57.3 +_12.7 81.6-+8.51

64.6 ± 13.2 87.7+_6.52

0.025

According to our findings, FEVI/FVC ratio and peripheral clearance were significantly decreased in water-pipe smoking group. Compared to passive smokers, increased central mucociliary clearance in ~atcr-pipe smoking may be due to increased humidity of the airway tracts.

PS_212

PS_214

COMPARISON WITH CLEARANCE OF TC-99M DTPA AEROSOL, AND CO DIFFUSING CAPACITY, AND LUNG FUNCTION TEST IN HOUSE PAINTERS

EVALUATION OF ALVEOLO-CAPILLARY MEMBRANE PERMEABILITY AND PULMONARY PERFUSlON ABNORMALITIES IN PATIENTS WITH TYPE II DIABETES MELLITUS

M. Kaya (1), A. Salan (1), E. Tabako~lu (2), N. Aydo~du (3), M. Y0ksel (1), Y.S. Saiiho~lu (1), O.N. YiOitba} (1), S. Berkarda (1). (1) Department of Nuclear Medicine; (2) Department of Chest Disease; (3) Department of Physiology, Trakya University, Edirne, Turkey.

G. An (1), O. (3zdo~an (2), B. De~jirmenci (2), O. Itil (1), A. ~6mlek~i (3), H. EItidokuz (4). (1) Department of Chest Disease;/2) Department of Nuclear Medicine; (3) Department of Endocrinology; (4) Department of Public Health, Dokuz Eyl01 University, Medical School, Izmir, Turkey

An increased risk of airway problems have been shown in the house painters.The objectives of this study were as follows: (I) to investigate changes in lung permeability in house painters using the rate of inhaled Tc-99m DTPA as a permeability index; and (2) to compare with CO diffusing capacity, and lung function test in house painters. Methods: 10 non-smoking house painters (28,8 ± 8,76 yrs) and 10 healthy voluntary nonsmoking subjects tattled out Te-99m DTPA aerosol scintigraphy. After inhalation of radiotracer through a nebulizer for 5 minutes, dynamic sciatigrams (1 frame/rain, up to 10 rain) were taken from both lung. gOl's were drawn over the both lung area, and time-activity curves were obtained and half-time (TIcz ) of DTPA was measured from the curves, CO diffusing capacity was measured in all house painters. Rasults: The mean TI~" values (min ± SD) were calculated to be 93,74 ± 32,79 for house painters, and 90,96 ± 40.02 for control group, respectively. There was no significantly differenees between house painters and control groups. We found a positive correlation between the mean Tic2 and duration of working (mean; 14,9 ± 8,2 yrs), and also a negative correlation to CO diffusing capacity (mean; 35,25 ± 9,64 ml/min/mmHg) (r---0,78, p=0,007; r=0,82, p=0,006), respectively. We did not found any correlation between the mean TI/2 and the other spirometrie measurement, Conclusion: Our preliminary findings indicate that lung epithelial permeability in house painters is normal when using Tc-99m DTPA aerosol scintigraphy.

Diabetes MeHitus (DM) is a chronic, systemic, metabolic disease that affects pulmonary system secondary to diffuse microvascular disease. The aim of this prospective study was to evaluate the alveolo-capillary membrane permeability changes, pulmonary perfusion abnormalities, pulmonary function tests (PFT). To define the relations of the results with the duration of DM, the presence of microvascular disease and the degree of diabetic control in patients with DM. Methods: 25 patients (5 women, 20 men) with type 1[ DM were included in the study. The mean duration of disease was 9.4±7.5 (0-30) years. | 0 healthy individuals (6 women, 4 men) were included in the control group. The moan ages both groups were 55.6±9.9 (33-68) and 46.8±10.4 (33-65) respectively. Tc-99m DTPA aerosol inhalation scintigraphy, Tc-99m MAA lung perfusion scintigraphy, PIT, ophthalmoscopic eye examination, determination of HbA IC levels, determination of creatinine, protein and microalbumin levels in 24-hour urine sample were obtained. The perfusion seintigraphy was evaluated qualitatively and the aerosol inhalation scintigraphy was evaluated qualitatively and quantitatively by calculating peripheric penctration indexes and alveolo-capillary cluarence time of whole lungs and upper, middle and lower zones. Results: Micmvascular disease was detected in 12 (48%) and diabetic control was poor in 6 (24%) patieqts. There was no statistical difference in clearence time and peripheric penetration indexes between DM patients and control group although the ciearence time of both upper zones is longer in DM patients than in control group and in patients with microvascular disease. The duration of DM and the level of diabetic control (HbAIC) had no affect on ctuarence time, peripheric penetration indexes and pulmonary perfusion abnormalities. Small subsegmenter and nonsegmenter perfusion defects were observed in 6 out of 12 patients (50%) with microvascular disease and 3 out of 13 (23%) patients without microvascular disease. Conclusion: DM affects pulmonary system to a lesser extend than the other systems. Perfusion abnormalities are common in DM patients having microvascalar disease.

1130

• OTHER CLINICAL SCIENCE. LUNG

PS_215

PS_217

REGIONAL PULMONARY VENTILATION FUNCTION IN PATIENTS WITH LUNG CANCER: QUANTITATIVE EVALUATION WITH MAXIMAL INSPIRATION AND EXPIRATION XE-133 EQUILIBRIUM IMAGES

A QUANTITATIVE STUDY OF THE DIFFERENCE IN PULMONARY PERFUSION IN DIFFERENT RESPIRATORY PHASES

H. Hirota (1), Y. Ishikawa (1), J. Sato (1), N. Shuke (1), A. Okizaki (1), T. Aburano (1), A. Yatsuyanagi (2), T. Sasajima (2), N. Yazaki (3), Y. Ohsaki (4), K. Kikuchi (4)(1) Department of Radiology; (2) Department of Surgery 1; (3) Clinical Laboratory; (4) Department of Internal Medicine 1, Asahikawa Medical College, Asahikawa, Japan

Radiology, Kochi Medical School, Nangoku, Japan.

For quantitative evaluation of regional pulmonary ventilation (RPV) function in patients with lung cancer, a simple method is proposed. Methods: Ventilation scan with Xe- 133 was perthrmed on 20 patients with lung cancer before and after Iobectomy. In the equilibrium phase, lung spot images at maximal inspiration and expiration were acquired with an acquisition time of 10 seconds each. Regions of interest (ROIs) were drawn over right and left lungs separately on these spot images. Using the counts in the lung ROIs at maximal inspiration and expiration (Cinsp, Cexp), an index of lung residual volume fraction (XRV) ",,,'ascalculated by dividing Cexp by Cinsp (XRV = Cexp / Cinsp). XRV was calculated for total lung and separately for the unresected and resected sides before and after lobectomy. XRV was compared between before and aRer lobectomy in relation to the changes in vital capacity (VC) and forced expiratory volume in I second (FEV l) for references. Mean transit time I'M'IT) from the washout phase was compared with XRV in relation to the changes in VC and FEV I. Results: Total XRV showed significant correlations with VC (-0.359, p<0.03) and FEVI (r~0.502, p<0.03) before Iobectomy, but MTT did not. VC and FEV 1 at~er Iobectomy showed significant differences from those before Iobectomy (p<0.0001, p<0.002). XRV of the resected side showed significant decrease after Iobectomy (p<0.0008), but XRV of the unresected side showed no significant ditt~rence. On the other hand, MTT showed no significant difli:ronce between before and atier lobectomy on either side. Conclusion: These results suggested that XRV could be better than MTT in reflecting RPV lhnction. This method could be useful for preoperative evaluation of RPV function in patients with lung cancer.

S. Yoshida (1), W. Don (1), M. Fukumoto (2), N. Akagi (2), H. Seguchi (1). (1) Department of Anatomy and Cell Biology; (2) Department of Pulmonary perfusion scintigraphy with Tc-99m MAA can demonstrate the exact distribution of pulmonary perfusion in differentposition of the subject during the tracer injection. It is influenced by many correlated factors. One of them is physiological gravity. This study is aimed at investigating the physiological pulmonary perthsion in different maximum respiratory phases with using quantitative analysis. Methods: 4 nonsmoking healthy volunteers underwent SPECT after the injection of Tc-99m MAA in a dose of 185 MBq in each maximum respiration phase at a week's interval. Tbe tracer was injected while the subject was in a supine position and holding breath for 20 seconds at each maximum inspiration phase and expiration phase. Quantitative analysis by calculating the normalized center of perfusion intensity were performed, that was originally devised for this study. Results: Quantitative measurement, normalized center of perfusion intensity, certified that the average of normalized Y ( ventrodorsal component) values transt~r from 51.4 to 44.8 ( shift : 13% ) in the upper part of the lung, from 54.6 to 48.5 ( shift : 10.5 % ) in the middle part and from 63.5 to 52.6 ( shi~2 : 17 % ) i n the lower part. These indicated that the pulmonary perfusion activity in the maximum expiration phase moved towards ventral direction compared to that in the maximum inspiration phase. The average of normalized Z ( cranioeaudal component )values ranged from 57.0 to 58.6 ( shit~. : - 3 % )in the upper part of the lung, from 47.8 to 49.5 ( shift : - 3.6 % ) in the middle part and from 41.9 to 41.4 ( shift : 1.3 % ) in the lower part. These values indicated that the pulmonary perfusion activity in the maximum expiration phase moved towards caudal direction compared that in the maximum inspiration phase in both the upper and middle parts of the lung, while in the lower part it moved slightly towards cranial direction. ~n X( horizontal component ) direction, pulmonary perfusion activity indicated no agreement in movement direction. The values are all within the range of( 1,100 ). Conclusion: We found change pattern of pulmonary perfusion between maximum expiration phase and inspiration phase, as well as in difl'erant parts of the lung, by quantitatively measuring the normalized center of perfusion intensity.

tO

PS_216

PS218

RELATIONSHIPS BETWEEN HYPOXEMIA AND VENTILATIONPERFUSlON RATIO DISTRIBUTION STUDIED WITH 99MTC,MAA/81MKR DUAL ISOTOPE PLANAR LUNG IMAGING

VENTILATION/PERFUSION SCAN IN PULMONARY EMBOLISM: STILL THE BEST SCREENING TEST?

D. Vilain (1), M. Stern (2), D. Daou (3), P. Puyo (4), S. Friard (2), C. Tainturier (1). (1) Department of Nuclear Medicine, Foch Hospital, Suresnes, France; (2) Department of Pneumology, Foch Hospital, Suresnes, France; (3) Department of Nuclear Medicine, Antoine-BL=clereHospital, Clamart,

France; (4) Department of Thoracic Surgery, Foch Hospital, Suresnes, France .

.

.

.

.

99m

Dual Isotope planar lung scmugraphy (DIPLS) reahzed wah Tc-macroaggmgated albumin C~Tc-MAA) and XLmKrmay be useful for the characterization of the regional distribution of lung ventilation-perfusion ratio (VA/Q). The aim of our study was to evaluate whether quantitative variables derived from the lung VA/Q distribution histogram calculated with DIPLS correlate to the severity of arterial hypoxemia. Methods: The population studied consisted of 42 consecutive patients investigated for sus~.~Tcetedpulmonary embolism (n=32) or lung cancer (n=10) who had arterial blood gases and -MAA / 81mKr DIPLS and 10 asymptomatic patients (control group), with normal 99mTcMAAflt=K.r DIPLS and no known pulmonary disease. Lung regions of interest (ROll were drawn manually on posterior view of the ventilation - perfusion scans and a corresponding VA/Q functional image reflecting a pixel-by-pixel VA/Q ratio was computed. Two VA/Q lung distribution histograms were computed by plotting the percentage of overall perfusiun or ventilation counts against VAJQ on a log scale abscissa and corresponding standard deviations were calculated from both the %parfi~iun-VA/Q (sdP) and %vantilation-VA/Q (sdV) distribution histograms. The standard deviation of VA/Q value below (sdP-, sdV-) and above (sdP+, sdV+) the mean of %perfusion-VA/Q and %vantilation-VA/Q distributions, the % of perfusion with VA/Q<0.5 (P%v/q<0.5) were also computed. Quantitative parameters of VA/Q lung distribution histogram below mean+3sd of control group values were considered normal. Results: 25/42 patients bad at least one abnormal quantitative parameter derived from their VA/Q lung distribution histogram and all parameters showed significant correlation with arterial PO2 (p<0.001). The best correlation (p<0.05) with atterial PO, was encountered with SdP(r--- 0.72) as compared to the other parameters (r---0.59, -0.55, -0.55, -0.50,-0.50, and -0.44 tbr respectively sdP, P%v/q<0,5, sdV-, sdP+, sdV, sdV+). P%v/q<0.5 was significantly higher for the 15/42 patients with abnormal sdP- (9.4+10.8% versus 0.12:L'0.2%, p<0.0001). PO 2 values were significantly lower for these 15/42 patients (61+8 mmHg versus 76:L'9 mmHg, p
t~

S. Carmona (1), J. Sequeira (1), M. Filipe (1), MJ. Carapinha (1), B. Abrantes (1), A, Quintal (1), L. Vieira (1), M.J. Furtado (2), A. Tomaz (3),

A.I. Santos (1). (1) Servk;o de Medicina Nuclear; (2) Servk;o de Radiologia; (3) Servi~o de Medicina, Hospital Garcia de Orta, Almada, Portugal. The aim of this study was to evaluate the clinical impact of lung scans for the diagnosis of pulmonary embolism, on a hospital within a community of 350 000 inhabitants, with a nuclear medicine department equipped with a single headed gamma camera (I 0 hours/day, 5 days/week) and a radiology department with Spiral CT (24 hours/day, 7 days/week). Methods: Between 01-January-1999 and 3 l-December-2000, 230 ventilation/perfusion lung scans (V/QS) were performed in 199 patients: 192/230 (83,5%) for suspicion offirst episode of Pulmonary Embolism (PElt 38/230 (16,5%) for follow up of previous episodes of PE. In 21/230 exams, there was also a Spiral CT (sCT) with a delay < 12 days from the V/QS. On the first group of 192 V/QS, 72 (37,5%) had COPD (11/72) and/or cardiopathy (65/72). The following risk factors were identified: previous surgery - 29 (15,1%); hormonal therapy - 4 (2,0%); cancer - 12 (6,3%); puerperium - 2 (1,0%); and vein thrombosis - 29 (15,1%). The V/QS was performed with inhalation of 99mTc-Technegas and infusion of macroaggregated albumin labelled with Tc-q9m. They were classified as: normal; low probability (LP) - I or less segments (or equivalent) mismatch vantilatiun/perfusion; high probability (HP) - 2 or more segments (or equivalents) mismatches ventilation/perfusiun; and medium probability (MP) - > I and < 2 segments (or equivalent) mismatches. Results: We have found 44/192 (22,9%) V/QS normal; 51/192 (26,6%) HP exams, 11/192 (5,7%) MP exams, 86/192 (44,8%) LP exams. In this last group, 67/86 (77,9%) V/QS showed other pathologies. On the 21 studies which could be correlated with sCT, we have found: 1 with both studies normal; 17 HP V/QS vs I2 positive sCT and 5 negative sCT; t MP V/QS with a non diagnostic sCT; 2 LP V/QS vs I sCT non diagnostic and I negative sCT. Conclusions: The role of lung scans for screening of pulmonary embolism still persists, which makes clinicians ask for it, even in hospitals with low nuclear medicine resources, We have found very few non diagnostic or medium probability studies. Although the number of studies evaluated is small, the accuracy of Spiral CT for the diagnosis of pulmonary embolism doesn't seem higher than the one of lung scans.

1131

e-

e~

(n O n

• OTHER CLINICAL SCIENCE. LUNG

PS_219

PS_221

THE SClNTIGRAPHIC PULMONARY PERFUSlON ABNORMALITIES DO NOT REFLECT THE HEMODYNAMIC SEVERITY OF CHRONIC POST EMBOLIC PULMONARY HYPERTENSION

ALVEOLAR TO BLOOD CLEARANCE OF INHALED TC-99M DTPA IN PRIMARY PULMONARY HYPERTENSION (PPH)

D. Daou (1), C. Coaguila (1), O. Sitbon (2), E Parent (2), B.O. Helal (1), M. Humbert (2), G. Simonneau (2). (1) Department of Nuclear Medicine; (2) Pneumology Department, Antoine Beclere Hospital, AP-HP, Clamart, France. Aims: The value of pulmonary peffusion scintigraphy for the differential diagnosis of chronic post embolic pulmonary hypertension (CPE-PH) is widely admitted. However, whether the extent of pulmonary perfusion abnormalities evaluated with puImonary perfusion scintigraphy reflects the severity of the disease is not well defined, We aimed to evaluate the correlation between the pulmonary vascular occlusion evaluated with pulmonary perfusion scintigraphy and the severity of pulmonary hypertension as reflected with total pulmonary resistance (TPR). Methods: Twenty-eight patients with CPE-PH were studied. Mean age was 55±15 years, and 16/28 were males. Nineteen patients had pulmonary thrombo-endarterectomy. All 28 patients had pulmonary perfusion scintigraphy before PTE and the 19 patients with PTE had perfusion scintigraphy at 3 months after operation. The pulmonary vascular obstruction (PVO) score was calculated as previously repotted: each lobe assigned a weight based on the regional distribution of pulmonary blood flow, and for each lobe a semi-quentitative perfusion score from 0 to I was estimated from the film density (0, 0.25, 0.5, 0.75, I ) by comparison with an apparently normally perfused area. Then, a PVO score was calculated as (1-overall perfusiun score)xl00. Results: Preoperative and post-PTE PVO scores were 68±14 and 55±18 % with an absolute paired difference of 12±17 %. The preoperative and post-PTE TPR were 31±11 and 13±7 ULm2 with an absolute paired difference of 19±11 Ul.m2. No correlation was found between preoperative, postoperative and paired difference of respectively PVO score and TPR. Conclusion: Pulmonary perfusion scimtigraphy may be valuable for the etiologic diagnosis of pulmonary hypertension but it is not correlated to the hemodynamic severity of the CPEPH neither preoperatively nor post-PTE. Moreover, the PVO score variation between preoperative and post-PTE levels is not correlated to the variation in the hemodynamic severity of the CPE-PH.

M. Sofia (1), M.L. De Rimini (2), M. Catalano (2), A. Stanziola (1), V. Ippolito (2), P. Muto (2). (1) Dpt Respiratory Disease, University Federico II, A.O. Monaldi; (2) Department of Nuclear Medicine, A.O. Monaldi,Naples, Italy. PPH is a rare and progressive disease which is characterized by unexplained severe pulmonary hypertension associated to remodelling of pulmonary vascular bed. Impairment of alveolar diffusion to inhaled gases has been reported in PPH but it is unknown if alveolar-capiIIary permeability to inhaled solutes is affected. Aim: Nuclear Medicine contribute in evaluating alveolar-capillary permeability to inhaled solutes compromission in PPH. Methods: we performed ventilation lung scan (Tc-99m DTPA nebulization) in two patients affected with PPH and normal lung function test. Overall and regional T/2 in minutes were calculated as an index of alveolar to blood clerance and they were compared to perfusion images. The effect of the inhaled prostacyclin stable analogue lloprost on 99mTcDTPA T/2 was also assessed. Results: Delayed T/2 DTPA clerance resulted in one case matching decreased perfusion in the same lung. Inhaled lloprost at doses of 25 to tO0 meg was associated to a significant decrease of prolonged T/2 DTPA in the same lung. In the other case where disomogenous perfusion pattern was present, T/2 DTPA clearance resulted within the control values recorded in 5 non smocking subject. Conelnslnn: This report shows that alveolar to blood clearance of inhaled solutes could he delayed in PPH in lung zones with decreased perfusion. This finding could be relevant when the effect of inhaled pulmonary vasodilators and/or follow-up non invasive studies are scheduled for PPHpatients.

PS_220

PS_222

DO PATIENTS RECEIVE NECESSARY SClNTIGRAPHIC FOLLOW-UP AFTER PULMONARY EMBOLISM? CLINICAL EXPERIENCES FROM A GERMAN UNIVERSITY HOSPITAL

DOES THE CLINICAL PROBABILITY OF PULMONARY EMBOL|SM (PE) DETERMINE WHETHER PATIENTS HAVE FURTHER INVESTIGATION FOLLOWING NON-DIAGNOSTIC VENTILATION PERFUSlON (V/Q) LUNG SCAN

M. Gotthardt, M. Schipper, H. Hoeffken, D. Brandt, U. Welcke, K. Joseph, T.M. Behr. Department of Nuclear Medicine, PhilippsUniversity, Marburg, Germany. Aim: Little is known about the rate of persisting perfusion defects after pulmonary embolism (PE). We determined the number of persisting perfusion defects in pulmonary perfusion scintigraphy (PPS) in those patients diagnosed to have pulmonary embolism (PE). We also investigated how many of our patients received scintigraphic follow-up after the diagnosis of PE had been made by PPS. Methods: Between 199l and 1999. a total number of 3640 patients received PPS in our department. We included those patients into our study, that had perfusion defects (or persisting perfusion defects, respectively) in PPS meeting the PIOPED criteria of an .intermediate" or ,,high probability" lung scan. A persisting perfusion defect had to be unchanged over a time period of more than one year. Results: From 3640 patients, 451 (12.4%) had intermediate or high probability perfusion scans. Of those, 119 (26.4%) received a scintigraphic follow-up. 19 of these patients (16%) had persisting perfusion defects. In 62 patients (52.1%), a reperfusion of the defects was found. In 38 patients (31.9%), the defects persisted within a follow-up period of up to 12 weeks but no PPS was performed after a year. Out of the 119 patients receiving a scthtigraphic follow-up, only 26 (21.8%) had a follow-up over more then one year, 19 of those had persisting perfusion defects. Conclusions: Only a limited number of patients diagnosed with PE received a scintigraphic fonow-up, o f those who did, nearly three quarters were found to have persisting perfusiun defects. In many cases, there was no follow-up even if no reperfusion of the defects had been visible in early follow-up perf~sion scans. Our data show an inadequate scintigraphic followup of patients with PE. Patients end referring physicians should be made aware of the necessity of scintigraphic follow-up as persisting perfusion defects mimicking fresh PE may lead to unnecessary treatment possibly causing severe side-effects.

1132

M. D. Stewart (1), R Kemp (2), V. Lewington (2), H. H. Gray (1). (1) Wessex Cardiothoracic Centre; (2) Department of Nuclear Medicine, Southampton General Hospital, Southampton, United Kingdom. Introduction:Accurateassessmentof the importanceof a non-diagnosticventilationpcrfusion scanrequiresprior assessmentof the clinical probabilityof PE. Wepresentevidencethat inadequateclinical assessmentand failurem integrateclinical probability into the interpretation of these scans results in subsequent under investigation of patients Method: Over a six-month period the medical records of 284 in-petients referred for V/Q scanning were reviewed, and the clinical probability of PE, as documented by the admitting medical team was recorded. Where this was not recorded a retrospective assessment of the clinical probability was made using an established scoring system. Referral for further investigation after the V/Q scan was recorded. Results: Of the 284 scans, 151 were felt to be diagnostic (94 normal, 57 high probability) and 63 patients had both a low V/Q and low clinical probability. None of these patients were considered to require further investigation by existing protocols. 25 patients had an intermediate or indeterminate probability V/Q scan, only 12 (46%) of these underwent further investigation to exclude PE. An intermediate or high clinical probability was identified in 14 patients with a low probability V/Q scan, with only 5 (35%) of these undergoing further investigation. In the remaining 31 patients, with low V/Q probability, the clinical probability was not documented by the referring medical team and could not be determined due to inadequate clinical information. 4 of these 31 (13%) underwent further investigation. 70% of patients with a non- diagnostic V/Q scan, and high, intermediate or undetermined clinical probability, had no further investigation to exclude PE. Conclusion: Our results show that. following an inconclusive WQ scan, relatively few patients were referred for further investigation. Ctinical probability is poorly utilised in the determining the requirement for further investigation end highlights the potential for underdiagnosis of PE. These findings may indicate that referring clinicians mis-understand the reporting of this investigation.

• OTHER CLINICAL SCIENCE. LUNG / NEUROLOGY / PSYCHIATRY 2 PS_223

PS_225

ONE MORE REASON FOR LUNG VENTILATION STUDIES

EFFECTS OF ACUTE TREATMENT WITH COCAINE AND GBR 12909 ON THE IN VIVO BINDING OF D1 AGONIST R-[C-11]SKF 82957 IN RAT BRAIN

I. Bofilias. Clinic of Nuclear Medicine, Technical University, Munich, Germany. A renaissance in Lung Ventilation Studies (LV) is unavoidable; if a subtle identification of the regional extent of the various syndromes in their pure and mixed forms of obstructive, restrictive and hyperinflate is possible in assessment of follow up examinations. The realization of the ,Three Phases Bolus Inhalation Scintigraphy" (3P-BIS, single breath (SB), equilibrium (AE) and wash out (WO)), with a y -Camera and 33Xe is sensitive enough to distinguish clearly pure and mixed components in beth groups of patients suffering of emphysema and sarcoidusis 11 and lff degree. Method. The patient was sitting in front of the "/-Camera rebreathing into a spirometer. The t33x¢ was inhaled as bolus at the maximal expiration level, so that the SB-Phase corresponds to the Vital Capacity (VC). The AE-Phase was found to be proportional to the Actual Lung Volume (ALV) and the Intrapulmonary Transit Time Constant (ITTC) quantified the WOPhase. These parameters were always evaluated for 6 lung regions. Physiological values of ITTC has been found to lie in 20 healthy patients between 0.18 and 0.22, whereas values greater than 0.24 describe the degree of the obstructive component. The total acquisition time was 320 s by 80 frames and 4 s per frame. Pure restrictive and hyperinflated lung regions was defined by %VC < 80% and %VC > 120% respectively by normal values of I'IT'C, whereas mixed types was accompanied by delayed WO-Phase with ITTC > 0.24. Results. In 30 patients suffering from COLD hyperinflation was observed in 23% of all the lung regions with mean values of %VC greater than 130%±15% relative to the normal region and in 42% of all regions the %VC has been found lower than 70%± 10% by ITTC > 0.24 and by relative homogeneous ALV in the AE-Phase. Normal values of VC, AE and ITTC were found in the rest oftbe regions. [n t7 patients with sarcoidosis II and I11 the most characteristic t~:atures were the multifucal regions in which elevated values of more than 120% of VC accompanied by retention with ITTC > 0.40 by inhomogeneous ALV. In 61% of all the other regions show low mean values of %VC (63%±15%) by increased ITTC and inhomogeneous ALV. In I I patients following anti-obstructive medication a slightly normalization in LV was observable of a reduction of the hyperinftated component (%VC< 110%) and retention (1"[q'C=0.26+-10%) in obstructive areas. Conclusions. The 3P-BIS differentiate quite sensitively among the various pure and mixed components in COLD associated with parenchyma destruction or airspace enlargement and safe assess the course of therapyt~ renaissance in LV.

J.N. DaSilva, V. Sanci, S. Houte. Centre for Addiction and Mental Health PET Centre, University of Toronto, Toronto, Canada. Dysregulation of the dopamine (DA) system with changes in endogenous DA concentration has been implicated in a number of neuropsychiatric disorders. Previous PET studies revealed no difference in striatal binding of D I antagonist radioligands compared to controls, following treatment with amphetamine. In theory, D I receptor (DIR) high-affinity state (Di HIt;H) is functionally coupled to the Gs protein, and only an aganist tracer is capable of selectiveIy assessing in vivo DI HI(lit using BET. Maximal internalization of cell surface DIR into intracellular endocytic vesicles occurs in vivo in rats within - 2 0 min after agonist treatment and intracellular DIR are still detectable after 5 h (Dumartin et al., J Neurosci 18:1650, 1998). This study was carried out to delermine the effects of increased endogenous DA o n D I agonist R[=IC]SKF 82957 binding following cocaine or GBR 12909 treatments, before, during or after maximal internalization of DiR. Both cocaine and GBR 12909 are DA transporter blockers, and increase extracellular DA levels. Methods: Rats were injected with R-[HC]SKF 82957 at time (T) =0. Cocaine (30 mg/kg, i.p., 20 rain prior, n=7 -17 per group) or GBR 12909 (7 mg/kg, i.v., 30 rain prior, n=6-9 per group) were administered at T=-24h, -6h, -20rain. 0, or +20min. Animals were killed 45 rain after radioligand injection and various brain regions were dissected. Results: The region-to-cerebellum binding ratios of R-[ IIC]SKF 82957 showed no significant difference compared to controls (received vehicle, combined group n=51 ), except cocaine protreatment (T=-24h) which caused a significant increase in the striatum (n=l 7 rats). Conclusions: Except for striatal increase following cocaine treatment at T=-24h, these results indicate that R-[ IIC]SKF 82957 is not sensitive to competition from acute increases in synaptic DA levels for binding to DIR, which are either partly internalized (T=-20min, and possibly -6h, -24h) or on the cell surface (T=0). R-[IIC]SKF 82957 agonist binding, which should produce receptor internalization, was also not affected by increased endogenous DA IT=+20 rain). These results are similar to those reported using the DA releasing agent amphetamine (Soc. Nucl. Med. Annual Meeting 2001). (Supported by the M RC/CIHR of Canada #13258)

iO k~

NEUROLOGY / PSYCHIATRY 2

PS226

PS_224

GBR12909 DOPAMINE TRANSPORTER OCCUPANCY: ARE 11C-COCAINE AND 11C-WIN35,428 PET MEASUREMENTS COMPARABLE?

O~

A.M. Catafau (1), C.J. Endres (1), O. Gay (1), A.S. Dogan (1), J. Hilton (1), S. Cherstniakova (2), R.B. Rothman (2), K.C. Rice (3), L Shin (3), L.R. Cantilena (3), D.F. Wong (1). (1) Johns Hopkins Medical Institutions, Baltimore, MD, USA; (2) Uniformed Services University of the Health Sciences, Bethesda, MD, USA; (3) IRP, National Institute On Drug Abuse, Nih, Baltimore, MD, USA.

O1 C IX

A FULLY VALIDATED SIMPLE METHOD FOR IN VIVO QUANTIFICATION OF STRIATAL DOPAMINERGIC D2 RECEPTOR DENSITY IN BABOON, USING PET

M. Bottlaender, C. Loc'h, F. Dolle, H. Valette, C. Fuseau, C. Coulon, M. Ottaviani, J. Delforge. Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay, France The follow up of the dopaminergic D2 receptor density in the striatum is of great interest in progressive neurodegenerative disorders such as Parkiuson and Huntington diseases. The interaction between FLB-457, a D2 specific antagonist, and receptor sites has been previously studied using a multi-injectioo approach (Delforge et al, 1999). Due to the very high affinity of FLB457, all model parameters (including receptor concentrations) have been estimated in vivo using PET in baboon. However, this method, using data from a multi-injection protocol, is complex and difficult to perform routinely. Thus, we propose a method that allow the quantification of the D2 receptor concentration in the striata using a simple experimental protocol suitable for repeated measurements, Methods: Simulations, performed using the parameters from the multi-compartmental modelisation, demonstrate that the D2 receptor density can be obtained directly by measuring the PET cancentration al~er injection of a single saturating dose of FLB-457 (>40 nmol). This simplified protocol was tested using FLB-457 labeled in two different positions, with bromida-76 or with carbon-11. D2 receptor concentrations obtained using this method were compared with the receptor concentrations determined by the reference method. Four experiments were performed in baboons with each tracer with injected mass ranging from 58 to 88 nmol (67 ± 13 and 79 ± 10 nmol for bromide-76 and carbon-I 1 labeled FLB-457, respectively). Results: PET concentrations of F E B 4 5 7 measured in caudate nucleus and putamen during 20 minutes (4 frames of 5 min each) showed a good stability with beth tracers (2% variability in both structures). Values in caudate and putamen are 37.0 ± 1.2 and 41.6 ± 1.1 pmol/ml with 76BrFLB and 45.4 ± 2.2 and 54.9 ± 2.0 pmot/ml with 11C-FLB. These values do not differ significantly from the values of the D2 receptor density obtained with the multi-injection method (44.0 ± t2.8 et 44.7 ± 12.6 pmol/ml in caudate and putamen, respectively). Moreover, the measurement obtained with the simplified method is robust since the concentrations are independent of the injected dose and of the time of measurement. Conclusion: The extreme simplicity of this method, could allow to perform the folFow up of the striatal D2 receptor density in animal model of neurodegeneratives diseases by monitoring the disease progression and the effects of neuroprotective treatments

GBRI2909 (GBR) is a dopamine transporter (DAT) binding drug that can potentially be used for treatment of cocaine addiction. PET imaging can be used to assess drug-induced DAT occupancy. However, the choice of the PET ligand may be critical, since kinetics of the ligand might influence PET measurements. Aim: To compare PET measurements ofGBR DAT occupancy at steady state using a rapidly reversible binding DAT ligand such as tiC-Cocaine (COC), and a slowly reversible binding DAT ligand such as 11C-WIN35,428 (WIN). Methods: Two baboons were treated with GBR (2mg/kg/day i.rn.). Each baboon underwent both COC and WIN PET scans at baseline (before treatment) and after 16 days of GBR treatment. GBR p;asma levels (GBRpI) were measured from day 10 to day t6 of treatmem and during the GBR PET scans. Binding potential (BP) measurement was obtained from a two-tissue compartmantal modeling with a blood input function atter metabolite correction for both ligands. DAT occupancy was calculated as %BP change from baseline to GBR PET scans. Results: GBRpl were stable in both baboons prior to the PET scans (baboon#h 33.4±9.9 ng/ml, baboon#2:35.7±3.1 ng/ml). Baboon#1 presented stable GBRpl during the two PET scans (33.2±2.3 vs. 31.1±1.1 ng/ml) and similar %DAT occupancy measured with both COC (22.7 %) and WIN (28.5 %). In baboon#2, GBR.pl increased during the PET scans, and was highest during the WIN scan (59.0~6.8 vs. 78.0~5.7). Consistent with this change in GBRpl, a higher DAT occupancy was measured with WIN (41.4 %) than with COC (25.9 %) in baboon#2. Conclusion: PET measurement of DAT occupancy using the slowly reversible ligand WIN is comparable to that of the more rapidly reversible compound COC under equilibrium of chronic GBR dosing. Therefore, when steady state of the inhibitor drug is achieved, results obtained with these two PET ligands may be comparable.(Grant DA09482)

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• NEUROLOGY / PSYCHIATRY 2 PS_227

PS_229

DOES MRI-PET COREGISTRATION INFLUENCE MEASUREMENT OF AMPHETAMINE INDUCED STRIATAL DOPAMINE RELEASE?

REPRODUCIBILITY OF SEMIQUANTITATIVE 1-123-1BZM SPECT INVESTIGATIONS

A.S. DoOan, A.M. Catafau, Y. Zhou, A.H. Crabb, D.E Wong. Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

E. Ambrus (1), G. Szekeres (2), T. Sera (1), Z. Janka (2), P. Laszlo (1). (1) Department of Nuclear Medicine; (2) Department of Psychiatry, University of Szeged, Szeged, Hungary.

D-amphetamine (AMP) is known to decrease the binding potential (BP) of D2 receptor antagonist I IC-raclopride by increasing endogenous dopamine levels in the synaptic cleft, which can be measured by PET indirectly. However, MRI-PET co.registration (CRG) has not been consistently used tot measuring AMP induced dopamine release. Objective: To investigate if CRG would influence measurement of AMP induced dopamine release in striatum. Methods: Five healthy adult volunteers (33±11 yrs.) underwent two high specific activity 1IC-raclopride PET studies before and after iv. administration of AMP (0.3 mg/kg). Anatomic ROIs on caudate, putamen and cerebellum were drawn blindly both on PET directly (without CRG) and on MRI images after CRG with PET. Two tissue compartmental modeling with equilibrium volume (Ve) constraint (Ve=Ki/k_," estimated from reference tissue cerebellum) was applied to obtain BPs for caudate and putamea. Percentages of BP change between baseline and AMP PET scans were used to assess AMP induced dopamine release. Results: As seen on Table. no significant differences were found in the decrease of BP when the studies were analyzed with and without CRG (Wilcoxon U-test). Conclusion: I IC-raclopride PET measurement of amphetamine induced dopamine release in striatum is not influenced by the use of CRG. This study may validate previous data on AMP challenge PET studies pertbrmed without using CRG. These results need to be confirmed with a larger sample size.

Several methods are known for the semiquantitative evaluation of [I-~3-IBZM-SPECT. The most frequently applied procedure is based on the calculation of the striatum/cortex activity ratio. The aim of the present study was to examine the reproducibility of a semiquantitative evaluation method. Method: Twenty-three II-']-IBZM-SPECT examinations were performed in 13 chronic schizoprenic patients (lO patients underwent control examinations). Two independent observers drew an ellipse to the striatum, and then mirrored it to the frontal and occipital cortex. From these data, activity ratios were calculated for both hemispheres. Results: One observer's data, on the right (R) side were as follows: striatum (S)/frontal cortex IF) activity ratio: 1.62_+.0.1,S/occipital cortex (O) activity ratio: 1.66+0.15. On the left ILl side, S/F was 1.64_+0,11, and S/O was 1.71_+0.15. The other observer's activity ratios were: R S/F: 1.63-+0.12, R S/O: 1.65-+0.13, L S/F: 1.64+0.1, and L S/O: 1.73-+0.1. There were no significant differences between the two observers data (R S/F: p=0.57, R S/O: p=0.65 L S/F p=0.85, L S/O p=0.71). The correlation coefficients were as follows: R S/F: r=0.87, JS/O: r-0.77, B S/F: re0.61 and BS/O: r=-0.82. Conclusion: The reproducibility of our semiquantitstire evaluation of 11:31BZM-SPECT is good. This method can readily be applied for determination of the D2 receptor density

Table: Percent BP change with AMP

caudate putamen

CRG -22.1±27.3% -29.9±22.2%

no CRG -20.7±26.8% -28.6±21.9%

NS NS

NS: not significant

PS_228

PS_230

HOW RELEVANT IS THE RECONSTRUCTION-FILTER FOR THE SENSITIVITY AND SPECIFICITY OF 1-123-1BZM-SPECT?

IS THE RELIABILITY OF 1-123-FP-CIT-SPECT DEPENDENT ON

H. Hoeffken (1), A. Gerstner (2), W.H. Oertel (2), T.M. Behr (1). (t) Dept. clinical nuclear medicine; (2) Dept. Neurology, Hospital of the Philippsuniversity Marburg, Marburg, Germany.

H. Hoeffken (1), A. Gerstner (2), W.H. Oertel (2), T.M. Behr (1). (1) Dept. clinical nuclear medicine; (2) Dept. Neurology, Hospital of the Philippsuniversity Marburg, Marburg, Germany.

1-123-1BZM-SPECT has been reported to be able to distinguish between Parkinsom
Due to its high binding potentialto dopeminetransportproteins,1-123-FP-CIT-SPECTwas reported to provide a powerful tool in the diagnosis of Parkinson<~s syndrome even by visual assessment without using semiquantitative evaluation techniques. But there are only poor data on the influence oftbe filter used for reconstruction. In order to study the influence of the filter, we studied 51 Patients and 10 normal subjects with 1-123-FP-CIT using two different filters for the reconstruction of the transverse data sets.

1134

RECONSTRUCTION TECHNIQUE?

Methods: Theageof the lO normalsubjectsand 51 patients,19 femalesand42 maiea,ranged between 25 and 80 years. According to the clinical diagnosis, 46 patients suffered from Parkinson~
• N E U R O L O G Y / PSYCHIATRY 2

PS_231

PS_233

NON-INVASIVE METHODS FOR ABSOLUTE CEREBRAL BLOOD FLOW MEASUREMENT USING 99M-TC-ECD : A CORRELATION STUDY

EFFECT OF GENDER ON CEREBRAL 18FDG AND 11C-METHIONINE UPTAKE: A DIRECT COMPARATIVE PET STUDY

K.J. Van Laere (1), M. Koole (2), F. Dumont (3), J. Versijpt (1), G. Slopers (3), R. Dierckx (1). (1) Department of Nuclear Medicine; (2) Medical Image Processing; (3) Radiopharmacy Department, Ghent University, Ghent, Belgium. Aim: Radionuclide angiography with ~Tc-ethyl cysteine dimer (ECD) allows non-invasive estimation of absolute cerebral blood flow (CBF), either by graphical Patlak-Gjedde analysis (PGA) or by spectral analysis (SA). Other methods have estimated CBF by means of single arterial or venous sampling. The aim of this study was to evaluate radionuclide scanning and single-point venous sampling as potential clinical methods for CBF determination in a large set screened healthy volunteers over the adult age range. Methods: 83 healthy volunteers (20-81 years, 43 M, 40 F) underwent planar radionuclide angiography with 925 MBq 9~Tc-ECD. After correction fur camera deadtime loss, hemisphethc CBF was calculated from brain perfusion indices (BPI) : BPI~; for the PGA, and BP/s from SA. Of the volunteers, 49 also underwent venous sampling 6 minutes postinjection from which the lipophilic octanol extraction fraction and hemispheric brain fractionation index (BFI) was determined. All datasets were correlated and evaluated as a function of age and gender, lntrasubject variability for the BPI measurements was assessed in 11 volunteers by repeat study within 2 weeks of the first acquisition. Results: Graphical and spectral analysis BPI were strongly correlated (R = 0.849, p < 0.00001). The BFI was weakly correlated to both BPI indices (BPI c' : R = 0.34, p = 002; and BPI s : R = 0.3 I, p - 0.04). The right hemisphere showed significant asymmetry for BPIs (AI = 2.7 ± 4.3 %, p<0.001). All three indices were inversely related to age, with an increased gradient after the age of 55 . . . . . (~ s • . years, whde there was no slgmhcan gender difference. The ratio of BPI /BIP , which is a measure of the cerebral extraction fraction for ~ T c - E C D , was not dependent of age. Intersubject variability was 15.5 % in both radionuclide scanning based methods and 18.2 % for venous sampling, all independent of age. A much lower intrasubject variability was observed for BPI s (7.2 %) versus BPI t' (12.6 %). Conclusion: This study provides reference values for normal perfusion indices assessed by graphical and spectral analysis. The results also inter that spectral analysis allows the most reproducible estimate related to hemispheric perfusion by an operator-indepandent and objective approach. Whereas accurate calibration of normal /3PIx vaTues tu CBF with established methods needs to be per/brined, this method may allow non-invasive absolute quantification of cerebral blood flow by means of ~ T c - E C D with direct applicability in clinical routine settings.

M. Lacic (1), G.J.R. Cook (2), I?K. Marsden (2), I. Fogelman (2), M.N. Maisey (2). (1) Department of Oncology and Nuclear Medicine, University Hospital ; (2) The Clinical PET Centre Guy's and St. Thomas' Hospital Trust, London, UK. Aim: The aim of this stud~8was to evaluate t h ~ f f e c t of gende . . . . . ~ional and global ~ r e bral uptake of 2-deoxy-2- fluoro-D-glucose ( FDG) and L-methyl- C- methionine ( CMET) in a direct comparative positron emission tomography study (PET). Methods: Thirty-five patients (20 male, 15 female) aged between 3 a~i 61 years (m~_ 32} with suspected brain tumour were studied. All patients underwent a C MET and FDG PET scan ~ d at least on~8anatumical brain scan (CT or MRI). Regional and global cerebral uptakeof C-METand FDG were measured semi-quantitatively. 18 Results: There was no significant difference between the uptake of FDG in female and male patio,s population in any of evaluated cerebral regions (p>O.05). When the cerebral uptake of "-FDG were compared ber~,.ean female and male patients in the group of patients older than 18 years, statistically significant difference in all evaluated regions i1~_ been achieved (p<0.05). The group of female patients had significantly higher uptake of FDG in comparison to the group of male patients in all evaluated regions. The difference in global cerebral uptake of FDG between fer~le and male patients was statistically significant (p<0.05). The global cerebral uptake of FDG was ~nifieantly higher in the female group of patients in comparison to male one. The regional C-MET cerebral uptake did not differ significantly between female and male patients (p>O.05). In the g r o ~ of aduh patients (older than 18 years) female patients had significantly higher uptake of C - M ~ in all evaluated brain regions (p<0.001). The dift'erence in global cerebral uptake of C-MET between {~male and male patients was statistically significant (p<0.05). The global cerebral uptake of C-MET was significantly higher in the female group of patients in comparison to male one. Co~:lusion: We et~cluded that gender-related changes in regional and global cerebral uptake of - ' C - M E T and --FDG could be observed inthe patients nopulation older than 18 years lg: I'[ Higher regional and global cerebral uptake of FDG and C-MET could be measured in adult female patients.

O

PS_232

PS_234

THE EFFECT OF ACETAZOLAMIDE ON BRAIN PERFUSION IN RIGHT-HANDED SUBJECTS: ANALYSIS WITH SPM

AGE-DEPENDENCE OF SEROTONIN TRANSPORTER DENSITY MEASURED BY IODINE-123-!3-CIT-SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY (SPECT)

S.H. Kim (1), Y.A. Chung (1), I.R. Yoo (1), E.N. Kim (1), H.S. Sohn (1), Y.H. Park (1), S.K. Chung (1), Y.W. Bahk (2). (1) The Catholic University of Korea; (2) Sung Ae Hospital, Seoul, Korea. Objectives: The purpose of this study was to investigate the effect of acetazolamid¢ on ~mTcHMPAO uptake pattern in brain perfusion SPET of right-handed normal volunteer by means of statistical parametric mapping (SPM) analysis. Materials and Methods: The study populations were 9 right-handed matched healthy volunteers (male: 3, female: 6, age range: 24-52 years). We performed baseline brain perfusion SPET using 20 mCi of Tc-99m HMPAO. Two clays later, acetazolamide brain perfusion SPET was obtained. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the baseline and acetazolamide SPET images were statistically analyzed using SPM-99 software. The difference between two sets of brain perfusion SPET was considered significant at a threshold of uncorrected P values less than 0.001. Results: The perfusion was definitely increased in left frontal and basal ganglia areas on subtracted images in 7 out of 9 subjects. SPM analysis revealed sigaaificamly higher uptake in left inferior frontal cortex in acetazolamide SPET compared with baseline SPET. Conclusion: The results suggest that brain perfusion is increased in the left cerebral hemisphere, especially frontal region of right-handed persons on ecetazolamide SPET. This study would helpful in understanding of neurophysiology.

S. Hesse (1), H. Barthel (1), T. Mural (2), U. Mfiller (3), D. Sorger (1), R. Kluge (1). (1) Department of Nuclear Medicine, Leipzig University, Leipzig, Germany; (2) Department of Neuropsychiatry, Faculty of Medicine, Kyoto University, Kyoto, Japan; (3) Psychiatry, University Hospital, Leipzig University, Leipzig, Germany. Objectives: Tile central neurotransmirterscrotonin plays a major role in a number of neuropsychiatric disorders. To understand mental disorders in different life*conditions the dependence of age on the central serotonin transporter (SERT) density has to be evaluated. Aim of this study was to investigate age-related changes of SERT density. Methods: SERT density was analyzed in control patients without evidence of neuropsychiauic disorders as well as in healthy control subjects (n=22, 14 female, 8 male, age range 1883 years) using [~231]-213-carbomethoxy-313-(iodopbenyl)tropane ([t•31][3-ClT) and a brain dedicated single photon emission computer tumography (SPECT) system (Ceraspect. DSI, Waltham, USA). The radiotracer uptake in SERT-rich brain areas was quantified using a semiautomatic quantification system (Hermes software, Nuclear Diagnostics, London, Canada). Results: SERT density and age showed a significant inverse correlation (y = 0.03518x+4.786, r = - 0.688, p = 0.01, hypothalamic region). Mean difference of values of one experienced investigator (intra-rater variability) was 0.3% with a standard deviation of 21.5%. SERT density declined 55% within the age range ofoor patients (11,5% per decade). Conclusion: The data indicate a relevant age-dependence of SERT density, which must be considered in future clinica| studies.

1135

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NEUROLOGY / PSYCHIATRY 2 / TECHNOLOGY PROGRAM 1

PS_235

PS_237

DIFFERENT UPTAKE OF 99MTC-ECD AND 99MTC-HMPAO IN THE NORMAL BRAINS: ANALYSIS BY STATISTICAL PARAMETRIC MAPPING

DETECTION OF LOCAL INFLAMMATION FOCl WITH

H.S. Sohn, E.N. Kim, S.H. Kim, Y.A. Jung, I.R. Yoo, S.K. Chung. Departments of Nuclear Medicine, College of Medicine, St. MaryAes Hospital, The Catholic University of Korea. Aim: This study investigated the differences between technetium-99m ethyl cysteinate dimer (99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) uptake in the normal brains by means of statistical parametric mapping (SPM) analysis. Methods: We analyzed retrospectively age- and sex matched 53 cases of normal brain SPECT, Thirty-two cases were acquired with 99mTc-ECD and 21 cases with 99mTc-HMPAO. No one had abnormal finding on brain MRI. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the 99mTc-ECD and 99mTc-HMPAO SPECT images were statistically analyzed using statistical parametric mapping (SPM) 99 software. The difference between two groups was considered significant at a threshold of corrected P values less than 0.05. Results: SPM analysis revealed significantly different uptake of 99mTc-ECD and 99mTcHMPAO in the normal brains. On the 99mTc-ECD SPECT images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the basal ganglia and thalamus and in the superior region of the cerebellum. On the 99mTc-HMPAO SPECT images, relatively higher uptake was observed in subcortical area of frontal region and medial temporal lobes. Conclusion: Uptake of 99mTc-ECD and 99mTc-HMPAO in the same normal-looking brains was significantly different on SPM analysis. The selective use of 99mTc-ECD or 99mTcHMPAO in brain SPET imaging appears especially valuable for the interpretation of cerebral perfusion. Further investigation is necessary to determine which is more accurate for diagnosing dif~rent clinical conditions.

199TL-CHLORIDE SClNTIGRAPHY V. Zavadovskaya (1), O. Kilina (1), V. Skuridin (1), V. Tchernov (2), Y.U. Lishmanov (2), K. Zavadovskiy (1). (1) Siberian State Medical University, Tomsk, Russia; (2) Institute of Cardiology, Tomsk, Russia. Adequate delineation of variety of inflammatory conditions, including abdominal or lung abscess and bone infections, is an important, clinically relevant issue. One of the newer agents suggested for scintigraphic evaluation is 199Tl-chloride. Aim. The aim of the study was to evaluate usefulness of 199Tl-chloride in detection of inflammation foci of various location. Material and methods. 24 patients (10 males, 14 females, aged 39-+7 years) with suspected inflammatory disease of skeleton (n--9), abdomen (n =13) and lung (n=2) were included. The IqqTI-ch[oddc imaging ',,.as performed 20 and 60 min after injection of 150 MBq. Diagnosis was verified by x-ray, morphological tests and clinical follow-up. Results. Results of scintigraphy were reported as positive if local uptake of 199Tl-chloride was observed, lqqTI-scan showed 20 true-positive (TP), 2 true.negative (TN) and 2 falsenegative fiN) results. TP results were observed in 2 pts with infected diabetic foot, in 2 pts with frostbite, in 3 pts with osteomyelitis and in 13 females with salpingitis. The absense of FP scans resulted in a specificity of 100%. Sensitivity and accuraricy were 90,2% and 91,6% respectively. The highest degree of 199Tl-chloridc uptake was seen in 20 min afer injection and moderately decreased on 60 min alter scan. TN results were revealed in 2 pts with hip prosthesis locking. Two Iung inflammation cases showed FN patterns. Conclusion. 199TI-scan is a safe and reliable method and can be suggested as an ahernative to labelled leucocytes techniques to reveal both bone and abdominal inflammatory foci and to assess results of treatmem.

TECHNOLOGY PROGRAM 1

PS_238

PS_236

A STUDY OF MULTIFOCAL FLAT PHANTOM FOR BETTER UNDERSTANDING OF SENTINEL NODES DETECTION IN SCINTIGRAPHY

ACCURACY OF CPU VERSUS VECTOR PROCESSOR BASED RECONSTRUCTIONS OF 2D AND 3D PET SCANS WITH THE ECAT HR+ PET SCANNER S.C.M. Balen, R. Boellaard, A.A. Lammertsma. Clinical PET Center, Free University Medical Center, Amsterdam, The Netherlands. Purpose: To determine the quantitative accuracy of CPU based reconstructions using FBP and iterative reconstruction (OSEM) of 2D and 3D scans as compared with reconstructions using dedicated 'vector processor' hardware (VP). Methods: 30 rain 2D and 3D 30rain emission scans were acquired with an ECAT HR+ PET scanner for thren phantoms, each filled with 74MBq F-I 8 : (I) a 5cm diameter phantom; (2) a 20cm diameter phantom and: (3) a NEMA phantom with cold air, water en Teflon inserts. Transmission scans of 30rain were performed after a 12 hr interval. FBP (Harming 0.5) and OSEM (2 iterations with 16 subsets) recoostructions included measured attenuation correction, decay and scatter correction. Reconstructions were performed both on the VP and CPU. Regions of interest (ROI) analysis was performed to determine the average pixel value or activity concentration (Ct) within each compartment of the phantoms. The average Ct derived from CPU reconstructed images were compared with those obtained from VP reconstructions. In addition, for the NEMA phantom the effects of CPU and VP reconstruction on the ratio between the average pixel value within each insert and the beckg~oond region was studied. Analysis was performed for both 2D and 3D data. Results: For 2D scans agreement within 2% between VP and CPU reconstructed Ct was found for all phantoms. OSEM reconstructions yielded higher average pixel values within the NEMA inserts than FBP reconstructions. These results were consistent for VP and CPU data. 3D CPU reconstructed images yielded 6°/'0 and 13% higher Ct for the 5 and 20cm diameter phantoms, respectively, compared with VP data. VP reconstructed data were within 2% of the Ct derived from samples counted using a calibrated well counter. The ratio of the Ct within the Teflon (bone) insert and background region of the NEMA phantom was 0.20 and 0.09 for the CPU and VP reconstructions respectively, For the air insert these ratio's equalled -0.03 and 0,07. Conclusion: For 2D acquisitions CPU and VP reconstructions have comparable accuracy for both FBP and OSEM, The higher pixel values withth the NEMA inserts observed for OSEM are explained by the non-negativity constraint applied with OSEM. Differences in pixet vaIua within the NEMA insert between 3D CPU and VP reconstructions are probably caused by the different 3D scatter correction models implemented for both reconstructions.

1136

H. Sayman, M. Demir, S. Ahmed, C. Nisli, E. Dirlik, I. Uslu. Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. Background. Lymphoscintigraphy being an emerging branch of nuclear oncology, highactivityat the injection-site is still of a great concern nowadays, Sometimes, it's also confusing to differentiate two nearby sentinel nodes because of star/ flashing effects due to high nodal activity. Aim. The object of this study is to choose most proper collimator and its dependence to different depths for any particular medium. Method. We performed our study with a multifooal flat phantom made out of plexiglass with point holes in it. The center point contained 100 IzCi Tc-99m and other 10 points contained l~tCi each. All the points were arranged in a helical way at distances of lcm, 2cm, 3cm.....,A0 cm within a background medium containing 10gCi/5 It. We used three types of collimators: Low energy high resolution (LEHR), low energy all purpose (LEAP) and medium energy all purpose (MEAP). Entirn study was performed by Siemens Digitrac 75 Planar Camera. We placed the phantom at three distances from the collimator: i) Surface position ii) 5 cm depth of water iii) 10 cm depth of water. In static mode, we acquired 170,000 counts in 256x256x 16 m a r x . Results and discussions+ We normalized all the readings with respect to the background for three collimators at different depths individually and determined the ratio of point counts and background. The value shows maximum variation at LEAP and minimum at LEHR collimator. The variation is reasonable for MEAP collimator. The images with MEAP at surface position and at 5 cm depth are free of flashing and star effects. All other images show more or less both of the effects with highest intensity at images acquired using low energy high resolution (LEHR) collimator. Furthermore, These images (LEHR), at different depths show a lack of spatial resolution which is very significant to be considered in practice. Conclusion. Medium energy all purpose (MEAP) collimator seems to provide better delination of injection sites that most concerned with sentinel nodes detection.

• TECHNOLOGY

PROGRAM 1

PS_239

PS_241

MEASUREMENT OF DOPAMINE TRANSPORTER (DAT) DENSITY IN

GENDER VARIATIONS IN GASTRIC EMPTYING RATE: ARE SEPARATE NORMAL RANGES NECESSARY?

HUMAN STRIATUM BY PET WITH 11C ALTROPANE S.A. Barrow, A.A. Bonab, E. Livni, B.K. Madras, P. Meltzer, A.J. Fischman. Department of Nuclear Medicine, Massachusetts General Hospital, Boston MA.

N. Storry, I. Jones. Southern Derbyshire Acute Hospitals NHS Trust, Nuclear Medicine Service, London Road, Derby, UK.

Aim: 12~llabeled Altropane (E 1231-21]-carbometboxy-3{3- (4-fluorophenyl)- N-(I-iodoprop- Ien-3-yl)nortropane is a new radiopharmaceutical with high affinity and selectivity for dopamine transporter (DAT) sites in the striatum. Recently, dynamic SPECT studies demonstrated the utility of this reagent for DAT imaging in healthy volunteers and patients with early Parkinson's disease (Synapse 1998;29:128-141). Since maximal striatal accumulation of 1 labeled Altropane occurs within 30 m n. at~er rejection, we hypotheslzad tha C labeled Altropane would be useful for PET imaging of the DAT. 23

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Methods: The precursor for preparing C Altropane was synthesized by acid hydrolysis of 27 1 Ahropane. This compound was then methylated w th CH31 and put t ed by HPLC. Healthy human subjects were injected with -15 mCi of Uc Altropane and dynamic PET images were acquired over 90 minutes using a PC-4096 PET camera. The images were reconstructed using a standard filtered back projection algorithm to an in-plane resolution of 6 mm FWHM Arterial blood was sampled in parallel with imaging and metabolite analysis was performed by HPLC. The PET and metabolite corrected arterial blood data were used to calculate k]/Iq by a linear graphical method for reversible ligands. .

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The aim was to determine if a significant variation existed between the sexes in gastric emptying rates and, if so, was there a need for different normal ranges to be applied. A proprietary available cottage pie was used as a semisolid meal. The potato layer was labelled with 12 MBq of~Tc m labelled DTPA. Imaging was commenced immediately upon completion of the meal. Anterior and posterior projections of the stomach were recorded for thirty seconds using a 128 matrix at 0,5,10 and 20 minutes and then every 15 minutes up to 125 minutes. Exact time of acquisition, referenced to meal completion, was recorded. Gastric counts in each projection were analysed using an Excel spreadsheet. For each time interval, the data was decay corrected and a geometric mean value calculated. These values were then expressed as percentage of meal remaining in stomach. Variation in gastric emptying with gender was investigated retrospectively in 110 patient datasets (55 female, 55 male). Mean and standard deviation values for each gender dataset and the whole population were determined at each time interval (+/- 2 minutes). Appropriate t-testing was performed to compare male-female, male-total and female-total populations. The result of this analysis showed male gastric emptying to be significantly faster than female for a semi-solid meal. However, this gender difference is not significantly great to necessitate separate normal ranges.

Results: The PET images showed superb striatal definition, with clear separation of caudate nucleus and putamen. In addition, there was minimal accumulation of tracer in brain regions with high 5HT transporter density. Striatial time-activity curves displayed the pattern characteristic of a reversible tracer and metabolite analysis demonstrated that at 60 minutes after injection, approximately 80% of circulating radioactivity eluted with intact l IC Ahropane. The average value for k]/k4 was greater than 3.5. Conclusions: These results indicate that HC Ahropane is a usethl PET tracer that combines the favorable characteristics of: 1) rapid and specific striatal binding; 2) reversible binding kinetics and 3) high,i selectivity for DA vs. 5-HT transporter sites. These properties will almost certainly make C Altropane an important PET ligand for quantitative measurements of DAT density in Parkinson's disease and other neurological disorders.

co

PS_240

PS_242

PC BASED DATA ACQUISITION SYSTEM FOR ANGER SCINTILLATION CAMERA

FROSTBITE INJURY: SClNTIGRAPHIC PREDICTION OF SOFT TISSUE AND BONE VIABILITY

M. Petrovic (1), N. Stojanova (1), D.B. Popovic (1), V. Artiko (2), V. Obradovic (2), V. Bosnjakovic (3). (1) Faculty of Electrical Engineering, University Of Belgrade, Yugoslavia; (2) Nuclear Medicine Institute, CCS, Belgrade, Yugoslavia; (3) Center for High Technology, CCS, Belgrade, Yugoslavia.

V. Zavadovskaya, O. Kilina, [. Sinilkin, S. Ekimov, O. Shulga, L. Ekimova. Siberian State Medical University, Tomsk, Russia.

Aim: The design of a modular, adaptable to clinical needs, ready for integration in the PACS and HIS information systems PC based data acquisition system for Anger scintillation camera. Methods: A high-performance analog to digital (A/D) PCI card (National Instruments, Austin, TX) was selected as an interface between a standard PC computer and Anger scintillation camera. The manufacturer guarantees the linearity, sampling rate and other technical performances of the A/D board. The device is CE certified. The three outputs from the Anger camera (X and Y co-ordinates, and the summing up Z signal) were connected to the three inputs of the high speed A/D card. The Z signal was also used as a trigger for starting the A/D conversion. Windows NT operating system and LabVIEW 4.1/5.0 (National Instruments, Austin, TX) provided the basic tools for the development and testing of the s o l , rare, and the system as a whole. The system is designed for planar (static, dynamic) and SPECT studies (including the gated studies), using the multiple energy windows. The sot~ware supports different recording protocols developed by almost any institution or manufacturer of Anger camera. The data acquisition system supports image formats used by the leading manufacturers of nuclear medicine instrumentation, yet it primarily supports the DICOM standard. Results: The system was experimentally tested using the phantoms (e.g., dead time < 3gs, bar phantom spatial resolution < 3 ram, no constraints to the SPECT system). The computer system was clinically evaluated by examining the consecutive 159 clinical static and dynamic studies in 112 subjects. The evaluation was blinded; the clinical expert evaluators of the acquired images were not aware which system was used for data capturing. The same images were captured in parallel with both new PC based computer system and Siemens, ,,Miarodelta" system at the Clinical Center of Serbia. The three blinded clinically experienced observers have found the present system diagnostically more efficient in 94%, 91% and 87% of the analysed studies, respectively. Conclusions: A new PC based computer system for real-time image capturing and later analysis of the data from an Anger scintillation camera was developed. This development follows the world trend of designing medical instrumentation: use of general-purpose PC computer or workstation with a high quality interface. The novel system improves, and facilitates diagnostics in numerous nuclear medicine units and maximise the performance to cost ratio.

Frostbite injuries occur in extremely cold climates during cold periods, lead in many cases to soft tissue and bone infarction that required amputation. The major obstacle is the difficulty in estimating the extent of dead tissue early aRer the cold injury but betbre the development of gangrene. Aim. The aim of the study was to assess value of 2-phase scintigraphy in detection of soR tissue and bone necrosis during deep frostbite. Material and methods. II pts (10 males, 1 female) aged 40!-_6years, having frostbite (3 pts of both hands, 3 pts of both feet, 5 pts of both hand and feet) were scanned in 3 to 20 days from the onset of cold injury during winter 2000-2001 using 370MBq of 99mTc-MDP. Results. 9 pts studied revealed 4-th degree frostbite which pattern included ,,cold" areas both in bones and soft tissues for equal distance. 2 pts with the 3-rd degree of frostbite revealed ,,cold" area in the soft tissue and preserved visualization of bones. Scintigraphic border of ,,silent" area coincided with clinical demarcation line (DL) in 6 pts who were investigated later than 10 days after frostbite. Scintigraphic DL was established in 5 pts 3 days after cold injury and was verified later by clinical follow-up, surgical inspection and by microscopic pathology. DL was revealed scintigraphica]ly in the projection of distal in~rphalangeal joints of hands and feet (n=5), of middle third of feet (n--4), of radiocarpal joints (n=l) and of mean third ofcms (n=l). Coneluslon. 2-phase scintigraphy is a safe method for early prediction of bone and son tissue necrosis degree and allows to work out optimal ways to treat deep frostbite.

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• TECHNOLOGY PROGRAM 1

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DEVELOPMENT OF A NEW WHOLE BODY TABLETOP: GAINING IMAGE QUALITY BY DECREASING DISTANCE BETWEEN PATIENT AND G A M M A C A M E R A DETECTOR

CENTRAL BENZODIAZEPINE RECEPTORS IN DEMENTIA OF VASCULAR AND ALZHEIMER'S TYPE

N.J. Mijnders (1), I.M.A. van Rooijen Beuman (1), C.J.H. Smits (1), G. van der Wilt (2). (1) Dept. of Nuclear Medicine, Amphia Hospital, Breda, The Netherlands; (2) Kokke van der Wilt Contracting, Boxtel, The Netherlands.

A. Panzacchi (1), G. Riz.zo (1), C. Messa (1), C. Gobbo (1), RM. Moresco (1), G. Frisoni (2), M. Alberoni (3), C. Mariani (3), A. Carpinelli (1), G.B. Rossini (2), E Fazio (1). (1) LNB-CNR, Universit& Milano - Bicocca, Scien. Inst. h San Raffaele; (2) IRCCS Fatebenefratelli, Brescia; (3) IRCCS Don Gnocchi, Milano, Italy.

Aim: Modem gammacameras are well suited to perform all kinds of examinations in just one hardware set-up. The patient tabletop is optimised for SPECT acquisitions. The design is narrow, curve shaped and oRen uncomfortable for obese patients (o~en with pain) undergoing whole body scanning. We developed a tabletop for whole body scanning and spot imaging to decrease distance between patient and detector and hence to gain image resolution and contrast. Methods: A removable tabletop was designed with a maximum of patietu area to fit within the gammacamera gantry, as thin as possible, maximum bend of I8 mm when loaded with 100 kg in the centre, maximum weight allowance of 180 kg. Four candidate materials were tested for the least mass (total weight!) and the least attenuation for 140keV. The current and new tabletops were tested for sensitivity and resolution for 99mTc. Ten patients, injected with a standard dose of 550 MBq 99mTc HDP. were scanned twice approximately 3 hours post injection with the current and the new tabletop. The used gammacamera was a Toshiba GCA 7100pi equipped with a low energy high resolution (LEHR) collimator. Scanspeed was 10 cm / min. Scintigrams were reported blindly. Results: A 2 mm thick atuminium alloy with a specific gravity of 2.64 g/era3 was used to construct a fiat, cone shaped table top. Measured system sensitivity was 79.0 (no tabletop installed), 73.5 (current) and 75.8 cnts/sec/MBq (new). Resolution at 10 cm from the collimator surface was 8.31 (no tabletop installed), 8.40 (current) and 8.38 mm (newl Contrast and image quality dramatically increase in all ten patients. Especially in areas where the distance between patient and detector v, as decreased, like spine, limbs and hands. All patients pret'erred the new tabletop fur its comfort, as they weren't tied up. Conclusions: The maximum of image quality can be achieved when the gammacamera detector is placed closest to the patient. This is a major basic principle in nuclear medicine imaging. Curve shaped tabletops are ideal for SPECT acquisitions but deteriorate whole body imaging. A fiat table top with more patient comfort increases image contrast just by decreasing the distance between patient and gammacamera detector.

Aim In a previous study, no significant differences in [lIC]flumazenil (FMZ) binding bet~een patients with dementia of vascular type (VD) and with Alzheimer's disease (AD), were observed. To understand the possible impact of this finding on disease classification, we now report the PET results in a slightly larger group of VD patients compared with the same AD patients and their relationship with the severity of disease. Methods 14 patients, 6 with AD and 8 with VD diagnosed according to NINCDS-ADRDA and NINDS-AIREN, were recruited. Age and severity of disease assessed by MMSE score were 73±5 and 15~-5 in AD and 73±2 and 2f~:5 in VD. Images of BDZ distribution in the brain were acquired dynamically with a 4.5 mm resolution PET camera (GE Advance) a~er i.v. injection of 3.7MBq/Kg of[I IC]flumazenil. Blood arterial samples were collected from a radial artery for calculation of metabolite corrected plasma input function. HC-flumazenil delivery to brain tissue (K1), which depends on blood flow and the tissue distribution volume (DV), which is a measure of tracer binding to benzodiazepine (BDZ) receptors, were obtained using a two compartment model. Images were normalised into the MNI space (SPMq6) and, using a basis function, transformed into parametric normalised images of KI and DV. Regional values of KI and DV were obtained with ROIs and compared a) between AD and VD patients and b) between patients with MMSE scores lower In. = 6) or greater In. = 8) than 18, using repeated Student's t-tests. Results: No significant differences in KI or BDZ binding between AD and VD patients could be tbund in any of the regions examined. On the other hand, when patients were regrouped according to the MMSE scores, a significant difllzrence (P<0.05 uncorrected) in the parietal and lateral temporal cortices was found Ibr DV only, being these values lower in the more severely affected patients (2.9 ± .7 in MMSE< I 8 vs. 4 ± 1.1 in MMSE> 18 for the parietal cortex). Conclusions: A reduction in BDZ binding but not in K1 values was tbund only when demented patients were grouped according to the severity of cognitive decline and not to the standard clinical-anatomical classification. Such finding may represent a pure neuronal regional loss related to the severity of disease and it is independent on blood flow changes.

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PROBLEM BASED LEARNING IN NUCLEAR MEDICINE

A SUGGESTED PANEUROPEAN IMPLEMENTATION MODEL FOR RADIOPHARMACIES FOR RADIOPHARMACEUTICAL RECONSTITUTION PRACTICES

A.W.M. Tops, W. Hoorn van, M. Weberink. Fontys University of Professional Education, Department MBRT, Best, The Netherlands. Aim At this poster the twelve years of experience that now exist with this problem based curriculum for teaching nuclear medicine will be highlighted. An introduction will be given to the program, the choice for Problem Based Learning (PBL) will be explained and motivated and some figures about student in-and output will be shown. Methods When the curriculum was designed, the profession was analyzed not only with regards to it's contents, but also to the circumstances of practice and to some meta-skills that are being demanded by the employers to be. By designing the curriculum it was a must that this new curriculum had to exist next to the other hospital based, inservice curriculums for each Diagnostic Imaging and Radiation Therapy separately. Results As a result of that analysis the new program was based upon the didactical concepts of Problem Based Learning. Among other things this means that the program is integrated, teacher extensive, theme centered rather than subject centered and relying heavily on self study, on groupwork by the students and on in-school skills traning in a specially designed skills lab. These practical wanings at school are completed by periods of practical training in hospital departments. Conclusions In 1989 the Dutch started a universitary based combined BSc-carricalum in all Diagnostic Imaging modalities and Radiation Therapy. Graduates are licensed to work as technologist in Radio Diagnostics including CT and MRI, and in Ultrasound, Nuclear Medicine and Radiation Therapy. The objective is to bring forth graduates who are trained in a wide variety of skills, at entry level.

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D. O'Leary (1), J. McCavana (2), L. Rainford (1). (1) School of Diagnostic Imaging, UCD, Herbert Avenue, Elm Park, Dublin 4, Eire; (2) Nuclear Medicine Department, St Vincent University Hospital, Elm Park, Dublin 4, Eire. AIM: The European Guide to Good Manufacturing Practice and the UK Audit documents for Radiopharmacy provide established methods of evaluation, enable investigation of current standards and facilitate recommendations for acceptable levels of practice in Radionuclide departmants. These recognised European guidelines suggest that reconstituted products not manufactured according to the guidelines may leave the radiopharmacies open to legal challenge. The aim of this work is to examine awareness of these guidelines and to establish the extent of their implementation into Radiopharmacy reconstitution workstations and work practices. METHOD: Following visits to various European and UK radiopharmacy locations, to access the compliance of these with reeoguised guidelines, the questionnaire format for use in a full Irish survey was completed. Visits and structured interviews in all Irish radiopharmacies were undertaken. Direct comparisons are currently being made between radiopharmacies in the Irish Republic, the UK, and other European centres and the results will be judged in light of recommendations in the published literature. RESULTS: Preliminary results indicate that many radiopharmacies in Ireland and some centres in Europe are open to legal challenge as the radiopharmaceutical t~constitution methods do not follow European Good Manufacturing Practice Guidelines. Remaining data is currently being analysed and it is anticipated that results will be presented at this meeting, CONCLUSIONS: Preliminary data from this investigation provides evidence that guidelines are not being adhered to. A panEuropean model for a dedicated radiopharmacy, which reconstitutes radiopharmaceuticals beyond legal challenge, is recommended. By assessing any shortfall in the existing radiopharmacy service, these issues will be open for further debate and findings of this work will facilitate change in radiopharmacy standards.

• TECHNOLOGY PROGRAM 1 / CARDIOVASCULAR 4 PS_247

CARDIOVASCULAR 4

DUAL ENERGY X-RAY ABSORPTIOMETRY (DXA) AND TOTAL HIP PROSTHESES: METHODOLOGICAL PROBLEM

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G. d'Arnaud, R. Kingma, I.C. Heyligers, J.C. RoDs. Nuclear Medicine Vrije Universiteit Medical Centre, Amsterdam, The Netherlands.

SPECT IMAGING AND TL-201 LUNG UPTAKE

Aim. We use DXA for follow up of bone mineral density (BMD) measurements in patients with a total hip prostheses. We noticed that the total area of the ,,Global Region" (GR), meant to correct for soft tissue, influences BMD in the chosen subregions of interest around a prosthesis. The only instruction given by the manual about this GR is that it ,,should be large enough to contain enough soft tissue". We investigated the influence of GR size in 7 subregions medial of the prosthesis (R I. the upper part of the minor trochanteric area; R7, an area just below the stem of the prosthesis) in 8 patients Methods. All patients had an uncemented total hip prosthesis (type Meridian; Stryker/Howmedica/Osteonics). The DXA scans were performed on a Hologic QDR 2000plus. BMD in RI - R7 was analysed with the standard software for prosthetic hip implants with metal removal option. We varied the GR size from maximal (the scanned area) to minimal (the area just around the 7 subregions) and analysed the effects on area, bone mineral content (BMC) and BMD in R1 - R7). Results. Irrespective of the chosen subregion, the change in GR area resulted in a change o f 15 to + 35 % for the area o f the subregion, - 22 to + 4 1 % in BMC and - I3 to + 5 % in BMD. The mean percentage change (+/- standard deviationl decreasing the GR from maximal to minimal is given for the area, BMC and BMD per subregion in the Table. % chan~e +/- SD RI R2 R3 R4 R5 R6 R7

Area II.0 +/2.2+/-0.5 +/-I.7 +/-3.5 +/-4.6 +/0,0-H-

12.7 4.1 2.6 3.6 6.0 6.6 1.5

BMC 8.5 +i- 15.7 I.I +/- 5.4 -2.1 +/- 3.5 -3.9 +/- 5.6 -7.9 +/- 8.9 -9.9 */- 10.1 - I . 0 - / - 2.7

BMD -2.2 +/-4.6 -I.I +/-2.5 -I.5 + / - 2 6 -2.1 +/- 2.9 -4.7 +/- 3 8 -5.7 +/- 5. I -1.0+/-1.5

Conchesion. The GR size chosen during analysis of BMD around a hip prosthesis influences the outcome in BMD substantially. Further research is warranted to investigate the optimal GR size in relation to accuracy.

PROGNOSTIC VALUE OF COMBINED MYOCARDIAL PERFUSION M. Kaminek (t), M. Myslivecek (1), M. Skvarilova (2), V. Husak (1), R Koranda (1), I. Metelkova (1), O. Lang (3). (1) Department of Nuclear Medicine, University Hospital, Olomouc; (2) Department of Internal Medicine, Universisty Hospital, OIomouc; (3) Dept. of Nucl. Med., Univ. Hospital, Prague-Vinohrady, Czech Republic. Aim: It is generally accepted that TI-201 lung uptake has an important prognostic value in patients (pts) with coronary artery disease. The use ofTc-99m-MIBI SPECT imaging for risk stratification has also been reported and validated; however, the pulmonary uptake of this radiopharmaceutical has usually not been calculated. The aim of our study is to explain in which group ofpts assessed by exercise SPECT the quantification of TI-201 lung uptake helps to evaluate the prognosis. Methods: 149 pts - 74 after myocardial infarction (MI) - underwent exercise TI-201 SPECT. The SPECT patterns were divided into norma~ (n=45), fixed defects (n=29) and inducible ischemia (n=75). Anterior planar image was perlbrmed before SPECT acquisition to calculate the lung-to-heart ratio (L/It). L/H<0.5 was considered as a normal result. An average followup of pts was 20+_9 months and a cardiac event was defined as either cardiac death or nonfatal MI. Results: We registered cardiac events in 21 pts (8 deaths and 13 nonfatal M[). L/H ratio was higher in pts with cardiac event (average value 0.57) than in those without it (0.45); L/H ratio depended on the severity of the cardiac event: average value 0.54 in nonfatal MI and 0.7 in cardiac death. Among 45 pts with normal SPECT, no hard event was observed and L/H ratio (average value 036; range 0.22-0.58) was not helpful for risk stratification. In 29 pts with the presence of fixed defects, we registered four cardiac deaths (all in pts with L/H>0.5). annual event rate being 21. I% for L/It>0.5 versus 0% for L/H<0.5: P < 0.05. Pts with ischemia had 17 events, annual event rate being 15.4% I~.~rL/H>0.5 versus 13% for L/H<0.5; P = not significant. Conclusions: Our results suggest the benign prognosis in all .pts with normal SPECT. Conversely, pts with ischcmia are at high risk for future cardiac events (irrespective of L/H ratio). The quantification of the TI-201 lung uptake helps to predict futore cardiac events in pts with fixed detects (significantly higher risk in pts with L/H>O.5). Therefore, for assessment of the prognosis in pts alter MI we prefer TI-201 instead of MIBI.

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PROTOCOL FOR INTRAOPERATIVE MEASUREMENT OF RENAL

D U A L ISOTOPE IN C H R O N I C C O R O N A R Y A R T E R Y DISEASE. INCREMENTAL VALUE OF STRESS G-SPECT

BLOOD FLOW U. Dopichaj-Menge, H. M~ller, D. Sandrock, D. L. Munz. Clinic for Nuclear Medicine, University Hospital Charit& Berlin, Germany. Aim: Durir~g cardiac surgery there is an altered circulation situation (volume and blood pressure, flow instead of pulse wave circulation), especially, if the heart-lung machine (HLM) is in use, This often results in a decrease oftbe urine excretion during the intervention. Hence, it was the aim of this study to develop an adapted protocol fur measuring the renal blood flow and proof its feasibility and suitability under intraoperative conditions. Methods: Based on calculated compartment assumptions, the following protocol was created: i.v. injection of 10 MBq 1-123-orthoiodohippurate (OIH) 30 min before start of HLM; blood sampling 15 rain before and at least three times during HLM. Al~er the end of HLM, again i.v. injection of 10 MBq OIH (for better count statistics) was done and at least one blood sample was drawn until 15 rain p.i.. The detailed surgical procedure, HLM-protocol, and exact time points of blood drawings were tried to be obtained from the perf~siooist and anesthesiologist. Additionally, sex, age, and hematocrit were noted. The protocol was tested in 37 patients (pts., l 1 women, 26 men; aged 41-84 years). Results: In four pts. (I 1%) it was not possible to obtain a blood sample before start o f HLM, During HLM running (41-181 min, mean 88 rain) seven pts. (19 %) had three blood samples, 23 pts. (62 %) had four, five pts. (14 %) had five, and two pts. (6 %) had six samples. There was only one pt. without any sample after the end of HLM. 24 pts. (65 %) had one sample, ten pts. (27 %) had two, and two had three samples, respectively. The exact documentation of the sampling times, surgery and HLM-protocol could be achieved in all pts. Conclusions: This protocol is feasible under surgical conditions in most cases. Communication with the anesthesiologist and perfusionist and exact documentation are indispensable,

M.L. De Rimini (1), M. Catalano (1), A. Scatzone (2), R. Merenda (2), V. Ippolito (1), P. Muto (1). (1) Nuclear Medicine Dpt; (2) Cardiovascular Dpt, A.O. Monaldi, Naples, Italy. In patients (pts) affected with chronic CAD and Left Ventricular (LV) dysfunction, Rest Thallium-201 has high prognostic value, Streas-SPECT myocardial imaging can provide enhanced risk stratification and Gated-SPECT yield greater incremental prognostic value for prediction of hard event than stress perfusion SPECT alone. Aim of the study was to verify the extension of myocardium viability with a Dual Isotope myocardial scintigraphy in chronic CAD, by combining assessment of post-stress LV function and regional myocardial thallium activity? Methods: Dual Isotope (TI-201 SPET Rest 20' - Rest 24h; Stress-Gated-SPET-Tc-99m Sestamibi) protocol was performed in 12 pts affected with chronic dysfunctional CAD. Combined assessment of of LV function was given from GATED-SPET scan. Tracers myocardial uptake was quantified in 264 segments (S) as % of peak in a 4 points scale (from 0 as normal to 3 as severe defect), using a 22 segment scheme. Defects were classified as fixed (F) or as reversible (Rev.>60% of peak) or partially reversible (PRey.>50% o f peak)., in presence of 10% uptake increase at rest with respect to stress, Threshold uptake for viability criteria was 50%. LV Rest Ejection Fraction and regional wall motion as % of thickening (%T) were obtained from Gated data at Empty analysis, Results: Preserved Rest-thallium and Stress-Sestamibi uptake were found in 192 segments; in pathological S, Stress-Sestamibi defects showed an incremental prognostic value for ischemie extension than comparated each-other thallium 20' and 24h scan. Tot.S SPETSestamibi-Stress Defect : tot. 72 S TI201 - 20'Defect: tot. 5 7 S TI 201 - 24h Defect: tot. 30 S

Score I 18 S (25.%) 27 12

Score 2 24 S (33. %) 18 11

Score 3 30 S (41,%) 10 7

Stress-G-SPET-Sestamibi, in corresponding defects areas showed: goT: <- 10 as dyskinesia in 3 S; % T = 0-10 in 30 8; %T = 20 - 30 in 28S. Post stress global dysfunction in 8 pts: LVEF < 37%, Conclusion: In patients with chronic CAD and Left Vantricular dysfunction, our data confirm that Stress-G-SPECT myocardial imaging can provide enhanced risk stratification and the high role of rest-redistribution thallium SPET.

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INTERPRETIVE REPRODUCIBILITY OF STRESS THALLIUM 201 SPECT PERFUSION IMAGING IN OBESE PATIENTS

ASSESSMENT OF THE EFFECTS OF ATENOLOL-INDUCED HEART

P. Lecouffe, P. Tellier. Department of Nuclear Medicine, Clinique Ste Catherine, Arras, France. Aim : In routine clinical practice, cardiac thallium 20[ SPECT images are of poor quality in obese patients. So, the aim o f this study was to assess the reproducibility of their clinical interpretation. Methods : 100 patients (61 men, 39 female), with a body mass index > 30 kg/m2 were prospectively included. Two experienced readers interpreted stress (58 treadmill exercise and 32 dipyridamole) and rest thallium 201 SPECT images. A first interpretation was done without any clinical data. A second reading was performed using all clinical and stress data. Images were classified as normal or abnormal for ischemia. Reproducibility was assessed by use of percent agreement and Kappa statistic, Results : Without clinical data, agreement was mild (75 %, Kappa = 0.34). Addition of clinical data significantly increased agreement (86 %, Kappa = 0.59, p < 0.05). Discrepancies concerned both inferior and anterior wall in female, but were highly more frequent in inferior wall in male patients. No difference was observed between dipyridamole and treadmill exercise tests. Conclusion: As expected interpretive reproducibility of thallium 201 SPECT perfusion images is mild in obese patients. Nevertheless, this study point out that clinical data are of importance in interpretation of perfusion images, especially in obese patients, leading to an acceptable interpretive reproducibility in clinical routine practice.

RATE DECREASE ON MYOCARDIAL PERFUSION AND CONTRACTILITY IN PATIENTS WITH CORONARY HEART DISEASE USING 99MTC-MIBI GATED SPECT

L. Samoylenko, E. Safonova, V. Mikheev, E. Zharova, V. Sergienko. Department of Nuclear Medicine, Cardiology Research centre, Moscow, Russia. Aim: To assess the effects of atanolol-induced heart rate decrease on myocardial perfusion (MP), systolic and diastolic function in patients with chronic coronary artery disease (CAD) and mildly depressed myocardial contractility. Methods: 17 males (mean age 51±.3 yrs) with stable angina (10 pts with CCS functional class 11 and 7 pts with CCS functional class liD, angiographically confirmed CAD (10 pts with 3vessels disease, 7 pts with 2-vessels disease, and 11 pts with previous myocardial infarction) and mildly depressed systolic function (mean LVEF 44.4%) were underwent rest/stress 99mTc-MIBI gated SPECT before and after I0 days administration of atanolol (mean dose 100 mg/day) (12 pts) or placebo (5 pts). Atenolol dose was titrated to reach decrease in the heart rate at least by 20% from the baseline. The results were processed using Siemens Quantification and GS Quantification program. Results: After 10 days atenolol treatment course the heart rate decreased from 79±8 to 58±5 bpm (p=.01), whereas in placebo group there were not significant changes. Myocardial perfusion improvement was shown in all patients treated with atenolol. 10 days treatment course with atenolol compared with placebo was associated with significant decrease in the ischemic score (25.7±5.0 to 18.0-2_2.4 [p<.01] vs 23.6_+4.6 to 21.3+5.1 [NS]) and increase in LVEF (43.8±10 to 50.8±8 [p<.01] vs 45.0±7 to 43.1±7 [NS]). LVEDV decreased from 147±46 ml to 139±48 ml in atenolol group (p<.05). Diastolic time lengthened from 465+186 ms to 632±145 ms (p<.01) in the atenolol group and did not significantly changed in placebo group (430:t:150 to 440±i45; NS). In addition, there was improvement in the symptoms and increase in the total workload time in the atenolol group. Conclusion: Heart rate decrease by 20% on atenolol is associated with the myocardial perfusion improvement as well as systolic and diastolic function in patients with chronic CAD.

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IS REST-REDISTRIBUTION THALLIUM TOMOSClNTIGRAPHY A PREDICTOR OF LONG TERM CLINICAL OUTCOME OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION?

EARLY REST AND LATE STRESS - REST 99MTC - TETROFOSMIN SPECT AFTER ACUTE MYOCARDIAL INFARCTION, IN IDENTIFYING MYOCARDlUM AT RISK AND EXERCISE-INDUCED ISCHAEMIA

E. Tran-ngoc (1), P. Martin (1), B. Peperstraete (2), N. Duroarey (1), J. Devriendt (2), J. Paternot (1), R. Gheldof (1), R Decoodt (2), M. Verhas (1). (1) Nuclear Medicine CHU Brugroann; (2) Cardiology CHU Brugmann, Brussels, Belgium.

L. Petrovici (1), R. Capalneanu (1), C. Medrea (1), C. Sfangeu (2). (1) Department of Nuclear Cardiology, Heart Institute ; (2) Department of Nuclear Medicine, County Hospital Cluj-Napoca, Romania.

Aim : to assess if the presence or absence of 201 TI redistribution (R) in recent acute myocardial infarction (AMI) could predict favourable or unfavourable late clinical outcome of the patient (reinfaretion, death). Methods : from 01 1996 to 05 1997, 65 patients (64 +/-13y) with AMI had 201 TI rest-redistribution (R-R) myocardial tomoscintigraphy (180i acquisition, Sopha DSX rectangular tomocamera, late acquisition without reinjection 3 hours later). 58 pts. had a clinical fullowup until september 2000 (16 non Q wave AMI and 42 Q wave AMI). Coronal slices were divided into 3 or 4 segments whom activity was normalized to peak activity, to which a 100% value was assigned. R was considered + in case of a gain > 10% of activity with initial value of<75%. Results : according to this, R+ was 29% (12/42) in Q wave AMI (19% inf. AMI and 44% ant. AMI) and R+ was 69% (ll/16) in non Q wave AML The clinical outcome was more favourable in 34/42 (81%) Q wave AM[ (92% inf. AMI and 8 t % ant. AMI) than non Q wave AMI 8/16 (50%). 100% o f Q wave AMI with R+ had a favour'able evolution in regard with 55% of R+ non Q wave AML We also found a high percentage of favoumble clinical outcome in Q wave AMI with R- 25/30 (83%) in regard with 2/5 (40°/0) of non Q wave AMI independently of localisation. According to this, the sensibility and specificity of R+ to predict late clinical evolution was 40% and 62% respectively. Positive predictive value was 78,3% and negative predictive value was 23%. We conclude that taken separately, R- in Q wave AMI did not predict a bad evolution. For Q wave AMI, R+ was associated with favourable outcome hut this trend is not significant as compared with R- Q wave AMI, from a statistical point of view (Chi2 test p--0,13, n.s.). Half of the patients with non Q wave AMI, independently of R+ or R-, had an unfavourable outcome : this is in accordance with the literature data which predict a worse outcome for these patients. The higher % of favourable clinical outcome in inferior AMI in spite of a higher rate of R- could be due to a more limited functional consequence of inf. AMI.

1140

PURPOSE: As myocardial infarction is often due to haemodynamical insignificant coronary lesions, myocardium at risk and exercise -induced iscbemia may differ. The objective was to compare early and late rest SPECT with late exercise SPECT, to identify myocardium at risk and ischemia. METHODS:28 patients (19 men, 9 women) were examined at rest in the first two weeks after a first acute Q-wave MI (17 anterior, 12 trombolysed and 11 inferior, 5 trombolysed). All of them were reexamined later (42-124 days) with a two-day rest-stress protocol. All studies were performed at 1 hour after the i.v.administration o f 740 MBq 99m-Tc tetrofosmin. All studies were imaged on the same one-head camera, Philips ARC 3000 with ADAC Pegasys X workstation. The myoeardium was divided in I9 segments, uptake was scored from 0 (absent) to 3 (normal). All patients underwent coronary angiography. There were 14 univascular, 6 bivascutar and 9 multivascutar patients. RESULTS: From 134 segments (25%) with an uptake of 0-1 at early rest, only 85 (16%) were present at late rest There were 51 (10%) segments with an uptake o f 0-2 at exercise, reversible at [ate rest. From these segments with reversible defects 26 (5%) had an uptake o f 0-1 at early rest, normal at late rest and 25 (5%) were normal at booth rest studies. From the 26 partially reversible segments at early rest and reversible at late rest, 15 were in univascular patients, 3 in bivascular patients, 8 in multivascular patients. From the 25 reversible segments at booth rest studies, 3 were in univascular patients, 4 in bivascular patients, 18 in multivascular patients. CONLUSIONS: After acute myocardial infarction, early rest even at 2 week late rest-exercise 99m-Tc tetrofusmin can differentiate myocardium at risk from exereise-induced ischemia. Differences between them are quite common. Myocardium at risk and exercise-induced iscbemia in the same segments are more often in univascular patients, in different segments more often in multivascular patients.

• CARDIOVASCULAR 4 PS_255 Abstract withdrawn

PS_257 PROGNOSTIC VALUE OF MYOCARDIAL TC-99M TETROFOSMIN GATED-SPET IN PATIENTS UNDERGOING THORACIC SURGERY M.L. De Rimini (1), M. Catalano (1), A. Scalzone (2), R. Merenda (2), A. D'Amico (3), V. Ippolito (1), P. Muto (1). (1) Department of Nuclear Medicine; (2) Cardiovascular Department; (3) Anesthesiology Service, A.O. Monaldi,Naples, Italy. Patients (pts) undergoing major surgical procedures with scintigraphic evidence of stress induced ischemia have a significantly higher incidence of per±operative cardiac events. However, it is also well demonstrated that poor lef~ ventricular function places pts at increased jeopardy of per±operative events. Aim of the study was to evaluate prognostic value of Myocardial Gated-SPECT in presurgical assessment of cardiac risk in high risk pts. Methods: we enrolled 12 pts, all male, mean age 66 years, affected with lung carcinoma undergoing to surgery, 5 of them with history of CAD and previous myocardial infarction over one year. Double-day Tc-99m Tetrofosmin Dipyridamole and Rest rnyocardial GatedSPECT were performed during beta-blockers therapy. A 22 segment (S) model, with a total of 264 (S), was used to analyse Tetrofosmin myocardial perfusion uptake. LV Rest Ejection Fraction and regional wall motion as % of thickaness (%T) were obtained from Gated data at Emory analysis. Results: Severe reversible defects, corresponding areas: %T< 10-20% and Rest LVEF < 40% were found in I pts; moderate but extens¢ reversible defect with abnormal %T and LVEF > 50% in 2 pt. All of them underwent angiography and planning for simultaneous myocardial riperfusion and lung carcinoma surgery was programmed. Low-Moderate reversible defects, LVEF >50% and no severe abnormalities of %T were found in 4 pts, suggesting beta-blockers treatment before, during and after lung surgery. No myocardial perfusion abnormalities or LV function in 5 pts were found. Conclusion: Our data suggest that Dipyfidamole test can better reproduce stress surgery induced and showed the incremental prognostic value provided from Gated Perfusion SPECT data to perfusion study

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PS_256

PS_258

THE ROLE OF RFS (RADIONUCUDE FRACTIONAL SHORTENING) IN QUANTITATIVE EVALUATIONS OF MYOCARDIAL INFARCTIONS

IMPORTANCE OF PHASE ANALYSIS IN EARLY ASSESSMENT OF SEGMENTAL CONTRACTILITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

M. Atalay (1), Y. Duman (2), A. Altmtl~ (3), E. Teber (1), H. Akin (1). (1) Department of Nuclear Medicine, Atat~irk State Hospital; (2) Department of Nuclear Medicine, Ege University Hospital; (3) Department of Cardiology, Ege University, Izmir, Turkey. The aim of the study is to evaluate the relationships between RFS (Radionuclide fractional shortening) values, first pass radionuclide angiography, LV(LeR ventricule) ejection fraction LVEF values, SPECT examination (to determine the site and the size of infarcted area ) and gated perfusion examination findings in patients with myocardial infarction based on clinical, enzymatic or electrocardiographic criteria. Methods: All the patients were performed with first pass mdionuclide angiography of Tc-99m MIBI, rest SPECT and gated perfusion studies, The sizes of defected areas were determined(%) in SPECT examinations. Gated cardiac examination was end diastol (ED) and sistol (ES) visions were obtained le~ anterior oblique projection, Vertical and horizatuat axis were drawn in their anteroposterior wall(ap) and septum-lateral(sl) positions. The lenght of each axis was calculated by the formula below. GIobalRFS(%) = (EDao+EDsl)-(ESao+ESsI~ x 100 EDap + EDsl Results: Linear correlation was found between LVEF and global RFS values. It was found that there were opposite correlation between % defectiveness with LVEF and global RFS. Conclusions: Global RFS seems to be good pammetar showing ]et~ ventricular function capacity.

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A. Cickusic (1), N. Latic (2), Z. Kusljugic (3). (1) Deparment of Nuclear Medicine Cantonal Hospital Zenica, Bosnia and Herzegovina; (2) Deparment of Nuclear medicine Cantonal Hospital Zenica, Bosnia and Herzegovina ; (3) Department of cardiology, Internal Clinic UKC Tuzla Bosnia and Herzegovina. Myocardial infraction impairs the heart muscle contractility. Regional disorders of the heart walls motions arc very characteristic and sensitive indicators of the left ventricle function afier AIM. The aim of this study is to establish the frequency and the level of the segmental contractility disorder in the early stage afcer AIM by means of a phase analysis of radionuclide ventriculography. Forty two subjects have been analyzed, 36 males and 6 females of an average age of 51.31 ± I 1.28. The study has encompassed 23 subjects with AIM of the front and 19 subjects with AIM oftbe lower wall. Method: Radionuclide ventriculography in equilibrium has been carried out on 4.33 ± 0.25 day from the onset of symptoms. Contrast vantriculography with selective angiocardiography has been carried out on 28.08 ± 21.19 day in relation to the onset of symptoms. In 42 subjects 462 segments have been assessed. Out of that 56.56% of segments have been dysinergic. The greatest frequency of dysinergy has been observed in the septal and apical region and the lowest one in the lateral region of the LV. Result: Using contrast ventriculography as a golden standard, sensitivity and specificity of our method have been.determined with regard to the level and localization of the segmental contractility disorder. The sensitivity of our method in determination of the level of the segmental contractility disorder amounts to g9%, specificity 93% and predictive value 89%. The sensitivity of our method with regard to the segmental disorder localization amounts to 89%, specificity 89% and predictive value 86%. RNV is a very important non-invasive method in determination of the level and degree of the segmental contractility disorder in an early phase of acute myocardial infarction what is an important predictor of prognusis as well as in decision making with regard to the choice on fiJrtber therapeutic treatment in an early phase of acute myocardial infarction.

1141

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• CARDIOVASCULAR 4 PS_259

PS_261

THE ACCURACY OF ST CHANGES DURING TREADMILL EXERCISE IN PREDICTING OF LOCALISING REGIONAL MYOCARDIAL ISCHAEMIA

THE NITRATE ENHANCED TC°99M MIBI SPECT IN DETECTING VIABLE MYOCARDlUM IN PATIENTS WITH CORONARY ARTERY DISEASE AND LV DYSFUNCTION

N.W. Garvie, C..J. Cooke, F. Salehzahi. Royal London Hospital, Nuclear Medicine Department, London E1 1 BB, UK.

M. Kostkiewicz, W. Tracz, M. Olszowska, T. Przewlocki, P. Podolec. Department of Nuclear Cardiology, Jagiellonian University, Cracow, Poland.

Despite the increasing cliniuai acceptance of stress myocardial perfusion imaging (MPI) in the diagnosis and management of ischaemic heart disease (IHD), the Exercise Tolerance Test (ETT) remains the most popular technique employed by cardiologists. This paper examines the significance of ST changes developing during ETI" procedures, performed as part of a stress MPI protocol. Methods 212 patients with clinically - suspected IHD underwent MPI, using a 2 day MIBI protocol. ETT was used as the stress procedure. All patients attained their target heart rate betbre isotope injection. ST depression, when present, was graded minor (lmml significant (2mm) or marked (>2ram), and the location was charted. Results 37 patients were found to have isehaemia on the basis of the subsequent MPI images. 16 of this group (43%) showed ST depression, of which 7 (19%) were minor, 5 (14%) were significant, and 4 (11%) were marked. In 11 instances (69%) the location the ST changes matched the site of ischaemia on MPI. Of the 175 normal patients 50 (29%) showed ST depression, of which 34 (19%) were minor, 15 (9%) significant and I (~ 0.0%) marked. Six of the patients with proven ischaemia (16%) developed angina - type symptoms (ATS) during ETT, compared to 36 (21%) of the normal group. Conclusions Minor (Imm) ST depression occurred equally amongst patients with proven IHD and normal patients (19%). This feature is, however, frequently regarded by cardiologists as 'borderline', and therelbre an indication for stress MP[. Significant (2ram) depression was slightly more predictive of LH.D (PPA, 60 %). but only marked ST depression appeared to adequately discriminate, (although the number in this group (5) is really too low for analysis). The presence of ATS was of no predictive value. The absence of ST changes during ETT dries not reliably exclude IHD. Conversely ST changes, even if significant, are not a reliable guide to the existence of disease.

In patients with chronic coronary artery disease and the depressed left vemricu]ar function. assessment of residual viability in akinetic myocardium is vital for therapeutic management. In the present study a direct comparison between perfusion imaging with nitrate enhanced Tc 99mMIBl imaging and wall motion pattern in echocardiography was carried out, as well as the usefulness of this modality for detecting myocardial viability was assessed. Methods and Results: Twenty-four patients with coronary artery disease underwent Tc 99m MIBI imaging during intravenous nitroglycerine infusion. Eighteen patients had their echocardiograms repeated after revascularization. Perfusion and wall motion scored from I to 3 (absent to normal). The sensitivity for the rest -nitroglycerine perfusion scan was 87%. The specificity for this procedure was down to 55%. Positive predictive value achieved 89% while the negative predictive value did not exceed 40%. Conclusions: Nitroglycerine enhanced Tc99m MIBI imaging is a useful technique for detecting underperfused, viable myocardium. There is high concordance between perfusion and echocardiographic imaging. The ultimate selection of therapy should ideally be based on a comprehensive range of complementary methods.

PS_260

PS_262

BRAIN NATRIURETIC PEPTIDES (BNP): RELATION WITH SLEEPRELATED BREATHING DISORDERS (SRBD) IN PATIENTS WITH STABLE HEART FAILURE (SHF)

PROGNOSTIC VALUE OF SIZE AND SEVERITY OF PERFUSION DEFECTS IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION

J. Ldpez (1), M. Villa (2), E. Quintana (3), R. Alvarez (1), R Gbrnez (1), D. G Solis (1), F. G Pesquera (1), A. Martinez (2), A. Cayuela (4), A. Ramos (1), R. Vdzquez (1)(1) Department of Nuclear Medicine; (2) Department of Cardiology. HUV Rocio, Sevilla, Spain; (3) MedicalSurgical Unit of Respiratory Diseases. HUV Rocio. Spain; (4) Supportive Research Unit. HUV Rocio. Sevilla. Spain Aim: Brain natriuretic peptides (BNP) are markers of several heart diseases. We wanted to analyze if their levels have a relation with the presence of sleep-related breathing disorders (SRBD) in patients with stable heart failure (SHF). Methods: We have consecutively studied 19 patients with left ventricutar ejection fraction <45% who were clinically stable (symptoms or signs of heart failure had not changed in the previous 4 weeks) and had received standard therapy. Baseline assessment included determination of BNP (quantitative determination by immunoradiometric assay: SHIONORIA BNP), and isotopic vuntriculography. All patients underwent a full-night polyanmnography.SRBD was defined with an apnea-hipopoea index (AHI) >10. We used U-Mann-Whitney test to analyze the results. Results: 6 patients had SRBD (group l) and there were 13 patients without SRBD (group 0), There were no significant differences between both groups in age, sex, body mass index and left vuntricular ejection fraction. BNP median was 37.3 in group 1 (Pereentil 25: 14.3; Perceatil 75: 227.72) and 17.1 in group 0 (Percenti125: 17.1; Pereenti175: 42.75); p 0.32. Conclusions: Although there were no significant differences in BNP between both groups, our results show higher levels in group 1 (SRBD present). The correlation of this finding with the prognostic of these patients, it would be determined.

1142

V. Chernov (1), S. Salpagarova (2), J. Vesnina (1), Y.U. Zayblov (2), Y.U. Lishmanov (1). (1) Nuclear Medicine Laboratory; (2) Out-patient Department, institute of Cardiology, Tomsk, Russia. Aim. The aim of this study was to estimate the prognostic value of size and severity of perfusion defects in patients (pts) afier acute myocardial infarction (AMI) by adenosine (A) - rest (R) Tc-99m MIB[ SPECT. Me/hods: 155 CAD pts (all males, mean age 52_+4) were underwent A-R Tc-99m MIBI SPECT, echocardiography and bicycle test 3-4 weeks after AML The next indices were assessed: A (ADS) and R perfusion defect size (RDS), integral indices of A (IIAD) and R (IIRD) perfusion defect, as well as ejection fraction (EF) and exercise tolerance (ET). A cardiac event was defined as either cardiac death (CD), nonfatal AMI, unstable angina requiring further revascularization (UA). Results: During an average follow-up of 18+_6 months all pts were divided into two groups: Gr.l (105 pts) with benign current of disease and Gr.2 (50 pts) with cardiac events (5 - CD, 12 -AMI and 33 - UA). The myocardial perfusioo parameters in these patients are presented in the Table.

Indices ADS ~%) RDS (%) IIAD (%)

IIRD (%)

i Gr. M_+m 23,9~j,I 18,0+_1,0 I0,5+1,0 5.7+_0,5

2 Gr. M_+m 52,7+2.2 27,2+2,1 16,5_+_2,1 9,3+1.l

(),001 0,0000 0,01

F 16.53 I 26.3 6,25

0,001

ll,ll

R ~: 0,10 0,15 0,05 0.07

The low level of EF and El" had own prognostic value, but did not add prognostic value to 99mTc-MIBI SPECT. Conclusion: The extensive sizes of perfasion defects at rest and at peak of adenosine test was shown to predict future cardiac events.

• CARDIOVASCULAR 4 / DIAGNOSTIC ONCOLOGY 7 PS_263

PS_265

A WASHOUT RATIO OF 1231-15-(P-IODOPHENYL)-3-R,S-METHYL PENTANOIC ACID (BMIPP) AS A GOOD PREDICTOR OF MYOCARDIAL FUNCTIONAL RECOVERY AFTER THE FIRST ACUTE ANTEROSEPTAL MYOCARDIAL INFARCTION

THE ROLE OF INTRASURGICAL G A M M A PROBE COMBINED WITH LYMPHOSCINTIGRAPHY IN IDENTIFICATION OF SENTINEL NODE IN MELANOMA AND BREAST CANCER

H. Yamawaki (1), M. Ueeda (1), K. Takeda (1), K. Kono (1), M. Obika (1), Y. Nagano (1), M. Imai (1), S. Kusachi (2). (1) Division of Cardiology, Mitoyo General Hospital, Kagawa, Japan; (2) Department of Medical

Technology, Okayama University Medical School, Okayama, Japan. Aim: The preserved tree fatty acid metabolism in an infracted myocardium is an evidence for viability. We conducted this study to clarify whether a washout ratio of t-~31-BMIPPcould use as an indicator of preserved free fatty acid metabolism and a predictor for myocardial functional recovery. Methods: The study population was 23 patients with first acute anteroseptal myocardial infarction. All patients received a successful direct percutaneous coronary intervention within 12 hours after the onset. A resting -~(HTI_1231 BMIPP dual SPECT study was conducted at the 7-10th day. FiReen minutes and three hours alter the injection of both radioisotopes, we collected SPECT data as early and delayed images, respectively. The Bull's eye maps were automatically divided into 25 segments, and we picked up percent uptakes and washout ratios of thallium and BMIPP in both infracted and control area. A coronary angiography and a left ventriculography (LVG) were perfurmed at the 3rd week, and several functional data were compared to S PECT data. Results: Significant correlations were observed between global LVG ejection fraction (LVGEF) and TI %uptake in the inlhrct area (r=0.72. p
S. Koukouraki (1), E. Sanidas (2), A. Velidaki (1), I. Askoxilakis (2), T. Tsagatakis (2), D. Tsiftsis (2), N. Karkavitsas (1). (1) Department of Nuclear Medicine; (2) Department of Surgical Oncology, University

Hospital,Crete, Greece. Pumose: The puq~ose of this study is to evaluate the potential of the gamma ray detecting probe (GDP) in combination with lymphoscintigraphy, to detect sentinel nodes in patients with melanoma and breast cancer. Methods : 60 patients with operable palpable breast turnout and 30 patients with melanoma were estimated befure and during su~ery using a gamma ray detecting probe (Neoprobe 1500) and a lymphoscintigraphy befure surgery. 2-4 hours before surgery, l-l.5mCi 99mTcRe(SC) was injected intradermally around the lesion . A ? camera GE Millenium provided with a LEGP collimator was used. Planar views were taken at I0', 30' and 2 hours p.i. In the same time the GDP was used to locate the node emitting the greatest activity, before and during the surgery. Isosulfan was also used during surgeD'. Results: Both techniques revealed one or more lymphonodes within the first 30 min in all cases. Axillary nodes were revealed in 60/60 patients(100%) with breast cancer. In 1/20 an internal mammary node was also revealed. In all cases of melanoma the localization of SN was succesthl . Lymphoscintigraphy, GDP and isosulthn showed the same nodes in all patients (the node in the internal mammary chain was revealed by lymphoscintigraphy and GDP only) Conclusion: The use of lymphoscintigraphy which allows accurate preoperative localization of the SN in association with the use of GDP which identil~, the SN before the incision, maximise the success of sentinel node localization.

0

DIAGNOSTIC ONCOLOGY 7

PS_266

PS_264

ACTIVITY-DEPENDENT IMAGING OF AFFERENT LYMPH VESSELS IN SENTINEL-NODE SCINTIGRAPHY

RADIOGUIDED BIOPSY OF SENTINEL NODE IN MALIGNANT SKIN MELANOMA L. Feggi (1), G. Soliani, L Bergossi, S. Panareo, E.F. Jorizzo, N. Prandini, A. Ciprian, U. Maestroni, W. Pagani, P. Carcoforo. (1) Nuclear Medicine, St. Anna Hospital; (2) Dermatology Unit, Hospital of Rovigo; (3) Nuclear Medicine, University of Ferrara; (4) Clinical General Surgery, University

of Ferrara, Italy The biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of skin melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviates the need for lymph node dissection; a therapeutic dissection is then performed only in patients with proven nodat disease. Material and methods: The study, began in November 1997, comprised 87 patients aged between 31 and 82 years (mean 59) with histologically proven cutaneous melanoma stages 1 and It (according to the American Joint Committee on Cancer staging criteria) located on the neck in 6 cases, on the trunk in 43 cases, in the upper limbs in 7 cases and in the lower limbs in 31 case. The Breslow thickness ranged from 0.81 to 3.94 mm. All patients underwent preoperative lymphoscintigraphy to demonstrate the lymphatic basins at risk for metastatic disease. The injection of 99m-To nanoeolloid (t0MBq) was performed in 4 intradermafiy spots around the surgical scar of the primary tumour in the morning of the surgery: the scintigraphy was then performed within t hour. [n all the cases of our series we utilized a probe (Pol.hi.tech. sd) specific for collimation for the intranporative detection of SN. After induction of general or local anesthesia, lsosulfan blu vital dye was also injected around the excision scar. Results: Identification of one or more SNs was possible for 86 patients of the 87 patients (98.86%); in only one case it was not possible to identify the SN because the lymphatic mapping was dramatically modified by radical excision of melanoma. The accuracy of Iymphatic mapping was examined by comparing the histopathology of SN and non SN specimens and the result was 100%: i.e. we didn't find any thlse negative. In 1 patient the SN was identified only by probe and not with lymphoscintigraphy. Conclusion: The experience indicates that preoperative lymphosciotigraphy and intraoperative mapping can accurately identify the SN in skin melanoma. The SN biopsy is a cost-effective procedure because reflect the status of the regional nodal basin and represent a minimally invasive and highly accurate screening technique often possible in local anesthesia saving discomfort, time and money.

G. Altenvoerde (1), J. Meller (1), M. Funke (2), K. Lehmann (1), D. Hempel (1), W. Becker (1). (1) Department of Nuclear Medicine, Georg-AugustUniversity, GSttingen, Germany; (2) Department of Radiology, G0ttinge,

Germany. Aim: Sentinel-node scintigraphy imaging of the afferent lymph vessels can supply important anatomical informations to the surgeon. Aim of the retrospecive study was the evaluation wether the imaging of lymph vessels depends on the activity given. Methods: We performed dynamic sentinel-node seindgraphy in 42 patients (age 58y ± 14y, range 31y - 84y, median 62y, 23 male, 19 female) with malignant melanoma. Malignant melanoma were Iocalised at the head (n=l), at the upper limbs (n=8), at the upper part of the body (n=10), abdominally (n=5) and in 18 patients at the lower limbs. We injected 0.1ml Tc99m-NANOCOLL (NYCOMED AMERSHAM SORIN) intraeutaneous peritumorally. Planar acquisition with one-headed-camera (Marconi SX I00, LEHR-collimator, 30 minutes, 15s/frame) was performed, tn 18 patients we injected <50MBq activity (38.3MBq ± 1.9MBq, range 37MBq - 43MBq, median 37.5MBq), 24 received >50MBq activity (98.3MBq ± 18.0MBq, range 58MBq - 119MBq, median 102.5MBq). Result: In 40 (90%) of the patients the sentinel lymph node could be identified. The afferent lymph vessels could be imaged in only 3 (16.7%) of the patients with activities <50 MBq. Conversely the afferent lymph vessels were seen in 23 (95.8%) of the patients with higher activities >50MBq. Conclusion: In sentinel-node scintignaphy the use of higher activities (>50 MBq) is necessary for the identification of the afferent lymph vessels, without a significant increase of the patients radioactive b'qrden. This can be helpful if an en-bloc-resection of tumor and lymph vessel is planned.

1143

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DIAGNOSTIC ONCOLOGY 7

PS_267

PS_269

ACCURACY ENHANCEMENT OF LYMPHOSClNTIGRAPHIC IDENTIFICATION AND LOCALIZATION OF SENTINEL NODES (SNS) OF CUTANEOUS MALIGNANT MELANOMA (MM) BY TEMPORARY SHIELDING OF HOT SPOTS

THE NUCLEAR MEDICINE GLOBAL APPROACH TO SENTINEL NODE (SN) TECHNIQUE IN PATIENTS WITH BREAST CANCER AND CUTANEOUS MELANOMA

S. Maza (1), L. Geworski (1), V. Ivancevic (1), A. Zander (1), E. Dr~ger (2), H. Winter (2), W. Sterry (2), D.L. Munz (1). (1) Clinic for Nuclear Medicine; (2) Clinic for Dermatology, Charite, Berlin, Germany. Aim: The sentinel lymph node mapping offers a minimally invasive way of assessing the regional lymph node basins draining a cutaneous melanoma. The detection of the ,,true" SN(s) and, hence, the staging of regional lymph nodes is essential for management and prognosis in MM. In this study it was prospectively evaluated whether simple temporary shielding of hot spots could improve the accuracy of SN diagnostics. Method: In 100 consecutive MM-patients (45 women. 55 men; age, 11-91 years) dynamic and static lymphoseintigraphy in various views was performed after strict intracutaneous application of Tc-99m-nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumor (3Ix) or the biopsy scar (69x, safety distance I cm) (gamma camera, LEAP collimator, 256x256 matrix). The images were acquired up to 2 hours p.i. with and without temporary lead shielding of the most prominent hot spots (injection site, drainage area (DA). Results: In 33/100 patients I-2 additional less tracer accumulating or smaller (<1.5 cm) SNs were detected after shielding of the prominent hot spots in the DA. In 4/33 patients metastases were found even in the less accumulating/smaller SNs, the non-SNs removed in the subsequent elective lymph node dissection were tumor negative. In 3/100 patients hot spots in the DA proved to be lymph vessels (LV), intersections or vessel ectasies after temporary shielding, hence, the node interpreted secondary at first glance proved to be the real SN. In 2 of these patients lymph node metastasis was histologically confirmed, the non-SNs were tumor free. In 7/100 patients the exact course of LV could be mapped after shielding, in one of these patients 2 additional SNs (with metastasis) could be detected. In total, 43/1011 patients the temporary shielding of hot spots in the DA showed an improvement of the accuracy of lymphoscintigraphy. Conclusion: The temporary shielding of prominent hot spots in the DA of a MM leads - in combination with dynamic acquisition in various views - to accuracy improvement of the identification and localization of SNs by lymphoscintigraphy.

S. Severi, F. Matteucci, C. Corbelli. Nuclear Medicine Dpt, Faenza, Italy. INTRODUCTION: the SN technique has been largely developed in recent years and great will be the request of tymphoscintigrapby in the future also from outlying centre. In our department we cover four different hospital and deal with 13 different surgeons at least. In this conditions it is important to offer a complete assistance from the SN localization to the surgical excision, in order to ensure an high exam sensibility. MATERIALS: in the last two years we performed 140 SN procedure; I10 were done for breast cancer and 30 for melanoma. As a standard we did a subcutaneous injection of 17 MBq 99roTe Nanocoll in 0,2 ml, in melanoma and superficial breast cancer. In breast cancers distant more than 1,5 cm from the skin we did a deep injection with the same radioactivity in 0.5ml under echography control. In deep breast turnouts we had sometime (10%) the necessity to perform a second superficial tracer injection due to a lack of SN localization. Dynamic and static view were acquired with particular attention to the lateral and oblique projections to get either the marker of the SN projections on the skin and the identification of possible secondary sentinel lymphnodes involved. RESULTS: thanks to the mentioned procedure we had a 100% SN localization and also a 100% SN surgical excision with a plateau learning curve of all the 13 surgeons involved. The effectiveness of the SN excision was made by probe measure and, when ever possible, gamma camera images. The number of double SN is about 15% and we also had, in one melanoma of the back, 3SN. The mean number of lymph-nodes exceeded was 4 standing the very little wound performed in patients that were generally awake. CONCLUSIONS: the necessity to perform an high number of procedure for SN detection schould not cause a lack of Nuclear Medicine personnel presence also considering the high number of surgeon frequently involved. Moreover the complexity of the procedure, number of SN involved and differentiation between the lymph-node exceeded, require the presence of well trained operators in order to avoid false negative results.

PS_268

PS_270

LYMPHATIC MAPPING AND SENTINEL LYMPH NODE BIOPSY IN MELANOMA

SONOGRAPHIC CARACTERISTIGS OF SENTINEL LYMPH NODES IN PATIENTS WITH MALIGNANT MELANOMA

G. ~ivi (1), H.B. Sayman (11, Y. Aydm (2), H. Arslan (2), K. (3zcan (11, B. Kanmaz (1), L. Kabasakal (1), I. Uslu (1). (1) Department of Nuclear Medicine; (2) Department of Plastic Surgery, I.U. Cerrahpasa Medical Faculty, Istanbul, Turkey.

M. Lacic (1), M. Stance (2), M. Ivkic (3). Z. Stance (4), Z. Kusic (1). (1) Department of Ontology and Nuclear Medicine, University Hospital ; (2) Department of Surgery, Cancer Institute, Zagreb, Croatia; (3) Department of Head and Neck Surgery, University Hospital ; (4) Department of Surgery, University Hospital, Zagreb, Croatia

Aim: Lymphatic mapping with selective lymphadenectomy is an attractive approach in melanoma patients to avoid unnecessary elective lymph node dissectiun (ELND). We performed lymphoscintigraphy (LS) in 20 patients with strong clinical suspectiun of melanoma (13) or diagnosed as melanoma by biopsy preoperatively (7). 8 patients had melanoma of the extremities (1 upper, 7 lower), 4 patients had melanoma of the trunk and 8 of the neck. Methods: Prior to surgery, 37 MBq Tc- 99m tin colloid in Ice was injected ID in 4 quad. of lesion in equal doses to define the regional lymphatics and sentinel lymph node (SLN). Following injection, 3 rain dynamic images were acquired until any SLN(s) appeared. In all cases, a CdTe gamma probe (GP) was used to skin-mark the SLN in accordance with the peak count rate observed and vital blue dye (VBD) was also used during smgery. After wide excision of the primary lesion, investigation of the SLNs were also continued intraoperatively and the operation was completed by SLN(s) excision. The pathology of the primary lesion and SLN(s) were defined by HEO staining. Results: In 1 patient the primary lesion was found to be a basal-cell carcinoma with a metastatic SLN. Preoperatively in a|i cases at least I SLN could he detected by LS and GP. In 1 case, while only I SLN was detected by LS and GP preoperatively, it is found to be a pack of SLNs intraopemtively and pathologically. Each SLN which was detected preoperatively could be verified intraoperafively by GP and VBD except 2 cz~es. One of them was unable to be detected intraoperatively despite it was visualized preoperatively, because of a timing problem. The other was detected pro and intraoperatively by GP but could not be visualizod by VBD. In one case intraoperative mapping also revealed additional SLN sites. In 13 cases, SLN(s) were invaded by malignant cells. These patients underwent axillary LND (1), inguinal LND (3) and radical neck dissection (2) by ranperation. SLN(s) were the only malignant LNS in 5, while in 1 case 2 more LNS other than SLN were found to be invaded by malignant cells pathologically. No distant metastases were found in any of the cases. Conclusion: These results demonstrated that lymphatic mapping and SLN biopsy using a GP is an attractive approach in melanoma to avoid morbidity and mortality caused by unnecessary ELND.

1144

Aim: The aim of this study was to evaluate the sunographic characteristics of the sentinel lymph nodes (SLNs) in patients (pts) with malignant melanoma (MM). Methods: Sentinel lymph node scintigraphy was parformed in 124 pts, 57 female and 68 male, aged from 12 to 80 years (mean 49 years). Up to 74 MBq ofTc-99m nanocolloid were injected intradcrmatly around the skin lesions (4 pts) or the biopsy scar (120 pts), followed by dynamic planar imaging until the SLNs became visible. The SLNs were marked on the skin using an external radioactive marker. Gray-scale sonogrephy, followed by Color and Power Doppler analyses have been done using a 10 MHz linear probe. A hand held gamma probe and/or a blue dye technique were used for intra--operativ¢ mapping of SLN. Results: SLNs were successfully detected in 123 from 124 pts on scintigraphy. 199 SLNs (1.6 per pts) were visualized on scintisraphy in 162 lymphatic basins (1.4 per pts). Among the 53 operated pts. 13 (25%) had positive SLN for MM. In 7 (54%) of these 13 pts SLN was the only metastatic node. 131 regional lymphatic basins in 94 pts were evaluated sonographicaly. Sonography was unable to differentiate SLNs from surrounding fatty tissue in 34(36%) pts. In 49(52%) pts SLNs had benign sonographie appearance. SLNs changes suspected to be metastatic lesions were detected in I 1 (12%) pts on sonography. In 9(82%) of these 11 pts suspected metastatic lesions were histologically confirmed. Four (31%) of 13 pts with histologically proven SLNs metastasis had no sign of disease on sonography. A signal of increased blood flow within SLNs was detected in 7/94 (8*/*) pts on Color and Power Doppler sonography. Conclusion: Scintigraphically guided, preoperative, sonographie evaluation of drained lymphatic basins seems to be a reasonable diagnostic approach to the management of pts with MM.

• DIAGNOSTIC O N C O L O G Y 7

PS_271

PS_273

GAMMA-PROBE-GUIDED SENTINEL LYMPH NODE BIOPSY IN MELANOMA PATIENTS

THE USE OF PREOPERATIVE LYMPHOSCINTIGRAPHY AND INTRAOPERATIVE GAMMA PROBE GUIDANCE IN THE DIAGNOSIS OF SENTINEL NODE IN MALIGNANT MELANOMA

M. Papos (1), J. Varga (2), T. Sera (1), M. Lazar (1), K. Kapitany (2), J. Olah (2), I. Korom (2), G. Mohos (2), A. Dobozy (2), L. Pavics (1). (1) Department of Nuclear Medicine; (2) Department of Dermatology, University of Szeged, Szeged, Hungary. Correct sentinel node (SN) Iocalisation plays a crucial role in the planning of the surgical approach in melanoma patients. The value of preoperative and intraoperative SN Iocalisation techniques is analysed, Forty-three patients (25 males, 18 females, mean age: 52 years, range: 30-77 years) with malignant melanoma (MM) were investigated. The Iocalisations of the MM were as follows: trunk: 20, extremities: 23. On the Clark classification: l: 7, II: 25, IV: 11). Twenty-four hours before surgery, the SN was localised visually by a gamma camera technique. For intraoperative Iocalisation of the SN, the gamma-probe and blue dye methods were applied. Preoperatively, SNs were detected in all patients (43/43, 100%). One SN was detected in 35 cases (81%) and two SN were verified in 8 cases (19%). The preoperative localisation of the SNs matched with the intraoperative gamma-probe findings in 39 patients (90%), wheeas there was a mismatched Iocal isation in 4 patients (10%). The gamma-probe and blue dye techniques gave identical SN Iocalisation in 38 cases (88%). In 2 cases, the SNs were not stained, and in another 3 patients the blue SNs could be found only with the help of the gamma-probe. The SNs were tbund to be positive for MM involvement by histology in I I cases (25%). Block dissection was carried out only in these patients. Histological analysis of the removed lymph nodes revealed MM involvement in 2 cases. Conclusion: Preoperative SN Iocalisation is helpful for the planning of the surgery. The intranperative gamma-probe technique is the most accurate method for the Iocalisation of SN. The biopsy of SN can reduce the number of unnecassary lymph node dissections.

V. Voliotopoulos (1), G. Limouris (1), A. Stavraka-Kakavaki (1), I. Ioannovits (2), D. Tsoutsos (2), L. Vlachos (1). (1) Areteion University Hospital, Nuclear Medicine Dept; (2) G.Genimatas General Hospital, Plastic Surg.Dept, Athens, Greece. Purpose: The detection of the sentinel node (SLN) in patients with malignant melanoma is of considerable prognostic value. Aim of this study was to localize the sentinel node either with lymphscintigraphy or using ~ntraoperative~y gamma probe guidance. Methods:120 patients, in three years, with histologically proven malignant melanoma were preoperativelly examined with lymphoscintigraphy using 300 ? Ci Tc-99m-nanocolloid intradermally around the primary lesion. The first lymph node identified was marked on the skin of the patient. After that the patient was reffered to the operation room,were using the gamma probe the surgeon was guided towards the site with high uptake of the previously administrated radiotracer. After excision of the node, SLN, the lympatic basin was cheked for radioactivity. Results: The "hotest'lymphonode was found in all patients in the preoperativelly marked lymph node. Histolically in 20 patients metastatic involvment of the lymph node was found and the surgeons proceed in radical lymph node excision. Conclusion: The preoperative lymposcintigraphy and the intraoperatively mapping with the gamma probe is of a great importance for the exact localization of the SLN

c, ou

PS_272

PS_274

CLINICAL ROLE OF SENTINEL NODE BIOPSY IN SKIN MELANOMA

DIAGNOSTIC VALUE OF DELAYED SCANS IN THE DETECTION OF SENTINEL NODES IN PATIENTS WITH MALIGNANT MELANOMA

J. Sequeira (1), A.I. Santos (1), C. Martins (2), A. Paraes (3), V. F'arricha (3), S. Carmona (1), M.J. Brito (4), J. Giria (3). (1) Servi(~o de Medicina Nuclear; (2) Servk;o de Dermatologia; (3) Servi~;o de Cirurgia; (4) Servk;o de Anatomia Patolbgica, Almada, Portugal Introduction. Elective lymph node dissection (ELND) for patients with malignant melanoma of the skin (MM) was classically indicated in patients with primary lesions >- 3ram of thickness. At present, although ELND is still controversial, the majority of the authors proposes the biopsy of the first tumour draining lymph node, sentinel node (SN), which can be identified by means of radionuclide techniques. Aim of the study. To demonstrate that, in patients with MM, the sentinel node biopsy is a much more accurate method for selection of candidates for ELND. Patients and Methods. We have selected 28 patients with MM with primary lesions _>1 mm of thickness and without clinical suspicion of lymph node involvement (10 with MM of the legs, 9 of the trunk, 6 of the arms end 3 of the head and neck). 26/28 patients had melanoma < 3 mm thickness. A lymphoscintigraphy (LS) was performed, using planar acquisitions (Matrix 128), beginning immediately after pericicatricial or peritumoral i.d. injection of colloidal (Re) sulphide labelled with Technetium-99m, to define the regional lymphatic basin and identify the sentinel node. In the same day, biopsy of the sentinel node was performed with per-operatory (PO) detection using a surgical gamma probe in all patients and, in 17 patients, also with patent blue (PB) dye injection. The pathological examination of the sentinel node included examinations of hematoxilin-eosin staining and immunohistoehemistry for S-100 and HMB45 MoAB. Results. The sentinel node (SN) was detected in a total of 28/28 (100%) patients (LS+PO+PB); LS+PO correctly localized SN in all (100%) patients, although PB only localized 10/17 (59%) SN. Five SNs of the retrieved were positive for metastases. Three patients with metastases found in SN had tumours with thickness of 5 ram, 3 mm end 1,1 mm; the other two had unknown thickness. These patients were submitted to elective lymph node dissection; in 2/5 eases SN was the only positive node. Conclusions: Lymphoseintigraphy and gamma probe are useful for identification of SN, allowing for biopsy to be performed. This technique is a more reliable method for selecting patients for lymphadenectomy than the thickness of the primary lesion.

t~ ¢..

R Koranda (1), M. Myslive~ek (1), P. Benes (2), S. Pallov~i (3), M. Kohoutek (2), V. Huak (1), M. Kaminek (1). (1) Dept. of Nuclear Medicine; (2) Dept. of Oncology; (3) Dept. of Plastic Surgery, Palack University, Olomouc, Czech Republic. Aim: Delayed scans are considered to be an essential part of lymphoscintigraphic detection of sentinel lymph nodes (SN) in patients (pts) with malignant melanoma (MM). The purpose of this study was to evaluate the diagnostic impact of these scans. Methods: 61 consecutive pts with 62 MM were studied using the lymphoseintigraphy (LS). 80 MBq of 99mTc-nanocolloid in 0.5 ml was administered in six to eight small portions intracutaneously around the melanoma or on both sides of the scar after diagnostic excision. The initial study (IS) was started immediately a~er administration of radiopharmaceutical. Dynamic scintigraphy was performed for 6 rain acquiring l frame/20s. Subsequently, a series of static scintigrams (100s acquisition time) in anterior and posterior and lateral projections was made 5-45 min p.i.; patient's body contour was outlined by moving a 57Co marker. The delayed scan (DS) was acquired 2-3 hours p.i. All scans were performed using a dual-head gamma camera equipped with parallel-hole HR co/limator. Results: Localization of MM Nr. of MM Nr. oflTmphatic basins on IS Nr. of I;¢mphatic basins on DS Nr. of SN on IS Nr. of SN on DS Better visualization of nonsentinel lymph nodes on DS than on IS

trunk 40 66 67 86 87 21

extremities 22 23 23 41 42 13

total 62 89 90 127 t29 34

SN were detected in all MM during IS, mean time of SN visualization being 7.3 min (median 5 rain). 2 additional SN and 1 lymphatic basin were found on DS but these findings did not change the staging of MM in our study, Conclusions: Our results indicate that the most important part of lymphoscintigraphic detection of SN is IS enabling precise differentiation between SN and early imaged second- and third-echelon lymph nodes (LN). Delayed scans detect unknown SN relatively seldom, however, they gi~,e often more infurmation about nonsentinel LN. In spite of the former fact we consider DS to be an integral part of lymphoscintigraphic detection of SN

(n

.= O. L ¢n O 13,

• DIAGNOSTIC ONCOLOGY 7 / DIAGNOSTIC ONCOLOGY 8 Probe

PS_275 SENTINEL NODE DETECTION WITH MALIGNANT SKIN LESIONS

TC99M

-

DEXTRAN IN

S. Neubauer (1), I. Mena (1), R. Schwartz (2), J.C. Acevedo (2), R. Iglesis (2), L. Gomez (2), A. Leon (2). (1) Department of Nuclear Medicine; (2) Department of Surgery, Clinica I_as Condes, Santiago, Chile. Purpose : The aim of this work is to evaluate the ability of lympboseintigraphic sentinel node identification with Tc99m - Dextran node in skin lesions. Materials and Methods : Forty tbur consecutive patients, 23 women and 21 men, 48 _+ 17 years, (mean age + SD), ( range 5 - 79 years ), had perilesional intradermal injection of Tc99m-Dextran 2 hours befure surgery. Gammacamera serial images and gamma detection with a handheld probe were used to direct sentinel node biopsy pre and intraoperatively. The skin lesions were 41 melanomas , 2 Merkel cell tumors and I squamous cell tumor. The lesion was located in the limbs in 21 cases, in thorax and pelvis in 19cases, in the head and neck in 4 cases. Results : In 42/44 patients lymph channels and a total of 56 sentinel nodes (one to three sentinel nodes/petient) could be demonstrated. In two patients, one with melanoma of the dotsum and one with melanoma of the face, lymphoscintigraphy |ailed to show lymph channels or sentinel nodes. All 56 sentinel nodes could be fuuod and excised at surgery. They were submitted to microscopic analysis. In our study group 8 sentinel nodes had metastasis corresponding to five patients with melanoma graded as Breslow 4, one patient with melanoma graded as Breslow 3 and two patients with melanoma of unknown originaI thickness. Conclusion : lymphoscintigraphy with Tc99m-Dextran provides satisfactory definition of lymph channels and sentinel node localization to direct surgery by means o f a haodheld probe. Unexpected drainage sites and more than one lymphatic channel draining the tumor bed demonstrated by lymphoscintigraphy directed the surgeon in patients with skin lesions to a rational lymph node excision.

Detector Diam detector FWHM

Neoprohe I 0tl0 Cd-Te(Zn) 12mm

Neoprohc 2000 Cd-Te(Zn) 14mm

Scintiprobe

EuroProbe

Navigator

CsI(TI) 18mm

CsI(TI) 14mm

Cd-Te(Zn) 14ram

Crystal Probe Cd-Te(Zn) 14ram

3.6

1,6

1,8

2,4

1,5

1,8

Conclusions: In our opinion, considering the actual use of the probes, the simulation technique is very useful to correctly evaluate the typical characteristics in a standard situation specifical for a sentinel node localization.

DIAGNOSTIC ONCOLOGY 8

PS_277

PS_276

INSTITUTIONAL LEARNING CURVE FOR SENTINEL LYMPH NODE B I O P S Y IN BREAST CANCER: A STEP TOO FAR FROM VALIDATION ISSUES?

USEFULNESS OF A SIMULATION MODEL COMPARING THE PHYSICAL CHARACTERISTICS OF 6 GAMMA PROBES S. MeSs±ha (1), R. Tarducci (2), I. Palumbo (1), B. Palumbo (1), T.O. Moschini (1), S. Ricci (2), R. Palumbo (1). (1) Dept. of Nuclear Medicine, University of Perugia; (2) Unit of Biochemical Physics, Perugia General Hospital, Italy. Aim: The aim o f our study was to pertbrm a simulation model with 6 different gamma probes able to reproduce an idealised form of the clinical situation. Methods: The probes studied are: Neoprobe 1000 (Neoprobe Corporation), Europrobe (Eurorad), Scintiprobe M RI 0 0 (Polytach), Neoprobe 2000 (Neoprobe Corporation), Crystal Probe (Crystal GmbH), Navigator (United States Surgical Corporation). Stint±probe MR I 0 0 and Europrobe are equipped with a CsI(TI) detector, while all the other probes have a CdTe(Zn) detector (with a diameter of 12 mm for Neoprobe 1000, of 14 for Neoprobe 2000 and Navigator). Measurements were performed in a water bath (2/3 filled) being the source (37 MBq of 99roTe) positioned in a box of lead with a hole of 1 mm of diameter. The source block was placed either at I cm or at 3 cm of depth, in order to better simulate the injection site and node position. The probe held per!0endicular to the water surface by a clamp was mechanically moved for a frame o f I mm. Data acquired (Cps/MBq) were organized in order to obtain a simulation process. The position of injection site and of the node was reconstructed by overlapping measurements carried out with the source either at 1 cm of depth or at 3 cm of depth. The data obtained with the source at 3 cm of depth were reduced of a factor of 1/10 (to simulate the ideal node uptake) and moved along the axis of abscissas. Results: In our study the different probes show similar characteristics in the common practical, except Stint±probe MR 100 that, being equipped with a dedicated software, allow a management by computer. The probes provided with a CsI(T1) detector are confirmed to be more sensitive with respect to probes with a Cd-Te(Zn) detector. Among the last mentioned is the most sensitive was Neoprobe 2000, probably for the type electronic equipment associated with detector. Furthermore about the spatial resolution, reported as the FWHM, Neoprobe 2000 with a 14 mm detector, Stint±probe MR 100 with a 18 mm detector and Navigator with a 14 mm detector disclosed the best results, while Neoprobe 1000 showed the worst resolution, as evidenced in the table.

114E

S. Drago (1), M. Catarci (1), G. D'Errico (2), L. Mar±no Cosentino (1), G. Longo (1), M. Rernedi (1), S. Negrini (1), G. Ricci (1), G.B. Grass± (1). (1) Surgical Oncology, San Filippo Neri Hospital, Rome, Italy; (2) Nuclear Medicine, Catholic University, Rome, Italy. Aims: To assess the learning curve and institutional validation series of sentinel lymph node biopsy (SLNB) in breast cancer in a prospective study on 30 consecutive cases carried out in a major community hospital. The main aim o f this evaluation was the validation of the center for enrolling patients in an ongoing multicenter national trial. Methods: Over a twelve months period, thirty consecutive patients with preoperative evidence ofT1-2 breast cancer and clinically negative axillary nodes were enrolled in the study upon agreement to an informed consent on the investigational purposes of the study. They were all submitted to preoperative lymphoscintigraphy, intraoperative injection of a vital dye (Blu Patent V 2,5%) and scanning with a hand-held gamma probe (Navigator=, U.S.S.C., Norwalk, U.S.A.) performed by one of four surgeons in close cooperation with the nuclear medicine specialist. Axillary lymph node dissection was completed in all eases. No case was excluded and final analysis was carried out on an intention-to-treat basis. Main outcome measures were length of the procedure, rate of visualization of the sentinel node, overall accuracy and false negative rate. Results: We recorded no toxicity from the injection of the tracer or the vital dye. Overall length of the procedure (mean ± sem) was 16.4 ± 5,8 minutes. It was significantly higher in the first five cases (24.2 ± 2,7) than in the last five ones (9.7 ± 2.1). One or more sentinel node(s) were identified using all the three methods in all but two eases (93.3 %). Accuracy in detecting axillary metastasis was 86,6% (13 out of 15 cases). Overall accuracy rate was 92.8% (26 out of 28 cases). We recorded two false negatives (6.6%). Conclusions: We accepted a close cooperation with the nuclear medicine specialist and followed the guideline to use both vital dye techniques and nuclear medicine imaging in order to enhance the accuracy rate during the learning curve. Thirty consecutive cases were sufficient to acquire the technical skills in order to successfully perform the procedure, but overall accuracy did not match the recommendations of a national scientific board. Nonetheless. every day many surgeons are becoming eager to perform SLNB in breast cancer without axillary dissection beyond any trial, ofien under the pressure o f patients aware o f the procedure and media advertising, without asay consideration o f the risk o f disrepoting the technique by adversely affecting the prognosis o f their patients. It appears more logical and appropriate to separate the two issues by overtaking the learning curve and then proceeding to the evaluation of institutional series for validational purposes.

•

DIAGNOSTIC ONCOLOGY 8

PS_278

PS_280

THE SMALL BREAST CANCER TREATMENT WITH COMPLETE SENTINEL NODE (SN) PROCEDURE: LOCAL VERSUS GENERAL ANAESTHESIA

RADIOGUIDED SURGERY: A NOVEL APPROACH IN PATIENTS WITH MALIGNANT GLIOMA

S. Severi, E Matteucci, C. Corbelli. Nuclear Medicine Dpt, Faenza, Italy. INTRODUCTION: although the definitive results of the trials pertbrmed to verify the accuracy of the SN procedure are not published, many patients (pt) are conscious of the possibility to avoid axillary dissection in case of SN negativity and ask to be treated in this way. We tested the feasibility to operate small breast cancer in general and local anaesthesia in a group of voluntary pt, in order to veri~, which is the more comtbrtable, practical and economic approach. MATHERIALS: we studied pt with proved monolbcal invasive breast cancer smaller than 1,5 era., never operated bctbre, with clinically and ecographically negative axilla, who subscribed a detailed intbrmed consensus. Our population was divided in two group of 25 pt each (GI and G2) afferent from two different hospitals. In GI pt were operated in general anaesthesia with frozen sections study either of the tumour and of the SN. The axillary dissection was performed in positive SN. In (G2) pt were treated in local anaesthesia with quadrant or nodulectomy of the tumour and SN excision. A delayed axillary dissection was performed tbr SN positivity, The lympho-scintigraphy was pertbrmed the day betbre surgery injecting 99mTc 18MBq Nanocoll superficially (in 0.2 ml) or deeply (in 0,4 ml) according to the tumour distance from the skin (cut off [,5 cm). Dynamic and late static view were acquired also comprehensive of lateral and oblique. In the second day the pt was operated atler a probe mapping and with a superficial reinjection of the unfound SN deeply injected. RESULTS: ag the SN were ~bund with 10% reinjection of the cases deeply injected. "l'he Excision of the SN was always efii:ctive and in 12% we had a double SN. Of the G I pt 6 had the SN positive and were treated with axiltary dissection that showed a complete negativity of all the lymphnedes. In I case the frozen sections of the SN exam were negative and the final diagnosis positive. This pt had a delayed dissection. O f the G2 pt 2 had the SN positive and had a delayed axiltary dissection with negative axillary lymphnodes. The mean length of the GI procedure was 90-120 min whereas the G2 mean duration was 45 rain. All the pt were included in an accurate Ibllow up. CONCLUSIONS: in our opinion the complete SN procedure may be applied only after a spetitle pt request and in small breast cancer. In these cases the operation may be performed in local anaesthesia to have turnout quadrantectomy and SN excision all together. This kind of procedure offers minor invasivity, secure diagnosis, lower morbidity, ~b.st recover and economic gain

G. Boni (1), G. Parenti (2), G. Manca (1), S. Suriano (1), B. Lenzi (2), G. Grossi (2), M. Grosso (1), D. Volterrani (1), E Bianchi (1), R. Bianchi (1). (1) Division of Nuclear Medicine, Department of Oncology; (2) Division of Neurosurgery, Department of Neurosciences, University of Pisa, Pisa,

Italy. Surgical cytoreduction is the first step in the treatment of cerebral gliomas. Although the advancement o f neuro-lmaging t~cilitates the surgical approach and the preservation of functional brain areas, radical tumor removal is still a problem. In order to obtain a better localization and extension of the tumor during surgery, we developed a novel radioguided surgical technique. It is based on the use of a gamma-probe Ibr the intraoperative detection of the cerebral neoplastic tissue, which was previously labeled with an oncotropic radiopharmaceutical. The protocol consisted of two steps. In the preoperative phase, the mapping of the prolifera. . . . ,,,gm . . tive areas of the tumor was obtained by the l.v. rejection of 740 MBq of Tc-tetrotosmm. A SPET scan o f the brain was per/brined 30-60 rain alter the injection to check the presence and the distribution of the radiopharmaceutical within the tumor. Finally, the surgical procedure was pertbrmed within 24 hours fi'om the scan. We used a 10 mm diameter-collimated probe connected to a gamma ray detector (Scinti Probe MR 100 - PoLhi,tech., Aquila - Italy) to scan the neoplastic lesion. The counts were recorded on the neoplastic area and on the normal brain tissue and a tumor-to-background ratio was calculated, Then the surgeon started to remove the neoplasm and used the gamma probe to check the radioactivity on the resection margins and estimate the tumor remnants. The removed specimens of the tumor were counted with the probe and analyzed histopatologically. We studied 16 patients (10 men and 6 women, age range 35-76 years) affected by malignant gliomas (tumor size range 15-80 mm). There were five patients with recurrent neoplasms. A good uptake of the tracer was demostrated in all the tumors by scintigraphy and by the intrasurgical gamma-prebe measurements. The tumor-to-background ratio ranged from 1.4 to 3.7. Scintigraphic and gamma-probe data regarding tumor localization and extension were correlated with the radiological imaging and the surgical findings. The intraoperative detection by gamma-probe was easy to pertbrrn and uset~tl to localize the tumor remnants. In conclusion, these preliminary data suggest that this radioguided surgical technique could help the neurosurgeon to distinguish the neoplastic tissue from the macroscopically intact brain tissue and to pcr|brm a better resection of the tumor.

0

PS_279

PS_281

MISTAKES IN DETECTING THE SENTINEL LYMPH NODE, WHO IS RESPONSIBLE FOR THEM?

RAD1OGUIDED SURGERY IN PRIMARY HYPERPARATHYROIDISM

E Puns, S. VidaI-Sicart, E Martin, M. Ortega, J.J. Mateos, D. Fuster, EJ. Setoain, A. Muxi, E Lornefia. Department of Nuclear Medicine,

Hospital Clinic, University of Barcelona, Spain. Sentinel lymph node (SLN) technique has led to the rebirth of lymphoscintigraphy as wefi as having provided an opportunity tbr nuclear medicine physicians to take part in surgical operations. However, when a SLN is not tbund or it is erroneously identified, nuclear medicine physicians are blamed. AIM: To try to explain the reasons for erroneous SLN identification based on our experience. METHOD: We retrospectively reviewed oar first 500 patients who had undergone the SLN technique. Three hundred and forty five melanoma patients (Breslow > 0,76 and AJCC 1/11 stage), 140 breast cancer patients (65 TI and 75 T2) and 15 vulvar sqaamous cancer patients (8 TI, 4 T2 and 3 T3 tumours) were studied. Lymphoscintigraphy was performed on all of them the day before surgery by injecting 74-111 MBq of nanocolloid-Tc99m. After radiotracer administration, dynamic and static images were acquired. The SLN location was marked externally on the skin. On the day of surgery, blue dye was injected about 15 minutes before surgical incision. A hand-held gamma probe was used to precisely Iocalise the SLN. RESULTS: In melanoma patients SLN identification was incorrect in 2,9% (t0 patients). Out of the 10 patients, SLN was not identified ia 3 cases (2 of them with a conclusive lymphoscintigraphy), in 2 eases the surgeon decided not to harvest the SLN (to avoid facial nerve damage) and in the remaining 5 the SLN was a false negative finding (in three of them the pathological molecular studies showed a positive result for metastases). In breast cancer patients the SLN identification was not correct in 10.7% (15 patients). From this group, SLN was not identified in 9 cases (in 5 of them the surgeon/nuclear medicine specialist team was not the regular SLN surgical team) and in the remaining 6 a false negative result was observed (immunohistocbemistry studies showed micrometastases in 4 of them). In the vulvar squamous cancer patients SLN was not detected in one case (6.6%) which was a T3 turnout. CONCLUSIONS: SLN identification needs the implementation and collaboration of several physicians of diverse specialities. This particular point can imply a number of mistakes in the SLN identification (surgical team changes, absence of thorough histologie study). However, SLN technique allows performing a correct stagement and avoids considerable morbidity in these patients. However, it is not possible to completely explain why, in a very small percentage of cases, the SLN was erroneously identified.

N.0. KQ~Qk (1), S. Ko(~ak (2), P. Ancan (1), G. Aras (1). (1) Department of Nuclear Medicine; (2) Department of Surgery, Ankara University, Ankara,

c

e~

Turkey. Surgical neck exploration is usually made in primary hyperparathyroidism (PHPT). Localisation o?the adenoma or detection of hyperplasia may reduced the operation period and limit the extention of the surgery. In this study the efficacy of preoperative Tc-99m MIBI scintigraphy and intraoperative gamma probe was evaluated. Material-Method: 6 patients with PHPT preoperative Tc-99m MIBI parathyroid scintigraphy and intraoperative gamma probe (IGP) was used surgical neck exploration. Results: Parathyroid adenoma was observed in 2/6 patients in the scintigraphy (the right retrnclavicular region and the left lobe of the thyroid). Both of them were clearly detected by IGP during the surgery and easily removed by the surgeon in a short time (35 rain) with a small incision. Pathologic examination confirmed to the parathyroid adenoma. Abnormal MIB[ uptake was not observed in scintigraphy in 4/6 patients. Parathyroid hyperplasia was identified with IGP in two of thase patients and removed then. Conclusion: Preoperative Tc-99m MIBI scintigraphy and use of IGP may limit the exploration and then operation time and surgical complications reduce.

1

• DIAGNOSTIC ONCOLOGY 8

PS_282

PS_284

LYMPHOSClNTIGRAPHY AND DETECTION OF SENTINEL NODES WITH SURGICAL GAMMA PROBE IN HEAD AND NECK CARCINOMA

DEPICTION OF SENTINEL LYMPH NODES IN GASTRIC AND RECTAL CANCERS

N.0. KO~;Lik(1), P. Artcan (1), A. Demiretler (2), G. Aras (1). (1) Department of Nuclear Medic{he; (2) Department of Otorhinolaryngology, Ankara University, Ankara, Turkey.

K. Yokoyama (1), S. Kinami (2), S. Kinuya (1), K. Nakajima (I), G. Nishimura (2), 1". Kobayashi (2), K. Miwa (2), T. Michigishi (1), N. Tonami (1). (1) Department of Nuclear Medicine; (2) Second Department of Surgery, Kanazawa University, Kanazawa, Japan.

The prognosis in patients with head and neck cancers due to lymphatic metastasis. In the presence of micrometastasis in the first draining lymph node, the surgical exploration must be extended to the contriateral and ipsilateral lymph nodes. Lymphoscintigraphy and surgical gamma probe to detect lymphatic drainage and sentinel lymph node has been commonly used in breast cancer and melanoma. Aim: The aim of this study was to evaluate the efficiency of lymphoscintigraphy to show lymphatic drainage and the value of surgical gamma probe to detect sentinel lymph node in head and neck cancers. Material-Method: 8 patients with head and neck cancer were included in the study (2 larynx cancer, 2 parotid carcinoma, 1 gingiva cancer, 2 tongue cancer, 1 tonsillar cancer). In all patients, USG, CT and/or MRI demonstrated no signs of lymph node metastasis. 148 MBq Tc99m filtered sulfur colloid was injected peritumorally (37 BMq/01ml each at 4 different locations) all the patients except two larynx ca patients. Planar images were obtained of 30, 45, 60 and two and four hours from anterior, right lateral, left lateral if necessary oblique views. 2 patients with larynx ca were evauiated only with surgical gamma probe without tymphoscituigraphy because of the necessity of general anesthesia for injection. During the operation, the lymph nodes which were detected with surgical gamma probe were explorated and histopathalogical examinations were made. Results: The lymphatic drainage were clearly demonstrated with lymphoscintigraphy in all patients, especially cross drainage, ipsilateml and contrlateral drainages were shown. They were also identified with surgical gamma probe. Histopathological examinations were made and metastasis were detected in 6/8 patients. Conclusion: Lymphoscintigraphy combined with surgical gamma probe is feasible method to detection of lymphatic drainage and sentinel lymph node(s). This technique may guide the surgeon to decide the extent of resection when micrometastasis is observed in sentinel lymph node in the patients with head and neck cancers.

