P260 SPECT/CT in the neuroendocrine tumours (NET) assessment by means of 111InOctreotide somatostatin receptors scintigraphy (SRS) . F. Dore1, C. Di Russo1, M. de Denaro2, M. Mucci1, L. Cattin3, L. Piscopello3; 1Department of Nuclear Medicine Hospital Maggiore-Trieste, Trieste, Italy, 2Hospital Trieste Medical Physics, Trieste, Italy, 3Department of Clinical, Morphological and Technological Sciences, University of Trieste,, Trieste, Italy. Aim Aim of our study was further confirm of additional clinical effectiveness by using SPECT/CT with 111In -Octreotide. Methods and Materials We studied 37 patients (pts) 21 males and 24 females; average age 63.18 +/-15.3; 6 pts suffered intestinal carcinoid (G1), 8 pts NET pancreas (G2); 11 pts (G3) clinical and instrumental suspicion of NET (4 pts) or carcinoid localization in lungs (2 pts), breast (1 pt), malignant tymoma (1pt), medullar thyroid carcinoma (3 pts); 12 pts (G4 ) had ophthalmopathy (4 pts ) and hypophysis macro-adenoma (8 pts). 111InOctreotide SRS was performed using Infinia Hawkeye SPECT/CT hybrid system (G.E. Healthcare). The SPECT/CT images of the same area (abdomen or chest) were obtained, after injection of 185 Mbq 111InOctreotide, at 4 and 24 hours using 120 frames at 45s/frame and 3° rotation-angle, 128 x 128 matrix. The CT part was acquired over a 220° arc at a 10-mm slicestep, and at a14-sec. slice-time. Reference for presence or absence of disease was the histopathology test after surgical operation, when present or follow-up images and clinical negative evolution. Results SRS was positive in 27 pts and negative in 8; it changed clinical and surgical management in 40% of G1 G2 G3 cases (10/25); SPECT/CT revealed 16% of further lesions undetected by conventional CT: 2 cases of unsuspected lesions in lumbar vertebras (1 G1 and 1 G2 pts), gastro-epliploic ligament (1 G1 pt), pancreatic recurrent NET (2 G2 pts) and 1 insulinoma (confirmed by complementary radio-guided surgery), 1 G3 pt with previous breast NET had metastases in lungs and left axillary’s cavity. Among 8 pts with negative SRS, 1 G1 pt was in follow-up; 2 G2 pts (1 with liver metastases and 1 with following pathological histology of colon adeno-carcinoma) and 2 G4 cases had lesions without 111In-Octreotide uptake; in 4 negative G3 pts further clinical and pathologic evaluation excluded NET aetiology. SPECT/CT in G4 pts was positive in 3/4 of ophthalmopathy cases and in 7/8 pts with hypophysis macroadenoma and all positive cases underwent to cold ligand somatostatin receptors treatment.Conclusions: Our data confirm an increased diagnostic accuracy of the SRS with 111InOctreotide using hybrid systems; SPECT/CT is an useful instrument for NET detection and provides the anatomic localization of functional lesions undetected by conventional morphologic diagnostics; SPECT/CT is important for patient management, contributing to plan a better clinical or surgical NET treatment .

P261 New minigastrin derivatives for labeling with 99mTc, 90Y, 177Lu and 111In in comparative evaluation - synthesis, labelling and preliminary biological studies. B. Janota1, R. Mikolajczak1, C. Decristoforo2, E. von Guggenberg2; 1Radioisotope Centre Polatom, Otwock, Poland, 22. Clinical Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria. The aim Recently, Gastrin Receptor Scintigraphy GRS has become a useful tool for imaging of tumours as an adjunct to the Somatostatin Receptor Scintigraphy. DOTA and HYNIC derivatives of minigastrin have shown promising properties labelled with 99mTc and 111In, however they showed limited stability and a tendency towards oxidation of Met in the peptide chain. A range of new minigastrin analogs has been designed in order to study their suitability in the CCK2/gastrin-R-tagreted imaging of tumors such as medullary thyroid cancer (MTC) and small cell lung cancer (SCLC). Materials and Methods The minigastrin analogues (X-D-Glu-Ala-Tyr-GlyTrp-Y-Asp-Phe; X=DTPA,DOTA,HYNIC; Y=Met,Nle,Ile) were synthesized in our laboratory on solid phase by F-moc - strategy using Sasrin resin to obtain COOH at the C-terminus and rink amide MBHA resin to obtain CONH2 group. HYNIC was coupled in solution to the respective peptide sequence. DTPA and DOTA were coupled on solid phase. Peptide protecting groups were removed in one step by adding 90% TFA/TIS, Thioanisol, H2O. The crude conjugate peptide was purified by preparative HPLC. Radiolabelling was performed with 111In and 68Ga for X=DTPA, DOTA and with EDDA as coligand for 99mTc, X=HYNIC. In vitro tests included stability in plasma and plasma protein binding, internalisation and receptor binding assays using a CCK-2 receptor positive cell line (AR4-2J). Results Different minigastrin analogues were synthesized with DTPA, DOTA or HYNIC as coupling agent and by replacing methionine with norleucin and isoleucin. Radioligands with high labelling yield at high specific activities and low amounts of impurities, showing high stability in plasma and low protein binding could be selected. However, differences in receptor affinity and internalisation rates could be observed. Initial evaluation in vivo in AR42-J tumour bearing nude mice showed low but still significant tumour uptake for 68Ga- (1.0±0.06%) and 111In-DOTA-Ile-MG(1.24±0.20%), while very low kidney retention was observed. Conclusion Peptide conjugates were obtained in 10-20% overall

yields by solid phase techniques, allowing radiolabelling at high specific activities. The evaluation in vitro and first results in vivo allowed selection of new promising radioligands with high metabolic stability for imaging CCK-2 receptor positive tumours.

P262 Diagnosis and patients' follow-up with neuroblastoma (nb) submitted to autologous bone marrow transplant (abmt), applying a "score" to the I123mibg scintigraphy M. P. Orduña, L. Díez, M. E. Rioja, A. Crespo; Ramón y Cajal Hospital, Madrid, Spain. AIM: To evalue the "score" as evolutionary and predictive criterion for patients with NB submitted to bone marrow transplant.Materials and Methods: 19 patients with stage III or IV neuroblastoma were studied from 1990 to 2005 with follow-up by I123 MIBG scintigraphy. Four scintigraphies were performed: at diagnosis, after the induction chemotherapy , pre-transplant and post-transplant. They were valued by means of a "score" of the Committee for the Neuroblastoma of the European Society of Paediatric Oncology.Results: 2 patients (10.5 %) died post-ABMT for inherent complications in this one (sepsis and haemorrhage). 7 patients (36.8 %) died for post-ABMT relapse and except one, all of them presented "score" raised (> 10) at diagnosis, with partial response to the chemotherapy and with important elevations(increases) of "score"" before the death. 8 (42.1 %) is in clinical remission (CR), 5 of them had a "score"> 10 at diagnosis, and 3 had complete responses to the chemotherapy. After the ABMT they all presented a "score" of 0. 2 patients (10.5 %) present disease in this moment. One of them with progressive disease and the other one meets in partial reference. Both of them with "score" raised up at diagnosis (> 10) and after the ABMT.Conclusions: 1) we haven’t observed differences between the "scores" at diagnosis in the groups; 2) better results of the "score" are observed after the chemotherapy in the patients in CR with regard to the deceaseds and those that they are with persistent disease; 3) in the patients in CR the "score" preABMT is lower in the bone locations and from bone marrow than the group of deceaseds; 4) I123 MIBG scintigraphy values the response to the chemotherapy, verifies if active disease exists and states a real CR; 5) a raised "score" to the diagnosis doesn’t represent a predictive value.

P263 Clinical utility of somatostatin receptor scintigraphy: a retrospective analysis of one year’s data B. Yazici, A. Oral, N. Mutlukoca, O. Erdim, Z. Burak; Ege University Medical Faculty Department of Nuclear Medicine, Izmir, Turkey. AIM: The aim of this study was to re-evaluate the indications of somatostatin receptor scintigrapy (SRS) in clinical practice and to find out its clinical utility.Materials and Methods: From January to December 2005, patients who were referred for In-111 pentetreotide (octreotide) scintigraphy were retrospectively reviewed. A total of 30 patient files (17 women, 13 men) were analyzed. The data were divided into 3 groups as follows: Group1: patients who had pathological diagnosis of neuroendocrine tumor and examined for staging purposes. Group 2: patients who had clinical suspicion of a neuroendocrine tumor but had no pathological evidence and Group 3: patients who were evaluated for the receptor status of various tumors to guide the somatostatin analogue treatment.Results: The majority of the patients were examined for staging purposes, there were 14 patients in Group 1 (47%). 8 of them were investigated for a mass lesion and had neuroendocrine tumor diagnosis after the surgical operation. SRS demonstrated unknown lesions in 5 of 14 patients and changed the therapy plan. Group 2 consisted of 7 patients (23%), all had positive laboratory findings suggesting a neuroendocrine tumor but no primary focus. 4 patients had clinical suspicion of insulinoma (all were negative in SRS), 1 possible carcinoid and 1 gastrinoma also had negative scan results. Only 1 patient with MEN1 had positive somatostatin accumulation. The clinical impact of SRS in patients without pathological confirmation of a neuroendocrine tumor was only 14%. Group 3 consisted of 9 patients with hepatocellular carcinoma (3 pts), anorectal carcinoma and poorly differentiated neuroendocrine carcinoma (5 pts). Most of the patients were in stage 4 with multiple hepatic and lymph node metastasis. Somatostatin analogue treatment could be applied only 2 patients with positive SRS. Conclusions: Our results showed that the majority of patients admitted for SRS were investigated for the staging process of neuroendocrine tumors and also to explore the somatostatin receptor status of various tumors to guide synthetic somatostatin treatment. The clinical impact of SRS was high in both staging and therapy planning. However, the role of SRS was limited in patients who had positive clinical findings suggesting a neuroendocrine tumor but negative pathological evidence.

P22 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Oncology: Varia 1 P264 18f-fluorine and 18f-fdg small animal PET for the evaluation of human xenograft murine models of Ewing sarcoma: preliminary results. C. Nanni1, C. Pettinato1, G. Nicoletti2, P. Lollini1, V. Ambrosini1, S. Trespidi1, A. Spinelli1, M. Bucci1, C. Quarta1, R. Franchi1, M. Farsad1, P. Castellucci1, K. Scotlandi3, G. Montini1, S. Fanti1; 1S Orsola-Malpighi Hospital, Bologna, Italy, 2Patologia Clinica, Bologna, Italy, 3Istituti Ortopedici Rizzoli, Bologna, Italy. Small Animal PET is a molecular imaging technique used to evaluate in vivo several neoplastic diseases, reducing the number of animals for each scientific protocol as it allows a longitudinal

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carcinoma (2 patients). All patients were submitted to CT of the thorax and abdomen and Octreoascan SRS was performed 4 hours (total body and SPECT acquisition) and 24 hours (planar views), post iv injection of 185MBq of the radiolabeled compound. Three of the patients with diarrheic syndrome suspect of intestinal carcinoid tumor with a positive SRS, plus one patient with adenocarcinoma of the pancreas, with a positive SRS (accumulation of the radiopharmaceutical at the place of the gallbladder), were finally diagnosed as inflammatory intestinal disease and gallbladder dilatation, respectively. At the time of the evaluation 14 of the other patients were free of disease, concerning secondary involvement. In these cases, CT and SRS studies were matched each other, with no pathological lesions and no abnormal accumulation of the radiopharmaceutical respectively. Concerning pathological cases, only one SRS study in a patient with rectum carcinoid was normal, with liver lesions in the CT study. These lesions were considered as subtypes 2,3 and 5 somatostatin receptors negative. According to these results, sensitivity of SRS study was 97% and specificity 77.8%. It is the authors’ belief, that molecular imaging of somatostatin receptors with Octreoscan, is a sensitive method for the evaluation of patients with GEP tumors. However, in cases of intestinal disease, we should be aware of false positive results due to inflammatory processes and the presence of lymphocyte infiltration.

observation of disease progression in the same animal. In this way it is possible to early detect disease onset and localization, and to assess metabolic activity semi-quantitatively. This feature acquires importance when new anti-cancer therapies are tested in vivo, because a measurement of metabolic activity changes before, during and after therapy can give an early index of therapeutic efficacy. The use of Small Animal PET in a pre-clinical oncological study follows the selection of the proper positron emitter radiotracer, capable to better visualize the chosen cancer cell lines. The aim of this study was to set up a preliminary protocol to in vivo study human xenograft murine models of Ewing’s sarcoma, in order to subsequently in vivo observe the tumor kinetic of growth and the tumor response to experimental therapies. We studied 4 female nude mice. 3 animals (Nr.1,2 and 3) were inoculated with three different human Ewing’s sarcoma cell lines(TCpsil/CD99, IOR-BRZ, IOR-NGR) in the subcutaneous tissues of the right lower limb (5x 106 ). 1 animal (Nr.4) was inoculated with 2 x106 human Ewing’s sarcoma cells (TCscr106) intravenously. 2 months after the inoculum, all the animals underwent Small Animal PET scan. Each animal was iv administrated with 20 MBq of radiotracer (18F-Fluorine and 18F-FDG in two different days) under gas anaesthesia and then was allowed to wake up. Uptake time was 60 minutes. The whole body scan (GE, eXplore Vista DR) was carried out under gas anaesthesia and images were reconstructed with OSEM 2D. All the animals were sacrified after the completion of imaging procedures and PET results were compared to necropsy results. Histological analysis of nodes and other PET positive findings is in progress. 18F-Small Animal PET identified only 1 out of 3 cancer masses that was clearly calcified, while FDG Small Animal PET identified 3 out of 3 Ewing’s sarcoma masses. FDG gave good quality images with high masses uptake. FDG identified 3 tiny positive lymphnodes preliminary identified at necropsy as metastatic. 18F never identified secondary lymph nodes. FDG is therefore the most suitable radiotracer to study human xenograft murine models of Ewing’s Sarcoma.

