2 SCATTER CORRECTION

99mTc-HMPAO-SPET is a functional way to study the brain function by assessing the changes in cerebral blood flow (rCBF) when the brain passes from basal to stress situations.Registration of the two sets of images is necessary prior to quantification of differences. The downhill simplex algorithm was employed for registration. We used two functions of merit to be maximized, the correlation coefficient (COR) between the images and the mean value of the distribution which is obtained by calculating a local correlation coefficient (LOC) for each point after using a matrix of 5x5x5 pixels. The two functions w e r e used to register SPET photic stimulation studies in which the differences are limited to a small area and to register images of the Wada test, in which the stress is produced by a pharmacological intervention which reduces the rCFB in a whole hemisphere. The alignment methods were tested in simulated studies obtained from real ones. The table show the mean values over ten runs of the maximum error in translation and rotation. The good results of COR for registration of photonic activation studies and the robustness of LOC in activation and in Wada test should be pointed out. II ;thod

ACTIVATION Trans.(pix) I Rotat.(°)--

WADA test Trans.(pix)

Rotat.(°)

:OR

~

0.040

I

0.190

0.170

0.650 ,,

OC ,,, .....

II

0.040

I

0.210

0.040

0,240

METHODS. The Scatter Elimination by Spectral Acquisition Memory Extension (SESAME) from Trlonix was compared with the scatter

correction method based on the one Effective Scatter Path model (ESP) (Phys. Med. Biol. 1994; 39: 719-734). M e t h o d : Phantoms (Jaszczak and an&tom/cal cardiac) and patients (brain, liver and heart) studies acquired on a Trionix XLT20 camera were reconstructed with the EM-ML algorithm and also with an accelerated version of the EM-ML, namely the FL algorithm (Eur. J. Nucl. Med. 1996; 23: 1521-1526). The colllmator-crystal nonstationary Point Spread Function (PSF) and the phantom (or patient) attenuation map measured with the Trionix XLT20 transmission device were included in the reconstruction urocess. Results: Both scatter corrections resulted in similar reconstructed images showing a contrast improvement, as well with phantoms as with patient studies. The fact that the two methods are based on approximations fully independent, can be seen as a mutual validation, further confirmed by the accuracy in reconstructing the activity of the phantoms (error less than 7 pc for both models). SESAME reconstructed images were a little more noisy. That results from the fact that SESAME corrects scatter by subtracting events from the photopeak window and thus decreases the counting statistics. On the other hand the ESP model utilizes all the events, scattered and unscattered, in the photopeak window, without making any subtraction. Conclusion: Both methods can be used in clinical studies to improve the contrast and the uptake quantitation. In contrast to ESP, SESAME scatter correction is fully performed during the acquisition and so is independent of the reconstruction process, especially of the regularization method used in iterative reconstructions. However ESP does not need any specialized hardware, and thus is suitable for all existing cameras.

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This work has been supported in part by the CICYT(SAF96/0062)

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J.S. Lee, ~.M. Kim, C. Kwark, K.S. Park, D.S. Lee, J-K. Chung, M.C. Lee, and C-S. Koh, Seoul National University Hospital, Department of Nuclear Medicine and Biomedical Engineering, Seoul, Korea

V. RaDDoDort, W.S. Kim, R. Ranallo, C.B. Trionix Research Laboratory, Inc. R. Butt, V A Medical Center, Indianapolis

Lim,

Multi-Energy Simultaneous Acquisition A STUDY ON TEE COUNT RATE INCONSISTENCY OF BACKPROJECTION RECONSTRUCTION WITHOUT PRE-FILTERING : EFFECT ON THE QUANTITATION USING FAST DYNAMIC SPECT in fast dynamic SPECT study which consists of various acquisition time protocoL, simple backprojection without pre-filtering could give rise to the inconsistent count rates which are variable according the to signal-to-noise ratio of projection image. We evaluated the count inconsistency using phantom experiment under the dynamic SPECT protocol, and investigated the effect of this inconsistency on the quanti
Simultaneous imaging of 18F FDG and 99mTc HDP provides "a map" of the location of FDG uptake in relationship to bone. Simultaneous study of 18F FDG and 99mTc MIBI allows comparison of cardiac metabolism and perfusion. Multi-Energy Simultaneous Acquisition (MESA) provides an ability to acquire simultaneously images from multipeak isotopes or in m u l t i - i s o t o p e studies. M E S A includes h a r d w a r e and software for linearity and uniformity calibrations and on-the-fly corrections for up to four photopeak energies simultaneously. Camera intrinsic and extrinsic performance characteristics were m e a s u r e d on Triad XLT 9 and XLT 20 three h e a d e d systems for simultaneous acquisition of 99mTc and 18F. Extrinsic characteristics were measured with 511 keV collimators for both isotopes. In addition to detector uniformity, sensitivity, and spatial resolution, mis-registration for these two isotopes were m e a s u r e d using a p h a n t o m consisting of 13 syringes filled with a solution of 0.5 cc of 99mTc and 18F. R e c o n s t r u c t e d images were compared, and average m i s - r e g i s t r a t i o n was: ~ 0.5 m m for XLT 9 with pixel size of 1.78 ram, and ~ 1.0 nun for XLT 20 with pixel size of 2.24 mm. Simultaneous imaging of 18F FDG and 99mTc HDP is p e r f o r m e d at VA Medical Center, Indianapolis. Total imaging time is 30 min. using a 10-15 mCi dose for each of FDG and HDP. Time b e t w e e n injection and study is about 90 min. Bone or bone marrow metastases are easily identified as are soft tissue lesions. In addition, other m u l t i - i s o t o p e studies are of a big importance for oncology application, e.g. 99mTc & lllIn three peak imaging.

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J.AK. Blokland, W. de Vos, E.K.J. Pauwels, Leiden University Medical Centre, Department of Radiology, Division of Nuclear Medicine, The Netherlands

R.Giubbin!, P.Rossini, R.Campini, O.Zoccarato, A.Terzi, E.Milan. Nuclear Medicine Dpts, Spedali Civili, Brescia & Fondazione S.Maugeri, Veruno (No) Italy.

CONTRAST ENHANCEMENT IN TL-201 MYOCARDIUM PERFUSION STUDIES BY SCATTER CORRECTION

MYOCARDIAL SPECT IMAGING: THE INFLUENCE OF THE PARTIAL VOLUME EFFECT ON

Reading of SPECT TI-201 studies is hampered by the low contrast of the images due to the poor resolution of the gamma camera and inclusion of scattered photons in the acquisition data. Triple Energy Window scatter correction (TEW) may improve the contrast by removing most of the scattered photons. In this study we have investigated the contrast enhancement through TEW in myocardial perfusion of studies 30 patients, both after stress and reinjection ofTI-201. Contrast was assessed by measuring the minimum count density in the LV cavity and maximum count density in the LV myocardium in four consecutive mid-myocardial slices, thereby excluding the apical and basal slices. Also the minimum and maximum densities within the myocardial wall were measured. The contrast was computed as the difference between the maximum and minimum the value divided by their sum. Each patient study was analysed with and without scatter correction. All other reconstruction parameters were equal for both situations. In the stress studies the mean contrast between the LV cavity and the LV myocardium without scatter correction was equal to 0.54 (0.20 - 0.96). After scatter correction this contrast increased to 0.76 (0.29 - 1.51). In the rest studies contrast improved from 0.52 (0.32 - 1.08) to 0.78 (0.34 1.75). Contrast improved in all studies, the average increase of contrast values was 43 % for stress studies and 48 % for rest studies. The mean contrast within the myocardial wall increased from 0.33 to 0.42 for stress studies and from 0.31 to 0.41 for rest studies. Readability of the scintigrams after TEW may degrade due to the decrease of the signal-to-noise ratio. In this study, however, we only saw this phenomenon ]n patient studies which initially had a low signal-to-noise ratio and were difficult to assess. Thus, we conclude that TEW may improve the readability of T1-201 myocardium perfusion studies by increasing the image contrast.

The partial volume effect (PVE) affects scintigraphic imaging if the size of the object is below the resolution of the system. To evaluate the effects of the PVE on myocardial SPECT imaging we realized a phantom constituted of 2 cylinders eccentrically fixed one inside the other.The chamber between the two cylinders, simulating the left ventricular wall, ranging 0-30 ram, was filled with a homogeneous solution of 99mTc. After transaxial reconstruction of transverse sections, the circumferential profile (cp) of the peak activity was displayed. Being the solution homogeneous the exclusion of the PVE should cause cp to be a straight line. The use of 2 different back-projection filters (BPF),Wiener (WR(dumping factor=0K FWHM=11mm) and Butterworth (BT) (cut off freq=0.35, order=5) was also taken into account. The relationship between wall thickness and recovered counts (% of the max)is summarized in the following table:

P 390 D.S.Thakrar~ I.R.Croasdale, ].B.Cwikla, J.R.Buscombe, A.J.W.Hilson Nuclear Medicine, Royal Free Hospital and School of Medicine, London, UK

Thickness(mm 30 27 24 21 18 15 12 9 6 3 Wiener 92 96 98 100 100 97 92 78 63 39 Butterworth

~8 100 99 97 92 84 77 62 49 31

The integrals of the recovered counts were significantly different using WR and BT BPF{p<.001). The max. count density was registered at 18mm (WR) and 27 mm(BT), respectively. Thus the PVE determines a significant, artifactual count loss when the size of the wall is below 1 cm, averaging 6.5%/mm between 3 and 9 mm, partially depending on BPF.

P 393 J.Billet, D.O. S l o s m a ~ Division de M@decine Nucl@aire, H6pital Cant6nal de Geneve

UNIPLANAR FAN BEAM COLLIMATORS IN A FIXED GEOMETRY TWO HEADED GAMMA CAMERA

IMPROVEMENT OF QUANTIFICATION IN SPECT USING TRANSMISSION COMPUTED TOMOGRAPHY: COMPARISON BETWEEN THALLIUM AND TECHNETIUM TRANSMISSION

The use of double headed gamma cameras has increased over the past 5 years so that they are now often considered essential for most nuclear medicine departments. Though variable geometry cameras are available they may not be ideal for a mixed work load of whole body and SPECT imaging. A fixed gantry is more stable and may be able to take a thicker crystal and heavier collimators for higher energy work. Recently a uniplanar low energy collimators, designed for cardiac work have become available, which improve the resolution of fixed 1800 geometry twin headed gamma cameras with improved sensitivity. Such a system was tested on our twin headed gamma camera with fixed 180o geometry. The collimators have a field of view dependent on the radius of rotation and can only be used in smaller organs such as the heart. A initial assessment was performed in 20 patients undergoing T1201 stress and rest myocardial perfusion imaging. In each case a 10 minute acquisition was compared with a 15 minute acquisition at stress and rest. In 17 patients there were only minor changes, non clinically relevant, between the image sets. In the remaining 3 patients the rest image was of such poor quality, in both 10 and 15 minute acquisitions due to low count rate, that interpretation was difficult. The collimators have now also been used in over 50 other patients for brain and bone imaging. Excellent images of the feet and lumbar spine are obtained with a pixel size of 2.3-2.5mm (depending on radius of rotation) in a 128 word acquisition matrix compared with 3:lmm with the parallel hole collimator. This has been achieved without loss of sensitivity, so that individual tarsal bones in the foot and the lumber vertebral cortex can be resolved. Uniplanar fan beam collimators provide high resolution, high sensitivity SPECT imaging for twin headed gamma cameras with 1800 fixed geometry.

SPECT images are degraded by attenuation within the human body. New reported methods permit to correct for attenuation using transmission computed tomography (TCT). This study was performed to assess quantitatively the contributions of the attenuation correction methods with different transmission isotopes: ~gmTc and 2°~TI. Fourteen brain phantoms containing 6 external sources, and 3 internal sources corresponding to the activity of 3 external sources, were investigated. For every phantom we acquired 2 simultaneous transmission and emission computed tomography respectively with the ~ T c and Z°~Tl transmission isotopes. The difference between the external source activity and the corresponding internal source activity provide an index of the efficiency of the correction: Lower it is, better is the correction. Our results shows that l)the corrections methods improved significantly the image quality and the SPECT quantification 2)the TCT methods are more efficient than the Chang method 3)the activity concentration images obtained with the 3 2°ITi sources were almost identical to those obtained with ~9~Tc source. This result allow us to approach quantification analysis by performing SPECT acquisition with 2°~Tl transmission using a 3 heads camera and 3 rods sources.

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H. Harke, H. Fricke, W. Burchert, J. van den Hoff, B.O. Knoop, H. Hundeshagen, Abteilung Nuklearmedizin und Spez Biophysik, Medizinische Hochschule Hannover, Germany

A.M. Palmer. Radiopharmacy Unit, United Bristol Healthcare NHS Trust, Bristol General Hospital, G u i n e a Street, BRISTOL, E N G L A N D BSI 6SY.

COMPARISON OF GD-153, AM-241 AND TC-99M AS TRANSMISSION SOURCES FOR TRANSMISSION/EMISSION CARDIAC SPECT. A three-headed SPECT system (Siemens Gammasonics, Hoffman Estates, Illinois) is equipped with two high resolution parallel hole and an asymmetric fanbeam collimator with a transmission line source. For this geometry we have developed an iterative EM-ML reconstruction algorithm including attenuation and scatter correction. Acquisitions were performed sequentially as well as simultaneously with Tc-99m (MIBI) and TI-201 (-chloride). The respective transmission scans were obtained with Am-241, Gd-153 and Tc-99m. Acquisitions were performed with an asymmetric body phantom with rods (5cm diameter) of different absorbing materials, and this body phantom with Jaszczak heart insert and patients with standard cardiac perfusion acquisition protocol. After reconstruction transverse slices of rod phantom images were visually compared with the known distribution regarding geometrical shape and activity distribution. Regional activity analysis was based on ratios of activity. Reconstructed images of the heart phantom and the patient data are shown in a 3D display as a very sensitive tool for detecting small activity differences. Circumferencial activity profiles gave only small (+5%) differences from the average value. Rod phantom data show a very homogeneous activity distribution and the undistorted geometrical shape. The contrast inside the inactive rods ranges from 6% (teflon rod) to 78% (air rod) without and from 22% (teflon rod) to 25% (air rod) with scatter and attenuation correction. Additionally reconstructed patient and heart phantom studies using scatter and attenuation correction showed the according improvement in activity distribution.

B I N D I N G O F T c - 9 9 m - H M D P TO S E R U M P R O T E I N S . Literature review indicates that protein binding of the T c - 9 9 m - l a b e l l e d b o n e i m a g i n g a g e n t s ranges f r o m 7 to 90% in vivo a n d 8 to 80% in vitro. A variety of measurement methods and phosphate compounds h a v e b e e n studied. The o b j e c t i v e s of this s t u d y w e r e to m e a s u r e b i n d i n g of T c - 9 9 m - H M D P to serum proteins in vitro by several e x p e r i m e n t a l methods, "the e f f e c t of the m e t h o d on the s t a b i l i t y of Tc-99m-HMDP, and to i d e n t i f y particular serum proteins or fractions which p r e f e r e n t i a l l y b i n d Tc-99m-}{MDP. Materials and Methods: Binding was measured by precipitation with trichloracetic acid (TCA), ammonium sulphate (AS) or heat, gel filtration, ultracentrifugation and membrane dialysis. The effect of TCA, AS and heat on Tc-99m-HMDP s t a b i l i t y was a s s e s s e d . B i n d i n g of TC-99m-}{MDP to p u r i f i e d s e r u m p r o t e i n f r a c t i o n s was m e a s u r e d b y T C A and AS p r e c i p i t a t i o n . S e r u m b o u n d to T C - 9 9 m H M D P was f r a c t i o n a t e d u s i n g g r a d e d c o n c e n t r a t i o n s of A S and b y c e l l u l o s e a c e t a t e e l e c t r o p h o r e s i s . R e s u l t s : A p p a r e n t b i n d i n g v a r i e d b e t w e e n 51% and 97% d e p e n d i n g on the technique used. T C A was found to degrade TC-99m-HMDP underestimating protein binding. AS fractionation showed that m o s t of the l a b e l l e d m a t e r i a l p r e c i p i t a t e d out at AS c o n c e n t r a t i o n s of 40% a n d 50%. T h e s e f r a c t i o n s c o n t a i n some g a m m a g l o b u l i n s , m o s t of the b e t a and a l p h a g l o b u l i n s together w i t h albumin. The electrophoresis experiments suggested preferential bnding to gamma globulins with s i g n i f i c a n t b i n d i n g also to the a l p h a - 2 and b e t a fractions. The proportion bound to gamma globulins increased with decreasing concentration of T c - 9 9 m - H N D P s u g g e s t i n g t h a t this w o u l d be the predominant f r a c t i o n b i n d i n g in vivo. B i n d i n g to albumin was low. Binding to purified serum f r a c t i o n s c o n f i r m e d this b i n d i n g p a t t e r n .

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KJkkerman I, K.A.Bergstr~m 1, C.Halldin 2, S.L~tjSnen 1, P.Heikkinen 3 ~ 1 , M.X.Yu ], j.T.Kuikka 1, J.Hiltunen 4, C.G.Swahn ~ J.L.Neumeye?, ~University Hospital and University of Kuopio, Finland; 2Karolinska Institute, Sweden; ~VERIFIN, Finland; 4MAP Medical Technol. Oy, Finland; 5RBI Research Biochemicals International, USA.

*D. Guilloteau, *P. Emond, °C. Halldin, *S. Chalon, °G.S. Swahn, °L. Farde, *C. Belzung, *V. Mauclaire, *J.P. Chiron, *J.C. Besnard, *INSERM U316, Univ., Tours, France. °Karolinska Institutet, S-17176 Stockholm, Sweden. Cis Bio Industrie, France.

AN HPLC-MS/MS METHOD FOR IDENTIFICATION OF LABELED METABOLITES OF ]3-CIT For the development of new I3-CIT analogues with lower degree of metabolism, it is important to know metabolic pathways of I3-C1T and analogues. The metabolite pattern of [I-123]13-CIT is previously determined using HPLC. Results showed 4-5 labeled mctabolites in plasma of which two have been identified. We have now tested an HPLC-MS/MS method'for identification of labeled metabolites of 13-CIT. Reference standards of several 13-CIT metabolites and proposed metaboIites were synthesized. A dose of 1-2 mg/kg of [3-CIT (containing small amounts of labeled ]3-CIT) was given to a Cynomolgus monkey. Ten blood samples of 2 ml were taken at 0-60 minutes after injection. The plasma was separated and proteins were precipitated with acetonitrile. Samples of 1 ml were purified with two different HPLC methods. The samples were analyzed with ¥ G AutoSpecQ mass spectrometer equipped with atmospheric pressure chemical ionization or electrospray interface combined to Merck-Hitachi HPLC purnp and Rheodyne injector. Before the analysis the samples and standards were dissolved in an appropriate volume of LC eluent: water-methanol I:1 containing 0.I% formic acid. A 20 gl of diluted sample or standard was injected into the LC system using either flow-injection or LC column apparation with flow rate of 0.6 ml/min or 30 ~I/min straight to into the APCI or the ES interface respectively. A mass range ofm/z 100-700 was scanned in all experiments and the product ion spectra of the protonated molecular ions were produced at a mass range of m/z 20-500. Spectra of reference standards suggest that 50 ng should be a sufficient amount of sample in order to support the identification of the metabolites, when reference spectra are available. A amount of collected 13-CIT was high enough to give good spectra with presented method, but for metabolite identification the amount was too small. Recent experimets with rats allowed higher doses of f3-C1T to be used, which gave l0 times higher concentration of metabolites in urine, this with an HPLC-MS/MS method should give more information of the structures of 13-CIT metabolites

DOPAMINE TRANSPORT EXPLORATION: TOXICOLOGICAL PRECLINICAL EVALUATION OF ~-CIT N u c l e a r m e d i c i n e m a y play an important role for the diagnosis and follow-up of neurodegenerative diseases such as Parkinson's. Recently, new tracers have been proposed for exploration of the presynaptic side based on dopamine transport mechanism. The cocaine congener 2~-carbomethoxy-3~-(4'-iodophenyl)tropane(~-CIT) is a promising radioligand and explorations in human have already been performed. As cocaine possess toxic characte~ ristics, we need additional data about p h a r m a c o logical properties and potential toxic effects of ~-CIT. For this, we p e r f o r m e d acute toxicity, mutaqenicity and locomotor activity determinations. Acute toxicity was studied in mice and rats after IV injection of ~-CIT from 0 to 40 mg/kg. A n i m a l s were observed for m o r t a l i t y and toxicity signs. M u t a g e n i c i t y of ~-CIT was performed using the Ames test on five clones derivated from Salmonella Typhimnrium. Locomotor activity was measured on mice using a circular open-field, and d e t e r m i n e d by counting section crossing. The calculated LD50 was 20 mg/kg in mice and 5 mg/kg in rats. Results of ~es test showed that ~-CIT had no mutagenic effect at a concentration !0 6 times higher than the amount found in human blood during ecintigraphic exploration. ~-CIT had a dramatic effect on locomotor activity in mice, since we observed at a dose of 1.2 m g / k g a 200% increase compared to controls~ In conclusion, ~-CIT as well as cocaine increases locomotor activity. This is in favour of a bindlng of ~-CIT to the dopamine zransporter and then of Its use as a marker for this site. Moreover, it seems :hat ~-CIT has no mutagenic effect, but has a higher acute toxicity than cocaine. However, the i n j e c t i o n dose for scintigraphic exploration is about i0 ~ times lower than LD5O showing that good security could be assumed for patient.

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S.J. Wang, C.H. Kao and S.P. Wey. Taichung Veterans General Hospital, INER, Taiwan.

E.Th.M. Dams I W.J.G. Oyen ~, O.C. Boerman ~, G. Storm 2, P. Laverman 1, J.W.M. van der M e e / , F.H.M. Corstensk University Hospital Nijmegen ~, Nijmegen and Utrecht University 2, Utrecht, The Netherlands.

TRIAL OF LABELLING LEUKOCYTE$ WITH STABILIZED TC-99M D,LHMPAO BY METHYLENE BLUE.

COMPARISON OF Ga-67 AND THREE NEW Tc-99m-LABELED AGENTS FOR LOCALIZING FOCAL INFECTION t N NEUTROPENIC RATS Scintigraphic studies can be very useful for detecting infection in granulocytopenic patients, who often lack localizing signs and symptoms. Since labeled leukocytes cannot be employed, Ga-67-citrate is the only routinely available radiopharmaceuticah We studied the potential of three new Tc-99m labeled agems (polyethylene glycol (PEG)-eoated liposomes, 2-iminothiolano lgG (Teehnesean HIG), and hydrazinonicotinate (HYNIC) IgG) to image infection in a granulocytopenic rat model. A focal S.aureus infection was induced in the left calf muscle of rats with cyclophosphamide induced granulocytupenia. Granulocytes were < 0.1x109/l throughout the experiment. Twenty-four hours after the bacterial inoculation, Tc99m-PEG-liposomes, Tc-99m-HYNIC-IgG or Technescan was administered intravenously. For comparison, a group of rats was injected with Ga-67-citrate. The animals were imaged with a gamma camera up to 24 hr. In a separate group of rats, the biodistribution of the radiolabel was determined at 24 hr p.i. The three Tc-99m-labeled agents all showed significantly higher accumulation in the infectious focus than Ga-67-citrate. Tc-99m-liposomes and Tc-99mHYNIC-IgG had the highest abscess uptake (1.33 ± 0.31%ID/g and 1.40 _ 0.16 %ID/g, respectively, at 24 hr p.i.). Uptake in the abscess with Ga-67-eitrate was only 0.03 ± 0.01%ID/g. Abscess-to-muscle ratio calculated from the 24 hr biodistribution data, was highest for Tc-99m-liposomes (72.1 ± 19.1), followed by Tc-99m-HYNIC-IgG (18.3 ± 3.3), Technescan (9.5 _+ 1.8) and Ga-67-citrate (4.4 ± 0.7). All agents visualized the S.aureus infection within 2 hr postinjection. In addition, Tc-99m-liposomes and Tc-99m-HYNIC-IgG showed increasing activity up to 24 hr. The results of this study show that Tc-99m-PEG-liposomes, Tc-99m-HYNICIgG and Technescan can visualize focal infection in granulocytupenic rats. The high abscess uptake and abscess-to-muscle ratios of Te-99m-liposomes and Tc99m-HYNIC-IgG suggest that these two radiopharmaceuticals might replace Ga67-citrate for infection imaging in granulocytopenic patients.

We attempt to label leukocytes with stabilized Tc-99m d,I-HMPAO by methylene blue (M-HMPAO). The results will compare each other with unstablized Tc-99m d,I.HMPAO. M-HMIOAO was obtained by reconstituting a commercial vial of d,IHMPAO (Ceretec, Amersham). A method of stabilizing the kit by the addition of 0.5ml of 1% methylene blue into 4.5ml buffer solution. The leukocytes were labelled using an in-house method (J Nucl Med Technol 1992;20:224). The test samples of M-HMPAO and unstabilized HMPAO were prepared immediately, and stood for 0.5, 1, 2, 4, and 6 hrs respectively at room temperature before being studies. In comparison with unstabilized HMPAO: (1) the radiochemical purity of M-HMPAO was higher (95.2--+2.8%, 94.1 ±2.1%, 93.4±3.4%, 92.8~ 3.1%, 90.8-+2.2%, and 88.4_+4.5% Vs 86.5-+3.6%, 75.3_+4.5%, 64.7_+ 4.2%, 51.3_+5.3%, 37.7_+4.6%, and 33.7~4.8% respectively, n=30); (2) the labelling efficiencies of M-HMPAO labelled leukocytes were higher and consistent (7"8.9_+6.8%, 76.2±57%, 75.6_+_7.3%, 75.5-+7.2%, 731 •+7.8%, and 70.2-+4.8% Vs 75.1 -+8.2%, 53.3±5.6%, 41.5-+6.2%, 27.8-+ 5.5%, 20.5_+ 4.3%, and 18.6_+3.6% respectively n = 30) ; and (3) the disintegrated percentages from M-HMPAO labelled leukocytes in plasma after labelling were was lower than those of those labelled with unstablized HMPAO (9.7_+2.3%, 11.4--+3.2%, 12.3_+3.2%, 15.3-+3.5%, and 30.4_+6.2% Vs 16.4_+2.1%, 18.3-+ 1.6%, 24.4_+3.5%, 31.2-+ 2.4%, and 45.6--+3.2%, at 1, 2, 4, 6, and 18 hrs respectively, n=25). We conclude that M-HMPAO is more stable than unstabilized HMPAO and can provide higher leukocyte labelling efficiency. M-HMPAO, therefore, has the potential to replace unsta~flized HMPAO as a more suitable leukoeyte-labeUmgagent.