Sentinel lymph node biopsy has provided less invasive surgery for breast cancer and melanoma. We have attempted to apply the sentinel node concept to gastrointestinal (GIT) cancer's, which are the major cause of cancer death in Japan. Moreover, it is favorable for the patients' quality of life after surgery to optimize extent of node dissection. Methods: Twenty-four cases consisted of II gastric and 13 coloractal cancer patients were enrolled in this study at~er obtaining the informed consent. Using a fiber endoscopy, I 11-148 MBq of T¢-99m-phytate was injected into the submucosa of the peritumoral areas. Although there is no approved radiopharmaceuticals in our district suitable for lymphoscintigraphy, Tc99m-phyrate is reported to form particles when interacted with cationic calcium ion. Moreover, our previous study on sentinel lympboseintigraphy of breast cancer has confirmed the applicability of this radiopharmaceutical. Lymphoscintigraphy was performed at 15, 60 rain and 3 hr and the patients were operated upon the following day. The surgical gamma probe and patent blue dye were used for sentinel node mapping. In some cases, a hand-held palm-sized gamma camera equipped with the CZT semiconductor detector was utilized to obtain the intraoperative hnyphoscintigrams. All the resected lymph nodes was measured in a well-type scintillation counter and pathologically examined. Results: The mean numbers of hot nodes detected intraoperatively for gastric and colorectal cancers were 4.6 and 3.8. respectively. These numbers were not significantly different from those detected by the dye for colorectal and gastric cancers: 5.2 and 4.0. In case of the tumors located in the inferior part of the colon, the dye method could not find the sentinel nodes because of the surgenn's field of view. All of the nodes with micromemstases from 4 cases showed higher radioactivity than the rest of the regional nodes. Although the lymph nodes scintigraphyicany imaged were less in number, those gave better navigation for surgeons to search the appropriate area including the sentinel node. The surgical palm-sized gamma camera helped investigate broader area than the pinpoint view with a gamma probe. Conclusions: The sentinel node concept could be applied to the gastric and rectal cancers when Tc-Ogm-phytate was administered via an endoscopy.

PS_283

PS_285

SENTINEL LYMPH NODE BIOPSY IN SQUAMOUS CELL CARCINOMA OF THE ORAL CAVITY AND THE OROPHARYNX: A PRELIMINARY EXPERIENCE

FEASIBILITY OF LYMPHOSCINTIGRAPHY OF THE CASTROESOPHAGEAL JUNCTION

L. Feggi (1), G. Turetta, A. Tarabini, D. Turetta, N. Prandini, P. Carcoforo, A. Pastore. (1) ENT Clinic and Clinical General Surgery, University of Ferrara, Italy; (2) ENT Division, Hospital of Rovigo, Italy; (3) Nuclear Medicine Dpt., St. Anna Hospital, Ferrara, Italy. The presence of regional metastatic tymphnodes (N+) is one of the most important prognostic factors in cervico-facial carcinomas. Accurate neck staging is therefore fundamental for planning a therapeutic strategy. In spite of this, 30% of cases clinically NO present occult metasla. sis diagnosable only after comprehensive (I-V levels) or selective neck dissections, that are the current gold standard treatment. Nevertheless neck dissection becomes over-treatment for 70% of patients: the aim of this study is to valuate the application of the Sentinel Node (SN) biopsy strategy, in the therapeutic approach of head and neck carcinomas, in order to avoid ~nocess~'ytymphadeoectomy. MateHnB and methods: The study comprised I l patients aged between 58 and 75 years (mean 65) affected by TI (seven patients) and "1"2(four patients) carcinomas, clinically NO, of the oral cavity and oropharynx: five patients with tongue edge cancer, two with tunsillar cancer, three with retromolar region cancer and one with inferior alveolar process cancer. In the afternoon before the surgery we inject a nanocolloid (Nanoeoll", Amersham) at the four poles of the primitive neoplasm and within 30 minutes we perfom the seintigraphy. The dose is calculated in order to have 10 MBq of 99roTe at the moment of the surgery the day after. In all the eases we utilized a probe collimated for intraoperative detection of SN (which is examined separately from the remaining lymph nodes): lsosulfan Blu vital dye was also injected around the neoplasm intraoperatively. Functional comprehensive neck dissection was always performed. Results: SN was always shown at the seintgrapby. In eigth eases the SN resulted negative for metastatic infiltration at the histologic examination like the remaining lymph nodes. In three eases the SN presented micrometastasis where the remaining lymph nodes were negative: we never had false negative SN. In all cases the SN was located ipsilateral tu the lesion. Conclusions: The application of the SN technique in the carcinoma of the oral cavity and the oropharynx is easy and repeatable. An important factor is selection of the patient (clinical NO, no past surgery or radiotherapy of the neck) and good multidisciplinary collaboration between sugeon, nuclear medicine and pathologist. The possibility of introducing the management of patients affected by carcinoma of the oral cavity with neck NO into clinical practice would lead to a reduction in the morbidity: a fundamental condition for the success of this project is the application of this experimental phase in other centers in order to enlarge the group.

1148

G.W. Sloof (1), J.M. Klaase (2), R Fockens (3), J.J.B. Van Lanschot (2). (1) Department of Nuclear Medicine; (2) Department of Surgery; (3) Department of Gastro-Enterology, Academic Medical Center, Amsterdam,NL. The surgical approach of carcinoma of the gastric cardia (gastro-esophageal junction) is controversial because of its borderline location. A total gastrectomy may be performed when the tumor is limited to the cardia. Some argue in favour of an esophagectomy with proximal gastric resection because of epidemiological and histological similarities with esophageal cancer. Further, metastatic spread to the paraesophageal lymph nodes is found in approximately 20% of patients. However, morbidity and mortality rates are higher for esophagectomy compared to gastrectomy. This study was tmdertakan to assess the feasibility of tympboacintigraphy of the cardiac area and the detection of paraesophageal lymphatic drainage. Methods: eight patients elected for ¢sophagoctomy with proximal gastric resection because of esophageal c ~ c e r located at least 3 cm above the Z-line were enrolled in this study. On the preoperative day an endoscopy was performed and I00 MBq 99m-Technetium labelled nanocolloid (n=5) or sulphur colloid (n=3) was injected submucosally in the eardia, which was free of tumor. Lympboscintigraphy, including SPECT, was obtained 30 minutes, 4 and 20 hours after injection. Surgery was started shortly after the last acquisition. Just preoperative, blue dye was injected at the same site of the radiolabelled tracer, again using an endoscopic procedure. After resection of the esophagus-cardia including the site of injection, Iocoregional lymph node stations were measured systematically for radioactivity by a gamma probe. TberaaRer, the resection specimen itself was measured for radioactivity, both by gamma probe and camera, and investigated on the presence of blue nodes. RcsnRs: In each patient at least I radioactive lymph node was detected. In total 2t lymph node drainage areas were detected: 2 left paraeardial, 4 right pamcardial, 6 lesser curvature, 4 celiac trunc, 3 radix mesenterica, 3 splenic artery and 1 paraasophageal. Detection of preoperative scintigraphy and per operative gamma probe measurements were similar, except for one, obese patient in which a radioactive lymph node was detected by the gamma probe but was missed by gamma camera acquisition. In only about half of the radioactive nodes, blue nodes could be clearly detected. Conclusions Lymphoseiutigraphy of the gastric cardia is feasible. The scintigrams can accurately determine the location of radioactive lymph nodes in the mediastinum and upper abdomen. Paraesophageal drainage was present in 1 out of 8 patients; further studies are warranted to assess the clinical utility of lympboseintigraphy of the upper digestive tract.

• DIAGNOSTIC O N C O L O G Y 8 PS_286

PS_288

SENTINEL LYMPH NODE IDENTIFICATION IN VULVAR SQUAMOUS CANCER

IS THERE A "SENTINEL LYMPH NODE" FOR THE PROSTATE? LYMPHOSClNTIGRAPHIC PAI-rERN IN PROSTATE CANCER

F. Martin (1), S. Vidai-Sicart (1), L.M. Puig-Tintore (2), M. Ortega (1), J.J. Mateos (1), J.A. Lejarcegui (2), E Pons (1,3). (1) Department of Nuclear Medicine, Hospital Clinic, University of Barcelona; (2) Department of Gynaecotogy, Hospital Clinic, University of Barcelona; (3) IDIBABS, University of Barcelona, Spain.

O. ~nbmy (1), I. Ba~ogh (1), J. Varga (2), B. Ruszinko (2), Z. Toth (2), K. P6cza (3), GY. Janoky (4). (1) Dpt. of Nuclear Medicine, Uzsoki Hospital, Budapest, Hungary; (2) Urological Dpt,Uzsoki Hospital, Budapest, Hungary; (3) Pathological Dpt., Uzsoki Hospital, Budapest, Hungary; (4) OSSKI, Budapest, Hungary

AIM: Sentinel lymph node (SLN) biopsy is a new technique that represents a considerable

Patients with early stage (TINxM0) prostate cancer are mostly asymptomatic. Elevated PSA blood level on screening can be the only sign of the disease. If there is no contraiodication of operation, after staging examinations the patients undergo suprapubic radical prostatectomy with ablation of external iliacal and obturator lymph node basins. Aim: We would like to evaluate the lymphatic drainage of prostate with scintigraphic method, to find out: is there any well repeatable, characteristic, preferred draining lymph node(s) of the prostate, and how can we help to find them easily and quickly during operation. Patients: We examined 6 patients with early stage of prostate cancer, before suprapubic radical prostatectomy. Methods:We did lymphoscintigraphy with bone marrow SPECT and blood pool scintigrapby before the operation, The radiopharmakon was injected transperineally into the prostate in two depots. 2-3 hours and 24 hours later we did lymphoscintigraphy. The 2 hours lymphoscintigraphy was combined with one marrow SPECT. We performed blood pool scintigraphy as well to identify the relation of lymph nodes to blood vessels. We repeated the perineal injection and lympboscimigrapbic procedure the day before the operation. During the operation we searched the radioactive lymph node with intraoperative gamma probe (Navigator). After ablation of radioactive lymph node the surgeon removed non-radioactive lymph nodes of the region as well. The harvested lymph nodes were evaluated for metastases by the pathologist. Results: We could find radioactive lymph nodes on the scintigram in every case. The pattern of radioactive lymph nodes were the same on both lymphoscintigraphy, In these cases the surgeon could find radioactive lymph nodes during the operation as well. In 4/6 cases the radioactive lymph nodes were outside the routinely harvested lymph node basin. One of the radioactive lymph node was metastatic, it would not be removed without intraoperative gamma detection. Conclusions: The number oftbe cases is low so we need further e,/aiuation. Preoperative lymphoseintigraphy combined with bone -marrow SPECT. blood-pool scintigraphy and intraoperalive radiodetection can identify draining lymph nodes of prostate cancer, Instead of routine ablation of statistically stated lymph node basin this method can ,,lead the hand of the surgeon" to a patient-specific draining lymph node.

improvement in our ability to evaluate the turnout status of the regional lymph nodes and could be useful in selecting patients for adjuvant therapy. Our goal is to describe our initial experience in SLN identification in vulvar squamous carcinoma and its relationship with regional lymph nodes, in order to, in the future, to perform the regional lymphadenectomy only on patients with metastatic SLN. MATERIAL AND METHOD: We studied prospectively 20 patients with vulvar squamous carcinoma. Seventeen of these patients had T1 or T2 tumours. The remaining three presented a "1"3tumour. A lymphoscintigraphy was performed on afi of them the day before surgery by injecting 74-1 tl MBq of nanocolloid-Tc99m. After radiotracer administration, dynamic and static images were acquired. The SLN location was marked externally on the skin. On the day of surgery blue dye was injected about 15 minutes before surgical incision. A hand-held gamma probe was used to precisely Iocalise the SLN. After SLN identification a standard inguinal lymphadenectumy was performed. All surgical samples were referred for pathological study. RESULTS: SLN was locabsed by lymphoscintigraphy and a hand-held gamma probe in all but one patient (19/20 = 95%). SLN was not identified in the patient with T3 tumour. Blue dye stained SLN in 15/20 patients (75%). A total amount of 36 SLNs were harvested, two of them being metastatic (2 patients). In these two patients a total amount of 13 regional lymph nodes were harvested, only one of them being positive for metastases. In SLN negative patients all regional lymph nodes removed were negative for metastases, CONCLUSIONS: This short series of patients indicates to us that SLN identification of vulvar malignancies is a simp(e and reliable method for selecting patients tbr lymphadenectomy. Its accuracy improves in small tumours (TI or T2) with minimal misidentification.

¢..

,O E

PS_287

PS_289

SENTINEL LYMPH NODE (SLN) DETECTION IN CERVICAL CANCER

LYMPHOSClNTIGRAPHY IN A PATIENT WITH NON-HIV KAPOSI SARCOMA

J. Grimm (1), C. Kujat (1), 1. Lantzsch (2), J. Buchmann (3), H. Koelbl (2), T. Mende (1). (1) Department of Nuclear Medicine; (2) Department of Gynaecology; (3) Institute of Pathology. Aim: The SLN-biopsy is an international established method in patients with melanoma or breast cancer. The purpose of the study is to verify the feasibility of the SLN-procedure in patients with evidence of cervical cancer, Methods: We explored 17 women with early stage cervical cancer (TI/T2). One day before surgery a lymphoscintigraphy was done. We injected subepithelialty on average 88 MBq °°'nTc-labelled human colloides (Albu-Res") in the cer,,'ix at 3, 6, 9 and 12 o'clock. The volume was about 0,2 ml NaC1 each. The colloid was filtered before to obtain the small particle fraction between 200-450 nm. Images were recorded immediately after injection (dynamic scintigraohy from anterior view with 28 images, 1 minute per frame). Additional we made static images, 5 minutes per image, 30 and about 120 minutes after injection from anterior, right and left lateral view. The SLN locations were marked on the skin, The SLN were intraoperatively identified using a hand-held gamma probe. In all cases a complete pelvic lymphadenectumy was done. Results: Imaging was in 15/17 cases successful. In 7/15 cases lymph channels have been visualized. We found in 13/15 cases intraoperatively one or more radioactive lymph nodes (on average 2 SLN). In all eases of detected SLN we found no lymph node metastases at all (SLN and other lymph nodes tumor-free). In the 2 cases of no presentability of SLN, which should always result in a complete lymphadenectomy, we found lymph node metastases. We did not found any tumor-positive non-SLN in case of tumor-negative SLN. Conclusion: We need larger studies to evaluate the accuracy of the selective SLN-biopsy in patients with cervical cancer. After this study with 17 patients we have no reasonable certainty if the detected SLN is the real first-tumor-draining lymph node. What is with women, who had a conization before lymphoscintigraphy (injection site is not equal to the tumor site)? Is the lymphdrainage of the ectocervix equal to the eodocervix (injection site ectocervical, tumor sometimes endocervical)? However 15/I7 patients underwent a lymphadenectomy with no benefit for survival and with a high rate of morbidity, in future we have to estimate the reliableness of this method to avoid radical lymphadenectomy in patients with tumor-free SLN.

e,-

T.A. Balcl (1), H. Komek (1), Z. AytuO (1), H. Kaya (1), N. Kihnc (2). (1) Department of Nuclear Medicine; (2) Department of Pathology, Dicle University Medical Faculty, Diyarbaklr, Turkey.

e~

Kaposi sarcoma is an uncommon, opportunistic, multisentric, vascular neoplasm charactefised with the proliferation of a mixed cell collection included endothelial cells. It is usually associated with AIDS and HIV positivity; but it can be occur in every immunosupressive situations. It can be in the form of fuiminant disseminated visseral involvement and besides it can also show benign skin involvement merely. Lymphedema can be occur by the involvement of the lymphatic vessels. The patient (70 years-old, male) diagnosed as Kaposi sarcoma by skin biopsy refered us with mild lympbedema of the lower limbs, and the disseminated, purple-red plaques on the legs. Skin of these areas was very tough. He was HIV (-) and had no known immunosupressive situation except his old-age. Doppler ultrasonography of the lower extremities were normal. There was no significant abnormality in the laboratory findings. However he had a story of upper gastrointestinal system bleeding and the diagnosis of prepyloric ulcer. We performed lymphoscintigraphy by injecting intradermal 500 IxCi (17 MBq) Tc-99m sulphur colloid to the first interdigital spaces of the feet bilaterally. We obtained static images d th th from the lower extremities and the pelvic region on the 2 n , 4 and 24 hours, We visualised focal radiotracer accumulations on the right leg (bigger plaques than the others), no accumulation on the fight pelvic region, and delayed and decreased visuatisation of the left pelvic lymph nodes.

O IX

1149

• DIAGNOSTIC ONCOLOGY 8 / GENERAL TOPICS PS_290

GENERAL TOPICS

PEROPERATIVE RADIOISOTOPIC EVALUATION OF OSTEOID OSTEOMA

PS_292

G. D'Errico (1), V. Valenza (1), M. Galli (2), M.A. Rosa (2). (1) Nuclear

PATIENTS' AND PERSONNEL'S PERCEPTIONS OF SERVICE QUALITY AND PATIENT SATISFACTION IN NUCLEAR MEDICINE

Medicine Institute, Catholic University of Rome; (2) Orthopaedic Institute, Catholic University of Rome, Italy. Introduction! drawback of surgery of osteoid-osteoma, a benign but painful and small size bone lesion, may be an incompIete excision of the ,.nidus", and recurrences, rare complication, maybe the result of a partial excision of osteoid-ostenmas, Since osteoid-osteomas concentrate ~Tc-methyleoc-diphosphonate (MDP), radionuclide imaging has become an established technique for the localisation of these turnouts, aim: the Authors report on the use of peroperative radionuclida Iocalisation of osteoid-osteoma performed to evaluate the clinical efficiency of this technique. Material and methods: approximately three hours belbre surgery fourteen young patients ( 9 osteoid-osteoma of femoral diaphysis, 3 of femoral condyle, I of ulna and 1 of talus) were injected intravenously with ~ T c - M D P at dose of 740 MBq to pertbrm three-phase seintigraphy. Bone scan showed increased uptake of the bone seeker in the ,,nidus'" and in the perilesional sclerosis; anterior, lateral or oblique views were acquired to better define the position of the ,nidus-within-the-selerosis". With a fine radioactive marker the region of focal abnormality was Iocalised and the skin was marked at that precise site by pen. ROIs were plotted out the hot-spot-area and adjacent bone region (background) to calculate the ,,ratio" between target/background. A preoperative detection, using a handheld probe, was pcrfurmed to Iocalise the ,,hot-spot-area" compared to an adjacent control region. In the operative field measurements of radioactivity were carried out by means of the same sterilised _-probe guiding the surgeon to determine the orientation of the nidus. Results: high activity at .nidus-within-the-sclerosis'" ",,,as lbund in all the intraoperative measurements; the preoperative detection was useful to correctly approach, at surgery, the bone lesion and to guarantee complete removal of the le.~ion. In tact. because the closer collimation and the ability to respond in a directional manner of the _-probe, the nuclear physician was able to show to the surgeon the exact Iocallsation of the nidus deep. In order to detect possibtc pathological residual activity on bone alter removal of ostcomas the nuclear physician rescanned the cavity after curettage verifying the residual radioactivity. About 20 days al}cr surgery all the patients underwent three-phase scintigraphy to confirm the complete removal of osteoid osteoma. Conclusions: the Authors conclude that the peroperative nuclear medicine, e.g., the preoperative Iocalisation of the ,,nidus" and of the active surrounding part of the osteoid ostcoma and next successful detection of lesions at surgery can represent an effective aid lbr conservative surgical excision assuring a complete removal of lesions.

S. De Man (1), P. Gemmel, R Vlerick, R. Dierckx. (1) Faculty of Economics and Business Administration, Ghent University, Belgium; (2) Faculty of Psychology and Educational Sciences, Ghent University, Belgium; (3) Division of Nuclear Medicine, Ghent University Hospital, Belgium. Aim: SERVQUAL, the most commonly used service quality measurement scale, has been used in a department of Nuclear Medicine. The aim of this paper is to demonstrate the use of SERVQUAL for measuring patients' perceptions of health care quality in an ambulatory care clinic, the hnk between service quality and patient satisfaction, the relationship between perceptions of service quality and patient satisfaction of patients and personnel. Method." 75 patients visiting the department of Nuclear Medicine tilled in a serf-administrated patient questionnaire. The questionnaire included demographic questions, SERVQUAL for measuring ser,,ice quality perception and a question about overall patient satisfaction. The personnel of the Nuclear Medicine department filled in a similar self-administrated questionnaire. Results: The results indicate that SERVQUAL appears to be a reliable scale to measure health care service quality. Itov, ever, the proposed five dimensions (Tangibles. Assurance, Responsiveness, Reliability and Empathy) of SERVQUAL are reduced to four. Tangibles and Assurance are perceived as one dimension of service quality, where the other t:actors are Responsiveness, Reliability and Empathy. The results also indicate that perceived health care service perlbrrnance by patients is associated with patient satisfaction (r=.756). The factor Reliability correlates strongest with overall patient satisfaction (r=.729 L which means that Reliability has the strongest effect on patient satisf,~ction. Patients and personnel did not differ significantly in service quality perception (t=-.993, p>.01). Only lbr the Tangibles-Assurance fhctor, there is a different perception of patients and personnel (t=3.181, p<.01), where the personnel perceives_the Tangibles and Assurance dimension less good ( x = 5.42, s.d. = .59) than the patients ( x = 5.88, s.d. = .95). Health care personnel seem to estimate very well the overall patient satisthetion (t=-1.444, p>.OI ). Conclusion: SERVQUAL appears to be a reliable instrument to measure service quality perccptions in Nuclear Medicine. Patients and personnel of a Nuclear Medicine department seem to have a similar perception of service quality. Only 'langthlcs and As:,uram:¢ is perceived significantly dilti:rent by the personnel what is an illustration of the deticicncy m patient knowledge t~ evaluate the technical quality of the ,;ervice. Management must he av.arc that investments in Tangibles-Assurance will not ha~e higher service quality perceptions of patients as result. The SERVQUAL instrument can be used as a management tool to recognize areas to improve in order to build a more patient-|bcused attitude towards service delivery.

PS_291

PS_293

LYMPHOSClNTIGRAPHY IN NON SMALL CELL LUNG CANCER

NUCLEAR MEDICINE SERVICES IN THE KINGDOM OF SAUDI ARABIA

F. Scopinaro (1), O. Bagni (2), R. Salvatori (2), G. Baiano (2), R. Massa (1), M. Carletti (2), A. Saltarelli (2), M. Iozz.ino (2), O. Schillaci (3). (1) University ; (2) General Hospital, University of Rome, Rome, Italy. Aim: Surgery is the best choice tbr curing patients with non small cell lung cancer (NSCLC). The status of hilar and mcdiastinal lymph nodes is of primary importance thr selecting surgical candidates and fur prognosis; moreover, radical lympboadenectomy improves survival. The aim of this study was to develop a new scintigraphic technique to evaluate the lymphatic drainage in NSCLC. Methods: Eight male patients (age range: 53-72 years) were considered; in all of them a CT-scan guided double perilesional injection of about 0.3 ml of Tc-99m labelled sulfur colloid particles (-= 17 MBq) was made. Multiple planar static images of the chest were obtained at 15, 30, 60 and 120 minutes postinjection in various projections, using a large field of view gamma-camera. An intraoperative gamma-detecting probe was used in 6 patients during surgery, performed 3-6 hours aRer lymphoscintigraphy. Results: In 6 patients images demonstrated ipsilateral both hilar and mediastinal drainage, whereas in the other two patients only ipsilateral hilar drainage was observed. In one case an atypical drainage from a NSCLC in the right superior lobe to a lymphnode in the right triangularis ligamentam was revealed. During surgery, the lymphatic drainage patterns were easily detected. Conclusions: Our preliminary results suggest that this new lymphoscintigraphic technique is useful in patients with NSCLC. It allows an accurate lymphatic mapping of possible turnout spreading, with a better staging of the disease, and cart help and guide the surgeon in the resection.

1150

R.Y. AI-Mazrou (1), J. Prince (2), A. Arafah (31. (1) Biomedical Physics Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; (2) Physics Department, University of North Texas, Denton, Texas, United States; (3) Nuclear Medicine Section, Radiology Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. A postal survey was distributed to the 29 nuclear medicine departments existing in the Kingdom of Saudi Arabia asking for details of current practice and technology in nuclear medicine. The aim of the survey is to create a complete database of available equipment, quality control and clinical procedures performed in these departments during the years 1997, I998 and 1999. From this database, the level and sophistication of nuclear medicine services in the Kingdom will be known. Method: The survey form was sent to the Heads of the 29 nuclear medicine departments in the Kingdom. A covering letter accompanied the form explaining the objectives and the importance of the questionnaire. Three months later a reminding letter was sent to nonresponding departments. This was further followed up by telephone and fax. Results: Data were received from 27/29 (93%) departments. These departments have 44 gamma cameras, 12 of these cameras are dual headed and 2 are triple headed. A total of 49638 procedures were performed in year 1997, while 55399 procedures in year 1998 and 50763 procedures in year 1999. Imaging procedures composed 94.7%, 93.1% and 93.5% for the years 1997, 1998 and 1999 respectively. While non-imaging procedures composed 4.1%, 5.5% and 5.2% for the same years and therapy procedures composed 1.2%, 1.4% and 1.3% for the same years. Number of scans performed per camera are 1069, 1172 and 1079 for the years 1997, "1998 and 1999 respectively. Bone scan was the most frequent imaging procedure performed in all years with percentages of 17.0, 16.1 and 16.5 of the imaging procedures for 1997, 1998 and 1999 respectively. Myocardial Perfusion scan came as second for all years with percentages of 13.5, 13.9 and 14.8. This survey also showed that only few centers performed acceptance testing on their cameras and few of these centers perform the minimum required periodic quality control procedures for their gamma cameras. Conclusion: number of nuclear medicine procedures performed in the Kingdom of gaudi Arabia is below the average numbers in the European countries. Policy makers should plan to educate the users of these cameras on the importance of quality control procedures. The nuclear medicine services in the Kingdom do need a lot of efforts from its community to improve this specialty and educate the referral physicians about the importance and ability of this modality.

•

GENERAL TOPICS

PS_294

PS_296

MAJORITY OF EANM MEMBER SOCIETIES AIM AT EANM-GUlDELINES

THE RELATIONSHIP BETWEEN PERCEPTION OF SERVICE QUALITY AND WAITING TIME IN NUCLEAR MEDICINE

J.D. Kuyvenhoven, E. Busemann Sokote, PP. van Rijk, A. Plachcinska, M. Clausen, S. Steien, H. Sayman, B.A. Dierckx. EANM Task Group on Quality Assurance and Standardisation.

S. De Man (1}, P. Gemmel, P. Vlerick, R. Dierckx, M. Decoussemaker. (1) Faculty of Economy and Business Administration, Ghent University, Belgium; (2) Faculty of Psychology and Educational Sciences, Ghent University, Belgium; (3) Division of Nuclear Medicine, Ghent University Hospital, Belgium; (4) Faculty of Economy and Business Administration, Ghent University, Belgium

Background: The various efforts undertaken in the past towards management of quality in nuclear medicine were mainly national initiatives on an ad-hoc basis. Some degree of harmonisation to assure the quality of radiopharmaceuticals and the performance of nt~c/ear medicine instrumentation existed in 1996. In EANM member societies, nationally accepted procedures existed in 6 of 23 and 18 of 23 had set up a quality assurance committee. However, nationally accepted guidelines reflect differencus in legislation, available equipment, customs and reimbursements. Supranational guidelines and standards that gradually cover the entire nuclear medicine service could be a possible strategy to implement a systematic quality management in nuclear medicine. Aim: To achieve insight in the current status of guidelines in EANM member societies and their future plans. Methods: A postal questionnaire was addressed to the national delegates of the EANM member societies in July 1999. This questionnaire fi.~cussed on: - Current status of national guidelines - Specification of the cover and the level of national guidelines - Future plans for national, EANM and SNM guidelines Results: Complete response rate was 96% (n = 27). Guidelines are required by lq member societies, initiated by the member societies in 16 and provided by 13, of which 12 in the national language. In 10 societies, staff other than nuclear medicine physicians take the ~ead on some guidelines, in particular physicists in 7 and radiopharmacists in 5 societies. Active collaboration with other medical societies in developing guidelines exists in 9 societies, of which 7 with cardiology societies Currently, only 18% of the items of necessary procedure guidelines are covered. A commitment for future development of guidelines is shared by 26 member societies. 25 indicate a high priority need |br guidelines and 21 prefer EANM guidelines to national guidelines. Conclusions: Two thirds of EANM member societies require guidelines and half of them currently provide them. Various professional groups are involved in setting up guidelines. Most of procedure items are left uncovered. Compared with 1906, the relative proportion of societies that provide guidelines has douh#cd, indicating progress. Almost all member sncieties share a commitment for lhture development of guidelines and the majority prefer the EANM route at present.

Aim: Service quality is an overall judgement similar to an attitude and related, but not equivalent to consumer satisfaction (Parasuraman Zeithaml and Berry, 1988). Service quality is a subjective concept and is measured as the gap between perception and expectations (Parasuraman et al., 1985). This also means that evaluating quality is a subjective process. In literature, waiting time is supposed to have a significant influence on service quality perception (Mowen, Licata and McPhail, 1993). Because the specific nature of Nuclear Medicine, departments of Nuclear Medicine are usually confronted with long waiting times. Method: 192 patients visiting the department of Nuclear Medicine filled in a self-administrated patient questionnaire. The questionnaire included demographic questions, questions about subjective waiting time and waiting time behavior, SERVQUAL fur measuring service quality perception and a question about overall patient satisfaction. Different waiting times (before injection, before scan and total waiting time) for the patients were registered. Results: The subjective waiting time for scanning is significant smaller than the objective waiting time for scanning (t= -3.054, p < .01). Although patients must wait longer than expected (t=-2.843, p<.Ol ), most patients are satisfied with the waiting time ( x = 5.21, s.d. = 1.4). Only 6.3% did not know to that they had to wait between injection and scanning. Age ( =.209, p<.05)) and objective waiting time fur injection ( = - . 0 3 6 , p<.05) have a significant influence on the perception of service quality (R_ = . 185). Conclusion: Patients perceive waiting time shorter than the objective waiting time. Almost all patients are in/brined about the waiting time between injection and scanning. Older patients with a shorter objective waiting time tbr injection perceive service quality higher.

PS_295

PS_297

THE DYNAMIC RELATIONSHIP BETWEEN WORK PRESSURE, PRODUCTIVITY, WORK INTENSITY AND SERVICE QUALITY IN NUCLEAR MEDICINE

WATING PERIODS OF PATIENTS REFERRED TO NUCLEAR MEDICINE DEPARTMENT

S. De Man (1), P. Gemmel, R Vlerick, R. Diemkx. (1) Faculty of Economics and Business Administration, Ghent University, Belgium; (2) Faculty of Psychology and Educational Sciences, Ghent University, Belgium; (3) Division of Nuclear Medicine, Ghent University Hospital, Belgium. Aims: The financial pressure to reduce labor costs, combined with a cyclical shortage of health care labor might lead to higher work pressure. Work pressure can be defined as the relationship between the amount of work and the available labor capacity. There are several different strategies to deal with high work pressure: Obtaining additional resources through investment in capital or labor Increasing the work intensity (available labor works more hours than agreed in the contract). Increasing productivity (one is spending less time to the patients). The aim of this research is to investigate the relationship between work pressure, work intensity, productivity and service quality in a dynamic way and from a combined economic and psychological point of view. We formulate the following hypotheses: Pressure to increase the work intensity and/or the productivity (following a situation of continuous high work pressure) leads to the erosion of service quality if insuffieiant capacity is available. In personal-interactive services the patient will use the perceived time of contact as compared with the expected time as an important determinant of service quality. In task-interactive services (Nuclear Medicine) the service quality is determined by other factors. Consequently hypothesis I is not longer valid in task-interactive services. Many different variables will further have an impact on this relationship: Service quality is a subjective concept and is measured as the gap between perception and expectations. This also means that evaluating quality is a subjective process. Different agents involved in the hospital (such as management, personnel and patients) perceive quality in a different way and react differently on changes in the level of quality. There exists different 'gaps' between how quality is understood by the customer, personnel and management. In health care special attention must also be paid to how physicians perceive the level of quality, There are many structural and organizational factors that determine how fast the service quality is eroded following high work pressure. Such [~actors are technology, prol~ssional quality standards, training( Methods: We set up a longitudinal study in which different operational measures (work pressure, quality, structural and organizational factors) of a department of Nuclear Medicine are tracked. The process of this longitudinal study will discussed on the congress.

cO k~ e"

E Sakar, H. Durak. Depertmant of Nuclear Medicine, Dokuz Eyl01 University, Medical School, Izmir,Turkey. There is a rising demand for continuous improvement of health services due to the increased needs and expectations of patients. Patients expect to be diagnosed and treated with novel techniques in the shortest time with accuracy. The aim of this survey was to analyze the waiting time of the patients and the effective factors in order to minimize the patient discomfort in

nuclearmedicine. Methods: A flow chart was created for each patient starting from the appointment time until receiving the final report for 10 consecutive working days. The time elapsed between each unit was calculated. Total of 200 patients (53 thyroid, 38 bone, 25 DMSA, 26 myocardial perfusion, 9 parathyroid scintigmphies, 49 miscellaneous scintigraphies) were followed. History taking which lasted for 9 minutes occurred 23 minutes after the admission of the patient. Intravenous injection of the radiopharmaceutical happened 75 minutes after admission. The reason for this delay was using a single vial for more than one patient, and waiting for all the appointed patients to arrive before preparing the radiopharmacantical. A mean of 2 hours and 11 minutes elapsed between injection and imaging. Routine imaging lasted 27 minutes, but 19 minutes were spent for additional views. The patients waited between the routine imaging and additional views, for decision making for the necessity of these extra views and they left the imaging unit 2 hours and 32 minutes after their first enterance to the camera room. The patients spent 4 hours and 11 minutes in the nuclear medicine department. This period was 6 hours and 22 minutes for parathyroid scintigraphy, 6 hours and 2 minutes for thallium tumor imaging, 5 hours and 30 minutes for bone imaging. The shortest residence time was for lung scintigraphy (1 hour). Conclusions: Nuclear medicine imaging seems to take more time than other moralities related to the nature of the radiopharmaceutical used. This may cause a disadvantage when compared to other modalities. We need to decrease the waiting times in order to minimize the patient discomfort. New radiopharmaceutieals with shorter localization times and effective instruments to improve the counting rate need to be developed to provide a better health service for the patients.

1151

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O

• GENERAL TOPICS / OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 2 PS_298 DESIGNING A NUCLEAR MEDICINE DEPARTMENT FOR OPTIMUM PERFORMANCE IN THE 21ST CENTURY

E.D. Williams (1), M.P. Bewick (1), R. Blair (2), A.C. Knight (1). (1) Regional Medical Physics Department, Sunderland Royal Hospital, Sunderland, UK; (2) Regional Medical Physics Department, Newcastle General Hospital, Newcastle upon Tyne, UK. The expectations of both patients and staffare continually rising, concerning their experiences when using clinical departments, and present a challenge when providing efficient, safe services. Nuclear Medicine is a particularly complex operation, where the needs of radiation safety rules and radiation-sensitive equipment can be in conflict with the demands of a clinical environment. Our aim in developing design guidance for nuclear medicine was to meet these challenges. Methods: The approach employed was to describe design needs based on expertise gained from many years' experience in building and operating nuclear medicine departments at 13 hospitals over our region. This experience, including the results of patient surveys, was used to develop principles and features which could be applied to designing a nuclear medicine department. Results: The resulting principles govern the layout of the department. The main point is separation between 'patient' and supporting 'staff only' areas, which enables both groups to feel comtbrtable. Other significant areas include the working and usage relationships between diffurem functional areas (imaging rooms, dose administration etc ), and the overall ambience of the environment, including colour, furnishings, lighting and noise level. Features developed were a large number of specific points, including details within each special purpose room to provide sat~ty and comfurt in use, and optimisation of the design of specialised areas: the radiopharmacy is a particularly difficult area to design for efficiency of use and economy of floor space while meeting regulatory specifications. The range of radionuclides expected to be used was also considered, and allowance made for some future development. The results of applying these principles in practice to a newly constructed department, within the constraints of a larger building scheme, showed that they could largely be achieved. Conclusions: We conclude that these principles should be generally applicable to new building schemes for nuclear medicine, and are important not only for service efficiency, but also for the well-being of patients and staff.

OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 2 PS_300 EVALUATION OF ESOPHAGF.AL SCINTIGRAPHY IN CHRONIC RENAL FAILURE AND THE ROLE OF HEMODIALYSIS TREATMENT

B. Okudan (1), B. Okudan (1), Y. 0st0nda~] (2), N. GLil~elik (3), M. Kayatas (3). (1) Department of Nuclear Medicine; {2) Department of Gastroenterology; (3) Department of Nephrology, Numune Research and Training Hospital, Ankara, Turkey. Aim: Foregut motor dysfunction especially in the esophagus has been commonly reported in uremic patients. However, as far as we know there is scarce data on esophageal motor functions in uremia. Esophageal scintigraphy provides a non-invasive demonstration of gastrointestinal motor abnormalities. In this study, we investigated esophageal motor functions by using scintigraphic method. Method: Twenty-six patients chronic renal failure and 10 healthy subjects were enrolled into the study. Male to female ratio was 13/13 in patients and 4/6 in controls. Mean age of the patients and the controls were 45.58:1:13.52 yrs (range; 29-77) and 38.8+_16.68 yrs (range 1967) respectively. Fil~can of 26 patients were being on regular hemodialysis treatment and the rest were terminal renal failure patients who were in predialysis period. The age and sex distributions were similar in both groups. Neither of the patients had amiloidosis, diabetes mellitus or collagen vascular disease, nor was using drugs, which can affect gastrointestinal motility. Esophageal scintigraphy was made using an Elcint SPX-6 Gamma camera with low energy-muhipurpose, parallel hole collimator. The radiopharmaceutical is 200-400 IxCi of DTPA in 15 ml of water. With the patient supine the liquid is taken into mouth through a straw and then a single swallow is performed. Rapid sequential images (2 per second) are acquired fur 1 minute. Dry swallows tbllow this at 15 seconds intervals lbr up to 10 minutes. Computer analysis is performed using a region of interest over the esophagus and used to evaluate the progression of the bolus. Results: Esophageal residual activity (RAt is that is defined as percentage of liquid bolus let~ the esophagus within tO seconds of time measured in each patient and controls. The mean RA was 84.1+13. 1% (49-98 %) in patients and 81.63_+17.52 % (53-98 %) in controls. The difference was not significant statistically (p>O.05). The hemodialysis group has mean RA of 89.01±7£ (?0-96.6) and. the rest of patients had mean value of RA 76.78-t-15.65 (49-97.8 %). The difference was tbund to be significant (p<0.05). Conclusion: As a conclusion, we believe that esophageal motor functions are abnormally affected in predialysis chronic renal Ihilure patients possibly due to neuropathy or myopathy in association with uremia and, this abnormality can be corrected by bemodialysis treatment.

PS_299

PS_301

AMIFOSTINE (AF) AND RADIOTHERAPY (RI"): PHASE III STUDY

COMPARISON OF DIFFERENT DIURETIC RENAL SCINTIGRAPHY PROTOCOLS ( F+20, F+0 AND F-15) IN PATIENTS SUSPECTED OF URETEROPELVIC OBSTRUCTION

D. Di Gennaro (1), M. Alfieri (2), B. Curcio (1), G. Scimone (1), C. Bianco (1), A. Losco (1), E. Falcone (1), S. Di Fiore (1), R. Pacelli (3). (1) Department of Radiation Therapy Salerno Hospital; (2) Pharmacy Mercatosanseverino Salerno Hospital; (3) Department of Radiological Science Federico II Naples University. Purpose: to evaluate the tolerance and efficacy of Amifostirt¢ (WR-2721) as a radioprotector Methods: in 2999 we began a clinical study to evaluate AF as radioprotector; till now we have used in ni24 patients, with an age varying from 16 to 36 (median age 25), affected by nil8 Hodgkin Limphomas (HL) (mantle field - dose: 30Gy/20 fract.), ni6 Non-Hodgkin Linphomas (NHL - Neck field - Dose: 41.4 Gy/23 fract.), and I patient, age 53 years, affected by a pelvic mass from a cervix ca, (dose:61 Gy), already surgically treated (ureteral-bladder-ileotomy) for iatrogenic toxicity ( bilateral ureteral necrosis) caused by eisplatin. The bladder was created from an ileal loop, and was highly prone to radiation necrosis. AF was used: a)in young patients treated to Head and Neck (to prevent xerostomia) b)in young patients treated with mantle field (to prevent xerostomia, esofagitis and second chemo-radiation turnouts) c) in patients already treated (higher risk of radionecrosis). AF was given at a dose of 500 mg. diluted in 5 co of fisiologic solution, s.c., in two different subministrations 15 m' before RT. We always gave antiemetic profitaxis with serotinin - antagonists. Subeufis way was more useful, for our department (100 patiants/day), Results: We did not notice bad effects caused by subeutis subministration o l A F ; we noted 4/1 g acute radiation toxicities (Grade 2 esophagitis), but no acute xerostomia, and a complete compliance to radioprotector and radiotherapy schedule. Conclusion: AF is safe and useful, and now is routinely given in our department to this subgroups of young patients.

!152

S. T0rk61mez (1), T. Atasever (1), K. TLirk01mez (2), O. G6~0s (2). (1) Department of Nuclear Medicine, Gazi University, Ankara, Turkey; (2) Department of Urology, Ankara University, Ankara, Turkey. The aim of this study was to compare three different diuretic renal scinfigrapby protocols (F+20, F-15. F+O) for evaluation of suspected upper urinary tract obstruction. Methods: A total of 22 patients (28 kidneys) suspected of ureteropeivic junction obstruction were performed three diuretic protocols, Twenty of the patients were adults and 2 were infants, their ages ranged from 3 to 43 (mean 28). The three protocols were identical, except for the time of injection of furosemide. In the F+20 study, furosemide was given 20 minutes after the injection of Tc-99m MAG3. In the F-15 scan, furosemide was injected 25 minutes before the injection of radioactivity. In the F+0 scan, furosemide and radioactivity were injected simultaneously. F+O protocol could not be performed in one and F-J5 in two of the patients. Each of the three protocols were performed for the rest of the patients. Results: The results were classified as nonobstructive, equivocal and obstructive according to the renogram images and curves. None of the patients showed equivocal results in both F+0 and F-I 5 protocols. In the F+20 studies, 9 of the 28 kidneys wereevaluated as equivocal. Of these, 6 kidneys showed nonobsmactive and 3 kidneys obstructive renogram patterns with the other two protocols ( F+O and F-15 ), Moreover, one of the 14 kidneys which was evaluated as nonobstructive in F+20 protocol showed obstructive pattern in both F+0 and F-15 protocols. All of the kidneys that showed obstructive pattern in F+20 study also revealed obstruction in F+O and F-15 investigations. We could not find difference between the renogram patterns of F+O and F-15 investigations. Conclusion: As a conlusion, there is no need for further investigation when obstruction is determined by F+20 protocol. F+0 and F-15 protocols allow clarification in cases of equivocal F+20 studies. We suggest F+0 protocol when equivocal results are obtained by F+20 study since it is more practical and shorter.

• OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 2 PS_302

PS_304

COMPARATIVE STUDY OF CAPTOPRIL RENOGRAPHY / CR/IN CHILDREN AND IN ADULTS WITH HYPERTENSION

SClNTIGRAPHIC EVALUATION OF THE ALLOGRAFTED KIDNEYS TRANSPLANTED FROM THE SAME CADAVERIC DONOR

I. Kostedinova (1), A. Simeonova (1), R. Krasteva (2), V. Petrova (3), A. Gedavelov (4), B. Deliiska (2). (1) Departments of nuclear medicine; (2) nephrology; (3) paediatrics, Medical University; (4) Department of electronics, University of Chemical Technology,Sofia

A. Akta~ (1), G. Moray (2), H. Karakayah (2), M. Haberal (2). (1) Department of Nuclear Medicine; (2) Department of General Surgery, Ba~kent University, Ankara, Turkey.

The aim of the study was to apply CR in children and in adults with hypertension in order to compare the obtained results, regarding the age of the patients/PtsL CR was perfurmed in 20 children with mean age 10.2 years, mean blood pressure 160/106mmHg and in 38 adults with mean age 40.4 years, mean blood pressure 165/104mmHg. According to the weight, 37-74 MBq 99mTc-MAG3 was administered during basal study and Ib after oral intake of 12.550rag CaptupriL Different qualitative / shape of the curves/and qualitative criteria / divided renal function, Tmax., Retention index /were considered. For making final diagnosis, renal angiography was performed in 21 Pts with positive result from CR for renal vascular hypertension/RVH/ and/or high renin level / more than 2.gng/ml / and/or positive result ~om DupLex Doppler sonography. As a clinical background, we have found that only 20% of children had essential hypertension and in the rest-75% had kidney etiology of the disease. In the adults, essential hypertension was revealed in 5 I% of them and in the rest - kidney etiology in 53% of Pts. In the children/n=20/, CR gave rightly positive result in 6 of the cases, rightly negative - in 13, with a sensitivity of 100%, specfficity-92,8% and accuracy-95%. In the adults/n = 38/CR gave rightly positive result in 10 of the cases, rightly negative - in 21 with a sensitivity of 71,4%, specificity- 87,5% and accuracy-81,5% These results show that the stenosis of renal arteries in children is more often haemodinamically significant, which explains higher sensitivity of CR in children than in adults and predicts better clinical outcome after eventual revascularization. The less accuracy of CR in adults could be explained with more Iong-Iasting hypertension with microangiopathy which hinders the evaluation of the exact influence of Captopril on renography. Conclusions: I.CR for a detection of RVH in children has a higher sensitivity than in adults.2. Hypertension in children is ofien associated with kidney's etiology, which in addition necessitates performing renography,

This study was designed to compare the early postoperative course of allografted kidneys transplanted from the same cadaveric donor by the use serial renal scintigraphy. Fifteen pairs of recipients were being evaluated by serial radionuclide imaging during the early post-transplant period. For seintigraphic imaging, every patient was administered with 7 mCi of Tc-99m DTPA, Images were acquired at every second for the first one minute, and at every 30 sec during the rest of the study (20 minutes). Scintigraphic perfusion index was calculated by the method described by Hilson. Functional parameter of scintigraphy included the calculation of uptake (the ratio of peak kidney activity to background activity). Patients were imaged on the second and fifih post-operative days and as required thereafter. Although, on perfusion, 3 pairs of recipients and on function, 4 pairs of recipients had discordant pattern; no statistically significant difference has been observed for recipients of the same donor for perfusion and function. The pairs having an abnormal scintigraphy on the first study demonstrated a similar course of recovery. In conclusion, our results have shown that allografted kidneys transplanted from the same cadaverie donor demonstare similar perfusiun, uptake and recovery function on renal scintlgraphy obtained during the early transplant period.

0

PS_303

PS_305

RADIONUCLIDE EVALUATION OF RENOVASCULAR HYPERTENSION USING RENAL SCINTIGRAPHY WITH 99M TC-DMSA.BEFORE AND AFTER CAPTOPRIL

THE ROLE OF INFLAMMATORY MARKERS IN SELECTION OF UTI CHILDREN INDICATED FOR 99MTC DMSA SClNTIGRAPHY

C

S. Bykov (1), V. Smolkin (2), I. Garty (1), R. Hatevi (2), A. Klimov (1). (1) Nuclear Medicine Department; (2) Pediatric B Department, Haemek Medical Center, Afula,lsrael.

e~

Non specific signs and symptoms in infants and low age children make the clinical differentiation of lower urinary tract infection (LUTI) and acute pyelonephritis (APN) very difficult. At present time the 99roTe DMSA scintigraphy is considered the most reliable technique in the diagnosis of APN, However. the indications for this study still remain debatable. The aim of this study is to assess the role of infectious markers for selection of patients indicated for 99roTe DMSA scintigraphy. Methods: A prospective study was conducted in 56 infants and young children (2 m o n t h s - 3 years of age, mean 16 months, 41 females and 15 males) admitted with a first episode of high fever and bacteriuria, suspected for APN. All children were investigated by 99roTe DMSA scintigraphy, proealcitunin (PCT), c-reactive protein (CRP) and white blood cells blood counts (WBC), within first 7 days after admission and 6 months later for control. Patients, who had pathological findings on both first done and control 99mTc DMSA scintigrapbies (cortical scarring) were excluded from the study. Results:

0

M.J. Acosta-Gbmez, A. Rodr[guez, J.M. Llamas, J.M. Lopez, M. Gomez, A. Moral, M.A. Muros, A. Ramirez, G. Sabatel, S. Ortega. Department of Nuclear Medicine, Virgen de (as Nieves Hospital, Granada, Spain Aim: Value the utility of studies with '~mTc-DMSA with captopril (scintigraphy imaging and unilateral renal function) in identifying renovascular or renal disease in hypertension patients with high probability of renovaseular hypertension. Methods: We studied 27 hypertension patients (12 males, 15 females) mean age 49 years, SD: 9.46, with high probability of renovaseular disease. General analysis and radiology was made to all of them including renal arteriography as gold standard. Two renal scintigraphy with ~m Tc-DMSA were made to all of them, baseline study and one hour after administration ofS0 mg of captopril, a week between both studies. Renal suintigraphy (anterior and posterior images) was obtained 4 hours after the administration of 111 MBq (3 mCi) of w~ Tc-DMSA and results were evaluated quantitatively and qualitatively calculating unilateral renal function. We considered positive for renovaseular hypertension studies with impaired of more than 5% in unilateral renal function or a new defect absent in baseline study, Scintigraphic results were compared with arteriography to determine sensitivity, specificity and predictive values, Results: Arteriography demonstrated significant renal artery stenosis in 18.50~ of patients, 99m Renal scintigraphy with eaptopril using Tc-DMSA demonstrated sensitivity of 60%, specificity of 91%, positive predictive value of 60% and negative predictive value of 91%. Were identified 3 patients with segmental defects of uptake consistent with chronic pyelonephritis scarring. 99m Conclusions: Studies with Tc-DMSA using captopril present high specificity and are useful in patients with high clinical probability of renovaseular hypertension, identifying high number of patiants with significant renal artery stenosis. The possibility o f DMSA in identify renal abnormalities, as specially pyelonefritis scarring, add value to renal studies with captupril using others tracers, May identify renal etiologies of renovascular hypertension different to renal artery stenosis.

DSMA scintigraphy Normal ~n=10) APN (n=16) Total (n=56)

PCT normal 36 I 37

PeT Elevated 4 15 19

CRP normal ? 7

CRP elevated 33 16 49

PCT showed 90% and 94% specificity and sensitivity respectively. CRP showed 17.5% and 100% specificity and sensitivity respectively. There was no significant difference between WBC in APN and LUTI. Conclusions: This study shows a significant correlation between positive 99mTc DMSA seintigraphic findings (APN) and elevated plasma concentration of PCT. Since P e T plasma level is considered as a reliable adjuvant for the diagnosis of APN, we suggest that elevated plasma PeT may be successfully used for selection of patients with UTI indicated for subsequent 99mTc DMSA scintigrapby.

115,~

• OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 2 / PEDIATRICS PS_306

PS_308

REPRODUCIBILITY OF TC-99M MAG3 CLEARANCE IN PATIENTS WITH IMPAIRED RENAL FUNCTION

ALGODISTROPHY AND AVASCULAR NECROSIS OF HEAD FEMORAL IN THE POST-RENAL TRANSPLANT: DIFFERENCIAL DIAGNOSIS BY TRIPHASE BONE SCINTIGRAPHY

T.Y. Erdil (1), F. ~en (1), S. Tu~lular (2), F. Dede (1), O. Noshari (1), C. Ozener (2), E. Ako~lu (2), T. Turo~lu (1). (1) Department of Nuclear Medicine; (2) Section of Nephrology, Department of Medicine, Marmara University Hospital, Istanbul, Turkey.

A. Bagnato (1), R. Bonofiglio (2), R. Tavotaro (1), A. Lanzillotta (1), N. De Napoli (2), PC. Loizzo (1). (1) Department of Nuclear Medicine; (2) Department of Nephrology, Annunziata Hospital, Cosenza, Italy.

The aim of this study was to test the reproducibility of the mercaptoacetyltriglycine (MAG3) ciearance determinations in patients with impaired renal function. Methods: Seven male and five female patients (mean age: 55,9yr ± 7.53 yr. range 45 yr- 68 yr) with a history of chronic renal failure (plasma ereatinine levels = 3.33 mg/dl ± 0.79 mg/dl, range: 2.1mg/dl-~.6 mg/dl) were included in the study. The patients were not yet on dialysis during the study. Two seperate multiple sample clerance studies were performed in each patient within a week under similar physiologic conditions. Alter intravenous injection of the tracer, 10 blood samples were taken between 5 to 180 minutes. The clearances were calculated according to Sapirstein and corrected fur body surface area. The mean difference between two studies were expressed as a percentage of the mean value of the two studies, and the standard deviation of these percentages represented the precision. Results: The plasma clearances of first studies ranged from 26.5 ml/min to 93 ml/min with a mean of 59.4 • 24.7 ml/min. The clearances of the second studies ranged from 22.4 rnl/min to 125 ml/min with a mean of 60.8 ± 2 9 2 ml/min. There was no statistically significant differonce between the two clearance studies (p = 0.69). The mean difference (systematic bias) between the first and second measurements was 1.11% (in six patients, the differences were 29.3%, 20%, 16,7%, 15.3%, 14.5% and 13.1%, in other six patients it was less than 10 %) and the precision was tbund to be 15.6%. Conclusion: We did not observe a very good precision of MAG3 plasma clearance in patients with poor renal function; therefure, it should be interpreted cautiously in daily routine practice.

Algodystrophy and avascular necrosis of heed femoral represent two distinct complications in the transplanted patients receiving CsA and steroids. The exact prevalence in transplanted patients is unknown and several factors can determine influence its development, such as immunosuppressive therapy, steroids and diagnostic criteria. The symptomatology, characterized by pain of the hip, is common of the two entities and only a correct diagnosis permits the differencial diagnosis. The aim of our study was to ex,aluate the diagnostic value of the bone thiphase scintigraphy in the differencial diagnosis between algodystrophy and avascular necrosis of head femoral. Methods: In a group 0 f 9 8 patients with renal transplant we have selected 14 pts (M 10 ; F 4) age raging from 35 to 58 years and with transplant age raging from 3 to 60 months, admitted in our ward for pain of the hip and tbr functional limitation. All patients were in triple theraphy (CsA / or Tacrolimus, Azathioprine or Mycophenolate. Steroids). In all patients, bone triphase scintigraphy were pertbrmed after suitable position under gamma camera and after injection of 550 MBq of99mTc- MDP. Results: 6 patients (M 4; F2) did not show mark of bone pathology of the head femoral; in the remaining 8 patients (M 5; F 3) we made diagnosis of algodistrophy in 5 (M 3; P2) and of avascular necrosis in 3 (M 2; FI). In the group of patients with algodystrophy, the bone triphase scintigraphy showed on the head femoral an increased per]articular radionuclide activity during the vascular and parechymal phases. In the patients with avascular necrosis of the head femoral , the bone scintigraphy showed a reduction of blood flow on the epiphyseal region, while during blood pool and retarded phases we showed an area of uptake that surrounded the ipoactive head femoral. Conclusions: Bone triphase scintigraphy represents a useful, non invasiv tool for the di(t~renciat diagnosis between algodystrophy and avscular necrosis of head lemoraI.

PS_307

OTHER CLINICAL SCIENCE. PEDIATRICS

THE EFFECT OF FUROSEMID ADMINISTRATION ON THE ACCURACY OF DMSA SPLIT RENAL FUNCTION DETERMINATION IN PATIENTS WITH PELVIC RETENTION

C. T(Jrkrnen, O. (3zrnen, N. Alan, M. Halag:, K. (~zcan, C. (~nsel, L. Kabasakal, K. S6nmezoOlu, I. Uslu. Department of Nuclear Medicine, Cerrahpa~a Medical Faculty, Istanbul University, Turkey. It has beenproposed that split renal function determination using Tc-99m DMSA (DMSA) may overestimate differential renal function in patients with excretion abnormalities due to pelvic retention of DMSA. It is also recommended that furosemid injection may be useful in these particular patients to calculate differential renal function. Aim: The aim of the present study was to evaluate the effect of diuretic administration in determining differential renal function using DMSA scintigraphy, Methods: For this purpose 19 patients, ages ranged from I month to 64 years (12.1±13.3 years, 15 m, 4 f) who had documented pelvic retention were included to the study. DMSA scintigraphies were performed to all patients 2 hours a~er injection and 6 planar images were obtained. Right aRer the standard study the furosemid was injected to all patients end same number of images were also obtained. DMSA split renal function was calculated for each patient end from each study by using arithmetic mean method, The precision of split renal function determinations were estimated by calculating the difference between the corresponding DMSA split renal function for the kidney with the lowest uptake. The mean of differences represented the systemic bias and the SD of the mean of the differences represented the precision of the technique. Result: We did not observe any significant difference between the split ~nal function values obtained before and aRer diuretic administration (p>0,5), The values of split renal function ranged from 8.3% to 49.5% and from 7.7% to 49.2% in before end after diuretic administration respectively. Differences between values of the lowest split renal function obtained before end at~er diuretic administration varied from 2,6% to 0.2%. When we compared DMSA split renal function values the mean of the differences was only 0.2% and the SD was only 0.9%. Conclusion: In conclusion we did not observe interference from pelvicalyceal activity in these patients who had documented pelvic retention and diuretic administration may be a useless intervention for improving the accuracy of split renal function determination.

1154

PS_309 QUANTITATIVE ANALYSIS OF 9 9 M T C - D M S A DURING ACUTE PYELONEPHRITIS (APN) FOR PREDICTION OF LONG TERM RENAL SCARRING

A. Hitzel (1), A. Liard-Zmuda (2), A. Manrique (1), I. Gardin (1), J.E M6nard (3), F. Gutman (1), A. Sanson (1), J.N. Dacher (4), R V~ra (1). (1) Service et GIE de M6decine Nucleaire, CH Becquerel et CHU Charles Nicolle, Rouen, France; (2) Service de Chirurgie Pediatdque, CHU Charles Nicolle, Rouen, France; (3) Service de Biostatistiques, CHU Charles Nicolle, Rouen, France; (4) Service de Radiologie, CHU Charles Nicolle, Rouen, France Aim. To evaluate whether 99mTc-DMSA renal planar scintigraphy (DMSA) performed during APN could discriminate kidneys that would develop scarring fie remain abnormal) from those that would not fie normalize). Methods. DMSA was performed in 43 children (85 kidneys) at acute phase (DMSAI) and 7-+-2 months after APN (DMSA2). All DMSA were graded using a 9 point-semi-quentitative uptake score (each kidney divided in 3 thirds graded from 0 (no uptake) to 3 (normal uptake)) considered to be gold-standard. Renal scarring was defined as a score <7 on DMSA2. A comparison between the scores of DMSA l and DMSA2 leaded to classify each kidney as: normal stable (iNS) when scores an DMSAI end DMSA2 were >7. abnormal improved (AI) when score was <7 on DMSAI end had improved by 2 points or more on DMSA2 end abnormal stable (AS) when score was <7 on DMSA1 but improved by less then 2 points on DMSA2. For quantitative analysis of DMSAI, successive thresholds (20, 30, 40, 50, 60, 70 and 80%) were automatically applied to the posterior view ofench kidney. For each threshold, the number of pixels and the count rate were expressed as a percentage of the total number of pixels end the maximal count rate over each kidney respectively. The ANOVAs and ROC curves analyses were performed. Results. The distribution of kidneys was NS = 59, AI= 14 and AS= 12. Scarring was better predicted by the count rate ratio than that of the number of pixels ratio. Using ANOVA, it was possible to discriminate the NS, AI and AS kidneys by the count rate ratio (F =14.6, p <,0001). For the count rate ratio, a 70% threshold best isolated the AS from the Al kidneys (p =.004) and the NS from the AI kidneys Lo <.0001 ). On ROC curve analysis, this 70% threshold provided the best AUC tbr prediction of renal scarring. Using a cut off value of .45 the sensitivity, specificity, positive and negative predictive values of the 70% threshold count rate ratio to predict scarring were .78, .83, .84 end .77 respectively.

• OTHER CLINICAL SCIENCE. PEDIATRICS Conclusion. A .45 cut-off value t't~r the 70% threshold count rate ratio calculated on 99mTcDMSA scintigraphy pertbrmed during acute pyelonephritis may help to predict renal scarring. Patients with a value > .45 did not develop renal SCmTingafter their pyelonephritis.

PS_311 PROGNOSTIC VALUE OF DMSA SClNTIGRAPHY IN CHILDREN WITH ACUTE PYELONEPHRITIS: FIRST RESULTS FROM A PROSPECTIVE STUDY V. Roelants (1), D. Tuerlinckx (2), T. Vander Borght (1), G. de Binderling (2), E. Bodart (2). (1) Department of Nuclear Medicine; (2) Department of Pediatrics, Yvoir, Belgium. Aim: The aim of this prospective study was to report the evolution of various dimercaptosuccinic acid scitoigraphy (DMSA) patterns observed in children with acute pyelonephritis (APN) and to evaluate the ability of DMSA to identify patient at risk tbr renal scarring. Methods: The study group included 21 children with no previous history ofAPN (15F/6M; mean age: 44 months; range: 3-168 months) who presented with an APN as defined by a rectal temperature >38i, :t flank pain or non specific symptoms and a positive urine culture. All patients underwent a DMSA within 2-3 days of admission and 6.8±1.1 months later and were treated with the same antibiotic regimen for 15 days followed by prophylactic antibiotherapy until DMSA was repeated. Scans were performed 4 hours after IV injection of a weight adjusted dose of Te-99m-DMSA and at least 4 planar views were obtained (anterior, posterior, right and left posterior oblique; 200-300 kcounts/view). Images from both scan sessions were visually interpreted according to a 5-grade scale (grade 0: normal; grade I : moderate hypoactive cortical area without outline deformation; grade 2: severe hypoactive cortical area without outline deformation; grade 3: wedge-shaped cortical defect and grade 4: deformed outline = scar) and compared together. Differential renal function was calculated using the geometrical mean method (a relative uptake between 45 and 55 % was considered as normal). Results: Initial DMSA was abnormal in 16/21 patients (76%) and 29 lesions were observed (grade 1: n=16, grade 2: n=8; grade 3: n=3; grade 4: n=2). No patient suffered a second APN before the repeated DMSA. At 7 months, all normal DMSA remained normal, 9/16 patients (56%) normalized their scan while 4/16 (25%) demonstrated an improved pattern and 3/16 (19%) had a grade 4, consistent with scar. 23/29 lesions (79%) either improved or normalized, whatever their grade at the first scan. An altered initial differential renal function (n=3) was always associated with at least one lesion which severity remained unchanged 7 months later, whatever its grade. So far, none of the other non scintigraphic reported risk factors for scar was confirmed by this study. Conclusions: These results suggest that differential renal function could be a reliable scintigraphic parameter to predict which patient with APN will develop persistent renal damage at 7 months. They also suggest that cortical retraction may not always correspond to renal scar and that 7 months may be insufficient for complete recovery of cortical function.

e. o

PS_310

PS_312

STUDY OF THE RELATIONSHIP BETWEEN RECURRENT LOWER RESPIRATORY TRACT INFECTION, GER AND BRONCHIAL.ASTHMA IN CHILDREN

QUANTIFICATION OF LEFT-TO-RIGHT CARDIAC SHUNTS BY EXPONENTIAL EXTRAPOLATION OF SHUNT ACTIVITY IN LUNG CURVES

L. Kabasakal (1), N. Alan (1), O. ()zmen (1), M. Hala~ (1), H. Gokugras (2), Y. Gam~;oOlu (2), G. (~nsel (1), I. Uslu (1). (1) Department of Nuclear Medicine ; (2) Department of Pediatrics. Cerrahpa~a Medical Faculty, Istanbul University, Istanbul, Turkey, Istanbul, Turkey.

A. Stanicic (1), R. Jakl (2), D. Ivancevic (3), S. Popovic (3), Z. Milas (4), V. Gapkun (1). (1) Department of Nuclear Medicine, Clinical Hospital, Split; (2) Department of Pediatrics, Clinical Hospital, Split; (3) Department of Nuclear Medicine and Radiation Protection, University Hospital, Zagreb; (4) Faculty of Engeneering, Split, Croatia

Gastroesophageal reflux (GER) has been suggested as a cause of recurrent respiratory infections, bronchial asthma and sudden death syndrome. GER scintigraphy has been shown to be a sensitive, noninvasive and a simple test in detection of GER. The aim of the present study which is a part of CRP conducted by IAEA, was to evaluate the relationship between GER and respiratory disorders using the outcome of therapy as final diagnosis, For this purpose 41 patients, mean age 48.3±28.3 months, 23 f, 37 m. who had recurrent respiratory infections were included to the study. All patients were followed clinically for 3 to 6 months to evaluate the outcome of medical antiacid therapy. All patients underwent GER scintigraphy using Tc99m labeled colloid and up to 24 hours images were obtained from all patients. The number and the severity of GER episodes were evaluated visually and by generating the time activity curves of esophageus as well, All patients who had scintigraphic GER were treated using a standard antiacid treatment, Results: GER was determined in 68% of patients (n=28). GER was observed 82% of patients who had vomiting as primary symptom (n=l 1) and 40% of patients who had bronchial asthma as primary symptom, Antiacid treatment was given 86% of patients(n=24) who had GER, Among patients who received antiacid treatment 83% (n=20) of patients have demonstrated clinical improvement. Surgical treatment was performed in 1 patient and 3 patients were died due to severe broncopolmonary insufficiency. Among the patients who did not show GER and who received only symptomatic treatment for pulmonary diseases 70% (n=10) have demonstrated clinical improvement. In conclusion, GER scintigTaphy is a noninvasive and sensitive test in the evaluation of patients with recurrent respiratory infections and may be useful in the management planing of these patients. This study is a part of Coordinated Research Program conducted by International Atomic Energy Agency.

Radionuclide methodology offers the data for quantification of lefr-to-right cardiac shunts as good as those from dye curves obtained during cardiac catheterization, Therefore it still deserves efforts for improvements. The possibility to separate the shunt activity from the systemic recirculation activity in lung curves is expected to give data for a more precise quantitative analysis. Methods: A hydrodynamic model of left-to-right without systemic recirculation was used to analyze the time relationships between the single passes of radionucfide. An exponential decline of shunt activity was observed, as in left-to-fight shunts a constant fraction of indicator leaves the central pool in each circulation. Pulmonary time-activity curves obtained by radionuclide angiocardiography from 31 patients aged l week to 28 years (mean 14.5 years) were analyzed. The diagnosis of a left-to-fight cardiac shunt was established by cardiac catheterization. We also analyzed 20 curves obtained from patients without shunting. Results: After subtraction of normal activity between the first pass and systemic recirculatioe components, a logarithm of the difference curve (i.e. of the shunt activity) could be fitted with a straight line for an interval comprising almost the entire three initial passes of activity through the lung, and with coefficients of correlation higher than 0.98. By extrapolation of the straight line, the systemic recirculation activity could be separated from shunt activity. The Qp/Qs ratio obtained by the standard method was tested using the extrapolation data. Gamma variate curves for successive shunt recirculatioas were added at time intervals which were based on the data from the hydrodynamic model and the data from the two first gamma variate fits. In the successive step changes in the second dowrtsiope of the second gamma vafiate fit were made. The Qp/Qs ratio which could reproduce the experimental curve with the lowest coefficient of variation was accepted. A good correlation with oximetry data was found with the regression line close to the line of identity, The errors in the computed shunt size would be within ±4% of pulmonary flow. Conclusions: Radionuclide method can be easily applied in all age groups and data acquisition last for a short time. The error in the computed left-to-right shunt size is significantly lower than the reported values obtained by other methods.

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OTHER CLINICAL SCIENCE. PEDIATRICS

PS_313

PS_315

URINARY N-ACETYL-BETA-GLUCOSAMINIDASE

IN CHILDREN

WITH UPPER URINARY TRACT INFECTION, IN RELATION TO TC-99M DMSA SCINTIGRAPHY

G. (~apa Kaya (t), Y. Ta~kiran (2), M. Bak (2), A. Aydm (t), O. Toksavul (2), Y. Uslu (2), E. OztLirk (2), H. Durak (1). (1) Department of Nuclear Medicine, Dokuz EylLil University Medical School, Izmir, Turkey; (2) Beh~:et Uz Children's Hospital, Izmir, Turkey. N-acetyl-beta-glucosaminidas¢ (NAG), a lysosomal enzyme, is located in the renal proximal tubule cells. In recent studies, urinary NAG levels has been used to localize urinary tract infection (UTI) and demonstrate epithelial necrosis of proximal tubule cells. The aim of this study was to investigate the relationship between Tc-99m DMSA scintigraphy and urinary NAG and NAG/creatinine in acute pyelonephritis. Methods: Hundred children with the mean age o f h . l ± 3.0 were included in this study. All children had positive urine culture. Tc-99m DMSA scintigraphy was performed within 3 days after the diagnosis of UTt. Plasma C reactive protein (CRP), erythrocyte sedimentation rate (ESR), leucocyte count, urinary NAG levels and NAG/creatinine ratios were also obtained. Thirty children had focal or diffuse decreased uptake, segmental cortical thinning and cortical irregularity in Tc-99m DMSA scintigraphy (Group I). DMSA scintigraphy was normal in 70 children (Group 2). Results: CRP, ESR and leucocyte count in group I (7.9~:8.1 rag/It, 56±26 ram/h, 15277~:9162, respectively) were significantly higher than Grap 2 (1.0±1.8 rag/It, 24±15 ram/h, 9626~:3833, respectively). Urinary NAG levels and NAG/creatinine ratios are shown in the table. Group I Tc-99m DMSA (+)

Group 2 Tc-99m DMSA (-)

P vatuas

NAG (U/L)

11.7 ± 2.5

2,6 ± 2.4

? 0.05

NAG/creatinine(U/gr)

16.6 ± 5.6

3.6 ± 3.3

? 0.05

In the localization of UTI, cuboff value was found as 5 U/L for NAG, 7 U/gr for NAG/creatinine ratios. There was a significant correlation between Tc-99m DMSA scindgraphy and uri. nary NAG (r = 0.864. p = 0.01) and NAG&reatinin (r = 0.863, p = O.01). Urinary NAG and NAG/creafinine had a sensitivity of 100 %. specificity of 94 %, positive predictive value of 88 %, negative predictive value of 100 % for acute pyelonephritis. Conclusion: In this selected group or" patients, urinary NAG and NAG/creatinine can be used to localize upper UTI when compared to Tc-99m DMSA scintigraphy.

RADIONUCLIDE ASSESSMENT OF GLOMERULAR AND TUBULAR FUNCTION IN CHILDREN WITH PRIMARY VESICOURETERAL

REFLUX M. Vlaikovic (1), M. Bogicevic (1), M. Rajic (1), S. Ilic (1), G. Lilic (1), D. Mitic (1), A. Slavkovic (2), V. Artiko (3). (1) Department of Nuclear medicine, Clinical Center, Nis,Yugoslavia; (2) Clinic for Pediatric Surgery, Clinical Center, Nis, Yugoslavia; (3) Institute of Nuclear Medicine, Clinical Center Serbia, Belgrade, Yugoslavia. OBJECTIVES:The purpose of this study was to investigate whether the glomerular and tubular renal parameters are in concordance in children with primary vesicoureteral reflux (VUR). MATERIAL AND METHODS: A total of 94 children with 117 refluxing nefroureteric units (NU) were grouped according to the International Reflux Study Committee grading system as follows: Group [ (VUR grades I, n=lT), Group 11 (VUR grades ll-ll[, n=70) and Group Ill (VUR grades IV-V, n=30). Findings were compared with those obtained in 64 healthy children. Overall and single kidney function was assessed using 99mTc-DTPA dynamic and clearance studies and 99mTc-DMSA static and uptake (2h and 24b) studies, respectively. RESULTS: Significant correlation was found between relative function of kidneys in children with VUR obtained using 99mTc-DTPA of 50.0~7.0% and both 99mTc-DMSA uptake after 2h of 50.0~7.9% (R=0.906, p
PS_314

PS_316

DOPPLER US IN THE DIAGNOSIS OF ACUTE PYELONEPHRITIS: COMPARISON WITH TC-99M DMSA SClNTIGRAPHY

SClNTIGRAPHIC SUPRANORMAL DIFFERENTIAL RENAL FUNCTION IN THE FIRST YEAR OF LIFE

G. (~apa Kaya (1), Y. G6ktay (2), A. Aydln (1), M. Seqil (2), I.Y. Ta~klran (3), M. Bak (3), H. Durak (1). (1) Departments of Nuclear Medicine, Dokuz Eyl~l University Medical School, Izmir, Turkey; (2) Radiology, Dokuz Eyl(]l University Medical School, Izmir, Turkey; (3) Behget Uz Children's Hospital, Izmir, Turkey.

A. Biyi (1), H. Lottmann (2), G. D'Amore (1), Y. Aigrain (2), B. Bok (1), E Bonnin (1). (1) Department of Nuclear Medicine, Seaujon Hospital, Clichy, France; (2) Department of Surgery, Robert Debre Hospital, Paris, France.

The appropriate treatment of urinary tract infection requires to assess the localization of infection. Tc-99m DMSA scintigraphy is considered as a gold standard in the diagnosis of acute pyelonephritis. The aim of this study was to compare Tc-99m DMSA scintigraphy with Doppler US (DUS) in children with clinically suspected acute pyelonephritis. Methods: Eighty seven children (mean age: 5.1 ± 3.1, 72 girls and 15 boys) with the first episode of urinary tract infection and positive urine culture were included in this study. In all children, Tc-99m DMSA seintigraphy and DUS were performed within 3 days after the diagnosis of urinary tract infection. Focal or diffuse decreased uptake, segmcmal conical thinning and cortical irragnlarit3, in Tc-99m DMSA sciatigraphy were interpreted as an abnormal. Evaluation was performed both for each kidney (total of 169 kidney) and for each region as the upper, middi¢ and lower regions separately (total of 522 regions). Results: 25 of 169 kidneys were evaluated as an abnormal on planar images of Tc-99m DMSA scintigraphy. 14 of 25 kidneys were abnormal in DUS. Sensitivity (SEN), specificity (SPE), positive predictive values (PPV) and negative predictive values (NPV) were 56%, 88%, 45% and 92% for DUS, respectively For each kidney, SEN and PPV were 64% and 47% for left kidney, 45% and 39% for right kidney. When the evaluation was performed according to regions, DUS was positive in 19 of 30 regions with abnormal DMSA scintigraphy and SEN, SPE, PPV and NPV were 63%, 96%, 48% and 98% for DUS, respectively. Upper region of the right kidney had the lowest SEN (33%) and middle region of the left kidney had the lowest PPV (48%). Conclusions: We concluded that the sensitivity of DUS is relatively low in the diagnosis of acute pyelonephritis and sensitivity rate can be changed according to the kidney and region in which the lesion is localized.

can be seenon the side of the dilatation. The aim of this paperwas to assesswhetherkidneys

1156

In neonates with unilateral hydronephrosis, a supmnormal differential renal function (DRF) with normal and supranonnal DRF have the same scintigraphic evolution during the first year of life. Methods: 131 consecutive cases with unilateral hydmnephrosis detected before birth by ultrasound were reviewed. The surgical management was identical for all children. In each case, one renal seintigraphy (RS) was performed at 3 months of age (range: 1-6 months), and one 6 months later using the same protocol¢ (mercaptuacetyltriglycin¢ labelled with 15 MBq of 99mTc; standardized hydratation). The DRF (area method) and a ratio S (surface of the dilated kidney divided by the surface of the normal kidney) were derived from all KS using regions of interest which were manually drawn on images taken 2 to 3 minutes after the tracer injection. DRF values and S values ware compared cuing ANOVA and paired t tests. Results: At the first RS, 24 neonates ([8%) had a supranormal DRF (14 cases -group lunderwent surgery and f0 -group 2- were not operated) and 107 cases had a normal DRF (16 group 3- underwent surgery and 91 -group 4- were not operated). Between the two RS, 23% (30/13l) of the children were operated including 46% (14/30) of cases with supranormal DRF. At the second RS, the variations of DKF and S values were different in the 4 groups (0<0.05). In group 1, the values of DRF decreased from 57±2% to 52±4% (0<0.05) and the values of S decreased from 48~:33 to 15±19 (0<0.05). In group 2, the DRF values were unchanged and the S values increased non significantly. In group 3 and 4, the DRF and the S values were unchanged. Conclusion: In the first year of life using the same criteria for surgical decision for all kidneys, the post-surgical changes of DRF and size of the dilated kidneys are different whether the DRF is normal or supranormal.

• OTHER CLINICAL SCIENCE. PEDIATRICS

PS_317

PS_319

COMPARISON OF SINGLE INJECTION RADIONUCLID METHODS WITH CLASSICAL CREATININE METHOD FOR CLEARANCE DETERMINATION IN CHILDREN ON PERITONEAL DIALYSIS (PD)

THE CLINICAL USEFULNESS OF TC-99M ECD BRAIN SPECT IN MEASLES ENCEPHALITIS

A. Bogdanovska (1), S. Kuzmanovska (2). (1) Department of Nuclear Medicine; (2) Pediatric Clinic, Medical Faculty, Skopje, Macedonia. 51 Cr-EDTA is very suitable radiopharmaceutical for GFR determination as a substitute for inulin clearance . The single injection method and monoexponential expression of plasma disappearance rate is well established in nuclear medicine. The idea was to use the method in patients undergoing PD in order to simplified the cumbersome procedure for creatinine clearance with fluid collection. Six children aged 9.6 (6-14) years on PD were studied in hospital .51Cr-EDETA (3MBq) And 99m Tc-DTPA (200MBq) were injected simultaneously after the filling of peritoneal cavity with dialysata fluid.Blood samples were drawn at 4,24, and 48 hours after injection.Samples of 2 ml plasma and standards were counted on scintillation counter. Peritoneal clearance was calculated taking the necessary data from the fitted monoexponential curve. There is high correlation between 51Cr-EDTA and 99mTc-DTPA clearance (r=).985,r+0.995)for any combination of two plasma samples, so the number of plasma sample could be reduced on two . We tried to obtain peritoneal clearance with single injetion method using one plasma sample.For that purpose we correlated the activity ration of the given dose and plasma sample (D/P) with clearance calculated with three plasma samples.The following coefficient of correlation were obtained : r= 0.751 for 4 h , r=0.986 for 24h and r=0.974 for 48h.Thc regression equation for 24h sample clearance =1.11 I+0,278(D/P) may be used for injection of clearance with one plasma sample , withdrawn 24 hours after injection of radiopharmaceuticaI.Mean error for clearance calculated in this way is 3.0% CONCLUSION: The single injection radiotraser method can be used for clearance estimation in patients on PD. Number of plasma samples may be reduced in one with most appropriated time after 24 hours.

S.T. Lim (1), M.H. Sohn (1,3), J.C. Kim (2). (1) Department of Nuclear Medicine; (2) Department of Pediatrics; (3) Clinical Medical Reserch Center, Chonbuk National University Hospital, Chonbuk National University Medical School, Chonju, Korea. Purpose: Since the prognosis of measles encephalitis is poor, early diagnosis and proper management are very important to improve clinical outcomes, We compared Tc-99m ECD brain SPECT (SPECT) with MR imging (MRI) for the detection of mesles encephalitis. Materials and Methods: Eleven patients (M:F-4:7, age range 18 months-14 yrs) with measles encephalitis were enrolled in this studies. All of them underwent both MRI and SPECT. The results of SPECT were scored from 0 (normal) to 3 (defect) according to perfusion state. We compared two image modalities for the detection of brain abnormality in measles encephalitis. Results: Seven of 11 patients (63.6%) revealed high signal intensity in the white matter on T2WI of MRI, on the other hand all patients (100%) showed hypoperfusion on SPECT. Severe perfusion deficits above score 2 were located with decreasing frequencies in the frontal lobe (81.8%), temporal lobe (72.7%), occipital lobe (27.3%), basal ganglia (27.3%), and parietal lobe (9.1%). Conclusion: We conclude that SPECT is more useful than MRI for the detection of brain involvement in patients with measles encephalitis.

tO

PS_318 PROGNOSTIC VALUE OF THE ACUTE DMSA SCAN IN CHILDREN AT FIRST URINARY TRACT INFECTION A. Biggi (1), G. Pomero (1), P. Cussino (2), L. Dardanelli (1), GF. Camuzzini (1). (1) S.Croce e Carle Hospital, Cuneo, Italy; (2) Ss. Annunziata General Hospital, Savigliano, Italy. Therecognitionof a groupof patientsat risk to developsequelaeamongchildrenwith urinary tract infection (UTI) in order to modulate the treatment and the radiological investigation is of great clinical importance. Aim. In this prospective study we attempted to verify in 101 children at first UTI if it is possible to identify groups of patients with different risk of developing renal scarring, by taking into account both the extent of kidney involvement documented in the acute phase of infection using DMSA scan, and the presence or absence of vesicoureteral reflux (VUR). Methods. We included only children at first symptomatic UTI, in whom the interval between the onset of symptoms and the diagnosis of UTI was less than 6 days and in whom DMSA scan was performed no later than 15 days following the presentation, the others being excluded. This study design consists of performing an acute DMSA scan (acute scan) for the detection of renal parenchymal involvement in the acute phase of infection, eystoorethrography for vesicoureterat reflux detection and grading, and a follow-up scan (late scan) performed if the acute scan was abnormal. 101 children, 60 females and 41 males were inlcuded in the study. The mean age was 18 months (range I month - 13 years). Results. Of the 101 children included, 31 had normal kidneys; 9 of the 70 children with pyelonepbritis had bdateral disease. A follow-up scan was available in 59 of 79 kidneys with positive acute DMSA scan. 16/59 (27%) of abnormal kidneys had persistent lesion. The frequency of persistent lesions in kidneys with mild-moderate lesions (less than 50% of kidney involvement) in presence of VUR or in non-refluxing kidneys was similar (p=0.1447), while the frequency of persistent lesions in kidneys with severe lesions in presence of VUR was significantly higher than the frequency of persistent lesions in non-refiuxing kidneys (p=0.0089). Conclusions. The extent of kidney involvement and the presence of VUR make possible the identification of different categories of risk of scarring: in the ,,low risk group" (normal kidney with/without VUR) the risk of scarring is (Y)A; in the ,,intermediate risk group" (mild lesions with/without VUR; extensive lesions without VUR} the risk of scarring is between 14% and 38%, while in the ,,high risk group" (extensive lesions with VUR) the risk of scarring is 88%. Quantifying the risk of scarring could help in planning the treatment or in modifying later strategy.

PS_320

t~

BONE SCINTIGRAPHY AND SPINE INJURY IN CHILDREN o~

E. Urbanova (1), J. Preis (2), J. Vizda (1), P. Kafka (1), M. Netikova (1). (1) Department of Nuclear Medicine; (2) Department of Pediatric Surgery, University Hospital, Hradec Kralove, Czech Republic. Children with a suspicion of bone damage mostly after sport, or home accident were admitted to the hospital. They were referred for bone scintigraphy, The most common reason for referral were the exclusion of spine occult fractures or infractions. The aim of this study was to assess the role of bone scintigraphy in comparison with X-ray investigation. Methods: We evaluated 58 children during seven years. Bone seintigraphy and SPECT SCanning were performed 2h after intravenous injection of 99mTc-MDP. The interval from injury to scintigraphy was 5-14 days. The mean time between bone scintigraphy and X-ray investigation was 3 days (range 2 - 8 days) Results: Normal results in both methods were in 23 of the 58 patients. The pathological findings were identical in 16 pts. In 19 from all investigated pts. bone scintigraphy concurred with X-rays as to the number and localisation of abnormalities, For 13 pts. bone scintigraphy proofed new or additional foci when compared with X rays and in 6 pts. only bone scintigraphy showed loci of spine. Conclusions: Bone scintigraphy has a significant role in the investigation of spine pain after injury. The wider availability of SPECT has increased the number of clinical applications and enhanced sensitivity and specificity compared with planar imaging. Nuclear medicine provides information to identify the significance of structural changes found on anatomical imaging. Some of them may be asymptomatic.

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• PEDIATRICS / RADIOPHARMACY / RADIOCHEMISTRY 2 PS_321

RADIOPHARMACY / RADIOCHEMISTRY 2

MYOCARDIAL SPECT IN CHILDREN WITH SICKLE CELL ANEMIA C. Maunoury, P. Acar, I. Hallaj, L. Barritault. Hopital Necker-Enfants Malades, AP-HP, Paris, France. While cerebral and bones strokes are well documented in children with sickle cell anemia (SCA), impairment of myocardial perfusion is an unknown complication. ConventionaI techniques such as exercise testing and ecbocardiography have a low sensitivity and specificity to detect myocardial ischemia in patients with SCA. The aim of this prospective study was to assess myocardial perfusion with TI-201 SPECT in children with SCA. Methods: Thirteen patients, aged 12±4 years, were included. Myocardial perfiJsion was assessed by TI-201 SPECT after stress and 3 hours later after reinjection on a single head gammacamera equipped with a LEAP collimator (64x64 matrix size format, 30 projections over 180i, 30s per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium rsdionuclide angiography at rest on the same day. Results: Myocardial perfusion was impaired in 6/13 patients: 3 had reversible defects and 3 had fixed defects• The left ventricular cavity was dilated in 7/13 patients. The mean LVEF was 62±9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. Conclusion: Myocardial perfusion is frequently impaired in children with SCA. Prospective studies with a larger number of patients could assess the incidence and potential complications of myocardial ischemia in patients with SCA.

PS_322 EVALUATION OF GASTRIC EMPTYING SClNTIGRAPHY AND 13C-BREATHING TEST IN PEDIATRIC PATIENTS N. Hamscho (1), J.H. Risse (1), B. Braden (2), P. Ahrens (3), M. Diehl (1), F. Gr0nwald (1). (1) Dept. of Nuclear Medicine; (2) Dept. of Internal Medicine; (3) Center of Pediatric Medicine, University of Frankfurt, Germany. Gastric emptying scintigraphy has been predominantly described in adult patients. The aim of this study was to evaluate gastric emptying scintigraphy on pediatric patients who presented with branehopulmonary diseases and to define typical gastric emptying curve patterns in correlation to tbe i3C-acetate- breathing test. Methods: We performed gastric emptying scintigraphy on 32 patients aged between 4 and 16 years with recurrent broncbopulmonary infections which were thought to be due to gastroesophageal reflux. A semiliquid test meal was applied (rolled oats 5g, milk 75ml. sugar 3g, 40-60 MBq egmTechnetium-Nanueoll, L3C-ecetate). This was followed by dynamic images over 60 rain. The results of the scintigraphy were correlated with motility examinations and with the results of the =3C-breathing test. The scintigraphic reference range of the gastric emptying was adopted from adult patient populations (tl/z=60 rain) because of the lack of reliable pediatric references. Results: Out of 32 children 23 showed physiological, 7 obvious pathological and 2 borderline gastric emptying time (ha=60 rain). The comparison with the 13C-breathing test showed a strong correlation between the half-life ranges of gastric emptying and those of the 13Cbreathing test (tin=90 rain). Conclusions: Our data may help to improve the standards of gastric emptying scintigraphy in pediatric patients. We could show a strong correlation between the gastric emptying seintigraphy and the nC-breathing test in both pathological and physiological curve types,

1158

PS_323 RGD-DTPA-OCTREOTATE, AN ANALOGUE FOR TUMOUR IMAGING AND RADIONUCLIDE THERAPY M. De Jong (1), H.E Bernard (1), A. Capello (1), W.A.P. Breeman (1), A. Srinivasan (2), M. Schmidt (2), E.P. Krenning (1), P.M. Van Hagen (1). (1) Erasmus University Medical Center Rotterdam, The Netherlands; (2) Mallinckrodt Medical Inc., St Louis Mo, USA. Introduction and Aim: receptor-targeted scintigraphy and radionuclide therapy using radiolabelled somatostatin analogues are successfully used to detect and treat somatostatin receptorpositive (mainly subtype 2 (sst2)) tumours. Also interesting for these purposes are RGD(ArgGly-Asp) peptides as they can antagonise tumour angioeeogenesis, e.g. by binding to alpha~beta 3 receptors on newly formed blood vessels, and induce apoptosis. Methods and Results: we evaluated Tyr3-octreotate. chelated with DTPA or DOTA, and found 177 3 very high affinity binding to sst~, leading to high uptake of Lu-DOTA-Tyr-octreotate in sst,-positive turnouts in patients and rats. Radioooclidc therapy in rats using the latter compound resulted in dose dependent responses with up to 100% cure after 555 MBq, showing its great promise. Moreover, we introduced the RGD analogue c(Arg-Gly-Asp-D-Tyr-Lys)chelated with DTPA. In vitro and in vivo the analogue appeared to bind with high affinity to alpha~beta~ receptors on blood vessels and turnout cells in different rat and human cancers. To combine turnout uptake via sst~ and alphavbeta 3 receptors, we synthesized an RGD-DTPATyr]-octreotste hybrid peptide. Labelling studies showed good labelling with HIIn. In vitro binding studies showed that the radiolabelled compound bad retained affinity for both sst.~ and alphavbeta 3 receptors, binding could be blocked with an excess of the different competing analogues. In animal studies, the high uptake thund in the (sst~_-and alpha~beta~ receptor-positive rat pancreatic CA20948) tumour was mainly via sst~ targeting, presumably because of the higher affimty ofTyr -octreotate for sst, than that ot RGD tor the alpha beta1 receptor. The therapeutic effects of DTPA-Tyr -octreotate. RGD-DTPA-Tyr ..octreotate and DTPARGD Iabelled witb tbe Auger electron emitter ~IZ[n, were evaluated in vitro in a single celt, colony forming assay ( 100 cells/well in 6-well plates, 1 h incubation with HI[n-labelled peptide. 10 days colony growth) using CA20948 cells. These cells showed relative radioresistance in external beam radiation studies (survival after I and 2 Gy was 70*/0and 5 0 0 of control). In our in vitro system, all analogues were able to control tumour growth 10% survival). the effects were dependent on radiation dose, incubation limc and specific activity used. Conctusion: this hybrid peptide radiopharmaceutical is suitable not only thr turnout scintigraphy, but it has potential Ibr radionuclide therapy as well.

PS_324 VENTRICULAR NATRlURETIC PEPTIDE (BNP) IN HEART TRANSPLANTATION. CORRELATION OF PLASMA CONCENTRATIONS OF BRAIN NATRlURETIC PEPTIDE AND ENDOMYOCARDIAL BIOPSY I. Hervas (1), L. Alrnenar (2), R Gonz~llez-Cabezas (1), A. Saura (1), J. Osca (2), R Bello (1), J.L. P~rez-Pastor (1), J.F. Martf (1), A. MateD (1). (1) Department of Nuclear Medicine; (2) Depratment of Cardiology, University Hospital, Valencia, Spain. Aim: Ventricutar natriuretic peptide (BNP) is a novel cardiac hormone that may play a pathophisiologyc role in cardiac disorders. High levels of plasma ventricular natriuretic peptide have been identified after standard orthotopic cardiac transplantation~ The aim of this study was to determine whether elevated plasma BNP levels observed after cardiac transplantation are related to the severity of rejection on the endomyocardial biopsy (EB). Methods: We have studied 80 consecutive heart transplant patients (11 women and 69 men). In all of them we have determined the BNP levels using a mdioimmunometric assay at the moment of the heart transplantation and the same day that were admitted to perform an EB. We have compared 223 BNP levels in serum with the grade of rejection on the EB (graded according to the International Society of Heart and Lung transplantation Standarized Grading System). For comparing that we have divided the patients in four groups according to the results on the endomyocardial biopsy: The first group (n=56) were the EB graded 0. The second (n=77) graded 1 A and 1 B. The third (n=60) graded 2. The fourth (n=30) graded 3 A, 3 B and 4. As statistical tool we have used the student's t test. Results: The first group presented a mean BNP value = 171.8 pg/ml, the second a mean BNP value = 182.38 pg/ml, the third a mean BNP value = 263.69 pg/ml and the fourth a mean BNP value = 3~t.56. The fourth group (with suspicion of cardiac allogralt rejection on the EB) had significant increased BNP levels (I)<0.05) comparing with the other groups ( with no suspicion of cardiac allograft rejection). Conclusion: Mean BNP levels increased according to the increase of degree on endomyecardial biopsy. The group with suspicion of cardiac allograR rejection on the EB presented significant increased BNP values. These data suggest that BNP plasma levels could form the basis for a new, non-invasive screening test to predict acute cardiac allograft rejection.

• RADIOPHARMACY / RADIOCHEMISTRY 2

PS_325

PS_326

PREPARATION OF THE LIPOSOME ENCAPSULATED PLATINUM[1251]IODOHISTAMINE COMPLEX. PRELIMINARY RADIOCHEMICAL AND BIOLOGICAL STUDY

PRECLINICAL COMPARISON OF FOUR YTTRIUM LABELLED SOMATOSTATIN RECEPTOR-SPECIFIC PEPTIDES AS CANDIDATES FOR CANCER TREATMENT

P. Garnuszek, I. Licifiska, A.P. Mazurek. Drug Institute, Warsaw, Poland.

A. Laznickova (1), M. Laznicek (1), F. Trejtnar (1), H. Maecke (2), K. Eisenwiener (2), J. C. Reubi (3), S. Wenger (3). (1) Faculty of Pharmacy of the Charles University, Hradec Kralove, Czech Republic; (2) Nuclear Medicine Department, University Hospital, Basel, Switzerland; (3) Institute of Pathclogy, University of Bern, Switzerland.

It hasbeendemonstratedboth in laboratoryand in clinical trials that applicationof multifactorial cancertherapy,e.g. by combinationof an ionisingradiationand chemotherapeuticagents, enhance anticancer potency of the treatment. In a previous work we synthesised the platinum[*l]iodohistamine complexes possessing cylostatie activity beth in vitro and in vivo. The present work aims Io study the potential use of liposomes for specific targeting of the radioactive ptatinum-iodohistamine complex. Methods: Liposomes with positive surlace charges were tbrmed in the presence of stearylamine (18 mmoles), phosphafidylcholine (63 mmoles), and cholesterol (9 mmoles) (Sigma kit L4395). Eneapsulations of the Pt-[l"Sl]iodohistamine (specific activity ca. 0.5 MBq/mmol of Pt) were studied using a dift'erent molar ratio of the complex and lipid, likewise various incubation procedures. The yield of the complex entrapment into liposomes was monitored by TLC and RP HPLC. The comparative biodistribution study in healthy Wistar rats was done . . . . . " " aider intravenous administration ol. the encapsulated and rea Pt-[ i,'5l]lod ohlstamme. Results: The highest yield of the encapsulation (ca. 80%) was achieved after mixing the complex solution in DMSO with the freeze-dried liposomes in the molar ratio of the lipid to Pt 1.5:1, lbllowing by rehydration with saline and incubation for 1 hr at 50°C with shaking and occasional sonication. There were significant difterences in the organ distribution between of the two preparations of the radioactive platinum complex (table 1). The concentration oftbe activity in blood after 2 hrs p.i.v, was two times lower for the encapsulated complex, and uptake of the radioactivity by liver, spleen, and lungs were more than twice that obtained with the free Pt-[t'~Sl]iodohistamine preparation. Table I. Comparison of tissue uptake of the two preparations of platinum-[l'~51]iodohistamine in rats (2 hrs p.i,v., %lD/g, mean and SD, N = 4) Tissue Blood (,I ml) Heart Th]croid ~,land Lun~ l.ivcr

Spleen Kidney, Stomach Intestine

pt -( ~'~IllodoH istamiae 1.16 ± 0,14

0.46 ± 0.09 0.80 ~- 0.40

0.60 ~- 0.02 1.86 ~ 0.27 1.00 ~ 0.33 2,37 ± 0.37 2.113 ~ 0.77 '0.71 ~: 0.03

Liposome-Pt-( ' '~I ]lodoHistamine 0.54 x~ 0.07 0.41 ± 0.05 0.21 ± 0.06

1.82 4.42 2.47 1.33

= ~ ± *

0.19 0.31 11.44 0.37

0.90 ± 0.26 0.52 ± O.ltl

Conclusion: The results of present study indicate that platinum-[l"~lJiodohistamine can be efficiently incorporated into cationic liposomes. However, evidently uptake of the encapsulated complex by the liver and spleen macrophages demands further modification of the lipid membrane. A variety of the existing protocols lbr coating of liposomes surthce make possible an opfimisation of the specific system for targeting of the platinum-radiopharmaceutical.

Visualization of somatostatin receptor-positive tumours with the employment of In/lll/DTPA-octreotide indicates potential applications of octreotide analogues labelled with a suitable therapeutic radionuclide (such as Y-90) for cancer treatment. The purpose of the present study was to compare biodistribution characteristics and to analyze elimination mechanisms of two octreotide analogues, namely Y-DOTA-octreotide (Y-DOTA-OC) and Y-DOTA-Tyr/3/octreotide (Y-DOTA-TOC), and two octreotate derivatives, namely Y-DOTAGA-Tyr/3/octreotate (Y-DOTA-GATATE) and Y-DOTAtGA-Tyr/3/-octreotate (Y-DOTA-t-GATATE), in rats. Methods: Radiolabefied peptides were prepared by adding an acidic yttrium/88/ chloride solution to the peptide in acetate buffer with gentisic acid. After incubation at 90-951C for 25 minutes, radiochemical purity was determined by gradient RP-HPLC analysis. Y/88/isotope instead Y/90/",,.,as used as a label because of its more suitable physical characteristics lbr oreclinical experiments. For biological experiments, male Wistar rats were used. For the analysis of elimination mechanisms, the perfused rat liver and the perfused rat kidney were employed. Results: Radiochemical purity of the peptides under study was higher than 98%. Biodistribution studies showed a similar radioactivity-time decrease in the blood and most organs in interdrug comparison. Binding to plasma proteins and blood cell accumulation were negligible for all agents. Radioactivity concentrations in organs with a high density of somatostatin receptors (the adrenals and pancreas) increased in the order Y-DOTA-OC < YDOTA-TOC < Y-DOTA-t-GATATE < Y-DOTA-GATATE and radioactivity excretion by thecos a~so increased in the same order, The main elimination pathway was urine excretion of radioactivity in all peptides. Perfusion experiments confirmed that the peptides were eliminated in the kidney mostly by glomerular filtration. Bile clearance in the perfused rat liver was very low for all agents. The main obstacle lbr therapeutic applications of radiolabelled peptides under study was high and long-term radioactivity uptake in the kidney. Conclusions: Radiolabelted peptides under study represent new drugs targeted for the radiotherapeutic treatment of somatostatin receptor-expressing tumors. The most promising candidate in this field is probably Y-DOTA-GATATE. The study was partly supported by the Grant Agency of Charles University - Grant No. 264/21)0 I, and partly by the Czech M inistry of Education - Project No. J 13/98: I 1600002

co

PS_327 TC(99M)-EDDA/HYNIC-TYR(3)-OCTREOTIDE: PHARMACOKINETICS IN RATS AND COMPARISON WITH IN(111)-DTPA-OCTREOTIDE M. Laznicek (1), A. Laznickova (1~, C. Decristoforo (2), S. J. Mather (3). (1) Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic; (2) Nuclear Medicine Department, University Hospital Innsbruck, Austria; (3) Nuclear Medicine Research Laboratory, St. Bartholomews Hospital, London, UK. For the detection of somatustatin receptor positive tumours, Tc(99m)-Iabelled HYNIC-Tyr(3)octreotide (HYNIC-TOC) using ethylene diamine diacetic acid (EDDA) as the co-ligand appears to be a promising agent to replace currently used oetreotide derivatives labelled with ln(t 11). The aim of this study was to determine biodistribution and elimination characteristics of the agent in rats in comparison with that of ln(I 11)-DTPA-octreotide (DTPA-OC). Methods: Tc(99m)-EDDA/HYNIC-TOC was prepared by a kit procedure with high specific activity and purified with the use of a SepPak mini cartridge. Radiochemical purity of the labelled peptide, determined by HPLC, was greater than 98%. Male Wistar rats were used for biological experiments. Distribution in 22 selected organs and tissues was determined 5 rain, 1 hr, 2 hrs, 24 his, and 48 hrs after administration of the peptides. Results: Distribution profiles of radiolabelled peptides under study in rats were very similar. Both agents exhibited rapid clearance from the blood and most organs, and the activity was eliminated mostly by urine. The fraction bound to plasma proteins was 0.15 for l n ( l l l ) DTPA-OC and 0,36 for Tc(99m)-HYNIC-TOC. High (but comparable) and long-term kidney uptake of radioactivity in both peptides was determined. On the other hand, radioactivity concantrations in sematostatin receptor-rich organs (the pancreas and adrenals) were significantly higher after Tc(99m)-HYNIC-TOC when compared with In(II1)-DTPA-OC. Radioactivity elimination into urine was somewhat slower and radioactivity excretion by faeces was higher (more than twice) after Tc(99m)-HYNIC-TOC in comparison with In(IlI)-DTPA-OC. Bile clearance of both agents, determined in the perfused rat liver, was very low and comparable, Conclusions: The results indicate similar pharmacokinetics of Tc(99m)-HYNIC-TOC and In(Itl)-DTPA-OC in rats and confirm that Te(99m)-HYNIC-TOC seems to be an excellent candidate for visualization of sematostatin receptor-positive tumours. The study was partly supported by the Grant Agency of Charles University - Grant No. 34/99/C, and partly by the Czech Ministry of Education - Project No. J 13/98:11600002

115E

txl e.. (1)

t_ (1) o IX

• RADIOPHARMACY / RADIOCHEMISTRY 2

PS_328

PS_330

NEW PEPTIDE CONJUGATES AS LIGAND FOR CHOLECYSTOKININ RECEPTOR LABELLED WITH RHENIUM

LABELING OF THE A N T I - M E L A N O M A 14F7 M O N O C L O N A L ANTIBODY WITH RHENIUM-188 USING A PRE-LABELED MAG3 CHELATE: OPTIMISATION, IN VITRO, A N D IN VIVO ANALYSIS

C. Pedone (1), G. Morelli (1), S. De Luca (1), A. Dolmella (2), U. Mazzi (2), M. Saviano (1), D. Tesauro (1), R. Visentin (2). (1) Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, Universit& degli Studi di Napoli ; (2) Dipartimento di Scienze farmaceutiche, Universit& di Padova, Padova, Italy. Several human tumors overexpress receptor of cholecystokinin (CCK). For these reason in the last years in nuclear medicine the interest to use as scaffold CCKg is increased• Aim Based on the structural NMR characterization of the interaction between the type A cholecystokinin receptor and CCKs ligand we syntbetized a new peptide conjugate covalently bond to a new chelating system to bind Rhenium and Technetium (CCKIOPRe). We have also tried to assets at the MM and QM level: (i) if the modified ligand CCKIOPRe is a stable smacture compared to CCK8; (ii) the details of the interaction between CCKA-R and CCKIOPRe. Methods. CCK-8 was synthesized according to standard solid-phase schemes• This compound was covalentty coupled to the ligand by adding a Cys protected, a Gly and the phosphine PPhz(CH~.)zCOOH, to the NH 2 free terminus of the peptidc anchored to the solid support; acid treatment allows peptidc cleavage from the resin and deprotection of amino acid side chains. The conjugate was coupled to metal treating in acetonitrilc with ReOCI~(PPh3),. The identification were performed using spectroscopic methods. The modeling of the PPh2(CH2)2-COGly-Cys- modified dipeptide has been made using the molecular templates available in the PC Spartan Pro software. The most obvious distortions of the resulting arrangement have been removed by running a MM (molecular mechanics) minimization; a i'hll geometry optimization has then been performed at the QM (semiempirical quantum mechanics) level, and the fragment has been stored for further calculations• MM calculations have been performed with the MMFF94 force field; QM work has been made at the PM3-RHF level. Results: The IR, UV spectrum and mass analysis confirm the coordination of the metal centre The theoretical studies highlight two different effects which follow the modification of the CCK8 peptide: the MM work suggests that the elongation oftbe peptidc chain enhances the internal strain, while QM data indicate that the stabilizing charge interactions lower the energy of the system. In addition, the modified ligand substantially preserves the most important binding interactions, especially those involving Tyr27-Met28 and W39-Q40. Conclusion." CCK-8-PN2S appears to be a good candidate to label with Rename complex and potentially technetium also. The MM and QM calculations suggest that the modified ligand CCKIOPRe is a stable molecule and that the interaction of CCKIOPRe with the receptor is substantially similar to the one made by the natural substrate CCK8.

J.L. Crudo, M.M. Edreira, E.R. Obenaus, S.G. de Castiglia. Division Radiofarmacos, Comision Nacional de Energia Atomica, Buenos Aires, Argentina. The aim of the present study was to optimise the procedure for labeling the anti-melanoma 1417 monocIonal antibody (MoAb 14f7) with 188 Re, using an active ester of S-benzoylmercaptoacetyhriglycine (S-benzoyI-MAGj). Quality assurance tests were performed during the entire labelling procedure and on the final radiolabelcd antibody. Stability studies in saline and human serum were also performed and the biodistribution of the labelled antibody was evaluated in C57 mice with a solid tumour. Methods: This was a preconjugate approach with 3 steps. ]st step: labeling of S-benzoylMAGi with a fresh etutioo of a LSSW/18SRegenerator (18~W Tlcz=69.4/tSSRe Tz/2=l 7) in saline (370 MBq approximately). 2 "~ step: esterification of the S-benzoyI-MAG3-tSSRe with 2,3,5,6etrafiuorophenol (TFP) m order to obtain Re-MAG3-TFP actwe ester• 3 s ep: conjugatmn of the active ester with amines of monoclonal or polyclonal antibodies maintaining its biological activity. The labeled conjugated protein was purified and controlled by HPLC using a Protein Pack SW300 (Waters) column and the eluent was phosphate buffer at I ml/min. Results: Yields of more than 95% were obtained when the ratio of SnCIz.2H: O to 188 Re activity was higher than 3.13p.g/MBq and nearly quantitative yields were obtained when the ratio of S-benzoyI-MAG 3 to 188 Re activity exceeded 0.81[ag/MBq. This was a solid phase reduction of perrhenate by the stannous ion, with citrate used as transfer ligaod. The maximum labeling efficiency (46•9%) was obtained when the molar ratio of ester to protein was 333:1, in which case the specific activity of labelling was 90.3 MBq/mg antibody• In vitro stability assays showed that 80.0°/', and 70.3% of the activity remained bound to MoAbI417-MAG 3 alter incubation in saline and serum at room temperature respectively. Uptake of the antibody in the tumour amounted to 8.80±l.51and 7.23±1.30 %ID with a tumour-to-blood ratio of 0.55 and 0.68 for 24 and 48 hs respectively• Conclusions: The indirect method of labeling antibodies using a 188Re-labeled via the active ester MAG 3 produced a 188 Re-MAG3-MoAb 141"/complex of high specific activity and in vitro stability, and significant uptake by the tumour. •

188

•

rd

PS_329

PS_331

LABELING METHOD STUDY AND BIO-ACTIVITY EVALUATION ON RE-188-ANTI BLADDER CANCER MONOCLONAI..ANTIBODY BDI-1

FIBRIN BINDING PEPTIDES FOR DETECTION OF PULMONARY EMBOLISM

R.F. Wang, C.L. Zhang, L.Z. Yu, Y. Bat, Y.F. Guo. Department of Nuclear Medicine,Peking University First Hospital, Beijing, China.

M. Rusckowski (1), G. Liu (1), C. Wescott (2), A. Sato (2), N. Liu (1), S. Gupta (1), D.J. Hnatowich (1). (1) Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA; (2) Dyax Corp., Cambridge, MA, USA.

Aim: To prepare Re-188-BDI-I suitable for radioimmunotherapy (RIT) of bladder cancer, and investigate the optional labeling method and bio-activity of R¢-188-BDI-I. Methods: BDI-I- an anti-bladder cancer antibody provided by Peking University Immunology Department was reduced by 2-mereaptoothanol Two labeting methods including ligand exchanging and direct labeling method were used to prepare Rc-188-BDI-I. The influence of pH, reaction time and SnCI 2 concentration on the labeling yield was studied. Biodistribution and radioimmunoimaging were performed in nude mice bearing human bladder carcinoma at different time points following injection of 629 KBq and 111.1 MBq of Re188-BDl-I, respectively. The ratio of tumor to background (T/B) was calculated. Results: The optium labeling condition was at pH 4.4 - 5.0, reaction time 2 h for ligand exchanging method and SnCI2 concentration of 4.17 - 8.33 mg/m], pH 4A ~ 5.0, reaction time 1 h for direct labeling method and the maximum labeling yields were 3 t.2 % and 90.8 % respectively. The Re-lgg-BDl-t obtained from two labeling methods showed high T/B ratio of greater than 2.0 %ID;g 24 h postinjection, and the T/B ratio of Re-188-BDl-I from ligand exchanging (tumor/muscle 16.9%lD/g) showed higher than that of Re-188-BDl-I from direct labeling method (tumor/muscle 5.52%lD/g). Both oftbem had excellent tumor locating property on scintigram. Conclusion: R.e-lg8-BDI-I with good bioactivity could be obtained by both ligand exchanging and direct labeling method. Direct labeling method could obtain high labeling yield of ReI88-BDI-1, and was easy to perform and more available.

116C

By phagedisplay, low molecular weight peptidnshave been identified which show high specificity for human fibrin. Aim: The intent of this study was to investigate the in vitro and in vivo properties of two dndecepeptidesselected for high binding affinity to human fibrin for their potential as pulmonary embolism imaging agents. Methods: The peptidcs, DX-180 and DX-328 (MW-2kDa), were synthesizedwith HYNIC on the N-terminus via a hexanoic spacer for Tc-99m labeling. The peptides were labeled using either tricine or EDDA as coligand. Results: By SE-HPLC of scram (37°C) incubates, the radiochromatographic profile was virtually unchanged at 3hr using EDDA, whereas with tricine as coligand, about 50% of the activity was on serum proteins. This difference in serum binding influenced the biodistrihution results in normal mice. At each time point, differences in organ activity levels among the peptide/coligand complexes were evident, With tricine, both peptidas showed higher organ and blood activity. For DX-180, total organ activity at 3 hrs was 45% with tricine vs. 10% with EDDA while for DX-328, these values were 33% vs 6% respectively. Liver, kidney and blood accounted for the major differences. Of the four peptidedcoligands investigated, DX328/EDDA showed the highest excretion and lowest whole body activity. Using a rabbit model consisting of a human fibrin clot in one femoral artery retained by an embolization coil, all four peptide/coligand complexes were investigated along with AcuTect as a control. Animals were imaged for 2 hrs and then sacrificed for dissection. As in the mouse, DX-328 with EDDA showed the lowest levets of activity in tissues. For example, liver was 4.6-fold tower than with tricin¢, and 2.6-fold lower than AcuTect. The excised clotted artery to normal artery radioactivity ratio with DX-328/EDDA was 6:1 vs. 2:1 for AcuTect. Conclusion: These data, showing low background and high target to non-target ratios, suggest that pepddes can be selected by phage display as potential detection agents for pulmonary embolism.

• RADIOPHARMACY / RADIOCHEMISTRY 2

PS_332

PS_334

CLINICAL APPLICATIONS OF ANTI-TSH RECEPTOR AND ANTITHYROPEROXIDASE ANTIBODIES RADIOMETRIC ASSAYS IN GRAVES' DISEASE

CHROMOGRANIN-A AND NEURON-SPECIFIC ENOLASE IMMUNORADIOMETRIC ASSAY IN DIAGNOSIS AND FOLLOW-UP OF NEUROENDOCRINE TUMOURS

L. GiovaneUa, L. Ceriani, S. Garancini. University Hospital, Varese, Italy.

L. Giovanella, L. Ceriani, S. Garancini. Department of Nuclear Medicine, University Hospital, Varese, Italy.

The detection of autoantibodies to the TSH-receptor (TRAb) and anti-thyroperoxidase (AbTPO) are largely requested in clinical practice for the diagnostic work-up of Graves' disease. Aim: Aim of our work was the comparative evaluation of the diagnostic performance of TRAb and AbTFO in diagnosis of Graves' disease. Method: We evaluated the diagnostic performance of a newly developed 2"a generation TRAb assay (DYNOtest TRAb human", BRAHMS GmbH, Germany), a I 't generation TRAb assay (TRAK assay", BRAHMS GmbH, Germany) and an AbTPO assay (DYNOtest AbTPOn", BRAHMS GmbH, Germany) in 124 patients affected by Graves" disease, 156 patients affected by Hashimoto's thyroiditis and 188 patients affected by euthyroid nodular goiter. Results: The 2 r~ generation TRAb assay showed a better diagnostic sensitivity in Graves' disease (97%) respect the I ~t generation assay (85%) and AbTPO assay (64%). The AbTPO assay was positive in 94% patients affected by autoimmune thyroiditis while the I st and 2 "d generation TRAb assays were positive in 7% and 13% of patients affected by autoimmune thyroiditis, respectively, No patients affected by nodular goiter showed positive I '~ and 2 "d generation TRAb assay (specificity 100%) while AbTPO levels were positive in 9% of patients (specificity 91%). Conclusions: TRAb assay by 1 ~t and 2 nd generation methods is clearly more sensitive and specific than AbTPO assay in diagnosis of Graves' disease. Consequently, AbTPO assay should be not performed, never alone or in association with TRAb, in Graves' disease diagnostic work-up. Finally, the 2na generation TRAb assay is clearly more sensitive than the I s~ generation test and should be used in clinical practice to minimize the incidence of TRAbnegative Graves' disease.

Immunohistochemical detection of chromogranin-A (CgA) and neuron-specific enolase (NSE) is a very useful tool for diagnosis of neuroendocrine tumours (NET). lmmunoradiometric assay (IRMA) methods to measure both serum NSE and CgA are available in clinical practice. Aims: Aims of our work were: 1) to compare the sensitivity and specificity of serum CgA and NSE in NET patients and controls, 2) to investigate the relationship between serum markers and disease extension, 3) to compare serum expression of both markers with immunohistochemical findings and 4) to evaluate the role of both markers in the follow-up of the disease. Methods: We enrolted 124 patients affected by NET: aH diagnosis were histologicalJy confirmed and serum samples were obtained before surgery or other therapies. Evaluation of tumor extension was performed using lllln-pentetreotide scintigraphy and helical CT. Immunohistochemical stains were performed using avidin-biotin-complex and monoclonal antibodies against CgA and NSE. Serum CgA and NSE were measured by two-site IRMA methods (NSE Prolifigen", Byk Sangtec, Sweden and CgA RIA CT", Cis Biolnternationale, France). A group of 142 healthy b~ood donors was evaluated as control. A sub-group of 55 patients with one or both markers elevated at diagnosis was followed-up by serial markers assay and imaging methods for 12-48 mounths. Results: Basal CgA a nd NSE were elevated in 75 (60%) and 29 (33%) of the NET patients. CgA levels were significantly higher in NET patients than controls (U-test p<0.0001 ) and in limited versus extensive disease (U-test p<0.01). We found a significant overall positive correlation between serum and tissue CgA (Linear regression Re 0.896 p<0.01) while no differences were found in serum NSE levels. The use of markers and particularly of CgA in the follow-up showed a positive lead time of 5-23 mounths and can be employed to rule out unnecessary imaging tests or invasive procedures. The patients with basal elevation of NSE generally showed a more aggressive tumoural phenotype and a poor prognosis, Conclusions: Serum CgA is a reliable marker of NET and reflects both turnout burden and CgA granular content in tumoural tissue. Serial evaluation of CgA is useful to predict the relapse of the disease and to avoid other procedures if marker is negative. Serum NSE should be employed to identify poorly diH'erentiated turnouts but is not accurate in diagnosis of NET.

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PS_335

RADIOCHEMICAL CHARACTERISTICS AND BIOLOGICAL TESTING OF TECHNETIUM-99M LABELLED ANTIMICROBIAL CATIONIC PEPTIDES FOR INFECTION DETECTION

NEURON SPECIFIC ENOLASE {NSE), BETA-AMYLOID AND TAU PROTEINS AS MARKERS OF DEMENTIA

S. Mongera (1), M.M. Welling (1), A. Lupetti (2), P.H. Nibbering (2), U. Mazzi (3), E.K.J. Pauwels (1). (1) Department of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands; {2) Department of Infectious Diseases, Leiden University Medical Center, The Netherlands; (3) Department of Pharmaceutical Sciences, University of Padua, Italy. Recently we introduced 9~Tc labelled synthetic cationic antimicrobial peptides, i.e. ubiquicidine (UBI) and human lactoferrin (hLF) derivatives, for the detection of infections in mice and rabbits. Specific tagging of bacterial surfaces with these peptides allowed us to discriminate between infections and sterile inflammatory processes. The labelling mechanism of this direct method has been the subject of an interiustitutional study, revealing that reduction of 9°'=To pertechnetate is accomplished by stannous ion, whereas borohydrata maintains the 99"Tc in the reduced oxidation state. We report on our experiments regarding radiocbemical analysis and stability testing of the peptides using ITLC and HPLC techniques, as well as on the in vivo scintigraphic imaging and ex vivo analysis of activity distribution in mice injected with these radiolabelled peptidas. A scrambled peptide containing the same amino acids as one of the antimiarobial peptides (UBI 29-41), but in a different sequence, was used as a control agent for these studies. Using ITLC and HPLC we assessed high yields of labelling (>95%) already 10 rain after initiation of the labelling reaction. Until 24 h after starting the labelling the complex maintained stable under various challenging circumstances. Also, we studied the in vivo characteristics of the labelled peptides in healthy mice and observed fast clearance via kidneys and bladder as determined by seintigraphy and ex-vivo countings. Besides, we observed a good correlation (r>0.844, p<0.01, n=5) between these two methods of analysis until 1 hr post injection. Unless the radioactivity was not accumulating in liver and intestines both methods of measure the biodistribution remained in concordance. In conclusion, direct labelling of synthetic antimicrobial peptides with 99~Tc is a highly efficient and reliable method to study these agents for scintigraphic detection infection.

B. Palumbo (1), A. Bianchi (1), D. Siepi (1), V. Gallai (2), A. Lanari (2), S. Amici (2), S. Messina (1), I. Sabalich (1), L. Parnetti (2). (1) Dept. of Nuclear Medicine, University of Perugia; (2) Dept. of Neuroscience, University of Perugia, Italy. Aim: The identification of biochemical markers able to contribute to the diagnostic accuracy of dementia disorders represents a relevant issue. Cerebrospinal (CSF) levels of beta-amyloid (1-4zl protein (Abeta42), the main component of brain beta-amyloid plaques, appear significantly reduced in Alzheimer's disease (AD), while CSF concentration of the microtubuleassociated protein tau, a constituent of neurofibrillary tangles, is increased. Neuron Specific Enolase (NSE) levels in CSF are increased in several neurological diseases and represent an index of organic neuronal damage; a NSE conformational epitope cross-reacts with a monoclonal antibody raised against betaYA4-protain of AD brain. We measured CSF concentration ofNSE, Abeta42 and total tan in patients with different dementia disorders. Methods: We studied 66 patients, 37 affected by probable AD according to NINCDS-ADRDA criteria, 9 by Age-Associated Memory Impairment (AAMI) according to Crook's criteria, 11 by Fronto-temporal dementia (FTD) according to Lend and Manchester criteria, 9 by vascular dementia (VaD) according to DMS-1V R criteria. NSE was also measured in 15 controls referred to Urology Department for minor surgical problems requiring spinal anaesthesia. NSE was measured by a solid phase two-site immunoradiometric assay (ELSA-NSE, CIS bio lnternational-Schering), while Abeta42 and tau were dosed by ELISA assay (Innogenetics, Gent, B). Results: NSE levels were significantly higher in AD (meanb:SD: 23.14+7.9 ng/ml) vs controls (mean.'l:SD: 7.8+9.4 ng/ml, p<0.001), FTD (menn++SD: 15.45+6.6 ng/ml, P<0.05) and VaD (mean.'~SD: 14.77+5.8 ng/ml, p<0.05); NSE was also significantly increased in AAMI (mean~.+SD: 21.38+8.8 ng/ml) vs controls (p<0.001). On the other hand Abeta42 was significantly lower in A D than in AAMI (p<0.05), while tau was significantly higher in AD than in FTD (p<0.005). NSE was significantly correlated with P-tau (p=0.000, rZ=0.592). Conclusions: Our results show that CSF NSE, likely other well established biological markors, is altered in dementia, thus supporting the clinical accuracy of diagnosis. Finally it is worth of note that NSE is significantly increased not only in overt dementia but also in AAMI; this finding seems to support the hypothesis that AAMI might represent an early monosymptomatie phase of AD.

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• TECHNOLOGY PROGRAM 2

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PS_338

BACHELOR OF MEDICAL LABORATORY TECHNOLOGY, THE NEW TITLE FOR TECHNOLOGIST IN DENMARK

FOUR IMPORTANT TERMS OF RADIATION PROTECTION: DOSE, DISTANCE, DURATION, SHIELD

L. Kragh, L. Larsen, J. Lohse. Department of NuclearmedicineJphysiology, Rigshospitalet, Copenhagen University Hospital, Denmark. In Denmark there has been no special education for technologists who work in nuclear medicine. In 1996 a new 3-years education for technologists started, including nuclear medicine (and clinical physiology). The first students graduated July 1999. The structure of the training was classified in 7 modules. U I : I month Introduction in the Hospital U 2 + 5 + 6 : 4 + 6 + I months School periods I + 2 + 3 U3+4+7 : 6 + 6 + 18 months Laboratory period (e.g. Clinical Chemistry, Clinical immunology, Nuclear medicine) In the last period the students make a theoretical and practical 4-weeks project with essay and oral examination. With the new education of technologists (in Danish ,,bioanalytiker") the theoretical and practical skills in nuclear medicine have been much improved. From year 2001 the education has been changed to a more international system, with the introduction of European Credit Transfer System (210 ECTS points): - The school period will be 2 years and give 135 ECTS points - The Laboratory period will be I_ years and give 75 ECTS points - The students will be graduated as ,,Bachelors of Medical Laboratory Technology".

T. Arnold (1), E. M6d (2). (1) Nuclear Medicine, Radiologische Gemeinschaftspraxis Drs. Bader/Correll/Heim/Thiel, G6ppingen, Germany; (2) Nuclear Medicine, Radiologische Praxis Dr. Klimeck, Ludwigsburg, Germany. The harmonizing of the radiation protection in Europe makes it necessary to think about the possibilities of how to minimize radiation exposure. On the one hand there are new tasks tbr the staff in Nuclear Medicine, for example to the quality control] measures, whereas on the other hand you have to realise the new limit values tbr staff. To reduce the radiation to a minimum, itemsnecessary to know these four terms of radiation protection. Let's take a closer look: Dose: The Euratom-Guideline from June 1997 fixed under the catchword ,,optimisation" that there must be reference-values for examinations with radiation. These are not only dose-values, but also in case of radionuclide activity-values. In the case of children-examinations there exist recommendations of the Paediatric Task Group of the EAN M. Distance: the rule of the half dose as the square of the distance is one of the most important rules to limit radiation exposure. Several studies in diagnostical Nuclear Medicine came to the conclusion, that the radiation exposure can be limited to a dose which is tar below the dose set by the radiation protection regulations. Duration of stay: It is noticable, that the individual studies bring varied radiation doses for the technologists. This is not only a problem of the administered dose, but also of indigent patients. Ira patient required continual assistance, the radiation exposure would be higher, of course. Shield: leaded hot cells, shielded containers tbr transport and storage of syringes, mobile leaded shield These criteria should be respected in all categories of Nuclear Medicine, in quality assurance and especially in the daily work with patients.

PS_337

PS_339

EVALUATION OF BONE MINERAL DENSITY BETWEEN SPINE AND HIP IN DIFFERENT AGE POPULATION

ONE-YEAR EXPERIENCE ON THE UTILIZATION OF FDG PROVIDED BY EXTERNAL RADIOPHARMACY

K. Chun (1), M. Doonan (1), R. Goldfarb (2), K. Byun (2), L. Blunt (1), L. Freeman (1). (1) Montefiore Medical Center, Dept of Nuclear Medicine; (2) Beth Israel Medical Center, Dept of Radiology, Albert Einstein College of Medicine, New York, NY, USA.

M. Schiavini, R. Casati, A. Bruno, M. Castellani, R. Leo, A. Cascio, P. Cau, G. Maiocchi, F.R. Colombo, R GerundinL Department of Nuclear Medicine, Ospedale Maggiore-IRCCS, Milano, Italy.

Aim: To evaluate whether BMD measurement by T-score in the spine would correlate with the hip bone loss. Methods: Using DEXA (Hologic 4500C) in the spine and the hip, which were obtained in the same day, we compared BMD test results of 1049 women. 985 females were mostly peri/postmenopausal (45-92 yo.) and 64 females (<44 y.o.) were mainly with endocrine disorders, including secondary amenoa'bea or long-term steroid treatment. Data were classified according to the WHO criteria (T-score). A-P lumbar spine included LI-L4 vertebrae, Total hip BMD data was used instead of other hip region data for greater precision and higher reproducibdity. 577 cases were 45-64 y.o., 251 eases were 65-74 y.o.. and 157 cases were above 75 y.o. Results: In this studied population, 64 women (<44 y.o) showed spine BMD worse or equal to hip BMD in 62 cases. In 577 females (45-64 y.o.), 554/577 (96%) cases had the spine Tscores worse (320/577) or equal (243/577) to hip T-scores. Of 190/577 with N-hip, 149/190 had E-spine, 37/190 had O-spine. 134/577 had E-hip but O-spine. (N-normal, E-ostanpenia, O-osteoporosis). Older patients (>65 y.o.) trended to have worse hip T-scores than spine Tscores (6% in 65-74 y.o., 21% in 75-84 y.o., 50% in >85 y.o.). Degenerative changes with ostanphytas and/or collapsed vertebra may have been the influencing factors. Age (yrs) < 44 45-64 65-74 75+

Ostanpanic spine 33 241 94 51

Osteoporotic spine 17 194 109 49

Decreased S/H ratio* 37 (58%) 320(56%) 125(50%): 33(21%)

S = H**

Increased S/H ratio*** 25 (39%} 2 (3%) 243~42%) 14 (2%) 110(44%) 16 (,6%) 87(55%) 37(24%)

# of pts 64 577 251 157

*,[,S/H ratio: spine BMD score worse than hip (E-spine/N-hip, O-spine/N-hip, O-spine/E-hip) **S=H: congruent spine and hip BMD scores (N-spine/N-hip, E-spine/E-hip. O-spine/O-hip) ***TS/H ratio: spine BMD score better than hip (N-spine/E-hip, N-spine/O-hip, E-spine/O-hip) Conclusions: 96% of the patients (<65 y.o.) showed greater (56%) or equal (40%) bone mineral loss in the spine compared to the hip. The findings could be related to earlier bone mineral loss in the metabolically active spine (predominantly trabecular bone) than hip (predominantly cortical bone). The spine BMD information in this relatively younger age group (<65 yo.) can predict possibly less severe disease in the hip, potentially guiding prophylactic therapy for prevention of serious and costly hip fracture, while hip BMD measurement alone may underestimate the severity of spine BMD loss.

116;

At our department the installation of a PET camera has been accomplished in large advance compare to the Cyclotron and related Radiopharmacy. |nfact there was the need to use the PET camera without an internal production of FDG; it was verified that Switzerland was the only country in 1988 from where FDG could be imported (following the procedure indicated by the law of I I February 1997). After obtaining the authorization from the Italian authorities, a one-year experience of 152 shipments from Zurich to Milan has been carried out (4-5 hours transport time). This allowed 850 patient examinations The delivery has been done on the scheduled time 42% times, with a delay lower than 90 minutes 32% times, with a delay higher than 120 minutes 22% times and 2% times before the scheduled time. The arrived activity was 46% times on the range of+ I0%, 39% times lower and 15% times greater than the ordered one. Concerning the management of patient examinations: in 55% times the schedule has bccn in agreement, 28% times the number of examinations was less than schedule and 17% times one additional examination has been performed. The average of the cost per shipment (FIX] + transport) was about 5000 Euro. In conclusion, this experience demonstrated that the clinical use of a PET scan in a center not equipped with a cyclotron could be possible by supplying the FIX3 within 3-4hr delivering. However a less restrictive law that allows delivery from Italian producers to an Italian users is needed for reducing the drawbacks due to the long route and the costs of transportation.

• TECHNOLOGY PROGRAM 2 PS_340

PS_342

OPERATOR DEPENOENT VARIABILITY IN LVEF MEASUREMENTS FROM GATED SPECT

THE EFFECT OF EXREMELY LOW FREQUENCY ELECTROMAGNETIC FIELD (ELF) ON ROTAT_NG G A M M A CAMERA

L. ~kesson. Dept. of Clinical Physiology, Lund University, Lund, Sweden.

M. Demir (1), A. Sabbir (1), T. Kalkan (2), H. Sayman (1), I. Uslu (1). (1) Department of Nuclear Medicine; (2) Department of Biophysics, Cerrahpasha Medical Faculty, University of Istanbul, Turkey.

Aim. Left ventricular ejection fraction (LVEF) can be assessed using gated myocardial perfusion SPECT imaging. The processing from raw images to the final LVEF cafculatioos is to a great extent an automated process, but a few manual steps remain. The aim of this study was to evaluate the variability in LVEF measurements for different experienced operators. Methods. Thirteen patients who under,vent a gated SPECT using ~gmTetrofosmin were selected. The material included three patients with normal perfusion, five with large fixed apical deflects and five with reversible detects in the apical area. Eight experienced medical laboratory technologists (MLT) processed the post stress studies, starting from the raw projection data, creating short axis slices and finally using the Cedars Sinai quantitavive gated SPECT (QGS) program for calculation of LVEF. The studies were presented in a random order without any clinical information of the patients. The QGS program uses as input the short axis slices. For creation of short axis slices the operator has to define two alignment axes parallel to the long axis of left ventricle (in the transaxial- and obique plane).

Results. The LVEF measurements ranged from 8.9% to 66.1% (normal patients 59.3%- 66.1 %, fixed apical defects 8.9~.0.4 %, and reversible apical defects 41.6%-66.0%). Eight different LVEF measurements (one lbr each operator) were obtained for each patient. In three of five patients with a fixed apical deli:ct the differences in LVEF between the operators were 4%. In two of five patients with a reversible apical dcl;,:ct the differences in LVEF between the operators were 3%. For the remaining patients the differences were 2 0 or less. For each patient the eight operators defined two alignment axes. In 6 of the 13 patients the variability for one of the two axes was at least 10 degrees.

One of the physical factors affecting SPET's images is the extremely low frequency electromagnetic fields (ELF) radiated from electrical devices. Aim: The object of this study is to investigate the effects of extremely low frequency (50 Hz) electromagnetic fields on rotating gamma cameras. Method: In these experiments a Siemens Orbiter 7500 digitract gamma camera system and LEAP collimator were used. To create ELF we connected 8 serially combined solenoids to the mains supply (220 V, 50 Hz) with 4 ampers current flowing through them. The solenoids were o o o moved along the vertical plane below the face and 3 0 , 4 5 , 60 laterally of the detector to change the ELF intensity. Magnetic flux density of the created ELF was found to be between 0.05 mT and 1.2 mT at the center of the detector. For measuring the magnetic flux density of ELF, teslameter was used. ,

Results: We optained the countrates of ELF, applied to the center of the detector, in the 50-80 keV energy scale. We found that ELF had exponentially decreased the count rates of a ~mTc point source There was a complete loss of the counts as well as the individual photopeaks under the influence of the magnetic field. Homogenity and spatial resolution tests were taken under costant ELF (-I.2 roT) and at the same time the homogenity and resolutions were distotted. Results: According to our obser,,ations in these experiments magnetic fields higher than 0.4 mT cause serious del~ct in the field of view.

Conclusions. The reproducibility of the calculated LVEF between different operators was very high, even in patients with low LVEF%. The variability in definition of alignment axes between the observers did not have a major impact on LVEF.

PS_341

PS_343

THE PRACTICAL USE OF AN IMAGING PROBE IN NUCLEAR MEDICNE

PARTIAL RIB DISSECTION BY USE OF SURGICAL PROBE

N.M. Bruin (1), A. Van Lingen (1), E. Baumann (2), P.G.H.M. Raijmakers (1), T. Ijbema (3), G.J.J. Teule (1). (1) Department of Nuclear Medicine, Free University Medical Center, Amsterdam, The Netherlands; (2) Eurorad, CIT, Strassbourg, France; (3) PI-Medical Diagnostic Equipment Bv, Joure, the Netherlands. Aim:We investigated the physical and clinical use of a prototype device consisting of a 16xl6 array of CdTe elements (2.83x2.82x2.0 ram) with an effective field of view (FOV) of 49x49 mm and a tungsten collimator (15 mm thick, 7.7 ram" holes and 0.3 mm septa), weighing 1995 gram. Since this device was a prototype, proper certification and technical refinements were not undertaken until the significance of the performance is clarified. Methods: The detector unit was interfaced to an electronic ~'rad-out for 256 channels and coupled to a PC through a serial line. At this moment simple on-line imaging software shows the acquired data in colour, both the persistence and the accumulated image. Persistence rate can be set from 0.5 m 20 see. Currently a display matrix of 16x16 pixels is used. The energy window can be selected between 30 and 200 keV. Extensions (larger matrix size, smoothing and interpolation software) are under development. The image data is stored on disk as ASCII text files and earl be analysed with any software available. We used Matlab 5.3 (SE) for the image analysis, to evaluata the physics tests and for image processing. The prototype was applied to image sentinel nodes (SN's) of 18 breast cancer patients. As a reference, gamma camera images were obtained for initial loealisation. The area around the SN was then examined with the imaging probe. Furthermore, in 8 (of these Ig) patients we evaluated the optimum imaging time (2, 5, 10, and 60 see). Results: The system was physically ehamcterised by a spectral resolution of 6% FWHM per pixel (12% FWHM, if averaged over 256 pixel spectra) at 120 keV, 10% image uniformity (with correction), a spatial resolution of 6 mm (FWHM) on the collimator face and a counting sensitivity for 99roTe of 833 cps/MBq (30-200 keV) and 318 cps/MBq (100-200 keV). In 17 of Ig patients a SN was found with the imaging probe. In addition, 10 see of acquisition time proved sufficient. Conclusions: The physical performance is suitable for imaging sentinel nodes. Our experience so far was that the device still needs further technical developments, such a more on-line image processing. The largest impact may be in the operating theatre to confirm complete removal of the (multiple) nodes. Although the FOV is sufficient for SN imaging, for other applications it may be enlarged.

to c

C. de Haan (1), T. van Mesdag (2), G.M.M. Gommans (1), R.O. Boer (1), A. van Dongen (1), J.W.D. de Waard (2). (1) Department of Nuclear Medicine; (2) Department of Surgery, Westfries Hospital, Hoorn, The Netherlands. Partial rib dissection e r a scintigraphical marked hot spot ofien failed due to the fact that the patient at the operating theatre is not positioned in the same way as marked during the scintigram. The aim of this study was to investigate whether radioguidad biopsy of a scintigraphical hot spot can improve the localisation during surgery. Patienl~ and methods: In eleven patients (5 male and 6 female) with previous anamnesis of carcinoma a seintigraphical solitaire hot spot in one fib was found, No other pathology in this group of patients was found. In a twelfth patient (female) without prior history of malignancy a solitaire hot spot was found in one rib. All twelve patients underwent surgical biopsy by using the probe. Three hours before surgery all patients were injected with 500 MBq 99mTc HDP. Thirty minutes after injection a local scintigram was performed and the hot spot was marked on the skin. Three hours after injection just before the start of operating, above the hot spot, determination and adjusting of the probe settings took place. Using the radioguided probe, by minimal lavasiva surgical procedure all hot spots quickly were Iocalised and removed or biopted. Results: All 12 procedures were successful. In five patients a metastasis was found. In five patients rests of fracture were found and in two patients an osteoid osteoma was found. Using minimal invasiv¢ surgery by probe all procedures took place within 10-15 minutes. Conclusion: Although our series of twelve patients is small, it seems to be a reliable and useful procedure for partial fib Ioealisation, dissection or biopsy. Advantage of this method is a quickly diagnosis with less morbidity, reduced OR time and short recovery.

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• TECHNOLOGY PROGRAM 2 PS_344

PS_346

CHAYOTTE EXTRACT EFFECT ON THE LABELING OF RED BLOOD CELLS AND PLASMA PROTEINS WITH TECHNETIUM-99M: iN VITRO AND IN VIVO STUDIES

THE USEFULNESS OF PRONE LATERAL BREAST IMAGING IN THE SENTINEL NODE PROCEDURE

M. Bernardo-Filho (1), G. Dire (1), E. Lima (1), D.M. Mattos (1), M.L. Gomes (1), M.V. Castro-Faria (2). (1) Department of Biofisica e Biometria; (2) Department of Biofogia Celular e Gen6tica, Instituto de Biologie Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. The biodistribution of the radiopharmaceuticals can be altered by therapeutic drugs as the labeling of red blood cells with technetium-99m (~mTc) has been influenced by patient medications or the labeling conditions or the presence of extracts of plants. Chayotta (Sechium edule) is used as food or as medication in popular medicine. AIM: We evaluated the influence of chayotte on the labeling of blood elements with 9~°Tc. METHODS: In in vitro study, blood was incubated with chayotte macerated, (100% v/v). In in vivo study, the animals were treated with chayotte macerated, (100% v/v), as drinking water (15 days) and samples of blood were withdrawn. The blood samples were incubated with stannous chloride and with ~mTc. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractious (IF) separated. RESULTS: The fixation oftbe radioactivity on the blood elements isolated from samples of whole blood (from animals that have received normally water) which were treated with chayotto in vitro did not decrease (p>0.05) on the labeling of the blood elements. The distribution of the radioactivity on blood cells and in insoluble fractions of plasma and blood cells isolated from whole blood withdrawn from animals that have received chayotte (15 days), as drinking water decreased slightly (p<0.05) in RBC (from 98.16 + 1.57 to 90.35 ± 5.04) and strongly in the insoluble fraction of the plasma proteins.(from 83.96 :l: 4.28 to 53.26 + 6.60). The presence of toxic compounds was tested and we did not find them in the preparations of chayotte used in our experiments. CONCLUSION: The chemical agents present in the extracts obtained from Sechium. could, depending on the metabolization in vivo can induce the generation of active metabolftes that could, (i) bind (chelating action) to stannous and penechnetate ions and/or (ii) bind to the • • binding sites of q ~ m Tc in plasma proteins, chayo te would be capable o generate reactive oxygen species (ROS), these could to oxidize the stannous to stannic ion. Then, this fact could explain the decrease on the labeling of red blood cells and plasma proteins with ~°Tc in the presence ofchayotte, when the referred drug is administered in vivo.

S. Baank (1), P.A. Doodeman (1), LJ. van den Heuvel (1), C.M. Bauhuis (1), B. Pool (1), P.J. ranis (2), R.A. Valdes Olmos (1). (1) Department of Nuclear Medicine; (2) Department of Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands. A:M. The prone lateral breast technique also called hanging breast (HB)- technique, was origi-

nally developed for the scintimammography with ~mTc-sestamibi . We evaluated this technique in order to proof its usefulness in the sentinel node (SN)- procedure, especially for the detection of intramammary lymph nodes. MErliODS: We used an ADAC dual-head gamma camera. Following a 5-min anterior image performed 15 rain after a single injection of ~mTc nanocolloid, the camera is put in lateral position and the usual mattress is replaced with the mattress for prone acquisition of a lateral . . . . . 57 5-ram image. Both anteraor and lateral images, are performed with a Co flat-source for simultaneous transmission imaging and repeated at~er 2 and 4 hours. ReSuLts: The evaluation concerned 400 patients (mean age 55y, range 27y-85y) with TI-T3 N O breast cancer referred to the nuclear medical department for a mammary SN lymphoscintigraphy between January 1997 and November 2000. Scintigraphy showed 29 patients (7,3%) with drainage to intramammary SNs (Fig. 1), in 28 of them accompanied by axillary and/or internal mammary drainage. At histopathology isolated intramammary SN metastases were found in 2 patients and in another 3 patients together with axillary SN metastases. CONCLUStO~: The HB-technique can provide information about the presence of intramammary lymph nodes which may be overlooked using the supine lateral breast imaging technique. The HB-tachnique can also be useful to detect SNs located close to the injection site if the turnout is in the upper outer quadrant oftbe breast. A

Fig. I. A) Anterior image of a patient injected in the left breast (T) showing lymphatic drainage to SN (horizontal arrow) and second echelon lymph nodes in the left axilla. B) Prone left lateral image of the same patient showing the SN (vertical arrow) as an intramammary lymph node.

PS_345

PS_347

IFOSFAMIDE EFFECT ON THE BIODISTRIBUTION OF THE RADIOPHARMACEUTICAL TECHNETlUM-99M-MDp IN MALE C57BL/6J MICE

EFFECT OF INTRA-GASTRIC POLYETHYLENE GLYCOL° ELECTROLYTE SOLUTION (GOLYTELY) ON GASTROINTESTINAL DISTRIBUTION OF 18FDG IN RATS

M. Bernardo-Filho (1), R.O. Aguiar (2), J.K. Kwee (2), E.F. Paula (2), N.M. Fonseca (2). (1) Department of Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil ; (2) Serried de Pesquisa Basica, Instituto Nacional de Cancer, Rio de Janeiro, RJ, Brasil.

S.A. Barrow, M. Burker, C.D. McCusker, E.A. Carter, A.J. Fischman. Department of Nuclear Medicine, Massachusetts General Hospital, Boston MA, USA.

The biodistribotion of radiotracers used in diagnostic imaging can be grossly and recognizably altered by a wide variety of factors. The knowledge of such altered biodistribution is important in making diagnostic inferences from scans. Altered biologic behavior may also be due to interferences caused by pharmacodynamic effects of drags. When, the altered behavior is desired, the alteration is used for diagnostic intervention or drag therapy monitoring. However, when, it is undesired, it may due to toxicity in the organs or direct reaction with the radiopharmaceuticals and it can lead to misdiagnusis, lfosfamide, an analog of cyclophosphamide, also is activated in the liver and present some toxic effects (leukopenia, hemorrhagic cystitis, nephrotoxicity, central nervous system disturbances). Ifosfamide is a chemotherapeutic drug that is used in combination with other drugs for germ cell tasticutar cancer and is widely used to treat pediatric end adult sarcomas. AIM: As a drag can interfere in tho biodistribution oftbo radiopharmacenticals, we decided to investigate the effect of the ifosfamid¢ in the biodistribution of 99mTc-MDP radiopharmaceuticals in mice. METHODS: Ifosfamide (150mg/kg) was administered by ocular plexus via into male isogonic C57BI/6j mice (8-12 week-old) per day for three days. One hour afier the last dose, 99mTc-MDP (7.4 MBq) was injocted and aider 0.5 hour the animals (n=lb) were sacrificed. The organs were isolated, the radioactivity uptakes determined in a well counter and the percentages of radioactivity (% ATI) in the organs were calculated. The results were compared with the control group (n=15), without ifosfamide and statistical analysis were performed. RESULTS: The results have shown that the treatment with ifosfamide: (i) decreased significantly (t test, p<0,05) the uptake of the 99mTc-MDP in bone, (ii) increased the radioactivity in the whole blood (t test, p<0,05) and (iii) did not alter the uptake of the radiopharmacentical in inguinal lymph node, prostate, pancreas, testis, seminal vesicle, bladder, kidney, stomach, small intestine, spleen. thymus, heart, lung, brain, and muscle. CONCUSION: In conclusion, the effects of ifosfamide in the uptake of the 99mTc-MDP in bone and in blood, could be due to specific toxic effects as already reported. Moreover, although our results were obtained with animals, we suggest to take care with the interpretation of the bone scan obtained from patients submitted to the treatment with ifosfamid¢.

Aim: Interpretation of ZSFDG-PET studies of the abdomen is frequently complicated by accumulation of tSFDG in normal gastrointestinal tract. Several anecdotal reports have suggested that bowel preparation with agents such as GoLYTELY- may alleviate this problem. In this study we evaluated the effect of intm-gastric polyethylene glycol-electrolyte solution (GoLYTELY") on gastrointestinal distribution of =SFDG in rats. Methods: After 2 hrs of fasting, OoLYTELY" was administered intragastrically (60 ml/kg) to a group of 6 male Sprague-Dawtey rots (~150 g). Six untreated animals served as controls. Both groups of rats were fasted over night with ~ access to water. On the following morning, each animal was injected i.v. with 0.5 mCi of ]SFDG-PET. One hr later, the animals were sacrificed and biodistribution was determined. Results were expressed as % injected dose/gram (%lD/g) and % injected dose/organ (%lD/o), mean ± SD. Results: The animals in the treatment group demonstrated marked diarrhea. No other adverse effects were observed in either group of animals. As indicated in the table, the biodistrthution study demonstrated remarkably similar levels of =*FDG accumulation in both stomach and bowel (small plus larga intestine)• Similarly, GoLYTELY" treatment did not affect tracer accumulation in any other tissues of the rat.

Treatment • Contro

Stomach (%lD/~) Stomach (%lD/o) Bowel (%ID/~) 0.57±0.18 0.68=0.16 0.96±0.41 0.562=0.05 0.66~0.10 0.8 ±0.09

Bowel (%ID/o) I 3.99~1.05 4.58±0.42

I

Conclusion: These results clearly demonstrate that bowel treatment with GoLYTELY" does not alter tBFDG accumulation in the Gl-tract of rats.

• OTHER CLINICAL SCIENCE. BONE AND JOINTS 1 PS_348

PS_350

FDG PET AND BONE M A R R O W SCINTIGRAPHY IN PRIMARY HYPEROXALURIA TYPE 1

EVALUATION OF RECONSTRUCTION TECHNIQUES AND SCATTER CORRECTION IN BONE SPECT OF THE SPINE

C.T. Kadalie (1), M. Schreckenberger(1), O. Schreiner (2), E. Bayer (2), P.R. Galle (2), M. Otto (3), R Bartenstein (1). (1) Department of Nuclear Medicine; (2) Department of Internal Medicine; (3) Department of Pathology, University, Mainz, Germany.

S..~. Starck (1), S. Carlsson (2), J. Ohlsson (3), M. Areskog (3), M. Flailing (2), S. Sandstr6m (4). (1) Department of Hospital Physics, County Hospital Ryhov, J6nk6ping, Sweden; (2) Department of Radiology, Uddevalla Hospital, Uddevalla, Sweden; (3) Department of Clinical Physiology, County Hospital Ryhov, J6nk6ping, Sweden; (4) Department of Radiology, County Hospital, Sk6vde, Sweden

The case of a 29 year old woman with a history of renal failure at the end-stage renal disease is described. In the course of her illness she developed clinical signs consistent with a paraneoplastic syndrome. A bone marrow scintigraphy with Tecbnetium-99m labelled leucocytes (Tc-99m WBC) showed extensive homogeneous symmetrically distributed tracer uptake almost along the full length of the long bones of the limbs and a reduction of nuclid accumulation in the axial skeleton. F-18-fluorodeoxyglucose (FDG) PET images showed no signs of a malignant tumor, but increased, symmetrically distributed FDG activity in the bony.-chondral junction of the ribs. Either focally or diffusely increased tracer uptake was seen in the sternum, the scapulae and both the hip and sacroiliac joints. Finally primary hyperuxaluria type I was diagnosed, a rare genetic disorder due to a reduced activity oftbe liver enzyme alanine/glyoxylate aminotrans ferase (AGT). The systemic manifestation of the disease is called oxalosis. Affected patients may present in a clinical variable form. Since the only curative therapy is a combined liver-kidney transplantation, early diagnosis is important. Nuclear medicine imaging modalities contributed towards reaching the diagnosis: Tc-99m WBC findings indicated an underlying metabolic disease with bone marrow involvemeat. F-18-fiuorodeoxyglucose (FDG) PET helped to rule out a malignant neoplasia as the cause of a potential paraneoplastic syndrome. Furthermore the differential diagnosis of the distribution pattern of FDG activity pointed towards the skeletal manifestation of a metabolic disorder This report is one of the few published cases of primary hyperuxaluria type 1 with skeletal involvement documented by bone marrow seintigraphy and represents the first publication of a proven case of oxalosis in the field of PET.

A tomographic nuclear medicine examination can be reconstructed in several ways. Hitherto the most common technique involves two-dimensional pre-fihering of acquisition data followed by a reconstruction using filtered back-projection (FBP). Fast computers and efficient algorithms have made the iterative reconstruction technique (ITR) possible. Furthermore, attenuation and scatter correction can be applied as welI as three-dimensional post-filtering of reconstructed data. The aim of this study was to compare the effect of filtared back-projection and iterative reconstruction technique, different types of filters and scatter correction on bone SPECT using the concept of visual grading. Methods: Twenty-eight consecutive bone SPECT examinations were used in the study. The acquisition was made in 64 frames (360°), 20 s per frame and in 128x128 matrix using a single-head gamma camera with a high resolution collimator (FWHMI~=~=I6.6 mm). Three energy windows were used in order to perform the scatter correction. Each study, with and without scatter correction, was reconstructed using FBP and ITR and 3D post-filtering. The filters used were Butterworth fi}ters with a cut-off of 0.85-0.90/cm and Metz filters with filter factors 6-7. Each study was also reconstructed using the current technique in routine use in the department. This technique includes a 2D pre-filtering using a Meta-filter and FBP. These images were used as references. A total of 224 images of coronal and sagittal slices were analysed by 5 experienced observers. Visualisation of vertebras, spinal canal and vertebral processes together with an overall impression of the image was ranked on a scale -2 to +2 (clearly worse to clearly better) compared to the reference image graded as zero. Results: Combined mean scores for each technique averaged over all observers and the significance of the differences from the reference image. itr, metz no tew 0,638 p<0,01

itr, but. no tew 0,369 p<0,01

fop, metz no tew 0,342 p<0,01

itr, but. tew 0,246 "~<0,01

itr, metz tew 0,093 n.s.

fop, but. fop, metz no tew ~refilter 0,012 0 n.s

tbp, metz tew -0,001 n.s

fbp,but tew -0,125 9<0,05

(0,638-0,369, p<0,01 ) Conclusions: This study shows that scatter correction does not improve image quality due to the reduced number of counts and hence the increased noise. A contrast enhancing Metz filter together with iterative reconstruction is preferable to use in bone SPECT using a gamma camera of specified type.