P265 99mTc-Mebrofenin imaging is helpful activation of hepatic inflammation transplantation in the liver.

for assessing following cell

K. K. Bhargava1, B. Joseph2, G. G. Tronco1, C. J. Palestro1, S. Gupta2; 1Long Island Jewish Medical Center, New Hyde Park, NY, United States, 2 Albert Einstein College of Medicine, Bronx, NY, United States. Objectives: Recent studies established that interference with Kupffer cell activation and inflammatory cytokine activity improves transplanted cell engraftment in the liver. Enhanced cell engraftment will be beneficial in therapeutic liver repopulation. To obtain further insights into the role of inflammatory mechanisms in cell transplantation, we studied hepatobiliary transport of 99mTc-mebrofenin.Methods: Dipeptidyl peptidase IV-deficient (DPPIV-) F344 rats weighing 120-160g were used in groups of 3-6 each. Groups included untreated controls and rats with intrasplenic transplantation of 0.1 to 2.0 x 107 primary F344 rat hepatocytes isolated freshly by collagenase perfusion of the liver. Animals were studied for up to 4 weeks after cell transplantation. Induction of hepatic inflammation was assessed by measuring changes in IL-6 and TNF-Į by reverse-transcription PCR using total RNA extracted from liver samples. Cryosections were prepared from liver tissues to identify DPPIV-positive transplanted cells with histochemical staining. To analyze Kupffer cell activation, incorporation of 99mTc-sulfur colloid was analyzed. For 99mTc-mebrofenin studies, 7.4 MBq of tracer was injected intrasplenically with dynamic imaging at 10 sec/frame for 60 min., using 64x64x16 matrix and zoom factor of 2. Regions of interest were drawn in the liver and time-activity curves obtained, and the fraction of peak hepatic 99mTc-mebrofenin activity retained in the liver at 60 minutes post injection was determined.Results: After cell transplantation, hepatic expression of IL-6 and TNF-Į increased over the long-term. This was associated with prolonged Kupffer cell activation resulting in increased sulfur-colloid uptake in cell recipients compared with untreated controls, p<0.001. In untreated controls, <30% of the peak hepatic 99mTc-mebrofenin activity was retained at 60 minutes. In contrast, within 1 day after cell transplantation, 99mTc-mebrofenin excretion was markedly impaired in a dose-dependent fashion, such that transplantation of 2x107 cells produced hepatic retention of 80-90% activity, p<0.001. 99mTc-mebrofenin excretion was impaired in the long-term and returned to normal only after 3 weeks following transplantation of 1x107 cells.Conclusions: Cell transplantation in the liver activated hepatic inflammation leading to impairment in the hepatic excretion of 99mTc-mebrofenin. Therefore, 99mTc-mebrofenin imaging will be helpful for identifying hepatic inflammation following cell transplantation and for developing strategies to prevent inflammation-induced decreases in cell engraftment.

P266 Radionuclide esophageal transit study and gastroesophageal reflux disease V. Dedek; Faculty hospital, Ostrava-Poruba, Czech Republic. Background: Gastroesophageal reflux disease (GERD) is a spectrum of symptoms or sings of esophageal or adjacent organ injury secondary to the reflux of gastric content. Symptoms of GERD may be divided into two categories: esophageal, which includes typical complaints (heartburn, regurgitation, dysphagia and noncardiac chest pain) and extraesophageal (pulmonary, otolaryngologic and dyspeptic). Either heartburn or regurgitation is present in 60% patients monthly. Approximately 40% of patients with typical symptoms have normal endoscopy. According to the manometry studies 35% of patients with GERD have ineffective esophageal motility, that governs esophageal acid clearance. Aim: Clinical value estimation of radionuclide esophageal transit study (RETS) to detect esophageal dysmotility and eventually gastroesophageal reflux (GER) in patients with suspected GERD.Materials and Methods: 33 adult patients (pts) were divided into two groups according to the findings on RETS. Mean transit time (MTT), antiperistalsis, retention in esophagus and finally retrograde movement from stomach to esophagus (GER) were evalauted.RETS was performed by single swallowing bolus of 10 ml water labeled with 50 MBq 99mTc-sulfur coloid. Two sets of images were acquired. First step: high-speed framing (120 ms per frame) during 30 s. Second step: slower-framing (15 s per frame) during 30 minutes. Between steps patient was given orally (supine under gamma camera) 300-500 ml of water to fill stomach and try to catch GER.Results: Group A - 18 pts with MTT betweeen 6-12,6 s (avg. 8,7 s). None of them had antiperistalsis, retention and GER. Group B - 15 pts with MTT 8-26 s (avg. 17,9s). Twelve of them had antiperistalsis and nine prolonged MTT (over 12,6 s). Five pts had retention radioactivity in esophagus. No patient in both A and B groups had signs of GER. No patient in group A had positive endoscopy, while five pts in group B had endoscopically confirmed esophagitis.Conclusions: RETS may be a useful complementary

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(simple, noninvasive, physiologic, rapid, quantitative) test for detection esophageal dysmotility in patients with suspected GERD. Its typical findings is antiperistalsis and/or prolonged MTT (see group B), that may be the cause of decreased esophageal acid clearance ability. RETS does not seem to be suitable for detection GER because of quite short monitoring time (30 minutes). RETS may serve as selection to other (more invasive) diagnostic techniques (for instance 24hour pH-metry or intraluminal multiple impedance measurement).

P267 Value of 99mTc-DPD scintigraphy as early diagnostic modality in familial amyloidotic polyneuropathy. F. Perniciaro1, A. Herberg1, S. Baldari2, M. Martino1, S. Pulizzi1, S. Russo1, A. Mazzeo3, S. Vita3, S. Baldari1; 1Nuclear Medicine, Policlinico "G.Martino", Messina, Italy, 2Nuclear Medicine, Policlinico, Messina, Italy, 3 Neurology, Policlinico "G.Martino", Messina, Italy. Aim Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited form of amyloidosis associated with mutations of the transthyretin (TTR) gene. More than 80 point mutations of the TTR gene have been identified. Most TTR gene mutations are associated with peripheral neuropathy, autonomic abnormalities, cardiomyopathy, carpal tunnel syndrome, and vitreous opacities. Recent studies have investigated the diagnostic value of the bone scanning agent technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in this disease. Materials and Methods We studied with 99mTc-DPD nine patients (four males and five females, mean age 45 years, range 33-67 years) in whom molecular analysis of TTR gene evidenced a Glu89Gln mutation at exon 3 on one allele. Two patients had a two-three years history of recurrent episodes of pallor, sweating when assuming an upright position, weakness and paresthesia in the lower limbs with difficult walking. On examination tendon reflex were absent and there was dysesthesia in the feet and loss of pain sensation distally in the limbs. The others seven patients were asymptomatic. Neurological examination and neurophysiologic studies (emg) were normal in all cases. Each patient underwent whole body scanning ten minutes and three hours after injection. SPECT tomograms of the chest were also obtained. No patient had documented heart disease. Results In the symptomatic patients scintigraphy showed intense myocardial, intense soft tissue uptake, markedly reduced bone uptake; mean whole body tracer retention was 87% at three hours (respectively 83% and 91%), mean cardiac uptake was 9,7% at three hours (respectively 8.3% and 11%) and the mean heart/whole body uptake ratio was 10.8% (respectively 10% and 11.7%). In the asymptomatic patients scintigraphy was negative in six cases: mean whole body tracer retention was 52% at three hours (range 46-57%), mean cardiac uptake was 4.8% at three hours (range 4.3-5.8%) and the mean heart/whole body uptake ratio was 8% (range 6.8-8.7%) In one asymptomatic patient 99mTc-DPD scintigraphy was positive: whole body tracer retention was 66.4% at three hours, cardiac uptake was 8.2% at three hours and the heart/whole body uptake ratio was 12.4%. Conclusion 99mTc-DPD scintigraphy can reveal silent amyloidal deposits in preclinical patients with TTR gene mutation with a fair sensitivity and specificity. The technique is also useful for an early diagnosis of cardiac involvement in asymptomatic patients. Quantitative evaluation is releated to severity of the disease.

P268 18F-FDG and tumor vascularization: is there a correlation? Preliminary results in a murine model. C. Nanni1, F. Boschi2, M. Galiè3, M. Bucci1, C. Quarta1, P. Marzola4, V. Ambrosini1, E. Nicolato5, R. Franchi1, P. Farace5, A. Spinelli1, S. Trespidi1, C. Pettinato1, S. Fanti1; 1ospedale S. Orsola-Malpighi, bologna, Italy, 2 Università degli studi di Verona, verona, Italy, 3Unversità degli studi di Verona, Verona, Italy, 4Università degli studi di verona, Verona, Italy, 5 Università degli studi di Verona, Verona, Italy. In vivo pre-clinical Molecular Imaging is acquiring importance for the evaluation of different features of cancer masses and it’s one of the steps included in the translational medicine. In clinical PET, 18F-FDG is the most widely used radiocompound. Its uptake is related to tumor malignancy, but several other parameter can influence FDG metabolism like hypoxia and tumor histological type. Tumor vascularization could influence FDG uptake as well, but literature still presents controversial results on this topic. Aim of our study was to evaluate the influence of tumor vascularization and FDG uptake in a murine model of cancer. Seven animals that had been subcutaneously injected with a carcinoma (BB1) cell line underwent 18F-FDG Small Animal PET scan and DCE-MRI (dynamic contrast-enhaced magnetic resonance imaging). For what concerns FDG PET, each animal was iv administrated with 20 MBq of radiotracer under gas anaesthesia and then was allowed to wake up. Uptake time was 60 minutes. The whole body scan (GE, eXplore Vista DR) was carried out under gas anaesthesia and images were reconstructed with OSEM 2D. TBR was calculated by drawing a VOI over the whole tumor. TBR was calculated as mean counts in the tumor / mean counts in a background VOI in the soft tissues close to the tumor mass. DCE-MRI was performed on a Biospec scanner (Burker, Germany) by injecting Gd-DTPA-albumin (Contrast Media Laboratory University of California, USA). By locating a ROI over the whole tumor, we calculated fractional plasma volume (fPV) and transendothelial permeability (kPs). We found that TBR was not significantly correlated to fPV (R=0.3) nor to kPs (R=0.4) in our murine model. Nevertheless, TBR values present a trend towards an inverse correlation to fPV values as TBR decreases when fPV increases. This can be related to an activation of anaerobic glicolisis in poorly vascularized tumor cells, leading to an increase of glucose uptake. In conclusion, although preliminary, these results may suggest that a reduced oxygen supply to the tumor can lead to an increased FDG consumption.

P269 Cyanide-free synthesis of neolactosyl albumin, a receptor specific ligand of hepatocytes: Imaging and Biodistribution studies. P. Chaumet-Riffaud1, I. Martinez-Duncker2, N. Mignet3, F. Moati1, C. Richard3, M. Bessodes3, A. Prigent1, D. Scherman3; 1Hôpital BICETRE,

Aim: Kinetic studies of liver binding and blood cleareance of galactosylated ligands for the asialoglycoprotein hepatic receptor (ASGP-R) are validated for the quantification of liver function but have been poorly used in the clinical setting outside Japan and Korea. Synthesis of these products are based on cyanide derived reactants which could be associated with safety concerns according to the European Pharmacopea. The aim of this study was to develop, via cyanide-free synthesis, a chelating synthetic ligand for the ASGP-R and to perform pre-clinical studies to validate its use as a radiopharmaceutical for the quantification of liver function. Materials: Human Serum Albumin compliant with European safety regulations, linkerderivatized lactose and DTPA. Reactant buffers.Methods: The DTPA-neolactosylated albumin containing 4-7 DTPA molecules and 25-30 lactose residues was prepared in a fast one-step synthesis free of cyanide-derived products and labelled with 99mTc. Stability of labelling has been analysed. Imaging studies: Male Sprague-Dawley rats were injected through the penis vein with 200 ul of saline solution containing 750 ug of ligand and planar image sequences were acquired using a small-animal dedicated gamma camera (BIOSPACE, France) over a 30-90 min period. Animals injected with 99mTc-labelled albumin (HSA) were used as controls. Biodistribution studies: A total of 15 mice were used, with three per time point (10, 20, 30, 50, 90 minutes). Mice were injected via the tail vein with 100 ug of 99mTc-labeled ligand. Blood and twelve organ samples were collected. Radiopharmaceutical controls showed 98% labelling efficiency.Results: In mice and rats, 99mTc-HSA showed high blood pool activity; high activities in the kidney, the spleen and the liver reflected the high blood content in those organs. 99mTc-LSA accumulated mainly in the liver and negligible uptake was found in spleen. LSA was cleared from the blood of the mice with a half life of less than 15 min.Conclusions: A receptor-specific ligand for the asialoglycoprotein hepatic receptor has been developed using cyanide free synthesis and human serum albumin. The pharmaceutical validation of the process will need complementary studies. Imaging and biodistribution studies have confirmed hepatic targeting of this tracer and rapid blood clearance. Kinetic parameters provided by these experiments will be useful for the implementation of clinical trials in patients suffering from hepatic diseases.

P270 Finger doses from handling radioactive isotopes at a Nuclear Medicine department. A. Olsson1, A. Davidsson2, H. Pettersson1, A. Gustafsson1; 1Department of Radiation Physics, University Hospital, Linköping, Sweden, 2Department of Nuclear Medicine, University Hospital, Linköping, Sweden. Aim The dose burden to radiological personnel at the Linköping University Hospital is monitored by continuous measurements of the personal dose equivalent, Hp(10), using thermoluminescent dosimeters (TLD). Measurements of finger and eye doses are, however, performed more sporadically. The aim was to investigate the contribution of 99mTc, 111In and 123I to the finger dose from different work situations, and to identify any technologists working inappropriately. Material and methods Dose measurements were performed for each technologist. The preparation work i.e. preparing elution, kit and syringes, was separated from the other work situations (injection, image acquisition, patient handling). The equivalent dose to fingers was measured using TLDs (Li2B4O7). Two TLDs were worn on the index finger, in a ring and at the fingertip. A conversion factor was determined to account for differences between the ring dose, DR, and the fingertip dose, DF, after which only the dose to the ring was measured. To measure the personal dose equivalent, Hp(10), Rados Direct Ion Storage dose meter was worn at breast height. All handling of radioactivity by technologists during the preparation work was documented in a dosage program (Hotlab Management System, IBC-505). Each technologist also documented all handling of syringes during injection. Result The relation between dose to the ring and the fingertip, DF/DR, was 3.5 ± 1.3. The finger doses during preparation varied from 0.9 to 4.8 mSv/day and were, as expected, correlated to the handled activity. The mean dose was 0.03 mSv/GBq. One outlier was observed, consistently above the mean. Finger doses from other work were about 100 µSv/day. The personal dose equivalent, Hp(10), did not correlate with the finger dose. Occupational equivalent dose limits in Sweden are 500 mSv/year to skin, hands and feet. Our measurements indicate that a technologist performing preparation work once a week will receive 65 mSv/year to the fingers. Working on Mondays, when the activity is the highest or alternatively on Fridays, will result in doses of 90 mSv/year and 25 mSv/year, respectively. Working fulltime with other work will give 20 mSv/year to the fingers. Previous studies indicate that working with 18F-FDG contributes approximately 50 mSv/year to the fingers. Conclusions The dose levels to fingers at our department are well below the dose limits in Sweden. From our results, derived by measuring finger doses, we have been able to identify specific technologists in need of improving their work technique to reduce their doses.