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E. Th.M. D a m f , W.J.G. Oyen ~, O.C. Boerman 1, G. Storm 2, P. Laverman l, J.W.M.van der Meet ~, F.H.M. Corstens 1. University Hospital Nijmegen~, Nijmegen and University of Utrecht ~, Utrecht, The Netherlands.

C.J. van der_Laken., O.C. Boerman, W J . G . Oyen, M.T.P. van de Ven, D. Scott Edwards, John A. Barrett, J.W.M. van der Meer, F.H.M. Corstens. Dpts. of Nuclear and Internal Medicine, University Hospital Nijmegen, The Netherlands and Radiopharmaceuticals Division, The Du Pont Merck Pharmaceutical Company, North Billerica, MA, USA. IMAGING OF INFECTION AND STERILE INFLAMMATION WITH Tc-99m-LABELED CHEMOTACTIC PEPTIDES

A COMPARATIVE STUDY OF Tc-99m-PEG-LIPOSOMES, Tc-99mHYNIC-IgG AND Tc-99m-LABELED GRANULOCYTES IN THE ASSESSMENT OF EXPERIMENTAL COLITIS IN RABBITS. Seintigraphic techniques axe very suitable to evaluate the extent and severity of inflammatory bowel disease. Currently, the preferred radiopharmaceutical is Tc-99m-HMPAO-leukocytes. We studied two recendy developed Tc-99m-labeled agents (polyethylene glycol (PEG)-coated liposomes and hydrazinonicotinate (HYNIC) IgG) in a rabbit model of acute colitis, and compared them to Tc-99mlabeled white blood cells. To compensate for the relatively high lymphocyte count in rabbit blood (ca.50%), the granulocytes were purified to >90% and subsequently labeled and reinfused. Acute colitis was induced in rabbits by retrograde instillation of trinitrobenzene sulfonic acid. Forty-eight hours later, 35 MBq of each of the radiopharmaceuticals was administered intravenously. The animals were imaged with a gamma camera up to 24 hr. At 5 and 24 hr p.i. groups of rabbits were killed, and the uptake of the radiolabel in dissected tissues was determined. The affected colon was divided in 7 segments of 5 era each, and scored for severity of macroscopic inflammation (0=normal, 1=inflammation, 2=ulcer). For each affected segment the colitis-index (CI, affected-to-normal-colon-uptake-ratio)was calculated. All three agents visualized the colitis lesions within 2 hr postinjection. The CI correlated with the severity of the abnormalities. With increasing severity, the CI at 5 hr postinjection for liposomes was 3.89 __+0.73, 4.41 ± 0.47, and 5.76 ± 0.65, for lgG 1.67 ± 0.08, 3 . 9 2 + 0.44, and 6.14 + 0.65, and for granulocytes 2.90 ± 0.09, 6.15 ± 0.96, and 9.36 + 3.35. For liposomes, the CI increased during the 24 hr postinjection to 6.56 ± 0.84. 8.50 + 0.53, and 10.61 ± 1.34, respectively. The CI for the other two agents did not change significantly. Tc-99m-labeled grannlocytes, lgG and liposomes all rapidly visualized colonic inflammation in this rabbit model. Granulocytes and liposomes showed the highest CI. Tc-99m-labeled PEG-liposomes may be an attractive alternative for labeled leukocytes for imaging of inflammatory bowel disease, as they can be prepared off the shelf and no handling of blood is required.

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Several studies have demonstrated localization of chemotactic peptides in infection. The uptake of chemotactic peptides in infection is assumed to be specific, i.e. by means of high affinity binding to receptors expressed on locally present polymorphonuclear cells and monocytes. In the present study, the specificity of focal uptake was investigated directly in vivo by comparison of the in vivo behaviour of a synthetic chemotactic peptide with a control peptide of similar molecular weight with low receptor binding affinity. Furthermore, the potential to target to different infections and sterile inflammation was tested. Twenty-four hours after induction of Escherichia coli, Staphylococcus aureus and zymosan abscesses in the left thigh muscle, rabbits were i.v. injected with either 1 mCi 99mTc-labeled formyl-methionyl-leucyl-phenylalanyl-lysinehydrazinonicotinamide (99mTc-fMLFK) or 99MTc-labeledhydrazinonicotinamidemethionyl-leucyl-phenylalanyl-OMe(99mTc-MLFOMe, control peptide). Gamma camera images were obtained at 5 rain, I, 4, 8, 20 hr p.i. Biodistribution was determined at 20 hr p.i. 99"~Tc-fMLFK and 9VmTc-MLFOMe rapidly cleared from the blood in a similar fashion. However, 99mTc-fMLFK was retained in the E. coil-induced abscess, while 99mTc-MLFOMe was cleared from the abscess (0.049 -t-_0.011 vs 0.005 +_ 0.0003 %ID/g at 20 hr p.i.; p<0.0005). Abscess-to-contralateral muscle ratios of 99'~Tc-fMLFK increased to 36.8 + 4.3 at 20 hr p.i. The ratios of ~ T c MLFOMe were significantly lower: 6.0 +_ 0.8 at 20 hr p.i. (p<0.0005). The uptake in S.aureus and zymosan-induced abscesses did not differ significantly from the uptake in E.coli-induced abscesses. Abscesses in the three studied models could all be clearly visualized from 4 hr p.i. onwards. Abscess-tobackground ratios continuously increased to values varying from 4.4 :t: 0.2 (zymosan) to 7.1 i 0.6 (S. aureus). These in vivo studies show that fMLFK is retained in inflammatory tissue by specific receptor binding. Furthermore, the potential of fMLFK for imaging both acute infection and sterile inflammation was demonstrated.

P 404

P 406

M.X. Yu, K.A. Bergstr6m, J.W. Yang, J.T. Kuikka, Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, FIN-70210, Kuopio, Finland.

Mick Welling ~, Hans I.J. Feitsma ~, Wire Calame =, Ernest__.K.J. Pauwels 1

C O M P A R I S O N OF T L C M E T H O D S AND A C O L U M N M E T H O D IN THE T E C H N E S C A N Q I 2 Q U A L I T Y C O N T R O L TechneScan Q l 2 ® ([Tc-99m]Q12) is a promising new myocardial perfusion imaging agent. The aim of the study was to compare different quality control methods, a column method which was recommended by the manufacturer (Al-oxide minicolumn) and two different TLC methods. First TLC method was similar as previously used for [Tc-99m]MIBI (Al-oxide TLC (AI-TLC), ethanol). Second, silica gel TLC (Si-TLC) method was used also with ethanol. The affinity of Q12 to the A1-TLC sheet was much lower than that to Si-TLC sheet. The radiochemical purity of [Tc-99mlQ12 was (93,3~:l.3)% (mean±SD, n=5) by the column method with coefficient of variation (CV%) of 1.4%, (76.2~:4.4)% by the A1-TLC method with CV% of 5.8% and (87.5::0.5)% by the Si-TLC method with CV% of 0.62%. TLC methods separated [Tc-99m]QI2 from other labeled impurities very- clearly. AI-TLC separated [Tc-99m]Q12 from other impurities more effectively than Si-TLC because [Tc-99m]Q 12 moved much longer distance on AI-TLC sheet than on Si-TLC sheet. In the column method, [Tc-99mJQ12 should be eluted with 10 ml of ethanol according to quality control instructions. However, [Tc-99m]Q12 was eluted within 2.0 ml of ethanol, and the rest of 8.0 ml ethanol seemed to contain labeled impurities. In conclusion, T L C methods gave lower results than column method for radiochemical purity of [Tc-99m]Q12. Results indicate that AI-TLC method detects radioactive impurities more reliable than the column method.

1Deparl~nentof Diagnostic Radiology and Nuclear Medicine, Leiden University.Hospital, The Netherlands : Hercules European Research Center, Bameveld, The Netherlands LOCALIZATION OF A BACTERIAL INFECTION WITH TECHNETIUM-99MLABELLED HUMAN IgG: FURTHER IMPROVEMENT WITH ENRICHED IgG SUBCLASS PREPARATIONS

Objective: The aim of this study was to determine the contribution of various IgG subclasses to the scintigraphie detection of a staphylococcal infection. An experimental thigh infection'in mice was used to determine the accumulation of various 99roTe-labelled IgG preparations with enriched IgG1, IgG2 and IgG4 subclasses. Methods: For this m woo study, 18 hours after infection with 107 CFU Staphylococcus aureus bacteria (SA), 20 Itg of 99~Te-labelled IgG preparations, enriched with either IgGl (83%), IgG2 (80%) or IgG4 (26%) subclass by thiophilic absorption chromatography were administered intravenously and after seintigraphy target-to-non-terget (T/NT) ratios were determined at 15 minutes, lh, 4h and 24h after injection of the tracer. Moreover, the contribution to the accumulation of all IgG subclasses in the enriched preparations was determined. As a control agent 99~Tc-labelled polyclonal IgG (HIG) was used. Results: In vivo, the T/NT ratios were significantly (p<0.05) higher for lgG1 enriched preparation at all time intervals (T/NT resp. 4.7, 11.0, 11.6 and %4) and for IgG2 enriched preparation at 4h (T/NT 10.2) and 24h (T/NT 8.4) after injection, compared with HIG (T/NT resp. 1.9, 2.7, 5.1 and 4.0). In contrast, IgG4 preparation did not yield high T/NT ratios at any time. In each preparation the relation between the IgG subclass content and accumulation was calculated. Using multiple regression analysis it became evident that IgG3 at all time intervals, IgG1 in early scans (15 minutes, lh and 4h) and in IgG2 in later scans (24h) contribute significantly (p<0.05) to the accumulation. The composition of the preparations appeared to be of influence on the accumulation of the tracer at the site of inflammation. Conclusion: It is concluded that specific subclass enrichment of S~Tc-labelled IgG preparations improves the scintigraphic detection of staphylococcal infections at various time intervals and provide more insight in the progress of the infection.

P 407 M.A. Torres, K.K. Bhargava, M.B. Tomas, C.J. Palestro. Division of Nuclear Medicine, Long Island Jewish Medica! Center, New Hyde Park, NY USA

RADIOLABELINGLEUH~"ZTESWITH ~C-~4-PAOSTABILIZED

The aim of this work was ~o study the usefulness of the 9~Tc-d, I-HM-PAO obtained from a Ceretec~ fraction (0.5 mi in saline) stabilized with methylene blue for labeling of leukocytes. The radiolabeling of HM-PAO was performed using iii0 Mbq of 9~Tc-pertechnetate in i.i ml. The radiochem~cal purity 5minutes after labeling was 95.7% i 1.7. The 9~fc-d,l-HM-PAOwas stabilized by adding 0.16 ml of 0.6 mg/~ll methylene blue in saline. The radiochemical purity 2 hours later was > 85%.Two samples of 45 ml of blood were obtained from 8 volunteers. The leukocyte pellet from each sample was resuspended in 0.5 ml of autologous ACDplasma. 0.4 ml of fresh obtained 9~fc-HM-PAO were added to one of the leukocytes suspension and 0.4 mA of 2 hours old stabilized 9~Tc-HM-PAO to the other one. Both samples were incubated at 37°C for 30 min. Four ml of cell free plasma were added to each s~mple before the centrifugation (150 g, 5 min). The final plasma supernatant was clear enough to be removed without chsturbing the labeled leukocytes. The labeling efficiency was 70.1% ± 6.1 and 65.9 ± 9.2 using non-stabilized and 2 hours stabilized 9~Tc-HM-PAO respectively. Eosin Y staining technique yielded more than 98% of nonstained cells in all leukocytes samples. Conclussion: 9~Te-HM-PAO obtained from saline fraction and stabilized with methylene blue can be used for leukocyte labeling.

LABELING EFFICIENCY AND IN VITRO "STABILITY OF LABELED LEUKOCYTES: IN-II1-OXINE AND TC-99M-HMPAO.

Labeled leukocyte scintigraphy, radionuclide "gold standard" for imaging focal infection in immunocompetent patients, requires high quality images for accurate interpretation. Because it may not always be possible to reinfuse patients immediately after leukocyte labeling, we studied the effects that a protracted delay between cell labeling and reinfusion could have on label stability, & hence image quality. 40 cc of blood was withdrawn from each of 20 volunteers who were medication-free for at least 7 days. Each 40 cc sample was divided into 2 20 ec aliquots. WBC's from one aliquot were separated and labeled in saline with 10 MBq In- 111-oxine (In). WBC's from the other aliq~lot were labeled in plasma with 555 MBq Tc99m HMPAO (To). Mean labeling efficiency for In was 90.09% (±1.40 sem) vs. 40.75% (-+3.24 sem) for Tc. Labeling variability was significantly greater for Tc (20-72%) than for In (7599%) (F test p<0.01). Each 20 cc sample was then divided into two 10 cc samples. In-labeled cells remained in saline (S) in 1 sample, while in the other saline was replaced by an equal volume of plasma (P). For Tc-labeled cells, I sample remained in plasma, while in the other plasma was replaced by saline. After "free" radionuclide was removed by washing, the percent radionuclide bound for each sample was calculated. Mean percent bound for each group was;

InWBC (S) InWBC (P) TcWBC (P) TcWBC (S)

t-" o~

L

P 405 M. Roca, V. Garcia, F. Armero, V. Vallejos, M. Castell, Y Ricart and J. Martin-Comin. S. Medicina Nuclear. C.S.U. de Bellvitge. Barcelona. Spain.

WITH METHYIXI~ BLUE.

cO =mm

15 rain 95.00 95.45 95.40 94.35

30 m ~ 93.20 93.35 93.70 93.05

1 hr 92.40 91,70 91.25 91.05

2 hrs 91.20 90.05 88.95 89.10

4 hrs 89.90 87.85 87.40 87.10

24 hrs 83.10 79.85 77.85 77.20

InWBC in saline was the most stable preparation, but only TeWBC was significantly less stable (t test p< 0.05), and only at 24 hours, a time point with no clinical relevance. In summary, despite wide variations in labeling efficiency, once labeled & washed, In & Tc labels are both very stable over time. Consequently, while other time related factors may affect study accuracy, label stability, in and of itself, should not be cause for concern when an unavoidable delay between cell labeling & reinfusion occurs.

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ID O 13.

P 408

P 410

K. ZGphel, T. Grtining, G. Wunderlich, W.-G. Franke, A. Ktthne, J. Kropp. Department of Nuclear Medicine, University of Dresden, Germany.

P. Gamuszek 1, I. Licifiska 1, P. Fiedor 2, A.P. Mazurek 1 Drug Institute, Warsaw, Poland, 2 Transplantation Institute, Warsaw Medical Academy, Poland

D I A G N O S T I C V A L U E OF A N E W T E S T FOR A N T I - T G M E A S U R E M E N T IN V A R I O U S T H Y R O I D DISEASES.

Rationale. Established assays for anti-Tg often have a comparatively low specificity because the tube fixed Tg in these tests does not bind anti-Tg exclusively. This low specificity limits their clinical value in autoimmune as well as in non-autoimmune thyroid diseases. We investigated whether a new test for which a higher specificity was claimed allows further differentiation of previously raised titers of anti-Tg in thyroid diseases with a different clinical role of anti-Tg. Material and Methods. We compared B.R.A.H.M.S.'s Thyrak-Assay ® IRMA to their new DYNOtest ®anti-Tgn RIA. In this latter test polyclonal anti-Tg fixed to the tube surface and anti-Tg in the patient's serum compete for the epitopes of labelled Tg given into the tube. 179 patients were included in the study: 23 with Hashimoto's thyroiditis, 45 with Graves' disease, 33 with toxic nodular goitre, 51 with differentiated thyroid carcinoma, and 31 with endemic goitre. Results. We found the following constellation of anti-Tg titers: condition Hashimoto's Graves' toxic goitre carcinoma endemic goitre

anti-Tg raised raised negative negative negative

Thyrak-Assay ® DYNOtest ®anti-Tgn 18/23 (78 %) 13/23 (56 %) 15/41 (37 %) 15/41 (37 %) 23/33 (70 %) 20/33 (61%) 37/51 (73 %) 35/51 (69 %) 24/31 (77 %) 16/31 (52 %)

Conclusions. Diagnostic accuracy of anti-Tg measurement is considerably improved with this new test for Hashimoto's thyroidJtis, and the primarily non-autoimmune thyroid diseases. There was no change in patients with Graves' disease. Thus the clinical value of anti-Tg measurement is markedly increased with this new assay.

SYNTHESIS AND PRELIMINARY BIOLOGICAL STUDY OF DiCARBOXY DITHIZONE-[131I]IODOHISTAMINE CONJUGATE. Our previous studies strongly suggest that derivatives of dithizone (iododithizones) stain crimson viability of pancreatic islet cells. Aim of this study was to estimate applicability of the radiolabelled dithizone ([l~lI]dithizone) for survival stainning pancreatic islets following intravenous administration. We have synthesized the new carbexylic derivative of dithizone; orto-dicarboxy dithizone, and conjugated with [~3~I]iodohistamine. Biodistribution study on rats were done after intravenous and direct to splenic artery injections of 0.3 mL of the conjugate solutions (10 MBq /mL). Comparison of activity cumulated in or ans after different application ways of dithizone-[1311]iodohistamine con ate is shown in the table below. % of activity cumulated in organs post injections: Organ or Intravenous Direct to splenic artery tissue 60 min I 30 rain 45 min 90 min i Blood lmL 0.80 I 0.19 [ 0.14 0.40 0.16 Heart 0.26 I 0.14 0.13 0.31 Thyroid gland 10.86 [ 8.24 11.05 20.79 Liver 0.17 I 0.69 1.86 0.99 Spleen Pancreas

0.45

I

6.18

10.25

0.62

1.52 I 2.06 3.73 9.31 Kidney 2.68 I 2.89 6.52 2.23 Stomach 46.42 I 9.61 15.71 33.35 Intestine 16.23 I 0.07 0.93 1.77 Urine [ Biodistribution stud, resulted in observation that applied activity of carboxy dithizone-[13tI]iodohistamine conjugate, mainly accumulated in intestine and liver after intravenous injection. Direct application of the conjugate to splenic artery leads to high uptake of activity by pancreas after 45 rain. post injection. Our results indicate that the radioactive dithizone is a promising new diagnostic agent for detection the viability of transplanted pancreas or islets by radioisotope scanning techniques.

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P 411

M. Martin, P. Blockx. Antwerp University Hospital, Department of Nuclear Medicine, Wilrijkstraat I0, B-2650 Edegem, Belgium.

R.A.M.J. Claessens and Z. Kolar. University Hospital, department of Nuclear Medicine, Nijmegen and Interfaculty Reactor Institute, Delft, The Netherlands.

COMPARISON OF THE NEW 25OH-VIT.D3-RIA-CT FROM MEDGENIX/ BIOSOURCE WITH THE 25-OH VITAMIN D RIA KIT FROM INCSTAR.

A RATIONAL APPROACH TO THE DEVELOPMENT OFATIN-117m-LABELED AGENT FOR TREATMENT OF INTRACTABLE BONE PAIN.

The new coated tube RIA from Medgenix/Biosource (Med) for the determination of 250H Vitamine D3 was evaluated analytically and clinically and compared with the liquid RIA from INCSTAR (Inc). For the Med assay normal values for adults and children were established. In both assays standards and samples were firstly extracted with acetonitrile. After extraction Med uses coated tubes with inrnobilized specific antibody and the reaction is stopped by aspiration. Inc is a liquid RIA which needs an extra incubation with a second antibody precipitating complex to obtain phase separation. The calibrator curve for the Med assay is very steep with a difference in %binding between lowest and highest standard of 77% vs 58% for Inc, resulting in a better analytical sensitivity, 0.38 ng/ml vs 1.2 ng/ml for Inc. Within-assay precision was evaluated on duplicates: for both assays 67% (22/33) of the results had a CV <5%. The regression equation calculated on 33 patient samples in the range 7.2-89 ng/ntl was: Med = 13.02 + 0.87Inc (ng/ml). Normal values for the Med assay were established on a Belgian population. For adults, age 18-65 yrs (n=72), 250HVitD3 ranged from 9-62 ng/ml (median 23.8 ng/ml). For children, age 10-18 yrs (n=52) from 14-64 ng/ml (median 31.5 ng/ml) and for age 0.5-9 yrs (n=63) from 23-86 ng/ml (median 49 ng/ml). The new RIA for the determination of 25OHVitD3 from Medgenix/Biosource revealed several analytical improvements compared to the existing methods. Due to the coated tube technology, the procedure has been simplified and the analytical sensitivity has been improved. The within-assay precision was comparable. In a Belgian population, the normal values for 25OH vitamineD3 gradually decreased with increasing age. For children
Tin-117m DTPA has been proposed as a new agent for treatment of bone pain in patients with skeletal metastases. A high bone uptake and low retention in soft tissues have been obtained in vivo. However, for successful treatment a minimal uptake in normal bone is mandatory. In this study we tested a new iigand for labeling with tin with an improved target to non-target (TINT) ratio in bone. We performed simulations with a recently proposed computer model, which accurately describes the adsorption to hydroxy apatite (HAP) of diphosphonates and tin. We concluded, that a high affinity of the ligand for HAP as well as a sufficient stability of the ligand-tin complex are required to obtain a sufficient bone uptake and a sufficiently high TINT ratio in bone. We selected 4-chlorophenyl MDP (pClPMDP), which forms stable tin complexes as a candidate for further evaluation. Adsorption studies on HAP with both pClPMDP/Sn(II) and pCIPMDP/Sn(IV) and with C-14-DTPA/Sn(IV) (cone. range ligand: 1-10 mM/I; tin: 0.1-1 raM/I; 100 mg HAP) were performed. Tissue distribution studies with pClPMDP/Sn(IV) were performed in normal rabbits. In the presence of pCIPMDP the maximum tin adsorption was 30% higher with Sn(IV) than with Sn(ll). With DTPA the Sn(IV) adsorption was twice high as with pClPMDP. With DTPA all tin was adsorbed at all concentrations and no relation with the amount of available HAP-surface was observed. With pClPMDP the adsorption curves for both Sn(ll) and Sn(IV) showed a maximum at low concentrations (approx. 0.1 raM/I), indicative of a high TINT ratio in bone. Therefore, diphosphonate complexes show advantages as agents for treatment of bone pain as compared to DTPA. Unfortunately, tissue distribution studies showed unfavorable soft tissue retention of tin when given with pClPMDP. More polar derivatives of pClPMDP are under development to reduce the tin soft tissue retention, while maintaining the improved T/NT ratios in bone.

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P 412

P 415

N.Watanabe, K.Endo, H.Sawai, K.Shinozuka, H.Ozaki, Gunma University, Faculty of Medicine, Department of Nuclear Medicine, Faculty of Engineering, Department of Chemistry.

P. Brust, 1L Bergmarm, R. Bauer*, B. Walter', G. Vorwieger, F. FOchtner, I. Steinbach, E. Will, H. Linemann, B. Johannsen Research Center Rossendorf, 01314 Dresden; *Institute of Pathophysiology, 07740 Jena (Germany)

PREPARATION OF Y-90-ANTISENSE FOR CANCER GENE THERAPY

OLIGONUCLEOTIDES

The combination of antisense oligonucleotides (AS) with a cytotoxic radionuclide such as Y-90 is expected to injure cancer cells intensively, taking advantage of the specific binding of the mRNA and the high energy of beta emitter. The aim of this study was to investigate therapeutic potential of Y-90-AS. Phosphorothioate-backbone AS (15 mer) complementary to the translation start region of N-myc oncogene mRNA were synthesized, exchanging one thymine for a modified deoxyuridine (T*). Y-90-acetate was bound to the T* site of the AS via succinyl benzyl-EDTA. The Y-90-AS was purified by 2.0 % agarose gel electrophoresis (74 MBq/mg). The radiochemical purity of Y-90-AS incubated with human normal serum was estimated by 20 % polyacrylamide gel electrophoresis and showed as high as 96.2 ± 1.08 % at 24 hr after incubation and 90.3 ± 0.92 % at 72 hr. The hybridization of Y-90-AS with phosphorodiesterbackbone sense oligonucleotides was examined by 20 % pelyacrylamide gel electrophoresis at 24 hr after the labeling and did not demonstrate the loss. The biodistribution in normal mice following intravenous administration of Y-90-AS showed 1.00 ± 0 . 3 1 % ID/g in the bone at 24 hr (n=5), and 4.02 ± 0 . 3 1 % at 72 hr (n=5). The principal Y-90-activity was demonstrated in the kidney (30.8 ± 4.05 % ID/g at 24 hr, 15.0 ± 1.63 % at 72 hr). The stable radiochemical purity of Y-90-AS could be prepared at least for one duration of Y90-physical half-life. These data will contribute to the therapeutic potential of Y-90-AS.

THE DOPAMINERGIC SYSTEM IS ALTERED UNDER NEONATAL ASPHYXIA - STUDIES WITH [F-18]FDOPA There is evidence that the dopaminergie system is sensitive to asphyxia. However, the respective enzyme activities have not been measured in the living neonatal brain yet. In this study, FDOPA was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) and the relative changes of monoamine oxidase (MAO) and catechol-o-methyl-transferase (COMT) in the neonatal pig brain. Two PET studies were performed under control conditions and under 2-hour asphyxia in each of six piglets and combined with measurements of cerebral blood flow (CBF) and volume (CBV). Plasma metabolites of FDOPA were also determined by HPLC. As expected asphyxia elicited a 3-fold elevation of the CBF and increased the CBV by 40%. The blood-brain transfer of FDOPA, K1, and the clearance rate constant from brain, k2, were unchanged. However, the rate of [F-18]fluoro-dopamine synthesis, k3, was increased id stnatum from 0.038+3.016 rain"1 to 0.056_+0.028 rain"1. Also, the rate of conversion of FDOPA to 3-O-methyl-FDOPA (OMFD) by COMT in plasma decreased during asphyxia from 0.0080_+0.0015 rain"1 to 0.0046_+0.0010 rain"1. Measurement of metabolites in tissue indicates that similar changes occurred also in the brain. Furthermore, the amount of FDOPAC as product of brain MAO activity was significantly decreased under asphyxia. Increase of the extracellular level of dopamine is expected to be involved in severe disturbances of neuronal metabolism during asphyxia, e.g. by generating free radicals and quinones. In this study, evidence for an increase of the AADC activity and a decrease of M AO activity during asphyxia was obtained which may contribute tc the increase of extracellular dopamine.