PS_349

PS_351

99MTC-MDP BONE SCINTIGRAPHY AND GLOBAL SKELETAL UPTAKE CORRELATION WITH MARKERS OF BONE METABOLISM IN ADVANCED PROSTATE CANCER PATIENTS

SENSITIVITY AND SPECIFICITY OF DEXA METHOD IN OSTEOPOROTIC VERTEBRAL FRACTURES

G. Rubini (1), A. Fontana (2), D. Rubini (1), A. Niccoli-Asabella (1), J. Bagnoli (1), N. Pansini (2), A. D'Addabbo (1). (1) Department of Nuclear Medicine, University of Bad, Italy; (2) I Department of Clinical Patology, University of Bad, Italy. Aim: To correlate and integrate biphasic bone scintigraphy data with dosage of biochemical markers of bone metabolism (neoformation and riabsorption) in pts with advanced prostate cancer. Material and Methods: 25 pts with prostate adenocarcinoma (Glenson degree >8), without metabolic bone disease, and free from therapy affecting bone metabolism end normal kidney function were enrolled. 99mTc-MDP biphasic whole body bone scintigraphy (BS) was used to detect the presence, site and number of bone metastases (BM) and to evaluate the radiophamaceutical global skeletal up take at 4 hours after injection (4-h-GSU). In all pta, the serum dosage of Ostaocalcin (OS) (n.y. 1-25 mg/I), as a marker of bone neoformation, bone isoenzyme of alkaline pbesphatase (B-ALP) (n.v. 12-26 U/l) (ALKAPHASE - B; METRA BYOSISTEM) as a marker of bone neoformation and N-Telopeptide of type l collagen urinary escretion (n.y. 14-87 BeE/raM creat) (OSTEOMAK; OSTEX BOUTY) as a marker of bone riabsorption were performed. 4h-GSU evaluation was performed as follows: after i.v. injection of 99mTc-MDP (740 MBq), two whole body scans (anterior and posterior view), were performed after 30 sec and 4 hours. Comparison of counts in the whole skeleton region of interest at 4 hours with those of whole body in early scan gave the 4h-GSU as a percentage of injected dose. Results: In 11 pts BM were detected by BS (group A), 12 BM in I pt, 10 BM in 1 pt, 7 BM in 2 pts, 5 BM in 2 pts, 3 BM in 3 pts end 2 BM in 3 pts, in another 14 pts BS resulted negative (group B). In group A the B-ALP dosage was more than normal range, while OS dosage was higher than group B but within normal range. In group A OS, B-ALP, N-Tx and 4h-GSU resulted respectively 16,7+5,1; 99,9+59,6; 92,3+31,1; 45,8_+.3; in group B respectively 13,3+4,2; 26,2_+10,1; 86,2+17,6; 32,9+4,3. In group A, a significant (p<0,01), higher value of B-ALP, OS and 4h-GSU (p>0,001) was found. A good correlation between 4h-GSU and B-ALP (Speraman test p<0,01 ) was found. Conclusions: In pts with ostenlithie and ostaosclerotic BM due to advanced prostate cancer markers of bone neoformation, B-ALP and OS, resulted significantly increased, and permit to distinguish pts with or without BM, give information about the grade of skeleton involvement but do not detect the number and sites of BM. The NTx serum dosage in pts with ostenblastic and osteolithic simultaneously BM can not be clinically useful.

T. Erselcan (1), V. Nacitarhan (2), D. DoOan (1), O. Sumengen (3), S. ~)zdemir (1). (1) Departments of Nuclear Medicine,; (2) Physicat Therapy and Rehabilitation; (3) Radiodiagnostics, Cumhuriyet Univ., School of Medicine, Sivas,Turkey. The aim of the present study was to evaluate sensitivity and specificity of the fracture risk score (T) in DEXA method in osteoporotic vertebral fractures (wedge, biconcave or compression). 74 women (mean age'L-_SD=54.9_+10.8)were randomly included into the study from the out patient clinics, in whom anterior and lateral ra.diogram of the lumbar region by conventional radiology and bone mineral density measurement (LI-L4) by DEXA method (Hologic, 4500W, USA) were obtained. Three vertebral fracture index (wedge, biconcave or compression) were generated according to Eastell method by measuring anterior, posterior and middle heights in 294 vertebrae in lateral radiogram. Any of the fracture index < -3 SD in any vertebra was defined as fracture positive (37 vertebrae; 56 % wedge, 22 % biconcave and 22 % compression fractures). Increased fracture risk level in any vertebra was defined as T score < 2.5 SD in DEXA method. Results; sensitivity, specificity, positive and negative predictive values in the fracture risk estimation by DEXA method were 32%, 74%, 15% and 88%, respectively. On the other hand, if increased fracture risk level defined as T score < -1.5 SD then, above mentioned values were as follows; 57%, 47%, 13% and 88%, respectively. Meanwhile, DEXA was/east sensitive to the biconcave type vertebra/fractures. In conclusion; Vertebral fracture risk assessement by T score < -2.5 seem to be an insensitive parametre. One of the reason would be the ready-to-use (foreign) reference values that we used in the study. But even so, lowering the T score by 60% did not helped to make the test much more sensitive. We believe that the 2 dimentional vertebral surface measurement, as commonly used in DEXA devices is not a suitable technique.

1165

• OTHER CLINICAL SCIENCE. BONE A N D JOINTS 1

PS_352

PS_354

BONE GEOMETRY, BIOMECHANICS AND MINERAL DENSITY ASSESSED BY PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM SUBMITTED TO PARATHYROIDECTOMY

CONSECUTIVE QUANTITATIVE SPECT STUDIES IN CEMENTLESS TOTAL HIP ARTHROPLASTY. 5-YEAR FOLLOW-UP

C. Di Leo (1), A. Bestetti (1), A. Bastagli (2), L. De Pasquale (2), L. Tagliabue (1), G.L. Tarolo (1), L. Pepe (3). (1) Department of Nuclear Medicine, University of Milan - HSPaolo - Italy; (2) Clinical Surgery Division, University of Milan - HSPaolo - Italy; (3) L'ACN-Laboratori Scientifici, Milan - Italy. Aim: non-invasive measurement by peripheral quantitative computed tomography (pQCT) of bone geometry, biomcchanics, and mineral content in patients (pts) with primary hyperpamthyroidism (PHPT) enrolled to perform parathyroidectomy. Materials and methods: total, trabecular and cortical mineral density (totBMD, cortBMD, trabBMDL bone geometrical properties (total area. trabecuiar area, cortical area, trabecular area/cortical area) and biomechanical parameters (cortical thickness and strength-strain index), were assessed by pQCT at distal radius, in 17 (14 F; 3 M) consecutive pts with PHPT (mean age: 59 yrs; range: 30-77) enrolled to perform parathyroidectomy. Results: serum biochemical characteristics were: iPTH (407=317 pg/ml; range: 107-1438. normal: 30-65). Calcium (II,6±],1 mg/dt: range: 10.6-13.5. normal: 8.1-10,4) and Alkaline Pbosphatase (388±272 U/L; range:173-1174, normal: 98-279). Surgery and histology revealed fifteen solitary adenomas; the weight varied from 0.64 to 71 g (mean of 9,2±19) and the size from 1.2 to 5.5 cm (mean of 2.7±15). Compared with 50 healthy age-matched subjects, total, trabecular and conical bone densities were reduced in all pts (TotBMD: 229 mg/cm 3 vs ctr 343, -33%. p<0.02; TrabBMD: 80 mg/cm 3 vs ctr 146. -45%. p <0,003; CorBMD: 689 mg/cm ~ vs ctr 793. -13%. p <0,02). such as cortical thickness (0,145 cm vs ctr 0,159. -9%. p<0.04) and strength-strain index (576 mm 3 vs ctr 787. -27%, p
E. Zouboulis (t), P. Megas (2), D. Apostotopoulos (1), C. Giannakenas (1), T. Spiridonidis (1), A. Kaisidis (2), E. Lambiris (1), RJ. Vassilakos (2). (1) Department of Nuclear Medicine, University Hospital of Patras, Greece; (2) Orthopaedic Department, University Hopsital of Patras, Greece. A/m: Midterm fixation o£ cementless total hip implants and prognostic value of Q-SPECT analysis of periprostbetic ~n'Tc-MDP uptake are evaluated. Material-Methods: 31 patients (33-76 years), scheduled tbr a total hip anhroplasty due to primary ostaoarthritis were divided into 2 groups. Group A (n=18), where a proximal porous coated and B (n=13), where a smooth tapered design cemenfiess prosthesis, was implanted respectively. The choice of implant was made using a CAD/CAE technique. Patients were imaged 1 week pre-operative, and 2, 8, 36, 60 weeks and 4 years post-operative. Clinical and x-ray fbllow-up was perlbrmed accordingly. Quantitative measurements were perlbrmed with a Region Of Interest (RO[) technique by using the mean counts tbr each ROI and the the ratio of normal hone concetration. Q-SPECT analysis of the radionuciide uptake was performed in coronal, transaxial and sagittal projections, where the slice thickness was tour (4) pixels, fbr image matrix size 128X 128 pixeis. Elliptical angular anatysis in the two latter was also included. Results: Elliptical angular analysis serves tbr the in vivo estimation of the biomechanica] behavior of the cemendess implant and the type of fixation achieved. Qualitative criteria of the design characteristics of each implant are presented. Q-SPECT analysis of periprosthetic ~"'Tc-MDP uptake serves as an early prognostic tool tbr the final implant fixation. Corrolation of the imaging lindings with the clinical and x-ray lbtlow-up is presented. Four distinct types of ~mTc-MDP uptake, which correspond to different biomechanical and clinical performance of each implant, are obtained, - Type 1: adequate initial stability, Type I[: secondary fixation, Type 1[1: response to anelastic implant (excessive thigh pain) and Type IV: t'ailure of initial stability. Conclusions: Consecutive Q-SPECT studies in cementless total hip arthroplasty oft~rs the ability to assess in vivo the biomechanical properties of the ccmentiess implants, as well as n> establish early prognostic signs ['or the final implant outcome. Failure of achieving a ..steadystate" condition of pariprosthetie metabolism until the 60 Lhpost operative week is considered as a failure of achieving initial stability of the implant, probably leading to early aseptic kmsening.

PS_353

PS_355

QANTITATIVE EVALUATION OF SACROILIITIS IN THE PATIENTS WITH BRUCELLOSIS

COMPARISON OF TC 99M MOP, TC 99M HIG, TC 99M WBC SClNTIGRAPHY FOR THE DIAGNOSIS OF INFECTED JOINT PROSTHESIS

H. Kaya, A. Cobaner, T.A. Balci, S. Qer~i. Department of Nuclear Medicine, Dicle University Medical Faculty, Diyarbakir, Turkey. Brucellosis is an infectious disease with multiorgan involvement, especially the muscuIoskeletal system. We aimed to show the sacroiliac joint involvement in the patients with brucellosis presenting with back pain and to evaluate the value of the sacroiliac index (S[) by means of radionuclidc imaging. With this purpose we performed Tc-99m MDP bone scintigraphy to 56 patients and to the 15 control patients with no complaint of back. We obtained spot images from the lumbosacral region on the posterior projection and whole-body images. We drew ROl's with the same pixel over the sacroiliac joints and over the sacrum on the spot images and calculated SI by using the formula of [SI= Sacroiliac joint counVSacrom counq. All images also evaluated visually. Mean SI was 1.52t"0.03 and 1.13+0.25 in the patient group and the control group, respectively. Them was a statistically significant difference betwean the groups (p<0.05). We concluded that SI was a usoful parameter for the evaluation of sacroiliac joint involvcmant, namely sacroiliitis, in brucellosis.

S. Onal (1). (1) Department of Nuclear Medicine; (2) Department of of Ortophedics, Istanbul Faculty of Medicine, IstanbuI,Turkiye. Aim: The aim of this study was to investigate the role of Tc 99m methylene diphosphonate (MDP), Tc 99m human immunoglohufin (HIG), Tc 99m leukocytes (WBC) for the diagnosis of infected joint prosthesis. Methods: Thirty two patients ( 5 men, 27 female, mean age 59.4 year) with suspected infection of a hip or a knee prosthesis were studied prospectively. All the patients had undergone Tc 99m MDP (3 phase), Tc 99m WBC scinfigraphy ( 42 prosthesis ). Tc 99m HIG scinfigraphy could be performed only in 21 patients ( 30 prosthesis) These soindgraphic examinations were completed within 7 days. Focal or diffuse tracer uptake was scored visually according to 4 point scale for HIG and WBC sointigraphy. The pattern of uptake was also correlated with bone scan findings. Results: There were 42 prosthesis in 32 patients ( 3 bi|atcral hip, 6 bilateral knee, 4 unilateral knee and 20 unilataml hip). Final diagnosis was based on operative findings, culture, and clinical outcome. False positive HIG scans (7) were due to loosening of the prosthesis. There was only one fals~ positive scan for WBC. % Te MDP Te HIG Te WBC Tc MOP+ Tc H IG T¢ MDP+ T¢ WBC

S 87 83 89

Sp 79 7l 97

P pv 50 42 89

N pv 96 94 97

83

71

42

94

89

97

89

97

S: Sensitivity, Sp: Specificity, P pv: Positive pv, N pv: Negative Conclusion: These results indicate that high false positive scans and low specificity of Tc HIG scan eliminates its use. On the other hand Te WBC can be used safely for the diagnosis of infected hip prosthesis,

116E

• O T H E R C L I N I C A L SCIENCE. B O N E A N D J O I N T S 1 PS_356

PS_358

COMPARISON OF TC-99M HIG SClNTIGRAPHY AND THREE PHASE TC-99M MDP BONE SCINTIGRAPHY FOR EVALUATING THE EFFICACY OF YTTRIUM-90 SILICATE THERAPY IN RHEUMATOID KNEE SYNOVITIS

ALVEOLAR CAPILLARY MEMBRANE PERMEABILITY IN THE PATIENTS WITH RHEUMATOID ARTRITIS

A. Gen~:o~lu (1), G. Aras (1), O. KO.qfJk (1), S. Atarnan (2), A. Soylu (1), N. S6~j0t (1), E. Ibis (1). (1) Department of Nuclear Medicine; (2) Department of Physicial Therapy and Rehabilitation, Ankara University Medical Faculty, Ankara, Turkey. The aim of this study was to compare the value of quantitative Tc-99m human polyclona[ immunoglobulin G (HIG) scintigraphy to the value of quantitative three-phase Tc-99m methylene diphospbonate (MDP) bone scintigrapby tbr evaluating the efficacy of yttrium-90(Y90) silicate therapy in rheumatoid knee synovitis. Materials and Methods: 24 knee joints with chronic persistent synovitis in 15 rheumatoid arthritis patients (13 F and 2 M, mean age 53.5 -+ 8.4 years) were treated with 185 MBq "(-90 silicate. The patients were examined before and at 3, 6, q, and 12 months after Y-90 therapy using clinical evaluation, Tc-q9m H1G scintigraphy and three-phase Tc-qqm MDP bone seintigraphy. Each scan was evaluated quantitatively and the index of tracer uptake was calculated. The scintigraphic findings were then compared to clinical results at each subsequent assessment. Results:In the 14 knee joints that exhibited excellent or good clinical response to Y-90 therapy, the Tc-99m HIG index values at 3 months after radionucfide synovectomy were significantly lower than the pretreatment index figures (p<0.001). In 13 of these 14 joints, these values remained low throughout the study. 1/14 joint that showed recurrent arthritis at 9 months, the HIG index value was increased at this stage compared to the findings at 3 and 6 months, and it remained high at 12 months. In these 14 joints, the Tc-99m MDP index values (vascular and late phases) were statistically similar before and at 3 months after Y-90 therapy. At 6 months, the M DP index values were diminished in both the vascular (p<0.01) and late phases (p<0.05) in all 14 joints, and these low values continued to be observed in 13/14 of the joints at 9 and 12 months. In the one joint which developed recurrent arthritis at 9 months, MDP index value rose at this stage compared to the value at 6 months, and this was also true at 12 months. In the 10 knee joints that failed to respond to treatment, the MDP and H[G index values were statistically similar before and after the Y-q0 therapy. Conclusion: The study showed that quantitative Tc-99m HIG scintigraphy is a valuable method tbr evaluating the efficacy of Y-q() silicate therapy in rheumatoid knee synovitis, starling from the early post-treatment period. Quantitative three-phase Tc-99m MDP bone scintigraphy may he useful thr evaluating the efficacy of radionuclide synovectomy only in the late period.

H. Kaya, T.A. Ba/ci, M. Polat, S. Erdo~]an, O. G01en. Department of Nuclear Medicine, Dicle University Medical Faculty, Diyarbakir, Turkey. Rheumatoid artritis (RA) is a chronic nonspesifik systemic disease characterised by the inflammation of the peripheral joints. It causes progressive destruction on the joints. Because it is a systemic disease it may involve the lungs and especially interstitial pulmonary disease occurs in the course of time. The goal of this study is to evaluate if an alteration occurs on the puhnonary epithelial permeability in the patients with RA. Thirty patients had normal pulmonary function test and no pathological appearance on their chest x-rays. All of them were non-smoker. We constituded a heahy control group (15 subjects) with the similar pulmonary properties of the patient group. We carried out Tc-99m DTPA inhalation scintigraphy and just after that we obtained dinamic images on the posterior projection of the lung regions during 10 minutes. We draw 6 ROI's on the both lungs and calculated percentage of decreasing activity over the lungs and so we obtained capillary epithelial permeability values. CEP values of the patient group were lower than the normal group, and 0.827_+0.34% and 1.282_+0.27% in the patients group and control group respectively. The difference between the groups was also significant statistically (p<0.001). Pulmonary epithelial membrane permeability decreases in the patients with RA, and there was a relationship between the age of the disease and the reduction of the CEP values. CEP values can be used for follow up the deterioration of the disease in the patients without clinical findings of pulmonary involvement,

£ ¢ ',g

PS_357

PS_359

ROLE OF THREE PHASE BONE SCINTIGRAPHY IN THE EARLY DIAGNOSIS OF REFLEX SYMPATHETIC DYSTROPHY OF THE HAND

ANALYSIS OF UPTAKE PATTERNS IN METASTASIS AND BENIGN DISEASES ON SPINE SPECT: DIFFERENTIAL DIAGNOSIS IS POSSIBLE IN CANCER PATIENTS?

t-

A. Kumar (1), A. Pankaj (2), RP. Kotwal (2), R. Mittal (2), K.K. Deepak (3), C.S. Bal (1). (1) Department of Nuclear Medicine; (2) Department of Orthopaedics; (3) Department of Physiology, All India Institute of Medical Sciences, New Delhi, India. Aim: Post-traumatic reflex sympathetic dystrophy (RSD) of the hand can lead to severe physical disability, if not diagnosed and treated early. RSD is usually diagnosed on high clinical suspicion along with relevant history. However. early diagnosis is sometimes difficult because of paucity and variability of signs and symptoms and plain x-ray is usually non-contributing. Therefore, there is a need for a reliable diagnostic modality to diagnose it early. We tried to assess the role of three-phase bone scintigraphy and sympathetic skin response (SRS) in the early diagnosis of RSD. Methods: After complete clinical evaluation, three-phase bone scan and SRS was performed in 30 patients with clinical suspicion of RSD. Bone scan was done after injecting 20 mCi of Te-99m MDP, and taking immediate blood flow images, blood pool images and static images afier 2-4 hours. SRS was measured in both the hands after fixing electrodes to the palm and the dorsum of both hands and applying electrical stimuli of single square wave pulses of 0.I msec duration and 1-2 mA intensity. Results: Mean age of the patients was 42.6+12.3 years with equal numbers of male and female. In most of the patients, right hand was affected (77%). The commonest preceding event leading to the development of RSD was a simple fracture (67%), that too colles fracture (53%), Crush injuries and compound fracture, history of a surgical procedure and soft tissue injuries of the upper extremity were responsible for 7%, 10% and 16% of cases, respectively. Pain was the most disabling symptom and along with loss of motion was present in all cases, though with varied severity. The delayed phase of bone scan was positive in all cases, blood pool phase in 93.3% and blood flow phase in 90% cases, showing increased multiple periarticular tracer uptake in the affected limb. All patients with negative blood flow and blood pool images had > 3 months duration of illness. SRS was found abnormal in only 8 cases (27%) and in only 4 cases (33%) of < 3 months duration. Conclusion: Three-phase bone scintigraphy is a very sensitive corroborative test to confirm the clinical diagnosis of RSD, particularly during its early stage.

Y.Y. Choi, S. Cho. Department of Nuclear Medicine, Hanyang University Hospital, Seoul, South Korea. Aim: One or more abnormal vertebrae detected at bone scintigraphy is a common finding in clinical practice, and it could pose a diagnostic dilemma especially in cancer patients, as either metastasis or benign disease may cause the scintigrapbic abnormality. The purpose of this study was to determine whether additional spine SPECT has a role in differentiating malignant from benign lesions in cancer patients. Methods: We reviewed spine SPECT studies obtained over a 3-year period in 108 patients. Among them, fifty-two patients with abnormal SPECT and with clinically followed records were evaluated (20 cancer patients were included). Uptake patterns on SPECT images were classified as follows: I. Body ~) diffusely increased uptake(DIU), ® linear increased uptake of end plate(LIU), @ segmental increased uptake(SIU), @ cold defect and/or surrounding increased uptake(CD), 2. posterior element (9 posterior to body(PB): lamina ® posterior to intervertebral disc space(PD): facet joint ® spinous process(SP). Lesions were con'elated with radiologie findings and with final diagnosis. Results: Seventy-six bone lesions were detected on SPECT images.

Body

DIU LIU S1U CD

Posterior element PB PD SP

Metastasis (18) I Degenerative (28) Compression Fracture (21) 9 4 6 1 5 6 2

2

1

3

Failed back syndrome (9)

4 3 2

Conclusion: Cold defect and segmental increased uptake of body were characteristic findings of bony metastasis, but care should be taken because compression fractures showed segmental increased uptake in some cases, Degenerative diseases were easily diagnosed due to typical finding of linear increased uptake of end plate and facet joint uptake. Therefore, additional bone SPECT after planar bone scan would be helpful for differentiating metastasis from benign condition in cancer patients.

116"/

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a {/ C n

• OTHER CLINICAL SCIENCE. BONE AND JOINTS 1 / CARDIOVASCULAR 5 PS_360

PS_362

RELATIONSHIP BETWEEN 99MTC-HDP PETROSA BONE SPECT FINDINGS AND SENSORINEURAL HEARING LOSS IN PATIENTS

DYNAMICS OF MYOCARDIAL PERFUSION AND FUNCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: EVALUATION BY GATED SPECT (G-SPECT) WITH 99MTC-MIBI

WITH OTOSCLEROSIS D. Volterrani (1), S. Berrettini (2), F. Ravecca (2), G. Boni (1), M. Grosso (1), S. Sellari Franceschini (2), G. Manca (1), E Bianchi (1), R. Bianchi (1). (1) Division of Nuclear Medicine; (2) Division of Otorhynolaryngoiatry, University of Pisa, Pisa, Italy. Otosclerosis (OS) is a primary disease characterized by bilateral hearing loss (HL) and by the progressive replacement of the normal bone of the ossicles and otic capsule with a disorganized fibrous and osseas tissue. The diagnosis is usually based on family history, progressive HL, absence of stapedial reflex, on-off effect on impedance tympanometry. Although CT and HR-CT are reported to be useful, both false positive and false negative results can occur. In this study we evaluated diphosphonata bone SPECT findings in relation to the presence of OS and the degree of the sensorineural HL Methods: Thirty-six patients (72 ears) with surgically confirmed OS, affected by mixed (conductive and sensorineural) HL, and 12 normal hearing subjects free of any otoiatric disease, underwent a bone SPECT of the skull with 9QmTc-HDP. SPECT studies were carried out by using a dual head gamma camera equipped with LEHR collimators. FBP and a Butterworth prefiitering (cut-off 0.50 eycles/cm, order 10) were used for images recontroctinn, Attenuation correction was not applied A scintigraphic uptake index (UI) value was calculated by dividing the mean activity of the ROIs drawn along the petrosa bones by the mean activity for the occipital bone. Results: A statistically significant increase of diphosphonata uptake was found when comparing the scintigraphic UI values of the patients affected by OS with controls (2.21±1.70 vs 1.13±0.26; p<.OOOl). An inverse relationship (p <.005) between patients age and petrosa UI values was observed. A stright relationship was found between UI and the severity of sensorineural HL, revealing a statistically significant difference among UI values of patients with mild, moderate and severe sensorineural HL, especially when only younger (_<45 yrs) patients were considered. Conclusions: Petrosa bone SPECT seems to he an useful tool fur the assessment of Og. Moreover, SPECT could be a predictor for medical treatment efficacy with diphospbonates of patients with a more severe sensorineural HL by directely visualizing those active lesions which much more accumulate diphosphonate.

E. Egorova, E. Khodareva, M. Rucla, VoSergienko. Department of Nuclear Medicine, Cardiology Research centre, Moscow, Russia. dim." to assess the dynamics of myocardial perfusion and function for 6 months in patients (pts) with acute myocardial infarction (AMI) after reperfusion therapy (6 month follow up). Materials and method~. 29 pts with AMI were studied. All pts underwent reperfusion therapy (RT): systemic thrombolysis in 26 and PTCA in 3. Gated -SPECT (G-SPECT) with 99mTcMIBI was performed in each case before the onset of RT (area of risk), 24 hours later, before the discharge (10 days), I and 6 months after the development ofAM[. Resuhs were analyzed by ejection fraction (EF %) and the size of perfusion defects (DP, % LV). Resuhs: Depending on the RT efficacy all pts were divided into 2 groups: those with the infarct-related artery reperfiased (I St gr., n=19) and those with no evidence of rcperfusion (2 "a gr,, n=10). Results in 2 gr. of pts. are presented in the table.

DPI% )

EFt%)

I gr,

i

Before RT 31+_10,0

24 h. 25+10,2"'"

I 0 da~cs 21+9,7"'"

I 1 mnth 20_+8,7

6 mnths 20~_9,6

~r.

35+_ep,3

33±9,0

29±8,0""

29_+?,6

26_+8,5"

~r. gr.

43-+10 41±9

43+10 38±10

46_+7,1" 43+8

46_+6 42±7

47+-8 43±10

""-P<0.001, "'-PO.05 (paired t-crit). There was no initial difference in the extent and EF between the two groups. Pts with effective RT exhibited a decrease in the extent by 20% (p
CARDIOVASCULAR 5

PS_363

PS_361

ROLE OF THE 99M TC-SESTAMIBI G-SPECT IN THE EVALUATION OF SEPTAL DYSFUNCTION AFTER CORONARY ARTERY BY-PASS SURGERY

SYSTOLIC AND DIASTOLIC STUNNING 30 MIN AFTER EXERCISE IN PATIENTS WITH ANGINA PECTORIS: EVALUATION WITH GATED TC -99M-TETROFOSMIN SPECT

1". Kawasaki, T. Sakatani, H. Mani, 1". Kamitani, S. Kawasaki, H. Sugihara. Depertment of Cardiology, Matsushita Memorial Hospital, Sotojima-cho, Japan. Aim: We investigated whether systolic and/or diastolic dysfunction persists even 30 rain after exercise-induced iscbemia in patients with angina pectoris (AP). Methods: Twenty patients with AP and 15 controls(C) underwent exercise/rest Tc-99m-tetrofosmin (TF) gated SPECT 30 min after injection. Data acquisition was gated for 16 frames / cardiac cycle. Le~ ventricular (LV) volume curves were generated using QGS program and four harmonics of Fourier series was retained for the analysis. From this curve and its first derivative curve, we derived ejection fraction (EF) as systolic index and peak filling rate (PFR), time to PFR (TPFR) and 1/3 filling fraction (I/3FF) as diastolic indices. Results: Post exercise EF did not differ from resting EF in C. In 8 of 20 patients with AP, post exercise EF was > 5 % lower than the resting value. There were no difference in PFR, TPF and I/3 FF between post exercise and rest in C. Both post exercise PFR(O/dsec) and 1/3 FF(%) were less than the resting values in patients with AP (PFR 195.6~48.4 vs 225.0~:40.2, I/3FF 37.5~18.0 vs 42.5±14.0, p<0.01). Post exercise TPF was more prolonged than resting values in patients with AP (203.0±35.1 vs 185.0~:28.3, p
116E

R Sullo (1), E.M. Covelli (I), G. Mazzarella (1), A. Cardilio (2), A. Natale (2), C. Formato (1), F. Boccagna (1), C. Chieffo (2), G. Belfiore (1). (1) Diagnostic Imaging Department - Caserta Hospital; (2) U.O. Cardiologia Riabilitativa, Caserta Hospital, Italy. Abnormal septal wall motion is a possible complication due to pericardiotomy after coronary by-pass surgnry (CABG) and traditional noninvasive tachniques evaluating LV regional function are not reliable to assess this condition. Gated-SPECT (G-SPECT) with Tc99m labeled perfusion tracers allows simultaneous assessment of cardiac regional function and perfusion. Aim of our study was to investigate septal dysfunction and corresponding perfusion in patients with previous CABG. Methods: Thirty-nine patients (28M, 1 IF; mean age 60~12 years) with CABG for multivessel disease underwent rest Tc99m-sestamibi (925 MBq) G-SPECT using a 90 i dual-detector camera (Vertex, ADAC) and 2D-echocerdiography within I week. According to the standard QGS and QPS protocol, septal wall was divided in 6 (2 para-apical, 2 medial and 2 paraba.cal) of 20 segment model. Septal wall motion (SWM) was scored in corresponding segments from 1 (normal) to 3 (a-dyskinesia) on both G-SPECT and 2D-ecbocardiography, Segmental Tc-99m sestamibi uptake was quantitatively measured and expressed as percentage of normal region activity in reference population database. Results:Of the 234 seplal wall-related segments, 92 (40%) were a-dyskinetic, 127 (54%) hypokinetic and 15 (6%) normal on G-SPECT study; 2D-echocardiography revealed 90 (38%) segments with a-dyskthesia, 121 (52%) with hypokinesia and 23 (10%) with normokinesia. Agreement between G-SPECT and 2D.-echocardiography was observed in 193/234 (82%, k=0,66) segments. No statistically significant different sestamibi uptake was found in normal (65_+4), hypokinetic (63+5, p= n.s.) and a-dyskinetic (62+4, p= n.s.) segments, indicating normal perfusion stastus in all segment groups. Conclusions: These results suggest that Tc99m-sestamibi G-SPECT can reliable discriminate dysfunctional but normoperfused septal wall due to CABG and it might be accurate technique in the noninvasive evaluation of this patient population,

• CARDIOVASCULAR 5

PS_364

PS_366

ASSESSMENT OF RESIONAL LEFT VENTRICULAR PERFUSION AND FUNCTION WITH GATED-SPET IN PATIENTS WITH SURGICALLY REPAIRED TERALOGY OF FALLOT

EVALUATION OF DIFFERENCES BETWEEN POST STRESS AND REST LEFT VENTRICULAR EJECTION FRACTION ASSESSED WITH GATED MYOCARDIAL PERFUSION SPECT

T. Higuchi, J. Taki, K. Nakajima, H. Sumiya, S. Kinuya, N. Tonami. Kanazawa University, Department of Nuclear Medicine, Kanazawa, Japan.

H.J. Verberne (1), M.G.W. Dijkgraaf (2), B.L.F. van Eck -Smit (1). (1) Department of Nuclear Medicine; (2) Department of Clinical Epidemiology & Biostatistics, Academic Medical Center, University of Amsterdam, The Netherlands.

[Purposes] Intracardiac repair of teralogy of Fallot (TOF) may result in abnormal septal perfusion and function. The aim was to evaluate regional perfusion and function by ECG-gated perfusion SPECT (G-SPECT) in TOF. [Methods] Eight patients with TOF (aged 15±4) who had undergone intracardiac repair (TOF group) and ten age-matched normal control subjects (aged 14~:4) (control group) were enrolled. The average interval between the operation and postoperative G-SPECT in TOF group was 9±3 years. Tc-99m-MIBI (740 MBq) was injected at rest, and G-SPECT was performed. We evaluated left ventricular ejection fraction (EF), inward regional wall motion (WM), systolic % wall thickening (WT) and % tracer uptake with QGS program. Regional parameters were obtained in 20-segments model based on the functional polar map. [Results] There were no differences between TOF and control groups in global EF, regional % tracer uptake and WT in all segments. However, WM (unit: mm) in the 4 septal segment decreased compare with normal group (l.9±1.8 mm vs. 6.0±1.4 mm, p<0.01). [Conclusion] WM and perfusion in the septal segments show mismatch, indicating pseudoparadoxical motion after surgery. Thus, systolic wall thickening analysis is preferred to evaluate regional function in repaired TOF.

Aim. Gated SPECT has an additional value to routine myocardial perfusion imaging. The purpose of the study was twofold: I) to determine the reproducibility of gated SPECT assessed left ventricular (LV) ejection fraction (EF) and 2) to determine patient characteristics correlating to differences in LVEF assessed directly post-streas and at rest. Methods. In 229 randomly selected patients gated SPECT was performed post-stress and at rest. Reproducibility of LVEF measurement was determined in 22 patients by comparing two consecutive gated acquisitions at rest after patient repositioning. Data acquisition was performed I hour after administration of 500 MBq ~Tc-Tetrofosmin with a 3-headed SPECT system. The Germano Quantitative Gated SPECT (QGS) software was used to calculate LV dimensions and EF. Reproducibility of the repeated rest measurement was expressed as a mean difference and 95% confidence interval (95% CI). Multivariate regression analysis was used to correlate the difference between post-stress and rest LV-measurement (delta EF) and items concerning patient characteristics, clinical history, stress related factors and scintigraphic findings. Results. The mean difference between two consecutive measurements at rest was 0.09% EFunits with a 95%C1 from - 4 to 5% EF-anits. Independent predictors of delta EF were the presence of scintigraphically proven ischemia (standardized coefficient: 0.173, p= 0.009) and differences in hearl rate (HR) during acquisition (standardized coet'ftcient: 0.203, p= 0.005). End-diastolic volume, maximal HR during stress, scintigraphically proven infarct and stresstype (adenosine vs. ergometry) were no independent predictors of delta EF. Conclusions. Gated SPECT assessed LVEF is reproducible under standard clinical conditions. However, differences in LVEF between rest and post-stress assessment can be expected if HR has changed between two measurements and in patients with scintigraphically proven ischemia.

tO

PS_365

PS_367

CORRELATION BETWEEN POST-STRESS AND REST GATED

LEFT VENTRICULAR EJECTION FRACTION (LVEF), END DIASTOLIC VOLUME (EDF) AND END SYSTOLIC VOLUME (ESV) BY QUANTITATIVE GATED MYOCARDIAL PERFUSION SPECT (QGS). COMPARISON WITH ECHOCARDIOGRAPHY (ECHO) IN ACUTE CORONARY SYNDROME

MYOCARDIAL PERFUSION IMAGING : AN APPROACH TOWARDS THE BEST METHOD FOR MEASURING LEFT VENTRICULAR FUNCTION A.M. Garcia Vlcente, S. Rodado, V. Poblete, A. Soriano. Department of Nuclear Medicine, Alarcos Hospital, Ciudad Real, Spain. The ventricular function data obtained by gated SPECT reflect the condition at the time of acquisition while the perfusion data are dependent on conditions at the time of injection. Aim : to compare post-stress and rest ejection fraction, thickening and wall motion in patients with coronary artery disease and investigate the relationship between the development of perfusion abnormalities and the changes in left ventricular ejection fraction (LVEF) measurements. Methods: A same day post-stress and rest gated SPECT with 740 MBq and I I I0 MBq of Tc 99m-tetrofosmin respectively was performed on 28 patients (average age:57). 16 underwent an exercise test and 12 a pharmacologic stress test. All patients had known ischaemic cardiopathy (21 with previous myocardial infarction), Post-stress and rest tomograms were qualitatively analysed by using a 13 segment model, The perfusion images were interpreted independently by two experts assessing reversible and fixed defects. The data were analysed using a comparative analysis of independent variables (t-student). Results: The average LVEF for post-stress was 36,5 % and for the rest:37,6 %. These values did not show significative statistical differences (p=0,586). 3 of 9 patients (group 1) with LVEF higher in post-stress, showed significative statistically differences (>5%); 1 patient did not show any differences and 18 patients (group 2) showed lower LVEF in post-stress gated images compared with rest gated images (9 of them significatire). A total of 100 perfusion defects , 59 reversible and 41 fixed, were detected. 20 reversible defects showed thickening in rest gated and I0 in post-stress gated. The group 2 (18 patients) had more reversible defects (average: 2,8 segments) than group 1 (9 patients) who showed an average of I segment, There were no sigaificative statistical differences (15=0,646) between the number of fixed defects in group 1 (average: 1,5 segment) and group 2 (average: 1,3 segments). Motility alterations showed concordance between both methods in 24 patients. 10 of them showed agreement with perfusion abnormalities and 14 showed discrepancy, 9 were septal dyskinesia in 5 patients with left bundle branch block. Conclusions: Patients with more reversible defects showed lower LVEF in post-stress gated compared with rest gated but without statistical differences. The thickening of reversible defects was more evident in rest gated. The post-stress gated underestimated the viability determined by thickening but had a prognostic value, as a lower LVEF showed a great number of reversible defects and therefore myocardial in risk,

M.D. Marin (1), A. Gonzalez (2), M. Coronado (1), I. Roldan (1), R. Couto (1), T. Navarro (1), G. Riesco (1), R. Plaza (3). (1) Servicio Medicina Nuclear, Hospital; (2) Servicio Cardiologia, Hospital; (3) Servicio Radioproteccion, Hospital, Hospital Universitario, Madrid, Spain. The objective of this study is to evaluate left ventricular function and volumes measured by rest QGS and its correlation with eehocardiography and equilibrium ventriculography techniques. MATERIAL AND METHODS A total of 48 patients from 41 to 77 years old (men age 59.9 + 9.3, 46 males and 2 females), with non complicated acute myocardial syndrome (16 patients without ST segment elevation and 32 with ST segment elevation) were evaluated retrospectively by means of gated ventriculography, two dimensional echo and ~mTc-sestamibi gated SPECT stress/rest. A total of 46 underwent exercise test and 2 of them underwent pharmacological tesL Abnormal perfusion defects were found in 67% ofpafients and abnormal segmental wall motion were found in 62% of patients. These techniques were performed 5 days to 30 days after presentation of acute coronary syndrome. LVEF, EDV and ESV were assessed with Echo, automatic QGS and equilibrium ventriculography (LVEF only) RESULTS

QGS ECHO

54~4%± 11.5 51.9% + 10.4

107.3+ 28.9 ml 110.6 + 34 ml

I 50.g +23.8 ml I 55.2 ± 28.3 ml

EQUILIBRIUM VENTRICULOGRAPHY LVEF: 51,8 + 8.9 ml. Pearson correlation was used to compare the results between echo and QGS for LVEF (r=0.68); EDV (r=0,75) and ESV(r=0.82). This coefficient was also used to compare equilibrium ventriculography with echo and QGS for LVEF (1"=0.68 and r=0.72 respectively). CONCLUSIONS All QGS cardiac SPECT parameters correlated well with echocardiography and equilibrium ventriculography. Besides, it is a fast, objective and reproducible method and provides additional information about myocardial perfusion. The echocardiogmphy, on the other hand, has the disadvantage of being an observer dependent method and slower to perform.

1169

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e~

0

• CARDIOVASCULAR 5

PS368

PS_370

CORRELATION BETWEEN LEFT VENTRICULAR EJECTION FRACTION (LVEF) CALCULATED FROM TC-99M TETROFOSMIN GATED

RELIABILITY OF 201-TL ECG-GATED SPECT VERSUS PLANAR RADIONUCLIDE VENTRIVULOGRAPHY FOR THE MEASUREMENT OF LEFT VENTRICULAR EJECTION FRACTION

SPECT (GS) AND ECHOCARDIOGRAPHY (EC)

A. EI-Shirbiny (1), M. Islam (2), I. Seo (1), J. Luo (3), C. Horns (1), R. Kappas (1), W. Sy (1). (1) Nuclear Medicine Department, The Brooklyn Hospital Center; (2) Department of Cardiology, The Brooklyn Hospital Center; (3) Nuclear Medicine Service, Department of Radiology, St. Vincent's Catholic Medical Centers of New York, USA. Aim: Evaluation of accuracy of LVEF from Tc99m Tetrofosmin (TF) GS SPECT as compared to the commonly used EC. Method: We retrospectively compared LVEF form GS, using the commercially available Cedars Quantitative Gated SPECT software and EC using modified Simsons method within 15 days of each other in 199 patients. Results: Normal perfusion was found in 109, inferior wall perfusion detect in 40 and multiple perfusion defects in 12 patients. The results of comparison are shown in the following table and graphs. Whole GS Max 87 Min 16 Average 53.21 SD 14.95 t-Test 0.002 Correlation 0.697 Intercept 8.750 Slope 0.771

ECHO 86 15 57.66 13.52

EF < 50 GS 50 16 36.94 10.0[ 0.000 0.691 14.044 0.485

ECHO 72 ~r15 47.26 14.28

EF > S0 : GS 87 51 58.27 7.61 i 0.277 0.218 511.298

ECHO 86 39 62.02 8.70

0.191

Conclusion: LVEF calculated from Te99m TF (iS has overall acceptable correlation with EC (r = 0.69). However, EC overestimates LVEF at lower GS EF values < 50% and underestimates LVEF at GS EF values > 60%. Inferior wall and multiple perfusion detects had no effect on the correlation values.

D. Daou (1), C. Coaguila (1), B.O. Helal (1), I. Ponturier (1), T. Fourme (2), S. Dinanian (2), R. Lebtahi (3), M. Faraggi (3), M. Slama (2), D. Le Guludec (3). (1) Department of Nuclear Medicine, Antoine Beclere Hospital, AP-HP, Clarnart, France; (2) Cardiology Department, Antoine Beclere Hospital, AP-HP, Clamart, France; (3) Department of Nuclear Medicine, Bichat Hospital, AP-HP, Clamart, France. Objectives: Coupling myocardial perfusion to function is interesting. Good correlation between let ventricular ejection fraction (LVEF) calculated with '°IT1 ECG-gated SPECT (GSPECT) versus other modalities has been reported. But, its reliability for the study of LVEF has not been studied with :°~Tl GSPECT. Moreover, this reliability has not been compared in the same patients to that of planar equilibrium radionuclide angiography (RNA). We aimed to compare the reliability of GSPECT and planar left anterior oblique (LAO) RNA for the measurement of LVEF. Methods: Nine patients with coronary artery disease had both rest ~Q1TIGSPECT and planar LAO RNA. The rest 2°lTI GSPECT consisted of 2 acquisitions (8 framas/RR) realized at 15 min (Technician I ) and 4h after injection (Technician 2). This was followed by a planar LAO RNA (Technician 2). Then, the patient was allowed to rest in the waiting room for at least 15 rain and a second planar LAO RNA acquisition was realized (Technician I ). The LAO acquisitions were processed at 8 frames/RR with a widely validated software. The GSPECT were processed using 2 different sofwares: QGS (Cedars-Sinai) and SU (Stanford University). Processing was realized twice by 2 different observers with a one-week interval. The % variation between 2 measurements was calculated as the % of their difference normalized to their average. The intra and inter observer and interstudy % variabilities and paired absolute difference of LVEF were calculated and compared between planar LAO, QGS and SU. Results: The intra-obscrver, inter-obscrvcr and inter-study % variation lbr LVEF calculated with LAO. QGS and MD were respectively (0±7 %, 0±5 % and -5± 13* %; (*) p
PS_369

PS_371

LEFT VENTRICULAR EJECTION FRACTION DETERMINED BY GATED-SPECT MYOCARDIAL PERFUSlON IN CORONARY PATIENTS.COMPARISON WITH EQUILIBRIUM ISOTOPIC VENTRICULOGRAPHY

DETECTION OF TRANSIENT ISCHEMIC MYOCARDIAL STUNNING FROM EARLY AND DELAYED GATED SPECT THALLIUM-201 MYOCARDIAL PERFUSION IMAGING BY AUTOMATED QUANTITATIVE ANALYSIS

I. Cas~.ns-Tormo (1), A. Llacer (2), J.A. Ferrero (2), J. Ciudad (1). (1) Nuclear Medicine; (2) Cardiology Departments. Hospital Clinico Universitario. Valencia. Spain.

M. Mirzaitehrane (1), S. Heiba (2), F. Dede (3), J. Santiago (2), S. Jana (2), H. AbdeI-Dayem (2). (1) Department of Cardiology, St. Vincent's Catholic Medical Centers of New York; (2) Nuclear Medicine Service, Department of Radiology, St. Vincent's Catholic Medical Centers of New York; (3) International Research Fellow, Turkish Science Foundation, Marmara University, Turkey.

To assess the accuracy of l e t ventricular ejection fraction (EF) measurement by gated SPECT (GSPECT), we have studied 34 coronary patients proven by coronary angiogmphy, 17 of them with EF_<40% and the other 17 with EF>40%. Methods: SPECT myocardial perfusion was obtained with 99mTc-Tetrofosmin (2 day-protocol), with gated acquisition always I h aRer tracer injection, administered at peak exercise in 19 patients and at rest in 15 patients (8 frames/cycle, 180°. 64x64, 30 images, 45 s/image) and EF measurement by QGS program. An equilibrium isotopic ventriculography (EV) was obtained 48 h later, with EF determination by usual non-genmetric semiautomatic method. All studies showed suitable quality for quantification. We have assessed differences in mean EF values, correlation and agreement (Bland-Altman analysis) between the two methods. Results: Considering all patients, we have found high correlation in EF determination between GSPECT and EV (r: 0.96, p: 0.0001), although mean EF by GSPECT was 37.84:18.4%, and 40.8±19.3% by EV (p: 0.0001). Mean difference between both methods was 3.0~4.9, with limits of agreement from -6.8 to 12.8. In patients with EF>40%, the correlation was good (r: 0.82, p: 0.0001), with mean EF values of 53.8±9.4% (GSPECT) and 5g.0~8.9% (EV), p: 0.007 Mean difference betv, een methods was 4.1±5.5, with -6.8 to 15.2 as limits of agseement. In the group with EF<40%, the correlation was higher (r: 0.87, p: 0.0001), mean EF values were 21.8±8.1% by GSPECT and 23.7±7.9% by EV, p: NS. Mean difference between methods was lower: 1.8±4.1 and narrower the agreement limits: -6.4 to 10.0. Conclusion: Mean EF values obtained with gated SPECT were lower than the mean values determined by equilibrium ventriculography in the group of patients with higher EF, without significative differences in the lower EF group. Good correlation and agreement was found between both methods in EF determination in patients with higher EF and even better in patients with lower EF. So, gated SPECT provides suitable accuracy in quantification of EF in coronary patients with as without ventricular dysfunction.

!17C

AIM: We investigated the feasibility of automated quantitative analysis in detecting post ischemic myocardial stunning from immediate post stress and delayed gated SPECT imaging with Thallium-201. METHOD: We studied 1640 myocardial segments in 82 patients (52 men), average age of 60, who underwent treadmill exercise (n: 57) or dobotamine (n: 25) stress test with both early and delayed gated SPECT Tbellium-201 myocardial perfusion imaging using a commercially available soP:ware (autoQUANT~). Pcrfusion score, % wall thickening and degree of wall motion for each segment were derived from automated quantitative analysis. A scale of 5 points was used in the automated segmental summation perfusien score. Stunning was identified by increase in % wall thickening or degree of wall motion at delayed as compared to early images. RESULTS: There was good correlation between wall thickening and wall motion in post stress and delayed images in ischemic (Pearson correlation = .728 & .739) fixed defect (.652 & .695) and normal perfusion segments (.529 & .585). Of 1640 segments studied (in the 20 segment model), there were 482 segments with abnormal perfusion. Out of those abnormal segments, there were 338 ischemie and 144 fixed defect segments. In the 338 iscbemie segments the mean wall thickening increased from 25.33 to 29.33% (p <0.001) and mean wall motion score increased from 4.69 to 5.19 mm (p <0.001) between the immediate post stress and delayed images indicating transient stunning. When mild ischemie segments (only I score improvement at delayed images) were excluded, the mean wall thickening score in the remaining segments (120) increased from 24.4 to 29.4% (p <0.001) while the mean wall motion increased from 4.3 to 5 mm (p <0,005). These changes were also more significantly noticed in moderate or severely iscbemic segments than mildly iscbemic ones. No significant differences, however, were seen in the wall motion and thickening measurements between early and delayed images in segments with fixed perfusion abnormalities. CONCLUSION: In the post stress and delayed gated SPECT Thallium-20l studies, wall thickening and wall motion measurements derived from automated quantitative analysis correlate well in all types of myocardial perfusion. Both quantitative measurements can be used in the detection of post ischemic myocardial stunning and show significant relationship to the severity of myocardial ischemia.

• CARDIOVASCULAR 5

PS_372

PS_374

IMPROVEMENT IN ESTIMATION OF LEFT VENTRICULAR FUNCTION WITH TC-99M TETROFOSMIN GATED-SPECT : A MULTIVARIATE ANALYSIS

LEFT VENTRICULAR FUNCTION EVALUATED WITH REST 201TL NON-GATED SPECT AS COMPARED TO ECG-GATED SPECT

A. Okizaki, N. Shuke, H. Hirota, J. Sato, Y. Ishikawa, W. Yamamoto, K. Kikuchi, T. Aburano. Department of Radiology, Asahikawa Medical College, Asahikawa, Japan. Aim: The purpose of this study was to improve accuracy in estimating the quantitative parameters related to left ventricular function from Gated-SPECT through an empirical approach by multivariate analysis. Methods: Ninety-six patients with various cardiovascular diseases were studied. After an injection of Tc-99m Tetrofosmin (740MBq). Gated-SPECT was performed on a three-headed digital gamma camera system. Left ventricular ejection fraction (EF), enddiastolic volume (EDV) and end-systolic volume (ESV) were calculated from the gated SPECT data with the QGS program. Left ventriculography (LVG) was performed within 2 weeks after the SPECT. EF. EDV and ESV were also calculated from LVG by area-length method for references. Multivariate analyses were performed with EF, EDV and ESV from LVG as dependent variables and height, heart rate (HR), age and EF, EDV, ESV obtained by the QGS program as explanatory variables to determine empirical formulas for predicting these parameters. The predicted values of EF, EDV and ESV by the determined empirical formulas were compared with those obtained directly from the QGS program in correlation with the results of LVG. Results: Multivariate analyses could improve accuracy in estimation of EF, EDV and ESV. Results were summarized in the table, Statistically significant improvement was seen in EF. Although not statistically significant, improvements in correlation coefficients were seen in EDV and ESV. Conclusion: The empirical approach by multivariate analysis could improve the accuracy in estimating EF from Gated-SPECT.

EF EDV ESV

Multivariate Analysis R2 ISE 0.65504 * 8.94763 0.33670 40.71570 0.57285 27.38880

QGS Rz 0.48512 0.32418 0.51825

SE 10.63666 40.94073 28.61870

RZ: correlation coefficients SE: standard errors of estimates * p<0.05

D. Daou (1), C. Coaguila (1), B.O. Helal (1), T. Fourme (2), I. Care((2), R. Lebtahi (3), M. Faraggi (3), M. Slama (2), D. Le Guludec (3). (1) Department of Nuclear Medicine, Antoine Beclere Hospital, AP-HP, Clarnart, France; (2) Cardiology Department, Antoine Beclere Hospital, AP-HP, Clamart, France; (3) Department of Nuclear Medicine, Bichat Hospital, AP-HP, Clamart, France. Aims: Left ventricular (LV) function evaluated with :mTI ECG-gated myocardial perfusion SPECT (GSPECT) is valuable. It allows the estimation of LV end-diastolic volume (EDV), end-systulic volume (ESV) and ejection fraction (EF). These parameters have been largely validated, particularly with the QGS software. For different reasons gating may not be realized in some studies. We simulated this situation by summing a GSPECT study into a nongated study (aSPECT). This reduces the LV function information available with GSPECT into only one measure of LV volume (sV). We aimed to quantitate the amount of information provided by the sV measured with QGS on a sSPECT study as compared to LV function information provided by the corresponding GSPECT study (EDV, ESV, EF). Methods: Ninety patients with CAD having both a rest "~mTlGSPECT study and a planar left anterior oblique equilibrium radionucLide angiography (RNA) were studied. 48/90 patients had also radiological LV angiography (Rx). Using the QGS software, LV EDV, ESV and EF were calculated on the GSPECT. Then, a sSPECT study was generated from each GSPECT study and a corresponding LV sV was calculated with the QGS software. Were compared the correlations of sV and GSPECT EDV, ESV, and EF with respectively the EDV-Rx, ESV-Rx and planar RNA LVEF. The correlations of sV versus respectively GSPECT EDV+ ESV and EF were also studied. Results: The sV presents high coo'elation with the GSPECT EDV and ESV; similar good correlation to EDV-Rx and ESV-Rx as GSPECT EDV and ESV; good correlation with GSPECT LVEE However, as compared to GSPECT, sV presents a lower correlation to planar RNA LVEE LV r/ser ! Planar EF EDV-Rx SV -0.69 / 13 0.77 / 40 EDV-QGS 0.79 / 38 ESV-QGS EF-QGS !0.84/10 p=0.o01 for all linear regression correlations

ESV-Rx 0.86 / 27

0 8 7 / 26

sV

0 9 9 / 12 0.99 / 11 -0.77/ I0

Conclusion: Because of better evaluation of LV function, gated 'mTI SPECT should be prefurred to non-gated SPECT. In non-gated SPECT studies, sV presents good correlation with LV function and should be realized routinely.

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PS_373

PS_375

GATED 201-TL PLANAR PERFUSION IMAGING FOR SIMULTANEOUS EVALUATION OF PERFUSION AND LEFT VENTRICULAR

DETERMINATION OF LEFT VENTRICULAR EJECTION FRACTION

FUNCTION D. Sobic-Saranovic, S. PavIovic, N. Kozarevic. Institue of Nuclear Medicine, CCS, Belgrade. SPET and planar ECG-gated 99mTc-MIBI scintigraphy has been used during the past few years for the simultaneous evaluation of myocardial perfusion and ]eft ventricular ejection fraction (LVEF). Aim: The aim of this study was to evaluate the feasibility of planar ECG-gated 201-Tl scintigraphy (GTL) in the assessment of resting LVEF at the same time as evaluation of myocardial perfusion. Methods: Seventeen coronary patients, 14 with angina pectoris and 3 with previous myocardial infarction were studied. 20[-TI was administered at dose of 150MBq at the end of submaximal exercise, and stress SPET perfusion images, and 4 hours later redistribution images were performed. After stress perfusion images acquisition, eight frames per cardiac cycle studies were performed in LAO 45 view. After digital smoothing, regions of interest were drawn in all frames along the endocardia[ border of the left ventricle, LVEF was computed from time-activity curve. The results were correlated with LVEF determined in all patients by equilibrium radionuclida vantriculography (ERNV) performed within l week of the 201-TI study. Results:LVEF determined by GTL ranged from2]% to 82% (mean+l-S.D.:55+/-14%), while the mean LVEF assessed by ERNV was 59+/-t2% (p>0.05). Correlation between these two methods foe LVEF was r=0.88. Inter-observer variability for GTL LVEF was r=0.81, while intra-observer reproducibility was r-~).86. In 2 of 17 patients determination of LVEF was impossible because of left ventricular obliteration. Conclusions:Using gated planar 20t-Tl imaging, left ventrieular ftmetion can be evaluated at the same time as myocardial perfusion, with the same dose of 201-TI, but care is needed to obtain reproducible results.

BY GATED 99MTC-MIBI SPECT ON THE BASIS OF OUR EXPERIENCE. CORRELATION WITH ANGIOGRAPHY

M. Kobylecka (1), A. Rak (2), J. Kunikowska (1), L. Krolicki (1), G. Opolski (2). (1) Department of Nuclear Medicine, Medical University; (2) Chair and Department of Cardiology and Internal Medicine, Medical University, Warsaw, Poland. Left ventricuiar ejection fraction (LVEF) is one of the most powerful predictors of prognosis. There are several techniques providing the ejection fraction information used in clinical prac* tice. However the concordance between them is various in different medical centres. Aim of this study was the comparison between Gated 99mTc-MIB[ SPECT LVEF and LVEF obtained from contrast ventriculography in our hospital. Method: 28 patients (9 women 19 men) aged 34-68 (mean age 52, SD 9,43 ) with established CAD, reported for coronary angiography were included. All patients underwent the contrast ventriculography and the MIBl-perfusion study using a standard two days stress/rest MIB[ SPECT protocol with G-SPECT at rest. Ejection fraction (EF) was calculated from G-SPECT resting perfusion images using the commercial software (QGS-SPECT). A standard technique was used for EF calculation during contrast ventriculography, Results: EF obtained from G-SPECT ranged from 28% to 68% with a mean value 54,30 (SD

11.04) EF calculated from contrast ventrlculography ranged from 54% to 86% with a mean value 73.00 (SD I 1,70) The differences between G-SPECT EF and contrast ventriculography EF were significant (I)<<0,05), mean value 18,72 (SD7,10).The correlation coefficient calculated for EF between both mgdalitics was 0,81 G-SPECT tend to underestimate LVEF compared to contrast vantriculography. It is important to use only one technique for EF measurement for patients follow up studies. However if comparison of different modalities EF data is necessary, the calculated correlation coefficient would be helpful.

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• DIAGNOSTIC O N C O L O G Y 9

PS_376

PS_378

A NONINVASIVE METHOD TO DIAGNOSE MDR RELATED PGP EXPRESSION BY PARALLEL ADMINISTRATION OF 18FDG AND 99MTC-MIBI

CORRELATION OF TC-99M 0D DMSA AND TC-99M MIBI WITH CALCITONIN GENE RELATED PEPTIDE (CGRP) AND CALCITONIN (CT} 1MMUNOHISTOCHEMISTRY IN |NVASIVE AND PREINVASIVE BREAST LESIONS

T. M-~rian (1), N. Szincsak (2), H. Nagy (3), L Galuska (4), K. Goda (3), K. B~lint (2), L. Balkay (1), L Tr6n (t), Z. Krasznai (3). (1) PET Center; (2) Department of Dermotology; (3) Department of Biophysics and Cell Biology; (4) Center of Nuclear Medicine, University of Debrecen, Hungary To detect the presence of Pgp in the tumours of patients several assays have been worked out on the mRNA or Pgp protein level. However, these methods do not provide information about the dynamic function of the Pgp drug efflux pump. It was reported recently that ~mTc-hexakis-2-methoxybuthyl isonitrile (MIBI) uptake is drastically reduced in cancer cells that expresses the multidrug resistance (MDR) product, Pgp 170 kDa (Pgp), suggesting that '}~TcMIBI is a transport substrate for this transmembrane glycoprotein. The success of turnout imaging with PET and 2-deoxy-2-fluoro ISF]-D-glucose (ISFDG) is based on preferential • . tumours. The 15 FDG uptake s metabol -c rate dependen, In our accumulatton of s FDG in recent study, we explored if the Pgp substratc modulator verapamil modifies ISFDG and/or WmTc-MIBI accumulation in turnout tissues similarly to that of measured in vitro in cell culture, enable us better in vivo visualization of turnouts and provide non invasive method for the prediction of overexpression of the drug effiux pump P-glycoprotein. Methods: In a SCID BC-17 mice model, the drug-sensitive KB-3-1 human epidermoid carcinoma tumour and the KB-VI Pgp expressing human carcinoma tumour were grown in opposite flanks. In vivo visualization of multidrug resistance was done in a pinhole collimator equipped gamma camera. For validation, in vitro and biodistribution studies with 9°mTc-MIBI and JSFDG were carried out using gamma counter. The expression of the MDR product was proved by immunohistochemistry. Results: ~=Tc-MIBI uptake was significantly lower in KB-VI Pgp expressing human carcinoma tumours compared to the KB-3-1 human carcinoma turnouts MDR+/MDR= 0.61_+0.13, while the ISFDG uptake was 1.38_+0.06 times higher in the MDR+ turnouts (n--4). When the animals were preincubated |br 30 min with ",erapamil (0.1 mig~sg) the ~ T c MIBI ratio of the MDR+/MDR- tumours decreased to 0.38:f:0.05 while SFDG uptake increased to 2.08+0.33. Conclusions: Since verapamil treatment increases the ISFDG uptake with simultaneous decrease of the 9'~Tc-MIBI accumulation of MDR+ tumours, the parallel application of the drugs and verapamil treatment seems to be a good candidate for a noninvasire marker to diagnose MDR related Pgp expression in tumours.

V. Papantoniou (1), L Nakopoulou (2), J. Christodoulidou (3), E. Papadaki (1), V. Valotassiou (1), M. Souvatzoglou (1), A. Stipsaneli (1), A. Louvrou (4), A. Keramopoulos (4), S. Michalas (4), C. Zerva (1) (1) Department of Nuclear Medicine; (2) Department of Pathology University of Athens ; (3) Department Radiology; (4) Department of Obst. and Gyn. Alexandra Hospital University of Athens, Greece The purpose of this study was to derermine immunohistochemically the presence or absence of CGRP and Ct in invasive and prelnvassive breast lesions and further to investigate their correlation with tumour Tc-99m (V) DMSA and Tc-99m MIBI uptake by scintimammography. Material and Methods: 29 patients with histologically proven breast cancers have been submired to Tc-99m (V) DMSA and Tc-99m MIBI scintimmamography in separate sessions before surgery, 10 and 60 min after administration of 25-30 mCi (740-925 MBq) of each tracer. Immunohistochemistry for CGRP and Ct was performed on the surgical specimens. (V) DMSA and MIBI T/B ratio and retension ratio (RR=T/B delayed-T/B early) were calculated and correlated (t-test) with CGRP and Ct expression in invasive ([.C.) and invasive carcinomas associated with preinvasive lesions as DCIS or epithelial hyperplasia (I.C. + DCIS or E.H.). Linear regression analysis was also performed between (V) DMSA and MIBI retention ratio and CGRP and Ct concentrations in the invasive and the preinvasive component of the tumors associated with. The presence or absence of microcalciflcations was studied in relation to CGRP and Ct expression. Results: Histology confirmed 15 I.C. and 14 l,C. associated with DCIS or E.H. 7/15 (46%) I.C. and 10/14 (71,4%) I.C.+DCIS or E.H. were CGRP positive. T-test showed statistically significant difference between CGRP concentration in I,C. and I,C.+DCIS or E.H. (I.C. = 12,3±7,8 , I.C.+DCIS or E.H = 20-J:I0 , p<0,05). Ct positivity was found only in 2 cases where CGPR was also increased. All CGRP positive I.C.+DCIS or E.H. were grade I or l[ and all CGRP negative were grade Ill. (V) DMSA retention ratio demonstrated positive correlation with CGRP in the preinvasive component (r=0,600, p<0,05) MIBI retention ratio did not show a positive correlation. CGRP and Ct positivity was not observed to be related to the presence or absence of microcalcifications. Conclusion: CGRP is more frequently found than Ct in breast cancer cells. Its cellular concentration seems to be enhanced in cancers with DCIS or epithelial hyperplasia this is associated with the tendency of (V) DMSA to concentrate in such lesions and indicates a possible functkmal relationship between the two substances. The presence of CGRP in low grade cancers may reflect its precocious role in the process of cancerous cellular deformation, in view of its known relationship with the blood flow rate in breast vessels and its participation in ncoangiogenesis.

PS_377

PS_379

TISSUE-SPECIFIC HSV THYMIDINE KINASE (HSVTK) GENE TRANSFER ON GANClCLOVIR UPTAKE AND PROLIFERATION IN MEDULLARY THYROID CARCINOMA

NON-INVASIVE IMAGING OF AD-VECTOR-TRANSFECTED OVARIAN XENOGRAFTS

S. Jiang (1), A. Altmann (1), S. Sieger (1), F. Sch6nsiegel (1), J. Kleinschmidt (2), U. Haberkorn (1). (1) Clinical Cooperation Unit Nuclear Medicine; (2) Applied Tumor Virology, Cancer Research Center, Heidelberg, Germany. The calcitonin (CT) gene is expressed in thyroidal C-cells and in neoplastic cells derived from them and could be used fur tissue specific expression of therapeutic genes. However, the regulatory elements of the CT gone are weak in rAAV-mediated transgene expression. Theretbre, we investigated the effects of viral vectors with enhancer amplification on the expression of the HSVtk gent in medullary thyroid carcinoma (MTC) cells. Methods: Three CT enhancer fragments and tissue-specific elements (ElsE2) were linked to the CT promoter upstream of the HSVtk gone (rAAV3xCTanhCTHSVtk). At 44 h after infection of HeLa cells and rMTC 6-23 cells (rat medullary thyroid c~cinoma) with this construct and a construct bearir~g a single CT enhancer element (rAAVCtenhHgVtk) the ceils were 3 pulsed with 3H-GCV for 6 h. Furthermore, a 3H-thymidine (H-TdR) incorporation assay was performed after treatment with 12.5 I.tM GCV for 2 h. The radioactivity in the acid-insoluble fraction of the cells was counted and normalized to the viable cell number. Results: The 3H-GCV uptake in rMTC 6-23 cells infected with rAAVCtenhHSVtk was 2.4fold higher than that in HeLa cells. After infection of rMTC 6-23 cells with rAAV3xCTenhCTHSVtk the 3H-GCV uptake increased up to 17-fold of that in HeLa cells, whereas no significant difference between both tissue specific constructs was observed in infected HeLa ceils. 3H-TdR incorporation in rMTC 6-23 cells infected with rAAV3xCTenhCTHSVtk decreased to 2% of ceils without infection whereas the ]H-TdR incorporation in cells infected with rAAVCtenhHSVtk decreased to 79,4% of the controls. Concluslont The multi-enhancer elements of caleitunin not only significantly enhance HSVtk gone expression but also maintain a high tissue-specificity as shown by their effects on ganciclovir and thymidine uptake. These tissue specific effects should be detectable in viva using the corresponding radiolabeled compounds.

1172

T.R. Chaudhuri (1), B.E. Rogers (2), J.M. Mountz (1), E.E. Partridge (3), K.R. Zinn (1). (1) Department of Radiology, Division of Nuclear Medicine; (2) Department of Radiation Oncology; (3) Department of Obstetrics and Gynecology, Gynecologic Oncology, University of Alabama at Birmingham, AL 35294, UK. Aim: The purpose of the present study was to develop a light-based non-invasive imaging method to assess ovarian tumor during therapy in live mice. Methods: Ovarian tumor cells SKOV3 were transfeetad with adenoviral vector encoded for GFP. GFP-positive SKOV3 cells were implanted intrapedtunealy (i.p.) in 4 groups of six athymic nude mice. The sensitivity of the light-based imaging approach was evaluated by introducing only Ixl 06 GFP-positive cells, and by conducting imaging early after implantation. In the first experiment, the images were collected at l hour after i.p. implantation and after 4 days. Second experiment was conducted to test if the effect of adriamycin therapy could be visualized by light-besed imaging in live animal. This included 2 groups of mice (6/group). The first group was injected i.p. with adriamycin (50 gg/mouse) at 24 h after the implantation of the GFP-positive SKOV3 cells. The second group received 0.5 ml of normal saline i.p. For imaging, the mice were maintained under Enfturane anesthesia. Images were collected at I hour, day 3 and 5 using a fluorescence stereo microscope. In both experiments GFP-positive ceils, tumor nodules and peritoneal wash were collected in sterile media for culture, viability tests and cell counts. Results: [n the first experiment, at 1 hr in viva images showed multiple regions of green fluorescence outlining the intestine in all mice. From 4 day images, i.p. tumors were detected extamally in all live mice by light-based imaging. This experiment averaged 3.4+0.5 tumors/mouse. The size of tumors ranged between 0.2-1.5 mm in diameter from 4mm depth. In the second ¢xperimen4 GFP-positivo SKOV3 cells were killed by adriamycin in viva and the green flaorascence was diminished with time. By using special filters, GFP and orange fluorescence of adriamycin were simultaneously imaged in the same field without interfering eachother, Day 2 imagas showed the tumor; color tu be orange-green. In addition, a region in the same abdominal field was orange. The orange color was due to uptake of adriamycin. It was obvious that in the adriamycin-treated mouse the green fluorescence was greatly decreased, while the tumor region in the control mouse still retained the original brilliant green fluorescence. Day 4 images showed complete disappearance of green fluorescence and appearance of bright orange fluorescence. Cell viability test showed that adriamycin treatment

• resulted in significantly fewer GFP-positive cells on days 2, 4, and 5. On day 2, 2.2% GFPpositive viable tumor was measured from the adriamycin-treated mice. On day 4, only 0.03% GFP-positive viable tumor cells was measured. In vivo imaging on day 5 showed no GFPpositive region and viable tumor cells were not detected. Conclusions: The present study demonstrated that light-based imaging is a highly sensltive in vivo tool for the early detection and monitoring of human ovarian tumors in mice models. This provides valuable information for evaluation of anti cancer therapy. This would be of great diagnostic utility to gynecologists, especially in detecting primary and recurrent i.p. tumors at an early stage.

DIAGNOSTIC ONCOLOGY 9

PS_381 IODIDE UPTAKE IN CARCINOMA CELLS AFTER TRANSFER OF THE HUMAN THYROID PEROXlDASE GENE U. Haberkorn (1), A. Altmann (1), S. Jiang (1), I. Morr (1), M. Mahrnut (1), M. Eisenhut (2). (1) Clinical Cooperation Unit Nuclear Medicine; (2) Dept. of Nuclear Medicine, Cancer Research Center, Heidelberg, Germany. The human thyroperoxidase (hTPO) is critical for the accumulation of iodide in thyroid tissues. Poorly differentiated and anaplastic thyroid tumours which lack thyroid specific gene expression fall to accumulate iodide and, therefore, do not respond to 1311therapy. We, therefore, investigated, whether the transfer of the hTPO gene is sufficient to restore the iodide trapping capacity in undifferentiated thyroid and non-thyroid tumour cells. Methods: The human anaplastic thyroid carcinoma cell lines C643 and SW1736, the rat Morris bepetuma cell line MH3924A and the rat papillary thyroid carcinoma cell line L2 were used as in vitro model systems. Employing a bicistronic retroviral vector based on the myeloproliferative sarcoma virus for the transfer of the hTPO and the neomycin resistance gene the C643 cells and 5WI736 cells were transfeated while the L2 cells and MH3924A cells were infected with retroviral particles. Seven recombinant C643 and seven SW1736 cell lines as well as tour recombinant L2 and four MH3924A cell lines were established by neomycin selection. They were studied for hTPO expression using an antibody based luminescence kit followed by the determination of the enzyme activity in the guaiacol assay and of the iodide uptake capacity in presence of Nal"Sl. Results: Genetically modified cell lines expressed up to 1800 times more thyroperoxidase as compared to wild type turnout cells. The level of hTPO expression varied significantly between individual neomycin resistant cell lines suggesting that the recombinant retroviral DNA was integrated at different sites of the cellular genome. The accumulation of iodide, however, was not significantly enhanced in individual recombinant cell lines irrespective of low or high hTPO expression. Moreover, there was no correlation between hTPO expression and enzyme activity in individual cell lines. Conclusion: The transduction of the hTPO gene per se is not sufficient to restore iodide trapping in non-iodide concentrating turnout cells. Future studies have to concentrate on the possible expression of enzyma~ica]ly active proteins or the transtk'r of multiple genes involved in iodide trapping.

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PS_380

PS_382

CORRELATION BETWEEN IN VIVO AND IN VITRO DETECTION OF PROGRAMMED CELL DEATH IN AN INTRACARDIAC TUMOR

RADIOIODINATED BMIPP AS MPOSARCOMA IMAGING AGENT IN TUMOR SEARING NUDE MICE

RW.L. Thimister (1), L. Hofstra (2), E. Dumont (4), H. Boersma (1), A. DeBruine (3), TH. Elenbaas (2), G. Kernerink (2), C. Reutelingsperger (4), G. Heidendal (1). (1) Department of Nuclear Medicine, University Hospital Maastricht, The Netherlands; (2) Department of Cardiology, University Hospital Maastricht, The Netherlands; (3) Department of Pathology, University Hospital Maastricht, The Netherlands; (4) Department of Biochemistry, Cardiovascular Research Institute, University of Maastricht, The Nethertands

T.S. lee, Y.S. Suh, K.S. Woo, W.S. Chung, S.J. Lira, S.J. lee, C.W. Choi, S.M. Lim. Cyclotron Application Lab., Korea Cancer Center Hospital, Seout, Korea.

Aim: In vivo detection of cell death may aid the diagnosis and therapy selection in localized malignant tumours. Because high proliferation and apoptotic indices have been reported in rapid growing malignant tumours, information about the extent of cell death in the tumour may give insight into the biology of the process. This report describes the case of a 65 year old male patient with a large intra-cardiae tumour in which cell death was monitored both in vivo (by using 99mTc-Annexin V) and in vitro (immuno-histochemical analysis and post mortem investigation). Methods: The tumour was loc_alized by echocardiography. One day prior to surgery, approx. 800gg of Annexin V, (Apomate, Theseus Imaging Cambridge, MA, U.S.A.) labelled with 744 MBq of 99mTc was given intravenously. In order to correctly localize the heart, 201 TI was injected 4 hours after the injection of Annexin V. Single photon emission computerized tomography (SPECT) was performed 10 hours after the injection of Annexin V, using a dual emission protocol. After removal of the tumour, immuno-histucbemlcal analysis was performed for the detection ofAnnexin V and characterization of the tumour. Results: A large area of 99mTc-Annexin V uptake was seen, localized within the lel~ ventricle cavity as observed with Thallium perfusion scintigrapby, lmmuno-histocbemical analysis of the tumour showed a high-grade sarcoma, containing a high frequency of apoptutic cells as evidenced by the presence of active Caspase 3, correlating well with the scintigraphic results. Post mortem analysis showed a large tumour mass, which almost occluded the left ventricle. Conclusion: These data demonstrate the feasibility of the 99mTc-Annexin V imaging protocol to obtain non invasively information of cell death in malignant (cardiac) tumours, and the excellent correlation between in vivo and in vitro detection. This could be of importance for the evaluation of malignant tumours, especially in diagnosis and selection of the most appropriate therapy.

Objectives t231 labeled fatty acids are used for evaluation of the extent of regional myocardial metabolism. This study was aimed to evaluate the possibility of radioiodinated BMIPP as liposarcoma imaging agent. We compare m vitro uptake between liposarcoma(HTB-92) and giioma(9L) ceil 1inns and examine biodistribotion and in vivo images of 1231-BMIPP in liposarcoma bearing nude mice. Methods Glioma and liposarcoma cells were harvested and counted with counter af~er incubation of 5, 10, 15, 30, 60, 120, 180 rains with medium containing 1231-B/',AlPP.The difference of biodistribution was determined between non-feeding(water only) group for 18 hr and feeding group in normal mice(n=3 / group) at 0.5, 2, 24 hr. For liposareoma bearing nude mice model liposarcoma HTB-92, cell lines injected S.C. into left thigh of nuda mice. The biodistribution of 123I-BM[PPwasevaluatedat 0.5, 2, 24 hr (n=5 / group)and in vivo imageof ["~3IBMIPP was obtained with _ camera at 2, 24 hr in liposareoma bearing nude mice. Results HTB-92 cell line showed increased uptake than 9L with 1.5 times at 180rains. The uptake of 123I-BMIPP in liver, heart, muscle and fat tissues was higher in non-feeding group than in feeding group, especially at delayed time( 24 hr ) in the biodistribution of normal mice. In liposaraoma bearing nude mice, T(tumor)/B(blood) ratio of t231-BMIPP was 0.94, 0.75, 1.38 and T(tumor)/ M(muscle) ratio was 0.66, 1.53, 1.11 at 0.5, 2, 24br, respectively. mI-BMIPP was selectively localized in liposarcoma at 2, 24 hr image. Conclusions The ratio of tumor to background was the highest at 24 hr in biodistribution studies. The localization of t231-BMIPP was clearly defined in tumor in ]iposaraoma bearing nude mice at 24hr. m[-BMIPP may be used for the diagnosis of liposarcoma.

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• DIAGNOSTIC ONCOLOGY 9

PS_383

PS_385

DIFFERENTIAL ROLES OF OSTEOTROPIC TC-BISPHOSPHONATES ('rC-BP) AND TC(V)-DMS IN BIOLOGICAL AND PATHOLOGICAL ANIMAL MODELS AND BONE CELL CULTURE

BONE MARROW SCINTIGRAPHY USING TC-99M MONOCLONAL ANTIGRANULOCYTE ANTIBODIES IN DETECTING BONE METASTASES FROM BREAST CANCER

K. Horiuchi-Suzuki (1), S. Fukuda (2), A. Konno (1), Y. Fukuda (1), H. Kobayashi (3), H. Saji (1). (1) Pathofunctional Bioanalysis, Kyoto University, Kyoto, Japan; (2) International Space Radiation Lab., National Institute of Radiological Sciences, Anagawa, Chiba, Japan; (3) Diagnostic and Interventional Imagiology, Kyoto University, Kyoto, Japan.

J. O. Prior (1), G. Storto (1), G. Barghouth (1), A. Boubaker (1), J.-F. Delaloye (2), S. Leyvraz (3), A. Bischof Delaloye (1). (1) Department of Nuclear Medicine; (2) Department of Gynecology; (3) CePO Oncology Center, CHUV University Hospital, Lausanne, Lausanne, Switzerland.

During past decades, bone scintigraphy has been the most sensitive imaging method for detecting skeletal metastases but low specificity in suspected malignancy has decreased its ontological use. Bone scintigraphy has relied on Tc-BP agents with great affinity for the mineral phase, the hydroxyapatite. On the other hand, the pentavalent technetium complex of dimereaptosoccinic acid, Tc(V)-DMS, has been known for its usteotropic character in pathological bone (osteosarcomas, bone metastasis, Paget"s disease) and in non-mature bone (children, rodents) but absent in normal adult bone. Aims: Studies on the osteotropic affinity of TcBP and Tc(V)-DMS in various biological (aging) and pathological (OVX, low phosphate diet) animal models and in bone cellular system. Methods: As Tc-BP agent, Tc-MDP and TcHMDP kits, and Te(V)-DMS are used. Mice of different ages (5, 7, 9, II, 23 wk), ovariectomized (OVX) rats and hypophosphatamic mice (low Pi diet, 5 d) (HypoP) are comparatively screened. Moreover, in bone cellular studies, osteoblastic (OB) cells isolated from neonatal mouse calvaria by enzymatic digestion and cultured at 371~C (6-8 d) until cunfluency and osteoclastic (OC) cells harvested by co-culture of OB cells with mice (6 wk) bone marrow and isolated by Pereoll fractionation were used. The differential OB and OC cells uptake of Tc-agents carried out at 37fic using HEPES buffer at pH 7.4, at various incubation time. Results: Aging induced great decrease in mice bone accumulation of both Tc-agents but reduction was more dominant with Tc(V)-DMS. Only this agent showed an increased bone accumulation in OVX and HypoP groups, both pathological models of increased OC activity. Moreover, in cellular studies, differential OC accumulation of Tc(V)-DMS were clearly detected, differing 40 to 50 times over the OB cells; OB cells showed preferential uptake of Tc-BP agents. Conclusion: The osteotropic character of Tc(V)-DMS associated with pathological bone status of animal models with accelerated OC activity. Moreover, in cellular studies. accumulation of Tc(V)-DMS by OC rather than OB cells was clearly detected . Meanwhile, since in clinical studies, Tc-BPs are rather associated with OB cells activity (osteoblastic type metastases), consequences of this differential character of Tc(V)-DMS from Tc-BP in clinical diagnosis will be discussed.

Purpose: To prospectively evaluate bone marrow scintigraphy (BMS) in detecting bone metastases from breast cancer when performed as a complement to conventional bone scan (BS). Methods: We studied 60 women aged from 37-84 years (mean+-std:58-+9.6y) with breast cancer (stage 1:25, 11:27, 111:5,IV:4) who underwent conventional Tc-99m-DPD bone scan with a Tc-99m bone marrow scan, 1-35 days (9+7d) later. Anterior and posterior whole-body scans were performed on a dual-head gamma camera (Bind, Trionix, USA). Patients had neither chemotherapy nor radiotherapy in the 6 months preceding imaging. Bone marrow scan was performed 4-6 hours altar a 0.5-ling L~ injection of BW250/183 antigranulocyte antibodies directed against the non-specific cross reacting antigen NCA-~t5 ]abeled with 370MBq/70kg. Metastases on BMS were defined as photopenic lesions concordant to BS lesions or isolated focal lesions in the axial skeleton. Two-experlenced nuclear medicine physicians interpreted BS and BMS images and classified observed defects as indicative of benign or metastatic disease. Extension of bone marrow in long bones was also assessed. Results were compared to a gold standard composed of subsequent CT, MRI, X-rays, BS examinations and/or at least a 6month follow-up. Results: Metastases were present in 9 out of 60 patients (15%). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for BS and BS+BMS on a per patient basis (Table) and are statistically different (p<0.01), except for NPV. Bone marrow extension in long bones was observed in 57 patients (95%). Scintigraphy True True False False 5ensi(n=60) Negative Positive Negative Positive tivi~

Specifici~'

PPV

NPV

Accuracy

BS

36

7

I

16

88%

69%

30%

97%

72%

BS+BMS

44

8

0

8

100%

85%

50°/,

100% 87%

Conclusion: BMS supplements BS by improving sensitivity, specificity, positive predictive value and accuracy in detecting breast cancer bone metastases. BMS may thus be useful in patients with positive or equivocal BS tot metastases. Like BS, this method is limited by its inability to show micro-metastases and by its modified distribution after radiotherapy and/or chemotherapy thus possibly masking bone metastatic disease.

PS_384

PS_386

A SIMPLIFIED PROCEDURE FOR CONTINUOUS INTRAOPERATIVE

PROGNOSTIC VALUE OF FLOW C~tTOMETRIC DNA MEASUREMENTS IN INDIAN PATIENTS WITH THYROID CANCER

EXTERNAL MONITORING OF SYSTEMIC LEAKAGE. DURING ISOLATED LIMB PERFUSION CANCER THERAPY D. Casara (1), D. Rubello (1), P.L Pilati (2), R. Scalerta (2), C.R. Rossi (2). (1) Servizio di Medicina Nucleare 2, Azienda Ospedaliera di Padova, Padova, Italy; (2) Clinica Chirurgica 2, Universita di Padova, Padova, Italy. Regional isolated perfusion using high doses of chemotherapy has been proposed in patients with Ioco-regional cancer. A critical step for isolated limb perfusion (ILP) is the accurate monitoring of systemic leakage with the aim of avoiding chemotherapy toxic effects. In the present study we reported our experience in monitoring systemic leakage during ILP in a group of 113 patients affected by a limb cancer: 54 melanoma, 44 sarcoma, 3 squamous cell carcinoma, 1 lympboma. The majority of patients were treated during ILP with thermotherapy / chemotherapy alone or in combination with tumour necrosis factor (TNF). Regarding ILP technique, cennulas were placed in either external lilac / axillary artery and vein and connected with an extra-corporeal circuit. We used 99roTe-human serum albumin (99mTc-HSA) with 3 different techniques in monitoring the perfusete leak during ILP: the target was to limit the systemic leakage within 10./o of the total dose infused in the isolated circuit. Initially, we used the traditional procedure based on radioactivity measurement by means of gamma countar of systemic blood samples drawn from a peripheral vein every 5 rain, end compared with samples obtained from the isolated circuit. The second procedure used was based on the measurement of radioactivity counts of the 99mTc-HSA dose before infusion in the isolated circuit, and on the continuos monitoring of systamie radioactivity leakage through an external detaetor positioned over the hearth. The last procedure we have developed and we currently use, consists of following steps: 1) the 99mTc-HSA dose to be infused during 1LP is calculated as 0.5 MBq/kg/b.w.; 2) 72 hours before ILP, a simulation test is obtained injecting the patient with a 99mTc-HSA dose eorrnsponding to 10°,6 of total dose; 3) during the simulation test, radioactivity counts are continuously registered by means ofen external hand-held probe positioned over the hearth, and mean counts are calculated during a 30 rain time-interval. One of the major advantage of the simulation test is that it allows to depict the precordial area with the highest count-rate activity. This area is marked on patient skin and, the day of ILP, it allows to locate the probe in the same position of simulation test. Another advantage of this procedure is that physicians can know before the infusion therapy, the acceptance limit of systemic count-rate activity. In our experience, this procedure seems to be simple end accurate enough in monitoring systemic leakage during ILP.

1174

G.V. Punjabi (1), A. Kumar (1), A..K. Karak (2), S. Das (3), C.S. Bal (1). (1) Department of Nuclear Medicine; (2) Department of Pathology; (3) Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India. Aim: It is an well-accepted feature of carcinomas that they have a higher mitotic rate than normal, and they have an increased incidence of karyotypic abnormalities. The available data suggests that the nuclear DNA content of neoplasms reflect their biological behavior and diploid tumors in particular carry a better prognosis. However, no study has been carried out in Indian patients to evaluate ploidy as a prognostic factor in thyroid carcinoma. Methods: Cellular DNA content was measured using flow cytometfic method to analyze paraffin embedded tissue blocks from 74 patients with thyroid cancer. Mean age of the patients was 35.93+13.97 years (range 8-66 years). There were 32 males and 42 females (M: F 1:1.3). There were 18 (24.3) eases of follicular, 46 (62.2%) cases of papillary, 5 (6.75%) cases of medullary, 2 (2.7%) cases of Hurthle cell end 3 (4.0*,6) eases of Undifferentiated carcinoma thyroid. Results: DNA histograms were classified as diploid in 31 cases (41.9%) and aneuploid in 43 eases (58.1%). DNA aneuploidy was found in 9 (50%) of 18 follicular, 26 (56%) of 46 papillary, 4 (80*/*) of 5 medullary, 1 (50%) of hurthle cell and 3 (100%) of 3 undifferentiated carcinomas. Among patients with tumor recurrence, 14 out of 18 had aneuploidy. Local/distant metastases were seen in 42 cases (56.75%) (20 males end 22 females) with mean age of 36.23+t5.13 years. Thil'g¢ (71.4%) of these cases had eneuploidy. On univariata analysis, eneuploidy (p=0.03), male sex (p--O.01), and presence of local invasion (p=0.007) end metastasis (,o---0.007) at the time of diagnosis were significant predictors of a shortened disease free survival. However, it was not significantly related to tumor histology, patient age or tumor size. On multivariate analysis, only local invasion (RR - 4.80) end male sex (RR - 4.59) were found to be significant predictors of a shortened disease free survival. Conclusions: DNA eneuploidy is common in thyroid cancers in Indian population. It is associated with aggressiveness of the tumor, with the presence o f metsstasis, tumor recurrence and a shortened disease free st.trvival.

• DIAGNOSTIC O N C O L O G Y 9 PS_387

PS_389

ENHANCED EXPRESSION OF HSV THYMIDINE KINASE AND HUMAN SODIUM IODIDE SYMPORTER AFTER CHEMO- GENE THERAPY WITH GEMCITABINE AND ADENO ASSOCIATED VIRUS (AAV) VECTORS

SYNTHESIS AND FIRST IN VIVO EVALUATION OF [I-123]AZA-RGD1" A RADIOLABLED RGD-MIMETIC FOR THE NONINVASIVE DETERMINATION OF ALPHA(V)BETA3 INTEGRIN EXPRESSION

S. Jiang (1), A. Altmann (1), J. Kleinschmidt (2), U. Haberkorn (1). (1) Clinical Cooperation Unit Nuclear Medicine; (2) Applied Tumor

Virology Cancer ResearchCenter, Heidelberg,Germany. Induction of stress e.g. by co-infection with helper virus or by treatment with genotoxic agents results in induction of expreasion of AAV genes responsible for viral replication. Since the chemotherapeutic drug gemcitabine leads to DNA chain termination these reactions are expected after treatment with gemcitabine and may result in enhancement of suicide gone expression for gone therapy. Methods: Infection experiments were done in different cell lines (HeLa, MTC, MH3924A, NIH3T3) with and without pretreatment with increasing doses of gemcitabine using vectors bearing the genes tbr the enhanced green fluorescence protein (EGFP), the sodium iodide symporter (hNIS) or the HSV thymidine kinase (HSVtk). EGFP activity was determined using fluorescence microscopy and quantified with fluoroscan and FACS analysis. The hNIS gone expression was evaluated by iodide uptake. HSVr.k activit~¢ was determined by the uptake of 3H-ganciclovir or by growth inhibition and inhibition of H-TdR uptake after treatment with gancivlovir. Results: Gemcitabine treatment resulted in a dose-dependent enhancement (up to 21-told) of transgene expression as measured by all transferred genes• The expression after gemcitabine treatment was equivalent to that obtained after helper virus infection. Labeling of rAAV particles with Cy3 showed no difference between treated and untreated cells in their kinetics of internalization and transport to the nucleus. Furthermore evidence was tbund that rAAV integration to cell genome is elevated by gemcitabine. Gemcitabine treatment enhances AAV-mediated transgene expression, which may be measured in vitro using EGFP or in vivo with the HSVtk or the hNIS gone as in vivo reporter genes. C o n c l u s i o n :

R. Haubner (1), G. Sulyok (2), W. Weber (1), W. Linke (1), C. Bodenstein (1), H.J. Wester (1), H. Kessler (2), M. Schwaiger (1). (1) Department of Nuclear Medicine, Technische Universit~t M0nchen, Munich, Germany; (2) Institute of Organic Chemistry and Biochemistry, Technische Universit~.t M0nchen,Garching,Germany. The v _ 3 integrin plays an important role in turnout metastasis and turnour-induced angiogenesis. Recently, we demonstrated that RGD-containing peptides can be used for selective determination of v 3 expression" using' SPECT and PET. Here we describe the synthesisL~3and,biological evaluati°n of 5-{N'-(3-guanidinobenzoyl)-hydrazino]-3-(4-hydroxy-3-[" l]lodo)5-oxopentanoic acid ([=231]Aza-RGD-I) the first radioiodinated RGD-mimetic and compare the in vivo characteristics with the previously described glycopeptide [1251]cyclo(RGDyK(SAAI )-) ([t251]Gluco-RGD). Methods: Synthesis of the RGD-mimetic was performed by coupling of different building blocks using solid phase synthesis. Treatment of 3-methoxybenzaldehyde with ethyl acetoacelate and subsequent hydrolysis resulted in the glutaric acid derivative, which was coupled with protected hydrazine, and 3-aminobenzoic acid on the solid support. At~er guanylation and cleavage from the resin the methyletber moiety was cleaved using borontribromide. Labelling oftbe precursor was carried out using the lodoGen TM method. Melanoma M21-bearing nude mice were used for the in vivo studies• Planar -camera images were obtained 2h aider simultaneously injecting 7.40MBq [I-~31]Aza-RGD-/ and 1.85MBq [1251]Gluco-RGD. Imaging time was 10min. Subsequently, animals were sacrificed and biodistribution studies were carried out. Results: Biodistribution 3h afier simultaneous tracer injection showed an approximately 1.61bid higher uptake of [ 15 " I]GIuco-RGD (0.96±0.22%ID/g) in the tumour than of [ 13 2 I]AzaRGD- 1 (0.60~0.19%[D/g). Activity concentration in blood and muscle was 0.05+0.01%lD/g and 0.13+0.05%lD/g Ior [I:51]Gluco-RGD and 0,08-L'O.O2%ID/g and 0.12i-O.04%lD/g Ibr [1231]Aza-RGD-I, respectively. This results in lower tumour/blood (7.4 vs 19•2) and turnout/muscle (5.0 vs 7.4) ratios for [1231]Aza-RGD-I. However, distribution of [t:31]AzaRGD-I in most of the other organs was lower compared to [l'~S!]Gluco-RGD (e.g. kidney: 0.28+0.09%lD/g vs 0.89~'0.31%lD/g; liver: 0,23+0.09%[D/g vs 0.38±0.09%lD/g; lung: 0.17±0.04%lD/g vs 0 32±0.02%1D/~; skin: 0.31+0.08%lD/g vs 0.89+0,14%tD/g). This led to improved tumour/organ rabos tot [ I]Aza-RGD-I (e.g. kidney: 2.1 vs I.I; hver 2.6 vs 2.5; lung: 3.5 vs 3.0; skin: 1.9 vs I. 1). Aetivity concentration in the intestine and thyroid was comparable tbr both tracer. Planar _ -camera images using [I:ll}Aza-RGD*I confirmed the biodistribution data and showed a clearly contrasting turnout. Higher activity concentrations were Ibund in intestine and thyroid only• Conclusmns Compared o { I]Gluco-RGD accumulation of [Iz31]Aza-RGD-I in the v 3 expressing turnout is somev, hat lower. However. the small non-peptide tracer [I'~3I]Aza-RGDI showed further improved elimination kinetics compared with the glycopeptide and is a promising tracer tor the noninvasive determination of _ v 3 expression using SPECT. H Moreover, this readily available precursor also allows labelling with C-carbon and introduction of I~F-Iluorine. •

PS_388

.

.

.3

•

•

co

, u

e-

SIGMA RECEPTOR SClNTIGRAPHY WITH N-[2-(I'-PIPERIDINYL) ETHYL]-3-[1231]IODO-4-METHOXYBENZAMIDE, P[1231]MBA, IN PATIENTS WITH SUSPECTED PRIMARY BREAST CANCER

g~ ¢X

V. Caveliers (1), H. Everaert (1), C.S. John (2), A. Bossuyt (1). (1) Department of Nuclear Medicine, Free University Hospital, Brussels, Belgium; (2) Department of Radiology, George Washington University, Washington DC, USA.

O IX

Aim. To visualise in vivo accumulation o f a radioiodinated benzamide, P[=231]MBA, in primary breast cancer patients. Uptake of benzamides in breast cancer is based on a preferential

binding to sigma receptors that are overexpressed on the turnout cell membrane. The expression and density of sigma receptor sites has been shown to correlate with tumour proliferation. Methods. Ten patients with a newly diagnosed breast mass and two control patients were included in the study. Radiosynthesis of P[~2JI]MBA w ~ achieved by iododestsnnylation of its trimethyltin derivative using chioramine-T as oxidising agent:. Approximately two hours alter administration of 148-185 MBq P[tz31]MBA, whole body and lateral images of both breasts were obtained. Images were interpreted visually and quantified by ROI analysis. Final diagnosis of breast cancer was made based upon histological examination. Results. All of the patients were ultimately diagnosed with breast cancer. An increased focal tracer uptake within the suspected breast was demonstrated in eight out of ten patients. One patient presented a lesion in the contralateral breast that could not be confirmed as malignant. ROI analysis showed a mean turnout-to-background ratio of 2.04. The two control patients with benign breast conditions presented a normal scan. Conclusions. Uptake of P[~31]MBA was demonstrated in 80% of the patients with primary breast cancer, If a relationship between in vivo uptake and sigma receptor density can be established, P[I'~51]MBA scintigraphy may offer a powerhtt tool to non-invasively assess tumour proliferation.

1175

• DIAGNOSTIC ONCOLOGY 9 / DIAGNOSTIC ONCOLOGY 10 PS_390

DIAGNOSTIC ONCOLOGY 10

TENASCIN-C INHIBITS §1 INTEGRIN-DEPENDENT CELL ADHESION BY A DISIALOGANGLIOSIDE-MEDIATED SIGNALING MECHANISM

PS_392

P. Pesheva, R. Probstmeier, H.-J. Biersack. Department of Nuclear Medicine, University of Bonn, Bonn, Germany. A characteristic event following neoplastic transformation is often the upregulation of tenascin-C (TN-C) expression thus implying the modulatory role of this extraceflular matrix protein in oncogenesis, We have previously shown that TN-C inhibits §1 integrin-dependem cell adhesion to fibrenectin (FN) by its interaction with an RGD-independent cellular receptor. The aim of this study was to identify this TN-C receptor on tumor cells and to elucidate the molecular mechanism of inhibitory action induced by TN-C binding. Methods: Cell adhesion and protein kinase C assays using different tumor cell lines and activators, inhibitors or modulators. Results: We could demonstrate that the inhibitory effect of TN-C on §1 integrin-dependent cell adhesion on FN is mediated by the interaction of the protein with membrsne-associated disialogangliosides which interferes with protein kinase C-related signaling pathways. The tbllowing experimental data support these findings. (I) In substrate mixtures with FN, an RGD sequence-containing FN fragment or synthetic peptide, TN-C inhibited tumor cell adhesion by a disialoganglioside-dependent, sialidase-sensitive mechanism leading to an inhibition of protein kinase C. Similar to TN-C, immobilized antibody to GD2 (3F8) or sphingosine, a protein kinase C inhibitor, strongly inhibited RGD-dependent focal cell adhesion. (2) The interaction of intact or trypsinized, i.e. cell surface glycoprotein-free, cellswith immobilized TN-C was strongly inhibited by gangliosides or antibodies to gangliosides and TN-C. (3) A preincubation of immobilized TN-C with soluble disialogangliosides resulted in a delayed cell detachment as a function of time. (4) The degree of TN-C-induced inhibition of cell adhesion was proportional to the degree of disialoganglioside levels of expression by different tumor cells. Conclusions: In the present study, we describe a novel mechanism of inhibition of RGDdependent tumor cell adhesion to FN by TN-C which may play a crucial role in the molecular control of cell-matrix interactions during metastasis of highly malignant cells (i.e. neuroblastoma, glioblastoma, melanoma and breast carcinoma cells which express considerable amounts of disialogangliosides). Our findings thus provide a valuable tool towards the possible clinical application of radioactively labeled disialoganglioside-binding TN-C fragments to tumor diagnostics and therapy.

AUTORADIOGRAPHIC IN VIVO DISTRIBUTION OF 11 IIN-PENTETREOTIDE IN NEUROENDOCRINE GASTROENTEROPANCREATIC (GEP) TUMOURS AND COMPARISON WITH SCINTIGRAPHY Y. Petegnief (1), R. Lebtahi (2), C. Vissuzaine (2), J.P. Marmuse (2), I. Sobhani (2), M. Mignon (2), D. Le guludec (2). (1) Service de Medecine Nucl6aire H6pital TENON, Pads; (2) Service de Medecine Nucleaire H6pital Bichat, Paris. The in vivo distribution of I"[n-pentetreotide in neuroendocrine GEP tumours of patients scheduled for surgery was prospectively studied by autoradiography (AR) and compared to scintigraphic findings. Twenty patients (19 adults: mean age 52 + 7yr and I child) were i.v. injected with 135 + 30 MBq of mln-pentetreotide: I0 Zollinger Ellison syndrome (ZESh 5 carcinoids turnouts (CT), 5 nonfuncfioning neureendocrine turnouts (NET). Planar scintigrams (SRS) at 4 and 24 hr post injection and SPECT at 24 hr were obtained at the day before the surgery. Sections from 33 verified tumours (diameter: 1.8 to 50 ram, mean:17 ram) were analyzed by quantitaw, e AR 120-p.m thickness) and by immunohistochemistry (3-urn thickness). SRS tumour-to-background ratio (T/B), AR turnout uptake per unit mass of tumour (%lA/kg) were calculated, lntratumoral distribution of both activity and immunohistochemical expression of tumour markers of neuroendocrine differentiation were compared. SRS visualized 30/33 turnouts (91%) with variable T/B (2.2 + 1.5, range 1.05-10). SRS missed 3 turnouts with diameter of 3, 8. and 8 ram, and respectively uptake of 5, 2.4, 42 %IA/kg. AR confirmed a tumoral uptake in all 33 turnouts with high variations among patients (2.4 to 150 %lA/kg). Uptake was higher for ZES turnouts than lbr CT and NET (35.5 _+ t9.2 %lA/kg vs 12.1 + 5.8 %lA/kg. p<0.005). In 5 cases, intratumoral activity patterns were heterogeneous. This was not correlated with the immunohistochemical distribution of neuroendocrine markers. Uptake of l llln-pemetreotide was confirmed in 100% of G EP tumours studied by AR with highly variable uptake, significantly higher fur ZES tumours than CT or NET. lntra-tumoral heterogeneous distribution was sometimes lbund. SRS turnout-to-background findings did not directly reflect the density of somatostatin receptors. Autoradiographic results are more appropriate and confirm the potential of H IIn-pentetreotide tbr therapy specially for ZES tumours.

PS_391

PS_393

GLUT-1 IS OVER EXPRESSED IN HYPOXlC REGIONS OF HUMAN COLORECTAL LIVER METASTASES

1111N-DTPAOC SCINTIGRAPHY: PLANAR IMAGES VERSUS SPECT IN DIAGNOSIS OF CARClNOID TUMOR AND PANCREATIC NEUROENDOCRINE TUMORS

T. Akhurst (1), C. Heclvat (2), T. Kates (4), M. Mazumdar (3), I. Linkov (2), S. Mastorides (2), D. Klimstra (2), S.M. Larson (t), Y. Fong (4). (1) Department of Nuclear Medicine; (2) Department of Pathology; (3) Department of Biostatistics; (4) Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA Glutl, Glut3 and Hexokinase over-expression are all thought to play a role in FDG uptake into human colorectal cancers. The distribution of Glut-I expression in colorectal liver metastases has not yet been described, Objective: To investigate the distribution of Glut-I staining in colorectal cancer metastases to the liver. Methods: Histopathological samples from resected liver metastases of human colorectal cancer were obtained from sections of the tumor that looked grossly viable. Standard tissue fixation was then performed and immunohistochemical staining for Glut 1 transporter expression was performed using the streptavidin peroaidase technique. Blinded readings of the transporter expression were obtained in a four-point scale. 2 Data points were captured for each slide namely the degree of staining in perinecrotic areas (,.N") and the degree of stain in microscopically viable areas (.,V"). Results: From 24 patients, 69 specimens were available. The distribution of staining was as follows

Pert-necrotic N & scored 0 N & Scored I N & Scored2 N & Scored 3

Viable & Scored 0 V& Scored I

V& Scored 2

V& Scored 3

9 3 2 4

0 0 5 7

0

0 I I1 20

0 7

Due to the presence of clusters within ordinal data, a Mcnemar's test with correction for clustering was performed for the presence of any staining versus no staining (Chi-square of 8.555 with p=0.003). Conclusions: Glut-I staining in liver metastases is largely seen in pert-necrotic areas, and attempts at correlation with other markers of malignancy may be overwhelmed by this facL Correlations of HIF-I and Glut-I expression in colorectal cancer metastases remain to be investigated,

1176

J. Banzo (1), M.D. Abos (1), E. Prats (1), R Razola (1), E. Freile (2), S. Garoia (3), F. Gomollon (3), F. Garcia (1), T. Escalera. (1) Nuclear Medicine Department, University Hospital, Zamgoza, Spain; (2) Radiology Department, University Hospital, Zaragoza, Spain; (3) Gastroenterology Department, Miguel Servet Hospital, Zaragoza, Spain. Somatostatinreceptorscintigraphy(SRS) is the first line diagnostictool for stagingneurocndocrine tumors. Nevertheless.them is only slight informationaboutthe diagnostic influence of the SRS-SPECT. The aim o f our studv was to comparethe sensibility of planar scindgraphy and SPECT images in the detection of the primary tumors and metastasesin patients with carcinoid tumors(CT) or pancreaticneuroendocrinetumors(PNT),. Matherials and methods.- We have evaluated using SRS 33 patients, studied for disease staging (n=19) or for post-therapy follow-up (n=14). The patients evaluated for staging were 6 insulinomas, 4 bronchial cateinoids, 2 pancreatic CT, 2 gnstrinomas, 2 non-functioning PNT, 1 caminoid of unknown origin, 1 glucagonoma and I somastostatinoma. In the group of patients evaluated in post-therapy follow-up we included 4 bronchial CT, 3 ileal CT, 2 appendix CT, 1 ovarian CT, I thymic CT, lceeal CT, I stomach CT and 1 non-functioning PNT. Definitive diagnosis was performed by way of biopsy in all cases. We have compared planar images with SPECT study, 24 abdominal and 10 thoracic, obtained 24 h post nt In-DTPAOC injection (184 MBq) Results.- The sensibility of planar images in detection of primary tumors was 43,3% (9/19), whereas the sensitivity of SPECT study was 63,1% (12/19). Three primary tumors were demonstrated only with SPECT: 1 bronchial CT, I insulinoma and 1 glucagonoma. The sensitivity in the detection of metastases, hepatic and extrahepatic, was 77,7% (13/] 7) for planar images and 88,2% (I 5/17) for SPECT. ConclusiotT#,- In patients with neuroendocrine tumors, abdominal and/or thoracic SPECT increases the sensibility of planar images in the detection of primary tumor and their metastases. Therefore SPECT must be included in the SRS protocols.

• D I A G N O S T I C O N C O L O G Y 10

PS_394

PS_396

1111N-OCTREOTIDE BONE METASTASES DETECTION IN CARCINOID TUMORS AND PANCREATIC NEUROENDOCRINE TUMORS

IMAGING WITH TECHNETIUM-99M SESTAMIBI DOES NOT PREDICT DRUG RESISTANCE OR OUTCOME IN CHILDHOOD NEUROBLASTOMA

J. Banzo (1), M.D. Ab6s (1), E. Prats (1), P. Razola (1), S. Garcia (2), E Gomoll6n (2), F. Garcia (1), E. Freile (3), T. Escalera (1). (1) Department of Nuclear Medicine, University Hospital, Zaragoza, Spain; (2) Department of Gastroenterology, Miguel Servet Hospital, Zaragoza, Spain; (3) Department of Radiology, University Hospital, Zaragoza, Spain. There is slight information about the usefulness of somatostatin receptor scintigraphy (SRS) for bone metastases detection in neuroendocrine tumors. The aim o f the study was to retrospectively assess the usefulness of SRS in the detection of bone metastases in patients with careinoid tumor (CT) or neuroendocrine pancreatic tumor (NPT). Material and Methods. We included 48 patients whom we classified in two groups according to the request of the clinicians: Group A.- Staging of a known or a clinically or biochemlcally suspected CT or NPT(n=28): 13 CT, 6 insulinomas, 4 non-functioning NPT, 2 glucagonomas, 2 gastrinomas, 1 somatostatinoma, and Group B.- Follow-up studies (n=21): 20 CT and 1 glucagonoma. One patient was included in the two groups. In all patients the final diagnosis was established by way of biopsy. SRS images were obtained at 4 and 24 h post HtlnDTPAOC injection (184 MBq). Bone scans using ~mTc-MDP were performed when SRS demonstrated bone metastases or when the patient showed bone pain. Results. Five patients, 2 of group A and 3 of group B, showed bone metastases (prevalence: 10.41%) located generally in the axial skeleton. The bone metastases were multiple and symptomatic in 3 patients, multiple but asymptomatic in one patient and simple and asymptomatic in the other patient. Bone metastases were associated with liver metastases in all patients. Bone scan detected higher number of metastases than SRS. SRS false negative results corresponded with lesions located in ribs and dorsal-lumbar region, masked by lUln-DTPAOC physiologic activity in liver, spleen and kidneys. Conclusions. The SRS usefulness in the staging of CT and NPT is increased by its capacity in bone metastases detection. Nevertheless, SRS and bone scan must be considered as complementary techniques, and a normal SRS does not exclude performing a bone scintigraphy.

C. Van de Wiele (1), B. De Moerloose (2), G. Laureys (2), C. Dhooge (2), K. Swerts (3), Y. Benoit (2), J. Philipp? (3), R.A. Dierckx (1). (1) Department of Nuclear Medicine; (2) Departments of Pediatrics; (3) Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Gent, Belgium. A i m s : Tc-99m-sestamibi, a radiopharmaceutical used in tumor detection, has been shown to

be a transport subtrate reeogfused by P-gp and MRPI. Hence, imaging studies using Tc-99msestamibi became attractive to evaluate in vivo transport activities of P-gp or MRPI, and to predict drug resistance and therapeutic outcome. Methods : We evaluated Tc-99m-sestamibi imaging in children suffering from a neuroblastic tumor. These imaging results were compared with expression of P-gp and MRPI and with the clinical outcome. Twenty children (mean age : 39.5 months) with the diagnosis of neuroblastoma (14), ganglioneurobtastoma (t) and ganglioneuroma (5) were evaluated by Tc-99m-sestamibi imaging at presentation. Scintigraphy was performed 20-30 minutes and 3.5-4 hours after injection of 740 Mbq/l.73 m2 Tc-99m-sestamibi. P-gp expression and activity were determined flow cytometrically. An immunocytochemical APAAP assay was performed to evaluate P-gp and MRP1 expression. The median folfuw-up was 30.5 months. Results : Two patients were Tc-99-sestamibi positive. This correlated with the absence of Pgp in vitro but not with the clinical outcome of one of the patients who died from resistant disease. Sixteen others had no Tc-99m-sestamibi uptake in the tumor, which is suggestive for the presence of functional P-gp or MRPL This was confirmed in 13 of 15 patients tested in vitro. However, 12/16 Tc-99m-sestamibi negative patients are alive without evidence of disease. The others died from resistant disease but had other tumor characteristics associated with bad prognosis. In the remaining 2 patients, Tc-9qm-sestamibi scans could not be interpreted because of overlapping physiological tracer uptake. Conclusions : Tc-99m-sestamibi scanning in neuroblastoma is not useful in tumour detection or stagin. Absence of radionuclide uptake at the tumor site does reflect the presence of functional P-gp but does not contribute of clinical drug resistance in neuroblastoma patients and hence does not give practicle information concerning response to chemotherapy and outcome of the patients.

co

PS_395

PS_397

SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN THE FOLLOW-UP OF PATIENTS WITH BRONCHIAL CARCINOID

GLUCAGON-UKE PEPTIDE-1 (GLP-1) RECEPTOR TARGETING: A NEW DIAGNOSTIC OPTION? INITIAL EXPERIMENTAL RESULTS

(D t,O

S. Fanti (1), G. Savelli (2), A. Chiti (3), M. Salgarello (1), G.C. Montini (1), A. Fraternali (1), E. Del Giudice (1), C. Pettinato (1), E. Bombardieri (2), N. Monetti (1). (1) UO Medicina Nucleare, Policlinico S.Orsola-Malpighi, Bologna, italy; (2) Medicina Nucleare, Istituto Tumori, Milano, italy; (3) Medicina Nucleare, Istituto Clinico Humanitas, Milano, italy.

M. Gotthardt, I. Naeher, M. Fischer, J.-B. Holz, H. Jungclas, M. Beh~, K. Joseph, T.M. Behr. Department of Nuclear Medicine, PhilippsUniversity, Marburg, Germany.

[X

Somatostatin receptor scintigraphy (SRS) has been employed for the diagnosis of neuroeadocrine chest tumors, such as bronchial carcinoids (BC), and resulted to be a valuable tool for an accurate staging of BC. Aim: aim of this study was to evaluate the role of SRS in re-staging and follow-up of patients with BC. Methods: 25 patients (pts) with BC consecutively referred to the Nuclear Medicine Labs were reviewed (13 males 12 females). Overall, 36 SRS scans were obtained for patients re-staging and follow-up (28 scans in pts already treated with radical surgery and no evidence of secondat3, lesions; 6 scans in pts already operated on with known secondary lesions; 2 scans in surgically unopemble pts at follow-up). Pts were also studied with chest x-ray (28 scans), chest and/or abdominal CT (18 scans), chest MR (3 scans), liver sonography (6 scans). SRS was carried out at 4 and 24 hours after iv. administration of 250 MBq of 111ln*Pentetreotide; all cases were investigated with both total-body scan and SPECT. Results: out of 25 pts, secondary lesions were demonstrated in 14 and SRS was positive in 13 pts (19 scans). The remaining 11 pts had no evidence of disease, and SRS was negative in all of them (16 scans). Overall, in 16 pts SRS confirmed the information obtained by other diagnostic procedures (11 negatives and 5 positives with same number and site of lesions); in 7 pts SRS showed focal lesions not previously demonstrated; in 1 pt SRS showed less lesions as seen at CT (2 out of 4 hepatic lesions); in one patient SRS failed to show lung metastases suggested by CT and confirmed by pathology (metastatic diameter between 4 and 10 mm). Conclusions: our results indicate that SRS could be considered as the main follow-up procedure in pts with BC.

Aim: The problem of non-invasive detection of insulinomas is not appropriately solved by somatostatin receptor scimigraphy as its sensitivity is only about 50%. We investigated the biokinetics and specificity o f the uptake and degradation of the incretth hormone G]ucagonLike Peptide-I (glp-I) in a rat insulinoma cell line (RINm5F) in vitro and in vivo in order to demonstrata whether mdiolabeled glp-I may be suitable for visualization of insulinomas in vivo. Methods: The iodogen method was used for radioiodination of glp-1 (7-36)amide. The specificity of the 1-125-glp-l(7-36)amida uptake into RINm5F-ceUs was investigated as well as the lysosomal degradation. Degradation products of glp-I (7-36)amide in the cell medium were purified by HPLC, and their masses and amino acid sequences were subsequently determined by Cf-252-plasma-desorption mass spectrometry. The amount of mdiotracer incorporated into lysosomes was measured after differential centrifugation. Biodistribution studies were performed in a rat insuliooma model (NEDH rats and RlNm5P-cells) with 1-123-glp-l(736)amide and its more stable analog 1-123-exeadin 3. The same model was used for the scintigraphic visualization of insulinomas in vivo. Results: The uptake of radiotracer into insulinoma cells reaches a maximum after a few minutes and is inhibited by an excess of unlabeled peptide. Degradation products of the peptide are found in the cell medium after incubation; we were able to determine their mass and to derive their amino acid sequence. 1-125-glp-l(7-36)amide accumulates in the cells if lysosoreal degradation is inhibited. Radiolabeling of exendin 3 was more difficult than in the case of glp-1 because of the lack of tyrosin in its primary structure. The His moiety had to be used instead. Biodistribution studies showed rapid blood elearence and an uptake of the radiotracer into the tumor and the pancreas. We were also able to detect insulioomas in an animal model by external scintigraphy using radiolabeled glp-I (7-36)amide and exendin 3. Conclusion: Glp-1 (7-36)amide is specifically internalized into insulinoma cells by a receptormediated mechanism. Our results demonstrate that glp-l-receptor-directed scintigraphy may be a new method for the detection of thsulinomas in vivo. Due to the short half-life, its more stable analog exendin 3 may better suit this purpose in vivo. Labeling with radiometals is desirable in order to extend the methods clinical potential.

117"/

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n

• DIAGNOSTIC O N C O L O G Y 10

PS_398

PS_400

SOMATOSTATIN RECEPTORS SClNTIGRAPHY AND CHROMOGRANIN A(CGA) SERUM LEVELS IN NEUROENDOCRINE TUMOURS

INTRAINDIVIDUAL COMPARISON OF IN-111 LANREOTIDE AND IN-111 OCTR EOTIDE SClNTIGRAPHIES

M. Cimitan (1), E. Borsatti (1), A. Buonadonna (2), R. Cannizzaro (3), R. Ruffo (1), V. Canzonieri (4), L. De Apollonia (4), N. Dal Bo (3). (1) Department of Nuclear Medicine National Cancer Institute CRO Aviano Italy; (2) Department of Medical Oncology B; (3) Department of Gastroenterology; (4) Department of Pathology and Clinical Chemistry

V. Ivancevic (1), H. Gerl (2), H. Lochs (2), D.L. Munz (1). (1) Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University, Berlin, Germany; (2) Medical Clinic, University Hospital Charite, Humboldt University, Berlin, Germany.

A high density of somatostatin receptors has been fbund in many neuroendocrthe turnouts and the serum level of CgA has been recently validate as tumour marker in the clinical evaluation of the neureendocrine disease. In this work we report the results of somatestatin receptors scintigraphies and serum CgA levels of 47 patients with histological evidence of neuroendocrine tumours. Materials & Methods. We have evaluated 14 GEP carcinold turnouts, 12 GEP neureendocrine carcinomas, 9 extra-pulmonary small-cell carcinomas, 3 bronchial carcinoids, 3 Merkel-cell carcinomas, I medullary thyroid carcinoma, I pulmonary and I mediastinal neuroendocrine turnouts. Three others patients had histological diagnosis of metastatic disease from unknown neuroendoct'ine turnouts. In our series a total of 29 (62%) patients showed clinical evidence of distant metastases (stage IV). All patients underwent to somatostatin receptor scintigraphies 4 h and 24 h after i.v. injection of 185Mbq of ( 11 l)ln-pentetreotide (Octreoscan) with whole body and tomographic acquisition. The CgA assay (DAKO ELISA with normal value < 30 U/L) was carried out within a week. Results. Positive somatostatin receptors scintigraphies were found in 28 of the 47 (60%) patients examined and elevated serum CgA levels (ranged between 36 and > 450 U/L) were measured in 24 (51%). 20 (43 %) patients had both positive octreoscan scintigraphy and high CgA serum levels. However eight (26%) patients with positive octreotide scans had normal CgA serum levels (4 with GEP careinoid tumours, 2 with pancreatic neuroendocrine carcinomas, I with a bronchial carcinoid and I patient with Merkel-cell carcinoma). Among the 29 patients with distant metastases (stage IV) 21 (72%) had octreotide scan findings positive and 20 (69%) had high CgA levels. Discussion. In our series of. patients high serum levels of CgA often co-occurred with a positive octreotide scintigraphy (83% of cases). Therefore serum assay of the CgA in patients with neuroendocrine tumours may be used tbr planning the scintigraphic evaluation of somatostatin receptors.

Aim: At present In-I 11 octreotide is the standard tracer in somatostatin receptor scintigraphy of neuroendocrine turnouts. Promising results have been obtained with In-Ill lanreotide, another somatustatin receptor analogue which, due to its receptor afffnity profile, might also be valuable in non-neuroendeerine tumours, especially pancreatic cancer. We investigated the diagnostic performance of lanreotide and oclreotide in an intraindividual comparative study. Methods: In 16 patients (9 women. 7 men; age range, 31-82 years) somatostatin receptor scintigraphies with both ln-I I 1 octreotide (Mallinckrodt Medical, Petten, NL) and In-I 11 lanreotide (OEFZ Seibersdorf, A) were performed in planar spot and whole-body as well as SPECT techniques. There were 10 patients with verified gastrointestinal neuroendocrine turnouts, two without signs of relapse on follow-up, one palienl with an ectopic corticotropin producing turnout and one with an unknown primary. Another two patients presented with liver metastases of a pancreatic and renal ceil carcinoma, respectively. Results: Lanreotide and octreotide scintigraphies were true positive in 4/10 and 8/10 patients with verified neuroendocrine tumours, respectively. Vice versa, there were 6/10 and 2/10 false negatives, respecti','ely. There was only one patient with a true positive lanreotide but false negative octreotide scan. Both modalities were true negative in the two patients in follow-up of neuroendocrlne turnouts. Lanreotide and octreotide were false negative in the patient with ectopic corticotropin production which turned out to be located in the left lung and right adrenal gland, and in both patients with liver metastases. In the patient with unknown primary both methods were negative, and the primary remained unknown. With regard to comparative analysis, concordant scintigraphic results were obtained in 10/16 patients. Of these, 7 ~ere eoncordantly negative and 3 positive. In two of the 3 concordantly positive patients octreotide uptake in the lesions was much more intense than that of lanrentide. Conclusion: Lanreotide seintigraphy displayed a markedly higher rate of false negative findings than octreotide in patients with gastrointestinal neuroendocrine turnouts. In positive cases, lesion uptake of oetreotide was mostly higher than that of lanreotide. Both methods seemed not to be helpt~d in primarily non-ocurocndocrine turnouts. In spite of the small number of patients investigated, we conclude that lanreotide scintigraphy offers no advantage over octreotide in patients with gastrointestinal neuroendocrine turnouts.

PS_399

PS_401

CLINICAL ROLE AND ECONOMICAL ANALYSIS OF 111-IN-OCTREOTIDE IN GEP TUMORS

FUNCTIONAL IMAGING OF METASTATIC NEUROENDOCRINE TUMORS

R. Sciuto (1), S. Rea (1), A. Festa (1), A. Tofani (1), S. Bergomi (1), R Perri (2), C.L. Maini (1). (1) Dpt. of Nuclear Medicine, ; (2) Dpt. of Oncological Surgery, Rome, Italy.

C. Cheze - le rest, J. Bomanji. D.C. Costa, D. Visvikis, P.J. Ell. Institute of Nuclear Medicine, UCL, London, UK. Introduction: To optimize the prognosisand managementof neuroendocrinetumors, an efficient staging procedure is mandatory. For this puqoose, the best imaging strategy using either

The aim of the study was to clarify both the clinical and the economical role of reeeptorial scintigraphy with I I I-In-Octreotide (OCT) in the management of gastro..entero-pancreatic (GEP) tumors considering the elevated costs of the study. Methods: 150 scintigraphic studies were perfurmed in 135 patients with suspected or proved GEP tumors coming to our Institution with different research questions (primitive localization, staging, receptorial characterization). All the studies were performed with the followings methods: i,v. injection of 111-222 MBq I1 lln.-eetreotide (Octreoscan" Byk-Gulden, Milan -Italy) with imaging at 24 hrs and 48 his including whole-body, a minimum of two planars acquisitions of the thorax and abdomen and relative SPECT, Patients were followed 1 year al~er the scan to evaluate the clinical impact of the OCT studies on decision making and final outcome. CosrJbencfft analysis was employed considering the costs and the benefits related to all the performed scintigraphies. Costs analysis included both direct costs (radiotracer) and indirect costs (time and work costs); benefits were evaluated considering the costs of avoided octrentide therapy cycles. Results: Overall sensitivity for study was 80% and sensitivity for metastatic tumor sites was 90%. The clinical impact of the studies according to the research question resulted as follows: 40% in promoving early surgery of primitive tumor, 20% in modifying therapeutic strategy bocause of tumor staging change; 50% in selection for medical treatment with octreotide, 100% in identifying negative follow-up. Economical analysis identiffed the costs of the study (U =167,640) and the benefits (13 = 215.362) associated with the 150 studies with a cost/benefit ratio = 0.77. Conclusions: 11 l-ln-Octrentide scintigraphy is a reliable imaging technique in GEP tumors because is: - effective in the pro- and post-surgery staging; - useful in improving quality of life and survival; - economically sound as it has a favourable cost/benefit ratio.

1178

conventional radiology, functional imaging, or a combination of the two has not as yet been defined. Objective: To investigate the use of different imaging procedures for staging neuroeodocrine tumors, including the use of somatostatin receptor scintigraphy, MIBG scintigraphy and tSFDG PET imaging. Methods: We retrospectively compared all three investigations in patients with metastatic neuroendocrine tumors. Twenty patients (14 carcinoids, 6 paragangliomas) underwent all three studies within a period of one month. In the case of scintigraphy, planar images were acquired 1, 4, 24, and 48 hours following injection of ]tlln-DTPA-octrentide (mean activity of 150MBq)/1231-MIBG (2OOMBq). Whole body 2D PET scans were carried out between 45-60 minutes following injection of 370MBq of =SFDG. PET images were corrected for attenuation effects. Results: Somatostatin receptor scintigraphy was positive in 14/20 patients (56 lesions), MIBG was positive in 10/20 patients (80 lesions), while FDG PET was positive in 15/20 patients (145 lesions). All studies were negative in one patient, and all 3 studies were positive only in 2 patients (both of which were carcinoids). No single imaging procedure identified all metastatic sites. Conclusions: Our results demonstrate that the af~nity of neuroendocrinc tumors for octreetide, MIBG, and FDG is variable. Even a single tumor may have a different affinity for any of these, tracers. A complete staging should therefore include all 3 studies. The imagin,~ results may also be used to explain the partial response that can be achieved by using t31 MIBG, In octrentide, or Y DOTATOC for therapy.

• DIAGNOSTIC O N C O L O G Y 10

PS_402

PS_404

OPTIMIZED FUSION OF A B D O M I N A L MORPHOLOGIC AND FUNCTIONAL IMAGING WITH A SIMPLE TOOL

SKULL-BASE MENINGIOMAS: PROGNOSTIC VALUE OF 11 llNDTPA-OCTREOTIDFJ99MTC-DTPA INDEX |OCT/DTPA) IN LONG TERM FOLLOW UP AFTER GAMMA-KNIFE RADIOSURGERY

C. kaumann (1), G.J. Foerster (1), M. Enge(bach (2), K. Schunk (3), O. Nickel (1), 1:3.Bartenstein (1). (1) Department of Nuclear Medicine; (2) Department of Internal Medicine; (3) Department of Radiology, University of Mainz, Germany. Objectives: Because neuroendoerine tumors olden are very small exact correlation of somatostalin receptor binding abnormalities with the morphological correlate is important for the planning of the surgical intervention• Problems in image fusion of abdominal datasets result fi'om different positions of the patient and differences in investigation techniques. Aim of this study was to evaluate the quality of image fusion aRer standardization of patient position with a vacuum cushion. Methods: 5 hr p.i. of 110 MBq Hi in.Octreotide, 7 patients with metastases of a carcinoid tumor were fixed in a vacuum cushion (MED-TEC, Vac-Loc) and investigated with helicalCT in middle breath position (Siemens, Somatom Emotion)• Directly following the CT, a SPECT study (SPECTI) (Marconi, IRIX) of the abdominal region was performed without changing the position of the patients. 24 hr p.i. a second SPECT study (SPECT2) was done with the patients repositioned in their individually preformed vacuum cushion. A total of 8 markers suitable tot imaging with CT and SPECT were fixed on the cushion. Datasets of CT/SPECTI and CT/SPECT2 were fused by means of internal landmarks (e.g. metastases or margin of abdominal organs) or of the external markers using commercially available sot~ware (Image Volume Registration, Marconi). Results: Image fusion using external markers was fast and easy to handle compared to the use of internal landmarks (fusion time: 3-5 vs 10-15 rain). Using this technique, all lesions (n= 15) detectable by SPECT appeared exactly superpositioned on the respective CT morphology by visual inspection. Geometry of markers remained almost identically between both SPECT investigations. Image fusion o f CT/SPECTI and CT/SPECT2 showed a mean deviation of the external markers smaller than the voxelsize of 4 67 ram: 4.15mm (CT/ SFECTI; SD 0.71) and 4,65mm (CT/SPECT2; SD 1.93), respectively. Using internal landmarks the mean deviation of the chosen landmarks was 6,17mm (SD 1,71) and 7.71ram (SD 1,56). Image quality of CT and SPECT was not at'l~cted by the vacuum cushion• Conclusion: The use of the vacuum cushion results in a high quality of image fusion of SPECT to a CT in middle breath position regardless whether the patients were repositioned or not. Thus the proposed technique is able in a simple and cost effective way to generate abdominal datasets suitable tbr image lhslon. External markers positioned on the cushion allow/:or a rapid and robust overlay even if no internal landmarks are detectable. This technique is in principle also suitable for MRI/SPECT lhsion.

D. Grigolato (1), A. Nicolato (2), M. Zuffante (1), M. Cavaggioni (1), R Braggio (1), I.P. Pasquin (1), M. Gerosa (2), P.G. Giorgetti (1). (1) Departmentof Nuclear Medicine; (2) Department of NeurosurgeryUniversity, Verona, Italy. AIM: Our previous experiences showed that OCT/DTPA index is useful for differential diagnosis between skull-base turnouts (meningiomas versus other lesions), the decreasing of OCT/DTPA index after 7-knife radiosurgery (GKR) treatment revealed to be positive prognostic factor of a favourable outcome at short follow up, With this review we investigate the impact of OCT/DTPA index in long term follow up. METHODS: SPET is performed with multiple peak acquisition 4 hours after OCT and 2 hours after DTPA injection by means of a double-head gamma-camera IEIscint Helix; UHR collimators; 64 matrix; 10% window for 3 peaks; 60n steps of 60 see. each). The OCT/DTPA index was calculated combining the uptake ratio obtained from the somatostatin receptor scintigraphy and DTPA brain scintigraphy of the lesion]eootrolateral occipital skull on the same transverse slice for each isotope. All patients were evaluated with double tracer SPECT before and 6 months after GKR. with MRI and neurological evolution before treatment and after 6, and from 12 to 36 months after. RESULTS: We prospectively studied 10 patients (pts) with diagnosis of meningioma from December 1997 to February 2001.8/10 pts had an early neuroclinical improvement stable in time and a decreased OCT/DTPA index• Among them, only one pt experimented a RMI shrinkage above 50%, obtained at 21 months after GKR, four pts showed a decreased MRI volume below 50% (only one pt 7 months after GKR, the others after 18 months). Three pts had a stable disease on MRI imaging with a follow up of 18 months. 1/10 pt had no clinical changes despite of a reduction of OCT/DTPA index and a MRI shrinkage below 50%, reached 12 months after GKR. 1/10 pt was clinically asymptomatic also betbre radiosurgery treatment and had no change of OCT/DTPA index but MRI imaging revealed a decreased volume below 50%. CONCLUSION: In agreement with previous reports, the decreasing of OUT/DTPA index at~er GKR is predictive of a positive evolution, allowing better correlation with clinical and neurological improvement despite no or low evidence of lumber shrinkage obtained with RMI. Thus, tbr the high prognostic value, the OCT/DTPA index points out patients with meningioma with a flavourable outcome both at short and long Ibllow up atier GKR.

cO .m

PS_403

PS_405

NON-INVASIVE DUAL MODALITY IMAGING OF OVARIAN CANCER IN MICE

I N l l 1-OCTREOSCAN AND F18-DG PET IN NEUROENDOCRINE TUMORS (NETS) OF ABDOMINAL ORIGIN: WHICH ROLE FOR BOTH?

C

T.R. Chaudhuri (1), B.E. Rogers (2), K.R. Zinn (1). (1) Department of Radiology; (2) Deparment of Radiation Oncology; (3) Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

E Chierichetti (1), C. Pasquali (2), C. Sperti (2), P.L. Zanco (1), A. Fini (1), B. Saitta (1), M. Marcolin (1), S. Pedrazzoli (2). (1) U. O. Medicina Nucleare - Centro PET, Castelfranco Veneto, Italy; (2) Patologia Speciale Chirurgica, Universita di Padova, Padova, Italy.

O.

Aim: The purpose of the present study was to develop a non-invasive combined imaging method of gamma camera and fluorescence stereomicroseopy to assess ovarian tumor in nude mice. Gamma camera imaging offered high quantitative analysis and simultaneous fluorescence stereomieroscopic imaging offered high spatial resolution. Methods: Ovarian tumor cells SKOV3ip. t were implanted intraperitonealy in 2 groups of six athymic nude mice• ARer 15 days, a replication defective adenoviral vector (Ad-GFPhSSTR2) encoding the genes for both green fluorescence protein (GFP) and human type 2 • , . 6 • somatos aim receptor (hSSTR2) was injected mtrapentonealy (Ixl0 pfu) m one group of mice and 0.5 ml of saline in control group of mice. Two days after viral transfeetion, the mice were intravenously injected with Tc-99m-labeled somatoststin peptide (P2045, Diatide, lne)(23 MBq). The mice were imaged simultaneously (initial and 5 h) with an Anger gamma camera equipped with pinhole collimator for nuclear imaging and with a fluorescence stereomieroscope for GFP imaging, Following 5 h imaging mice were terminated for biodistribolion analysis, Additional stereomicroseopic images were collected after removing the abdominal wall• Results: Expression of hSSTR2 was detected in intraperitoneal tumors of all mice as indicatod by imaging at 5 h after injection of the radiotracer. Expression of GFP was clearly visualized in vivo at 5 h by fluorescence stereomicroscopy and imaged simultaneously in the same mice with high spatial resolution of small intraperhoneal tumor lesions. Nuclear images showed the uptake of radiotracer by all peritoneal rumors. ]n the same location of same mouse, GFP-positive minors were visualized in live animals in non-invasive way. After removal of abdominal wall, the GFP-positive tumors were visualized more clearly including single cell. Under bright fieId microscope, tumor as small as 0.2ram diameter from 4ram depth was not possible to be detected. H~wever, by fluorescence stereomicroscopy, this small size tumor due to green fluorescence contrast, was visualized in vivo. GFP-positive cells were recovered from peritoneum and cultured in tissue culture media and SKOV3 cells grew. All GFP-positive tumor cells were radioactive as confirmed by gamma counter. Control mice did not have expression of either hSSTR2 or GFP. Imaging and cell count data indicated that GFP-positive cells were mainly cancer celts Gamma camera and light-based imaging were complementary to each other• Conclusions: The present study demonstrated that simultaneous dual modality imaging of light-based and gamma camera offered a highly sensitive in vivo tool for the early detection and monitoring of human ovarian tumors in mice.

AIM OF THE STUDY: in our PET center we studied many patients with NETs. In this report, we considered a group of selected subjects with abdominal masses to evaluate the role of nuclear medicine in the final diagnosis of NET. METHODS: 50 patients (mean age 62 years) among whom 10 cases of MEN where submitted to FIg-DG PET with a dedicated tomograph. Sethtigraphy (planar and SPECT) with lnl I I-Octreoscan was performed in 46 out of tbem with a double head camera. At the radiological examinations 49 had an abdominal mass (pancreatic in over than 90=/0) and 23 presented liver and or nodal metastases, too. In one case liver metastases without primitive tumor radiologieally localized. At the final diagnosis, surgically or clinically proved, and by a 2 years follow up, the patients were divided into two groups: 25 were affected of aggressive NETs, according to the size of primary lesion and to the presence of spread disease (among whom 3 out of 10 cases of MEN), and 25 of non aggressive tumors (comprising 5 insulinomas, the smallest one 1 cm diameter). In the first group Inl 1 l-Octreosean was performed in 24 and in the second one in 22. RESULTS: the overall results are reported in the table below. In the 25 cases of aggressive tumors, F18-DG PET identified both primary and secondary (lung metastases in 2 and mediastinal nodes in 1, too) lesions in 20 patients including the primary lesion in breast in a woman with liver metastases. PET was positive in a larger number of aggressive NETs than receptor scintigraphy but. this last technique localized a greater number of metastases in 4 cases (abdominal nodes). In the group of 25 non aggressive lesions lnl 11-Oetreoscan correctly identified every site of tumor in 11 out of 22 the examined patients, among whom the one affected of the smallest insufinoma, We had no false positive lesions for both methods. 2INoo 5 ) ' Aaggres" g g r e s s(25) (i v e

0=

520PETp°sitlve

20~ETne~ative

[l?Octre. . . . . pos.

8Oct¢¢. . . . . .

~'l

CONCLUSIONS: a common opinion is that F18-DG PET is a powerful mean to localize malignant lesions but, in our patients, it was negative in 20% of aggressive tumors, l n l l l Oetreoscan was negative in 50% of non aggressive lesions and positive in 66% of aggressive tumors. Our results show that the contemporary use of F Ig-DG PET and receptor seintigraphy are useful to assess the extension of disease and to select patients tor surgery and/or tbr further medical treatments: both of them must be recommended when abdominal NET is clinically suspected. Our data are based on a short term follow up and a Longer one is required to better understand if F i8-DG PET may be a marker of prognosis rather than malignancy.

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• DIAGNOSTIC ONCOLOGY 10 / ENDOCRINOLOGY 1 PS_406

PS_408

SOMATOSTATIN RECEPTOR SCINTIGRAPHY IN PARAGANGLIOMAS

IS IT SAFE TO OMIT 1-131 UPTAKE MEASUREMENTS WHEN TREATING BENIGN THYROID DISEASE WITH RADIOIODINE?

M.D. Abos (1), J. Banzo (1), E. Prats (1), E. Freile (2), J. Velilla (3), P. Razola (1), T. Escalera (1), F. Garcia (1). (1) Department of Nuclear Medicine, University Hospital, Zaragoza, Spain; (2) Department of Radiology, University Hospital, Zaragoza, Spain; (3) Department of Internal Medicine. Miguel Servet Hospital, Zaragoza, Spain.

T. Buhl, P. Hanson, W. Christensen, B. Hesse. Dept. of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.

Paragangliomes are relatively infrequent neuroendocrine tumors that express somatostatin receptors. There is little intbrmation about the role of the =HIn-DTPAOC scintigraphy, or somatostatin receptor scintigraphy (SRS), in the management of these tumors. The aim of this study was to assess the utility of the SRS in the diagnosis, staging and follow-up of patients diagnosis from paraganglioma. Material and Methods: We included 7 patients (5 females, 2 males) with histologic diagnosis of paraganglioma (4 quemodectomas, 2 extra-adrenal paragangliomas and I syndrome of Came~. In these patients we performed 8 SRS (148 MBq), 4 J~I-MIBG scans (370 MBq) and 3 mTc-MDP bone scans (740 MBq). In two patients the SRS was performed for the staging of a known or suspected tumor, whereas in the other 6 patients the SRS was performed during the post-therapy follow-up: embolization or surgery associated with radiotherapy or metabolic therapy. One patient was explored twice, before and after surgery. Results: SRS was positive in 6 patients. In two of them (I jugulo-tympanic paraganglioma and I extra-adrenal paraganglioma) the SRS demonstrated an unsuspected metastatic dissemination, whereas in other patient (syndrome of Carney) the SRS scan detected multiple unsusLit 123 pected paragangliomas. Of the 4 patients studied with both, In-DTPAOC and I-MIBG scans, similar information was provided in 2 patients with both explorations (I metastatic extra-adrenal paraganglioma and 1 quemodectoma), in one patient the SRS was normal (bone metastases of an extra-adrenal paraganglioma) and in the other one the Iz31-MIBG scan was normal (I carotid quemodectoma). One patient with local recurrence and metastatic dissemination of an extra-adrenal paragangtioma was treated with t~II-MIBG. Conclusions: SRS permits to detect, to stage and to assess the therapeutic response in patients with paraganglioma. The abilit~ of obtaining whole body images provides the detection of unsuspected lesions. SRS and i'31-MIBG scan are complementary techniques, particularly in the study of metabolic therapy candidate patients.

OTHER CLINICAL SCIENCE. ENDOCRINOLOGY 1 PS_407 DOES THE ORBITAL 1111N-OCTREOTIDE UPTAKE DEMONSTRATE THE ACTIVE DISEASE IN PATIENTS WITH GRAVE'S OPHTALMOPATHY:ITS RELATION WITH CLINICAL ACTIVITY SCORE i. Ak (1), N. On (2), E. Zor (1), E. Vardarel (1), N. Yddmm (2). (1) Department of Nuclear Medicine; (2) Department of Ophtalmology. Eski~ehir, Turkey. Accumulation of the 11 Iln-Octreotide in patients with Grave's Ophtalmopathy (GO) is most probably due to the presence in the orbital tissue of activated lymphocytes bearing somatostatin receptors. Alternative explanations are binding to receptors on other cell types such as myoblasts, fibroblasts or endothelial cells or local blood pooling due to venous stasis by the autoimmune orbital inflammation. Clinical Activity Score (CAS) is a classification based on the classical signs of inflammation such as pain, redness, swelling, and impaired function in patients with GO. In this study, we assessed the correlation between CAS and Somatosatin Receptor Scintigraphy (SRS) with 1l lln-Octmotide in patients with GO. Methods: Thirty five patients with GO and 8 control subjects were included in this study. AI'~r the clinical examination CAS of each patients were determined, ranging from 0 to 10 points. According to CAS (>/= 4/10 and <4/10), patients were classified as clinically active GO (n=12) and clinically inactive GO (n=23). Planar imaging was obtained at 4 and 24 hr aRer intravenous injection of 111 MBq of 11 lln-Octreotide. Orbital uptake was assessed by the ROls generated for both orbits and brain. Using the mean counts an uptake ratio between the orbits and the brain was determined. Results: The results of SRS showed an increased orbital accumulation of 11 lln--octreotide in patients with clinically active GO compared to patients with inactive GO and controls (orbitbrain-ratio: 2.35 -+ 0.75, 1.25 + 0.20, 1.29 -+ 0.29, respectively, p<0.05). Patients with clinically inactive GO show a similar orbital accumulation of radioactivity compared to controls (p>0.05). We found a significant correlation between the CAS and SRS (7<0.0t). Conclusion: SRS with 11 lln*labeled octmotide correlates with Clinical Activity Score in patients with clinically active GO. The value of SRS lies in its ability to act as a measure of inflammation and may be useful as an activity parameter when planning therapeutic procedure as well as for GO follow-up.

118(3

It has never been documented that determination of the iodine uptake ratio improves the longterm clinical outcome for patients treated for benign thyroid diseases (toxic and non-toxic goiter). On the other hand it is imperative not to treat patients with a very low iodine uptake. Determination of iodine uptake is time consuming and usually closely related to pertachnetate uptake, which is much quicker and less expensive. Aim: To investigate whether a Tc-99m-portachnetate (TcO4") scintigraphy can replace the 1131 iodine uptake measurement prior to radioiodine treatment of patients with benign thyroid disease. Methods: In a retrospective series of 100 patients with toxic (N=87) or non-toxic (N=I3) gnitre Tc-99m (TcO4) scintigraphy was visually graded in 3 degrees (low, intermediate and high) by two experienced specialists and compared with the 24 h 1-131 iodine uptake grouped in intervals (< 30 %, -> 30 % - < 60 %, and >_60 %). In 13 of the patients it was still possible to calculate a semi quantitative score by drawing ROIs around the thyroid gland, a salivary gland, and the background. Count ratios between the thyroid gland and the salivary gland and the background, respectively, were calculated. Results:

N= 100 1-131 uptake 1-131 uptake 1-131 uptake

~<30% 1_>30%-<60% ;>_60%

Tc-99m TOO4 LOW 4 2 0

Tc-99m TcO,1 INTERMID. 2 20 17

Tc-99m TcO 4" HIGH 0 10 45

There is a good correlation between 1-131 iodine uptake and visual evaluation of Tc-99m (TcO4") scintigraphy (see table. Semi-quantitation in 13 patients showed a good correlation between 1-131 uptake and Tc-99m (TcO4") thyroid gland/salivary gland or Tc-99m (TcO4)/background ratios being R = 0.87 and 0.88, respectively, and the correlation to 1-131 uptake compared with the visual evaluation was improved. Conclusion: It seems acceptable to calculate 1-131 iodine doses from estimation of the size of the thyroid gland and a Tc-99m scintigraphy. In particular, the risk of treating patients with low iodine uptake seems negligible.

PS_409 THE RESULTS OF RADIOIODINE THERAPY IN PATIENTS WITH HYPERTHYROIDISM AFTER ONE YEAR FOLLOW UP M. Argon, O. (3zyurt, K. KumanlioOlu, H. (3zkllic. Department of Nuclear Medicine, Ego University, Izmir, Turkey. Radioiodine 0-131) is one of the accepted forms of treatment for thyrotoxicosis. The aim of this retospective study was to evaluate the results of radiodine theraphy in patients with hyperthyroidism. Methods: 132 Pts were (44 Graves" disease, 43 toxic adenoma and 45 toxic multinodular goiter) (85 female 64%-47 male36%) analyzed who were treated with radioiodine from 1997 to end of 1999 and still on follow up. Graves' disease Pts.' ages ranged from 30 to 74 (main 50"J:10,4), (28 female, 16 male). The doses ranged from 6 to 20 mCi (mean 12.3±4.2), 27 Pts recieved single dose, 17 needed 2 doses. Toxic adenoma Pts.' ages ranged from 30 to 78 (main 56.8:t:11.1)(22 female, 21 male), the doses ranged from 8 to 30 mCi (mean 18-+5.6), 32 Pts received single dose, needed 2 doses, 2 needed 3 doses. Toxic multinodular goiter Pts." ages ranged from 36 to 75 (main 60-+10.5), (35 female, 10 male), the doses ranged from 8 to 30 mCi (mean 20.8+6.1), 33 Pts received single dose, 12 needed 2 doses. Results: ARar one year follow up in Graves" disease; 15 Pts were euthyroid (34%), 25 Pts were hypothyroid(57%), 4 Pts were persistently hyperthyroid (9%). In toxic adenoma; 29 Pts were euthyroid (67%), t2 Pts were hypothyroid(28%), 2 Pts were persistently hyperthyroid (5%). In toxic multinodular goiter 34 Pts were euthyroid (75.5%), 7 Pts were hypothyroid (15.5%), 4 Pts were persistuntly hyperthyroid (9%). There was not any complication of 1-131 treatment. Conclusions: The main problem of raioiodine treatment was hypothyroidism and this was easily treated with L-thyroxine. Hypothyroidism was noted most commonly in Graves' disease Pts. Euthyroid state was obtained mostly in toxic multinodular goiter. The ranges of adminestered second or more doses were low. The radioiodine treatment was prefered in elderly patient rather than young Pus.

• OTHER CLINICAL SCIENCE. ENDOCRINOLOGY 1 PS_410

PS_412

DETERMINATION OF THYROID VOLUME PRIOR TO RADIOIODINE THERAPY: ULTRASONOGRAPHY VS MRI

EFFICACY OF 131-1 TREATMENT IN PATIENTS WITH GRAVES-BASEDOW DISEASE

P. Reinartz, M. Zimny, O. Sabri, B. Nowak, U. Cremerius, K. Setani, W. Sch~fer, P. Meyer, U. Buell. Department of Nuclear Medicine,

A. Saura, I. Herv~ts, P. Gonz&lez-Cabezas, A. Rivas, J. Alonso, P. Bello, A. Mateo. Department of Nuclear Medicine, University Hospital,

University Hospital, Technical University Aachen, Germany.

Valencia, Spain.

Aimt For radioiodine therapy, thyroid volume is one of the most significant factors in calculating the individual delivered activity. Method of choice for the exact determination of the thyroid volume is uhrasonography using the formula 0.5 x length x width x depth for each lobe separately. Aim of the study was to ascertain how exact the results of this technique are in comparison to MR1. Methods: In 50 patients with confirmed Graves<< disease ln=24) or muhinodular toxic goiter (n=26) ultrasonography (Hitachi LSC 7500, 7,5 MHz) was performed by two experienced referees (US-Ref-I, US-Ref-2). Additionally, a 3D fast field echo MRI sequence (Philips Gyroscan NT, 1,5 Tesla) of the neck area was acquired with a voxel size of 3 mm. Acquisition time was four minutes each. Thyroid volume was assessed by using the formula mentioned above for ultrasonography as well as for MRI (MRI-e). Standard of reference was the thyroid volume determined by a region of interest technique applied to the MRI data set which calculates the exact volume aRer encircling the thyroid gland in each slice (MRI-r). Results: Mean measured thyroid volume was 55.9 + 39.4 mL for MRI-r, 51.4 + 36.6 mL for MRI-e, 44.0 + 29.3 mL )br US-Ref-I, and 43.1 ± 29.6 mL for US-Ref-2. The table shows the mean absolute and relative difference as well as the standard deviation (sd) and the level of significance p (Wilcoxon test) between the different techniques.

Aim: To assess in our Hospital the et~cacy of 13 l-I in patients with Graves-Basedow disease. Methods: We have studied all the patients with Graves-Basedow disease (thyroid scintigraphy showing diffuse goitre, without nodules confirmed by ultrasonography and with thyroid hyperfunction) with no definitive control of the disease with the oral treatment with antithyroid drugs (ATD), treated in our Department since June-1998 until march-20O0. We have studied 126 patients, 36 males and 90 females: age 20-81 years (average age 49 years approximately). All of them were treated with ATD: Carhimazol (average dose 20rag/day). 4% of patients left the oral treatment 30 days before treatment with 131-1. The other 96% left the oral treatment in the habitual period (7-10 days). The administered activity of 131-I was calculated depending on the glandular size (scintigraphy and palpation) and the hormonal state. The activity administered varied between 6,2 mCi-i6,3 mCi (229 MBq- 603 MBq). The average dose was 10,63 mCi (393 MBq). Results: At 01/March/2001 : 77% of patients were controlled with one dose of 1-131 and 11% needed a second dose of 131-1. None of them needed a third dose,51% presented hypothyroidism in 1-12 months (average 4 months), needing an average dose of 100~tg of thyroid hormone (Levotroid R) interval (50-150). 26% of patients remained with euthyroidism. 23% of patients presented a relapse of the hyperthyroidism, and I I% of them were treated again with 131 -f (second 131-1 dose). The following table contains the dose of ATD, gender, age and hormonal state after the first dose of 131-1. RESULTS

mean absolute A + sd [mL]

mean relative A + sd [%]

p

MRI-r vs MRI-e

7.8+10.1

13.2--.8.4

0.30

MRI-r vs US-Refl

14.0± 15.8

22.6+ 15.1

<0.01

MRI-r vs US-Ref'2

14.3+ 131

25.8+ 14.8

US-Refl vs US-Ret2

7.0 + 7.3

<0.01 0.47

Conclusions: While there is a high level of agreement between the MRl-techniques on the one hand and the uhrasonographic results of the referees on the other hand, a significant difference could be Ibund between the thyroid volume determined by uhrasonography and MRI with a mean difference of approximately 14 mL (>20%). It seems advisable to perlbrm the short MRI sequence especially in patients with large or irregular shaped goiters in order to ensure a correct individual delivered activity.