P271 Measurements of inhaled airborne 99mTc to technologists during Technegas ventilation studies H. Karlsson1, E. Angland1, A. Davidsson2, A. Gustafsson1, H. Pettersson1; 1Department of Radiation Physics, Linköping, Sweden, 2Department of Nuclear Medicine, Linköping, Sweden. Aim Internal contamination to technologists due to inhaled 99mTc during Technegas ventilation examinations is a potential health risk. The aim of this study was to investigate the amount of activity inhaled by technologists. Therefore, a sampling and radiometric procedure was developed in this work. Material and methods Airborne 99mTc was collected on a particle filter (mixed cellulose ester, pore diameter 0.8 µm) connected to an air sampling pump (Leland Legacy®) giving a constant air flow. In order to relate to inhalation of 99mTc , the filter was attached to the technologist’s shirt collar during the examination, and the amount of air flowing through the filter was related to the amount of inhaled air. After the examination, the filter was analyzed by HPGe spectrometry (Ortec® HPGe), calibrated for 99mTc gamma at 140 keV. At our nuclear medicine department, the room used for Technegas ventilation examinations has a ventilation system, originally used during anaesthetic examinations. The amount of inhaled

activity was investigated, both with and without the ventilation system operating. Results The mean inhaled activity, with ventilation system operating, was 2.7 ±3.6 kBq (one standard deviation). Without the ventilation system, the mean inhaled activity was 8.4 ±16.5 kBq. Conclusion A fast and easy procedure to measure airborne activity has been developed. The total time from starting the measurement to obtaining the result is less than 90 minutes. The method can be applied to other isotopes, such as 131I. The mean activity, calculated on a yearly basis (assuming 20 examinations per technologist, each examination lasting 60 minutes), was 0.11 MBq with the ventilation system operating (corresponds to 0.015 % of ALI for 99mTc). Without the ventilation system operating, the corresponding mean activity was 0.45 MBq. The standard deviations of the amount of inhaled activity per examination are quite large, mainly due to factors as number of inhalations of the patient, the time the technologist is present in the examination room, and that only a few measurements has been performed. Although, it’s clear that the ventilation system reduces internal contamination of 99mTc during Technegas ventilation examinations.

P272 Absorbed dose from daily routine practice in an 18F-FDG producing radiopharmacy K. Marzo, G. Tosi, A. Chiti; Istituto Clinico Humanitas, Rozzano - Milano, Italy. Aim: We evaluated the average daily exposure to ionizing radiations from fluorine-18 of workers in a radiopharmacy laboratory producing 18f-fluoro-deoxy-glucose for clinical activityMaterials and Methods: We used portable electronic dosimeters MGP-DMC 2000s to evaluate effective and equivalent doses. These instruments can measure doses (Hp(10)) and dose rates due to photon with energies ranging from 50 keV to 3 MeV, with a confidence interval lower than 20%. An electronic dosimeter was placed on the chest of one operator, to estimate effective and superficial dose on a daily basis. Measures were taken during 48 working days over a time period of 3 months, in which 90 18F-FDG synthesis were performed. The daily routine production required setting up two 18F-FDG synthesis modules (one module for each synthesis); 18F-FDG quality controls for chemical, radiochemical and radionuclide purity, and residual solvents. The mean end of synthesis 18F-FDG activity was 21.6 GBq. Moreover the fractionating of an average of 17 patient’s doses was operated using an automatic system.Results: The mean daily effective dose during the observation period was 5± 3 µSv (range 1-13 µSv) while the superficial dose was 11± 6 µSv (range 2-32 µSv). From this data we speculate the highest contribution to the operator’s effective dose is related to the setup of the synthesis module, which is still active after about 20 hours from the previous synthesis. No significant dose is due to dose fractionating, thanks to the use of an automatic systemConclusions: We concluded effective doses to the operators are well below the accepted limits (20 mSv/year) and an improvement can be achieved reducing the time required for the synthesis module setup.

P273 99mTc-pertechnetate scintigraphy demonstrates in vivo Sodium-iodide Symporter expression in cancer patients J. Fuertes, M. Estorch, E. Rivera, A. Rodríguez-Revuelto, V. Camacho, A. Flotats, M. Quera, I. Carrió; Sant Pau Hospital, Barcelona, Spain. Aim: Sodium-iodide symporter (NIS) is an intrinsic membrane protein of thyroid gland follicular cells and it is present in other tissues, such as nasopharyngeal mucosa, salivary glands and thymus. NIS has been described in thyroid cancer but also in breast and gastric carcinomas. Uptake of 99mTc-pertechnetate is present the most times in those tissues, and it is NIS mediated. The aim of this study was to describe our experience in the utility of 99mTc-pertechnetate scintigraphy in different tumors that express NIS symporter.Materials and Methods: Six consecutive patients (4 male, mean age 61 years) with different types of cancer were included. Five patients had pulmonary metastatic disease, two of them from parotideal cylindroma, one from cancer of unknown primary origin, one from minor salivary gland adenocarcinoma and one from cavum angiosarcoma. Another patient had bone metastatic disease from cancer of unknown primary origin. Pulmonary and bone metastatic disease had been diagnosed by thoracic computed tomography or by bone scintigraphy. All patients underwent a whole body scintigraphy and thoracic SPECT-CT two hours post-injection of 740 MBq of 99mTc-pertechnetate. Degree of uptake was visually assessed as mild, moderate or intense.Results: 99mTc- pertechnetate scintigraphy showed uptake in lung nodules in all patients with pulmonary metastatic disease. Three of them showed mild degree uptake, one moderate uptake and one intense uptake by lung nodules. The patient with bone metastases presented intense uptake of radiotracer by them.Conclusions: The above described results suggest that 99mTc-pertechentate scintigraphy may help to demonstrate in vivo NIS expression in cancer patients. If NIS is expressed, NIS mediated 99mTc-pertechentate uptake may be observed.

P274 Renal function evaluation with radioisotopic studies (99mTcDTPA, 99mTc-DMSA, e 99mTc-EC) in patients underwent chemotherapy with nephrotoxic agents B. A. L. Abreu1, J. Soares Junior2, P. H. C. Melo3, R. J. V. Valença3, G. S. Pinheiro3, E. L. de Abreu1, E. L. Abreu4, J. S. Britto5, N. A. B. Melo1, J. B. Abreu1; 1Centro Bionuclear de Diagnóstico, Teresina, Brazil, 2 Universidade de São Paulo, São Paulo, Brazil, 3Hospital São Marcos, Teresina, Brazil, 4Universidade Federal do Piauí, Teresina, Brazil, 5 Universidade Estadual do Piauí, Teresina, Brazil. Aim: Renal toxicity is often reported among the side effects of chemotherapy. Routine evaluation of chemotherapy-induced nephrotoxicity include biochemical tests such as serum creatinine, urea, and also electrolyte determinations in blood and/or urine. The aim of this work is to evaluate the role of nuclear medicine for monitoring renal function in patients submitted to chemotherapy with nephrotoxic drugs (cisplatin, ifosfamide, methotrexate) as well as to compare these findings with laboratory measurements and evaluate findings obtained when using different radiopharmaceuticals.Materials and Methods: This work is a prospective longitudinal study

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Poster Presentation

Université Paris SUD, Kremlin bicetre, France, 2Faculty of Science, Morelos State Autonomous University, Cuernavaca, Mexico, 3Chemical and Genetic Pharmacology Research laboratory U640, Inserm FRE2463 CNRS, Paris, France.

carried out between October 2003 and January 2005 on oncologic patients from Hospital São Marcos, of the Sociedade Piauiense de Combate ao Cancer, (Terezina, PI, Brazil). In this study 35 patients who received chemotherapy for various malignances, underwent renal scintigraphy with 99mTc-DTPA, 99mTc-DMSA and 99mTc-EC and biochemichal evaluation at three different moments of the antineoplastic treatment: before, during and after treatment, respectively (Ev1) (Ev2) and (Ev3). These evaluations were: (a) nuclear medicine procedures with radiopharmaceuticals and (b) routine laboratory tests (determination of blood urea nitrogen levels, plasma creatinine, and urine analysis of abnormal sediments, proteinuria and hematuria). Glomerular filtration by Cockroft-Gault formula using empirical formulas was calculated.Results: No significant changes were observed at different moments of evaluation in the following parameters under study: serum urea and creatinine, Crockoft/Gault index and other ones calculated through using empiric formulae. Related to 99mTc-DTPA, no statistical significance were detected in the following parameters: time to peak (Tmax) - moment of maximal activity RK (p=0,482), LK(p=0,701) and relative uptake between the kidneys. However, statistically significant differences were found at: average time (T½) , glomerular filtration rate values (GFR), total (p<0,001), of each kidney and corrected (p<0,001), as calculated through Gates` method. Concerning to 99mTc-DMSA, the relative quantification did not show significant alterations for any of the kidneys , (RK p=0,626 LK p=0,20), but the absolute quantification showed diminished value for both (p<0,001). As to 99mTc-EC, this agent was not able to detect any significant alterations related to treatment with any of the nephrotoxic drugs used.Conclusions: Authors conclude that renal function tests routinely used in oncologic practice, did not show any statistically significant changes as consequence of therapy with such nephrotoxic drugs. Otherwise, studies using 99mTc-DTPA and 99mTc-DMSA showed considerable alterations both in the course as at the end of antineoplastic chemotherapeutic treatment. Relating to 99mTc-EC, no significant changes were evidenced, at any moment.

P275 Correlation of two methods of planar and SPECT scintigraphy with Tc-99m RBC in detection of liver hemangioma A. Fard Esfahani, B. Fallahi, K. Khatami, M. Eftekhari, M. Saghari, D. Beiki, A. Takavar; Research Institute for Nuclear Medicine, Tehran, Iran (Islamic Republic of). Aims: Hemangiomas are the most frequent benign tumor of the liver and detecting them from metastasis of other malignant hepatic tumors is of outmost importance. Tc-99m RBC is a highly specific method and is the method of choice for this differentiation. This scintigraphy is performed in Planar and SPECT modes. These two scans are compatible most of the times, and considering that SPECT is more expensive and more time consuming we planned a study to evaluate the correlation of these two methods. Materials and Methods: 62 patient (age range 2080 yr, mean age 42 yr), 41 women (67%) and 20 men (33%),who were evaluated for liver masses found on abdominal ultrasound or CT scan , underwent Tc-99m RBC scan with both Planar and SPECT methods and the data were processed. Results: Planar scan was positive in 42% and negative in 59% of cases, while for SPECT study these values were 68.9% and 31.1%, respectively. The correlation between Planar and SPECT scan results is 48%, and there were 17 lesions (27%) which were not detected by SPECT. SPECT scan determined 35% of the posteriorly located hemangiomas, and 58.3% of hemangiomas less than 3 cm, which were not detected by Planar scans. Also 75% of livers with multiple lesions, showed more lesions by SPECT compared to Planar scan. Conclusion : Although there is correlation between SPECT and Planar scan, SPECT is considered the more reliable method in hemangioma diagnosis and this is especially true when the hemangioma is of small size, it has a posterior location or in cases of multiple hamangiomas. Key words: 99mTc-RBC, liver hemangioma, SPECT, Planar, Scintigraphy, Space Occupying Lesion

P276 Renal dynamic scintigraphy with 99mTc - DTPA in patients with abnormal kidneys M. P. Yaneva, A. Botushanova, M. Marovska, B. Popova; University, Plovdiv, Bulgaria.

Medical

Horseshoe like kidneys belong to the inherited abnormalities of the kidneys. They can be connected either with their upper parts and more frequently with their lower parts and the connection between them can be connective or kidney tissue. Often one of the kidneys shows changes in its size and structure. The aim of the study is to evaluate the function of the horseshoe like kidneys with renal dynamic scintigraphy with 99mTc - DTPA Materials and methods. A retrospective study of the renal dynamic scintigraphies done between 2003 to 2005 year was done. Out of 1436 renal scintigraphic examinations 8 patients with horseshoe like kidneys were found- 3 men and 6 women with age ranges from 26 to 77 years. In all of them diagnosis horseshoe like kidneys was put for the first time due to the scintigraphic examination. The scintigraphy was done on a gamma -camera Siemens according to a predefined protocol with quantitative measurements in two phases: perfusion and secretion-excretion. 222 MBq/70kg /99mTc - DTPA was injected as bolus at the very beginning a quality assessment and quantitative determinations of T max, T ½, relative function of each kidney and glomerular filtration rate /GFR/ were done. Results. In 5 /62.5%/ of the patients a smaller size left kidney was seen. In 2 /25 %/ patients kidneys were with preserved equal size. In all patients kidneys were connected with their lower parts and the connection was kidney tissue in 4 /50%/ of the patients and connective tissue in the rest 4 /50 %/. In 1 patient /12.5%/ GFR was suppressed. Structural changes in the kidneys with reduced secretion and excretion was seen in 7 /87.5%/ patients. In 1 /12.5%/ patient only reduced excretion was seen. Conclusions. We establish a small rate of horseshoe like kidneys in our randomly selected patients. Renal dynamic scintigraphy with 99mTc - DTPA can be helpful either for the diagnosis and for the evaluation of the function of the horseshoe like kidneys.

P277 Setting up and organization of hot lab and radiopharmacy in respect of the laws in force. The experience of Centre of Oncological Reference of Basilicata (CROB).