C O

| m

C L_

P 413

P 416

K.A.J.McKellar(l~, C.G.Gemmell(2), J.B.Neilly(3) J.H.McKillop(3), A.T.Elliott(1). Depts of Clinical Physics(1), Bacteriology(2), Medicine(3), university of Glasgow.

K. Kawabata, H. Tachibana, M. Sugita and M. Fukuchi* 5th Department of Internal Medicine and Department of Nuclear Medicine*. Hyogo College of Medicine, Nishinomiya JAPAN

IMAGING INFECTIOUS/IHFL~&TOHY R&DIO-IODIHATED & N T I - T N F - ~

COMPARATIVE SPECT STUDY WITH 1-123 IOMAZANIL AND 1-123 IODOAMPHETAMINE IN PARKINSON'S DISEASE

FOCI

WITH

The diagnosis of infectious/inflammatory lesions as early and accurately as possible presents a significant clinical challenge. TNF-u is a pivotal cytokine in the pathogenesis of inflammation and is present at high concentration at sites of acute infection as well as at sites of synovitis. We have directly radio-iodinated a rat monoclonal antibody raised against murine TNF-u and evaluated it for its ability to detect infectious / inflammatory foci in a murine model of septic arthritis. Mice were injected intravenously with 5xl07 cfu of an arthritogenic strain of S. aureus. At 2 days post infection iodine-123 labelled antiTNF-~ (2MBq) was injected i.v. and its tissue distribution measured after 6 hours by gawaua camera imaging and by' tissue specific radioactivity counting. Results demonstrate a generalised uptake in tissues of infected animals compared with matched controls in addition to focal uptake at infected joint lesions, at this stage the model is undergoing a septicaemia phase and is developing infectious joint lesions. Further studies are underway at 7 days post infection (when joint lesions are visibly detectable); these involve bio-distribution and ganm~ camera imaging studies, investigation of the association of radio-activity to bacteriological tissue counts. Studies involving 99mTC-HSA (which in addition will be conducted at 2 days post infection) to evaluate the role of vascular leakage in the uptake mechanism.

1-123 iomazenil (IMZ) is a ligand for SPECT imaging of brain benzodiazepine (BZ) receptor binding. BZ receptor and gammaaminobutylic acid (GABA) receptor comprise a receptor complex in the cerebral cortex. Early IMZ SPECT is reported to reflect brain perfusion status, and delayed IMZ SPECT to reflect specific binding to BZ receptors. We reported preliminary data showing impaired IMZ binding in Parkinson's disease (PD) at the EANM Congress 1996 (Abstract No. PMo655). In the present study, we compared IMZ SPECT with 1-123iodoamphetamine (IMP) SPECT in fifteen PD patients. IMZ SPECT and IMP SPECT were performed with a single-head gamma camera system (Starcam 3000XC/T) at an interval of six or eight days. The early and delayed IMZ SPECT scans were started fifteen minutes and three hours, respectively, after injection of 167MBq of IMZ. The IMP SPECT scan was started 30 minutes after injection of 111MBq of IMP. The ratio of cerebral-to-cerebellar counts was calculated as the count index (CI) in nine pairs (left and right) of cerebral and cerebellar regions in each SPECT study. The CIs for BZ receptor binding in the delayed IMZ study were significantly correlated with motor disability in the frontal, temporoparietal, parietal and occipital cortices (P<0.05 in each region), but not correlated with age, illness duration, 1-dopa dose, or mental status. In the IMP SPECT study, no correlations were found between the CI in any of the cerebral regions except the temporal cortex and age, illness duration, motor disabil ity, t-dopa dose, or mental status. The CI in the temporal cortex was only correlated with illness duration (P<0.05). The CIs in the early IMZ study were significantly correlated with those in the IMP study in the temporal, temporoparietal, parietal and occipital cortices (P<0.05 in each region). These results suggest that the brain GABA/BZ receptor complex in PD is impaired in proportion to the severity of the motor disability, and that delayed IMZ SPECT provides different information on brain function from IMP SPECT. IMZ SPECT is superior to IMP SPECT for evaluating the pathophysiological state in PD.

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O

P417 A. Hertel, M. Weppner**, H. Baas*, M. Schreiner, F.D. Maul**, R.P. Baum, P.A. Fischer*, G. HSr Department of Nuclear Medicine, Department of Neurology*, Klinikum der Johann Wolfgang Goethe-Universitft Frankfurt/Main, BRD, Department of Nuclear Medicine, Stfdtisches Klinikum Karlsruhe**

P 419 A. Soricelli P.P. Mainenti, A. Varrone, A. Discepolo, M.R. Grivet Fojaja, G. De Michele, A. Filla and M. Salvatore. Departments of Diagnostic Imaging and Neurology, National Research Council, University of Naples Federico II. BRAIN PERFUSION WITH SPECT COMPARED TO MR IMAGING IN SPINOCEREBELLAR DEGENERATIONS (SCD).

QUANTIFICATION OF IBZM DOPAMINE RECEPTOR SPET IN DE NOVO PARKINSON PATIENTS BEFORE AND UNDER THERAPY

SCD are an heterogeneous group of disorders including hereditary and non hereditary forms. Early Onset Cerebellar Ataxia (EOCA) and Friedreich's disease (FD) are most common in youngs, while Autosomic Dominant Cerebellar Ataxia (ADCA) and Idiopathic Late Onset Cerebellar Ataxia (ILOCA) in adults. The aims of this study were to assess the regional cerebral perfusion (rCP) in patients with SCD and to correlate the rCP reduction to the degree of brain atrophy detected with MRI. Five patients with ADCA (3 m, mean age 47_+9 yrs), 11 with ILOCA (6 m, 56+8 yrs), 6 with FD (4 m, 31_+7 yrs) and 6 with EOCA (4 m, 31_+8 yrs) were studied after the injection of 740 MBq of 99mTcHMPAO with a brain dedicated SPECT system (Ceraspect, DSI). Images were reconstructed and analysed visually and using a semiquantitative method (average regional counts/average reference counts) to obtain rCP values for each group. These values were compared with those of 4 different control groups, age and sex matched. The ADCA patients showed a significant (p<0.01) decrease of rCP in brain stem, cerebellum and caudatum, the EOCA in parietal (p< 0.05) regions, the FD in cerebellum (p<0.05), in parietal (p<0.01) and temporal (p<0.01) areas, the ILOCA in brain stem (p<0.05), cerebellum (p<0.01) and right temporal (p<0.05) regions. The MRI scans showed different degrees of atrophy of the cerebellum, brain stem and cerebral cortex in the 4 groups of patients. The degree of hypoperfusion was correlated to the severity of atrophy in cerebellum (R=-0.47; p<0.01) and in brain stem (R=-0.55; p<0.01). No correlation was found between severity of hypoperfusion and degree of atrophy at cortical level. In EOCA and FD series the presence of a mild degree of cerebral cortical atrophy in 2 patients was associated with a significant reduction in temporoparietal rCP, which was not due to diaschisis or to anoxic or vascular disease. These results suggest that the reduction of rCP evident in the early onset forms of SCD, may represent the first sign of cerebral involvement, not detected with anatomical techniques. Further investigations are necessary to define typical patterns for each group and correlate them with the prognosis and clinical evolution of the diseases.

IBZM dopamine receptor SPET has been evaluated in several neurodegenerative diseases affecting dopamine receptors like Parkinson's disease. Differential diagnosis is based on semiquantitative determination of striatal uptake in the basal ganglia (BG). 7 different procedures for calculating BG uptake were compared and checked statistically in 28 previously untreated de novo parkinsonian patients before and in 14 patients (after a mean of 9 months) after initiation of antiparkinson medication. IBZM SPECT was performed on a sophy SPECT camera 10 minutes and 2 hours after injection. Filtered back projection was applied with butterworth filter of 6th order. In 21 hemiparkinsonian patients 16/21 studies demonstrated a contralaterally increased uptake ( right to left difference a mean 8 percent, sensitivity 76%), in the most robust uptake procedure. Differentiation between clinical side-affection and contralateral(y increased uptake (mean 6%) was significant (p=0.02). Mean basal ganglia/frontal cortex ratio (BG/FC) was 1.55 +/- 0.14 (attenuation corrected). Attenuation correction did not influence the relative ratio of BG-uptake (p=0.01). Antiparkinson medication did not produce any significant changes in follow-up IBZM BG/FC uptake, but initial uptake could separate responders from non responders (mean 1.58 vs. 1.39 in non responder). IBZM can be routinely used for differentiation of de novo parkinsonian patients regarding hemiparkinson and therapy responsiveness in drug naive patients.

P 418

P 420

H.Rieck,*R.Pichler,*W.Maschek,

J.S. Lee H-C. Song, S-C. Cho, B.N. Kim, C. Kwark, D.S. Lee~ K.S. Park, J-K. Chung, M.C. Lee, and C-S. Koh, Seoul National University Hospital, Department of Nuclear Medicine, Neuropsychiatry, and Biomedical Engineering, Seoul, Korea

E.Deisenhammer

L a n d e s n e r v e n k l i n i k Linz, D e p a r t m e n t of N e u r o l o g y and *AKH Linz, 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 T R I A T A L U P T A K E OF PARKINSON'S DISEASE

[123J]~-CIT

FOR

DIFFERENTIATION

OF

Methods: SPECT was p e r f o r m e d w i t h a t r i p l e headed r o t a t i n g garmma c a m e r a 20 hours a f t e r a p p l i c a t i o n of 5 m C i [123J]~-CIT. For s e m i q u a n t i t a t i v e analysis, a cons t a n t q u a d r a t i c ROI of 5x5 p i x e l was u s e d to m e a s u r e the h i g h e s t count rate w i t h i n the striattun in the axial slices. The same ROI size was a p p l i e d to get a m e a n count rate in the d o r s a l p a r t s of the c e r e b e l l a r h e m i s p h e r e s as a r e f e r e n c e . The r a t i o s t r i a t u m / c e r e b e l l u m was s t a t i s t i c a l l y a n a l y z e d and Chi 2 test was c a r r i e d out w i t h a c u t o f f of 8,0. Patients: G r o u p A c o n s i s t e d of 20 p a t i e n t s w i t h c l i n i c a l l y diagnosed P a r k i n s o n ' s d i s e a s e of at least 3 years d u r a t i o n and v a r i o u s s e v e r i t y and types, m e a n age was 63 ±9 yrs, ii were male. G r o u p B were 20 p e r s o n s not f u l f i l l i n g the c l i n i c a l c r i t e r i a of PD. T h e y s u f f e r e d o t h e r n e u r o logical diseases and were without drug treatment influencing dopamine metabolism (age 60 ±12 yrs, ii male). Results: The count rate ratio of s t r i a t u m / c e r e b e l l u m was 6,1 ±2,6 in g r o u p A and 13,5 ±4,9 in g r o u p B. The ratio decreased moderately with age in group B (y[ratio]= 17,8-0,071x[age], r=-0,17) and correlated w i t h H o e h n and Yahr score in g r o u p A. A c c o r d i n g to Chi 2 test (group A vs. B, r a t i o <8,0 vs. >8,0) the d i s c r i m i n a t i o n b e t w e e n the 2 g r o u p s was h i g h l y s i g n i f i c a n t (p <0,001), w i t h a s e n s i t i v i t y and s p e c i f i c i t y of 90%. C o n c l u s i o n : [123J]~-CIT S P E C T is a r e l i a b l e m e t h o d for d i f f e r e n t i a t i n g PD p a t i e n t s f r o m n o n - P D p a t i e n t s . Its reliability for d i f f e r e n t i a l d i a g n o s i s in i n c i p i e n t PD has to be i n v e s t i g a t e d in f u r t h e r studies.

1044

QUANTITATION AND LOCALIZATION OF REGIONAL CEREBRAL BLOOD FLOW RECOVERY AFTER DRUG THERAPY IN ATTENTION DEFICIT HYPERACTIVITY DISORDER(ADHD) USING SEQUENTIAL TC-99m-HMPAO BRAIN SPECT AND 3D IMAGE REGISTRATION TECHNIQUE. Three dimensional image registration is required for the assessment of rCBF recovery after drug therapy in patients with psychiatric disorders. We have quantitatively estimated and localized this rCBF recovery using the parametric images of normalized difference ratio (PINo~=(Cpost--Cpre)/Cpre× 100%). Twenty-three patients with attention deficit hyperactivity disorder(ADHD) underwent a series of Tc-99mHMPAO brain SPECT studies before and after treatment with methylphenidate. For the assessment of therapeutic effect, ?INDR were produced and the relationship between clinical improvement and rCBF recovery after therapy was evaluated. 3D registration program was developed to compensate for repositioning errors between repeated SPECT imagings. Preand post-therapy scans were normalized, which matches the total counts in the cerebral regions. Normalized difference ratio of greater than 20% was considered as significant increase of rCBF. Twenty percents of reduction in CoRner's Parent Rating Scales and subjective improvement assessed by parent and neuropsychiatrist were used as the criteria of clinical improvement. The results showed that PINnR with 3D image registration could localize the focal spots that demonstrated rCBF recovery in frontal lobe and basal ganglia, and these were closely correlated with clinical improvement (sensitivity=0.83, specificity=0.73, PPV=0.?7, NPV=0.80). Our results suggest that reduced rCBFs in frontal lobes and basal ganglia are associated with ADHD. We conclude that image registration and parametric image of normalized difference ratio of brain SPECT could rCBF clinicalimrovement

. . . . . ful in th . . . . . . . . . . t of rCBF recovery after treatment in ADHD.

iec~verv I

120

1

i

~

P 421

P 423

H.Abu-Judeh,S.Levine*, S.Naddaf, H.El-Zeftawy, H,AbdeI-Dayem. St. Vincents Hospital and Medical Center of NY Medical College. *Beth Israel Hospital. NewYork, N.Y. Tc-99m HMPAO SPECT BRAIN P E R F U S I O N (BP) AND F-18 FDG FINDINGS IN C H R O N I C F A T I G U E SYNDROME (CFS) We aim to present data from an ongoing study comparing Te.-99m HMPAOSPECT BP changes and F-18 FDG glucose uptake in 11 pts with CFS. Eleven pts (9 F, 2 M) age 34-52 (mean : 40.2 ) with the diagnosis of CFS (the diagnosis of CFS was made after exclusion of all causes of organic brain diseases that can lead to similar symptoms) bad both studies l-8 days apart. SPECT images were acquired using"TRIONIX"triple head gamma camera,2hrs after IV injection of Tc-99m HMPAO (19-22 mCi). The images displayed 2 pixels thick in the transverse, sagittal, and coronal sections, 10 color scale adjusted for 100% max. uptake in the cerebellum. Any region of < 70% in the cerebral cortex and basal ganglia, or <50% in the medial temporal was considered abnormal. One hour following the injection of 2-5 mCi of F-18 EDG images were acquired using coincidence imaging, "ADAC" dual headed system, total of 64 projections (32/head) acquisition time 60-80 sec per projection.Projection data were reconstructed by filtered back projection with butterworth filter including scatter, and attenuation correction.. The images were displayed 2 pixels thick in transverse sections, 8 color, and grey scale and read 1 )ert Nuc. Med. sician. The results are in the followin table: I

2

3

4

5

6

7

8

9

10 " 11

N

L* STO

N

L P

DSTH +LF

L FP

B/L AIF

MCD

N L SF

N

N N N

SPECT

N L FP

DSTH +BG

R N L B/L C Is AIF

N DSTH

N-aormal,L-lefl, S-supefior, F=frontaI,P=parietal,DSTH~difl'use supra tentorial hypoperfusion, BG=basalgang[i% R=right, C-cerebral cortex, ls=insular,A=Anterior,l=inferior,STO-superior temporo-occipital, B/L=bi[atera[ *? positioning problem

We conclude that Coincidence detection using duaI headed gamma camera is technically available and useful for metabolic brain imaging. In CFS there seems to be uncoupling between brain perfusion and glucose uptake changes.

L. CinotLi*°, S.M. Gogoleva*P, M. Sindou °, G. Fischer °, A. Jouvet °, G. Saint Pierre °, P. Ryvlin *°, J.C.Froment °, L. Veyre*, F. Maugui6re *°. *CERMEP, °H6pital P. Wertheimer, Lyon, FRANCE, P Sakha University, YAKOUTSK, C.I.S. "GLUCOSE BRAIN METABOLISM WITH FDG-PET BEFORE AND AFTER SURGICAL RESECTION OF CAVERNOUS ANGIOMAS. Cavernous angioma (CA) has a low prevalence in the population but its diagnostic is easy using MRI. Epileptogenic and hemorragic potential of CA leads to surgery but definitive conclusions concerning the evolution of surrounding tissues remain difficult. Because epilepsia often presents with a low metabolic region, we therefore used FDG-PET 1) to establish the possible presence and the extent of perilesional metabolic modifications and 2) to address if the surgical resection of the CA could modify, locally or at distance, the brain glucose metabolism. We selected 15 patients presenting with epilepic seizures and CA on MRI. During EEG controlled studies, we quantitatively measured the interictal brain glucose metabolism (CMRGlu) before and one year after the simple surgical resection of the CA. Pathology assessed the cavemomatous character of the lesion and studied the adherent brain tissues when present. Global brain CMRGIu remained unchanged after surgery (8,33 -+ 1,15 vs 8,33 _+ 1,70 ml/min/100g). CMRGIu decreased significantly in the CA hemisphere (2-way ANOVA, p=0,016), this was not modified by surgery (no interactions between the side and surgery factors). Regions of interest (ROIs) close to the lesion, even inside the hemisphere, were less metabolic than remote ROIs (3-way ANOVA, p=0,035). This pattern was not modified by surgery (no significant interaction between factors). CMR total CA normal close ROI close ROI remote ROI rein. ROIl Glu brain side side CA side nl. side CA side nl. side i before 8,33 8,99 9,39 8,63 9,05 9,28 9,38 after 8,33 8,89 9,12 8,47 8,76 9,12 9,19 The existing metabolic gradient around the lesion is generally not sharp enough to help delineating a region for surgical resection. Modifications of a potentially epileptogenic zone are not noticable either. The absence of post- surgical variations may indicate that the metabolic consequences of the lesion are replaced by those of the surgical scar. Brain surgery does not appear to produce metabolic variations in follow-up studies, provided the intervention was simple and a sufficient time was waited for.

co =l c-

o tfl o o,,

P 422

P 424

~ro!icki %., D o m ~ a ! A., ~ w [ ~ c i ~ s k i H. D~p. of N u c l e a r Eedicine, Dep. of N e u r o l o g y M e d i c a l S c h o o l of W a r s a w , Warsaw Poland

C. Dannenberg. A. Bosse-Henck*, A. Weiser, H. Barthel, WH. Knapp, Departments of Nuclear Medicine and *Internal Medicine, University of Leipzig, Germany.

CBF-SPECT

IN

AMIOTROPHIC

LATERAL

x__

O O II.

SCLEROSIS

A L S is a p r o g r e s s i v e degenerative disorder of N o t o r n e u r o n . The p u r p o s e of t h i s s t u d y is to report our experience in the e v a l u a t i o n of C B F in p a t i e n t s w i t h ALS. We e v a l u a t e d 62 patients. The e v a l u a t i o n included: EMG,clin.exam neuropsychologioal testing, MRI and CBF-SPECT. CBF-SPECT (99mTc-HM-PAO, 740MBq ) was performed w i t h O r b i t e r 75 ( S i e m e n s ) . M R I w a s m a d e of TI, T2 and PD g a t e d a x i a l , c o r o n a l and s a g g i t a l images (Magnetom, 1.ST, S i e m e n s ) . MRI i m a g e s r e v e a l e d h i g h s i g n a l in T2 and PD a l o n g the p y r a m i d a l t r a c t in the i n t e r n a l capsule and c e r e b r a l pedducle in 25 p a t i e n t s . CBF-SPECT showed regional decrease of t r a c e r uptake in 25 p a t i e n t s . Regions of d e c r e a s e d C B F w a s s e e n in the f r o n t o - p a r i e t a l regions, frequently asymmetrically. Aditionnally a decrease u p t a k e of the t r a c e r w a s o b s e r v e d in frontal or t e m p o r a l regions in 7 c a s e s . Location and s e v e r i t y of C B F d i s t u r b a n c e s did not c o r r e l a t e w i t h the s e v e r i t y or d u r a t i o n of A L 5 or MRI f i n d i n g s . Decrease of C B F in the f r o n t o - p a r i e t a l region is p r o b a b l y associa ted w i t h m o t o r - c o r t e x disease. However SLA produces more general,disseminate CNS l e s i o n s w h i c h c a n be r e s p o n s i b l e for o t h e r s i t e s of CBF disturbances. We a s s u m e the C B F e x a m i n a t i o n may play a role as a c o m p l e m e n t a r y method in e v a l u a t i o n of SLA p a t i e n t s .

BRAIN PERFUSION ABNORMALITIES IN PATIENTS WITH SEVERE SLEEP APNEA SYNDROME (SAS) Patients with SAS tend to have cognitive dysfunction. This may result in characteristic cerebral perfusion deficits. It was hypothesized that perfusion abnormalities might be related with polysomnographic data. Patients: n = 73 (age 55 -+ 12 a) with severe SAS (RDI 65.05 _+27.9, O2$-time < 90 %: 173 _+96 rain). SPET-acquisition after injection of 600 MBq Tc-99mECD with high-resolution camera (CERASPECT, DSI). ROl-quantl'tatien (reference: cerebellum) and visual scoring by 3 experts (scale 0 to 3, 0 = normal local activity, 1 = non significant deficit (normal), 2 = significant deficit (abnormal), 3 = large defect. Results: 1. Visual scoring: 3 1 % of patients had local activity deficits the majority of which were located in frontal and temporal lobes. 2. ROI-anaIysis: Correlations between depth of the frontal precentral activity defects and minimal nocturnal O2-saturation (r = - 0.42, p = 0.001), O2$-time < 90 % (r = 0 33, p = 0.008) and the duration of apnea and hypopnca per night (r = 0 25, p - 0.022) were significant. Less significant correlations were found between depth of the activity defects in the left mesial temporal lobe and minimal nocturnal Oz-saturation, O2$-time < 90 %~ and between the the depth of prefrontal activity defects and minimal nocturnal O2-saturation. Conclusion: Cerebral perfusion defects in patients with SAS are predominantly localized in frontal and temporal lobes. The depth of the perfusion deficits in some cortical areas correlates significantly with polysomnographic parameters. Further studies have to show the potential contribution of vigilance to this observation

1045

P 425 Chin-Hung Kao, Department of Nuclear Medicine, Veterans General Hospital, Taichung, Taiwan.

P 427 Taichung

TC-99M HMPAO SPECT, FDG-PET, AND MRI QF BRAIN IN SLE PATIENTS WITH BRAIN INVOLVEMENT. Involvement of the brain is one of the most important complications of SLE, however its diagnosis is difficult due to the lack of effective imaging methods In this study, we compared multiple brain imaging modalities with clinical manifestations, to determine the most accurate imaging method for the diagnosis of brain involvement in SLE patients. Methods: Twenty SLE patients, aged 24 to 47, years were divided into two groups. Group 1 (G1) consisted of 10 patients with definite neuropsychiatric disorder (stroke, seizures, and psychosis). Group 2 (G2) consisted of 10 patients with minor neuropsychiatric disorder (headaches; dizziness, or recent memory impairment). Results (1) SPECT findings were abnormal in 10 (100%) G1 patients and 8 (80%) G2 patients. PET findings were abnormal in 9 (90%) G1 patients and 2 (20%) G2 patients. MRI findings were abnormal in 4 (40%) G1 patients and 0 (0%) G2 patients. (2) Parietal (18,90%), frontal (13,65%), and temporal lobes (11,55%) were common areas of brain involvement The occipital lobe (6,30%), thalamus (5,25%), cerebellum (5,25%), and basal ganglions (4,20%) were less common areas of brain involvement in neuropsychiatrio SLE patients. Conclusions: Tc-99m HMPAO brain SPECT when compared with FDG brain PET and brain MRI, has the best correlation with clinical diagnosis, and may provide objective information regarding brain involvement in SLE patients.

Garcia Solis D.. Ruiz J.. Sanchez Roman J.*, Garcia Hdez. F.*. Castillo MJ.*. Ocafia C.*. Mura Sanz J+., Mora J+. Serviciu de Medicina Nuclear. *Servicio de Medicina Interna Unidad de Conectivopatias. Hospital Universitario Virgen del Rociu de Sevilla. + Facultad de Psicologia de la Universidad de Sevilla. CORRELATION BETWEEN PSYCHOMETRIC TESTS AND BRAIN SPECT IMAGING WITH HMPAO-Tc99m IN THE STUDY OF THE NEUROPSYCHIATRIC DISORDERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOUS.