N umber of Patients Average age (years) Average dose of ATD Average activity of 131-1 (mCi} Average activity (mCi)

EUTHYROIDISM Male/Female I 1/22 47/47 3.75/3.25 m~/day

HIPOTHYROIDISM Male/Female 12/52 45/54 3.5/3.7 m~/da},

HIPERTHYROIDISM Male/female 13/16 56/44 3.75/4.75 rag/day

10.1/9.97 10

10 2/11.1 10.9

11.1/10.4 10.6

Conclusions: We did not found statistical differences between patients who developed hypo/hypcr or euthyroidism in relation with: dose of ATD previous to the 131-1 treatment, age, average activity of 131-1; It seems that males have more tendency to remain with normo/hyperthiroydism. The activity of 131-1 administered have been effective in the control of Gravcs-l~ascdow disease in a high percentage ol cases.

PS_411

PS_413

TECHNETIUM-99M METHOXYISOBUTYL ISONITRILE SCINTIGRAPHY IN VISUALIZATION OF SUPPRESSED THYROID TISSUE

THYROGLOBULINE AND PEROXIDASE AUTOANTIBODIES IN THE FOLLOW-UP OF SEQUENTIAL HORMONE-IODINE GOITER THERAPY

M. Yfldlnm (1), H. Uslu (1), F. Ak~ay (2), R. Bayrakdar (1), N. 0n0var (3), E. Varo~lu (1). (1) Atat0rk University Medical Faculty, Depts. of Nuclear Medicine; (2) Atat0rk University Medical Faculty, Depts. of Biochmistry; (3) AtatiJrk University Medical Faculty, Depts. of Endocrinology, Erzurum,

Turkey. We studied the significance of Technetium - 99m Methoxyisobutyl lsonitrile (MIBI) scintigraphy in patients with nonvisualized thyroid tissue, The thyroid tissue was suppressed depending on various drugs and salt containing iodine. Methods: Forty patients ( 30 women, 10 men; age range, 10-72 yra; average age: 43.6 yrs ) visualized on pertechnetate scanning were included in this study. Markedly reduced pertechnetate uptake was seen in all patients. At the same time, MIBI scanning was performed without thyrotropin ( TSH ) stimulation. Images of the neck were recorded at 30 rain, lh and 2 h after intravenous injection of Tc99-MIBI 5mCi ( I85MBq ). The results were correlated with neck ultrasound, serum TSH, TT3, TT4, FT3 and FT4 levels. Images were recorded with a small field of view camera ( GE Starcam 4000 ), equipped with a parellel-hole, all-purpose collimator, adjusted to record a photopeak of 140 keV with a 20% window, The MIBI scanning was analyzed both visually and semiquantitatively. For the semiquantitative analysis, regions of interest ( ROIs ) were generated over the right and left lobes of the thyroid gland, Mean counts in every ROI were calculated for MIBI. Results: The technique identified the following conditions: normally sized thyroid ( n = 2 ), diffuse goiter ( n = 7 ) and multinodular goiter ( n = 28 ). Moreover, substernal goiter was identified in 3 patients.The MIBI uptake ratios were 166.73 ± 158,2 at 30th rain, 131.13 ±117,7 at the 60th rain and 114.08 ± 110.4 at the 120th min. Conclusions:Our results suggest that Tc99m-MIBI scintigraphy may contribute to the diagnosis of thyroid pathology and planning of the treatment in patients with suppressed thyroid tissue in pertechnate scintigraphy.

0

o

M.J. Reinhardt (1), D. yon Mallek (1), H. Palmedo (1), U.J.T. Kuehr (1), A. Manka-Waluch (1), F. Gruenwald (2), H.J. Biersack (1), T. Krause (1). (1) Dept. of Nuclear Medicine, Univ. Hospital Bonn, Germany; (2) Dept. of Nuclear Medicine, Univ. Hospital Frankfurt, Germany. Aim: It is well known that iodine therapy may induce an increase of thyroglobuline (TG-ab) and thyroid peroxidase (TPO-ab) autoantthodies. The course of TG-ab and TPO-ab a~er switching from thyroid hormone to iodine therapy is currently unknown. Thus, the study retrospectively analysed the course of TG-ab and TPO-ab after changing thyroid hormone therapy of several years' duration to low-dose iodine therapy. Methods: 79 patients (51 women, 28 men; aged 39+13 years; 40 diffuse goiter, 39 nodular goiter) in whom thyroid hormone therapy was changed to iodine therapy were included in the study, Mean thyroid hormone therapy lasted 85+64 months and mean iodine therapy lasted 59±33 months. TG-ah and TPO-ab were determined with CantAK?-Anti-TG and CentAK?Anti-TPO kit from Medipan, Germany. Thyroid sonography and measurement of serum thyroid hormones and TSH were performed additionally. Suppression-scintigraphy was performed prior to the change to iodine therapy for exclusion of ~nctional thyroid autonomy. Results: Data were analysed in 3 groups. Group A (N=38) was treated exclusively with thyroid hormones and served as control. Group B (N=4 I) was treated with thyroid hormones followed by 100-200 w.g iodine daily. Group C (N=22) was a subgroup to group B and covered all patients with repeated follow-up measurements of TG-ab and TPO-ab during thyroid hormone and iodine therapy. In group A, TG-ab and TPO-ab were increased in 13% and 20% of patients, respectively. In group B, the frequencies were 18% and 23%. These differences were not significant. The intraindividual course showed a tendency towards increasing TG-ab during iodine therapy, while TPO-ab decreased. Conclusion: Application of 100 to 200 l.tg iodine daily did not induce a significant change of TG-ab and TPO-ab. This may be due to a possible immune-suppressive effect of the foregoing thyroid hormone treatment, which has been observed in patients with Hashimoto thyroiditis.

1181

0

n

• OTHER CLINICAL SCIENCE. ENDOCRINOLOGY 1 PS_414

PS_416

THE RELATIONSHIP OF PYRAMIDAL LOBE WITH THYROID DISEASES

LONG FOLLOW-UP-RESULTS OF NEARLY TOTAL THYROIDECTOMY IN EUTHYROID GOITER

M. Yfldmm (1), H. Uslu (1), R. Bayrakdar (1), C. Ak (1), B. Erdo~jmu~ (2), E Ak~:ay (3), E. VaroOlu (1). (1) Atat0rk University Medical Faculty; (2) Atat0rk University Medical Faculty, Depts.of Radiology; (3) AtatOrk University Medical Faculty, Depts. of Biochmistry, Erzurum, Turkey.

P. Mari8 (1), M. Thermann (2), G. Wolfes (1), O. H6ner (3), D. Emrich (1). (1) Gemeinschaftspraxis Radiology/Nuclear Medicine Dr. Stuckenholz & Partner, Bielefeld, Germany; (2) Klinik fiJr AIIgemein- und Visceralchirurgie, St&dtische Kliniken Bielefeld, Germany; (3) Institut fur Sportwissenschaften, University Bielefeld, Germany.

We aimed to investigate the relationship of pyramidal lobe with thyroid diseases by retrospectively evaluating 4834 thyroid scintigraphies. Methods: 4834 patients visualized on pertechnetate scanning were included in this study. The results were correlated with neck ultrasound, serum TStt, TT3, TT4, FT3 and FT4 levels. Images were recorded with a small field of view camera ( GE Starcam 4000 ), equipped with a parellel-hole, all-purpose collimator, adjusted to record a photopeak of 140 keV with a 20% window. Results: Of 4834 patients, 534 ( I 1 % ) had pyramidal lobe: 62 % were Iocalised in isthmus, 20 % were closer to the left lobe and 16.8 % were localized right side. Of 534 cases. 11)9had nodular goiter, 96 diffuse goiter and 53 hyperthyroidism. The remaining ones had goiter with one nodule. Conclusions: It was concluded that pyramidal lobe was seen in approximately I 1 % of thyroid diseases and patients with noduler goiter were higher in number than ones with hyperthyroidism.

Aims: Iodine deficiency is still an important cause of goiter in Germany. 20 - 30% of'the population (82 millions) suffer from iodine-deficient goiter. TSH and various growth factors induce diffuse goiter developement followed by nodular degeneration. Because medical treatment may be unsuccessfull in nodular goiter still about 80,000 surgical operations of nodular goiter are performed in Germany annually. The surgical methods used are: nodule-oriented partial thyroidectomy and near tota~ thyroidectomy (NTT). Criteria of surgical quality assurance are considered as goiter recurrence-rate, hypoparathyreoldism and cord paralysis. Reports on follow up after operation because of euthyroid goiter suffer ti'om several items. Methods: Out of 263 pts with euthyroid nodular goiter (mean age 50,2 ± 13.2 yrs. thyroid volume 82,8 a: 56,7 ml) operated by NTT during one year (1992) using an uni form technique 216 (82%) were reinvestigated after 7 yrs (clinical investigation, thyroid volume by sonography, TSHb, £1"4.tT3). Results: One had a relapse of goiter, none had a cord paralysis and 3 pts had hypoparathyroidism. II of the medicated pts were latent or overt hypothyroid with elevated TSHb (4,5 - 15,3 uU/I) due to insufficient medication. The remaining 205 pts were subdivided as follows: no medication: n = l l , thyroxine < I.I ug/kg: n=27, thyroxine ?1.1 ug/kg: n=136. 3 pts received iodide supplementation alone and 28 pts a combination of thyroxine and iodide with different doses. The residual mean thyroid volume was higher in the non medicated group (8.1 ± 5.2 ml) compared to the thyroxine medicated pts (2.7 ± 2.0 ml, p < 0.001) and the mean TSHb was higher and the mean FT4 was lower (both p < 0.001 ). In pts under high thyroxine medication (? 1. t ug/kg)) the residual thyroid volume was significantly lower (2.3 ± 2.0 ml) compared to those under low doses (?1.1 ug/kg) (4.3 ± 3.2 ml, p < 0.01) in combination with a higher TSHb (p < 0.05) and a lower FT4 (p < 0.01). In conclusion nearly total thyroidectomy prevented goiter recurrence in 215 of 216 operated pts at~er 7 years. T4 medication kept the residual thyroid volume significantly lower dependent on its dosage.

PS_415

PS_417

A LONG TERM FOLLOW-UP IN PATIENTS AFFECTED WITH GRAVE'S DISEASE TREATED WITH RADIOIODINE

THE STUNNING EFFECT IN GRAVE'S DISEASE: INFLUENCE IN THE COURSE OF RADIOIODINE THERAPY

B. Santaniello (1), E Schenone (2), G. Curti (1), M. Carletto (1), H. Rouhanifar (1), A. Piccarclo (1), L. Tommasi (1). (1) Nuclear Medicine Service, DiMI - University of Genoa, Genoa, Italy; (2) Nuclear Medicine Service, IST - University of Genoa, italy.

I. Bofilias. Clinic of Nuclear Medicine, Technical University, Munich, Germany.

From 1954 to 1976, 1778 pts affected with Grave's disease were treated with =]( I. The aim of the study is to evaluate the results of therapy after a long period of time: from 23 to 46 yrs as in a previous evaluation where our incidence of hypothyroidism resulted quite different from other reports. Before the therapeutic dose the maximal thyroid uptake of 1311tracer dose was calculated at~er 2h, 6-8h, 24h and 48h, The therapeutic dose was included within 80-120 nC/g of thyroid tissue. The first control of therapy effect was performed on 428 pts; actually we have studied 85 pts (medium age 68.3 yrs). The mean time (MT) between the actual check and the last therapeutic dose was 32 yrs. Our controls included clinical examination, FT3, FT4, TSH determination. In the first control in 1977, 4% of the pts were still hyperthyroid, 42,2% were normal and 55.37 were hypothyroid. Actually, 42 pts (49,4%) are euthyroid, and 43 (50,6%) are hypothyroid. In the first group the mean global dose of 1311 was 8,45 mCi and the MT from the last dose was 26,45 yrs. In the second group 22 pts affected with a clear hypothyroidism received a MGD of 9,6 mCi; the MT from the last dose has been 0f27,6 yrs. The remaining 21 pts showed a subclinical hypothyroidism. The MGD was 11,3 mCi and the MT from the last dose was 22 y~. The life table study of our statistics showed 52,6 % of probable hypothyroidism aRer 3 yrs and a 57,2% at~er 44 yrs.

1182

We examine the stunning effect in Grave's disease (GO) because a) stunning may influence the thyroid absorbed Dose (Dabs) during the course of therapy, and h) the recurrence rate of thyrotoxicosis in GO lies with (30-50%) quite higher than other hyperthyroid subgroups. The recent introduction of a thyroid stunning constant ( D t a - 1 0 0 Gy) allows easily a) the characterization of the thyroid radiosensitivity to the therapeutic absorbed Dose in thyroid benign diseases, b) a subtle comparison among our data and other published results, and c) among the various thyratuxic subgroups. We retrospectively calculated the Ditz in 45 pts with Grave's disease, in which a second t311 treatment was performed. Two different stunning constants have been significantly distinguished, indicating the existence of two different radiosensitive behavior follicular types. They are obviously related to the high or low degree of the thyrotoxicosis recommending a modification of the current therapy abs. Dose concept. Method: Daily 131 I thyroid uptake measurements of first MFU and second MSU treatment and Dabs calculations in Grave's disease in the Acute Therapeutic Stage (ATS, DATS)show in 39 patients (20%, total n=195 pts) a reduction MSU relative to MFU depending on the DAr s already induced during the ATS. Individual values for Dr/2 were calculated. Two dif. mean values were observed using the t-test as well as higher order polynomials. Results: 18 (40%) of the 45 pts showed a significantly lower value of Oto.Jo, = 71+ 15% Gy and in 11 pts (24°/'0) the Dta~i # mea/l value was 113 :l: 17% Gy (p<.05). Calculations could not be performed for the remaining 6 (13%) cases because inversion of the relation (MSU/MFU > 1) occurs due to the discontinuation of ATD during therapy. For low aggressive types a Dabs of 150-200 (175 ± 15%) Gy was derived, whereas for high aggressive the current Dabs value remains unchanged. Conclusions: The derivation of the two different stunning constants in Graves' disease reflects the existence of two radiosensitive different follicular behavior types, according to the degree of their thyrotoxicosis. Keeping the actual abs. Dose eoocept for high aggressive unaltered and changing the Dabs to 150-200 Gy for low types, the hypothyroidism rate may be considerably reduced. A comparison with other published data revealed that stunning constnnts varied greatly to each other. Further developments are needed.

• E N D O C R I N O L O G Y 1 / INFECTION AND I N F L A M M A T I O N 1 PS_418

PS_420

RESULTS OF TREATMENT WITH CALCULATED DOSES OF RADIOIODINE DEPENDING ON GLAND SIZE AND MORPHOLOGY IN GRAVES-DISEASE, ANALYSIS OF VARIABLES

TC-99M MIBI IN PULMONARY TUBERCULOSIS EVALUATION

S. Rodado (1), A.M. Garcia (1), V.M. Poblete (1), A. Soriano (1), C. Martinez (2). (1) Department of Nuclear Medicine, Alarcos Hospital, Ciudad Real, Spain; (2) Deparment of Investigation, Alarcos Hospital, Ciudad Real, Spain. Aim: To assess the efficacy of administered doses of Radioiodine (RAI) in the treatment of patients with hyperthyroidism in Graves~,disease calculated depending on gland size and morphology (assessment by palpation and scintigraphy ) , analyzing which variables influence on the final result (hypothyroidism, hyperthyroidism and euthyroidism ) of our sample, and on the early development of hypothyroidism. Methods:99 patients diagnosed of hyperthyroidism in Graves~disease and treated with RAI between April 1996 and November 2000 were evaluated retrospectively.77 females and 22 males, mean age 44 years (range :tS-76).Sixty -seven patients received treatment with antithyroid drugs , which were stopped seven days prior to and after of the treatment with RAI .The doses were administered depending on gland size and morphology , which were detcrminated by palpation and 99mTc-pertechnetate scintigraphy (doses range: 185-629 MBq ).Success was defined as elimination of hyperthyroidism ; and early hypothyroidism which appeared in the six months after therapy. Resuhs:The distribution of results accompanied by mean dose in each case is shown below : t HYPOTHYROIDISM 53(9)

[ 30 EUTHYROIDISM (9.3)

[HYPERTHYROIDISM 16(8.3)

84 % of patients were controlled with one dose of RAI and 90% with one or two doses. 43% developed hypothyroidism within the first year of lbllow up ( 30% within the first 6 months). By means of the Discriminant Analysis stepwise method we found that only the time of evolution influenced in the final results .The rest of the variables ( gender, age, doses, treatment with antithyroid drugs ) did not influence them .Using Logistics Regression we studied the relationship betwcen the appearance of early /late hypothyroidism and the administered doses: there were no significant statistical differences. On the other hand we found a certain tendency fur early hypothyroidism to appear in the youngest patlenls.(p=0.111 ). Conclusions:-The administered doses in our Department have shown to be effective in controlling tyrotoxicosis .The high range of hypothyroidism in the first year strongly supports the need lbr frequent initial controls. -In our sample, only the time of evolution influenced on the final results of the patients. -l'he age was the only factor which showed a certain tendency in the ewdution to early/late hypmhyroidism.

'4. Rusu (1), C. Stefanescu (1), [3. Boisteanu (2), D. Simion (2), D. Diculencu (2), I. Raileanu (1), T. Mihaescu (2). (1) Department of Biophysics and Nuclear Medicine; (2) Department of Pneurnology, UMF, lasi, Romania. Our aims were to assess the possible usefulness of Tc-99m MIBI for the: I) scintigraphic evaluation of pulmonary tuberculosis (PTB); 2) scintigraphically evaluation of PTB treatment efficacy (at 6 and 10 months, which rest to be done); 3) finding of new sites of PTB (in relation with the radiolngic sites). Methods: We have studied 28 active pulmonary tubereu~osis new diagnosticated patients, without treatment (11 women and 17 men, mean age 29 years, 22 BK positive microscopically, 6 BK negatif). Each of them had i.v. received 7.4 MBq (0.2 mCi)/kg of Tc-99m MIBI. Scintigraphic images have been realised as follows: an anterior planar 3 000 000 counts image on the thorax at 15 minutes, followed by a SPECT acquisition and another anterior planar (same number of counts, same region) image at 60 minutes slier radiotracer administration. Two nuclear physicians have analised the images and indexes (counts/pixel) lesion/heart (I-1) and lesion/normal (1-2)were calculated. Results: In all active PTB the images were positive with 1-1 comprised between 1.3 and 4.2, with differences between 15 minutes and 60 minutes images, for the same patient. In 9 BK positive patients suplirnentar images have been seen projected in the pulmonary fular aria, more eviden at 15 minutes. From the 6 BK negatif patients, 4 had positive images (coresponding to macronodular radiologic Lesions). In 5 cases new sites (nonrelated to radiologic sites) have been seen. I0 positives patients examined again 7 days aRer the beginning of the treatment had decresed lesions uptake. Conclusions: 1) Tc-99m MIni is asefull for the functional imagistic of PTB; the time interval and degree of positive images seems to depend on the constitution of the lesion. Images at 15 and 60 minutes have relative distinct significance, earlier images being more evident in high BK positive patients. 2)Tc-99m MIBI scintigraphy in pulmonary tuberculosis could be a very earlier marker fur the efficiency of PTB treatment, the radiotracer uptake decreasing only in some days, also more evident on the 15 minutes images. 3) Tc-99m MIBI pulmonary scintigraphy can make evidence of new tuberculosis lesions (not evident on X-ray images). These data suggest that the radiotracer uptake elements in the constitution of PTB lesion are different, and Mvcobacterium Tuberculosis seems to have a great, role, which can be understood by correlated in vitro studies.

c-

OTHER CLINICAL SCIENCE. INFECTION A N D I N F L A M M A T I O N 1 PS_419 INFECTON: 99MTC-LABELLED CIPROFLOXACIN IN THE DIAGNOSIS OF BACTERIAL INFECTION. THE ISRAELI EXPERIENCE

C.L Ben - Horin (1), A. Altschuler (2), A. Raitblat (1). (1) Nuclear Medicine Department ; (2) Radiology Department, Bar-zilai Medical Center, Faculty of Health Sciences, Ben Gurion University of The Negev, Ashkelon, Israel. The diagnosis of infectious diseases is still a serious problem despite the wide range of imaging techniques and new therapeutic approaches. Known imaging techniques can be grouped in 2 categories: I) those able to demonstrate local changes in the anatomy due to infection, in example, computerized tumography and ultrasound; 2) examinations that can demonstrate physiologic changes like those performed in nuclear medicine. Nuclear Medicine has an important role in the diagnosis of infectious diseases in the human body. Today there is a wide range of well-known examinations, like 99mTc-MDP-bone scan, 67Go scan, or 111In labeled white cells. Each test has particular indications and the spectrum of differential diagnosis in the case of a positive study is large. We use, for the first time in Israel, a new radio pharmaceutical, 99mTc ciprofloxacin (Infectun) in order to imaging and diagnosis bacterial infections. The aim of this study was to check the accuracy of lnfeeton related to other imaging techniques in the diagnosis of bacterial infections. 29 patients (30 scans) were included in the study. All of them had an Infecton scan performed according to manufacturer instructions. Other imaging techniques were 19 ultrasound, 13 computerized tomography, 5 echocardiography, 13 different scans (99mTc MDP bone and 67Go scans). Blood culture was obtained in 16 patients. From 30 studies, 17 cases (56%) were considered true positive for bacterial infection; 8 cases mac negative (26.6%); 3 cases were summarized as false positive (10%) and 2 cases (6.8%) a false negative. Our sensitivity was 89.1% and our specificity 72.7%. Coneluslon: lnfectun is a promising imaging technique to be used in the diagnosis of bacterial infections,

PS_421

o ,m spa t~ r"

UTILITY OF 99MTC-LABELLED ANTIGRANULOCYTE FRAGMENTS (LEUKOSCAN e} IN JOINT PROSTHESIS INFECTION S. Caduccio, L. Trombettoni, B. Palumbo, D. Siepi, G. Fiorucci, F. Giuffrida, R. Falchi, A. Bianchi, R. Palumbo. Dept. of Nuclear Medicine, University of Perugia, Italy. Aim: To investigate the value of ~'~"Tc-labelled antigranulocyte fragments (Leuknscan "~) in our patients we performed immunoscintigraphy in association with three phase 9~"Tc-MDP bone scan in patients with infected prostheses. Methods: We studied 40 patients with suspected infected joint prostheses (22 hip, 12 knee, 6 femur). All patients underwent Leukoscan ~ (740 MBq i.v.; image acquisitlon after 4 and 24 hours) and three phase ~mTc-MDP bone scan. Fifteen out of the 40 patients underwent a ~Tc-HMPAO-WBC-scan (740 MBq i.v.; image acquisition aRer 4 and 24 hours) can'ied out 2 months before Leukoscan ~ for the same clinical suspicion, In addition in I0 out of the 40 patients a three phase evaluation with Leukoscan ® was carded out in order to compare the data obtained with the results of three phase WmTc-MDP bone scan. Ten patients underwent again Leukoscan = 4-6 months after the first exam for monitoring the effectiveness of therapy or for a worsening of the cfinical conditions. Results: 31 pts (77.5%) had positive Leukoscan* suggestive for sepsis, while 9 (22.5%) negative. The diagnosis was later confirmed by clinical follow up and a positive correlation (p<0,00; r2=0.894) was observed between Leukoscan ® and follow up. The Leukoscan ® technique in our subjects was sensitive and specific, showing 2.7% of false negative cases, 21.6% of true negative and 75.7% of mac positive, No false positive cases were observed in our study. Patients with a second Leukoscan ~ presented results that were in agreement with the clinical situation. Previous 99mTc-HMPAO-WBC-scan data of the patients studied were well related with the subsequent Leukoscan ~ (8/10 had the same results, while 2 had an increased uptake at Leukoscan®), being the comparison possible because very short was the interval between the 2 exams for the reason of a persistent pathology. Punbermore three phase evalua® 99 lion with Leukoscan in our patients provided similar results of three phase mTc-MDP bone scan, although scarce is the number of patients studied with both the three phase scans and a statistical analysis is not actually possible. Conclusions: In our study Leukoscan t is confirmed as a valid indicator of infection of prostheses, while particularly interesting in our opinion seems to be the three p h,ase evaluation, might probably being able to represent an alternative choice to three phase =Tc-MDP bone scan, Further studies with an increased number of patients are necessary to strengthen these data.

O

• INFECTION AND I N F L A M M A T I O N 1

PS_422

PS_424

TC-99M IGG SClNTIGRAPHY IN PATIENTS WITH BEHCET'S DISEASE WITH AND WITHOUT ACTIVE UVEITIS

THE USEFULNESS OF NUCLEAR MEDICINE PROCEDURES IN THE DIAGNOSIS AND MANAGEMENT OF THE DIABETIC FOOT

E. VaroOlu (1), G. GOlIOlO (2), H. Uslu (1), I. Akyol (2), M. Ylldmm (1), C. Ak (1), M. Demirci (1), A.R. Odaba} (3), R.A. San (3). (1) AtatOrk University Medical Faculty, Dept. Of Nuclear Medicine; (2) Atati~rk University Medical Faculty, Depts. of Ophtalmology; (3) Atat(.irk University Medical Faculty, Depts. of Internal Medicine, Erzurum, Turkey.

F. Matteucci, S. Severi, C. Corbelli. Nuclear Medicine Dpt, Faenza, Italy.

The purpose of this study was to evaluate the role of Tc-99m IGG scintigraphy in the differentiation of active uveitis from inactive uveitis in patients with Behcet's Disease. Methods: This study included 15 Behcet's patients and 7 healthy volanter as a control group. Total 30 eyes of the patients with Behcet's Disease and 14 eyes of control subjects were studied with Tc-99m IGG scintigraphy. There were 4 Behcet's patients with bilateral and 2 with unilateral active uveitis. Thus, 10 eyes with active uveitis of 6 patients with Behcers Disease were examined. Remaining 2 single eyes of these patients, 18 eyes of 9 patients with inactive uveitis and 14 eyes of control subjects were also studied. Four hours at~er I.V injection of 20 mCi Tc-99m IGG, anterior planar images were obtained. Semi-quantitative analyses were performed drawing RO[ around both eyes and on the scalp. Eyes to background activity ratios expressed eye / scalp indices were calculated. Results: The eye / scalp indices of 10 eyes with active uveitis, 20 eyes without active uveitis and 14 eyes of coutrol group were 1.69 ± 0.20, 1.49 ± 0.18 and 1.52 ± 0.27 respectively. The eye / scalp indices of the patients with active uveitis significantly greater than those of the patients without active uveitis, and normal subjects as well ( p = 0.007, p = 0,0t, MannWhitney U test ). Conclusion: Our results indicated that Tc-99m IGG scintigraphy could accurately use to dill ferentiate active from inactive uveitis in patients with Behcet's Disease

Early and accurate diagnosis of infection in diabetic foot is the key to successful management: diagnosis is difficult because the clinical likelihood of OM often does not appear through radiographic imaging. Objectives: the aim of our study was to evaluate the diagnostic value of 99m-Tc-HMPAOleukocyte scan (WBS) in combination with qqmtc-MDP bone scintigraphy (BS) lbr detection OM in diabetic patients (pts). Methods: we have studied 35 pts (14 male and 21 female) with mean-age 59 (range 22-74 yr) with insulin dependent-diabetes, foot ulceration and suspicion of OM; all pts were submitted to clinical examination, radiography, uhrasonography and bacterial culture. All pts underwent BS with 740 MBq Tc-99m-MDP while injected, five minutes and three hours after being injected; a week later they were submitted to WBS, 4 and 24 hours after the administration. BS and WBS images were compared and defined positive or negative for OM. The final diagnosis was established by clinical follow-up and histological findings. Results: OM was confirmed in 18 eases with WBS and BS; in 9 pts WBS and BS were negative for OM, confirmed by clinical follow-up; in 3 pts who resulted affected by OM, BS was negative while WBS was positive. In 3 pts giving negative results, BS showed a thlse-positive pattern, while in 2 pts with OM and BS positives, WBS was false negative. The sensitivity, specificity and accuracy resulted of 91%, 100% and 94% for WBS, while for BS, 87%, 75% and 83% respectively. Conclusions: our study confirms the importance of tbe nuclear medicine procedures in the diagnosis of OM; compared with BS, WBS proved to be more sensitive, specific and accurate.

PS_423

PS_425

THE USE OF 99MTC-WBC SPECT IN SEPTIC CARDIOSURGERY: CLINICAL EXPERIENCE

SClNTIGRAPHIC EVALUATION OF ACUTE PANCREATITIS PATIENTS WITH 99MTC-HMPAO LABELLED LEUKOCYTES

G. Khubulava (1), N. Fadeev (2), V. Soukhov (2). (1) Military Medical Academy, Saint Petersburg, Russia; (2) Central Research Institute of Roentgenology and Radiology, Saint Petersburg, Russia. The risk of septic complications remains high in spiteof cardiosurgery techniques develop-

H. Uslu (1), A. Bahk (2), M. Yddmm (1), R. Bayrakdar (1), I. Haclbeyo(~lu (1), B. Seven (1), E. Varo~]lu (1), I. Ydmaz (2). (1) Atat~rk University Medical Faculty, Dept. of Nuclear Medicine; (2) Atat0rk University Medical Faculty, Dept. of General Surgery, Erzurum, Turkey.

ment. This is really true for prosthetic valve endocarditis (PVE) which diagnosics is the most difficult up to day. The inadequacy of such diagnostic procedures as CT, MR[ and transesophageal EchoCG required more informativ¢ survey for the detection of PVE signs. For the solving of this problem whole-body scans and thoracic SPECT with ~ T c - H M P A O (hexametylpropilenaminoxim) labeled autoteococytes in patients with PVE were performed. WB-scans and tomographie slices offiRy nine patients (27 females and 32 males) aged 16-56 years were evaluated. In 1, 3 and 24 hours postinjection inflammatory loci within the heart were seen as the areas of pathogenic activity. To ensure topic diagnostics we use 201TISPECT in the same position of the patient (Pateteuted 1998) In 18 patients the circumscribed activity seen in relation to prosthetic heart valves convincingly demonstrated abscesses 8-15 mm in diameter, and in 29 - vegetations. Eighteen patients had the scintigraphic evidence of pancarditis. The remaining patients showed a negative scan over the heart correlated with echocadiographic data, but whole body scanning revealed extracardiac infection (frontitis, spbenoiditis, ulcerative colitis, cholecystitis, empyema of pleura, mediastlnitis and septic complication of postpoperative wound). The data demonstrated that ~ To-leucocytes imaging is a feasibe method for the detection of PVE, other septic complications of cardiosurgery and also noocardiao infection.

Our purpose was to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis and to evaluate the contribution of the 99mTc-HMPAO labelled leukocyte in the prognostic assessment of patients with acute paocreatids. Methods:The study was performed on 15 patients (9 females, 6 males, age range 26-86 yrs, mean age 55 yrs). Labelled leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT) were performed to all patients. According to Ranson criteria, 8 patients had mild (group A). 5 had severe (groupB) and 2 had necrotic (group C) paocreatitis. Ten patients had biliary pancreatitis and the other five patients had no

1184

obviouscause. Resolts:A|l patients of group C, three of group B, one of group A had a positive leukocyte scan.The sensitivity of leukocyte seintigraphy for the detection of a lethal course of acute pancreatitis was 100 %, of a severe course 60 % and of a mild course 12.5 %. The results of leukocyte scinfigraphy were compared with the those of CT. All the patients with pancreatic necrosis in CT had a positive leukocyte scan. But two of ten patients without detectable pancreatic necrosis in CT had a positive laukocyte scan. Conclusions: There was a correlation between the severity of the disease and leukocyte infiltration.Considering these results, we believe that leukocyte infiltration in the acute panereatitis can be demonstrated by noninvasive 99mTc-HMPAO labelled leukocyte sciutigraphy.

• INFECTION AND INFLAMMATION 1

PS426

PS_428

REFLEX SYMPATHETIC DYSTROPHY SYNDROME: DIAGNOSIS AND FOLLOW UP OF THE TREATMENT

POSTOPERATIVE FEVER: PROSPECTIVE EVALUATION OF 18 FDGIMAGING WITH A DOUBLE HEAD COINCIDENCE CAMERA (DHCC)

G. Fountos (1), I, Schina (2), L. Disnitsas (3), E. Kounadi (4), G. Papedopoulos (3). (1) Department of Medicat Physics. Pammakaristos General Hospital of Athens, Greece; (2) Department of

J. Meller, G. Altenvoerde, K. Lehmann, C. Sahlmann, I. Meyer, M. Behe, H. Luig, W. Becket. Department of Nuklear Medicine, University of

Nuclear Medicine. University Hospital of Ioannina Greece; (3) Department of Anaesthesiology. University Hospital of Ioannina Greece; (4) Department of Medical Physics. Alexandra General Hospital of Athens, Greece Reflex Sympathetic Dystrophy Syndrome (RSDS) is a malfunction of the sympathetic neural system causing movement dysfunction in acroteria. These symptoms are accompanying with pain, swelling in an extremity, vasomotor instability and dystrophic skin. Diagnosis of (RSDS) have difficulties despite that have described from the past century. The scintigraphy as a method of diagnosis rely mainly in enhanced periar~icular radionuclide activity in affected extremity in three phase bone scan. Aim of this study is to investigate the sensitivity of the diagnostic method when using MDP-99mTc scinfigraphy combined with NANOCOLL99mTc scintigraphy instead of MDP-99mTc scintigraphy alone. Also the ability of the method to follow up treatment is investigating. Method: The study was performed in seventy (70) patients ranging from 18 to 67 years. The average age was 42 years. These patients were examined with both scintigraphic methods, 53/70 were examined once only befure treatment, 25/53 suffered from (RSDS) while 28/53 suffered from other disease. 17/70 were examined and aider therapy. The scinfigraphic diagnosis were based in each case by both I) MDP-99mTc dynamic scintigraphy and 2) NANOCOLL-99mTc dynamic scintigraphy. The scintigraphy applied in the acroteria diseased area. Results: I) Three tthase dynamic scinti~ratthv with MDP-99mTc: The increased blood flow in first and second phase was not observed in all patients with (RSDS) while in the third phase in all patients was observed increased uptake of the radionuclide periarticular in joints of the affected extremities. During and ai~er treatment the changes in scintigraphic images were not usefull to following up treatment. 2) Three t~hase dynamic scintfurat~hv with NANOCOLL-99mTc: The increased blood flow ~n first phase was observed in all patients with (RSDS) while in second and third phase we observe that was unable to visualize the structure of vessels and in many cases increased diffusion of the radionuclide in the affected extremity was record. Also in all patients changes in scintigraphic images was observed during and after treatment. Conclusions: The clinical diagnosis of (RSDS) was confirmed using three phase dynamic scintigraphy with MDP-99mTc in all patients while the ct~mbination of the two scintigraphic methods provide increased sensitivity in the diagnosis of (RSDS) and the ability to fullow up treatment.

G6ttingen, Germany. Aim: [18F] 2.-deoxy-2-fluoro-D-glucose (FDG) has been shown to be an effective tracer in the diagnosis of malignant and inflammatory disease. The aim of our study was the prospective evaluation of FDG-imaging with a double head coincidence camera (DHCC) in patients with undetermined postoperative fever (POF). POF was defined as fever >38,3 i C, with unset within the first two postoperative weeks. Methods: This study is a prospective analysis of 15 POF-patiants (18 investigations) who underwent transaxial F-18- FDG- imaging with a double head coincidence camera (DHCC). Imaging was performed one hour following the intravenous injection of 300 MBq FDG. The final diagnosis was established by clinical follow up, X ray studies including high resolution helical CT, magnetic resonance imaging, bacteriological cultures, biopsy and endoscopy. The FDG images were interpreted by two investigators both blinded to the results of other diagnostic modalities. Results: Infection was present in 7 patients (47%; 10 investigations; Group A). In this group FDG-imaging revealed 9 loci outside the surgical wound (inflammation n= 8, malignant disease n=l) responsible for fever. 5 loci were restricted to the surgical wound but only two of these loci represented inflammation (duration of POF> 8 weeks). 3 loci were due to granulation tissue (duration of POF< 8 weeks). In one patient with urosepsis we found a thlse negative FDG-study. Infection could subsequently excluded 8 patients (53%; 8 investigations: Group B). 7 of these patients had a negative scan. In one patient a FDG-accumulation was fuund within the surgical wound but again granulation tissue was present (duration of POF< 8 weeks). Overall sensitivity of FDG-imaging in detecting the tbcus of fever was 91% but specil]ty was only 64% respectively. Conclusion: I. In the context of POF FDG transaxial tomography perthrmed with a DHCC is sensitive in the diagnosis of inflammation and malignant disease within and outside the surgical wound. 2. The specifity of the method of detecting the fucus of fever within the surgical wound is poor and therefore In-Ill white blood cell imaging remains the scintigraphic procedure of choice in the diagnostic work up of POF.

c-

, oi

PS_427

PS_429

COMPARATIVE STUDY OF MONOCLONAL ANTIBODY SCAN (LEUCOSCAN) WITH 99MTC MDP BONE SCAN AND GA 67 .IN DIAGNOSING BONE AND JOINT INFECTION. PRELIMINARY RESULTS

DETECTION OF INFLAMMATORY LYMPH NODES BY TC99M-HIG IN RABBITS

S. Koukouraki (1), A. Velidaki (1), H. Vevouranakis (2), A. HatzipavIou (2), N. Karkavitsas (1). (1) Department of Nuclear Medicine, Crete, Greece; (2) Department of Orthopaedics, Crete, Greece. Aim : the accurate diagnosis of bone and joint infections is very important for the decision of the therapeutic procedures in many clinical conditions, The purpose of this study is to compare the diagnostic accuracy of a new radionuclide scan Leucoscan, with 99mTc MDP bone scan and Ga67 in bone and joint infections. Methods : Twenty two patients with suspected bone and joint infection ( 10 with total hip prosthesis, 4 with knee prosthesis, 2 with vertebral infection and 6 with long bone infection) were included in this study. All patients underwent conventional Rx, bone scan, Ga67 scanning and Leucoscan. Three phase 99mTe-MDP and Ga67 were performed using standard procedures. The monoclonal antibody, Leucoscan was labeled with 25 mCi of 99roTe and was injected intravenously. Planar images were taken lh and 2h p.i using a GE Millenium ? camera provided with a LEGP collimator. The images were evaluated as score I ( no abnormal uptake in the region of interest), 2(probably positive), 3(definitely infected), according the intensity of abnormally increased uptake. Leucoscan results were compared with 99mTe MDP bone scan and Ga 67 scans, The final diagnosis was given by the surgical verification with histupathology or culture. Results : Seventeen of 22 patients had surgically or pathologically proven infection. 5/22 patients were negative for infection .14/17 with proven bone or joint infection had positive Leucoscan, and 12/17 positive Ga67 scanning. 4/5 patients with proven absence of infection had negative Leucoscan and 3/5 negative Ga 67 . Leucosean showed a sensitivity 90% and specificity 80%.and Ga67 87% and 75% respectively. Conclusion: Radiolabelled monoclonal antibody scan (Leucoscan), despite the small number of patients seems m be more sensitive and specific than Ga67 in diagnosing bone and joint infections.

to

,4.1 r'-

EL. Erg0n (1), ME Bozkurt (1), M. Ercan (1), S. Ruacan (2), B. ~;ener (3). (1) Department of Nuclear Medicine; (2) Department of Pathology; (3)

Department of Clinical Microbiology, Hacettepe University, Ankara,Turkey.

tZ

O

Aim: ~mTc-HIG is known to be useful in the detection of inflammatory lesions. It was also

found to be a successful and promising new agent for the visualization of lymphatic system.Our aim was to investigate the feasibility of demonstrating inflammatory lymph nodes with 'r'mTc-HIG. Methods: Ten adult New Zealand rabbits were used initially (Group A).ln baseline study, 37 MBq ~'~Tc-HIG (0.1 ml) was injected in both hind legs of the rabbits and sequential posterior gamma imaging oftbe rabbits lying prone was performed at 5, 30, 60, 90 and 120 min. under a single-headed gamma camera (Toshiba GCA G01 E). One week later, microorganisms (Staph.aureus) were injected in 0.1 ml volume intradermally into the web space between the second and third toes in bilateral hind legs of each rabbit in order to obtain inflammation in the popliteal lymph nodes and after 4 days 37 MBq ~mTc-HIG (0.1 ml) was injected in hind legs of rabbits and sequential imaging was done as described (the second study). Another group of 10 adult New Zealand rabbits (Group B) was injected by the same microorganisms in the right hind legs only. After 4 days seintigraphie imaging was carried out in the same way as described above (the third study). Regions of interests were drawn over the.injection sites and popliteal lymph nodes on each image for semiquantitative analysis. Count rates for each were calculated and decay correction was applied. Time-activity curves were generated to show the percent retention of radioactivity in each region. After seintigraphic imaging, some of the Group B rabbits were killed by intravenous injection of pentobarbitune (100~150 mg/kg). Both left and right popliteat lymph nodes were removed for microscopic examination. Results: The baseline study showed good visualization of lymphatic channels and nodes. In the second study, bilateral popliteal lymph nodes were visualized more prominently than the baseline study. The right popliteal lymph nodes of Group B rabbits were more dominantly and clearly imaged in the third study. Semiquantitative analysis showed higher percentage uptake of radioactivity in the right compared to the left popliteal lymph nodes in Group B rabbits. Microscopic examination demonstrated inflammation in the right popliteal lymph nodes of Group B rabbits. Conclusion: This preliminary study showed that 99mTc-HIG is a new promising agent for demonstration and evaluation of inflammatory lymph nodes.

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• INFECTION AND INFLAMMATION 1 / MISCELLANEA 1 PS_430

PS_432

TC-99M C|PROFLOXAClN IMAGING IN VARIOUS CLINICAL SETTINGS: EXPERIENCE AT INHA UNIVERSITY, SOUTH KOREA

EVALUATION OF PULMONARY ARTERIAL BLOOD FLOW WITH 99MTC-MACROAGGREGATE ALBUMIN FIRST-PASS SCINTIGRAPHY

W. Choe (1), D.Y. Chi (2), M.W. Im (3), M.H. Chung (4), J.S. Ryu (4), J.K. Suh (5), S. Kim (1). (1) Nuclear Medicine; (2) Chemistry; (3) Obstetrics-Gynecology; (4) internal Medicine; and 5 Urology, Inha University, Inchon, South Korea Te-9qm Ciprofioxacin imaging was initiated by Solanki et al (J Nucl Med 34:11qp, 1993). and is an imaging method to differentiate infection from inflammation. Furthermore, it can visualize a focus of infection specific to bacterial infection. Interestingly enough, it also claims to show an area with viable, proti|;erating bacterial population that is actively using DNA gyrase, which the Ciprofloxacin inhibits. The aim of this study was to confirm these characteristics using our own custom-formulated Tc-99m Ciprofloxacin. Methods: PreparationofTc-99m Ciprofloxacin:Two mg of Ciprofloxacin were mixed with I mg of formamidine sulfinic acid in a 10 ml sterile serum vial, and dissolved on a vortex-gene 2 for 3 minutes. Ten mCi of Tc-99m were added to the vial. The air from the vial was evacuated, and the vial was microwaved in a 1000W microwave oven for 12 seconds. It was then cooled at room temperature for 5 minutes. Distilled water was added and filtered prior to intravenous injection. For quality control, instant thin layer chromatography was performed. Imaging: Immediate, I, 4, and 24-hour (in some cases) images of the whole body and/or spot views in the anterior and posterior views were obtained, SPECT images were added when necessary. We have imaged 70 patients in the following clinical settings: patients with 1) orthopedic surgical prosthesis with suspicious bacterial infection, 2) soft tissue infection, 3) female pelvic irtfiammatory disease (PID), 4) pulmonary tuberculosis, and 5) chronic prostatitis. Results: We achieved a 94% labeling efficiency. I) Excellent visualization of the peri-prosthetic infection and verification of the previous reports of others, 2) detection of bacterial infection of the soft tissue in bacteremic patients, 3) verification and localization of PIDs that corresponded to physical examination, 4) visualization of active pulmonary tuberculosis, and 5) more uptake in the area of the prostate in the patients compared with the normal subject were shown. Conclusion: Our custom-formulated Tc-99m Ciprofloxaein is as valid and convenient to use as any other previously reported in visualizing bacterial infection. The data obtained in this study suggests further validation and application of this imaging method in verifying periprosthetic int;~ction, soft tissue infection, PID, and exacerbation of the chronic prostatitis, and in following-up the active pulmonary tuberculosis biologically.

OTHER CLINICAL SCIENCE. MISCELLANEA 1 PS_431 GLUCOSE UPTAKE IS PERFUSION-INDEPENDENT IN RESTING SKELETAL MUSCLE V. Oikonen (1), R Peltoniemi (2), U. Ruotsalainen (3), R Nuutila (1), J. Knuuti (1). (1) Turku PET Centre, University of Turku, Turku, Finland; (2) Dept. of medicine, University of Turku, Turku, Finland; (3) DMI/Tampere University of Technology, Tampere, Finland. Aim: There is some controversy over whether insulin increases perfusion in skeletal muscle and to which extent the increased blood flow would affect muscle glucose uptake. The relations between perfusion and glucose uptake in resting skeletal muscle were studied using positron emission tomography (PET) and [ISF]fluoro-2-deoxy-D-glucose (FDG). Methods: FDG PET data from healthy young men, five in fasting state and five during an euglycem]c hypennsuhnemle clamp ( mUa(kg body weight) mm ), were analyzed using a four-compartmental model with six rate constants k~-I~,and vascular volume fraction V^. The three tissue compartments in this model are the concentrations of FDG in the extracellular space and in the intracellular space, and the intracellular concentration of phosphorylated FDG. Results: The perfusion and endothelial permeability (k 0 was 27 % higher and FDG transport increased three-fold in the insulin studies. Phosphotylation rate (ks) was too high to be reliably measured in the insulin studies. The FDG uptake constant K, calculated as K = klk3ks / (kzlq+kzk~+k3k~) increased six-fold from 0.0016±0.0003 rain "~ to 0.0093±0.0038 rain"t.

Parameter

i k1 k~ VA

Fastin~ 0.017±0.001 0.224:L-0.023

Insulin 0.022±0.007 0,178±0.136

0.039±0.014 0.019±0.012 0.025:'.'.'.~.008

0.123±0.039 0.003±0.004 0.721~.83

0.018±0.010

0.015±0.009

A simple simulation showed that in the fasting state even a I00 % increase in the two perfu-

sion-dependent parameters, k I and k2, causes only a 5 % increase in K, which is in direct relation to glucose consumption by the muscle. During hyperinsulinemia, the increase in K would be 25 %, if glucose transport and phosphorylation were not down-regulated subsequently. Conolusions: The effect of insulin on perfusion to muscle is minimal when compared to its impact on glucose transport. Increased perfusien is not expected to markedly enhance glucose uptake in resting skeletal muscle in healthy and especially not in insulin-resistant subjects.

1186

M. Sapienza (1), F. Hironaka (1), T. Watanabe (1), C. Ono (1), P. Aguirre Costa (1), I. Endo (2), S. Lewin (2), M. Marone (2), C. Buchpiguel (1). (1) Centro de Medicina Nuclear, University of Sao Paulo, Brazil; (2) Hospital Samaritano, Sao Paulo, Brazil. Pulmonary artery blood flow is polsatile, with a systolic and a diastolic peak intervened with a low amplitude retrograde flow. Retrograde flow probably occurs due to wave reflection in arterioles, a level where the available techniques are limited in the evaluation of pulsatility. AIM: The purpose of this study was to develop a scintigraphic method to detect pulsatite events in peripheric pulmonary arteries. METHODS: 10 healthy volunteers (34:1:10 year old, 2 males) underwent a first-pass study using '~"Tc-MAA, with high temporal resolution (16 frames/see) and ECG eoregistration. Systemic shunt was excluded by whole body images. A time-activity curve (TAC) was generated for the lateral third oftbe right lung, and 4 to 6 heartbeats were selected in the phase with the highest slope in lung activity. Lung activity variation during these heartbeats depends only upon arterial flow and, as a result, the first derivative oftbe TAC mirrors pulmonary arterial flow. RESULTS: TAC derivative shows two positive peaks (anterograde flow) and a negative peak (retrograde flow) between them, that was statistically significant by Poisson based statistics. The retrograde flow in the lateral third oftbe lung is higher than that described in central vessels, and similar to the one calculated by mathematical models. CONCLUSION: Although still under investigation, the method described can increase our understanding of pulmonary llow polsati]ity in physiological and pathological conditions.

PS_433 PREFERENTIAL VAGINA TO UTERUS PHYSIOLOGICAL CONNECTIONS EVALUATED BY SERIAL RADIONUCLIDE SCAN G. Rubini (1), E. Cicinelli (2), D. Rubini (1), A. Niccoli-Asabella (1), M. Mete (1), P. Gatantino (2), A. D'Addabbo (1). (1) Department of Nuclear Medicine; (2) I Department of Gynecology and Obstetrics, University of Bad, Italy. Aim: The aim of the study was to investigate in vivo and in humans preferential physiological connections between the vagina and uterus in post-menopausal woman by serial scintigraphic evaluation. Material and Methods: In pre-surgical (hysterectomy for benign disease) assesment phase 5 postmenopausal women received one vaginal administration of 0,2 ml of 99mTcPertechnetate corresponding to 15 MBq. Before administering the radionuclide, in 2 pts, the cervical canal was sealed by means of surgical glue. The biodistribution and kinetics of the radionuclide were monitored from radionuclide administration for 6 hours. Anterior and right lateral views (128 matrix, pre-set time:300 see) of the pelvis and anterior view of the neck and abdomen were collected every 30 rain. Redionuclide distribution was assessed in the area of administration and in the whole body. The biodistribution of intravaginat administration compared to intravenous injection was evaluated. As a control, uterine and extrapelvic organ uptake of the same radionuclide was evaluated at~er intravenous administration in 5 postmenopausal woman undergoing thyroid scintigraphy. Results: A~er intavaginal administration radioactivity was found only at the injection site for 60rain. After 60 rain the uterine activity began to appear and gradually reached the maximum at~er 180 rain. In 3 pts uterine activity was maximal at 180 and in 2 pts at 210 min, then gradually decreased. ARer 330 min no uterine uptake was detectable. The 2 pts with occluded cervical canal showed the same biodistrthution and kinetics as pts in whom the cervical canal had not been occluded. Extrapelvic uptake in the thyroid, salivary gland and stomach was detected in all pts but with a delay of 30 min after uterine visualization. In thyroid the uptake stazted 210 rain and reached the maximum at 360 and than decrease, A lower uptake was detected in salivary glands and stomach with same time course, l,v. administered radiopharmaceuticals showed no uierine uptake, while thyroid salivary glands and stomach uptake was rapid and massive after just 30 min. Conclusions: This study demonstrates the possibility of vaginal absorption of 99mTcPertchnetate as well as other pharmaceuticals. It is mediated by vaginal absorption of substances and subsequent preferential transfer mechanism to the uterus and not simply by cervico-uterine canal passage. The results of the study demonstrate ,,in vivo" and in humans, and specifically in postmenopausal women that there are preferential vagina-to-uterus vascular connections and gives an insight in to the mechanisms underlying this phenomenon.

• OTHER CLINICAL SCIENCE. MISCELLANEA 1 PS_434

PS_436

SCINTIANGIOGRAPHY IN THE EVALUATION OF PERFUSION IN NECROTIC TOES

EVALUATION OF EXTRAPULMONARY GA-67 UPTAKE IN SARCOIDOSISoA RETROSPECTIVE ANALYSIS

P. Ylikangas (1), T. Lantto (2), R. Mokka (3). (1) Department of Clinical Chemistry and Nuclear Medicine, P~ij~,t-H&me Central Hospital, Lahti, Finland ; (2) Department of Laboratory Centre, Tampere University Hospital, Tampere, Finland; (3) Department of Surgery, P&ij~.t-H~me Central Hospital, Lahti, Finland.

N.O. K0~:0k, E. Ozkan, B. Gulev, G. Aras, M.K. Kit. Department of nuclear medicine, Ankara University, Turkey.

The aim of this study was to evaluate the perfusion in clinically necrotic or blue, cold toes by seintiangiography. M e t h o d : 93 toes in 10 patients were imagined and the case records of the patients were studied retrospectively. 28 of 93 toes were clinically blue or in such necrosis that resulted into amputation within one month after the scintigraphy. 740 MBq 99m-Tc-pertechnetate was injected.into a superficial vein of arm. Potassium perclorate was given orally before the injection to inhibit the accumulation of radiuaetivity in thyroid gland. Dynamic imaging of feet was done during circulation, and a static image was taken patient's feet against the collimator. The heads of the toes were marked with cobolt pen. Results: There was no perfusion in scintiangiography in 25 of 28 clinically necrotic toes (true positives). We did not find any clinically vital toe, which was not perfused in scintiangiography (no false positive findings). In 3 of 33 later amputated toes, perfusion was normal in scintigraphy (false negative findings). 2 of those 3 toes were blue, not necrotic. 65 of 93 toes were clinically normally perfused, and the perfusion in scintiangiography was normal too (true negatives). The sensitivity of scintiangiography in this study was thus 89% and the specificity was 100%. In addition, we imagined a patient, who had serious ischemia in his toot. 4 of 5 toes were clinically black, but the perf~sion in toe was normal in scintiangiography. The patient went through a vascular by-pass operation, which improved the circu[ation in his foot, and no amputation was done, Conclusions: Scintiangiography is a simple, non-invasive method for evaluation of the peripheral perfusion in feet. If the toes look necrotic, but have some perfusion left in scintiangiography, a vascular by-pass operation may be considered to improve the circulation in a foot in some cases. No false positive scintiangiographic images were found.

Ga-67 whole body imaging is frequently used in the diagnosis and prognosis of sarcoidosis. According to the disease activity pulmonary involvement is most commonly seen but it can also involve other organs (%10-15). Ga-67 scintigraphy at 47 patients with sarcoidosis was investigated to evaluate the extrathoracie involvement retrospectively. 10/47 (21%) patients had normal Ga-67 whole body scintigrsphy, 14/47 (30 %) had hilar and mediastinal uptake ( ambOa sign ) and 15/47 (32 % ) had only hilar uptake and 3/47 (6 % ) had only mediastinal uptake, 5/47 ( 1I% ) had diffuse lung parenchymal uptake. In the examination of extrathoracic involvement ; the most characteristic extrapulmonary uptake panem was the 'panda sign" in 11 patients (23 %). The most common site of prominent extrapulmonary uptake was the lacrimal glands in 21 patients (45 %). The lymph node uptake was observed in 9/47 patients ( 3 inguinal, 3 supraclavicular, 1 axillary, 3 abdominal 19 %) 4/47 patients had articulary uptake ( 1 knee, 3 shoul- der, 9% ). Breast uptake was seen in one patient and one had cranial uptake Ga-67 whole body scintigraphy demonstrates not only pulmonary but also extrapulmonary involvement, and helps the clinician to evaluate the extension and activity of the disease.

c, om

PS_435

PS_437

DACRYOSClNTIGRAPHY IN THE EVALUATION OF N A S O L A C R I M A L DUCT PATENCY

B I O C H E M I C A L AND DENSITOMETRIC EVALUATION OF POST-MENOPAUSIC OSTEOPOROTIC PATIENTS SUBMITTED TO ANTI-REABSORPTWE TREATMENT DURING ONE YEAR

P.S. Sundaram (1), S. Padma (1), R Ravi (2), N. Jaganath (3). (1) Nuclear Medicine, Amrita Institute of Medical Sciences & Research Centre, Cochin, India; (2) Nuclear Medicine, S V Institute of Medical Sciences, Tirupati, India; (3) Ophthalmology, S V R R Hospital, Tirupati, India. PURPOSE: Dacryocystitis is a common ophthalmic clinical condition in certain parts of India which is due to inflammation of lacrimal sac. It is a chronic condition usually involving the lower strata of society which can be easily controlled on early diagnosis, Dacryoseintigraphy can be instrumental in the diagnosis of nasolacrimal duct obstruction which leads to dacryocystitis.lt is a simple, easy to perform imaging modality which is an alternative to dacryocystography , an invasive non physiological radiological procedure .The purpose of presenting this study is to highlight ; The extreme sensitivity & simplicity of this imaging modality. The high incidence of dacryocystitis in low socio-economic segment of Indian population. The physiologic basis of this investigation. METHODS: A total of 55 patients were screened, of which 40 were symptomatic and the rest (I 5) constituted the control groop.99m Technetium Pertechnetate (TcO4) was instilled at the lateral canthus simultaneously in both eyes.Dynamic and late static images were acquired using a single head Gamma Camera with High Resolution Collimator. RESULTS: Bilateral obstruction were noted in 22 patients of whom 9 had clinically unilateral Presentation. Unilateral obstruction was seen in 18 patients ( right = 8 & left = I0 ). CONCLUSION: We inferred from our studies that; a) Number of cases of bilateral obstructions exceeded unilateral cases .b)Peak incidence was found in middle aged females. C) It was closely associated with low income group, d) Members of the same family should be closely assessed, e) Bilateral obstruction are prevalent in unilateral clinical presentation. Time, manpower and equipment should not be a constraint in performing this simple inexpensive investigation. Dacryoscintigraphy is physiological, non-invasive and has better patient compliance. So, screening of families should be undertaken by dacryoscintigraphy to enable early diagnosis of this condition. During imaging high resolution collimator is an efficient substitute to conventional pinhole collimator & it is advantageous as both eyes can be imaged simultaneously. It has also been found that image acquisition in sitting posture has an edge over supine position.

A. Rodrigues (1), R Lourenco (1), R Ferreira (2), A. Garrett (1), E. Mourn (1). (1) Laboratorio de Radioisotopos, Faculdade de Medicina, Universidade de Coimbra; (2) Servi~:o de Medicina Ill, Hospitals da Universidade de Coimbra, Portugal. I n t r o d u c t i o n : Osteoporosis is an important public health problem, especially among postmanopausic females due to its morbidity and mortality. Therapy has to be maintained over a prolonged period of time and its resutt can be verified only by radiologic deasitometry after one or two years.

Biochemical markers permit the evaluation of bone metabolism and may therefore be useful in early monitoring oft~atment in order to adjust dosesand to promote compliance. M e t h o d s : Ooe hundred and three post-manopausicwomen mfen'cd from their GP, were randomly assigned to one of three therapoutic groups: 1 - calcium and vitamin D; 2 - calcium and calcitonin; 3 - calcium and alendronate. Levels of bone alkaline phosphatase (BAP), ostoocalcin (OC), deoxypyridinolino (Dpd) and cross-linked N-tetopeptide (NTx) were determined at baseline and after three, six and twelve months of treatment. One year after starting therapy, the lumbar spine, proximal femur and distal forearm were evaluated by DEXA (Hotogic QDR 4500 Elite). Results: The patients treated with alandronate had a significant increase of bone miocral dansity (BMD) in the lumbar spine. After three months there was a statistically significant decrease of BAP and NTx levels in the group treated with alendronate. In these group there was also a statistically significant decrease in the level of all markers determined after twelve months. Conclusions: The group treated with alandronate was the only one to show significant increase on BMD after one year of treatment. In this very group the determination of BAP and NTx levels aficr three months showed a biochemical profile consistent with a response to anti-reabsorptiv¢ treatment.

1187

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• OTHER CLINICAL SCIENCE. MISCELLANEA 1 / NEUROLOGY / PSYCHIATRY 3 PS_438

PS_440

CONTRALATERAL EFFECTS OF ACUPUNCTURE ON REGIONAL CEREBRAL BLOOD FLOW ELOW EVALUATED BY 99M TC-ECD

GALLIUM-67 SPECT SClNTIGRAPHY IN THE DIAGNOSIS

BRAIN SPECT AND STATISCTICAL PARAMETRIC MAPPING

H.-.C. Song (1), S.M. Kim (1), H.S. Born (1), S.G. Ahn (2), H.J. Kang (3). (1) Department of Nuclear Medicine, Chonnam National University Hospital, Kwangju, South Korea; (2) Department of Acupuncture & Moxibustion, Coltege of Orienta[ Medicine, Wonkwang University, Kwangju, South Korea; (3) Department of Circulatory Internal Medicine, College of Oriental Medicine Dong-shin Univarsity, Kwangju, South Korea. Purpose: To study correlation of the brain areas with acupoints to evaluate the hypothesis that selecting acupoints on the lelt side to treat disorders on the right side and vice versa is known as the crossing combination of acupoints. Methods: Rest/acupuncture-stimulation ~mTc-ECD brain SPECT using a same-dose subtraction method was performed on 13 normal male volunteers (age range from 20 to 32 years) at acupoint, LI. 4 on the right hand. And 5 normal male volunteers (age range from 27 to 30 years) using acupuncture at acupoint. LL 4 located on the le~ hand. In the control study needle location was chosen on a non-meridian focus lcm posterior to the right fibular head. All images were spatially normalized, and the differences between rest and acupuncture stimulation were statistically analyzed using SPM97 for Windows. Results: Stimulation at LI. 4 located on the right hand increased rCBF in the lel~ hemisphere, mainly the left parietal and frontal lobes, and a part of the lelt temporal lobe Stimulation at LI. .4 located on the left hand increased rCBF in the right hemisphere, mainly the right parietal lobe, and a part of the right temporal lobe. In the control stimulation, no significant rCBF increase was observed. Conclusion: The results demonstrated rCBF increase in the contralateral cerebral hemisphere of acupoint. Therefore, this result suggests that the action mechanism of acupuncture have a neural basis operating through the ascending neural tract crossing the midline at a certain level.

OF TEMPORAL ARTERITIS C.L. Ben - Horin (1), T. Raitblat (2), A. Raitblat (1). (1) Nuclear Medicine

Department; (2) Reurnathologic Outpatients Clinics,, Bar-zilai Medical Center, Faculty of Health Sciences, Ben Gurion University of The Negev, Ashkelon, Israel. Temporal arteritis (TA) is a common syndrome in the elderly, consisting of persistent pain in the temporal area, jaw claudication, sudden visual loss, high erythrocyte sedimentation rate and teademess on palpation in the temporal area. The diagnosis of this condition is relatively straightforward when the typical symptoms and positive temporal biopsy are present. Only half of the patients have positive temporal biopsy. Other diagnostic procedures such as color Doppler sonography or superficial carotid angiography have been proven to be useful for the diagnosis of TA but these techniques do not discriminate between inflammatory and noninflammatory temporal artery disease. Gallium-67 planar scan is known to be useful in the diagnosis of the disease. Quantitative Gallium-67 SPECT may rise the accuracy of the diagnosis. The aim of the study was to check the effectiveness and usefulness of Gallium-67 SPECT scintigraphy in the diagnosis of TA and to diminish the influence of surrounding areas on quantitative relative Gallium-67 uptake estimations. Methods: 8 patients (5 male and 3 female; mean age 65 y) with diagnosed TA and 6 controls (2 male and 4 female; mean age 65 y) were included in the study. All of them received 370 MBq Gallium-67 IV 48 hours before the scan. Gallium-67 uptake ratios were calculated on transaxial and coronal slices for: (1) temporal region/out of temporal area bone (TR/Bone) and (2) temporal region/inside of skull region (TR/Bkg) Prednisolone treatment was started in the diagnosed patients a~er the Gallium-67 imaging was completed• Results: All patients showed increased uptake in the temporal area compared to out of temporal area bone. The calculated ratio was significantly higher in the TA group than in controls:

Transaxial Slices Coronary slices

TR/Bone (SD) TPJB KG (SD) TR/Bone (SD) TPJBkg (SD)

TA 1.31(0.14) 5.46Q.08) 1.47 (0.16) 5.71 (1.14)

Controls 1.04 (0.09) 4.12 (0.47) 1.11 (0,006) 3.86 (0.34)

P <0.001

<0.001
Conclusion: our data suggests that Gallium-67 skull SPECT may be useful in the diagnosis of TA especially if the uptake ratio in the area is calculated. Further studies are needed to confirm these data.

PS_439

NEUROLOGY / PSYCHIATRY 3

DETECTION OF HELICOBACTER PYLORI INFECTION USING 14-C UREA BREATH TEST V. Obradovic (1), V. Artiko (1), M. Petrovic (2), N. Petrovic (1), B. Davidovic (1), V. Bosnjakovic (1), G. Adanja (1), T. Milisavljevic (1), D. Nastic (1). (1) Institute for Nuclear Medicine; (2) Institute for Digestive Diseases, Clinical Center of Serbia. Purpose: Helicobacter pylori infection is supposed to be one of the major causes of digestive and other diseases. Among a lot of invasive and noninvasive methods for its detection, none is ideal. The aim is assessment of the Helocobacter pylori infection in stomach using breath test and comparison to other diagnostic methods. Material and method: 62 patients underwent the breath test (BT) and endoscopy. Biopsy samples (B) were taken from antrat gastric mucosa for histological analysis and rapid ureas¢ test. Afrer mgestton of the C-urea capsule, m the presence of enzyme ureas¢ from H.Pylon, tt is 14 14 broken down into CO 2 and NH 3, CO= is absorbed and is exhaled by the lungs. Radioactivity in the collected exhaled air is detected using beta counter before (background activity) and 30 rain afrer ingestion of the capsule. Significant increase of the activity indicates the presence of this bacterium. Results: According to our results, the rise of over 100% of activity over background was considered as positive. 17 patients were both B and BT positive, 41 both negative, one was breath test indeterminate and histology +, one was breath test indeterminate and histology - , while two were breath test positive and histology r~egntNe. Sensitivity was 94%, specificity 93%, positive predictive value g9%, while negative predictive value was 100%. Conclusion: Breath test can be useful in diagnosis but is a method of cboiea in following up the patients alter therapy for H.pylori infection, because it is nonivasive, fast and precise. •

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PS_441 CEREBRAL BLOOD FLOW SPECT IN ELDERLY LATE-ONSET MAJOR DEPRESSIVE DISORDER. PRELIMINARY RESULTS F. Martin (1), F. Lomefia (1,3), V. Navarro (2), J. Mateos (1), C. Gasto (2), J. Pavia (1,3), M. Ortega (1), F. Pons (1.3), T. Marcos (2). (1) Department of Nuclear Medicine; (2) Department of Psychiatry; (3) IDIBABS, Hospital Clinic, University of Barcelona. AIM: Depression is the most prevalent psychiatric disorder among the elderly. Olten it is difficult to differentiate clinically a progressive degenerative dementia from a depressive disorder combined with cognitive impairment. Our aim is to determine the changes in the regional cerebral blood flow in elderly patients with late.onset major depression and evaluate the utility of brain SPECT in the clinical management of these patients. METHOD: We studied prospectively with Tc~m-HMPAO SPECT 42 unmedicated patients over 60 years, presented consecutively at the Psychiatric Department of our hospital with lateonset unipolar major depression. All the patients fulfilled DSM-IV criteria for major depressive event for at least one month, No patient showed cognitive impairment (Mini-mental State Examination score >25), The severity of depression was rated using the Hamilton Depression Rating and Newcastle Scales. The SPECT was performed with a dual-head gammacamera (Helix, GEMS), with high resolution fan-beam collimators. A visual analysis was performed from the SPECT images. In the first 30 patients who responded to the antidepressive treatment, we performed retrospectively a semi-quantitative analysis using a template of anatomical ROls placed over ten 7.8ram thick frontocerebeller slices to calculate regional uptake ratios (cerebellum as reference). We used as a control group, 20 sex-age-and vascular risk factor-matched healthy subjects. RESULTS: The SPECT was visually normal in 18/42 and abnormal in 24/42 patients (frontal region lower uptake=9, basal ganglia lower uptake=6, frontal and basal ganglia lower uptake-~)). The patients who responded to the antidepressive therapy showed statistically low uptake ratios only in the left anterior frontal region (94.84.+.3.52 vs 100.25+9.88; p<0.O01) and in the right frontal region (98.03.+.3.12 vs 101.35+3.27; p<0.001). No correlation was found between the anterior frontal uptake ratios and the demographic and clinical characteristic. CONCLUSIONS: Our results suggest that the patients with late-onset unipotar depression may have lower cerebral blood flow in the anterior frontal region that the elderly without depression. Nevertheless, brain SPECT was visually normal in 43% of depressive patients and this is a relevant fact for their clinical management.

• NEUROLOGY / PSYCHIATRY 3

PS_442

PS_444

EFFECT OF MODIFIED GROUP PSYCHOTHERAPY AND FLUOXETINE TREATMENT ON SEROTONIN TRANSPORTERS IN OBESE BINGE EATING WOMEN

RELATIONSHIP BETWEEN CEREBRAL BLOOD FLOW AND GLUCOSE METABOLISM IN NORMAL SUBJECTS AND SCHIZOPHRENIC PATIENTS

J.T. Kuikka (1), K. Bergstrom (1), L. Tammela (2), L. Karhunen (2), A. Rissanen (3), E. Vanninen (1), E. Repo (2), J. Hiltunen (4), H. Naukkarinen (3), J. Tiihonen (2), M. Uusitupa (2)(1) Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; (2) Departments of Clinical Nutrition and Forensic Psychiatry, University of Kuopio and Kuopio University Hospital, Kuopio, Finland; (3) Department of Psychiatry, Helsinki University Hospital, Helsinki, Finland; (4) MAP Medical Technologies Oy, Helsinki, Finland

S. Mizuno (1), T. Mornose (1), A. Abe (1), S. Oku (1), Y. Kurnakura (1), Y. Kojima (1), Y. Nakashima (2), K. Ohtomo (1). (1) Department of Radiology, University of Tokyo, Tokyo, Japan; (2) Department of

Aim: Serotonin transporter density has been shown to be decreased in obese women with binge eating disorder. In order to investigate the effect of treatment on serotonin transporters we performed SPET imaging with iodine-123 labelled nor-~-CIT with obese binge eating women before treatment and after the modified group psychotherapy and fluoxetine medication. Methods: Five obese women with binge eating disorder were studied. Their mean age was 38 year (range 32 - 53 year). A dose of 180 - 2 I0 MBq of I-123 nor-~-ClT, which can be used as a tracer for SPET to visualise serotonin transporters in the brain was intravenously injected into the subjects antecubital vein. Scans were performed using a Siemens MuhiSPECT 3 gamma camera with fan-beam collimators. The specific binding was calculated from the 24 h images as (midbrain - cerebellum) / cerebellum. Alter the first study the subjects participated modified group psychotherapy and were treated with 40-60 mg/day fluoxetine tbr several months. The SPET study was repeated 9 - 18 months later. Fluoxetine medication was stopped 3 months before the second SPET study. Results: There was a significant increase in 1-123 nor-~-CIT specific binding for serotonin transporters after the modified group therapy and fiuoxetine treatment when compared to the baseline (2.42 + 0.46 vs. 1.92 + 0.34; mean + SD; t = 2.24, p < 0.05). Conclusion: To our knowledge, this is the first time to show the effect of combined group psychotherapy and fluoxetine treatment on serotonin transporters in obese binge eating women. The results tentatively suggest that the serotonin transporter density can be et'fected and the specific binding for serotonin transporters increases in obese binge eating women alter the treatment.

Psychiatry, Mitsui memorial hospital, Tokyo, Japan. Aim: Since Roy and Sberrington, relation between blood flow and metabolism is an important issue in neurological sciences. Although coupling between I2ow and metabolism in whole brain was demonstrated in animals, it remains unclear whether or not flow-metabolism coupling exists regionally in human. In this study, we performed positron emission computed tomography (PET) to determine the relationship of regional distribution between cerebral blood flow (CBF) and glucose metabolism in normal subjects and schizophrenic patients. Methods: Ten normal subjects without any previous history of psychiatric disease and ten non-hospitalized medicated schizophrenic patients were studied. We obtained quantitative measures of regional cerebral blood flow (rCBF) and regional glucose metabolism (CMRglu), using water labeled with oxygen- 15 (O- 15 H:O) and fluoro deoxy glucose (F- 18 FDG) at rest under identical conditions and analyzed the distribution of CBF and glucose metabobsm using statistical parametric mapping 99 (SPM99) in each group respectively. We also compared the results of this statistical analysis with regions of interest (ROI) studies. Results: GIocose metabolism was statistically higher than CBF in the cerebral cortex and stratum (p<0.01) and lower than CBF in the hippocampus and cerebellum (p
co

PS_443

PS_445

ASSESSMENT OF CHANGES IN REGIONAL CEREBRAL BLOOD FLOW IN PATIENTS WITH UNIPOLAR AND BIPOLAR DEPRESSION USING TC-99M*HMPAO SINGLE EMISSION TOMOGRAPHY

LOW STRIATAL DOPAMINERGIC D2 RECEPTOR OCCUPANCY: A MAIN DIFFERENTIAL CHARACTERISTIC OF ATYPICAL ANTIPSYCHOTICS?

M. Kula (1), A. Tutu~ (1), E. Esel (2), T. Turan (2), AS. Gbn01 (2), M. Reyhancan (2), M. Ba~t0rk (2). (1) Department of Nuclear Medicine; (2) Department of psychiatry, Erciyes University, Kayseri, Turkey.

A. Tembl (1), I. Corripio (2), A. Catafau (1), Y. Aguilar (1), JC. Martin (1), D. Puigdemont (2), V. Camacho (1), E. Mena (1), V. P~rez (2), I. Carri6 (1). (1} Department of Nuclear Medicine; (2) Department of

The aim of this study was to compare regional cerebral blood flow (rCBF) in patients with unipolar and bipolar depression to that of healthy subjects and to examine the relationship between rCBF and depressive symptoms. Method: Eleven patients (6 M, 5 F; 48.18+9.17 yr) who met the DSM-IV criteria for major depressive disorder (recurrent) and 8 patients (4 M, 4 F; 39.42:1:11.08 yr) diagnosed with bipolar 1 disorder-depressive episode were included in the study. Control group consisted of age and sex matched healthy volunteers (25.56:t:8.76 yr). To evaluate the severity of the clinical symptoms of the patients, Hamilton Rating Scale for Depression (HAM-D), Clinical Anxiety Scale (CAS), Mini Mental State Examination (MMSE), and Brief Psychiatric Rating Scale (BPRS) were performed. All the patients had been free of psychotrophic medications for at least 2 weeks before Tc-99m HMPAO brain SPECT study. The SPECT imaging was performed after 20 minutes following the injection of 550 MBq Tc-99m HMPAO. For the semiquantative analysis of the data, rectangular region of interest (ROI) drawn over upper and lower frontal, temporal, parietal and occipital regions were used to obtain activity ratios, taking cerebellum as reference. Mean cortical/corebetlar ratios (C/c) calculated for each ROI in patient and conlrol groups. Results: We found that rCBF values decreased in bilateral frontal, left temporal and lez2 parietal areas in the unipolar depressive patients compared to the controls. Bipolar patients exhibited lower rCBF values than those of the controls in all brain regions investigated except occipital cortices. No significant differences in rCBF emerged between the bipolar and the unipolar patients. Negative correlations were found between the fight parietal rCBF and CAS scores (r= -0.726, p< 0.05), and between length of illness and the left parietal rCBF (r= 0.720, p< 0.05) in unipolar patients. Conclusion: These data reveal that both the patients with unipotar and bipolar depression show reduced rCBF in frontal, temporal and parietal regions, and support the idea that this finding is a common feature of various depression subtypes.

Psychiatry, Hospital Sant Pau, Barcelona, Spain. Mechanism of action of antipsychotics has been related to striatsl dopaminergie D2 receptor (D2R) occupancy. A low incidence of extrapiramidal symptoms (EPS), which might be explained by a low D2R occupancy, has been proposed as the main differential characteristic of atypical antipsychotics in comparison to tipical antipsychotica. However, whether low D2R occupancy is a differential characteristic of atypical antipsychotics h a still not been demostrated, AIMS: 1) To compare D2R occupancy induced by different atypical antipsychotics with the typical antipsycbetic hatoperidol, using J23I-IBZM brain SPECT. 2) To investigate the relationship between D2R occupancy and EPS. METHODS: I'~]I-IBZMSPECT was carried out on 39 patients diagnosed with psychotic disorder (DMS-IV), who were under treatment with stable doses ofdifferant antipsychotica (12 hours al~er the last dose): haloporidol (n = 8, 10-20 reg./d); risporidone (n = 18, 3-9 reg./d); ziprasidone (n = 8, 80-160 reg./d); olanzapiee (n =3, 5-10 reg./d) and clozapine (n = 2, 200-250 reg./d). Percentages of D2R occupancy were calculated by means of basal ganglia/occipital (BGO) uptake ratios and applying the following formula: 100-(100*(BGO-1)/(1.84-1)), being 1.84 the average BGO value previously obtained from 9 drug-naive patients. EPS were evaluated using the Sympson-Angus scale. RESULTS: Percentages of D2R occupancy were: haloperidol, 77.5~:8.4%; risperidone, 61.6~:16.4%; ziprasidoee, 51.2.~:I9.3%; olanzapine, 52.4±29.1%; clozapine, 22.0"~4.2%. Significant differences between haloperidot-ziprasidene, haloperidol- clozapine and risperidone-clozapine ( ANOVA, p< 0.001, post-hoc ScbetY? p< 0.05) were found. No statistically significant differences were found between haloperidol and risperidooe. Olanzapine showed highly variable percentages of D2R occupancy (22.6, 53.5 and 80.9%). Patients on atypical antipsyehotica showed much less EPS than patients on haloporidol. Whereas EPS were present in all patients on haloperidol and in 2/3 patients on olanzapine, only 9 patients on risperidone, 2 on ziprasidone, and none on clozapine showed EPS. No relationship was found between D2R occupancy and EPS (Sympann.Angus scale scores), neither with haloperidol nor with atypical antipsychotios (Spearman correlations, p NS). CONCLUSIONS: This study shows that not all atypical antipsychotics present a low degree of D2R occupancy, and that EPS are not dependent on the degree of D2R occupancy. Therefore, a low D2R occupancy seems not to be a main differential characteristic of atypical antipsychotics. These results suggest that the low incidence of EPS presented by atypical antipsychotias is not explained by a low D2R occupancy. Other recently proposed mechanisms, such as the kinetics of drug-receptor interaction, may account tbr the mechanism of action of atypical antipsychotics. (FIS 00/0335)

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• NEUROLOGY / PSYCHIATRY 3 PS_446

PS_448

CEREBRAL BLOOD FLOW CHANGES DURING RETRIEVAL OF TRAUMATIC MEMORIES BEFORE AND AFTER PSYCHOTHERAPY

ELEVATED BRAIN MONOAMINE TRANSPORTER AVAILABILITY (SEROTONIN) IN CHILDREN WITH ASPERGER SYNDROME

A. Newberg (1), J. Peres (2), J. Carnpos (3), M. Pares (3), A. Magalhaes (2), M. Pares (3), R. Cavini (3), M. Simao (3), J. Moll Neto (2), R. Veras (2). (1) University of Pennsylvania, USA; (2) Instituto Nacional de Terapia Regressive Vivencial Pares; (3) Departarnento de Psiquiatria da Faculdade de Medicine de USR

K.A. Ahonen (1), M. Dahlstr6m (2), H. Ebeling (2), S.L. Linna (2), J. Heikkil& (3), M. Kielinen (2), R Torniainen (3), E. Jansson-Verkasalo (3), T. TepiD (3), I. Moilanen (3). (1) Division of Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland; (2) Department of Pediatrics, Clinic of Child Psychiatry, University of Oulu, Oulu, Finland; (3) Division of Nuclear Medicine, University of Oulu, Oulu, Finland.

Aim: Exposure to stressful events often determines how people subsequently organize their perceptions of themselves and of others. Traumatic experiences have been linked to difficulties in emotional and psychological development• Exposure-based therapy for reduction of emotional response to traumatic memories is effective when the traumatic event is comprehended and in a new schematic representation of reality. However, no previous studies have investigated the neural substrates which mediate the psychotherapeutic process in the scope of the traumatic memories• In this study, ECD SPECT was utilized to determine if such therapy would alter cerebral blood flow associated with the retrieval of primary traumatic memories. Methods: Six patients with traumatic memories were examined with SPECT using equal doses of 99Tc-ECD in two studies, one during the first psychotherapy session while the patient retrieved the traumatic emotion-laden memory (emotion state). The second SPECT scan was done during the retrieval of the same traumatic memory after sixty days from the psychotherapy session (non-emotional state). Each of the brain scans were resliced in the same plane and regions of interest (ROI) were overlayed onto each scan. Values were generated for each ROI and normalized to the average whole brain activity. The percentage change between the baseline and activation state was calculated as well as correlations between changes in activity• Results: There was a significant decrease (p<0.05) in activity in the parietal lobes during the first memory retrieval (emotion condition) with the right decreased by a mean of 10% and the left decreased by a mean of 7%. There was also a significant decrease in the activity in the left hippocampos by 1 I% (p<0.05) during the emotional condition• There was also a significant positive correlation between the change in activity (between the two conditions) in the left prefrontal cortex and the change in the left thalamus (R=0.92, p=0.01); and also between the change in activity in the left prefrontal cortex and the change in the left parietal lobe (R=0.88. p=0.02). Conclusions: The present study demonstrated several changes in cerebral blood flow associated with the retrieval of traumatic memories before and after psychotherapy• These findings indicate that psychotherapy has an important role in revisiting painthl, traumatic memories in order to restructure the basic beliefs about these memories for the patient regain a sense of control and safety• Furthermore, these effects are associated with a measurable change in cerebral function•

Aim: Asperger syndrome has now been defined as a diagnostic entity, where genetic factors play a significant role. It is a form of pervasive developmental disorder (PDD), and has thus some common features with autistic disorder. Methods: We examined 41 drag-naive children and adolescents (aged 7-17)with various neuropsyehiatric disorders (non-PDD including 31 patient depression present and 10 without depression) and 12 children (aged 7-12) with Asperger syndrome using 1-123 beta-ClT in SPET imaging of brain monoamine transporters. Imaging was carried out using a dual head gamma camera equipped with fan beam collimators. The first scans were taken at one and four hours (a~:peak value times) mainly revealing serotonin transporters (SERT) in thalam/c (TH) and hypothalamic/midbrain regions (HMB). At one day after the tracer injection dopamine transporters (DAT) at equilibrium state in striatal regions (STR) were imaged. Occipital (OWM) and frontal (FWM) white matter regions were used as the reference regions (representing non-displaceable tracer uptake). The significances of the differences between the groups were tested using ANOVA and t-test with Bonferroni method• Results: SERT binding ratios (HMB/OWM) at one hour in HMB were in Asperger syndrome 1.48L,'0.09 (mean+sd). Correspondingly, in non-PDD depressive pts revealed SERT ratio values 1.28+0.11 and pts without depression 1.18-4"0.12. Children with Asperger syndrome had highly significantly increased SERT values in comparison with depressive and nondepressive children and adolescents (ANOVA F=20.34, p=0.000). Also at four hours in HMB region differences in SERT values between previous groups were also statisticaIly highly significant. Contrary to those results at one day in HMB region statistically significant difference could be found only between Asperger and non-PDD depressive pts, but surprisingly, SERT values were even lower in Asperger syndrome (I.94:LO.19) compared with non-PDD depressive pts(2.27-L-0.33)! In TH region SERT ratios revealed no significant differences. DAT binding ratios (STR/OWM) at 24 h in STR were 9.1+0.7 in pts with Asperger syndrome and correspondingly in non-PDD pts; 9.15+1.25 in pts with depression and 9.11+1.24 without depression. Conclusions: Our findings in Asperger syndrome suggest highly significant increase in SERT availability in HMB region at the optimal imaging times (at one and four hrs) compared to patients with non-PDD (l~3th depressive and non-depressive children and adolescents)• Our preliminary SERT imaging results are first ones published indicating the possibility of biochemical disturbances behind Asperger syndrome and supporting the idea of hereditary background of this disease.

PS_447

PS_449

STATISTICAL PARAMETRIC MAPPING ANALYSIS WITH 99MTC-ECD SPECT IN OBSESSIVE COMPULSIVE DISORDER PATIENTS

TC-99M-HMPAO SPECT FINDINGS IN DRUG ABUSE HEADACHE

P. Li, X. Jiang, WAHUA Guo, LINGLI Zhang, CHENMO Zhu. Department of Nuclear Medicine, Ruijin Hospital, Shanghai Second Medical University, Shanghai, China. This study is to investigate alternations in regional cerebral blood flow (rCBF) in obsessive compulsive disorder (OCD) patients using statistical parametric mapping (SPM). Method: • ~m • . rCBF measurements usmg Tc-ethyl cystemate dtmer (ECD) SPECT was performed on 14 OCD patients and 23 agn-matched healthy volunteers. The rCBF distribution was compared in these two groups with SPM under the conditions of increased and decreased perfusion, and with regions o f intarest (ROls) using cerebral template. P value was set at 0.Ol lever. Result: SPM analysis showed that tCBF decreased in cerebral areas including bilateral putamen, superior temporal gyms and precuneus, and right orbital gyms, superior and middle frontal gyrus, and left temporu-occipital Iobul¢ and superior parietal gyrus, and vermis, rCBF was also increased in left inferior frontal gyrus and posterior corpus callosom. With ROls method, rCBF was decreused in right anterior frontal and temporoparietal Iobul¢, and left temporooccipital Iobule. Conclusion: Our study supported the viewpoint that rCBF abnormality of frontostriatal circuits was involved in OCD patients. SPM method is a forceful tool in analyzing cerebral regional character.

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T. BasoOlu, F. Canbaz, T. Ozbenli, M. ~;ahin, S. Albayrak. Department of Nuclear Medicine Ondokuz Mayls University Hospital, Samsun. Turkey. Analgesic drug abuse is commonly observed in chronic headachepatients. Abuso of various compounds frequently leedsto a state of dapendancy.lthas bcea suggestedthat the most frequent cause for the transformation of a periodic headache into a daily headache is drug abuse.Our aim was to evaluate the cerebral cortical perffLsion in patients with drug abuse headache(DAH). Methods : 30 patients(M/F = 3/27, 38 ± 8.9 years, drug abuseperiod =13 ± 5 months) with the diagnosisof DAH underwentSPECT imaging 30 minutes following Lv. administration of 555 MBq of 99mTc -HMPAO before and after prophylactic treatment. The second imaging was performed after ceasing the abused drug and treatment with propranolol or valpronat during one month.Counts were obtained from regions of interest drawn around a total of 45 brain regions and the ratios to eerebellar counts were calculated. Results :In the initial study, no significant ( p > 0,05 ) uptake esmmetry was found between the hemispheres, neither focal uptake anomalies were observed in the medial single regions. The global baseline / post-treatment comparison of the quantified results showed significant ( p <0,05 ) decrement of tracer uptake in 12 of 45 brain regions .Visual evaluation showed regional post treatment hypoperfusion in 9/30 patients. Clinically,19 of 30 patients had a dacreament of headache. 7 of 9 patients showing visually post-treatmeat hypoperfusion, presented also with clinical improvement after hreatment. Conclusions: No significant cortical Tc-99m-HMPAO uptake asymmetry and no focal uptake anomaly was observed during drug abuse. Treatment with propranolol or valpronat appears to have a positive clinical effect on DAH. A relation between rCBF and DAH could only be partially demonstrated. The finding of regional post-treatment hypoperfusion needs to be further clarified.

• NEUROLOGY / PSYCHIATRY 3 / PRECLINICAL STUDIES PS_450

PS_452

ABNORMAL NEURONAL NE'I3NORK IN ANOREXIA NERVOSA WITH

IN VIVO EVALUATION OF SEROTONIN-2A RECEPTORS IN NORMAL CANINE BRAIN: ASPECT STUDY WITH A SELECTIVE 5-HT2A RECEPTOR LIGAND LABELLED WITH 1231

1-123-1MP SPECT T. Takano (1), T. Shiga (1), N. Kitagawa, T. Koyama, C. Katoh (1), E. Tsukamoto (1), N. Tamaki (1). (1) Department of Nuclear Medicine; (2) Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, JAPAN. The etiology of anorexia nervosa is not thlly understood, but probably consists of multi factors, including biological factors. Aim: We assessed the brain perfusion SPECT findings in patients with anorexia nervosa and normal controls by statistical parametric mapping Methods: Fourteen patients wi~'h anorexia nervosa and eight healthy female volunteers were enrolled. They underwent brain SPECT scans with Iodine-123- iodoamphetamine (I-123IMP). The automatic voxel-based analysis on the CBF-SPECT images was carried out using Statistical Parametric Mapping sollware (SPM96 for windows). Statistics across the entire brain were displayed as Z scores (threshold: p<0.05). Results: The statistical parametric image of Z value indicated the patients with anorexia nervosa had hypoperfusion in the region including the medial prefrontal cortex and the anterior cingulate (Zmax= 3.19) and hyperperfusion in the thalamus and the amygdala-hippocampus region(Zmax= 3.50) when compared with healthy volunteers. Conclusion: The CBF abnormality in anterior cingulate and thalamus may be due to the dysfunction as neuronal network. These results suggest the dysfunction in the neuronal circuits may be related to the anorexia nervosa.

K. Y. Peremans (1), K. Peremans (1), K. Audenaert (2), R De Bondt (3), C. Van de Wiele (2), F. Dumont (4), E Jacobs (2), G. Slegers (4), F. Verschooten (1), H. van Bree (1), R. Dierckx (3). (1) Department of Medical Imaging, Faculty of Veterinary Medicine, University of Ghent, Belgium; (2) Department of Psychiatry and Medical Psychology, University Hospital Ghent, Belgiume; (3) Division of Nuclear Medicine, University Hospital Ghent, Belgium; (4) Laboratory of Radiopharmacy, Faculty of Pharmaceutical Sciences, University of Ghent, Belgium I¢ltrodttction: Serotonin (5-HT) is a central and a peripheral neurotransmitter. Impairments of the serotonergic neurotransmitter have been associated with a variety of human mental disorders, including psychotic disorders, mood and anxiety disorders, eating disorders and dementia. In aggressive, impulsive dogs a decrease in 5-HIAA, a metabolite of 5-HT2a, is detected in the cerebrospinal fluid. A highly selective radiolabelled 5-HT2a antagonist, 1231-5-IR91150 was developed for single photon emission tomography (SPET). The feasibility of the tracer was tested in rats, non-human primates and humans. Our aim was to study the l~asibildy of this l igand in the normal dog brain. Methods: Nine healthy shepherd type dogs (4F, 5M), free of neurological disorders and behavioural problems, were included. Age varied between I and 9 years and weight between 23 and 41 kg. The injected activity ranged from 0.11-0.21 mCi/kg .The interval between injection and acquisition ranged from 100 to 120 minutes. Acquisition was performed with a triple head gammacamera (Toshiba GCA-9300A) equipped with high resolution fanbeam collimators. A 153-gadolinium transmission scan was acquired. Images were reconstructed with FBP and a Butterworth-fiher (cut-off 0.16 cycli/pixel, order 8). Sorunsen attenuation correction with a uniform attenuation coefficient of 0.12 /cm and triple-energy window scatter correction were applied. Images were analysed with ROI's drawn around fronto-, temporo, parieto-, occipito-cerebral, thalamic regions and the cerebellum. 3"he uptake in the cerebellum (a region free from 5-HT2A receptors) was used as a reference for non-specific binding in addition to free ligand. The binding index (BI) is defined as (target activity - background activity in brain) / (background activity) which was operationally estimated as (counts/pixel in regional cortex) / (counts/pixel in cerebellum). Results: Highest uptake was noted in the frontal cerebral region (145%) followed by the temporal area (133% RT, 134% LT). The parietal, occipital and thalamic regions had a similar lower degree of uptake (RP, LP: I I q%; RO: 120%, LO: I 18%; Thalamic region: 121%). Dose and weight did not significantly influence distribution of activity, nor did gender and age. ConcluMons: The use of the specific 5-HT2a receptor ligand is feasible for SPECT brain imaging in the dog. This tracer is a tool to visualisc the binding index of the specific 5-HT2a receptors and has the potential to be useful in work on canine brain disease attributed to serotonlne deficiencies.

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OTHER CLINICAL SCIENCE. PRECLINICAL STUDIES PS_451 IN VITRO AND PRECLINICAL STUDIES OF TARGETED ALPHA THERAPY FOR HUMAN BREAST CANCER USING 213BI-LABELEDPLASMINOGEN ACTIVATOR INHIBITOR TYPE 2 B.J. Allen (1), Z. Tian (1), Y. Li (1), N.J. Andronicos (1), S. Rizvi (3), M. Ranson (1). (1) Department of Biological Science, University of Wollongong, NSW 2522 Australia; (2) St George Cancer Care Centre, Gray St, Kogarah, NSW 2217 Australia; (3) UNSW, Kensington, NSW Australia. Many breast cancer patients receive minimal long-term survival benefit despite undergoing surgery and adjuvant therapy, indicating that micrometastases are not eradicated. We are developing a new adjuvant therapy for the control of metastatic breast cancer based on alphaemitting nuclides. This therapy exploits the involvement of celt-surface receptor bound urokinase plasminogun activator (uPA) in the metastatic spread of breast cancer cells. Once bound to specific cell-surface receptors, uPA efficiently activates plasminogen to the broad-spectrum protease, plasmin. A large body of experimental and clinical evidence implicates the uPA system as a marker of malignancy and therefore a useful and accessible specific target for therapy. We have successfully labeled recombinant human PAI2 with the alpha radioisotope ~13Bi to produce alpha-PAl2. Labeling efficiencies of up to 95% are obtained, the alpha-PAl2 is stable in serum and the uPA inhibitory activity is maintained as determined by complex formation with uPA and by inhibition of uPA activity. Low doses of alpha-PAl2 are highly cytotoxic towards breast cancer cell lines in vitro, whereas non-specific alpha-BSA had no cytotoxic effect. Furthermore, alpha-PAl2 was not found to be cytotoxic with freshly isolated, normal human leukocytes reflecting that non-targeted cells are immune from alpha-PAl2. In vivo toxicity studies in nude mice show that up to 6 mCi/kg of alpha-PAl2 (ip) is well tolerated. In vivo efficacy experiments in nude mice demonstrate in 5/5 mice that a local injection of alpha-PAl2 can completely inhibit the growth of turnout at 2 days post-cell inoculation. Further, systemic (iv) administration of alpha-PAl2 at 2 days post-inoculation can also cause tumour growth inhibition in a dose dependent manner, with 3/5 tamours uncontrolled at 1.5 mCi/kg, 2/5 at 3 mCi/kg and 1/5 at 6 mCi/kg. These results indicate the promising potential of alpbe-PAl2 as a novel therapeutic agent for micrometastatie breast cancer.

PS_453 THE EFFECTS OF BOTULINUM TOXIN INJECTION INTO GASTRIC MUSCLE TO THE GASTRIC EMPTYING TIME IN RATS

o

M. Hala(~ (1), K. S~nmezoOlu (1); B. Apaydm (2), C. Nisli (1), L. Kabasakal (1), F. Aydo~]an (2), I. Karabl~;ak (2), E. Altmh (2), I. Uslu (1). (1) Department of Nuclear Medicine; (2) Department of Surgery, Cerrahpa~a Medical Faculty, IstanbuI,Turkey.

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Botulinum neuromxin type A (Botox, Allergan lnc, USA) produces a temporary and ultimately reversible blockade of neuromuscular transmission. It also provokes autonomic dysfunction by blocking sympathetic and parasympathetic ganglion cells and postganglionic parasympathetic neurons. It can be hypothesized that Botuiinium-toxin injection into gastric muscular layer in antro-fundal junction may create a model of truneal selective vagotomy. In this study we aimed to make an experimental model of pharmacological selective vagotomy by using Botulinium-toxin and to ascertain its effect to the liquid and solid gastric emptying times. Methods: 31 male Wistar rats underwent Botulinium-toxin injection into gastric muscular layer during a standard laparotomy procedure. For control groups, 22 rats also underwent laparotomy with saline injection instead of Botulinium-toxin into the same gastric region. Liquid and solid gastric emptying studies were performed in two separate groups. For liquid phase study, 17 rats with Botulinium-toxin injection and 12 control rats with saline injection were used. 14 models and 10 controls were used in solid phase studies. Both liquid and solid phase studies were performed 10 days after the laparotomy procedure. 10 MBq Tc-99m DTPA within 1 ml milk and 15 MBq Tc-99m tin colloid within particulated scrambled egg were instilled intragastrieally under ether anaesthesia for liquid and solid phase, respectively. After intragastric instillation of radioactivity, the animals were placed on a rat holder under a gamma camera and static images were acquired at the beginning and at 90 rain for both liquid and solid emptying. T9 analyse the data, a region of interest was drawn around stomach outline on both images and the emptying ratios at 90 rain for both liquid and solid phases were calculated. Results: The liquid emptying rate was accelerated while solid emptying time was decreasing in the Botulinium-toxin injected rats comparing to controls (Table). These findings are similar to those seen after the surgical tnmcal selective vagotomy. Group Control BoNT/A injected p

Liquid emp~in[ % 20.4 -+ 15.8 31.1 + 22.1 0.03

Solid emptying % 52.7 + 21.6 21.2 -+ I 1.3 < 0.001

Conclusions: Botulinium-toxin injection into the gastric muscle may mimic the effects of surgical truncal selective vagotomy related to liquid and solid gastric emptying times.

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• OTHER CLINICAL SCIENCE. PRECLINICAL STUDIES PS_454

(This work v,as supported by the Grant Agency of Charles University, grant No. 17/I999/B and by the research proiect No. J13/98:11600002 of the Czech Ministry of Education)

STUDIES IN GENETIC MUTANT ANIMALS INDICATE THAT ABCB4 (MDR1) AND ABCB1 (MDR2) GENES REGULATE HEPATIC SESTAMIBI TRANSPORT

K. Bhargava (1), B. Joseph (2), J. Kandimalla (2), H. Malhi (2), M. Afriyie (1), M. Schilsky (3), C.J. Palestro (1), S. Gupta (2). (1) Division of Nuclear Medicine, Long Island Jewish Medical Center, New Hyde Park,USA; (2) Liver Research Center, Albert Einstein College of Medicine, Bronx, USA; (3) Division of Liver Diseases and Transplant Institute, Mount Sinai School of Medicine, New York, USA. Aim:Recent studies suggested that the multidrug resistance (Mdr) gone regulated hepatic sestamibi excretion. Mdr 1 and 2 genes have been renamed Abcb4 (ATP-binding cassette, subfamily B [MDR/TAP] member 4) and Abcb~, respectively. Ahcb4 gone may be upreguIated in cancer, including hepatocellular carcinoma, whereas deficiency of Abcbl gene product impairs biliary phospholipid excretion, which leads to progressive familial intrahepatic cholestasis. To understand regulation of hepatic sastamibi handling, we utilized inbred normal, as well as mutated mice and rats in genetically defined backgrounds. Methods: Tc-99m sestamibi was injected as an intraspleaic bolus injection followed by imaging at 5 frames per rain for 60 min. Blood, liver and bile samples were obtained for assays as appropriate. Results: In normal FVB/N mice and Long-Evans Agouti (LEA) rats, sestamibi was incorporated in the liver rapidly and approximately 50% hepatic activity was excreted over 60 rain. in knockout mice deficient in either Abcb4 or Abcbl gone in the FVB/N background, Tc-99m sestamibi excretion was impaired similarly and twice as much activity was retained in the liver at 60 min compared with normal control mice. p<0.001. In double-knockout mice deficient in both Abcb4 and Abcbl genes, Tc-99m sestamibi excretion was impaired much more and hepatic Tc-99m sestamibi excretion at 60 rain reached only approximately 50% of that in mice deficient in Abcb4 or Abcbl genes alone, p<0.001• To determine whether Tc-99m sestamibi excretion was affected by chronic liver disease, we studied Long-Evans Cinnamon (LEC) rats, which are syngeneic to LEA rats, but with mutated atp7b gone, copper toxicosis and significant hepatic injury, identical to Wilson's disease. The kinetics of hepatic sestamibi handling in LEC rats were similar to LEA rats, although in one LEC rat biliary Tc-9m sestamibi excretion was greater. Conclusions: Abcb4 and Abcbl genes beth regulate hepatic sastamibi excretion. In chronic liver disease, scstamibi excretion was unaffected indicating that Abcb4 and Abcbl gone function remained intact in this situation. Utilization of sestamibi for assessing Abcb gone function should take into consideration the relative contribution of subfamily gone members.

PS_455

PS_456

BIOEL|MINATION OF NEW RECEPTOR-SPECIFIC PEPTIDES LABELED WITH INDIUM-111 AND YTFRIUM-88 IN THE KIDNEY

OPTIMIZATION OF [18F]FLUORIDE ION WHOLE BODY SKELETAL IMAGING IN MICE UTILIZING MICROPET AND MICROCAT

F. Trejtnar (1), M. Laznicek (1), A. Laznickova (1), H.R. Maecke (2), K. Eisenwiener (2), J.C. Reubi (3), S. Wenger (3). (1) Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic; (2) Division of Radiological Chemistry, University Hospital, Basel, Switzerland; (3) Institute of Pathology, University of Berne, Switzerland.

F. Berger (1), A. Loening (1), A. Chatziioannou (1), A. Zisman (1), C. Tso (1), T. Yoneda (2), J. Lieberman (1), C. Sawyers (1), S. Gambhir (1). (1) University of California at Los Angeles, Los Angeles, USA; (2) University of Texas Health Science Center at San Antonio, San Antonio, USA.

Aim: Somatostatin receptor-specific peptides labeled with convenient radionuclidas can be

used for diagnosis or therapy of somatostafin receptor-expressing tumors. Renal excretion is the main elimination pathway of radiolabeled somatostatin analogues• Significant renal uptake of the octreotide analogs reduces the sensitivity of scinfigraphy for detection of small tumors in the perirenal region and the renal radioisotope cumulation can result in radiotoxicologieal injure of the kidney. The aim of the study was to analyze excretion parameters, mechanisms of excretion, metabolism and retention of newly designed somatostatin receptor-targeted peptides kIlln-DOTA-GATATE, Jliln-DOTA-t-GATATE, gsY-DOTA-GATATE, and SSy-DOTA-tGATATE in the rat kidney in vitro. Methods: Renal handling of the peptides was studied using the methods of the perfused rat kidney. Instead for therapy useful beta-emitter ~0y, the labeling with chemically equivalent gamma-emitter SSy was used, enabling simple detection of the peptide concentrations in biological samples. The isolated rat kidney was perfused with Krebs-Hensaleit solution containing bovine albumin, washed rat erythrocytes (6 %) and a mixture ofamineacida in a recirculation regimen. To consider possible metabolism in the kidney by renal peptidasas, an analysis •of the urine by gel chromatography was performed. Results: Only nonsignificant differences were found between renal clearances of the peptides in the perfused rat kidney. The clearances were lower than the values of glomerular filtration rate. The filtrated amount of the compounds was considerably higher than that excreted in urine. It means that some reabsorption of the peptide complexes in renal tubules may exist. However, the differences between total renal and filtration clearances were not significant. Ratio of radioactivity in the kidney and the perfusate at the end of the perfusion was higher in . . . . . . ss case of the pepttdes labe ed with tndlura- 111. The retantton was relatively lower m Y- and t"In-DOTA-t-GATATE, The analysis of the urine did not show any significant presence smaller Iow-moleeuler metabolic products of the peptides under study. This fact can document no significant destruction of the peptidas by the kidney or a relatively effective tubular reabsorption of possible metabolites in the kidney. Conclusions: Somatustatin receptor-specific radiolabeled peptides Hlln-DOTA-GATATE, i i tln.DOTA.t.GATATE" sSy.DOTA.GATATE, and sSY-DOTA-t-GATATE were excreted in in the perfused rat kidney by glomeru[ar filtration, almost in unchanged form. While the found renal excretion parameters were similar, the renal retention of DOTA-GATATEs was higher than that of DOTA-t-GATATEs•

119;

Objectives: Mouse models for studying fundamental cancer biology are needed for non-invasire and repetitive imaging of bone metastases in order to better understand underlying cancer biology and therapeutics. The aim of this study was to optimize the reproducibility of fluoride ion bone scanning in normal mice and in tumor models. Methods: Eight Swiss Webster mice were tail-vein or i.p. injected with 750gCi [ 18F]Fluoride ion and repetitively imaged on a microPET over 4 weeks. Optimal tracer uptake time for whole body scans (wbs) (5 rain/bed position) was determined by performing dynamic scans. images were reconstructed using an itemtive and a tilter-back-projection method. Quantitative reproducibility of the bone signal was measured using RO1 based counts normalized to the (a) injected dose. (b) area under the heart image time-activity curve, (c) ROI over the whole skeleton. Mouse models for traumatic, primary tumor and metastatic bone lesions were developed and imaged over time. Functional imaging results were correlated with a dedicated small animal CT scanner (MicroCAT, Imtek inn, Knoxville, TN, USA) utilizing a 200 gm image resolution (8 min acquisition). Results: Optimal peak and plateau of 18F-fluoride uptake for wbs was estimated to be 60 minutes after injection of the activity (for either i.p. and i.v. injection). The highest reproducibility was achieved by normalizing bone c/p/m to an ROI over the whole skeleton, with a mean variation in a given mouse of <15% over serial images. Primary ostenlytic bone tumors, metastases /rod traumatic lesions as small as 2 tara were successfully repetitively imaged. Correlation of microPET with microCAT demonstrated the high sensitivity of the functional imaging approach; microCAT was especially helpful in detecting small ostenlytic lesions. Conclusion: We have studied Fluoride ion whole body bone imaging and shown that this approach is reproducible and can be used to serially monitor normal and pathological changes to the mouse skeleton. This work sets the foundation for quantitative, high-resolution functional bone imaging of mice, which will be useful for numerous applications in basic small animal research.

• OTHER CLINICAL SCIENCE. PRECLINICAL STUDIES PS 457

PS459

UPTAKE OF RADIOLABELED HERCEPTIN BY EXPERIMENTAL MOUSE MAMMARY CARCINOMAS

HISTOLOGICAL CHANGES IN THE RATAoS TISSUES AFTER LOCAL APPLICATION OF THE HO-166-CHITOSAN COMPLEX ATTACHED TO BIODEGRADABLE SOLID MATERIAL

M. Mirowski (1), R. Wiercioch (1), E. Balcemzak (1), J. Switalska (2), G. Birnbaum (2), E. Byszewska (2), D. Pawlak (2), R. Wierzbicki (1). (1) Department of Biochemistry, Faculty of Pharmacy, Medical University of Lodz ,Poland; (2) Radioisotope Center, Polatom, OtwockSwierk, Poland. Recombinant humanized anti-c-ErbB~ monoclonal antibody (herceptin) is new agent for the treatment of women with tumors that overexpress epidermal growth factor receptor 2 (c-ErbB~). Aim of the present study was to determine biodistribution of t311-herceptin in experimental mammary carcinoma to predict the radiodiagnostic utility of this antibody. Methods: lodination of 13Ll-herceptin was based on the chloramine T method. Biodistribution study of the radioactive compound was done in healthy and in tumor-bearing mice. Tumors were growth in C3H/Bi mice by injection of cell suspension prepared from spontaneously growing mammary tumors. Amplification of the e-erbB, gene in experimental tumors was detected by the polymerase chain reaction technique and its protein product expression by Western blot analysis. Results: The histological analysis by eosin and hematoxylin (E&H) method showed that above 90% of investigated tumors can be classified as edenocarcinomas. Most of the tumors after Western blot analysis revealed c-erbBz uncogene protein products expression. In more than 50% of tumors the amplification of c-erbB: gone was detected. Biodistribution study showed increased accumulation of t311-berceptin in time with the maximum at 48 hours since injection (7% ID/g). At this point tumor/muscle ratio was the highest (about 20). After 96 131 hours l.herceptin accumulation in tumor tissue was 2.5 times higher than in the blood. Conclusion: I-hercepdn has high affinity to the mouse mammary adanoearcinomas wbaI might suggest their usefulness in imaging ofc-erbB2 expressing tumors in humans.

J.S. Lee (1), S.J. Lira (2), W.S. Jung (2), T.S. Lee (2), K.S. Woo (2), S.J. Lee (2), C.W. Choi (2), S.M. Lira (2). (1) Department of Orthopedic Surgery; (2) Laboratory of Cyclotron Application, Korea Cancer Center Hospital, Seoul, Korea. The aim of this study was to find out a clinically applicable method to insert a biodegradable solid material containing holmium-166-chitosan complex into the surgical field, and to evaluate the histological changes in the normal tissues after irradiation from Ho-166 according to the dose, period and type of tissues. Methods: 111 MBq, 50 p.I of the liquid state Ho-166-chitosan complex was attached to the absorbable gelatin sponge, the size of which was 7 x 7 x 5 mm. After 24 hours in the sterile bench for drying up of the liquid Ho-166-chitosan complex, the radiation activity measured by dose calibrator was 56 MBq. These Ho-166-chitosan complex containing absorbable gelatin sponges were inserted into thigh muscles and over the femur bones of the Wistar rats, weighed by 300 grams. The control group was prepared by inserting only absorbable gelatin sponge. One control case and 10 radioactive absorbable gelatin sponge cases were evaluated at 2, 4. 6 weeks after insertion (total number; 33) with respect to the histological changes of . . . . i66 • the sofi tissues, bones, the depth of the ttssue necrosis, and the changes of the Ho-cbltosan complex containing absorbable gelatin sponges. Results: The histological changes at 2 weeks after the Ho-166-chitosan complex insertion were as follows; In the muscle, coagulation necrosis, degenerating myocytes, regenerating myocytes, intermuscular edema, and inflammatory cells were observed. The average necrosis depth was 3.3 rnm (range; 2.5-4.0, SD; 0.54). In the bone, there sere no osteocytes in the lacuna of cortex (empty lacuna), marrow fibrosis, inflammation, and the average necrosis depth was 2.9 mm (range; 2.0-4.5, SD; 0.82). At 4 weeks, in the muscle, calcification and increased fibrosis with average necrosis depth by 3.3 mm (range; 2.5-4.0, SD; 0.48) were found in addition to the findings of 2 weeks. In the bone, additional findings were, increased marrow fibrosis with necrosis depth by 3,3 mm (range; 1.5-5.0, SD; 1.0). At 6 weeks, soft tissue shrinkage, increased fibrosis and granulation tissue formation, and nearly resolving inflammatory reaction were the findings. Conclusions: The local application of the Ho-166-chitosan complex attached to biodegradable gelatin materials with surgery in the laboratory animals resulted in no mortality, no wound complication, and satisthctory tissue necrosis was induced by ~-ray irradiation.

co

PS_458

PS_460

DETECTION AND IDENTIFICATION OF SENTINEL LYMPHNODE IN CANINE ONCOLOGICAL PATIENTS

THE USE OF 99M-TC-CIPROFLOXACIN (INFECTON) IN THE DIAGNOSIS OF INFECTION IN THE DOG: 2 CASES

L. Balogh (1), G. Andocs (1), D. Mathe (1), J. Thuroczy (2), E. Perge (3), I. Erdelyi (4), K. Rodo (1), A. Polyak (1), G. Janoki (1). (1) Department of Applied Radioisotopes; (2) Department of Gynecology and Obstretrics, Faculty of Veterinary Medicine, Szt Istvan University, Budapest, Hungary; (3) Department of Pathology, Central Institute of Animal Health, Budapest, Hungary; (4) Department of Pathology, Faculty of Veterinary Medicine, Szt Istvan University, Budapest, Hungary

K.Y. Peremans (1), F. De Winter (2), F. Verschooten (1), H. van Bree (1), R. Dierckx (2). (1) Department of Medical Imaging, Faculty of Veterinary Medicine, University of Ghent, Belgium; (2) Division of Nuclear Medicine, Ghent University Hospital, Belgium.

Aim: Tc-99m HSA colloid lymphoscintigraphy is used for the detection and imaging sentinel lymphnodes in human breast cancer, melanoma and other soR tissue tumor patients. Different human protocols are available concerning the optimum particle size of applied colloids, the ideal time of imagination and intraoperative guiding after application. The aim of this study was to compare the effectivity of detection sentinel lymphnodes by injecting radioactive particles mixed with blue stain and blue stain alone in spontaneously oecuring ontological dog patients. Methods: Altogether 14 dog patients with the history of mammary tumors (11), skin tumor (I) or other soft tissue tumors (2) in the oral cavity and the neck underwent within 3 days fine needle biopsy, thoracal radiography and hematological examinations. Three-six hours before surgical removal of tumors 20-37 MBq/0,1mL Tc-99m HSA colloid (Senti-Stint-, N.R.I.R,R.) mixed with blue stain (Patent blau) was injected subcutaneously. Gamma camera imaging (Nucline X-ring, Median Ltd) and intranperative gamma probe (Europrobe, Eurorad) was used for localizing sentinel nodes. Another group of 16 dogs having mammary tumors was injected only with blue stain (Patent blau) and visual localization of sentinel lymphnodes was carried out 30-60 minutes later. Removed tumors and lympbnodes were investigated by pathologist. Results: Eightteen sentinel lymphnodes in the 14 oneological dog patients were localized by using the combined method. Thiaeen of the nodes (72%) were found to be painted by the blue stain intranperatively. Only 12 lymphnodes (67%) were clearly identified by gamma camera imaging and t0 (55%) were palpable before surgery. Fourteen sentinel lymphnodes in the 16 dogs were found by injecting only the blue stain. Forty % of all the excised lymphnodes found to be positive by histupathological examination. Conclusions: Palpation, blue stain localizing method and gamma camera imaging alone resulted not satisfactory data on sentinel lympbnode detection. Intraoperative radioactive guided surgery combined with blue stain seems to be the superior method for localizing sentinel lymphnodes in dogs like in human beings.

[ntroduction: [nfecton® is a win-technetium labelled radiopharmaeeufical based on the fluoroquinolone antibiotic ciprofloxacin. The advantages of this radiotracer lie in the isotope used (technetium is widely available, cheapand has good characteristics regarding radioprotection) and in the fact that synthesis is quick and is available as a kit. The pharmaceutical has an antibacterial activity through binding and inhibiting bacterial gyrase. It does not target death bacteria and sterile inflammatory lesions. One case included involved a complication after total hip replacement. The other was a case of chronic fistulation at the level of the metatarsal bones. Materials and methods: Case 1.: german shepherd, female, 2 years old. Total hip replacement with a non-cemented prosthesis was performed. Sudden lameness was noted two months post-operatively and radiographic examination was non-eooclusive. Infecton® was injected (10mCi) IV. The scan was taken 3 hours post-injeetiun and at 24 hours. Increased activity in the region of the femoral prosthetic element and in the acetabular region was found. Bacteriologic examination revealed resistant Pseudomunas Aeroginosa. Case 2: greyhound, male, 6 years old. This dog suffered from two fistular tracts at the metatarsal region of unknown duration. Radiographs showed minor periosteal reaction at the lateral side of the fourth metatarsal bone. Infeeton® was injected (10mCi) IV. Acquisition was performed 3 hours and 24 hours postinjection. A hot spot was noted at the lateral side of the fourth metatarsal bone and one was located more centrally at the level of the second and third metatarsal bones. Bacteriology from the bone curretage material rendered Streptococcus Canis. Conclusion: In the first case the Infectun® scan rendered a clear differential diagnosis of aseptic loosening versus chronic infection. In the second ease infectious bone involvement was demonstrated with this technique. It was shown in these two cases that Infecton® can be a valuable aid in the diagnosis of infection in the dog.

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o3 o 13.

• OTHER CLINICAL SCIENCE. PRECLINICAL STUDIES PS_461

PS_463

CAN TC-99M-HL91 UPTAKES IN THE TUMOUR PREDICT THE RESPONSE OF RADIOTHERAPY

BIODISTRIBUTION OF 99MTC-LABELLED LOW MOLECULAR PEPTIDES AND PROTEINS IN AN ANIMAL MODEL OF INFLAMMATION

K. Nakamura, T. Suzuki, T. Kawase, A. Kubo. Department of Radiology, Keio University School of Medicine, Tokyo, Japan. We previously reported that Tc-99m-HL91 (H L91 ) uptake reflected the hypoxia in tumours. Aim: The aim of this study was to evaluate if HL91 can predict the radiotherapy response before and following radiation since a strong correlation between tumour hypoxia and poor response to radiotherapy is observed. Methods: Athymic mice bearing human epidermoid carcinoma, KB-31 or lung adenocarcinoma, HLC in the flank underwent planar imaging before and every three days for 15 days after receiving radiotherapy. In the image at four hours after injection of HL91, ROIs were placed on the turnout in one flank and the muscle in another flank. The HLgl uptake was shown by the ratio of radiointensities in two ROIs. Results: Before radiotherapy, the HL91 uptakes in tumour xenografts were 1.4-2.2 for small (less than 70 mm 3) KB-3I. 2.1-3.4 for big (more than 150 mm ~) KB-31, and 2.l-3.0 for any size of HLC. The eontrol group that did not receive radiation showed the increase in HL91 uptake to 4.0-7.7 and 6.5-7.0 for KB-31 and HLC, respectively. The HLC mmours did not show any response to radiotherapy and their HL91 uptakes kept increasing after the radiation. The KB-31 tumuurs responded to radiotherapy and their H L91 uptakes did not increase for a t~.w days after radiation. KB-31 turnout xenografis where HL-91 uptakes were reduced showed tumour shrinkage, and then some of them (HL91 uptakes were less than 1.0) disappeered 15 days later The KB-31 tumours of which HL91 uptakes did not change after radiation showed the growth delay, but they were re-grown a few days after showing the increase in HL-91 uptakes. Conclusions: The failure to respond to radiotherapy could be predicted by high HL91 uptake in the turnout. The increase in tumour HL91 uptake after radiation indicated the presence of hypoxic area, suggesting that radiation effect was not satisfactory. The decrease in turnout HL91 uptake after radiation indicated the reduction of viable cells, suggesting the success for response. The HL91 uptake could assess the response of the turnout to radiotherapy a few days before they show their clinical appearance.

P. Komarek (1), I. Kleisner (2), M. Konopkova (3), I. Komarkova (4). (1) Department of Pharmaceutical Technology and Drug Control, Postgraduate Medical School, Prague, Czech Republic; (2) Department of Nuclear Medicine, Kralovske Vinohrady University Hospital, Prague, Czech Republic; (3) Department of Radioisotope Diagnostics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; (4) Department of Radiopharmaceuticals, State Institute for Drug Control, Prague, Czech Republic Aim: To evaluate accumulation of the low molecular pcptides and proteins labeflcd with 99mTc in rat inflammatory/infection loci. Methods: Peptides (human leukocyte dlalysate - HLD, thymosin fraction 5 - TF5. aprotinin - APT), proteins (human lgG - HIG) were labelled with 99roTe using a redox polymer [NecI.Med.Rew. 3, 2000. 65-72]. The labelling efficiency was evaluated using paper, TLC and/ur column chromatography and electropboresis. The biodistribution of the labelled substances was evaluated in Wistar rats with Staphylococcus aureus infection or with sterile kaolin suspension-induced inflammation in the left inguinal region 24 h after abscess induction. Accumulation of 99mTc activity was determined both by external gamma camera imaging and by counting dissected tissues I-4 hours after administration. Results: The evaluated peptides and proteins show a high labelling efficiency (99mTc-HLD > 98%, 99mTc-TF5 > 95%, 99mTc-APT > 98%, 99mTc-HIG > 95%). Use of redox polymer for labelling raises the stability of 99roTe-labelled substances so that the labelling efficiency remains to be virtually the same (95-98%) after 8 hours at least. In experimentally induced inflammation, the amount of 99mTc-peptides and 99rnTc-HIG activity accumulated is 2.5-6.5 and 5.3-10.6 times, respectively, that in control tissue. A comparison of two types of model inflammations (inflammation induced by kaolin and Staphylococcus-induced inflammation) revealed the values measured with 99mTc-peptides are more than a double that induced by kaolin suspension. Conclusions: The studied low molecular peptides labelled with 99mTc allow rapid localisalion of infection loci in the animal model. 99mTc labelled HIG seems to be usclhl tbr the detection of both inl;ections and inflammatory lesions. The study was suppertcd by grant NoNL/6071-3. awarded by the Internal Grant Agency of the Ministry of Health, Czech Republic.

PS_462

PS_464

LABELING MONOCLONAL ANTIBODIES WITH TC-99M AND RE-186: A COMPARISON BETWEEN THE TRICARBONYL METHOD AND THE HYNIC METHOD

VINCRISTINE EFFECTS IN MICE: EVALUATION OF THE MASS AND HISTOLOGICAL STUDY OF THE ORGANS AND OF THE DISTRIBUTION OF RADIOPHARMACEUTICAL

E.B. Koenders, O.C. Boerman. J. van Eerd, F.H.M. Corstens. Dept. of Nuclear Medicine, UMC St Radboud, Nijmegen, The Netherlands.

M. Bernardo-Filho (1), D. Mattos (1), M. Gomes (1), R. Freitas (1), A. Nascimento (2), J. Carvalho (2), E. Boasquevisque (1). (1) Departamento de Biof'sica e Biometria; (2) Departamento de Histologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil.

Aim: A new method for labeling proteins with Tc-99m has been developed recently (Waibcl et al. Nature Medicine 2000). This tricarbonyl method comprises the synthesis of the tricarbonyltriaquaion complex [Tc(CO)3(H.~O):~+ ] as an intermediate, and the subsequent reaction of this aquaion with the antibody. This method can be used to label proteins and peptides not only with Tc-99m (I), but also with Re-186. In our department we have extensive experience using the bifunctional chelator S-HYNIC, for labeling antibodies with Tc-99m. Here, we compared both methods to label the anti-CEA antibody MN-14 with Tc-99m. Method: The immunoreactivity and the in vitro stability of the both radiolabeted antibody preparations were determined, The in vivo tumor targeting potential of both antibody pr~]~oarations was determined in athymic mice with LSI74T tumors. Mice received 1850 kBq mTcMN-14 i.v. and were dissected at 4, 24 and 48 h p.i. Results: HPLC analysis indicated that the aquaion intermediate could be formed with an efficiency of ~mto 9 0 * . The overall labeling efficiency, immunoreactivity and the in vitro stability of both Tc-labeled MN 14 preparations are summarized in the table. Summary of the characteristics of ~"Tc-MNI4 labeled according to the tricarbonyl and the HYNIC method.

Labeling,:efficiency [mmunoreactive fraction In vitro stability in PBS In vitro stability in serum

Tricarbonylmethod

H~,nicmethod

60% 70% 88% 95%

96% 62% 94% 97%

The behaviour of the two WmTc-MN-14 preparations differed markedly in nude mice with LSI74T tumors. The preparation labeled according to the tricarbonyl method cleared more rapidly from the blood than the HYN[C preparation ( blood levels at 48 h pi : 4 % [D/g vs 10 % ID/g) and showed a lower tumor uptake ( 15% ID/g vs 40% ID/g, 48 h p.i. Tumor-to-blood ratios of both preparations were similar at all time points and reached a value of 4 at 48 h p.i. Conclusions: In summary, the MNI4 antibody can be labeled with Tc-99m using the tricarbonyl method. The Tc-MN 14 preparations arc stable in vitro during at least 24 hours. The antibody labeled via the HYNIC method showed a higher tumor uptake in nude mice with LS [ 741" tumor, most likely due to a better in vivo stability.

1194

Unintended alteration of the biodistribation of the mdiopharmaceuticals can lead to sub-optimal outcome of nuclear medicine procedure. Altered biologic behavior of an administered radiopharmaceutical may be due to interferences caused by pharmacodynamic effects of therapeatic drugs. The vinca alkaloids are cell-cycle-specific agents. AIM: As chemotherapeutic drugs can alter the growth of child and present important toxic effects, we have studied the effect of vincristine on the mass of organs from female mice and are trying to develop a model to evaluate the action of chemotherapeutic drug on the biodistribution of radiopharmaceuticals. Vincristine was administered by ocular plexus via into Balb/c mice. METHODS: The organs were isolated and their mass determined in an analytical balance. To study the distribution 99mTc-DTPA, vincristine was administered by ocular plexus via into female Batb/c mice in three doses with a total interval of 96 hours. One hour after the last dose, 99mTc-DTPA were injected by the same via. After 0.5 hour the animals were sacrificed and the percentage of total radioactivity per gram (%ATFg) in each organ were calculated. RESULTS: The results have shown that the mass has been decreased significantly (Wilcoxon test, p<0.05) in thymus, spleen) lymph nodes, ovary, uterus, kidneys, pancreas, and liver. The biodistribution results have shown an increase of the %AT1/g to the radiopharmaceuticals in ovary, uterus, splecen, thymes, lymph nodes, lungs, heart, liver, kdneys and bone. As 99mTc-DTPA is used to evaluate the ~nal function, we decided to study deeply the ultrastructure of the kidney. A fragment of the kidney isolated from the animals treated with vineristine was cut into strips and fixed with 2.5% glutaraldehyde and 0.25% tannic acid in phosphate buffer pH 7.2 overnight at 40C. The strips were washed in phosphate buffer pH 7.2 and postfixed in I% osmium tetroxide and potssium ferricianate 0.8% in phosphate buffer pH 7.2. After a second washing, the tissues was dehydrated in graded series of ethanol, and Epon embedded. Ultrathin sections were prepared and observed in transmission electron microscopy. The comparison between the electron photomicrographies of the kidney of the treated animal and the control revealed important alterationsin the basal lamina of the capilar endothelium. C O N C L U S I O N : In conclusion, we suggest that the modifications induced for the vincristineis capable to alterthe uptake of the studied radiopharmaceutical in the kidney.

• PRECLINICAL STUDIES / RADIONUCLIDE THERAPY / DOSIMETRY 2 PS_465 COMPARISON OF THE PROTECTIVE EFFECTS OF DIMETHYLSULPHOXlDE AND METHYLPREDNISOLONE AGAINST THE WARM ISCHEMIA ON LIVER PARENCHIMA USING HEPATOBILIARY SClNTIGRAPHY M. Y~ksel (1), A.R. Hatipo~lu (2), E. Temiz (2), Y.S. Saliho~lu (1), S. Berkarda (1), O.N. YiOitba~ (1). (1) Department of Nuclear Medicine; (2) Department of General Surgery, Trakya University, Edirne, Turkey. Warm iscbemia due to Pringle maneuvre during liver operations leads to parenchyma~ damage as a result of ischemi',greperfusion injury (I/R-l) accomplished with the duration of iscbemia on liver parenchym. Radical oxygen species, generated after reperfusion, play important role by this I/R-I. Dimethylsulphoxide (DMSO) and methylprednisolone are two radical scavengers, and are used to protect the liver parenchima against the I/R-L We aimed to investigate, the role of hepatobiliary scintigraphy (HBSc) in detection of the protective effect of DMSO and methylprednisolone liver parenchymal damage. Methods: Total of 18 rabbits (A:Control; B: DMSO+PM; C:Methylprednisole+PM; n=6 each group) were injected 37MBq Tc-99m-mebrofenin through the ear veins. Dynamic scintigrams were taken for 60 minutes (I frame/rain). In group A, HBSc was perlbrmed without any surgical application. In group B DMSO and in group C mg/kg methylprednisolone are injected to every rabbit before PM-application. PM was applied in group B and C for 30 minutes and after 15 minutes of ending of PM, tissue specimens lbr electron microscopy were taken from liver parenchym. Then HBSc was perlormed in groups B and C. From dynamic images timeactivity-curves (TAC) were obtained for each group and the time of peak uptake (TPU) and the time tbr half of the activity to clear fi'om the liver (T 12) values were calculated. Results: TPU and TI~.,of the control group were significantly lower than group B and C; p<0.0003 and p<0.002, tbr TPU respectively, and p<0.02 and p<0.005, tbr TI/2 respectively. However, there was no statistical significant difl~rence between the groups B and C for TPU and TI/2 values. Electronmicroscopic examination showed that there was no histopatbological difference between the groups B and C. Groups

TPU (rain)

Ttz2(mini

A B C

3.20~0.45 10.8+-.2.48 I 1.33±3.51

12.06-+I. 11 30.35-1-13.57 33.47±26.5 !

Conclusion: According to our results, we suggested that hepatobiliary scthtigraphy might be used as an non-invasive imaging technique to evaluate the protective elt~zct of DMSO and methylprednisolc, and that the protective eft;tot of DMSO is not dil/~renl than mcthylprednisolone against the ischemia/rcperfasion injury on liver parenchym.

RADIONUCLIDE THERAPY / DOSIMETRY 2 PS_467 METHODS TO REDUCE RENAL TOXICITY DURING 90Y-DOTATOC THERAPY M. Cremonesi (1), M. Ferrari (1), L. Bodei (1), L. Leonardi (1), M. Chinol (1), E. Sacco (1), M. Stabin (2), A. Holmerg (3), J. Hiltunen (3), G. Paganelli (1). (1) Divisions of Nuclear Medicine and Medical Physics, European Institute of Oncology, Milan, Italy; (2) Department of Radiology and Radiological Sciences Vanderbilt University, Nashville, TN, USA; (3) MAP Oy, Helsinki, Finland. Dosimetric studies have shown that high activities of ~Y-DOTATOC can be injected with low myelotoxicity, although the absorbed dose for kidneys raise concern on possible delayed nephrotoxicity. Aim: The aim of this work was twofold: i) to investigate the absorbed dose sparing to kidneys with the inlhsion of suitable renal protective agents; ii) to recalculate the maximum injectable activity. Methods: Fifteen pts {5 pts/group) were enrolled into the protocol in order to investigate the renal protective efficacy of three different agents available at our institute. Within 2 weeks. each patient underwent two dosimetric evaluations: the l'C basal, and the 2"J associated with the infusion of a protective agent. In both cases 185 MBq of tlIIn-DOTATOC was administered as a bolus i.v. injection. The drugs under investigation were the lbllowing: LAL (mixture of Lysine and Arginine, 400 mg/kg), PEP-10 (Positively Charged Protein-lO; 2 mg/kg); PLyCD (Poly-Lysine Compound D; 2 mg/kg). The MIRD tbrmalism was used tbr dosimetric calculations. Kidney dose reduction alter LAL, PCP-10, PLyCD was obtained with an intrapatient analysis, in order to avoid patient variability. Results: The time-activity curves tbr kidneys showed the same trend, with and without protection. Mean kidney absorbed dose reduction (%) resulted: 31±25 aRar LAL, 50±13 alter PEP-10, and 51±24 after PlyCD infusion. Side effects, mostly grade l-II gastro-intcstinal, occurred with LAL and PEP-10. At present, PEP-10 and PLyCD seem to be the most effective protectors. Conclusions: Co-infusion of positively charged molecules during '~IY-DOTATOC therapy reduces kidney irradiation, enabling a 30-50% increase of cumulative injectable activity. Accepting 25 Gy as the renal dose limit, total activities up to 12 GBq of ~Y-DOTATOC can be administered after PUP-10 and PLyCD protection.

ro

PS_466

PS_468

TUMOR UPTAKE AND TUMOR RETENTION OF A MONOMERIC AND A DIMERIC TC-99M-LABELED RGD-PEPTIDE

HIGH-DOSE 111-INDIUM-PENTETREOTIDE RADIOTHERAPY FOR METASTATIC NEUROENDOCRINE TUMOURS

ID ffl

O.C. Boerman (1), M. Janssen (1), C. Frielink (1), W. Oyen (1), S. Edwards (2), S. Liu (2), M. Rajopadhye (2), E Corstens (1). (1) Nuclear Medicine, University Medical Center Nijmegen, Nijmegen, the Netherlands; (2) Dupont Pharmaceuticals, N. Billerica, MA, USA.

E. Seregni, G. Savelli, A. Chiti, F. Pallotti, E. Bombardieri. Istituto Nazionale Tumori, Milano, Italy. Aim ]JJIn-pentetreotide ( i i tIn-OCT) has become the standard rediopharmaceutiual for local-

e~

ization of neuroendocrine tumours that overexpress somatostatin receptors type 2 and 5. Experimental evidences demonstrated that this radioligand is partially internalized and it can induce cytotoxicity by emission of Auger electrons. Aim oftbe present study is to evaluate the feasibility of radiotherapy with high-dose of ~liln-OCT in patients affected by metastatic gastro-antero-pancreatic (GEP) neuroendocrine tumours. Methods Four patients with metastatic and progressive GEP neuroendoerine tumours were enrolled in this study. All patients were refractory to conventional medical and hormonal treatment. Each patient received a 6 GBq HLtn-OCT therapy every month with a cumulative dose ranging from 48 to 72 GBq (8-12 cycles). The main characteristics of the examined patients are reported in the table. Patients were evaluated al~er 4 and 8 cycles by means of conventional imaging technique including computed tomography, abdominal ultrasound and bone scan. Toxicity and response to therapy were assessed according to the Common Toxicity Criteria and the WHO criteria, respectively.

0 0.

Aim: RGD peptides selectively bind to the Ctv[33 integrin expressed on newly formed endothelial cells and on various tumor cells, Because tumors have enhanced ctv~3 expression, radiolabeled RGD peptides localize preferentially in tumors. Theoretically, peptides with more than one RGD sequence could bind the target cell multivalently, and thus more avidly. Multivalent interaction could result in higher uptake and/or better retention in the tumor. Here we compared the tumor targeting characteristics of a monomeric RGD peptide with those of a dimeric RGD peptide in mice with human tumor xenografis. Methods: The monomeric peptide (RGDfK) and the dimeric peptide ([RGDIK]:-E) were derivatized with hydrazinonicotinamide (HYNIC). The molecular weight of the monomeric and the dimeric peptide was 841 Da and 1534 Da, respectively. Both peptides were radiolabeled with ';'~Tc (100°C, 15 rain). Quality control was done with ITLC and RP-HPLC. Identical doses of the radiolabeled peptides (30 nmoles) were i.v. injected in nude mice with s.c. NIH:OVCAR-3 human ovarian carcinoma xenografts. The biodistribution of the rediolabel was determined at 10, 30 rain, 1, 2, 4 and 24 h pi (5 mice/group). Results: RP-HPLC indicated that the radiochemical purity of both peptides exceeded 90% (<2% colloid). Both peptides rapidly cleared from the blood: blood levels of the radiolabeled peptides decreased between 10 rain and 24 hrs p.i. from 2.8 to 0.04 %ID/g (monomer) and from 2.2 to 0.05 %lD/g (dimer). The uptake of the monomeric peptide in the tumor showed a gradual decrease between 10 min and 4 h p.i. from 5.8 to 2.6 %lD/g, while the uptake of the direaric peptide in the tumor was stable until 4 his p.i.. Maximum tumor-to-blood ratios were similar for both peptides: 60 and 65, respectively. Both peptides were excreted exclusively via the kidneys, Activity concentration in the other organs examined (lung, spleen, liver, kidney, intestine) decreased with time. Conclusions: These two HYNIC-derivatized RGD peptides preferentially localized in the tumor in this tumor model. While the maximum uptake of the peptides in the tumor was similar for both peptides, the retention oftbe dimeric peptide was slightly better.

ID t 2 3 4

Gender M F M F

Age 55 45 52 71

Primar'/tumour Ileum i Pancreas I Rectum I Pancreas

Disease extension Nodes, skeleton Liver, skeleton Liver, lun~ iLiver, skeleton

No. of cycles 12 8

Results No major treatment-related adverse reaction was observed. Only 2 of 4 patients experienced a mild (Grade I-ll) reduction of haemoglobin. Clinical benefit was observed in all the patients. In fact t patient achieved a partial response with a striking reduction of the skeletal and nodal metastases while the other 3 patients showed a stable disease. The time to progression were 18 and 12 months for patient I and 2 respectively, whereas patients 3 and 4 are still without any clinical signs of progression. Conclusions, In spite of the small series of the treated patients, our study indicate that high • dose ILlIn-OCT rathotherapy could be effectwe in patients with advanced otherwise untreatable GEP neuroendoerine neoplasms. Indeed, the therapeutic dose is well tolerated and yield a noteworthy clinical benefit to the patients. In order to define the optimal dosing scheduled and the appropriate timing of the administration further investigation are needed.

1195

• RADIONUCLIDE THERAPY / DOSIMETRY 2 PS_469

PS_471

1-131-MIBG IN THE TREATMENT OF NEUROENDOCRINE INDICATIONS A N D PERSPECTIVES

MODULATION OF IODIDE UPTAKE IN RAT HEPATOMA

TUMOURS:

V. Rufini (1), A. Tornesello (2), S. Mastrangelo (2), A. M. Samanes Gajate (1), M. Salvatori (1), R. Mastrangelo (2), L. Troncone (1). (1) Department of Nuclear Medicine; (2) Division of Pedriatic Oncology, Universit.~ Cattolica del Sacro Cuore, Rome, Italy. Since its initial application, l-131 -MIBG has been considered a potemial therapeutic agent for neural crest tumours, Since 1984, 66 patients have been treated at our institution: 51 neuroblastomas (NB), 7 malignant pheochromocytomas/paragangliomas (PHEOS), 5 medullary thyroid carcinoma (MTC) and 3 carcinoid tumours. The therapeutic procedure consisted off a) evaluation of MIBG uptake and retention by scintigraphy; b) thyroid blockade; c) administration of high specific activity l-I 31-MIBG (3.7-9.5 GBq by i,v, infusion); d) monitoring of the patient during the infusion; e) post-therapy whole body scintigraphy; assessment of tumour response 4-6 weeks after therapy. 1) In PHEOS, MTC and careinoids, MIBG was effective with persistent partial reduction of primary tumoral lesions and palliation in metastatic disease; in patients with less advanced stage it could eradicate the residual turnout. The overall results obtained in this group of patients were: 2 CR, 3 PR, 6 SD, 4 PD. 2) In NB, MIBG therapy was initially applied in patients with refractory or progressive disease; 18 cases of stage 3 and 4 refractory NBs were treated. Pain relief was observed in almost all cases; an objective long-lasting therapeutic response was obtained in 12 patients:l CR, 4 PR, 7 SD, In 5 cases of stage 3 and 4 NB 1-131-MIBG was used as a first-line therapy (objective responses in 3 cases). At present, experiences combining chemotherapy and MIBG therapy are in progress• So far, 28 patients were treated. In the first 7 patients, cisplatin and [-131-MIBG were combined. Later on cyclophosphamide (Cy) was added to cisplatin prior to a single dose of l- 13 IMIBG in l i cases. An intensification of the chemotherapy regimen by adding VPI6 and vincristine was applied in other l0 cases. The overall response rate of the last two regimens showed I CR, 2 VGPR, 14 PR, I mixed R, 3 SD. MIBG therapy was well tolerated. With the exception of hypertensive crises in one case of NB and leukaemia after 7 years from therapy in another case of MTC, the major side effect recorded was myelosuppression. Conclusions I-t31-MIBG is a treatment which is effective for a wide range of neural crest tumours. In metastatic disease MIBG therapy has an important palliative role. In early stage disease it can eradicate the residual/recurrent turnout. In NB, the innovative combination of MIBG therapy and chemotherapy may represent an important route of investigation to improve final outcome in patients with advanced disease.

U. Haberkorn (1), A. Altmann (1), M. Henze (2), I. Morr (1), M. Mahmut (1), P. Peschke (3), M. Eisenhut (2). (1) Clinical Cooperation Unit Nuclear Medicine; (2) Dept. of Nuclear Medicine; (3) Clinical Cooperation Unit Radiotherapy, Cancer Research Center, Heidelberg, Germany. The ability of thyroid cells to accumulate iodide is a prerequisite for successfull radioiodide therapy of benign thyroid diseases and differentiated thyroid carcinoma_ The transport of iodide across the cell membrane is the first step in the iodide accumulation process which is mediated by the sodium iodide symporter (hNIS). We, therefore, investigated whether the accumulation of iodide may be induced by the rctroviral transfer of the hNIS gene in non-thyroid tumor ceils• Methods: Employing a bicistronic retroviral vector for the transfer of the hN|S coding sequence and the hygromycin resistence gene rat Morris hepatoma (MH3924A) ceils were infected with retroviral particles and 32 hNIS expressing cell lines were generated by hygromycin selection. After incubation of the genetically modified and wild type hepatoma • 125, ceils as well as the rat thyroid cell line FRTL5 with Na I the uptake and the effiux of iodide was determined In addition, the iodide distribution in rats beating wild type and the genetically modified hepatomas was monitored• Results: Genetically modified MH3924A cell lines accumulated up to 235 times more iodide when compared to non-infected hepatoma cells. The maximal iodide uptake in the cells was observed after 60 minutes incubation time. Competition experiments in the presence of sodium perehlorate revealed a dose dependent decrease of the iodide uptake (87% to 92%). Moreover, FCCP led to a loss of accumulated I- (32%) whereas D[DS increased the I" uptake into the cells (22%). However, a rapid efllux of the radioactivity (80o/o) was observed during the first 10 minutes after 12~[.containing medium had been replaced by non-radioactive medium. In rats, the hNtS-expressing tumors accumulated six times more iodide when compared to the eontralateral wild type tumor as monitored by scintigraphy. The ex v i m quantitation of the iodide content performed I hour after tracer administration in Ig tumor tissue revealed a 17-:bid higher iodide accumulation in the genetically modified tumors. In accordance with the in vitro data we also observed a rapid efllux of the radioactivity out of the tumor in vivo. Conclusion: The transduction of the hNIS gene per se is sufficient to induce 12S]- transport in Morris hepamma cells in vitro and in vim. With regard to a therapeutic application, however, additional conditions need to be defined which inhibit the iodide efflux out the tumor cells.

PS_470

PS_472

THE INHIBITORY EFFECT OF RADIOLABELLED OCTREOTIDE ON INTRAHEPATIC T U M O U R GROWTH AFTER PARTIAL HEPATECTOMY

188-RE-LIPIODOL" PREDICTION OF THE PATIENT DOSE BASED ON 131-I-LIPIODOL BI-PLANAR SCANNING AND MONTE-CARLO SIMULATION

W.A.P. Breeman (1), G.D. Slooter (2), R.L. Marquet (2), E.P. Krenning (1), C.H.J. van Eijck (2). (1) Nuclear Medicine; (2) Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands.

K. Bacher (1), H. Thierens (1), S. Van de Putte (1), B. Brans (2), M. Monsieurs (2), R.A. Dierckx (2). (1) Departement of Medical Physics; (2) Division of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.

The inhibitory effect of radiolabelled octreotide on intrahepatic turnout growth after partial hepatectomy Background: Most neuroendocrine tumours and several other turnouts such as breast carcinoma and malignant lymphoma express somatostatin receptors. Lesions expressing these receptors can be visualised in vivo by receptor scintigraphy using tow radioactive doses of the •

II

o

.

.

.

.

.

.

somatostatn analogue [ In-DTPA ]octreot de. The same agent given n a high rad oact ve dose can be used for peptide receptorradionuclide therapy(PRRT). The aim of this study was to evaluatewhether PRRT with .ill [ In-DTPAo]octreotide is able to reducetumour growth even under :amour growth-stimulating conditions induced by partial hepatectomy.Methods: Rats underwent 70% partail hepatectomy(PHx) or sham-operation. The development of hepatic metastaseswas determined 21 daysafter direct injection of ss-g-positive or -negativetumour cells into the portal vein. Groups of typically 8-9 animals that underwent PHx or sham--o~eration were treated with octreotide 50p.g/kg se. twice daily or with 370 MBq [ =llnDTPA°]oetmotide iv. on day 1 and 8. Both treatments were compared to control treatment. Forty non tumour-bearingrats were usedto determine the influence of PRRT on liver regeneration after PHx. Results: PHx induced an increase in turnout growth in all groups (p<0.0t). Octrentide treatment did not influence turnout growth aRer PHx or sham operation. PRRT could effectively reduce turnout growth in the liver of SS-R-positive turnouts also under conditions of increased tumour growth as generated by PHx (p
119E

Aim: In this study we consider the Ioco-regional targeted radionucfide therapy, using 13t-I-

bpiodol for the treatment of hepatoceliular carcinoma (HCC). Because o f his better physical properties (half-life: 17 hrs, max G-energy: about 2 Mev), 188-Re-lipiodol, would cause less mdioprotection problems and a lower effective patient dose. We made a prediction of the patient dose based on 13 l-I-lipiodol bi-planar scanning• Methods: After the inUa-arterial administering of the 131-1-1ipiodol (mean activity: 1850 MBq), the biological half-life of the 131-l-lipiodol in the body of l0 patients (especially in the liver, tumor, lungs and thyroid) was calculated, using bi-planar images made at different time points (one week and two weeks after the therapy). Therefore, appropriate regions of interest (ROt) were selected for the organs and for the background correction. For the liver and tumor an attenuation correction is made, using the patient geometry from CT images. Assuming an identical distribution when 188-Re-lipiodol would have been used, a patient dosimetry was performed by a Monte-Carlo simulation in an MCNP environment. A mathematical phantom of an average patient was generated by the computer. The tumor geometry (size and location in the liver) is calculated by using CT images of the patient and is also implemented in the computer phantom. Results: For a same tumor dose, a significant lower patient dose was calculated in the case of 188-Re-lipiodol. The liver dose decreased with a mean of 19.1%. Heart and kidney dose decreased with a mean of 82.4%. Consequently, the effective dose decreased with a mean of 25%. Conclusions: If the in-vivo distribution and stability is the same as 131-1-1ipiodol, 188-Re-lipiodol would be an excellent mdiopharmacantical for the treatment of HCC. 188-Re-lipiodol would cause a lower patient dose and less mdioprotection problems.

• RADIONUCLIDE THERAPY / DOSIMETRY 2 PS_473

PS_475

TREATMENT OF NEUROENDOCRINE LIVER METASTASES WITH INTERVENTIONAL NUCLEAR MEDICINE

BIODISTRIBUTION OF 111 IN LABELED TUMOR ANTIGENASSOCIATED MACROPHAGES IN A PHASE I OF IMMUNOTHERAPY IN METASTATIC MELANOMA

R. Buscombe, M.E. Caplin, A.J. Watkinson, J. Tibbles, A.J.W. Hilson. NET Clinic, Royal Free Hospital, London UK. Metastatic neuroendocrine turnouts (NETs) can be limited to the liver. These patients are often symptomatic. If surgery and emobolisation cannot be offered, liver transplantation may offer help but outcomes can be poor and ot~en there is a long wait for a liver. Therefore we have developed a new way with which to treat these patients. 7 patients with proven NETs (6 carcinoid, I islet cell tumour, 2 women youngest) within the liver only have been selected for the initial treatment 2 patients have had 2 treatments. In all patients 900-1000 MBq of 1-131 Lipiodol (Lipocis-CISbio) was infused into right or left hepatic artery (depending on tumour site) using a 5 French catheter. Infusion was performed with fluoroscopic screening to ensure tumour filling and prevent reflux of Lipiodol up the gastro-duodanal artery. The patient was then nursed in an isolation bed for up to 96 hours. One patients died of a pre-existing cardiovascular disease, another pa:ient died of their tumour but the remainder are well with good symptomatic response with minimal post procedure side effects In the 4 patients secreting 5-HIAA there has been a drop in levels. Objective evidence has not shown a reduction of more than 50% in turnout size. No patient has shown any further progression 1-131 Lipiodol therapy of metastatic neuroendocrine appears to stop cancer growth in 5/7 (72'/,) and reducing excretory function of the cancer in 4/7 (58%) patients. It may not however result in significant tumour shrinkage.

A. Moisan (1), E. Garin (1), C. Lesimple (1), A. Carsin (1), A. Devillers (1), V. Quillien (1), I. Ollivier (3), C. Leberre (2), J. Lecloirec (1), L. Toujas (1). (1) Department of Nuclear Medicine, Centre Eugene Marquis, Rennes, France ; (2) ETS, Rennes, France; (3) CHU Dermatology, Rennes, France. Aim: Tumor antigen vaccination represents a newly-introduced treatment of malignant melanoma. Tumor celt antigens recognized by cytotoxic T lymphocytes have a well-defined peptidic structure. They can be associated for vaccination with antigen-presenting cells, either macrophages or dendritic cells. In this study, we investigated the biodistribution of 111 In labeled tumor antigen associated macrophages injected along various routes and specially into peripheral lymph vessels. Methods: Seven HLA-A2 positive patients with metastatic melanoma expressing MAGE-3 mRNA were treated with autologous macrophages (AM) associated with a MAGE-3 peptide. At monthly intervals, six AM aiiquots were thawed, exposed to MAGE-3 peptide and injected into each patient along various routes : intradermally (ID), subcutaneously (SC), into lymph nodes (IN) and into catheterized peripheral lymph vessels (ILl. Thirty six AM injections were realized. Eleven l llln-radiolabeling of AM were performed. The biodistribution of labeled AM was investigated by scintigraphy 3 and 24 h post injection, at most twice, in a given patient (2 ID, 2 SC, 2 IN and 5 ILl. Results: 2,5 x 106 to 20 X 10~'(mean value: 12.7 x I06) AM were labelled with 4 MBq of I I 1In oxine. Labeling efficiency was 69 +/- 20 %. The mean radioactivity injected was 2.8 +/- 0,4 MBq. Scintigraphic images and variation of radioactivity uptake between 3 and 24 hours at the injected site, suggested that macrophages injected ID, SC and IN did not diffused from the injection site. In contrast, those injected into a superficial lymph vessel of the dorsal region of the foot, migrated well to popliteal and inguino-crural lymph nodes and remained at 24 hours.No significant activity was tbund in bone marrow and liver at 24h, attesting of good binding of I I 1In to labeled cells. The treatment was well tolerated. Conclusions: In a phase 1 of immunotherapy in metastatic melanoma, scintigraphy of 11 lln macrophages demonstrates that administration of labeled peptide-loaded antigen presenting cells through peripheral lymph vessels appeared feasible. 111In oxine labelled macrophages are a suitable tool for kinetics study of adoptive immunotherapy.