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N. Urbano, S. Modoni; Nuclear Medicine Unit, Centro Di Rifermento Oncologico della Basilicata, Rionero in Vulture, Italy. The Nuclear Medicine Department of CROB in Rionero in Vulture (Italy), is one of the most recent Departments opened in Italy. In the our Department was projected and realized a protected area comprising radiopharmacy, hot lab and clinical laboratory to ensure the best quality in radiopharmaceutical preparation, in agreement with new regulations contained in XI Official Pharmacopoeia of the Italian Republic. Its setting up was realized in compliance with UNI 1491/1995 and ICRP 57 regulations. Protected area is characterized from an independent air conditioning system, ventilation (6-10 changes of air per hour) and air filtration with HEPA filters. The access to hot lab, where is maintained a negative pressure, is permitted through two filter areas equipped with hands-foot-clothes monitors and decontamination showers for male and female staff. Inside the hot lab are placed: a) Pb-shielded laminar flow cell for manipulation of gamma-emitter radioisotopes, with its own dose calibrator and shielded tunnel for the passage of the radioactive doses to the adjacent administration room; b) Pb- and plexiglass-shielded laminar flow cell for manipulation of beta-emitter radioisotopes, with its own dose calibrator; c) three different Pb-shielded (2-10 cm) strong boxes; d) thermostatic bath and refrigerator for “cold” pharmaceuticals. In the surroundings of the hot lab are located the clinical laboratory and radiopharmacy reserved to cells radiolabeling, radiopharmaceuticals’ quality controls and research. In particular, the laboratory contains a laminar flow cell also used for preparation of sterile compounds, a gamma-counter, a centrifuge, a freezer, and a radiochromatographic system equipped with two probes (BGO and Geiger), respectively for gamma and beta-emitters detection. Inside the radiopharmacy are located the autoradiographic system using high performance storage phosphor screen, radio-HPLC and different instruments given up to research. The responsibility of protected area is assigned to the Radiopharmacy Manager belonging to Nuclear Medicine Staff, who draws up the operative procedures for registered and extemporaneous radiopharmaceutical preparations with related quality controls, authorizes their release and administration to patients, optimizes their dosage in cooperation with nuclear physician and carries out researches on radiolabeling of new bio-molecules. Moreover, she coordinates the activities of technicians in the protected area, supervises on the correct use of existing instrumentations (calibration, maintenance and quality controls) and keeps all the paper documents (SOP, methods, registrations and material safety data sheets). The rational rooms settlement and organization in the protected area assure that the service given the last user, the Patient, is of high qualitative level.

P278 Comparison of noise, hot and cold contrast of eight tomographic camera models A. E. J. J. Seret, T. Nguyen; University of Liege, Liege, Belgium. Aim. To compare the performance in terms of noise and contrast of most of the tomographic camera models used in the geographic area of Liege and neighbourhood. Material and methods. Eight cameras were examined: 1 General Electric Magicam, 1 Siemens Multispect-3 and 1 DST, 1 DST-XL, 2 DST-Xli, 2 DSX from SMV. The on-site available low energy collimators with the highest resolution were used: ultra-high-resolution (UHR) for the DST-XL, one DST-XLi and one DSX, high-resolution (HR) for the other cameras. Three inserts made of plexiglas, 7 hot rods (4-20 mm) in cold background, 7 cold rods (6-25 mm) in hot background and a grid, were introduced in a 20 cm-diameter cylindrical phantom while leaving a volume free from any object. The phantom was filled with 750 MBq Tc99m. Two tomographic acquisitions were recorded using a 23 cm-radius circular trajectory for a total of 28 (Acq1) and 112 (Acq2) Mcounts. The 128 projections were stored in 128*128 matrix. Hardware zoom was used to achieve a pixel size in the range 2.7-2.9 mm (2.5 mm for the SMV DST). Data were reconstructed using filtered backprojection without apodizing filter and Chang attenuation correction (µ = 0.12 cm-1). For 7 cameras, the reconstruction and the reconstructed slice analysis were performed with a GE Vision (6.0) Powerstation. For the Siemens camera, slices were reconstructed using the Siemens Icon software (9.5) and then transferred to the Vision Powerstation for analysis. Coefficient of variation (COV) in the uniform region, contrast for the hot and the cold rods were measured by drawing ROIs on the adequate reconstructed slice regions and using standard formula. Results. COV was 53.7 % (Acq1) and 27.9 % (Acq2) for the Magicam, 54.0 % (Acq1) and 29.5 % (Acq2) for the Multispect-3. Mean COV was 63.8 ± 3.1 % (Acq1) and 35.5 ± 1.5 % (Acq2) for the SMV cameras. For hot rods, contrast was maximum when their diameter reached at least 16 mm with HR collimators and 20 mm with UHR collimators. For cold rods, contrast reached a maximum at 20 mm-rod diameter with all cameras and all collimators. The largest contrasts were always obtained with the UHR collimators and the Magicam camera. Conclusion. For the examined cameras, the contrast clearly depends on the resolution performance of the collimator and on the camera type. The SMV cameras were found to produce noisier images than the GE or Siemens cameras involved in this study.

P279 Incidence of peripheral vascular Rajshahi City Slum dwellers.

disorder

among

the

M. R. Uddin1, M. A. Matin2, F. U. Ahmed3, N. Begum3, M. Haque4; 1Bio Science Division, Dhaka, Bangladesh, 2Rajshahi, University, Rajshahi, Bangladesh, 3Nuclear Medicine Centre, Rajshahi, Bangladesh, 4Rajshahi University, Rajshahi, Bangladesh. Four Hundred volunteer were selected from the Rajshahi City slum dwellers and were investigated to asses the incidence of peripheral vascular disorder among the dwellers belong to poor socioeconomic urban community. Most of the slum dwellers use to engage in the profession of bicycle Rikshaw pulling or general labour. Volunteers were collected from both the groups and sub groups as smokers and non-smokers to observe the influence of heavy muscle exercise and smoking. Initially screening were performed using in-vivo nuclear medicine technique followed by live 3D colour Doppler and a few cases with peripheral angiographies. About 3 mci Tc99m pertecnate were injected under the conventional Gamma Camera (Mediso, Hungary), placing the lower limb just under the field of UFOV. About 12.25% of the volunteers were screened to have the evidence of peripheral arterial disorders resulting reduced flow of blood responsible for the incidence of peripheral arterial disease in future. From the data, it appears that due to exercise 38.77% were in the category of rickshaw pullers whereas 61.22% were found from non-rickshaw pullers out of the suspected positive cases. Among the positive cases, it is

observed that 24.49% were smokers involved in rickshaw pulling whereas 14.28% were nonsmokers of the same category. Also 38.77% were obtained in the volunteers of labour category (non-rickshaw pullers) having smoking habit but 22.45% were seen in non-smokers of the same class of volunteers. The screenings were compared with that obtained using colour Doppler and Angiographies in most of the cases agreements were found. The results of this present work are also found to agree with clinically identified factors that increase the risks of PVD. From the study it is appeared that simple blood flow study can be used as a simple tool to screen the PVD patients. The evidence of the collected data ensures that heavy exercise of lower extremities reduces the risks of the incidence of peripheral vascular disease with respect to that observed in the same category of people those who lack exercise program. The recorded findings also ensure that the effect of smoking increases the occurrence probability of the disease compared to that in non-smoker group of volunteers from the same community. However, it is suggested to maintain a life style with exercise programs and to stop smoking. If life style fails to control the progression of PVD, it is surely better to consult immediately with a physician for further step.

has been studied in patients with either multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). The aim of the present study was the evaluation of the diagnostic value of 99mTc-MIBI and its potential predictive value in the detection of bone marrow involvement in patients suffering MM and MGUS. Materials & Methods: We conducted a retrospective analysis of 64 patients (26 women, 38 men; age: 26-92 years; mean: 65.1 years), 37 with MM and 27 with MGUS, between 2000 and 2005, who underwent 99mTc-MIBI scan. The scan results were compared with bone marrow biopsy. All scans were performed prior to the treatment. Whole-body images were obtained 20 min and 2h after intravenous administration of 666-740MBq of 99mTc-MIBI. Results: 99mTc-MIBI scan was positive in 46 patients: 14 false positive, all with MGUS, and 32 true positive, all with MM. In 18 patients 99mTc-MIBI scan was negative: 5 false negative, all with MM, and 13 true negative, all with MGUS. The overall sensitivity and specificity of the 99mTc-MIBI scintigraphy was respectively 87% and 48%, the positive predictive value was 70% and the negative predictive value was 73%. Conclusion: 99mTc-MIBI scintigraphy is a useful adjunct to the investigation of multiple myeloma.

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P283

Improvement in the management of the patient in the isolated room for radioiodine treatment using telemedicine system

Neural network modeling to predict skeletal metastases in prostate cancer

K. Hwang1, D. Choi2, S. Yoon3, K. Han3, S. Yang4, C. Hwang4, M. Yoon1, W. Choe1; 1Department of Nuclear Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea, 2Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea, 3MCC, inc, Incheon, Republic of Korea, 4Network team, Gil Medical Center, Incheon, Republic of Korea.

Y. Wang, J. Chiu, L. Wei, T. Hung; Hospital, Chiayi County, Taiwan.

Aim: The advent of prostate specific antigen (PSA) has revolutionized the diagnosis of prostate cancer and is widely adopted to monitor disease progression, response to treatment and disease recurrence. Whole body bone scintigraphy has been the reference procedure for detecting skeletal metastases. The purpose of this study was to evaluate the usefulness of artificial neural network (ANN) to predict the presence of bone metastases in men with prostate cancer.Methods: The enrolled subjects consisted of 111 consecutive male patients (age 72.41 ± 7.69 years) with prostate cancer. The predictors included age of the patient and radioimmunometric serum PSA concentration. The outcome variable was dichotomous, either metastatic or non-metastatic groups, based on the results of technetium-99m methylene diphosphate whole body bone scintigraphy. A leave-one-out cross-validation was utilized for resampling process. To assess the performance for classification model in clinical investigation, the discriminatory ability of the final best ANN was calculated.Results: Sixty-seven patients (60.4%) had bone metastasis based on the scintigraphic diagnosis. The final best architecture of ANN model was 3-layered perceptrons with 6 hidden neurons. The area under the receiver-operating characteristics curve (0.87 ± 0.03) revealed a good discriminant power (p < 0.001) with best simultaneous sensitivity (89.6%) and specificity (75.0%). The diagnostic odds ratio was 25.57 derived from the likelihood ratio for positive test (3.58) and likelihood ratio for negative test (0.14).Conclusions: ANN appears to be a promising method for stratifying metastatic bone disease in prostate cancer patients.

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P23 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Completion and management of a nuclear medicine centre in “service”

Oncology: Varia 2

A. Niccoli Asabella, A. Pisani, A. Gaudiano, F. Iuele, D. Rubini, M. Pisciotta, G. Rubini; Dept. Nuclear Medicine, University of Bari - Italy, Bari, Italy. AIM To value the possibility of giving in “service” the completion and the management of a conventional diagnostic nuclear medicine centre to exceed administrative problems of employed staff engagement; to complete instrumental equipment and to curtail times of beginning of diagnostic activities that there are not present in the considered geographic area. MATERIALS AND METHODS It was valued the request for diagnostic services of users in accordance with resident population, natality and death rate, for sanitary migration towards areas with nuclear medicine centres, influence and prevalence of pathology that need scintigraphy (cancers, cardiovascular, neurologic and endocrinologic desease), basing on Italian national tariff. It was valued the request for scintigraphic exams in users basins similar in population and territory characteristics to that where will be activated diagnostic activity. It was considered the existence of a ward of about 600 meters equipped with only two gamma-camera without any furnitures, without systems of radioprotection and without authorizations. The problems of completion depended on the block of engagements of medical, technical and administration personnel and the expert to radioprotection, on the lack of funds to adjust ward and to acquire equipments and authorizations. RESULTS For users of about 250000 inhabitants, with a request of 2850 scintigraphies, considering the cost of each kind of scintigraphies and the percentage compared to the total, the middle cost of each performance is of 110 euro. Our results showed that the costs to complete the ward and to manage for five years were equals making only 2500 annual exams. CONCLUSIONS It was prepared a tender for the completion of rooms, of diagnostic equipments, of radioprotection systems, the furniture of medical rooms, diagnostics and secretary, the acquisition of radiopharmaceuticals, the material to print images and report and the necessary for operating of the ward.Moreover it was provided the number of weekly work shifts and business hours, possible exams that were not included in the contract or to introduce in the course of contract, going into operation by six months and final acquisition of every goods from the hospital.

P282 The value of 99mTc-Sestamibi scintigraphy in multiple myeloma and monoclonal gammopathy of undetermined significance F. Vieira, C. Rocha, D. Cardoso, G. Costa, A. Albuquerque, A. FerrerAntunes, J. Pedroso de Lima; Hospitais da Universidade de Coimbra, Coimbra, Portugal. Aim: Multiple myeloma is characterized by excessive numbers of abnormal plasma cells in the bone marrow and overproduction of intact monoclonal immunoglobulin. 99mTc2metthoxyisobutylisonitrile (99mTc-MIBI), also called Sestamibi, is a safe and effective scanning agent in cardiology and oncology. So, its use in imaging lesions in multiple myeloma

P284 Evaluation of circulating Thyroglobulin mRNA and serum Thyroglobulin as markers for Thyroid cancer S. Sophocleous1, M. Koptides2; 1Nuclear Medicine Center Agios Therissos, Strovolos, Cyprus, 2Department of Life and Health Sciences, Intercollege, Nicosia, Cyprus. Monitoring for thyroid cancer recurrence after total thyroidectomy and radioactive iodine ablation is routinely done through measurement of serum thyroglobulin and 131I whole-body scanning. Measurement of serum Tg has proven to be a useful marker for residual disease, but its major limitations include a low sensitivity during thyroid hormone suppression therapy, as well as interference with Tg antibodies. Although the sensitivity of the above mentioned method increases after thyroid hormone withdrawal, this induces symptomatic hypothyroidism, causing significant morbidity in many patients. Recently, recombinant TSH has been suggested as an alternative method to achieve maximum sensitivity of the test, but this method is too expensive for routine use. In an attempt to circumvent these limitations we used RT-PCR to detect cancer cells in circulation by amplifying and detecting thyroglobulin mRNA. The results obtained by RT-PCR were compared with serum Tg levels. Furthermore, each one of the patients was screened for DTC by ultrasound and 131I-WBS. In our study we measured the circulating TgmRNA and Tg levels in 30 patients. Among 16/30 patients with no evidence of the disease based on Tg levels, Tg mRNA was detected in 3, and 13 out of 14 patients with elevated Tg levels were tested positive for Tg-mRNA. Based on our data the concordance between Tg-mRNA and serum Tg levels was 86.66%. Our results indicate that screening for Tg-mRNA in peripheral blood is a sensitive marker and can be use as an adjunctive test for monitoring thyroid cancer.