Nervous system disturbances (NPSLE) have been found in between 14 and 75% of patients with SLE. The must frequent clinical features are epilepsy, stroke and organic brain syndrome. Moreover. many patients complain of several symptoms of difficult interpretation (headache, mood changes or minor cognitive disorders) that could unreveal subclinical neuropsychiatric disturbances. NPSLE entails a diagnostic challenge due to its difficult clinical assessment and the lack of diagnostic resolution of the usual neuroirnaging techniques. The aim of this study is to evaluate the diagnostic and prognostic usefulness of brain SPECT with HMPAO-Tc99m in patients with SLE and its correlation with psychometric tests and conventional neuroimaging teclmiques. MATERIALS AND METHODS: We have studied fifty-six patients with SLE (with or without NP manifestations) by means of: (1) Clinical and activity assessment (SLEDAI) (2) Brain SPECT with HMPAO-Tc99m (3) Brain IvlRI (4) Cognitive function tests: Memory assessment (Weschler), attention (letters square test), verbal intelligence (PMA) and logical reasoning (PMA), and personality tests (MMPI). RESULTS: We have found cerebral blood flow alterations in the brain SPECT in 90% of the subjects. According to the pattern of involvement, these were distributed in three groups: multffocal (impairment of three or more loci), focal (less than three loci of low uptake) and diffuse (generalized decrease). 85% of the patients showed impairment in the psychometric tests (at least in one of the examined variables). The multivariated analysis showed some linear correlations (Pearson): multffocal involvement pattern with clinical neurological manifestations (p=0,009) and positive rheumatoid factor. The multffocal pattern shows correlation with the following tests: verbal function(p=0,04 ff the left anterior area is affected, p=0,03 ff there is right or left posterior involvement, p=0,002 with left anterior parietal involvement, and p=0,016 ff it involves the left posterior parietal region), logical reasoning test (with left posterior parietal) and a strong correlation with abnormal results in the attention tests. On the whole, there is a strong correlation between the cognitive tests battery (with at least one of the variables being abnormal) and the multifocal pattern, and specially with SCO. CONCLUSION: Our results show the presence of a multffocal pattern with involvement of tempo-parietal regions and a left predominance in the SPECT, but with no correlation with MRI, and a severe impairment of "frozen intelligence" (that implies complex cognitive abilities and that does not decline with the inespectfic or "normal" deterioration caused by aging) as evaluated by means of the verbal intelligence test.

P 426

P 428

P.Colamussi,C.Cittanti,M .Giganti,M.Govoni*,F.Trotta*,R.Ricci°,G B a r balella#,A.Piffanelli. Cattedra di Medicina Nucleare, Div. Reumatologia*, Universifft e O s p . S . A n n a , Ferrara: Servizio di Neuroradiologia ° Osp.Bellaria, 1.CO.C.E.A.-CNR#, Bologna - Italy

H, Barthel, J. Berrooschot , S. Hesse. S Bettln. C Danneuberg, D Schneider , WH. Knapp. Departments of Nuclear Medicine and Neurology. University of Leipzig, Germany

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

EFFECT OF CASCADE FILTRATION ON CEREBRAL PERFUSION AFTER ACUTE STROKE - EVALUATION WITH Te-99m-ECD SPECT

The diagnosis of Central N e r v o u s System (CNS) involvement is a major problem in Systemic Lupus Erythematosus (SLE) patients with only minor clinical signs and with normal brain anatomy at morphological imaging evaluation (CT or MRI). Five SLE patients with only mild neuropsychiatric manifestations were studied with magnetic resonance imaging (MRI), brain perfusion S P E T with " ' T c H M P A O and localized proton magnetic resonance spectroscopy ( H - I MRS). The H - I MR spectra were obtained from different v o l u m e s of interest localized in normally and abnormally perfused regions on SPET evaluation. No abnormalities were found on the MRI studies. S P E T revealed hypoperfused brain regions in all patients. H - I M R S s h o w e d metabolic abnormalities in the regions corresponding to hypoperfused areas w h e r e a s it was within the normal range in the regions exhibiting a normal SPET image. The most remarkable results of the present study are: a) the correlation between the findings o f H- 1 MRS and the perfusion pattern of the S P E T images: b) since the same abnormal regions give normal magnetic resonance, H-1 MR spectroscopy and SPET appear to be more sensitive than MRI in revealing CNS involvement of SLE patients; c) brain tissue abnormalities can be demonstrated even in absence of morphological lesions "in vivo detectable".

Recemly a number of regimens for treatment of acute ischemic stroke have been tested So far. positive therapeutic effects ~;cre not verified, except first promising results of thrombolysis studies. This investigation was designed Io monitor therapeutic effects of cascade filtration (CF) which rapidly decreases plasma viscosity due to extraction of high-molecular substances (fibrinogcn. LDL. o:2-MG). Patients. n = 28 (10 f. 18 m). age = 57 - 81 y ( m v 68 ~ 6 y). were studied prospectively. Diagnosis: severe (Scandinm,ian Stroke Scale (SSS) = 24 ± 9) acute medial cerebral ariery stroke Group 1: CF (n = 16). group 2: placebo (n = 12). Protocol: 4 CF (I.CF within 12 h after onset of stroke symptoms, further CFs eveu' 24 h). 3 SPECT investigatians (before ICF. after 1. and after 4.CF). 400 - 600 MBq Tc-99m-ECD. brain dedicated SPECT system (Ceraspect, DSI/. SPECT analysis: using transverse slices of SPECT studies, activity deficit defined with irregular ROIs using contour detection program: volume (V) and depth (count density, related to injected dose (D)) of aelivity deficits, ratios between SPECT 2 / SPECT 1 (V2m Dzul), SPECT 3 / SPECT 2 (V3/2, D3/2) and between SPECT 3 / SPECT i (V3,1. D3/I), respectively. Correlation of SPECT parameters with data on neurological outcome (Modified Ranking Scale. SSS. Barthel Index). Results: The followin~ table gives the above ratios (m.v. ± SEM) ~group 1 (CF) ~roup 2 (placebo) p (~,roups 1, 2) V2/1 0.93±0.54 n.s. 1083±0.14 n.s. n.s. 0.79±0.42 p<0.05 1 . 4 0 ± 0 . 9 2 p<0.05 0.09 V-~/1 0.87±0.67 us. 1.26±0.71 n.s. 0.27 DT/I 141~-0.31 p<0.01 1.31±0.49 n.s. n.s. D~p 0.87±0.25 n.s 0 . 7 0 ± 0 5 0 ns. n.s. Dan 1.32±0.46 p<0.05 1.02±105 n.s. 0.42 In CF patients there was a linear correlation benveen D3/2 and SSS ratios after corresponding time intervals (r = 092, p < 0.01). Even with a relatively small number of patients significant reductions in peffusion deficits after acute stroke were shown. However. there was only a trend suggesting therapeutic benefit by CF. Statistic verification of this benefit has to await larger patient populations

1046

P 430

P 432

M. lerardi, O, Schillaci, F. Scopinaro, R. Danieli, N. S. Tiberio, E. Di Luzio Dpt of Experimental Medicine,Sect.of Nucl. Medicine, Univ. "La Sapienza" Rome, Italy

Arturo Chiti ~, Giordano Savelli~, Angela Molitcrni2, Antonella Spinelli1, Lorenzo Maffioli!, Monica Terenziani2, Paola Tagliabue2, Emilio Bombardieri1. 1Nuclear Medicine and 2Medical Oncology "A ", Istituto

99mTc-MIBI SCAN IN THE RECURRENCE AFTER BREAST CANCER SURGERY

OF

CANCER

Ma~mography is very sensitive in screening breast lesion but shows several difficulties when recurrence of cancer after lumpectomy or partial m a s t e c t o m y has to be assessed. We performed 99mTc MIBI s c i n t i m a m m o g r a p h y (SM) in 22 patients o p e r a t e d w i t h conservative surgery and 15 patients w i t h total mastectomy. A well defined node of e n h a n c e d uptake was found in 3 out of the 22 patients with conservative surgery. All of them had inconclusive mammography. M o r e o v e r one patients showed a positive SM in the controlateral breast. Two patients with total mastectomy shewed recurrence of cancer. The biopsies carried out after positive SM were always p o s i t i v e for cancer. One year follow up in the patients with negative SM did not show any clinical or mammographic change. All the patients w i t h partial m a s t e c t o m y showed an oblique b a n d of m o d e r a t e uptake of 99mTc MIBI in anterior v i e w w i t h i n 1 year from operation. This has to be considered to avoid false p o s i t i v e findings. Our p r e l i m i n a r data have to be confirmed by more extensive series. However SM seems to be a sensitive and specific exam to detect recurrence of cancer after surgery.

Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy

99m-Tc-SESTAMIBI (MIBI) SPET TO ASSESS RESPONSE TO PRIMARY CHEMOTHERAPY IN BREAST CANCER The aim of this study was to assess M1BI SPECT in evaluating the response to primary chemotherapy in breast cancer. Methods. Nine women (mean age 46.6 years, range 25-53) with T2 (n=7) and T3 (n=2) breast cancer were enrolled in this study. Two patients were N2, 3 were NI and 4 NO. Primary chemotherapy with doxorubicinpaclitaxel (AT) was delivered every 3 weeks for 4 courses (A= 60 mg/m2 iv bolus; T = 200 mg/m2 by 3-hour infusion). MIBI SPECT was performed before and at the end of the chemotherapy course. Patients were intravenously injected with 925 MBq of the tracer. Acquisition of SPECT (120 steps/360°, 20 s/step, matrix 128x128, zoom 1) started 20 minutes later. All patients underwent quadrantectomy and complete axillary dissection within 2 weeks from the MIBI acquisition. Results. Prior to chemotherapy MIBI showed 9/9 primary tumors and 5/9 metastatic axillae, in concordance with instrumental and clinical data. After chemotherapy 2/9 primary tumors were positive at M1BI SPECT while all the axillae were negative. Pathological examination showed no evidence of the primary tumor (non-homogeneous parenchyma) in 2 breasts and ductal infiltrating carcinoma in 7. Metastatic axillary nodes were demonstrated in 7/9 axillae. Conclusions. Although we evaluated a limited number of patients, MIBI SPECT does not seem to be useful as a parameter of chemotherapy response. In fact, the negative postchemotherapy MIBI SPECT could be related both to response to treatment and to changes in the biological behavior of the tumor. This work has been partially supported by AIRC project

P 433

Arturo Chiti 1, Roberto Agresti2, Giordano SavelliI, Antonella Spinelli1, Lorenzo Maffioli1, Riccardo Giovanazzi~, Marco Greco2, Emilio Bombardieri I. ~Nuclear Medicine and 2Surgical Oncology "B", lstituto

K.D.M.StumDe, M. Urbinelli, H. C. Steinert, Ch. Glanzmann, G. K.von Schulthess. Department of Medical Radiology, CH-8091 Zurich, Switzerland

99m-Tc-SESTAMIBI (MIB1) SPET TO DETECT METASTATIC AXILLARY NODES IN EARLY BREAST CANCER Axillary lymph node involvement is pivotal in breast cancer staging. Clinical evaluation of the axilla is an unreliable diagnostic tool, therefore a method for performing presmgical assessment of axillary metastases would spare the patient unnecessary surgical procedures. In addition, omission of axillary lymph node dissection would be costeffective. The aim of this study was to evaluate MIBI SPECT for the preoperative detection of axillary metastases in breast cancer. Methods. Twenty-seven women with 28 tumors (mean age 54.7 years, range 38-74) with TI-2 breast cancer were enrolled in this study. Twelve tumors were NO and 16 were N1. Patients were intravenously injected with 925 MBq of the tracer. Acquisition of SPECT (120 steps/360°, 20 s/step, matrix 128x128, zoom 1) started 20 minutes later. All patients underwent quadrantectomy and complete axillary dissection two days after the acquisition. Surgical marks were positioned on each single level for a more accurate pathological evaluation. Results. MIBI sensitivity was 96% (27/28) for the primary tumor and 82% (9/11) for the axillary nodes. The false-negative tumor was a ductal infiltrating carcinoma of the right breast, 5 mm in diameter. The 2 false-negative axillary resuhs were one N1 (pN1, 2/35 metastatic nodes) and one NO (pNl, 2/18 metastatic nodes). Only 1 of the 12 NO patients was upstaged after MIBI. Conclusions. These preliminary results showed that, while the overall sensitivity of MIBI SPECT for axillary metastases could be considered for further evaluation of the method in larger series of patients, in NO patients this technique seems to add little value to clinical examination. This work has been partially supported by A1RC project

FDG-PET FOR STAGING OF LYMPHOMA: AND COMPARISON WITH CT

t~ ¢-

x.._

P 431

Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy

c=O m

EFFECTIVENESS

P u r p o s e : To r e t r o s p e c t i v e l y evaluate FDG-PET in patients w i t h lymphoma and compare it with CT. M a t e r i a l s a n d M e t h o d s : 71 whole body (WB)FDGPET and 48 CT scans were performed in 36 patients w i t h Hodgkins'disease ( H D ) (12f/24m) and 14 w i t h N o n - H o d g k i n lymphoma (NHL) (5f/gm). Eleven HD and 4 NHL evaluations were pretherapeutic. PET and CT scans were compared to a standard of reference defined by all clinical and imaging information for the appropriate time. R e s u l t s : C o m p a r e d to the standard of reference in HD patients, PET and CT were true positive (TP)in 48 and 19, false p o s i t i v e (FP)in 1 and i0 and false negative (FN) in 4 and 3 patients, respectively. In NHL the numbers were TP in 17 and II,FP in 0 and 4 and FN in 1 and 1 cases, respectively. Sensitivities in HD were 92% and 86% for PET and CT (NHL 94% and 92%). In 12 patients w i t h HD (4 with NHL)PET was more accurate, in 3 patients with HD (i with NHL) CT was more accurate and in 17 patients w i t h HD (ii w i t h NHL) both imaging methods were equally valuable. C o n c l u s i o n : PET is a highly accurate staging m o d a l i t y in lymphoma and at least as sensitive as CT. In addition, CT has a substantial number of false p o s i t i v e results because it is unable to d i s t i n g u i s h b e t w e e n active disease and involuting tissue.

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o

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L Manse, PF Rambaldi, V Cuccurullo, M Quarantelli, A Laprovitera, E Procaccini. II University of Naples. Institute of Radiological Science, Nuclear Medicine.

V.Zaichick, P.Firsova, F.Medvedev, S.Zaichick, Medical Radiological Research Centre, Obninsk, Russia

Semiquantitative analysis of Tc99m-Tetrofosmin scintimammography: assessment of the acquisition protocol. Aim of the study was to evaluate the effect of different acquisition protocols on the lesion detectability in Tc99m-Tetrofosmin (TF) scintimammography in breast cancer patients. 27 patients (age range 24-71years) affected with breast cancer were included in the study. Ten minutes after intravenous injection of 555740 MBq of TF in the arm contralateral to the affected breast, static planar images were acquired for 5'. An anterior view was acquired with arm lifted over the head, including breast, axilla, supraclavear region and sternum in the field of view. Lateral view was performed with the camera under the table and the patient in lateral recumbence, omolateral arm lifted; a thin lead shield was placed between the two mammary glands slightly compressing the one on the table The prone lateral projection was performed with patient lying prone on a special table with holes for the mammary glands and the omolateral arm lifted. Quantitative analysis was performed drawing circular region of interest over the lesion, and an irregular background region over the omolateral hemitorax excluding the heart for left sided lesions. The tumour region, after a 25% increase in size, was automatically excluded from the background The mean turnout to background ratio (T/B) was 1.3, 1.7 and 1.6 for the anterior, lateral and prone view, respectively, with the lateral view providing the best contrast, particularly for left-sided and medial lesions. In 13 pts a delayed scan was performed 2 hours post injection; the average counts decrease in the late acquisition, after decay-correction and background subtraction, was 26.6, 40.2 and 27.8% for anterior, lateral and prone view, respectively, providing a 10.8 and 7% decrease in T/B for lateral and prone views, respectively, remaining unchanged in the anterior projection.Early acquisition with lateral view provided, in this cohort of patients, the best T/B.

NUCLEAR METHODS FOR STUDYING BREAST NORMAL, BENIGN A N D MALIGNANT TUMOURS

ELEMENTS:

Aim: To evaluate contents of essential and toxic chemical elements in intact, tumour and surrounding tissues of benign and malignant breast. Methods: The breast resections were taken from 42 women: 19 diagnosed with cancer, i0 with fibroadenoma, and 13 with fibrocystic disease. Samples of normal breast were obtained during autopsy of !0 healthy women died unexpectedly. Tissue samples were divided into two parts to be analysed m o r p h o l o g i c a l l y and elementally. Contents ©f 20 chemical elements (Ag, AI, Br, Ca, Ci, Co, Cr, Cs, Fe, Hg, K, Mg, Hn, Na, P, Rb, Sb, Sc, Se, Zn) were estimated by instrumental n e u t r o n activation analysis (INAA) using nuclear reactor. Results: Contents of many elements and especially K, Na, CI, Ca, P, Hg, Mn, and A1 in :umours are several times higher than those in intact tissue. Changes in the element contents of malignant tumours are expressed most clearly. Conclusion: Changes in contents of K, Na, C!, Ca, Mg, and Mn can be applied for express differential diagnostics of malignant and benign tumours using INAA results of biopsy puncture material. The changes obtained are the basis for developing a new non-invasive method of diagnostics by neutron activation m a m m a r y tomography.

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F. Scopinaro,G. De Vincentis*,R. Pani,R. Pellegrini,A. Soluri*,M. Ierardi,R. Danieli, N.S. Tiberio,L. Ballesio Dpt of Exp. Medicine, Univ. "La Sapienza",*CNR ITBM, Rome, Italy

O. Alonso,* L. Delgado, F. Mut,* I. Alonso, G.Lago,* M. N6fiez,* G. Sabini, I.M. Muse, J. Gaudiano,* E.Touya,* Nuclear Medicine Center (*) and Department of Clinical Oncology, Clinical Hospital of the University of Uruguay, Montevideo, Uruguay.

SINGLE PHOTON HIGH RESOLUTION EMISSION SCINTIMAMMOGRAPHY (SPEM): PRELIMINARY CLINICAL RESULTS 99m-Tc Prone s c i n t i m a m m o g r a p h y (PSM) shows low sensitivity w h e n breast cancer ( B C ) sized less than 1 cm are concerned. We present a clinical application of a high resolution gamma camera able to image the breast in similar conditions of X ray mammography.10 patients were submitted to PSM by Anger Camera and to SPEM (craniocaudal view with the breast under m o d e r a t e compression) 1 h after having given 20 mCi of 99mTc MIBI i.v. 2 lesions were T2, 4 Tic and 2 Tlb carcinomas, while the remaining 2 were fibroadenomata(F) . SPEM correctly diagnosed all the 8 malignant lesions;on the contrary PSM failed to detect the 2 Tlb BC. A n g e r Camera showed negative findings in the case of b e n i g n lesions,l F showed moderate uptake at the SPEM image with questionable diagnostic results. SPEM increases the sensitivity of s c i n t i m a m m o g r a p h y improving the detectability of small sized breast tumors. The increase of sensitivity can probably mean a moderate decrease in specificity. Exact measurement of tumor/breast activity ratio is however possible in compressed breast w i t h high resolution images (data not shown) with substantial improvement of the diagnostic value of SPEM. Our data encourage further studies on high resolution scintimammography.

SCINTIGRAPHIC EVALUATION CANCER Id¢ITH Tc-99m MIBI.

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BREAST

Scintimammography with Tc-99m MIBI has been proposed as an accurate test for the detection of primary breast cancer (BC) in patients (lots) with indeterminate mammograms. However, the value of this technique in the evaluation ofpts with advanced disease has been less studied. Furthermore, Tc-99m MIBI has been reported to be extruded fi'om tumoral cells by the Pglyeoprotein encoded by the MDR1 gene. The aim of this study was to study the potential of the technique in the detection of advanced BC lesions and to evaluate the possible relation between MIBI uptake and chemotherapy response in assessable lesions. We studied 19 pts with advanced BC (median age: 50, range: 35-69): 8 pts with advanced locorregional disease, 6 with loeorregional and metastatic disease, and 5 with recurrent disease. In pts with loeorregional disease, two lateral (prone imaging) and one anterior thoracic views were obtained 10 minutes and 1 hour after the injection of 740 MBq of Tc-99m MIBI. A whole-body acquisition was performed in all pts and additional static views on selected eases. All pts with indication of cytotoxic treatment received combination chemotherapy containing doxorubicin. In these patients the lesions were imaged 2-8 days prior combination chemotherapy and after a minimun of 2 cycles. Tumor-to-normal tissue uptake ratios (T/N) were calculated in each assessable lesion. The technique could detect 93% of tumoral lesions (14/14 breast tumors, 13/13 pts with axillary nodes, 2/2 local relapses, 2/3 pts with non regional lymph nodes, 6/7 pts with bone, 2/2 with lung, and 1/2 with liver metastases). Twenty-two lesions were evaluated for response to chemotherapy. Early T/N were significantly higher in lesions that showed a complete or partial remission than in non responding lesions (1.85, 1.5-2.9 vs. 1.40, 1.3-1.6; median, range respectively; p=0.0006). No lesion with a T/N
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A.R. BOrner I, M.Weckesser 1, U. Nitz 2, L. Kemna 1, H. Herzog l, H.G. Bender, H.W. Miiller-G~irtner ~ lInst, ofMed., Res. Cent. Jiilich, 2Dept. of Obstetrics, University Hospital Dfisseldoff, Germany.

R.Danieli,O.Schillaci,F.Scopinaro,°S.Angeletti, R.Tavolaro,*E.Polettini,P.Cannas,*G.Gualdi,°G. DelleFave,A.CentiColella. Nucl.Med.,°Gastroent., *I Ned., Univ. "La Sapienza",Rome,Italy.

P E T I N C O M P A R I S O N T O CT IN O V A R I A N CANCER Ovarian cancer is the most common gynecologic malignancy alter breast cancer causing one fit'~h of cancer death in women in Western Europe and the United States. More than 75% of the patients are diagnosed in stages FIGO III and IV with intraperitoneal or distant metastatic disease. Staging is done by CT, MRI and/or ultrasound. The aim of our study was to investigate whether PET is a more sensitive diagnostic tool. A total of 21 scans were performed in 1'7 non-diabetic patients with ovarian cancer FIGO III or IV after primary therapy with surgery and adjuvant platinumbased chemotherapy. Four of these patients were imaged twice. 20 mCi (740 MBq) F-18-FDG were admitfistered to the fasting patient if blood glucose levels were below 100 mg %. Imaging of the abdomen and pelvis was performed three hours after injection. Iterative reconstruction and 3-D-reprojected whole-body views were used for firml analysis. 18 of 21 scans showed local glucose hypermetabolism (local recurrence: 7, lymph node metastasis: 8, both: 3, all CT negative). Two patients were primarily diagnosed disease&ee by all methods, 3 of 4 at the second PET. One metastasis of the omentum majus and one liver metastases were diagnosed by CT, but not by PET. No false positive results were obtained with PET. Diagnoses were confirmed at second-look surgery in 13 cases. A comparison o f F 18-FDG images to CT scans showed that all involved lymph nodes were below 1.2 eva in diameter. PET is more sensitive in diagnosing lymph node metastases or recurrence of ovarian cancer compared to CT. Small metastases of the omentum majus remain the domain of CT.

VALUE OF SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN THE DETECTION OF LIVER METASTASES IN GASTROENTEEOPANCREATIC E N D O C R I N E T U M O U R S (GET). In the evaluation of patients (pts) with (GET) is imperative to establish the presence or the absence of liver (L) metastases (M), in order to plane p r o p e r treatment. The aim of this study was to compare the a b i l i t y of somatostatin receptor scintigraphy to other conventional imaging modalities (CT and MRI) in the detection of LM in GET. Seventy-two pts with GET (31 carcinoids, 25 gastrinomas, 8 nonfunctioning islet carcinomas, 3 insulinomas, 3 somatostatinomas and 2 vipomas) were considered. All underwent total body p l a n a r images (at 4, 24 and 48 hours) and abdominal SPECT at 4 hours after the injection of In-lll pentetreotide (P). Abdominal CT and MRI were performed within one month of the scintigraphy. Planar images detected a total of 56 L lesions in 23 pts, SPECT 102 L sites in 36 pts and conventional image 84 L localizations in 28 pts. In particular, SPECT was the only imaging m o d a ! i t y able to localize L sites in 8/36 (22.2%) pts. The detected LM were then h i s t o l o g i c a l l y proven. In conclusion, these data indicate that In-lll P SPECT is essential to be performed for the clinical management of pts with GET: in fact, this imaging m o d a l i t y is the most sensitive noninvasive m e t h o d to detect LM, and should be the initial examination for an accurate staging of the extent of the disease. Moreover, planar images are not useful in the study of the L, that always shows variable individual In-lll P uptake.

F-18-FDG

cO

= m

e-

x.._

L

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.. 12 . 3 A.R. B6mer ' , D Simon, M.Weckesser 1,2 , K.J. Langen l, H.D. ~ . Mfiller-O~tner ,2 ~Inst. of Med., Res, Cent. Jialich, and 2Dept. of Nuclear Medicine, 3Dept. of General and Trauma Surgery, University Hospital D/,isseldorf, Germany

M. Lonneux, Ph. Declercq, D. Delval, R. Bausart, F. Jamar, R. Moens, H. Zreik and S. Pauwels. PET Laboratory, Univ. of Louvain Medical School and H6pital St-Jean, Brussels, Belgium.

ISOTRETINOIN THERAPY IN PATIENTS WITH ADVANCED STAGE T H Y R O I D CANCER Hitherto no therapeutic regimen is effective in advanced stage thyroid cancer with metastatic disease showing no iodine accumulation. As isotretinoin has been successfully applied in a variety of malignant tumors we investigated it's influence in patients with intractable metastatic thyroid cancer. Ten patients were hospitalised for pretherapeutic evaluation of radioiodine and glucose metabolism (F-18-FDG PET) of their tumors and metastases. Thyreoglobulin was measured in hypothyroidism before and during isotretinoin therapy. Therapy with isotretinoin 1.5 mg/kg bodyweight per day was started after the first diagnostic session. Six weeks later the same diagnostic procedures were repeated during therapy with isotretinoin. Before the treatment was started 4 of 10 patients showed residual iodine metabolism of their tumors insufficient for radioiodine therapy, in 6 patients iodine accumulation was not measurable. In 8/10 patients local glucose hyperrnetabolism was found, Glucose hypermetabolism was reduced in all patients during treatment. Tg levels decreased in 3 of 10, showed a decreased slope in 5 of 10 and increased unchanged in 1 of 10 patients. One patient showed stable Tg levels during therapy, During treatment iodine accumulation was visible in 5 of 10 patients, but dosimetry revealed no possibility of therapeutic use. In terms of thyreoglobulin changes, iodine metabolism and glucose metabolism differentiation therapy with isotmtinoin was able to ameliorate tumor progression in half of the patients and showed a partial response in 4/10 patients treated. No response was seen in only one patient.