0

PS_474

PS_476

BORON DISTRIBUTION IN MALIGNANT BRAIN TUMOURS FOR BNCT

REPEATED SM-153 EDTMP I.V APPLICATIONS IN REFRACTORY PAINFUL PROSTATE METASTASES FOR LONGER LASTING ANALGETIC THERAPY

e~

N. Baziotis (1), V. Voliotopoulos (2), A. Zissimopoulos (1), A. Zafirakis (1), A. Stavraka-Kakavaki (2), G. Limouris (2). (1) St. Savvas Anticancer Hospital, Nuclear medicine Dept, Athens Greece; (2) Areteion University Hospital, Nuclear Medicine Dept, Athens Greece.

0 a.

L. Menichetti (1), V. Calderone (2), D. Petroni (1), L. Cionini (3), R Salvadori (1). (1) National Research Council - Institute of Clinical Physiology, Pisa, Italy; (2) Department of Psychiatry, Neurobiology and Farmacology, University of Pisa, Italy; (3) Department of Oncology, University of Pisa, italy. Boron Neutron Capture Therapy (BNCT) is a radiotherapy modality based on the side emission produced by the capture of epythermal neutrons by Boron-10 atoms and is under investigation for the treatment of brain Glioma and skin Melanoma. p-boronophenylalanine (BPA) is extracted in these tumours at concentration 2-3 times higher than in normal tissues. Increasing the delivery of Boron within the target tissues as welt as the need of new methodologies for the quantitative determination in vivo and non invasively are the crucial aspect for a the development of BNCT. A combined approach using Positron Emission Tomography (PET) and digital autoradiography on animal models has been adopted in order to evaluate both the cerebral extraction of BPA, thus covering the lack of methods to asses the biodistribution and the concentration of the borouated drug in target and non target tissues. To this purpose ISF-BPA and 3H-BPA are used and preliminary results of BPA biodistributioo are given in the present work. A turnout bearing animal model has been set up (the cellular line of Glioma C6 has been selected and implanted in rat brain) and used to develop a method for autoradiographic turnout imaging. Using the tritiated analogue of BPA, the microdistributioo data have been evaluated. Typical values 3-4 times higher of BPA extraction have been detected in turnout and an ubiquita~ extraction in control animals has been found. ISF-BPA will be used to study BPA pharmacokinetic in vivo. The study of tritiatad F-BPA is ongoing and the extraction ratio within the region of interest will be compared to BPA. The ftuoriuated analog of BPA has been synthesised using acetyl hypofluorite and the procedure has been optimised for ISF-BPA production: synthesis, separation and quality control techniques have been set up with a remote control approach. The use of isF-BPA for both digital autoradiographYl0 . and PET is in progress m" order to a) monitor drug localization, b) calculate the B tissue concentration, c) assess the extant and homogeneity of turnout uptake. Following this approach, in vivo behaviour and tumour extraction of BPA and its fluorinated analog have been clarified and some limitations in technology have been resolved: this will allow a better understanding of the efficacy of BNCT for human application.

Management of metastatic pain becomes particularly important in patients with prostate cancer in whom overall survival may be relatively long even with advanced disease, while the quality of life is frequently poor. The aim of this study was to evaluate the efficacy ofSm-153 EDTMP in refractory painful bone metastases secondary to prostate cancer after repeatad injection strictly according to the developed myelotoxicity. Materials/Methods: Thirty seven MBg/kg Bw of Sm-153 EDTMP (CIS Bio Intern Gif sur Yvette) were i.v. injected in 22pts (aged 54 to 81 yrs) with multiple painful societal metastases due to hormone resistant prostate cancer and maintained on analgetic medication, often including narcotics. The efficacy of the treatment was assessed by a pain and performance questionnaire that patients were asked daily to complete and by comparison of booe scans, CT or MRI images, Kamofski indexes and BSI, before and at least 9 months after the initialitation of the therapeutic shceme. Strict criterion to repeat the radionuclide injection was the developed mylotoxicity. Results: 15 out of 22 patients responded (2 with moderate pain ,10 pain free) after the first injection. 4 out of the rest 7 patients responded (2 with moderate pain,2 pain free) after the 2 injection.It is worthwhile to point out that the moderate responds of the first injection became pain after the second one. Given that a third dose could lead to aplastic disorders and that already the 13 patients underwent blood tranfusioo the therapeutic scheme was stopped. The accumulative radiation deposition of the reputed scheme was calculated to be approximately 6700 and 1500mGy/MBq in bone surface and bone marrow respectively. Conclusion: The sum of the radiation has been ciusidered as still paliative rather than curative,although CT scans 9 months post treatment show recalcificatioo of the lyric component interpreted as response to therapy.

• RADIONUCLIDE THERAPY / DOSIMETRY 2 PS_477

PS_479

THE VIENNA-PROTOCOL ON REPEATED LOW-DOSE 153SMEDTMP THERAPY INDUCES PAIN PALLIATION AND LESION REGRESSION / STABILISATION

RADIATION EXPOSURE IS VERY LOW TO THE FAMILY MEMBERS OF PATIENTS TREATED WITH YTTRIUM-90 ZEVALIN = ANTI-CD20 MONOCLONAL ANTIBODY THERAPY FOR LYMPHOMA

H. Sinzinger (1), K. Weiss (2), S. Granegger (1), S. Oftuoglu (1), CH. Kratzik (3), CH. Hajek (2). (1) Department of Nuclear Medicine, University of Vienna, Vienna, Austria; (2) Department of Radiology and Nuclear Medicine, Hospital of Wiener Neustadt, Austria; (3) Department of Urology, University of Vienna, Vienna, Austria.

G. Wiseman (1), B. Leigh (2), T. Witzig (1), D. Gansen (1), C. White (2). (1) Mayo Clinic, Rochester, MN, USA, Department of Nuclear Medicine; (2) Idec Pharmaceuticals, Corp., San Diego, Ca, Usa, Department of Ontology & Hematology, Rochester, USA.

In order to achieve therapeutic effects beyond pain palliation we introduced the Vienna-protocol (30 mCi [I,I GBq] 153Sm-EDTMP, 5 times in 3-months intervals) in prostate and breast cancer patients with multiple bone recurrences on an outpatient base. We are going to present in a total of 50 patients (36 - 96 a) with prostate cancer, finishing this first part of the I-year protocol, lesion regression documented by scintigraphy, and in part by radiography, CT and MR, as well as by a decrease (> 7 1 % ) of PSA (in 64 % after a temporary increase). Bone uptake of IS3Sm-EDTMP ranged between 47 and 82 %, onset of pain palliation was alter 3 to 15 days. 48 % had complete pain palliation, 40 % partial, 5 % showed minor improvement, the effect lasted fur at least 9 weeks in all the responders. Quality of li1~ significantly improved. No correlation between the pain palliating effect, the bone uptake or the flair phenomenon and the extent of regression was monitored. The drop in peripheral blood cells (platulets - 28 %, white blood cells - 23 %, red blood cells - t8 %) showed a nadir after 3 - 6 weeks. No significant cumulative bone marrow damage was noted after the fifth treatment. The Vienna-protocol looks promising to achieve beyond pain palliation lesion regression / stabilization with minimal bone marrow damage at low costs on an outpatient base.

Aim: Yttrium-90 (Y-90) is a beta-emitting radioisotope used in clinical trials for the radioimmunotberapy of patients with cancer. Although Y-90 emits no penetrating gamma photons, low levels of bremsstrahlung radiation are expected. Our aim was to quantify the radiation absorbed dose received by family members following a sirig~e dose of Y-90 ibritumomab tiuxelan (Zevalin), an anti-CD20 radioimmunotherapy under development for patients with B-cell non-Hodgkin's lymphoma. Methods: B-ceil lymphoma patients receiving a single intravenous dose of 14.8 MBq/kg Y-90 Zevalin were instructed to avoid body excretion contamination but were not advised to isolate or keep a distance from family members. The family member anticipated to have the closest contact with the patient during the seven days after the Y-90 Zevalin infusion was assigned to wear a DoseGUARD Plus electronic personal dosimeter (AEA Technology QSA, Inc., Burlington, MA). In addition, an ion chamber device was used to measure radiation exposure at a distance of I meter t~-om the lower chest of patients immediately after the Y-90 Zevalin doseResuhs: Radiation exposure was measured in 13 patient family members following Y-90 Zevalin therapy. All patients confirmed that the personal dosimeter was worn at all times (including at night) when in the same building, car or airplane as the patient. The median deep dose equivalent radiation exposure was 0.035 rosy total accumulation over seven days with a range of 0.014-0.079 mSv. The median radiation exposure at one meter from the patient immediately following the Y-90 Zevatin dose was 0.00295 mSv/hour with a range of 0.0024-0.0039 mSv/hour.Conclasions: In many medical centers, Y90 radioimmunotherapy does not require hospitalization. Patients are treated as an outpatient to return home after receiving the radiopharmaceutical. We have found that, even without patient isolation or shielding, radiation exposure to l~mily members during the seven days following Y-90 Zevalin is very low and in the range of backgruund.

PS_478

PS_480

AMIFOSTINE (AF) AND RADIOTHERAPY (RE) : PHASE 1 STUDY

USE OF RADIOLANREOTICE TO TREAT SOMATOSTATIN RECEPTOR POSITIVE TUMOURS

D. Di Gennaro (1), M. Alfieri (2), B. Curcio (1), G. Scimone (1), A. Losco (1), C. Bianco (1), E. Falcone (1), S. Di Fiore (1). (1) Radiotherapy Unit A.O. ,San Giovanni Di Dio E Ruggi d'Aragona" - Salerno, Italy; (2) Pharmacy Mercato San Severino Hospital (SA), Italy. Purpose: to evaluate the tolerance and efficacy of Amifostine (WR-2721) as a radioprotector ~,'lethods: in 1999 we began a clinical phase I study to evaluate AF as radioprotector; until now we have used AF in ni25 patients, with an age varying from 16 to 36 (median age 25), affected by n i18 Hodgkin Limphomas (HL) (mantle field - dose: 30Gy/20 ftact.), hi6 NonHodgkin Linphomas (NHL - Neck field - Dose: 41.4 G y / 2 3 fract.), and 1 patient, age 53 years, affected by a pelvic mass from a cervix ca. (dose:61 Gy), already surgically treated (ureteral-bladder-ileotomy) fur iatrogenic toxicity ( bilateral ureteral necrosis) caused by cisplatin. The bladder was created from an ileal loop, and was highly prone to radiation necrosis. AF was used: a) in young patients treated to Head and Neck (to prevent xerostomia) b) in young patients treated with mantle field (to prevent xerostomia, esofagitis and second ebemoradiation tumours) c) in patients already treated (higher risk of radionecrosis). AF was given at a dose of 500 mg. diluted in 5 cc of fisiologic solution, s.c., in two different subministrations 15 m' before RT. We always gave antiemetic profilaxis with serotonin - antagonists. Subeutis way was more useful, for our busy department (100 patients/day). Resultn: We did not notice bad effects caused by subeutis subministration o l A F ; we noted 4/18 acute radiation toxieitiea (Grade 2 esophagitis), but no acute xerostomia, and a complete compliance to radioprotector and radiotherapy schedule. Conclusion: AF is safe and useful, and now is routinely given in our department to this subgroups of young patients.

R. Buscombe (1), M.E. Caplin (1), J. Hepplewhite (1), G. Johnson (1), R Bouloux (1), T. Meyer (1), D. Hochhauser (1), I. VirgoUini (2), 1. Ah Yong (3), A.J.W. Hiison (1). (1) NET Clinic Royal Free Hospital, London UK; (2) University of Lienz, Vienna, Austria; (3) Queen Elizabeth Hospital, Hong Kong, China. Targeted therapy with Y-90 Lanroetide may be appropriate in patients who have turnouts which express somatostatin receptors. Many of these patients, for example those with carcihold, do not respond to chemotherapy or external radiotherapy. The aim of this study is to review our experience in using Y-90 Lanreotide on such turnouts A total of 53 cycles o f Y-90 lanreotide have beart given to 23 patients over an 18 month period. All patients had failed or found to be unsuitable for other cancer treatments. There were 15 patients with carcinoid, 5 with gliomas, 1 fibrolamellar cancer, 1 ACTH secreting cancer and one malignant histiocytoma. Patients were infused with 0.8-1.2 GBq on a 3-4 weak basis for 3 treatments and if there was response this was repeated afer a 3 month gap. Those with intra..cerebral tumours were treated with 200-400 MBq Y-90 Lanreotide intra-arterially into

the tumourbed. Most patients had fatigue for 7-10 days post treatment. There has been mild bone marrow toxicity in 4 padents and no renal ~oxicity. Response as measured by >50 reduction in turnout size on CT has occurred in 6 patients, stability of previously growing disease in 8 patients. All the remaining 9 patients with progressive disease have died of their disease. Poor prognostic indicators are massive tumour bulk and bone or lung metastases. Y-90 Lanrentide can induce stability or regression in 56% o f patients but may not be appropriate for those with very advanced disease

• RADIONUCLIDE THERAPY / DOSIMETRY 2 / BONE AND JOINTS 2 PS_481

PS_483

FEASIBILITY OF HIGH-ACTIVITY SAMARlUM-153-EDTMP THERAPY FOLLOWED BY AUTOLOGOUS PERIPHERAL BLOOD STEM CELL REINFUSION IN UNRESECTABLE OSTEOSARCOMA

RADIATION HAZARD FOR PATIENTS AND RELATIVES AFTER PAIN PALLIATION WITH 30 MC1153SM-EDTMP

C. Franzius (1), S. Bielack (2), S. Flege (2), J. Sciuk (1), H. J0rgens (2), 0. Schober (1). (1) Department of Nuclear Medicine; (2) Department of Paediatric Haematology and Oncology, MOnster University, MOnster,

Germany. Aim: Sm-153-EDTMP (samarium-153 ethylenediaminetetramethylene phosphonic acid) has been introduced for palliative pain therapy of osteoblastic bone metastases. The distribution of Sm-153-EDTMP is comparable to that of Tc-99m-MDP in bone scintigraphy. Osteoblastic osteosarcomas producing abundant primitive bone matrix usually present as 'hot spots' on a diagnostic bone scan. Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Patients and Methods: 6 patients (4 male, 2 female; %41 yrs.) with unresectable primary osteosareoma (n=3) or unresectable recurrent sites of osteosarcomas (n=3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). Whole-body scans were acquired immediately after Sm-153-EDTMP application, 4h, and 24h later. In all patients autologous peripheral blood stem cells had been asservated before Sin-153-EDTMP therapy. Results: No adverse reactions were observed in the 6 patients neither during the injections nor during the hours following the application. In one patient bone pain increased during the first 48 h after therapy. Another patient had complete pain relief within 48 h. Autologous peripheral blood stem cell reinthsion was performed on day +14 in all patients to overcome potentially irreversible damage of the hematopoletic stem ceils. In one patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and polychemotherapy was continued. 21 months later this patient is still free of progression. I patient died 6 months after therapy, the other 4 patients are still alive (follow-up 3-15 mo). Conclusion: These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrant further evaluation of efficacy. The combination with external radiation, and polychemotherapy seems to be most promising. Although osteosareoma is believed to be relatively radloreslstant the total t'~cal dose achieved may delay local progression or even achieve permanent local tumor control.

University of Vienna, Vienna, Austria. J53Sm-EDTMP is one of Ihe radioisotopes of choice for treatment of pain ful bone recurrences. Radiation exposure data of staff; patients and their relatives after therapy ot painful bone metastasis with IS3Sm-EDTMP are extremely rare. We determined radiation dose in 14 patients being treated for bone metastases after breast (n=6) or prostate cancer (n=8) receiving a single treatment with 30 mCi (I,I GBq) )5~Sm-EDTMP. Radiation dose was also measured in the panners of 5 of the patients. Patients received 2,79 + 0,87 mSv, their respective partners 0,24 _+ 0,14 mSv. Female partners exhibited higher radiation dose (0,40 - 0,49 mSv) as their male counterparts (0,24 - 0,42mSv). Their dose was 16,26 % for female and 10,25 % for male partners from treated patients. Furthermore, we assessed the finger dosis of the staff (tracer preparing technician and applying physician) with and without lead shielding of the syringe containing the radioisotope. Shielding resulted in an increase of finger dose for the technician (+ 20 %) due to a longer preparation time, while the physicians one was decreased (to 20%). Our findings show, that family members are exposed to about one tenth of the patients exposure and that at least four treatments with a dose of about 30 mCi 153Sm-EDTMP can be administered to a patient to keep his partner within the tolerated limits of I mSv/a.

tO

PS_482 ANALYSIS OF STRONTIUM-89 INDUCED REGRESS OF BONE METASTASES IN PROSTATE CANCER YU. Ussov (1), E.V. Barysheva (1), V. Obradovic (2), '4. Baltic (3), S.R Selivanov (1), S.N. Isaeva (1), S. Regoe (3), V. Artico (2), J.E. Riannet (1), S.A. Vetichko (1). (1) Tomsk Medical Research Center, Tomsk, Russian Federation; (2) Serbian Clinical Center, Belgrade, SR

Jugoslavia; (3) Institute of Oncology, Sremska Kamenica, SR Jugoslavia. Sr is now widely used as agent of choice for pain relief in extensive metastatic bone disease• Nevertheless the anatomic features of bone metastases (rots) in the course of S~Sr-therapy remain not well studied, Here we aimed to analyse the clinical, bone scan and MRI data in prostate cancer patients with extensive spread of disease (No. of mrs >10) and in patients with amount of metastases < 5, all of whom received SgSrtherapy. 47 patients with bone metastatic spread of prostate cancer, already on antiandrogen therapy, were treated with s9Sr (MedRadioPreparate Ltd.) and studied before, and in 3-6 months after injection of 89St. In everyone whole-body ~ T c - M D P (4h post-injection of 370 MBq) and T1and T2-we~ghted MRI scans were performed. Both Tc-MDP and MRI images were quanUfled as {Metastasis/Background} pixel count ratio. Patients were gathered into groups of persons with extensive disease (Gr 1, No. of rots >10, 31 pts), in whom severe pain syndrome was present in 26 of 31, and those who did have minimal bone involvement (Gr.2, No. of rats < 5, 16 pts) and obvious pain symptoms in 9 pts only. Everybody demonstrated prominent improvement in severity of pain syndrome with full pain relief in 27 (21 of Group 1 and 8 of Group 2). Duration of pain-free period was 2,9 sd 0,8 months in Group 1 and exceeded 4 months in every patient of Group 2. The {Metastasis/Background} ratios have been changed by 89SrC12as :

before treatment 3-6 mnths after Sr-89 injection

H. Sinzinger (1), S. Ofluoglu (1), E. Havlik (2), S. Granegger (1). (1) Department of Nuclear Medicine; (2) Institute for Biomedical Physics,

Group I (n=31 ) '~"Tc-MDP 3,89 sd 2,75 1,84 sd 1,94 p<0,05

T l - w MR1 0.51 sd 0,14 0,78 sd 0,23 p<0.05

Group 2 (a=16) ~Tc-MDP 1,81 sd 1,57 1,39 sd 1,12 p<0,05

T l - w MRI 0,81 sd 0,23 0,93 sd 0,16 p<0.05

The decrease in 99mTc-MDP uptake after 89Sr treatment correlated significantly with pre-treatment uptake both in Gr. 1 (as -0,63+0,36X, F0.67) and Gr.2(as -0,49+0,47X, r=0,86). Thus, agSr induces substantial regress of usteoblastic bone metastases in prostate cancer, regardless extent of disease, more prominent and lasting longer in cases with small number of mets.

OTHER CLINICAL SCIENCE. BONE AND JOINTS 2 PS_484

o

QUALITATIVE AND QUANTITATIVE ANALYSIS OF TC99M LABELED HUMAN IMMUNOGLOBULIN G (HIG) SCINTIGRAPHY IN SYSTEMIC RHEUMATIC DISEASE (SRD)

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I,..

A. Leondi (1), M. Souvatzoglou (1), E. Papadaki (1), J. Datseris (1), E. Moulopoulou (2), CH. Zerva (1), CH. Kostopoulos (3). (1) Department of Nuclear Medicine, Alexandra Hospital Athens, Greece; (2) Department of Radiology, Aretaion Hospital, University of Athens, Greece ; (3) Therapeutic Clinic, Alexandra Hospital, University of Athens, Greece. The aim of this study is to evaluate H1G Immunoscintigraphy by qualitative and quantitative analysis in the assessment of pulmonary involvement in patients with SRD. Material and Methods: 42 patients (34 females, 8 males, mean age 55,9 + 12,4 years, mean disease duration 8,5 _+.7,3 years), 23 systemic sclerosis, 13 rheumatoid arthritis, 3 lupus erythematusus and 3 CREST and without evidence of concomitant pulmonary infection or heart failure, underwent HIG scintigraphy (ling polyclonal human IgG-HIG- labeled with 750 MBq 99mTc, 4h p.inj. ,high resolution collimator, 600kcts, matrix 256x256, sophy camera NXT), as well as High Resolution Computed Tomography (HRCT) of the lungs (gold standard). Ten control subjects were also studied with HIG, because of painful hips. Qualitative interpretation of the scans was done by two independent nuclear medicine physicians. Quantitative analysis was performed on the posterior view (3 ROIS at Right Lung, 3 ROIS at Left Lung compared to Left Ventricular ROI) and the Average Score for every scan was calculated. Results: HIG scintigraphy revealed increased HIG uptake in the lungs (diffuse, focal or over the large pulmonary vessels) in 37/42 pts and in none of the controls. There was no statistically significant difference in the results between HIG and HRCT, The quantitative analysis of the controls' scintigrams revealed a mean value of the av. Score 1,48 + 0,09 (range 1,3- 1,58), of the patients' negative scintigrams 1,5 + 0,08 (range 1,4- 1,57) and of the positive scintigrams 1,9 + 0,23 (range 1,6- 2.61). Scans with a score > 1,60 were considered as positive. The comparison between the qualitative and quantitative analyses showed that all scintigrams that were interpreted as positive had a score > 1,60. There is a significant difference between the group with negative scans and the group with positive scans (p<0,001). Conclusions: HIG immunoscintigraphy of the lungs represents a highly sensitive, non invasive method for the detection of the pulmonary involvement in SRD. Quantitative analysis could be an indicator of the activity of the disease. This could contribute to the better management of the patients. __

119£

• OTHER CLINICAL SCIENCE. BONE AND JOINTS 2 PS_485

PS_487

ENHANCED EFFECT OF F6-1,25(OH)2D3 ON RADIOACTIVE CALCIUM DEPOSITION IN OSTEOBLASTS

PROGNOSTIC VALUE FOUR PHASE BONE SClNTIGRAPHY FOR REFLEX SYMPATHETIC DYSTROPHY SYNDROME IN HEMIPLEGIA

H. Seto (1), Y. Kamisaki (1), N. Watanabe (1), M. Shimizu (1), T. Miyahara (2), T. Shimoura (2), N. Osafune (2). (1) Department of Radiology; (2) Department of Toxicology, Toyama Medical and Pharmaceutical University, Toyama, Japan.

B. Okudan (1), S. Sertta~ (2), C. (~elik (2). (1) Ankara Numune Training and Research Hospital Nuclear Medicine Department; (2) Ankara Physical Medicine And Rehabilitation, Ankara, Turkey.

Purpose: Bone-seeking radiopharmaceutieats have been used as the therapeutic agents to relief intractable bone pain in patients with metastatic bone disease, in which the greater the osteoblastic activity, the greater the concentration of the agents in and about the tumor. Until now, several pharmaceuticals such as vitamin D3, PTH or androgen have been tried to enhance the deposition of radioactive agents, no routine clinical use is, however, available. In this study we assessed the enhanced effect of 26, 27-hexafluoro-lOt, 25-dihydroxy vitamin D3 (vitamin F-D3) on radioactive calcium deposition in osteoblastic cells as compared to the effect of vitamth D3. Methods: Fetal osteoblastic cells (SV-HFO) were cultured for 3 days in a a-MEN medium with 10% t~tal bovine serum. Then, [~-glycerophosphate (13-GP) and dexamethasone were added to induce the development of ossification. Moreover, vitamin D3 or vitamin F-D3 were added to enhance the deposition of calcium in osteoblasts. The medium was changed every 2 days. After the observation of ossification, radioactive calcium (Ca-45) was added to the medium, and was cultured for 24 hours. Then, osteoblasts were separated from the culture and radioactivity of Ca-45 in the osteoblasts was measured. Results: Ca-45 deposition in the osteoblasts increased as the [5-GP concentration increased from 0 to 10 mM. Addition of vitamin D3 enhanced the deposition of Ca-45 about 1.4 fold as compared to [3-GP only. Moreover, vitamin F-D3 showed a strong enhanced effect on the deposition of Ca-45 about 16.4 fold as compared to [~-GP only. Conclusions: A new pharmaceutical, 26,27-hexaflanro-ltx, 25-dihydroxy vitamin D3 (vitamin F-D3) has a potential enhanced effect on the deposition of calcium in osteoblasts. This pharmaceutical might be effective in patients with metastatic bone disease and osteomalacia instead of vitamin D3.

Background: Reflex sympathetic dystrophy syndrome (RSDS) is a painful disabling problem, the diagnosis of which can be difficult to confirm by objective measures. Although the pathogenesis of RSDS remains unknown, most hypotheses are based on an event (stroke) that triggers an abnormal central reflex arc. Bone scintigraphy is frequently used to confirm the clinical suspicion of RSDS. Aim: This trial was carried out to investigate the correlation between four phase bone scan (FPBS) and clinical manifestation of RSDS in upper extremity of hemiplegia. Methods: We have investigated 34 pts. (17 males, mean age 64-+8; 17 females, mean age 59±12; mean disease period, 2-12 weeks) with cerebrovascular accident (CVO) confirmed by head computed tomography (infarction or hemorrhage). All patients received four phase bone sciotigraphy {perfusion, blood pool, late blood pool and osseous phase). We analyzed perfusion and exact site was obtained every second for 60 seconds followed by first immediate static (early blood pool), second static after 20 minutes (late blood pool) and third static images after 3 hours for 500.000 counts. Results: All patients received tour phase bone scans; 25 scans positive for RSDS. Nine patients with negative scans except one had no symptoms of RSDS. Eleven patients with positive scans had symptoms at the time of bone scanning. Eight out of 14 asymptomatic patients with positive scans developed symptoms following six months. We found a significant correlation between positive FPBS and positive clinical symptoms of RSDS (p
PS_486

PS_488

THE EVALUATION OF BONE MINERAL DENSITY IN EPILEPTIC CHILDREN RECEIVING VALPROIC ACID

CORRELATION OF BONE MASS MEASUREMENT AMONG LUMBAR SPINE AND HIP

M. Kaya (1), S. KarasalihoOlu (2), N. Oner (2), H. Carman (2), F. 0st0n (1), C. (~eltik (2). (1) Deparment of Nuclear Medicine; (2) Department of Pediatrics, Trakya University, Edirne, Turkey.

R. Garcia (1), J. Lopez (1), M. Gonzalez (1), J. Luis (2), R. AIvaraz (t), P. Gomez (1), M. Herrador (2), R. Vazquez (1). (1) Department of Nuclear Medicine; (2) Department of Medical Physics, H.H.U.U.Virgen del Rocio, Seville, Spain.

Atraumatic fractures are often seen in epileptic children. Several factors including immobilization and antiepileptic treatment lead to osteopenia causing increased bone fragility. Antiepileptic drugs such as phenytoin, phenobarbital, primidone are established contributors to osteomalacia and rickets. Recently valproic acid-induced changes in bone mineral density have been reported. The aim of this study is to evaluate the relationship between the bone mineral density and the dosage and duration of vatproic acid therapy: The relationship between the bone mineral density and biochemical parameters such as calcium, phosphorous, alkaline phosphates, vitamin D, osteocalcin and parathormone are also evaluated. Methods: Bone mineral density was meesm'ed by dual-energy x-ray absorbtiometry at L2-L4 levels of lumbar vertebrae, the femoral neck and the greater trochanter in 27 children ( mean age; 7.3 ± 3,5 yrs) with uncomplicated idiopathic epilepsy treated with valpsoic acid for more

than 6 months. Results: Mean serum levels of valpsoic acid was 60.57 ± 14.3 p.g/mL and mean duration of treatment was 18.5 ± 12.6 months, respectively. Mean bone mineral density values at L2-L4 levels of lumbar vertebrae,the femoral neck, and the greatertruchantar was calculated to be 0.55 ± 0.2 g/cm,2 0.61 ± 0.2 g/cm,2 0.53 :t: 0.1 g/cm2, respectively. • We found a neganvecorrelation betweenthe dosageof valproic acid and the bone mineral density at lumbar vertebrae, the femoral neck and the greater trochanter (r=0.47, p-~).015, r--0.49, p=O.01, ~0.55, p-O,003, respectively). There was a positive covratation between the serum level of alkaline phosphates and the bone mineral density at the femoral neck and the greater trochanter (r=0.43, # . 0 2 , r=0.40, # . 0 4 , respectively). There was no correlation between bone mineral density and duration of valpsoic acid therapy and other biochemical parameters. Conclusion: Based on these results, it is suggested that the measurement of bone mineral density and biochemical supervision of the patients is required during high-dose vaiproic acid therapy.

120(2

Dual -energy x-my absorptiometry (DEXA) allows non-invasive direct measurement of bone mineral density(BMD). Only few data are available comparing the results of BMD measurement among various sites. The aim ofonr retrospective study is the assessment of the correlation of BMD among lumbar spine and hip. METHODS: BMD of the lumbar spine and hip was studied in 2108 patients. Bone mass measurement was performed with dual energy x-ray absorptiometer (DEXA) Hologic QDR 4500W. Relationships were analysed using Pearson's coefficients of correlation and its statistical significance test. RESULTS: The resuRs revealed a significant high correlation of BMD of total hip and lumbar spine (r'=0.705 p<0.O0 l).Nevertheless BMD of the spine was mostly correlated with BMD of trochanteric site (r---0.709 p<0.001) and least correlated with B MD of intertrochaoteric region 0"=0.651 p<0.001). CONCLUSIONS: BMD of spine and hip are highly correlated. Though there is some heterogeneity of bone mass density among different measurement sites practically with this good level of correlation, bone mass meesurament of lumbar spine might be used to predict the BMD of the hip.

• OTHER CLINICAL SCIENCE. BONE AND JOINTS 2 PS_489

PS491

MANAGEMENT OF CONDYLAR HYPERPLASIA ASSOCIATED WITH MANDIBULAR ASYMMETRY

ASSESSMENT OF BONE SClNTIGRAPHY AND SPET IN THE VIABILITY DIAGNOSIS OF MICROVASCULARIZED FIBULA GRAFT USED IN MANDIBULAR RECONSTRUCTION

A. Fawzy (t), B. Gamal (2). (t) Nuclear Medicine Department, Faculty of Medicine, Cairo University; (2) Surgery Department, Faculty of Oral and Dental Medicine, Cairo University, Egypt. Condylar hyperp}asia is a malformation of non-neoplastic origin involving the size and morphology of one or both mandibular condyles. Unilateral cases lead to facial asymmetry. Aim: To evaluate the role of osseous scintigraphy in determining the metabolic status of the condyle and assessing the actively growing condyles in patients with unilateral facial asymmetry. Also, assessing the addition of SPECT and quantitation to the planar images in offering an objective response and hence diminishing the false positive and negative results. Methods: The study included 25 adult patients, who were divided into 2 groups (t5 with unilateral facial asymmetry and I0 control patients). Both clinical and conventional radiological evaluation confirmed the presence of unilateral hyperplasia and disturbed occlusion in the I '~ group, All 25 patients were subjected to bone scan after the IV injection of 740 MBq Tc-99m MDP and the mandible was imaged 2 hours later, both planar and SPECT, as well as the lumbar vertebrae as a reference point. Quantitation of the right and left condyles as well as the lumbar vertebrae was evaluated. The I s~group patients were all subjected to a corrective surgery (condylectomy) via a periauricular approach, and the removed condyles were evaluated histopathologically. Results: The mean age of the patients was 21.8+4.1 years while that of the controls was 21.6+3.6 years. In the patients group there were 10 females and 5 males, while in the control group there were 6 females and 4 males. In the patients group, there were 9 fight and 6 left condylar hyperplasia. The mean count in right condyle of the patients group was 6859+_97I, in the left 5948_+.1t 97 and in the 4 th lumbar vertebra was 4631+418. While. in the control groups it was in the right condyle 4729_+53 I, in the left 4698+485 and in the 4 ch lumbar vertebra was 4697+_452. The ratios right/left condyles, right/lumbar and left/lumbar in the patients were 1.18+0.29, 1.47+0,21 and 1.29+_0.25 respectively, while, in the control group they were 1.0t+0.06, 1.01+_0.05 and 1.00+0.04 respectively. The histopathological diagnosis showed numerous hyperplastic osteocytes in the periphery of the condyle. Conclusion: SPECT osseous scintigraphy is a useful indicator of continued bone activity. Also, osseous scintigraphy is of immense value in choosing the management of patients with mandibular asymmetry.

I. Hervfis (1), UM. Florin (2), P. Bello (1), A. Saura (1), P. Gonzfilez (1), R. Perez (1), M.C. Baquero (2), A. Mateo (1). (1) Department of Nuclear Medicine; (2) Department of Maxillofacial Surgery, University Hospital, Valencia, Spain. Aim: Bone allografis are ofien used in reconstructive mandibular surgery, generally following extensive oncologic resections, posttraumatic pseadoartthrusis or osteomyelitis. Vascularized fibular bone grafts have the advantages over other bone grafts in the restoration of the contour and function of defective mandibles. Bone scintigraphy has o~en been used to assess revascularization of bone, because positive uptake of 99mTc-HMDP reflects patent anastomoses and viability of the grafted bone. Nuclear medicine techniques have the advantage, regarding the angiography, that they are bloodless. The aim of this study is to assess bone scintigraphy and SPET in the detection of viability of the grafts. Methods: Mandibular reconstruction with a free fibula flap was done in 13 patients in the last four years. Bone scintigraphy and SPET was applied in the follow up of nine patients. For bone scintigraphy 740 MBq of 99mTc-HMDP was administered intravenously. We have considered the blood pool and late images (which were obtained two hours after the administration of the radiopharmaceutical). In each view (anterior and both lateral from the skull) until 400000 counts were reached. The study was carried out on the fifth day. Control scituigraphies were performed in two patients (at month 5 and I year). SPET studies were acquired immediately after planar imaging. Sixty frames of 30 s each were collected during a 360 rotation. The projections were reconstructed in a 64X64 matrix. Transaxial, sagittal and coronal mandibular tomograms were obtained and analyzed. Semiquantitative assessment of the grafts was done with a six-grade scoring system, based on comparison of tracer uptake in the graft and in the calvarium. Results: Complications were observed in one graft. Planar scimigrams showed a tracer uptake higher than grade five in grafts with an uncomplicated course. SPET were performed in addition to planar imaging in three patients showing a higher graft uptake. A lack of tracer uptake was observed in the failed graft. Conclusions: It is conclude that bone scintigraphy performed within the first week after the mandibular reconstruction is a useful tool to monitor the viability and early complications of microvascularized fibular grafts and plays an important role in the process of decision-making on surgical reexploration. SPET is more sensitive than planar imaging for the assessment of graft viability. The microvascularized fibula flap is optimal in mandibular reconstruction.

c.O m

PS_490

PS_492

THE VALUE OF BONE SPECT TO EVALUATE LOW BACK PAIN ETIOLOGY: IN COMPARISON WITH PLANAR BONE SClNT|GRAPHY

LEUKOSCAN IN CLINICAL PRACTICE

,.i..a cO

P.J. Ryan. Department of Nuclear Medicine, Medway Maritime Hospital, Gillingham, U.K.

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M. Aydm, A.E Yapar, N. Yolo~lu, H. Yalcln. Department of Nuclear Medicine, Baskent University, Adana Hospital, Adana, Turkey. Aim: The purpose of this study was to evalute the additional value of hone SPECT compared to planar images in the revealing cause of low back pain. Methods: Twemy-two patients (7 M, 15 F, age range 19-74 yrs, mean age 53±14) who suffered from low back pain were studied. Nine of 22 patients had known primary malignancy (4 breast, 2 lung, I thyroid, I prostate, and I renal cell carcinoma). Whole body bone scan, spot images and lumbosaaral SPECT (360 °, circular rotation, 128x128 matrix, 64 frames with 20 seconds acquisition time) were performed 3 hours after the injection of 20 mCi (740 MBq) Tc-99m MDP with a dual head gamma camera (Siemens e-cam). All patients underwent Xray, 8 patients MRI and 4 patients CT. Results: Three patients had increased uptake only in sacroiliac joints in planar and SPECT images (group 1). The remaining 19 patients had abnormal tracer uptake in the lumbar vertebrae (group 2). All of the group 1 patients were diagnosed as sacroiliitis by radiological and clinical findings, In group 2, the vertebral lesions classified into anatomical regions in SPECT images as whole vertebra, vertebral body, pedicle, facet joint and spinous process. Seven whole vertebrae, 5 vertebral body, 7 pedicle (4 only in pedicle, 3 in pedicle+facet joint), 10 facet joints and 1 spinous process lesions were found. The lesions that were only in the pedicle (4 patients) were confirmed as metastases by radiological techniques. Conclusion: Our findings indicate that SPECT had no superiority to planar images in sacroiliac joint lesions. On the other hand, in the evaluation of vertebral lesions, SPECT images can localize abnormalities to the ve~ebral body, pedicle, facet joints or spinous process and this can result in additional diagnostic information, and might be routinely used in the evaluation of low back pain etiology.

Aim: The imaging of orthopaedic infection with Te 99m antigranulocTte Fab' fragments (leukoscan) has shown impressive results from the limited published studies. This method of imaging infection has advantages of being less labour intensive and enabling completion on a single day. Data for this technique remains limited and there is a need for further corroborative data. This study examined the success of Lcukoscan in the detection of orthopaedic infection in routine clinical practice. Methods: 35 adult patients were investigated using 750 MBq Tc 99m Leukoscan injected intravenously with planar imaging performed 2 aqnd 6 hours post injection. The results of the isotope studies were compared to the evanmal orthopaedic diagnosis by review of patient medical records with information noted including ESR, WBC, correlative anatomical imaging, microscopy and culture from sites of infection and clinical judgement. Results: Of the 35 patients, 19 were total knee replacements (TKR), 6 operative internal fixations, 2 total hip replacements, 3 septic arthritis, 2 chronic osteomyelitis, and 3 other. There were 15 positive infections and overall sensitivity, specificity, positive accuracy and negative predictive accuracy were 82 %, 75 %, 60 %, and 90 % respectively. For the TKR group with 6 cases of infection the respective results were 85 %, 67 %, 67 %, 85 %. Concluslons: We conclude that Leukoscan can be used successfully to investigate suspected orthopaedic infection with its strength being a high negative predictive accuracy. Positive studies may require further imaging to establish the diagnosis.

1201

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• OTHER CLINICAL SCIENCE. BONE AND JOINTS 2 / CARDIOVASCULAR 6

PS_493

PS_495

SCINTIGRAPHIC IMAGING OF HISTOLOGIC OTOSCLEROSlS

DIFFERENT PERFORMANCES OF BONE DENSITOMETERS IN THE REGION OF NORTH HOLLAND

M.J. Reinhardt (1), U.H. Ross (2), H. Freudenberg (3), D. von Mallek (1), H.J. Biersack (1), 7". Krause (1). (1) Dept. of Nuclear Medicine, Univ. Hospital Bonn, Germany; (2) Dept. of Oto-Rhino-Laryngology, Univ. Hospital Freiburg, Germany; (3) Institute of Pathology, Univ. Hospital Freiburg, Germany. Aim: Detection of sclerotic fixation of the stapedial fuotptate by tympano-cochlear scimigraphy (TCS) in-vivo to identify patients with progressive hearing loss due to otoselerosis. Methods: 44 patients with otosclerosis prior to stapes surgery were included in the study. TCS was performed on a Siemens Basicam equipped with a one-pinhole collimator. Tan-minuteimages of the middle-/inner ear were obtained 2.5 hours after i.v. injection of 700 MBq Tc99m DPD in a modified Mayer-projection. Accumulation of radiolabeled diphosphonate was compared with bistologic findings of the surgically removed material. Results: Sclerosis of the stapedial footplate is characterized by an enlargement of the bony part and a concomitant reduction of the cartilage part (I). Thus, histologic changes of the stapedial footplate were classified in 3 groups according to hone/cartilage ratio: normal (1/3 bone, 2/3 cartilage), slight or moderate sclerosis ( 1/2 bone, I/2 caailage), and severe sclerosis (2/3 bone, 1/3 cartilage). While only I of 18 patients with a normal bone/cartilage ratio had a lbcal accumulation in TCS, 18 of 20 patients with slight or moderate sclerosis and 5 of 6 patients with severe sclerosis showed increased uptake on seintigraphic images. Sclerotic enlargement of the stapedial footplate could be scintigraphically detected with a sensitivity of 88.5 %, a specificity of 94.4 % and a diagnostic accuracy of 90.9 %. Conclusion: Sclerotic enlargement of the stapedial footplate can be differentiated in-vivo by means of tympano-cochlear scintigraphy (TCS) with a high diagnostic accuracy. Because the definite diagnosis of otosclerosis is made histologically, TCS might be helplhl in the differential diagnosis of progressive hearing loss. Reference." 1) Damjanov & Linder (eds.). Anderson's Histology, 10~hed. 1994: 2894-95, Mosby press, St. Louis, Missouri

K.P. Staal (1), J.C. Roos (1), R.A. Manoliu (2), R Lips (3), P.J. Kostense (4). (1) Nuclear Medicine; (2) Radiology; (3) Endocrinology; (4) Epidemics and Biostatics, Free University Medical Centre, Amsterdam, Holland Objectives: After the introduction of dual X-ray absorptiometry (DXA) to measure bone mineral density (BMD) the differences between the machines have been recognised as a difficult problem. Differences in equipment, calibration and ret~rence population cause variation in the diagnosis of osteoporosis. Methods: In the region North Holland, including Amsterdam, we tested all the available DXA-machines (I Norland, 2 Lunar DPX, 2 Lunar Experts, I Hologic 1000, 3 Hologic 2000 and 8 Hologic 4500). Two anthropomorphic phantoms (Hologic lumbar spine and hip phantom) and 1 semi-anthropomorphic geometrically defined phantom (European Spine Phantom (ESP)) were used. Every phantom was measured 5 times at baseline and aRer 2 months. Between every measurement the phantoms have been repositioned. The measured values were interpreted by the tested DXA-machines as if they were derived from a fictive caucasian male or female person of 40 years old, 70 kilograms weight and 170 em height. Results: There was no significant drift in the measured values after a 2 months period. The coefficients of variation over repeated measurements were below 1.0%, except in the femoral neck (between 1.6 and 4.6%) and in the high density region of ESP (between 0.9 and 3.7%). Interpretation of the measured values by the software of the tested machines (expressed in Tscores) shows more variation: in the lumbar spine region up to 0.8 SD for men and 0.9 SD for women and in the total hip region up to 1.5 SD for men and 0.8 SD for women. The variations in T-scores is for about two third caused by the different reference populations installed on the tested DXA-machines and for about one third by the differences in the measured BMD values. Five different reference populations were used in our region, as well for the lumbar spine as for the hip ConcIusion: The observed difl;zrences in T-scores may cause a shifi in diagnosis from normal to osteopenic and from osteopenic to osteoporosis from 10-20% between the different hospitals. Standardisation of reference populations is of utmost importance to achieve more uniformity in bone densitometry measurements and diagnosis of osteoporosis.

PS_494

CARDIOVASCULAR 6

COMPUTED TOMOGRAPHY AND "I'YMPANO-COCHLEAR SCINTIGRAPHY IN THE DETECTION OF FENESTRAL AND COCHLEAR OTOSCLEROSIS

PS_496

M.J. Reinhardt (1), U.H. Ross (2), A. Berlis (3), D. yon Mallek (1), H.J. Bier.sack (1), T. Krause (1). (1) Dept. of Nuclear Medicine, Univ. Hospital Bonn, Germany; (2) Dept. of Oto-Rhino-Laryngology, Univ. Hospital Freiburg, Germany; (3) Dept. of Diagnostic Radiology, Univ. Hospital Freiburg, Germany. Aim: To compare sensitivity and specificity of computed tomography (CT) and tympanocochlear scintigmphy (TCS) for detection of fenestral and cochlear otosclerosis in the differential diagnosis of progressive hearing loss. Methods: 95 patients (54 women. 41 men; aged 43±[3 yrs., range 15-72 yrs.) with progressive hearing loss in 120 ears were included in the study, Conductive hearing loss was present in 67 ears and sensoneurinal hearing loss in 53 ears. CT was performed on a Siemens Somatum AR in bone algorithm (70 mA, 3 see. scanning time, 130 kV, window 3200, center 600-1000). Continuous 2 mm slices were obtained in a clivus parallel position. TCS was performed on a Siemens Basicam equipped with a one-pinhole collimator. Images of the middle-/ inner ear were obtained over 10 rain. in a modified Mayer position 2.5 hours after i.v. injection of 700 MBq Tc-99m DPD. The findings of CT and TCS were compared on the basis of clinically diagnosed otosclerosis, Results: Tone- and speech audiometric and ear microscopic findings and tuning fork tests and stapedius reflex measurements confirmed clinically-suspected otosclerosis in 76 ears. The otosclerotie process was confined to the oval window in 46 cases and to the cochlea in 30 cases. The comparison of CT and TCS is shown in table 1. Sensitivity of TCS was significantly higher for detection of fenestral otosclerosis than that of CT. The difference between sensitivity of CT and TCS for cochlear otosclerosis was not significant. (9tosclerosis Fenestral CT TCS Cochlear CT TCS

True pos.

True neg.

9 27

21 21

30 25

23 23

False pos.

[0 0 1

False neg.

Sensitivity

Specificity

37 19

19.6%* 58.7 %*

100% 100 %

0 5

100 % 83.3 %

95.8 % 100 %

Table 1. Comparison of CT and TCS in the differential diagnosis of clinical otosclerosis. * p < 0.01 (X'-test) Conclusion: Tympano-cochlear seintigraphy proved to be a useful tool in the differential diagnosis of progressive hearing loss.

1202

MYOCARDIAL ADRENERGIC INNERVATION IN PATIENTS WITH NEUROCARDIOGENIC SYNCOPE MEASURED WITH 1231-MIBG UPTAKE

L. Galuska (1), I. L6dncz (2), I. Garai (1), J. Varga (1). (1) Department of Nuclear Medicine; (2) First Department of Internal Medicine, University of Debrecen, Hungary. Background, Neurocardiogenic (NCS) - vasovagal - syncope is one of the most common

problemsin clinicalpracticeandit mayresultfrom variouspathologicabnormalitiesor physiologicchanges. There are data about biochemical abnormalities (catecholamines) during syncope, hut it may be hypothetized adrenergic myocardial structural damage. Aim: To study the global and regional adrenergie myocardial innervation in patients (pts) with NCS which was demonstrated by head up tilt table testing (HUTT). Patients and methndes: 14 adult pts with NCS were studied. The avarage age of pts group was 42±11 years (1%68), 8 were female and 6 were male. According the HUTT result two pts had cardioinhibitory, 8 pts had vasodepressor syncope and 4 pts suffered from mixed type NCS. The average time of onset of positive reaction was: 18,5:1=12minutes (1-45). The isehaemic heart diseases were excluded by normal 99m Tc-MIBI rest-stress dipyridamol SPECT results. To investigate cardiac sympathetic innervmion 250-370 MBq 1231-M]BG was used. After 15 minutes of intravenous administration of 1231-MIBG early, and 3 hours later delayed myocardial planar seintigraphy and SPECT were performed. The heart to mediastinum count ratio (H/M) was calculated for both early and delayed images with normalised wash out rate ( w g ) too. The regional 123I-MIBG uptake was visualised on SPECT slices and polar map pictures. The regional uptake was registered pathological below the 50% comparing to normal uptake site. Results: The mean value of late H/M ratios was 1,6=I_,0.31 9 (Normal range (1,6-1,8) 9 from 14 pts the late H/M ratio was below the normal range. All pts. have regional uptake 1231MIBG deficit in different regions: 5 in inferior, infero-septal and 9 in anteriolateral separately. The mean WR was 24+4,2% (normal: 20-30*/o). Conclusion: In our NCS pts group the global 1231-MIBG deficit occured freqently, and all pts. have regional adranergic nerve function deficit. This alterations may play role in clinical symptoms and have importaney in treatment planning. The 1231-MIBG seintigraphy and SPECT is usefull methnde in the diagnosticat algorythm ofNCS pts. This study, was supported by a grant from the Health Science Council (ETT)

.

• CARDIOVASCULAR 6

PS_497

PS_499

99MTC LABELLED LIPOSOMES FOR DIAGNOSIS OF PULMONARY EMBOLISM IN RABBITS

USEFULNESS OF DUAL-ISOTOPE IMAGING WITH GA-67 CITRATE AND TC-99M MIBI FOR THE DIAGNOSIS OF CARDIAC SARCOIDOSlS

S. Ninio (1), J. Palachev (2), S. Kovacheva (3), I". Nejcheva (1), D. Petkova (1). (1) Institute of Biophysics, Bulgarian Academy of Sciences ; (2) University Hospital ; (3) University Hospital, Sofia, Bulgaria.

S. Tsuchimochi, M. Nakajo, D. Tanaka, H. Tanabe, M. Nakajo jr, T. Umanodan. Department of Radiology, Kagoshima University Hospital, Kagoshima, Japan.

The diagnosis of pulmonary embolism is a very complicate and hard assessment. In this study we have investigated the possibility of the application of multilamellar 99mTc labelled liposprees from phosphatydylcholine and cholesterol ( 2:1 molar ratio) for testing pulmonary perfusion and ventilation after embolism in rabbits. Methods. Multilamellar liposomes were prepared by the method of the reversed phases and lyophilised in the presence of SnCI 2 . Lyophilised liposomes were labelled with 2ml NaTcO4 (250 MBq) for 15 rain immediately before application. The labelling efficiency was determined by scanning column gel chromatography on Sephadex G-25 and was 68%. Results. Pulmonary embolism was provoked by injection of 0.2 ml air into ear vein of rabbits. For testing the pulmonary perfusion after embolism we used 99roTe- Lyo MAA (130-160000 particles) or 99mTc labelled liposomes ( 5Ltm diameter). 200000 counts were obtained for each frame during scanning of four standard positions ( AP, LPO, PA, RPO) 30 rain after application of each radiopharmaceutical by spate gamma camera. The two images of pulmonary perfusion show that after application of 99mTc-liposomes the scanning demonstrated in more details changes in the affected lung compared to that of 99roTe Lyo MAA. Pulmonary ventilation was investigated as well by application of 99roTe- DTPA or 99mTc-liposome aerosol using nebulaizer equipment. The particle size was 1-21am and the air flow was 9-11 I/rain. The two images revealed that the central deposition into the main bronchi and trachea was more intensive after liposome application. The dynamic of the elimination of liposome radioactivity was also investigated. The calculated slopes of the curves describing the elimination of the radioactivity after application of 99mTc-liposomes or 99mTc- Lyo MAA were almost equal thus the rate of radioactivity release ought to be one and the same in the both cases. Conclusions. These results allow us to conclude that 99mTc-liposomes might be used for clinical testing of pulmonary perfusion and ventilation since the scanning demonstrated in more details changes in the affected lung due to their smaller size compared to the particles of 99mTc- LyoMAA.

Objectives: It is well known that Go-67 citrate accumulates in the lesion of surcoidosis. However, it is difficult to determine whether Ga-67 citrate accumulates in the heart or lung in the patients suspected of having cardiac sarcoidusis by Ga-67 citrate imaging alone. Therefore, we evaluated the usefulness of dual isotope imaging with Ga-67 citrate and Tc99m MIBI, a myocardial perfusion imaging agent, for cardiac sarcoidosis. Methods: A total of 9 patients suspected of having cardiac sarcoidosis were included in this study: Sareoidosis was finally diagnosed to involve the beans in 5 patients and not to involve them in the remaining 4 patients. Go-67 citrate SPECT was performed 48 hr after injection of 111 MBq of Ga-67 citrate (energy window for Go-67; 93, 184 and 296 KeV + 10 %). Then dual-isotope SPECT was perfurmed 15 min after injection of 740 MBq of Tc-99m MIBI (energy window for Ga-67; 184 KeV + 12.5 % and Tc-99m; 140 KeV + 5 %). Both Ga-67 and dual-isotope SPECT examinations were performed with 64 x 64 matrix, 6 degree x 60 steps and 25 see/step. The crosstalk was estimated to be 1.40 - 3.45 % from Tc-99m to Ga-67 and 0.37 0 . 9 1 % from Go-67 to Tc-99m. These examinations were also performed attar steroid therapy in a patient with cardiac sarcoidosis. Results: The table shows the sensitivity, specificity and accuracy of Ga-67 SPECT, Tc-99m MIBI SPECT (obtained from the dual-isotope examination) and dual-isotope SPECT for cardiac sarcoidosis. Dual-isotope SPECT showed the accuracy of 100 %. Ga-67 citrate uptakes in the defect portions of Tc-99m MIBI cardiac SPECT images disappeared after steroid therapy in the treated patient. Conclusion: Dual-isotope SPECT with Go-67 citrate and Tc-99m MIBI may be a useful means for the diagnosis of cardiac sarcoidosis.

PS_498

PS_500

PULMONARY EMBOLISM AND NATRlURETIC PEPTIDES

EFFECTS OF STATINS ON LIPOPROTEIN METABOLISM IN HUMAN MAST CELLS AND BASOPHILS

S. Cabezbn (1), M. Villa (1), J.E. Mordn (1), P. Gbmez (2), J. Lbp~z (2), R. Otero (4), A. Cayuela (3), E G Pesquera (2), A. Ramos (2), R. Vbzquez (2), A. Martinez (1)(1) Department of Cardiology; (2) Department of Nuclear Medicine; (3) Supportive Unit Research; (4) Medical-Surgical Unit of Respiratory Diseases, HUV Rocio, Spain Natriuretic peptides (NP) have a role in left heart diseases prognostic. They have also high levels in chronic cur pulmonale. Aim: Analyze if brain natriuretic peptides (BNP) play a role as marker of acute right ventricular pression overload. Methods: We consecutively have studied 15 patients with clinical suspect of pulmonary embolism (PE). Diagnosis of acute pulmonary embolism was made by the evaluation of the clinical and laboratory findings and lung scan. We have excluded patients with left or right heart disease and also those with pulmonary hipertension. Baseline assessment have included signs and symptoms of PE, two-dimensional ecbocardiographic examination in the first day, ventilation/perfiasion lung scan in the first 48 hours, and determination of brain natriuretic peptides (BNP; radioimmanoassayoRIA) in the times: 0, 72 hours and 168 hours. Our laboratory reference of normality is t8.5 ng/dl. Ecboeardiography may reveal dilatation of right ventricle, pulmonary hypertension (PAP above 30 mmHg), paradoxical saptal encroachment (without left bundle branch block) and dilatation of supprahepatic venous. We have considered that right ventricular pression overload was present if the study had two of the previous findings. Results: Pulmonary embolism was diagnosed in 10 patients (PE group ), and was not diagnosed in 5 patients (Non PE group). 7 of 10 patients in the PE group had BNP high levels (>18.5 ng/dl) in time 0: median: 37.0 (Pereentil 25: 16.7; percentil 75: 217.5). 0 of 5 patients in the Non PE group had BNP levels in time 0 above our reference: median: 16.6 (Pereentil 25: 14.15; pereantil 75: 17.5). 8 of 10 patients of PE group had echocardiographic RV pression overload; 7 of these 8 patients presented high BNP levels. In the PE group BNP levels experimented a progressive reduction during the first week.

Ga-67 citrate Tc-99m MIBI Dual-SPECT

sensitivity (%) 40 (2/5) 80 (4/5) IO0 (515)

specificit), (%)

l O0(4/4) 25 (]/4) l fi0 (4/4)

accuracy (%) 67 (6/9) 56 (5/9) 100 (9/9)

0

S. Li (1), P. Valent (2), A. Kurtaran (1), E. Koller (3), M. Baghestanian (4), C. Novotny (1), E. Minar (4), R. Dudczak (1), I. Virgolini (1). (1) Department of Nuclear Medicine; (2) Department of Hematology and Hemostaseology; (3) Department of Physiology; (4) Department of Angiology, Internal Medicine I, University of Vienna, Austria Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, are widely used to treat hyperlipidaemia. Recent studies suggest that not only the lipid-lowering potential of stafins, but also other beneficial effects such as improved endothelial fimction of statins may contribute to the positive effects of statin treatment. Basophils and mast cells have been shown to play an important role in the lipid metabolism and atherogenesis. However, the effect of statins on lipoprotein binding to human mast cells and basophils is unknown. The aim of this study was to investigate the effects of statius on the interactions of 1231-low-density 125 lipoprotein ( I-LDL) with human basophils (KU812 cell line) and a human mast cell line, HMC-I. Methods: The metabolic fate of LDL in HMC-I and K u g I 2 was studied by radiolabeling the LDL with 12sI. Direct binding assay was performed. Binding data were calculated according to Scatchard analysis. Results: Seatchard plots indicating two class of specific binding sites on KUgl 2 cells and on HMC-1 cells, respectively. Exposure to HMG CoA reductase inhibitora, atorvastatin, simvastatin and cerivastatin increased significantly (p<0.05-0.0l) the binding sites for )2SI-LDL on HMC-I cells and KU812 cells in a dosis dependent manner. The rank order of potency for inureas¢ the binding sites for LDL on HMC-I cells was cerivastatin > aturvastatin > simvastatin. The binding capacity of 12SI-LDLm KU812 was significantly incereased by pre-incubation with eerivastatin :~ semivastatin > atorvastatin. The statins - induced increase of 12SI-LDL binding sites was accompanied by increased ~H-thymidine incorporation. However, no increase of adenosine 3<(-5(
Conclusions: BNP can become biochemical markers of RV acute pression overload in PE. Future investigation may confirm this BNP test useful in the diagnosis of PE.

1203

eff)

o I1.

• CARDIOVASCULAR 6 PS_501

PS_503

IS THE EFFECT OF SPINAL CORD STIMULATION IN PATIENTS WITH ANGINA AND NORMAL CORONARY ARTERIES RELATED TO AN IMPROVEMENT OF ADRENERGIC CARDIAC FUNCTION?

THE CHANGE OF MYOCARDIAL SYMPATHETIC NEURONAL FUNCTION BEFORE AND IMMEDIATELY AFTER RADIATION THERAPY AND/OR SYSTEMIC CHEMOTHERAPY FOR LUNG CANCER

A. Giordano (1), G.A. Lanza (2), M.U Calcagni (1), A. Sestito (2), F. De Seta (3), E Pasutto (1), F. Reale (1), L. Romano (1), M. Massaro (4), E Bellocci (2), L. Troncone (1)(1) Istituto di Medicina Nucleare, Universit& Cattolica del S. Cuore, Rome, Italy; (2) Istituto di Cardiologia, Universita Cattolica del S. Cuore, Rome, Italy; (3) Medtronics Italia SPA, Italy; (4) Dipartimento di Medicina Interna, Universit& Tor Vergata, Rome, Italy Spinal Cord Stimulation (SCS) is capable to significantly improve symptoms in patients with angina and normal coronary arteries (NCA). It can be hypothesized that this effect is due to the improvement of neuroadrenergic cardiac function which is often abnormal in these patients. AIM of this study was to verify whether SCS improves neuroadrenergic cardiac function in patients with angina and NCA using I123-MIBG scintigraphy. METHODS: we studied 7 patients (4 males, 3 females, 59 _+.11 years old) with NCA, who underwent SCS device implantation because of anginal pain refractory to full medical therapy. Each patient underwent to MtBG-rast and Sestamibi-stress/rest scintigmphies both in basal conditions (SCS device switched off) and during active SCS (device switched on for I month). Overall, 28 scintigraphic studies were performed. 1123-MIBG studies were done by early and delayed planar and SPECT acquisitions using 185 MBq of high-specific-activity agent. Global MIBG cardiac uptake was assessed by heart/mediastinum ratio (H/M ratio); regional M1BG uptake was assessed by an Uptake Defect Score based on the sum of the scores qualitatively attributed by 2 expert observers to 24 LV segments. Tc99m Sestamibi SPECT studies were performed within 2 days from MIBG studies, using single-day stress/rest technique. LV perfusion was qualitatively assessed in 24 LV segments. RESULTS: in our pts the number of anginal episodes and nitrate consumption were both reduced by SCS, as compared to baseline conditions (p<0.001 and p<0.004, respectively). In 5/7 patients we found global and/or regional abnormalities of MIBG cardiac uptake; in all cases the scintigraphic panem was unchanged in presence or absence of active SCS. The delayed H/M ratio in presence and absence of active SCS was 1.78+0.4 and 1.77+0.4, respectively (p=NS); similarly MIBG Uptake Defect Score was 18.6+26 and 18.4+25 (p=NS). Reversible exercise induced perfusion defects were detected in 4/7 patients in the absence of active SCS; in 2/4 patients perfusion defects improved during active SCS. CONCLUSIONS: I) our data confirm that MIBG cardiac abnormalities are frequent in pts with angina and NCA; 2) SCS does not significant affect MIBG abnormalities, thus its clinical benefit seems not related to the functional status of the cardiac neuroadrenergic system; 3) SCS caused an improvement of reversible perfusion defects in 2 pts, suggesting that its antiischemic effects can be scimigraphically verified, however the mechanisms of SCS clinical benefit and the non-constant correlation of its effects with myocardial perfusion remain to be clarified.

S. Tsuchimochi, M. Nakajo, D. Tanaka, H. Tanabe, M. Nakajo jr. Department of Radiology, Kagoshima Unversity Hospital, Kagoshima, Japan. Objectives: Effect of radiation (RT) and systemic chemotherapy (SCT) on myocardial sympathetic neurons remains to be elucidated. Therefore we evaluated the change of myocardial sympathetic neuronal function before and immediately after RT and SCT by 1-123 MIBG imaging. Methods: A total of 9 patient(pt)s with lung cancer (5 males and 4 females, age range; 52 - 75 yrs) were included in this study. None of them had cardiac diseases and cardiac involvement by cancer. RT of total doses of 50 - 60 Gy for the primary lesion including some part of the heart and SCT (cisplatin 80 rag/body and docetaxe1150 rag/body) were performed in 6 pts, and other 3 pts were treated with SCT (cisplatin 75 rag/m2 and docetaxel 90 rag/m2) alone. All pts were evaluated with ECG, UCG and 1-123 MIBG planar imaging and 20 rain and 4hr SPECT before and after therapy (within l week of the start and end of therapy). The whole myocardial % uptakes and washout rates of 1-123 MIBG were calculated. Results: In the 6 pts treated with RT+SCT, some new abnormalities were detected after therapy on ECG in 4 pts (depression or inversion o f T wave), and on UCG in 3 pts [mild valvular insufficiency (VI); 3 pts, and a small amount of pericardial effusion; 2 pts]. In the 3 pts treated with SCT, a pt showed mild Vl on UCG, hut no pts showed any new abnormalities on ECG. There was no significant changes betbre and after therapy in the whole myocardial % uptakes (RT+SCT: 5rain; 2.57+0.14 vs 2.65+0.86, 2fimin; 2.38+0,I0 vs 2,51+0,86 and 4hr; 1.80+0.18 vs 1.99+0.48, and SCT: 5rain; 2.67+0.45 vs 2.48+0,67, 20rain; 2.46+0.56 vs 2.30+0.67 and 4hr; 1.90+0.79 vs 2.04+0.75) and washout rates (%/hr) of MIBG (RT+SCT: from 5rain to 20rain; 28.9+9.0 vs 23.2+14.4, from 20rain to 4hr; 6.7+1.7 vs 4.9+5.3, and SCT: from 5rain to 20rain; 35.0+22.6 vs 30.4+21.0, from 20rain to 4hr; 6.8+3.8 vs 3,2+5.8), There was also no significant changes in the regional myocardial uptakes and washout rates before and after therapy in the patients with RT+SCT and SCT. Conclusion: Although new mild abnormalities are sometimes occurred on ECG and UCG, myocardial sympathetic neuronal function may not change immediately after RT and/or SCT.

PS_502

PS_504

THE ROLE OF 1-131-MIBG AND TL-201 SCINTIGRAPHY IN THE EXAMINATION OF MALIGNANT VENTRICULAR TACHYARRHYTH MIAS

WHAT FACTORS DO RELATE WITH BNP CONCENTRATIONS? A STUDY BY NUCLEAR CARDIOLOGY

I. Balogh (1), I. Balogh (1), B. Merkely (2), E. Zima (2), L. Gell6r (2), J. Krrnyei (3). (1) Department of Nuclear Medicine, Uzsoki street Teaching Hospital, Budapest, Hungary; (2) Department of Cardiovascular Surgery, Semmelweis University, Budapest, Hungary; (3) Isotope Institute, Budapest, Hungary. Aim: Investigating the pathomechanism of the malignant ventricular tachyarrhytmias (MVT) causing sudden death we studied the role of the sympathetic innervation (SI) of the heart in MVT. We examined the abnormalities of St by MIBG scintigraphy (SC) and myocardial perfusion feature by myocardial perfusion scintigraphy (MSC) in patient (pts) with MVT having implantable cardioverter defibrillator (ICD) to prevent the dangerous complications. Seeking the correlation between the clinical and scintigraphic signs we compared the scintigraphic abnormalities with the frequency and severity of MVT on ICD registrations. Patients and method: Rest MSC (with T1-201 Chlorid) and MIBG SC (with high specific activity 1-13 I-MIBG) were performed in 31 pts with MVT and ICD (14 myocardial infarction (MI), 11 dilatativ cardiomyopathy (DCM), 6 primer ventricular tachyarrhythmias (PVT)). We examined on MS the severity and extension of the perfusion abnormalities. On MIBG SC we calculated the diffuse MIBG uptake by measuring the mediastinum/heart ratio and analysed the severity and extension of regional MIBG uptake abnormalities. Result: In the group of pts with MI, MIBG uptake decreased diffusely in 12/14 cases (in 3 cases severely) and comparing the regional MIBG abnormalities with the abnormalities on MS, the fnding on M1BG was more severe and more extensive in every case. In the group of pts with DCM in addition to diffuse diminution of MIBG uptake (in 10/11 cases) we could find in all I1/11 cases severe regional abnormalities as well. The finding of MS scintigraphy was less positive than MIBG in 10/11 cases. In the group of pts with PVT the MIBG uptake decreased diffusely in 4/6 pts, and in 2/6 pts the inhomoganous uptake was the only abnormality on MIBG SC. The results of MS were better than the results of MIBG in every case. Among the pts with MVT registered on ICD (25/31) the most severe arthythmius on ICD registration (repeated ventricular tachyc~rdia and/or fibrillation) associated with the most severe MIBG abnormalities and with much better perfusiun abnormaiitius on MS. Summarizing our results: among the pts with MV'I" the MIBG SC was positive in every case. The diffuse decrease and / or regional abnormalities of MIBG uptake reflecting the damage of SI seems to be a characteristic sign in M VT (31/31). Because the most severe damage of it associated with the most severe clinical signs registered by ICD the SI may have a high prognostic value.

M. Sarai (1), 1". Sato (1)~K. Oshima (1), 1". Kondo (1), S. Kakisawa (1), M. Tokuda (2), T. Furuta (1), H. Kurokawa (1), M. Nomura (1), H. Hishida (1), Y. Watanabe (1)(1) Department of Cardiology, Fujita health university, Aichi, Japan; (2) Department of Cardiology, Meitetsu hospital, Aichi, Japan. Aim: Although plasma brain natriuretic peptidc (BNP) concentrations correlate with left veatricular end-diastolic pressure, it is not defined weather BNP correlates with myocardial adrenergic activity or LV volumes. To investigate what factors correlate with BNP plasma concentrations, Iodine-123 metaiodohenzylguanidine (MIBG) and sesta-MIBl myocardial imaging were performed in various heart diseases. Methods: 83 patients with various heart diseases (male/female; 57/26, mean age: 63.9~13.6 years, 22 OMI, I I AMI, 5 AP, 14 DCM, 4 HCM, 2 RCM, 8 arthythmia, 9 MR, 3 AS, 2 AR, 2 TOE, l ASD, 1 HT) underwent Iodine-123 metaiodobenzylguanidine (MIBG) and sasta.MIBI myocardial imaging. Plasma BNP levels were determined by commercial radioimmunoassays (Shionogi). Planar MIBG images and sesta-MlBl myocardial SPECT were obtained in a day in these patients. Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio (H/M(early) and H/M(delay)) in early and delayed images. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 rain to 4 h afier isotope injection. HR, BP and body mass iodex(BMl) were simultaneously measured. LVEDV, LVESV, LVEF, cardiac output (CO) and cod-systolic pressure volume relation (ESPVR) wen= calculated using QGS program. Results: In stepwise regression analysis, IogBNP significantly correlated with H/M(delay)(F=17.1, P<0.0035), BMI(F=21.6, P<0.003) and ESPVR(F=12.1, P<0.0001 ). Conclusions: The present data suggest that BNP correlated with not only LVEDP but also myocardial adranergic nerve activity (H/M delay), cardiac cachexia (BMI) and LV contractility (ESPVR).

• CARDIOVASCULAR 6

PS_505

PS_507

ASSESSMENT OF SYMPATHETIC INNERVATION IN PATIENTS WITH DILATED CARDtOMYOPATHY USING 1123-MIBG AND THE

SYMPATHETIC INNERVATION IN PATIENTS WITH LBBB USING

CORRELATION WITH FUNCTIONAL PARAMETERS M. Koutelou (1), A. Theodorakos (1), G. Athanassopoulos (2), V. Tsapaki (1), A. Kouzourni (1), E. Nygaren (1), D. Cokkinos (2). (1) Department of Nuctear Medicine; (2) 1rst Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece. In heart failure (HF) patients (pts) sympathetic dysfunction (SD) is associated with unfavorable prognosis. We assessed cardiac SD in pts with dilated cardiomyopathy (DCM). METHODS: 123 1-metaiodobenzylguanidine (MIBG-123) single photon emission tomography (SPECT) was performed in 29 pts (18 male, I 1 female) of D C M , mean age of 52.7+14.9 years. All were studied with early planar MIBG (10 rain) and delayed MIBG SPECT acquisition; 15 pts underwent delayed planar acquisition and we calculated the washout tWO). Cardiac MIBG uptake was measured as the heart (H) to upper mediastinum (M) activity ratio (H/M). All underwent cardiac catheterization and echocardiography. Coronary arteriography did not reveal significant >50% coronary artery stenoses. Severity of HF was NYHA grade 1 7 pts, grade II 9 pts, ,grade 111 10 pts and 3 pts grade IV. Mean left ventricular ejection fraction (LVEF) was 28+7%. Fit'teen underwent cardiopulmonary exercise tests. The reduction in MIBG uptake was evaluated visually. The myocardium uptake was studied in 6 segments (anterior, septum, posterior, inferior, lateral from the short axis and apex from long vertical axes) using a 4-point scale (0=normal, I=moderately diminished, 2=severely diminished and 3=no uptake). Scores for all 6 segments (SG) was defect score (DS). We also calculated the mean counts/pixel of each segment. RESULTS: The endiastolie (EDD) and endsystolic (ESD) diameter of LV were 71+10.5 mm and 59.7+-11.2 mm respectively. The mean exercise time (mET) was 349+196.4 seconds and the peak oxygen uptake (VO2) was 15.3_+4.8ml/min/Kgr. The H/M early and H/M delayed were 1.6+-0.3 and 1.4+-0.2 (p=0.03), the WO 37.7+-9% (normal limits _<20%) and the M1BG score was 8.5_+2.5. Mean eounts/pixel for SG was: anterior=59.4+_93, septum=62.6+-97, inferior=26.73±42, posterior=25.48+41, lateral=60.3±98.5 and apex=38.5±71. The reduction of counts/pixel in posterior and inferior SG was significant compared to other segments (p<0.00001). Delayed MIBG H/M correlated with LVEF (r=0.5, p=0.05) and with age (r=0.6, p=0.03). MtBG score correlated with age r=0.5 (p=0.005) and reduction in uptake in inferior and posterior SG with LVEF, EDD, ESD with r=0.5 (p=0.0002), 0.52(p=0.01) and 0.54 (p=0.007) respectively. There was no con'elation between VO2 and the scintigraphic parameters nor with H/M and WO. CONCLUSION: In DMC pts age, diminution o f contractility and LV dilatation are correlated with sympathetic dysfunction.

MIBG

M. Koutelou (1), A.T. Theodorakos (1), G. Athanassopoulos (2), V. Tsapaki (1), A. Kouzoumi (1), V. Cokkinos (2). (1) Department of Nuclear Medicine; (2) 1rst Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece. INTRODUCTION: Patients with Ieft bundle branch block (LBBB) frequently demonstrate left ventrieular functional abnormalities. We assessed myocardial adrenergic activity using iodine- 123 metaiodobenzylguanidine (MIBG). METHODS: MIBG was performed in 17 patients(pts) with LBBB on ECG and all underwent coronary arteriography (CAR), echecardioaraphy and adenosine-thallium studies(AD-TL). Three pts had coronary anery disease and normal cardiac function (cad-group l),13 pts dilated cardiomyopathy with normal coronary arteries (CA) and heart failure (group 2) and one patient valvular disease and normal CA (group 3). All underwent MIBG planar images 5 minutes after the injection of MIBG and single emission tomography (SPECT) 4-5 hours post injection. To evaluate the myocardial accumulation of MIBG the heart/mediastinal (H/M) activity ratio was calculated. MIBG and AD-TI SPECT images were visually evaluated; We divided into 6 segments: anterior, septal, inferior, posterior, lateral and apical and graded as follows: o=normal uptake, I=mildly reduced, 2=severe reduced uptake and 3=no uptake obtaining a global score. All pts had abnormaI SPECT MIBG imaging, in group I, H/M ratio was 1.7+0.3, the MIBG score was 7 +1.5 and A D - T L was 3+1.5. Group 2 had H/M ratio 0.8+0.1 in pts with LVEF<30% and 1.9+ 0.4 in pts with LVEF>30% (P<0.0005), the MIBG and AD-TL score was 6.6+_1.2 and 0. 2 respectively and Group 3 (one patient with valvular disease) had H/M ratio 1.8, MIBG score 5 and normal AD-TL. RESULTS: All pts with LBBB had multiple and extensive dencrvated segments independently of myocardial systolic function; diminished HIM was observed only in the patients with severe heart failure. The limitation of this study is that delayed planar images were not obtained to assess the MIBG washout into the 3 groups CONCLUSION: _he major finding of this study is the extensive myocardium denervation in pts with LBBB regardless of the LVEF. The significant decrease of the H/M ratio only in severe cardiac systolic dysfunction can be attributed to the downregulation of neuronal receptors.

co

PS_506

PS_508

CARDIAC 1231-MIBG UPTAKE -WHAT IS NORMAL?

THE EVALUATION OF CARDIAC SYMPATHETIC INNERVATION IN

C. Novotny, G. Zettinig, A. Staudenherz, B. Fueger, A. Kurtaran, R. Dudczak. Department of Nuclear Medicine, General Hospital Vienna, Austria. Aim: Reduced 1231-Metaiodobenzylguanidin (MIBG) uptake in the heart is considered to be useful for the differential diagnosis of the parkinsonian syndromes. Reduction of cardiac 1231MIBG uptake is reported to occur only in Parkinsons disease but not in related neurodegenerative diseases with parkinsonism. However, cardiac 1231-MIBG uptake is also hampered by cardiovascular disorders and several drugs, and the normal range of cardiac 123I-MIBG uptake in the average population is not well defined. The aim of this retrospective study was to evaluate cardiac ~I-MIBG uptake in a large cohort of patients who were all referred for ~231-MIBG scintigraphy. Methods: The scans of 149 patients (75 males / 74 females) who underwent JUI-MIBG scintigraphy for evaluation of a adrenal tumor between I / 1998 and 12 / 2000, but were negative in this respect, were analysed retrospectively. None of the patients had medication known to affect mI-MIBG uptake. Planar images of the chest from an anterior view 20 hours after application of 350 MBq J2JI-MIBG were analyzed by 2 nuclear physicians. Cardiac uptake was interpreted visually and ranked in 3 categories (no, faint, clear cardiac uptake). All patients with absent or low cardiac uptake were further evaluated. Results: In 7 / 149 individuals (5 %), tracer distribution in the heart region was absent, and 25 / 149 patients ( 17 %) showed a faint uptake in the heart equal to the mediastinum. In 117 / 149 patients (78 %), the myocardium was clearly visible. In 24 individuals of the 32 patients with low c~diac uptake, detailed evaluation was possible; from 7 outpatients, no clinical information could be obtained. Parkinsons disease known at time of scan was found in only [ / 24 patients. None of the patients with lower cardiac uptake had angiographically documented coronary artery disease; 17 / 24 had hypertension, and in 2 / 24 individuals, a dilatative cardiomyopathy had been diagnosed. Conclusion: These findings demonstrate low cardiac mI-MIBG uptake in 22 % of our patients, thus the diagnostic use of low cardiac 123I-MIBG uptake is questionable.

o

PATIENTS WITH DIFFERENT CARDIAC PATHOLOGY I. Igor, V. Sergienko, V. Naumov,.L. Sarnoylenko. Department of Nuclear Medicine, Cardiology Research centre, Moscow, Russia. Aim: The aim of our investigation was to assess the cardiac sympathetic innervation disorders in patients with arterial hypertension (AH), hypertrophy cardiomyopathy (HCM) and coronary artery diseases (CAD). Methods: We performed 123.J-metaiodbenzylguanidine (MIBG) scintigraphy in 9 pts with AH, 12 pts with HCM, 14 pts with CAD and 8 healthy volunteers. The sympathetic innervation was evaluated by using planar and SPECT scintigraphy. The heart/mediastinum ratio (H/M) was calculated for early (15 rain) and delayed (4 h) planar images. Difference of MIBG uptake in anterior, posterior, lateral, septum and apex regions was detected by using semiquantitative SPECT analysis. We compared H/M ratio among all groups and among early and delayed images. Perfusion defects we evaluated by scintigrapby with 99m-Tc-metaiodbutilisenitril. Results: There were significant differences between volunteers and patients in each group (P<0.001) but we could not find significant differences between AH, HCM and CAD group. Also there were no significant differences among early and delayed images - H/M ratio was 1.9-k0.44 (early) and 2.0-2_-0.52(delayed) in pts with HCM, 1.6+-0.44 (early) and 1.6±0.15 (delayed) in pts with CAD, 1.8_+0.1 (early) and 1.9-+-0.3(delayed) in pts with AH. The defects of MIBG uptake were found in 5 pts with AH (56%), 10 pts with HCM (83%) and in I1 pts with CAD (79%). Perfusion defects were found in 6 pts with AH, 11 pts with HCM and in all pts with CAD. All pts who has perfusion defects had also defects of MIBG uptake, there localization was congruent. Conclusion: There is the decrease of M[BG accumulation in pts with AH, HCM and CAD. The reason of it's difference in pts with hypertrophy perhaps an accelerated washout of M1BG from sympathetic vasicules. Oppositely, the sympathetic innervation is absent in scar regions in pts with CAD.

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• CARDIOVASCULAR 6 / DIAGNOSTIC ONCOLOGY 11 PS_509

DIAGNOSTIC ONCOLOGY 11

SERIAL CHANGE OF SYMPATHETIC NERVE ACTIVITY OF THE PATIENTS WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM) TREATED WITH PERCUTANEUS TRANSLUMINAL SEPTAL MYOCARDIAL ABLATION (PTSMA) H. Matsuo, S. Watanabe, T. Yamaki, M. Iwama, T. Hirose, S. Tanaka, A. Murata, S. Miyata, T. Kadosaki, T. Segawa, M. TomitaDepartment of Cardiology, Gifu Prefectural Hospital, Gifu, Japan. Background : PTSMA is a effective non-surgical technique for achieving the reduction of the pressure gradients of LV outflow and patients symptoms dramatically. However, the effect of this approach to the sympathetic activity is not well known. Purpose and methods: To investigate the time course of the sympathetic nerve activity, we evaluate the sympathetic activity by MIBG seintigraphy performed just before, Iweek after, and 3 months after the procedure in 6 patients with severe HOCM. H/M ratio in early and delayed images and washout rate was used as the indexes showing sympathetic function. Results: The procedures were all successful without severe complications. CPK release ranged from 976 to 3642 IU, LV outflow PG decreased markedly from 110±16mmHg to 45±31mmHg and concomitant improvement of NYHA classification was evident ( pre-PTSMA:2.5±0.8 post-PTSMA:l.2±0.4). MIBG demonstrates the transient increase of washout (pre:34±5% post:44±6%) and decrease of H/M ratio of delayed images (pre:l.9±0.8, post:l.7±0.2) at I week after procedures. 3 months after procedure, significant decrease of washout(3M:30±8%) and increase of H/M ratio(3M:2.0±0.3) was observed. Conclusion: Transient overactivation of sympathetic nerve probably associated with iatrogenie infarction was observed early after PTSMA. However, sympathetic activity was gradually reduced at chronic phase suggesting the favorable effect of this therapy on loading conditions oftbe hypertrophied heart.

PS_510 ASSESSMENT

PS_511 MANAGEMENT OF DIFFERENTIATED THYROID CARCINOMA BY THYROGLOBULIN AND 1311 SCINTIGRAPHY AFTER RECOMBINANT HUMAN TSH AND 9 9 M T C - S E S T A M I B I

SERUM

G. Villa (1), M. Giusti (2), R. Zoccola (3), B. Guazzini (2), E. Molinari (1), F. Castagnola (1), L. Bertolazzi (3), E Minuto (2). (1) Nuclear Medicine Service, DiMI - University of Genoa, Genoa, Italy; (2) DiSEM - University of Genoa, Genoa, Italy; (3) Nuclear Medicine Service, Civic Hospital, Alessandda, Italy. AIM: Whole-body scan (WBS) and thyroglobulin (Tg) assay are methods of evaluating patients (pts) who have undergone surgery for well differentiated thyroid cancer (DTC). The use of recombinant human (rh)-TSH is a promising method in order to avoid LT4 discontinuation. We evaluated the sensitivity of Tg after rh-TSH versus WBS using both t~ll and ~mTcSestamibi in detecting residual thyroid cancer or normal tissue after surgery and radioiodine ablation. SUBJECTS: Fifieen pts (29-78 yrs) on LT4 regimen were studied after 12 months (median) from primary treatments. METHODS: Favourable results were considered: Tg levels <0.5 ng/ml after rh-TSH and neg131 99 ative scans after I (185 MBq) and ~Tc-Sestamibi (740 MBq). Pts received rh-TSH (0.9 mg Lm., days I and 2); 24 h after the second dose, 1 was administered and WBS was performed 48 h later. Serum Tg levels were evaluated on days 0, 3 and 6. WBS with ~mTcSestamibi were performed within 4 weeks. RESULTS: In 12 pts Tg levels were <0.5 ng/ml in the first determination. In the other pts ranged from 0.8 to 28.0 ng/mL A Tg change < I /ml og was noted after rh-TSH in 10 pts, while in the 5 ranged tYom 1.8 to 803.9 ng/ml. 1311 was positive in 3 pts and suspect in 2. WBS using 9'~Tc-Sestamibi was negative, suspect and negative respectively in 7, 4, 4. In all ~atiants with positive I WBS occurred uofavourable Tg results after rh-TSH and positive mTc-Sestamibi scans. Five pts, showing a positive or suspect '~mTe-Sestamibi scan, had an increased Tg after rh-TSH. CONCLUSION: Uodeteetable Tg level followed by a Tg change <1 og/ml after rh-TSH seems to be the best index on normality on follow-up in pts with a history of DTC. WBS with Tc-Sestamtbl seems to be sensitive but not specific. Without LT4 discontinuation, Tg assay 13/ after rh-TSH seems to be more sensitive than I-scan. -

I M

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PS_512 OF CARDIAC ADRENERGiC

NERVOUS SYSTEM

WITH 1-123-MIBG SPECT IN PATIENTS SUBMITTED.TO

TRANSo

MYOCARDIAL LASER REVASCULARISATION. PRELIMINARY DATA A. Teresifiska (1), M. (Eliwifiski (2), S. Konieczna (1), M. Szymafiska (2), P. Hendzel (2), Z. JuraszyRski (2), A. Wojnowski (2), A. D6.bski (3), B. Szumilak (1). (1) Department of Nuclear Medicine; (2) Cardiosurgery Clinic; (3) General Cardiology Clinic, National Institute of Cardiology, Warsaw, Poland. The aim of our program is to study the range of influence of the laser energy on cardiac adrenergic nervous system and to assess if disruption of this system can be one of the mechanisms responsible for clinical improvement observed after TMLR. Methods: The patients with high pre-operative probability of having sole TMLR or TMLR combined with only I bypass are studied before the operation with Tc-99m-MIBl SPECT (perfatsion test) and with 1-123-M1BG SPECT (neuronal activity test). The patients (if they were operated according to the assumption) are studied postoperatively with 1-123-MIBG SPECT as early as possible ftom clinical point of view and will be studied with Te-99m-MIBI and 1-123-MIBG SPECTs 6 months after operation. Up to now, in 14 patients the preoperative tests were performed and 3 patients had early postoperative (3-39 days) 1-123-MIBG SPECT. The group characteristics: 8M and 6F; age: 54-69), av. 63::r.Sy;all the patients in Ill/IV CCS class; 8 patients after 1-4 MI (av. 1,1:1:1,2 MI per patient); 1 patient after earlier CABG. Registration of 1-123-MIBG SPECT images was started 4 hrs after injection of the radiopharmaceutieal. All SPECT studies were assessed in 17 segments (seg) of the LV. Results: Preoperatively, there were 5-13 (av.9,5+7,5) underperfusod segments per patient in Tc-99m-MIBI studies and 5-15 (av. 10,4+9,8) segments per patient with lowered 1-123-MIBG uptake. On average, 1-123-MIBG uptake deficiency was occupying more segments and was more severe in a patient than Te-99m-MIBI deficiency. In 3 patients submitted to TMLIL postoperative I-123-MIBG uptake deficiency was occupying larger areas (1-3 segments more) and was more severe (in 3/34 segments uptake was the same, in 2/34 segments uptake improved, in 29/34 segments uptake decreased). Conclusion: Our observations from all three studied patients support the hypothesis that TMLR reduces the activity of cardiac adrenergic nervous system, what can be one of the mechanisms responsible for clinical improvement noted after TMLR. (supported by State Committeefor Scientific Research. grant 4 POSB 02418)

AND 201TL IMAGINGOF THYROID WITH COLD NODULE 99MTC-MIBI

Y.L. YU, J.F. Yu, L.B. Chen, H. Ji, R.S. Zhu. Department of nuclear medicine,Shanghai 6th people's hospital, Shanghai, China. The clinical value of "'~Fc-MIBI and 2°lTI imaging of thyroid with cold nodule were assessed. Methods 87 patients with cold thyroid nodule were imaged with WmTc-MIBl(early 15rain, delayed 60rain) and :°iT1 (early 15rain, delayed 120rain). Regions of interest(ROls) were generated over the cold nodule and normal tissue on each image. The semi-quantitative analysis was performed by using a lesion to non-lesion ratio of early(ER) and delayed(DR) images. Retention iodex(Rl) was calculated by dividing delayed-early subtraction to product ER. Results Them was significant difference in the ER,DR and RI between malignant and • ~ bemgn lesions for Tc-MIBI and TI (p<0.05). The difference was no slgntficant between carcinoma and inflammation(p>O.01), but there was significant difference between carcinoma • 201 • • < . . . . . . •

201

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•

.

and cysacadenomafor TI =magmg(p0.01).Thesenstttv~ty,spectficJtyand accuracyusing semi-quantiflcationfor bothagentsweresignificantlyhigherthanvisualmethod(p<0.01),and DR.RIfor bothagentswerehigherthanER(p<0.05).

A~ents ~mTc -MIBI

201TI Including;

"~Te-MIBI

2mTl

Patholo~,';~ Tumor Non-tumor Tumor Non-tumor Cystic adenoma inflammation

ER 1.08±0.25 0.82±0.23 1.02±0.19 0.80±0.22 0,65±0.18 0.82±0.17

DR 1.22±0.16 0.87±0.20 I. 11±0.13 0.81±0.18 0.79±0.11 0.80i0.15

RI 0.08±0.09 0.02±0,02 0.09-J:0.08 0.01±0.04 0.01±0.02 0.03±0.02

ER DR RI ER DR RI

Sensitivit~ 68.8%(5/8) 87.5%(7/8) 75.0%46/8) 68.8%Q 1/16) 75.0%(12/16) 75,0%(12/16)

Speciflcit}~ 62.5%424/47) 55.3./0~26/47) 68.8*/,(27/47) 57.7./0(41/71) 60.6./.443/71) 66.2%447/71 )

Accurac), 52.7%(29/55) 60.0%(33/55) 60.0*/°433/55 ) 59.8%452/87) 63.2%t55/87 ) 67.8%459/87)

Conclusions '~'~Tc-MIBI and -'aITl imaging of thyroid cold nodule using ER,DR and RI had higher clinical application value than visual method. :°lTI delayed imaging had the possibility of identifying cystic adeooma from carcinoma.

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[] DIAGNOSTIC O N C O L O G Y 11

PS_513

PS_515

THYROID CARCINOMA FOUND AT PARATHYREOIDECTOMY : ASSOCIATION WITH PARATHYROID CARCINOMA. A CASE REPORT

ROLE OF M|BI-99MTC SCAN IN DETECTING LOCAL AND DISTANT METASTASES OF DIFFERENTIATED THYROID CANCER IMMEDIATELY AFTER TOTAL THYROIDECTOMY

A. Fotopoulos (1), S. Koukouraki (1), G. Schoretsanitis (2), A. Velidaki (1), D. Tsiftsis (2), N. Karkabitsas (1). (1) Department of Nuclear Medicine; (2) Department of Surgical Oncology, University Hospital of Crete, Greece. Nonmedullary thyroid carcinoma is known to occur in associationwith primary hyperparathyroidism (PHPT). Parathyroid carcinoma is a rare cause for PHPT. A combination of parathyroid carcinoma and nonmedullary thyroid carcinoma is rare. A retrospective review was performed, of patients who underwent surgery for PHPT between 1998 and 2000. Among 34 surgical patients with PHPT at this institution, four patients (12%) were found to have parathyroid neoplasms. Histological examination of parathyroid tumors revealed one pamthyroid adenoma and three parathyroid carcinomas. In one case coexistence of parathyroid and papillary thyroid carcinoma was detected. Therefore in the diagnosis of PHPT it is necessary to take into consideration association between malignant thyroid disease and hyperplastic or neoplastic parathyroid tissue

S. Baldari (1), A. Campenni (1), M.A. Violi (2), G. Restifo Pecorella (1), E Martino (1), D. D'Oppido (1), E Trimarchi (2), E Vermiglio (2). (1) Nuclear Medicine Unit, Department of Radiological Sciences; (2) Endocrinology Unit, Department of Experimental Medicine and Pharmacology, University of Messina, Italy. The optimal management of primary brain tumor represents a significant challenge for clinicians and researches. Despite recent advances in neuromdiological imaging, neurosurgica] treatment, neuroncologicai strategies, and nuclear medicine procedure, the preoperative assessment of cerebral lesions needs further noninvasive semiquantitative insights. 99mTechnetium-Sestamibi (MIBI) has been proposed as an useful radiopharmaceutical pert'usion agent, which has been recently used as an imaging SPET agent for various neoplasms, including brain tumors. This technique can predict brain tumor grading and the behavior of glial tumors in terms of clinical aggressiveness. In addition, MIBI has been used in the differential diagnosis of some difficuh cases. Aim of this study is to describe the experience obtained at our Institution in preoperative evaluation of 22 patients harboring a brain lesion, and evaluated during the last 18 months. They were II men and 11 females, ranging in age between 6 and 73 years (mean 47 yr.). Of these lesion, 21 (96%) were located in the supratentorial compartment, while in one pediatric case the lesion was located within the brain stem. O f these cases. 6 were low-grade glioma, 5 glioblastoma muhiforme, 4 anaplastic astrocytoma, 2 meningiomas, 2 metastasis, and I epidermoid. Two additional cases were represented by benign nonneoplastic hemorrhagic diseases. SPET was performed within 10 minutes after intravenous injection of 10-20 mCi MIBI. The images were obtained with a dual headedgamma camera using a high resolution collimator Transverse, coronal, and sagittal views were reconstrueed. MIBI uptake has been evaluated on the transverse slices, and expressed as tumor/background ratio. Two subgroups of patients were identified. MIBI uptake was found in 16 (72.7%) patients. The tumor/background ratio correlated with tumor histology, as proved from surgical or bioptica[ sample. In two patients of this group, a benign non-net)plastic disease has been detected, and proved on late neuroradiologica} observation. We Ibund a marked difference ( p < 0.001) between the M[B[ uptake in non-tumor and low-grade lesions (I.1 ± 0,45) vs high grade tumor (2.3 ± 0.14). According to our results, the specilqcity and sensitivity of MIFII brain SPET has been proved to be high. This tumor confirms the MIBI SPET as a valuable noninvasive semiquantitative tool. useful in the management of brain tumor patients, that offers clinically relevant pre-oparative information in problem-solving session, such as differentiating neoplasms, and categorizing glial tumors in terms of clinical aggressiveness.

cO

PS_514

PS_516

TC99M PERTECHNETATE WHOLE BODY SCANNING IN DIFFERENTIATED THYROID CARCINOMA IN COMPARISON WITH 1-131 WHOLE BODY SClNTIGRAPHY

THE VALUE OF 99MTC-GLUTATHIONE (GSH) IN DETECTION OF METASTASES OF DIFFERENTIATED THYROID CARCINOMA

A. Dirlik, M. Kayaho~jlu, S. Erhamamci, O. ~)m0r, Z. Ozcan, K. Kumanho{~jlu, H. (~zkll=c. Department of Nuclear Medicine, Ego University Medical Faculty, #zmir, Turkey. Aim: 1-131scintigraphy is sensitiveand specificfor thedetectionof functioningresidualand metastatictissuein patientswith differentiatedthyroid carcinoma(DTC). However. it has beenreportedthat diagnosticwhole-body1-131scanningmay impair suhscqocntthe uptake of a therapeutic dose. The aim of this study was to investigat¢ the value of Tc99m pertechnetare whole body scan (WBS) in comparison I-131 WBS prospectively. Methods: Thirty-four patients (6 male, 28 female; range 12-67 y.o.) who had undergone total thyroidectomy for DTC (22 papillary and 12 follicular) ware included in study population. Following thyroid surgery and during the clinical follow-up, all patients underwent Tc99m pertechnetate WBS with a dose of 10-20 mCi. Tc99m pertechnetate WBS preceded 1-131 WBS while these patients were withdrawn thyroxine for at least 4 weeks. Tc99m pertcthnetare WBS findings were evaluated comparatively with following posttherapeutic / postablative 1-131 WBS findings, The number of loci of abnormal uptake was recorded for Te99m pertechnetate and 1-131 WBS. Results: When 1-131 WBS was taken as reference, Tc99m per~chnetate WBS detected lesions in thyroid bed 33/39 (84,6%), in pulmonary metastasis 13/29 (44,8%), in mediastinal metastasis 7/10 (70%), in lymph node, metastasis 9/11 (gl,g%), in bone metastasis 11/13 (84,6%). Interestingly diffxlse lung infiltration confirmed with 1-131 WBS could not be visualized on Tc99m parteehnetate WBS and lung CT. On the other hand, we obtained 4 false positive results (neck, mediastinum, tung, bone) with Tc99m pertechnetate WBS. Conclusion: Although 1-131scintigraphy is more sensitive in demonstrating residual and metastatic tissue than Tc99m pertechnetat¢ seintigrephy, it may decrease subsequent iodine uptake and reduce therapeutic efficacy. Therefore, Tc99m pcrtochnetate WBS may be used as the first approach with its low cost and easy availability. In addition, positive Tc99m pertcchnotate WBS may allow early detection and treatment of the disease in a subgroup of patients.

M. Argon, O. ~)zyurt, O. (~m0r, M.S. Taner, Y. Duman. Department of Nuclear Medicine, Ege University, Izmir, Turkey. ~"~Tc-Glutathione (WmTc-GSH)was used in many malignant tumoursand metastases as a radiopharrnaceuCical. Recent studies has been showed that GSH was increased in adenomas and papillary carcinomas by 17% compared to normal thyroid while no changes were seen in goitras. In this preliminary study the aim was to test the feasibility of scintigraphic detection of metastases of differentiated thyroid carcinoma (DTC) with ¢'~Tc-GSH. Methods: 14 patients who had metastases of DTC, (5 follicular, 9 papillary) diagnosed with ml images and other radiological methods were studied. They were under T4 suppression and had several i311treaUnents. Their ages ranged from 40 to 61 years (mean 50.16, SD 5.1 years). GSH was labelled with WmTc by Sn *+ reduction method with an efficiency >97%. Following IV injection of 500MBq s'n"Tc-GSH, seintigraphic views were obtained at five minutes tbr imaging blood pool and 6 hours. Images were interpreted by visually. Results: [n all patients, there wasn't any ~"'Tc-GSH uptake at six hours images and any activity accumulation at five minutes blood pool images in metastases focus which were detected with I- 131 images and other radiologica[ method Conclusions: Our preliminary results showed that 9';"Tc-GSH was not a potential radiopharmaceutical for detection of metastases of DTC. Despite high glutathione levels in thyroid carcinoma, Tc-GSH didn't accumulate in metastases of DTC

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• DIAGNOSTIC O N C O L O G Y 11

PS_517 A WARNING ABOUT USING ONLY OFF T4 SERUM HTG LEVELS IN FOLLOW-UP OF DIFFERENTIATED THYROID CANCER D. De Palma (1), L. Giovanella (1), P. Vanoli (2), L. Ballada (1), L. Ceriani (1), A. Fachinetti (1), S. Garancini (1). (1) Department of Nuclear Medicine; (2) Department of Radiotherapy, Osp. di Varese,ltaly. AIM: Recently an interesting debate arouse about the true usefulness of a diagnostic radioiodine total body scan (DTBS) in patients that underwent total thyroidectomy and remnants ablation with 1311 because of differentiatad thyroid cancer (DTC) when serum hTG levels are undeteetable (i.e. less than 2 ng/ml) after withdrawal of T4 treatment (off r4) in presence of normal levels of Ab against hTG. We actually performed routine DTBS one year after ablation (standard activity 3700 MBq) in all patients with previous DTC, independently from the results of post-ablation scan, if TG levels are undetectable during T4 therapy. We reviewed DTBS performed in the last two years (1999-2000) analysing the incidence of positive DTBS with undetectable hTG. M ETHODS: DTBS and o tTl'4 hTG assay were performed after four week withdrawal of the T4 therapy. DTBS was acquired 48 hour after oral administration of 185 MBq of 13 II; a confirmation spot view was acquired 24 hours later in case of doubt, hTG assay was performed by an high sensitivity IRMA method (IRMA Tg-s, BRAHMS, Germany; functional sensitivity 0.3 ng/ml). The mean TSH level attained after T4 withdrawal was 65 mlU/ml, range 28-100. RESULTS: 196 DTBS were reviewed. 11(5.6%) patients showed focal areas of abnormal iodine uptake in the cervical region, for a total of 15 loci, 6 from lymphonodal involvement and 9 from thyroid bed remnants/relapse. All patients had undetectable hTG and Ab against hTG levels. 6 patients had papillary DTC and 5 follicular variant of papillary DTC. All these patients underwent a new treatment with therapeutic activity of 1311 (5550 MB9); the DTBS performed until nov• showed disappearance of the uptake in three cases and persistent nodal disease in a fourth. CONCLUSIQN$: OflT4 serum hTG levels showed indeed a negative predictive value of 94.4%. In deciding to do not perform DTBS with undetectable hTG we must be aware that this choice implies to leave some patients with residual disease. The prognostic implication of this fact remains unclear.

Tab2 ~mTc-DTPA Aerosol Clearance Rates Metastases 0.05 >0.05

241-370GBq(n) 54.9±13.2(14/ 51.4±14.7/3 ) 0.466 4.54 >0,05

>370GBq(n) 52.1±15.6(12) 50.3±18.5(3) 1.289 4.67 >0.05

Only one female, 43 years old, had received 518GBq(1400mCi) radioiodine over a 8-yr period. Pulmonary function test showed evidence of restrictive lung disease, chest x-ray showed haziness and DTPA half-time clearance was 26.4min,which is suggestive of interstitial fibrosis. Conclusion The effect of cumulative radio-iodine doses and sex had not statistics significance for pulmonary function. Interstitial fibrosis should appropriately be prevented when cumulative radioiodine doses were over 370GBq.

PS_518

PS_519

EFFECTS OF RADIOIODINE THERAPY ON PULMONARY METASTASES WITH WELL-DIFFERENTIAL THYROID CANCER

THE INFLUENCE OF THE DELAYED 131-IODINE ABLATIVE THERAPY TO THE OUTCOME OF PATIENTS WITH DIFFENTIATED THYROID CARCINOMAS

Y.L. Yu, C.Q. Jin, L.B. Chen, H.K. Lu, R.S. Zhu. Depatment of Nuclear Medicine,Shanghai 6th People's Hospital, Shanghai, China. The effects of radioiodine therapy on pulmonary metastases from well-differentiated thyroid cancer were investigated. Methods 85 volunteers(58 with pulmonary metastases, 19 without pulmonary metastases and 8 normal controls) were studied utilizing chest X-ray, pulmonary function test and "~Tc-DTPA aerosol clearance rates. Pulmonary function test determined vital capacity(VC), forced vital capacity(FVC), forced expiratory volume at 1 sec,(FEVi) and . . . . 9~m . . maximum voluntary ventdation(MVV). The patient Tc-DTPA aerosol mhalad by tidal volume breathing. The data were acquired and analyzed for clearance half-time from the lungs with the SPECT. Results The data of polmonary function test were no difference between various groups of cumulative radiation doses(p>0.05). The difference of VC, FVC and FEV I was 99m not remarkable between groups of sex(p>0.05)but MVV(p<0,01). Tc-DTPA aerosol clearanee rates of between various groups were no difference(p>0,05). Tabl Lung Function Test N VC(%) < 300 24 93.08±20.30 301--650 8 100.18±13.41 651~1000 14 98.74±10.97 >1000 12 89.32~tl,30 F 1.230 Fn ost~ ~4~ 2.78 P >0.05 Male 32 91.08±I 1.53 Female 26 99,03±19.19 F 1.633 Fo osrl s~ 4.01 P >0.05

1208

FVC(%) 87.50±23.19 86.53±14.55 93,84±15.05 91.65±10,21 0.826 2.78 >0.05 89.73±15.68 95.23±19.01 0.631 4.01 >0.05

FEVI~% ) 86.70~23.33 78.13±23.76 93.16~23.87 84.08±10.74 0.490 2.78 >0.05 84.39-a:23.02 91.40±21.71 2.788 4.01 >0.05

MW(%) 89.83±32.25 78.83±29.56 87.03=I:15.42 92.02±35.02 0.539 2.78 >0.05 79.10-~:I 5.62 I00,31±38.54 13.446 (Fi/,eltL,~6~.7,1~) (<0.01 )

A. Koutsioumpa, E. Trivizaki, S. Saranti, R Natsis, L. Iordanidou, V. Babali, K. Pateniotis. Department of Nuclear Medicine, Piraeus, Greece. This study aimad to evaluate the influencc ofthe delayed ablative 131-iodineadmthistration at~er the suggested two months interval from the surgery to the outcome of patients with DTC. The reason for this possible delayed 131-iodine therapy was the small number of the dedicated beds in public Hellenic hospitals (only 17 for a population of 10 million) while there is a continuous increment of our needs (including a significant number of young people). Material: Up to day we evaluated 91 patients (71 women, 20 men) with a follow- up time ranged from 8 to 173 months, mean 31.6 months. All studied patients bad negative whole body scan and they were clinically free of disease, The patients were divided in three groups. Group A: 21 patients who received the ablation therapy within a period of two months after the surgery with a mean age of 39.6 years. Histologically there were 11 papillary, 9 mixed and 1 medullar-mixed carcinomas. Group B: 35 patients with the ablation dose received 3-6 months after surgery, mean age 47.3 years (22 papillary, I follicular, 10 mixed and 2 Hunhle cell carcinomas). Group C: 35 patients with the ablation dose received six or more months aRer the surgery, mean age 51.6 years (21 papillary, 2 follicular, 11 mixed and 1 Hurt.hie cell carcinomas. All clinical and laboratory parameters were also evaluated for the studied population. Results: In group A 9/21 pts. (45%) had negative whole body scan (WBS) after the ablation dose and 11/21 pts. (52,4%) after two therapeutical doses. In group B 25/35 pts. (71,8%) had negative WBS after the ablation dose. In group C 26/35 pts. (74,3%) had negative WBS after the ablation dose. In 4/19 pts. who received two doses, the second dose was given because the Tg was elevated, while the WBS was negative after the ablation dose. According to our data the administration of multiple therapeutical doses seemed to be related with the aggressiveness of the histological type and we believe there is a relative correlation with the size of the inHltered nodule. Conclusion: According to our results we did not observe a negative influence on the outcome of the DTC patients when the ablation dose was administered in a period of time longer than two months after surgery, it should he mentioned that during the pretreated period the patients must have the appropriate follow up and the adequate suppression therapy, always under the condition that there isn't aggressive tumor pathology.

• D I A G N O S T I C O N C O L O G Y 11

PS_520

PS_522

RADIOIODINE IMAGING (WBS) AND SERUM THYROGLOBULIN(TG) IN MANAGEMENT OF THYROID CANCER (DTC): RANDOMISED STUDY WITH RECOMBINANT HUMAN TSH (RHTSH) AND WITHOUT THYROID HORMONE

ADDITIVE CLINICAL VALUE OF PINHOLE IMAGING IN FOLLOW-UP OF WELL DIFFERENTIATED THYROID CANCER AFTER SURGERY

L. Bertolazzi (1), R. Zoccola (1), M. Giusti (2), G. Villa (3), M. Scattina (1). (1) Department of Nuclear Medicine; (2) DISEM; (3) DIMI, University of Genoa, Italy. Aim The purpose of this study is to prove if rhTSH, in patients after postsurgical radioablation of thyroid residue and treated with tiroxine (PtsT4), gives same outcomes in order to underline patologic values of Tg and thyroid tissue and/or metastasis with radioiodine imaging (185 MBq of 131 J) compared to patients in protracted hypothyroidism (Pts TH). Methods During last year, we underwent 70 patients, with DTC and near-total thyroidectomy, to radiometabolic therapy (3700 M Bq of 13 L J) : 32 of them (all without metastasis in post-therapeutic WBS) were divided in two groups of 16 patients with same pathology (papillary cancer T1-T2), age and sex. In all patients no interference from anti-Tg antibody was present. After 4-5 months we treated the first group with rhTgH while second suspended the hormonal therapy to achieve hypothyroidism (>60 mU/ml). Results The first group (11 F and 5 M age 29-78) presented 3 patients with at baseline detectable but low Tg (> 1.5 ng/ml) while after rhTSH the abnormal values of Tg were five. WBS was positive in six patients (3 thyroid tissue and 3 neck's nodes) : 4 with increased Tg and 2 with unchanged Tg after rhTSH. The negative WBS presented (after stimulation) a Tg value of 2.15 ng/ml. The second group (12 F and 4 M age 29-74) presented 9 elevated Tg (5 at baseline). WBS was positive in all these patients and in one other patient with normal Tg (4 thyroid tissue, 3 neck's nodes and 3 pulmonary metastasis). Both group stood WBS preparation without important upset. Conclusions rhTSH group rhTSH increase the sensitivity of serum Tg in PtsT4 hypothyroidism group we have average Tg higher than rhTSH group (respectively 45 and 32 ng/ml) greater number of positive patients (on the whole 10 PtsTH vs 6 PtsT4) C) in both group WBS underline the presence of thyroid tissue in more patients than Tg value The our preliminary trial confirm that. after radiometabolic therapy, protracted hypothyroidism is best diagnostic approach. Only after negative results, we can continue patient follow-up with rhTSH.

S.T. Lim (1), S.A. Park (1), M.-.H. Sohn (1,2). (1) Department of Nuclear Medicine; (2) Clinical Medical Reserch Center, Chonbuk National University Hospital, Chonbuk National University Medical School, Chonju, Korea. Purpose: It is well known that pinhole collimator (PH) has better resolution than high resolusion parallel-hole collimator (HRPH). We performed this study to compare PH with HRPH for the ability to differentiate of metastatic cervical lymphadenopathy (MCL) from remnant thyroid tissue (RT) after surgery for the treatment of thyroid cancer. Materials and Methods: One hundred forty three studies in 71 patients (M: F=I2: 59, age 43.3±13.9 yrs) were analyzed. One hundred and eleven of 143 studies used 1110 MBq of 1-131, H RPH and PH were performed 3 days after the radioiodine intake. PH images were obtained with 6 mm aperture for 10 minutes. Markers were placed to the submental and sternal notch regions. We compared two image modalities for the detection of MCL and RT in cervcal region. Results: All patients had well differentiated thyroid cancers (papillary:follicular=68:3). Sixty five of 111 studies (58.6%) showed concordant results but 46 of I I 1 (41.4%) discordant results. In the group showing discordant results, PH study was more useful for the detection of lesions with RT and MCL 25/46 (54.3%) and 29/46 (63%), respectively. Conclusion: In well differentiated thyroid cancer after surgery, we conclude that PH has more useful to monitor therapeutic response than HRPH, and provides additive information for the necessity of high dose radioactive iodine therapy in patient with MCL.

PS_521

PS_523

ROLE OF SClNTIGRAPHIC IMAGING IN METASTATIC MEDULLARY THYROID CARCINOMA (MTC): RESULTS ON 84 PATIENTS .

DIAGNOSTIC ACCURACY OF RADIONUCLIDE IMAGING USING IODINE-131 NOR-CHOLESTEROL OR MIBG IN PATIENTS WITH HYPERSECRETING OR NON-HYPERSECRETING ADRENAL TUMORS

0 ~.~ ¢,.

D. Casara (1), D. Rubello (1), G. Saladini (1), M.E. Girelli (2), B. Busnardo (2), P. Tamagnini (3), M.R. Pelizzo (3). (1) Servizio di Medicina Nucleare 2, Azienda Ospedaliera di Padova, Padova, Italy; (2) Servizio di Endocrinologia, Universita di Padova, Padova, Italy; (3) Clinica Chirurgica 3, Universita di Padova, Padova, Italy. From 1991 to 2000, 84 MTC pts entered the study: 45 F, 39 M, mean age 53.7 yr; 37 of tbem had sporadic MTC, while in 47 pts MTC was associated to MEN. Nine pts were studied before surgery, whereas 75 during follow-up after first surgery because of elevated serum calcitonin and/or CEA levels. All pts were studied by 99mTc-MIBI scan, neck US, chestabdomen CT, abdomen US; 99mTc-MDP scan was also performed in 56 pts, 111ln--octrentide scan in 16 pts, 18FDG-PET in 7 pts. Surgical findings In. 21), biopsy In. 14) and/or clinical outcome were taken as gold standard. In 5/9 pts studied preoperatively, MIBI scan correctly visualized primary tumor and Ioco-mgional lymph node rots (LNM); moreover, in I case MIBI scan revealed also bone rots IBM). Regarding the group of 75 pts studied during followup: cervical LNM were showed by MIBI scan in 34 pts (45.3%) and by US in 25 (33.3%); moreover, a complementary role between MIBI & US was found in 5 pts. Mediastinal LNM were showed by M1BI scan in 11 pts (14.7%), and by CT in 6 (8%). It is worth noting that in 3 cases with MIBI scan positive for loeo-regional LNM, lllln-octreotide scan and IgFDGPET were negative (1 case) or revealed less metastatic foci than MIBI scan (2 case). Conversely, in 2 MIBI scan negative cases, 1 llln-octreotide scan revealed the presence of mediastinal rots; thus, a complementary role between MIBI and lllln-octrentide scan was found in 5 pts. Pulmonary mrs (PM) were detected both with MIBI scan and CT in 7 pts (9.3%). BM were detected by MIBI scan in 7 pts (9.3°/,), and by MDP scan in 11 (14.6%). Liver rots (LM) were showed by US/lllln--octreotide/18FDG PET/ laparoseopy in 7 pts (9.3%), while MIBI scan was positive in only 1 of them (1.3%). In our experience, Ioccregional LNM represent the most frequent site of rots in MTC, and MIBI scan associated with US and 1111n-octreotide scan appears to be the most sensitive imaging protocol in visualizing this type of mrs. Early detection of Ioco-regional rots is extremely important in MTC pts because they can be treated by surgery that is considered the most effective treatment for this type of tumor. Imaging modalities other than MIBI scan should be used to visualize MTC distam rots.

S. Maurea (1), M. Klain (2), R. Rossi (3), F. Izzo (4), M. Ziviello (1), M. Salvatore (2). (1) Medicina Nucleare e Radiodiagnostica, Istituto Nazionale Tumori, Napoli, Italy; (2) Centro per la Medicina Nucleare del CNR, Universit& Federico II, Napoli, Italy; (3) Endocrinologia, Universit" Federico II, Napoli, Italy; (4) Chirurgia C, Istituto Nazionale Tumori, Napoli, Italy Aim: The aim of this retrospective study was to evaluate the diagnostic accuracy of nor-cholesterol and MIBG radionuclide imaging in two separate groups of patients with adrenal tumors to characterize lesions as adenoma or pheochromocytoma. Methods: We studied 75 patients (22 M and 53 F, mean age 47+15 years) with hypersecreting (n=32) or non-hypersocreting (n-~*3) unilateral adrenal tumors detected by CT or MR scans. Iodine-181 nur-cbolesterol adrenal scintigraphy was performed in 41 patients, lodine-131 MIBG imaging was acquired in the other 34 patients. Pathology examinations (n=58) or CT follow-up studies (n=l 7) were obtained. Adrenal lesions were represented by 44 adenomas, 4 cysts, 1 myelolipoma, 1 pseudotumor, 1 ganglioneuroma, 16 pbeochromocytomas, 3 carcinomas, 4 metastases and 1 sarcoma. Radionuclid¢ studies were qualitatively evaluated and the corresponding results were classified as true-positive (TP), true-negative, false-positive (FP) and false-negative. Diagnostic sensitivity, specificity and accuracy as well as positive (PPV) and negative (NPV) predictive values were calculated. Results: The diagnostic values of nor-cbolesterol scintigraphy to identify adrenal adenomas were: sensitivity 100%, specificity 71%, accuracy 95%, PPV 94% and NPV 100%; of note, 2 FP eases were observed represented by a pbeochromocytoma and a myelolipoma. The diagnostic values of MIBG scintigraphy to recognize pbeochromocytoma were: sensitivity 100%, specificity 95%, accuracy 97%, PPV 94% and NPV 100%; only 1 FP case occurred consisting of a carcinoma. Conclusions: In the large majority of cases, adrenal scintigraphy using uor-cholesterol or MIBG is able to characterize specific lesions such as adenoma and pbeochromocytoma, respectively. These findings show relevant clinical impact particularly in patients with nonhypersocreting adenomas or pheochromocytomas. However, unusual findings may be rarely observed; nor-cholesterol uptake has been found in rzon-adenoma tumors such as myelolipoma and pbeochromocytoma; similarly, MIBG accumulation may occur not only in lesions arising from medullary chromaffin tissue, but also in cortical adrenal carcinoma.

Q.

0 n

• DIAGNOSTIC O N C O L O G Y 11

PS_524 Abstract withdrawn

PS_526 MARROW TOXICITY ESTIMATES OF IODINE-131 THERAPY FOR THYROID CANCER Y.L. Yu, L.B. Chen, Q.Y. Luo, H. Ji, R.S. Zhu. Depatment of Nuclear Medicine,Shanghai 6th People's Hospital, Shanghai, China. The variance of peripheral blood cells in iodine-131 treatment of thyroid cancer was investigated to estimate marrow toxicity. Methods: WBC,RBC,Hb and PLT of 177 patienus with thyroid cancer were tested separately, investigating variance of peripheral blood cells in different sex, age, accumulative iodine- 13 I dose, cancer type and metastasis mode. Results: WBC and PLT did not vary in sex (Fw=0.399, Fe=O.903_O.05), but RBC and Hb of female were markedly decreased (Fr = 25.217, FH=30.895, >FooulTsl=6.785_P<0.01). The variance of blood cells had no statistics signification in age, cancer type and Tab. l Correlation between peripheral blood cell count and accumulative 13=1dose(nil77) dose(MBq) 1480 9200 9201 18500 18501 27700 27701 37000 37001 46200 46201 53576 F

P

n 67 47 24 20 12 7

WBC(10~/L) 6.73±1.37 6.73±1.26 6A4±1.09 5.32±0.88 5.23±1.43 4.86±0.80 8.840 <0.0 t

RBC(, 10'~/L) 4.48±0.39 4.51±0.44 4.57±0.42 4.34±0.47 4.19±0.42 3.75±0,73 5.285

<0.01

Hb(~/L) 132.56±12.77 133.08±13.73 134.42±12.79 126.61±13.94 124.78±10.14 119.10±17.89 2.832 <0.05

PLT(_I0~/L) 213.45±48.55 198.93±49.00 197.50±45.55 176.26±4983 163.42±61.55 182.94±72.92 3.255

<0.01

F011515.1711=2.265 Fu Oh5.I711=3-112 metastasis. The blood ceils' mean of each group of iodln¢-131 dose was within ordinary range, but difference of within groups was very marked(FwB(=8.84, Frac=5.285, FeL¢~3.255, >F~ums.171t=3Al2, PFu0515.17~= 2.265, Pr~ut~175~= 0.195_tb>t~ltlTsl= 2.576 P<0.01 ). Conclusions: Though peripheral blood cell's counts were within ranges of normal value, it is certain lbr iodine-131 therapy to effect marrow toxicity. There were markedly negative correlation between peripheral blood cell's count and accumulative iodine-131 dose.

PS_525

PS_527

DIAGNOSIS, THERAPY, FOLLOW-UP AND SURVIVAL RATE OF PATIENTS WITH MEDULLARY THYROID CARCINOMA (MTC)

99MTC-TETROFOSMIN AND 99MTC-MIBI WHOLE BODY SClNTIGRAPHY FOR DETECTING DISTANT METASTASES FROM DIFFERENTIATED THYROID CARCINOMA

M. Malesevic (1), S. Popadic (1), J. Bogdanovic (2), N. Stjapic (3), LJ. Miljkovic (4), D. Savic. (1) Department of Nuclear Medicine; (2) Clinics for Oncology; (3) Department of Pathology; (4) Clinics for Internal Oncology, Institute of Ontology, Sremska Kamenica, Yugoslavia In this paper we evaluated diagnosis, therapy, follow-up and survival rate of patients with MTC in the period from 30 th January 1976 to 10~hMarch 2001. MATERIAL: There were 27 patients (pts) with sporadic MTC: 16 women (aged 29 to 73; mean age was 47.1 + 9.8) and 11 men (aged 39 to 75; mean age was 53.7 + 12.0). METHODS: Diagnosis was done by the means of scintigraphy (99mTc or 131-1), ultrasonography, FNB, CIT analysis and ex-tempore biopsy of the nodular gland; follow-up and a therapy according to the Protocole for MTC of the Institute and the survival rate (SR) was determined according to Kaplan Meier's analysis together with Log rank programme. RESULTS: Clear and suspect C1T findings for malignancy, in pre-oporative diagnosis of the patiunts with MTC were 21(77.7%). All the pts were operated (total thyreoidectomy in 21(77.7%), Ioboctomy with isthmeoctumy in 404.8%) and nodulectomy in 2 (7.4%). The additional therapy was as follows: a radiological one in 5, polychemio in 4, radiological/polychemio in 4 and reoporation LGN in 4 pts. All pts were under the substitution of L-thyroxine. Them were |0(37%) pts in a stable remission, there were 10(37%) pts in a partial remission while 7(25.9%) died. According to pTNM there were Stage(S0 1=2(7.4'/,), St I[==9(33.3%), St I11=11(40.7%) and St 1'¢=5(18.5%). The pts were followed-up by the means of: thyrocalcitonin (TCI') (x=708.7 + 848.0), cancerocmbrionie antigen (CEA) (xffi77.3+69.3), and the dg. whole-body scintigram with 99mTc DMS(v) (12(52.1%) with pathological, 11(47,9%) normal while in 4(14.8%) pts the scintigram was not done)- Mediana of the follow-up was 5yrs and 11 days. The survival rata (SR) for women was 0.79 for 5.18 yrs; for men it was 0.38 for 8.5yrs (p--0.1). SR for all pts was 0.61 for 8.5 yrs. In St [ and St II the pts were alive; in St IlL SR was 0.44 for g.Syrs and in St IV, SR was 0.40 for 5.18yrs (p=0.17). CONCLUSION: Diagnosis should be fast obligatorily with FNB, CIT findings and ex ternpore biopsy in pre-operative diagnosis. For better SR the total thyreodectomy with maximal disection of LGN is obligatory. The follow-up of pts with MTC is very convenient by the means ofTCT, CEA and dg.sc. 99mTc DMS(v), because we can appropriately react by radiological therapy, polycbomio therapy and reoperation of LGN. The SR of all the patients with MTC was very well and for pta in St III and St IV it is satisfying from the oncological point of view.

121£

J. Drac-Kaniewska (1), I. Kozlowicz-Gudzinska (1), H. TomaszewiczKubasik (1), M. Kaniewski (2), P. Godlewska (2), M. Czetwertynska (2), A. Chaladaj-Kujawska (2). (1) Department of Nuclear Medicine; (2) Department of Brachytherapy, The Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland. 99mTc-Tetrofosmin (TF) and 99mTc-MIBI (MIBI), non specific tumor-seeking tracerswere evaluated for their ability to detect distant metastases from differentiated thyroid carcinoma (DTC) and reliability in the follow-up studies. Methods. Whole body scintigraphy was performed 20-30 rain after intravenous injection of 740 MBq 99mTcTF or 740 MBq 99mTcMIBl using dual-headgammacamera (followed by spot or SPECT if needed)in [0g patients with DTC ; 22 pts in clinical remission ( no signs of neoplasm dissemination by imaging methods and thyroglobulin level within normal range units) and 86 pts with distant metastasas in 1311 whole body scintigraphy ( 5 3 ) or in other visual metods (rtg,CT,asg )(I4) or with negative 131I whole body scan and elevated thyroglobulin level(19). Patients were randomized in two groups: 52 of them received TE 34 MIBL Results. TF. In group of 52 pts with signs of neoplasm dissemination 36 showed positive TF whole body scan (69%), 16 pts were TF negative (3t%). 23 o f 34 pts (68%) with 13 lbpositire whole body scan were also TF positive, I 1 of 34 pts (32%) were TF negative. In a group of 7 pts with metastases in rtg,CT or other methods 4 were "IF positive (57%), 3 were TF negative(43%). 9 of 11 pts with negative 13 l J whole body scans and elevated thyroglobolin level were TF positive (82%), while 2 were "IF negative (18%). MIBI. Among 34 pts with distant metastases 2i (62%) presented positive MIBI whole body scans, while 13 (38%) were MIBI negative. 9 of 19 pts with positive 1311 whole body scan were also MIB[-positive (47%); 10 were MlBl-negative (53%). In a group of 7 pts recta-positive in rtg,CT or others 5 demonstrated MIBI positive scan (71%), 2 were MIBl-negetive (29%). 7 of 8 pts with negative 131I whole body scan and elevated thyroglobulin were MIBI-positive (87%) ; 1 was MIBInegative. In a control group of 24 persons( 22 wim DTC in clinical remission, 11 "IF and I 1 MIBI, 2 disease-free) "IF or MIB1 scans were negative in all cases. Conclusions: TF and MIBI are clinically useful for detecting distain metastases of DTC and deserve complementary clinical application in follow-up studies. TF and MIBI are highly satisfactory in patients with negative radioiodine whole body scan and elevated thyroglobulin level.

•

PS_528

Patient

THE PREOPERATIVE STAGING OF THE LARYNX CARCINOMA BY 99MTC-TETROFOSMIN SCINTIGRAPHY: A PRELIMINARY STUDY M. Grosso, B. Fattori, E Bianchi, G. Boni, G. Manca, D. Volterrani, A. Nacci, F. Ursino, R. Bianchi. Department of Nuclear Medicine, University of Pisa, Pisa, Italy. Primary laryngeal carcinoma represents the most common malignancy of all tumors of the head and neck. The preoperative staging is usually performed with neck uhrasonography (US) and CT scan. Nevertheless, latero-cervical lymph node metastases can be observed in 60% of the patients (pts) at the time of diagnosis and can influence the surgery approach, the prognosis and the subsequent treatment. Aim of our study was to evaluate the utility of 99mTcTETROFOSMIN in the preoperative staging of patients with larynx carcinoma.Twenty-two men patients (males, age 65-±9 yrs). with a diagnosis of carcinoma obtained by MLSD, underwent 99mTc-TETROFOSMIN scan (WBS and SPET study of the neck and chest 10 min. after iv injection of 740 MBq), neck US and CT scan. Ten oftbem underwent total laryngectomy and functional lymphoadanectomy, one patient total laryngectomy and total lymphoadenectomy, two patients partial laryngectomy and total lynpboadenectomy. Seven patient received radiotherapy and chemotherapy with extensive latero-cervical lymph node metastases. The remaining two are waiting for surgery. Pathologic results classified four lesions as well-differentiated squamous cell carcinomas (18,2%). sixteen as medium-differentiated (72.7%) and two (9 I%) as poor-differentiated. Cervical lymph node metastases were demonstrated by histological finding in 4 out 13 pts. 99mTc-TETROFOSMIN scintigraphy was positive fur primary lesion in 21/22 patients and in 3 of 4 patients with latero-cervical lymph node metastases underwent surgery, while was positive in I of 7 patients underwent radio and chemotherapy, The specificity of lymph node metastases was 100% for Tc-99m-Tetrofusmin and 54*/0 tbr CT, with a significant statistical difference (p=O.02). On the other hand the diagnostic sensitivity was highest for CT (89%) versus scintigraphy (44%) (p=0.06). In conclusion, on the basis of our experience, we believe that Tc-99m-tetrofosmin can be useful as a complementary imaging technique to CT scan tbr detecting primary disease and fur a better application oftbe therapeutic and surgery protocols,

DIAGNOSTIC ONCOLOGY 12

2 3 4 5

Sex M M M F F

Age 34 41 48 73 55

Primary tumor Liposarcoma Breast Prostate Breast Breast

6

F

35

Breast

7

M

70

Larynx

8

M

69

NHL

9

F

61

Burkitt

10

F

55

Breast

11 12

F M

29 65

Breast Prostate

I

NCS Bilateral Bilateral Bilateral Bilateral Right mandible Right mandible Right mandible Right mandible Lefl mandible Left mandible Bilateral Left

Bone SPET Ne[[ative Bilateral Bilateral Right Right

MIBI SPET Negative Bilateral Bilateral Left Right

MRI Negative Bilateral Bilateral Bilateral Right

Right

Negative

Negative

Negative

Negative

Negative

Right

Negative

Left

Pterigoyd area Left

Negative

Negative

Negative

Positive

Ri[[ht Lefl

Mentat Left

N.A, Left

NCS is a rare condition, related to a dismal prognosis, which has a negative influence on the quality of life. Due to the complexity of skull base and mandible anatomy, it is difficuh to obtain useful information concerning the aetiology of this condition. These first results suggest that these nuclear medicine procedures can play an important role in decision making concerning treatment.

t,O m

PS_529

PS_530

SESTAMIBI AND HMDP SPET FOR THE EVALUATION OF THE

THE ROLE OF 99MTC-SESTAMIBI SPET IN THE PREOPERATIVE

t~ cO

NUMB CHIN SYNDROME

MANAGEMENT AND DIFFERENTIAL DIAGNOSIS OF CEREBRAL LESIONS

ta

G. Savelli (1), A. Caraceni (1), H. Dool (2), F. Simonetti (1), M. Maccauro (1), M. Testoni (1), E. Bombardieri (1). (1) Istituto Nazionale Tumod, Milano, Italy; (2) Leiden University Medical Centre, Leiden, The Netherlands. Facial numbness restricted to the distribution of the mental nerve is called numb chin syndrome (NCS). This uncommon neuropathy may be caused by a number of conditions such as metastases involving the mental nerve, the trigeminal roots, the Gasserian ganglion and the meninges. The exact localization of these metastases is pivotal in the management of mental neuropethy. Twelve patients with malignant disease and presenting with NCS were enrolled in this study. Imaging methods included magnetic resonance imaging (MRI), planar and Single Photon Emission Tomography (SPET) with Tc-HMDP and =Tc-Sestamibi SPET of the skulI. Five patients had NCS involving both lefi and right mandible, 4 patients had NCS on the right side and 3 on the left. Bone SPET was performed 3 hours after the i.v. administration of 555 MBq of~"Tc-HMDP. Sestamibi SPET was performed 5 minutes after the i.v. administration of 740 MBq of 99mTc-Sestamibi. Both these examinations were performed using a Picker Prism 3000 triple-beadod gamma camera, equipped with low-energy ultra-high resolution parallel-hole collimators. Images were reconstructed using filtered back-projection (Ramp/Winner filter, 0.2-0.4). MRI was performed after the nuclear medicine procedures. One patient did not undergo MRI because of claustrophobia. All the examinations were reported independentl~y nuclear medicine physicians and radiologists. In 9 patients Tc-HMDP SPET was able to identify the location of the metastasis. Moreover, ~"~rc-Sastamibi SPET evidenced 8 areas of uptake suspicious for metastases. MRI correctly identified 6 metastases. ~mTc-HMDP SFET showed 3 metastases and Sestamibi SPET 2, missed by MRI. In one case MRI demonstrated a metastasis not evidenced by both the nuclear medicine procedures. The imaging procedures in combination identified 10 of the 12 metastases.

S. Baldari (1), G. Restifo-PecorelM (1), RE Angileri (2), R. Lipari (1), A. Germano (2), S. Cosentino (1), A. Herberg (1), D. d'Avella (2), N. Bonanno (1). (1) Department of Radiological Sciences - Nuclear Medicine; (2) Department of Neurological and Neurosurgical Sciences, University of Messina, Messina, Italy. The optimal management of primary brain tumor represents a significant challenge for clinicians and researches. Despite recent advances in neuroradiological imaging, neurosurgical treatment, neuroncological strategies, and nuclear medicine procedure, the preoperative assessment of cerebral lesions needs further noninvasive semiquantitative insights. 99mTechnetium-Sestamibi (MIBI) has been proposed as an useful radiopharmaceutical perfusion agent, which has been recently used as an imaging SPET agent for various neoplasms, including brain tumors. This technique can predict brain tumor grading and the behavior of glial tumors in terms of clinical aggressiveness. In addition, MIBI has been used in the differential diagnosis of some difficult cases. Aim of this study is to describe the experience obtained at our Institution in preoperative evaluation of 22 patients harboring a brain lesion, and evaluated during the last 18 months. They were 11 men and 11 females, ranging in age between 6 and 73 years (mean 47 yr.). Of these lesion, 21 (96%) were located in the supratentorial compartment, while in one pediatric ease the lesion was located within the brain stem. Of these cases, 6 were low-grade glioma, 5 glioblastoma multifurrne, 4 anaplastic astrocytoma, 2 meningiomas, 2 metastasis, and I epidermoid. Two additional cases were represented by benign nonneoplastic hemorrhagic diseases. SPET was performed within 10 minutes after intravenous injection of 10-20 mCi M1B[. The images were obtained with a dual headedgamma camera using a high resolution collimator. Transverse, coronal, and sagittal views were reconstruced. MIBI uptake has been evaluated on the transverse slices, and expressed as tumor/background ratio. Two subgroups of patients were identified. MIBI uptake was found in 16 (72.7%) patients. The tumor/background ratio correlated with tumor histology, as proved from surgical or bioptical sample. In two patients of this group, a benign non-neoplastic disease has been detected, and proved on late neuroradiological observation. We found a marked difference ( p < 0.001) between the M1BI uptake in non-tumor and low-grade lesions (1.1 ± 0,45) vs high grade tumor (2.3 :~ 0.14). According to our results, the specificity and sensitivity of MIBI brain SPET has been proved to be high. This tumor confirms the MIBI SPET as a valuable nnninvasive semiquantitative tool, useful in the management of brain tumor patients, that offers clinically relevant pre-operative information in problem-solving session, such as differentiating neoplasms, and categorizing glial tumors in terms of clinical aggressiveness.

1211

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• DIAGNOSTIC ONCOLOGY 12 PS_531

PS_533

99MTC-TETROFOSMIN BRAIN SPECT VERSUS CT AND MRI IN ASSESSMENT OF OUTCOME OF TREATMENT OF BRAIN TUMORS

SERUM TUMOR MARKERS VERSUS IMMUNOSClNTIGRAPHY AND INTRAOPERATIVE RADIOIMMUNODETECTION IN COLORECTAL CANCER

H. Moustafa (1), A. Faww (1), H. Nasr (1), E. EI-Ghoneimy (2), M. Moustafa (2). (1) Nuclear Medicine Department; (2) Oncology Department, Faculty of Medicine, Cairo University, Egypt. Anatomic imaging modalities, such as X-ray, CT and MRI are often unable to differentiate post radiation gliosis from residual or recurrent tumor. Physiological imaging methods, such as ISF-FDG PET and SPECT (2°lTI, '~mTc-Tetrofosmin or ~'~Tc-MIBI) have become an increasingly imponam method in solving this problem. Aim: To evaluate the role of 9~Tc-Tetrofosmin brain SPECT imaging in diagnosis of patients with viable residual or recurrent astrocytoma versus post radiation gliosis during their postoperative therapy course. Methods: The study included 55 patients (14 females and 41 males). Their mean age was 33.2 :~15.6 years with a range of 4-80 years. Thirty-one patients had astrocytoma while 24 patients had glioblaatoma multiform¢, All patients had performed prior surgical tumor excision followed by radical radiotherapy in the form of whole brain irradiation followedby localized radiotherapy or stereotaxy. Nine patients received chemotherapy as well. All patients . brain .SPECT .imaging. us ng 740 . MBq with mag ng a were subjected to ~mTc-Tetrofosmm 20 minutes• Also radiological brain imaging (CT and/or MR[) were performed for comparison. The total number of SPECT studies performed and compared to CT or MRI were 61 studies• Results: Forty-seven SPECT studies were positive while 10 studies were false negative due to cystic or small lesions <1 cm evident in CT or MRI. Four studies were equivocally diagnosed by CT or MRI and were found to be true negative by SPECT The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SPECT to detect residual or recurrent lesions versus fibrosis as compared to CT or MRI was 82.5%, 100%, 100%, 28.6% and 83.6.1% respectively. • ~gm . . Conclusion: Tc-Tetrofosmm brain SPECT is an additional complementary valuable diagnostic method in assessment of residual or recurrent viable brain tumors, and could be of help in therapeutic decision-making.

J. Vizda (1), P. Hladik (2), E. Urbanova (1), E. Malirova (1), B. Dlabalova (1), P. Kafka (1), M. Netikova (1). (1) Department of Nuclear Medicine; (2) Department of Surgery, University Hospital, Hradec Kralove, Czech Republic. Immunoscintigraphy of tumors makes non-invasiv¢ in vivo imaging of tumor antigens distribution in whole body possible, lntraoperative radioimmunodetection with a hand-held gamma-detector probe in addition to preoperative immunoscintigraphy finds a pathological tissue during operation (radiolmmunoguided surgery = RIGS). The aim of the present study was compare immunoscimigraphic findings with following RIGS and three serum tumor markers in 121 patients with histologicaly verified colorectal cancer. Two radiopharmaceuticals were used. Materials and methods: lmmunoscintigraphy (2x whole body scans from two projections and single photon emission computed tumography of abdomen) and radioimmunoguided surgery were performed in 106 pts. with primary and t 5 pts. with recurrent colorectal cancer. As radiopharmaceuticals were used monoclonal antibody against TAG72 labeled with tllln (Oncoseint) in 56 pts. and fragments of monoclonal antibody against CEA labeled with 99~Tc (CEA-Scan) in 65 pts. Prior to injection of radiopharmacentical blood samples were taken for determination of tumor markers (CEA, CA72.-4, CAI9-9) and HAMA in all patients. Postoperative the activity of resected tissue was measured and histological examinated, in controversial cases immunohistochemistry was performed. The ratio of activity tumor/healthy tissue was determined intraoperative and postoperative. Results: The tumor tissue was detected with Oncoscint by immunoseintigraphy in 93% pts. and intraoperatively in 98% pts., with CEA-Scan by immunoscintigraphy in 92% pts. and intraoperatively in 100% pts. Average ratios tumor/healthy tissue were 2.2 (intraoperative) and 2.9 (postoperative) in Oncoscint group, 3.3 and 3.5 in CEA-Scan group. Serum levels at least one of tumor markers were increased in 58% pts. studied with Oncoscint (CEA in 48%, CA72-4 in 31%, CA19-9 in 33%) and in 56% pts. studied with CEA-gcan (CEA in 35%, CA72-4 in 38%, CAI9-9 in 26%). Conclusions: The results show expressive lower sensitivity of serum tumor markers in comparison with immunoscintigraphy and intrsuperative radioimmunodetection. The determination of a greater number of serum tumor markers is necessary Patients with high level of some tumor marker in serum have a higher probability of cancer but on the contrary normal levels do not exclude malignant disease. There is no correlation between serum levels of lumor markers and the rate of radiopharmaceutical uptake in tumors. (This study was supported by the grant No.45323 of Czech Ministry of Heahh)

PS_532

PS_534

INTRAARTERIAL INFUSION OF 99M-TC-ALBUMINE MICROSPHERES FOR DEPOT EFFECT ASSESSMENT OF A REGIONAL CHEMOTHERAPY IN COLORECTAL CARCINOMA PATIENTS WITH LIVER METASTASES

DUAL-PHASE ANGIOHEPATOSCINTIGRAPHY IN ESTIMATION OF HEPATIC TUMORS VASCULARITY AND ASSESSMENT OF CHEMOEMBOLIZATION EFFICACY

E. Piperkova (1), G. Kurteva (2), P. Kurtev (3), M. Beeva (4), M. Dimitrova (1). (1) Department of Nuclear Medicine; (2) Department of Chemotherapy; (3) Department of Surgery; (4) Department of Radiology, National Hospital for Active Cancer Treatment, Sofia, Bulgaria The failure of systemic chemotherapy in the treatment of colorectal cancer patients with liver metastases has led to considerable interest in regional chemotherapy administration. The aim of this prospective study is to estimate the radiolabclled albumine-micrispheres'distribution, administered into the hepatic artery infusion pump, their concentration and remains in the blood flow of the hepatic metastases for getting depot effect of following regional chemotherapy in colorectal cancer patients with liver metastases Method:.Seven patients have been subjected to intmarterial application of the 99mTcMacrot¢cMono (Sorin Biomedica), injected through ,,port-jet"into the hepatic artery before the intraarterial infusion of chemotherapy. Dynamic control of radiolabelled particles (diameter 10-90 micrometers, 3,5 MBq/kg activity) distribution has been carded out in two phases on a gamma-camera ,,DIACAM"(Siemens):the first 1000ms/flame (60 frames), the second 30 000 ms/frame 30 frames. Results: Scintigraphic control, planar and SPET on the 2 ~, 4 th and 24 th hours showed that mierospheres remain in the vaacularised liver metastases more than 24 hours, resulting in prolonged local effect of the applied chemotherapeutic agents. Clearly good results have been established in five of the patients by CT and SPETmonitiring, Conclusion: Embolizing, biodegradable particles can be coedministered with anticancer drugs to show temporarily the arterial blood flow end to increase drugs uptake within the metastatic-bearing liver. -

1212

R Fadeev, D. Granov, A. Ivanova, V. Soukhov, T. Dubrovina. Nuclear Medicine Dept., Central Research Institute of Roentgenology and Radiology, St-Petersburg, Russia. Chemoembolization(CE) at presentis the methodof choicein patientswith hepatictumors (especially in cases of multi focal metastatic lesions). While the success of CE mainly depends on the obtaining of the objective information about vascularity of tumor, The purpose of this study was to evaluate dual-phase angiohepatoseintigraphy (DP-AHSG) for estimation of vascularity and assessment of (CE) efficacy in patients with hepatic tumors. Mataial and methods: Twenty five patients (middle age 42 yrs) with hystologicaly verified malignant lesions of the liver (hepato-cellular cancer - 5 pts, and metastatic tumors - 20 pts) were evaluated. 18 patients were studied before and 7 patients - after CE. DP-AHSG using 99m -colloids was performed on APEX SP-6 gamma-camera (Elseint) just after i.v. injection of bolus o f tracer in dynamic mode: in early (anglo) phase for the first 60 seconds and late (parenchimae) phase. The frames of each time interval were summarized and the sums of the second phase were subtracted from the first ones. The uptake of radiopharmacontical at the resulting seintigrams noted the vascularity of hepatic lesions (Patent _ 2156112). Results: In 22 of 25 patients the hypervasculer loci were visualized: in 5 pts with HCC and in 17 - with hepatic metastases of different tumors. DP-AHSG data were compared with the angiography results in the same patients: in 88% there were concordance of the results, in 12% - DP- AHSG data were false-negative. 7 patients assessed by means of DP-AHSG before and after CE showed successful embolization and in one patient CE was ineffective. Conclusion: DP-AHSG is non-invasive and safe method with low radiation dose that feasible for repeatad studies and can be used in vascularity estimation and assessment of CE efficacy in patients with hepatic tumors.

• DIAGNOSTIC ONCOLOGY 12 / OTHER CLINICAL SCIENCE. ENDORINOLOGY 2 PS_535

PS_537

TECHNETIUM-99M SESTAMIBI BRAIN SPECT IN THE FOLLOW UP OF GLIOMA FOR THE RESPONSE TO CHEMOTHERAPY

SERIAL INDIUM-111 CAPROMAB PENDETIDE (PROSTASCINT) IMAGING IN PATIENTS WITH RECURRENT OR LOCALLY ADVANCED PROSTATE CANCER (LAPC) UNDERGOING COMBINED MODALITY THERAPIES

E Prigent (1), E Dubois (2), S. Blond (2), M. Steinling (1). (1) Deprt of Nuclear Medicine; (2) Depart of Neurosurgery, Hospital R Salengro. Lille, France. Aim : Standard treatment of glioma consists in surgery followed by radiation therapy. Chemotherapy is used in case of recurrence. Because of lots of potential considerable sideeffects of chemotherapy, early tumor response evaluation is necessary for clinicians to adapt the treatment. However, the response monitoring with computed tomography or magnetic resonance imaging is often difficult. The aim of this study yeas to evaluated the interest of repeated ~mTc-MIBI SPECT for these patients. Methods Fifteen patients treated lbr recurrent high grade glioma were followed during their chemotherapy. Different chemical protocols were used (PCV, T?mozolamide, Fot?mustine). SPECT was performed one hour after the injection IV of 555 MBq of 9qmTc-MIBl, using a dedicated SPECT system (Tomomatic® 564. M?dimatic. Dk). A total of 57 investigations were performed. A MIBI uptake index was computed as the ratio of counts in the lesion to those in the controlateral region. Previous studies have shown a cut off value at 2.0. SPECT indexes were compared to neurologie evaluation, CT or MRI. This assessment was performed every four months during and after the treatment. Results : Three types of response were observed, so we classify our patients into three groups. In the fisrt one, 6 patients showed an increased MIBI index associated with a clinical or radiological progressive disease during chemotherapy ; this demonstrated an immediate resistance to treatment. In the second one, afier initial response to therapy, 3 patients showed an increased MIBI index despite chemotherapy, demonstrating a secondary resistance to therapy. In the third group, 6 patients showed decreased MIBI index, demonstrating a good response to therapy. There is no correlation between the initial MIBI index value and the disease progression. The 9 first patients died shortly after the last tomoscintigraphy (on an average : 7 months). The therapeutic protocol was modified in 6 cases, but only successfully in 2 cases. In 9 cases, the tumor evolutivity was diagnosed with the tomoseintigrapby earlier than with clinical signs and in 4 cases earlier than with MRI. C o n c l u s i o n : g~mTc-MIBI SPECT is able to predict an early response or a resistance to chemotherapy. So this functional brain tumor imaging could be considered in the case of patient treated for recurrent high grade glioma as a valuable tool to adapt the therapeutic protocol effectively, and also to stop the treatment after a return to normal index (group 3).

I. Sarikaya (1), A. Hussain (2), N. Bacetti (1), E. Siegel (1), L. Holder (1), B. Line (1). (1) University of Maryland Medical Center, Division of Nuclear Medicine, Baltimore, MD, USA; (2) University of Maryland Medical Center, Greenbaum Cancer Center, Baltimore, MD, USA. We have incorporated Prostascint imaging into two clinical trials that we are conducting in patients (pts) who ( 1) experience rising serum PSA afier undergoing definitive therapies [radical prostatectomy (RP) or/and radiation (XRT)] for localized prostate cancer, or (2) who present with locally advanced disease. In one trial, we are combining weekly Taxol chemotherapy with concurrent XRT and hormone ablation (to date 18 pts), while in the second trial we are using single agent Taxotere for 4-6 cycles followed then by I year of hormone ablation (to date 26 pts). Pts entered onto either trial get a baseline Prostascint scan, and those who have positive findings on initial scanning undergo subsequent imaging at the completion of therapy. Our aim is to determine the potential role of Prostascint imaging in assessing baseline disease status as well as in response to combined modality therapy, and to possibty correlate such findings with clinical outcome. So far, we have obtained 44 baseline and 9 follow-up Prostascint scans. Of the 44 patients entered onto the two trials, 10 had LAPC from the very outset, 8 were status post definitive XRT, 15 had undergone prior RP, while I I had salvage XRT after initial RP. Overall, 30 (median PSA 15.05 ng/ml) of 44 (median PSA 13.7 ng/ml) pts had positive baseline Prostascint scans: 7 had uptake in prostate/prostatic bed, 14 had uptake in regionaVabdominal or thoracic lymph nodes, while 9 had uptake in prostate area plus lymph nodes. Nine of the 18 pts entered onto the Taxol/XRT/hormone ablation trial have completed initial therapy, and have had follow-up Prostascint scans: 7 of the 9 show partial (n=3) or complete (n=4) resolution in areas of increased activity identified pro-therapy. In these 9 pts, the median pro- and post-treatment PSA values are 23.7 and 0.22 ng/ml, respectively. Follow-up Prostascint scans on the other pts will be obtained as they complete their treatment programs, In addition to traditional imaging and biochemical parameters, serial Prostascint scanning may provide potentially relevant information with respect to clinical response and outcome.

¢-

PS_536 USEFULNESS OF DIASTOLIC RADIONUCLIDE PARAMETERS FOR

OTHER CLINICAL SCIENCE. ENDORINOLOGY 2

,O m

olD

THE PREDICTION OF ANTHRACYCLINE CARDIOXICITY K. Massaloux-tarozzi (1), D. Mestas (1), C. Thouly (1), P. Chollet (2), J. Maublant (1). (1) Department of Nuclear Medecine; (2) Department of medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France. Objectives : Diastolic parameters determined by gated blood pool scintigraphy (GBPS) were evaluated before treatment in cancer patients (pts) in an attempt to predict cardiotoxicity of anthracyclines. Methods : From April 1998 to July 2000, we prospectively analyzed data of GBPS realized during cardiac follow.up of 50 cancer pts treated by polychemotherapy based on anthracycline. Twenty pts had cardiovascular risk factors (R+), 13 had formerly received anthracycline (A+). Left vantricular ejection fraction (LVEF), peak filling and ejection rates (PFR and PER, both expressed in end-diastolic volume per second), and time to PFR and PER were determined before and altar a treatment with a mean cumulative dose of 500 rag/m_ doxorubicin equivalent. Results before treatment were compared with normal values established in a control group of 64 pts without any cardiac risk factor nor former anthracycline treatment. Results : In the 50 cancer pts, significant differences of pre-treatmant LVEF, PFR and PFR/PER were observed with controls. When considering pts history, differences were significant only for R+. n 64 50 20 13 * p
Controls Treated R+ A+

LVEF 63.5 ~: 5.5 61.4±6.4" 58.0 ± 4.2 63.3 • 5.0

PFR 3.0 ± 0.7 2.9±0.8* 2.6 ± 0.7* 3.3 ~: 0.6

PFR/PER 0.88 ~: 0.2 0.91±0.2' 0.82 ± 0.4* 0.93±0,2

In predicting a fall of LVEF of > 5% in the overall population, R.OC analysis showed that the most efficient parameter was a pre-treatmant PFR/PER < I, with positive and negative predictive values of 52% and 78%, respectively, and sensitivity and specificity of 80% and 48%, respectively. When combined with HR _> 82 bpm (ROe analysis threshold), these values rose to 75%, 82%, 71% and 85%, respectively. Conclusion : This study shows that PFR/PER combined with HR. are very useful GBPS parameters to predict anthracycline cardiotoxicity.