P285 In vitro and in vivo evaluation of 123I-labeled Monoclonal Antibody against Membrane type-1 matrix metalloproteinase. M. Van Steenkiste#1, R. Oltenfreiter#1, F. Frankenne2, C. Van De Wiele3, F. De Vos1, G. Slegers1; 1Laboratory of Radiopharmacy, Ghent University, Ghent, Belgium, 2Laboratory of tumour and Developmental Biology, Liège University, Liege, Belgium, 3Division of Nuclear Medecine, Ghent University Hospital, Ghent, Belgium. Aim The suitability of 123I-labeled Monoclonal Antibody against Membrane type-1 matrix metalloproteinase for tumor diagnosis with SPECT was assessed in vivo. Methods mAb MT1MMP was radiolabeled using the Iodogen method and characterized. PCR and Western Blotting analysis were performed to evaluate the expression profile of MT1-MMP in different tumor types. Evaluation of tumor uptake and imaging was performed in A2058 and S15 inoculated

S283

Poster Presentation

Purpose: High-dose radioiodine treatment of patients with thyroid cancers requires a cumbersome isolation of the patient for radiation safety, and the patient has a great trouble from the isolation. In this study, telemedicine system was set up in the isolation room and we evaluated the influence of the system on the management of the patient.Methods: The telemedicine system consisted of personal computers, web camera, audio-facilities, software and mobile communication devices. Thus, the system enabled the patient to communicate with the medical staffs anywhere, instantly and the patient's relatives. A total of 16 patients (Male:Female=3:13, Age=48±13) who received radioiodine therapy using telemedicine system were analyzed. We evaluated the patient’s satisfaction using a questionnaire.Results: Most of patients with the aid of telemedicine system complained less gastrointestinal symptoms and insomnia. In the questionnaire, patients expressed their satisfaction with patient care and life quality in 65% of items questioned.Conclusions: Telemedicine system improved the patient’s satisfaction through instant and mobile communication. It may be helpful in managing the patient in isolation room for the radioiodine treatment. Keyword: Telemedicine, Wireless, Internet, Isolation room, Radioisotope, Thyroid cancer

Buddhist Dalin Tzu Chi General

athymic mice using a Toshiba GCA-9300A/hg SPECT camera in planar mode equipped with a high-resolution parallel-hole collimator. Results The radiochemical yield was 76% ± >4% (n8) and radiochemical purity was > 98 %. SDS-PAGE and Cyclone phosphor scanning confirmed the correct size of the purified 131I-mAb MT1-MMP without degradation. Stability was • 89 % at 24h in all conditions. Biodistribution in NMRI mice showed no long term accumulation in any organs (48h: < 2.5 %ID/g). Up to 4.08 %ID/g was accumulated in blood until 168h pi. In vivo experiments in A2058 inoculated mice, showed a +/- constant tumor uptake of 2.74 ±1.21 %ID/g at 3 h pi until 72 h pi. (3.01 ±0.4 %ID/g) with a tumor/blood ratio of 0.45 ±0.13 and tumor/muscle ratio of 7.50 ±2.47 at 72h pi. Biodistribution in S15 (A2058 transfected with pc3MT1800S vector) inoculated mice, showed analogue results: +/- constant tumor uptake of 3.10 ±0.76 %ID/g at 3 h pi until 48 h pi (2.22 ±0.55 %ID/g) with a tumor/blood ratio of 0.28 ±0.16 and tumor/muscle ratio of 3.71 ±1.66 at 24h pi indicating other influences of vector insertion than the intended higher MT1-MMP expression. Planar imaging in A2058 and S15 inoculated mice revealed a significant uptake compared to the contra lateral background areas. RTB were calculated from ROI’s resulting in 3.12 ±1.03, 2.60 ±0.32, 2.66 ±0.77, 4.70 ±1.16 at 1, 6, 24 and 48 h pi ratios for A2058. The cell line overexpressing MT1-MMP however, showed no higher RTB ratios (2.19 ±0.13, 3.01 ±0.09, 3.41 ±0.34 and 2.86 ±0.30 at 1, 6, 24 and 48 h pi) probably related to vector insertion. Conclusion These results indicate that mAb MT-MMP as a radiotracer could be interesting for elaboration of a non-invasive diagnostic method for a wide range of tumor types. Vector insertion influences and metabolite analysis will be performed later. Keeping in mind the disadvantages of full antibodies, smaller fragments could be more powerful imaging agents and should be developed and evaluated. Supported by EU Grant LSHC-CT-2003503297 ‘Cancerdegradome' # equal first author

P286 Biological characterization in vitro and in vivo of a new EGFR binding Affibody molecule E. Nordberg1, M. Friedman2, F. Nilsson3, S. Ståhl2, B. Glimelius4, A. Orlova3, V. Tolmachev1, J. Carlsson1; 1Oncology, Radiology and Clinical Immunology, Uppsala, Sweden, 2Royal Institute of Technology, Stockholm, Sweden, 3Affibody AB, Bromma, Sweden, 4Radiology and Clinical Immunology, Uppsala, Sweden. Aim: The Epidermal Growth Factor Receptor 1 (EGFR) is overexpressed in malignant tumours like gliomas, bladder cancer and various squamous cell carcinomas. Overexpression of EGFR is often associated with a poor prognosis and it is therefore important to detect these cancers as early as possible. Radiolabeled EGFR binding Affibody molecules could be of importance in future imaging applications.Methods: Affibody molecules which are based on a 58 amino acid residue staphylococcal protein A-derived Z domain, that target the EGFR were selected using phage display. Dimer constructs were produced and the EGFR targeting Affibody molecule with the best binding capacity (ZEGFR:955)2 was then selected for further studies. The dissociation equilibrium constant (kD) was determined using both a saturation assay on A431 cells and a biacore biosensor instrument on an EGFR-ECD immobilized sensor chip. The Affibody molecule used in in vitro studies was labelled with 125I using an indirect labelling method. In the in vivo studies the Affibody molecules were coupled to CHX-DTPA and chelated to 111In.Results: The 125I labelled (ZEGFR:955)2 binds specifically to the extracellular domain of EGFR and can be blocked both by the natural ligand, epidermal growth factor (EGF), and by the monoclonal antibody cetuximab. The affinity of the Affibody to native cell associated EGFR was estimated to 2 nM but to recombinant immobilized EGFR approximately 50 nM. To test the binding capacity in vivo a biodistributation study and imaging with a gamma camera were done with the 111In labelled (ZEGFR:955)2 Affibody in A431 bearing tumour nude mice. The binding of [111In](ZEGFR:955)2 was EGFR-specific and gave a tumour to blood ratio of about 9 after 4 hours.Conclusions: The results indicate that 111In CHX-DTPA labelled (ZEGFR:955)2 is a good candidate for future imaging applications with the purpose to detect EGFR overexpressing tumours.

P287 Imaging of HER2-tumours with a site-specifically 99mTclabelled Affibody containing a cysteinyldiglycyl chelator T. Tran1, T. Engfeldt2, A. Orlova3, C. Widström4, A. Bruskin5, V. Tolmachev1, A. Eriksson Karlström2; 1Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, 2 School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden, 3Affibody AB, Bromma, Sweden, 4Hospital Physics, Uppsala University Hospital, Uppsala, Sweden, 5Russian Research Centrum, Institute of Biophysics, Moscow, Russian Federation. Aim: The Affibody molecule ZHER2:342 has a high affinity towards the oncogene product HER-2 (human epidermal growth factor receptor 2), which is often overexpressed in breast and ovarian cancers. Imaging of HER2 expression may enable to select patients, who would benefit from treatment with the monoclonal antibody Herceptin. The goal of this study was to evaluate the tumour targeting properties of 99mTc-labelled ZHER2:342, containing a cysteinyldiglycyl (CGG) chelator, which was incorporated into ZHER2:342 during peptide synthesis.Materials and Methods: The Affibody CGG-ZHER2:342 was assembled using Fmoc/tBu solid phase peptide synthesis. Biochemical characterization was performed by RP-HPLC, ESI-MS, biosensor (Biacore) studies and circular dichroism. The 99mTc-labelled conjugate was evaluated in vitro regarding to its binding specificity and antigen binding capacity to HER2-expressing SKOV-3 ovarian carcinoma cells. The stability of 99mTc-CGG- ZHER2:342 was assessed in PBS and by cysteine challenge tests. The tumour targeting properties of the labelled conjugate were determined in SKOV-3 tumour-bearing nude mice. Gamma-camera imaging of grafted tumours was performed.Results: CGG-ZHER2:342 had an apparent affinity to HER2 of 300 pM. The labelling yield was over 90%. 99mTc-CGG-ZHER2:342. was stable in 300 molar excess of cysteine at 37oC for 2 hours. Its binding proved to be receptor-specific in living HER2expressing SKOV-3 cells. Cellular retention was high and 50% of the radioactivity was still cellassociated at 24 hours after interrupted incubation. Biodistribution in tumour-bearing mice revealed rapid blood clearance and low uptake in most organs. Tumour uptake was HER2specific, since it could be blocked with an excess of non-labelled ZHER2:342. The conjugate demonstrated an uptake of 5.7 ± 2.2 IA/g and a tumour-to-blood ratio of 9 at 6 h post-injection in

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tumour-bearing mice . Imaging with 99mTc-CGG-ZHER2:342 showed clear visualization of tumours at 6 h post-injection. Conclusions: 99mTc-CGG-ZHER2:342 demonstrated good capacity for visualization of HER2 expression in malignant tumours. The CGG chelating sequence, containing only natural amino acids, can also be used for site-specific labelling of recombinant multimeric Affibody molecules, which can not be produced in a reasonable yield by peptide synthesis. #

P288 Characterisation of hbp-1, a specific head and neck carcinoma binding peptide E. Knapp, S. Zitzmann, S. Krämer, C. Herold-Mende, W. Mier, U. Haberkorn; University of Heidelberg, Heidelberg, Germany. Although quality of life has been improved in head and neck (HN) tumor patients, a significant increase of live expectancy is still pending. Therefore, new targeted therapies which provide a specific accumulation of the drug in tumors are necessary. Via phage display a head and neck carcinoma binding peptide (HBP-1) was identified and its in vitro and in vivo features were investigated. The method of phage display was applied for identification of specific binding peptides. One phage library comprises 109 different displayed peptides. After 5 in vitro selection rounds with HNO 223 tumor cells and previous negative selection with immortalized oral mucosa keratinocytes (HPV-16-GM) tumor binding phages were enriched. The peptides expressed on the surfaces of the isolated phages were identified by sequencing their DNA. Subsequently, one of these peptides was produced by Fmoc solid phase synthesis. Human HNO 97 cells and the peptide labeled with I-125 were used for in vitro binding studies, kinetics and determination of the IC50-value. Peptide stability was ascertained in human serum at 37°C. In vivo biodistribution of I-131 labeled peptide was determined using HNO 97 tumor bearing nude mice. A specific binding peptide was identified by applying phage display screening on HN tumor cells. This peptide, HBP-1, was found to be enriched in 13 out of 21 sequenced phages. Labeled with I-125, HBP-1 showed a binding of up to 14% of the applied dose per 1 million cells for 5 different HN tumor cell lines. The binding is considered to be specific as it is nearly competed with unlabeled HBP-1. In addition an average binding of 8% to MCF-7 mamma carcinoma cells was asserted. Further in vitro experiments with HBP-1 showed an IC50-value of 66 nM and a T1/2 = 55 min in human serum. In the organ distribution study of HN tumor bearing nude mice, an accumulation of the I-131 labeled peptide could be observed in the tumor up to 45 min after application. The determined features of the HN tumor specific peptide HBP-1, represent a promising base for further research. Future investigations of HBP-1 binding to tumor tissue slices could reveal universal application for HN tumors and their metastasis in respect of tumor therapy and tumor imaging.

P289 Effective and equivalent doses from low-dose CT in patients examined by SPECT/CT D. Kotalova1, A. Kvasilova2, H. Krizova2, L. Judas1, M. Samal2; 1General Teaching Hospital, Prague, Czech Republic, 2Charles University Prague, Prague, Czech Republic. Low-dose CT (140 keV, 2.5 mA) produces significantly lower intensity of the beam than x-ray diagnostic CT. However, growing interest in hybrid SPECT/CT and the number of examinations require monitoring of additional dose in order to keep radiation burden on patients as low as possible. The aim of the study was to assess the radiation burden on patients from low-dose CT in SPECT/CT examinations. Method: Effective (E) and equivalent doses in several types of SPECT/CT examinations performed on scintillation camera Infinia/Hawkeye [GE Healthcare] were calculated using ImPACT CT Patient Dosimetry Calculator [www.impactscan.org]. On input, the program requires the computed tomography dose index in the air (CTDI) measured in the CT stability test, x-ray tube voltage and current, slice thickness, patient's gender, and the extent of transmission scan marked on a schematic picture of human body (part of the calculator program). Using the program, E and equivalent doses for individual organs were estimated in patients with SPECT examination of the heart (n=5), parathyroid glands (n=5), bones (n=6), and tumours (n=19). The doses from low-dose CT have been compared with those from radionuclides used in SPECT. Administered activity in MBq was transformed to the dose using conversion tables [ICRP] for respective examinations. Results: E from low-dose CT was 0.59±0.09 (0.50-0.70) mSv in gated myocardial perfusion SPECT (that is <10% of E from 1000 MBq of 99mTc-MIBI), 0.25±0.05 (0.20-0.33) mSv in SPECT of parathyroid glands (that is <4% of E from 700 MBq of 99mTc-MIBI), and 0.66±0.36 (0.25-1.30) mSv in bone SPECT (that is <20% of E from 700 MBq of 99mTc-MDP). In oncological examinations using 111In-octreoscan and 123I-MIBG, E was 1.15±0.41 (0.45-2.00) mSv that represents <50% of E from 200 MBq of 123I and <20% of E from 180 MBq of 111-indium. In SPECT of the heart, the equivalent dose to the lungs was 0.22 mSv. In SPECT of parathyroid glands, the equivalent dose to the thyroid was 0.17-0.18 mSv. In oncological SPECT, in case of maximum extent of scanning (48 slices from the head to pelvis), the equivalent dose was 0.37 mSv to the gonads, 0.32 mSv to the lungs, 0.30 mSv to the stomach, and 0.20 mSv to the red bone marrow. Conclusion: Radiation burden from low-dose CT did not exceed 50% of that from SPECT alone and in most examinations was lower than 20%.