ACCURACY OF P E T vs 511KEV IMAGING IN STAGING OF LUNG CANCER USING 18-

ID O

IX FDG. Anger cameras equipped with 51I keV collimators (51lkeV) have been proposed as an alternative to PET scanners for imaging of positron emitter tracers. We have prospectively evaluated the accuracy of both methods in the staging of 17 pts with lung cancer. On basis of the results of conventional staging procedures (cfiest-liver-brainCT, bone scan), 10 pts had metastatic disease, 6 resectable disease and 1 non reseetable N3M0 disease. Primary tumor size ranged from 1.0 to 3.2 cm. Nodal status was confirmed by histology in 7 pts (surgery in 6, mediastinoscopy in I). PET and 51 IkeV imaging were sequentially performed in all pts as followed: I) injection of 370 MBq FDG, 2) whole-body PET imaging, 3) reinjection of 185 MBq FDG, 4) 5I lkeV SPECT imaging of chest (30 rain duration) and whole-body anterior and posterior planar views. _ _ Accuracy of PET vs 51 lkeV imaging Primary

PET 511keV

NYpls) ~

17 16

)

M s t a g i n g (17pts) O v e ~ n g

4 3

15 I2

t[7 pts)

15 10

A 1-cm primary lesion in the right upper lobe was not visible on 511keV images. One brain metastasis was missed by PET whereas 3 pts with proven metastases (brain, vertebra and right adrenal) were understaged by planar imaging. Three pts with NI-2 disease were classified NO by SPECT whereas one NI lesion was missed by PET. In spite of discrepancies in nodal staging, all 6 resectable diseases were correctly selected for surgery by PET and 51 I keV. However, non resectable diseases were falsely classified as resectable diseases in 3 cases by 51 IkeV and I case by PET. These data indicate that the reduced sensitivity of FDG 51lkeV imaging, as compared to PET, may limit its usefulness in staging of lung cancer.

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G.. Mariani, E. Baiza, B. Gaggero, C. Augeri, C. Motta, h . Lasku, A. Dorcaratto, P. Castellani, G. Viale, and L. Zardi. Nuclear Medicine Service, DIMI, and Institute of Neurosurgery, University of Genoa; and National Cancer Institute (IST); Genoa (Italy).

Silvi~_h, Ch. Wogritsch, M. Bechinie, 1. Hurtl, F. Prascb, G. Baumgartner, R. Dudczak Dept. of Nuclear Medicine, 5th Med. Dept., Gen. Hosp.Lainz, Vienna, Austria

IMPROVED TUMOR TARGETING FOLLOWING AFFINITY CHROMATOGRAPHY PURIFICATION AFTER RADIOLABELING OF ANTI-ONCOFETAL F1BRONECT1N MoAb BC- 1.

TC 99M-MIBI-UPTAKE REFLECTS BONE MARROW ACTIVITY IN MULTIPLE MYELOMA PATIENTS

The IgGj monoclonal antibody (MoAb) BC-I detects a human fibrenectin isoform (B ÷) which has extremely restricted distrbution in normal adult tissues while it is highly expressed in fetal and tumor tissues. This antigen represents therefore a novel marker of angiogenesis. We studied the biodistribution of MoAb BC-1 (labeled with la*I by the iodogen technique at the initial specific activity of 370 MBq/mg) in a total of 36 nude mice bearing subcutaneous human melanoma implants (SKMEL28 line). The tracer MoAb was injected i.v. either immediately after mdioiodination or after the following procedure. The mdioiodinated MoAB BC-1 was purified by immuno-affinity chromatography (IAC) using the recombinant (B*)-fibronectin fragment 7B-8-9 coupled to CNBr-activated Sepharose 4B. The adsorbed tracer was eluted with 0.1 M triethylamine buffer (pH 11), and the eluted MoAb was concentrated and extensively dialyzed against PBS using Amicon Centricon-10 tubes. Final recovery of ~2SI-BC-1 was about 10% of the starting radiolabeled material. The organ-tissue hiodistribution was measured in groups of animals (n = 3-5) sacrificed 24-144 hr after administration of t25I-BC-1 injected without further purification, and 24-264 hr for the IAC-purified tracer. Although favourable uptake in the SKMEL28 implants was observed for 125I-BC-1 injected as such, the IAC-purified tracer exhibited much higher tumor targeting values: 6.49 + 1,07 %ID/g v e r s u s 3.49 ± 0.25 %ID/g at 24 hours. Furthermore, while tumor-incorporated activity decreased over time for ~2~I-BC-1 iniectedwithout purification (1.59 ± 0.55% ID/g at 144 hr), IAC-purified ~2~I-BC-1 showed remarkably constant tumor targeting values (7.49 ± 2 . 1 % I D / g at 264 hr). Non-specific uptake in the bone marrow, skeletal muscle, etc. was much lower than in tumor implants for both types of tracer, The experimental results obtained in this study emphasize the need for taking into account several important factors related to tracer preparation when performing tumor radioimmuno-targeting studies.

The aim &this study was to investigate, ifTc 99m-MIBI scintigraphy can reflect the activity of disease in patients (pts) with multiple myeloma (MM). Patients and Method: 23 pts with MM were studied, 6 CAD pts served as controls. Staged by Salmon and Durie criteria, 9 pts (39%) had stage I disease, 4 pts (17%) stage II and I0 pts (44%) stage III disease. 3 pts had a second MIBl-scan in clinically complete (n=2) or partial (n=l) remission (C/P R). Whole-body planar images were obtained in all pts with a dual headed gamma camera 20 rain and 120 min after i.v. injection of 925 MBq Tc 99m-MIBI. Images were interpreted visually. In addition target (e.g. spine and femur)/non-target-ratiosand wash-out rates were calculated. 4 pts had additionally MRI, while 5 other had Tc 99m-MDP bone-scintigraphy. Results: In controls faint M1BI uptake was seen in the spine but not in the femur region. The same was found in stage 1pts. In contrast stage II and 111pts had a clear visualisation of the spine in 86% and the femur in 64% (of both in 57%). Most stage II and [II pts (n=l 1) showed more than one lesion (skull, spine, ribs, pelvis and long bones). The majority had visualisation of the spine (12 pts), pelvis as well as long bones were seen in 9, ribs and skull in 8 and 5 respectively. Lytic bone lesions in the skull manifesting as focal uptake were only seen in 3 pts. Wash-out rate was not different between groups. The target/non target ratio (median) increased with stage (p<0.001): The controls were similar to stage 1 (spine: 1.5, IQR-0.35; femur: 0.8, IQR=0.I). The ratio for spine (and femur) in stage I1 was 2.1, IQR=I.03 (I .I, IQR=0.35) and stage lII 2.3, IQR=0.3 (1.4, IQR=0.29). In stage I1 and Ill pts the ratio in other locations was 2.4, IQR=0.8 and 2.9, IQR=0.7. C/P R was accompanied by a decrease in the ratio. MIBI and MRI were concordant; MRI substantiatedthe hypotheses that MIBI reflects bone marrow activity. As expected bone scintigraphy was not instructive. Conclusion: Tc 99m-MIBI can not serve as an indicator of lytic bone lesions. MIBI uptake reflects the extent of bone marrow involgement and the activity of disease in MM pts, however.

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L.T,Jl,Lg.C,JlgL K.Seybold, P.Lind* Kantonsspital, Aarau (Switzerland), *Landeskrankenhaus Klagenfurt (Austria)

1D.Hui6~ 2V.Ivan6evi6, AN-S.Richter, 2D.L.Munz, ~Clinical Department of Nuclear Medicine and Radiation Protection, University Hospital "Rebro", Zagreb, Croatia, 2Clinic for Nuclear Medicine, University Hospital Charity, Humboldt University, Berlin, Germany

NEUTROPENIA INDUCED BY DIAGNOSTIC MONOCLONAL ANTIBODIES In animal models several authors have observed a transient, but dose dependent neutropenia after the injection of certain neutrophil receptor specific agents such as monoclonal antibodies (mabs). In many clinical studies, however, significant hemopoetic alterations have been denied, although not studied in detail. W e looked for effects on leucocyte counts and distribution after intravenous injections of mabs in 44 patients examined for routine tumor staging and infection diagnostics. Two different antigranulocyte mabs were used (mab-47 and B W 250/'183) and the protein amounts injected were 120 }.tg and 300 ~tg respectively. Three different automatized counting systems were used for double cell counting of each probe. Results were statistically analysed using the paired t-test. Results: There was a highly significant (p<0.0001) drop of neutrophil numbers five minutes after the mab injection with respect to the preinjection values (mean difference 351) and an highly significant (p<0.0001) rebound of cell numbers 6 hrs p.i. (mean difference 1355; Therefore, our data confirm in humans the reported animal results. Tb~ underlying mechanism by which mabs induce neutropenia is not yet understood. The reticular endothelial system seems to be involved, but other factors must be considered such as cell adherence, chemotactic stimuli or changes of membrane surface charges.

1050

BONE MARROW IMMUNOSCINTIGRAPHY IN PATIENTS WITH INFECTION AND MALIGNANT TUMOURS The aim of our study was to investigate the influence of infection and various malignant tumours on Te-99m labelled monoolonal antigranulocyte antibody (AGAb) uptake in human bone marrow. One hundred and sixty-nine whole-body bone marrow scans {BMS) were performed and quantitatively analysed using the sacroiliac-tobackground uptake ratio (UR) in 162 patients without clinical evidence of bone marrow depression (73 women, 89 men, mean age 54 years, range 3-85 years). In 50 patients with COmpletely normal bone marrow scans (considered as a normal group) mean URs were significantly age related, amounting to 8.5±1.8, 7.5±1.9, 6.1±2.0 in the patients younger than 40 years, between 40 and 59, and 60 years or older, respectively (p=0.0025). The mean UR values of 115 patients, who underwent AGAb scanning because of infection or pyrexia of unknown origin (PUO), with and without signs of acute intectior~ present (C-reactive pratein>lO rag/I, body temperature>37°C, white blood call ceunt>lO G/I) were not significantly different (7.5±2.1 versus 6.8+2.0, p>0.40), but a moderate bone marrow extension was observed mere often in patients with signs of acute infection (39% versus 14%). There was not significant difference in UR between the normal group, patients with primary diagnoses of solid malignant tumours (N=7), lymphomas or plasmacytomas (N=16}, and patients with malignant diseases and "cold" lesions in the bone marrow (N=16) (5.7+1.5, 7.6-tl .8, 7.7±2.9, respectively, p>0.10). In conclusion, infection/PUO and matignant diseases do not alter the AGAb UR significantly in patients without depression of bone marrow function. Normal UR values are age dependent, which has to be considered when interpreting bone marrow uptake ratios.

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H Young, D Bailey, L Livieratos, D Glass, AM Peters, T Jones, DJ Brooks. Departments of Imaging and MRC Cyclotron Unit, Hammersmith Hospital, London, UK.

O. R. Mawlaw_ii, H. W. D. Yetmg, H. Macapinlac, Y. E. Erdi, H. Kalaigian, J. L. Humm, and S. M. Larson. Memorial Sloan-Kettering Cancer Center, New York, NY.

VALIDATION OF A 3D PET SCANNER, THE ECAT ART, FOR QUANTITATIVE ASSESSMENT OF 18-F-DOPA UPTAKE. Reduction in 18-F-DOPA striatal uptake is related to the severity of symptoms in Parkinson's disease and may have a role in differential and early diagnosis of the disease. In this study we have validated a non invasive, quantitative clinical protocol with a low cost, 3D, partial ring, rotating PET scanner, the ECAT ART to assess 18-F-DOPA uptake. Count rate performance was assessed using an 18-F uniformly filled elliptical head phantom. The accuracy of deadtime correction, applied at image reconstruction, was assessed using ROI analysis of a dynamic image sequence acquired for a 18-F uniformly filled 20cm cylinder. Data correction, particularly scatter correction, was assessed by imaging a Utah phantom with different 18-F concentrations in each compartment. I0 subjects with suspected or known Parkinson's disease were scanned. 18 frames of 5 minutes duration were acquired post injection of 18-FDOPA (185MBq). Paramtric images of the influx constant (Ki) were generated using Patlak analysis with the occiput as an input function. The maximum noise equivalent count (NEC) was 60kcps for an activity concentration of 25kBq/mi and a trues rate of 130kcps. Deadtime correction was accurate up to an activity concentration of 20kBq/ml with a trues rate of 100kcps. The trues rate did not exceed 60kcps for clinical imaging. Activity concentration was measured to within +/5% for the Utah phantom. Decreased Ki values corresponded with symptomatic Parkinson's disease.

EFFECT OF TRANSMISSION SCAN DURATION ON THE IMAGE QUALITY AND SUV ON PET IMAGES. Purpose: To evaluate the effect of decreasing transmission scan duration (TSD) on PET image quality and measured activity/SUV. Method: An anthropomorphic phantom was filled with water in which 10 mCi of F18FDG was added to simulate the activity level usually seen in whole body scans. A sphere (0.55cc) in the chest wall was separately filled with water containing 6 uCi/cc of F 18-FDG in order to simulate a typical lesion. Six minute emission scans were then obtained, followed by transmission scans of duration from 2 to 20 minutes, on a GE Advance camera with 2 transmission rod sources (Ge68) of I6 mCi total. Image reconstruction was done with non-quantitative (Nfilter) and Gaussian reconstruction filters (Gfilter), using a cutoff of 8 and 15 for the 2 filters. Attenuation corrected images were assessed visually. Identical ROIs were drawn in the lesion and the mediastinum of all the images and the measured radioactivity was recorded. Results: 1. On visual inspection, the lesion in the chest was seen in all the images. The image quality obtained with the Nfilter appeared similar until the TSD decreased to 2 minutes, at which significant image degradation was evident. With the Gfilter streak artifacts appeared at TSD of 6 minutes or less. 2. Measured activities in the ROIs showed no significant change for all the different TSD with the Gfilter. 3. With the Nfilter the measured activity showed no significant change for TSDs from 20 minutes down to 6 minutes. When the TSD decreased to 4 minutes, the measured activity was down by 4% and at 2 minutes it was down by 12%. 4. The results were identical regardless of the cutoff frequency used for the different filters. Conclusions: At the activity levels usually encountered in clinical practice and using the Nfilter to avoid streak artifacts, the transmission scan duration can be safely shortened to 4 minutes without significant adverse effect on the image quality or the measured activity/SUV.

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I:l. P 453 M.Imbriaco, Y.Erdi, O.Mawlawi, H. Macapinlac, H.Yeung, K.Kolbert, J.Hulum, and S.M.Larson. Memorial Sloan-Kettering Cancer Center, NY PET IMAGE THRESHOLD METHOD FOR TUMOR VOLUME ESTIMATION IN PATIENTS WITH NON SMALL CELL LUNG CARCINOMA: A COMPARATIVE STUDY WITH CT Purpose: The aim of this study was to validate an adaptive PET image thresholding method (Erdi et al. Tumor Targeting 2(3):146;1996) which estimates the volume of lung lesions and to evaluate its efficacy in comparison to CT. Method: Fourteen patients (10F/4M, Mean Age=58+9) with newly diagnosed non small cell lung carcinoma (NSCLC) were studied with whole body PET-FDG and with chest CT. The whole body PET images were acquired 45 to 60 minutes after the intravenous injection of 370 MBq of F-18-FDG. Image reconstruction was performed with measured attenuation correction. Corresponding lesions were identified on PET and CT scans. The CT lesion volumes were computed by fitting an ellipse to the lesion in each slice and summing all slices where the lesion appears. CT lesion volumes were further validated by using a three dimensional internal dosimetry program (Kolbert et al. J Nucl Med 1997 in press). The corresponding PET lesion volume was estimated by applying phantom derived optimal thresholds using PET lesion contrast and CT lesion volume. The pixels (areas) in thresholded PET lesion images were counted for volume determination. Results: The use of the optimum threshold schema showed a good correlation (0.998) between the lesion volumes obtained with CT and those derived from FDG-PET. Analysis by a 2 for CT and PET derived lesion volumes yielded a p<0.005. The percent mean difference for these volumes was 13.1+ 14.1. Conclusion: The adaptive threshold method allows a precise estimation of tumor volume during PET imaging in patients with NSCLC. (Supported in part by DOE #DE-FG02-86ER60407 and the Gerschel Foundation)

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ID

O.R. Mawlawil Y.E. Erdi2, M. Imbriacol, J.L. Humm2, F. Daghighian1, S.M. Larson1. (1) Nuclear Medicine Service, (2) Dept. Of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY.

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0. Motion Effects on Recovery Coefficients 01Cs) in Positron Emission Tomography (PET) Imaging. PURPOSE: The aim of this study was to investigate the effect of patient motion on RCs in the presence and absence of background activity. METHODS: A cylindrical Jaszczak phantom fitted with six spheres ranging from 1.5 to 21 cc. was imaged at six different elevations from the center of the field of view. The spheres were filled with 3.5 uCi/ec ofF-18 and positioned in such a way that their centers lay in the same plane while formiflg a circular pattern. Fifteen minutes emission and 10 minutes transmission (T+E) scans were then collected at each elevation using a GE Advance PET scanner. The study was performed with 1) no background activity and 2) with 0.85 aCi/ce background activity. All scans were collected in 2D mode. The images were reconstructed and corrected for decay, scatter, and deadtime. A Hann filter with a cutoff frequency of 2.6/ram was applied. To simulate the effect of motion, the reconstructed image at each position was added to the image at zero elevation (e.g. 0 mm image + 5 mm image, 0 mm image + 10 mm image etc.). An ROI was then drawn around each sphere for each of the composite images and the maximum pixel concentration was recorded. The same procedure was repeated for images with and without background activity. RESULTS: The results of this study show an inverse relationship between the amount of motion and RC of a particular sphere size in both studies. However, the amount of variation in RC in the presence of background activity was found to be 24% smaller than that measured in cold background. This is due to the effect of increased number of scattered events into the sphere volume. Moreover, the average variation of the RC with sphere size in the no motion study was found to be 47% smaller than those with motion in the cold background study. A similar observation however of a lesser magnitude (26%) was made for the spheres in hot background. CONCLUSION: Movement during data acquisition results in image blurring which leads to overestimating an object's volume and hence underestimating its activity concentration. To compensate for this drawback, a set of RC curves are generated to correct for this movement artifact. By implementing such a correction, accurate lesion volumes and activity concentrations would be possible thus improvingthe efficacy of PET imaging.

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P 457 LG. Strauss,G. van Kaick Dept of Ontological Diagnostics and Therapy, German Cancer Research Center, He=delberg, Germany

Efficient implementation of an iterative image reconstruction (IIR) algorithm for quantitative PET studies on a conventional low-cost Pentium platform

M.J.Carrol[, K.E.Britton. Dept. of Nuclear Medicine. St Bartholomew's Hospital.

Projection Based Image Registration Using Phase Correlation

We have implemented a MLEM (maximum likelihood expectation maximization) algorithm for the reconstruction of the measured sinograms from the CTI/Siemenu EGATEXACTHR+ PET scanner. It imwell known that such iterative methods, which inmorporate the stochastic nature of the emission process, are producing images of better quality than the conventional Filtered bamkprojection (FBP) algorithms. In particular, MLEM outperforms the FBP algorithms, currently implemented by the PET scanner vendors, in low-count and high-contrast studies, e.g. short-interval dynamic acquisitions. In addition, MLEM IIR allows the straightforward quantification of the collected data and the calculation of parametric images from dynamic recordings of the tracer kinetics in tissue. Although very active research in MLEM IIR techniques has been undertaken during the last 15 years, the extensive computation requirements of these techniques have significantly impeded the use of these methods in the clinical routine. Severalgroups have proposed the use of dedimated supercomputing systems and expensive parallel architectures in order to address this issue. We report here on an efficient implementation of a MLEM-based IIR algorithm on a conventiona{, low-cost Pentium platform (double processor, 200 MHz), running Windows NT. The nonzero elements of the transition sparce matrix are pre-computed using a Monte Carlo method. An efficient mparce-matrix representation is used in order to toad these elements in memory during the reconstruction and each of them is visited exactly twice during each iteration. For a reconstruction on a 128 x 128 image grid and mashing factor of 2 (288 x 144 lines of response per slice), the reconstruction of one frame (63 slices per frame) requires lessthan 1 hour. No accelerating schemes(over-relaxation parameters, multigdd approaches, ordered-subsets methods, etc.) have been implemented yet, however we expect significant reduction in the reconstruction time with the use of an appropriate acceleration technique. Since each slice can be reconstructed with the MLEM algorithm independently of the other slimesin each frame, a multiprocessor (2, 4 or 8 processors)architecture can be used for further reduction of the reconstruction time. This man be achieved by distributing the reconstruction load to the muitiprocessor Pentium-based platform, where each processor will share the same memory with the others. With this approach, a lowcost PC platfrom man be efficiently used in order to achieve high reconstructed image quality for PET in clinically meaningful time, We expect to extend this approach in the calculation of parametric (SUV, Patlak, etm,) images and further in the analysisof the reconstructed PETdata.

The objective of this study is the rapid and accurate measurement of patient movement during tomographic and dynamic acquisitions, e.g. cardiac and renal studies. The technique applies the method of phase correlation to the projections or summed profiles of the horizontal and vertical image directions. The discrete phase correlation function is obtained by computing the fast Fourier transforms(FFT) of the ldimensional projections of two neighbouring image frames, forming the cross power spectrum and at each spatial frequency extracting its phase. The reasoning that underlies this approach is that all of the information about the translation of two images resides in the phase of their cross-spectrum. In particular in the case of images having undergone pure translation a delta function is produced at the shift location.The application of a Blackman windowing function to the profiles prior to correlation reduces edge effects, for example bladder uptake in renography. The use of the phase rather than the magnitude in the correlation makes this approach very robust to changes in image content , for example conventional correlation matching is prone to drift in the vertical direction in renogram studies because of the change in global distribution of activity due to excretion. Interpolation of the projection data e.g. from 64 to 256 points allows the detection of fractional shifts of the order of 0.25 pixels. This technique effectively detects if patient movement has occurred , corrects for pure translations and pinpoints those frames that may require more costly procedures e.g. to determine rotational motion.

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Wudel E, Schoenhard G, Koppenhagen K. Nuclear Medicine. Free University of Berlin. University Hospital Benjamin Franklin. Hindmnburgdamm 30 D-12200 Berlin.

R. Thill, U. Cremerius, J. Neuerburg*, M, Zimny, G. Wagenknecht, R. Guenther*, R. Osieka ÷, U. Buell. Depts. of Nuclear Medicine, *Radiology and + Internal Medicine IV, Aachen University of Technology, Aachen, Germany

A METHOD FOR THE AUTOMATIC

PARTIAL-VOLUME-CORRECTION OF SUV IN MALIGNANT LYMPHOMA.

RECOGNITION

OF THE KIDNEYS

IN

A DYNAMICRENAL STUDY AIM: The region of interest (ROI) of the kidneys of a study with Tc-99m-MAG3 is constructed manually or by user controlled iso-activlty-line usually. Our algorithm takes into account some elementary knowledge (e.g. heart and liver at the upper part in the early phase, later the urinary bladder at the lower part), then we use a fuzzy logic approach on the histogram of automated selected parts of the image in order to identify the kid-" neys. The criterion of the zero-crossing of the second derivative of the activity profile has its difficulties, METHOD: Almost symmetric adjustment of the kidneys in the study, disappearance of the cardiac region. Studies of children and adults, group (A) with nearly normal renal anatomy, (S) with great differences in the location topic or with great defects in the parenchyma. ALGORITHM: (i) segmentation of the region of the bladder, heart and liver (if needed), dividing line between the left and the right kidney (relative minimum of the added-up columns), resulting 2 sub-images containing each kidney mre analysed separately. (2) The most intensitive gray values are part of the kidneys, this is the outstanding working hypothesis! The search of the threshold is performed by the fuzzy entropy threshold approach [Mnrthy CA, Pal SK: Inforn.Scien. 1992;60:i07-135]:membership function values of each pixel, standard S-function, the entropy of am image is obtained hy Shammon's fuzzy function for every possible threshold. That of the multiple minima of the entropy function in the searched threshold, which produces a separated, connected and simple-connected region not containing to much pixel (background). RESULT: The concurrence of the visually detected edge and the segmentation result of the algorithm in the group A is very good (16/20 kidneys). In the group B there are clear differences because every condition can falsified by nnother exceptiommll renal study. These cases need more implemented knowledge. CONCLUSION: Until now the control of an operator and the poeslbility to change the ROI cannot be negleted. But it is surprising that a histogram based method is able to detect the contour line. The fuzzy entropy method is better than the iso-activity method, a combination with other methods could improve the identification. KEYWORDS: image processing, segmentation, kidney

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Aim of the study was to develop a method to assess the size of [ymphema foci and to correct the padial-volume-effect in FDG-PET without using other examinations. Methods: 30 patients suffering from high-grade malignant [ymphoma before therapy were examined with FDG-PET. After a fasting period of at least 12 hours, 190-290 MBq F-18-FDG were injected, emission scans were started 45 min. p.i. with an ECAT 953/15-Scanner. Attenuation correction was performed by transmission scans, all studies were reconstructed with an iterative algorithm. Patho[ogic hypermetabolic loci found by visual interpretation with corresponding lesions in X-ray CT were subsequently evaluated with a ROl-based quantification method. Maximum (Max) and background (BG) activity concentration were measured and half-maximum (HM) was calculated. The value of HM was used to define an isodensity-ROI that surrounded the focus. The activity concentration inside this Re{ represented the uncorrected standard-uptake value (nc-$UV). Assuming a circular Re{ the diameter of the focus (DpE~) Was calculated from the area of the ROh With a recovery coefficient, depending from D~ET,the partiaFvolumecorrected standard uptake value (SUV) was calculated. The diameter of a lesion in X-ray CT (DcT) was taken from the maximum transaxial diameter. Results: Depending on the X-ray CT the 78 lesions were classified as single nodal lesions (N, n=44), bulky lesions (BULK, n=30) and extranodal lesions mE, n=4). SPEARMAN-Correlation between DCT and DPETwas linear for N. (Fig.) 5O

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P< 0.0001 a 2o

r = 0.75 3o

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60 DCT

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In the groups BULK and E no significant correlation was found. Conclusion: Because the relation between [~CT and DpETiS linear in single nodal lesions, the described method enables to measure their size by PET reproducibly without use of CT. Therefore it is suitable to correct SUV for the partial-volume effect. in bulky lesions the method is not sufficient because of in-homogenous FDGmetabolism in coexisting viable and necrotic tissue.