PS_538 LONG-TERM FOLLOW-UP OF PATIENTS WITH BONE METASTASES FROM DIFFERENTIATED THYROID CARCINOMA - SURGERY VERSUS CONVENTIONAL THERAPY

B.J. Fueger (1), G. Zettinig (1), C. Passler (2), C. Pinch (1), I. Kaufmann (1), S. Meghdadi (1), A. Becherer (1), K. Kaserer (3), R. Dudczak (1), B. Niederle (2). (1) Dpt. of Nuclear Medicine; (2) Dpt. of Surgery; (3) Dpt. of Pathology, University of Vienna, Austria. AIM: Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This retrospective study was performed (I) to analyse patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bonemetastaseson survival. Patients and Methods: We analysed 4t consecutive patients with bone metastases from differentiated thyroid carcinoma who had thyroid surgery at Vienna University Hospital since 1966. Median follow-up time was 12 years. There were 24 female and 17 male with a mean age of 60 + 12 years. The primary tumour was follicular in 35 and papillary in 6 patients. Radioiodine treatment was performed in 32 patients with a mean administered activity of 2.7 ± 2.4 GBq 131-I. Metastases restricted to the skeleton were found in 22 patients whereas in 19 individuals, additional extraskeletal dis~mt metastases were seen. Twenty-seven patients had multiple bone metastases. In 21 individuals, up to 5 bone metastases were surgically removed with the intention to keep the patient free from bone metastases. Statistical analysis of age, sex, tumour stage, histology, thyroid and lymph node surgery, presence of extraskeletal metastases, and surgery of bone metastases was performed using a cox regression model. A p value < 0.05 was considered as statistically significant. RESULTS: Univanate analysis identified total thyroidectomy (p 0.005), lymph node surgery (p 0.002), radioiodine therapy (p 0.046), and the absence of ¢xtraskeletal distant metastases (p 0,021) as significant predictors of survival. Yet, in that small collective, multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified in addition to thyroid and lymph node surgery also the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (p 0.038). CONCLUSION: These findings indicate that in patients without additional extraskeletal dislant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma is associated with improved survival.

D.

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IX

• OTHER CLINICAL SCIENCE. E N D O R I N O L O G Y 2

PS_539

PS_541

TC-99M SESTAMIBI PARATHYROID SClNTIGRAPHY IN PATIENTS WITH MULTINODULAR THYROID GLANDS

THREE-DIMENSIONAL SPECT MAXIMUM INTENSITY PROJECTIONS (MIP) OF TL-201 SClNTIGRAPHY: A NEW APPROACH FOR DIAGNOSIS OF DIFFERENTIATED THYROID CARCINOMA

M.B. Tomas, T. Kalapparambath, G.G. Tronco, M.D. Afriyie, C.J. Patestro. Division of Nuclear Medicine Long Island Jewish Medical Center, New Hyde Park, NY, USA. Aims: The sensitivity of preoperative "gmTc- Sestamibi parathyroid lesion localization in primary hyperparathyroidism is 90 - 95% and the specificity ranges from 85 - 90%. Coexisting thyroid nodules and cervical lymph nodes are the most commonly reported causes of false positive results. Although primary hyperparathyroidism and a mullinodular thyroid gland may coexist in the same patient, there are limited data about the effect of thyroid mulfinodularity on preoperative parathyroid scintigmphy. This retrospective review was undertaken to evaluate the erect of concurrent muhinodular thyroid glands on preoperative parathyroid lesion localization in patiems with primary hyperparathyroidism. Methods: Twenty-eight patients, 23 women and 5 men, 25 - 80 years old (mean age = 62 years), with primary hyperparathyroidism and multinodular thyroid glands were included in this review. All patients underx,cent surgical exploration within 2 weeks of parathyroid imaging, Pinhole neck imaging was performed 90 - 120 minutes after the intravenous injection of 555 - 925 MBq (15 - 25 mCi) of 9W~Tc-sestamibi followed by injection of 185 MBq (5 mCi) ~"Tc-pertechnetate and thyroid imaging. Images were background subtracted and normalized and the thyroid image was subtracted fi'om the sestamibi image, Focally increased uptake was considered positive for a parathyroid lesion. Results: Thirty-two parathyroid lesions were excised from the 28 patients. Twenty-five patients had I lesion each. 2 had 2 lesions each and t patient had 3 parathyroid lesions. All lesions were in the neck; 11/32 lesions (34%) were ectopic in location. There were 30 adenomas and 2 hyperplastic glands, ranging from 100 - 9300 mg in weight (mean weight = 3461 rag). 31/32 lesions were correctly localized (Sensitivity = 97%). A 190-rag adenoma was not identified preoperatively. There were 6 false positives (Specificity = 79%); three of these occurred in patients with a dominant thyroid nodule in a muhinodular gland. Two of these 3 false positives were on the contralateral side of the parathyroid lesion, Conclusion: In summary, our data indicate that although the specificity of '~'~Tc sestamibi parathyroid imaging is lower in patients with multinedular thyroid glands, than in the general hyperparathyroid population, its sensitivity is preserved. Consequently, it is still usethl because it is a localizing rather than a diagnostic procedure.

R. Nishii (1), S. Noguchi (2), S. dinnouchi (3), S. Negamachi (3), K. Kawai (4), T. Murakami (1), S. Tamura (3). (1) Department of Radiology, Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan; (2) Department of Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan; (3) Department of Radiology, Miyazaki Medical College, Miyazaki, Japan; (4) Central Research Laboratories, Miyazaki Medical College, Miyazaki, Japan Background: Due to the accumulation of normal tissue and inflammation, the conventional planar images often fail to depict tumors with thyroid malignancies in TI-201 seintigraphy. Purpose: The aim of this study was to assess the usethlness of the maximum intensity projection (MIP) method, three-dimensional projection image, for detection of differentiated thyroid carcinoma in TI-201 scintigraphy. Materials and Methods: Twenty-two patients with differentiated thyroid carcinoma had TI-201 seintigraphy using a gamma camera. Patients were injected 74 MBq of TI-201 chloride intravenously. A conventional planar image and SPECT image of neck and chest were acquired in early phase (10 rain after the tracer injection) and in delayed phase (120 min), respectively. tbr 10 rain each. We applied MIP algorithm to SPECT images, and compared this MIP images with the conventional planar images. Tumor location and tumor size detected were evaluated. Results: The scanning time of SPECT was only t0 rain that was the same time of planar imaging. Three-dimensional MIP images were easily obtained because they can be added to SPECT with only a few minutes of additional post-processing time. Because of emphasis the hot uptake, MIP images could depict the cancer location better than the conventional planar images. There were no cases, which could be diagnosed by planar image in spite of t~ilure in MIP images. Minimum tumor size clearly recognized on MIP images was approximately I cm, however, that was dit'ficult to diagnose on the conventional planar images. One case had pulmonary metastases and could pe detected a lung nodule on only MIP images. Conclusions; MIP method is a promising technique tbr the easy preliminary assessment of tumor deteclion of differentiated thyroid carcinoma.

PS_540

PS_542

STRATEGY OF INITIAL EVALUATION AND ONE YEAR FOLLOW-UP OF DIFFERENTIATED THYROID CARCINOMA

DOUBLE-PHASE PARATHYROID 99MTC-MIBI UPTAKE CORRELATES WITH SERUM IPTH LEVELS IN URAEMIC PATIENTS

A. Blaimont (1), J. Benoliel (1), J. Damourt (1), X. Fontana (1), E Ettore (2), F. Demard (3), F. Bussiere (1). (1) Department of Nuclear Medicine; (2) Department of Anatomopathology; (3) Department of Head and Neck Surgery, Centre A. Lacassagne, Nice, France.

D. Fuster (1), J. Ybarra (2), M. Ortega (1), F. Martin (1), M.J. MartinezOsaba (3), J.V. Torregrosa (2), F.J. Setoain (1), S. Fuertes (1), F. Pons (1). (1) Department of Nuclear Medicine; (2) Renal Transplant Unitin; (3) Hormonal Department, Hospital Clinic, Barcelona, Spain. Aim: WmTc-MIBI identifiesthe presenceof hyperfunctioningautonomousglandsin patients with SecondaryHyperparathyroidism(SHP). The objective of this study was to assess whetherchangingscramcalcium, phosphorus,iPTH and vitamin D concentrationscorrelate

The follow-up of differentiated thyroid carcinoma (DTC) is based upon the measurement of serum thyroglobulin levels (Tg) and 1131 Whole Body Scan (WBS). There is no definitive agreement on the follow-up protocol. Recent publications have proposed to use Tg alone. Aim.~ The aim of this study is double: l/to analyse the performances of Tg and WBS in detection of metastases immediately after radical thyroidaetomy to determine the immediate strategy (follow-up alone, another surgery, second therapeutic dose of I 131 ). 2/to compare the performancas of the measurement of Tg alone to the protocol including WBS + Tg aRar one year follow-up. Methods: 112 patients (80 famales, 32 males) were studied retrospectively between March 96 and December 98 (98 papillary, 13 follicular and 1 mixed papillary-medullary cancer). The protocol consisted (attar thyroid hormone withdrawal): 1/4 to 8 weeks aRer surgery: measurement ofTg (Tgl), WBS 5 days after administration of the therapautic 1131 dose (3,7 GBq) (WBSI).2/8 to 12 months after ablative I131 therapy: clinical examination, Tg measurement (Tg2), WBS 72 hours after 185 MBq 113I (WBS2), neck ultrasound (US) and chest X rays. The results of the two year follow-up (clinical examination, US and Tg measurement with WBS and/or another diagnosis procedures if necessary) served as reference. Results: On the first evaluation, 99 thyroid remnants and 13 cases of metastases were discovered. After one year, 75 patients had a complete remission, 6 benign local remnants, 12 malignant local remnants, 11 lymph node metastases and 8 distant metastases. ROC analysis showed that optimal Tgl threshold was 15 ng/mL The sensitivity and specificity for lymph nodes metastases detection were 43% and 81% for T g l , 86% and 99 % for WBSI and canceroing pulmonary metastases 100% and 82% for Tg I and 100 and 98,9% for WBS 1. On the second evaluation one year later, the sensitivity and specificity were 51% and 95% respectively for Tg2 alone (Tg2 threshold=2 ng/ml) and 89% and 93% for Tg2 + WBS2. Conclusions: We confirm the role of WBS and Tg measurement during the first year after surgery for the detection of metastases and patient managemctu .We demonstrated the usefulness of WBS after one year of follow up and the advantage to combine Tg and WBS.

1214

with MIBI<
• OTHER CLINICAL SCIENCE. ENDORINOLOGY 2

PS_543

PS_545

COMPARISON OF TC99M-MIBI AND TL2.01 / TC99M SUBSTRACTION SClNTIGRAPHY IN PATIENTS WITH HYPERPARATHYROIDISM

RESULTS OF A THERAPEUTICAL TRIAL OF THYROID EYE DISEASE USING THE LONG-ACTING SOMATOSTATIN ANALOG SANDOSTATIN LAR IN PATIENTS REFRACTORY TO PREVIOUS THERAPIES

H. Uslu (1), M. Ylldmrn (1), E. Varo~lu (1), R. Bayrakdar (1), F. Akqay (2), N. Un~ivar (3), M. Demirci (1). (1) Atat0rk University Medical Faculty, Dept. Of Nuclear Medicine; (2) AtatQrk University Medical Faculty, Depts. of Biochmistry; (3) AtatiJrk University Medical Faculty, Depts. of Endocrinology Erzurum, Turkey. TL201 / Tc99m pertechnetate substraction seintigraphy is recognized as a useful procedure in the preoperative localization of parathyroid adenomas. Tc99m -MIBI has recently been introduced for parathyroid imaging. The aim of this study was to compare diagnostic accuracy of parathyroid scan performed with Tc99m-MIBI and TL2Ol / Tc99m pertechnetatu substraction in patients with hyperparathiroidism Methods: Twenty-one patients (17 F, 4 M, mean age: 50 yrs) with a clinical and laboratory diagnosis of hyperparathyroidism were included in the study. TL201 / Tc 9qm pertechnetate substraetion and early-delayed cervico-thoracic images of Tc99m -MIBI scans were performed in all patients. The results of parathyroid imagings obtained with Tc99m -MIBI were compared with those obtained with TL201 / Tc 9qm pertechnetate substractiun scintigraphy, ulttasonography and histopathological findings after surgical exploration of the neck Results: Positive scans in the seven and negative scans in the twelve patients were showed in both imaging methods. In one case, Tc99m -MIBI scan was negative but TL201 / Tc99m pertechnetate substraction scan was positive. In another case, while Tc99m -MIBI scan was positive TL201 / Tc99m pertechnetate substraction scan was negative. Surgical exploration of the neck was performed in patients In=9) with positive Tc99m -MIBI and TL201 / Tc 99m pertechnetate substraction scans, Parathyroid adenoma in 7 and hyperplasia in 2 patients were detected. Ultrasunography was also negative in 12 patients whose both scans were negative. There was one false negative in TcgOm -MIBI scan and one false negative in TL20i / Tc 99m pertechnetate substraction scan.. The sensitivity rate of the both scans was 88 %, the specficity rate of the both scans was 100 %. Conclusions: Both Tc99m -MIBI and TL201 / Tc 99m pertachnetate suhstraction scans had the same sensitivity rate for the detection of pathological parathyroid tissue. Scintigraphy is simple, safe and first step imaging technique tbr the detection of hyperfunctiuning parathyroid glands.

R. Moncayo (1), C. Waffah (1), I. Baldissera (2), K. Petrova-Schumann (3), A. Sztankay (3), E. Donnernilier (1), H. Eder (1), C. Bacher Stier (1), E. Donnerniller (1), G. Riccabona (1). (1) Dept. of Nuclear Medicine; (2) Dept. of Ophthamology; (3) Dept. of Radiation Therapy, University of Innsbruck, Austria. Aim: To evaluate the efficacy of a long acting somatostatin analog (Sandostatin LAR) in the therapy of thyroid eye disease in patients who had not responded adequately to previous treatments. Octreotide scanning is done routinely at our Institution in order to evaluate the degree of activity in thyroid eye disease. The uptake of Octreotida in the retrobulbar space is taken as a sign of immune activation which depends on the expression of specific somatostatin receptors. This receptor availability provide an ideal setting for the use of long acting analogues (Sandostatin LAR) as a therapeutic option. Methods: Eight patients presenting with therapy resistant thyroid eye disease were included in this series. All of them presented tracer uptake of OctreoScan in the retrobolbar space. The therapeutic scheme contemplated a monthly dose of 30 mg i.m. over a period o f 6 months. In 2 cases Sandostatin LAR was given parallel to external radiation therapy (single dose of 1 Gy/fraction, total dose 20 Gy, 8MV). Results: The administration of Sandostatin was well tolerated in 7/8 patients. Clinical improvement of inflammatory eye signs was alredy seen after 3 days. Pressure sensation and eye pain showed an improvement during the first month of treatment, After 6 months of treatment a constant improvement remained in 6/7 patients. Hyperthyroidism and eye signs relapsed in one male patient (persistent smoker). In one female patient presenting GI side eft;eels [br more than 4 weeks, eye disease also relapsed. She was taken off the drug. The 2 patients receiving the combined treatment (Sandostatin and radiation) showed a clear improvement by the time the radiation cycle was finished. In 2 cases gallstones developed 2-3 months al~er therapy was finished. Conclusions:Our observations show the positive effect of Sandostatin in the treatment of thyroid eye disease which has been resistant to previous therapies. GI side effects are usually mild. The efficacy of Sandostatin LAR in newly diagnosed cases of thyroid eye disease remains to be evaluated.

tO

PS_544

PS_546

USEFULLNESS OF ABLATION DOSE OF 131-1 IN PATIENTS WITH DIFFERENTIATED THYROID CANCER WITH HIGH 131-1 UPTAKE DUE TO SUBTOTAL THYROIDECTOMY

THE DEPENDANCE OF THYROID HORMONE LEVELS ON GLOMERULAR FILTRATION RATE (GFR} IN PATIENTS WITH ACUTE RENAL FAILURE (ARF)

V. Prassopoulos, J. Elias, N. Sifakis, M. Alevizaki, S. Gerali. Nuckear Medicine IASO Hospital, Athens, Greece.

S. Ilic, M. Vlajkovic, M. Rajic, D. Mitic, M. Bogicevic. Department of Nuclear medicine, Clinical Center, Nis, Yugoslavia.

AIM : Patients with differentiated thyroid cancer undergo total thyroidectomy. Many of them. though, have a high postoperative 13 l-I uptake due to partial thyreldcctomy. Aim of this study is to present the results concerning the mode of administration of high doses to 131-1 for tota} thyroid ablation MATERIALS - METHODS: In the past l0 years 67 patients who underwent thyroidecbomy due to differentiated thyroid cancer (52 females -15 males) (age : 16-70 years) presented a high postoperative 13 l-[ uptake at 48 hours post-administration (range : 13%-32%). All of them had a negative brain CT scan and 6/67 had a positive whole body scan (adm dose : 4 mCi 13 l-l) for metastastic disease (3/6 : lung, 3/6 : bone). The ablative dose of 131 -[ was 50+_20 mCi, with no adverse reactions. RESULTS : 5 lpatients were re-evaluatad 6 months after the initial dose of 131-1 was administrated 17pts (33,3%) had 13 I-I uptake < 2%. 1/I 7 received a second ablative dose. 34 pts (68,6%) received a second dose of 131-1. After a period of 6ran. 33/34 had a 131-1 uptake < 2%. 1/6 pts with metastatic disease had a 131-1 uptake < 2% aficr the first administration of the ablative dose and 4/5 after the second one. CONCLUSION: In most cases in postoperative I31-I uptake is -> 10%, total ablation is reached after the administration of 2 or more relatively low doses of 131-1. In cases with metastatic disease the administration of high doses of 131-I (100-150 mCi) is mandatory.

Thyroid hormone disturbances are well known to occur in various nonthyroidal diseases. This study was aimed to establish the relationship between thyroid hormones levels and GFR in ARF patients. M A T E R I A L AND M E T H O D S : RIA of thyroid hormones serum levels were performed in 32 oligounuric patients within 7 days after ARF onset. The patients were divided into two groups according to the values of glomeru]ar filtration rate. The first group included 17 patients with 99mTc-DTPA clearance values over 25 ml/min (35~8), while the second group consisted of 15 patients with the clearance mean value of 16±7 rnl/min. The serum creatinine value of the first group was 326+ 68 I~moVI and that of the second group 676± 162 I~rno[/I. RESULTS:The comparison of patienLs hormones levels with those of 15 healthy subjects showed a significant decrease of total and free thyroid hormones levels in the first group IT4 90~t7nmol/I, T3 1.3±0.12 nmo[fl, FT4 15±2.5 pmo[/I, FT3 4.1±0.9 pmol/1), and a more marked decrease in the second group IT4 50~9 nmoV1, T3 0,5=1=0,10 nmoV1, FT4 5.0~=1.1 prno}/I, FT3 !.2±0.3 pmol/1). The fall of hormones levels was severely expressed for T3 compared to T4 as well as free hormones related to total hormones. Reverse T3 was found increased in both the studied groups of patients (41±10 and 35±9 pmol/1) white TSH values were within the normal range. Regression analysis indicated a significant correlation between thyroid hormones and GFR in both groups. C O N C L U S I O N : The presented data suggest that the level of thyroid hormone disturbances is in proportion with the impairment of renal function. These alterations could be induced by a body dafence reaction to stress, with a higher production of the metabolically less active hormone. The effect of uremic toxins upon pituitary-thyroid axis with the consequent suppression of hormones synthesis should be also considered,

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0

• ENDORINOLOGY 2 / INFECTION AND INFLAMMATION 2 PS_547

PS_549

PITUlTARY-TESTICULAR AXIS IN MALE PATIENTS AT M A I N T E N A N C E HEMODIALYSlS. THE EFFECT OF RESIDUAL RENAL FUNCTION

COMPARISON OF CEREBRAL B L O O D FLOW A N D MENTAL STATES BEFORE A N D AFTER T H E R A P Y IN PRIMARY ALDOSTERONISM

S. Ilic, M. Bogicevic, M. Rajic, M. Vlajkovic, D. Mitic, V. Stefanovic. Department of Nuclear medicine, Clinical Center, Nis, Yugoslavia.

S. Tsuchirnochi, M. Nakajo, M. Nakajo jr, H. Tanabe, T. Urnanodan, Y. Nakabeppu. Department of Radiology, Kagoshima Unversity Hospital, Kagoshima, Japan.

The aim of this study was to show the effect of the residual renal function upon the pituitarytesticular axis in patients on maintenance hemodialysis. MATERIAL AND METHODS: Follicle stimulating hormone (FSH), Iuteinizing hormone (LH), prolactin (Pr) and testosterone were determined by RIA in serum of 30 healthy persons and 39 male patients on mainterlance hemodialysis. According to the residual renal function, estimated by 24 hr urine output, all hemodialysis patients were classified into three groups: Ist -urine output under 500 ml, 2~ - urine output 501-1000 ml and 3 ~d -urine output above 1000 ml. RESULTS: In patients on maintenance bemodialysis the serum concentration of LH (19.8±2.0 mlU) and Pr (843±127 mlU/l) were found to be significantly higher (p<0.001), while testosterone concentration (5.0-20.3 ng/ml) was significantly lower (p<0.001). The comparison among the groups with various residual renal functions shows a significantly higher(p<0.001) Pr concentration in patients with small urine output (I st- 1126±192 mlU/l, 2ra-893±233 mlU/I, 3'~-426~44 mlU/I). The testosterone concentration was significantly lower (p<0.05) in the first group (3.9-3:0.5ng/ml) than in the second group (5.58±0.5 ng/ml). CONCLUSION: The obtained results show an the increase of LH and Pr and the decrease of testosterone level in male patients on maintenance harnodialysis. A dependence of the serum levels of Pr and testosterone from the residual renal function was also established.

Objectives: We often met with anxiety or depression in patients with primary aldostaronism. It was previously reported that depression returned to normal after removal of an adenoma in a patient with primary aldostaronism, or that abnormal regional cerebral blood flow (rCBF) was shown in major depressives. Therefore, we evaluated the correlation of rCBF with plasma aldos~.erone levels and mental states in patients with primary aldosteronism. Methods: This study was consisted of 6 patients with unilateral aldosteronoma. The measurements of plasma aldosterone levels, psychological tests (STAI for anxiety, SDS for depression and Y-G test for both depression and nervousness) and Tc-99m ECD SPECT were performed before and a month after therapy (2 patients received tumor resection and 4 patients received transcatheter adrenal arterial embolization). Comparison of the rCBF between pre- and post-therapeutic conditions was made using statistical parametric mapping (SPM '96). Results: There was a significant difference in the levels of plasma aldostarone before and after therapy (288 + 81 vs 87 + 69 pg/mL p < 0.05). However, there were no areas which showed significant differences in rCBF before and after therapy. Before therapy, definite abnormal scores were obtained in 1 patient in SDS, in 2 patients for characteristic anxiety scores and in 5 patients for conditional anxiety scores in STAI and in 3 patients for depression scores and in 2 patients for nervousness scores in the Y-G test. After therpay, the scores improved in 3, 5, I, 2 and 3 patients, respectively and worsened in l, 0, 3, t and I patients, respectively. Conclusion: The plasma aldostarone levels do not affect rCBF and phychiatric changes may not be related to rCBF changes in primary aldosteronism.

PS_548

OTHER CLINICAL SCIENCE. INFECTION AND INFLAMMATION 2

CORRELATION BETWEEN RETINOPATHY A N D ISCHEMIC H E A R T DISEASE IN NON-INSULIN DEPENDENT DIABETES M E L L I T U S PATIENTS A. Fawzy (1), M. Abo-Zeid (2), M. Thabet (2), N. AI-Sayed (2). (1) Nuclear Medicine ; (2) Internal Medicine Departments, Faculty of Medicine, Cairo University, Egypt.

Background: Retinopathy and coronary artery disease (CAD) may have similar pathophysiological background related to widespread vascular damage. The risk of CAD is higher in

patients with non-insulin dependentdiabetesmellitus (NIDDM) than in non-diabetic subjects. Aim of the study: To correlate betweendifferent degreesof diabetic rctinopothy changesand CAD eventsin Non-insulin diabetesmellitus. Patients and Methods: 40 NIDDM patients were divided into 2 groups with retinopathy (n=30) and without (n=10). They were all anrmotensive,non.smokers, no history of anginal pains and normal lipid profiles. They were subjectedto fidl laboratory evaluation, resting and exercise ECG, echo heart and Tc-99mTetrafosminemyocardial perfusion SPECTscintigrams. Results: Echo heart was negative in all group B patients and was only positive in only 2 patients in groupA. Also, there was evidenceof ischemia in the myocardial perfusion scintigraphy in 80°/0of patients of group A, out of these 43.3% were reversible and 63.7%were irreversthle. Among group B patients, 40% were positive and reversibleand 60% were normal. None of group B had irreversible ischemia(p <0.05). Conclusion: Diabetic retinopathy was associatedwith higher incidencesof CAD in NIDDM patients and should be considered as a landmark for CAD. Also, myocardial perfusion is more sensitivethan ECG and Echo for identifying silent CAD in diabetic patients.

PS_550 FIVE YEARS EXPERIENCE WITH CIPROFLOXACIN-TC99M (INFECTON) IN T H E BONE INFECTED PATIENT V.E. Soroa (1), R.C. Cabrejas (1), C. Alonso (2), K.K. Solanki (3), K.E. Britton (3). (1) Centro de Medicina Nuclear. Htal.Clinicas, UBA/CNEA, Bs.As, Argentina; (2) Servicio de Traurnatologia- Division Ortopedia Htal.Clinicas, UBA, Bs.As, Argentina; (3) Department of Nuclear Medicine -Division Radiopharmacy. St.Bartholornew's, London, UK. The purpose of our work was the evaluation of the outcome of 99mTc-ciprofioxacin

(lnfecton) scans in suspected orthopedic infected patients, as welt as the impact of follow-up scans in their clinical management. Methods: Out of 258 patients (125 males, 160 females) 93 follow-up lnfecton scans were performed (36%). Forty one percent ware on antibiotics (including ciprofloxacine). Frequent pathologies were ostcomyelitis, hip, knee & lumbar prosthesis (86%) while the othar 14% were abscess, septic arthritis & cellulitis. Flow, 1, 4, 24h planar or Spect images were acquired with i.v. 444-518MBq. lnfecton. Complimentary intra-comparison laboratory, anatomical and one other nuclear scans ware provided (MDP, 99roTe-Leucocytes, 99mTclmmunoglobulins, Gallium-67).

Results: Neither adverse reactions, nor any relation of the scan outcome with the use of antibiotics were found. Positive uptake, read in the 24h images, was considered as persistent infection. Eleven percent of follow-up patients had 3-4/nfecton scan before negative results were achieved.The re-scanning was obtained in 3-4 monthstime from the former.Absenceor decreaseduptake at 24h images was obtained in 30%. Infecton Negative scans were taken as cure, while positivity implied persistent infection and antibiotic treatment continuity. Late intestinal activity found in 60% of studied patients, was usually accompaniedby pesitivity in stools, with no relation with clinical symptomsor'local infection. Conclusions: In our studied series the highest specificity (80%) was achieved by the lnfecton scan with a sensitivity of 93%. lnfecton scan needs no blood manipulation and is recommended as a safe specific bacterial detector technique for osteoarticular infection and its follow-up.

121E

• OTHER CLINICAL SCIENCE. INFECTION AND INFLAMMATION 2 PS_551

PS_553

THE STUDY OF BONE INFECTIONS WITH 99MTC-ClPROFLOXAClN

THE CLINICAL VALUE OF GALLIUM-67 SCINTIGRAPHY IN WEGENER'S GRANULOMATOSIS

N. Prandini (1), L. Feggi (1), S. Panareo (1), A. Ciprian (1), L. Massari (2), A. Galla (2), M.C. Danzi (3), M. Solbiati (3), K. Britton (4). (1) Department of Nuclear Medicine, Azienda Ospedaliera Universitaria, Ferrara, Italy; (2) Department of Orthopedics, Azienda Ospedaliera Universitaria, Ferrara, Italy; (3) Department of Infective Disease, Ospedale Civile Verona, Italy; (4) Department of Nuclear Medicine, S.Bartholomew's Hospital, London, United Kingdom The use of radiolabeI/ed white b~ood cells has been studied and evaluated in several pathologies and is still the reference method in the study of bone infections. Moreover in central bone and in chronic infection WBC scintigraphy often results in unspecific ,,cold areas". We report an experience with Technetium99m-Ciprofloxacin an antibiotic that represent a specific tracer of bacterial active infection. We performed 58 studies with 99mTceiprofloxacin for a suspicion of infections of the vertebral column (24), hip prosteses (13), leg fractures (16), knee (2), foot (1), shoulder (2), and 1 polithrauma in 46 patients. The scintigraphies were obtained 1 and 4 hours after injection: further imaging at 8 or 24 hours were used in doubtful cases. All vertebral infections underwent SPECT. In 23 patients, and in all peripheric infections, the results were compared with a 99mTcHMPAO WBC study. All patients but 9 resulted positive on 99mTc-lnfecton study: the uptake of antibiotic was always higher and wider than WBC's. A ratio of target/normal uptake lower than 1.5, or an activity that significantly decreases in late imagings were cmasidered a negativity criterion. The results of Infeetun were 45 TP, 8 "IN, 4 FP and I FN with an accuracy of 91%, a sensitivity of 97,8% and a specificity of 67,7%. We found a concordance with WBC in 23 positive and 4 negative patients. In 3 cases the WBC study was doubtfial and resulted FP in 2 and TN in 1 on lnfecton. In 4 patients with spoodilodiskytis, I with sterno-clavicular septic arthritis, and in 2 with hip prosteses WBC study showed a cold area not signicant for the diagnosis of infection. Only in a patients with suspect of leg osteomyelitis the study with infecton resulted false positive and only 1 year after bone resection become negatve. In spondylodiskytis the lnfecton study was always conclusive in contrast to the low sensitivity of WBC, and the useless of MRI and CT to assess persistence of infection in alterated vertebral bone: 2 of these positive studies were resulted positive for tubercular diskitis. in conclusion, the accuracy of In fecton is comparable to WBC in peripbcric osteomyelitis but it is more effective than WBC in central bone infections such as spondilodiskytis.

R.H.J.A. Slart (1), P.L. Jager (1), L. Poot (1), D.A. Piers (1), JW. Cohen Tervaert (2), C.A. Stegeman (2). (1) Department of Nuclear Medicine; (2) Department of Internal Medicine, Division of Nephrology, University Hospital Groningen, Groningen, The Netherlands. Introduction: Diagnosis of active pulmonary and pars-nasal involvement in patients with Wegener's granulomatosis can be difficult, especially in case of unclear clinical presentation. Usual diagnostic tools like ANCA-levels, inflammatory blood parameters and biopsy are not always conclusive. Gallium scintigraphy is sometimes used in these difficult cases, but its diagnostic contribution is unclear. Aim: to evaluate the added diagnostic value of gaUium scintigraphy in patients with suspected granulomatuus or vasculitic inflammation in pars-nasal and chest region. Methods: We retrospectively evaluated 40 chest- and 20 head planar gallium scans of 28 patients who were evaluated for possible Wegener's disease activity. Gallium scans were reviewed qualitatively and were grouped in normal or increased uptake for the chest and paranasal region. True active pulmonary or para-nasal involvement was concluded if histologically proved or in case of clinical diagnosis with appropriate response to treatment. Active infection had to be excluded. Results: Four (14%) patients had active pulmonary Wegener disease, 3 (11%) patients had active pars-nasal activity and I (4%) patient had both. In all these patients, chest and parsnasal scans showed increased gallium uptake (sensitivity 100%). In the group of patients (n=20) without active Wegener's disease, gallium scans were negative for pulmonary activity in 23 out of 35 scans (specificity 66%), and negative for pars-nasal activity in 12 out of 16 scans (specificity 75%). False positive findings were caused by bacterial or viral infections. Following treatment, a follow up scan showed normalisation of pulmonary or para-nasal gallium uptake in all patients (n=3) with a true positive chest or para-nasal scan at diagnosis. Conclusion: Gallium scintigraphy of the chest and nasal region has a high sensitivity for the detection of disease activity in Wegener's granulomatosis. However, due to positive scans with bacterial or viral infections, specificity was considerably lower. Since detection of disease activity can be difficult, gallium scans may be clinically helpful as a negative scan virtually excludes active Wegener disease

¢,O m

PS_552

PS_554

IMAGING OF FUNGAL INFECTIONS WITH 99MTC-LABELLED FLUCONAZOLE AND ANTIMICROBIAL PEPTIDES

COMPARISON OF IN VITRO ANTIMICROBIAL ACTIVITIES OF 99MTC-INFECTON AND ClPROFLOXAClN

c

A. Lupetti (1), M.M. Welling (2), S. Mongera (2), A. Paulusma-Annema (1), P.H. Nibbering (1), E.K.J. Pauwels (2). (1) Department of Infectious Diseases; (2) Department of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.

H.C. Song (1), S.M. Kim (1), H.S. Born (1), J.H. Shin (2), H.J. Jeong (1), J.Y. Kim (1). (1) Department of Nuclear Medicine; (2) Department of Clinical Pathology, Chonnarn National University Hospital, Kwangju, South Korea.

D.

Fungal infections are difficult to diagnose in immunocompromised patients and a tracer for such infections could be very instrumental in initiating the the~lpy in such patients with febrile episodes. In the search for such a tracer, accumulation of ~mTc-labeled floconazole, ~'~Tcdabeled synthetic peptides derived from human lactuferrin (hLF 1-11) and ubiquicidin (UBI 18-35, UBI 22-35, UBI 29-41) in Candida albicans infections in immunocompetent mice and Aspergillusfumigatus infections in leukocytopenic mice was compared with that in bacterial infections and sterile inflammatory processes. The results showed that 99'nTc-labeted fluconazol¢ detects C. albicans infections, but not infections with A. fumigatus, bacterial infections, or inflammatory processes. [magi~rr of C. albicans infections in mice was already achieved within the first hr after injection of roTe-labeled floconazole and maximal accumulation of the tracer, i. e. target-to-non-target (T/NT) ratios between 3 and 4, was reached at 2 hrs after injection of this tracer. Furthermore, a good correlation between T/NT ratios for this tracer and the number of viable C. albicans was found, indicating that radiolabeled fluconazole may be useful in monitoring the efficacy of antifungal therapy in C. atbicans infections, Furthermore, radiochemical analysis of To-labeled fiuconazote indicated that this tracer remained stable for 24 hrs at 37°C. Another finding of this study was that ~'nTc-labeled peptides were able to distinguish fungal infections from sterile inflammations but not from bacterial infections. Together our observations suggest that the combination of radiolabeted UB1 peptides and fiuconazole can be a useful strategy since it allows discrimination between infections and inflammations while discriminating infections with C. albicans from infections with other micro-organisms.

Objective: We hypothesized that antimicrobial activity of 99roTe-labeled amine-ciprofloxacin (Infecton) could be an indirect evidence of its specificity to bacterial infection. To evaluate the hypothesis we compared in vitro antimicrobial activities of lnfecton and ciprofloxacin. Methods: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Infecton and ciprofloxacin against three standard strains of bacteria, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were measured. Results: MtCs of [nfecton and ciprofioxacin were 1.122-0.20 (0.8-1.6) lag/ml and 0.36i'0.04 (0.2-0.4) lag/ml for S. aureus, 0.03---'-'-~.005 (0.025-0.05) gg/ml and 0.011+0.001 (0.006--0.012) /.rg/ml for Ecoli, and 0.96¢0.16 (0.8-1.6) p.g/ml and 0.56-L'0.098 (0.4--0.8) ~g/ml for P aeruginosa, respectively. MBCs of Infecton and ciprofloxacin were 2.56i-0.39 (I.6~3.2) Ixg ml and 0.88:t0.2 (0.4~1.6) p.g/ml for S. aureus, 0.04¢0.06 (0.025-0.05) p.g/ml and 0.02:L-0.0t (0.025-0.05) p-g/ml for E.coli, and 2.24-20.39 (1.6o-3.2) p~g/ml and IA4+0.16 (0.8-1.6) lag/mi for P aeruginosa, respectively. Conclusion: Although both MICs and MBCs of lnfecton were higher than those of ciprofloxacin, all three standard bacterial strains were sensitive to lnfecton. It is an indirect evidence of specificity of 9'~Tc lnfectoo to bacterial infection.

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• OTHER CLINICAL SCIENCE. INFECTION AND INFLAMMATION 2 PS_555

PS_557

PLATELET GEL, AS A NEW METHOD TO IMPROVE WOUNDS' HEAMNG AND TISSUE RIGENERATION IN PATIENTS WITH STERNAL WOUNDS INFECTIONS {SWIS) AND BOMTC-HMPAO LABELLED GRANULOCYTES SCINTIGRAPHY AS A DIAGNOSTIC PROCEDURE

POTENTIAL USEFULNESS OF TC-99M- H U M A N POLYCLONAL IMMUNOGLOBULIN G (HIG) SCINTIGRAPHY IN EVALUATION OF SJOGREN'S SYNDROME

M.C. Sacchi (1), R. Zoccola (3), L. Bertolazzi (3), E. Cornaglia (1), M. Serra (2), D. Medici (2), A. Levis (1), L. Ressia (2), I? Scotti (2), G. Sinaccio (2). (1) Department of Hematology and Transfusional Medicine; (2) U.O.A. Cardiac Surgery; (3) Department of Nuclear Medicine. A i m Clinical trials seem to reveal that platelet gel, a source of multiple autologous GFs, can be considered a useful and available tool to increase either the quality or the final quantity of new-conformed bone and to stimulate the healing of chronic wounds resulting in accelerated granulation tissue furmation and epitheiization. Surgical wound infections are a serious problem in openheart surgery despite continuing eft'orts to improve post-operative conditions. Early and accurate detection of SWIs is important because this complication performed by sternotomy carries high morbidity and mortality rates. The aim of this study is to assess the c imca use of scmtlgraphy with Tc-HMPAO- abelled granulocytes m he diagnosis of postoperative SWIs, before and after this innovative treatment. Methods During last year, 454 patients underwent a cardiac surgery procedures, 333 oftbem coronary bypass. II patients developed SWIs post-operative. Bacteriological analyses of wound secretions were performed in all patients with SWIs. Platelet concentrated (PC), prepared starting from a low quantity of whole blood (60 ml), is activated by a Batroxabine-calcium gluconate blend to obtain a platelet gel. According to the clinical signs and microbiological findings we applied this gel to 5 patients (all were given informed consent before inclusion in the study) for a period of I month, twice a week, on lesion . We exposed all patients with suspected SWl to scimigraphy with HMPAO-Tc99m labeled granulocytic frac. tions: a) before the treatment with the aim to distinguish between superficial and deep SWI; b) after the treatment ( I month from the outcome] to evaluated the healing or the persistence of infection. The method used for the separation and labelling of granulocytes with 99mTcHMPAO (Amersham) was as described by Ferrante et al. with some modifications. We obtained scintigraphy with acquisitions at 3 h and 20 h after injection in 3 projections (anterior, lat.right and left) planars and SPET. Results The diagnosis of SWIs was obtained in all patients enrolled in this sperimental study before the treatment with platelet gel. The scintigraphic analysis, performed I month alter the outcome, confirmed the recovery of all the patients treated. Conclusion These preliminary data seem to demonstrate the effective of platelet gel to improve and accelerated the heahng ol SWIs, completely correlated by Tc-HMPAOlabelled granulocytes scintigraphy, in according to the extreme sensitivity of this nuclear methods. Ethical aspects This study has been projected following the indications of Helsinki's Declaration, Good Clinical Practice's laws (GCPI and D.M. 18.3.1998.

G. Karanikas (1), K. Bobacz (2), A. Becherer (1), K. Wiesner (1), R. Dudczak (1), K. Machold (2), K. Kletter (1). (1) Department of Nuclear Medicine; (2) Department of Rheumatology, University of Vienna, Vienna, Austria. Sjrgren s syndrome is an autoimmune disease that affects the salivary and lacrimal glands. It is characterized by lymphocytic infiltration and destruction of gland tissue. In the diagnosis and evaluation of Sjrgren's syndrome, an objective examination is required, since patient complaints do not necessarily reflect the severity of salivary gland disease. Radiolabeled human non-specific polyelonal immunoglobulin G (HIG), is used for the diagnosis of inflammation/infection, In this study we evaluate the potential usefulness of Tc-99m- HIG scintigraphy in patients with Sjrgren's syndrome. Methods: Ten consecutive patients with verified secondary Sjrgren's syndrome according to the Copenhagen criteria were included in this prospective study. The control group consisted of seven patients with Lupus erythematodes; none had clinical signs of Sjrgren's syndrome. Planar and SPECT images of the head were performed six hours after i.v. administration of Tc-99m HIG (500-550MBq). Results: Nine out of ten patients with secondary SjSgren's syndrome showed a positive result (sensitivity 90%) in planar as well as in SPECT images, while one of tbem was false negative according to the Copenhagen criteria. Tracer accumulation in patients with positive scintigraphy demonstrated a great variability. In five patients tracer accumulation was enhanced in the oral region, in four increased uptake was seen in the salivary gland and in one additionally in the lacrimal sinus. All patients of the control group showed a correct negative result. Conclusions: Our data suggest that Tc-99m HIG scintigraphy is a modality with high sensitivity for the diagnosis of Sjrgren's syndrome and can provide objective information on the severity oftbe disease.

PS_556

PS_558

BIODISTRIBUTION AND DOSIMETRY OF F18 FDG LABELED LEUKOCY'FES (F-18-FDG WBC) IN A NORMAL HUMAN SUBJECT

ROLE OF COMBINED 3-PHASE BONE SCAN & TC-99M LABELLED ANTI-GRANULOCYTE ANTOBODY FAB' IMAGING IN DIFFERENTIAL DIAGNOSIS OF INFECTED AND NON-INFECTED LOOSENED PROSTHESIS

L. Forstrom, B. Mullan, J. Hung, V. Lowe, L. Thorson, W. Dunn. Nuclear Medicine, Mayo Clinic, Rochester, Minnesota, USA. Aim: This study was performed for preliminary assessment of FIg FDG WBC dosimetry in man. Methods: Using methods previously reported from our laboratory, a mixed cell suspension of autologous leukocytcs in heparin-salioe was labeled with FIg FDG by incubation at 37 ° for 20 minutes. After washing and re-suspeasion, 315 MBq F] 8 FDG WBC was administered by slow IV injection in a normal volunteer subject. A GE Varicam with 511 keV collimation was used for whole body imaging a t , 1, 2, 4 and 6 hours. Blood samples were obtained at corresponding times, as well as hourly urine samples. Results: FI8 FDG WBC uptake was seen predominantly within the RE system, consistent with physiologic leukocyte distribution. Urinary excretion (6.7 % at 6 hrs) and brain uptake (2.1% at 6 hrs) were consistent with minor elution of F l g FDG, likely due to intracellular depbosphorylatinn, Calculated organ dosimetry based on image analysis is as follows: 0.013 mGy/MBq to brain, 0.07 mGy/MBq to liver, 0.036 mGy/MBq to lungs, 0.405 mGy/MBq to spleen, 0.0708 mGy/MBq to red marrow, and 0.012 mGy/MBq to whole body. Conclusions: Preliminary estimates of organ dosimetry using 315 MBq F l 8 FDG WBC in a normal subject arc comparable with reported results for teukocytes labeled with 18.5 MBq In111 oxine. Further studies of F 1g-FDG WBC as a potential agent for PET imaging of inflammation/infection appear warranted,

1218

D. Rubello (1), G. Saladini (1), A. Pellicano (2), D. Casara (1). (1) Servizio di Medicina Nucleare 2, Azienda Ospedaliera di Padova, Padova, Italy; (2) Unittl Operativa di Ortopeclia e Traumatologia, ASL 16, Padova, Italy. Twenty-oneconsecutivepts with painful loosenedprosthesis(P) suspectedto be infectedon the basis on clinicaland laboratory findingsentered the study:t9 ofthem had hip P (4 bilateral) and 2 knee P, implanted 5 too.to 10 yr (median 3 yrs) before nuclear medicine evaluation. In allpts,Tc-99m-HDP 3-phase bone scan (BS) was followed by Tc-99m-labelled anti-granulocyte antibody Fab'-fragment (Tc-AGA) (LeucoScan', lmmunomedics) imaging obtained 4

hrs and 18-24 hrs post-injectinn. The peri-prosthetic tracer uptake intensity was graded by means of a 4-point scale: oormal=0, mild=l, moderate=2,intense uptske=3. Scintigraphies were blindly evaluated by two nuclear medicine physicians. Surgical findings were taken as gold standard in the 21 loosancd P: 9 P were diagnosed to be infected,and 12 non infected. Moreover. in pts with bilateral hip P, the 4 painless P were taken as controls. BS was positive in all 21 cases of loosened P. Despite we did not observe a BS pattern specific for the infected vs non-infected P. however, it is worth noting that the BS flow-phase was positive in all 9 cases with infected P while in only 3/10 cases with non infected P. Tc-AGA scan was positive in all 9 cases with infected P (BS +, Te-AGA +), whereas it was negative in 10/12 cases with non infected P (BS +, Tc-AGA -). False positive Tc-AGA results were recorded in 2 loosened non-infected P: in these pts the P was implanted 5 too. and 7 too. before, respectively, and in both cases a mild to moderate diffuse peri-prosthetic tracer uptake was recorded. On the other hand, both BS and Tc-AGA were correctly negative (BS -, Tc-AG -) in the 4 cases of asymptomatic hip P. On the basis of these preliminary data, we can conclude that: a) BS is a highly sensitive technique in differentiating loosened from asymptomatic P; b) BS is not able to differentiate infected from non-infected loosened P, even if a positive flow-phase has to lead the physician to suspect infection; c) Tc-AGA scan appears to be accurate enough to differentiate infected from non-infected loosened P, even if some false positive results can be observed when scintigraphic evaluation is performed in the first period following surgery.

• INFECTION AND INFLAMMATION 2 / MISCELLANEA 2 PS_559 DETECTION OF FOCAL CARDIOVASCULAR AND SOFT TISSUE INFECTIONS WITH 9 9 M - T C - L A B E L E D ANTI-GRANULOCYTE ANTIBODY FRAGMENTS U. Kampen, C. Jaekel, W. Brenner, M. Zuhayra, N. Czech, E. Henze. Clinic of Nuclear Medicine, Kiel University, Germany. Aim: Elevated inflammatory blood parameters without any distinctive focus or fever of unknown origin are still challenges in clinical diagnostics. These patients require a quick and easy-to-perform whole-body examination protocol for the detection of possible inflammatory loci which can not be achieved by conventional radiology. Application of an antibody fragment labeled with 99m-To and directed against surface antigens of human granulocytes (LeakoScan) is a promising method, although it is primarily approved for diagnosis of usteomyelitis. Therefore, the aim of our study was to look for the diagnostic impact of immenoscintigraphy with LeukoScan in patients with signs of inflammation but without any distinctive knowledge of the responsible focus. Methods: A total of 36 patients (I 7 female, 19 male, aged 17-81 years) were enrolled into this retrospective study. Clinicians demanded immunoscintigraphy with LeuknSean because of suspected infections in the cardiovascular system (n=8), soft tissue involvement (n=I6) or even without any idea of localization (n=12). Planar whole-body imaging was performed 3 hours after injection of 600MBq 99m-Tc-LeukoScan, completed by SPECT or delayed imaging al~er 24 hours whenever necessary. Scintigraphic data were compared to the final diagnoses, proven by histopathology or by carefully directed radioiogical diagnostics, e.g. CT. MRI or conventional tomography, guided by the LeukoScan images. In cases without any positive scintigraphic finding, clinical follow-up was taken for proof. Results: lmrnunoscintilgraphv showed the followins results: n Su~-pecro,f true + true false + 8 Cardiovascular kgcus 6 1 0 12 Origin unknown 3 8 1 16 Soft tissue focus 6 3 1

false 1 0 6

Se~. 0,86 1,0 O.5

StTec. 1.0 0.89 O,75

The over-all sensitivity and specificity was calculated as 0,68 and 0,86, respectively. A high number of false negative results in soft tissue infection, which accounts tbr the lower over-all sensitivity was possibly due to tour cases with an abscess, known to have a significantly reduced blood supply resulting in a lack of local tracer deposition. Two other patients had a proven nephritis in which LeukoScan is known to be ineffective because of tubular stacking of the antibody f~'agments. False positive results were caused by both misinterpretation of unspecific tracer deposition in the gut and local granulocyte accumulation after surgery. Conclusion: Immunoscintigraphy with LeukoScan showed encouraging results in patients with cardiovascular infection and lever of unknown origin. In case of soft tissue infection, its diagnostic impact is decreased by a high degree of false negative results.

OTHER CLINICAL SCIENCE. MISCELLANEA 2 PS_561 SOMATOSTATIN RECEPTOR SCINTIGRAPHY A N D BETA-2-MICROGLOBULIN IN THE DIAGNOSIS, STAGING A N D FOLLOW-UP OF MALIGNANT L Y M P H O M A S D. Vassileva (1), S. Sergieva (2). (1) National Centre of Haematology and Transfusiology; (2) National Centre of Oncology, Sofia, Bulgaria. Various turnouts contain high number of sematostatin receptors, which enable the use of somatostatin receptor scintigraphy (SRS) for visualisation of these tumours. The purpose of this study was to assess the value of SRS, serum beta-2-microglobulin and the correlation between them for diagnosis and staging and follow-up of patients with malignant lymphomas. Forty-five patients with malignant lymphomas were investigated (20 with non-Hodgkin's lympbomas and 25 with Hodgkin's Disease). Planar and SPECT images were performed 24 hours and 48 hours after i.v.injeetion of 110-185 MBq Ill-In labelled octreotide (Mallinckrodt, Petten) on the rotating gamma camera (Diacam, Siemens). SRS results were compared with the data of conventional methods (clinical examination, x-ray, CT, bone marrow biopsy). Beta-2-microglobulin levels were measured by radioimmunoassay using the lmmunotech international microtest. The SRS was true positive in 36 patients with malignant lymphomas. Ninety-two lesions were identified. Twenty-three of them were with extranodal Iocalisation. Seven previously unknown localisations were visualised in 5 patients, Additional CT and ultrasound examinations confirmed the presence of a turnout tissue. Clinical staging of all these patients were changed. Significant correlation was found in patients with true positive SRS and higher serum beta-2-microglobulin in patients with an advanced disease. In 2 patients false positive results on the SRS were found. True negative scans were obtained in 7 patients. These data indicate that malignant lympbomas express somatostatin receptors in sufficient quantity and density to allow a tumour visualisation with I I I-In labelled octreotide. In conciusion, SRS provides a sensitive non-lnvasive diagnostic modaiity to localize a turnout tissue of malignant lymphomas and the positive scintigrsphy shows a good correlation with the data of serum beta-2-microglobulin in different stages of the disease.

O k~

PS_560

PS_562

DIAGNOSTIC VALUE OF TC-99M-CIPROFLOXACIN (INFECTON) IN PATIENTS WITH PROSTHETIC IMPLANTS OF SUSPECTED INFECTION

DOES 111 IN-OXlNE PLATELET SEQUESTRATION PATTERN HAVE ANY IMPACT IN THE MANAGEMENT OF PATIENTS (PTS) WITH CHRONIC IDIOPHATIC TROMBOCY'FOPENIC PURPURA (ITP)?

K. Srnmezo~lu (1), M. Halaq (1), I. Akg~n (2), C. TLirkmen (1), C. Nisli (1), C. 0nsel (1), N. ErdoOan (1), B. Kanmaz (1), I. Uslu (1). (1) Department of Nuclear Medicine; (2) Department of Orthopedics, Cerrahpa~a Medical Faculty, Istanbul University, Istanbul, Turkey.

A. Sevilla, P. Colarinha, H. Camejo, T. Rezio, G. Ramos, M. Vieire. Instituto Portugurs de Oncologia F.G., Lisbon, Portugal.

Aim: In this prospective study we have evaluated the diagnostic value of Tc-99m-labelled ciprofloxacin (INFECTON), a new and bacteria specific infection localizing agent in the patients with prosthetic implant infections. Methods: 21 patients with 26 prosthetic implants (11 total hip prosthesis, 11 total knee prosthesis, 3 intramedullary femoral nails and 1 hip screw) were referred to our department for the investigation and/or confirmation of clinically suspected infection. All patients underwent both Tc-99m-HMPAO WBC and INFECTON scans. Biochemical, radiologieal, microbiological data and clinical follow-up (at least 3 months) contributed along with the scintigraphic techniques in deciding on the presence or absence of infection. Seintigraphic images from the areas of interest were performed at I and 4 hr postinjection of 370-400 MBq of Tc-99mINFECTON or 185-200 MBq of Tc-99m.HMPAO-WBC ia at least two projections. There were at least 2 days and at most 7 days between two scintigraphic studies. Results: 15 of 26 prosthetic implant sites of suspected infection were finally considered positive for ostenmyclitis. In the remaining 11 sites, there was no proven evidence of infection. INFECTON scans gave positive results for 14 of 15 sites of infected implants. WBC imaging was positive in 11 of 15 sites with osteomyelitis. There were 14 mJe-positive, 1 false-positive. 10 true-negative and 1 false-negative results with INFECTON. With Tc-99m HMPAO WBC, the figures were 11, 2, 9, and 4, respectively. Values for sensitivity, specificity and accuracy are 93 %, 9 1 % , 92 % with INFECTON scan, and 73 %, 82 %, 77 % with WBC scanning. Differences between the two agents were statistically significant (p < 0.05) Conclusion: We concluded that INFECTON is a better agent for detecting prosthetic implant infections comparing to Tc-99m HMAPO WBC scintigraphy. The lacking of bone marrow uptake of INFECTON makes it more powerful agent particularly in proximal extremities, mostly where prosthetic implants present

In chronic ITP when conicostaroid therapy failed and splenectomy is considered necessary just 80% of patients will afford cure of disease. The aim of this work is to assess the clinical impact of the platelet kinetic studies in the management of chronic ITP patients. Method: It has been reviewed the management and treatment result of a group of 43 chronic ITP patients with platelct lifespan longer than 4 days and submitted to a ptatelet kinetic study. Abnormal platalet sequestration site (spleen, liver, spleen & liver) has been correlated with the management (proposed spleneetomy vs. others therapeutic options). Therapy results have been checked (complete remission vs. trombocytoponic). Platclet sequestration site analysis was based on external probe spleen and liver counts. Each measure was acquired under identi-

cal conditions so that a day-to-dayprofi ]e could be recordad (at~er ]l) In decaycorrection). Sequestration was analysedaccording to the following activity ratio: (Spleen at last day of platalet lifespan/Spleanat 30thmineS) and (Liver at last day of platelat lifespan/Liver at 30th rain. eL). Abnormal high platelet sequestratiun was considered when the ratio value was >1,20. Four different sequestrationpattaroshavebeenfound: Splenic (S->I,2&LI,2&L>I,2) and Absent (S
Results: Splenectomy has been the therapeutic option for 24/31 pts with splenic sequestration and for 2/11 pts with hepatic and mixed. Up to now 19pts* have already been operated with complete remission for all except one** case of mixed sequestration. Sequestration pattern

Splenic (,=31 pts)

Hepatic (n= 7 pts)

Mixed (n= 4 pts )

Proposedsplenectom;¢ 24

l

I

0

Spleneetomized * Others therap, options

I 6

t ** 3

0 1

17 7

Absent (n=lpts)

Conclusion: The sites of abnormal platelet sequestration have been taken into account in the management of the disease concerning this group of 43 chronic/'IF patients, Splenectomy is mainly considered in purely splenic sequestration and mainly avoided in hepatic and mixed sequestration pattern.

1219

O

.=

O

13,

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OTHER CLINICAL SCIENCE. MISCELLANEA 2

PS_563

PS_565

R A D I O N U C L I D E I M A G I N G OF E S O P H A G E A L AND P U L M O N A R Y

INVOLVEMENT IN PROGRESSIVE SYSTEMIC SCLEROSIS

CURRENT ROLE OF LYMPHOSCINTIGRAPHY IN THE STUDY OF CHRONIC LYMPHEDEMA OF THE LOWER EXTREMITIES

N. Prandini (1), R. La Corte (2), L. Feggi (1), A. Cipnan (1), S. Panareo (1), D. Santilli (2), E Trotta (2). (1) Department of Nuclear Medicine; (2) Department of Rheumathology, S.Anna Hospital, Farrara, Italy.

M. Mitjavila, M.A. Balsa, L. GaCafiamaque, P. G'AIonso, F.J. Penin, V. Tortes, C. Pey. Nuclear Medicine Department, H.U.Getafe, Medrid, Spain.

Esophageal transit scintigraphy and Tc99m-DTPA alveolar permeability seem to be valid methodologies to assess impaired esophageal motility and active alveelitis in systemic sclerosys (SS). We compared the results of 126 esophageal scintigraphies and lung clearances performed in 114 SS patients (10 patients had 2 double studies and one 3 double studies). After an overnight fast, all subjects underwent to repeated transit of single radionoclide swallows, using both liquid end semisolid boll (10 ml fruit puree) labelled with 99roTe-sulfur colloid, orally ingested in upright and supine positions. A visual analysis of condensed images and a calculation of mean transit time (integra! method) were performed independently by two physicians: the patients were scored from 0 (all normal transit) to 4 (all pathological transit). Within 2 weeks the same patients underwent to a measure of pulmunary epithelial permeability calculating the half time afier ventilation of Tc99m-DTPA: an half time higher than 60 minutes was considered normal; values of half time between 40 and 60 minutes were considered mild accelerated and values lower than 40 minutes were considered highly pathological. The table summarize our results comparing the two scores obtained with esophageal scintigraphy and lung clearance: only 9 patients resulted normal with both procedures. Most of the patients had alterations of either pulmonary alveolar permeability or esophageal transit time and 83 of both. These findings indicate that in SS the visceral involvement of the disease is frequent. The radionuclide studies are useful methods to demonstrate the early involvement of both respiratory and digestive apparata.

Patients: 31 patients (25F, 6M) complaining of swelling one or both lower extremities were studied. 9/31 patients had associated pathologies: 2 neoplasm, 4 venous pathology, 2 leg trauma and I retroperitoneal fibrosis. Method: The Iymphosciutigraphy (LS) studies were performed by interstitially injecting I I I MBq (3mCi) 99mTc-Sn sulphur microcofioid, divides into four equal portions ofO.l ml, into the webbed spaces of both feet. Whole body images were obtained at 20 minutes and 2-4 hs afier injection. Qualitative assessment of images was performed: I) presence of asymmetries of lymphatic vassels and groin nodes and 2) signs of imparied lymph flow (pooling of radionuclide, intradermal hackflow and identification of collateral vessels). The diagnostic categories ranged from: normal, hypoplastic, aplastic, megalymphatics and dermal backflow. ECO doppler of lower extremities was also performed on all patients, pelvic CT on 2 patients and MRI on other two. Results: In 12 patients there were no signs of lymphedema, in 19 patients the presence of lympbedema was diagnosed, 5 of them secondary. In 12/19 patients hypopiastic or aplastic lymphedema was found and megalymphatics in 3. In 7/19 patients dermal backfiow was observed whith or without other categories (hypoplastic 2, megalymphatic I). In patients with vascular problem in lower extremities lymphatic involvement was showed by scintigraphy in 2. Conclusion: In patients with limb swelling, lymphoscintigraphy is a noninvasive, simple and useful procedure in the differential diagnosis of lymphedema from other sources of edema.

PS_564

PS_566

AN IMPROVED PROTOCOL FOR INCREASING THE POTENTIAL OF LYMPHOSClNTIGRAPHY IN PATINTS WITH PERIPHERAL LYMPHEDEMA

PLASMA VOLUME (PV) MEASUREMENT IN SUSPECTED POLYCY'FHAEMIA - DIRECT MEASUREMENT OR INDIRECT MEASUREMENT?

G. Teddei (1), F. Buffoni (1), P. Erba (1), M. Carletto (1), M. Bagnasco (1), G. Agnese (1), F. Castagnota (1), F. Boccardo (2), G. Villa (1), C. Campisi (2), G. Mariani (1)(1) Nuclear Medicine Service, DiMI - University of Genoa, Genoa, Italy; (2) Microsurgery Unit, University of Genoa, Genoa.

N. Nagaraj (1), K. Shrnueli (2), F. Nadir (3). (1) Department of Nuclear Medicine; (2) Department of Medical Physics; (3) Department of Haernatology, Chafing Cross Hospital, London, UK.

Objectives: To improve the conventional protocol of lymphoscintigraphy in patients (pts) with peripheral lymphedema, with the aim of increasing the diagnostic potential of this prOCedure in the characterization of both the Superficial Lymphatic Circulation (SLC) and Deep Lymphatic Circulation (DLC). Methods: A total of 137 consecutive pts were evaluated, 90 women end 47 men with mean age 51.7gs:18.03 yr (median 53, range 0,33-86): lymphadema was primary in 31 and secondary in 108 pts, affecting the lower limbs in 106 pts, the upper limbs in 36 pts (about 50% of the pts had bilateral lymphadema). The DLC was evaluated first, by injecting sS"Tc-nanocolIoid albumin (most of the particles between 30-80 rim) in aliquots of 300-500 pCi (11-18 MBq) in the aponeurotic sites of the palms or soles using a 2SG needle. The pt is then asked to exercise for 5 rain, and gamma-camera images are recorded until complete visualization of regional draining lymph nodes (usually within about 10-15 min). The SLC is evaluated next, by injecting similar tracers doses intradermally at approximately the same sites end applying massage. Static scans are then recorded similarly as done for DLC, and superficial regional lymph nodes are usually visualized within 5-10 rain (recording is continued until visualization of the liver). Results: Based on semiquentitative evaluation, the lymph flow was found to be normal in 37% and, respectively, 37% for the DLC and SLC, while it showed mild delay in 51,7% DLC and 50,4% SLC, moderate delay in 26,6% DLC end 31,6% SLC, and severe delay in 21,7% DLC end 18% SLC (the latter was associated with dermal back-flow in 0.5% D[c end 10.5% SLC). Correlation between the overall lymphoseintigraphic pattern and the site of obstruction was found in 98% of pts with monolateral and in 60% of pts with bilateral lymphedema. Instead, there were no differences between the DLC end SLC patterns in primary or secondary lympbedema. Conclusion: Evaluating both the DLC and the SLC in the same scintigraphic session enabled to better classify the various pattern of abnormal lymph flow. In particular, knowledge of the DLC pattern increased sensitivity of the procedure by about 20%.

cythaemia, the additional measurement of PV helps in the interpretation of the results and subclassificalion of patients. Due to cost and limited shelf life [-13 [ HSA required for PV measurement may not always be available end PV is indirectly estimated from the measured RCM end venous Haematuurit (Hv) using the formula PV = RCM [1/(0.91 x Hv)- 1] To compare the two methods &determine the clinical relevenee of differences if any, we indirectly estimated the PV of 60 consecutive pts with suspected polycytheemia whose PV & RCM were measured directly using 1-125 HSA end 51-Cr respectively. The results were interpreted according to [CSH criteria based on surface area. The final diagnosis based on actual measured rasuiLs and clinical follow up were True polycythaemia (TP) (28) end apparent polyeythaemia(AP) (32). Differences between the two methods was calculated as estimated- measured/measured end ranged from -24% to +28%. Although the indirectly estimated method demonstrated only <5% difference in 55% of the cases, there were larger discrepancies with >'a:10% difference in 25% of the cases of which 5 pts had differences >+-25%. Since the hallmark of TP is an elevated red cell mass, diagnosis was not affected in this group despite >-210% differences in the estimated PC. In AP gp, primary diagnosis was not affected by indirect method despite overestimation of PV in 4 pts end underestimation in 3 pts resulting in incorrect subeategnry placement within the same group. However, incorrect subcategnrisation did not affect the clinical management and the reasons for this will be discussed. In conclusion, although direct measurement of PV in suspected polyeythaemia is preferable, indirect estimation from actual measured RCM end venous haematocrit may be substituted effectively for routine clinical purposes.

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Although only red cell mass (RCM)meeanrement is requiredto evaluatepts with poly-

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OTHER CLINICAL SCIENCE. MISCELLANEA 2

PS_567

PS_569

COMPARISON OF PENTETREOTIDE INDIUM 111 AND GALLIUM 67 SCINTIGRAPHIES IN LYMPHOMAS

THE BEHAVIOUR OF CONCENTRATIONS OF INTERLEUKINES IL-1BETA AND IL-6 IN PLASMA AND IN LYMPHOCY'rES OF PATIENTS WITH B-CELL CHRONIC LYMPHOCYTIC LEUKAEMIA WITH REGARD TO DISEASE PROGRESSION

D. Huglo (1), M. Nocaudie (1), B. Quesnel (2), E Morscchauser (2), X. Marchandise (1). (1) Department of Nuclear Medicine; (2) Department of Haernatology, Hopital C. Huriez, C.H.R.U. of Lille, Lille - France. FDG uptake in lymphoma is usually compared to gallium 67 citrate (Ga67) uptake. The aim of this prospective study was to compare pentetreotide-indium 111 (OetreoScan, Malliockrodt) and Go67 uptakes in residual masses of lymphomas. Methods : Patients with Hodgkin's disease or with intermediate-grade or high-grade of nonHodgkin's lymphoma were considered before therapy. Patient was included if he had at least a superficial palpable mass or a mass bigger than 7 cm. Whole body study (8 cm/min.) and static images (600 s per frame) were acquired 24 hours after intravenous injection of 185 MBq of pentetreotide-indium I I1 and 72 hours al~er injection of 260 MBq of gallium 67. A SMV DSX gamma camera equipped with a ME collimator was used. Scintigraphies and CT-scan were performed first at diagnosis before therapy (n = 9), then after 4 cycles of chemotherapy (n = 6) and finally at the end of therapy (n =5). Results : Nine patients were included, 3 with Hodgkin's disease, 6 with non-Hedgkin's lymphoma. At diagnosis, all abnormalities were seen with both radiopharmaceuticals in 8 patients ofg, but there were differences between uptakes according to sites. The contrast was always higher with Go67 but bone uptake of this tracer could be a real problem. For 1 patient with mantle cell lymphoma, no uptake of pentetreotide was registered on the sites positive with Go67. After 4 cycles of chemotherapy, two other patients did not want to proceed ; all abnormal sites had decreased uptake or had no uptake. Two patients had no residual uptake. Residual uptake was seen either only with Ga67 (n = 2), or only with pentetreotide in = 2). At the end of therapy (n = 5), one of these later patients could not be studied, the other showed again on the same site uptake of pentetreotide alone, in agreement with CT scan which evoked an active residual mass. The scans of the 4 other patients were normal (except in one case uptake of pentetreotide-indium secondarily to radiotherapy). Conclusion : The weak number of patients did not allow to demonstrate greater performances of one tracer over the other, but our results show that pentetreotida and Ca67 scans are complementary rather than opposite. Differences between the uptakes of the tracers deserve more detailed cellular studies.

A. Parfienczyk (1), B. Kiersnowska-Rogowska (2), F. Rogowski (1), E. daroszewicz (1), A. (3itko (1). (1) Department of Nuclear Medicine; (2) Department of Haematology, Medical University, Bialystok, Poland. B-cell chronic lymphocytic leukaemia (BCLL) belongs to malignant lymphomas and originates from the immunological system. The etiopathogenesis of the disease has not been fully explained yet. Cytokines propably take part in the development and in the course of the BCLL Therefore the aim of the study was determination of the concentrations of [L-I~ and iL-6 in blood plasma, culture supernatant and in isolated, ultrasonically broken lymphocytes obtained from patients with BCLL (12 individuals in 1 stage and 12 in I11 stage according to the Rai classification, aged 45-65 years) and from 10 healthy volunteers (staff members of Nuclear Medicine Depanment). The double two hour limphoeyte cultures of each patient were conducted with and without mitogene (Neupogen, Roche) simultaneously. Methods: The measurement of the concentrations of the interleukins mentioned above was made using immunoradiometric kits from Bioscouree Europe, S.A. (Belgium). Mitogene was added to trigger blastic transformation and lymphocyte activation. Results: A significant increase in IL-1~3 and IL-6 concentrations were ibund in blood plasma in 1 and in I11 stage of BCLL, before and at~er stimulation in the super'natant culture and in the isolated, broken lymphocytes in 1 and in I11 stage of BCLL. A significant difference was observed between the levels of cytokines in the nonstimulated and stimulated with Neupogene cultures at the same time. In most cases these concentrations were higher afier stimulation. Conclusions: Increased concentrations of IL-I~ and IL-6 in the plasma and in the culture supematant may indicate that leukaemic lymphocytes release these interlcakines known as the stimulators of the leukaemic proliferation. Elevated concentrations of IL-I~ and IL-6 in the broken lymphocytes may be characteristic t~ature of neoplasmatically changed lymphocytes.

0

PS_568

PS_570

NON-INVASIVE VERSUS INVASIVE METHOD OF PLATELET PRODUCTION ESTIMATION IN THROMBOC~fI'OPENIC PATIENT

ROLE OF GFR AND ERPF IN PREDICTING RENAL DYSFUNCTION IN ANAEMIC PATIENTS WITH NORMAL SERUM BIOCHEMISTRY

M. Todorovic-Tirnanic (1), V. Obradovic (1), S. PavIovic (1), M. Colovic (2), N. Suvajdzic (2), I. Elezovic (2), V. Starcevic (3), N. Milic (3), V. Bosnjakovic (1). (1) Nuclear Medicine Institute, Clinical Center of Serbia, Belgrade, YU; (2) Haematology Institute; (3) School of Medicine, Belgrade, YU.

(3..S. Bal (1), A. Ghosh (2), B.L. Jailkhani (2), A. Kumar (1). (1) Department of Nuclear Medicine; (2) Department of Laboratory Medicine, New Delhi, India.

e~

Objective: Anaemia causes multisystemic functional changes, including that of kidneys.

0

The aim was to compare results of non-invasive (PI, platelet production index) and invasive (Mk, megakaryocyte abundance) method of platelet production estimation in thrombocytopenic patients. Methods: P[ was calculated on the basis of l l ! ln-oxinate labelled platelet life span (LS) and Pt blood count (BC) determination for subjects with linear platelet survival curve (formula 1). Pll = (LS h x BCi)/(LSi x BCh) (I) Ple=(Ri x BCi)/(Rh x BCh) (11) Formula 11 was used for PI calculation in the eases with exponential platelet survival curve, R is the platelet renewal; i, investigated person; h, healthy subject. Platelet renewal was calculated using the formula: R=[In2/(T/2)] x 100 = (69,3)/(T/2), where T/2 is the labelled Pt half-life. Megakaryocyte abundance was graded as I. numerous, 2. present, 3. poor Pt production, 4. rare megakaryocytes.Fifty-five persons were investigated: 49 TP, tbrombocytopenic patients (40 [TPc, chronic idiopathic thrombeeytopenic purpura; and nine MDS, myelodysplastic syndrome) and six C, control, healthy subjects. In TP both methods (PI and Mk) were applied, while in C only PI was determined. Results: We obtained linear platelet survival curve in all MDS and C subjects. Mean value for LS in MDS was 8,2 days, while in C group it was 8,9 days. There was no significant difference in LS between MDS and C group. In ITPc patients we obtained exponential platetet survival curves and shortened platelet LS (mean LS value was i,l day). There was highly significant difference in LS between ITPc and C group, and also between the two TP groups: ITPc and MDS (p<0,001). The mean value for PI in C group was 1,0 (SD=0,2); in 1TPc 1,2 (SD=0,5), while in MDS it was 0,2 (SD=0,2). Highly significant difference was noticed in PI between the two TP groups: ITPc and MDS (p<0,01), as well as between MDS and C group (p<0,01). P[ was significantly lower in MDS than in ITPe or C group. Mean value for Mk in ITPc group was 1,0 (SD=0,8) and in the MDS group it was 1,0 (SD=I,4). There was no significant difference in Mk between [TPc and MDS group (p>0,05). Conclusions: Non-invasive method of PI determination is better method for Pt production estimation than invasive megakaryocyte abundance determination. Together with Pt LS determination, PI non-invasively and reliably differentiates between thrombocytopenia caused by inadequate Pt production (MDS) and thrombocytopenia caused by increased Pt production (ITPc).

However, in early stages, biochemical parameters for renal function may remain within normal limit. We tried to find out the role of GFR and ERPF in such conditions. Methods: Seventy-six subjects were recruited in this study. They were divided into following groups: group A: patients with Hb < 3 gm/dl (n=33); group B: patients with Hb < 6 but > 3 gm/dl (n=33); group C: healthy controls with normal renal function and Hb > 12gm/dL Thirty-six patients had iron deficiency anaemia (A=20, B=I6), 24 had aplastic anaemia (A=II, B=13) and the rest 6 had megaloblastic anaemia (A=2, B=4). No subject had hypertension, diabetes, primary renal disease or any other systemic illness, affecting kidney. Various biochemical parameters for renal function along with GFR with Te-99m DTPA and ERPF with 1-131 OIH were calculated. Results: Average duration of anaemia was 3.5 months. Fourteen patients had mild to moderate pedal edema (A-10; B-4). Out of them, 8 had palpable liver and signs of systemic congestion. Signs of raised systemic venous pressure (raised JVP) were found in 7 patients from group A. Urine output was >600 ml/day in all cases. Demographic and clinical profile of all the subjects is given in the following table: Table: Demographic and clinical profile

Diagnostic indices A~e Sex (M:F) HaemosIobin (ms/dL) Blood urea nitrogen (mg/dL) Serum Creatinine (mg/dL) Serum Potassium (mEq/L) Serum Calcium (m~/dL I Serum Phosphate (mg/dL) Routine Urine Examination GFR/ml/min/1.73m e BSA) ERPF (ml/min/m 2 BSA)

Group A 32.7+_3.8 3, I 2.6+0.05 28+_2.38 1.06+0.05 4.49+0.09 8.98+0.15 4:3+0.16 N 60.0+0.71 362+18.4

Group B 32.0_+3 0.94 5.3+0.11 23+1.3 0.81+0.04 3.67+0.09 8.74+0.11 4.1 t+0.15 N 72.0-+1,43 422+19

Group C 31+2 4.0 13.5_+0.3 16.5+2.2 0.81+0.06 3.8+0.12 8.97+0.23 3.98+0.4 N 109-+2.9 559+_38.5

Values are e x p re sse d as m e a n + I S E M : N = n o r m a l

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• OTHER CLINICAL SCIENCE. MISCELLANEA 2 / NEUROLOGY / PSYCHIATRY 4 Although, Blood urea nitrogen, serum creatinine and serum potassium was relatively higher in severely anaemic patients, all biochemical paramete~ for renaI function were within normal reference range, used in our laboratory. However, GFR and ERPF were significantly reduced among patients, indicating sub-clinical renal dysfunction; the reduction was correlating well with the severity of anaemia. Conclusions: Anaemia leads to sub.clinical renal dysfunction. Though biochemical parametees for renal function may remain normal in early stages, GFR and ERPF are significantly reduced in such patients and can help in early diagnosis.

PS_572 DIPYR|DAMOLE STRESS TEST FOR EARLY EVALUATION OF CEREBRAL CIRCULATORY DISORDERS T. Molnar (1), K. Zambo (2), E. Schmidt (2), E. Udvaros (2), L. Bogar (I). (1) Department of Anaesthesia and Intensive Care; (2) Department of Nuclear Medicine, University Medical School of Pecs, Hungary. Aim: The diagnosis of transient ischaemic attack (TIA) is mainly retrospective, based on the clinical symptoms presented by the patient. Professionals in nuclear medicine have made a successful attempt to da~ect TIA by single photon emission tomography (SPECT) imaging using stress test (e.g. acetazolamide) which is well known in literature. Dipyridamole stress test combined with SPECT imaging of patients with ischaemic heart disease is regularly performed in our department. After injecting dipyridamole intravenously we have found various forms of transient neurologic deficit.This is a retrospective study of SPECT brain scan using dipyridamole as a stress agent to assess transient cerebral circulatory disorders in patients with ischaemic heart disease. Methods: The criterium of inclusion was transient neurological deficit during cardiac dipyridamole stress test. Selected TIA positive patients (23/100) were examined further on. We performed SPECT scanning of the brain with, and one week later, without dipyridamole stress. Dipyridamole was given intravenously according to the protocol (0.57mg/kg) before infusion of 99mTc-HMPAO. Patients were studied 30rain later using a rotating gamma camera. Visual analysis of the scans was based on the consensus of two independent investigators. Neurological examination was also obtained before, during and after dipyridamole stress. Results: The brain SPECT combined with dipyridamole stress was positive in all patients of the TIA positive group. Localizations of hypoactive fuci were compared to the clinical topography based on neurological examination and good correlation was revealed. The brain SPECT imaging in resting condition showed variable regression (total, partial) of the pet'fuslon abnormalities. However, permanent perfusion deficit in resting condition indicates subclinical lesion if the neurological status is negative. Conclusion: The transient neurological deficit observed in 23% of the dipyridamole stressed patients with ischaemic heart disease is a considerably higher incidence than reported previously in literature (1.22/10,000). This test may be suitable to provoke TIA safely, therefore combined with brain SPECT it could play an important rote in neurologic diagnostic procedures, stroke prevention and preoperative management of patients scheduled for cardiac surgery.

NEUROLOGY / PSYCHIATRY 4

PS_573

PS_571

REGIONAL CBF QUANTIFICATION IN ANEURYSMAL SUBARACHNOID HEMORRHAGE

BRAIN SPECT IN ACUTE CRANIOCEREBRAL INSULT PATIENTS: COMPARISON WITH DIFFUSION AND PERFUSION MAGNETIC RESONANCE IMAGES

M. Hosono, K. Machida, T. Matsui, N. Honda, T. Takahashi, A. Kashimada, H. Osada, Y. Shimizu, M. Ohmichi, S. Dei, T. Asano Department of Radiology, Saitama Medical Center, Kawagoe, Japan. Regionalcerebralbloodflow (rCBF)may variablychangedue to cerebralvasospasmaswell

E.N. Kim, H.S. Sohn, S.H. Kim, Y.A. Jung, I.R. Yoo, S.K. Chung. Departments of Nuclear Medicine, College of Medicine, St. MaryAos Hospital, The Catholic University of Korea.

as surgical invasion in aneurysmal subarachnoid hemorrhage (SAH). To date, cerebral perfusion imaging has been useful in monitoring patients (pts) with SAH. In this study, rCBF was quantified by using 99mTc-ECD to determine if rCBF changes were observed and if the rCBF measurement enabled the detection of symptomatic vasospasm. Methods: Thirty-five consecutive pts with SAH (55±12 yo) who underwent clipping had 99mTc-ECD examinations at days I and 7 aRer surgery, mCBF was measured by Patlak plot analysis and then SPECT was performed with calculation of absolute rCBF values using Lassen's correction as previously reported. Regions of interests were placed at 12 regions on rCBF maps, that is, the bilateral cerebellar hemispheres, frontal, temporal, occipital lobes, basal ganglia, thalami, rCBF-changn was calculated as (rCBFdayl-rCBFday7)//rCBFdayl. Results: Nine of 35 pts had vasospasm confirmed by angiography, CT and/or MR. When decrease of more than 10 % in rCBF from days t to 7 was considered significant, numbers of regions showing significant perfusion-decrense were 6.8 ± 3.8 and 2.2 ± 2.6 (!o=.002) for pts with or without vasospasm, respectively. In terms of ability of discriminating vasospasm and non-vasospasm, number of perfusion-decrease regions showed (with a cutoffof 4 regions) the sensitivity, specificity, positive predictive value, and negative predictive value were 88.9 (8/9 pts), 73.1 (19/26), 53.3 (8/15), and 95.0 (19/20) %, respectively. Moreover, the absolute rCBF values indicated no significant differences between vasospesm and non-vasospasm in any oftbe 12 regions at either days 1 and 7. On the other hand, there were significant differtrices in rCBF.-changes between vasospasm and non-vasospasm in 6 of 12 regions (rt cerebellum p=.O16, h cerebellum p=.009, rt frontal p-=.037, it frontal p=.002, rt temporal p=.036, n occipital p=.005). Conclusion: Significant rCBF changes were observed extensively in the brain in the course of SAH. The rCBF-cbnnge from day 1 to day 7 after surgery may be more useful than the absolute rCBF values for the detection of vasospasm.

Aim: In this study, we compared findings of brain SPECT with conventional T2- weighted magnetic resonance image, diffusion- and perfusion weighted brain MRI in acute craniocerebral insult patients. Methods: Seven acute craniocerebral insult patients were studied by Tc99m HMPAO brain SPECT, conventional MRI, and diffusion- and perfusion brain MRI. Brain SPECT was obtained and processed using two head gamma camera (ECAM; Siemens, Erlangen, Germany), and MR images were obtained using 1.5 Tesla machine (Vision Plus; Siemens, Edangen, Germany) and processed using home made software written in IDL and C ++. All images were taken within 3 days. We compared the findings of these modalities and clinical situations of patients. Results: In all images ¢xoept conventional T2 weighted image, insult-related changes ware relatively well observed. The lesions on the brain SPECT were largest of all other medalities. On brain SPECT, insult-related changes of cerebral blood flow were well observed with higher signal tu noise ratio (SNR) than cerebral blood flow map on perfusion MRI. However, with brain SPECT alone, we could not differentiate recent insult related changes from blood flow changes resulting from previous insult prior to recent insult. Diffusion weighted MRI demonstrated cytotoxic edema areas with highest SNR and shortest acquisition and post-processing time. Perfusion weighted images could demonstrate other information such as time to peak map, cerebral blood volume map, and mean transit time map in whole brain as well as cerebral blood flow map, but with relatively low signal to noise ratio and longest post-processing time. The findings of brain SPECT and diffusion weighted images showed better correlation with clinical situation of the patients. Conclusion: Diffusion weighted MR and brain SPECT are more useful than conventional T2 weighted images and perfusion weighted MR in patients with acute craniocerebral insult patients due to their higher SNR and short post-processing time.

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• NEUROLOGY / PSYCHIATRY 4

PS_574

PS_576

DEVELOPMENT OF SUPER RAPID DYNAMIC SPECT, AND ANALYSIS OF 99MTC-ECD DYNAMICS IN ISCHEMIC LESION

IMAGE-FUSION OF BENZODIAZEPINE RECEPTOR SPECT AND BRAIN MRI IN PRESURGICAL ASSESSMENT OF TEMPORAL LOBE EPILEPSY

A. Kornatani, Y. Sugai, T. Hosoya. Department of Radiology, Yamagata University, Yamagata Japan. Aim: Development of super rapid dynamic SPECT (single photon emission computed tomography) system, and analysis of early phase dynamics of 99mTc-ECD (ethyl cysteinata dimer) in ischemic lesion using the SPECT system. Methods: We newly developed a super rapid SPECT system, which enabled to take a SPECT series every 2 seconds. Each SPECT series contain maximal 16 slices (6.6ram thickness) in matrix size of 32 x 32. This system was designed originally based on the ,,CERASPECT" (DSI, lnc, Waltham, MA, U.S.A), Twenty patients with ischemic lesion that was detected clearly by 133Xe-rCBF (regional cerebral blood flow) SPECT but unclear on the static 99mTc-ECD SPECT were examined, For the dynamic SPECT, 700MBq of 99mTc-ECD were injected intravenously, and dynamic SPECT data was acquired every 2 or 3 second during 90 second or more. The serial dynamic SPECT and time-activity curves at some reduced lesion in rCBF and at the contra-lateral normal brain were analyzed. These dynamic SPECT data were compared with conventional static 99rnTc-ECD SPECT and quantitative 133Xe-rCBF SPECT. Results: The sensitivity of this system was 175 kcps/MBq/ml/em slice thickness, and resolution was 17mm FWHM at the center of 20cm$B&U(B water phantom. All of mildly or moderately reduced rCBF lesions on the 133Xe-rCBF SPECT were recognized as a low activity region only at the early phase (about 2-20see.), and vanished the lesion gradually. These lesions were not recognized on the conventional static SPECT taken after the dynamic study. Conclusions: This study suggests that the esterase activity participate in ECD retention is tolerated ~o the mild or moderate ischemla. The tolerance may be one of the most important causes of the non-linearity in correlation of ECD accumulation with the cerebral blood flow.

M. Wissmeyer (1), R. Wiest (2), K. Schindler (2), J.R Wielepp (1), L. Mariani (3), G. Schroth (3), B. Weder (4), F. Donati (2), D. Luescher (1), J.A. Kinser (1). (1) Department of Nuclear Medicine, University of Berne, Berne, Switzerland; (2) Department of Neurology, University of Berne, Berne, Switzerland; (3) Departments of Neurosurgery/Neuroradiology, University of Berne, Berne, Switzerland; (4) Department of Neurology, Cantonal Hospital, St. Gallen, Switzerland Aim: The aim of this study was to evaluate the usefulness of the image-fusion of benzodiazepine receptor (BDR) SPECT using 1-123-1omazenil and brain MRI in the presurgical assessment of patients (pts) with therapy- refractory temporal lobe epilepsy (TLE). Methods: We evaluated 21 pts with therapy-refractory TLE due to mesiotemporal sclerosis or other focal brain anomalies. 16 pts have been operated, 5 were inoperable due to the extent of the focal brain anomalies. To delineate the epileptugenic zone and to locate the presumed extent of resection, clinical evaluation, video-EEG recordings using scalp and semi-invasive foramen ovate electrodes, high resolution brain MRI, interictal CBF SPECT using Tc-99mECD and BDR SPECT were performed. Brain MRI and BDR SPECT were fused using a standardised computerised brain atlas (CBA). Results: Of the 16 pts treated operatively, 10 pts had a 12-month outcome of Engel class 1, 5 pts of Engel class I1 and I patient of Engel class Ill. lctal semi-invasive foramen ovale EEG recordings located the epileptogenie focus in all pts in the temporal region. Reduced BDR density and correct delineation oftbe epiLeptogenic focus was shown in 20/21 pts. Brain MRI failed to detect morphological lesions in 2 pts. whereas BDR SPECT revealed a focal anomaly in both cases. There is a significant correlation between positive EEG/MRI findings and BDR SPECT with a sensitivity, a speciflty and a positive predictive value of 0.94. The additionally performed interictal CBF SPECT Iocalised the epileptoganic focus correctly in 16/21pts, corresponding to a sensitivity of 0.80. a specifity of 0.90 and a positive predictive value of 0.89. Conclusion: BDR SPECT using 1-123-1omazenil fused with brain MR[ is a non-invasive procedure that provides useful functional information in the delineation of temporal lobe epilepsy, especially in pts with negative morphological imaging techniques.

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PS_575

PS_577

ICTAL AND INTERICTAL TC-99M HMPAO BRAIN SPECT IN PEDIATRIC MIGRAINE WITH AND WITHOUT AURA

ICTAL AND INTERICTAL SUBTRACTION CBF SPECT FUSED WITH HIGH RESOLUTION BRAIN MRI IN THE PRESURGICAL EVALUATION OF EPILEPSY: PRELIMINARY RESULTS

M. Sahin (1), T. KarslJ (2), S. Uysal (2), T. Baso~jlu (1). (1) Department of Nuclear Medicine; (2) Department of Pediatrics,19 May=s University, Samsun, Turkey. The objective of this investigation was to evaluate changes in regional cerebral blood flow (rCBF) on pediatric patients suffering from migraine with aura (classic migraine) and without aura (common migraine). Methods:Nine patients with aura (age ranges: 11-16, mean age-2:sd: 13.5.+.2) and 12 patients without aura (age ranges: 7-16, mean age-k.sd: 12.3+3) were studied. Tc-99m HMPAO study was performed during the headache- free (interictal) and headache periods (ictal). Transaxial slices parallel to orbitomeatal line (by adding 3 slices passing from the cerebellum, basal ganglia, supraventrikuler region and vertex) were used to determine the mean corticocerebellar ratio of total 17x2 brain regions. Paired-t test was used the compare the mean rCBF values in ictal and interictal period images of patients with aura and without aura, Student-t test was used to compare the mean rCBF for ictal images in patients with aura and without aura, as well as to compare interictal images. Results: lctally, decreased rCBF values were found in 8/9 patients with aura and 6/11 patients without aura. Decreased rCBF values were observed in 6/9 patients with aura and 2/11 patients without aura during the interietal period. Two patients without aura showed hyperperfused areas in addition to hypoperfused areas in ictal period, Any patient showed new lesion in interictal period, Significant differences were detected between patients with aura and without aura in ictal and interietal periods, as well as between ictal and interictal rCBF values in patients without aura, No significant difference was detected between ictal and interictal rCBF values in patients with aura. The distribution of hypoperfused brain regions in brain lobes was indicated in table.

Frontal Parietal Temporal Oksipital

With Aura Ictal 33/1444%23 ) 1 5 / 7 2 (%21) 9/36 (%25) 7 / 27 4%26)

Interictat 19/1444%13.2 ) 11/72 (%15.2) 6/36 (%16.6) 2 / 27 4%7.4)

Without Aura Ictal 12/1764%6.8 ) 1 4 / 8 8 (%15.9) 3/44 (%6.8) 3 / 33 (%9)

Interictal 2 / 1 7 6 (%1.1) 4 / 8 8 4%4.5) 1 / 4 4 (%2.2) I / 33 ~"/03)

Conclusions: Migraineurs with aura revealed more prominent brain lesions than migraineurs without aura in both ictal and interictat period. _nterictal SPECT imaging alone underestimated number and extent of pathological areas. Therefore, ictal rCBF evaluation should be used to determine brain perfusion pattern.

M. Wissmeyer (1), K. Schindler (2), R. Wiest (2), P. Ritter (1), K. L6vblad (3), B. Weder (4), F. Donati (2), K. Oswald (3), D. Luescher (1), J.A. Kinser (1). (1) Department of Nuclear Medicine, University of Berne, Berne, Switzerland; (2) Department of Neurology, University of Berne, Berne, Switzerland; (3) Department of Neuroradiology, University of Berne, Berne, Switzerland; (4) Department of Neurology, Cantonal Hospital, St. Gallen, Switzerland Aim: The aim of this study was to determine the usefulness of the fusion of ictal and interictal subtraction CBF SPECT with high resolution brain MRI in the Iocatisation of epileptogenic loci in patients with therapy-resistant epilepsy. Methods: We evaluated 5 patients (2 male, 3 female; 30-37 years old) suffering from intractable epilepsy performing video scalp EEG registration and CBF SFECT using Tc-99mECD in the interictal state followed by an ictal CBF SPECT during a seizure with an injection on time (cutoff 30 seconds after EEG onset) in 3 cases and late injection in 2 cases. ARer normalisation of the SPECT data in all patients, interictal scans were subtracted from the ictal scans. All voxels with a difference of more than 3 standard deviations (SD) from the mean

intensity of the subtractionscanwereconsideredto truely delineatethe epileptugenicfocus. Additionally, bothSPECTscanswerecomparedwith studiesof beaRhyvolunteers(n=16)in order to determinethe extent(more than 3 SD) of the ictal hyperperfusionand interietal hypoper~sion.The resultsof this voxel-basedstatisticalprocesswerefusedwith high resolution MRI scans using the Brain Voyager software (Brain Innovation). Results: The subtraction CBF SPECT scans located the epileptogenic focus correctly in circumscribed areas of the temporal lobe in all patients. The lataralisation to the right (n=4) and left (n=l) hemisphere corresponded with the video-EEG findings in all patients, whereas comparison with the MILl showed concordance in only 3/5 cases (1 patient with a normal MRI scan, 1 patient with a contralateral morphological abnormality). The fusion of the statistically processed subtraction CBF SPECT data with the high resolution brain MRI scans of the patients revealed involvement of the hippocarnpus in 2 patients, the insular cortex in 2 patients and the frontal pole of the temporal lobe in 1 patient. Subtracting only the ictal CBF SPECT data from the sampled normal scans of the healthy volunteers, we additionally found that the ictal hyperperfusion extended all over the temporal lobe ipsilateral to the presumed focus, affecting the mesial temporal lobe in each patient, and to distant areas corresponding to homotope areas of the contralateral hemisphere, which may correlate to the differing ictal injection times. Conclusion: The fusion of ictal and interictal subtraction CBF SPECT with high resolution brain MRI provides independent functional information in the presurgical evaluation of epilepsy, especially in patients with normal or discrepant MRI findings.

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• NEUROLOGY / PSYCHIATRY 4 PS_578

PS_580

THE USEFULNESS OF REPEATED ICTAL SPET FOR LOCALIZATION OF EPILEPTIC FOCUS IN PATIENTS WITH NEOCORTICAL OR MULTIFOCAL SEIZURE: COMPARISON WITH IMAGING ANALYSIS BY SUBTRACTION A N D ICTAL SPET SPM

INTERICTAL R-CBF BRAIN SPET, BRAIN M R I / C T AND EEG IN THE CLINICAL CHARACTERIZATION OF LESlONAL A N D CRIPTOGENETIC PARTIAL EPILEPSY (PE)

M.C. Lee (1), Y.K. Kim (1), D.S. Lee (1), J.S. Yeo (1), J.S. Lee (1), S.K. Lee (2), C.K. Chung (3), J.K. Chung (1). (t) Department of Nuclear Medicine; (2) Department of Neurology; (3) Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. Introduction: In neocortical or multifocal seizure,the ictal perfusion changesmay be subtle or have complex pattern. It is particularly di~cuh to localize the epileptic focus by EEG, MR or conventional brain SPET. In this study, we investigated whether repeated ictal SPET during video-EEG monitoring could improve the sensitivity in localization of the epileptic focus. We compared the visual analysis of repeated ictal SPET with the results of the analysis using subtraction ictal image and ictal SPET SPM. Methods: Twenty-two patients (8 FLE, 3 PLE, 2 lateral TLE, 1 OLE and 8 multifocal seizure) were included in this study. All patients got the unexpected or inconclusive results in first ictal SPET and performed repeated ictal SPET (second ictal SPET in 17 and more in five). Also, fourteen of these patients performed interictal SPET. After normalization using interictal SPET, subtraction images were acquired and co-registrated to standard MR. Using SPM analysis, the ictal perfiJsion in each scan was compared with the perfusion of 15 young healthy controls. Ictal image interpretation was performed independently and side-by-side analysis with interictal SPET. Result: The first ictal SPET correctly lateralized seizure origin in 10 of all patients (45%), but localized epileptic focus in only 5. In another 12 ictal SPET (55%), no hyperperfusion area was founded. In second ictal SPET, ictal hyperperfusion localized correctly epileptic origin in additional 3 patients with single epileptic focus and the sensitivity improved from 29 % to 50 %. In cases of eight multifocal seizure, first ictal SPET indicated one seizure origin in 7. In second ictal S P E T , another seizure focus was reveled in 5 (63%). SPM analysis with first ictal SPET gave the additional information for localization or lateralizatun in four, confirmatory information in five (corrected p
R. Benti (1), E. Mariani (2), A. Antonini (2), F. Zito (1), M. Gasparini (1), C. Sdraiati (1), G. Pezzoli (2), P. Gerundini (1). (1) Department of Nuclear Medicine, Ospedale Maggiore-IRCCS, Milano, Italy; (2) Neurosciences Department,lstituti Clinici di Perfezionamento,Milano, Italy. Ictal r-CBF SPET is an established adjunct to EEG in the pre-surgical localization of epileptogenetic zones unresponsive to medical treatment. However, the role of r-CBF SPET assessment in PE is still debated, lnterictal SPET, routine EEG and MRI/CT brain studies were obtained in 28 PE patients diagnosed according to the [LAE criteria (age 45±8 ys; duration 17.7±5 ys). Clinical localization was temporal (15) occipital (6), frontal (4), parietal (I) and fronto-parietal (2). PE presented as secondary (SPE) to brain lesions (16 cases) or as cryptogenie partial epilepsy (CPE) with normal MRI. SPET was performed after Tc-99m ECD injection using a dedicated gamma-camera; after iterative reconstruction, focal ipoperfusions were assessed by visual analysis and quentitated by ROIs analysis vs. contralateral structures. EEGEpileptifom Abnormalities (EA) where present in 20/28 cases: 16 consisting with the clinical seizure presentation (CSP) and in 4 patients consisting with a non-specific findings. SPET showed 29 focal defects (24 cortical, 5 subeortical) in 23/28 patients, mean r-CBF impairment in SPE and CPE foci detected was 27.1±10.8 % and 16.4±3.6 respectively. In the SPE group, SPET localization matched clinical seizure presentation (CSP) better than EA (9/16 vs 12/16 patients, p=0.02), whereas lesion location/extension assessement by MRI/CT was related to CPS in 6/16 cases only. Moreover EA, SPET end CPS matched in 4 extralesional foci showing normal MRI/CT findings. In CPE group, interictal EA was present in 6/12 and focal hypoperfusions in 9/12 patients. EA and SPET patterns in CPE positively matched CPS in 33% and 58% respectively (p<0.05), in 4/12 both EEG and SPET positively matched CPS. Interictal SPET pattern of focal hypoperfusiun positively correlated with the presentation of seizure in SPE (75%) and CPE (58%), and localized clinical foci better than interictal EEG (p<0.02) and MRI/CTI (p<0.001) in PE patients evaluated.

PS_579

PS_581

COMPARISON OF STATISTICAL PARAMETRIC MAPPING AND SUBTRACTION ICTAL IMAGE CO-REGISTERED TO MRI TEMPLATE: IN EVALUATION OF ICTAL BRAIN SPET

IGTAL AND INTERICTAL BRAIN SPECT IN CHILDREN WHIT ELECTRICAL STATUS EPILEPTICUS DURING SLOW SLEEP (ESES)

M.C. Lee (1), D.S. Lee (1), J.C. Peeng (1), J.S. Yeo (1), H.J. Jeong (1), Y.K. Kirn (1), S.K. Lee (2), C.K. Chung (3), J.K. Chung (1). (1) Department of Nuclear Medicine; (2) Department of Neurology; (3) Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea. The subtraction ictal SPET has been reported to have improved diagnostic power with using co-registration to MRL And meanwhile,statistical parametric mapping (SPM) was introduced and reported to b¢ helpful to the performance of ictal SPET. In this study we compared the performence of thesetwo methods. Methods: Forty-nine patients with medically intractable epilepsy (age 26.9±8.8 years, 33 male end 16 female) end 15 normal volunteers were enrolled, All of the patients had surgically end pathologically proven diagnosis of epileptic focus. Thirty-five patients were diagnosed as temporal lobe epilepsy (TLE) and 14 patients, as neocortical epilepsy (NE). lctal and interietal SPET were performed before operation in all patients and SPET was also performed in normal volunteers as the control group, letat SPET end SPET from normal patients were analysed using SPM99 software. The epileptic focus was localized by perfuaion increase relative to normal control, with corrected threshold P value of 0.05 end 0.01. Afterwards, the subtraction ictal images were reconstructed and co-registered to MRI template for the better anatomical correlation. With this image, the epileptic focus was also localized by increased ictal perfusion relative to interictal one. The localizing power of these two methods were compared. Results: In TLE patients, 27 were localized with SPM analysis (77%) end 21 of them were correct (78%). Subtraction and co-registratiun methods localized 26 (74%) patients and 24 of them were correct (92%). Among 8 patients who were unloealized in SPM, 4 were additionally localized correctly in subtraction end co-registration method. In NE patients, 9 (64°/,) were localized end 8 of them were correct (89%) with SPM while 8 (57%) were localized and 5 (63%) of them were correct with subtraction end co-registration method. Among 6 patients who were unlocalized in SPM, no one was additionally localized with subtraction end co-registration method. Conclusion: When the SPM was used in the interpretation of ictal SPET, the method of subtraction and co-registratiun to MRI template had some additive value in TLE. But the method did not have any additive value in neocortieal epilepsy.

M. Dondi (1), G. Fagioli (1), S. Zoboli (1), M. Salgaretlo (1), S. Fanti (2), M. Farsad (1), A. Moretti (1), C. Pettinato (3), G. Montini (2), S. Meletti (4), C.A. Tassinari (4)(1) Department of Nuclear Medicine Maggiore Hospital Bologna; (2) Department of Nuclear Medicine S.Orsola-Malpighi Hospital Bologna ; (3) Department of Health Physic S.Orsola-Malpighi Hospital Bologna; (4) Department of Neurology Bellaria Hospital Bologna, Italy Back~ouod: ESES is a neurological diseasecharacterized by elccu~cal status epilepticus in children which, if unrecognized,drives to aphasia,memory tossand other cognitive disorders. Nuclear medicine, either PET or SPECTstudies, has been employed m evaluatebrain perfusion in areasof possthle epileptogenic activity. Aim of the study; we aimed at evaluatingthe contribution of brain SPECT in detectingpossible epileptogenic foci in patients with electrical epi[epticus status during slow sleep. Studies were performed in childran injected awakened(intarcfitical studies) end during sleep(critical studies). Materials and i~ethods: Three children (g, g and 9 years old) with diagnosis of ESES who under,vent both ictal and inter-ictal brain SPECT have been enrolled in this study. Brain SPECT was carried out by meansof a three-headvariable angle system, equippedwith ultrahigh resolution collimators. For ictal studies (injection given asleep) children were preparod with a venous access placed on and then continuously monitored by experienced personnel until seizures appeared. [njectiun (Tc99m ECD at an amount adjusted for weight and age) was immediately carried out end imaging performed within 45-60 minuteS. For interictal studies, injection was given with children awakened. Possible epileptic loci were identified from visual comparisofi of both iota] end inteHctal studies. SPECT results were compared to clinical, EEG and MRI findings. Localizations were considered true positive when SPECT results were congruent with at least two of the other findings. Clinical results: on EEG end clinical data, we had 2 cases of temporal (right) and I case of parietu-occipital EEG localization of seizure. SPECT results: in case 1 and 2, SPECT showed a regional blood How increase in the right temporal lobe and in case 3, where the EEG localizatiun directed towards the right parieto-occipital lob(:, SPECT showed a regional blood flow increase in the right temporal lobe. Conclusions: Clinical characteristics of ESES (electrical activity detectable only during slow sleep end no typical MRI findings) brain SPECT performed with children asleep remains the

only methodsto investigatethis rate disease.

1224

• NEUROLOGY / PSYCHIATRY 4 / PHYSICS / INSTRUMENTATION 2 PS_582

PHYSICS / INSTRUMENTATION 2

THE ROLE OF INTERICTAL SPECT IN MANAGEMENT OF PATIENTS WITH COMPLEX PARTIAL EPILEPSY ACCORDING TO EEG AND

PS_584

RESPONSE TO MEDICAL THERAPY

S. Crnkovic (1), R. Petrovic (1), S. Hajnsek (2), Z. Poljakovic (2), Z. Jurasinovic (1), M. Poropat (1), D. Dodig (1). (1) Clinical Department of Nuclear Medicine and Radiation Protection; (2) Clinical Department of Neurology, University Hospital Zagreb, Zagreb, Croatia. Management of patients with complex partial epilepsy (CPE) is a significant neurological problem requiting interdiscip]inary co-operation, because they are often medically resistant and consequently, surgery remains an important treatment option. The aim of our study was to evaluate the diagnostic usefulness of interictal SPECT and to correlate SPECT findings in these patients with clinical symptoms, EEG and response to therapy. Methods: Interictal SPECT was used to examine regional cerebral blood flow (rCBF) in 21 patients with CPE (13 female, 8 male, median age 25 years, range 17-42), treated with different kind of ant[epileptic drugs. Of them, 64% had temporal lobe epilepsy (TLE), and 36% experienced seizures of extratemporal origin (Ext). All patients underwent EEG monitoring as well as CT/MRIs for comparison. SPECT scans were acquired 20 minutes after injection of 740 MBq of Tc-99m-ECD by IRIX triple headed rotating gamma camera and analysed on Odyssey FX 820 workstation. Images were analysed visually and semiquantitativelly. Results: All of our patients had normal CT/MRI findings. In 8 patients SPECT failed to identify any perfusion abnormality and correlated with mild clinical symptoms, EEG (normal in 10 patients, asymmetric in 2 and diffusely paroxysmally dysritmic in I) and good response to ant[epileptic therapy. However. 13 patients had abnormal SPECT (temporal hypoperfusion in 3 patients, frnntotemporal hyperperfusion in 5, basal ganglia hyperperfusion in 2, global hypoperfusion in 2). All of these patients had frequent seizure episodes, pathological EEG (diffuse paroxysmaly dysritmic, frontotemporal and temporoparietal focuses), and were refractory to medical treatment. Only in patients with TLE, SPECT lesions corresponded to EEG seizure focuses, while in patients with Ext focuses were dlfHcult to [oca/ise. Pattern of hyperperfusion corresponded to particularly intractable CPE patients. Conclusion: Although the SPECT brain imaging was performed on the patients during the interictal phase, there was a high correlation among SPECT findings, clinical diagnosis, EEG and response to medical therapy. We recommended it as a valuable diagnostic procedure, simultaneously with EEG monitoring, in medically refractory group of CPE patients with negative CT/MRIs, especially those undergoing surgical treatment. In a group of satisfactory treated patients interictal SPECT is of no particular clinical value, thus the performance of an ictal study is required.

ACCEPTANCE TESTING OF HYBRID GAMMA CAMERAS USING THE NEW NEMA PET DRAFT STANDARD G. Minear (1), G. Dobrozemsky (2,3), P. Schaffarich (2), H. Bergmann (2,4). (1) City Hospital, St. Poelten, Austria; (2) Department of Biomed. Eng. and Physics, University of Vienna, Austria; (3) Department of Nuclear Medicine, University of Vienna, Austria; (4) L. BoJtzmann Institute of Nuclear Medicine, Vienna, Austria Aim: Hybrid cameras when used in coincidence mode exhibit inferior image quality compared to conventional ring PET scanners. The new NEMA draft standard NU 2-2000 for performance measurements of PET systems accommodates both types of equipment and should emerge as a basis for comparison of performance parameters. Up to now no performance parameters were available from manufacturers. Methods: Following the new protocols three hybrid cameras from 3 different manufacturers underwent a set of acceptance tests, including measurements of spatial resolution, scatter fraction, count losses and randoms measurements, system sensitivity and image quality. The measurements were made with the axial collimation, energy window(s) and reconstruction software recommended for routine use by the manufacturers. The phantoms specified in the standard were produced locally. Manufacturer independent software for the evaluation of the measurements was used. All cameras passed the planar and SPECT acceptance procedures. Results: Tomographic spatial resolution in the center in air was 5.9, 6 2 and 6.3 mm FWHM for camera (I), (2) and (3) respectively. The scatter fraction was 46% for camera (1), 50% for camera (2) and 34% for camera (3). Count losses and randoms reflected by the NEC curves were measured for (2) only, since uncorrected raw data required for the calculations were not available on systems (I) and (3). System sensitivity was measured with the method of staggered sleeves of aluminium tubes. The axial sensitivity profiles showed essentially fiat profiles on both 3-D and 2-D systems. Image quality was visually assessed from tomographic slices through the centers of the hot spheres, and quantitatively determined by contrast measurements. At a target to background ratio of 8:1 the smallest sphere that could be visualized on camera (1) was ] 3 ram, camera (2) 13 mm and camera (3) 10 ram. Conclusions: Although we find the proposed draft of great value for camera-scanner intercomparison it is hard to strictly implement with current hybrid coincidence gamma cameras. Software and hardware requirements such as disabling random corrections and choosing the type of rebinning algorithm (SSRB vs. FORE) were not accessible for the end user on all systems. The main difference to NU 2-1994 is to use large phantoms that extend outside [ranger's axial field of view, which better simulates clinical imaging conditions. The effect was most clearly noted on relative high scatter fractions and lower peak NEC values than previously reported. ¢O

PS_583

PS_585

MALADAPTATION OF CEREBRAL PERFUSION IN THE SPINAL

CORD INJURED INDIVIDUALS

A TRIPLE-HEADED-HYBRID G A M M A CAMERA: PRELIMINARY EVALUATION OF COINCIDENCE PHYSICAL PERFORMANCES

I. Cho (1), K. Chun (1), K. Won (1), H. Lee (1), S. Ahn (2), K. Hayashida (3). (1) Department of Nuclear Medicine, Yeungnam University Hospital, Taegu, Korea; (2) Department of Rehabilitation, Yeungnam University Hospital, Taegu, Korea; (3) Department of Radiology, National Cardiovascular Center, Osaka, Japan.

F. Zito (1), G. Tarantula (2), S. Arrigoni (2), A. Bruno (1), R. Secli (2), M. Rognoni (1), D. Locatelli (2), M. Gasparini (1), B. Gaggia (2), V. La Bella (2), R Gerundini (1)(1) Nuclear Medicine Department, Ospedale Maggiore IRCCS, Milano, Italy; (2) Marconi Medical Systems Italia, Vimercate (MI), Italy.

Orthostatic hypotension is a common problem in the spinal cord injured (SCI) individuals with quadriplegia and paraplegia due to an impaired sympathetic nervous system. The aim of this study was to compare tilt-induced alteration of cerebral perfusion of spinal cord injured individuals with able-bodied (AB) individuals. Methods: Supine and uptight sitting brain-perfusian SPECT imaging was performed using a l-day protocol and 9'~Tc-ethylcysteinate dimer (ECD) in lI SCI individuals (2 women, 14 men; mean age, 32.6 y), with lesions between C3 and T4, and 5 AB individuals (2 women, 3 men; mean age, 31.4 y). Res~aits: In the SCI individuals, brain perfusion SPECT showed postural cerebral hypoperfusion in the frontal, temporal and parietal areas, of which the mean count ratio of the cerebralto-cerebellas area between the uptight and supine positions significantly changed. No postural changes in cerebral perfusion was evident in the occipital lobe, basal ganglia and thalamus in the SCI individuals. In the AB individuals, there were no such changes in cerebral perfuaion during the upright test.

Aim: The aim of this work was to evaluate the physical performances of a triple-headed coincidence gamma camera, in order to determine the best acquisition procedure and data processing for clinical applications. Methods: All the studies were performed with the IRIxTM- PETAz (Marconi, ClevelandOHIO-USA) having three _" NaI(TI) crystals with a 480x390mm coincidence FOV. ,,U" shape configuration (180i between heads 2 and 3) and axial collimators were used. Sensitivity profiles and spatial resolution were assessed with a 260 kBq 2:Na point source, placed at different distances from the axis of rotation (off-axis). Tomographic studies were acquired in listmode with 511 keV 4-20% energy window at different radii of rotation (ROT=15, 20, 22, 29, 35.5 cm). Projection data were generated from 2D rebinning (transverse acceptance angle=32i, axial acceptance angle=J6[). Spatial resolution in the three different directions (radial, tangential and axial) was measured in terms of FWHM of the point spread functian on transaxial and sagittal slices more representative of the point source, reconstructed with FBP

The mean count ratio of the cerebral-to-cerebellar area between the upright and supine positions in SCI individuals (n=14) Frontal : area Uptight 0.74±0.13 Supine 0.80i-O.12 P <0.01

Temporal area 0.80a:0A 1 0.86±0.13 <0.01

Parital area 0.93±0.13 1.06±0.15 <0.001

Occipital area 1.09~0.15 1,08±0.17 >0.05

Basal [an~;lia 1.11±0.14 1.17~0,17 >0.05

Thalamus 1.14-~-0.12 1,15±0.15 >0.05

Conclusion: Postural cerebral hypoperfusion in the frontal, temporal and parietal areas in the SCI individuals might relate to maladaptation of the vascular response during the upright position.

andRAMPfilter. Results: Spatial resolution, Fixed the source position, this parameter didn't depend on the radius of rotation, while moving the source off-axis it worsened tangentially and axially, as can be observed from the following data: (on-axis) radial--tangential=5.4mm, axial=6.2mm; (10 era off-axis) rad!al=5.2mm, tangantial=7.9mm, axial=13.5mm. Sensitivitv. Keeping the point source on axis and varying the ROT from 15 to 29era it had a constant value (_--0.8 cps/kBq), while it decreased of 8% using a 35.5cm ROT. For each radius of rotation, a uniform sensitivity profile was obtained moving the point source off-axis, showing that the third detector allowed the recovery of lines of response escaping from the two opposite heads which cause the typical linear decrease of double-headed coincidence systems. Conclusions: These preliminary results pointed out that a triple headed coincidence gamma camera has a uniform sensitivity profile across the FOV, resulting into an effective increasing of sensitivity with extended radioactive sources. In order to better characterize this system and improve its clinical performances, fiarther studies concerning noise-equivalent-count (NEC) and image quality analyses of anthropomorphic phantoms are under examination.

1225

t~ e-

t~

O~ O IX

• PHYSICS / INSTRUMENTATION 2 PS_586

PS_588

-

TRIPLE HEAD COINCIDENCE IMAGING ON GAMMAPET CAMERA SOME CLINICALLY RELEVANT PERFORMANCE TESTS

A PROGRAM CALCULATING NEMA RESOLUTION PARAMETERS IN GAMMA CAMERA SYSTEMS, BASED ON INTERFILE

D. Grosev, S. Loncaric, D. Dodig. Department of Nuclear Medicine and Radiation Protection, REBRO Hospital, Zagreb, Croatia.

H. Lonborg-Jensen. Dept. Nuclear Medicine, Glostrup University Hospital, Copenhagen County, Denmark.

Gamma cameras with the capability of coincidence imaging, when compared with dedicated PET scanners, have comparable spatial resolution but their sensitivity is still several times lower. Most currently available gammaPET cameras perform dual head coincidence with two opposite detectors. Adding additional detector would improve sensitivity of such systems. Our triple head gamma camera IR1X (Marconi Medical Systems, Inc. Cleveland Ohio, USA) is capable of pertbrming coincidence imaging with all three heads. We present some test imaging performed to determine optimal parameters regarding clinical acquisition of gammaPET Tomo studies. Methods: Count rate curves were obtained using two uniformly filled cylindrical phantoms: ,,.short" (de20 cm, h=20em), and ,,long" (d = 15 cm, h=gO cm) with range of F-lg activity concentrations 2-37 MBq/L and 0.5-10 MBq/L respectively. Two tomogrephic phantoms, one cylindrical with cold rods and cold spheres segments, and one elliptical with cold rods sagments, were filled with various amounts of F-18 activity to determine: I) possible image degradation when random coincidences start to predominate; 2) optimal choice of energy windows during acquisition to improve sensitivity; 3) resolution limit by observing the smallest group of phantom objects that are visible on reconstructed slices. Results: For maximum head radius of 35.5 cm, count rate curve for shun phantom is linear up to activity concentration of 17 MBq/L . For long phantom linearity of response is preserved up to 6 MBq/L. For long phantom, decrease of head radius from 35.5 cm to 28 cm leads to increase in count rate by 20 kcps on linear part of the curve. Loss of image contrast on elliptical ECT phantom slices, for head radius 28 cm, is visible for concentration up to 8 MBq/L. Using two energy windows (Photupeak + Compton) leads to more than 30% increase in total events rebinned compared with Photopeak window only. Resolution limit for cold objects is I0 ram. Conclusions: This investigation helped us to establish a preliminary clinical protocol: ) hour after injection of 370 MBq of FDG the first acquisition is started with Photopeak+Compton window. Two consecutive tomographic acquisitions can be preformed within an hour. without significant loss in sensitivity.

Calculating NEMA resolution parameters in planar, SPECT or PET gamma camera imaging. during acceptance testing or routine quality assurance, requires analysis of thousands of line spread functions. The commercially available gamma camera systems seldom offer simple solutions to this problem, leaving a time consuming problem to the physicist testing the

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To assist in solving this problem a MS Windows based program has been developed, allowing analysis ofrasolution measurements convened to [NTERFILE 3.3 format.

The program supports calculating FWHM and FWTM values from single or multiple slices of defined slice width in the tbtlowing matrix formats: 128*128*2bytas. 256*256*2bytes and 1024*1024*lbyte. Calculated parameters can be exported in various formats fur further analysis. The program has been tested on data from two gamma camera manufacturers.

PS_587

PS_589

COMPARISON OF LINE PROFILE VS FWHM METHODS IN QUANTIF3flNG OBJECT VOLUME ABOVE & BELOW SYSTEM'S LEAST RESOLVABLE VOLUME IN HYBRID PET IMAGING

EVALUATION AND CORRECTION OF COUNT LOSSES RELATED TO DEADTIME DURING CLINICAL TRIALS OF RADIOIMMUNOTHERAPY WITH IODINE-131

M.O. Afriyie, P.V. Pugliese, K.K. Bhargava, T.R Kalapparambath, M.B. Tomas, C.J. Patestro. Division of Nuclear Medicine, Long Island Jewish Medical Center, New Hyde Park, NY. 11040, USA.

L. Ferrer (1), G. Delpon (2i, A. Lisbona (1), M. Bardies (2). (1) Department of Nuclear Medicine, Centre Rene Gauducheau, Nantes, France ; (2) Inserm Unit 463, Nantes, France.

AIM: Accurate tumor staging, including differential imaging of metastatic vs recurrent tumors is dependent on the accuracy of volume detection in patient images. In volumetric imaging as in Hybrid PET, volume quantification depends on how faithfully the Apparent Volume (ApV) of the images data represents the object volume. Theoretical cutoff in volume resolution is defined as the Least Resolvable Volume (LRV) of a system, 6.3cc in our case. Object volume larger than LRV may be resolved & smaller than LRV may be overestimated. There are two methods frequently employed to estimate dimensions of an object. Using the dimensions so obtained. ApV of an imaged object can be calculated: Line Profile (LP) & FWHM methods are the commonly used methods by which dimensions of imaged objects are obtained from their images. This work compared the ApV (imaged volume) obtained by both methods to object's Actual Volume (AcV) to determine which method best restores volume of ohjccta. METHODS: 6 cylinders of axial diameter (d in cm) & known Volume (V in cc) of 3.2 &50,2.2 & 25,1.5 & 10. 1.0 & 5, 0.8 & 3, 0.5 & 1 were filled with nF-FDG solution of 0.74 MBq per ce. The cylinders were arranged in PET resolution phantom. Emission and transmission scans ( 137Cs source) were acquired. The attenuation corrected Transaxial images were then reconstructed into 3D images, the ApV. The base radius r and height h in cm. of each imaged cylinder were estimated by two methods: LP method; a line profile was drawn on respective images, r & h were calculamd. FWHM methods; Full Width at Half Maximum of the line profiles across the width and height were calculated, registered as r and h respectively. ApV was calculated mathematically using r & h in V(cylinder) = pi x r" x h & compared. RESULTS: ApV calculated using data from FWHM methods agreed exactly with AcV for every AcV that was equal to or greater than the system's LRV. For AcV smaller than the sysram's LRV, FWHM methods overestimated ApV by 2x. ApV estimated by using data from LP methods, however, resulted in 2x overestimation for volumes larger than system's LRV, & 4x overestimation for volumes smaller then system" LRV. CONCLUSIONS: Data show that for volumes above system's LRV. FWHM methods yield an ApV that is an accurate representation of the AcV. whereas LP overestimates AcV regardless of size ofobjoct volume.

Introduction: When dosimctric studies are performed during treatment (rather than after tracer injection), the high activities involved make quantification difficult because of gamma camera deadtime. This study in which count losses were considered in a matistic context proposes a correction method applicable to acquisitions during clinical trials (i.e. considering geometric and scatter conditions that influences count losses). Materials and methods: An initial evaluation step consisted in estimating the number of counts observed as a function of the real count rate. Increasing iodine-131 activities (up to 2.22 GBq) were added in a water tank, while ensuring a uniform source volume, images in list mode (energy: 0-750 keV) were acquired during 30s on a DST-XIi camera (SMViGEMS). To study the spatial distribution of count losses, several list mode images were acquired, first a standard source (37 MBq) then this latter juxtaposed with sources of increasing activity (up to 740 MBq). The acquisition of the standard allows the sensibility to be estimated without losses, The loss of sensibility on the standard on other acquisitions defines a correction factor that takes into account the geometric and scatter conditions. This method was tested in air on the previous acquisitions, and in scattering conditions on acquisitions performed on an Alderson anthropomorphic phantom with liver containing 740MBq. Results: Losses due to deadtime reached 20% for an observed count rate of 15 kcps on the 2 0 0 window (i.e. around 150 kcps for 0-750 keV). Our camera behaved like a paralysable system, with a maximum count rate of around 30 kcps on the 20% window. Losses before correction reached 30*/0 on the 740 MBq source and 22.5% on the standard. Acquisition from the 740 MBq source alone, together with spectral analysis, showed that this difference resulted from septal penetration through the collimator, which led to an underestimation of the cor~ction factor. However, the method allowed quantitative error due to count losses to be reduced to less than 10% for acquisitions with the anthropomorphic phantom. Conclusion: This study shows that count losses arc high for 15 kcps on the 2 0 0 window, h is possible to use a known activity standard to estimate losses occurring in the sources to be measured. Septal penetration leads to a quantification bias, but the difference with the real count value is less than 10%. Improvement of method precision would require the use of a high-energy, high-resolution collimator (which would also reduce the sensitivity of the gamma camera),.

122E

• PHYSICS / INSTRUMENTATION 2 PS_590

PS_592

MULTICENTRIC COMPARATIVE EVALUATION OF ABSOLUTE CALIBRATION OF POSITRON EMISSION TOMOGRAPHS

A COMPARISON OF THE QUALITY OF THE THYROID SCANS OBTA_NED BY 5 MM AND 7 M M PINHOLE INSERTS

L. Geworski (1), M. de Wit (2), V. Ivancevic (11, R. Bares (3), D.L. Munz (1). (1) Nuclear Medicine, Charite, Berlin, Germany; (2) Oncology, Hamburg, Germany ; (3) Nuclear Medicine, Tuebingen, Germany.

C. Ta~ci, G. (~apa Kaya, R. Bekis, (3. (3zdo<~qan,E. Demirta~, B. De~jirmenci, H. Durak. Department of nuclear medicine, Dokuz Eyt~l

Aim of this study was to test the accuracy of the scanners' calibration by correlating the image-pixel values to the true activity concentrations [Bq/ml] in tissue represented by a suitable phantom. This has been done comparatively for all devices included in a multicenter study. Methods: Measurements were carried out on a total of 23 tomographs of 7 difl;crent types. (Of these, 16 were investigated in both 2D and 3D mode, while 4 and 3, respectively, could be operated in 2D or 3D mode only. Measurements were done with a cylindrical phantom of 20 cm diameter and 20 cm axial length. Three emission scans with adequate counting statistics were acquired for each acquisition mode. All data were corrected for attenuation (transmission scan) and scatter as implemented in the scanners" standard soft:wares. The scanners" absolute calibration was checked by comparing the activity concentration in the phantom, known from volume and activity as determined in the dose calibrator, with the ROI data derived l~'om the image, and the cross calibration with two samples from the phantom and measured in a well counter. The dose calibrators were tested using always the same three Ge-68 standards containing 42 MBq, 4.03 MBq and 0.383 MBq, respectively. Results: All of the PET scanners investigated were suitable for visual data analysis. Five sets of measurements had to be repeated due to incorrect scanner calibration. Three tomographs had to be cross calibrated again, because their errors were significantly higher than 10%. In 2D mode thirteen out of twenty (65%) scanners showed errors <5% and another 4 (20%) errors around 10%. The respective error ranges were found in 10 (53%) and 5 (26%) of the 19 scanners tested in 3D mode. All the other scanners had errors from 5% to 10%. Due to hardware and sotb,vare problems the measurements performed on two tomographs could not be analysed adequately. Conclusion: In multicenter studies merging quantitative PET data from different institutions. a thorough investigation of the absolute calibration of the tomographs used is mandatory. (This research project was supported by the ,.Deutsche Krebshilfe" grant no. 70-2329).

Thyroid imaging using 5 mm pinhole insert (PI) increases the image quality but takes long time. The aim of this study was to compare the thyroid scans in quality and imaging time obtained fi'om the same patient using 5 ram. and 7 ram. Pf.'s. Methods: Twenty nine patients (mean age = 43.1 -+ 13.61 were included. All the patients had one or more thyroid nodules defined by uhrasonography. All the scans were 150.000 counts from ANT, RAO, LAO positions. After intravenous injection of 5 mCi Te99m pertechnetate, imaging was started with 7 mm Pt and continued with 5 mm PI. All the scans were evaluated by four Nuclear Medicine specialists independently and without knowing the imaging techniques. The specialists visually evaluated the scans from the aspects of the differentiation of the boundary of thyroid gland (first parameter) and the lesion detection from thyroid parenchyma (second parameter). They scored these two parameters (0: poor, 1: medium, 2: good, 3: high in quality) and noted the number of nodules as the third parameter. Student's t test for paired data and Pearson correlation test were used. Results: The mean imaging time of ANT projections obtained using 5 mm Pl (9.1 + 4.3 minutes) was significantly longer than those using 7 mrn PI (3.6 :t: 1.6 minutes). The mean score of only one o f the five observers for the first parameter was found meaningfully high in scans by 5 mm PI (p=0.05). The mean number of nodules counted b y / b u r of the observers were significantly high in scans by 5 mm PI (p=0.001, p=O.O00, p=0.046, p=0.030 respectively). There was no difference between the mean scores of the second parameter of two techniques evaluated by each observer. The correlation between the mean number of nodules counted by each observer fi~r each patient is found statistically meaningful (for 4 observers, r = 0.88, r = 0.78, r = 0.76, r = 0.71, respectively and p 0.011. Conclusions: While the mean imaging time using 7 mm PI is significantly shorter, the mean number of nodules observed in scans by 5 mm P! seems to be higher. If it is necessary to use 7 mm PI for thyroid imaging in local situations, it should be considered that there may be a risk of detecting lesser number of nodules.

University School of Medicine. Izmir, Turkey.

PS_591

PS_593

COUNTING SENSITIVITIES OF LOW ENERGY-COLLIMATORS IN 1-123 IMAGING: DEADTIME COUNT LOSS MEASUREMENT

CHOICE OF OSEM PARAMETERS DEPENDING ON TOMOGRAPHY ACQUISITION CONDITIONS

A. Kojima (1), M. Matsumoto (2), N. Katsuda (31, S. Tomiguchi (31, M. Takahashi (3), N. Motomura (4). (1) Radioisotope Research Center, Kumamoto University, Kumamoto, Japan; (2) Department of Radiological Technology, College of Medical Science, Kumamoto University, Kumamoto, Japan; (3) Department of Radiology, Kumamoto University School of Medicine, Kumamoto, Japan; (4) Medical

D. Huglo, Y. Venel, A. Delcourt, H. Benticha. F. Lejeune-Prigent, S. Perez, Y. Djagba, G. Nemchi, E. Hector, T. Prangere, M. Steinling Department of Nuclear Medicine, Hopital Huriez, CHU of Lille, Lille,

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Engineering Laboratory, Toshiba Corporation, Tochigi, Japan Radiopharmaceuticals labeled with 1-123 (159 keV) are employed in the SPECT studies for the brain and the myocardium. However, for quantitative 1-123 SPECT imaging, adequate collimator selection should be considered because of scatter or collimator penetration of higher energy photons emitted from 1-123. The aim of this study was to investigate counting sensitivities of low energy-collimators in 1-123 imaging with measuring deadtime count loss. Methods: Two low energy-coUimators were investigated: a Iow-anergy, high resolution (LEHR) collimator and a low-energy, general purpose (LEGP) collimator. Images and energy spectra for two low energy-collimators were acquired in air using a syringe containing 1-123 (300 MBq) and a digital gamma camera. A Tc-99m syringe (5.67 GBq) was also counted in air as the comparative radioisotope. For 1-123 and Tc-99m, counting rates were measured during about four days continuously and these time-decayed counting rates were correlated with counting rates by a radioisotope dose calibrator. Imaging energy windows were t59 keV ± 7.5% for 1-123 and 140 keV ± 7.5% for Te-99m, respectively. The source to camera distance was 10 cm for each measurement. Results: For 1-123, count loss occurred at 5.5 kcps (--45 MBq) for the LEGP collimator and 4.0 kcps (-37 MBq) for the LEHR collimator. For Tc-99m, however, count loss occurred at 55 kcps (-500 MBq) for the LEGP collimator and 55 kcps (~1000 MBq) for the LEHR collimator. For 111 MBq of 1-123, count losses were -3.5% and ~7% for the LEGP collimator and the LEHR collimator, respectively. For 222 MBq of 1-123, count losses became greater, ~7.2% and ~17.3% for the LEGP collimator and the LEHR collimator, respectively. For other larger amount of 1-123 , dead time count loss of the LEHR collimator became severer than one of the LEGP collimator. Conclusion: For the low-energy collimators, higher energy photons (440 keV, 529 keV, and so on) emitted from 1-123 cause deadtime count loss in the 159 keV imaging window at lower counting rate as comparing with Tc-99m and the count loss is affected by the amount of 1-123. Therefore, suitable low energy-collimators with low septal penetration for higher energy-photons should be selected in quantitative [-123 imaging.

France. Fast itarative reconstruction methods such as the ordered-subset expectation maximum (OSEM) usually provide better results in bone SPECT than filtered beckprojection. With the OSEM no filters am chosen but two parameters have to b¢ fixed : the subset number iS) and the number of iterations (11. In bone SPECT with 64 projections, 8 subsets and 2 iterations are recommended in the literature as being the best visual compromise. The aim of this study was to determine the best parameters in pulmonary SPECT and bone SPECT with 32 projections. Method: All the tomography data were obtained with a Sophy DST-XLI (SMV) gamma-cam99 era. For studies of pulmonary perfusion, at~er injection of 110-150 MBq of mTc-MAA, 64 projections (64x64, 20 seconds per projection) were recorded over 360 i. For the bone SPECT, 2 hours al~er injection of 740 MBq de 99mTc-DPD, 32 projections (128x128, 40 seconds per projection) were recorded in proeubitus over 180 i. In each study, 12 reconstructions were produced using Vision's OSEM program (SMV), with I varying from 2 tO 5 and S equal to 4, 6 or 8. The same slices, centred on anomalies when these existed, were printed out and examined separataly by 6 nuclear medicine specialists. For each study, each observer chose 1 to 3 best reconstructions and ranked them in 1~, 2 "l and 3 'd order. For each reconstruction, the number o f the choices were summed without weighting and then with weighting (3 for 1x choice, 2 pour 2 ~ and I for 3rd). Results: Three patients were studied for the pulmonary perfiasion SPECT, In decreasing order without (and with) weighting the choices were 13-$6 : 9 (23), 12-$8 : 9 (21), 13-$8 : 8 (8) and I4-$6 : 7 (14) then the other combinations. For the bone SPECT, 6 patients were studied. The choices were 12-$6 : 22 (571, I3-$6 : 15 (29), 13-$4 : 13 (20), 12-$8 : 11 (16) and 12-$4 : 9 (25) then the other combinations. Conclusion: For the pulmonary perfusion SPECT (64 projections o f 64x64), 2 iterations with 8 subsets or 3 iterations with 6 subsets were the best choice of OSEM parameters with very discrete visual differences. For bone SPECT, although only 32 projections were obtained because of a smaller number of projections per subset than with 64 projections, the best choice of OSEM parameters was clearly 2 iterations and 6 subsets.

0

• RADIOPHARMACY / RADIOCHEMISTRY 3 PS_594

PS_596

RADIOSYNTHESIS OF 4-[18F]FLUORO-H88, AN ANALOGUE OF H89, A POTENT CYCLIC AMP DEPENDENT PROTEIN KINASE INHIBITOR: REDUCTIVE AMINATION OF 4-[18F]FLUOROCINNAMALDEHYDE

SYNTHESIS OF 2'-DEOXY-2'-(18F)-FLUORO-1-BETA-DRIBOFURANOSYLURAClL

K. Takahashi, S. Miura, M. Ibaraki, J. Hatazawa, E. Shimosegawa, H. Ito, H. Tamura, K. Okane, I. Kanno. Radiology and Nuclear Medicine, Reseach Institute for Brain and Blood Vessels -Akita, Akita, Japan. For studying intracellular signal transdoction system in the human brain, several radiolabeled compounds for positron emission tomography (PET) were investigated, for example, it iC]dia. eylglycerol; a protein kinase C activator, and [i ;C]rolipram; a phosphodiasterase-4 inhibitor. But it has not reported to label a cyclic AMP dependent protein kinase (PKA) inhibitor, such as H89 (N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide). Potent PKA inhibitors labeled with positron emitter would be useful for imaging cyclic AMP function in . . . . . . . s the hwng human tissue using PET. The aim of this study was to synthaslze 4-[ F]fluoro-H88 . . . . . . ts (N-[2-(4-flunrocmnamylammo)ethy1-5-~soqumohne-sulfonamlds) , a [ F]olabeled analogue of Hg9, via a novel labeled precursor 4-[ JSF]fluorc¢innamaldehyde. Methods: No-carrier-added [ISF]fluoride was produced by 18 Mev proton irradiation of [ISO]water. The [ISF]flunride produced was activated by tetrabutylammonium carbonate under anhydrous condition. The nucleophilic aromatic substitution of 4-trimethylammonium. cmuamaldehyde inflate by the activated [ F flunr=de was performed m DMSO at 120 C for I0 min. The 4-[ISF]fluorocinnamaldehyde produced was isolated by SEP-PAK silica purification, and subsequently, was reductively aminated with H9 (No(2-aminocthy)isoquinoline-5sulfonamide), using sodium cyanoborohydride and acetic acid. Reaction was complete upon heating to 120 °C for 5 min in DMSO. The 4-[l~F]fluoro-H88 produced was purifed by a preparative reversed phase HPLC system. After evaporation of solvent, the final product was dissolved in saline and passed through a sterile filter. Results: The radiochemical yield of 4-[18F]fluorecinnamaldehyde was typically 40-60 % based on [ISF]flunride. The radiochemical yield of 4-[l"F]fiunro-H88 was 30-40 % based on 4-[ISF]fluorocinnamaldehyde, and the radiochemical purity was better than 95 % (HPLC: InertsiI-ODS2; 4.6 mm x 250 ram, O.IM AcONH4/CHzCN/AcOH = 500/500/I, flow rate = 2 ml/min, retention time = 3.0 rain). The over all time of synthesis including purification and sterilization was 80 rain after end-of-bombardment, The formulated products, ready for biological studies, proved sterile and pyrogan-frea. Conclusions: 4-[ F]fluoro-H88, a [ F]-labeled analogue of H89, has been synthesized in a good yield under no-carrier-added condition. This radiotabeled tracer will provide further biological studies for clinical applications with PET. Both aromatic [l~F]-flunrination of cinnamaldehyde and reductive amination of 4-[~F]fluorocinnamaldehyde gave good yields. The labeled cinnamaldchydc may be a useful synthetic precursor for the radiosynthcsis of other complex radiotracers for use with PET. .

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S.H. Ahn, Y.S. Cho, K.S. Chun, S.D. Yang, Y.S. Suh, C.W. Choi, S.W. Hong, S.M. Lira. Cyclotron Application Lab. Korea Cancer Center Hospital Secul Korea. Aim: I~F labeled 2'-flunro-I-I:~-D-ribonucleosides can be important candidates for cancerrelated imaging tracer, especially in the field of the cancer gene therapy using herpes simplex type I virus thymidiea kinase(HSV-tk) suicide gene as well as in cancer diagnostics. The presence of the 2'-fluoro-ribo substituent has been shown to confer biochemical stability to pyrimidine nucleoside as in the case of 5 o(2-[I-'Sl]iodovinyl)-2 '-fluoro-2 'deoxyuridine(IVFRU). But the direct stereospecific introduction of radiofluorine at the 2'postuon" " of the sugar moiety in pyrimidinc~s '-d nucleosides has not been tried so much. Here we report an symhetic method for [ F]2 eoxy-2'-fluoro-[~-D-ribonucleosides from O-tetrahydropyranyl- precursor, useful in that its protecting group is easy to intreducc and remove. Methods: 3',5'-di-O-tetrahydropyranyl-l-[~.D.arabinofuranosyluracil was converted to 2'-O(trifluoromethane sulfonyl)-3",5"-di-O-tetsahydropyranyl-l-[]-D-arabinofuranosyluracil (triflare) with 40% yield. Fluorination of the triflate with tetrabutyiammonium fluoride in THF for several hours gave the desired product. It was also prepared from 3',5'-di-O-tetrahydrepyranyl-I-[LD-atabinofuranosyluracil by the diethylaminosulfur trifluoride(DAST) and identified by rH NMR spectroscopy. For radiocbemical synthesis, I~F-fluoride was placed in a vial containing K2CO3/Kryptofix and evaporated to dryness. The dried fluoride was reacted with 2'-O-trifate in acctonitrile at I t0°C for 20rain, then followed by acidic hydrolysis for 20min. The crude product was purified by C-18 Sep-Pak cartridge and analyzed by HPLC. Results: The radiochemical yield was 10-20% with >99% radiochemical purity in 3 runs. Synthesis time was 80-10Omin from the EOB. Conclusion: 2"-O-(Trifluoromethanesut fonyl)-3 ',5"-di-O-tetrahydrepyranyl- 1-[3-D-arabino furanosylurscil was labeled with ISF and deprotected easily in good yield. This method can be applied to preparation of new 2'-radiolabeled ribofuranosylnucleosides for PET studies.

PS_595

PS_597

AUTOMATED FLT SYNTHESIS USING 3-N-BOC-I-{5-O-(4,4,,DIMETHOXYTRITYL)-3-O-NOSYL-2-OEOXY-§-D-LYXOFURANOSYL)THYMINE AS PRECURSOR

PREPARATION OF LIPIODOL SOLUTION OF 188RE-4-HEXADECYL2,2,9,9-TETRAMETHYL-4,7-DIAZA-I,10-DECANEDITHIOL (HTDD) FOR TREATMENT OF LIVER CANCER

C. Mosdzianowski (1), M. Eisenhut, J. Martin, J. Eisenbarth, C. Korenjak, M. Nader. (1) Coincidence Technologies s.a., Liege, Belgium; (2) DKFZ Heidelberg, Abt. Radiechemie, Heidelberg, Germany; (3) Argos Zyklotron Gesmbh, Klagenfurt, Austna.

J.-K. Chung (1), Y.J. Kim (1), J.M. Jeong (1), Y.-S. Lee (1), D.S. Lee (1), Y.-G. Suh (2), M.C. L (1). (1) Department of Nuclear Medicine; (2) Pharmaceutical Manufacturing Chemistry, Seoul National University College of Pharmacy, Seoul, Korea.

Aim: [ISF]FLT (3'-fluoro-3'-dcoxythymidine) has been developed as a thymidine analogue for PET imaging in vivo. We investigated the use of a commercially available FDG synthesizer based on a disposable kit system for the synthesis of [=SF]FLT. Methods: The automated [ F]FLT synthesis was based on the method recently developed by is Martin et al. The first steps of the synthesis are identical to the first steps of the [ F]FDG syn. ennched. water recovery . . . exchange cartridge, elutton of isF using 7 thests: throug~ an anlun mg of K2CO 3 and 22 mg of Kryptofix 222, evaporation of the solvents before labeling and dissolving of the precursor in 3.5 ml of acetonitrile. ARer evaporation the precursor, 3-N-Bocl-(5-O-(4,4'-dimethoxytrityl)-3-O-nosyl-2-
It has been reported that lipiodol solution of ISSRe-2,2,9,9-tctramethyl-4,7-diaza-l,10decanedithiol (TDD), a kind ofN2S ~ derivatives, accumulates in the liver cancer effectively if injested through the hepatic artery. However, its therapeutic effect might not be ideal as it dif. . . . fitses out of the cancer tissue m several hours. To increase the retent on of R©-TDD m the liver cancer, we introduced long chain alkyl groups to TDD, which will increase van der Wanls interaction with lipiodol molecules. Although the tissue uptake and retention increased as the introduced chain length become longer, labeling efficiency decreased in reverse. The low labeling efficiency is mainly related with the low solubility of the ligand. We tried to find out adequate condition for labeling lsaRe-HTDD-Iipiodol. Methods: 5-Hexedecyl-3,3,10,10-tatramethyl-l,2-dithia-5,8-diazacyclodecane was synthesized by N-alkylation with iodohexadecane in the presence of potassium carbonate in acetonitril¢. HTDD was obtained by reducing 5-hcxedecyl-3,3,10,10-tatramethyt-l,2-dithia-5,8diazacyclodecane with zinc powder in concontrated hydrochloric acid. To 1 mg HTDD, tartaric acid (30.-40 ms), SnClz.2HzO (3 rag) and lURe-petrhunate (37-590 MBq/3 ml) were addod. To adjust pH, adequate amount of 0.5 M trisodium phosphate, 2 M disodium phos, sodium bicarbonate were added. After heating for 1 hr at 100°C, 10% sodium phate and 10% bicarbonate was added to adjust pH 8.5. Lipiodol (3.--4 ml) was added to the reactant and mixed. Upper water phase was removed aRer cuntrifugation at 3000 tpm for 10 rain. Radiochemical yield was determined by moasuring the radioactivity of each phase. Radiochamical purity was checked by 1TLC-SG/ethyl acetate or saline. Results: At pH 4.5, 5.5, 6.5, 7.5, 8.5, and 9.5 radiochcmical yields were 18.7 + 10.9% (n=7), 6.7%, 23A%, 46.2 + 8.0 (n=7), 35.4%, and 33.9%, respectively, and radiochemical purities were 93.1 + 2.5% (n=5), ND, ND, 96.2 + 1.0% (n=6), 95.4%, and 95.5%, respectively. In the preparations using 2 M sodium phosphate for pH adjustment, a whitcqaycr between aqueous and lipiodol phase was formed. Radioactivities of the white-layers were 35.5~69.7~. Conclusions: We established an optimal condition to [abe[ Re-HTDD-lipiodol that can be used for liver cancer therapy.

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• RADIOPHARMACY / RADIOCHEMISTRY 3 PS_598

PS_600

EDTMP DRY KIT FOR TC-99M, SM-153, LU-177 AND OTHER LANTHANIDES LABELLING

SERUM CA 125 LEVELS VERSUS DISEASE CHARACTERISTICS IN PATIENTS WITH NHL

R. Mikolajczak (1), D. Pawlak (1), P. Garnuszek (2), I. Licinska (2). (1) Department of Radiopharmaceuticals, Radioisotope Centre POLATOM, Otwock/Swierk, Poland; (2) Radioisotopic Drugs Department, Drug Institute, Warsaw, Poland.

I. Zaharos (1), I. Ilias (2), E. Petreli (1), C. Batsakis (2), G. Panoutsopoulos (2), P. Roussou (1), I. Christakopoulou (2). (1)Third University Department of Medicine, ; (2) Department of Nuclear Medicine, Athens, Greece.

The aim of our study was to develop the freeze-dried kit for preparation of EDTMP chelates with radio-lanthanides e.g.: Sm-153, Lu-177 or Ho-166, likewise with ,.diagnostic" Tc-99m a potential bone scanning radiopharmaceutical. Methods: Stannous chloride and ascorbic acid were added to the kit. Low specific activity ' Lu-177 (1 and 7.6 GBq/mg of Lu) was used for formation of t?7Lu-EDTMP. Labelhng y ie Id s 177 99 of Lu-EDTMP and ~Tc-EDTMP were investigated in function of ligand, stannoas chloride and stabiliser concentrations. Stability, and biodistribution in healthy rats was compared to 153Sm-EOTMP (EDTMP 17.5 mg/ml, 153SmCI3of spec. act. 35 GBq/mg Sm). Results: Our previous studies on EDTMP complexes confirmed that stable chelates were formed easily, in the broad range ofpH and stuichiometry. In present study, we observed that deposition of the ~mTe-EDTMP activity in femur increase with decreasing of the ligand concentration. Looking for compromise between yield and bone deposition, we used 15 mg of the ligand in the kit, which has been designed for total volume of 2 ml for lanthanides (spec. act. rain 2GBq/mg), and of 5 m] for Tc-99m (total act. m a x 8GBq). Addition of 0.2 mg of the stannous chloride was sufficient for '~Tc(VII) reduction and obtaining stable ~ T c - E D T M P complex. The same kit used for t77Lu-EDTMP preparation showed good stability, especially when higher specific activity t77Lu was used, Biodistribution studies of 177Lu- and ~mTc-EDTMP revealed similar tissue uptake and clearance to those observed with 153Sm-EDTMP (see Table). The most significant difference was found in retention of activity in kidney, which in the case of'~mTc-EDTMP was the highest reaching ca. 6 % of the accumulated dose after 90 min p.i.~ The normalised EDTMP chelate accumulation in the rats tissue 30 and 90 minutes p.i.v. (percent of accumulated activity in lg of tissue x BW/100)

CA 125 is a glycoprotein expressed by epithelial ovarian tumors, pelvic inflammatory disease, hepatic disease and tuberculous effusions. Few studies have shown CA 125 to be also elevated in patients with non-Hodgkin~(s lymphoma (NHL), especially in the presence of serosal involvement. The aim of the present study was to further evaluate CA 125 levels versus NHL characteristics in patients with and without plenral and/or peritoneal involvement, We studied 21 men and 21 women (mean age~SD: 59±17 y.o.) at the initial diagnosis of the disease, as well as during treatment and/or at the end of therapy. The following clinical parameters were taken into consideration: sex, age, disease stage, presence of symptoms, disease localization as well as serum LDH. CA 125 levels were measured with IRMA (normal< 30 ng/mL) and assessed, using multiple correlation analysis - implementing Bunferroni<
Tissue

~Sm(lll) n = 15) 30 rain p.i.v. Lun~,s 0.67+0.23 Liver 0,27_+0.I I Kidne},s 4.05_+2.05 Femur 7.43+-0.22

~'JLu(Ill) (n = I1) 90 rain p.i.v. 30 min p.i.v. 0.07+0.04 0.44+0.14 0.13+-0.01 0.21 +0.07 0.84+-0.13 3.31+-1.34 11.05+-1.27 8.15+-0.95

~Tc(1V) In=9} 90 rain p.i.v. 30 rain p.i.v. 0.10_+0.05 0.69±0.17 0. I 0~0.04 0.38+-0.18 1.29+-0.52 7.36+-2.03 10.83+1.10 7.78+-0.93

90 min p.i.v, i 0.20+-0.18 0.20-2_0.09 5.98+-3.25 9.55-+0.69

Conclusions: The developed freeze-dried kit Ibr EDTMP chelate formation can be utilised for preparation of bone-seeklng radiopharmaceuticals Le. '~mTc-EDTMP as well as 177Lu-EDTMP, and due to similar chemistry, can be used for other ,,medicaP' radio-lanthanides. The kit content (15 mg EDTMP, 5 mg ascorbic acid. 0 2 mg Snell) ensures a one-step radiopharmaceutical preparation of a high radiocbemical purity, as well as sufficiently long shelf-life.

co

PS_599

PS_601

STUDY ON A NOVEL POTENTIAL PERFUSION IMAGING AGENT

PERFORMANCE OF MYOVIEW KIT: HIGH SPECIFIC ACTIVITY AND SPLIT DOSES

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R. Saponaro, G. Cannizzaro, C. Aprile. Nuclear Medicine Serv,, Fond. S.Maugeri- CI. Lav & Riab. IRCCS, Pavia, Italy.

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R.E Wang (1), C.L. Zhang (1), S.L. Zhu (1), Y.B. Miao (2), Z.G. Tang (2), B.L. Liu (2). (1) Department of Nuclear Medicine, Peking University, Beijin, P.R.of China; (2) Department of Chemistry, Beijing Normal University, Beijing, P.R.of China. A i m : To search for a novel potential SPECT cerebral blood flow perfusion imaging agent. Methods: Tridentated MPBDA with N2S obtained from chemical synthesis and characterized

by IR spectrum, IHNMR, element analysis and MS was labeled with Tc-99m under optional conditions. Biodistributiun in 25 mice was performed at different time points after intravenous injection of 100 laL 555 ~ 740 kBq Tc-99m-MPBDA. The dynamic imaging in 2 monkeys was immediately acquired following rapid injection of 218.3 ~ 333 MBq Tc-99m-MPBDA or Tc-99m-ECD, and monkey whole body imaging and cerebral tomographic imaging were performed at 70 rain postinjection. Preclinical studies including toxicity and pyrogen tests in mice and rabbits were taken. Results: The radiochemical synthetic yield and radiechemical purity of MPBDA labeled with Tc-99m were more than 95 %, 97 %, respectively. Biodistribution results of Tc-99m-MPBDA showed high uptake and good retention in mouse brain, and blood clearance half time was less than 15 rain. The cerebral dynamic blood flow perfusiun imaging in monkey demonstrat* ed at 2 rain after administration to attain the maximum radioactivity of Tc-99m-MPBDA in the brain (Tin=). In comparison with activity at 2 min postinjection, 83 percents of initial activity remained in brain at 60 min images. It was showed that the brain uptake reached to 2,7 %ID at 70 rain postinjection from the whole body imaging, which was slightly inferior to that of Tc-99m-ECD (2.9%ID). The tomographic images showed that the activity remained in gray matter was higher than that in white matter, with good contrast of imaging, No death, toxic and side-effects, pyrogen in mice and rabbits after injection of Tc-99m-MPBDA was found. Conclusion: The results of this study revealed that Tc-99m-MPBDA possessing similar property of Tc-99m-ECD, and the initial high brain uptake and ideal brain retention in monkey was favorable for SPECT imaging. This pruposed compound as a radiopharmaceutical showing safe and reliable in vivo appeared to b¢ a novel potential cerebral flow perfusion imaging agent.