P290 Methods of radiation protection of workers used at departments of nuclear medicine in the Czech Republic results of questionnaire survey II J. Ptáþek1, V. Hušák2, K. Petrová3, Z. Pašková3, I. PĜidal1; 1University Hospital, Dept. of Medical Physics and Radiation Protection, Olomouc, Czech Republic, 2University Hospital, Dept. of Nuclear Medicine, Olomouc, Czech Republic, 3State Office for Nuclear Safety, Prague, Czech Republic. Aim. To give a review of a state of occupational radiation protection at 45 departments of nuclear medicine in the Czech Republic in 2003 focused on the use of radiation protection aids and facilities and an estimate of their effectiveness. Method. Departments were sent a questionnaire

P291 Individual Dosimetry in a PET Unit M. T. Rézio, M. R. Vieira; IPOLFG, E.P.E., Lisboa, Portugal. Aim The aim of this study is to demonstrate that all the people working in the PET Unit are in good safety and radiation protection conditions against ionizing radiation. Method The doses (fingers and hands) of the personnel are investigated using thermoluminous material. One dosimeter is around the wrist and the other is used as a ring in the right hand. All the professionals who work in this unit are monitored with the ring. The physicians and the technicians with the two types of dosimeters. The physicist only with the ring dosimeter. The measurements are made once a month. Results The absorbed dose values in the hands and fingers, are between 0,2 mSv/year and 2,9 mSv/year for hands and between 0,09 mSv/year and 5,5 mSv/year for fingers, for the physicians, technicians and the physicist. Conclusions The recommended dose limits for effective and equivalent doses for hands and feet, for occupational exposure are: 500 mSv/year to the hands and feet and 500 mSv/year to the skin. The effective dose (H) to an individual is found by calculating a weighted average of the equivalent dose to different body tissues, with the weighting factors (W) designed to reflect the different radiosensitivities of the tissues:H = ™i Ei Wi The equivalent dose (HT) is a measure of the radiation dose to tissue where an attempt has been made to allow for the different relative biological effect of different types of ionizing radiation. Equivalent dose (E) is calculated by multiplying the absorbed dose (D) with the evaluation factor. The radiation weighting factor (wR) should be used as the evaluation factor. It is calculated by multiplying the quality factor Q and the modified factor N. The equivalent dose is thus calculated by the equation: HT,R = WR DT,R as where DT,R is the averaged absorbed dose in the tissue or organ T as a result of radiation R. We evaluate the results of the last 3 years (2003, 2004 and 2005) in terms of equivalent doses. Those results are far below the legal established limits. We can conclude that the work inside the PET Unit in good conditions of safety and protection against ionizing radiation.

P292 Radiation exposure of nuclear medicine workers in the Czech Republic in 2003 and its relation to various factors - results of questionnaire survey I V. Hušák1, J. Ptáþek2, K. Petrová3, Z. Pašková3, M. Mysliveþek1; 1University Hospital, Dept. of Nuclear Medicine, Olomouc, Czech Republic, 2 University Hospital, Dept. of Medical Physics and Radiation Protection, Olomouc, Czech Republic, 3State Office for Nuclear Safety, Prague, Czech Republic. Aim. To give a review of radiation exposure of 826 workers at 45 departments performing nuclear medicine procedures in vivo in 2003 and to present results of the study of some factors which can influence it. Method. Data from the SONS Central Registration System of occupational radiation exposure and the results of questionnaire were used. The questionnaire sent to all departments asked an additional information as to division of workers into professional groups, total activity of radiopharmaceuticals handled in 2003, number of examinations in vivo, staff rotation and others. Results. The mean personal annual effective dose E calculated on the basis of equivalent dose measured by film dosimeters was found to be 1.12 mSv. In groups the mean E were: physicians 0.98 mSv, staff preparing radiopharmaceuticals 1.2 mSv, ambulatory staff 1.44 mSv, in vitro staff 0.35 mSv, ward nurses 0.83 mSv, physicists 0.51 mSv and assistant staff 0.62 mSv. Mean annual hand dose measured by ring thermoluminiscent dosimeters was evaluated in three groups: radiopharmacy staff 25.4 mSv, physicians 4.73 mSv and ambulatory staff 6.43 mSv. Unfortunately, practically no correlation was found between personal effective dose, total activity of radiopharmaceuticals, number of examinations in vivo etc. Several causes of this finding will be discussed, obviously the most important factor affecting it being the frequent rotation of workers doing highly exposed procedures. Conclusion. Relatively low occupational radiation exposure which is far below radiation limits and somewhat lower than in other countries indicates the appropriate use of radiation protection methods including the extensive employment of available protective tools. Ways are investigated how to decrease large differences in the mean personal effective dose E varying by a factor as large as 8 among departments.

P293 Cat brain perfusion with a multi-pinhole SPECT imaging system. A. Dobbeleir1, K. Audenaert2, K. Peremans1; 1Department of Medical Imaging, Faculty of Veterinary Medicine, Ghent, Belgium, 2Department of Psychiatry and Medical Psychology, University, Ghent, Belgium.

are used for mouse and rat studies. We tested the system on the brain of a middle-sized animal like the cat.Methods: Pinholes with 6 apertures of 2.5 mm inner diameter each designed for rat studies (Bioscan Inc.) were mounted on a Trionix triple-head gamma camera. A Jaszczak phantom with hot rods ranging from 2.0 mm to 2.5 mm was scanned at varying detector radius from 180 mm to 220 mm. Cat brains were scanned at a radius of 199 mm. This radius is about 30 mm larger than a typical rat scan. Images are reconstructed using a dedicated OSEM algorithm (Scivis GmbH).Results: The 2.0 mm rods of the phantom are clearly separated at a radius of 180 mm. The resolution loss was about 0.1 mm per 10 mm radius increase. The resolution of the cat brain scan can be estimated at 2.2 mm. The quality of the cat brain scan is at least equal to the perfusion SPECT of humans using fanbeam collimators. The different cortical areas can be discriminated and semi-quantification of the regional activity is possible.Conclusions: This system allows diagnostic brain perfusion imaging of the cat brain. This small animal SPECT system can be used to evaluate the cat brain for research purposes.

P294 Pinhole scintigraphy using 99mTc tetrofosmin in mice: timing of VEGF Expression for the formation of Stable and Mature Blood Vessels . S. Tafuro1, F. Dore2, S. Zacchigna1, C. Di Russo2, M. de Denaro3, M. Giacca1; 1Molecular Medicine, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy, Trieste, Italy, 2 Department of Nuclear Medicine Hospital Maggiore-Trieste , Italy, Trieste, Italy, 3Department of Medical Physics Hospital of Trieste , Trieste,Italy., Trieste, Italy. Aim Aim of this study was to determine the functional capability of the newly formed vessels and to assess the kinetics of the angiogenic response by determining the optimal duration of the VEGF stimulus required to promote functional vessel formation in mice using Pinhole scintigraphy with 99mTc tetrofosmin. Methods and matherials To assess the kinetics of the angiogenic response and to ascertain the optimal duration of the VEGF stimulus required to promote functional vessel formation, we have constructed novel AAV vectors in which the VEGF165 gene expression is regulated by an inducible Tet-On system . The vectors were delivered to the tibialis anterior muscles in mice. Expression of the VEGF mRNA in vivo was stimulated by administration of doxycycline in the animals drinking water. In order to determine the functional capability of the newly formed vessels, we performed static scintigraphy by using a gamma camera equipped with pinhole collimator (Siemens Ecam), after 30 days of VEGF expression and after withdrawing the doxycycline for 15 days. At both time points functional images of the mice legs were acquired by injection of 3.7mBq of 99mTc Tetrofosmin in basal condition and 37MBq after 10minutes of hind-limb muscle contraction, to resemble physiological exercise. Moreover we performed confocal microscopy analysis by injection of fluorescent lectins. Results Qualitative and semiquantitative analysis of activity distribution of 99mTc Tetrofosmin showed after muscle contraction a worsening of muscle perfusion in the treated leg after 30 days of VEGF stimulus. After switching off VEGF expression, the perfusion in the treated leg increased significantly after exercise. The injection of fluorescent lectins followed by confocal microscopy analysis confirmed remarkably increased leakiness after one month of continuous VEGF expression, and revealed the formation of large cloud-like arteries surrounding the skeletal muscle fibers. Following the cessation of the VEGF stimulus, the number of vessels remained stable, while normal structure and permeability was restored. Conclusion Our results clearly indicate that functional blood vessel formation requires appropriate duration of the VEGF stimulus, which should be longer that 30 days, but not indefinite. Pinhole scintigraphy 99mTc tetrofosmin seems to be an appropriate tool to demonstrate the functional proper timing of VEGF expression. Moreover scintigraphy analysis allows to investigate physiology variation during prospective research.

P295 Determining viability of demineralised bone matrix and autogenous bone grafts in early stages by three phase bone scintigraphy G. Koca1, N. Sungur2, M. Korkmaz1, Y. Kankaya2, K. Demirel1, M. Oruç2, S. Türkölmez1, E. Özdemir1; 1Department of Nuclear Medicine, Ankara Training and Research Hospital, Ankara, Turkey, 2Department of Plastic and Reconstructive Surgery, Ankara Training and Research Hospital, Ankara, Turkey. Aim: Demineralized Bone Matrix (DBM) is a product, which has been developed to improve incorporation and formation of new bones. Here, in this study, we aimed to identify whether autogenous bone graft or DBM is better for early bone formation.Materials and Methods: One squarecentimeter sized and 1 mm depth bone defects were made on parietal bones in 12 one year old rabbits (Oryctolagus Cuniculus L.). Autogenous bone grafts taken from right parietal were placed on contralateral defects. DBM was placed to right side defects and defects were surgically closed. Two weeks later, 3-Phase Bone Scintigraphies by using pinhole collimators were performed after iv injection of 20 mCi Tc99m-HDP under general anesthesia. Early blood flow, blood pool and late static images were evaluated visually and quantitatively.Results: Parietal regions were evaluated both visually and quantitatively. Blood flow and blood pool patterns were similar for all rabbits and relatively increased flow and hypermia were determined in right regions with DBM. When late static images were evaluated, increased osteoblastic radioactivity accumulation on DBM placed sides were more impressive. Quantitative analysis was applied on bilateral parietal and occipital Region of Interests (ROI). Left parietal ROI/right parietal ROI were found to be 0.81±0.12. Left parietal ROI/occipital ROI was 0.62±0.10 and right parietal ROI/occipital ROI was 76±0.10. Paired Samples Test determined a difference of 0.14 (min: 0.10, max: 0.18 at 95% confidence interval), (t=7.302 and p < 0.0001) between correlations for right parietal ROI/occipital ROI and left parietal ROI/right parietal rates.Conclusions: DBM, which actively induces bone development was found to be more effective than autogenous grafts for early bone formation. However, more research on this subject still needed to be carried out in future.

Purpose: HiSPECT is a small animal SPECT system. The system consists of pinhole apertures fixed on a multi-detector gamma camera. Normally this system and other micro-SPECT systems

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Poster Presentation

asking a detailed information as to the use of radiopharmaceuticals and radiation protection equipment. All 45 completed questionnaires and answers to supplementary enquires were analyzed. Results. Replies ranged over the following topics: administered radiopharmaceuticals for diagnostics and therapy and their activities, preparation, storage and dispensing of radiopharmaceuticals, types of dispensing cabinets, location of scintillation cameras and lead glass observation windows, shielding of a patient bed in the imaging room, shielded waste containers, rotation of staff members and others. Concerning the particular items of protection equipment (tongs, lead containers, vial and syringe shields, syringe carriers, moveable lead shields, waste shielded containers, eye protection, lead aprons etc.) this information was evaluated: the extent to which protective tools were used, their purpose and origin (commercial or home-made), approximate design etc. The effectiveness of syringe shields, lead aprons and movable lead glass screens in reducing exposure of workers were assessed in detail. Conclusion. Results of the extensive survey confirm a fairly good quality of radiation protection in nuclear medicine in our country. The acquaintance of departments with some shortcomings found is believed to stimulate nuclear medicine workers to continue improving local radiation protection in compliance with legislative requirements.

P296 A single sample 51Cr-EDTA clearance for the early detection of renal dysfunction in cats. E. Vandermeulen1, I. van Hoek1, C. De Sadeleer2, A. Piepsz3, H. R. Ham2, T. Bosmans1, A. Dobbeleir2, S. Daminet1, K. Peremans1; 1Faculty of Veterinary Medicine, Gent, Belgium, 2UZ Gent, Gent, Belgium, 3Saint-Pierre Hospital, Brussels, Belgium. Aim: Chronic renal failure is frequently seen in middle-aged and elderly cats. An early diagnosis of renal dysfunction is possible by measuring the glomerular filtration rate (GFR). This study investigates the feasibility of a single-blood sample (SBS) method with Chromium 51 Ethylene Diaminic Tetraacetic acid (51Cr-EDTA) for determining GFR. Materials and methods: This study included 46 cats, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism (blood analysis and pertechnetate scan); 19 were healthy (blood analysis and clinical examination). After intravenous injection of 51Cr-EDTA (average dose: 4.25 MBq ), blood was drawn at 5, 15, 30, 60, 120, 180 and 240 minutes. Reference GFR was calculated in ml/min and ml/min/kg bodyweight, using a biexponential model. The best SBS clearance was then determined by comparing systematically each plasma concentration to the reference multisample clearance. Results: Global GFR using a biexponential model was calculated in ml/min and ml/min/kg bodyweight, based on an biexponential model. The average plasma clearance of 51Cr-EDTA for all cats was 14.9 ml/min or 3.7 ml/min/kg. The clearance in hyperthyroid cats was on average 16.4 ml/min or 4.3 ml/min/kg; for the normal cats these values were 10.3 ml/min or 2.4 ml/min/kg. Processing of the data showed a high grade of correlation between plasma clearance calculated from a SBS, and the plasma clearance calculated from the series of 7 blood samples based on a biexponential fitting. The optimal time for taking this SBS was one hour after the injection of 51Cr-EDTA (R² = 0.9714). Conclusion: This study showed that it is possible to use 51Cr-EDTA plasma clearance to assess the global GFR in cats, which is useful in case of suspicion of renal dysfunction. A SBS taken 1 hour after intravenous injection of 51Cr-EDTA is sufficient and reliable to determine GFR in cats.

P297 Optimization of intraoperative identification of the sentinel lymph node and its molecular staging in melanoma patients. G. Manca1, A. Romanini2, D. Pellegrino1, G. Boni1, D. Volterrani1, D. Genovesi1, V. Mattone1, L. Bruselli1, B. Dell'Anno1, I. Raugei1, R. Murr2, S. Sarti2, C. Orlandini2, V. Zucchi1, G. Mariani1; 1Regional Center of Nuclear Medicine, Pisa, Italy, 2Division of Medical Oncology, Pisa, Italy. Aim The aim of this study was to reduce false negative rate in the identification of metastatic disease in melanoma sentinel lymph nodes (SLNs) by adopting a 20% threshold for intraoperative counting and by employing RT-PCR in addition to conventional pathology (PATH) for detecting micrometastases. Materials & methods. Patients with primary stage I-II cutaneous melanoma underwent radiocolloid lymphatic mapping and radioguided SLN biopsy. To determine how often a less radioactive sentinel node is positive for tumor when the most radioactive lymph node is not, we considered as SLNs both those with the highest counts and any additional radioactive lymph nodes counting 20% or more of the hottest node. SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). Results. SLNs were identified in 99.2% of patients (124/125 patients), harvesting a total of 197 SLNs. 68/197 SLNs (34.5%) had evidence of metastatic disease by PATH and/or RT-PCR analysis. Nodal metastases were detected in 41 nodal basins in these 124 patients. RT-PCR identified 17/41 (41%) positive nodal basins which would have been considered negative if analysed solely by PATH. 15 positive nodal basins from 15 patients were identified in which more than one sentinel node was identified. In 5 of these 15 nodal basins (33%), one less radioactive lymph node was positive for tumor when the most radioactive SLN was negative. By harvesting all nodes >20% of the hottest node and assessing the SLNs by RTPCR we observed the lowest false negative rate (0%) in the identification of metastatic nodal basin (as assessed by extended follow-up). No statistically significant difference was detected among radioactive counts between positive and negative SLNs. Conclusions. We suggest both the threshold of • 20% and RT-PCR analysis be applyied for optimal detection of nodal metastases in melanoma patients.