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J _._~, S M 81end, S Brint, D Hier, T Jobe. University of Illinois Hospital, Chicago

A Barnes, D Dai, D Montaldi, J P a t t e r s o n and D Wyper. Institute of N e u r o l o g i c a l Sciences, S o u t h e r n General Hospital, Glasgow, Scotland.

ANALYSIS OF SPECT HMPAO BRAIN ACTIVATION IMAGES

~ K ~ G E QUALITY VS. S T A T I S T I C A L POWER IN N E U R O ACTIVATION.

By comparing single baseline and activation studies, several SPECT brain activation methods were developed in the past, and recently a version of SPM95, developed originally for PET brain activation analysis, was applied to SPECT data. In difference to PET, SPECT is limited to only one independent HMPAO acquisition per day. The effect of the propagation of registration across a population of patients on the accuracy of the SPM method is still unknown. An argument can be made that it is substantial, especially in brain malformation and surgical cases, resulting in a lower sensitivity to activation. Further, the accuracy of both approaches is decreased by not including measures of the intra-variability (differences between serial baselines of the same case). We have developed two new methods for detection and localization of brain activation by SPECT. They do not require a cross-case registration to detect activation. The first method compares the activation study to two (or more) baseline studies of the same case and does not require a reference database of cases. Consequently, the propagation of cross-case-registration errors is eliminated. The activation degree is measured either by a relative counts change or by the statistical significance of this change. The second method classifies clusters of potentially activated voxels as likely/unlikely to occur in a baseline study. As this method uses cluster measures based on both the cluster size and counts, a need for Bonferroni type correction is decreased or eliminated. The classifier utilizes activation cluster information from the database of cases and can be further improved by using approximate location of clusters. Both methods have been successfully tested on ten cases. A possibility of merging these methods with SPM96 is being investigated.

In this s t u d y w e h a v e i n v e s t i g a t e d w h e t h e r S P E C T s t u d i e s of n e u r o a c t i v a t i o n might benefit from a similar a p p r o a c h u s e d in PET, i.e, i n c r e a s e the n u m b e r of s c a n s p e r t a s k a n d a c c e p t p o o r e r individual scan quality. Different study paradigms were simulated by v a r i a t i o n of s c a n n i n g p a r a m e t e r s ; a) dose p e r scan b) number of scans per task and c) slice a c q u i s i t i o n time. The m a x i m u m total d o s e r e c e i v e d b y each s i m u l a t e d s u b j e c t r e m a i n e d w i t h i n I@00HBG. A r e a s of a c t i v a t i o n of v a r y i n g s i g n a l s t r e n g t h were added to the s c a n s u s i n g a customised graphics package. In order to e s t a b l i s h the s t a t i s t i c a l effects of the d i f f e r e n c e s b e t w e e n the paradigms, the data sets w e r e put t h r o u g h the SPH95 statistics software. The m e a n z-scores for a 3% focal activation are listed in T a b l e I. STUDY SLICE TIME DOSE UNITS DOSE UNITS MEAN NO. PER SCAN PER SCAN Z-SCORE 1 120s 1 2 (A,B) 3.81+/-1.25 2 240s 1/2 4(A,B,A,B) 6.54+~2.42 3 120s i/2 4(A,B,A,B) 5.83+/4.66 T h i s s i m u l a t i o n has s h o w n that w h e n a n S F M i n v e s t i g a t i o n is u s e d for d a t a a n a l y s i s , s t u d y r e p l i c a t i o n is m o r e i m p o r t a n t than the i n d i v i d u a l image quality typically available from a high performance SPECT system. It a l s o o f f e r s the possibility of c o m p a r i n g multiple activation conditions, therefore enabling subtle differences in tasks to be investigated.

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G. Glatting, J. Kotzerke, M. Rentschler, R. Weller, S.N. Reske, Abteilung Nuklearmedizin, Universit&t UIm, UIm, Germany.

H. Speckter< K. Darabi-~,P. Stoeter~, P.Benz 4, O. Nickel~, A. Bockisch5, J= Andreas< JDept of Nuclear Medicine Mainz, 2Dept of Neurosurgery Mainz, 3Dept of Neuroradiology Mainz, 4pET University Mainz, SDept of Nuclear Medicine Essen, Germany

TREATMENT OF RADIOACTIVE DECAY IN PHARMACOKINETIC MODELLING: INFLUENCE ON PARAMETER ESTIMATION Radioactive decay during measurement can be accounted for by either a decay correction of the measured data before modelling (DbM) or by direct implementation of decay into the pharmacokinetic model (DIM). Purpose of this study was to quantify the influence of the type of decay correction on the calculated parameters for the example of a three compartment model used for the calculation of myocardial perfusion with N-13 ammonia and positron emission tomography (PET). Methods: For a given input function (F(t) = c t exp(-a t)) the tissue uptake for two parameter sets of K1, k2, k3, MBV (corresponding to values measured at rest and stress) were calculated for 20 frames (12 x 10 s, 4 x 30 s, 3 x 120 s, 1 x 300 s). These values were mathematically deteriorated by various noise levels according to Poisson statistics (10000 simulations)= These ,,experimental" data were fitted by a Levenberg-Marquardt algorithm. The results for K1, k2, k3, MBV were compared to the ,,true" values. Estimated parameter means and coefficients of variation of the fitted parameters were calculated for the DbM and DiM case. Results: While for small noise levels the mean values for all parameters for both decay correction methods were of equal quality, DiM is better for large noise.The important figure for a single fit, i.e., the coefficient of variation of the fitted parameters, is - for large noise in the data - up to a factor" 3 smaller in the DiM case for the clinically rnost relevant K1 parameter. Conclusion: The decay correction should be taken into account during modelling. This is important especially if the noise level in the data is large.

NONINTERACTIVE ALIGNMENT OF PET AND MRI AND CT IN STEREOTACTIC NEUROSURGERY Aim: Systems for image guided surgery have advanced significantly over the past years and are expected to become an important tool in surgery. In order to apply the meaningfulness of functional brain data, we combine fused images of PET and MRI with stereotactic X ray tomograms on a neurosurgical stereotactic and navigation system. Methods; All image fusion procedures are based on cranial bone segmentation. First PET and MRI images are automatically fused using a method developed in our department: The clearly recognizable bone structure in reconstructed transmission tomograms of the PET study is matched to the segmented bone structures of the MRI images using a fast genetic algorithm. The transformation parameters for the emission data are derived from the reorientation of the aligned transmission images. These combined images are transfered to a stereotactic workstation, where they are matched to the CT with a stereotactic frame. .Results: We developed a new representation for alignments of MR1 with PET data and verified the accuracy of the gradual matching procedures using fiducials. By now this method is tested in stereotactic biopsy and surgery. Conclusion: We have combined different matching techniques to join functional data into a stereotactic coordinate system. This is the first step towards verification of functional imaging during stereotactic or open surgery. It aIIows us not only to compare anatomy with function, but atso different imaging modalities (PET, functional MRI).

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PJ Slomka, GA Hurwitz, P Radau, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.

INITIALCLINICALEXPERIENCEWITH PERFIT PERFIT is an automated quantification software package for myocardial perfusion tomography. In this study we compared visual clinical reading to PERFIT results. PERFIT calculates stress and rest 'defect size, severity, location, and ventrieular volume in a singlebutton operation. These parameters are calculated after a multistage lterative algorithm and shape adjustment of individual ventricles to three-dimensional gender-matched normal models, followed by template erosion algorithm for further shape adjustment. We compared PERFIT defect size results in stress and rest images in a group of 125 male patients representing a spectrum of abnormal and normal cases (normal, single, and multiple vessel disease, infarction, and dilated ventricle). Studies were read by a consensus reading of 2 observers and assigned a percentage defect value for stress and rest. Average defect sizes in each of the 12 abnormal groups (n=8) derived visually (V) and numerically by PERFIT (P) were compared. Visual and machine readings correlated closely in most territories. PERFIT defect sizes were somewhat smaller on the average in all abnormal groups (n=96) (V =11.4 % , P=9.6% -rest P=22.3%, V= 23% on stress). There was a systematic difference in reading the scans in the RCA zone where PERFIT found defects smaller than the visual observer (average P=7%, V=10% for stress) and LCX zone where PERFIT found larger defects (average P=22%, V=18% for stress). 2 cases were read abnormal by both P and Y analysis in the normal group (n=29). We conclude that PERFIT reading is consistent with visual analysis. Some differences remain probably due to difficulties in visual interpretation of attenuation artefacts and non-uniform count distribution.

J. van den Holt, W. Burchert, H. Fricke, G.-J. Meyer, H.Hundeshagen. Dept. of Nuclear Medicine, Medical School Hannover, Germany

BENEFITS OF ITERATIVE RECONSTRUCTION FOR THE GENERATION OF PARAMETRIC MAPS IN PET The determination of individual rate constants has usually to be based on dynamic acquisitions which sufficient temporal resolution. The resulting short time frames lead to strongly reduced statistical accuracy especially during the early phase of the study. Iterative image reconstruction is well known to yield superior image quality under these conditions in comparison to filtered backprojection. We have investigated how the use of iterative reconstruction influences the quantification of rate constants. We focused on 15-O-water studies of the brain and 13-N-ammonia studies of the hem~. Quantification was performed with linearized one- and two-compartment models. In the case of the 15-O-water studies the use of iterative reconstructed images yields a remarkable improvement of the partition coefficient image. The statistical accuracy of the blood flow image was also improved. In the case of the 13-N-ammonia studies the iterative reconstruction allows the identification of the myocardium within the time interval which strongly influences the flow determination (= 2 min.). One thus avoids most of the problems associated with patient movement during the investigation which occur if automatic delineation of the myocardium or manual ROI definition has to be based on images of the late uptake phase (= 20 min.). A reduction of statistical fluctuations of the parameter estimates is also observed. We conclude that the use of iterative reconstruction for the quantification of dynamic PET investigations does have distinct advantages for investigations where reliable and accurate quantification is otherwise a frequent problem. For these cascs the improvements in accuracy outweigh the disadvantage of increased reconstruction times.

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M. Henze 1 H. Elser 1, F. J. Spierer 2, P, Georgi 1

J. Varg~, ~niversity

1University of Heidelberg, Department of Nuclear Medicine 2psychiatric Clinic Wiesloch SEMIQUANTITATIVE 99mTc-HMPAO-SPECT AND DEMENTIA OF THE ALZHEIMER TYPE: INFLUENCE OF THE SELECTION OF RECONSTRUCTION-FILTER AND REFERENCE-REGION Aim of the study was to clarify, whether the selection of the referece-region and / or the reconstruction-filter influences the result of the semiquantitative analysis of a 99m Tc; HMPAO*SPECT that was conducted to diagnose the dementia of the Alzheimer type (DAT). Methods: A group of 19 DAT-patients according to the criterions of NINCDS-ADRDA and DSM-III-R was examined together with a comparison group (n = 14) with normal cerebral perfusion. Three reference-regions (cerebellum, whole slice, occipital cortex) and four reconstruction-filters (Hanning fc=0,7 and 1,0 Nyquist; Butterworth (n=8) fc=0,5 and 0,9 Nyquist) were applied to twelve standardized regions of interest (per patient) respectively. The data was evaluated through a ROC-analysis. Results: It has been showed, that the bilateral parietotemporal perfusion reduction as a characteristic of DAT depends on the filters and reference-regions used. The most secure separation of both groups of patients was obtained through a Butterworth-filter (n=8; fc=0,5) in combination with the cerebellum as reference-region. Conclusion: The selection of the reference-region and the reconstruction-filter has an important influence on the results of a semiquantitative analysis. Therefore standardisation in dependency on the actual questioning seems to be necessary. 1054

Medical

School

of Debreeen,

Hungary

A M E T H O D TO R E D U C E THE A R T I F A C T P R O D U C E D BY R E S T O R A T I O N F I L T E R S AT THE EDGES OF THE FIELD VIEW

OF

if the edge of the gamma c a m e r a field of view intersects an active region, Wiener and Metz restoration filters artificially increase the activity beside the border. In case of one d i m e n s i o n a l data, a p p e n d i n g a long c o s i n e - s h a p e d tail r e d u c e d this kind of a r t i f a c t . We a d a p t e d this method to the two dimensional case, ,,spreading" the image o u t s i d e the field of v i e w (omitting p i x e l s o n l y p a r t l y inside). In order to test the e f f e c t of our m e t h o d on the r e s u l t s of filtering, various kinds of r e c t a n g u l a r images w e r e m a s k e d u s i n g a c i r c u l a r r e g i o n of i n t e r e s t (ROI) to s i m u l a t e a smaller, circular field of view. Restoration filters were applied to the original, truncated, and ,,spread" images, and the difference of i m a g e s i n s i d e the ROI as well as normalized residual mean square difference (NRMSD) values were calculated. The filtered ,,spread" i m a g e s were m u c h m o r e similar to the f i l t e r e d o r i g i n a l (not truncated) images than the filtered truncated ones; the h i g h - a c t i v i t y rim a l o n g the edges d i s a p p e a r e d . This m e t h o d p r o v i d e s a simple solution to the most annoying side effect of r e s t o r a t i o n filters.

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O. Sipil~ 1'2, M. Kortesniemi ~'3, P. Nikkinen t, S. Savolainen 1, tHelsinki University Central Hospital, 00290 Helsinki, 2Helsinki University of Technology, 02150 Espoo, 3University of Helsinki, 00014 Helsinki, Finland

G.D.Flux ~, S.Chittenden", M.Guy ~, M.A.Flower ~, R.J.Ott ~, S.Meller b, "Joint Dept. of Physics and bDept, of Paediatric Oncology, Royal Marsden NHS Trust, Sutton, Surrey

OPTIMIZING A PROTOCOL EOR Tc-99m-DMSA SPET STUDIES

DOSIMETRY FOR mIBG RADIONUCL1DE THERAPY

Phantom studies were performed to define a protocol for clinical DMSA SPET studies. The phantom consisted of an elliptical cylinder including two cylinders or balls with volumes of 54-220 ml simulating the kidneys. The activity concentration in the objects was 159-337 MBq/1. The concentrations were computed in such a way that according to the biokinetic model used in DMSA studies the total activity to the patient would be 148-185 MBq. The background concentration was 0.5-9.8 %. The phantom was imaged using two devices: Picker Prism 2000 2-head camera with LEHR-PAR and LEUHR-PAR collimators (180°: 3° step, 128x128 matrix) and Picker 3000XP 3-head camera with LEUHR-PAR (120°, 3° step, 128x128 matrix). The images were prefiltered using Butterworth low pass, Wiener and Metz filters and reconstructed using filtered backprojeetion with ramp filter. Voxel size in the images from the 2-head camera was 3.2x3.2x9.3 mm a and for the 3-head camera 3.2x.3.2xT.1 mm 3. The images were analyzed using thresholding or region growing and by computing the volumes and total count ratios of the objects. To achieve comparable statistics the imaging time requiered was 35% (10 rain) less with the 3-head camera. The sensitivity was 1.6 times higher with the LEHRPAR than the LEUHR-PAR collimator but reconstructed system spatial resolution was 1-2 mm worse. Conclusions: 1) LEUHR-PAR collimator provides an adequate count rate and the high resolution essential for the study, 2) a Butterworth low pass filter should be used to avoid filtering artefacts in the images, 3) thresholding does not provide optimal results, 4) attenuation correction is recommended, and 5) rendered 3D images are sensitive to filtering artefacts. The protocol has also been suecesfully applied to patient studies.

Dose limiting toxicity for 131I metaiodobenzylguanidine (mlBG) systemic therapy is determined by the absorbed dose to bone marrow. In this study wholebody doses were determined following therapy, and the results compared with predictions made from a tracer dose of I23I mIBG and from a formula based on body weight. Mean and maximum tumour doses were also assessed, and initial work has commenced on determining 3D absorbed dose distributions. Prior to therapy, the patient is administered with 185MBq of 123I mIBG. Wholebody retention is determined by measurements on a sodium iodide wholebody counter and three SPECT scans are taken to determine the tamour uptake as a function of time. Mean and maximum turnout doses and the dose to the wholebody are predicted using standard MIRD methodology. A series of SPECT scans are also taken following 131I mIBG administration and are registered with each other and with corresponding CT data using a point-based method with externally attached markers. Dose distributions are then determined by considering the source activity on a voxel-to-voxel basis, and by convolving the cumulated activity with the 131I point source dose kernel. tn 18 studies wholebody doses predicted with the tracer have agreed with final results within a range of -37 to +42% whereas those predicted with the weight-based formula have been within -156 to +33%. Image registration and the production of dose distributions enable dose-volume histograms to be determined, which it is hoped will lead towards quantification of tumour-control probability.

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H. Fricke, W. Burchert, J. van den Hoff, H. Hundeshagen Medizinische Hochschule Hannover, Abteilung for Nuklearmedizin

J. Sandell C.-G. Swahn, *K. N~gren and C. Halldin. Karolinska Institute, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden. *Turku PET Center, Turku, Finland.

IMPROVED PET WHOLE-BODY IMAGING IN ONCOLOGY THROUGH ITERATIVE IMAGE RECONSTRUCTION AND MAXIMUM INTENSITY PROJECTIONS

CARBON-11 LABELLING OF (S)-DES-4-AMINO-3-IODOZACOPRIDE (DAIZAC), A POTENTIAL 5-ITT-3 RECEPTOR RADIOLIGAND FOR PET

Recently, there has been an increased interest in oncological PET investigations because most neoplasms and their metastases show strong uptake of 18-F-deoxyghicose (FDG). The clinical usefulness of oncological PET is severely limited by the small field of view of current PET scanners (10-15 cm). This limitation has been overcome with the wholebody acquisition technique, where the area of interest is sequentially scanned after accumulation of FDG. However, there are still a few problems with this approach: a) For a reasonable time frame, acquisition time for each bed position has to be much shorter than for static FDG uptake imaging. This causes noisy images. b) The high contrast near kidneys and bladder causes streak artifacts in conventional FBP images. c) The examiner has to inspect a large number (>150) of slices. For improved whole body imaging we have combined the use of iterative image reconstruction and maximum intensity projection (MIP). Iteradvely reconstructed images show less noise artefacts and better contour definition than FBP images. This is most important for pelvic imaging. The MIP can generate a variable number of projection images from the reconstructed transaxial slices. A set of eight images in steps of 45 degrees is useful for clinical documentation. Alternatively, a set of 64 images animated in a cine Mop provides a pseudo-3D-display of the complete data set. 3D-viusalization allows for more accurate localisation of pathological processes. We use both types of processing in daily clinical work.

Serotonin 5-HT-3 receptors have been implicated in psychiatric disorders and 5-HT-3 antagonists have shown to be able to modify behavior in animal models of anxiety and drug abuse. This has led to the suggestion that 5-HT-3 receptor antagonists have potential as novel antipsychotic agents and may also find use in the treatment of psychoactive substance abuse. The benzamide [H-3]zacopride, a potent and selective antagonist of the 5-HT-3 receptor, has been used to characterize 5-HT-3 receptors in the human brain. Considering its moderate affinity (Kd=l.5 riM) together with the comparatively low density of 5-HT-3 receptors in the human brain (1-3 pmol/g tissue) limits its potential as an in vivo imaging agent. Recently (S)-des-4-amino-3-iodo-zacopride (DAIZAC), an analogue of zacopride, has been labelled with iodine-125 (Kd=0.15 nM) (Mason et ai 1996). The presence of a methoxy group on the aromatic ring makes DAIZAC suitable for labelling with a straightforward [C-11]methylatior procedure. Unlabelled DAIZAC was prepared in a six step synthesis starting frorr 5-chlorosalicylic acid. Esterification of 5-chlorosalicylic acid gave th~ corresponding methyl ester which was iodinated to yield methyl 5-chloro 3-iodo-2-methoxybenzoate. After hydrolysis of the benzoate it wa transformed to its acid chloride which was subsequently condensate, with (S)-3-amino quinuclidine to yield DAIZAC. The overall yield wa about 4%. The precursor used for C-11 labelling, nor-DAIZAC, wa synthesized from DA/ZAC with BBrJCH2C1z as demethytating reagen Labelling of [C-11]DAIZAC was accomplished by O-alkylation of noJ DAIZAC with [C-11]methyl triflate in acetone using NaOH as a bas~ The incorporation of [C-11]methyl triflate to yield [C-11]DAIZAC was a high as 80% and no subsequent heating was needed. The high affinit 3 the apparent iipophilicity (log P=2.35) and the straightforward labellin makes [C-I 1]DAIZAC a potential PET radioligand for examination of HT-3 receptors in the human brain.

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E.Sutinen, S.Leskinen, M.Haaparanta, T.Gr6nroos, P.Lehikoinen, K.Ngtgren. Department of Oncology and Radiotherapy, Turku Universi~ Central Hospital and Turku Medical Cyclotron/PET Center, Turku, Finland. CARBON- 11-METHYLAMINOISOBUTYRATE (C- 11-MeAIB): NEW TRACER FOR STUDIES ON AMINO ACID TRANSPORT BY PET

I.Vandersteene, G. Slegers, K.Audenaert and RA.Dierckx. Department of Radiopharmacy, University of Ghent, Ghent, Belgium.

Carbon-ll labelled amino acid analogue MeAIB is specific for the system A amino acid transport and is not metabolized. The biodistribution of C-11-MeAIB was measured in rats to evaluate the usefulness of the tracer for PET-studies. Healthy Spraque-Dawley rats (n=15) and a rat with DMBA induced tumors (5 tumors) were anesthetized, and a bolus of 300 (96-562) MBq C-11-MeAIB was injected i.v. The rats were killed 5, 20, 40 and 60 rain after the injection, and the tissue samples were weighted and counted for C-11-radioactivity. The uptake of C-11-radioactivity in several organs (liver, lung, spleen, kidney, adrenal gland, bone marrow, intestine, testis, fat, muscle, eyeball, pancreas, myocardium, brain, cerebellum), in blood and urine and in tumors was calculated using SUV (standardized uptake value). High accumulation of C-11- MeAIB was detected in following organs: SUV Stain(n=7) 20 min (5) 40 min (2) 60 min (1t blood 1, 35 O,73 0, 55 0, 52 adrenal gL 1,23 2,29 2,36 2,14 intestine 1,01 2,35 2,16 4,10 kidney 5,98 t4,2 12,6 3,26 marrow O,52 O,99 I, 36 2, 56 pancreas 3, 52 8, 01 7,86 7,52 SUV in tumors was 0,81 (0,63-1,04) 20 min after the injection. Amino acid uptake in tumors seems not to be related to increased activity in system A. High uptake of C-11-MeAIB in tissues in comparison to the radioactivity concentration in the blood encourages to continue to human studies by PET on the physiology and pathology of system A transport.

SYNTHESIS OF [C-11]-GRANISETRON AS A P O S S I B L E P E T L I G A N D F O R T H E 5-HT3 R E C E P T O R .

Serotonine (5-hydroxytryptamine) is an important neurotransmitter in both the peripheric and central nervous system and is involved in numerous physiological and pathophysiological processes. 5-HT3 receptors are unique among the serotonine receptor subtypes as ligand-gated ion channels and their function as well as their pharmacology has been intensely studied. 5-HT3 antagonists are therapeutically used as inhibitors of radiation-induced emesis and pain and in the treatment of several psychiatric disorders, such as anxiety, psychoses and schizophrenia. For the in vivo study of the 5-HT3 receptor we developped the synthesis of [C-Illgranisetron, a selective and high affinity antagonist. N-demethylation of granisetron was used to synthesize a suitable precursor. [C-ll]granisetron was synthesized using [C-II] methyl iodide as the labelling agent. Reaction parameters and conditions were optimized and the product was purified by straight phase semi-preparative HPLC. After 40 min the chemical and radiochemical pure product is obtained in a 35% radiochemical yield with specific activity 9-15 GBq/~mol. Animal distributions were carried out to determine the usefulness of this tracer as a possibl e PET-ligand for the 5-HT3 receptor subtype.

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W.NEF, G. WESTERA, J.T. PATI', P. A. SCHUBIGER Klinik and Poliklinik f'tir Nuklearmedizin, Universit~itsspital, Ztirich

C. Gilissen, G. Bormans, T. de Groot, A. Verbmggen

N-ACETYL-2-(TRIMETItYL.STANNYL)-4-BUTOXYCARBONYLOXY-L-PHENYLALANIN-ETHYLESTER (4) FOR THE PRODUCTION OF 2-FLUOROTYROSINE [18F]-2-Fluorotyrosine is a useful compound to image some tumors presumably because it shows aminoacid uptake. Direct fuorination of tyrosine with [18F]F2 gives a mixture of 2- and 3-fluorotyrosine which is difficult to resolve. No carrier added [tSF]-2-fluorotyrosine can be made by a circuitous route. The no carrier added status is not necessary however. For routine purposes it would be advantageous to be able to label tyrosine by regioselective radiofluorodestannylation of the corresponding protected 2-trimethylstannyl compound. Thus we have made (4) via a complicated scheme.

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2-F-tymsine Coupling of (S)-(-) 1-Boc-2-tert -butyl-3methyl-4-imidazolidine with 4-bromomethyl-3-nitroanisol (1) yields after hydrolysis and acetylation L-2-nitro-N-acetyltyrosine (3). Reduction, diazotisation, iodination and stannylation of the appropriately protected derivatives then yields (4).