AIM Although manufacturers discourage the adoption of any procedure other than strictly according to instructions, ,,in house" procedures, when supported by quality control and validation schemes performed in compliance with good radiopharmacy practice, may provide accurate and reliable products. In this work we have tried out an alternative method for the labelling of Myoview (Nycomed Amersham Sorin). METHODS Eleven whole Myoview kits were reconstituted with the recommended volume of ~ T c but with an activity between 60 and 120 MBq/l.tg of tetrofosmin (TF), highly exceeding the upper limit of 39 MBq/~tg specified by the manufacturer, As a second step we analyzed ,,in vitro" the effect of reconstitution, freezing and thawing of splitted Mynview kits on the labelling efficiency of the stored products. The kits were reconstituted with sterile nitrogen purged 0.9% saline and subdivided into fractions; 12 fractions were labelled immediately after reconstitution with saline, 12 were stored at -70iC and thawed for labelling at different times up to 66 days, Radiochemical purity (RP%) was checked by the usual TLC method (Gelman 1TLC-SG strips and acetone/dichlorumethane as solvent) 30 minutes after labelling. Finally, 17 of the 35 Myoview preparations, after appropriate testing for stability and sterility, were used ,,in vivo", and a blind observer compared the clinical images provided by Myoview prepared as recommended with those provided by the alternative methods, RESULTS The RP% of the 11 whole kits proved in all cases >90% and the labetted product was stable up to 6 hours, No significant differences in RP% were found between fractionated Myoview and whole kit, as well as between freshly prepared and frozen fractions. Also, the labelling of all frozen doses did not seem to be affected by storage time at least up to 35 days, when a downward trend was observable. No significant differences could be detected in the ,,in vivo" biodistribution of Myoview prepared with the two labelling methods. n. Whole kit ,,Freshly prepared" fractions Frozen fractions

Activity MBq/Ltg TF Mean Ran~;e I I 104 60-120 12 187 57-330 12 131 64-20

RP% Mean ± SD 96.8 ± 2.46 96,6 ~: 2.49 93.3 ± 4.11

range 91-99 91-99 87-98.6

CONCLUSIONS Myoview allows higher specific activity than recommended and the practice of ,,kit splitting". This approach offers advantages in terms of radiation dosimetry to the operator, reduces cost per patient/dose and optimizes work management, without significantly affecting ,,in vivo" test performance.

1229

O IX

• RADIOPHARMACY / RADIOCHEMISTRY 3 / CARDIOVASCULAR 7 PS_602

PS_604

BIODISTRIBUTION OF GA-67-DOTA-LANREOTIDE IN ANIMALS

TECHNETIUM LABELING OF SURFACTANT PROTEIN B (SP-B)

I. Szilvasi (1), J. Janoki (2), P. Angelberger (3), I. Virgolini (4). (1) Dept. of Nucl. Med., Semmelweis University, Budapest, Hungary; (2) FJC National Inst. For Radiobiology, Budapest, Hungary; (3) Research Center, Seibersdorf, Austria; (4) Dept. of Nucl. Med., University of Vienna, Austria

M. Wenger (1), R. Alberto, C. Decristoforo, A. Amann, R. Moncayo, G. Putz. (1) University Clinic of Nuclear Medicine; (2) University Clinic of Anaesthesiology, Insbruck, Austria.

Lanreotide is a long-acting somatostatin analog with binds to all 5 subtypes of somatostatin receptors. High affinity binding of Ga-67-DOTA-lanreotide to a variety of tumour ceils has been previously tbund. Aim of the present work v, as to study the biodistribution of Ga-67-DOTA-lanreotide in dogs and tumour-bearing nude mice. Methods: 20 microgram of DOTA-lanreotide was labelled with 20-40 mCi of Ga-67-GaCI3 with high specific activity. Labelling etticiency was more than 92 per cent by ITLC and HPLC techniques. Gamma camera images were taken in 5 beagle dogs at 10 minutes, 2, 24 and 48 hours after i.v. injection of 2-4 mCi labe|ied substance. Activity of blood samples taken lbr 48 hours were also measured. Scintigraphy of 3-3 nude mice bearing MKN..45 and HT-29 tumours were performed. Organ distribution of activity in mice was measured ex vivo after 48 hours. Results: scintigraphic images of Ga-67-DOTA-lanreotide were similar to ln-IIl-octreotide images in normal dogs. Activity of the liver was high and a predominant renal excretion was found. Half-time of disappearance of activity from the blood was 98.5 minutes. 14.1 per cent of the activity - measured at 5 minutes - were present in the blood al~er 24 hours. 6.33 and 7 . 4 1 % per gram tissue of the injected activity were found in MKN-45 and HT-29 tumours respectively. Conclusions: Ga-67-DOTA-lanreotide may provide the basis tbr producing a Ga-68 labelled somatostatin receptor imaging radiopharmaceutical.

Lung surlhctant is a lipid (90%1 - pn)tein (10%) mixture, produced by lung alveolar cells type II, which lowers the surthce tension of the lung under physiologic conditions. In acute respiratory distress syndrome (ARDSI the lung surthctant system is altered with respect to both composition and surface acti,,ity. Treatment by instillation of lung surihctant into ARDS lungs has lead to controvcrsal results. Aim of the study was to develop a Tc-99m labeling technique of bovine surfactant tbr the seintigraphic observation of its spreading in vivo. Methods: Bovine surfactant was isolated according to the method of Van Eijk and directly incubated with [Tc(COh(H20)3" ] at 65-70iC under various conditions. Determination of radiochemical purity was perthrmed with paper chromatography and size exclusion chromatography. The protein characterisation was done by means of silver staining and Western blot analysis combined with enhanced chemoluminescence using a SP-B antibody. Spreading experiments were perlbrmed in a rectangular 2-D glass trough filled with isotonic butler. The spreading of the surthctant on the butter surtat:e was observed by 1) surface tension measurements (Wilhelmy technique), 2) Gamma camera imaging (Siemens ZLC, static [64 x 64 matrix, I s frames]and dynamic [256 x 256 matrix, 200000k]mode). Results: Tricine/SDS PAGE gel electrophoresis revealed no differences between labeled and unlabeled SP-B. The labeling yield in the organic phase was more than 70%. The labeled protein showed high stability. Only SP-B together with phosphlipids showed marked surthce activity, the control runs were negative ([99mTc(COI3 (H20)3]+ or TcO4- mixed with natural surfactant extract; 99mTc-SP-B without other components). Conclusions: Direct and specific 99mTc-labeling of the hydrophobic surlactunt protein B was achieved using the [Tc(CO)3(H:Oh']prccursor. This procedure can easyly be used to prepare specifically labeled surtactant mixtures with spreading properties that coincide with those of unlabeled surlhctant, i.e. the presented labeling method does not diminish the biological activity.

PS_603

CARDIOVASCULAR 7

OPTIMIZING CONDITIONS FOR RADIOLABELLING DOTA-PEPTIDES AT HIGH SPECIFIC ACTIVITY

W.A.P. Breeman (1), M. de Jong (1), T.J. Visser (2), W. Goedemans (3), J.L. Erion (4), W.H. Bakker (1), E.R Krenning (1). (1) Nuclear Medicine; (2) Internal Medicine; (3) Mallinckrodt Medical, Petten, NL; (4) Mallinckrodt, Discovery, St Louis, USA Objectives: DOTA-conjugated peptides, such as [DOTA°,Tyr3]octreotate (DOTA.tate) and t 4 61 9o [DOTA-Pro ,Tyr ] bombesin, can be stably labelled with radionuclides such as Ga, Y, /Hln and 177Lu. These radiolabelled peptides are nowadays in use in the field of Nuclear Medicine, including peptide receptor radionuclid¢ therapy (PRRT). Radioligands for PRRT require high specific activities (SA), since the amount of ligaod that can be administered is limited: A. an increase in ligand will also increase the competition between ligand and radioligand for the same receptor and B. in case the peptide is bioaetive Le. bombesin. Parameters influencing the reaction kinetics during radiolabelling were investigated, as well how to obtain the highest achievable SA with maximal radiochemical purity. Results: Reaction kinetics were optimal at pH 4-5, while pH ~; 3 strongly slowed-down the kinetics. Above pH 5 reaction kinetics varied: the solubility of the radionuclide becomes uncertain, due to rapid formation of hydroxides, The reaction kinetics of labelling with the radionuclides were also 177 found to be different. The reaction was complete for Y and Lu after 20" at 80? and for iii ,7 . . was .~erformed . at mlcroscale: . In after 30 at 100.. gadtotabelhng 1-10 mCt In lf-ffl p.L, and at macroscale: _> 500 mCi in -> 2 mL. J= In-DOTA-tate was labelled up to SA of 25 mCi Hiln per nmoles, which is half of the theoretical maximum SA. Radioehemical purity of > 98% directly after, and > 90% 24 h after the start of the labelling, could only be achieved after additions of Na-ascorbate and/or gentisic acid (during the reaction) and even longer by further dilution, and/or the addition of ethanol directly post labelling. The additions proved to be very efficient to prevent radiolysis, as revealed by ITLC and HPLC. Conclusions: DOTApeptides can be radiolabelled at very high SA with high radiochemical purity.

1230

PS_605 INTRACORONARY INJECTION OF TC-99M TETROFOSMIN IN INFARCT RELATED ARTERY: A COMPARISON TO IV INJECTION FINDINGS IN REST SPECT STUDIES AFTER ACUTE MYOCARDIAL INFARCTION T. Bai~oOlu (t), E Canbaz (1), M. Elcik (2), M. ~ahin (1), S. Albayrak (1), O. Yapml (1). (1) Department of Nuclear Medicine; (2) Department of Cardiology, Ondokuz Maym University, Samsun, Turkey. 99m-To Sestamibi SPECT is a well accepted method in the measurement of the infarct size .which is an important indicator of the efficacy of therapy in acute myocardial infarction (AMl).Clinical investigations regarding the diagnostic power of the more recent agent Tc-99m Tetrofosmin (TF) in this issue are necessary. Our objective was to compare the rest SPECT findings in AM! patients aRer selective intracoronary (IC) and intravenoUS (IV) injections of TF, that has a lower first-pass myocardial extraction fraction compared to 99m-Tc-Sestamibi. METHODS: Sixteen patients 13 M, 3F (54+10 yrs) with AMI were examined. We performed two rest TF-SPECT acquisitions within 10 days after admission and tTombolytie therapy (TT).Coronary sogiograpy (CAG) was performed for all patients after Yr. First SPECT was performed within 30 minutes following IC injection (IC-SPECT) of 74 MBq TF only in the infarct related artery (IRA) during CAG. Two days at~er CAG, second SPECT was acquired 45 rain after IV injection (IV-SPECT) of 740 MBq TF. Regional TF defects of the infarct area were visually scored (DS) by a 4-point system. A score index (SI) was calculated in both studies (SleDS/Number of infarct related segments). RESULTS: Global correlation of SI values between IC-SPECT and IV-SPECT in all 16 patients was significant(Re0.75, P=O.001). No global correlation could be found between the degree of IRA stenosis and S[ values in both studies. Statistical analaysis was repeated after exclusion of 6 patients with multivessol disease and 1 patient with single vessel disease having visible collaterals in CAG (Rentrop=2). Remaining 9 patients had single vessel disease and no visible colletarals on CAG (RENTROP=0). Correlation coefficient of SI between IC-SPECT and IV-SPECT in these 9 patients was higher (R=0,81,p=0,O08). The degree of IRA stenosis and SA values were also correlated (R=0.67,p=0.047 for IC-SPECT and R=0.75,p=0.001 for IV-SPECT) in these patients. CONCLUSION: The high correlation between IC-SPECT and IV-SPECT in a relatively standardized subpopulation indicates reliability of conventional TF-SPECT in infarct size determination. Further experimental and clinical studies, particularly from the acute or subacuta to the chronic stage of AMI are necessary to confirm this finding.

• CARDIOVASCULAR 7

PS_606

PS_608

CORONARY RISK FACTORS AND ABNORMAL LONGITUDINAL BASE TO APEX PERFUSION GRADIENT BY PET BLOOD FLOW MEASUREMENTS

ATTENUATION CORRECTION IN 99M-TC SESTAMIBI STRESS/REST CARDIAC SPECT

M. Hernandez Pampaloni (1), J. Sayre (2), F. Keng (15, T. Kudoh (1), H. Schelbert (1). (1) Division of Nuclear Medicine, Department of Molecular & Medcial Pharmacology, UCLA School of Medicine, Los Angeles, USA; (2) Department of RadioIogy, UCLA School of Medicine, Los Angeles, USA. Aim: A longitudinal, base to apex, myocardial perfusion gradient has been described in patients with coronary artery disease (CADI and was attributed to diffuse coronary luminal narrowing. We asked whether this abnormal perfusion gradient also exists in patients without CAD but with coronary risk factors as hypercholesterolemia or long-term smoking, assessing also if any of these risk factors is more related to its severity. Methods: Regional MBF was measured in absolute units with 13N-ammonia and PET at rest and during dipyridamole hyperemia in 12 hypercholesterolemic (total cholesterol >240 mg/dl) patients (8 female, 57±9 years) and I I long-term smokers (3 female, 49±10 years) without documented CAD or other coronary risk factors. Values obtained were compared to those of 12 age-matched participants without coronary risk factors (6 female. 53:~10) and ~n i3 young (7 femaIe, 25±5 yearsl norreals to exclude an aging effect. MBF was determined globally, for each of the three coronary territories and in the mid and the apical sections of the left ventricle (LV). Results; Myocardial perfusion on qualitative analysis was normal at rest and during hyperemia and no flow del~cts were present. MBF in absolute units was similar in the three coronary territories. Hyperemic MBFs in the apical LV section were lower than in the mid LV section both in the hypercholesterolemic patients (I.89±0.57 vs 1.67±0.5 mL .g-L min -I, p<0.05) and smokers (1.79±055 vs 1.61±052, mL .g-L min -i p<0.05) but not in the age-matched and young norreals. However, the magnitude of the perfusion gradient was similar between the 2 groups (p=NS).Conclusions: The abnormal longitudinal perfusion gradient, observed during dipyridamole MBF in smokers and hypercholesterolemic patients suggests the presence of a functional and/or morphological alteration of the coronary circulation related to the presence of coronary risk Factors. Smoking and hypercholesterolemia seem to equally account for the presence of this pert'asion gradient.

R. Couto (1), M.D. Madn (1), M. Coronado (15, T. Navarro (15, R. Plaza (2), A. Gonzalez (35, G. Riesco (1), J. Coya (15. (1) Servicio Medicina Nuclear, Hospital; (2) Servicio Radioproteccion. Hospital; (3) Servicio Cardiologia. Hospital, Madrid, Spain. BACKGROUND: The aim of this study is to evaiuate the impact of attenuation correction (AC) on the diagnostic accuracy of conventional stress/rest ~qmTc-sestamibi SPECT studies, which are otten impaired by artefacts induced by nonuniform attenuation. M E T H O D S : We studied 34 patients (pts), 28 men and 6 women , ages from 22 to 91 years old(mean 61-+13,9).They were remitted with suspected of acute coronary syndrome (CAD): 19 pts. with previous diagnose of CAD, and 3 with another associated cardiac disease. Conventional exercise/rest perfusion SPECT was performed in 25 pts. and pharmacologyc /rest in 9 pts; all of them with AC and without (NAC), using a dual-head SPECT camera with a 133Ba source, The left ventricular myocardium was divided into 16 segments (seg), corresponding to: left anterior descending artery (LAD) territory (8 segments) ; right coronary artery (RCA) territo ry (5 segments); and circumflex artery (LCx) territory (3 segments). Qualitative analysis was performed by two nuclear medicine experts (NM), following the scale: Fixed defect-hipeperfusion (FD). reversible defect-hipoperfusion (RD), paradox delecthipoperfusion (PD) and normal perfusion (N). Coronary angiography was realised in 12 pts to establish diagnose ofischemia or infarction We compared angyographic and SPECT findings on RCA with and without AC. RESULTS: LAD territory FD PD RD N TOTAL RCA territory FD Pl)

RD N

TOTAL

I N M , NAC N7 se~ / % 38 / 14 2 / 0,7 I0 / 3,7 222 / 81,6 272 / 100

I NM, AC N? se~; / % 25 / 9,2 2 / 0,7 12 t 4.4 233/85.7 272/ I00

2 NM, NAC N? se~, / % 39 / 14,3 2 / 0,7 I0 / 3.7 221 / 81,3 272 / . I00

2 NM, AC N? se~; / % 25 / 9,2 3 / 1,1 10 / 3,7 234 / 86 272/ 100

1 N M , NAC N? se~ / % 61 / 35,9 2 / 1,1 22 / 13 85 / 50 170 / 100

I NM, AC N? sag / % 26 / 15,3 0 / 0 20 / 11,7 124/ 73 170 / 100

2 NM, NAC N? se~;/ % 78 / 46 2 / 1,1 13 / 7,6 77 / 45,3 170 / lO0

2 NM, AC N? se$ / % 30 / 17,7 0 / 0 1 5 / 8,8 125 / 73,5 170 / 100

I NM,NAC N? se~ / % 14 / 13,7 0 / 0 5 / 4.9 83 / 81,4 102 / I00

I NM, AC N? se~; / % 8 / 7,8 0 / 0 6 / 5,9 88 / 86.3 102/ 100

2 NM, NAC N7 se~; / % 17 / 16,6 0 / 0 5 / 4,9 80 / 78,5 102 / 100

2 NM, AC N? se~ / % 11 / 10,8 0 1 0 4 / 3,9 87 / 85,3 102 / 1 0 0

tLCx territory

PS_607 ATTENUATION CORRECTED STRESS MYOCARDIAL SPECT CAN REDUCE THE NUMBER OF UNNECESSARY REST INVESTIGATIONS O. Belohlavek, K. Taborska, I. Kantorova, D. Janeba. Dept.of Nuclear Medicine, Na Homolce Hospital, Prague, Czech Republic. Aim: Attenuation-corrected (AC) imaging shows frequently normal stress myocardial perfusion while non-corrected (NC) imaging shows hypoperfusion. It is unclear whether it is necessary to continue with resting examination in this situation or to leave it and save money and radiation burden. The aim of this work was to carry out retrospective evaluation of this situation. Methods: Suspected isehaemia was found on AC and/or NC stress imaging in 121 consecutive patients, and therefore the rest examination was carried out. Emission and transmission data were acquired in the same time into 4 energetic windows by Siemens E.CAM camera equipped with Profile system. AC and also NC standard slices of the left ventricle were divided into 17 segments and retrospectively re-evaluated visually by an experienced physician. Results: Stress AC imaging was normal in 29 patients, while hypoperfusion was found in at least one of the segments with NC imaging. At rest the AC and NC finding has not changed in 27 of this patients, which means that the stress iscbaemia was not demonstrated. One female was normal AC finding both at rest and stress, but NC showed stress-induced ischaemia in the antero-septal segment. Subsequent coronarography was completely normal. A similar situation was detected in one male in the basal part of the posterior wall. The patient refused coronarography and remains under monitoring. Vice versa normal stress NC finding was present at one male only, while AC imaging revealed hypoperfusion of the anterior wall. At rest the AC and NC findings did not change in this case. The NC imaging in males showed hypoperfusion most frequently in the posterior segment (Fig.), in females in anteroseptal and posterior segments. Conclusions: Additional resting examination add no information in 28 of 30 cases. In the remaining two patients NC in contrast to AC showed stress-induced isehanmia. In one case this was a false positive finding, in the other one there is no final conclusion. It means that the resting examination did not bring any benef3ts in 29 - 30 cases out of 3O (96.7 to I00.0 %). If the results of this study are considered accordingly, in our group approximately one fourth of the resting examinations (29 to 30 out of 12 I) could be saved.

FD PD RD N TOTAL

Findings of coronary angiography: Normal or insignificance disease: 4 pts; one vessel disease:l pt (LAD);two vessel disease:4 pts (3 pts LAD and RCA; I pt LCx and RCA) ;three vessel disease :3 pt ( LAD, RCA and LCx), Coron'ariography compared with SPECT on RCA: sensibility NAC~85% and AC: 72%.Especifieity NAC 40% and AC 80%. Accuracy NAC:60% and AC :70%. C O N C L U S I O N : The results of our study indicate that AC reduce the number of FD due to attenuation artefacts, especially on RCA territory (40%). However, diagnostic accuracy presents no slight improvement in our serie.

1231

, iO

¢} {h e~

t/} O

ft.

• CARDIOVASCULAR 7

PS_609

PS_611

ITERATIVE RECONSTRUCTION AND FILTERED BACKPROJECTION OF 201-TL GATED SPECT PROVIDE SIMILAR ACCURACY FOR THE MEASUREMENT OF LVEF

ATTENUATION CORRECTION OF THALLIUM MYOCARDIAL PERFUSlON SPECT

D. Daou (1), L Pointurier (1), C. Coaguila (1), B.O. Helal (1), T. Fourme (2), I. Carol (2), R. Lebtahi (3), M. Faraggi (3), M. Slama (2), D. Le Guludec (3). (1) Department of Nuclear Medicine, Antoine Beclere Hospital, AP-HP, Clamart, France; (2) Cardiology Department, Antoine Beclere Hospital, AP-HP, Clamart, France; (3) Department of Nuclear Medicine, Bichat Hospital, AP-HP, Clamart, France. Objectives: Coupling myocardial perfiasion to fimction with '°~TI ECG-gated SPECT (GSPECT). iszolinteresting.Previous studies have reported good correlation" between LVEF calculated with TI GSPECT and other imaging medalities. All these studies have used filtered back-projectiun (FBP) reconstruction We aimed to evaluate whether the use of iterative (1) reconstruction with '°lTl GSPECT as compared to FBP may ameliorate the reliability of the measurement of LVEF. Methods: Twenty-four patients having both rest 2°iTI GSPECT at 15 rain and 4h (8 frames/RR) after injection and equilibrium planar radionulcide angiography (RNA) in the left anterior oblique projection (LAO) (,processed at 8 framas/RR). FBP was done with a BW 5/0.25 filter and I reconstruction was done with the OSEM software (2 iterations, 8 subsets). Processing of GSPECT studies was done with the QGS software. Then, the correlation of LVEF provided with FBP and l at 15 rain to LVEF provided by planar LAO RNA were compared. Then, the variance of the paired absolute difference between the lSmin and 4h GSPECT studies with FBP and I were studied. Results: Results are reported in the Table. I Linear FBP

re~ression r

1.04"EF-QGS.03,EF.QGS

00:99;

ser

77:22:

p

paired absolute difference

~:00~001l

:22.-+8~31";

P-J. Ryan, D. Hausenlot. Department of Nuclear Medicine, Medway Maritime Hospital, Gillingham, U.K. Aim: The use of attenuation correction using a Gadolinium line source during scan acquisition was applied to routine clinical practice after phantom data indicated significant benefits. The accuracy of routine attenuation correction of myocardial perf~sion thallium SPECT imaging was investigated in relation to angiographic findings. Methods: A sample of 83 consecutive patients who underwent thallium myocardial stress redistribution perfusion SPECT and who also had coronary angiography within the subsequent 6 months were examined. Patients were of age 39 - 74 years and 61 male and 22 female. Stress modalities were treadmill exercise 38, adenosine 33 and dobutamine 13. For whole heart analysis coronary artery narrowing of 50 % in any artery was considered significant, For individual analysis the same criteria applied. 64 patients had angiographic demonstrated coronary artery disease and 78 had abnormal thallium scans. The 3 coronary artery territories were assigned as LAD - apex, anterior wall and septum, LCX - lateral wall and RCA - inferior wall. Both fixed and reversible defects were considered positive on thallium imaging. Results: Results are displayed below.

Sensitivity,, Specificit:¢ Pos Accarac~,, Neg Accuracy

Whole Heart 97 % 11% 80 % 60 %

LAD 87 % 90% 93 % 77 %

LCX 37 %

89% 71% 7t %

RCA 82 % 70% 76% 79 %

Conclusions: Attenuation corrected SPECT thallium myocardial perfusion imaging produces good results in clinical practice and enables it to be used with confidence in a clinical setting. The results are particularly reliable for LAD and RCA disease.

Conclusion: The use of I and FBP reconstruction with rest 2°lTl GSPECT studies provide similar correlation and reliability for LVEF as compared to planar LAO RNA.

PS_610

PS_612

MYOCARDIAL SPECT WITH ATTENUATION CORRECTION IN THE DIAGNOSIS OF CORONARY ARTERY DISEASE. A PRELIMINARY STUDY

CORONARY CALCIFICATIONS IN CHRONIC RENAL FAILURE: CORRELATION WITH MYOCARDIAL BLOOD FLOW DETERMIED BY PET

I. Banzo, J. Jimenez-Bonilla, C. Guede, F.J. Penn, R.H. Allende, R. Quirce, J.M. Carril. Servicio de Medicina Nuclear, HU Marques de Valdecilla, Santander, Spain.

M. Hernandez-Pampaloni (1), J. Goldin (3), I. Salusky (2), B. Gales (2), H.R. Schelbert (1). (1) Division of Nuclear Medicine, Molecular & Medical Pharmacology Department; (2) Division of Pediatrics; (3) Department od Radiology, UCLA School of Medicine, Los Angeles, USA.

Aim." Attenuation correction (AC) has been proposed as a method to increase the spocificity of myocardial SPECT in the diagnosis of coronary artery diseasc (CAD). The aim of this study was to evaluate preliminary and prospectively the diagnostic contribution of the attenuation correction with scatter compensation (AC+SC) in patients with suspicion of CAD. Materials: We applied AC+SC on 202 patients in whom CAD was suspected. This study included the 24 firsts consecutives patients who underwent to coronary angiography. A conventional myocardial non-corrected SPECT (NC-SPECT) and myocardial corrected SPECT (AC+SC SPECT) were obtained using a one day protocol (stress / rest with 300 and 925 MBq of 99mTc-Tetrofosmin respectively) in a two head camera equipped with a multiarray line sources of 153Gal. The studies were evaluated by visual analysis, by consensus of 4 observers using a score 0-4 (0 = normal pcrfusion; 4 = defect of perfusion). A myocardial SPECT score degree > 2 and a coronary angiography with stenosis > 7 0 % were considered pathologicals. R e s u l t : Coronary angiography was normal in 12 patients, showed angiographie stanosis < 7 0 0 in 3 and angiographie stanusis > 70% in 9; 3 one vessel, 4 two vessel and 2 three vessel. In the 9 patients with stanosis > 70% NC-SPECT showed abnormalities in 8 (sensitivity 89%) and the AC+ SC SPECT in 7 (sensitivity 78%). NC-SPECT had false positive results in 11 of 12 patients with normal coronary angiography; AC+CS SPECT had false positive results in 5. For major coronary arteries, specificity of NC-SPECT was 33% for right coronary (RCA), 66% for circumflex artery (CX) and 50 % for left anterior descending artery (LAD). AC+SC SPECT had a specificity of 91% for RCA, 9 1 % for CX and 58% for LAD. Conclusion: In clinical evaluation of CAD, myocardial AC+SC SPECT led to relevant increase of the specificity of NC-SPECT. This improvement in specificity was more importam in RCA and CX territories.

Aim: Risk factorsfor developmentof coronaryarteryand endstagerenaldiseaseoftenoverlap. We hypothesized that coronary calcifications may represent a more advanced stage of the atherosclerotic disease and that these calcifications might correlate with vasomotion coronary abnormalities. Methods: We measured myocardial blood flow (MBF) at rest and after dipyridamole induced vasodilation (DIP) by 13N-ammonia and PET and the coronary calcifications by EBT, in 42 major coronary territories (defined by polar map approach) of 14 hemodialysis patients equally divided in 2 groups depending on their calcium score. Seven patients had coronary calcifications (357±34 Hounsfield unita)a=(6 female, 32~=7 years) and 7 (2 female, 24~:7 yeats) had not. We compared these findings with the same number of coronary territories of 10 age-matched healthy volunteers (6 female, 25:t:4 years) without coronary calcifications on the EBT. Results: All had normal and homogenous resting and DIP perfusion studies. MBF at rest was higher in hemodialysis (HMD) pts than in normals (I.15±0.38 and 1.01±0.35 vs 0.57±0.12 mL/min/g; P<0.0 I), regardless of the calcifications and proportionate to the rate pressure product (RPP) in HMD pts (RPP; 12.5+9.9 vs 6.0~1.5 mmHg/min • 103; P<0.05). However, MBF was higher in the territories with calcifications when compared to the territories without calcifications of the HMD pts (1.15~0.38 vs 1.01±0.35. p<0.05), with a higher RPP. (12.5+9.9 vs 10.5+9.0 mmHg/min • 103; P<0.05). Hyperemic MBF response to DIP reached normal values in both groups (2.23 vs 2.21 vs 2.08-L-0.41mL/min/g in normals; NS). Minimal coronary resistances during hyperemia (calculated from the ratio of mean blood pressure to MBF) remained higher in the regions with calcifications, compared to the others (58±24 vs 47±16; P<0.05) and to normals (54±21 vs 49-~:10; P<0.05). Regions with calcifications showed a significantly lower flow reserve than the ones without calcifications (1.89+0.31 vs 2.27±0.43; P<0.05), in both cases reduced if compared to normals (3.5e0.59;

P<0.05). Conclusions:Coronarycalcificationsmaycorrespondto a moreadvancedstagein the athcrosclerotic process. Longitudinal studies would be required to completely define the role of coronary calcifications in the coronary vascular disease of chronic renal failure patients.

123~

• CARDIOVASCULAR 7

PS_613

PS_615

COMPARISON OF GATED TL-201 SPECT WITH OR WITHOUT ATTENUATION CORRECTION AND CONTINUOUS ATTENUATION CORRECTED SPECT

SERIAL CHANGE OF FATTY ACID METABOLISM DURING ACUTE PHASE OF MYOCARDIAL INFARCTION ASSESSED BY 1231 BMIPP

H. Siljander, J. Heikkonen, M. Ventil~, K. Virtanen. Helsinki University Central Hospital, Division of Cardiology, P.O.Box 340, 00029 Helsinki, Finland. The most pronounced factors affecting image quality in perfusion scintigraphy are attenuation, scatter and motion of the heart. The aim of this study was to compare the capability of three different algorithms o f thallium scintigraphy to correctly identify diseased territories of left ventricular myocardium For this purpose gated SPECT was acquisited and reconstraeted with (gt) and without (gc) attenuation correction and a separate acquisition of continuous SPECT with (ct) attenuation correction was done. Methods: Ten patients (8 male and 2 female) were studied with TI-201 (lO0 MBq) in stress and rest using double headed Toshiba 7200A/DI gamma camera. In gated studies two energy windows were used and triple energy window (TEW) method was used in continuous SPECT study. For attenuation correction an uniform plate source filled with water containing 1.3 GBq Tc-99m was on the head of A-camera, Acquisition matrix size was 64x64 and sampling angle 6°/step. Main window level was 20 % and lower sub window 7 %. The continuous rotational SPECT acquisition was performed immediately before or after gated study with TEW method (7, 20, and 7 %) as nongated. Images were displayed as normal tomographic planes, maps of myocardial SPECT results and as numeric data for each segment and were compared with coronary angiography. R e s u l t s : Ten patients had 15 diseased vessels in angiography. Six detects were in left artery (LAD), five in right coronary artery (RCA) and four in left circumflex artery (LCX). Attenuation corrected continuous SPECT detected all 15 diseased vessels and attenuation corrected gated SPECT study detected 14/15. Both methods showed two "false" defects not matching the coronary angiography. Gated SPECT study without correction detected 10/15 vessels but there were no false defects. The results are summarized in the table.

Correctly identified de fects "False" defects

15/15 2

14/15 2

S. Watanabe, H. Matsuo, 1". Yamaki, M. Iwama, T. Hirose, S. Tanaka, A. Murata, S. Miyata, T. Kadosaki, Y. Matsuno, M. Tomita Department of Cardiology, Gifu Prefectural Hospital, Gifu, Japan, Background: Discrepancies between 1231-1abeled-15-iodophenyl-3-methyl- pentadecanoic acid (BMIPP) uptake and regional myocardial blood flow were reported in patients with myocardial infarction, Mismatched segments with relatively more reduced BMIPP uptake were observed more often in acute as opposed to chronic and more often in reperfused as opposed to non-reperfused rnyocardium. These mismatched area are assamed to represent the viable myocardium that is exposed to severe ischemia. But the relationship between the abnormal area with abnormal BMIPP uptake and the severity of ischemia at the time of hospital referral, and the time course of metabolical recovery of these myocardium has not been established. Purpose: This study was designed to clarify the time course of abnormality in fatty acid utilization from acute to chronic ( I M) phase in patients with acute anteroseptal infarction, and to determine if this time course may be influenced by the status of coronary reflow. Study groups: Consecutive series of 28 patients with acute anteroseptal myocardial infarction, who were successfully recanalized (TIMI 3 flow) within 6 hours from onset, were divided into 2 groups (14 patients with TIMI 0 or 1 flow, and 14 patients with TIMI 2 or 3 flow at the time of emergency catheterization). All of patiants had severe chest pain of at least 30 minutes in duration, typical ST elevation in at least 2 contiguous leads in Vt-V4 and CPK elevation more than 6001U/ml (3 times the normal upper limit). Conclusion: Metabolicaly abnormal area was smaller than area at risk and larger than infarct area. However the abnormal fatty acid utilization assessed by 1231-BMIPP showed drastic changes during the acute phase of myocardial infarctionooCmetabolic abnormality in salvaged myocardium still persisted at least until 4 weeks after myocardial infarction. The severity of metabolic abnormality and the degree of this improvement was influenced by the severity of coronary obstruction (TIMI grade) at the time ofemerger~cy catheterization.

0/I 5

Conclusions: This preliminary study shows that with attenuation correction results in better sensitivity as compared with diminution the effect of cardiac motion at the expense of slight loss in sensitivity. Attenuation corrected continuous SPECT study is a last and useful method in myocardial scintigraphy but larger patient series should be studied before this issue can be settled.

tO

PS_614 Abstract withdrawn

PS_616 e-

DOES QUANTIFICATION CHANGES THE RESULTS OF MYOCARDIAL PERFUSlON SPECT

R. Buscombe, (3. Gopinathan, A.J.W. Hilson. Nuclear Medicine, Royal Free Hospital, London, UK. Many gamma camera systems are now sold with cardiac quantification packages. These are said to increase the accuracy of reporting. However the use of such quantification packages may change the clinical report as read form the tomographic slices. The aim of this study w a s to quantify the differences between visual reporting and quantification. The qualitative report of stress and rest myocardial perfusion scintigraphy was performed in 333 segments of the h e m (9 segments/patiant) in 37 patients imaged with a one day stress rest protocol using Tc-99m tetrofosmin. A defect was defined by a reduction in activity of >50% in each of the segments, on the tomographic slices reconstructed using interative reconstruction with a Wiener smoothing filter, Quantification used an Emory bullseye system with gender and age matched normal controls, There were number of abnormal segments seen on the slices were 119 at stress and 79 at rest. For the bullseye plot 98 were seen at stxess and 76 at rest. 33 segments (10% were abnormal on the slices alone and 7 (2%) were abnormal alone on bullseye. O f 55 segments reported as ischaemi¢ on slices, 26 (48%) were normal on bullseye, 13 of these in the right coronary artery (RCA) territory segments. Oft.he 67 segments reported on the slices as an infarct t0 (l 3%) were normal on bullseye, 7 of these in the territory of the RCA segments, Therefore there are significant differences in the results of reporting scans using a bullseye plot especially in identifying inferior ischaemia. Therefore before using such a quantification method a full assessment of the accuracy of each method should be performed.

1233

n

o n

• CARDIOVASCULAR 7 / DIAGNOSTIC ONCOLOGY 13 PS_617

PS_619

DETERMINATION OF INFARCT SIZE BY ENZYMATIC CRITERIA AND BY GATED-SPECT

COMPARISON OF LEFT VENTRICULAR VOLUMES AND EJECTION FRACTION BETWEEN STRESS AND REST GATED PERFUSION SPECT IN PATIENTS WITH ISCHEMIC HEART DISEASE

S. Canclini. P. Rossini, A. Terzi, C. Pizzocaro, U. Pajoro, B. Panarotto, B. Paghera, R. GiubbinL Nuclear Medicine, Spedali Civili di Brescia, Italy. Infarct size is a major prognostic determinant and influences LV remodelling after uncomplicated myocardial infarction. The infarct size may be determined by imaging procedures and estimated from EKG or enzymatic criteria, Aim of the present study was the comparison between infarct size determined by either Tc99m Sestamihi SPECT or enzymatic criteria peakCK-MB and cardiac. Methods. 23 pts with acute MI were imaged by Tc99m Sestamibi SPECT within 96 hours ftom the onset of chest pain. The infarct size was quantified by comparison with a gender matched polar map. Peak CK-MB was calculated using a protocol with sample collection every 6h from pt admission; Troponin T(cTnT) concentration was measured in a single sample at day 3 after admission. Both tests were determined by Roche Elecsys system. Results. A significant dift~rence in plasma concentrations of CK-MB (164,3_+150,5 vs 574,3+484,8 I,tg/I, p
J. Lee, B.C. Ahn, S.W. Lee, K.B. Lee. Deparment of Nuclear Medicine, Kyungpook National University Hospital, Taegu, South Korea. The purpose of this study was to evaluate the differences of end-diastolic volume(EDV), endsystolic volume(ESV) and ejection fraction(EF) between stress and rest images measured by gated myocardial perfusion SPECT in subjects with isohemic heart disease. Methods: Forty-seven subjects(M/F=34/12, ranged 43 to 84 yrs, mean age 64yrs) with myocardial perfusion defect were selected for this study. Dual head SPECT camera(Vertex plus, ADAC) was used to acquire ~)mTc-MIBI myocardial perfusion SPECT and EDV, ESV and EF were measured by AutoQuant program(Pegasys X, ADAC). Acqusition of stress image was performed at 1 hour after iv administration of radiopharmaceuticals with myocardial stress. Results: There were no significant differences in EDV and ESV, whereas EF was lower in stress gating SPECT. Excellent correlations of EDV. ESV, EF between stress and rest gating images(Pearson's correlation test, r=0.961, p<0.01, r=0.977, p<0.01, r=0.921 p<0.OI, respectively). EDV, ESV and EF measured by AntoQuant program at stress and rest gating myocardial perfusion SPECT in patients with perfusion detect parameters Stress ~atin~ EDV~ml) 105.2±35.5 ESV(ml / 56.4±30.7 EF(%) 48.6~-I 1.2 ns means not significant

Rest ~atin~ 105.7±37.0 55.1±31.1 50.3±11.4

Correlation r=0.961, p<0.01 r=0.977, p<0.01 r=0.921, p<0.01

paired T test(p) ns ns p=0.014

Conclusion: EDV, ESV and EF are well correlated between stress and rest gating SPECT in subjects with perfusion defect. EDV and ESV measured by AutoQuant program are not different, but different EF was noted between stress and rest SPECT, probably due to stunning of ischemic myocardium.

PS_618

DIAGNOSTIC ONCOLOGY 13

DOES LONGTERM SMOKING INFLUENCE LUNG HEART RATIO (L/H) OF TC99M SESTAMIBI (MIBI) DURING ADENOSINE MYOCARDIAL PERFUSlON IMAGING (MPI)?

PS_620

N. Nagaraj, J.E. Prosser, J.S. Grime. Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK.

THE ASSESSMENT OF MEDIASTINAL LYMPH NODES USING 99MTC TETROFOSMIN SPECT IMAGING IN PATIENTS WITH NONSMALL CELL LUNG CANCER(NSCLC):COMPARING WITH CT

Aim: L/H ratio obtained during MIBI MPI is a recognised method of providing supplementar)' information of lefr ventricular function. The effect of smoking on pulmonary MIBI uptake is not well assessed. The aim of this study was to determine whether smoking increases the pulmonary MIBI uptake in the absence of significant CAD as this would affect the interpretation of L/H ratio of smokers, Method: Quantitative assessment of L/H ratio of 39 patients with low pro-test likely hood of CAD and normal MPI was performed. Group A -21 non-smokers (mean age 59, 5M, 16F) & group B- 19 smokers of ? 20 pack years of cigarette smoking (moan age 59, 2M, 17F). PIs with hypertension, LBBB, AF, valvular heart disease, diabetes, renal failure, advanced COPD, abnormal baseline ECG, ECHO & MUGA were excluded. A 2 day adenosine stress/rest protecol was employed and SPECT acquisition at 60 minutes post injection performed (180degree orbit, 32 angles, 45 see/per projection). ROts were drawn around the myoeardium and a representative area of the left upper lung on summed anterior SPECT projections. I_5t ratios were calculated for both stress and rest studies. Results:

Stress Rest

Lung/Heart Ratio Smokers Mean SD 0.40 ± 0.06 0.48 ± 0.08

Non Smokers Mean SD 0.41 ± 0.05 0.47 ± 0.06

P = NS P = NS

Conclusion: In conclusion, long term smoking does not independently affect the L/H ratios obtained from anterior summed SPECT projections during adenosine stress MPI using Tc99m Sestamibi and L/H ratio interpretation remains valid in smokers.

1234

H. Wang (1), Q. Wei Chen (2), T.I.A.N. Wei Jia (1), P.A.N. Zhi Lai (3), Z.H.U. Cheng Mo (1). (1) Department of Nuclear Medicine; (2) Department of Surgery; (3) Department of Radiology, Rui Jin Hospital, Shanghai, China. Aim: The preoperative accurate detection of mediastinal lymph nodes (MLNs) in NSCLC is ver¢ im~rtant In order to study the involvement of MLNs ,this work reported the clinical role of Tc-Tetrofosmin SPECT imaging in comparison with CT scan. Methods: 76 patients (47 males, 29 females,age range 39-81 years) with suspected primary lung cancer were investigated. Staging~,rocodures included radiography, CT scan and fiberoptic bronchoscopy. Both CT scan and mTc-Tetrofosmin imaging were performed within one week before surgery, in all patients.The metastatic involvement of mediastinal lymph nodes was assessed by histopathology aRer surgery and in 7 cases by mediastinoscopy. In this study, the results of Tc -tatrofosmin SPECT and CT were directly compared with surgical findings for evaluating the lung and mediastinal lymph node lesions. Results: Primary NSCLC was confirmed in 64 patients (21 squamous cell cancers, 32 adenocarcinomas, I I large cell carcinomas); in 4 patients we found 2 metastases and 2 tuberculoses. 8 pts were not submitted to surgery. MLN involvement was demonstrated in 31 of the 64 patients (48%) and 9~'~Tc-Tetrofosmin SPECT imaging correctly staged 25 of 3 lpatients and 29 of 33 patients without mediastinal nodes, with a diagnostic sensitivity of 80.6% and a specificity of 87.9%, We had 4 false positive result and 6 false negative results. CT scan gave 16 true positive, 10 false positive, 23 true negative and 15 false negative results, with a sensitivity of 5 [.6'/* and a specificity of 69.7%. Conclusions: The study shows that ~'~'~Tc-tetrofosmin-SPECT is an accurate and useful tool to assess mediastinal lymph node involvement in NSCLC and its diagnostic accuracy is better than that of CT scan. This technique may play an important role in reducing the number of invasive staging procedures.

• DIAGNOSTIC O N C O L O G Y 13 PS_621

PS_623

TL-201 UPTAKE AND ITS RELATIONSHIP WITH CHEMOTHERAPEUTIC RESPONSE, METASTASIS, P53 STATUS, AND SURVIVAL IN PRIMARY LUNG CANCER

THE RELATIONSHIP BETWEEN TC-99M MIBi UPTAKE AND CHEMOTHERAPEUTIC RESPONSE, METASTASIS, PGP, P53, AND

T.F. (~ermik (1), M. Y(Jksel (1), C. Karhkaya (21, L. Do~janay (3), E. Qaklr (2), A. Salan (1), M. Ture (4), O.N. Yi~jitba~l (1), S. Berkarda (1). (1) Deparment of Nuclear Medicine; (2) Deparment of Chest Disease; (3) Deparment of Pathology; (4) Deparment of Statistic, Trakya University, Edirne, Turkey

M. Y~ksel (1), T.F. (~ermik (1), L. Do~]anay (2), C. Karhkaya (3), A. Salan (1), E. (~akir (3), M. Ture (4), S. Berkarda (1), O.N. Yi~itba~l (1). (1) Department of Nuclear Medicine; (2) Department of Pathology; (3) Department of Chest Oisease; (4) Department of Biostatistic, Trakya University, Edirne, Turkey

TI-201 scintigraphy has been used to detect malignant pulmoner disease. In this study, TI-201 was used to clarify the relationship between TI-201 uptake and response in chemotherapy and metastasis and survival. Methods: 47 patients with lung cancer underwent TI-201 SPET. From SPET images early (ER) and delayed (DR) turnout/normal lung ratios were obtained. In 19 patients p53 status were measured with immuno-histochemical staining. Patients were divided into subgroups according to change of the tumour size in CT scan taken after 4 cure of chemotherapy; responders [R(+)] and non-responders [R(-)]. metastasis (+) and (-), and p53 (4-) and (-). Results: ER, DR and retention index were not different according to either response to chemotherapy or p53 status. While ER of patient with metastasis was significantly lower than those patients without metastasis, DR was slightly lower in patients with metastasis, but this difference was not different, significantly. Although there was no significant difference for ER and DR according to p53 status, we found a significant inverse correlation between TI-201 uptake and p53 status, r=-0.48 and p=0.028 for ER, and r=-0.49 and p=0,027 for DR. The step wise regression analysis confirmed that the TI-201 uptake ratio was an independent prognostic factor for survival.

Higher MIBI uptake in lung cancer is reported with positive response to chemotherapy. In various types of tumours, it was noted that Pgp expression had a negative correlation with MIBI uptake and it plays important role in chemotherapeutic failure. Additionally, p53 status may play important role in chemo- and radioresistance, metastasis and prognosis However, in lung cancer the results of published studies were conflicting. The aim of this study was to evaluate the relationship between MIBI uptake and Pgp, p53, metastatic status and prognosis. Methods: Total of 56 patients with lung cancer underwent Tc-99m MIB[ SPET before the chemotherapy. From SPECT images early (ER) and delayed (DR) tumour/normal lung ratios were obtained. In 26 patients P-glycoprotein expression and in 28 patients P53 status were measured with immuno-histochemical staining. Patients were divided into following subgroups; responders [R(+)] and non-responders [R(-)] according to change of the tumour size in CT scan taken after 4 cure of chemotherapy, metastasis (+) and (-), Pgp (+) and (-); and p53 (+) and (-). Results: Patients had follow-up period 1-30 months with a mean value of 9.02±6.62 months, ER and DR of R(+) were significantly higher than those of R(-). Patients with metastasis had higher DR than those without metastasis, their ER was slightly higher. We found no significant difference between Pgp (+) and (-) group for ER and DR values. Interestingly patients with p53 (+) had significantly higher ER and DR values than those with p53 (-).There was no correlation between the uptake of MIBI and the degree of Pgp or p53 expression. Stepwise regression analysis showed that MIBI uptake did not effect the prognosis of patients.

I RESPONSE

(+)

~-)

NO 15 15 ER 3.29±1.26 2.76"20.95 DR 3.56~I.37 3.02±0.8I (+) vs (-): *:p<0.04;

PROGNOSIS IN LUNG CANCER

/H ETASTASIS

p53

(*)

(-)

t +)

I-)

18 2.44±0.91 2.82±0.92

19 3.21±1.21" 3.40~1.27

11 2.72:t:0.92 3.14±0.66

8 3.45:t:1.15 3.98±1,35

Conclusion: The inverse correlation between TI-201 uptake and p53 status and the lower T1201 uptake values of patients without metastasis suggested that lung cancer patients with lower TI-201 uptake tends to be more metastatic. Additionally, our results suggested that patients with higher TI-2()I uptake tend to response positive to chemotherapy

Response /+} t-)

Hetastasis +) (-)

Pgp ~+)

(-)

p53 (+)

I-)

n 19 22 ~9 27 18 8 19 9 ER 3.52:~1.18 2.26~:093' !!.33±1.06 2.91±1.18 2.62±1.01 2.64+1,29 2.21::081 3.26:t:1.29# DR 3.5821.43 2.52+1.08# L35±107 3.19~1.32# 2.66±1.02 2.79+1.28 3.26±0.71 3.34+[.37# I+) vs (-): *:p<0.0005; #:p<0.02

Conclusion: According to our results, in lung cancer we suggested I .) that patients with higher MIBI uptake tend positive response to chemotherapy and tend to be less metastatic. 2.) that Pgp expression seems to play not an important factor for the chemotherapeutic response, and 3.) that patients with p53 (+) status have higher MIBI uptake than those of with p531-).

e-

o

PS_622

PS_624

QUANTIFIED 99MTC-TETROFOSMIN SPECT IN PREDICTING CHEMOTHERAPEUTIC RESPONSE IN NON-SMALL-CELL LUNG CANCER

ASSESSMENT OF THYMIC ABNORMALITIES WITH TL-201 SClNTIGRAPHY IN PATIENTS WITH MYASTHEN|A GRAVIS

D. Fuster (1), N. Vifiolas (2), C. Mallafr~ (3), C. Falc6n (4), F. Martin (1), F.J. Setoain (11, M. Ortega (1), J. Pavia (11, E Pons (11. (1) Department of Nuclear Medicine, Hospital Clinic, Barcelona, Spain; (2) Department of Oncology, Hospital Clinic, Barcelona, Spain; (3) Aim: To evaluate iftumour uptake of °°=Tc-tetrofosmin can predict response to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods: We prospectively studied nineteen men (mean age 57±9.9 years) suffering from advanced NSCLC cancer confirmed by histology. We included 11 cases of squamous cell carcinoma and 8 of adenocarcinoma. The mean size of tumour lesions was 5.1±1.1 era. Thorax scintigraphy (SPECT) was performed 2 hours alter an i.v. injection of 740 MBq of 9~r"TcTetrofosmin. The equipment consisted of a dual-head gamma camera fitted with a low energy, high resolution collimator. The tumoural uptake was quantified in SPECT images using the Wansvemal slice where the tumour was best visualized. The response to chemotherapy was evaluated at three months upon completion of treatment. Based on computed tomography (CT) results, patients were classified as responders (significant size reduction by CT) or nonrespooders (no changes or size increase by CT). Results: There was no relationship between the histologic type or turnout size and ~=TcTetrofosmin uptake. 12/I 9 patients responded to chemotherapy and 6/19 did not. One patient could not be evaluated because of premature death at 3 weeks after treatment administration. Those which responded to chemotherapy showed higher 99=Te-Tetrofosmin uptake (2.17±0.16) than non-responding patients ( 1.27±0.63) (p<0.001 ). Conclusions: These results suggest that '~'=Tc-Tetrofosmin SPECT can be useful in the assessment of patients with NSCLC prior to chemotherapy treatment.

t~

t-

T. Higuchi, J. Taki, S. Kinuya, H. Sumiya, K. Nakajima, K. Yokoyama, N. Tonami. Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan. The preoperative evaluation of thymic status is important for the planning of the therapeutic strategy in patients with myasthania gravis (MG). CT examination was reported to demonstrate insufficient results, therefore we aimed to determine the ability of thallium-201 (T1) single photon emission computed tomography (SPECT) to evaluate thymic lesions, including lymphoid follicular hyperptasia (LFH) and thymoma, associated with MG. Methods: Forty-six patients with MG who underwent thymectomy were included. TI SPECT and computed tomography (CT) were performed preoperatively. TI SPECT was performed 15 rain (early image) and 180 rain (delayed image) after the injection o f T l (IIlMBq). The results were visually assessed, and TI uptake ratio (thymic lasional count density / lung count density) was obtained for quantitative analysis. TI uptake was analyzed among three groups of normal thymus, LFH and thymoma. Diagnostic ability ofTI seintigraphy and CT were compared. Results: In the histological examination, 19 had normal thymus, 16 had LFH and 11 had thymoma. CT correctly diagnosed only 5 of 16 patients with LFH. The mean (95"% C1) of uptake ratio in normal thymus, LFH and thymoma was 0.97 (0.90 - 1.03). 1.15 (1.04 - 1.32) and 1.94 (1.56 - 2.25) of the early image and I. tO (1.00 - 1.181, 1.69 (1,48 - 1.851 and 2.12 (1.65 - 2.50) of the delayed image, respectively. On the early images, thymoma showed more intense T1 accumulation than normal thymus (p<0.01) and LFH (p<0.01). On the delayed images, both thymoma (p<0.01) and LFH (p<0.01) revealed more intense uptake than normal thymus. 1"] SPECT, accurate diagnosis was obtained in 87.0% (40/46), and in contrast, 69,6% (32/46) with CT. TI uptake ratio was more sensitive in detecting LFH than CT (13/16 vs. 5/161. Conclusions: TI SPECT can differentiate normal thymus, LFH and thymoma and has greater sensitivity for the diagnosis of LFH than CT in patients with MG. TI SPECT is recommended as a preoperative examination of the thymus in patients with MG.

1235

o o.

o ft.

•

DIAGNOSTIC ONCOLOGY 13

PS_625

PS_627

ASSESSMENT OF CARTILAGINOUS TUMOR WITH TL-201

THE ROLE OF BONE SClNTIGRAPHY AND TUMOR MARKERS IN THE ASSESSMENT OF BONE INVOLVEMENT IN MALIGNANT DISEASES

SClNTIGRAPHY T. Higuchi, J. Taki, S. Kinuya, K. Nakajima, H. Sumiya, K. Yokoyarna, N. Tonami. Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan. Histological diagnosis and grading of cartilaginous tumor should be essential element, because it has an important bearing on its prognosis. We aimed to make clear the character of TI-201 uptake in various histological types and grading of cartilaginous tumors and assessed its clinical values. Methods: A total of 23 lesions of histologically proven cartilaginous tumors - 2 enchondroma, 16 conventional chondrosarcoma (low grade = 10, moderate grade = 6), 3 mesenchymal chondrosarcoma, I myxoid chondrosarcoma and l dedifferentiated chondrosarcoma - was assessed. Fifteen minutes after the intravenous injection of TI-201 (llIMBq), we recorded planar and SPECT images. TI-201 uptake in the tumor lesion was evaluated visually using five-grade scoring system: 0 = equal to background activity, I = slight increase in uptake, 2 = moderate increase in uptake, 3 = strong increase in uptake and 4 = uptake stronger than heart uptake. Results: TI uptake scores were 0 in 2 / 2 lesions with encbondroma, 9 / 10 with low grade conventional chondrosarcoma and 4 / 6 with moderate graded conventional chondrosareoma. TI uptake scores were I in 2 / 6 lesions with moderate graded conventional cbondrosarcoma, myxoid chondrosarcoma and 3 / 3 lesions with mesenchymal cbondrosareoma. TI uptake score were 3 in dediffereatiated chondrosarcoma. Conclusions: No TI-20I uptake in cartilaginous tumor indicated enchondroma or low grade conventional chondrosarcoma. However, when the TI-201 uptake was obvious, higher grade chondrosarcoma or other special types of chondrosarcoma should be considered.

PS_626 THE VALUE OF TC-99M-TETROFOSMIN SClNTIGRAPHY AS AN INDICATOR OF MALIGNANCY AMONGST BONE AND SOFT-TISSUE TUMORS

Z. Yapar (1), M. Kibar (1), S. Ozbarlas (2), A. U0uz (3), S. Zorludemir (3). (1) Department of Nuclear Medicine; (2) Department of Orthopedia; (3) Department of Pathology, Cukurova University School of Medicine, Adana, Turkey. Tc-99m-tetrofosmin (TET) has been developed as a radiopharmacantical for myocardial imaging. Resently, tumor uptake and prediction of multidrug resistance have also been reported regarding this tracer. In this study, TET was evaluated for its ability to detect malignant and benign lesions from bone and sofl-tissua massas. Methods: Thirty three patients (23 malignant, t0 benign lesions) with various bone and softtissue lasions were studied. Radinnuclide angiography with TET was done except one patient, and planar images of the lesions were obtained at 30 rain postinjcction. The TET uptake ratio (UR) was calculated by dividing the lesion count by the background count. The planar images and the pcrfuaion phase were also evaluated visually based on a scoring system. The lesions were resectad by open biopsy to obtain a histopathological diagnosis. Results: In visual analysis, twenty two of 23 (96%) malignant lesions and 4 of 10 (40%) benign lesions were visualized on TET images. On radionuelide angiography, 100°..6(22/22) of the malignant lesions and just 30% (3/10) of the benign lesions could he visualized. In quantitative analysis, the mean uptake ratio derived from malignant lasions was significantly higher than that of benign lesions (3.67 + 2.47 versus 1.24 + 0.42, respectively; p< 0.001). Among 10 benign lesions, there were 2 (20%) of which the UR exceeded the lower limit of malignant lesions' UR range. Among 23 malignant lesions, there were 3 (13%) of which the UR corr~pondcd to the benign lesions' UR range. Conclusions: According to our results, TET accumulation in malignant and benign bone/softtissue lesions differs significantly. In addition, blood flow could be assessed by radionuclidc angiography with TET.

123E

S.H. EI-Haddad, A. Fawzy, W. Metnawy, M. Abo-Gabal. Nuclear Medicine and Clinical Oncology Department, Faculty of Medicine, Cairo University, Egypt. Bone scan is the most sensitive complementary examination used to detect bone metastases. [CTP (type 1 collage telopeptide) is a new biochemical marker that has been introduced to assess bone resorption in different bone diseases including metastatic disease. Aim: To evaluate the role of ICTP for the diagnosis and follow up of bone metastases. Methods: The study included 80 patients having primary malignant. They were subjected to conventional whole body osseous scintigraphy following 740 MBq of Tc-99m MDP as well as measurement of serum ICTP level. They were divided into two main groups according to the results of the bone scan whether negative or positive. Furthermore, metastatic patients were classified according to the metastatic burden (number of metastases) into four grades. Results: The mean serum ICTP level was higher than the reference interval (I.3-5.2 _g/L) in both the negative and positive groups (8.3+4.9 _g/L and ] ].3+6.3 ~,/L respectively). On correlating the ICTP level and bone scan results, 28 patients (73.7%) of the negative group (38 patients) had elevated [CTP levels and only 30 patients (71.4%) of the positive group (42 patients) had elevated ICTP level with no statistical significant difference in both (P > 0.05). In comparing the ICTP level with the bone scan results, it was found that ICTP had a reasonable sensitivity of 7 t %, a low specificity of 26~/o with a positive predictive value of ~2%, a negative predictive value of 45% and 50% accuracy. On comparing the serum [CTP level with the metastatic burden of the patients, no significant statistical difference could be obtained between the ICTP level and the grade of bone deposits (P > 0.05). The positive finding in this study was the highly significant statistical difference that was obtained on correlating the complaint of patients with the bone scan results as 27 patients (71%) of the negative group were asymptomatic, while 32 patients (76%) of the positive group were complaining of bony pains (P < 0.001). An obvious finding that ICTP level was elevated on follow up of two cancer breast patients keeping with the progression state of their bone scans. Conclusion: ICTP cannot replace bone scan in diagnosis and follow up metastasizing tumors but it may be used in the follow up of these tumors to monitor response to therapy in conjunction with bone scintigraphy.

PS_628 MARKED TL-201 UPTAKE IN GIANT-CELL TUMOR OF BONE

T. Higuchi, J. Taki, H. Sumiya, S. Kinuya, K. Yokoyama, K. Nakajirna, N. Tonarni. Department of Nuclear Medicine, Kanazawa University, Kanazawa, Japan. Giant-cell tumor of bone (GCT) is a benign and a primary skeletal neoplasm. There are no reports that assess the precise features of TI uptake in GCT lesion. We hypothesized intense TI uptake in GCT lesions, because of their abundant blood flow and cell density. Accordingly, we aimed in this study to elucidate TI uptake in GCT )esions, and discuss its clinical value. Methods: Twenty-one patients with histopathologically proven GCT (22 lesions; 18 primary lesions and 4 recurrent lesions) underwent TI scintigraphy. We also studied conventional osteosareoma (10 lesions), a most common primary malignant bone tumor, and chordoma in the sacrum (4 lesions), an entity requiring differential diagnosis from GCT in the sacrum. Early and delayed planer imaging was performed at 15 min and 3 hr after the intravenous injection of TI chloride ( I 11MBq). TI uptake ratio was calculated by dividing the count density of the tumor region of interest (ROD by that of the background ROI. Results: All GCT lesions showed increased T1 uptake in both early and delayed images. The mean T1 uptake ratios of primary GCT were 4.69~ 2.67 in the early images and 2.19-a:0.66 in the delayed images, and those of recurrent lesions were 5.84± 3.97 in the early images and 2.71:i:1.09 in the delayed images. These values tended to he higher than those of osteosarcoma, 3.12:t:1.06 in the early images and 1.76~0.41 in the delayed images. Chordoma did not show appreciable TI uptake; whose uptake ratio was 1.19~0.22 in the early images and 1.14~--0.12 in the delayed images. Conelusions: GCT, a benign lesion, shows intense T1 accumulation, probably reflecting abundant vascularity and viable ceil number in the lesion. In the differential diagnosis, GCT can he excluded if T1 does not accumulate in the tumor lesion. It be also may helpful in diagnosing recurrent lesions on post-oporative follow up.

• DIAGNOSTIC ONCOLOGY 13 / GASTROENTEROLOGY 3 PS_629

PS_631

MONITORING THERAPY IN CHILDHOOD EWlNG'S SARCOMA WiTH THALLIUM SClNTIGRAPHY AND MAGNETIC RESONANCE IMAGING

THE POSSIBILITY TO QUALIFY PATIENTS WITH CANCER FOR BONE SC1NTIGRAPHY ACCORDING TO COLLAGEN TURNOVER MARKERS : PICP, PINP, ICTP, CTX.

G. Vural (1), E. Ozalp (1), S. Berbero~lu (2), N. Er~akrnak (1), I. Ilhan (2), A. Cila (4), I. Pak (3), B. Turgut (1). (1) Department of Nuclear Medicine, Ankara Oncology Hospital, Ankara,Turkey; (2) Department of Pediatric Oncology, Ankara Ontology Hospital, Ankara,Turkey; (3) Department of Pathology, Ankara Oncology Hospital, Ankara,Turkey; (4) Department of Radiology, University of Hacettepe, Ankara, Turkey

M. Konieczna, G.W. Chmielowski, M. Dziuk. Department of Nuclear Medicine, Central Clinical Hospital Military Medical University, Warsaw, Poland.

Ewing's sarcoma is a highly malignant neoplasm. Magnetic resonance imaging (MR/) is the imaging modality to evaluate the extent of the primary lesion and to monitor the response to therapy. Aim: The purpose of the study was to evaluate the value of Thallium (TI-201 ) scintigraphy in monitoring therapy in childhood Ewing's sarcoma patients. Methods: 10 patients (7 male, 3 female; mean age: 14 ± 4.6) with Ewing's sarcoma were evaluated with pretreatment and serial post-treatment MRI and TI-201 scintigraphy ( 4 times). Lesion size, signal intensity relative to muscles (in TIw, T2w and STIR images) and enhancement patterns were evaluated in MRI. TI-201 planar and whole body images were obtained at 10 minutes and 2 hours afier iv injection of 2.5 mCi (92 MBq) of TI-201. Thallium uptake was evaluated visually. All patients received chemotherapy according to the EICESS 92 protocol and radiation therapy. Four patients had surgical resection. Results: In pre-treatment images all patients showed marked TI-201 uptake in the affected sites. In 8 patients. TI-201 uptake disappeared in the first scintigraphic evaluation after chemotherapy while MRI showed stable disease. Two patients showed decreased but still positive uptake in the first scintigraphic evaluation. They died because of metastases in followup. In one patient, TI-201 uptake was re-observed at third scintigraphic evaluation and also MRI showed progression, and this patient was diagnosed relapse in primary tumor histopathologically. In MRI the earliest sign of therapy response was disappearance of edema in surrounding muscles. In 6 patients with good response to chemotherapy, regression of soft tissue component within 2 to 7 months was the most striking finding. Signal changes within the atI~cted bone persisted even in patients who were considered to he in remission. Therefore STIR sequence was very sensitive but nonspecific for tumor versus post-therapeutic changes in the bone. Conclusion: MRI and TI-201 scintigraphy are sensitive methods for determining the tumor response to treatment, however TI-2Ol determines the metabolic activation of the tumor tissue and viability more specifically and it provides also whole body evaluation which is especially important in patients with Ewing's sarcoma where skip metastases develop fi-equently. Therelbre, we suggest that serial TI-2(11 scintigraphy, especially the first evaluation, seems to he very valuable and can be sufficient in monitoring and planning therapy.

Aim. It is known that bone metastases change bone metaholizm.Therefore the markers of collagen turnover (indicators of metabolic bone activity) can be helpful to determine patients who need scintigraphy.The aim of study was to asses the diagnostic efficacy of various bone formation and resorption markers in comparison to bone scintigrapby. Methods:We enrolled 150 patients , 74 with prostate cancer, 61 with breast cancer, 10 with lung cancer and 5 with other type. According to results of bone scintigraphy they were divided into three groups.Group 0 - no change in bone scan, group 1 - single nonspecific hot spot, group 2 - multiple lesions. Bone scintigraphy was performed on the Apex SP-6, Elscint gamma camera after intravenous injection of 925 MBqTc-99m MDP. As bone formation markers we evaluated amino- and carboxyterminal propeptidas of procollage I type ( PfNP, PICP ). The markers of bone resorption were: carhoxyterminal telopeptide of collage I type (ICTP) and carhoxy octapeptide (CTX). Results:There was no significant difference between group 0 and 1. The levels of markers in group 2 are significsnt bigger. The Z scores for PINP, ICTP. PICP, CTX were 2.9, 1.56, 0.5, 0.46 respectively. In discriminant analysis PINP had best coefiqcient of eorelation with discriminating function. The sensitivities were 96%, 69%, 27%, 56% for ICTP, PINP, PICP, and CTX respectively. The negative predictive values were 99%, 93%, 86% and 89% respectively. Conclusions:PINP is best discriminating marker.The ICTP and P[NP markers within reference limits may enable avoiding unnecessary bone scintigraphy

tO

PS_630 COMPARISON OF 3-[1231]IODO-L-A-METHYL TYROSINE TRANSPORT IN HUMAN FIBROBLASTS AND EWlNG'S SARCOMA CELLS C. Franzius (1), K. Kopka (1), F. van Valen (2), V. Eckervogt (2), B. Riemann (1), J. Sciuk (1), O. Schober (1). (1) Department of Nuclear Medicine; (2) Department of Orthopaedics, M~inster University, MOnster, Germany. Aim: 3-[1231]lodo-L-o~-methyl tyrosine (I231-IMT) scintigraphy of extracranial malignant tumors has been described recently. But up to now, little is known about the transport characteristics of 1231-1MTuptake into extracranial cells. Therefore, the aim of this study was to determine the transport systems of the 1231-1MTuptake in extracranial tumor cell lines (human Ewing's sarcoma cell lines) in comparison to non-neoplastic extracranial cells (human fibrob-

lasts). Methods: The time course of [I'~31]IMTuptake into human fibroblasts and the Ewing's sarcoma cell-linas VH-64 and CADO-ES-I was examined between 1 and 60 rain. [1231]1MTuptake rates with varying concentrations of [~231]IMT(5-300 ~M) were determined to assess the precise kinetics of the [ t23I]IMT transport. Furthermore, competition experiments of [ L23I]IMT uptake with other amino acids were performed to determine the distinct transport systems involved in the [12~I]iMT uptake. Results: The kinetic analysis of the [tZSl]IMT uptake rates into the ceils was concordant with the predominance of a single, sodium-indepandant transport system. The apparent Michaelis constants 1 ~ were 116.2 + 18.9 ~M (fibroblasts), 46.3 + 1.9 IJ.M (VH-64), and 105.3 + 21.3 p.M(CADO-ES-l).respectively. The maximum transport velocities V m amountedto 191.6+ 13.9 pmol, l0 6 cells" i . rain" t (fibroblasts), 270.4 ± 3.0 pmol. t0 6 cells~ • rain" i (VH-64), and 351.9 + 30.6 pmol o 10s cellst , rain"t (CADO-ES-I). Competitive inhibition experiments revealed solely a sodium-independent transport of [1231]IMT into fibroblasts (79 + 3 % via system L, 22 + 4 % unspecific uptake). In the Ewing's sarcoma cells [12]I]IMT was mediated via system L (6l + 1% (VH-64), 67 + 3 % (CADO-ES-I)) and via sodium-dependant systems A and/or B o+ ' / B 0 (18 + 1 % (VH-64), 17 + 2 % (CADO-ES-I); unspecific uptake: 16 + 3 % (VH-64), 14 + 3 % (CADO-ES-I)). Conclusion: While [1231]IMTuptake into the human Ewing's sarcoma VH-64 and CADO-ES1 cells is mediated mainly by the sodium-independent system L and to a minor extent by sodium-dependent systems A and/or B°"/B ° , [12]I]IMT is exclusively transported into human fibroblasts via system L. Furthermore, sodium-independent maximum transport velocities Vm~ arc about 1.5 times higher in Ewing's sarcoma cells as compared with fibroblasts, suggesting a higher expression of amino acid transport systems in Ewing's sarcomas cells than in non-malignant fibroblasts.

OTHER CLINICAL SCIENCE. GASTROENTEROLOGY 3

t-Q

.= ¢X

PS_632 POSTOPERATIVE DYSPHAGIA IN ORAL CANCERS: SCINTIGRAPHIC EVALUATION

O

F. Reate (1), J. Galli (2), G. D'Errico (1), L. D'Alatri (2), G. Almadori (2), V. Valenza (1). (1) Nuclear Medicine; (2) Otolaryngology, Catholic University of, Rome, Italy. Oral cavity cancers need an aggressive surgery for the high local malignancy, so it follows a permanent damage with clinical findings linked to swallowing difficulties. The aim of this work is to study and evaluate the alterations of oral and pharyngeal swallowing phases complained about the patients (pts) underwent oral surgery, with great attention to dysphagia and aspiration, by oro-pharyngo scintigraphy lOPS). Patient population: We studied 13 pts (12 males and 1 female, mean age 60, range 36-74), 4 with tongue cancer, 3 with palate cancer, 5 with tonsil cancer and 1 with jaw cancer respectively. We studied I7 healthy volunteers as control group. Method: OPS was performed administering 10 ml of water with 37 MBq of 99Tc-SC and acquiring sequential images (0,125" frames for a total 60" examination) with patient standing in front of the gamma camera in a 80 i right anterior oblique position. The study of the sequential seintigraphie images and of A/T curves permitted a qualitative (multiple deglutitions, nasopharinx refluxes, premature ingestion of the bolus) and quantitative analysis (oral and pharyngeal transit times and retention indexes, tracheal aspiration percentage) of swallowing disorders. Results: OPS qualitative analysis showed: multiple deglutitions in 9 pts (69%), refluxes in nasal cavity in 5 (38%), premature ingestion of the bolus in 6 (46%). OPS quantitative analysis showed alterations of the following phases: oral transit time in 7pts (54%) and oral retention index in 9 (69%), pharyngeal transit time in 10 pts (77%) and pharyngeal retention index in 9 (69%); moreover 7 pts (54%) showed tracheal aspiration. Conclusions: All patients except one showed one or more scintigraphic alterations. We demonstrated OPS is a sensible and simple technique to evaluate these disorders, it is well tolerated, with tow irradiation dose for pts.

1237

• OTHER CLINICAL SCIENCE. GASTROENTEROLOGY 3 PS_633

PS_635

A NEW EVALUATION METHOD USING LIVER ACCUMULATION RATE WITH 99M-TC-GSA SPECT : VERIFICATION OF BLOOD KINETICS AND CLINICAL UTILITY

ALTERATION OF INTESTINAL PERMEABILITY IN PATIENTS WITH GYNECOLOGIC CANCERS TREATED WITH PELVIC RADIOTHERAPY

Y. Sugai, K. Takahashi, A. Komatani, T. Hosoya. Department of Radiology, Yamagata University, Yamagata, Japan.

A. Dirlik (1), M. Taner (1), S. Erhamamcl (1), Z. Ozcan (1), I. Karado~an (2), M. Esassolak (2). (1) Department of Nuclear Medicine; (2) Department of Radiation Oncology, Ege University Medical Faculty, Izmir, Turkey.

A new evaluation method using the liver accumulation rate with 9~Tc-GSA SPECT was designed at our hospital. The aim of this study was to evaluate the accuracy and clinical utility of this easy to use method as a liver function index compared it with blood concentration change and conventional hepatic function tests. Methods: One hundred and eighty-sevan subjects were recruited from the total number of patients who underwent '~'~Tc-GSA SPECT between 1997 and 1999 at our hospital. Liver uptake ratio using SPECT (LURI5. %) is the added SPECT count in the whole liver slices divided by the whole SPECT counts of the syringe SPECT value. We compared the results of the conventional and clinical liver function indexes. The liver uptake rate t 5 minutes after the injection of'~mTc-GSA (Liver Uptake Rate 15: UTRI5) corresponding to the disappearance rate of '~"Tc-GSA in the blood at 15 minutes postadministratiun, was calculated from a regression equation for 35 patients { 100-(Y0+Ae'ls )}. The LURI5 and UTRI5 values were compared to examine the relationships and the accuracy. Results: LURI5 correlated well with every functional index, but a high correlation was found especially with cholinesterase, ICGRI5, and KICG in particular. There was the extremely high correlation between LURI5 of the whole liver and UTR15 from the blood concentration (Y=-7.179+0.966X, 1"=0.878, p<0.0001 ). Conclusions: The accuracy, reliability, and clinical utility of our new simple liver uptake ratio method using ~mTc-GSA SPECT was confirmed by comparison with the change in ~'°TcGSA concentrations in the blood and clinical hepatic function tests.

Aim: Pelvic radiotherapy (PRT) is an inevitable therapeutic morality in patients with cervix and endometrium cancer. However, PRT has known to cause intestinal adverse effects, which cannot be estimated beforehand. Additionally any objective test demonstrating intestinal injury occurring at~er pelvic radiotherapy has not been suggested yet. In the current study it is aimed to investigate the alteration of intestinal injury due to PRT in patients with gynecologic cancers. Methods: The study group included 12 patients with cervix cancer and 13 patients with endometrium cancer in an age range of 42-75 yrs. Primary PRT was applied in 10 inoperable patients and postoperative PRT was applied in 15 patients. Pelvic radiotherapy doses were determined according to the patients" characteristics and ranged between 5040-6300 cGy. Clinical grading of acute and subacute toxicity was determined according to International Union Against Cancer criteria (grade 0-IV). Before and I week after therapy, patients received 0.5 mCi Te-99m DTPA orally fullowing an overnight fasting and urine samples were collected for 24 hrs. Urine samples and standards were measured in gamma counter and urine Tc99m DTPA excretion ratio was calculated, Results: When the pre-therapeutic and post-therapeutic urine Tc99m DTPA excretion were compared a significant rise in intestinal permeability is noted following PRT (3,60~:1,35% and 7,49±3,65% respectively; p
PS_634

PS_636

GRAFT FUNCTION MONITORING IN LIVER TRANSPLANT RECIPIENTS USING QUANTITATIVE TC-99M MEBROFENIN SClNTIGRAPHY

PERFORMANCE OF SALIVARY SCINTIGRAPHY IN A SPANISH POPULATION WITH SJI~GREN'S SYNDROME DIAGNOSED BY THE EUROPEAN CRITERIA

A. Gen~;odjlu (1), H. Karakayah (2), M. Haberal (2). (1) Department of Nuclear Medicine; (2) Department of Surgery, Ba~kent University Medical Faculty, Ankara, Turkey.

R. Martinez-L,~zaro (1), A. CortesoBlanco (2). (1) Department of Nuclear Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain ; (2) Member of the Spanish Society of Nuclear Medicine, Zaragoza, Spain.

Liver transplantation is a successful treatment method for patients with end-stsge liver disease. The post-opomtive follow-up is very important in liver transplant recipients, because various complications, which affected graft liver function, arise in this period. The aim of this study was to evaluate the efficacy of serial quantitative Tc-99m mebrofenin scintigraphy in the monitoring the graft function after the liver transplantation. Materials and Methods: 8 orthotopic, 8 beterotopic total 16 liver transplant recipients (6 F,10 M, mean age 19.2e 2.9 years) were studied. The cause of liver failure was Wilson's disease in 6 patients, hepatitis B in 2, Alagille syndrome in 1, autoimmune hepatitis in 1, Byler's disease in 3, criptogenie cirrhosis in 3 patients. 9 patients recived cadaveric grat~s and 7 patients recived grafts from living-relatad donors. The mean follow-up period ailer liver transplantation was 3.9e 0.6 years. Tc-99m mebrofanin seinfigraphy and grail liver biopsy were porformed at regulary intervals beginning with the early postoperative period. Hepatobiliary scans were evaluated quantitatively and hepatocyte extraction fraction (HEF), time to maximum activity (Tmax) and time to half of maximum activity (TI/2) parameters were nsod. Seintigraphic findings were then compared to biopsy results at each subsequent assessment. Results: In the early post-traneplantatiun period, 11116 liver grates had normal seintigraphy (HEF >%90,Tmax approximately 15 min,T1J2 approximately 30 rain) and biopsy. The scintigraphic parameters of other 5 g~ils were below the normal values in the early post-operative period. In these 5 8rafts biopsy results were 2 acute rejection and 3 hepatecelluler damage. All of the 5 patients grail functions returned to normal levels after the episodes of acute rejection or hepatoeellular damage. In the follow-up period, I grail had chronic rejection and 7 grails had hepatocelluler damage episodes. During these episodes, grafts functions diminished and HEF, Tmax, TI/2 values were abnormal in all 8 patients. Scintigraphi¢ parameters returned to normal values in the serial scintigraphies in 5 of these 8 grate. In the other 8 grafts, seintigraphic findings and biopsy results remained normal throughout follow-up. Conclusion: Serial quantitative Tc-99m mebrofanin scintigraphy is a sensitive and valuable method for the monitoring grail liver function in liver transplant recipients.

AIMS: I) Evaluating the performance of the qualitative reading of salivary s¢intigraphy (SSC) for the detection of Sj?gren's syndrome (SS) based on the European classification criteria in a Spanish population. 2) Performing a clinical quantitation of this test in the Spanish population with SS according to the Eurnpoan criteria, xerostomic patients without SS as a control group and healthy participants as a normal group, and differentiating these three groups. 3) Establishing the most discriminatory seintigraphic parameters for the diagnosis of SS. METHODS: This cross-sectional study included 76 patients diagnosed of primary or secondary SS on the basis oftbe European classification criteria and 61 xerostomic controls who did not fulfill those criteria, both groups referred for SSC since August 1998 in order to evaluate a suspicions or known SS, and 56 healthy volunteers. A 16-minute dynamic SSC with Tc-99m pertechnetate was done and it was intenpreted by qualitative reading and clinical quantitatien. RESULTS: The qualitative reading demonstratod a normalcy fraction of 100%, sensitivity of 85.5%, specificity of 42.6% and accuracy of 66.4%. A normal database displayed a dispersion higher of 20% for function scintigraphic parameters. Normal area and function did not differ between right ~md left salivary glands. Normal uptake and excretion in partuid glands were significantly higher than in submandibular glands. SS patients showed significantly lower salivary gland areas, inferior parotid uptake and lower submandibular excretion than ennU~ols and normals. No optimal threshold of salivary gland area or function data, on an individual manner, had higher performance for the diagnosis of SS than the qualitative reading. CONCLUSIONS: This is the first study which evaluates the performance of SSC for the detection of SS using the European classification criteria for diagnosing it. Qualitative reading of SSC shows high sensitivity and suboptimal spocifmity for the diagnosis of SS. Normal salivary gland function displays a wide standard deviation and higher values in perotid than in submandibular glands. There is not lateralisation righVleil in normal salivary area and function. Salivary gland area, parotid uptake and submandibular excretion decrease in patients with SS. Clinical quatuitation and qualitative reading of SSC appears to be complementary for diagnosing of SS.

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• OTHER CLINICAL SCIENCE. GASTROENTEROLOGY 3 PS_637

PS_639

COLONIC TRANSIT DISORDERS IN PROGRESSIVE SYSTEMIC SCLEROSIS

HAS SILDENAFIL A ROLE IN ACUTE DIABETIC GASTROPARESIS? TWO CASES EVALUATED WITH RADIONUCLIDE STUDY

S.J. Wang (1), J.L. Lan (2), D.Y. Chen (2), Y.H. Chen (2), T.Y. Hsieh (2), W.Y. Lin (1). (1) Department of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan; (2) Division of Rheumatology, Taichung Veterans General Hospital, Taiwan.

V. Valenza (1), A. Bianco (2), G. D'Errico (1), A. Grieco (2), G. D'Andrea (1), B. Atfei (2). (1) Institute of Nuclear Medicine; (2) Institute of Internal Medicine and Gerontology, Catholic University of Rome, Italy.

Aim: Progressive systemic sclerosis(PSS) alters smooth muscle function throughout the gastrointestinal tract. The esophagus is the gastrointestinal segment most often involved. Involvement of the colon, though less common, may lead to life-threatenting complications. This study attempted to evaluate colonic transit in patients with PSS, using Tc-99m DTPA labeled charcoal in commercial enteric capsule. Method: We studied 15 unselected patients with PSS and 20 age matched healthy controls using radionuclide colon transit study. The geometric center (GC) at 4 and 24 hours was used to summarize overall transit in the colon. Result: In patients with PSS, colon trasit was delayed (GC4:0.42+/-0.58 vs 0.85+/-0.46; p=0.018) (GC24:1.65+/-1.10 vs 2.58+/-I.09; p=0 017). Abnormal geometric center values were observed in 10/15(66.6%) and 5/15(33.3%) PSS patients at 4 hours and 24 hours, respectively. Conclusion: These findings suggest that delayed colon transit is common in patients with PSS. Radionuclide colonic trasit study is a valuable diagnostic tool tbr evaluating colonic transit in PSS.

Introduction and Aim: Sildenafi] is a drug that modulates the Nitric Oxide dependent innarvalion of smooth muscle fibers. On this basis the Authors supposed that the drug could affect neurotrasmission in the muscle layers of the stomach and, consequently, have a role in acute diabetic gastroparesis. Two patients, bospitalised for this pathology, were evaluated to assess the possible therapeutic effect of Sildenafll. Methods: following informed consent 10 healthy volunteers were investigated to define normal patterns of gastric emptying scintigraphy, e.g., lag phase in minutes (LP), T 1/2 in minutes (T I/2), and Residual Activity at 120' in percentage (RA% 120"). The gastric emptying scintigraphy was performed only one time: after an overnight fast each subject assumed, in five minutes, a solid meal of a sandwich with two ~mT¢-MAA-scramhled eggs (74 MBq) and a glass of water. The acquisition started at the end of the meal in anterior view, lbllowed 1 minute later by a posterior view; the frame of each acquisition was of I minute on a 64x64 matrix. Both anterior and posterior views were acquired every 15 minutes to 120 minutes. After an overnight fast two female patients, 45 and 40 years old, affected by acute diabetic gastroparesis, underwent three times specific radionuclide study. The gas~c emptying scintigraphy was perlormed the first day to obtain a baseline study. The second and the third day the scintigraphy was taken 30 minutes alter the oral assumption of two different drugs: Sildenafil (50 rag) and placebo (A vitamin) respectively, to evaluate the different effects of the drugs on gastric emptying. Results: The results are rel~rted in tab)e I. Patient A LP IT I/2

Patient B RA% 120 LP I T 1/2

Normal value

< 30'

88"± 16"

35 ± 10

< 30'

88'5:16'

35-+ I0

t 1 Basal Studio 2) Sildenafil Stud~' 3) Placebo Study

45" 30' 30"

94' 67' 97"

43 27 31

90" 30' 20'

213' 68' 548"

g0 25 75

RA% 120'

The studies showed that after Sildenafil there was an improvement of scintigraphic parameters in the two patients and relief of gastric symptoms. Conclusion: the Authors suppose this new therapeutic approach as a usethl aid to resolve acute diabetic gastroparesis. Due to the Favourable results it would be advantageous to further evaluate Sildenafil and stomach motility considering the gastric scintigraphy a simple and well complying method to explore the effects of the drug on gastric emptying.

c, on

PS_638

PS_640

DETERMINATION OF INTESTINAL PERMEABILITY BY 99MTC-DTPA IN PROTOZOAN INFECTIONS

CROHN'S ESOPHAGITIS VISUALISED BY ANTYGRANULOCYTE ANTIBODIES

M.S. Taner (1), M. Argon (1), K. K~)seo~lu (1), H. Da~cl (2), S. 0stiJn (3), S. Budak (2), Y. Duman (1). (1) Department of Nuclear Medicine; (2) Parasitology; (3) Gastroenterology, Ege University, Turkey.

D. Huiae (1), D. Dodig (1), M. Premu~i~e (2), :7. Krznariae (2), B. Vuceliae (2). (1) Department of Nuclear Medicine and Radiation Protection; (2) Department of Gastroenterology, University Hospital, Zagreb, Croatia.

Intestinal permeability (IP) studies using macromolecules have been assumed to demonstrate the intactness of intestinal mucosa. The aim of this study was to determine the IP, measured by oral W"Tc-DTPA in protozoan infections (PI) such as Giardia intestinalis (G1), #lastocystis horninis (BH) and Entamoeba coil (EC) and assess the applicability of this nuclear analysis technique. Method: 39 patients with PI and 10 healthy volunteers were studied. IP was measured by orally administration of 0,5 mCi 9';~Tc-DTPA dissolved in 50 ml or'water. All cases were asked to fast overnight and to empty their bladder prior to starting the test. 24-b urine collection was obtained. To calculate the percentage of urinary excretion of W"Tc-DTPA, 2 ml urine and 2ml of a 1/1000 solution of a standard dose of'~"~Tc-DTPA with the same activity of the administered dose were counted and used a formula as follows;

The involvement of the upper gastrointestinal tract has been considered to be a rare manifestation of Cruhn's disease. We report herein the case of 49-year-old woman with 20 years history of Crohn's disease. The patient presented with progressive dysphagia, heartburn and weight loss. Esophagoscopy revealed diffuse erythema with mucosat inflammation. Eodobiopsy specimens were described as esophagitis. Radiologica[ studies showed normal small bowel transit and fistula between rectum and vagina. With a view to estimate the spread of the disease the scintigraphic study with Tc-99m labelled anti-NCA 95 antigranulocyte antibodies (AGAh) was performed. Whole-body scans were obtained five hours aRer i,v. injection of 740 MBq AGAb. Very high uptake in thoracic and cervical esophagus was observed. Appearance of abdomen was normal without pathological AGAb accumulation. To the best of our knowledge and according to MEDLINE base this is the first visualisation of Crohn's esophagitis by using AGAb and even the first with any seintigraphic method. Alter the oral administration of metilprednisotone and masalamine patient's symptoms were resolved.

DTPA ~ = Urine cpm x Urine volume x 100 / Standard cpm x 1000.

Results: IP was increased in Ptswith compared to the controls patients (7,20 ± 5,32 % vs 4,47 + 0,65 % P= 0,0017). IP and P values were 9,91 ± 10,5 % , P = 0,0025 in GI Pts, 6,81 ± 2,25 % P=- 0,00037 in BH Pts, 5,78 + 2,84 %, P = 1,40 in EC Pts. Conclusions: IP increases in patients with G. intestinalis and B. hominis but not in with E. coiL This finding supports that IP increases in Pl which causes damage to the intestinal wall, Non pathogenic PI has no effect on IP in patients with B. horainis raises the idea that B. hominis can be a pathogenic protozoan. IP measurement by using oral 9~mTc-DTPA is a noninvasive screening test and can be used in place invasive technique

1239

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O ft.

• GASTROENTEROLOGY 3 / NEUROLOGY / PSYCHIATRY 5 PS_641

NEUROLOGY / PSYCHIATRY 5

THE EFFECT OF PRESENCE OF ESOPHAGITIS AND HEUCOBACTER PYLORI INFECTION TO THE GASTRIC EMPTYING TIME

PS_643

K. SSnmezo~lu (1), O. C)zlem (1), Z. Y0ce (2), C. Nisli (1), A. Dobrucali (2), A. (~elik (2), I. Uslu (1). (1) Istanbul University; (2) Istanbul University, Cerrahpa~a Medical Faculty, Department of Gastroenterology, lstanbul, Turkey. Aim: The aim of this study were to I ) investigate the relationship of the severity of esophagitis and gastric emptying time; 2) ascertain whether the presence of Helicobacter pylori infection affect gastric emptying time. Methods: 37 patients (age range 17-80 years; mean age 47.3 ± 16.8) with subjective and/or objective evidence of esophagitis; and 14 normal volunteers (age range 25-72 years; mean age 49.2 ± 16.8) were included in this study. All participants underwent upper gastrointestinal endoscopy and radionuclide gastric emptying studies with both solid and liquid meals. According to esophagoscopic examination, the severity of esophagitis was graded into 4 scores. The presence and density of Helicobacter infection was confirmed by antral biopsies. Gastric emptying was measured using a Tc-99m sulfur colloid labelled scrambled egg for solid phase and a Tc-99m DTPA labelled orange juice for liquid phase using a double-head gama camera and gastric emptying time was expressed as TI/2 (time required for peak counts to decrease by halt~ for both liquid and sotid phase studies. There was at least 2 days between two seintigraphic studies Results: Comparing to control group, there was no statistically significant differences of both liquid and solid gastric emptying time in the patient group with no evidence of esophagitis (grade 0) and with mild esophagitis (grade 1). However, there is a significant acceleration of solid emptying time in severe esophagitis group (Table 1). On the other hand, there was no significant relationship between the presence of Helicobacter pylori infection and gastric emptying time. Conclusion: We concluded that while severe esophagitis accelerate the solid gastric emptying time, the presence of helicobacter pylori infection does not affect neither liquid nor solid gas° tric emptying time.

Table I. Relationship oftbe severity of esophagitis and gastric emptying time

Liquid phase (rain) Solid phase Imin / * p < 0.05

Control group (n = 14) 35.7-+15.1 61.5±12.8

No esephagitis Grade 0 (n=91 49.2+38.9 62.4+_23.4

Mild esophagitis Grade 1 (n=16) 50.6+28.8 74.1+17.2

Severe esephagitis Grade_>2 (n=12) 38. I+2.0.0 46.2+10.2"

ON THE TRANSPORT OF KETONE BODIES ACROSS THE BLOOD-BRAIN BARRIER G. Blomqvist (1), M. Alvarsson (1), V. Grill (1), G. vonHeijne (2), M. Ingvar (2), J.O. Thorell (3), S. Stone-Elander (3), L. Wid?n (2), K. Ekberg (4). (1) Department of Endocrinology and Physiology, Karolinska Hospital; (2) Department of Clinical Neuroscience, Karolinska Hospital; (3) Karolinska Pharmacy; (4) Department of Physiology, Karolinska Hospital, S-17176 Stockholm Sweden The cerebral utilization of ketone bodies at hyperketonemia (plasma concentration of §hydroxybutyrate, [§HB, equal to 1.0~0.3 mmol/L) has been studied with PET using R-§-[ILIC]hydroxybutyrate as tracer. In a Gjedde-Patlak plot the tissue uptake data fall along a straight line through the origin. Further, fit of a two tissue compartment model indicates that the transport across the blood-brain bamer (BBB) is irreversible during the scan time and that the volume of distribution of un-metabolized ketone bodies (DV~,~) is compatible with zero. The previous interpretation of these results was that the transport across the BBB is the ratelimiting step. However, in a recent study using MR technique at hyperketonemia it has been shown that DVf,~ in the brain is substantial, close to 0.4, at [§-HB] equal to 1.0 mmol/L(I). Therefore we ha~e re-examined our data to see if they are compatible with a high concentration of un-metabelized ketone bodies in the brain at hyperketonemia. Methods: Six healthy subjects and six IDDM patients were included in the study. Infusion of §HB started one hour before the bolus injection of [tlc]-§HB (acquisition time 10 rain in ECAT EXACT HR). The time course of tracer in arterial plasma was measured. A two tissue compartment model v.ith three rate constants was applied to the average time-activity curves of the brain, with two constraints imposed on the rate constants. First, the constraint D V ~ = kJ(k.~+k~) = 0.4 was imposed. Second, the constraint kz <100,k 3 was imposed, forcing the yintercept in the Gjedde-Patlak plot (,,apparent" DV) to be close to zero, even when DVI~ ¢ is appreciable. Within the framework of the applied two tissue compartment model, the relationship between these two quantities is: DV~pv= DVl~.k.,/(k.~+k3). Results: For both groups the constrained two tissue compartment model was found to give equally good fits to the data as the corresponding unconstrained model. According to this analysis there is a substantial concentration of ketone bodies in the brain tissue at hyperketanemia, and yet the transport across the BBB is essentially unidirectional. Conclusions: The quoted MR and PET studies are compatible only if the transport across the BBB is not the rate limiting step, and if there is some mechanism that suppresses the transport of ketone bodies from brain back to the blood. ( 1)Pans et at. J cereb Blood Flow Metab 20:1502-1507 (2000l

PS_642

PS_644

99M-TC RED BLOOD CELL SCINTIGRAPHY (99MTC-RBC) PERFORMED WITH GAMMA CAMERA MOUNTED X-RAY TOMOGRAPHY IN A PATIENT WITH RECURRENT BLEEDING: A CASE REPORT OF AN INTESTINAL BLEEDING LOCALIZED WITH COMBINED CT/SPECT TECHNOLOGY IN A SINGLE DEVICE

ASSESSEMENT OF BLOOD-BRAIN-BARRIER INTEGRITY USING 99M-TC-DTPA SPECT IN PATIENTS WITH SEIZURES

A. Kurtaran (1), A. Staudenherz (1), G. Dobrozemsky (1), L. 0hler (2), S. Puig (3), W. Schima (3), E Kainberger (3), G. Kornek (2), E. Wenzel (4), R. Dudczak (1). (1) Department of Nuclear Medicine; (2) Department of Internal Medicine I; (3) Department of Radiology; (4) Department of Surgery, University of Vienna, Austria We report a case of upper intestinal bleeding that was diagnosed using 99mTc-RBC scan performed with combined CT/SPECT technology (GE Medical Systems, Millenium VG with Hawkeye) in a single device. To the best of out knowledge, this is the first case of localization of a gastrointestinal bleeding using such a system. The X-ray imaging system of this machine is composed of a low current X-ray tube and a set of detecturs mounted on the camera's slip ring gantry rotating around the patient following SPECT acquisition. A 74 year old woman with severe anemia was referred to our hospital because of recurrent gastrointestinal bleeding. All routine diagnostic approaches including upper and lower endoscopy, CT and multiselice-CT as well as visceral angiography to localize the bleeding sourcewere negative. Dynamic 99mTc-RBC demonstrated an active bleeding site in the lel~ abdomen which was beleived to represent a bleeding in the descending colon, yet exact anatomical localization was not possible. In a repeated anlonoscopy, however, no bleeding site in the colon could be detected. We hypothesized that a combined functional and anatomical study would help to localize the bleeding site. Thus, a 99mTc-RBC scan with a gamma camera-mounted anatomical X-ray tomography (GE MS Millanium VG with Hawkeye) was performed. With the help of the registered and fused anatomical/functional images, the bleeding site was shown to reside in the proximal intestine (duodenojejunal region). This precise anatumical information directed the surgeon to a selective surgical intervention. In the suspected region intraluminal-blood was found confirming the correct anatomical localization of preoperative diagnosis. However, also intraoperativelly no active bleeding source could be detected. Yet, since an upper gastrointestinal bleeding has been supposed, a devaseularization (ligation of rigth gnctric vessels, gastroduodenal vessels and tight gastroepiploic vessels) and a highly selective vagotomy was performed. Postoperativelly the patient is free of bleeding and is clinically stable. This case report emphasizes the potential role of combining anatomical and functional imaging in a single device also in patients with obscure gastrointestinal bleeding, guiding selective surgical intervention.

1240

H. Golan (1), A. Friedman (2), A. Korn (2), I. Shelef (3), I. Rachinsky (1), S. Lantsberg (1). (1) Departement of Nuclear Medicine, Soroka University Medical Center, Beer-Sheva, Israel; (2) Laboratory of Neurophysiology, Department of Neurosurgery, Soroka University Medical Center, Zlotowski Center of Neuroscience, Beer-Sheva, Israel; (3) Departement of Radiology, Soroka University Medical Center, Beer-Sheva, Israel. Introduction: Electroencephalography and regional cerebral blood flow single photon emission tumography (rCBF-SPECT) have been shown to be useful diagnostic tools in identifying 9~ the pathological electroactivity and perfusion defects in patients with clinical seizures. -TcDTPA SPECT has the ability to evaluate the integrity of the blood-brain barrier (BBB). BBB disruption is present in infectious, vascular and degenerative diseases of the brain. The correlation of BBB pathology with ~'~-Tc-ECD rCBF SPECT and tow-resolutian elec~rotomography (LORETA) in patients with seizures is presented. Objectives: To assess BBB integrity, brain perfusion and electrotomographic findings in patients with seizure disorders. Materials and methods: 13 patients, age 15-54 years, presenting with partial or complex seizures were included, 5 were 6-12 months post brain surgery for removal of a benign meningioma, 5 post-closed head trauma, 2 with idiopathic seizures and one subject 36 month post-radiosurgery for arteriovenous malformation. 99r"-Tc-DTPA and s~'m-Tc-ECD SPECT studies were performed in all patients and LORETA was acquired in 6. Results: 11 patients showed increased focal accumulation of ~ - T c - D T P A in the hypoperfused area identified on rCBF-SPECT with 99m-Tc-ECD, one was normal in both studies and one was positive only on the DTPA study. All subjects who had LORETA studies showed localized elevation of EEG slow wave in the areas identical to the SPECT findings_ Conclusions: '~"-Tc-DTPA SPECT can identify focal areas of BBB disruption that may alter neuronal activity and induce neurological symptoms including seizures.

• N E U R O L O G Y / PSYCHIATRY 5 PS_645

PS_647

CHANGES IN RCBF DISTRIBUTION ASSOCIATED WITH MUSCULAR TENSION AND PSYCHASTHENIA. FIRST 99M-TC-HMPAO SPECT STUDY

EFFECT OF TESTOSTERONE THERAPY ON CEREBRAL PERFUSION IN HYPOGONADAL MALES

M.M.E. Pagani (1), A. Gardner (2), D. Salmaso (3), G. Lindberg (2), C. Jonsson (4), R. Hatherly (4), M. Finnbogason (4), L. dohansson (4), H. Jacobsson (4), T. H&lstrOm (2), S.A. Larsson (4)(1) Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy; (2) Neurotec, Section of Psychiatry And Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden; (3) Institute of Psychology, CNR, Rome, Italy; (4) Section of Nuclear Medicine, Department of Hospital Physics, Karolinska Hospital, Stockholm, Sweden Aim: Muscular Tension (MT), subjective muscular tenseness and aches, and Psychasthenia (PA), low mental energy and difficulties in compensating for energy consumption, show altered corresponding scores on the Karolinska Scale of Personality (KSP). This scale rates 135 items with a four-point response format summed up to 15 scales focused on personality traits that are thought to have biological correlates. This study aims to investigate for the first time the regional cerebral blood flow (rCBF) changes in patients with significantly increased KSP scores in either Muscular Tension or Psychastenia scales. Methods: The rCBF distribution at rest in a group of 19 MT and in a second group of 19 PA pa~.ients was compared to that of 28 age-matched normal controls (CTR). 99mTc-HMPAO SPECT was performed using a three-headed gamma camera and intersubject group analysis was carried out by a Computerised Brain Atlas able to standardise brain anatomy in 3D space. The bilateral uptake in 27 functional subvolumes of the brain, including the most of Brodmann (B) areas, basal ganglia and thalamus, was analyzed by analysis of variance. The significance level was set at p = 0.05. Results: Both patients to controls comparisons showed a significant global interaction (p<0.03). In the CTX/MT comparison group x VOI interaction was significant with increases in prefrontal cortex in B9 and B I0 and decreases in posterior cingulate and parietal cortex in B31 and B39 respectively. Significant increases where found in the CTR/PA comparison in B9, B I0 and in the putamen. In none of the 2 comparisons hemispheric effect was seen neither did the KSP scores correlate to rCBF in any of the analysed functional subvolumes. Conclusions: rCBF changes in patients showing altered Muscular Tension and Psychastenia KSP scores were investigated for the first time. Prefrontal cortex, bilaterally, showed rCBF increase in both groups when compared to normal controls. Posterior cingulate and parietal associative cortex showed significant decreases in MT. These findings confirm that the symptoms reported by patients suffering of Muscular Tension and Psychastenia have an organic basis. They also suggest the usefulness of standardisation software and normal controls in reliably identifying both rCBF increases and decreases in psychiatric disorders.

N. Friedman (1), W.E. Barnes (1), N. Azad (2). (1) Dept of Nuclear Medicine; (2) Dept of Endocrinology, Hines VA Hopstal, Hines, II, USA. Aim: Testosterone replacement therapy is employed in adult males suffering from diminished libido and low testosterone levels. This study evaluated cerebral perfusion before and after testosterone therapy was initiated. Methods: 8 adult males with a mean age of 69 years (58 to 79), participants in an ongoing trial of testosterone replacement in documented hypogonadal males, were studied with SPECT perfusion imaging as part of an ongoing study. Each patient completed questionnaires during the study evaluating physical, sexual, memory and sleep performance and social interactions. Patients had a baseline cerebral SPECT scan performed with Tc99m HMPAO using a triple head gamma camera with ultra high resolution fanbeam collimation. Repeat scans were performed approximately one month and two months post initiation of testosterone therapy. Studies were analyzed visually and with statistical parametric mapping software (SPM96), comparing the difference between paired patient studies to the difference between 15 paired studies of normal subjects. Results: Visual analysis of studies failed to demonstrate any consistent differences between individual scans. SPM grouped analysis of the change from baseline to one month post thempy indicated large clusters of activation in the left antero-medial frontal lobe (corrected p value 0.056) and the left posterior thalamus(0.061). A comparison of baseline to the two month study showed a similar but less significant activation. No significant group differences were identified between the two post therapy scans. Conclusion: Testosterone replacement therapy in hypogonadal males appears to be associated with left frontal lobe and posterior left thalamic activation demonstrated by SPECT cerebral perfusion imaging. This change is associated with increased libido and sexual perfurmance in most of the patients.

tO

PS_646

PS_648

INCREASE IN CEREBRAL PERFUSION (CP) WITH GINKGO BILOBA (GB) LONG-TERM TREATMENT

TC-99M HMPAO BRAIN SPECT IN CHILDREN WITH DOWN'S SYNDROME

OJ 03

A. Barbieri (1), R. Santos (2), M. Sevillano (1), M. Castiglioni (1), G. Alonso (1), L. Itaya (3), O. Bueno (2), J. Galduroz (2). (1) Dept. Diagnostico por Imagem - UNIFESP S~o Paulo, Brasil; (2) Dept. Psicobiologia - UNIFESP S&o Paulo, Brasil; (3) Dept. Medicina Nuclear HIAE S&o Paulo, BrasiL

M. Kaya (1), S. AItay (2), A. G~ltekin (1), S. Karasaliho01u (2), O.N. Yi0itba~ (1), S. Berkarda (1). (1) Department of Nuclear Medicine; (2) Department of Pediatrics, Trakya University, Edirne, Turkey.

O,

Introduction: CP alterations during normal aging could be explained by several mechanisms. A dry extract of Ginkgo biloba is one of the many attempts to minimize the aging effects. Aim: GB long-term treatment effects on CP evaluated with ';~'~Tc-HMPAO in an old age group. Methods: Forty-eight right handed male between 60 to 70 years old, distributed randomly in two equal groups, received 80mg/day of GB or placebo for a 8 months period. CP was evaluated at the beginning and at the end of the treatment. CP was calculated by the difference between counts in 12 predefined regions of interest (ROI) and one in the cerebellum (Value = R01 - cerebellum) and another data (Table #1) showing the CP improvement was obtained subtracting the values post-treatment by pre-treatment. Results: Ginkgo biloba group has had better perfusion than placebo showed by the decrease in the difference between ROls and cerebellum. The inverse result was observed in the place-

bo group. Table#I- CP improvementbetweenpreandposttreatmentin the two groups. R01 Pons Frontal Temporal lateral Temporal medial Upper basal ~:an~;lia Lower basal ~;anglia Frontal Frontal-parietal Parietal Temporal-parietal Temporal Occipital

Placebo 1,7±6,5" -0,4±12,1 1,1±2,9 3,8±6,4* 0,0-'=:6,1" 2,0±6,3* 2,2±3,3* 0,4±2,7* -0,2±2,0* 0,6~3,3 0,8±2,7* 3,8±3,6*

Ginkgo biloba 6,3±7,5* 2,5±7,8 0,5±4,2 -0,4~7,5" -3,6±5,3* 3,9~3,9" -2,9±3,5* -2,3±3,0* -3,3±2,6* -0,5±4,3 -0,9~1,9" -0,7±2,4*

Down's syndrome is one oftbo most common chromosomal disorders (one in 800 births) and associated with developmental abnormalities of the central nervous system that result in mantal retardation and age-dependent Atzlaeiraer-type neurodegeneration. The aim of this (ongoing) study was to determine the regional cerebral blood flow alterations in children with down's syndrome, and to correlate IQ levels. Methods: In this study; Tc-99m HMPAO brain SPECT was used to examine regional cerebral blood flow (rCBF) in 16 patients with Down syndrome (7 girl, 9 boys; mean age 6.84 ± 4,1 years). SFECT scans were acquired 20 minutes after injection of 18,5 MBq/kg Tc99m HMPAO in a quiet environment. All the children underwent detailed clinical examination, and IQ evaluation and/or the Denver developmental screening test. SPECT images were analysed visually and semiquantitatively by defining side-to-side asymmetry index. The asymmetry indices was considered: < 6% as normal, between 6-12% as suspicious, > 12% as abnormal Results: Five children showed normal brain perfusion images. According to asymmetry indices, 4 cases showed abnormal conical brain perfusion, and 3 cases showed abnormal perfusion on basal ganglia, and one patient had abnormal cerebefiar perfusion. Suspicious perfesion abnormalities were determined in 4 patients. There was a positive correlation between IQ levels and fight, and left frontal regions (r=0,57, p=0.02; r=0.57,1o=0.02; respectively). Conclusions: Tc-99m HMPAO brain SPECT can be helpful to assess the developmental brain abnormalities and understand which region in the brain related to mental retardation in children with Down'ssyndrome.

P=0,004 - Student ,,t" test with Bonferroni correction. Conclusion: Ginkgo biloba promotes Cerebral Perfusiun increase in several areas in both hemispheres.

1241

03 O 0-

• N E U R O L O G Y / PSYCHIATRY 5 PS_649

PS_651

STATISTICAL PARAMETRIC MAPPING IN BRAIN SPECT AFTER CARBON MONOXIDE INTOXICATION

STRIATAL AND PONTO-CEREBELLAR HYPOPERFUSION IN HALLERVORDEN-SPATZ SYNDROM: A COMBINED PET AND MRI STUDY OF A CASE

N. Watanabe, H. Seto, K. Nouchi, M. Shimizu. Department of Radiology, Toyama Meal. and Pharm. University, Toyama, Japan. The purpose of this study was to assess regional cerebral blood flow (rCBF) in patients after carbon monoxide intoxication using brain SPECT and statistical parametric mapping (SPM 96). Methods: Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms alter carbon monoxide intoxication were studied with brain singlephoton emission tomography (SPECT) imaging with Tc-99m bexamethyl-propyleneamine oxime (HMPAO). 44 control subjects were also studied. We used the adjusted rCBF images in relative flow distribution (normalization of global CBF for each subject to 50 mL/lO0g/min with proportional scaling) to compare these groups with 5PM. Results: Using SPM, we revealed significantly decreased rCBF in the bilateral frontal lobes widly containing the bilateral insula and a part of the right temporal lobe in patients with delayed neuropsychiatric sequelae as compared with normal volunteers (p<0.005). In patients with no neuropsychiatric symptoms, significantly decreased rCBF in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased rCBF in the right frontal and temporal lobes, and insuia in patients with delayed neuropsychiatric sequelae as compared with no neuropsychiatric sequelae. Conelusiont SPM is a useful technique for highlighting difti~rence in rCBF in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced tCBF noted in this investigation suppor'~ the contention that brain damage following carbon monoxide intoxication may be prolonged and relapse particularly in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.

PS_650

M.J. Ribeiro (1), P. Castelnau (2), N. Boddaert (1,3), L. Hertz-Pannier (1,3), P. Evrard (2), M. Zilbovicius (1,4). (1) Service Hospitalier Freddric Joliot, DSV-CEA, Orsay, France; (2) Service de Neurologie P~liatrique, H6pital Robert Debre, Paris, France; (3) Service de Radielogie Pediatrique, H6pital Necker-Enfants Malades, Paris, France; (4) Inserm U316, Chu Bretonneau, Tours, France Aim: Hallervorden-Spatz syndrome (HSS) represent a group of rare and severe genetic disorders marked by optic atrophy extrapyramidal symptoms and iron accumulation in the pallidi usually visible on brain MRi (,.eye of the tiger"). The fimctioual correlate oi" such structural abnormalities remains to be determined. Therefore, we have measured regional cerebral blood 0ow (rCBF) and dopaminergic fianctiun using positron emission tomography (PET), respeclvely wlth H 2 0 and F-L-DOPA, m a yplcal HSS case. Methods: A 9 years old boy with a clinical and MR] diagnosis of HSS was examined in PET, using a 3D acquisition and a high-resolution tomograph. The relative rCBF was determined from the dJstrthutmn of rad~oact~vtty after a bolus mjectmn of H: O. The rCBF images were analysed with the statistical parametric mapping software and compared to those obtained in 10 control patients (8.1 - 2.l years old). Comparisons between groups were performed with the t-statistic further transformed into Z statistic. The dopaminergic function was assessed with ISF-L-DOPA. The uptake constant (Ki. rain-1) of this radiotracar was calculated in the caudate nucleus and the putamen, using the occipital activity as a non-specific input function and compared to the corresponding mean values calculated in controls (n=g, 40.4 _+ 14.9 years old). Results: Voxel by voxel analysis of rCBF images revealed a significant hypoperfusion in the right caudate head, the pons and the cerebellar vermis compared to controls (p<0.005). No CBF abnormality was lbund in the pallldi. The Ki values measured for the four striatal structures (0.0122 and 0.0121. respectively ['or the right and the left caudate and 0.0119 and O.0112, respectively for the right and the left putamen) were symmetrical and similar to those obtained for a control adults group (mean value + standard deviation: 0.0127 ± 0.0014 and O.O117 ± 0.001 I, respectively for the caudate and the putamen). Conclusion: To better define the pathophysiology of HSS, we performed a PET study using two different radiotracers. Our results indicate no metabolic variation in the pallidi where iron accumulates but a significant CBF decrease in the right caudate head, the ponto-cerebellum. Concerning the dopaminergic function, no visual localized abnormality was observed. However, the quantitative analysis was performed using the mean normal values obtained for a adult control group. These data support the notion that HSS pathogenesis is not restricted to the pallidi where iron accumulates and may provide elements to raise new pathogenic hypothesis.

PS_652

99MTC HMPAO BRAIN PERFUSlON IN FAMILY WITH

1-123 LABELED PYRIDINE BENZAMIDES AND THEIR DERIVATES

CHOREA-ACANTHOCYTOSIS

AMINE PYRIDINES AS POTENTIAL NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS

T. Milanez (1), J. Kobal (2), M. Grmek (1), J. Fettich (1). (1) Department of Nuclear Medicine; (2) Department of Neurology,University Medical Centre,Ljubljana, Slovenia. Chorea acanthocytosis (CA) is very rare autosomal recessive disorder charscterised neurologically by involuntary movements and progressive neurodegeneration. Degeneration of the basal ganglia, closely resembling that seen in Huntington disease, results in atrophy of the putamen and caudate nucelus. Cerebral perfusion studies with positron emission tomography (PET) showed significant hypoperfusiun of the frontal Iobua, caudam nucleus, putaman and thalamus in patients with clinically expressed CA. Aim of this study was to assess cerebral perfusion with more available and less expensive 99mTc HMPAO SPECT in patients with clinically expressed CA as well as in asymptomatic siblings of these patients. Patients and methods: Spect brain porfusion study with 99m Tc HMPAO was performed in four first degree relatives: two patients (age 48 and 46 years) with clinically expressed CA and two asymptomatic subjects (age 42 and 40 years) one with increased proportion of acamocytes and the other without acanthocytes in peripheral blood. Both patients with clinically expressed CA also underwent high-resolution MR] brain study. All examined subjects were free of other neurological disorders. Results: 99m Tc HMPAO brain SPECT perfiasion showed pathological decrease or lack of perfusiun of the basal ganglia in both brain hemispheres and slightly decreased perfu~ion of right parietal lobe in patients with clinically expressed CA. Lack of basal ganglia perfusiun in both brain hemispheres with 99mTc HMPAO SPECT were compatible with lesions found on high-resolution brain MRL Decreased perfusion of left parietal lobe was found in one asymptomatic brother with increased proportion of acantecytes in peripheral blood and borderline decreased perfusion of putaman unilaterally in the asymptomatic subjects without acantocytes. Conclusion: Our results of combined 99m Tc HMPAO brain SPECT perfasion/MRl are compatible to results of combined cerebral perfusion PET/MR[ studies in patients with clinically expressed CA. Because of very high sensitivity of99m Tc HMPAO brain SPECT seintigraphy it might be a useful too! to assess asymptomatic subjects with first degree family history of CA and increased proportion of acantocytes in peryphera[ blood.

H.-E Li, F.-J. Gildhaus, K. Tatsch, K. Hahn. Department of Nuclear Medicine, University of Munich, Machioninistr.11, 81377 Munich, Germany. Aim: Nicotinic acetylcholine receptors (nAChRs) are involved in a variety of neuropsychiatric disorders, such as Alzheimer's disease, Parkinson's disease, nicotine addiction and epilepsy. Until now, there is no nAChR ligand available which is suitable for clinical routine applications. Based on the structure of epibatidine, the aim of this work is to study the relationship between structure and brain uptake of different pyridine benzamides and their corresponding amine pyridine derivatives by synthesizing and radioiediuating these compounds and evaluatingtheirbiodismbutionin rats. Methods and results: Three pyridine benzamides and 3 amine pyridines were synthesized via . . . . . . . 23 two- and three-step-synthesis mcludmg the radtoacuve label ng w th n.c.a, [ 1]Nal us ng the lodogan method. The radiechemical yields ranged fi'om 60% to 85%. The partition coefficients (IogP) of these compounds were measured between 0.8 and 1.58. The biodistributinn

five compounds. The results of brain uptake (% ID/g) are summarized in the table below. Compound 2rain 15 rain 60 rain 120 rain IogP

o-OH)"]IPB m.OHJZ31PB p.OH.12~IPB 0.56 0.18 0.11 0.07 0.05 0.034 0.01 0.02 0.014 0.01 0.02 0.014 1.10 0,80 1.10

o.OH.1231AP m.OH.I~IAP 2.42 1.27 0.60 0.23 0.12 0.013 0.07 0.004 L38 L53

~.OH.lUlAP 0.10 0.03 0.02 0.02 1.28

Conclusions: The biodistribution data have shown that the brain uptake and the retention were not only related with the lipophiticity, but also with the position of the OH group on the aromatic ring. The compound o-OH- 123lAP had a significantly higher brain uptake than mOH-II3IAP, although both had the similar lipophiIicity. From the compounds tested, o-OHI~31AP appears to be a potentiaI radiotigand for the nAChR. Binding, blocking and autoradiography studies are presently corned out to fuffher characterize this promising ligand.

1242

• NEUROLOGY / PSYCHIATRY 5 / RADIONUCLIDE THERAPY / DOSIMETRY 3 PS_653

PS_655

THREE-DIMENSIONAL SURFACE PROJECTION PERFUSION IMAGES IMPROVE DIAGNOSTIC PERFORMANCES OF ECD-SPET STUDY FOR DETECTING ALZHEIMER'S DEMENTIA PATTERNS

RADIOSYNOVIORTHESIS WITH ERBIUM-169 (ER-169) CITRATE AFTER FAILURE OF LOCAL CORTICOSTEROID INJECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS

T. Tang (1), T. Vander Borght (1), J. George (1), L. Robaye (2), V. Roelants (1), M. Ossemann (2), C. Swinne (3), C. Reynaert (4), P. De Coster (1), P. Laloux (2). (1) Nuclear Medicine Division; (2) Department of Neurology; (3) Department of Geriatrics; (4) Department of Psychiatry, UCL, Belgium

L. Manil (1), A. Kahan (2), G. M~dder (3), J. T~bib (4), P. Verrier (2), A. Bonmartin (4), Y. De Rycke (1), E Chossat (1), C.J. Menkes (2). (1) For CIS bio international, France; (2) Rheumatology ADept, Cochin Hospital, Paris - France; (3) K5ln-Marsdorf, Germany; (4) Rheumatology and Nucl Med Depts, CHU Lyon-Sud - France

Brain perfusioostudywith Tc-99metbylcysteinatedimer(ECD)is routinelyusedin the workup of patients with cognitive impairment. In the current study, we evaluated the additional diagnostic value of rally automated stereotatie surface projection (3D-SSP) presentation to that of standard transaxial display in such clinical setting. Methods: 72 patients (mean _+ SD: 71 + 9 y; range 43-86) with cognitive impairment underwent neuropsycbologic testing, CTscan and/or MRI and brain SPET study, then were followed for 30 ± 7 months (range 20-48) tbr assessing the diagnosis. They were 27 patients with probable Alzbeimer's disease and 45 with other disorders including Parkinson's diseases (PD: 6), probable fronto-temporal dementia (4), vascular dementia (3), chronic hydrocephalus (2), tumours (2), psychiatric diseases (21). and various pathological conditions (7). Brain SPET studies were acquired on a triple-bead camera lh aRer injection of 740 MBq ECD. Images were reconstructed by FBP, and displayed as transaxial section presentation. In addition, surface projection perfusioo images were obtained by using a 3D-SSP technique (Minoshisma. J Nucl Med 1995;36:1238) Observers (#1 and #2) blinded to the diagnosis were asked to rate the degree of certainty of the diagnosis of AD pattern (grade t: definite AD to 5: normal) on transaxial presentation alone or with 3D-SSP images. Area under the ROC curves as well as, by considering grade I and 2 as positive diagnosis of AD, intra- and interobserver reproducibilities and respective diagnostic performances were calculated. Results: in comparison with transaxiaI section interpretation. 3D-SSP improved diagnostic ~erformances as well as intra- and interobserver reproducibilities (see table). Area under the ROC curve

Sensitivity ~%)

Specificity (%)

#I

#I

#2

#I

Transaxial 0.77+ 0.84 -+ 59 52 ; 0.06 0.05 3D-SSP 0.92+- 0.91 _+ 81 70 0.04* 0.05* Mean :i:SD; two-tailed p value * <0.05.

89 93

Reader

#2

#2

{%) #I

Accuracy #2

93

78

78

Kappa Intra Inter #I #I vs#2 0.73 0.50

98

89

88

0.88

Although Er-169 radiosynoviorthesis is an established local therapy in rheumatoid arthritis (RA), its effects have been less clearly demonstrated in eortioosteroid-resistant joints. This double-blind, randomised, placebo-controlled, international study was designed to assess the eft'icacy of radiosynoviorthesis with Er-169 citrate after failure of local corticosteroid injections in RA patients. Methods: 82 joints (46 metacarpophalangeal (MCP) and 36 proximal interphalangeal joints (PIP) in 43 RA patients) with failure of local intra-articular corticosteruid injections were randemised to receive within 6 months intra-articular injections of either Er-169 citrate (MCP: 30 MBq; PIP: 20 MBq) or placebo. Clinical assessment was performed before and 6 months after local therapy, using an visual analogue scale (VAS) and a 0 to 3 verbal rating scale (VRS) for pain, a 0-3 VRS scale for joint swelling and joint mobility. Results: Improvement at 6 months in the Er-169 treated joints was statistically better than with placebo for pain (VRS: p=0.016; VAS: p=O.06 (tendency)), joint swelling (p-N).O07), mobility (p=O.036), pain and swelling (p=O.O02), pain or swelling (p=O.04). MCP joints presented higher Er/piacebo ratios than PIP. Placebo effect was unexpectedly important, especially in the PIP. Conclusions: These results confirm the clinical efficacy of radiosynoviorthesis with Er-169 citrate even after failure of local corticosteroid injections in RA.

024

Conclusions: In the current series, visas[ analysis of ECD-SPET images has good overall accuracy in detecting AD patterns. However, fast automatic data processing lbr 3D-SSP presentation turther improves the reproducibility and the diagnostic performances of ECD-SPET study for the clinical management of patients with cognitive impairment.

eo

ii

RADIONUCLIDE THERAPY / DOSIMETRY 3

PS_656

PS_654

LONG TERM RESULTS OF YTTRIUM-90 RADIOSYNOVIORTHESIS IN CHRONIC KNEE SYNOVITIS OF DIFFERENT ORIGIN

PHYSICAL AND BIOLOGICAL DOSIMETRY IN PATIENTS UNDERGOING RADIOSYNOVIORTHESIS WITH ERBIUM-169 AND RHENIUM-186 L. Manil (1), P. Voisin (2), B. Aubert (3), D. Guerreau (1), P. Verrier (4), E Chossat (1), J.M. Menkes (4), J. T~bib (5), J.Y. Devaux (4), A. Kahan (4). (1) For CIS BIO international, France; (2) Applied to Medicine Radiobiology Section, IPSN, France; (3) Physics Dept, IGR, Villejuif, France; (4) Rheumatology A and Nuclear Medicine depts, H6pital Cochin, Paris, France Physical and, for the first time, biological dosimetric studies were performed in rheumatoid arthritis (RA) patients (n=.45) treated by radiosynoviorthesis (RSO) with Re-186 sulphide (medium sized joints) or Er-t 69 citrate (digital joints). Methods: Biological dosimetry consisted in scoring dicentrics in lymphocytes, cultured from blood samples withdrawn just before and than 6h, 24h and 7 days after treatment. Physical methods included repeated blood samples counts and seintigraphy data. For Er-169 (pure beta emitter), only bremsstrahlung could be measured and solely in the injection area. Fur Re-186 (both beta and gamma emitter), whole body scans and static images of joints and locoregional lymph nodes were performed. Dosimetry calculations were in accordance with the MIRDOSE 3 software and tables. For Er-169 (21 patients), either metacarpophalangeat (30MBq) or proximal interphalangeal joints (20MBq) of the hands were treated (one joint per patient) ; 18 patients (out of 21) were interpretable for biological dosimetry, 10 (out of I1) for physical dosimetry and 6 (out of 10for both. For Rc-186, 23 wrists, 9 elbows, 3 shoulders and 2 ankles were injected in 24 patients, with a maximum of 3 joints per patient (70MBq/joint); 20 patlants/24 and 10/10 were interpretable for biological and physical dosimetry, respectively, and 8/10 for both methods. Results: Er-169 biological dosimetry was negative in all interpretable patients, and physical dosimetry gave a blood dose of 15 ± 29 G y and an effective dose lower than I mSv/30 MBq. For rbonium-186, biological results showed negat!ve results in 16 patients/20 but a blood irradiation around 200mGy in the last four. A significant cumulative increase ofdicentrics 7 days after injection (16/10000 instead of 5/10000 prior to the treatment; p<0.04) was also noted. Gamma counts gave a blood dose of 23.9 ± 19.8 mGy/70MBq and the effective dose was found to be 26.7 :l: 5.1 mGy/70 MBq, i.e. about 380 _Gy/MBq. Conclusions: Er-169 RSO is very safe from both physical and biological dosimetry stoodpoints. Re-186 leak is greater, as demonstrated by the higher blood activity and the measurable, although limited, dicentrics induction in blood lymphocytes. However, the effective dose remains moderate, i.e. 30 times lower than in 1-131 therapy in benign thyroid diseases.

M. Szentesi, M. Szentesi, S. Takacs. Bemmelweis Univ., Chair of Rheumatology and Physiotherapy, Budapest, Hungary. Authors report on the results of Yttrium-90 radiosynoviortbosis in chronic synovitis of the knee joint. Out of these 213 patients 122 suffered from rheumatoid arthritis, 17 ankylosing spoodylitis,13 other seronegative spondylarthritis, 48 suffered from inflamed osteoarthritis, I hydrops aaiculorum intermittems, I synovitis villooodularis, I 1 from chronic traumatic synovitis. Evaulation was based on the criteria as described by Mtiller, Rau and Sciitte the score system was developed by the authors. In the first seven years excellent and good results were recorded in 71%. They achieved excellent as well as good results at 83% of patients with rheumatoid arthritis, at 50% of patienls with ankylosing spondylitis and at 55% of patients with osteoarthritis. Seven years after radiosynoviorthesis 65% of patients did not need another punction. Conclusion: Radiosynoviorthesis is as effectiv method of treating chronic synovitis as surgical synovectomy. Even after a sevan-yeer period 71% the findings were rated as excellent or good. 72% of the patients do not need another punction even after a seven year period. The effectiveness is worsened significantly by the stadium of the disorder and the local x ray phase and diagnosis. P 0.00001. The treatment must be done in rheumatoid arthritis Steinbrocker stadium I-II, local stadium 1II.

effl n

o

• RADIONUCLIDE THERAPY / DOSIMETRY 3 PS_657

PS_659

HISTOLOGIC STUDY OF EFFECTS OF RADIATION SYNOVECTOMY WITH RHENIUM-188 MICROSPHERE

RGD PEPTIDES LABELED WITH Y-86 AND IN-111: A COMPARATIVE DOSlMETRIC STUDY IN DOGS

S.J. Wang (1), W.Y. Lin (1), M.N. Chen (2), B.T. Hsieh (2), H. Huang (2), L.H. Shen (2), G. Ting (2). (1) Department of Nuclear Medicine, Taichung Veterans General Hosiptal, Taiwan; (2) Institute of Nuclear Energy Research, Taiwan.

W.C.A.M. Buijs (1), M. Janssen (1), O. Boerman (1), F. Roesch (2), E Corstens (1), W. Oyen (1). (1) Department of Nuclear Medicine, University Medical Center, Nijmegen, The Netherlands; (2) Department of Kemchemie, University Mainz, Germany.

Rhenium-188 microspbere is a relatively new radiation synovectomy agent developed for the treatment of rheumatoid arthritis. It has been shown that the levels of unwanted extra-articular radiation was negligible. A histologic study was conducted to assess the effect of radiation synovcctomy on synovium and articular cartilage after intra-articular injection different doses of Re-188 microspbere into the knee joints of rabbits, lntra-articular injection of R¢-188 microsphere into rabbit knee joints resulted in mild reactive inflammation and thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium could be seen 12 weeks after injection. No evidence of damage to articular cartilage was noted. The comparison of the articular pattam after 0.3 and 0.6 mCi Re-188 microspbere tailed to disclose any essential difference. This study suggests that a treatment dose of Re-t88 microspbere cause transient inflammation of synovium without causing any detectable damage to the articular cartilage of knee joint.

Aims: The pharmacokinctics and dosimetry of an 9°Y-labeled antibody can be estimated from the scintigraphic images of the I I~[n-labeled antibody. Whether this holds for ~Y-labeled peptides remains unclear. RGD peptides potentially target tumors by binding to the ~ 3 integrin, expressed on sprouting endothelial cells and on tumor cells. The objective of this study was to compare the pharmacokinetics and dosimetry of the 86y and HIln-labeled analogues of a dimeric RGD-peptide in beagle dogs. Methods: The DOTA derivatized dimeric RGD peptide (RGDfK):-E-DOTA was labeled with SSy or with rain. Quality control included RP-HPLC analysis and ITLC. Five beagle dogs were iv injected with 225 MBq mln-DOTA-E-(RGDfK)2 and 74 MBq 86y-DOTA-E(RGDfK) 2, respectively within a two-week period. The peptide dose was 315 ~g in both cases. Whole body images were recorded with a dual head gamma camera (Siemens Muhispect) and a PET camera (Siemens ART), respectively at one hour and at 1, 2 and 3 days post injection. ROIs were drawn, and the residence time of the radiolabel in the various organs was calculated after correction for transmission, scatter and build-up artefacts (gamma camera images) and transmission artefacts (PET camera). Using the MIRDOSE3 program the radiation dose of the +°Y-labeled peptide to the relevant organs in a patient were estimated. Results:

Dose (cG},/mCi) Organ Kidneys Liver Lungs Red Marrow Spleen Bladder Total body

IHlndium mean 5.4 2.8 3.0 2.5 8.4 4.0 0.6

SD 1.7 10.4 0.8 IA 3.8 o.g

0.1

St~Yttrium Mean 4.2 2.4

SD 0.9 0.4

1.0

0.3

2.0 4.0 3.8 0.6

0.2 0.7 0.9 0.1

Conclusions: The radiation dose of the ~°Y-labeled RGD-peptid¢ can be estimated accurately based on the images of the Lllln-labeled peptidc, although the radiation dose to the lungs is overestimated, significantly.

PS_658

PS_660

DISODIUM PAMIDRONATE/RE-186 HEDP COMBINED I.V APPLICATION FOR PALLIATION OF RECURRENT PAINFUL ENDSTAGE IDIOPATHIC OSTEOPOROSIS

THE EFFECT OF TARGETED THERAPY WITH RADIOLABELLED OCTREOTIDE ON COLON CARCINOMA CELLS TRANSFECTED WITH SOMATOSTATIN SUBTYPE 2 RECEPTOR IN A RAT LIVER METASTASIS MODEL

G. Limouris (1), V. Voliotopoulos (1), A. Frantzis (1), S.K. Shukla (2), A. Stavraka-Kakavaki (1), L. Vlachos (1). (1) Areteion University Hospital, Nuclear Medicine Dept, Athens Greece; (2) CNR Collab Nucl Med Dept, St Eugenio Hosp, Rome, Italy. The specificity and potency of pamidronate as an inhibitor of ostanclastic boneresorption provides the rationales for its therapeutic use in variety of conditions characterized by pathologically enhanced bone turnover, including idiopathic and steroid induced ostaoporosis,as well ostaolytic metastasis.Furtbermore.in recent studies we assessed that the addition of pamidronate to conventional antiostenporotic therapy not only arrests,but also reserves the loss of bone mass,a typical pathologic finding of idiopathic ostanperosis.Re-186-HEDP exclusively accumulates by chemisorption onto the surface of hydroxyapatite crystals of the ostaosklerotic osseous lasion,an other characteristic of the collapsed vertebral bodies of the endstage idiopathic osteoporosis. Three women aged 70 to yr. with tong life history of painful idiopathic ostaoporosis who were non-responsive to standard symptomatic therapies (sodium fluoride,calcitunine) were additionally treated with 180mg disodium pamidronate(Aredia, Ciba-Geigy Ltd. Basel) via i.v infiasion at onset/munthly and for three months.In all 3 ostenporotic patients the initial dose was associated ,after a two week interval.by iv administration of 1400 Mbq of Re-186-HEDP. The fullow-up period covered 16 weeks.The efficacy of the treatment was assessed by pain/performance questionnaire that the patients were asked to complete daily.A second technetium bone scan 12 weeks afler therapy still showed the same activity.albeit the comparison of Kamofski lndaxas,pain/porfurmance questionnaires and bone densities assessed a satisfactory and statistical significant improvement. Besides their main use in bone metastasis a cocktail disodmm Pamidronata/Re-186-HEDP application appears to be very promising for palliation of recurrent idiopathic osteoporosis,wbere conventional treatment remains without beneficial effect.However any objective assessment of the place of pamidronate in osteoporosis is still not easy,since number of the enrolled patients is limitad.On the other hand the applied new scheme prevents the development of hypercalcaemia,reduces bone pain,could prelude the risk of pathological fractures and increase mobility.

1244

A.R Breeman (1), A. Mearedji (2), L.J. Hofiand (3), E.R Krenning (1), C.H.J. van Eijck (2). (1) Nuclear Medicine; (2) Surgery; (3) Internal Medicine, Nuclear Medicine Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands. Introduction: Peptide receptor radionuclide therapy (PRRT) has proven to be a promising modality for turnouts expressing somatosatin receptors (SS g). SS R are expressed in most neuroeodocrine tumours and various other tumoura, like breast cancer and malignant tyrophoton. In previous studies we tested SS R-targeted therapy in a metastasised liver model with radiolabelled octreotide on SS R-positive and on SS R-negative tumours cells and found that SS R play a crucial role: PRRT was only successful in the SS R-positive model. The purpose of this study was whether the introduction o f a SS R on SS R-negative turnout cells by transfection with a SS R subtype 2 gane will make these cells also feasible for this therapy. Therefore, SS R-negative colon carcinoma cells (CC531, p53 oncogene deleted) were tmnsfected in vitro with a SS R subtype 2 gone (CC2B). The SS R status on the CC2B cells was confirmed in vitro: 12k per cell, with a high rate of specific intemalisation of the radioligand, and confirmed in vivo: specific uptake and retention of the radioactivity in the CC2B cells. For in vivo therapy: 4 groups of male WAG/P, ij rats (A-D, n=6-8) were formed. On day 0 CC531 cells (group A and B) or CC2B cells (group C and D) were injected into the portal vein. In addition. A and C were treated with 370 MBq [mIn-DTPA°]octreodde on day 1 and 8. At day 28 the rats were sacrificed, the liver was weight and the turnout colonies scored. Results: no differences between A and B were found, (p>0.05), however, also no differences between C and D were found (p>0.05). Conclusion: Although the high expression ofSS R on, and the uptake and retention of radioactivity in the SS R-positve tumour cells PRRT with radiolabelled octmotide did not have an antiproliferative effect on SS R-positive liver metastasis. Impaired efficiency of the p53-mediated cascade might explain the poor radiosansitivity of the SS R-positive CC2B cells in a rat liver model.

[] RADIONUCLIDE THERAPY / DOSIMETRY 3 PS_661

PS_663

BIODISTRIBUTION AND DOSIMETRY OF 99M TC-CIPROFLOXAClN, A PROMISING AGENT FOR THE DIAGNOSIS OF BACTERIAL INFECTION

ASSESSMENT OF THE ERROR IN CELLULAR DOSE ESTIMATE DUE TO TRACING CUTOFF OF ELECTRONS AT 10 KEV IN THE EGS4 SIMULATION

E De Winter (1), C. Van de Wiele {1), F. Dumont (2), J. Van Durme (2), K. Solanki (3), K. Britton (3), G. Slegers (2), R.A. Dierckx (1), H. Thierens (4). (1) Division of Nuclear Medicine, Ghent University Hospital, Belgium ; (2) Department of Radiopharmacy, Ghent University, Belgium ; (3) Department of Nuclear Medicine, St. Bartholomew's Hospital, London UK; (4) Department of Biomedical Physics and Radiation Protection, Ghent University, Belgium

E.H. Kim (1), C.W. Choi (2), S.M. Lira (2). (1) Lab. of Cyclotron Application, Korea Cancer Center Hospital; (2) Dept. of Nuclear Medicine, Korea Cancer Center Hospital, Seoul, Korea.

This study reports on the biodistribution and dosimetry of 99mTc ciprofloxacin, a radioligand developed for the visualisation of bacterial infection. Methods: Whole body scans were performed up to 24 h after intravenous injection of 370 MBq 99mTc ciprofloxacin in three male and three female volunteers. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole body clearance. Time activity curves were generated for the thyroid, heart, liver and whole body by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Results: The images showed low to absent brain, lung and bone marrow uptake as well as rapid predominantly urinary, and to a lesser extent liver uptake and excretion of 99mTc ciprofloxacin, resulting in excellent imaging conditions for both the thoracic and abdominal regions, even at early time points (60 min) p.i. In none of the volunteers the gallbladdar was visualised. Approximately 60% of the injected activity was recovered in urine by 24 h pi. The highest absorbed doses were received by the urinary bladder walI, the thyroid, the upper large intestine, the lower large intestine and the uterus. The estimated mean effective dose for the adult subject, taking into account the weight factors of the ICRP60 publication, was 0.0083 mSv/MBq. Conclusion: The amount of 99mTc ciprofioxacin required tbr adequate planar and tomographic imaging results in an acceptable effective dose to the patient.

Aim: EGS4 is a code of popular choice for simulating the electron transport to estimate doses in cancer treatment using beta-emitting radioisotopes. In the EGg4 simulation scheme, the electrons are assumed to deposi~ their whole kinetic energy in the local volume where their kinetic energy becomes below 10 keV. The range of 10 keV electrons in the liquid water is -2.6 _m. Since the cells, which are the critical targets responsible for radiation effect, are a few tens of micrometers in diameter at maximum, it is required to have the tracing cutoff energy for electrons much below 10 keV for accurate cellular dose estimation. In this study, we have assessed the error in cellular dose estimate caused by having the tracing cutoff energy for electrons at 10 kaV Methods: The MCNP Monte Carlo code has been employed to calculate the linear energy transfer (LET) along the track for the electrons of initial kinetic energy ranging from I to 10 keV The range of I keV electrons in the liquid water is -0.068 m and, therefore, we expect negligible magnitude of error in cellular dose estimate by assuming that the electrons deposit their whole kinetic energy in the local volume where they become below 1 keV. Using the LET data along the track, the energy deposited inside the cell has been calculated for a varying intrecellular location where the electron becomes below 10 keV considering the direction of the electron track relative to the radial direction from the center of the cell. The calculation has been performed for the cells of 5, 10, 15 and 20 _m in diameter. Rasuhs: The maximum energy loss by 10 keV electrons occurs at 1.5 _m from the starting point while it occurs at 0.4 m by 5 keV electrons. Cellular dose is overestimated by 38, 22, 15 and I 1% for 5, 10, 15 and 20 m-diameter cells, respectively, due to the tracing cutoffof the 10 keV electrons inside the cell. With 5 keV electrons stopped inside the cell, cellular dose is overestimated by 13, 6, 4 and 3 % for 5, 10, 15 and 20 m-diameter cells, respectively Conclusion: The accuracy of cellular dose estimate should be improved by expanding the energy range for tracing electrons down to I keV.

cO k=

PS_662

PS_664

TUMOR SURFACE BINDING AS A FACTOR IN UPTAKE OF RADIOLABELED ANTIBODIES BY HUMAN TUMORS IN VIVO

NEW COMBINED GENE-RADIONUCLEAR THERAPY WITH 1251VDU; INTRACELLULAR DISTRIBUTION OF 1251VDU IN HSV-TK EXPRESSED CELLS

R.P. Spencer. Division of Nuclear Medicine, Univ. Connecticut Health Center, Farmington CT, USA, AIM. Muttip}e thctnrs are likely involved in delivery and tumor uptake of radioiabeled antibodies which ara administered intravenously. For example: perfusion, peritumor space, cell surface characteristics, and internalization may each play a role. To begin to analyze this, a conceptual model was utilized to examine cell surface effects. METHODS. Call surthce area (A) can be approximated as a function of tumor volume (V). That is: A = f(V). Volume depends on (assuming a sphere) tumor radius cubed, while surface area is approximated by radius squared. A logarithmic formulation is thus a reasonable initial step. A consequence is that, with a fixed number of acceptor sites on the tumor surface, relative uptake of radiolabeled antibody will fall with increasing tumor volume. Thus: Log ( Parcent Uptake) = -k.Log (Tumor volume ) + B RESULTS. This formulation was utilized in assay of reported data on tumor uptake of radiolabeled antibodies given intravenously. For example, deBree and associates (Europ. J. Nuel. Med. 25:1562, 1998) assayed tumor uptake of 2 distinct labeled monoclonal antibodies in patients with head and neck residual squamous ceil carcinoma. In all 27 patients, tumor uptake was described by: Log (Percent Uptake) = -0.34 Log (Tumor volume) + 2.66. The p value was 0.0062. However, when results with the 2 antibodies were analyzed separately one had excellent correlation with the prediction, while the second did not. This suggests operation of additional factors such as antigenic modulation , loss of binding sites, induction of additional receptors, or changes in the quantity of radiolabeted antibody due to uptake by hepatic sites. CONCLUSION. Assays of uptake of radiolabeled antibodies by tumors, versus size and/or external characteristics, may be of assistance in delineating the multiple biologic events involved.

S.J. Lee, K.S. Woo, E.H. Kim, W.S. Chung, S.J. Lira, T.S. Lee, C.W. Choi, S.M. Lira, S.H. Ahn. Cyclotron Application Lab. Korea Cancer Center Hospital, Seoul, Korea. Objectives: =251UdRhas been used in intraarterial cancer therapy with its low energy Auger electron. 15 : IVDU can be used as a substrate of HgV-tk gane in gan¢ therapy monitoring. Viral t25 125 thymlthn¢ klnas¢ can phosphorylate [VDU, and phosphory[ated I V D U can be mcorpo. . . . . . . 125 "5 rated into the nucleus. We investigated the mtraccllular d stnbut on of [VDU and * IUdR in HSV-d( positive (MCA-tk) ceils and HSV-tk negative(MCA) cells and compared U~IVDU t25 with IUdR for the selective localization in nucleus of the cells. t5 12~ Methods: We synthesized "~[VDU and IUdR using TMS-VDU and UdR. MCA and MCAtk cells were incubated with I'~sIVDU and 1"~5[UdRin culture media. After lhr and 4hr incubation, ceils arc washed and ruptured with sonication. Centnfugation of a cell extract at -/00g for 15rain downed nuclei, mitocbondna at 7,000g, at 105,000g for 100ruth, eytosol remained the supernatant. Radioactivity of intracellular orgnnenes was measured with gamma counter. Results: The cellular uptake of 1"~SIVDUin MCA-tk cells was higher than that in MCA ceils (45 times at lhr, 100 times at 4hr). In MCA-tk cells, IZsIVDU was localized mainly in eytosol and mitocbondria (46.'/%, 27. I%) at lhr incubation. However, the radioactivity was increased in nuclei (15.37% to 40.57%), and d e c r e a s e d in mitocbond6a (2154%), in cytoso] (29.84%) at 4hr. In MCA cells, usIVDU was localized 2.74% in nuclei, 1.59% mitocbondria, 67.1% in cytusot. As time passed, intracellular dis~ibutJon of 1"sIVDU is unchanged. 1251UdRshowed similar intrecellular distribution and localized 56.9% in nuclei, 9.26% in mitocbondria, 34.68% in cytosol in 4hrs in both MCA and MCA-tk cells. Mierodosimetry in the intracellular organelles predicted significantly high radiation dose to the nucleus of HSV-tk positive ceils. Conclusion: In MCA-tk cells, uptake of iZsIVDU was shifted from mitochondria and cytosol to nuclei. In MCA cells, uptake of 1:5IVDU is negligible in nuclei. The shift of radioactivity into the nuclei is more eytotoxic to the HSV-tk expressed cells. We expect that the selective gene-radionuclear therapy with t:~IVDU can be applied. •

.

•

•

1245

e0J Ul e~

Ul O

IX

• R A D I O N U C L I D E T H E R A P Y / DOSIMETRY 3

PS_665

PS_667

ARREST AND APOPTOSIS OF CULTURED RAJI CELLS BY CONTINUOUS LOW DOSE RATE BETA IRRADIATION THERAPY WITH 188RE-PERRHENATE

RADIATION SYNOVECTOMY WITH HOLMIUM-166 FERRIC HYDROXIDE - A FIRST EXPERIENCE

G 2

S.J. Lim, K.S. Woo, E.H. Kim, W.S. Chung, S.J. Lee, T.S. Lee, C.W. Choi, S.M. Lira. Cyclotron Application Lab. Korea Cancer Center Hospital, Seoul, Korea.

S. Ofluoglu (1), E. Schwameis (2), E. Havlik (3), A. Wanivenhaus (2), H. Sinzinger (1), C. Pirich (1). (1) Department of Nuclear Medicine; (2) Department of Orthopedics; (3) Department of Biomedical Engineering & Physics, University Hospital of Vienna.

P u r p o s e : Beta emitting radionuclide therapy gives exponentially decreasing radiation dose rate and results in cell death presumably by epoptosis. We observed changes in DNA content and apoptosis in relatively low dose rate beta irradiation. Methods : Raji cells were cultured and incubated with 188Re-perrhenate (3.7MBq, 37MBq, or 370MBq/ml) fur 4 hours to give irradiation dose of 0.4, 4, or 40 Gy. After changing the culture media, cells were cultured for 2, 4, 8, 16, and 24 hours. The cells were stained with Trypun blue, Annexin-V and Propidium iodide (P]) to observe cell viability, cett membrane alteration by apoptosis and changes in DNA content respectively. Flowcytometry was done for Annexin-V and PI to quantitate apoptosis and necrosis in the irradiated cells. DAPI(4,6diamidino-2-phenylindole) stain was also done to observe the damage in the nucleus. Results : Cell viability decreased with an increasing radiation dose. Cells irradiated in 40 Gy showed early uptake of both Annexin-V and PI suggesting cell death by necrosis. Cells irradiated in 0.4 Gy showed delayed uptake of Annexin-V only, and later on PI uptake suggesting cell death mainly by apoptosis. The cells irradiated in 0.4 Gy showed G2 arrest in 16 hours afier irradiation, but the cells irradiated in 40 Gy showed early DNA fragmentation within 2 hours after irradiation. In DAPI stain, early nucleus damage was observed in the cells irradiated in 40 Gy. On the other hand, slowly increasing apoptotic bodies were observed in the cells irradiated in 0.4 Gy. Conclusion : These results suggest that continuous low-dose irradiation induces G2 arrest and progressive apoptosis in cells while continuous high-dose irradiation induces rapid necrosis. Therefore, we expect therapeutic effect by continuous low-dose rate irradiation with beta emitting radiopharmaceuticals.

Radiation synovectomy with tracers bound to ferric hydroxide particles has been shown to be effective and safe. Holmium-166 ( ~ H o ) offers promising physical proj~erties for radiation synovectomy as does its carrier ferric hydroxide (FH) macroaggregatas. IWHo FH is marketed tbr radiation synovectomy but there is a lack on clinical data. Aim of the study: to evaluate the efficacy and safety of 166HoFH in a prospective clinical trial in 16 patients suffering from chronic synovitis. Methods: Sixteen intra-articutar injections were performed in I6 patients receiving a mean activity of I.I 1 GBq (range: 1,0 - 1.24) I~Ho FH. Blood activity measurements and monitoring of activity distribution by whole body gamma camera imaging were performed for control of leakage 3 and 24 hours after injection of t~'Ho FH. Doses to non-target organs were calculated. Clinically the patients were evaluated before radiation synovectomy. I week, I month and thereafter in 3 months intervals by the parameters joint effusion, pennus, local pain and range of motion and by the assessment of the patient~
PS_666

PS_668

COMPARISON OF THE PREPARATION AND IN VITRO STABILITY BETWEEN 188RE-MAG3°LYM-1 AND 188RE-HYNIC-LYM-1 I M M U N O C O N J U G A T E S FOR RADIOIMMUNOTHERAI~Y

PHARMACOKINETIC EVALUATION OF 188RE-HEDP IN HEALTLY BEAGLE DOGS AND DOGS HAVING SPONTANEOUS OSTEOSARCOMA

T.S. Lee, S.H. Ahn, S.J. Lim, W.S. Chung, S.J. Lee, K.S. Woo, C.Wo Choi, S.M. Lim. Cyclotron Application Lab. Korea Cancer Center Hospital Seoul Korea.

G. Andocs, L. Balogh, K. Bodo, A. Polyak, D. Mathe, G. Janoki. National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary.

Objectives For Radioimmunotberapy, it is important that rapid labeling, high labeling yield and good stabthty. To prepare Re tmmunoaonjugates for ratholmmunotherapy, monoelonal antibody was indirectly radiolaheled with ISSReby MAG3 chelate or HYNIC-lym-I conjugate • • gs . • iss . . prepared tad olabeled w th Re-~cme. These Re-lym-I mmunoconjugates were compared with the preparation end M vitro Stability, IS~ is# Methods MAG 3 was radiolabeled with Re using SnCl 2. Re- MAG3-TFP ester was pre~arad by EDC and tetrafluoropbenol with ISBRe-MAG3and purified by Seo-pak C18. Purified ss 18s. Re-MAG3-TFP ester was conjugated with lym-l. For preparing Re-HYNIC-lym-I immunocoojugate, HYNIC-Iym-I was synthesized by HYNIC-NHS aster with lym-I and its coupling ratio was determined. Re-Tricine prepared using SnCI 2 was reacted with HYNIClym-l. ]SSRe-HYNIC-Iym-I end ISSRe-MAG]-Iym-I were purified by PD-10. ITLC end HPLC was used in each step. ISSRe-lym-1 immuneconjugatas were allowed to stand at 4 for up to 16hr to estimate its stability in presence of Ascorbic acid. Results. ISSRe-MAG~end ISSRe-MAG3-TFP was radiolabeled with 98 % yield. Radiolabeling iss • i~ yield of lym-I with Re-MAG 3 was 23 Yo. Re-Tricine was radiolabeled with 99 % yield. HYNIC coupling ratio to a molecule of lyre-1 was 3.6. ISSRe-HY~NIC-lym-I was prepared by bss . • 20 % labeling yield end non-specific labehng of Re-Tricme with lyre-1 was < 1 % . Preparation time of IgSRe-MAG3-1ym-I was 2 times higher than L 8 8 ,Re-HYNIC-Iym-I. iss, iss, Radiochemical purity of purified Re-MAG3-1ym-I end Re-HYNIC-lym-I were mainlathed at >80% after 16hr standing. Conclusions Both ISSRe-MAG3-1ym-I and tt*Re-HYNIC-Iym-I immunoconjugates showed 20% labeling yield and > 80% stability. Radiotabeling of lym-I with HYN1C chelate then MAG3 was more simple and time-saving method. Antibody radiolabeling with JgSRe using HYNIC chelate can be used for the preparation of radioimmunoconjugate for radioimntunotherapy

188Re labelled H EDP is a promising therapeutical radiopharmaceutical for palliation of pain in patient with primery bone tumors end multiple bone metastases of breast end prostate carcinoma. Aim of the study . We aimed at to examine the hiodistribution and pharmasokinetics oftbe 188Re-labelled compound in heahly Beagle dogs. Pharmacokinetic evaluation in dogs having spontaneous usteosamoma were also studied. Radiotoxicological side effects were followed throughout the study. Materials and methods. 188Re-perrhenate received from a tungsten/rhenium generator (Oak Ridge National Laboratory). Radiocbemical purity of 188Re-HEDP was determined by TLC before injection. For the pharmaookinetic study 20 MBq/body weight kg I88Re-HEDP was injected intravenously into 4 healthly Beagle dogs, end images were taken I, 3, 6, 24 end 48 h afier the injection by a digital gamma camera ( Nudine X-Ring, Mediso LTD.) with HEGP collimator. To follow the radiotoxicological side effects blood parameters (blood cell counts) were investigated before and for 4 weeks following the injection. [n dogs (2) having spontaneous usteosarcoma a whole body 99mTc-MDP scan was done before the rhenium injection, tO loealise correctly the primary bone lesion and the possible metastases, Fifty MBq/hody weight kg 188Re-HEDP was injected intravenously into the dogs having spontaneous osteusarcoma, end images were taken l, 3, 6, 24 and 48 h after the injection. Results. The labelling efficiency of 188Re-HEDP injected into dogs was always more then 90 %. In heclthly dogs late images were shown high 188R¢-HEDP uptake in the skeleton. 188Re-HEDP was excreted mainly by the kidneys• Blood count analysis showed small decrease of the white blood cell count only, but it normalized without treatment within weeks. Dogs having osteosarcoma showed very high I88Re-HEDP uptake in the primary bone tumor. Investigation of therapeutical effects are in progress. C o n c l u s i o n . Our preliminary results are showed that 188Re-HEDP is a safe agent and localising in high extent in osteosarcoma lesion allowing possible therapeutical effects in future experiment.