P298 The use of hand-held gamma probe in the detection of accessory spleens during laparoscopic splenectomy Y. Sanli1, I. Adalet1, U. Barbaros2, C. Turkmen1, M. Tamam1, A. Dinccag2, S. Mercan2, R. Kucukkaya3, S. Cantez1; 1Istanbul University, Istanbul Faculty of Medicine, Department of Nuclear Medicine, Istanbul, Turkey, 2 Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery, Istanbul, Turkey, 3Istanbul University, Istanbul Faculty of Medicine, Department of Heamatology, Istanbul, Turkey. Aim: Preoperative determination of the accessory spleen is still a major problem in the failure of either laparoscopic or conventional surgical exploration. The aim of the present study is to evaluate the usefulness and efficacy of gamma probe (GP) in identification of accessory spleen, performed in the laparoscopic exploration.Materials and Methods: Seventeen cases with laparoscopic splenectomy due to benign hematological disorders were evaluated. Preoperatively, all patients had ultrasonography, computerized tomography (CT) and heat-denaturated Tc-99m red blood cell (DRBC) scintigraphy for evaluating the size of the spleen and to search for the existence of the accessory spleen. The procedure was initiated with the injection of 50 mg of stannous pyrophosphate to all patients intravenously, on the morning of surgery. Fifteen minutes of the initial injection, 10 ml venous blood sample was collected in a heparinized syringe and transferred to sterile vial. Twenty mCi Tc-99m was added to the blood and the mixture was heated in a water bath at 49.5±0.5°C for 30 minutes. After splenectomy, DRBCs were reinjected to the patient in the operating room. Ten minutes after the injection, GP counts were obtained from left liver lobe, pancreatic tail and corpus, left kidney, omentum majus, gastric and

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abdominal wall with GP after introducing it through the port site of splenic removal. All patients had the postoperative control scans one month after the surgery.Results: In two of 17 cases, accessory splenic tissue was detected with GP confirming the preoperative diagnosis with CT. One of these patients had 3 accesorry spleens, however preoperative CT of this patient demonstrated two of them. With the aid of the GP, the third one was found to be located in the retroperitoneum. False positively, in two patients with preoperative CT determining accessory spleens, laparoscopic exploration and GP counts could not identify any accessory splenic tissue. Patients with accessory spleen were found to have the highest count on their accessory spleens with GP (mean count: 61200 cnt/10 second). In these patients, the mean counts of the left liver lobe was 60686 with GP. The mean counts of the above-mentioned organs were lower than left liver lobe. Post-operative control scans revealed no accessory spleen left behind in the abdomen.Conclusions: Preoperative imaging may misdiagnose the accessory spleen because of their insufficient sensitivity of examination. And GP technique may be an adjuvant method to laparoscopic exploration for locating the accessory splenic tissue in benign hematological disorders.

P299 Comparison between radioguided occult lesion localisation and needle-guided resection in breast cancer P. Paredes1, S. Vidal-Sicart1, N. Roé1, M. Velasco1, G. Santamaria1, G. Zanon1, X. Caparrós1, B. Intriago2, P. L. Fernández1, J. Duch1, J. Ortín1, F. Pons1; 1Hospital Clínic, Barcelona, Spain, 2Hospital Joan XXIII, Tarragona, Spain. Aim. To compare radioguided occult lesion localisation (ROLL) with needle-guide (NG) in nonpalpable breast lesions. Material and methods. The study included 40 patients, mean age 58 years, range 43-71, divided up in two groups: A) the lesion is removed using a NG and B) the lesion is removed by ROLL technique. Localization took place one day prior to surgery by intratumoural injection of 148 MBq of 99mTc-labelled nanocolloid in 0.2 ml, guided by ultrasonography imaging. Lymphoscintigraphy was performed 30 min and 120 min later to verify the absence of radiotracer spread and to localize sentinel lymph node (SLN). Lesion was removed using a NG (group A) or ROLL technique (Group B); afterwards, SLN biopsy was performed. Histopathological study was done to confirm lesion inclusion, clear margins and tissue volume. Results Lymphoscintigraphy. At least one SLN was detected in 38/40 patients (95%) and in 16/40 (40%) drainage to extra-axillary basins was seen. In 7 of these 16 cases lymphoscintigraphy detected SLNs out of the IMC. Surgery. Mammary lesion was removed in all cases. In group A (NG) the lesion was removed with healthy margins in 11/24 (46%). In the other 13 cases, an enlargement was only necessary in 7 cases (7/24: 29%). In group B (ROLL) the lesion was removed with healthy margins in 10/16 (63%), and an enlargement was required in 3/16 (19%). In one patient, the accumulation of activity on the surgical field involved an overresection, unnecessary by pathological criteria. This is why we consider it as a ROLL’s failure (4/16: 25%). Sentinel node. SLN could not be removed in 5/40 (13%), because of insufficient drainage in 2/5, benign lesions in 2/5, and in one case lymphadenectomy was performed at the request of the patient. Pathology. Histopathologic findings showed malignancy in 34 cases, 2 fibroadenomas, 2 fibrotic lesions, 1 neoepiteliosis and 1 papillomatosis. At least one positive SLN was found in 7/35 (20%) cases, and in 6/7 SLN was the only positive node. Conclusions The use of ROLL in non-palpable breast lesions allows a safe resection with healthy margins. Its results concerning healthy margins and enlargement are better than those of needle-guide, therefore a radiological procedure can be omitted. The detection rate of SLN is similar to that of other series; however, intratumoural injection seems to increase extra-axillary drainage.

P300 Development of a safe and accurate method for determination of biodistribution of lanthanide-labelled compounds A. Koivistoinen, M. Huttunen, M. G. Bergman; Karyon Ltd, Helsinki, Finland. Aim. Most pre-clinical detection methods for drug analyses in vivo are based on use of radionuclides. Production, handling, use and detection of compounds labelled with radionuclides require special laboratories and equipment. The short half lives of most used radionuclides make their use unconvenient and excludes even short storage periods of compounds. Karyon Ltd has developed a sensitive, safe and reliable non-radioactive detection application of PerkinElmer Life Sciences´s DELFIA technology. Using stable DTPA-europium (Eu) labelled compounds, biodistribution and dose finding studies on tumour-bearing animals have been performed. Material and Methods. Two Karyon Targeting Units (KTUs), peptides specific for NSCLC and melanoma, were conjugated with iodoacetamido activated DTPA-[Eu] from PerkinElmer Life Sciences, Wallac Oy. Experimental tumors were produced by inoculation of A549 and NCIH520 NSCLC cells and C8161 human melanoma cells in athymic nude mice. KTU-DTPA-[Eu] was injected into the tail vein, and the mice were perfused after 20 min. The Eu content of tumour and tissue lysates was determined using a Wallac 1420 VICTOR3™ V reader (timeresolved fluorescence; DELFIA). The same samples were measured using inductively-coupled plasma mass spectrometry (ICP-MS). Optimal dose finding was performed by injecting increasing amounts of KTU-DTPA-[Eu] in melanoma mice; measurements as above. Results. DELFIA technology is reliable for detection of lanthanide-conjugated compounds from tissue lysates. Eleven tissues from mice carrying A549 and NCI-H520 tumours were analysed with DELFIA and ICP-MS. The biodistribution profile of the compound was identical for both methods. The dose finding of the melanoma targeting KTU showed a linear dose increase in the blood, non-linear increases in many organs, and plateau levels in the liver, spleen and lung, and an optimal dose of 45 ug/animal for tumour accumulation. Conclusion. The DELFIA technology was reliable and convenient for determination of biodistribution profiles and dose finding of lanthanide chelate-conjugated compounds in animals. The low variability of the signal and the high sensitivity of detection, in combination with the safe use and storage stability of the labelled compounds make the described application suitable for any laboratory, and an excellent alternative for radionuclides. The DELFIA technology thus provides a platform for in vivo analyses in the early stages of drug development.

Role of Tc 99m (V) DMSA scintigraphy in detection of local, residual or recurrent colorectal carcinoma. S. I. El-Haddad, A. E. El-Taweel, A. A. Kandeel, M. A. Abo-GABAL; NEMROCK, Cairo, Egypt. Introduction: Colorectal carcinoma (CRC) constitutes 3% of all cancers among Egyptian patients. Tc-99m (V) DMSA has several advantages over other tumor imaging radiotracers being cheap, readily available, easily prepared, with superior physical properties and not excreted in the intestine. Purpose: The aim of this study is to evaluate the role of Tc-99m (V) DMSA scintigraphy in the assessment of CRC. Patients and methods: The study included 2 groups, Group (A) included 50 patients (28 females, 22 males, mean age 51.4±11.9 years) with a known gross loco-regional CRC (22 rectal, 28 colonic); Group (B) included 36 patients (13 females, 23 males, mean age 49.5±11.7 years) underwent complete excision of the primary tumor with safety margin. All patients underwent serum CEA and CA19.9 levels, abdomino-pelvic CT as well as Tc-99m (V) DMSA whole body scan with early (post 2 hours) and late (post 4 hours) static spot views for abdomen and pelvis as well as early and late quantitative lesion/non-lesion (L/NL) ratios. Results: All 50 patients in group (A) showed positive Tc 99m (V) DMSA uptake while CT was conclusive in 47/50. In group (B) 33/36 patients were negative on scanning (the 3 false positive cases were diagnosed as non-specific colitis by colonoscopic biopsy). The following table showed the Validity parameters of Tc 99m (V) DMSA scan and CT in detection of residual and/or recurrent colorectal carcinoma.

V. Y. Sukhov1, M. D. Sterpu, None1, L. A. Tyutin, None2; 1Military Medical Academy, St.Petersburg, Russian Federation, 2Central research Institute of roentgenology & radiology, St.Petersburg, Russian Federation. Purpose: To study the possibilities of indirect orchifuniculoscintigraphy (OFSG) for clarifying routs of lymphatic cancer spread aiming radiation therapy optimitization.Materials and Methods: Data of 31 patient examination with testis tumors at age of 17 to 47 y.o.by use OFSG were summurized. OFSG was performed by injection of 37-74 MBc 99mTc-colloid beneeth tunica albuginea of the tumor-affected testis prior to surgical resection or in stump of spermatic cord in patients with orchiectomy. Examinations were conducted 45-60 minutes p.i. on gamma-camera "E.CAM Var" (Siemens). Non-affected lymph nodes were seen on scintigrams as foci of intense accumulation of radiopharmaceutical. In case of decreased or absent uptake in lymph nodes projections with simultaneous imaging of the lymphatic vessels we drew a conclusion regarding potential lymphatic cancer spread. In such cases extra examinations were performed.Results: Data of OFSG point the direction of lymph outflow from the tumor-affected testis or the stump of the spermatic cord. Lymphatics were visualized with the normal and changed lymph outflow. The results of OFSG enabled determination of exactly the radiation area for preventive radiation therapy.Conclusions: 99 mTc-colloid lymph outflow studies help to early identification of cancer lymphatic spread thus assisting in irradiation fields planning.

P24 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Neurology/Psychiatry: Miscellaneous

Tc 99m (V) DMSA scan

CT

P304

Sensitivity

100%

94%

Clinical-tomographic correlation with patients with degenerative parkinsonism

Specificity

92%

94%

+ve predictive value

94%

96%

-ve predictive value

100%

92%

Accuracy

97%

94%

Overall L/NL ratios were 2±0.5 and 2.6±0.9 in early and late images respectively. Significant positive correlation (p<0.05) was found between degree of Tc-99m (V) DMSA uptake and pathologic grade as well as Dukes' stage of CRC. No significant correlation could be detected between serum CEA and CA19.9 levels and the degree of Tc-99m (V) DMSA uptake. Conclusions: Tc-99m (V) DMSA; although non-specific; but it may be a useful diagnostic tool in addition to other radiological investigations for localization of metabolically active local gross, residual and recurrent colorectal carcinoma lesions as well as in routine follow up of patients. Key words: Colorectal cancer, Tc-99m (V) DMSA scintigraphy.

P302 Prognostic factors in skin malignant melanoma submitted to lymphoscintigraphy and sentinel node biopsy C. De Gaudio1, V. Ciliberti1, R. Cecchi2, L. Buralli3, R. Tarchi1; 1Nuclear Medicine, Hospital Lucca, Italy, 2Dermatology Department, Hospital Pistoia, Italy, 3Surgery Department, Hospital Pistoia, Italy. Aims and background: Lymphatic mapping (LM) and sentinel lymph node biopsy (SLNB) provide important prognostic data in patients with early-stage melanoma and are crucial in guiding management of this tumour. The aim of the present study is to report our experience with LM and SLNB procedure in a group of patients with primary cutaneous melanoma. Patients and methods: 136 patients with stage I-II AJCC primary cutaneous melanomas underwent LM/SLNB from December 1999 up to December 2005, (75 m, 61 f; 27-87 yrs) affected by intermediate thickness malignant melanoma without clinical signs of systemic spreading (N0M0) were submitted to SN scintigraphy. 20-30 MBq, in 0,6 ml, of Nanocoll-Tc99m was injected intradermally 6 hours before surgery, around primary lesion. A dynamic scan and planar scintigrams were performed. After matching with an external radioactive marker, the skin projection of the first node was marked by ink. Preoperative intradermal, perilesional injection of vital dye was performed (Patent Bleu, 1 cc, 30 minutes before surgery). The SLN dissection guided by a hand-held gamma probe was performed through a 3-4 cm skin incision, in local anaesthesia. After removal, SLNs were submitted to serial sectioning and permanent preparations for histological and immunohistochemical examination. Complete Lymph Node Dissection (CLND) was performed only in patients with tumour-positive SLNs.Results: SLNs were identified and removed in all patients (detection rate of 100%), and metastases were found in 20 cases (14.7%). The incidence of metastasis in SLN was 1.8%, 15.8%, 28.6%, and 41.2% for melanomas 4.0 mm in thickness respectively. The incidence of metastasis related to sex was 9.8% in females and 18.7% in males, while respect of presence of ulceration of primary lesion, the inceidence of positive node resulted 7.7% in not-ulcerated lesion and 29.6% in ulcerated one. CLND was performed in 17 of 20 patients with positive SLN and metastases in non-SLNs were detected in only 3 cases (15.0%). Recurrences were more frequently observed in patients with positive SLN than in those with negative SLN (50.0% vs 4.0% at a median follow-up of 36 months, p<0.001). The false-negative rate was 1.5%.Conclusions: Our study confirms that LM/SLNB allow accurate staging and yield relevant prognostic information in patients with early-stage melanomas.