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Laboratory of Radiopharmaceutical Chemistry F.F.W., K.U.Leuven, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium SYNTHESIS OF N-IF- 18]FLUOROETHYL-N'-METHYLTHIOUREUM: A HYDROGEN PEROXIDE SCAVENGER A growing number of studies demonstrate that oxidative stress is implicated in many diseases. PET with an appropiate radiopharmaceutical would provide a tool for the in vivo investigation of oxidative stress and the evaluation of potential therapies. Dimethylthioureum (DMTU) is a freely diffusable molecule which is frequently used as an in vivo scavenger of hydrogen peroxide present in tissues exposed to oxidative stress. In the presence of hydrogen peroxide DMTU is oxidised to DMTU-dioxide, which can be trapped inside the cell due to its increased polarity. Thus radioactive derivatives of dimethylthioureum are potential probes for the localisation of tissue areas exposed to oxidative stress. We have synthesised N-[F-18]fluoroethyl-N'-methylthioureum (FEMTU), a fluorine-18 labelled derivative of DMTU. It proved to be impossible to prepare a precursor for a one step synthesis of FEMTU. Therefore, FEMTU was prepared by a three step procedure. First [F-I 8]FCH2CH2NH2 was synthesised by nucleophilic substitution of the O-tosyl group of TsOCH2CH2NHBoc with F-18 followed by acidic hydrolysis with HBr/HOAc to deprotect the amino group. After basification [F-18]FCH2CH2NH2 is distilled with a stream of nitrogen and trapped in dichloromethane where it is reacted with methylisothiocyanate to yield FEMTU. [F-181FCH2CH2NH2 was obtained in good yields (22-36 %), but yields of the last step have been variable (up to 20 %) and need to be optimised. Biological evaluation is in progress to investigate whether FEMTU is retained in tissue exposed to oxidative stress.

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C. Halldin ~, C. Lundkvist ~, D. Guilloteau 2, H. Olsson ~, P. Karlsson ~, H. Hal/, S. Chalon 2, P. Emond2, C.-G. Swahn I and L. Farde ~. )Karolinska Instituter, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176, Stockholm, Sweden. 2Lab de Biophysique Medicale/Pharmaceut Universite Francois Rabelais, 37200 Tours, France.

H. Hall I , C. Halldin l, C. Lundkvist I, F. Brunner-Ferber 2, L. Farde 1, and G. Sedvall I. 1Karolinska Institutet, Dept. of Clinical Neuroscience, Stockholm, Sweden, and Dept. Clinical Pharmacology, Hoechst Marion RousseI, Frankfurt-am-Main, Germany 2.

TtlE FIRST SELECTIVE R A D I O L I G A N D SUITABLE BOTH PET AND SPECT

DOPAMINE TRANSPORTER FOR Q U A N T I T A T I O N W I T H

Many ~-CIT analogs have been developed and used for imaging of the dopamine transporter with PET and SPECT. All have high affinity for the dopamine transorter but most of them also considerable affinity for other monoamine reuplake sites. A new analog, N-(3-iodoprop-2E-enyl)-2Bcarbomethoxy-3g-(4-methylphenyl)nortropane (PE2I), is the first selective compound for the dopamine transporter that can be labelled both for PET and SPECT. The affinity (gh values) of PE2I for DATT, 5-HTT, and NET are 17, 500 and >1000 aM which can be compared to B-CIT that in the same study have 27, 3 and 80 nM, respectively. The aim of this work was to develop [t 1C]PE2I as a PET radioligand for quantitation and examine the binding of [llcIPE2I in vitro with human post-mortem autoradiography and in vivo with PET in Cynomolgus monkeys. ["C]PE2I was used to visualize dopamine transporters in post-mortem human brain hemispheres by in vitro autoradiography. [nC]PE2I demonstrated a selective and high binding in the candate and putamen, brain areas known to have a high density of dopamine transporters. Binding in striatal regions where inhibited by GBR 12909 (100 gM). There was a rapid accumulation of radioactivity in the monkey brain after i.v. injection of [IICJPE2I (5% after 4 rain). There was a high accumulation of radioactivity in the striatum with a striamm to cerebellum ratio of about 9 at transient equilibrium (60-70 minutes). In a pretreatment experiment, radioactivity in the striatum but not in the cerebellum was markedly reduced after injection of OBR 12909 (5 mg/kg). Metabolite studies measured in plasma demonstrated only polar labelled metabolites (23% unchanged radioligand at 51 minutes). In conclusion, PE2I is the first selective dopamine transporter radioligand suitable for quantitation with both PET and SPECT.

AUTORADIOGRAPHIC LOCALtSATION OF 5-HT2A RECEPTORS IN THE POST-MORTEM H U M A N B R A I N USING [H-3IMDL 100907.

During the last decade, preclinical and clinical observations have indicated the involvement of 5-HT2A receptors in psychiatric disorders. Thus, various compounds with affinity for the 5-HT2A receptor have been used for studies as well as for clinical trials. One of the most selective 5-HT2A receptor antagonists is R)-(+)-4-[1-hydroxy-l-(2,3dimethoxyphenyl)methyl]-N-2-(4-fluoro-phenylethyl)piperidine (MDL 100907). MDL 100907 has a high affinity for the 5-HT2A receptors (Ki: 0.85 nM), with 100 fold lower affinity for other receptor types. MDL 100907 was radiolabelled with [H-3] to high specific radioactivity. The distribution of the 5-HT2A receptors was characterised in the normal post-mortem human brain using whole hemisphere autoradiography and [H-3]MDL 100907. The autoradiograms showed very dense and relatively homogenous binding to cerebral cortex, with only very low density of binding in basal ganglia, hippocampus and cerebellum. The labelling of human 5HT2A receptors with [H-3]MDL 10090"] was inhibited totally by the addition of the 5-HT2A receptor antagonist ketanserin, but not with for example the 5-HTIA receptor antagonist WAY-100635. [H-3]MDL 100907 had very low nonspecific binding or accumulation in the white matter. The in vitro autoradiography obtained with [H-3]MDL 100907 provide detailed qualitative and quantitative information on the distribution of the 5-HT2A receptors in the human brain. Moreover, the autoradiograms give complementary information for the interpretation of results on 5-HT2A receptor distribution in the human brain obtained at lower resolution with PET and [C-11 ]MDL 100907.

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C. Halldin ~, O. Langer ~'2, C. Lundkvist ~, J. SandelJ ~, H. Olsson ~, C.-G. S-wa-~n~'H. Hall J, P. Karlsson1, C. Loc'h 2, M. Bottlaender 2, B. Bendriem 2, B. Mazibrea and L. Farde ~. LKarolinska Institute, Department of Clinical Neuroscience, S-17176 Stockholm, Sweden. ~Service Hospitalier Frtddric Joliot, F-91406 Orsay, France.

WAP Breeman, HF Bernard, LJ Hofland, A Srinivasan,M de Jong, WH Bakker, TJ Visser, EP Krenning. Depts of Nuclear & Internal Medicine, University Hospital Rotterdam, Rotterdam, The Netherlands and Mallinckrodt Medical, St Louis, Missouri, USA

E X T R A S T R I A T A L DOPAMINE D2 RECEPTORS IN THE M O N K E Y AND H U M A N BRAIN V I S U A L I Z E D BY C-11 EPIDEPRIDE USING PET AND A U T O R A D I O G R P I t Y

Tissue distribution and metabolism of radloiodinated DTPA-0, D-Tyr-1 and Tyr-3 derivatives of octreofide in rats. Lesions containing somatostafin receptors (&qR) in rats and in man can be visualized in vivo using radiolabeled octreofide analogs.SSR scinl!graphyhas been initially performed with [I-123-Tyr-3]octreo~ide and later with [In-lll-DTPA0]octxeotide. With the latter the residence time of radioactivity (In-111)in SSR-pos targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect metabolism of radioiodinated DTPAoctxeotide analogs. [D-Tyr-1]oct~eotide(A), [DTPA-0, D-Tyr-1]octreotide (B), [Tyr3]octreotide (C) and [DTPA-0, Tyr-3]octreotide (D) were synthesized and all 4 showed high and specific binding to the SSR in vitro: Kd values in sub-nanomolar range. Metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 h pi, and the tissue/blood ratios were calculated. Urinary excre~/onwas 63, 67, 31 and 80 % of injected dose (ID)for the analogs A-D, resp. [DTPA-0, 1-125-Tyrq]octreotide showed highest ratio and residence time in 5SR-pos tissues, such as adrenals (30, 80, and 70 at 4, 24 and 48 h resp) and pancreas (14, 48 and 45 at 4, 24 and 48 h resp). Conclusion: Position of Tyr residues and addition of DTPA group influences metabolAsmand residence time of radioiodinated [Tyr]octreotideanalogs.

The function of extrastriatal brain regions may play an important role in diseases such as schizophrenia. In extrastriatal regions the potential for examination of dopamine receptors is limited by the low receptor densities, which are 10-100 times lower than in the basal ganglia. Epidepride ((S)(-)-N-(( 1-ethyl-2-pyrrolidinyl)methyl)-5-iodo-2,3-dimethoxybenzamide) and its bromo analogue FLB 457 are two substituted benzamides with very high affinity (Ki = 15-20 pM) and selectivity for dopamine D2 receptors. Iodine-123 labelled epidepride is used to visualize extrastfiatal D2 receptors in human brain with SPECT. The equipotent FLB 457 that has been labelled with carbon-11 or bromine-76 is used for quantitation of extrastriatal D2 receptors with PET. Recently, attempts have been made to quantify D2 receptors also with SPECT. In this context a radioiigand which can be labelled both for PET and SPECT will allow a direct comparison of data obtained from both techniques. The aim of this work was to develop [C-11]epidepride as a PET radioligand and examine the binding of [C-I1]epidepride in vitro with human post-mortem autoradiography and in vivo with PET in Cynomolgus monkeys. Human whole hemisphere autoradiography using [C-ll]epidepride demonstrated labelled receptors in nucleus caudatus, putamen and to a lower extent in extrastriatal areas such as thalamus and the neocortex which is in accordance with previous work where [I-125]epidepride was used. Binding in both striatal and extrastriatal regions were inhibited by raclopride (10 gM). In PET examination in a Cynomolgus monkey [C-I I] epidepride accumulated not only in the striamm but also in several extrastriatal regions. Uptake in the striatum, thalamus and neocortex was 9, 3 and 3 times higher than in the cerebellum, respectively. In extrastriatal brain regions radioactivity reached a plateau at about 50 minutes after injection. Pretreatment of the monkey with raclopride (1 mg/kg) blocked 50-70% of [C-11] epidepride specific binding. [C-11]Epidepride specific binding should be appropriate for a quantitative equilibrium analysis of extrastriatal dopamine receptor densities with PET.

% ID/g ligand A B C D

adrenals 4h - 24h 1.9- .58 1.0- .32 .37- .05 .55- .03

pancreas 4h - 24h ,65- .53 .47- .19 1.7- .14 1.7- .05

kidney 4h - 24h 4.5- 3.4 5.0- 2.3 .41- .06 .69- .15

blood 4h - 24.h .14- .04 .04- .00 .08- .02 .06- .00

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Marion de Jong 1, Bert Bernard~, Wout Breeman~, Willem Bakker~, Theo Visser1, Helrnut M~cke2, Eric Krenning1. ~Dapt of Nuclear Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands, 2Dept of Nuclear Medicine, Kantonspital Basel, Base/, Switzerland.

I. FOldes, A. Ldvay, E. Okos, I. Felde Department of Nuclear Medicine, Central Hospital of the Ministry of the Interior, Budapest, Hungary

D-LYSINE FOR REDUCTION OF RENAL [In-111-DTPA,D-Phe-1]OCTREOTIDE AND [Y-90-DOTA,D-Phe-1 ,Tyr-3]OCTREOTIDE UPTAKE. In-111-DTPA-octreotide (In-111-DTPAOC), successfully used to image sornatostatin receptor-posit!re lesions, is now applied for peptide* receptor-radionuclide-therapy (PRRT). For the latter purpose [DOTA,DPhe-l,Tyr-3loctreotide (DOTATOC), suitable for stable radiolabelling with Y~90, is even more promising. However, significant renal (re-)uptake and retention of these analogues exists, reducing the detection sensitivity of perirenal turnours and increasing radiotoxicity in the kidney during PRRT. We studied the inhibitory effects of D- and Lqysine on kidney uptake of In-111-DTPAOC and Y-90-DOTATOC. Methods: Wistar rats were given In-111-DTPAOC (0.2 MBq, 0.5 pg-0.5 rng; iv,ip or orally) or Y-90-DOTATOC (1 MBq, 0.5 ,ug; iv), with or without D- or L-lysine. At several time points, organs were isolated and counted. Results: D- or L-lysine, iv, 400 mg/kg, resulted in >50% inhibition of kidney In-111-DTPAOC uptake. Higher or repeated doses of lysine did not increase inhibition. Oral and ip administration of lysine was less effective. However, after L-lysine also uptake of in-111-DTPAOC in target organs was decreased. D-lysine did not have this negative effect. Renal uptake of Y-90-DOTATOC was reduced by 65% by D-lysine iv; uptake in target organs was unaffected. Conclusion: D- and L-lysine are promising for reduction of nephroradiotoxie effects during PRRT by preventing tubular re-uptake of the radiolabel. This method may be useful in other nephrotoxic modalities as well. D-lysine is preferred to obtain maximal radioactivity in the turnour.

CALCULATION OF THE ACTIVITY FOR RADIOIODINE TREATMENT OF SINGLE AUTONOMOUS THYROID NODULE 70 patients with single autonomous thyroid nodule were treated with radioiodine. The weight of the nodules ranged between 0,6-50,0 grams and the therapeutic dose of iodine-131 was between 104-550 MBq. Thyroid scan using Tc-99m-pertechnetate was performed in all patients before and not less than three months after therapy. 49 patients revealed complete response, the activity of the nodule became the same or less than the activity of the extranodular tissue, the pretherapeutic suppressed TSH increased to normal level (in two patients mild hypothyroidism developed). In 11 patients partial response has been observed, the activity of the nodule diminished, but remained higher than the activity of the extranodular tissue, however the TSH level became normal. In 10 patients the follow-up thyroid scan showed no change, the TSH concentration remained subnormal. In a retrospective study based on the data of the group(49 patients) treated with complete success, the relation between the weight of the nodule (W in grams) and the dose oI radioiodine delivered (D in MBq) was evaluated. Regression analysis gave the following equation: D -- 2 7 7 + 6 5 * l n W r = 0,764 This equation is valid between 0,6 - 50,0 grams and must not be extrapolated. According to this regression analysis a single autonomous nodule of 0,6 grams (with high extranodular uptake) needs 239_+16 MBq (mean+2SD). A nodule of 50 grams (negligible extranodular uptake)has to be treated with 529_+65 MBq radioiodine. The low dose of isotope and previous iodine exposition were the two main factors causing inefficacy of therapy. In conclusion, our equation describing the relation between the weight of a single autonomous thyroid nodule and the efficient activity of administered radioiodine, helps to calculate the dose for successsful therapy.

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J.C. Reubi 1, B. Waser 1, U. L~derach 1, and A. Srinivasan 2. 1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland; and 2Mallinckrodt Medical, St.Louis, MO, USA.

K.A.J.McKellar(1),C.G.Gemmell(2),J.B.Neilly (3), J.H.McKillop(3), A.T.Elliott (1).Depts of Clinical Physics (i), Bacteriology (2), Medicine(3), University of Glasgow.

PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTI DE (PACAP) I AND PACAP II RECEPTORS IN HUMAN TUMORS: IN VITRO BINDING OF DTPA-LINKED PACAP ANALOGS. Many human tumors have vasoactive intestinal peptide (VIP) receptors, enabling receptor imaging in vivo using radiolabeled VIP. PACAP, a VIP-related peptide, binds with high affinity to these (PACAP II) receptors as well as to PACAP I receptors (having only low affinity for VIP). Using in vitro receptor autoradiography with 125-I-VIP and 125-I-Ac-His-1-PACAP(1-27), we identified 3 groups of human tumors: 1) those expressing mainly PACAP II receptors (all prostate, breast, colon and bladder carcinomas); 2) tumors expressing PACAP I and PACAP II receptors (most glial tumors, endometrial and ovarian cancers, inactive pituitary adenomas); 3) tumors expressing almost only PACAP I receptors (some glial and ovarian tumors). Adequate PACAP radioligands, binding with high affinity to these 3 groups of tumors, would therefore be of great potential value for scintigraphy. The PACAP molecule is however difficult to modify chemically without loss of binding affinity. We designed several PACAP analogs linked to DTPA and tested them for their binding properties in human tumors expressing PACAP I or PACAP II receptors. The Table shows their rank order of binding potencies (relative to PACAP(1-27) set as 100): PACAP I-R PACAPII-R PACAP(1-27) 100 100 N-DTPA(piperidine amide)-PACAP(1-27) 2 4 N-DTPA-PACAP(1-27) < 0.1 < 0.2 N-DTPA-PACAP(6-38) < 0.05 < 0.05 N-DTPA-PACAP(1-38) Asp3,Glu4 irnide < 0.05 < 0.05 N-DTPA(piperidine amide)-PACAP(1-27) is a promising lead for the development of PACAP analogs suitable for in vivo scintigraphy of tumors expressing PACAP I and/or II receptors.

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RADIO-IODINATED SUBSTANCE AN AGENT TO IMAGE INFLAMMATION

P ANALOGUE INFECTION

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challenge.

The

increased expression of NKI receptors at the infectious/inflaIm~atory site, the target receptors for Substance P (SP), represents a potential target for radiopharmaceutical imaging. We have evaluated the ability of the radioiodinated tyrosine analogue of SP (SP[Tyr]-I) to identify infectious foci in a murine model of S. aureus septic arthritis; 5x107 cfu of an arthritogenic strain of S. a u r e u s were injected intravenously and over the next 7 days the development of swollen joints indicated the presence of joint sepsis. Iodine-123 labelled SP[Tyr] was injected i.v. at 7 days post infection and its bio-distribution measured 6 and 16 hours post injection by g ~ camera imaging and by tissue specific radioactivity counting. Results indicate a generalised increase in tissue uptake in infected animals in addition to specific uptake at clinically identifiable lesions. Focal accumulation demonstrated an increase in target to background ratio with time, indicating the potential value of this agent for the detection of localised infection and associated inflammation.

P 488

T1.1

J. Bogatzkv~ S. Gulflke, H. Bender, J. Sartor, F.F. (Russ) Knapp* and H.J. Biersack; Kiinik ftir Nnidearmedizin, Universitiit Bonn; *Nudear Medicine Group, Oak Ridge National Laboratory, (ORNL), Oak Ridge, TN. RECEPTOR BINDING STUDIES WITH RHENIUM-RC160, A DIRECTLYLABELED SOMATOSTATIN ANALOG, WITH MEMBRANES OF THE COLON CANCER CELL LINE HT 29, CHO CELLS AND OVARY CARCINOMA CELL LINE EFO-21

E. e b e r l, T.M. Behr I, R.M. Dura~2, S. Gratz I, A. Herrmarm1, H. Schmidberger~ and W W. Becker a. Departments of Nuclear Medicine ] and Radiation Oncology3 of the OeurgAugust-University of G6rtingen, Germany, and Garden State Cancer Center at the Center2, Belleville, NJ, USA.

Recent data suggest that functional somatostatin receptors (SSR1-SSR5) are expressed in a wide range of tumor types~ The octapeptade RC160 binds with high affinity m the SSR2 and SSR5 subtypes and might thus be complementary to Octrentide which preferentially binds to SSR2. Re-188 is obtained from an alumina based W-188/Re-188 generator system which represents an ideal matched pair to Tc-99m and can provide high activity levels of Re-188 in highly concentrated form for therapeutic appli~tions. We have already demonstrated the therapeutic potential of Re188-RC160 by extensive biodistribution studies, scintigraphy and also locore~genal tumor therapy in athymic mice with various tumor cell lines (Zamora et al. 1996). In our recent studies we have examined the binding properties of cartier-added (e.a.) versus no-carrier-added (n.c.a.) Re-188-RC160 with membranes of HT 29 and CHO cells in comparison to receptor negative Raft cells. Also we have investigated the in-vitro displacement of In-1 l 1-Octreotide with carrier-added Re-188-RC160 with membranes of HT 29, CHO and EFO-21 cells in comparison to receptor negative Raji cells. It was possible to displace In-1 l 1Octreotide in s concentration dependent manner. IC~0 values were obtained in the high nano-molar range, thus suggesting that directly labeled RC160 retains receptor affinity. Further studies with other tumor cell lines and additional invitro studies and in-rive studies will be of great interest in the development of this therapeutic agent. * Research at ORNL sponsored by the US. DOE under contract DE-AC059601122464 -~6th Locld-xeedMartin Energy Research Corporation.

Reliable, quantitative internal radiation dosimetry is not only mandatory for any dosimetry-based treatment planning, e.g., in radioimmunotherapy, but also allows for more adequate dosing in the therapy of metastatic differentiated thyroid cancer with Na~3]I; fi.u-thermore, it enables estimation of organ and whole-bedy doses in the radiosynoviorthesis with 90y or ~86Re,as well as lesion and whole-body dnsimetry 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 (mI, Is6llSSRe etc.) or bremsstrahlung emissions (pure 13--emitters,such as 9Oy)for quantitation. Conjugate view whole-body scans of patients are acquired at multiple time points. For r-emitting nuclides, the respective photo peal~ is used, whereas for yttrium dosimetry, bremsstrahhmg is recorded in a 120-300 keV window. An activity standard is measured under the same conditions as the patient; for ~0y, a 500-~tCi point source is placed in a body-like water phantom. Regions are drawn over the whole-body, organs and tumors, and appropriate backgmmd correction is carried out (Dunn RM et al., Med Phys 1995; 22: 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 buildup factor methodohigy (Wu/Siegel, Med Phys 1984; 11: 189-i92), which was shown to be more accurate than the geometric-mean method. Time-activity curves are generated, integrated, and cumulated 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 fimctions. The munulated activities of the red marrow are calulated from blood samples and imaging data. These data are entered into the MIRDOSE3 program (Stabin M, J Nucl Med 1996; 37: 538-546) which yieIds the organ, red marrow, tumor, and whole-body dosimetry according to the MIRD scheme, based on derived residence times. The automated dosimetry scheme as presented here 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 radioirnmanotherapy are in progress.

P 490

T 1.2

S. Guhike, P.O. Zamora*, J. Sartor, F.F. Knapp *~, B.A. Rhodes* and H.J. Biersack. Klinik ffir Nuldear M e ~ , University of Bonn, Germany. *RhoMed Inc, Albuquerque, NM, USA. **Nuclear Medicine Group, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN, USA

M . G ~ r a n s s o n and B.Jansson, Departments of Nuclear Medicine and Hospital Pharmacy,Huddinge U n i v e r s i t y Hospital, S-141 86 Huddinge, Sweden.

STABILIZATION OF RI]ENIUM-188 AND IODINE-131 LABELED PEPTIDES FOR RADIOTHERAPY.

ADSORPTION OF RADIOPHARMACEUTICAL INJECTIONS IN DISPOSABLE PLASTIC SYRINGES.

The aim o f this study w a s to evaluate methods to stabilize rhenium- 188 and iodine-131 labeled somatostatin-type peptides (RC-160 and somatostatin-14) against radiolyfic effects insulting from the high 13-flux in high a c t M t y preparations intended for radiotherapy. Re-188RC-160 in particular is being explored as an agent for local/regionally treatment o f somatostatin-receptor positive tumors. The comparative stability o f Re-188-RC-160, 1-131 labeled somatostatin-14 and unlabeled somatostatin-14, which w a s incubated with Re-188 perthenate only, w a s analyzed as a function o f time either by radioH P L C or by UV-absorption. Exposure o f the peptides to high radiation flux resulted in peptide degradation with a half life of approximately 2.5 hours and was independent o f the used radio isotope. The lytic effect w a s attributed to the presence o f any high flux radioactivity as the control experiment with unlabeled somatostatin-14 in presence o f Re-188 perrhenate also showed about the same degradation half-tlme as the radiolabeled peptides. The radiolytic effects could be overcome by the addition o f either ascorbic acid or gentisic acid to the preparations, Even at 24 hours post labeling the radiochemical purity w a s found to be greater than 80%. Most importantly, stability was also observed in Re-188-RC-160 preparations labeled with more than 3 G B q o f Re-188. In addition, both stabilizers (ascorbic acid and gentisic acid) are also mild reduetants which in the case o f Re-188-RC-160 help preventing Re188 re-oxidation. These studies support the feasibility o f using radiolabeled somatostatin analogues as radiotherapeutic agents.

AN AUTOMATED SCHEME FOR INTERNAL RADIATION DOSIMETRY IN NUCLEAR THERAPY: GAMMA- OR BREMSSTRAHLUNG-BASED DOSE CALCULATION IN THE THERAPY OF DIFFERENTIATED THYROID CANCER, RADIOSYNOVIORTHESIS, AND RADIOIMMUNOTHERAPY.

It is a w e l l - k n o w n fact that p r o t e i n solutions, e.g.,albumin adsorb in plastic syringes. Several preparations used in gamma-camera diagnostics, such as MAA, NANOCOLL, ALBURES are based on denaturated human serumalbumin. As part of our quality assurance programme we measured the activity retained from those and other frequently used preparations, We found quite a lot of activity remaining in the syringe both from a l b u m i n - b a s e d preparations and from some of the other radiopharmaceuticals. The measurements were made in connection with the examination of the patients as well as after simulated injections, where the dose was allowed to be drawn into an empty elution vial under negative pressure. The a c t i v i t y remaining in the syringe was then remeasured immediately. As a result of this finding we made a control of the retained activity, where we used syringes of different brands, different activities, various time-intervals b e t w e e n filling and emptying the syringes. We also made comparisons b e t w e e n Tc-99m-preparations from different manufacturers. We found that the adhesion differs considerably both between preparations from different manufacturers and between different syringe-brands. The remaining a c t i v i t y could be as high as 40%. The consequences of inadequate dosing can include inappropriate diagnostic response in patients, which may lead to m i s i n t e r p r e t a t i o n of the results, increase in the duration of treatment and of costs. Therefore, we find it essential that a c t i v i t y measurements in the syringe are made before and after each injection every time you introduce a new radiopharmaceutical or a new brand of syringe in your nuclear medicine department.

Research at O R N L supported by D O E under contract DE-AC0584OR21400 with Lockheed Martin Energy Research

1059

¢)

O')

_o

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O

T 1.3

T2.1

D Anstee, A Montgomery, C J Martin and T E Hilditch, Radionuclide Dis~nsary, Health Physics and Nuclear Medicine Delmrtments , Wetsern ~ r y , Glasgow.