1246

• RADIONUCLIDE THERAPY / DOSIMETRY 3 / CARDIOVASCULAR 8 PS_669

PS671

EFFICACY OF RADIOSYNOVECTOMY WITH YTTRIUM 90 IN THE TREATMENT OF INFLAMMATORY ARTHRITIS OF THE KNEE, RETROSPECTIVE ANALYSIS

PULMONARY DIFFUSING CAPACITY AND MULTIGATED RADIONUCLIDE VENTRICULOGRAPHY IN PATIENTS WITH HEART FAILURE - EFFECT OF MODERN MEDICAL TREATMENT.

S. Rodado (1), A.M. Garcia (1), V.M. Poblete (1), A. Soriano (1), C. Rubio (2). (1) Department of Nuclear Medicine; (2) Deparment of Rheumatology,Alarcos Hospital ,Ciudad Real ,Spain.

C.L. Petersen, A. Kj~er. Dept. Clinical Physiology & Nuclear Medicine, Frederiksberg Hospital H:S, University of Copenhagen, Denmark.

Aim :To evaluate the efficacy of radiosynovectomy with yttrrium 90 (Y90) in the treatment of arthritis of the knee, analysing retrospectively which factors influenced on the final success of our sample. Methods :We retrospectively analysed a total of 36 joints (knees) in 30 patients (19 women and I1 men) with a mean age of 54 years (range:14-80 years) who were treated with intraarticular injection of Y90 between November 1995 and December 2000.The underlying disease process was rheumatoid arthritis in 21 patients and other arthropathies in the rest .The mean duration of the disease before the therapy was ten years (range :2-45 years).A ,,threephases" bone scan for evaluating of degree of active synovdis oftbe treatad joint was carried out some days prior to therapy .All treatments consisted o f a intra-articular injection of 185 MBq of Y90.A scimigraphic imaging of activity distribution over the joint was performed immediately .Seven joints received a second therapy .We considered a good result when at least two of the next criteria improved :pain, swelling and limitation of motion ; medium if only one improved and no response if none improved .The factors which could be associated with response to the treatment were studied through logistic regression. Results :Of the 36 joints evaluated we found a good result in 23 (64%), medium in 5 (14%) and failure in 8.Therefore improvement was noted in 78% . the majority in the first month after therapy .Seven joints underwent a second treatment , tour improved and three did not response definitely.In the joints in which the treatment was successful, the mean duration of the disease was 8.8 years .Imaging of activity distribution showed a homogeneous activity distribution in 42% of the cases, whereas 58% had an irregular or non intra-articular distribution. Conclusions:-The radiation synovectomy with Yg0 has pro~ed to be an cft~ctive treatment of inflammatory arthritis of the knee. -Patients who received the most benefit from the procedure were in the early stages of the disease. -We did not find any relationship between scintigraphic distribution and the final result ; neither the age nor gender were predictors of resuhs .'l'his could be explained by the size of our sample and the reduced number of patients who did not respond to the treatment.

Aim: Substantial improvement in survival has been documented in patients with heart failure and reduced systolic cardiac function alter the introduction of ACE-inhibitor treatment. The purpose of this study was primarily to document a possible reduction in the lung diffusion capacity (TLCO) in patients with untreated heart failure (NYHA I1-111). Secondly, to elucidate the effect of intensive medical treatment with diuretics and ACE-inhibitor/ angiotensin-[t receptor antagonists on TLCO in patients with symptomatic heart failure and reduced systolic function. Methods: Patients with a relevant history, symptoms of dyspnea and echocardiographically estimated LVEF< 0.40 were included. Patients were characterized according to the results o f multigated radionuclide ventriculography as heart thilure if left ventricular ejection fraction was reduced (LVEF < 0.50). A total of 20 patients fulfilled the criteria. Patients were characterized by lung function test including diffusion capacity (TLCO) and by multigated radionuclide ventriculography (LVEF) before medical treatment (baseline) and after I year of treatment with diuretics and ACE-inhibitors/angiotensin-II receptor antagonists. As control of baseline lung function test of an age - and sex matched group of healthy volunteers (n =17) was performed. Results: Values are means) Pulmonary diffusion capacity Healthy: Heart failure: Left ventricular systolic function Heart lailure

Baseline, TLCO (mmol/sec x kPa) 0,127 (94% o f predicted mean) 0,099 * I76% of predicted mean) Baseline, LVEF 028

[ year o f treatment. TLCO (mmol/sec x kPa)

0.094 (ns) 1 year of treatment, LVEF 0.32*

*) P<0.05 Conclusion: Patients with symptomatic heart failure (NYHA I1-111) and reduced systolic function have respiratory dysthnction in the tbrm of reduced TLCO. Intensive medical treatment did not have any effect on the reduced TLCO whereas a marginal increment in LVEF was observed within the first year. The reduction in TLCO probably reflects permanent changes in the lung vasculature and may add to the dyspnea in these patients.

CARDIOVASCULAR 8

PS_672

PS_670

AMBULATORY RADIONUCLIDE ASSESSMENT OF THE EFFECTS OF WALK TEST AT DIFFERENT LEVELS OF HEART RATE IN PATIENTS WITH HEART FAILURE

CAUTION TO ESTIMATE CARDIAC FUNCTION IN PATIENTS WITH NONISCHEMIC HEART DISEASES USING ELECTROCARDIOGRAPHIC-GATED TECHNETlUM-99M TETROFOSMIN MYOCARDIAL SINGLE-PHOTON EMISSION T O M O G R A P H Y

A. Ferro (1), C. Duilio (2), M. Santomauro (2), A. Cuocolo (1). (1) Department of Biomorphological and Functional Sciences; (2) Department of Cardiology, University Federico II, Napoli, Italy.

S. Isobe (1), A. Ando (1), M. Nanasato (1), M. Nonokawa (1), M. Hirai (1), M. Yokota (2). (1) First Department of Internal Medicine; (2) Department of Laboratory Medicine, Nagoya University School of Medicine, Nagoya, Japan. Aim: It is now possible to obtain simultaneous assessment of perfusion and function using electrocardiographic-gated sing/e-photon emission tomography (g*SPET) with Tc99m labeled tracers, It is important to estimate left ventricular (LV) function in patients with chronic heart failure noninvasively. However, recent studies have demonstrated some potential limitations to estimate LV function in patients with iscbemic bean diseases using g-SPET. We intended to clarify factors which could influence LV function in patients with noniscbemic chronic heart diseases using g-SPET. Methods: Thirty patients with noniscbemic chronic heart diseases (21 men, 9 women, mean age 54 ± 18 y, 22 with idiopathic dilated cardiomyopathy, 8 with primary valvular diseases) were subjected to eight frames per cardiac cycle g-SPET with Tc-99m-tetrofosmin, ultrasound echocardiography (UCG), and contrast left ventriculography (LVG). Quantitative g-SPET (QGS) software was processed to determine LV functional parameters from g-SPET. The LV myocardium on SPET was divided into 17 segments and defect score was defined a 4-point grading scale. Total defect score (TDS) was calculated. Results: LV ejection fraction (LVEF) calculated by QGS was highly reproducible. There were significant correlations between LVEF from g-SPET end that from LVG as well as that from UCG (n = 30; r = 0.71, P < 0.001; r = 0.75, P < 0.001, respectively). When we excluded patients with a relatively large defect (TDS > 8), the correlations were slightly improved (n = 25; r = 0.72, P < 0.001; r = 0.77, P < 0.0005, respectively,). If we excluded patients with LV enlargement (LV end-diastolic volume index > 120 ml/m'), the correlations were moderately improved (n = 25; r = 0.83, P < 0.0005; r = 0.82, P < 0.0005, respectively). When we excluded patients with tachycardia (heart rate > 100 beats/min) or frequent premature beats (ventricular premature captures or supraventricular premature captures), the correlations were excellent (n = 22; r = 0.97, P < 0.0001; r = 0.94, P < 0.0001). Conclusions: Because tachycardia or arrhythmia may he more influential to measure LV function of nonischemic chronic heart diseases, caution is necessary to estimate LV function of nonischemic chronic heart diseases using g-SPET at eight frames per cardiac cycle, albeit gSPET is clinically useful. Heart rate should be appropriately controlled for this examination.

The effects of heart rate alone on lefl ventricular (LV) function during physical activity in patients with heart failure have not yet been investigated. The aim of this study was to assess the effects of chenges in heart rate on LV function during walk test in patients with bean failure. Methods: 13 patients (9 men and 4 women) with DDD pacemaker, implanted for complete heart block, were enrolled. Seven patients had depressed baseline LV ejection fraction (35±3%), history of congestive nonischemic heart failure (group A) and 6 patients had normal baseline LV ejection fraction (59±6%) without any relevant symptom at rest and during physical activity (control subjects, group B). [n all patients, LV systolic end diastolic function was continuously monitored by ambulatory radionuclida systam (Vest). All patients underwent three walk tests. Each walk test (6 rain) was performed at 70, 90 and 110 bents/min achieved by a programmed stimulation at fixed rate. Results: Under resting conditions, in group A, with increasing in heart rate, ejection fraction progressively decreased from 35±3% to 25±4% end to 22.~6% at 70, 90 and 110 beats/rain, respectively (all p<.05), as a consequence of slight reduction in end-diastolic volume and significant (p<.05) increase in end-systolic volume; whereas in group B, ejection fraction only decreased (!0<.05) at 110 bears/rain. At peak of the three walk tests, in both groups of patients, all parameters significantly (p<.001) increased, whereas end-systolic volume reduced (<.05) as compared to respective baseline value. In group A, comparison among rest-peak variations of all parameters during the three walk tests showed a significant (p<.05) reduction of LV ejection fraction and end-diastolic volume only during walk test performed at 1I0 beats/min. In contrast, in group B, no significant differences were observed. Conclusions: In patients with heart failure, during walk test performed at l I 0 beats/rain, there is a decline of LV performance as compared to walk tests performed at 70 and 90 beats/min. In contrast, in control group, the different levels of heart rate do not affect cardiac response to moderate physical activity. These data suggest the optimum heart rate ranging from 70 to 90 beats/rain to perform a physiological and moderate stress-test, on the other hand there is a negative effect of faster heart rate on LV function in patients with heart failure.

1247

co k~ 0= e0~

== e~

o rt

• CARDIOVASCULAR 8

PS_673

PS_675

OBESITY AND ITS RELATION TO RESTING LEFT VENTRICULAR FUNCTION AND VOLUMES

WHICH METHOD TO CALCULATE RIGHT VENTRICULAR EF CORRELATES BETTER WITH PEAK VO2 IN PATIENTS SUFFERING FROM CARDIOMYOPATHY: MUGA OR FIRST-PASS RNV?

O. De Winter (1), J. De Sutter (2), C. Van de Wiele (1), P. De Bondt (1), J. Versijpt (1), R.A. Dierckx (1). (1) Division of Nuclear Medicine; (2) Department of Cardiology, Ghent University Hospital, Belgium. Aim: Obesity is a well-known risk factor for coronary artery disease. However, conflicting data exist on the relation between BMI and left ventricular (LV) volumes and function. Methods: Data on BMI were collected in 297 consecutive patients (182 males, mean age 57±11 y, mean resting LVEF 58±1 I%) without a previous cardiac history who were referred for a diagnostic two-day Tc~m-tetrofosmin gated SPET study. In all patients LV enddiastolic and endsystolic volumes (LVEDV and LVESV) were determined from the resting gated SPET studies using QGS". LV ejection fractions (LVEF) were calculated from the obtained volumes. Resuhs: Results fur resting LV volumes and LVEF according to BMI are shown in the table.

BM[ (k~/m') LVEDV(ml) LVESV (ml) LVEF (%)

Restin[ stud~ >35 (n=17) 106±59 55±50 55±15

30-34 (n=48) 94±33 43+75 60±10

25-29(n=135) 102.+.35 46±27 58±10

< 25 (n=97) 104±48 5OL-_44 57±13

No differences fur LV volumes and LVEF were noted between the different subgroups for the resting studies. No significant correlations were found between BMI and resting LV function and volumes. Conclusions: When using gated SPET as a toll to measure LV function and volumes, obesity does not seem to be associated with a reduction of resting LVEF or an increase of resting LV volumes.

M. Hacker (1), A. Tausig (1), S. St?rk (2), R. Angermann (2), D. Stratakis (3), R.M. Huber (3), M. Weiss (1), S. Dresel (1), K. Hahn (1). (1) Department of Nuclear Medicine; (2) Department of Cardiology; (3) Department of Puimonology, LMU, Munich, Germany. Maximal exercise capacity (peak vO.~) predicts survival in candidates for heart transplantation. There have been reports that right ventricular ejection fraction (RVEF) calculated by multigated radionuclide ventriculography (MUGA) correlates well with peak vO:. Due to partial overlap it is well known that first-pass radionuclide ventriculography (FP-RNV) is superior to planar MUGA in terms of calculating ,,true" RVEF. Aim of this study was to evaluate, whether MUGA or FP-RNV correlate closer with maximal exercise capacity. Methods: In 87 patients (70 men, 17 women; age: 53 + 11.8 yrs), suffering from dilated or ischemic cardiomyopathy, 121 cardiopulmonary exercise testa (upright symptom-limited bicycle ergometry) were performed within 2.5 years. During exercise ventilatory and gas exchange data were recorded and peak vO 2 was calculated. On the same day, patients underwent FP-RNV and MUGA (in vivo labeling of RBC's, 740 MBq 9'~Tc: FP-RNV; Picker SIM 400 muhicrystal camera, projection: 30i RAO; MUGA: Picker Prism 2000, projection -40 i LAO) at rest. Results: Mean peak vOw_was 16 + 4.8 ml/kg/min. Peak vO 2 has been ? 10 in 14 pts. and between tO and 14 mt/kg,/min in 43 pts. Mean FP-RVEF was 44% ± IO, mean MUGA-RVEF was 42% ± I2. Patients with a FP-RVEF o f < 30% did have a significantly lower peak vO,. (12 ± 3.8 ml/kg) than pts. with an FP-RVEF o f ? 30% (16 ± 4.8 ml/kg; p=O,002). There was no statistically significant difference in peak vO2 for MUGA-RVEF values < 30% and ? 30% Ip=0.61 ). There was a moderate correlation between MUGA- and FP-RVEF (r=0.58). Peak vO; ~ml/k~/min) Peak vO_~? I 0 10 < peak vOw? I4 Peak vO~ > 14 Total

RVEF < 30% FP MUGA 4 5 6 3 I 12 I1 20

RVEF ? 30% FP MUGA I0 8 38 32 63 61 I 11 10t

Total FP 14 43 64 121

MUGA 13 35 73 121

Conclusion: It is well known that RVEF calculated by planar MUGA does not represent true RVEF since the right ventricle and the right atrium cannot be distinguished appropriately. As expected we fuund only a moderate correlation for RVEF calculated by MUGA and FP-RNV in patients with cardiomyopathy. However, mean RVEF was similar for MUGA and FP-RNV. Nevertheless there has been a highly significant difference concerning peak vO2 if RVEF was measured below or above 30% for FP-RNV acquisitions but no significant difference was found for MUGA data.

PS_674

PS_676

EFFICACY OF WALL MOTION ANALYSIS IMMEDIATELY AFTER EXERCISE IN DETECTING CORONARY ARTERY DISEASE USING SEPARATE ACQUISITION, DUAL-ISOTOPE GATED SPECT

TOMOGRAPHY ADDS QUANTITATIVE AND QUALITATIVE VALUE TO RADIONUCLIDE VENTRICULOGRAPHY

H. Ono, Y. Sato, M. Hashimoto, M. Mitsui, M. Muromoto, M. Kato, T. Horie, J. Kusama, T. Narumiya, T. Sakamaki, K. Kanmatsuse The Department of Cardiology, Nihon University Surugadai Hospital, Tokyo, Japan. Aim: The addition of regional wall motion analysis (WMA) using ECG-gated SPECT to myocardial perfusion SPECT alone has been reported to be of limited use in detecting coronary artery disease (CAD) because of reversal of ischemia after exercise cessation. We investigated whether nor not immediate data acquisition following exercise might improve the overall sensitivity of combined myocardial porfusion SPECT and WMA. Methods: 62 patients with angiographically proven CAD and 46 patients judged to have low likelihood of CAD determined according m the AHA/ACC guideline entered the study. A high-resolusion collimator with 1gO-degree acquisition over 64 projections and 25-45 seconds / projection (Siemens E-cam) was utilized. Following rest ECG-gntad T1-201 imaging, the patients underwent symptom-limited, multi-stage bicycle ergometer exercise. 99mTc-tetrofusrain (740MBq) was injected at the end of exercise. Immediately at~er exercise cessation, the patients underwent gated 99roTe imaging for 13 rain. This protocol allows post-stress imaging by 99mTc-tetrofosmin to be completed within 15 rain following exercise cessation. Results: The both rest and post-strass images were satisfactory for analysis of myocardial potfusion imaging and wall motion analysis in all patients with good separation of the heart from the liver. When only myocardial peffusion SPECT was applied, the sensitivity, specificity and diagnostic accuracy of the test were 89%, 87% and 88%, respectively. When perfusioo SPECT and wall motion analysis were combined, the sensitivity was improved significantly to 92%. The specificity and the diagnostic accuracy were 85% and 89%, respectively. There were 3 patients who exhibited wall motion abnormality without significant porfusioo defect. Conclusion: The addition of WMA immediately a~er exercise to myocardial perfusion SPECT improves the sensitivity and diagnostic accuracy for detecting CAD.

124~]

I.R Clements, B.R Mullan, B.H. Brinkman, M.K. O'Connor. Mayo Clinic and Foundation, Rochester, Minnesota, USA. Planar blood-pool radionuclida verltrlculography(RNV) is currently the most accurate, reproducible and readily available non-invasive method for measurementof left ventricuiar (LV) function. However,the addition of tomography (SPECT) promises to expand the usefulness of RNV. The ability of SPECT RNV to measureLV and right ventricular (RV) ejection fraction (EF) and volumes and wall motion was evaluated in 26 patients (using a dual-beadod gamma camera, 8-16 frames/cardiac cycle. 180? rotation, 30 images/rotation, 60 sec/stup). From this single acquisition, cardiac transaxial imagaswere reconstructedto generatecardiac long (horizontal and vertical) and short axis image slices. Simultaneous display of all three sets of images with superimposition of bars identifying a spocific slice location allowed identification of valve planes and facilitated quantitative analysis; horizontal long axis and short axis slices were optimal for analysis of the RV and LV respoctivety. Manually defined RV and LV regions of interest were used to determine RV and LV eod--diastolic and end-systolic volumes and ejection fraction; background correction was found not to be necessary. Good correlations (p<0.0001) were evident between $PECT RNV and concurrently obtained planar RNV with regard to LVEF (0.86) and end-systolic (0.81) and end-diastolic (0.76) volumes. RVEF and volumes were readily determined with SPECT R.NV but must be validated against another imaging method such as electron beam computerized tomography. The tomographic images also provided global evaluation of RV and LV wall motion. Thus a single tomographic acquisition maintained the ability of RNV to accurately assess the LV and greatly enhanced the qualitative and quantitative ability of RNV to evaluate the RV and cardiac wall motion.

• CARDIOVASCULAR

8

PS_677

PS_679

INDIRECT EVALUATION OF LV DIASTOLIC DYSFUNCTION WITH

UTILITY OF SClNTIGRAPHY WITH 99MTC-PYROPHOSPHATE AND 99 MTC- TETROFOSMIN SPECT IN THE DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION

MYOCARDIAL PERFUSION SCINTIGRAPHY TC-99M MIBI IN PATIENTS WITH MYOCARDIAL INFARCTION - CORRELATIONS WITH ECHO-DOPPLER PATTERNS

C. Medrea, A. Bogdan, R. Petrovici, C. Suciu, S. Mot, R. Capalneanu, M. Barsan. Clinical Cardiology, Heart Institute, Cluij, Romania. PURPOSE: To correlate the localization and the severity of the myocardial perfusion deflects in patients with MI with the degree of LV diastolic disfunction evaluated at cardiac echodoppler. METHODS: We studied 32 patients (age between 42-70 years, 22 male and 10 female) with MI older than one year. We excluded: moderate and severe LV hypertrophy, more severe than l-st degree mitral regurgitation, LVEF<40% and other disorders which could produce alterations in preload or afterload. All the patients underwent rest and stress myocardial perfusion scintigraphy with 99m-To MIBI SPECT in the two-days protocole. For regional analysis of perfusion, myocerdium was divided in 16 segments. In each patient, corresponding resting and stress 99m-Tc MIBI tomographic images were evaluated fur direct comparison and segmental tracer uptake was quantitatively analysed using a four-point scoring system (3=normal uptake, 2=slightly reduced, I=severaly reduced, 0=absant). Also a Gated SPECT for LVEF quantification was performed. Each patient was further investigated by coronary angiography in order to establish the coronary anathomy. The following parameters were measured using PW doppler with the sample volume at the tip of the mitral leaflets and in the left upper pulmonary vein: E/A, deceleration time, isovolumetric relaxation time and velocities of pulmonary flow, obtaining different patterns of diastolic disfunction (abnormal relaxation, pseudonormal and restrictive patterns). RESULTS; The terrytorial distribution of irreversible (i), accompanied or not by reversible (r) perfusion defects in the same or another region, was the following: 18p with necrosis in LAD teritory (10i and 8i+r),10p with necrosis in RC teritory (3i and 7i+r) and 4p with necrosis in Cx theritory (2i and 2i+r).12p of the LAD group, 4p of the RC group and 2p of the Cx group had scores 0 and I. 6p-LAD, 6p-RC and 2p*Cx had scores 2 and 3,EchoMoppler evaluation of diastolic function revealed a normal pattern for 3p (2p--Re, Ip-Cx) with scintigraphic scores 2-3, abnormal relaxation for 20p(10p-LAD, 7p-RC and 3p-Cx), pseudonormalization for 2p of the LAD group and restrictive patterns for 7p (5wLAD with score 0-1, Ip-LAD with score 2 and I p-RC). CONCLUSIONS: Myocardial necrosis situated in LAD theritory with a scintigraphic score 0I is more frequently associated with diastolic dysfunction of a restrictive type. compared to necrosis in RC or Cx theritory fbr the same scintigraphic score. Abnormal relaxation is more often found in patients with RC and Cx infarction without relation with the scintigraphic score and in LAD infarction with score 2-3.

A.M. Garc~a (1), V. Pcblete (1), S. Rodado (1), C. Rodriguez (2), L. Celemin (3), A. Soriano (1). (1) Department of Nuclear Medicine, Alarcos Hospital, Ciudad Real, Spain; (2) Department of Investigation, Alarcos Hospital, Ciudad Real, Spain; (3) Department of Cardiology, Alarcos Hospital, Ciudad Real, Spain Aim: To determine the utility of pyrophosphate scintigrapby (PYP-S) in the diagnosis of acute myocardial infarction (AMI) and to assess the location. To study if the tetrofosmin SPECT (I"SPECT) is helpful in this group of patients. Methods: 80 patients underwent PYP-S (59 males and 21 females) with an average age of 56 (16-82). The suspicious diagnosis was AMI in 70 patients and myopericarditis in 10. All patients bad at least two inclusion criteria (chest pain, high level of creatine kinase-MB and electrocardiogram alterations). Planarimages (g0 patients) and SPECT (23 patients) were carried out afier administration of 740 MBq of PYP and 185 MBq of tetrofusmin within a medium time of four and eight days afier the onset of the symptoms respectively. Results: 44 patients were diagnosed of AMl, 10 of angor, 15 of myopericarditis and I 1 with other no ischaemic diseases. The results of PYP-S were the following:

Of the 21 false negative, 15 corresponded to no Q infarction. The values of sensitivity, specificity, PPV, NPV and accuracy for PYP-S were 52,3%, 94%, 92%, 61,8% and 7 I% respectively. In 25 cases, PYP uptake was positive, 17 with focal uptake and 8 with diffused uptake. There were 16 cases of AMl with positive PYP and fucal standard, 10 of them had the same location with PYP-S uptake and AMI area. The medium time of PYP-S was 3,9 days in true positives and 4,1 days in false negatives. T-SPECT was realised in 23 patients. 14 of them showed an uptake defect compatible with infarction, 13 with final diagnosis of AMl and 1 with previous infarct (false positive for AMI) .5 cases resulted negative in both test. and only one of them was an AMI. 4 cases showed a diminished uptake within viability limits and the final diagnosis was ischaemia. 8 cases with negative PYP-S and final diagnosis for AMI (FN), showed positive T-SPECT in 7 cases, and only one resulted negative. Conclusions: The PYP-S demonstrated to be effective in the diagnosis of AMI with Q wave and showed a high specificity and PPV. However, it was not very sensitive. Final results of PYP-S were not influenced by the time of the scintigraphy. T-SPECT can be helpful in AIM cases with negative PYP-S.

cO

PS_678

PS_680

THE CLINICAL VALUE OF TC-99M-MIBI GATED SPECT FOR THE EVALUATION OF LEFT VENTRICULAR FUNCTION AND VOLUMES AS COMPARED WITH ECHOCARDIOGRAPHY

THE RELATIONSHIP BETWEEN THE RIGHT SYSTOLIC VENTRICULAR FUNCTION AND LEFT DIASTOLIC VENTRICULAR FUNCTION DEPRESSED: USEFULNESS OF THE RADIONUCLIDE

N. Alan (1), O. Ozmen (1), M. Hala~; (1), C. Nisli (1), L. Kclda~ (2), I. Ba,~ar (2), L. Kabasakal (1), H. Karpuz (2), C. Onsel (1), I. Uslu (1). (1) Department of Nuclear Medicine ; (2) Department of Cardiology, Istanbul, Turkey. Technical improvement has recently permitted in the routine use of gated SPECT in myocardial perfusion imaging for evaluation of attenuation artefacts. Ecbocardiography is the standard method of evaluating lefi ventricular function in clinical practice. Aim: The aim of this study was to determine if left ventricular function determined from gated-SPECT myocardial imaging adequately coincides with echocardiographic data .Method: For this purpose we studied 75 patients, ages ranged from 38 to 83 years (mean 59.7±10.5), who referred for myocardial perfusion imaging (52f, 23m). All patients underwent same day stress-rest Te-99m-MIBI gated-SPECT study and gated-SPECT was performed by 8 frames per cycle acquisition over a 180 degree rotation on 32 projections. Four gated-SPECT slices were obtained on midventriculer vertical long axis, horizontal long axis, apical and basal short axis planes. Ejection fraction (EF), end diastolic volume (EDV) and end sistolic volume (ESV) were calculated from gated-SPECT data using an automatic edge detection algorithm from resting perfusion images. EF, EDV(n=28), ESV (n=28), end diastolic diameter (EDD) and end sistolic diameter (ESD) were obtained from echocardiography using a standard technique. Results: EF values obtained from gated-SPECT ranged from 14 to 81 with a mean value of 57,2±11.4. EF values obtained from echocardiography were ranged from 27 to 72 with a mean value of 55.4±6.8 (p>0.5). The correlations between gated-SPECT and echocardiography with respect to left vantricular ejection fraction, end diastolic volume and end sistolic volume were ranged from good to excellent with correlation coefficients of 0.68, 0.61 and 0.93, respectively (p<0,001, Pearson's coefficient). Conclusion gated-SPECT has a good correlation with ecbocardiography for the assessment of lefi ventricular function and these results support the clinical use of gated-SPECT technique.

O O3

,o

ANGIOGRAPHY(RNA)

M.J. Accsta-Gbmez, A. McraI-Ruiz, M.D. Martinez, A. Rodriguez, M.A. Muros, G. Sabatell, S. Ortega, J.M. Llamas-Elvira. Department of Nuclear Medicine, Granada, Spain. Aim: To prove if exists relationship in the incidence of systolic right dysfunction and the left diastolic function. Patient and methods: Retrospective study of 650 patient sent to our laboratory by customary motives. All of them had measured through a RNA the ejection fraction of the left ventricle (LVEF), of the .,fight ventricle (RVEF), and the following diastolic function parameters of the VI: peak filling rates(PFR) and average(AFR), time of the PFR (TPFR), filling fraction to the first third expressed in percentage of volume Tele-diastolic (FF_EDV), and beat (FF VL). The population of study, the pathological groups and results are the following: N=650 Male Female AURIC. FIBR. LV DISF./ISQ. VALVULAR CARDIOTOX. MISCELLAN. AGE HEART RATE LVEF ~%) PFR (EDV/s.) (EDV/s.) TPR (ms.) FF_EDV (%) FF_VL (%)

RVEF<42% 228 (35.1%) ' 152 (23.4%) 73 (I 1.2%7 133 (20.5%) 30 (4.6% 7 6l (9,4% 7 83 (12.8%) Mean:t:Std.error 55.80 ± 0.83 80.21 ± 1.05 47.04 ± 0.82 2,46 • 0.05 1.32 :i: 0.03 164 ± 3.67 44.88 ± 0.92 21. I 0 ± 0.57

RVEF>-~.2% 154 (23.7%) 116(17.8%) 70 (10.8%) 72(11.1% 7 26 (4.0%) 25 (3.8%) 77 (11.8% 7 Mean±Std.error 57.18 ± 0.80 74.24 ± 0.89 55.13 • 0.76 2.66 ± 0.06 1.40 ± 0.03 173 ~: 4.25 41.72 ± 0.88 23.16 ± 0.57

T-test (2-Tail) N.S. N.S.

N.S. P<0.OI P<0.01 P<0.05 AFR P<0.05 N.S. P<0.05 P<0.01

Conclusions: Our results express that exists a association between the alterations of the diastolic function of the LV and the systolic dysfunction of the RV. The diastolic parameter with greater power of association is FF_VL.

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O IX

• CARDIOVASCULAR 8 / DIAGNOSTIC ONCOLOGY 14 PS_681

DIAGNOSTIC ONCOLOGY 14

RELATIONSHIPS OF LEFT VENTRICULAR MASS AND FUNCTIONAL PARAMETERS

PS_683

B.C. Ahn, J. Lee, S.W. Lee, K.B. Lee. Department of Nuclear Medicine, Kyungpook National University Hospital, Taegu, South Korea. The purpose of this study was to evaluate the relationship between lefi ventricular masses(LVM) and timctional parameters measured by gated myocardial perfusion SPECT. Methods: One hundred sixty-four subjects{M/F=94/70, ranged 32 to 84 yrs, mean age 58yrs) wenderwent ~mTc-MIBI gated myocardial perfusion SPECT with dual head SPECT camera. We measured LVM, end diastolic volume(EDV), end systolic volume(ESV) and ejection fraction(EF) of LV by AutoQuant program and evaluted the relationship of these parmeters using pearson's correlation test. Results: Forty-seven subjects(27%)sbowed perfusion defect in myocardial SPECT. EDV and ESV were positively correlated with LVM, and EF was negatively correlated with LVM in Stress and rest gated myocardial per fusion SPECT. Correlation of LVM and functional parameters(EDV. ESV. EF) measured by quantitative myocardial perfusion SPECT

GALLIUM SCAN IN THE CLINICAL MANAGEMENT OF ADOLESCENTS AND CHILDREN WITH HODGKIN DISEASE M. Castellani (1), G. Cefalo (1), C. de Graaf (2), M. Terenziani (1), S. Baio (1), G. Aliberti (1), M. Maccauro (1), E. Bombardieri (1). (1) Istituto Nazionale Tumori, Milano, Italy; (2) Leiden University Medical Centre, Leiden, The Netherlands.

All data mean correlation coett]cient(r) and p value(p) for LVM and functional parameters. Conclusion: LVM was positively correlated with EDV and ESV and negatively correlated with EF.

Gallium scan is a well consolidated diagnostic approach in Hodgkin's diseases of adult age. Very few reports are available in pediatric age. Gallium scan results in 74 consecutive patients, observed in our Institute between Apr 1985 and Jul 1999 and subsequently followed until today, were retrospectively reviewed. The aim of this study is to assess the clinical impact of gallium scan in the management of pafients with Hodgkin's disease, from the onset of disease, in correlation with response to therapy and. more in general, to the clinical course of disease. Methods: Seventy-four patients (mean age:13) underv.,ent gallium scans for initial staging, 71/74 (I 14 scans) repeated scintigraphy during the follow-up (usually two controls) to assess the achievement of complete response (CR), or in few cases (12) to confirm progression or relapse of the disease. A whole-body scan was performed afier 48 or 72 hours of the injection of 37-111 MBq of ~TGa citrate (related to body weight) using a large field gamma-camera with a medium energy collimator. Results: Patients were classified 36 stage 1-11.21 stage Ill-IllS stage, and 17 stage IV, At initial staging, gallium scans resulted positive in 72/74 patients (97%), detecting 264 of 309 lymph nodal sites of disease, Gallium scan was positive, concordant with the clinical findings, in 84% of the patients. The best sensitivity was observed in mediastinum 64/64 (I00%) and neck 124./146 (84%) and was lower in the axifia 16/22(72%) and retroperitooeum ( I 1/16: 69%). In case of visceral involvement gallium resulted effective tbr lung (11/15) and bone (4/5) detection. The aggressiveness of this lymphoma did not alter the sensitivity of the gallium scan for the detection of tymphnodes, as the sensitivity in stage [-II and IllS-IV were similar During the follow-up, gallium scan resulted concordant with clinical and radiological findings in 28/29 (97%) cases with confirmed or suspected relapse or progression. In 42 patients with a single scan, which achieved a CR during or at the end of the first line treatment, this CR was confirmed by gallium scans in 40 patients and by conventional techniques in 21 patients. Conclusion: On the basis of this results we can confirm the clinical usefulness of gallium scan in the diagnosis and tbllow-up of patients with Hodgkin's disease. Gallium appears eflbctive in confirming the absence of disease in patients with positive scan at staging.

PS_682

PS_684

EFFECT OF L-CARNITINE SUPPLEMENTATION ON MYOCARDIAL ENERGY SUBSTRATE UTILIZATION IN PATIENTS WI.TH CHRONIC RENAL FAILURE AND RECEIVING HEMODIALYSlS

TECHNETIUM-99M-SESTAMIBI AS A PREDICTOR OF RESPONSE TO CHEMOTHERAPY IN INDIVIDUAL T U M O R S OF PATIENTS WITH NON-HODGKIN'S LYMPHOMA

K. Fukushima (1), Y. Ishida (1), K. Fukuchi (1), M. Inubushi (2), K. Sugimura (3). (1) Department of Radiology, National Cardiovascular Center, Suita, Japan; (2) Department of Pharmacology, UCLA, I.A, USA; (3) Department of Radiology, Kobe University, Kobe, Japan.

H.-.C. Song (1), H.S. Born (1), J.J. Lee (2), H.J. Jeong (1), I.J. Chung (2), S.M. Kim (1), M.R. Park (2), H.J. Kim (2), J.Y. Kim (1). (1) Department of Nuclear Medicine; (2) Department of Hematology, Chonnam National University Hospital, Kwangju, South Korea.

A decrease in intraceltular L-camitine (L-C) concentration, which is a key substratc for myocardial fatty acid metabolism, has been observed and recognized to possibly induce the life-threatening myocardial dysfunction in patients with chronic renal failure (CRF) arc=" hemodialysis (HD). Based on this evidence, administration of L-C has been recommended for these patients. However, recent experimental studies in L-C deficient rats find that L-C increases glucose utilization rather than normalize fatty acid metabolism in myocardium associating with improvement of cardiac function. The aim of this study was to observe the effect on L-C treatment on myocardial energy substmtc utilization in patients with CRF after HD and with L-C deficiency. Methods: L-C was administrated orally at doses of 500 rag/day for 3 month in 5 CRF patients aRcr HD. To evaluate myocardial fatty acid end glucose utilization before end a f a r L-C treatmerit, 1231-labeled _-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) SPECT imaging and 18F-labeled fluorodeoxyglucose (FDG) PET imaging were performed in the fasting state. In the 15-rain early and 210-min delayed anterior planar imaging, myocardial BMIPP uptake estimated by the heart to mcdiastinum ratio (H/M) and myocardial BMIPP washout rate (WR) were determined. In the dynamic FDG PET imaging, myocardial glucose utilization (MGU) was determined by Padak plot analysis. Results: Free L-C concentration in blood increased from 37.5±9.1 molc/L to 75.5±13.5 _mole/L ai~er the treatment. H/M end WR in BMIPP imaging did not change (2.78~0.43 to 2.60±0.20, 18.5±4.2 to 16,4:~9.2, respectively), while MGU significantly ineres.sed from 1,52±0.96mg/g/min to 3.58±1.02 mg/g/min (p<0,05). In the 3-month follow-up, there was no significant improvemant in cardiac function. Conclusion: L-C administration augments glucose utilization rather then normalizes fatty acid utilization in myocardium under the L-C deficient state in humans. It may require further investigation whether this metabolic change improves cardiac function or not.

Objective: We evaluatedwhetherthe tumoral retentionof Tc-99m sestamibi was correlated with responseto chemotherapyin individual tumors of patients with non-Hodgkin's lymphoma(NHL). Methods: Seventeenpatients (9 women end 8 men, mean age 57+[2) with histologically provenNHL underwentMIB[ scanbeforestartingchemotherapy.Thirteen patientsweret~cat-

Subjects with perfusion defectln=117) Stress SPECT Rest SPECT EDV r=0.882, p<0.OI r=O.852, p<0.OI ESV r=0.859, p<0.01 r=0.827, p<0.01 EF r=-0.558, p<0.01 r=-0.541, p<0.01

Subjects without perfusion defect(n--47 t Stress SPECT Rest SPECT EDV r=0.875, p<0.01 r=0.892, p
¢d with C H O P regimen, 2 C H O P followed by |FRT, and 2 D H A P regimen. Both I0 rainand 3 hr image'swere obtainedaRer injectionwith 740 M B q of Te-99m sestamibiusing a dual-bead rotating g a m m a camera. Tumor-to-normal soi~ tissue ratios(T/N) were measured. Percent retention(%R) was defined as T/N ratioat 3 hrs divided by T/N ratioat 10 rain multipliedby 100. Results:A totalof 40 tumor lesionswere detectedin the patientsby physicalexamination and C T scans.Twenty-two of them (55%) showed Tc-99m sestamibiuptake.% R of tumors which dissppcared afterchemotherapy was significantlyhigher then % R of tumors which remained aRer chemotherapy (91.I+14.9% vs. 66.9-.t:I.86%,respectively,P = 0.04).Moreover, mean % R of tumors in patients showed negative correlations with serum L D H level (r--0.742,P=0.04),the score of internationalprognostic index (r = -0.717, P = 0.009), end Ann arbor stage(r = - 0.620, P = 0.024). Conclusion: These findings suggest that retention ofTc-99m sestamibi in individual tumors is

relatedwith responseto chemotherapyas well as prognosisof patientawith NHL.

• DIAGNOSTIC O N C O L O G Y 14

PS_685

PS687

PROGNOSTIC VALUE OF GALLIUM-67 SClNTIGRAPHY AS A PREDICTOR OF RESIDUAL TUMOR VIABILITY AND CLINICAL OUTCOME IN L'Y'MPHOMA'S PATIENT: A ELEVEN YEARS FOLLOW UP

TECHNETIUM TC-99M-TETROFOSMIN SCINTIGRAPHY IN THE DIAGNOSTIC ASSESSMENT OF PATIENTS WITH LYMPHOMAS: COMPARISON WITH CLINICAL AND RADIOLOGICAL EVALUATION: PRELIMINARY REPORT

M. Gasparini (1), M. Castellani (1), L. Maffioli (2), R. Benti (1), M. Rognoni (1), G. Biscontini (1), E. Bombardieri (3). (1) Department of Nuclear Medicine, Ospedale Maggiore-IRCCS, Milano, Italy; (2) Departmen of Nuclear Medicine, Ospedale A. Manzoni, Lecco, Italy; (3) Department of Nuclear Medine, Istituto Nazionale dei Tumori, Milano, Italy. Aim. The aim of this study is to evaluate the ability of gallium scintigraphy aPter 4 cycles of chemotherapy (CT) to predict the clinical outcome of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Methods. The study included 77 patients (48 HD and 29 NHL) who were prospectively evaluated for I1 years (follow up 132 mths; range 7-132 mths). All pts underwent restaging 2-4 weeks afrer the end of 4 cycles of CT. In 65 pts the results were compared with Magnetic Resonance (MR) and in 12 with Computed Tomography (CT scan). Failure-Free Survival (FFS) in pts with positive or negative test were compared by means of Kaplan- Meier curves using the significance of the differences. Results. Of 58 pts (41 HD and 17 NHL) with negative Ga-67 after 4 cycles of Ct, 53 (91%) remained in clinical remission (CR) after 132 mths (mean follow up 69,5 mths from presentation of the disease) and 5 pts died (mean follow up 16.5 mths) due to disease relapse. In this group the results of the scan was compared with MR in 51 pts; the results were discordant in 5 cases, 3 false positive for MR and 2 for Ga-67. The remaining 7 patient were compared with CT scan, wich showed one false positive result. Treatment failure occured in 13 of 19 pts with positive gallium scan after 4 cycles of CT (68.4%); the man follow up pf this group was 3 I mths. Six pts were considered in CR (mean follow up 72 mths). There was a significant difference in FFS between pts with positive and negative Ga-67 scan after 4 cycles o f C T (p
M. Kula (1), A. Tutu~ (1), B. Eser (2), HI. Sarl (3), O. Turhal (1), M. (~etin (2). (1) Department of Nuclear Medicine; (2) Department of Hematology; (3) Department of Internal Medicine, Erciyes University, Kayseri, Turkey. Tc-99m tetrofusmin imaging has been used in nuclear oncology, but its role in detecting lymphomas has not been widely investigated. Sixteen untreated patients (l I M, 5 F, aged 24- 70 years) with biopsy proven lymphomas (14 non-Hodgkin's and 2 Hodgkin's) underwent Tc-99m tetrofusmin whole-body imaging. Posttreatment investigations were also done in 6 of the 14 patients afrer first chemotherapy cycle. Focal pathological tetrofasmin uptake was seen in 37 sites in 11 patients, whereas computed tomography (CT) identified 42 pathologic regions 13 patients. Tc-99m tetrofosmin failed to visualize infradiaphragmatie 5 lesions in 3 patients. A total of six unknown tumor lesions in 3 of 16 patients were discovered on Tc-99m tetrofosmin scans. The tumor-to-background ratio ranged from 1.36- 2.12 (I.66+/- 0.24). A response to treatment was demonstrated by a reduction in localized Tc-99m tetrofosmin uptake in 4 of 6 patients, and by the disappearance of localized Tc-99m tetrofusmin uptake in 2 of 6 patients. Tc-99m tetrofosmin scintigraphy may be useful in patients with lymphomas for localization tumor lesions, especially supradiaphragmatic ones, and, hence, may be considered an alternative to gallium scanning. Tc-99m tetrofosmin scintigraphy seems to be a suitable method for the prediction of therapy outcome.

c-

PS_686 COMPARISON OF SESTAMIBI AND GALLIUM SCINTIGRAPHY IN THE ASSESSMENT OF LYMPHOMAS L. Feggi (1), S. Moretti (2), S. Panareo (3), N. Prandini (1), G.L. Scapoli (2), G.L. Castoldi (2). (1) Nuclear Medicine, St. Anna Hospital of Ferrara; (2) Haematology, University of Ferrara ; (3) Nuclear Medicine, University of Ferrara, Italy.

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PS_688

.co

co

Abstract withdrawn

Q,

t, O IX

Theaim of this studyis to evaluatethe usefulnessof MIBI versusGalliumscintigraphyin the assessmentof the minimal residualdiseasein malignantlymphomapatientsand to compare theseresultswith the standardimagingtechniques. Material and methods: Between 1996 and 2000 we studied 51 patients (27 female, 24 male) affected by malignant lymphoma: 23 high grade NHL, 2 low grade NHL, 26 HD. At the time of the diagnosis all patients were studied with CT: total body scinfigraphy with MIB[ (MS) and Gallium (GS) always associated to SPECT were also performed for a total of 448 segments examinated. MS was performed 10 minutes after the administration of 740 MBq of the radiopharmaceutical while GS was performed on the third day after the injection of 370 MBq of Ga. The patients were treated with chemotempy, radiotherapy and autologous peripheral stem cell transplantation. All the studies were repeated 6 months and ! year after the time of the diagnosis. While we don't have a reference examination in the assessment of |ymphoma we have compared our scintigraphical results with clinical and hematological remission status of the patients. Results: At the diagnosis, CT showed 43 positive supra-diaphragmatic, 5 subdiaphragmatie and 19 both supra- and subdiaphragmatic [ocafizations. Of 31 GS and 31 MS performed, respectively 90% and 87% resutted positive: on the basis of the intensity of the uptake the results were divided in high positive (respectively 6004 and 50% of cases) and low positive (30% and 37%) showing a similar behaviour. At six months from the diagnosis 49 patients were studied: CT resulted completely negative in 31% of the patients and the lymphoma disease resulted decreased of more then 50% in 28.5% of patients. In the same patients GS and MS resulted negative in 57% and 64% showing a similar behaviour. At one year from the diagnosis 46% of CT resulted negative and 61% and 70% of GS and MS respectively resulted negative. At the Spearman and ROC curve analysis the results, considering all 448 segments, were not statistically significative (p<0.05). Conclusions: Scintigraphy demostrated a high accuracy in the evaluation of minimal residual disease in lymphoma patients and we could not demnstrate a significative difference between GS and MS, especially in supra-diaphragmatic localizations. Because the physical properties (energy and irradiation) of 99mTc-MIBI, its daily availability in a Dpt of General Nuclear Medicine, we suggest the replacement of GS with MS in the assessment of lymphoma patients,

1251

• D I A G N O S T I C O N C O L O G Y 14

PS_689

PS_691

TL-201 IMAGING IN PATIENTS WITH LOW-GRADE NONHODGKIN'S LYMPHOMA RECEIVING LOCALISED LOW-DOSE IRRADIATION

COMPARING STUDY OF GALLIUM-67 AND 99M T C - - M D P SClNTIGRAPHY IN LYMPHOMA WITH BONE INVOLVEMENT

R.A. Valdes Olmos (1), R.L.M. Haas (2), C.A. Hoefnagel (1), D. de Jong (3). (1) Department of Nuclear Medicine; (2) Department of Radiotherapy; (3) Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Purpose: Localised low-dose irradiation has been introduced successfully in the treatment of low-grade non-Hodgkin lymphoma (NHL). We evaluated imaging with TI-201 chloride in low-grade NHL patients receiving this treatment modality in order to establish parameters of metabolic turnout response for therapy outcome. Methods: Total body images followed by SPECT were performed one hour after administration of 150 MBq of TI-201 chloride in 43 patients (mean age 60,4y, range 39y-86y) with lowgrade NHL scheduled for Iocalised radiotherapy of the affected areas with a dose of twice 2 Gy. Images were perthrmed before and 6-8 weeks after irradiation, and were compared with both clinical andradiological findings. Results: Before radiotherapy T1-201 imaging was positive in 39 patients (88%). Sensitivity to detect NHL at all affected sites was 65% (88/135), with 50% (23/46) for intra-abdominal lesions and 73% (65/89) for Iocalisatiens outside the abdomen. The sensitivity for the neck was 8t% (21/26). In 4 patients TI-201 detected new lesions. Thirty-one patients with initially a positive TI-201 study were investigated afier radiotherapy. TI-201 normalised in 20 of 22 patients who reached complete remission during follow-up (Fig. I), and remained abnormal in 9 patients with partial remission or stable disease. Conclusion: TI-201 may be helpful in the management of low-grade NHL patients treated with low-dose irradiation. The method is especially sensitive in detecting extra-abdominal lymphoma sites. TI-201 imaging appears to be very useful thr the monitoring of response to radiotherapy, and both a negative and a positive test alter treatment may be used to predict outcome.

H. Wang (1), C. yu (2), T.I.A.N. Wei Jia (1), B.O. Min Fang (1), Z.H.U. Cheng Mo (1). (1) Department of Nuclear Medicine; (2) Department of InternaI,Rui Jin Hospital,Shanghai,China. Purpose: Evaluation of Ga-67 imaging in lymphoma with bone invo]vement was performed by the comprasion with Tc-99m-MDP bone scan. Methods: In 63 patients with bone involvement of lymphoma proven by CT, X-rays or biopsy included 17 with Hod~in's lymphoma(HL) and 46 with Non-Hodgkin's lymphoma(NHL),Ga-67 and -.,r, Tc-MDP seintigraphy were performed after 48-72h of Go-67 injection (10 mCi ) and 3-4h of Tc-99m-MDP injection (20 mCi ) in all patients.Of these,42 patients were imaged after 4cycles of chemotherapy.Result ananlysis:l.Diagnosis of bone lesions:Any spot abnormal uptake of radioactivity in bone will be considered as positive lesion.2.Comprasion of prior- and post-therapy Ga-67 imaging: l)lf abnormal uptake of Ga-67 returned to normal after treatment,that suggested the complete remission of bone lesion.2)lf Ga-67 bone uptake remained abnormal,the bone lesion was defined as no remission.3.Compras~on of Go-67 and ' ~ Tc-MDP uptake density in the same bone lesion. Results: In 63 patients,total bone lesion is 128.The diagnostic sensitivity of Ga-67 and wm TcMDP scintigraphy is 89% and 98% respeetivel%The q~ Tc -MDP uptake is higher than Ga-67 in 31 bone lesions.but there are 21 bone lesions with higher Ga-67 uptake than 9e~Tc M DP.About monitoring therapy,accurate rate of Go-67 imaging is 91%,tbe bone lesions with no remission were still have abnormal uptake of Ga-67.Average time of follow-up is 1.5 years. Conclusion: Ga-67 scintigraphy comectly monitored the response to treatment in patients with bone involvement of lymphoma;Detection rate o f ' ~ Tc -MDP imaging was better than Ga-67 imaging in patients with bone involvement of lymphoma.

Fig. I. Anterior planar TI-201 images showing: A) Abnormal uptake in both sides of the neck as well as in both axillary and lung hilar regions belbre radiotherapy. B) A normal pattern alter low-dose irradiation.

PS_690

PS_692

COMPARISON OF TECHNETIUM-99M-TETROFOSMIN AND GA-67 CITRATE SClNTIGRAPHY IN THE ASSESSMENT OF LYMPHOMAS: PRELIMINARY REPORT

TC-99M TETROFOSMIN SClNTIGRAPHY IN THE DIAGNOSTIC ASSESSMENT OF PATIENTS WITH U M P H O M A S

A. Tutup (1), M. Kula (1), B. Eser (2), HI. San (3), A. Unal (2), M. Caycl (1). (1) Department of Nuclear Medicine, Erciyes University, Kayseri, Turkey; (2) Department of Hematology, Erciyes University, Kayseri, Turkey; (3) Department of Internal Medicine, Erciyes University, Kayseri, Turkey. The aim of this study was to compare Tc-99m tetrofosmin scintigraphy and Ga-67 scintigraphy in the diagnostic assessment of patients with lymphomas and to relate these results with those of radiological evaluation. Method: Sixteen untreated patients (11 M, 5 F, aged 24- 70 years) with biopsy proven lyrephotons (14 non-Hodgkin's and 2 Hodgkin's) were studied with 99mTc°tetrofosmin seintigraphy and then with Ga-67 scintigraphy before any therapeutic intervention. Post-treatment investigations were also done in 6 of the 14 patients al~er first chemotherapy cycle. Results: The diagnostic accuracy of Tc-99m tetrofosmin and Ga-67 imaging for lesion detection was 88% and 90%, respectively. A total of seven unknown tumor lesions in 3 patients were discovered on Tc-99m tetrofosmin and Ga-67 scans. Tc-99m tetrofosmin failed to visualize infradiaphragmatic 5 lesions in 3 patients, but 3 of 5 lesions visible on Ga-67 images. The tumor-to-background ratio was 1.66+/- 0.24 (ranged from 1.36- 2.12) for Te-99m tetrofosmin and 2.38+/- 0.48 (ranged from 1.68- 3.16) for Go-67. A response to treatment was demonstrated by a reduction in localized pathological uptake (Tc-99m tetrofosmin and Ga-67) in 4 of 6 patients, and by the disappearance of uptake in 2 of 6 patients. Conclusion: Te-99m tetrofosmin scintigraphy may be considered an alternative to gallium scanning for the localization tumor lesions and the prediction of therapy outcome in patients with lympbomas. However, the intense Tc-99m tetrofosmin activity in the lower chest and abdomen may limit the diagnostic sensitivity of this radionuelide technique in patients with lympbomas.

1252

F. Scopinam, A. Filippis, AR Anselmo, F. Monteleone, B. Campanella, R. Massa, E Capoccetti, V. De Santis, R. Maurizi Enrici, O. Schillaci, A. Centi Colella Exp. Medicine, Section of Nuclear Medicine University of Rome, Rome, Italy. Tc-99m tetrofosmin imaging hasbeen used in nuclear oncology, but its role in detecting lymphomas has not been widely evaluated. Methods: To assess the utility of Tc-99m tetrofosmin scintigraphy as a diagnostic modality in lymphnma, 17 patients (pts, 14 with Hodgkin's and 3 with non-Hodgkin's disease; 5 females and 12 males, age range: 10-59 years) were investigated. Planar and SPECT images of the supradiaphragmatic region (including neck and chest) were acquired starting 15 minutes postinjeetion. All pts had been untreated at the time of the first scintigraphy. Follow-up scans aRer therapy (ABVD chemotherapy, radiotherapy) were performed in 6 pts (in 5 twice), so a total of 28 scintigraphic studies were acquired. Mediastiual, pulmonary, cervical, supraclavicular and axillary activity was evaluated and results were compared in a blinded fashion with those of CT. Results: Tc-99m tetrofosmin imaging demonstrated pathological focal uptake at 38 sites (16 in the mediastinum, 8 in the lungs. 4 in the axillas, 8 in the supraelavicular and 2 in the cervical region) in 16 out of 17 untreated pts; CT identified 24 lesions (16 in the mediastinum, 2 in the lungs, 2 in the axillas, 2 in the supraelavicular and 2 in the cervical region) in 17 pts. Seintigraphy detected 22 out of 24 lesions demonstrated by CT and revealed 16 unknown tumour sites in 10 pts. The only negative pre-therapy seintigraphy was in a case with axillary lymph-node involvement. In the first post-treatment seintigraphy, there was a reduction in the number of visualized pathological sites (7 vs 16) in 5 out of 6 investigated pts. The second follow-up study demonstrated only 2 lesions in 2 out of 5 evaluated pts. There was a good agreement between post-therapy scintigraphic results, response to treatment and clinical outcome of pts. Coneluslnns: Our preliminary results indicate that Tc-99m tetrofasmin imaging is effective in depicting supradiaphragmatic lympboma lesions in untreated pts and suggest that serial scintigraphic studies may be suitable tbr monitoring response to treatment. However, larger series are needed to better define the possibte role ofTc-99m tetrofosmin scintigraphy in the followup of therapeutic response.

• DIAGNOSTIC O N C O L O G Y 14

PS_693

PS_695

USEFULNESS OF 67GALLIUM SCAN IN EVALUATING LONG-TERM EFFECTS OF CHEMOTHERAPY

PREDICTIVE VALUE OF 99MTC-SESTAMIBI (99MTC-MIBI) IN PATIENTS WITH MULTIPLE MYELOMA (MM)

I. Palumbo (1), B. Palurnbo (2), A.M. Liberati (1), T.O. Moschini (2), M. Trottini (1), D. Siepi (2), S. Messina (2), R. Palumbo (2). (1) Dept. of Internal Medicine and Oncology, University of Perugia; (2) Dept. of

L. Pace (1), L. Catalano (2), S. Del Vecchio (1), A. De Renzo (2), N. Tedesco (1), C. Califano (2), G. Annunziata (1), F. Di Gennaro (A), B. Rotoli (2), M. Salvatore (1). (1) Medicina Nucleare e Centro CNR Medicina Nucleate, Dip. Sc. Biomor'fologiche e Funzionali, Universita Federico II, Napoli, Italy; (2) Ematologia, Dip. Meal. Clin. e Sper., Univesit~ Federico II, Napoli, Italy.

Nuclear Medicine, University of Perugia. Aim: 67Ga scan was performed in patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma to investigate the clinical outcome and long-term effect of different kinds of therapy: conventional and high dose chemotherapy followed by autologous bone marrow transplantation (ABMT) with or without radiotherapy (RT). Methods: Fifty-two patients (24 M and 28 F, mean age _+ S.D.: 35.5+15.8 yrs, range of age: 15-73 yrs) were studied with a mean follow up of 31+~.3.8 (S.D.) months. 33 subjects were affected by HL (24 nodular sclerosis, 7 mixed cellularity. Ilymphocyte rich), showing 13 bulky mass (12 mediastinal. 1 extramediastinal); 19 patients suffered from high grade NHL (6 mediastinaI with sclerosis, 4 anap~astie large celI, 7 diffuse large ceil, 2 Symphoblastie), showing 10 bulky mass (9 mediastinal, 1 extramediastinal). Mediastinal (M) involvement was present in 20 subjects, mediastinal and extramediastinal (M/ExM) in 26, extramediastinal (ExM) in 6. 24 patients were treated with high dose chemotherapy, while 26 with conventional chemotherapy; 31 subjects (10 NHL, 21 HL) underwent consolidation radiotherapy. 67Ga scan and CT were performed at the same time, every 3-4 months and after last therapy cycle. 296 MBq of ~'TGa were injected to each patient. SPECT image acquisition (Starcam 3000, G.E.) was pertbrmed 72 hours after tracer administration. Results: On the basis of Kaplan-Meier method a negative 67Ga scan was predictive of a longer survival (mean ± S.E.: 87.29±8.89 months) as opposed to a positive 67Ga scan (mean ± S.E.: 52.60a:5.95 months), being the difference statistically significant (p<0.00I). Considering . • 67 the two different ypes of therapy conventional and high dose chemotherapy) a neganve Ga scan in our patients undergoing high dose chemotherapy was predictive of a significantly higher survival (24 in disease free survival, 5 in continuous disease; mean survival ± S.E.: 91.67±4.21 months), while a positive 67Ga scan in our subjects treated with conventional chemotherapy was predictive of a significantly decreased survival (mean survival ± S.E.: 52.57 ±5.95 months) (p<0.05). On the other hand a negative 6rGa scan in our patients treated with conventional chemotherapy could be considered as a valid indicator of survival, although not statistically significant (mean survival ± S.E,: 66.50~12 months). Conclusions: Finally our study discloses that ~rGa scan is a usethl predictor of survival and its ability to evaluate the long term effects of the two types of chemotherapy can suggest modification of therapy during treatment.

Aim. 99mTc-MIBI scintigraphy proved to be useful in evaluating patients with MM. The aim of this study is to evaluate its predictive role in patients with MM Methods. 118 patients constituted the study group. All patients underwent a baseline whole body 99mTc-MIBI) scintigraphy (10 minutes after e.v. tracer injection and were clinically re-evaluated at a mean followup of 19+9 months. The scans were classified as N (physiological uptake), D (diffuse marrow uptake), F (focal uptake), and D+F. The intensity of diffuse bone marrow uptake was semiquantitatively scored. Results. At baseline 99mTc-MIBI, of the 5I patients with Pattern N only 8 (16%) were in stage 11 or 111,of the 38 with pattern D 13 (34%) were in stage 1[ or 111, 0 f 2 9 with pattern F or D+F 27 (93%) were in stage 11 or 111 (C2 63.6, p<0,0001), At clinical re-evaluation, 20 patients were in remission, 49 were in stable condition, 32 had disease progression, and 17 had died. Nine of the 51 (17%) patients with baseline pattern N had progression of disease, 23 (61%) of the 38 patients with pattern D had disease progression, and 17 (59%) the of 29 with pattern F or D+F had disease progression (C2 26.5, p<0.001). Baseline bone marrow uptake score was significantly (p<0.05) different among patients in remission (2.8+0.8), patients in stable conditions (3.1+1,3), and those with progression of disease (3.9+1.4) Multiple logistic analysis showed that monoelonal component (standardized coefficient=0.18), 99mTc-MIBI pattern (standardized coefficient=0.33), uptake score (standardized coefficient=0.39), and x-ray (standardized coefficient=0.33) were significantly related to the status at re-evaluation (r=0.50, F=9.4, p<0.0001 ). Conclusions. The results of this study indicate that 99mTc-MIBI scintigraphy may help in predicting the clinical status at follow-up in patients with MM. Both scintigraphic pattern and the uptake score have a potential prognostic role in these patients.

tO

.m

PS_694

PS_696

MEDIASTINAL 'LAMBDA' SIGN IN THE SClNTIGRAPHY WITH 67 GA-ClTRATE IN THE CHILDREN WITH MALIGNANT LYMPHOMAS AFTER CHEMOTHERAPY

WASH-OUT OF 99MTC-SESTAMIBI (99MTC-MIBI) IN EVALUATING RESPONSE TO CHEMOTHERAPY IN PATIENTS WITH MULTIPLE MYELOMA (MM)

I. Makaiova (1), S. Kovacova (1), V. Procka (1), S. Podana (1), J. Vesely (1), A. Cizmar (2), A. Foltinova (2), E. Kaizerova (2), I. Holincova (1), L. Plank (3), J. Kausitz (1)(1) Clinic of Nuclear Medicine Medical Faculty UK and St.Elisabeth Cancer Institute, Bratislava, SIovak Republic; (2) Pediatric Cancer Department of Medical Faculty, Bratislava, Slovak Republic; (3) Institute of Pathologic Anatomy Medical Faculty UK,

L. Pace (1), L. Catalano (2), S. Del Vecchio (1), A. De Renzo (2), R. Fonti (1), G. Sica (1), G. Annunziata (1), C. Califano (1), B. Rotoli (2), M. Salvatore (1). (1) Medicina Nucleare e Centro C.N.R. Medicina Nucleate, Dip. Sc. Biomorfologiche e Funzionali; (2) Ematologia, Dip. Med. Clin. e Sper., Universit~ Feclerico II, Napoli, Italy.

t~

4--J

¢-

Martin, Slovak Republic. Aim: Residual anatomical masses of malignant lymphomas after therapy, especially in the area of the mediastinum cause in the CT or in MR imaging often difficulties, because can not give the information about the activity of them. On the other hand, the imaging with 67Gacitrate (or with 18FDG) can give the information about the tumorous activity or viability of the lesions. This property is for the follow-up of the malignant lymphomas crucial and therefore radiogallium is a long time and 18FDG in the last years used in the managmant of this disease also in the children, Despite of this, beacausa of the fianctional basis of this imaging arrised also the disadvantage of afalse positive,, uptake in other lesions as tumorous. Donahue et al. in 1981 the first time described the ~false positive,, uptake of gallium in the area of upper anterior mediastinum, which corresponded with the hyperplastic thymus after chemotherapy. As we know, this disadvantage is visible also in the imaging with 18FDG because the similarity of them, Methods: In this paper we refer about the retrospective study of the results gallium scintigraphy in the last 5 years (from 1995 till 1999) in the tO0 children (in age from 2-18 years) suffering from malignant lymphomas after chemotherapy. The children were dividing in two groups: 91 children with hodgkin (HD) and 29 children with nonhodgkin (NHL) types of disease, The retrospective study was focussed on the the area of mediastinum and the finding of hypertrophic thymus which was notes as a alambda,, sign ( a roof-shaped uptake on the anterior area of mediastinum ), In 10 children was made also the PET scanning with 18F-fiuorodaoxyglukose(FDG). Results: From all 91 children with HD in 9 (9,9%) of them there was ~ilambda,, sign, which from 20 patients with ,~lpositive,, gallium uptake in mediastinum was 4 5 % . In the group of all 29 NHL children was the ~fiambda,, sign found in 8 of them (27%), and from ~.positive,, gallium children it was 89% of them. Result of 18FDG was similar, but not the same as with 67Ga-citrate. Conclusion: Mediastinal ,lambda, sign in the 67Ga-scintigraphy represents the hypertrophic thymus, which can be in correlation with the effectivity of the systemic treatment in malignant lymphomas and stronger delineated in the more agressive cytostatic treatment in the non-hodgkin typ ofdiseasa. The similar result cart he visthie in the PET with 18FDG,

Aim. Wash-out of 99mTc-MIBI is reported to help in predicting response to chemotherapy in various turnouts. The aim of this study is to evaluate the role of 99mTc-MIBI in predicting response to chemotherapy in patients with MM. Methods. 40 patients with MM showing diffuse 99mTc-MIBI bone marrow uptake were included in the study. All patients underwent whole body scan at 10 and 60 minutes after tracer injection. Diffuse bone marrow uptake was semiquantitatively scored according to both extension and intensity on the 10 minutes scan, Wash-out was computed, after decay correction, as: (10 minutes eounts/pixel minus 60 minutes countsJpixel) divided by 10 minutes counts/pixel, All patients were clinically re-evaluated (mean follow-up 26+9 months) after chemotherapy (14 MP, 9 VAD, and 17 VMCP), Results. Of the 40 patients, 10 were considered to be in remission at re-evaluation and 30 showed disease progression. Neither the clinical status at presentation nor the therapeutic regimens were associated with the clinical status at re-evaluation (i,e. remission vs disease progression) (C2=1.8 and C2=1.0, respectively, p---n.s.). The bone marrow uptake score at the 10 minutes baseline 99mTe-MIBI scintigraphy was significantly (P<0.05) higher in patients showing disease progression (3.9+1.4) than in those in remission (2.7+1.4). 99mTc-MIBI wash-out was significantly (p<0,01) higher in patients with disease progression (18.3+9.8) than in those in remission (11.6+6,2), Of the 10 patients showing remission of disease after chemotherapy, the majority (7, 70%) had 99mTc-MIB[ wash-out <15% (which was the median for the whole group), while of the 30 patients with disease progression alter chemotherapy the majority (20, 67%) had 99mTc-MIBI wash-out > 15% (C2=4.1, p<0.05). Conclusions, Our preliminary data suggest that in vivo evaluation 99mTc-MIBI wash-out may help in predicting response to chemotherapy in patients with MM.

1253

o t~ e~

O IX

• DIAGNOSTIC ONCOLOGY 14 / NEPHRO-UROLOGY 3

PS_697 9 9 M - T C MIBI S C l N T I G R A P H Y IN M U L T I P L E MYELOMA: A POWERFUL IMAGING TOOL TO DETECT DISEASE ACTIVITY A. Varraso (1), G. Martino (1), P. Musto (2), F. D i c e m b r i n o (1), F. B a r b a n o (1), M. Guerra (1), M. Pirro (1), M. Greco (2), V. Frusciante (1). (1) Department of Nuclear Medicine; (2) D e p a r t m e n t of Hematology, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. Background: ~ T c - M I B I is a lipophilic cationic radiopharmaeentical which accumulates in tissues with high cell density and mitochondrial activation. Recently some papers have discussed the use of ~°Tc-MIBI in patients with multiple myeloma (MM), where evaluation of bone involvement is of high relevance. The most widely accepted imaging technique to assess MM is plain skeletal x-rays; however positivity at plain radiography is often due to a nonactive process; besides the results of biopsy are significantly conditioned by sampling errors; so an imaging tool. correlated to disease activity, is quite useful. Patients and methods: We have enrolled 47 MM pts. Diagnosis was made according to standard criteria. Pts were classified as A-(33) active disease (untreated, refractory, relapsed), B(5) stable disease (usually with reduction of monoctonal component >50%), C-(8) complete remission (absence of monoclonal component at immunofixation and no evidence of marrow plasma cells) after autologous stem cells transplantation, G-(l) incomplete remission after transplantation. 740 MBq of '~mTc-MIBI were injected; 15 mins after injection a whole body scan was acquired; scintigraphic pattern was classified on the basis of diffuse-D, focal-F, diffuse and focal -D+F uptake; D uptake was semiquantitatively scored according to the extension (E-three steps) and intensity of uptake (I - three steps). Four pts have been followed-up by sequential investigations (In). Results: Considerth~ clinical and hematolomcal narameters: In group A scintigmphy has correctly classified as diseased all the pts; in 18 In we have found D pattern, in 6 F pattern and in 9 D+F. In all B group pts our results were concordant (negative) In C group pts our results were discordant in 2/8 cases (6 cases negative, I F pattern and 1 D pattern). fu the one pt of G group scintigraphy was r~egative Five follow-up In have been performed (4 A group, I G group); results were concordant in 4/5 cases; in I A group pt hematological and clinical parameters were negative but scintigraphy was clearly positive (D patternl. Considering as true positive clearly evident local scintigraphic lesions sensitivity of scintigraphy was 97.37 % and specificity 85.71%. Conclusions: Our data clearly demonstrate that ~ T c - M I B I scintigraphy has a very high sensitivity and specificity in MM pts. It demonstrates clearly focal lesions in pts without clinical or laboratoristic evidence of disease; it will be important to check the clinical course of the 3 pts with negative hematological findings of disease but with F or D pattern.

OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 3

PS_699 ESTIMATION OF RISK FACTORS FOR DIABETIC NEPHROPATHY BY R A D I O N U C L I D E METHODS M. Rajic, M. Bogicevic, S. Antic, M. A v r a m o v i c , S. Ilic, M. Vlajkovic, V. Stefanovic. D e p a r t m e n t of Nuclear Medicine, Clinical Center, Nis, Yugoslavia. Introduction: Glomerular hyperfihration and nephromegaly are supposed to be predictive for progression from norton to microalbuminuria in patients with insulin-dependent diabetes mellitus (IDDM). The aim of this study was radionuclide assessment of nephromegaly incidence and its association with hyperfiltration, in order to select normoalbuminuric IDDM patients at risk of developing renal disease. Methods: IDDM patients (DM) with urinary albumin excretion < 20gg/min and duration of diabetes > 5 years were classified into groups with hyperfiltration (DM-hl and normofiltration (DM-n). Kidney size was expressed as a ratio of bipolar diameter on ~ Tc-DMSA ~sterior images and patient's height (BPD/PH), while GFR was determined by measuring Tc-DTPA clearance. BPD/PH over 6.97 x 10.2 (control mean value + 2SD) and clearance values higher than 136 ml/min/I.73m z (control mean value + 2SD) were accepted as criteria of hyperfiltration and nephromegaly. Results are displayed in the following table: Group

N°

1. Control 2. DM 3. DM-h

23 23 13

Age (~,ears) 41.1±8.7 39.1±8.0 39,2 ± 7.9

4. DM-n

10

39.0 ~: 8.I

~Tc-DTPA clearance 122±7

t36±15 + 147±7' t22±10"

BPD/PH

Incidence of nephrome~aly

6.45±0.6 7.19~0.55" 7,29±0.54"

56.5% (N"=I31 69.2% IN"=9)

7.09±0.55"

40.0% (N"-4)

Vs. control: =p<0.001, hp<0.01; vs. DM-h: 'p<0.001 Conclusion: A markedly higher incidence of nephromegaly in diabetics with hyperfiltration than in patients with normal GFR was shown by the results presented. Considering that normoalbuminuric IDDM patients with association of elevated GFR and renal hypertrophy are at a greater risk lbr developing nephropathy, radionuclide methods should be used for lbllow up or'their renal function.

PS_698

PS700

USE OF THE 67-GALLIUM SClNTIGRAPHY IN THE PROGNOSIS IN HODGKIN'S DISEASE

MEASURMENT OF KIDNEY TRANSPLANTS GLOMERULAR FILTRATION RATE USING RENAL SClNTIGRAPHY

I. Hervas (1), P. L6pez-Tendero (2), P. Bello (1), A. Segura (2), A. Saura (1), P. Gonzalez-Cabezas (1), A. Yuste (2), R. Perez-Velasco (1), M. Pastor (2), R. Diez (1), A. Mateo (1)(1) Department of Nuclear Medicine; (2) Department of Oncology, University Hospital, Valencia, Spain.

F. Chehade, N. Droubi, H. Kazma, A. Zaatari, H. A b o u Zainabe, M. Zaatad, F. Farhat. H a m m o u d HospitaI,Sidon,Lebanon.

Aim: Evaluation of the response to therapy is important in the clinical management of lymphoma. Gallium 67 scintigraphy has been considered a good technique for monitoring response after trentmcnt of patients with Hodgkin's disease. The aim of this study is to assess the clinical impact o f gallium 67 sciotigraphy before and after treatment and to compare the overall sutvivat between the patients whose gallium studies after treatment were negative and those whose studies did not become negative. Methods: We have studied 71 patients (39 women, 32 men) with histologically confirmed Hodgkio's disease controlled by the Department of Oncology of our Hospital. All the patients underwent 67Ga scintigraphy at the moment of the diagnosis (basal study) and in the case that basal study was positive (abnormal hyper-uptake focus) we performed fullow-up studies after the treatment, We have calculate the overall survival between the patients whose studies after treatment were negative (first group) and those whose studies did not become negative (second group) and between patients whose studies were negative at diagnosis (third group). Gallium sciotigraphy were performed 48-120 hours after the injection of 185-296 MBq (6-8 mCi) of 67Go citrate. The statistic analysis used to compare the overall survival of the three groups was chi-square test with Yate's correction. Results: Gallium scintigraphy was positive at diagnosis in 42 patients (59,2%). In 34 of them we could perform the follow up study a f t " the treatment. The follow up study was negative in 29 patients while in 5 patients the gaIIium scintigraphy remained positive after treatment. With a median follow-up of 8 years: In the first group (basal study positive and negative after treatment) the median overall survival was not reached (96.5% of patients remained alive). In the second group (basal study positive and positive after treatment) the median overall survival was 27 months (2 patients remained alive (40%)). In the third group (basal study negative) the median overall survival was 75 months (46% of patients remained alive).The overall survival was significant higher (p<0.001) in the first group comparing with the second group. The overall survival was higher in the first group comparing with the third one but statistic significance level was not reached. Conclusion: In Hodgkin's disease, if the 67Ga scintigraphy is positive at diagnosis, the normalisation of the study after treatment can be considered as a good prognosis factor.

1254

In order to assess the importance of expression of the cortical time of kidney transplants renogram in term of glomerular filtration rate (GFR) we have tested the correlations with the correspondent serum creatininc level (Cr). Subjects : 71 scintigraphies with Technotium-99m-labelled diethytenetriamine pcntaacetate (DTPA) were realized in 44 patients with renal allogmfts, transplanted between the years 1990 and 1999. Patients were 13 women and 31 men with mean age of 34~:t4 years (mean±SD) referred betwecn the years 1997 and 2000 for scintigraphic exploration of function deterioration of kidney transplants mainly due to rejection. Method : The GFR are calculated from renal scintigraphies using Gates method. The depth attenuation is corrected after measurement of transplants kidney depth, upon lateral view, betwecn an anterior abdominal wall marker and the center of the transplanted kidney. Simple linear regression analysis over Cr and natural logarithm of Cr (Ln(Cr)) were calculated for GFR and natural logarithm ofGFR (Ln(GFR)). Results : The mean Cr and GFR arc 2.5±2 mg/dl and 37±22 ml/min/l.73 m2 respectively. A good correlation exists between the GFR and the Cr (r=-0.65, P<0.001). The correlation is closest between the GFR and the Ln(Cr) (r---.0.67, P<0.001), and even more between the Ln(GFR) and the Lo(Cr) (r'=-0.80, P<0.001). Discussion : Deducted linear correlation coefficients from this study, which is carried out on a large number of kidney transplants scintigraphies, are highly signiftcatives (P<0.001). The weak mean GFR reflects the elevated mean Cr that indirectly reflects the renal cortical function. Moreover, this study shows that Cr is in good correlations with calculated GFR under different mathematical forms. Consequently, expression of the cortical time of DTPA renogram of kidney transplants in terms of GFR should adds an important quantitative dam to the scintig~phic exploration. Since renal scintigraphy is a reproducible test, scintigraphic measurement of GFR may serves as objective data to follow close the function evolution of kidney transplant under anti-rejection treatment. The best correlation is found between the Ln(GFR) and the Ln(Cr). The following mathematical formula can be deducted: Ln(GFR)=a.Ln(Cr)+.h, which also be written as GFR=(Cr)=.e b, where a=-0.8 and b=4.

• OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 3 PS701 MEASURING TC-99M MAG3 CLEARANCE WITH CAMERA BASED METHOD IN PATIENTS WITH IMPAIRED RENAL FUNCTION: COMPARISON WITH MULTIPLE SAMPLE TC-99M MAG3 CLEARANCE: REPRODUCIBILITY, ACCURACY AND REPEATABILITY COEFFICIENT T.Y. Erdil (1), F. Dede (1), S. Tu~lular (2), F. Ben (1), O. Noshari (1), C. ~zener (2), E. Akao(~lu (2), T. Turo~lu (1). (1) Department of Nuclear Medicine, Marmara University Hospital, Istanbul, Turkey; (2) Nephrology Section, Department of Medicine, Marmara University Hospital, Istanbul, Turkey. The aim of this study was to determine the reproducibility (REP), accuracy and repeatability coefficient (RC) o f the Tc-99m mercaptoacetyltriglycine (MAG3) clearance measurements with camera based method in patients with impaired renal function. Methods: Nineteen patients (10M, qF, mean age:56.6±10.3yr, range:44-83yr) with chronic renal failure (Cr=3.4 mg/dl:i:0.68 mg/dl, range:2. I mg/dl-4.6 mg/dl) were included in the study. MAG3 sc!ntigraphy and camera based clearance (CBCI) were performed according to QuanteEM method (2 see/flame for 24 flames. 15 see/frame for 16 frames, 30 see/flame for 40 frames). In each patient, at the same time with MAG3 scintigraphy, MAG3 plasma clearance (PCl) was also determined using single injection, muttisample (10 blood samples between 5 to 180 minutes), two compartment model of Sapirstein and corrected for body surface area. In 12 patients, seintigraphy and PCI studies were repetaed within a week under similar physiologic conditions. For the determination of accuracy, we calculated the differences between clearences obtained with CBCI and PCI methods. The mean and standard deviation (SD) of these difl'erences represented the systemic bias and accuracy of the technique respectively. The mean difference between repeated CBCI studies in 12 patients were expressed as a percentage of the mean value of the two studies, and the SD of these percentages represented the reproducibility. CBCI were determined twice by the same physician in each patient and RC was measured according to Bland and Airman Method (2 SD of the differences between two measurements). Results: The MAG3 clearance was fuund to be 56.7 ± 21.4 and 67.4 • 32.1 fur PCI and CBCI methods respectively (p = 0.06). The second measurement of the same camera study by the same observer was 67.4 ± 30.3 (p=0.86). The systemic bias and accuracy of CBC]. PCI method as a reference, were -8.8 and 29. REP of CBCI in 12 patients was lbund to be 40.31% and the mean difference was -5.31% (ranging from ~ . 0 % to 74.3%. RC of of the same study was lbund to be 3.9. Conclusion: We observed a poor accuracy and reproducibility of CBCI in patients with poor renal lunction. However, highly repeatable results of the same study was obtained. Therefore, CBCI is not sensitive tn evaluate the alterations oftbe renal lunction in patients with impaired renal timction.

PS_703 BACKGROUND SUBSTRACTION AND SPLIT RENAL FUNCTION IN TC-99M ETHYLENEDICYSTEINE RENOGRAPHY USING DIFFERENT

TIME INTERVALS O. ~zmen, N. Alan, M. Hala(;, L. Kabasakal, K. ~zcan, C. ~nsel, I. Uslu. Department of Nuclear Medicine, Cerrahpa~a Medical Faculty, Istanbul, Turkey. Tc-q9m EC is a new tubular tracer for renal studies. It is shown that type o f region of interest (ROI) for background correction and the time interval that the parameters are generated has been a potential error for estimation of relative renal function. Aim: The aim of the present study was to determine the accuracy of relative renal function obtained from EC with different type of background ROls generated from I-2, 1.5-2.5 and 2-3 rain. time intervals using DMSA as reference method. Method: For this purpose 4t patients ages ranged from 3 to 74 years with a mean of 31.6±21.0 years, were included to the study. Split renal function o f each EC study was calculated from 1-2, 1.5-2.5 and 2-3 minutes o f dynamic images using manually drawn perirenal, subrenal crescent, without background and lateral rectangular ROis. Within the same week DMSA scintigraphies were performed 2 hours after injection and 6 planar images were obtained. DMSA split renal function was calculated for each patient either by using only posterior views without renal depth correction and also using the geometric mean of posterior and anterior views. The accuracy of EC split renal function was estimated by calculating the difl~rence between the corresponding D M S A split renal function for the kidney with the lowest uptake. The mean of differences represented the systemic bias and the SD of the mean of the differences represented the accuracy of the technique. Results: No systematic bias was observed between first and second measurements giving a high reproducibility (SD
C 0

PS_702

PS_704

QUALITATIVE AND QUANTITATIVE ANALYSIS OF DELAYED TC99M DTPA IMAGES: DO TREY HAVE A STRONG IMPACTON THE DIAGNOSIS OF OBSTRUCTION ASSOCIATED WITH UNILATERAL ADVANCED NEPHROUROPATHY?

NORMALIZED RESIDUAL ACTIVITY (NORA): USUAL VALUES AND ROBUSTNESS OF THE METHOD

C I1J

A. Piepsz, J.D. Kuyvenhoven, M.-Tondeur, H. Ham. Department Radioisotopes, CHU St Pierre, Free University Brussels, Brussels, Belgium.

el.

S.H. Wagieh (1), O. Abdel Razzak (2), A. Khodier (3), H. Kiki (4). (1) Department of Nuclear Medicine, Cairo University, Cairo, Egypt; (2) Department of urosurgery, Cairo University, Cairo, Egypt; (3) Department of Nuclear Medicine, Ain Shamas University; (4) Department of Radiology, Cairo University, Cairo, Egypt Diuretic renography is a valuable method fur the diagnosis of equivocal UT obstruction, ),eL with the presence of poor renal function and dilated collecting system, its results are unreliable, as they represent important etiological factors for poor drainage in response to diuretic stimulus without obstruction. The aim of this study is to assess the value of qualitative and quantitative analysis of 4 and 24 hours delayed Tc99m DTPA images in the diagnosis of obstruction. Patients and Methods: Forty patients were included in this study al~er performing F+20 diuretic renography. They all have hydronephrotic changes of the affected kidney with split function < 20% and GFR < 16 ml/rain associated with normal urine flow kinetics of the contralateral kidney. All were subjected to reviewing all clinical, laboratory and radiological data and abdomino-pelvic sonography. MRI was performed if all clinical and radiological data give equivocal results as regards obstruction. Delayed Tc99m DTPA images were acquired 4 and 24 hours postin3ection for 5 and 15 minutes, respectively. Images were interpreted qualitatively for the assessment o f obstruction and to detect its IeveI and quantitatively by measuring the ratio between counts/pixel of the affected kidney to normal kidney in early and late images (OI & 02, respectively) with calculation of obstructive index O.l. ( O21 OI). Results: Clinical and radiological data confirmed the presence of obstruction in 19 patients and excluded the presence of obstruction in 21 cases. Obstruction was detected in 4 and 24 hours images in 19 patients with the detection of the level of obstruction in both sets of images. The 21 cases with non-obstructive dilatation showed complete clearance in 24 hours images, and only in 4 cases clearance occurred in 4 hours scintiscans. There was a statistically significant difference between 0 2 and O.I. values between both groups( p< 0.05 ). Conclusion: Qualitative and quantitative assessment of 4 and 24 hours delayed Tc99m DTPA images are of great value in the diagnosis of obstruction associated with advanced unilateral nephrouropathy, avoiding the patient to proceed to more invasive and costy procedures with proper early therapeutic intervention.

Aim :the objectives of this study were twofulds. First, to investigate the robusmess of the ,,normalized residual activity" (NORA), a parameter which has recentty been proposed for the estimation of renal emptying during renography;secondly to define the usual values of NORA in two categories of kidneys : those with normal renogram and those with dilated but definitely non obstructed kidneys. Methods : a large number o f Tc-99m MAG3 renograms were extracted from a data base. NORA was defined as the renal activity at a given moment tend of renogram, end of furoscmida acquisition, postmicturition image) divided by the renal activity between I and 2 minutes. Two variables which might influence the results of NORA were evaluated, the choice of beckground correction and an error in the estimation of the I-2 rain renal activity. In order to estimate the values of NORA in usual clinical conditions, two sets of data were analyzed :"normal" kidneys with normal renogram pattern; dilated but definitely non obstructed kidneys, Results : Using a perireaal or a subreual background correction, NORA was, on average, raspectiv¢ly 67% or 83% of the value obtained without background correction. The use of a lmin 20 sec to 2 rain 20 see renal activity instead e r a 1 to 2 min activity resulted in a systematic 10-15 % underestimation of NORA. The percentile 90 values of NORA were, in the normal group. 0.70 at 20 minutes, 0.23 at the end oftbe furosemida test and 0,10 after micturition. in the operated kidneys, the percanti[e 90 values were 3.92 at 20 rain, 2.9I at the end of the furosemida test and 1.99 after micturitiun. A good correlation was observed between NORA and output efficiency. Conclusion : [f adequately standardized, NORA is a robust and simple parameter, allowing the evaluation of renal emptying at any time of the acquisition. One should be aware of the fact that high NORA values, corresponding to poor renal emptying, can be observed in the operated non obstructed kidneys, even affer micturition.

1255

0 Q.

• OTHER CLINICAL SCIENCE. NEPHRO-UROLOGY 3 PS_705

PS_707

REPRODUCIBILITY OF SOFTWARE PACKAGES OF DICOM WORKSTATIONS OF DIFFERENT MANUFACTURES FOR SCHLEGEL ERPF AND GATES GFR MESAUREMENTS

OPTIMAL TIME WINDOW FOR CALCULATION OF TWO RENAL TRANSIT PARAMETERS: NORMALIZED RESIDUAL ACTIVITY AND OUTPUT EFFICIENCY

G. Marotta, V. Longari, R. Matheoud, V. Salvatore, F. Voltini, P. Gerundini. Department of Nuclear Medicine, Ospedale Maggiore - IRCCS, Milano, Italy.

J.D. Kuyvenhoven, H. Ham, A. Piepsz. GHU St. Pierre, Brussels, Belgium.

Aim: Because of ability to calculate the differential ERPF and GFR for each kidney and serial reproducibility in individual patients, the _camera methods to measure ERPF and GFR are widely used. Some recent _cameras transfer the data acquired with the DICOM protocol to their own workstations; so, all workstations with DICOM connectivity can process these data. Aim of this work was to investigate the reproducibility of Gates' GFR and Schlegel's ERPF measurements obtained by different software packages of four DICOM workstations and to evaluate the differences with the ERPF values from the single sample Tauxe method (Tx). Methods: Syringe static scans and dynamic renal scan, according to Schlegel's and Gates' methods, were pertbrmed in I0 patients (mean age 61 yrs, range 28-76) and 70 patients (mean age 54 yrs, range 21-82) respectively, with a GEMS Millennium VG5 camera. Data were transferred to four workstations: GEMS eNTEGRA (eNT), Marconi Odyssey (Od), SMV Vision POWERstation (SMV) and GEMS XPertPro (XP). All kidney and background irregular regions of interest were manually drawn by one operator. Results: The tables show the coefficient of correlation (r) and standard error (SEE in ml/min) of ERPF values of 20 kidneys calculated by Od, SMV, XP and Tx and of GFR values of 140 kidneys calculated by eNT. Od, SMV and XP and the mean (_SD) of their differences (in ml/min). All differences were statistically significant (p<0.0001). There was a good correlation between ERPF and GFR values obtained by Od and XP, but the Bland-Airman plots showed considerable underestimation of GFR by eNT compared to XP and of ERPF by Od versus XP. There is also a poor correlation between the ERPF and GFR values obtained by SMV in comparison with all other workstations. Conclusion: This study showed statistical differences in the calculation of Scblegel's ERPF and Gates' GFR between different workstations. As a consequence, at any workstation upgrade it will be mandatory to revalidate the method on each system (_camera+new workstation) versus the blood sampling method, ERPF r(SEE) diff SD GFR r(SEE) diff_SD

Od-XP .95 (19.3) -33.8 18.9 eNT-~P .96 (6.0) -11.8_6.6

SMV-XP .80(36,91 -22.7 42.1 Od-XP .98 (4.2) -7.2 4.3

SMV-Od

, ,81 (33.7) I1.1 41.8 SMV'-XP .70 (14.7) -t0.8_I5.6

XP-Tx .89 (37.9) -8.4 38.9 eNT-Od .98 (4.[) ~.6_4.4

Od-Tx .85 (44.3) -42.2 45.2 SMV-Od .69 03.9) -3.5 15.4

Background: Normalized residual activity (NORA) and output efficiency tOE) have been proposed for the measurement of renal transit. The calculation of these transit parameters at fixed time is common usage. However. as these parameters are strongly time-dependent, the choice of moment for calculating these parameters may affect their discriminating power. Aim: To evaluate whether there is an optimal time for calculation of transit parameters NORA and OE. Materials and methods: A series of renograms were generated in a simulation model by convolution of a plasma disappearance curve with various created retention functions. Mean transit time (MTT) was set, increasing with I-rain. steps, between 3 and 60 rain. For every MTT. 4 different shapes of retention functions were created. The ratio of the minimal transit time (MinTT) to MTT was fixed at 0.80 whilst the ratio of maximum transit time (MaxTT) to MTT varied between I. I 0 and 2.00. A total of 232 retention functions and corresponding renograms were created. Mean and standard deviation of the MaxTT to MTT ratio were respectively 1.40 and 0.27. For each of the created renograms NORA-t and OE-t were calculated for t equal to 10, 20, 30, 40, 50 and 60 min. Results: OE-20 is closely related to MTT for M~tq" shorter than 20 min. Therefore, for this range of M'l-f values, OE-20 is highly predictive of the value of MTT. If the MTT is higher than 20 min. OE-20 looses totally its discriminating power. The contrary is observed for OE60. which varies only slightly when MTT is less than 20 rain. This parameter reflects better the change in transit time in the range of 30 to 50 rain. Similar patterns are observed with NORA. For MTT less than 20 min., NORA-20 has the highest discriminating power, whereas NORA-50 is best for MTT ranging from 30 to 50 min. Conclusion: NORA and OE are strongly time-dependent and the choice of optimal time for calculating these parameters should be adapted to the clinical problem under investigation.

SMV-Tx .56 (69.2 / -31.1 7t.7 SMV-cNT .66 (12.8) 1.0_15.3

PS_706

PS_708

COMPARISON OF PLANAR AND SPECT 99MTC-DMSA SClNTIGRAPHY FOR THE DETECTION OF RENAL CORTICAL DEFECTS IN PATIENTS WITH URINARY TRACT INFECTIONS

INTEROBSERVER AND INTRAOBSERVER VARIABILITY AND REPEATABILITY COEFFICIENT OF RELATIVE RENAL TC-99M DMSA UPTAKE

H. Dernir, F. Berk, O. Erdingler, S. I~g6ren, C. Aktolun. Department of Nuclear Medicine, Kocaeli University, Kocaeli, Turkey.

T.Y. Erdil, F. ~en, F. Dede, O. Noshari, H.T. Turo~lu. Department of Nuclear Medicine, Marmara University Hospital, Istanbul, Turkey.

Renal cortical scintigraphy with '~'~Te DMSA provides an excellent imaging modality for the assessment of cortical damage secondary to urinary tract infection (UTI). In this study we compared the detection rates of renal cortical defects with 99mTedimereaptosuceinic acid (DMSA) using SPECT and planar cortical scintigraphy. MATERIALS AND METHODS: We imaged 75 kidneys in 38 patients (10 males, 28 females) with recent or recurrent GTI. Patients" age ranged between 2 months and 23 years (mean 7.37 + 4.44 years). Planar and SPECT studies of renal cortices were performed by Elseint SPX-6 gamma camera within 2 to 4 hours of injection 0,5-5 mCi °~Te DMSA intravenously. All studies were evaluated by two experienced nuclear medicine specialist. Paranchymal uptakes were classified as; normal (grade 0), equivocal (grade 1), single defect (grade It), more than 2 defects ( grade 111 ), contracted or small kidney (grade IV)and no visualization (grade V). RESULTS: Fifty six of 75 kidneys were normal in both planar and SPECT studies. Thirteen kidneys were pathologic in planar scintigraphy however 19 kidneys were pathologic in SPECT studies. Six kidneys had normal paranehymal uptakes in planar studies. [u SPECT studies; 3 out of 6 were classified as grade I and three of them as grade II. One kidney was grade 1 in planar study whereas it was grade II in SPECT study. All defects diagnosed by planar seintigrephy were also visualized by SPECT. Final grading were changed for, 7 out of 75, kidneys' according to SPECT results. CONCLUSION: SPECT has no significant advantage over planar studies, although some cortical lesions are missed by planar imaging. It must be considered as a complementary technique to renal cortical imaging.

The aim of our study is to evaluate the intraobserver, interobserver variability and repeatability coefficient (RC) of relative renal function (RRF) obtained with Tc-99m DMSA (DMSA). Methods: Two hundred and ninety three patients (pts) (mean age 6.9 ± 19.3, range 0.2-70 yr) underwent static DMSA studies in the supine position. Five hundred Kcounts were acquired in the posterior projection using high resolution collimator on a 256x256 matrix. All, but 7 pts had normal renal functions. In 26 pts, RRF of left kidney (LK) was above 60°/'0 and below 40% in 34 pts, Nine pts had hydronephrusis on right kidney and 30 on the LK. Atrophy or infection were present in the LK 0f33 pts and in the right kidney of 18 pts. RRF was calculated with and without background (beg) correction. The measurements for the intraobservar and interobserver variability and repatibility coefficients were performed by two independent o (Groupl, n=26), between 40%observers for all pts (total), for LK having a RRF above 60Y* 60% (Group 2, n=233) and below 40% (Group 3. n=34). Results: I BCG (+~ Correlation (r) Intraobserver Total 0.988 Group 1 0.996 Group 2 0.988 Group 3 0.997 BCG (9 r = Toml 0.999 Group 1 0.998 Group 2 0.993 Group 3 0.997

lnter~bserver 0.998 0.997 0,995 0.998

Regression line Intraobserver 1.995x+0,23 ).982x+1.33 0.98gx+0.59 [.006x+0.02

~=) Imerobserver 0.995x+0A4 1.005x-0.85 0.989x+0.49 1.014x-0.41

0.999 0.996 0.992 0.999

1.003x-0.2 1.005x-0.29 1.006x-0.3 0.999x-0.06

1.003x-0.1 0.983x+1.64 0.985x+0.82 0.983x+0.38

Re 1.66 1,11 1.27 3.4 RC 1.34 1.28 0.89 3.01

A good correlation was found for both intraobserver and intembserver variability for all comparisons. RRF calculated without bog correction showed slightly higher correlation and better repeatibility results as compared to those (its counterparts) with beg correction. However, this difference was not found to be significant. In Group 3, there was significant difference compared to other groups and the highest RC value was obtained from this group for both with and without beg correction.

125E

• NEPHRO-UROLOGY 3 / P H Y S I C S / INSTRUMENTATION 3 BCG (-) vs BCG (+) r= ~'= T G I G2 G3

0.998 0.985 0.989 0.998

0.951 x+213 0.946x+2.12 0.939x+2.83 0.986x+ 1.26

Conclusion: RRF obtained both with and without beg correction gave highly repatable and correlated results. However, in kidneys with RRF lower than 40%, higher variable results were obtained as compared to kidneys with RRF higher than 60%.

PS_710 INTERFILE: OLD, SIMPLE BUT USEFUL

A. Dobbeleir (1), A. Vervaet (1), K. Melis (2), G. Dutoit (3), A.S. Hambye (1). (1) Middelheim General Hospital, Antwerp, Belgium; (2) SintAugustinusktiniek, Veurne, Belgium; (3) Dutoit Medical, Antwerp, Belgium. In May 2000, several hospitals in Antwerp entered in partnership to purchase a GE Advance PET system. Each nuclear medicine department wanted to visualize interactively in 3D the PET whole body scans in his own location. Theretbre the PET system provides besides the native attenuation corrected transverse slices also Dicom transverse slices. Transmission of data over network communication links to other sites is easy, but system compatibility remains a problem: no available nuclear medicine system was able to read native nor Dicom PET data. (GE, Elscint, SMV, Trionix, Hermes, Link). Freeware viewers developed for Dicom like Osiris or Acculite were able to read the data but ordered and/or normalized the GE PET images in a wrong way. To solve the problem, we decided to transform the native GE PET whole body transverse slices to interfile. Using Unix and C++, an interfile header was created from the data in the study header of the PET data. Position and individual image normalization factors were extracted from the image headers. Images were ordered according to their bed position before being stacked together and normalized to one factor. Absolute activity was preserved in order to allow calculation of standard uptake values (SUV) in normal tissue and tumors in the different referring nuclear medicine departments. The program output of the transformed whole body PET data consists of interfile data typically containing between 205 and 240 transverse slices of 128-128 plxels matrix size. Thanks to the transformation into interfile, some nuclear medicine systems llke SMV and Trionix succeeded to import this non-cubic volume and display the transverse, sagital and coronal slices in their 3D viewer. Furthermore ray tracing and volume rendering became available for tumor localization. Despite the development of an elaborated transfer system like Dicom, the ability to easily convert images to interfile data readable by most nuclear medicine systems remains an important tool in daily practice. May be small developments in interfile deserves more attention by the nuclear medicine community.

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PHYSICS / INSTRUMENTATION 3

PS_711

PS_709

ON-LINE IMAGE PROCESSING OF A SMALL FIELD-OF-VIEW IMAGING PROBE

PACS IN NUCLEAR MEDICINE - ESSENTIAL PRECONDITION FOR PRACTICAL IMAGE FUSION

T. Kauppinen (1), P. Nikkinen (1), H. Pohjonen (2), I. Sippo-Tujunen (1), S. Savolainen (12). (1) Division of Nuclear Medicine; (2) Department of Radiology, Helsinki University Central Hospital, Helsinki, Finland. Aim: Efficient routine use of image fusion requires a PACS (picture archiving and communication system) to provide storage of image data in a standard digital format, a high-speed image network as well as an accurate and reliable image fusion software. The Hospital District of Helsinki and Uusimaa (HUS) has a PAC system called HUSpacs with the total amount of 800.000 examinations (20 TB) per year by the end of year 2003. According to Finnish legislation images have to be stored for 20 years. The purpose of this study was to introduce a PACS for practical clinical use in the divisions of Nuclcar Medicine, as a part of HUSpacs. The effect of PACS on customising image fusion in the division of nuclear medicine was also evaluated. Methods: The architecture of HOSpacs is based on local un-lin¢ archives (RAID) and two regional image databases linked together. The capacity of online archives is approximately two years of image data. Each department a short-term archive of its own, Lung-term archiving and back-up archiving are cantralised. There am two separate campus areas with three nuclear medicine divisions and 7 gamma cameras. Both campus areas have a replicating harddisk system of their own consisting of 3x60 GB disk space. All the data (approximately 10 GB per year) is transferred automatically to the global online database in a Dianm NM format. It is also possible to transfer images acquired by other modalities (e.g. MRI, CT) to this database for image fusion. The next step is to archive this data to the regional HUSpacs database. Results: Combination of anatomical and functional image data from the same part of the body is important and can enhance the understanding of functional abnormalities. Hence image fusion is important in clinical work. The new fusion programs is based on several different registering algorithms and works fine in most cases. Registering with external landmarks is also an accurate technique if markers are available. Conclusions: For routine use of image fusion it is essential to have a fast image network for transfemng images from different modalities and a PACS for storing them. It is also essential to have a common commitment to Dicom standard. Open-architecture PACS seems to remove the remaining difficulties in cusmmising image fusion. The introduced expanded HUSpacs will be one of the largest PACS in the world when completed in 2003.

A. van Lingen (1), N.M. Bruin (1), E. Baumann (2), T. Ijbema (3), P.G.H.M. Raijmakers (1), G.J.J. Teule (1). (1) Department of Nuclear Medicine, Free University Medical Center, Amsterdam, The Netherlands; (2) Eurorad, CIT, Strassbourg, France; (3) PI-Medical Diagnostic Equipment By, Joure, the Netherlands. Aim: To optimise by simulation the on-line processing of a 49x49 mm Held*of-view (FOV) imaging probe for per-operative applications. The physical performance of the device (e.g. 6 mm spatial resolution) has been reported before. The imaging software displayed in a grey scale only a matrix of 16xl6 pixels, in concordance with the array of the 256 CdTe elements of the collimated device. Methods: Using Matlab 5.3 (SE) on a PC, the effect of differunt image smoothing and interpolation schemes was studied. All images were presented in eolunr (blue is background, yellow is medium and red is hot). The interpolation consisted of a I-2-4 weighing scheme, with the higher weight applied to pixels closer to the central pixeh Subsequent application of the interpolation resulted in matrix sizes of 31 x3 l, 6 l x61, and 121x 121. With each interpolation a smoothing was performed either before or afterwards (pro- or post-smoothing). The processing schemes were applied to the following test images (16x16 matrix): single pixel value, checkerboard, an acquired image of a high activity point source and a low activity point source (100:1 intensity ratio and 10 mm apart), an acquired image (60 sec) of a sentinel node near the injection site in a breast cancer patient. The criteria for the best scheme were reduction of coarseness, preservation of resolutiun and image uniformity. Results: All teat images showed too much coarseness if presented by a 16x16 matrix. More interpolation resulted in increased refinemenL but also more noisy images. With pro-smoothing low activities tended to vanish, but were preserved with post-smoothing. The checkerboard images showed a better resolution with post-smoothing than with pro-smoothing. In the case of the 100:1 intensity ratio, the colder spot fused with the hot spot, when pro-smoothing was applied. This was not the case with post-smoothing. In the patient image, pro-smoothing caused an increase of activity between injection site and sentinel node, but not with postsmoothing. Conefusiuns: For on-line imaging with a device consisting of 16x 16 individual detector elements, the acquisition interface for the operator should be easy to interpret. A colour display is mandatory to resolve low contrasts. Furthermore, a 3-fold interpolation with post-smoothing is found to be optimal for on-line processing.

1257

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PHYSICS / INSTRUMENTATION 3

PS_712

Without attenuatiun correction OC/MC scatter traction seemed larger but was unaffected by the presence of the nail.

MULTI-COMPARTMENT MODEL FOR INTRAOPERATIVE MEASUREMENT OF RENAL PLASMA FLOW DURING USE OF HEART-LUNG MACHINE IN CARDIAC SURGERY D. Sandrock (1), S. Morgera (2), W. Heldwein (2), K. de Jonge (3), D.L. Munz (1). (1) Clinic for Nuclear Medicine; (2) Clinic for Nephrology; (3) Clinic for Cardiovascular Surgery, University Hospital Charit6, Berlin, Germany. Aim: The conventional measurement of the orthoiodohippurata (OIH) clearance for determination of renal plasma flow assumes a two-compartment model. During use of a heart-lung machine (HLM) in cardiac surgery these assumptions are not suitable. Aim of this study was to develop a multi-compartment model, which reflects the intraoperative situation in a more realistic manner. Methods: The determination of the renal plasma flow was done by measuring intranperatively obtained venous blood samples at~er i.v. injection of 10 MBq t-123-OIH in a gamma well counter. For creating the multi-compartment model, the tbllowing factors/spaces were taken into consideration (and measured by [volume corrected] fluid samples during 10 cardiosurgical interventions): blood volume (from nomogram), hematocrit (for calculation of plasma volume), infusion volumes, blood substitution, insensible water loss (IWL, open chest, I0 ml/kg body weight/h), urine/hemofiltration volume, filling volume of the bean-lung machine before use, volume changes according to the machine protocol, volume reflux of red blood cell concentrate at the end of use, blood loss. Results: The model shown below represents the measured spaces/volumes of a single patient (example) Conclusion: The multi.compartment model realistically describes the intraoperative vol. umes/spaces during the use of the heart-lung machine and allows the intraoperative measurement oftbe renal plasma flow.

Act. conc. ratios Act. in MC only - with att. corr. Act. in MC and OC - with art. corr - without att. corr.

With nail ICfMC

OC/MC

Without nail IC/MC

OC/MC

0.147

0.020

0.224

0.022

0.128 -0.070

0.040 0.043

0.237 0.414

0.041 0.045

Conclusions: An intramedullary nail reduces the cortical bone compartment density, as estimated from the Tx scan. However, the ratio of activity concentration (Bq/cc) in cortical bone and in soft tissue is not affected by the nail in the marrow compartment. Also, application of attenuation correction does not affect this ratio.

PS_713

PS_714

THE EFFECT OF AN INTRAMEDULLARY NAIL ON

COMPARISON OF TWO CT ORGAN VOLUME CALCULATION METHODS FOR MASS CORRECTION OF ORGAN BETA SELFRADIATION ABSORBED DOSE ESTIMATES

SEMI-QUANTITATIVE F18-BONE PET B.G. Hoving, A. Van Lingen, ToJ. Blokhuis, J.C. Boos, K. Boshuizen, A.A. Lammertsma. Clinical PET Center, Free University Medical Center, Amsterdam, The Netherlands. Aim: To evaluate in a phantom whether an intramedullary vanadium nail in a long bone fracture affects the semi-quantitative results of PET F-18 bone scans. Methods: A phantom was designed representing a human thigh: 28 cm long with three concentric cylindrical compartments: inner (marrow, ] cm diameter, IC), mid (cortex, 4 cm, MC), outer (soR tissue, 17 cm, OC). h/static emission (Era) scan (I 5 rain) was performed with the nail in the IC and 75 MBq F-I 8 only in the MC. ARer 12 hours of decay 10 rain transmission scans (Tx) were obtained. All acquisitions were repeated with the nail removed and with F-i8 activity in both MC and OC. The transmission p-values were determined for all compartments in both situations. Each scan was reconstructed by filtered back projection with a Harming filter (0.5 c/p), with and without attenuation correction. ROIs were drawn according to the cylinder diameters. The semi-quantitative parameters of interest were the ratios of activity concentrations (Bq/cc) of IC/MC and OC/MC. Results: No streak artefacts were seen in the transmission scans. The OC density was not affected by the presence of the nail. However, the MC appeared more dense (0.102 vs 0.090) with the nail present:

p.-values(cm") With nail Without na

IoC137

MC02

0.047

0.090

[ OC

0.095 0.094

With attenuation correction and only activity in the MC, scatter into the OC was approximately 2%, with or without nail. Scatter from MC into the IC amounts to 22.4% without the nail and reduced to 14.7% with the nail. Adding activity to OC, the nail caused a decrease in total scatter (23.7% to 12.8%) from MC and OC into IC.

125E

W. D. Erwin, M. W. Groch. Department of Nuclear Medicine, Northwestern University Medical School, Chicago, USA. Patient-specific organ beta self-radiation absorbed doses (_RAD) in radioimmunotherapy may be estimated by scaling absorbed dose according to organ mass. The purpose of this investigation was to compare calculated organ masses and corrected R A D estimates using two differant organ CT volume calculation methods. Methods: Kidney, liver, lung and spleen _RAD estimates (rad/mCi) were calculated in seven (7) lymphoma patients undergoing Y-90 radioimmunotherapy, with mass correction based on reference phantom:patient mass ratios (Stabin, SNM "98). Two slice-by-slice (2D) CT volume definition methods were employed to calculate organ masses. Method I (GE Medical Systems) employed semi-automated edge tracking, while method 2 (Osiris, ffrMpitaux Universitaires de Gen?va) used pixel value histogram windowing and region growing. Volumes (cc) were converted to mass (g) by multiplication by organ densities specified by the MIRD schema (.2958 g/co [lung] and .9869 g/cc [soR tissue]). Reference organ masses and uncorrected PAD estimates were derived from the MIRDOSE version 3 program (Oak Ridge Associatad Universities). Results: Calculated organ masses (n = 28) were (mean [range] in g): 1083 [227-2288] (Method 1) and 1035 [192-2211] (Method 2). Linear regression of volumes demonstrated excellent correlation (Method 2 = 0.97xMethod I - 15, r = 0.99). The mean absolute (g) and percent (%) differences (Method 2 - Method 1) were not statistically significant (-49 + 60 g and -6.7 + 7.5 %; p " 0.05, paired t-test). Bland-Altman analysis demonstrated slightly increasing absolute difference with increasing mass (Y = -0.03X - 18, r = -0.37), but slightly decreasing % difference with increasing mass (Y = 0.004X - I l, r = 0.40). Linear regression of resultant PAD estimates was excellent (Method 2 = 1.08xMethod 1 - 0.06, r = .99). Again, the m~an absolute (rad/mCi) and percent (%) differences (Method 2 - Method 1) were not statistically significant (.76 :i: 1.0 ra~mCi and 6.8 :[: 7.5 %; p " 0.05, paired t-test). BlandAltman analysis demonstrated slightly increasing absolute difference with increasing P A D (Y = 0.09X - 0.2, r=0.50), and slightly increasing % difference with increasing _PAD (Y = 0.24X + 4.3, r=0.17). Conclusions: In this study, the two CT organ volume calculation methods compared yielded no statistically significant difference in mass corrected P A D estimates. Thus, the methods appear capable of producing essentially equivalent results.

• PHYSICS / INSTRUMENTATION 3 PS_715 ESTIMATE OF PERSONNEL-S SKIN DOSE DUE TO CONTAMINAT I O N B Y R A D I O N U C L I D E S U S E D IN N U C L E A R M E D I C I N E

fr,~ = amount of injected tracer retained by in tissues fn~,d(el time) = physical decay during time elapsed between tracer injection and surgery f,,,,(depht) = tissue attenuation of the source

V. H u ~ k , K. Kleinbauer, P. Koranda, M. Mysliveeek. D e p a r t m e n t of Nuclear Medicine, University Hospital, Olornouc, Czech Republic. Aim: Personneh~s skin may become contaminated in incidents and accidents involving spills of unsealed sources of radioactivity. If contamination persists, an estimate of skin dose should be made. However, these estimates are very imprecise due to a series of factors a knowledge of which is often insufficient. Among them, two factors were investigated newly in our paper in an attempt to reduce partly an uncertainty in the determination of absorbed dose: an area of the contaminated skin and a residence time of radioactive substances on the skin. Methods: Critically evaluating the literature, a table was compiled of beta and gamma dose rate to the basal layer of the skin at 0.07 mm depth from contamination by radionuclides used in nuclear medicine. In our calculation, the dose rate was considered as the arithmetic mean of dose rates corresponding to two extreme geometries: an extended contaminated area on the skin (_> 100 cm -~) and droplet of radioactive substance on the skin (I cm2). A residual activity of any radionuclide which could not be removed by the repeated careful decontamination (performed immediately after incident), was supposed to be eliminated with the biological haft-life T b = 116 h as a consequence of the natural sloughing off of the skin. The residence time was calculated as 1.443Tffb/(Tf÷Tb) where T r is the physical half-life of the radionuelide. The skin dose was obtained as the product of the mean dose rate and the residence time. Results: Values of dose rate in mSv.h-I/(kBq.cm 2) and dose in mSv/(kBq.cm '~) (given in parentheses) for some radionuclidas: ~'~Sr 2 (306), 3;p 1.9 (238). L~ll 1.55 (161), 9Oy 2.1 (126), ~rRe 1.73 (127), 153Sm 1.52 (73), I~SRe 2 (43), Iltln 0.37 (23), 67Ga 0.36 (24), 2°1TI 0.25 (16), '231 0.35 (6), L~F 1.9 (5), ~'~Tc 0.23 (1.9). Our approximative results are valid on the assumption that residual activity of radionuclides persists predominantly in the superlicial layers of the epidermis. Conclusions: It is possible to determine easily, without knowing the contaminated area and on the basis of one measurement of residual activity in kBq.cm z by means ot'a monitor, rough values of doses to personneh
co

PS_716

PS717

A G E N E R A L F O R M U L A FOR R A D I A T I O N D O S I M E T R Y E S T I M A T E S FOR S E N T I N E L L Y M P H N O D E B I O P S Y IN B R E A S T C A N C E R SURGERY

A S S E S S M E N T OF R A D I A T I O N S A F E T Y O F T H E S E N T I N E L L Y M P H N O D E T E C H N I Q U E IN T H E O P E R A T I O N R O O M

C. Bagnara (1), G. Villa (1), E Buffoni (1), P. Erba (1), E Castagnola (1), M. B a g n a s c o (1), A. Pilot (2), G. Mariani (1). (1) Nuclear Medicine Service, DiMI - University of Genoa, Genoa, Italy; (2) Health Physic Unit, S. Martino Hospital - University of Genoa, Italy. Growing interest is recentlybeing devoted to radioguided surgery for sentinel lymph node biopsy, particularly in patients with breast cancer. In fact, after the pilot studies carried out under investigationa[ protocols, this approach is quickly being translated intu the clinical routine, although its long-term impact on the clinical outcome of patients has not yet been elucidated. In addition to the Nuclear Medicine staff administering the radiopharmaecutical and performing the in vivo evaluations (lymphoscintigraphy and intraoperative gamma-counting), the procedure intrinsically involves other personnel, such as the surgeon and the pathologist. Concern is therefore mounting on the possibility that the radiation burden to such personnel entails special protection procedures, especially when the number of such surgical procedures is relatively high. Methods: In this work we reviewed the results of the following experimental studies on the radiation burden to non-nuclear medicine Personnel involved in sentinel lymph node biopsy for breast cancer surgery, all based on the administration of ~mTc-labelled colloids: I. Pijpers et aL ~jdschr Nucl Geneesk 1997; 19: 144-7. 2. Cramonesi et al. Nucl Ivied Commun 1999; 20: 919-924. 3. Glass et aL gamin Nucl Mad 1999," 29: 57-68. 4. Stratmann et al. Am J Surg ]999; 178: 454-457. 5. Motta et al. Tumori 2000; 86: 372-374. 6. Waddington ¢t aL EurJNucl Med2000; 27: 377-391. Results and conclusion: Our analysis showed that, despite some important differences in the methods employed for such determinations, there was a remarkable consistency in the results obtained, after normalizing for injected dose, time elapsed between tracer administration and surgical procedure, duration of the surgical procedure. A general formula was therefore derived thereby a certain radiation dosimetry estimate could be calculated aRer introducing any given combination of the variables involved in radiogu/dsd sentinel lymph node biopsy. The equivalent dose (D) to personnel can therefore be estimated emplying the following general formula: z D = f ,tAob._t/d ¢if~tclfa~=a(el tlme)llf~n,.(depht)

t~

K. N a k a m u r a (1), H. Kikuchi (2), H. Fujii (1), Y. Kitagawa (3), T. Ikeda (3), K. Nakazato (2), M. Kitajima (3), A. Kubo (1). (1) D e p a r t m e n t of Radiology, Keio University School of Medicine, Tokyo, Japan; (2) Radiation Safety Office, Keio University S c h o o l of Medicine, Tokyo, Japan; (3) D e p a r t m e n t of Surgery, Keio University S c h o o l of Medicine, Tokyo, Japan. Aim: The purpose of this study is to assess radiation safety to the staff that performs the sentinel lymph node techniques by using radioactive materials in the operation room. Methods: The radiation dose to two surgeons; Surgeon I conducting the excision at the primary tumor and Surgeon 11performing probe-guided localization and excision of the sentinel nodes, was recorded using electronic personal dose meter in the chest and radiophotoluminascent glass dose meter at the fingers. The personal dose meter in her abdomen also determined the radiation dose to the nurse who assists surgeons. Results: The surgery of breast or GI (gastric, esophagus, or rectal) cancer was operated for 2.24 hours or 5.30 hours on the average, respectively. The mean radiation doses to the surgeons (Chest: 0.42 (D and 0.32 (I[) (Sv/hr; Fingers: 12.2 (1) and 5.1 (11) (Sv/hr) and nurse (0.00 (Svgnr) in the operation of breast cancer were smaller than those in the GI cancer operation (Chest: 0.54 (1) and 0.64 (I[) (Sv/hr;, Fingers: 12.6 (l) and 7.5 (Sv/hr; Nurse: 0.03 (Sv/hr), probably because Tc-99m was spread in the small area near injection turnout sites. When the operation of GI cancer was conducted under the ¢odoscopas, radiation dose to the surgeon's chest was reduced to 0.16-0.34 (Sv/hr, and doses at fingers of Surgeon [ and lI were decreased into 1.03-1.44 and 1.71-1.12 (gv/hr, respectively. The maximum radiation dose to surgical staff resulting from all surgeries (n= 20) performed on a sentinel node was 6 (Sv on the chest of Surgeon II and 129"_Sv at the finger of Surgeon 1 during the operation of gastric cancer. Conclusions: the radiation doses to staff groups involved in any kinds of cancer operation were small enough for the personal radiation monitoring to be omitted.

whore: f st = conversion constant (exposure-karma-dose factor) for W~Tc fi,o = injected activity t = duration of performance (surgery or pathology analysis) d = mean distance from the source

1259

0

0

• PHYSICS / INSTRUMENTATION 3 / RADIOPHARMACY / RADIOCHEMISTRY 4 PS_718

PS_720

NEW CONCEPT OF POSITRON EMITTERS SHIELDING: DECLINE VIAL POSITION FOR QUANTITAVE WITHDRAWING OF RADIOPHARMACEUTICALS

DOSIMETRIC PROPERTIES OF LI2B407:CU,AG,P SOLID TL

D. Janeba (1), P. Kralik (2), M. Penkava (2), J. Dudkova (1), O. Belohlavek (1), V. Vrana (3). (1) Na Homolce Hospital, Praha, Czech Republic; (2) Variotec Ltd., Rez u Prahy, Czech Republic; (3) Charles University General Hospital, Praha, Czech Republic. A i m : Loading the dose of positron emitters into syringe causes radiation exposure, especially

for the hands. The aim of this work was to develop an efficient shielding device for filling the syringes, which could be operated easily in the luminary flow box and would reduce radiation exposure. M e t h o d s : Primary shielding of vial (20 mm lead) provides continuous protection even during short time manipulation with vial and it is housed in the secondary shielding (40 mm lead). The vial in primary shielding is taken out of the transport container and inserted in decline position into a system designed for loading radiopharmaceutical into syringe (see figure), Two needles are inserted to the vial, one for filling the syringe, the other to balance the air pressure. Then the whole device is closed with a cover (40 mm lead) and the syringe is housed into additional shielding (30 mm lead). No f~rtber movement with the vial is necessary and the technologist can immediately load the radiopharmaceufical into the syringe. After syringe is filled, it is placed into a syringe shield and mobile transportation container. Results: The tests with the first prototype showed that the shielding considerably reduces radiation exposure (dose rate at 30cm from equipment is < 3p.Sv/hour for 5GBq 18FDG without any additional shielding). The conus of the needle is fixed which enables easy and exact connection and disconnection of syringes. The amount of radiopharmaceutical in the syringe can be continuously controlled by viewing the syringe scale in the mirror via a channel through the shielding. The mirror position may be optimised to lower the demands on accuracy of syringe positioning. The decline position of vial ensures almost total withdrawal of radiopharmaceutical inside. C o n c l u s i o n : The concept of the primary and secondary shielding with declined vial position showed its gain for reduction of radiation doses. The local shielding has proven to be very easy to handle and applicable in daily routine. The tests in routine practice showed that this system is compact for placement in luminary flow box and can be made compatible with dil= ferent types and sizes of vials and containers.

DETECTORS M. Prokic. Institute of Nuclear Sciences, Vinca, YU. Very flew thermoluminescent materials are tissue equivalent with an effective atomic number which is very close to that of soft biological tissue (7.4). Lithium borate based TL dosemeters appeared to be the most attractive, with an effective atomic number Zen=7.3. Methods: This paper presents the main dosimetric characteristics of newly prepared complete tissue-equivalent thermoluminescent detector LizB407:Cu,Ag,P in form of sintered pellets, developed at the Institute of Nuclear Sciences, Vin_a. As a result of an advancement in the preparation procedure by sensitizing of basical Li,B4OT:CU phosphor, significant improvement in the TL sensitivity of Li_,B4OT:Cu,Ag,P was gained. The thermoluminescent propenies of developed lithium borate TL detector examined in this study, include glow-cup, e shape, TL sensitivity, photon dose response, minimum detectable dose, relative photon energy response, fading, reproducibility, and recommended annealing procedure. Results: From the experimental results it is evident its very wide linear dose response range up to I0 ~ Gy. It is also evident that the glow curve consisted of well defined main dosimetric peak with a TL sensitivity which is about 4 times higher than that of commonIy used TLD, LiF:Mg,Ti (TLD-100). Li_,B~OT:Cu,Ag,P is an efficient TL detector for dose measurements of X, photon, electron, proton and neutron radiation. Also, as a result of an advancement in the preparation procedure, Li_~BaOT:Cu,Ag,P sintered pellets have shown a resistance to adverse effects caused by handling procedure, with no change on the TL response. C o n c l u s i o n s : Represented dosimetfic characteristics make sintered solid lithium borate TL dosemeter promising for different dosimetry applications, particularly in medical and clinical dosimetry and radiation protection.

The work was supported by projects LN00BI22 and NC 5975-3 and the developed system is patented (PV2000-3151). Authors appreciate the cfibrt of the Variotec Ltd. fur manul:acturing of the first prototype tested.

Acknowledgements:

PS_719 EVALUATION OF RADIOISOTOPE EXPOSURES USING AUTOMATED QUALITY CONTROL SYSTEM AND AUTOMATED INJECTION SYSTEM AT PET INSTITUTE HANDLING [LARGE AMOUNT OF SHORT HALF LIFE RADIOISOTOPES K. Tomiyoshi (1), S. Nagata (1), S. Fujiwara (1), M. Shinoda (1), M. Kawano (1), T. Tomemori (1), K. Nakagawa (1), K. Abe (1), K. Uno (1), T. Kanoi (2), M. Sasaki (3)(1) Nishidai Clinic Diagnostic Imaging Center, Itabashi-Ku Tokyo, Japan; (2) Universal Giken, Odawara-City Kanagawa, Japan; (3) Sumitomo Heavy Industries.Ltd, Shinagawa-Ku Tokyo, Japan. Because of a very short half life of radio-pharmaceuticals used for PET, a large quantity production of radio-pharmaceuticals is required for a clinical use. Attention has to be paid on the radioisotope (RI) protection. There are two chances for receiving large RI exposures. One is at production and quality control of radio-pharmaceuticals. The other is at injection of radiopharmaceuticals to many patients. To attain a great reduction of RI exposure, we constructed an Automated Quality Control (Q.C.) System (M-200) and an Automated Injection System (US-2000) for routine production and for routine injection. We presented original scheme of these systems and we reported how much R.1 exposure was reduced before and at2er in their use. Methods: Scheme of Autumatad Q.C. System (M-200) and Automated Injection System (US2000) M-200 has two main functions. One is to measure total volume and total activity of the radiopharmaceuticals and distribute a designated activity into container made of tungsten. Other function is quality control of the radio-pharmaceuticals. Semiconductor RI detectors and liquid sensor was employed to measure activity and volume to get a concentration of radio pharmaceuticals. Tungsten shield container transferred from M-200 was directly placed in the US2000 and a needle was connected to the sterile vial in the container. Radio-pharmaceutical was led by disposable sterile tubes controlled by several liquid sensors and RI sensors. A touch panel was used to obtain expected total activity and volume for injection. Patient is needle inserted to be ready to connected to a disposable tube from US-2000. Results: By employing M-200 and US-2000, Exposure dose was decreased to in the range of one hundredth to one thousandth of that not employing the systems. A correlation factor in measurement of RI activity for M-200 and US-2000 was 0.99 in the range of 0.1GBq to 1.0GBq. Average injection dose was fluctuated less than 10 percents from an expected one. A residue activity in the system was about 10% to be improved. C o n c l u s i o n : These two systems are very valuable and indispensable for handling large amount of radio-pharmaceuticals and many patients at PET Institutes.

1260

RADIOPHARMACY / RADIOCHEMISTRY 4 PS_721 EFFECT OF HIGHER 99MTC/99TC RATIO FROM A SECOND ELUTION IN LABELING COLLOID ALBUMIN G.M.M. Gommans (1), R.O. Boer (1), A. Dongen van (1), E. Gommans (2), F. Zant van der (1). (1) Department of Nuclear Medicine, Wesffries Hospital, Hoorn, The Netherlands; (2) Faculty of Chemical Engineering, University of Twente, Enschede, The Netherlands. The Aim: Following our previous studies in which we proved a better labeling we tried in this . . . . . . 9qm . study o Further improve labehng efficiency and radlochemlcal stabth y of Tc colloid albumin and to facilitate an optimal labeling protocol for WmTccolloid albumin Methods: To Further improve the labeling procedure of ~'~Tc colloid albumin, in-viwo stability of different concentrations prepared fi-om a second elution o f a 9~Mo / 99mTcgenerator at T = 2 hours were tested (ingrown T=0-2 h from a previous elution at T=0 hours. Concentrations of 2.5, 10, 20, 25, 30 and 37 MBq 9~'~Tc0.tg colloid albumin (Nanocoll-) under nitrogen and in vacuum were prepared and the quality of the solutions, radiochemical stability and efficiency of labeling after 0.5, 2, 5 and 8 and 24 hours were tested. Results: Using a second elution at T=2 (ingrown of 2 hours) hours for labeling 99rnTccolloid albumin under nitrogen and under vacuum, a maximum acceptable concentration of 30 MBq/gg was found and a 3.0-fold greater efficiency over the entire period of 24 hours was 90ra achieved. Coincidental we found that eluting a 99M0 / Tc generator twice a day (T=0 h and 99m T=2 h) will height the daily production of Te with 20% without loose of strength of the 99M0 / 9~Tc generator. Labeled under nitro=ten T=0h tin,town 24 h) MBq/m~; 0~5 h 2h 2.5 99.8 99~3 10 99.9 98.8 25 96.1 88.7 30 81.5 78.5 37 79.0 74.5 Labeled under nitrosen T=2h (ingrown 2h I MBq/m~ 0.5 h 2h 2.5 99.6 99.8 I0 99.5 99.4 25 100.0 97.5 30 97.2 96.8 37 98.6 96.0

5 h, 99.9 98.5 86.8 76.0 72.0

8h 97.9 98.0 85.6 75.4 [ 70.5

24h 97.5 97.0 84.0 72.0 68.0

5h 99.3 98.3 95.3 96.0 95.5

!8h 99.7 99.8 !95.6 95.2 94.8

24h 99,5 99,9 98.0 96.4 93.0

• RADIOPHARMACY / RADIOCHEMISTRY 4

PS_723

Labeled under vacuum T=0h (,ingrown 24h) MBq/m~ 0.5 h 2h 25 98.5 98.0 I0 99.6 98.0 25 98.1 97.8 30 96.5 95.1 37 i 94.5 88.3 Labeled under vacuum T=2h (ingrown 2h) MBq/mt~ 0.5 h 2h 2.5 100.0 100.0 10 100.0 100.0 25 98.6 99.0 30 98.7 99.3 37 98,8 97.0

5h 98.0 97.5 97.9 93.9 85.5

8h 99.0 96.7 97.1 93.7 83.9

24h 9&2 96.0 96.6 92.0 82.6

5h 100.0 100,0 97.5 99.2 94.4

8h 100,0 100,0 97.5 98.3 96.2

24h 100,0

100,0 98.0 97.6 93.0

Conclusion: Labeled ~"Tc colloid albumin from a second elution (T=2 h) with ingrown of 99 9~n , , two hours of a Mo/ Tc generator shows a 3.0 fold greater efficiency of labeling and is more stable than labeled at time T=0 h with an Ingrown Tc/ Tc of twenty-four hours. .

,

¢4m

9q

EXTRACTION AND DEEP PURIFICATION OF ALPHA-EMI'B'ING RADIONUCLIDES FOR MEDICAL APPLICATION

N. Nerozin, E. Smetanin, V. Pavlovich, D, Dubinkin, O. Vtorova. Department of Isotopes and Radiopharmaceuticals, Institute of Physics and Power Engineering, Obninsk, Russia. Nowadays monoclonal antibodies labelled by radionuclides find more and more wide application in oncologic disease diagnostics and treatment. Alpha-emitting radionuclides have doubtless advantage over 13- and ~/-emitters due to a high value of their linear energy transfer and smalt free path. Just few alpha.emitting radionuclides suitable for medical application can be picked out of a great number of them. Ac-225 is one of these radionudidcs, it serves as the parent isotope for Bi-213 recovery. Aim: This research has been carried out for studying chemical and engineering processes of recovery, purification and production of pure Ac-225 medications out of the seasoned Th-229. Methods: Smption methods of Ac-225 recovery and deep purification from Th-229 and daughter decay products have been used. Ae-225 produced has been analyzed for the chemical impurities and alpha-radionuclides concentration with the help of alpha-spectrometry. Chemical impurity concentration in Ac-225 is l0 "4 - lff 5 mg/ml in 21 elements. Alpha- and gamma-radiometric control of process solutions has been carried out at every research phase. Results: The research ofAc-225 generator basic design has shown that the most rational way is to develop Ac-225 generator consisting of the following operations: Th-229{228) long-term storage in H N O 3 solution; Th-229(228) sorption on anion-exchange resin; Sorbent washing by the same solution; Thorium desorption by HNO3, correction by Th solution and long-term storage before the lbl/owing processing; Raffinate and washing solution correction in HNO3 for Ac-225 sorption; Ac-225 sorption on cationite from - HNO3; Sorbent washing by HCI solution of the same acidity prepared isothermally on the base of twice-distillod product made in a quartz device; Ac-225 dasorption by HCI distilled in the quartz device; Analysis of the solution produced for Th-229(228) and Ra-224 contents, chemical and spectral analysis of chemical impurities. Conclusions: The process of Ac and Th separation followed by Ac purification from Th-229 daughter decay products has been developed. The principle design of the generator system for Ac-225 production has been proposed.

PS_722

PS_724

CLINICAL EXPERIENCE WITH PREPARATION OF IN-111 AND Y-90 LABELED ZEVAMN: RADIOCHEMICAL PURITY ASSESSMENT

STRUCTURAL COMPARISON OF THREE DOTATOC METAL COMPLEXES

A.M. Zimmer (1), P.C. Chinn (2nd), R.A. Morena (2nd), M.D. Wakefield (2nd), S.M. Spies (1st). (1) Nuclear Medicine Department, Northwestern University Medical Center, Chicago, IL, USA; (2) IDEC Pharmaceuticals Corporation, San Diego, CA, USA.

A. K~hlewein (1), M. Deshmukh (1), G. Gemmecker (1), H. M~cke (2), G. Scherer (2). (1) Institut fSr Organische Chemie und Biochemie II, Technische Universit~it M0nchen, Germany; (2) Institute of Nuclear Medicine Division of Radiological Chemistry University Hospital, Basel.

IDEC Pharmaceuticals has developed a cold kit for the prepamtion of In- 111 and Y-90 labeled Zevalin (ibritumomab tiuxetan), an anti-CD20 murthe IgGI monoclonal antibody. The cold kit consists of four color-coded components including acetate buffer (50 nM sodium acetate), conjugated moncclonal antibody, formulation buffer (PBS, 7.5% human serum albumin, I mM DTPA) and a reaction vial The purpose of the study was to evaluate the radiochemical purity of radiolabeled Zevalin utilizing thin layer and size exclusion high performance liquid chromatography. Methods: At Northwestern University Medical Center, 38 In-II 1 Zevalth and 58 Y-90 Zevalin preparations were formulated using aseptic techniques with the cold kit components provided. Y-90 chloride (40 mCi) or In-Ill chloride (5.5 mCi) was added to the reaction vial containing 50 nM sodium acetate in order to adjust the pH to approximately 4. Conjugated antibody was added and the reaction incubated for 5 or 30 minutes for Y-90 or In-I 11, respectively. Formulation buffer was then added (total volume 10 ml) to terminate the reaction and also to stabilize the mdiolabeled antibody. Radiocbemical purity (RCP) was assessed on each specific preparation in triplicate using instant thin layer chromatography-silica gel with normal saline. In addition, size exclusion high performance liquid chromatography (HPLC) was also used to assess radiochemical purity of selected radiolabeled antibody preparations. Chromatographic separation by HPLC was achieved using a TSKgel G3000SW molecular sizing column. Results: The RCP of all preparations, except one, exceeded the release specifications of 95%. A mean radiochemical purity of 97.3% + 1.8% (sd) and 97.7% _+ 1.1% (sd) was obtained for in-tl I Zevalin and Y-90 Zevalin, respectively. The RCP of the failed Y-90 Zevalin preparation was less than 10% and, upon further investigation, was attributed to a compounding error during the radiolabefing process. A close correlation in unbound radionualide levels was observed between thin layer and size exclusion HPLC. Further analysis of HPLC elution profiles showed no mdiolabeted antibody aggregates or other radiolabcled antibody breakdown products. Conclusion: The formulation of radiolabeled Zevalin, using the cold kit components, is relatively simple and reliable and results in preparations with consistently high radiolabeling efficiancics, as shown by thin layer and size exclusion HPLC.

Introduction:DOTATOC (DOTA-b-Phei-Tyr3-octreotide) has shown its suitability as a tumor targeting agent when labelled with diagnostic and therapeutic radionuclides. Patients with advanced somatostatin receptor positive tumors have successfully been treated with 90y. labeled DOTATOC. Other isotopes like 67"6~Gaand rain have been used for diagnostic applications. It was shown that sensitivity and biodistribution as well as recep!or affinity depend on the metal ion which is complexed by DOTATOC. This result is quite surprising, given that it should be expected that the pepfide part is solely responsible for receptor affinity, rumor uptake eta.This fact leads to the hypothesis that the nature of the metal ion has an influence on the three-dimeasional structure of the peptide. Here we compare the structore of three M011)DOTATOC (M(III)=Ga, Y, Eu) complexes. As Eu(III)-DOTATOC is most likely isostructural to YtlII)-DOTATOC we included this metal because of poteotial additional distance information obtained due to the paramagnetic character of Eu(lil). Methods: Structural investigations were performed using ID and 2D NMR experiments including TOCSY, DQF-COSY, E.COSY and ROESY. In addition, TI relaxation measurements were performed to/nvestigate the effect of the paramagnetic Eu(lIl) ion. Results: Important differences were observed between Ga(Ill)-DOTATOC and Y(III)-DOTATOC with regard to the geometry of the metal complex. Whereas the NH proton of D-Phe coupled to the DOTA chelator is strongly shifted in Y(III)-DOTATOC to lower field, indicating an interaction of the corresponding carboxy oxygen with the metal, this proton shows no shift in the Ga complex compared to the uncomplexed DOTATOC. This is a strong indication that the Ga(DOTA-D-Phe) moiety is hexacoordinatad whereas Y(DOTA-D-Phe) shows at least octacoordination in solution. Additionally, in Y(II1)-DOTATOC two sets of signals appear, one set most likely belonging to the cis isomer (about 25%) at the amida bond to DPbe. This is rather unusual as cis fractions in secondary amide peptid¢ bonds are usually below 1%. The solution structure of octreotid¢ was shown to consist of two conformations, a sheet-like conformation and a 3-10 helical conformation. Our results indicate that the metal ions have an influence on the population of these conformations as we}l as on the cis/trans equilibrium. Conclusion: High resolution JH NMR techniques allow the determination of smJctural and conformational differences of radiometal-peptide conjugates and help to understand differences in biological behavioua

1261

• RADIOPHARMACY / RADIOCHEMISTRY 4

PS_725

PS_727

IN-VITRO ADSORPTION OF TC-99M MIBI, TC-99M TETROFOSMIN, TC-99M FURIFOSMIN AND TC-99M 0 4 - ONTO TUBES

A NEW METHOD FOR N.C.A. COPPER-64 PRODUCTION

M. Rodrigues, E Chehne, H. Sinzinger. Department of Nuclear Medicine, University Hospital, Vienna, Austria. Adsorption of radiopharmaceutlcals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for invitro studies are extremely limited. The aim of this study was to assess the extent of adsorption ofTc-99m he×akis(2-methoxyisobutylisonitrile) (Tc-99m MIBI), Tc-O9m tetrofosmin, Tc99m furifosmin and Tc-99m O4onto tubes used for in-vitro measurement of cellular uptake of these radiopharmaceuticals. Methods: In each experiment, fur measuring the non-specific activity due to adsorption of radiopharmaceuticals, I ml of incubation medium for the cell lines was added to polystyrene round-bottom tubes and kept at 37"C lbr at least 1 hour lbr equilibration. The radiopharmaceutical (7.4x]05 Bq) was added to each tube. The intluence on adsorption of different incubation media [McCoys 5a (for SK-BR-3 cells). RPMl-1640 (tbr MCF-7 cells) and Leibovitz's L-15 (for liposarcoma cells)], temperature of incubation (37°, 32° or 22"C) and time of incubation (10, 20, 30, 40, 60, 80, 100 and 120 minutes after the addition of the radiopharmaceuticall was evaluated. Six samples of each combination of the above mentioned experimental conditions (i.e, incubation medium, temperature and time) were studied. The human adenocarcinoma breast cells SK-BR-3 (poorly differentiated epithelial-like) and MCF-7 (differentiated epithelial-like), and the human liposarcoma cells SW 872 were chosen to demonstrate the need to correct cellular uptake after measuring the adsorption of the radiopbarrnacenticats onto the tubes. The total (not corrected for adsorption) uptake was compared with the corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cells. Results: Levels of adsorption onto tubes ranging from 0.94±0.13% to 7.07±0.46% were tbund. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium (higher adsorption tbr Tc-99m MIBL Tc-99m furitbsmin and Tc-99m O4 with RPMI-1640, for Tc-99m tetrolbsmin with Leibovitz's L-15) and the incubation temperature (22iC>32iC>37iC). With Tc-99m furilbsmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Conclusion: Systematic investigations to evaluate the residual, adsorbed activity of radiopharmaceuticals onto materials ~sed during in-vitro studies sbould be regarded as a mandatory aspect of quality control.

M. Bonardi (1), C. Birattari (1), K. Abbas (2), E Groppi (1), M. Severgnini (1), D. Shaw (2), E. Menapace (3), M.F. Stroosnijder (2). (1) Radiochemistry Laboratory, LASh., Universit~t degli Studi and INFNMilano, Segrate, Milano, Italy; (2) Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Ispra (VA), Italy; (3) Enea, Applied Physics Division, Bologna, Italy. ~C'u is a suitableradioneclidefor labellingof a wide rangeof radiopharmaceuticalcompounds,fur both PET imagingand therapy.In fact. Cu(ll) forms a largeclassof stablecomplexesand chelates (acetate. TETA-octreotide, DOTA-biotin, DOTA-NR-LU-IO. Shill-base ligands, di-tio-carbamates (DTC) : ethyl-methyI-DTC and tio-semi-carbazonates: PTSM, ATSM, etc.). Several production methods have been investigated for ~Cu production, such as those using neutron irradiation of Cu and Zn (natural or enriched targets) and also proton beam irradiation of an enriched ~Ni target. The latter method yields a high specific activity product, however ~tNi is obviously very expensive. Irradiation with neutrons is nowadays problematic since the nuclear reactors are shutting down one after the other. In addition, either the specific activity of the final product is low or the production yield of the radiotracer is low. In this study, we present preliminary results on another promising method tbr N.C.A 64Cu production based on natural Zn irradiated with deuterons. A high purity (9N) Zn metal target ",,,as irradiated at the JRC Cyclotron (Ispra, Italy), which is a Scanditronix MC 40 variable energy machine, capable of accelerating deuteron beams up to 19 MeV, with a maximum extracted current o1"30 A. A fuw hours a|~er the EOB, HPGe gamma spectrometry analysis, perionmed on the activated sample revealed the presence of the tollowmg radlonuchdes: Ca, Cu, Cu. Ga, Ga. Zn and Zn. Ga and Ga are cooled off. To proceed wah the radiocbemical separation, the activated Zn Target has been dissolved in 7 N HCI. The Ga nuclides have been liquid-liquid extracted from both Zn and Cu, with a yield greater than t~q.99 %. In the residual solution of about I ml volume, radionuclides of Cu and Zn are well quantified with both gamma spectrometry and liquid scintillation counting. The Cu/Zn radionuclide separation has been carried out using an anion exchange column. The overall recovery of copper activity was greater than 95 % (~Cu and 67CHI. Impurities ot'Zn in the Cu fiaction are determined by atomic absorption spectrometry, some days after separation to alh)w the radioactive decay. At present, traces of gallium radionuclides are present in the copper fraction, even if the gallium extraction yield is larger than 99.99 %. Conclusion: This study presents a promising method for not only ~Cu production, but also Ibr ~rCu and ~TGa. The determination of both thick and thin target yields (cross sections) of the different radionuclidcs mentioned in this study is in progress.

PS_726

PS_728

DEVELOPMENT OF TARGET SYSTEM FOR [18F]FLUORINE PRODUCTION VIA THE 180(P,N)18F NUCLEAR REACTION WITH MC-50 CYCLOTRON

PREPARATION AND IN VlVO BIODISTRIBUTION OF 99M-TC LABELLED TRODAT-1 KIT

K.S. Chun, M.G. Hur, S.W. Kim, Y.S. Sub, S.D. Yang, S.H. Ahn, S.M. Lira, S.W. Hong. Cyclotron Application Lab., KCCH, Nowon-Ku, Seoul, Korea. Aim: The number of PET scanner installed in Korea has been sharply increasing for a few years. [tSF]Fluorine has been gaining increasing importance in various F-18 radiopharmaceuticals production because its electrophilic reaction can afford many versatile pathways in is . . . . . [ F]compounds synthesis. We have an ex,t~enence of success m making the enncbed O-18 water target for ourselves for the routine [ is.F]FDG production with nucleophilic substitution reaction. In order to produce new [ isF]eompounds, promising agents in ontology study, we decided to make the enriched i,Oz gas target system to produce [ IsF]fluorine. Method: Our lg 18 target system for [ F]fluorine production consisted of target chamber, enriched O2 gas loading/cryogenic recovery system, collimator/energy degrader, gas and vacuum control system. Conically shaped target chambers were fabricated of aluminum and Ni-plated aluminum and the target chambers were mounted on the multi-target irradiation station made by ourselves. Also, 4 sectors carbon collimator(_ t.0mm) was installed to control the proton beam on the target. All valves in the gas and vacuum control system were the VCO type of Swagelok product to maintain high pressure and vacuum. Conclusion: Now the target system is being tested for [tSF]fluorth¢ production with two step irradiation protocol and it is expected to increase the beam current up to more than 60mA with improvement of target system. The results of testing of the target system will be discussed.

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M. Csiszar (1), G. Toth (2), G. Jancso (3), B. Kanyo (1), L. Pavics (1). (1) Department of Nuclear Medicine, University of Szeged, Szeged, Hungary; (2) Isotope Institute Ltd., Budapest, Hungary; (3) Department of Physiology, University of Szeged, Szeged, Hungary. W~Tc is the mostcommonly usedradionuclidein routinenuclearmedicineimagingprocedures. A novel W'~Tc-labeled tropan¢ derivative, 9'~Tc-TRODAT-I, is useful as potential dopamine transporter (DAT) imaging agent. According to the data of the literature we developed a TRODAT-I kit. The aim of the present study was to optimize the kit formulation and to investigate the biodstribotion of the complex in rats. Methods: The composition of the lyophilized kit was varied. The amount of TRODAT-I ligand, sodium-glacoheptonate and the other kit contents was changed. The optimal conditions for labeling were examined, the radiolabeling yield and the radiocbemical purity was evaluated by HPLC method. The radioactivity for labeling was in the interval of 0,5-3,5 GBq. An ethanol solid phase extraction method on the Sep-Pak-Plus C-18 cartridge was developed to rid of the undesirable fractions. The reproducibility of our mensurmentas was also studied. The labeled and purified complex was i.v. injected into male Wistar rats (n = 9). After 60 minutes the rats was killed and biodismbution was measm'ed. The regional brain biodistribution was analysed at the cerebellum, striatum, hippocampua and cortex. Results: There is an optimal level for all kit components, the most drastical effect has the increased or decreased sodium-glucobeptonate content. The TRODAT-I ligand amount has not influenced the complexing significantly. If higher radiactivity than 2 GBq was used at the optimal kit content the radiolabeling yield was about 50-70%. Much better yield can be obtained with 1-1,5 GBq ~"T¢ (80-95% over 6 hours). The labeling yield can be improved for |5-20% by the ethanol extraction and cleaning method. The highest uptake in the rats was in the liver (16,26 + 5,26%). In the brain it was 0,12 -t- 0,05%. Examining the brain regions the highest specific uptake was in the striatum, the lowest in the cerebellum (the striatal-cerebellar ratio was 2,21 £'0,47). Summarizing our results and comparing them with the literature data we conclude that our TRODAT-I kit can be tested in human experiments. Conclusion: '~Tc-TRODAT-I binds selectively to DATs in the brain and that is potentially useful for in rive assessment of the loss of dopamine neurons in Parkinson's and other neurodegenerative diseases.

• RADIOPHARMACY / RADIOCHEMISTRY 4 PS_729 RUSSIAN TC-99M GENERATOR FOR NUCLEAR MEDICINE A. Semenova (1), D. Stepchenkov (1), G. Davydov (2), A. Sokolov (1), V. Basmanov (1), D. Frolov (1). (1) State Scientific Center of RF - Institute of Physics and Power Engineering; (2) Medical Radiological Research Center, Obninsk, Russia. Development of generator technology for Tc-99m radiopharmaceutical production shows that the aim is the impurity concentration reduction in eluate because the cold kits are very sensitive to stable chemical impurities. Aim. The aim of the research is the development of Mo-99/Tc-99m generator of high activity with eluate of good quality for diagnostic radiopharmaceutical production in hospitals. During the eluate quality evaluation special attention was paid to its chemical purity, namely manganese concentration. Manganese high concentration in eluate can result in its competitive participation in the following interactions between pertechnetate-ions and the cold kits during radiopharmaceutical synthesis at hospitals reducing their quality, Methods. Multi-layer adsorbent has been used. One layer is silica gel modified by manganese dioxide in acid form and the other layers are cbromatograpbic aluminum oxide in acid, alkaline and neutral forms. Results. Optimization of molybdenum-q9 dynamic adsorption has been carried out. It has been shown that the adsorption process from molybdenum-99 solution ofpH 5.5 - 6 0 is efficiently carried out during technetium-gqm generator production, It has been stated that the use of multi-layer adsorbent and molybdenum solution of the above mentioned pH results in the manganese concentration reduction at 1 - 2 orders in eluate and teebnetium-99m yield increasing at - 10% during the generator service life as compared with Russian adopted technology. The dependence of the manganese concentration in eluate on the generator service lit;.: has been studied. Teebnetium-99m generator production technology of world level with 0.1 - 4.0 Ci activity has been developed with Tc-qqm yield not less than 95%, Mn "~" and AI ~' ion concentrations - 0. I - 5.0 lag/rot and 0.3 - 1.0 I,tg/ml, correspondingly, and molybdenum-99 concentration - l0 4 10-5% of technetium-99m activity. The other quality characteristics correspond to the requirements of Russian, BP and USP Pharmacopoeia. Conclusion. Tc-99m generator production technology possesses a patent #2153357 of 03.08.2000 ,.Generator for technetium-99m sterile radiopharmaceutical production". Clinical application of the mentioned Tc-99m generators made in SSC RF IPPE (State Scientific Center of Russian Federation - Institute of Physics and Power Engineering) has persuasively presented the eluate high quality at the Department of Radioisotope Diagnostics of MRRC RAMS (Medical Research Rathological Center of Russian Academy of Medical Science). Wide range of cold kits made both in Russia (Diamed, Medradiopreparat) and in the foreign companies (CIS BIO, Nycomed Amersham. Mallinckrodt Medical) is used for radiopharmaceuticals production fi)r seintigrapby of brain (Ceretec), cardiovascular system (Technetryl, MIBL TCK-I, TCK-2, Cardiolite), lungs (Macrotech, Pulmocis), kidneys (TCK6, MAG3, TCK-12, Pentatech, Tecbnemec, Technemag), bepato-billiary system (TechnetryL Coren, Bromezida. Mezida, TCK-I, TCK-15), skeleton (Pyrphotech. Technefor, TCK-7) and tumors (Tecbnetrul, Carbomec). Clinical operation experience with Russian and foreign (CIS BIO, Nycomed Amersham, etc.) Tc-q9m generators results in a conclusion that as for the eluate high quality, reliability and safety Tc-99m generators made in SSC RF IPPE (Obninsk, Russia) are as good as the similar products of the leading foreign companies. • Variable collimator position: 0 = minimum collimation. 3 = maximum collimation.

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