N B Smith, A Notghi, L K Harding, Physics and Nuclear Medicine Deptartment, C i t y H o s p i t a l T r u s t NHS Trust, B i r m i n g h a m ,

C O M P A R I S O N O F T H E FERFORA&ANCE O F A SYRINGE SIIIEI.D A N D A s E ~ - A U T O I M A T E D D O S E DISFENSER

A Gamma Extremity Monitoring System (GEMS) has been used in a hospital Radionuclide Dispensary to assess the dose reduction benefits afforded by the use of a new type of extruded lead glass syringe shield and a semi-automated dose dispenser relative to unshielded manipulations. The relative dose-rate to the index finger was recorded by GEMS during the dispensing of three sets of known quantities of Tc99m. The same procedure was adopted for the three types of manipulations. The average dose received from the unshielded manipulations was approximately ten times that from shielded ones. While the dose dispenser provided a fractionally greater dose reduction than the syringe shield, the use of the syringe shield showed a better performance due to the more consistent activities dispensed and it allowed an incremental advancement of 0.01 ml compared to 0.1 ml for the semi-automated dose dispenser. Comparing the two shielded devices fhe lead glass syringe shield was more cost-effective, accurate and flexible, with comparable dose reduction benefits.

T 1.4

U. K.

W H A T S T R E S S R E G I M E FOR NUCLEAJR C A R D I O L O G Y - A TECHNOLOGISTS POINT OF VIEW Myocardial i m a g i n g has u n d e r g o n e changes which h a v e l e a d to a c h a n g e in the i n v o l v e m e n t of the technologist. In our d e p a r t m e n t t h e r e has b e e n an increase in myocardial imaging from 52 p a t i e n t s in 1993 to 458 in 1996, an i n c r e a s e of 900%. This t r e n d has f o l l o w e d the c h a n g e in the type of stress m o d a l i t used:Type No of Drug Time Side Dose to P a t i e n t s Cost T a k e n {ffect~ T e c h n ' n (mins} % (~Sv) {xercise 97 45
T 2.2

J HARRISON, R GADD, PJ MOUNTFORD, J OXTOBY

EA CZarke, A Not~hi, ~ ~ _ , ~ t ~ics and N ~ Medicine, C i ~ Hospital

NUCLEAR MEDICINE - NORTH STAFFS. HOSPITAL

Trust, Bizmingh~n BI8 7QH, t~.

of

ALARP A~D THE IDEAL I~ART ~ COMPETENCE BASED DEPARTMENTAL TRAINING PACKAGE IN RADIOPHARMACY FOR NUCLEAR MEDICINE TECHNOLOGISTS At the North Staffordshire Hospital routine radiopharmaceutical preparation is carried out by the nuclear medicine technologists. With the advent of clinical risk management, a Trust approved package was required in order to maximise patient safety. The purpose of this in-house traihing package is to address this need and train ~echnical staff to be competent practitioners i;l the radiopharmacy. The training package contains six topic areas: i. 2. 3. 4. 5. B.

Overview of radiopharmacy The radiopharmacy environment Aseptic technique The Amersham technetium generator The production arld dispensing of radiopharmaceuticals Blood labelling tech~iques

IT assumes the use of Amercare isolators within a clean room envirorlment. Assessment is competence based and incorporates the radiopharmacy competencies produced by the British Nuclear Medicine Society Technology Group and presented at the EANM Congress last year in Copenhagen. Assessments are performed by the Chief Technician arld the radiopharmacy production manager, these assessments being reviewed every two years and a certificate of competency being issued.

1060

Technologist radiation doses from myocardial perfusion studies h a v e been shown to be higher than the average nuclear medicine study. Although unlikely to exceed the proposed dose limits of 6 mSv per year (Category A workers) changes in practice were implemented to reduce doses (maintalning distance and speed). Technologists were also asked to wear a lead coat (0.35 lead equivalent) during all three parts of a heart study, with one digital pocket dosemeter (Harwell, i pSv sensltivity) positioned inside the coat and another outside. The average recorded dose to the technologist for each section of the stud, is shown in the table. Previous Outside Distance Inside Lead coat! study lead and tirae l e a d reduction (~Sv) reduction (~Sv) Rest imaging(n=6) 1.0 0.9 10% 0.4 56% E~ercise ima.qing(n=7) 2.5 1.4 64% 0.5 65% ~enosine (n=13) 2.0 1.7 15% 0.5 71% I~otals 5.5 4.0 27% 1.4 65% Alternatively the tiel :ath an tec ~gi== :, was covered with i lead blanket (0.4 ~ lead equivalent) during adenosine administration. The r e c o r d e d a v e r a g e dose to the technologist was i. 6 Day, a reductlon of only 6%. Om maintaining distance .and speed, _the measureraents wee a reouctlon rrc~ a ~o~a± o.D ~b~ per s~u~y to DSv (27%). However little reductlon was seen durlng adenosine administration. With the addition of lead coats for Adenosine tests only a significant reduction of 71% in dose was measured. An alternative strategy would be to maintain distance during imaging and wear a lead coat only during stress adminzstration. This would result in a radiation dose of 2.8 DSv. This would achieve a material dose reduction (50%) without the inconvenience of lead coats except during stress administration. Using this .strategy,. a technologist could perform 48 complete carct%ac stuc~es per week as opposed to 24 and a pregnant technologlst 26 studies as opposed to only 6.

T 2.3

T 2.5

A.&X. van D 0 n ~ Department of Nuclear Medicine, Utrecht University Hospital, The Netherlands.

K. Stein, K. Tatsch, K. Hahn. Department of Nuclear Medicine, LudwigMaximilians-University of Munich, Munich, Germany

MINIMISING LIVER AND BOWEL ACTIVITY IN MYOCARDIAL SPECT

Introduction Optimal myocardial perfusion imaging with 99m-Tc-tetrofosmin requires adequate hepatobiliary clearance to mininaise the interference between myocardial and hepatic uptake. However, the resulting increased intestinal or gastric activity may create a major problem in the visual and quantitative interpretation of the inferoposteroseptal myocardial wails, especially in rest SPECT imaging. Both scatter and halo effects in filtered baekprojection images affect quantitation of reconstructed activity in the myocardial wall. Therefore, minimising interfering liver and bowel activity is important for all types of acquisition.

Patients and methods 97 patients undergoing myocardial rest SPECT imaging with 99m-Tetetrofosmin were divided into 3 groups of 33, 27 and 36 patients respectively. In group I no steps were taken to influence biliary clearance. ~ group 2 the patients were given 200-300 cc of water 10 minutes prior to imaging, on the assumption that a filled stomach pushes the intestines in caudal direction, thus distancing intestinal activity from the myocardium, as well as reducing the effects of duodenogastric reflux. The patients in group 3 were given a glass of whole milk 10 minutes after injection of the radiopharmaceutical to stimulate biliary clearance. In all groups SFECT images were acquired >- 30 minutes after injection. Hepatic, intestinal or gastric activity was determined visually on uncorrected filtered backprojection images and on polar display in combination with reconstructed images. Activity was defined as interfering when it was thought to result in either art underestimation or an overestimation of the uptake in the myocardial walI.

Results Interfering activity was seen in 83% of the patients in group 1, 74% of the patients in group 2 and 33% of the patients in group 3. However, as the rest images were followed by a stress study in all patients the diagnosis was affected ha only a few cases.

Conclusion The interpretation of inferoposteroseptal wall activity in myocardial rest SPECT images is facilitated by having the patient drink a glass of whole milk prior to data acquisition.

D Y N A M I C XE-133 SPECT M E A S U R E M E N T OF R E G I O N A L CEREB R A L B L O O D F L O W O N A TRIPLE-HEADED G A M M A C A M E R A In patients with cerebrovascular disorders detection of regional perfusion abnormalities and quantitative measurement of vascular reserve capacity are important. Quantitative evaluation of regional cerebral blood flow (rCBF), however, is hampered by the limited availability of dedicated imaging devices required for this procedure. Thus, them is a necessity for such imaging modalities which provide the information mentioned above and which are suitable for routine use. For quantitative measurement of rCBF we used Xe-133, an inert and'diffusible gas. The rapid clearance of the tracer from the brain requires special SPECT systems with high sensitivity and rapid acquisition cycles. We implemented the measurement of rCBF before and after provocation with a carbonic anhydrase inhibitor (acetazolamide) on a commercially available triple-headed g a m m a camera (Prism 3000, Picker Int.). Spatial resolution of the system is 15ram FWHM, temporal resolution is 10s. Subjects connected with a Xenon inhalation unit (Simonsen, Denmark) are studied with their eyes and ears open in a dimly lit environment. Arterial input function is monitored with a CdTe detector placed over the right upper quadrant of the lung. The acquisition consists of 2 stages. In the first stage background information for both the brain and the lung is obtained (360 °, 6 ° intervals, 1.5s/projection, 64x64). During the second stage subjects are administered 0.74-1.1GBq/1 of Xe-133 in air for train., followed by a 6min washout period (360 °, 6 ° intervals, 0.5s/projection, 64x64). After examination of the lung curve transverse slices are reconstructed (filtered back projection, ramp filter). Using Kanno-Lassen and/or convolution algorithms r C B F is calculated in ml/min/100g brain tissue. After filtering and reformatting the generated peffusion map may be dispIayed in transverse, sagittaI and coronal slices. Dynamic SPECT with a commercially available triple-headed gamma camera has shown to be a suitable approach for quantitative evaluation of rCBF using Xe-133 as radiotracer. In contrast to older dedicated brain systems (e.g. Tomomatic) the advantage of the presented device is the disposal of full-volume instead of single slice images and an improved spatial resolution.

T 2.4

T 2.6

S. First, C. Kolligs, C. Kmschke, J. Stollfuss, S. Ziegler, M Schwaiger DeparWaent of Nuclear Medicine, Technische Universit~t Minchen, Klinikum rcchts der Isar, Munich, Germany

Th. Berthold, K. Henke*, B.Weber*, H.G. Wieser*, A.Buck, Division of Nuclear Medicine and Department of Neurology, University Hospital, Zurich, Switzerland

Comparison of Euglycemic Hyperinsulinemic Clamp and Oral Glucose Loading in Diabetic Patients for Stimulating Myocardial Glucose Utilization during Positron Emission Tomographie using FlS-fluorodeoxyglucose. Positron emission tomography (PET) using F18-fluorodeoxyglucose (FDG) is a widely used method for assessment of myocardial glucose metabolism. Myocardial glucose consumption, however, largely depends on metabolic conditions such as blood glucose and insulin level. Therefore, a standardization of the metabolic environment is necessary, especially in diabetic patients in whom homeostasis of glucose metabolism is altered. The aim of our study was to compare FI8-FDG image quality measured by myocardial uptake ratios after oral administration of glucose with that of euglycemic hyperinsulinemie clamp. Six diabetic patients (3 in group A and 3 in group B) with known coronary arte~, disease and diabetes mellitus were investigated. In group A, 50 g glucose was orally administered 60 rain before F18-FDG injection. Depending on the blood glucose level, insulin (>130 mg/dl 3 I.U, <130 mg/dl no insulin) was given prior to FIS-FDG injection. In the clamp study, insulin and glucose infusions were started and plasma-glucose was stabilized during a preinjection period of 60 min. 280-370 MBq F IS-FDG was administered and static imaging was started 40 rain p.i. F 18-FDG uptake, as a measure of image quality was calculated from ROFs using an 8 segment model (4 basal, 4 distal segments). Infarcted areas were excluded from analysis. FI8-FDG uptake ratios (m ,ocardium versus ventricular cavit were calculated as follows.

Segment

Euglyeemie

Clamp

Oral glucose

loading

mean cts ratio max cts ratio mean cts ratio max cts ratio anterior 2.09 1.92 1.30 1.29 inferior 2.05 1.83 1.38 1.24 septal 2.39 2.20 1.31 1.27 lateral 3.12 2.63 1.34 1.28 all 2.41 2.10 1.33 1.27 e found better :18-FDG-PET i] aage quality- in :liabetic patients' after stabilized metabolic conditions using the clamp technique compared to oral glucose loading. These findings are supported by the higher myocardial uptake ratios shown above. However, the higher logistic demands for viability s~udies in conjunction with the hyperinsulinemic clamp technique compared to the simpler oral glucose loading protocol must be weighd against the potential gain in image quality'.

MEASURED VS CALCULATED ATTENUATION NEUROACTIVATION [lSO]H20 PET

CORRECTION

IN

In brain PET attenuation correction can be performed with contours (C) or using a transmission scan (TS). In neuroactivation studies with multiple [~50]H20injections C would be preferred because of the shorter study time. Both methods were compared in a hippocampal activation study in 7 volunteers. Following the injection of 400 MBq [~O]H20 a 60 second scan was acquired following the arrival of the bolus in the brain. A total of 2 scans was performed, 1 during the hippocampal activation task and 1 in baseline. Both scans were reconstructed using C and a l0 minute transmission scan. The data were then transformed into stereotaxic Talairach space and statistical parametric mapping was performed using SPM95.

coronal ....

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transversal 1:p=0.13 2:p=O.09

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1:p=0.63 2:p=0.44

Results: The figure demonstrates projection maps of the activated pixels . The arrows point to the right hippocampus (I) and a left frontal area (2). With the transmission scan the p-values of the shown activations is markedly higher. Conclusion: There is a marked effect of the method of attenuation correction on the sigifieance level of the activated areas. Measured attenuation correction with a transmission scan yields higher contrasts.

1061

T 3.1

T 3.3

U. Dopicha!-Menoe, E. Wandke, D. Sandrock and D.L. Munz. Clinic for Nuclear Medicine, CharitY, Humboldt University Berlin, Germany.

S.P. Anroedt, J.J.N. Visser, J.C. Greve, F.M. van der Zant, M.M.C. Tielvan Buul. Academic Medical Centre, Department of Nuclear Medicine, Amsterdam, The Netherlands•

IMPROVEMENT OF IMAGE QUALITY OF BONE SCANS CONTROLLED HYDRATION ?

BY

DUAL I S O T O P E VERSUS S I N G L E I S O T O P E LUNG SCINTIG R A P I t Y IN THE DIAGNOSIS OF P U L M O N A R Y E M B O L I S M

Aim of this study was to assess the influence of hydration on the quality of bone scans. The whole skeleton and the filling of the bladder (pelvic bone structures) were judgded visually, and ratios of bone to s o f t tissue (ROIs, proximal thigh) were calculated. Patients to be enrolled in the study had to fulfill the following criteria: i) no history of kidney disease; ii) normal serum creatinine; iii) no bladder dysfunction/voiding problems; iv) faint uptake in normally shaped kidneys on bone scans. Whole body scintigraphy (HR-collimator, 15 cm/min, body contour in anterior view) was performed t80 (+/- 15) min after i.v. injection of 600 MBq Tc-99m MDP. Three groups of 20 patients each were studied: In group I they were requested to drink 1 I of water between I and 2 h p.i.; group 2 had to drink > 1.5 I beginning 1 h p.i.; group 3 had to drink < 0.25 I, also beginning 1 h p.i. All patients were requested to void before the beginning of the scintigraphic procedure. As expected, in group 3 there was the smallest number of (at least half) filled bladders (2•20) while in group 1 and 2 half of the patients had filled bladders. In no case, however, an additional pelvic view was necessary. Visual scoring resulted in the statement "poor image quality" in group 3 in 0 (of 20), in group 1 and 2 in 3 (of 40) patients, respectively. All other scans were rated to be of "good quality". However, there was a significant difference of the ratio of bone to soft tissue (group 3: 2.90; group 1: 2.47; group 2: 2.24). Conclusions: The best scans in terms of image quality and the highest ratio of bone to soft tissue were obtained in the group with the least hydration. Filling of the bladder caused no problems for image quality.

Dual isotope lung scintigraphy is a generally accepted technique in the diagnosis of pulmonary embolism (PE). Advantages of this method are an identical patient positioning and a shorter total study time. Disadvantages, however, are the Kr-81 scatter in the Tc-99m-channel, and patients with normal perfusion imaging unnecessary undergo ventilation scintigraphy. In this study, an attempt was made to determine the influence of the simultaneous use of Tc-99m MAA and Kr-81 in dual isotope lung scintigraphy, on the quality of the perfusion images, with respect to the Kr-scatter. First, a phantom study was performed using Kr-81 in a balloon, and Tc-99m in a vial, both seperately lying on a perspex phantome filled with water• The counts were measured in both, the Kr-8 l channel and the Tc-99m channel, using the MEGP- and LEHR collimator, respectively. Secondly, 10 patients with abnormal lung scintigraphy were included who were imaged by dual isotope lung scintigraphy, followed by single isotope perfusion imaging. Both images were scored in the same order for non high or high probability for PE and both techniques were qualitatively compared by a panel of 3 experienced nuclear physicians. Phantom experiment: medium collimator: 10,4% Kr in Tcchannel, and 2,9% Tc in Kr-channel. LEHR collimator: 4,4% Kr in Tcchannel, and 4,8 % Tc in Kr-channel. Patients: 4 patients were non high probability, while 6 were high probability for PE. This score did not change if the single isotope perfusion images were taken into consideration. However, in 3 out of 10 patients, the single isotope perfusion scan was found to be of a slightly better quality than the dual isotope scan. We conclude that, although the Kr-scatter in the Tc-channel is maximally 10% (medium collimator), the Kr-scatter in dual isotope lung scintigraphy is of minor influence on the quality of the Tc-99m-perfusion images. In the investigated small series of patients, it did not change the final outcome of the scan.

T 3.2

T3.4

$, Pr6vot, E. Cre~.enat, M. Toubeau, C. Touzery, C. Blasenbauer, C. BrailleL C. Ducarouge, F. Ferrara, B. Perrette, J. M. Riedinger, S. Roy, F. Brunotte Service de M~decine nucl6aire, Centre G. F. Leclerc, Dijon - France

Carter NJ~, Page CJ 2, Eustance CNP I, O'Doherty MJ l 2 1 Department of Nuclear Medicine, Kent & Canterbury 2

LUNG VENTILATION-PERFUSION DUAL ISOTOPE 99mTe-S~mKr IMAGING : HOW TO GET OPTIMAL QUALITY IMAGES IN THE DETECTION OF PULMONARY EMBOLISM Pulmonary embolism (PE) is a frequent and severe disease requiring a highly predictive diagnosis modality. Ventilation-perfusion scintigraphy enables to get an early diagnosis and adaptation of treatment. Images of high quality obtained in a short time are of prime importance. 99mTc-DTPA aerosols fall short of expectation and artefacts due to central deposition often make images difficult to read. 8hKr (photopeak 190 keV, Ti/2=13 s) is well suited to ventilation imaging in the diagnosis of PE. We have tested the 185 MBq Kryptoscan SIRb/SlmKr generator. Multiple projections are easy to perform either simultaneously or post perfusion without increasing the perfusion tracer activity (1 t 1 MBq). When performing a dual isotope acquisition with a low energy (LE) collimator, the main problem on ventilation images is the important blurring due to septal transparency and to leakage of s~mKr through the facemask especially in non-cooperative patients. The aim of this work was to choose an acquisition protocol optimizing ventilation imaging quality without impairment of perfusion images. Several unsatisfactory tests were attempted with LE and medium energy (ME) collimators before selection of • 99m o S m the following parameters: dual isotope Tc (140 keV-20 Yo)- Kr (190 keV-20 %), matrix 256 X 256, 2 minutes/view, 6 views performed with a ME collimator. The mean counts for perfusion images are 650 kcts and 250 kcts for ventilation. The effective dose to the patient (200 gSv) is tenfold less with 8'mKr than with 99roTe aerosol (2100 gSv). Using a 1.52 liters/minute flow, the calculated activity permanently present in the room is in the range 0.06 to 4.4 MBq without exhaust vessel, depending on patient lung volume. The corresponding maximal effective dose to technologist due to inhalation is 0.4 nSv/study. The mean dose rate measured at one meter from the patieat is 700 nSv/h. These measurements show the low risk of contamination and external exposure for the staff. Superposable ventilationperRision ilnages are obtained in less than 15 minutes under the most favourable dosimetric conditions for patients and technologists.

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Hospitals NHS Trust ~uys' and St Thomas' NHS Trust, London

THE SWIRLERTMNEBULIZER-AN EFFECTIVE SINGLE USE DELIVERY SYSTEM? The re-use of nebulisers for ventilating patients is a sensitive and debatable issue. The Swirler jet nebulizer is designed as single use. We have i n v e s t i g a t e d the particle size of the aerosol produced (Malvern M a s t e r sizer), the time to nebulise patients to a fixed end-point and room air contamination associated with the device. 37 patient studies were performed using two concentrations of 99mTc DTPA [a) 1000MBq/4ml; b) 2000MBq/4ml c) 1000MBq/2ml]. The particle sizes were approximately equivalent with and without a mouthpiece extension (3 devices measured, 3 times) and had an MMD (span) of 1.52~m (1.88). Room air contamination was measured on 20 patient studies with a mean level of 86Bq/l (range: 10.2Bq/l 510.8Bq/l). The mean time to achieve a count rate of 12U0cps (LEGP collfmator) was a) 6.5 min, b) 3.6 m i n and c) 2 min. U s i n g the s h i e l d i n g provided, a mean dose rate of 0.6~Sv/hr, 1.4~Sv/hr and 0.5~Sv/hr respectively was measured at 0.5 m. The nebulizer produced interpretable scans in all patients from both centres. The lead-shielded delivery system required a mouthpiece extension (supplied by manufacturer) to allow the patients to be ventilated comfortably. The nebulizing time is comparable to other devices available with the particle size slightly larger. The compact size of the nebuliser allows ease of storage prior to disposal.

T3.5

T7.1

MICROBIOLOGICAL AND RADIOLOGICAL CONTAMINATION FROM RADIOAEROSOL VENTILATION SCANNING: IS THERE A PROBLEM?

C. Greuter, T. de Vries, A. van Ginkel*, G.J.J. Teule, Department of Nuclear Medicine, Free University Hospital, Amsterdam, *Leidse Hogeschool, Leiden, the Netherlands.

R a d i o a e r o s o l lung i m a g i n g may r e s u l t in: a) M i c r o b i o l o g i c a l contamination of n e b u l i s e r c i r c u i t s (a p o t e n t i a l h a z a r d to p a t i e n t s if the circuit is re-used) and b) radioaerosol contamination of t h e a t m o s p h e r e (a h a z a r d to staff, p a r t i c u l a r l y if i n h a l e d / i n g e s t e d ) . R e c e n t D e p a r t m e n t of H e a l t h g u i d e l i n e s put the onus on the u s e r to d e m o n s t r a t e safety if " s i n g l e use" p r o d u c t s are re-used. M i c r o b i o l o g i c a l a s s e s s m e n t was c a r r i e d out on the c i r c u i t t u b i n g and m o u t h p i e c e s . Out of the i00 p a t i e n t s (40 H I V +ve), six had r e s p i r a t o r y f l o r a i s o l a t e d in the y - p i e c e / m o u t h p i e c e (always c h a n g e d between patients). Insignificant bacteriological g r o w t h was s h o w n in c i r c u i t tubing. Airborne contamination was assessed during r a d i o a e r o s o l i n h a l a t i o n w i t h and w i t h o u t an air extract device (NEDERMAN). An air sampler was p o s i t i o n e d im. f r o m the patient, set at 100L/min. A c t i v i t y c o l l e c t e d on a f i l t e r was m e a s u r e d by an automated gamma counter (COMPUGAMMA). Of 28 v e n t i l a t i o n s t u d i e s , the 17 w i t h air e x t r a c t i o n s h o w e d an a v e r a g e r e d u c t i o n of 364kBq/minute. Conclusion: a) T h e r e is n o s i g n i f i c a n t m i c r o b i o l o g i c a l h a z a r d to patients from multiple use of nebuliser circuits. b) Use of an air e x t r a c t d e v i c e can s i g n i f i c a n t l y r e d u c e a i r b o r n e r a d i o a e r o s o l contamination.

SYSTEMATIC SUPERVISION OF STUDENTS Formerly the training of student technologists in the department of nuclear medicine took place in the hospital. It was a practical training on the job next to a theoretical course. Now the students follow a full time course at the polytechnic over four years covering all theoretical aspects and clinical practice of nuclear medicine, radiology and radiotherapy. During this course a practical training in nuclear medicine of eight weeks takes place in the hospital. The students obtain supervision which is aimed at developing social and professional s k i l l s . The supervision entails regular meetings between student and supervisor at the working place. These meetings cover, after an introduction to the department, a planning of objectives over the practical period, problem solving support and evaluation of the set attainable and measurable objectives. The success of supervision depends upon the qualities of the supervisor/facilitator who must have an open mind and good communitive skills. Nevertheless, the student is responsible for his /her own learning process. The paper presented will explain in more detail the method of student supervision and the necessary requirements at the place of practical training.

T3.6 M. Cremones i *, M. Ferrari *, M. Fiorenza, G. Pri sco, E. Sacco*

L.Leonardi,M.Chinol,M.Bartolomei,G.Paganelli,G.Tosi* Division Medical Physics* ,Nuclear Medicine, European Institute of Oncology,Milan, Italy. RADIATION PROTECTION OF OPERATOR DOSIMETRY DURING LUNG VENTILATORY SCINTIGRAPHY WITH TECHNEGAS Technegas is a suspension of carbon micronized particles labeled with Tc99m. It distributes similarly to a gas (pseudogas), because of the fine size of the aerosol particles.The acquisition of lung ventilatory scintigraphy (LVS) by Technegas carries the risk of environmental and personnel contamination, that may be reduced by appropriate radiation protection systems.We performed different contamination measures in 30 cases of LVS.The time variation of activity concentration in the air was evaluated during the LVS acquisition time, by measuring the collected activity in active carbon filters inserted in a suitable air pump.Air activity concentration resulted not negligible( [A] max=33000_+10000Bq/m3 ) ;the activity in the operator' s lungs was estimated equal to i000 4300 Bq, with the assumption that 30% of the intaken activity is retained. Following the ICRP 68 criteria, the absorbed dose to the operator lungs was evaluated equal to 0. i-+0.03uSv. The monitored surfaces (lab coats, operator's skin and hair, floor, g-camera table) did not show any significant level of contamination, except for the gloves (4_+iBq/cm2 ) . Operator' s urine sample analysis demonstrated a limited internal contamination. Tc99m excreted by urine pathway was equal to 500_+150 Bq([A]max=1500_+ 400Bq/l)within 6h. The retention efficiency of masks of different materials and shapes were compared, in terms of tracer activity trapped.A simple surgical mask showed a satisfactory efficiency (70%4-5%).

=o =o

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