P303 Sentinel lymph nodes detection in patients with testis tumors using 99mTc-colloid orchifuniculoscintigraphy

123I-Ioflupane

in

C. Isla Gallego, C. Perera, R. Malo de Molina, M. A. Santana, J. Herrera, J. A. Arbelo, F. Armas, J. Uña, M. J. Hernández Briz; Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain. Objective: 1. To describe our experience with the correlation between the striatal imaging via 123I-Ioflupane SPECT of patients with parkinsonism and their different stages of evolution. 2. To assess the asymmetry index value of SPECT findings and their correlation with parkinsonism’s stages of evolution. Methods and materials: We studied 80 patients (47 men) with an average age of 61.41 (30-82); 10 of them displayed symptoms of essential tremor (ET) and the remaining 70 of parkinsonian syndrome: 48 with symptoms suggestive of parkinson’s disease (PD), 13 with parkinson’s plus (PP) and 9 with possibly secondary parkinsonism (SP). After SPECT, and given their evolution, they are currently diagnosed as follows: 12 cases of ET, 48 of PD, 13 of PP and 7 cases of SP. The patients suffering from PD were assessed according to the motor UPDRS scale and their condition was clinically classified as: mild (UDPRS-3 =10), moderate (11-25) or severe (>25). We undertook both a visual and semiquantitative analysis of the images, assessing transaxial cuts and establishing 4 degrees of affectation: I unilateral putaminal; II bilateral putaminal; III bilateral putamen and caudate; IV poor striatal definition. For the semiquantitative analysis, areas of interest were selected, establishing asymmetry (AI) and specific imaging (SII) indexes of caudate, putamen and bilateral striatum.Results: SPECT findings were pathological in 59 cases of parkinsonism (PD and PP) and normal in 2 (probably very initial stages), the average SII being: 1.96±0.51, 2.6±0.66 and 2.22±0.55 for putamen, caudate and striatum respectively. Out of the 46 cases of PD, 16 displayed a mild clinical affectation, 24 a moderate and 8 a severe affectation. SPECT findings reflected different degrees of affectation among them: Normal in 2 cases, I in 7, II in 23, III in 11 and IV in 5 cases, displaying good correlation with clinical severity. In the PP cases the correlation was less precise and it was established on the strength of clinical data (incapacity, atypical symptoms, etc). No correlation was studied among ET and SP patients. The AI among PD patients was 11.99 (10.06), 8.04 (5.86) and 2.39 (0.53) for putamen, caudate and striatum respectively; in cases of mild clinical affectation it was 14.16 (12.56) for putamen (a difference of no significance as regards other stages).Conclusions: 1. 123I-Ioflupane SPECT is useful in the monitoring of parkinsonism, displaying good clinical-tomographic correlation. 2. The asymmetry index showed limited usefulness in terms of identifying early stages of parkinsonism.

P305 A comparison of the clinical diagnosis and brain SPECT perfusion examination in cognitive disturbances R. Píchová1, A. Bartoš2, O. Lang2, H. Trojanova2, J. Kukal3; 1Univ. Hosp. Kralovske Vinohrady, Prague, Czech Republic, 2Charles Univ., 3rd School of Medicine, Prague, Czech Republic, 3Institute of Chemical Technology, Prague, Czech Republic. Introduction: Brain perfusion changes were detected in patients with cognitive disorders. Therefore we performed retrospective analysis of brain SPECT perfusion in patients with cognitive disorders evaluated in our department. Aim: 1) comparison of the clinical diagnosis with the brain perfusion SPECT examination; 2) assesment of the inter- and intraindividual variability of the results; 3) relation of patient laterality to entering SPECT perfusion pattern. Patients and methods: 68 patients (38 females and 30 men) were enrolled in the study -with an average age of 68 years (41-87 y); 33 with clinical diagnosis of Alzheimer’s disease, 13 with mild cognitive impairment and 22 with other cerebral diseases. The results were sorted into five groups according to the reassessment of their brain SPECT perfusion images: 1. vascular dementia (17 patients), 2. Alzheimer’s dementia (19), 3. mixed dementia (18), other diagnosis (11), normal (3).Results: 15/33 patients with clinicaly probable Alzheimer’s dementia have got typical SPECT images and 14/33 have got the result compatible with mixed dementia (altogether 87%). In 13 patients with mild cognitive impairment, all types of perfusion disorders were found. The interindividual agreement was found in 31 (89%) out of 35 randomly chosen examinations, intraindividual agreement in 75/91 (87%) findings. The right-sided dominance was established in 25 patients with Alzheimer’s dementia and mixed dementia. Of these, a brain perfusion pathology was described on the left side in 15, on the right side in 2 and bilateral involvement in

S287

Poster Presentation

P301

8 patients on the first examination.Conclusions: The majority of patients with Alzheimer’s dementia have got the first perfusion deficit in the dominant hemisphere. A satisfactory level of intra- and interindividual agreement of the SPECT descriptions was found. The heterogeneous patterns of brain perfusion correspond to a mixed population with mild cognitive impairment. For the evaluation of their importance, further study is essential. This study was supported by the research project MSMT 1M0002375201.

P306 Can F-18 FDG PET help in the diagnosis of bitemporal epilepsy? correlation with the invasive Gold standard ictal depth EEG and surgical outcome M. A. Antar, W. McIntyre; VAMC &SUNY, Northport, NY, United States. Aim: Presurgical evaluation of patients with intractable bitemporal epilepsy complex partial seizures (BTE) remains difficult. The objective is to evaluate the reliability of FDG PET scan in the lateralization of BTE versus the invasive Gold Standard Ictal Depth EEG and Surgical Outcome. Method: 25 patients (13 women and 12 men) with BTE were evaluated by MRI, interictal F-18 FDG, prolonged scalp EEG/video monitoring and depth EEG. 14 patients had brain surgery. The dose for PET was 5-10 mCi of F-18 FDG. Results: MRI was abnormal in 5 patients, of these only 3 showed lateralization (12%). Scalp prolonged EEG showed definite lateralization in 2 patients (8%). PET scan revealed lateralization (hypometabolism in one temporal lobe) in 17 patients. In these patients there was agreement in lateralization between PET and Ictal depth electrodes in 12 patients (71%) and discordance in 5 patients. In the remaining patients, there was bilateral temporal hypometabolism (non-lateralization) or equivocal PET scan. In this group, ictal depth electrodes findings agree with PET findings (non-lateralization) in 5 out of 8 patients. However, there was lateralization by ictal depth electrodes in 3 patients; two patients were shown to have a right temporal focus and underwent a right temporal lobectomy and the third patient showed a left temporal focus. Ten of 14 patients who underwent a lobectomy had a successful outcome. Conclusion: In patients with bilateral temporal epilepsy, MRI and scalp EEG prolonged monitoring showed lateralization in only a small percentage of patients. In contrast, there was overall concordance (for lateralizaton and non-lateralization) between FDG PET and depth EEG findings in 18/25 patients (72%). There was discordant lateralization in 5 patients and discordant non-lateralization in 2 patients. Hence, FDG PET has been helpful in the majority of these cases of bitemporal epilepsy and far better than MRI and prolonged scalp EEG monitoring.

P307 Fused interictal fdg-pet and mri guided surgery for the treatment of refractory epilepsy J. R. Garcia1, M. Simo1, A. Russi2, M. Soler1, G. Perez1, S. Lopez1, F. Lomeña1; 1CETIR GRUP MEDIC, Esplugues Llobregat, Spain, 2 Neurologia, Teknon, Spain. AIM: Fifteen percent of epileptic patients do not control seizures with medical treatment. These patients could benefit from elective surgery, thus being necessary to localize the epileptogenic focus presurgically.Materials and Methods: We studied 22 patients (17-46 y) with refractory epilepsy (medical treatment for 3-12 years). On the same day, MRI and Interictal FDG-PET studies were performed and both techniques were fused by software (MRico, Matlab). In 7 patients confirmation was obtained by invasive EEG monitoring and in 15 by surgery.Results: In 19 out of 22 (86%) patients, PET identified the epileptogenic site as a reduced FDG uptake Temporal (n:11), Frontal (n:4), Parietal (n:3), Occipital (n:1). In 3 out of 22 (14%) patients PET was normal, detecting seizure focus by invasive technique. Frontal (n:2), Temporal (n:1). In 15 out of 22 (68%) patients MRI and PET results were concordant, with. hippocampal sclerosis associated to FDG hypometabolism (n:7) In 7out of 22 (32%) patients there was a discordance/mismatch?? in both techniques In 6 studies PET identified seizure focus with normal MRI (Temporal 3, Frontal 1, Parietal 1) In 1 study MRI showed bilateral hippocampal sclerosis and PET allowed for the lateralization of the focus.Conclusions: In our group of patients with medical intractable epilepsy: 1. The most frequent finding was an FDG hypometabolism associated with hippocampal sclerosis. Fusion images of interictal FDG-PET and MRI allowed for elective surgery. Our clinicians designed a new strategy to avoid invasive EEG monitoring in these patients. 2. PET allowed for localizing seizure foci in patients with normal MRI.

P308 Cerebral perfusion changes in patients dysgenesis and pharmacoresistant epilepsy

with

cortical

R. Petrovic1, S. Divosevic1, Z. Jurasinovic1, D. Sporis2, M. Poropat1, D. Dodig1; 1Clinical Department of Nuclear Medicine and Radiation Protection, Clinical Hospital Centre Zagreb, Zagreb, Croatia, 2Clinic for Neurology, Clinical Hospital Centre Zagreb, Zagreb, Croatia. Aim: Cerebral cortical dysgenesis (CD) is a heterogeneous disorder of cortical development and organization with a variety of subtypes and comprises a significant proportion of children and adults whose epilepsy cannot be controlled with medications. The objective of this study was to investigate the clinical value of interictal SPECT in patients with medically refractory chronic epilepsy due to cerebral cortical dysgenesis.Methods: We selected 17 patients (2 men and 15 women with a median age of 27, range 17-37 years; median age at seizure onset 13.7, range 2 to 35 years) with pharmacoresistant epilepsy, identified by strict predefined criteria, with positive magnetic resonance imaging (MRI) and performed interictal SPECT and computed tomography (CT). SPECT scans were started 45 minutes after administration of 740 MBq of 99mTc-ECD, images were generated by IRIX triple head gamma camera, analyzed on Odyssey FX820 workstation semiquantitatively using region-of-interest based method, and normalized to the mean brain activity.Results: MRI was positive in all patients, revealing focal cortical dysplasia in 7 patients, focal macrogyria in 3 patients, focal polymicrogyria in 4, grey matter heterotopia in one patient, focal cortical microdysgenesis in one patient and agenesis of corpus callosum was present in one patient. Interictal SPECT scans demonstrated hypoperfusion defects in 76% patients (13 patients) showing excellent correlation with MRI scans (r=0,82). SPECT did not

S288

reveal hypoperfusion in 3 cases of focal polymicrogyria and in one case of focal cortical microdysgenesis. We didn’t find focal hyperperfusion in any of our patients. CT scans showed pathological findings in only 6 (35%) patients.Conclusions: Our current data are consistent with previous similar studies demonstrating changes in rCBF in majority of patients with medically refractory chronic epilepsy resulting from cerebral cortical dysgenesis and can provide useful additional information about cerebral perfusion, especially in patients with negative MR scans. MRI is method of choice for diagnosing structural brain changes in patients with CD while CT is ineffective and can be excluded from CD diagnostic protocols. Absence of hyperperfusion defects show that only ictal SPECT may be useful as a non-invasive presurgical method of investigation of patients with pharmacoresistant epilepsy and CD to define sites of epileptogenic foci, in order to generate a hypothesis that then may be tested with intracranial EEG recordings.

P309 Comparison of brain 18f-fdg pet/ct with mri imaging in epilepsy Y. Dang1, X. Zhang1, S. Chen2, S. Wang3, Q. Wang3, X. Xu4; 1Imaging Diagnostic Center of Nanfang Hospital, Southern Medical University, Guangzhou, China, 2Cancer Hospital Chinese Academy of Medical Sciences (CAMS), Beijing, China, 3PET/CT Center of Chang An Hospital, Xi’an, China, 4Department of Epileptology, Chang An Hospital, Xi’an, China. Aim: To investigate the diagnostic value of the brain 18F-FDG PET/CT combined with MRI imaging in epilepsy. Material and Methods: 203 epileptic patients (male 147,female 56 ) underwent PET/CT and MRI brain scanning with GE Discovery LS PET/CT and Philips 1.5T MRI. All images of PET/CT and MRI were retrospectively judged by two qualified doctors double-blindly. Comparative evaluation of PET and MRI were performed slice by slice. PET diagnostic criteria: Metabolism abnormality of the PET was based on FDG accumulation increase or decrease of 15% in two consecutive slices compared with the contralateral corresponding zone on the same patient. Anatomical structure abnormity of CT and MRI was estimated visually by doctors. Results: One, PET/CT and MRI double-blind judging: Abnormality rate of PET was 74.4% (147 patients with hypometabolism, 2 patients with hypermetabolism and 2 patients with both hypometabolism and hypermetabolism). Structure abnormality of CT and MRI was 26.1% and 33.5%, respectively. Two, Comparative analyzing PET/CT with MRI: (1).PET positive and CT negative in 100 patients and PET positive and MRI negative in 87 patients. After carefully reviewed negative images on CT and MRI based on positive image findings on PET we found that brain sulcus was wider on corresponding area than contralateral healthy site for CT 32 (32.0%) and for MRI 39 (44.8%). (2). PET negative and MRI positive in 3cases, all lesions was located in the deep region of the brain with diameter less than 1cm. (3).28 and 4 cases were diagnosed encephalomalacia and epiloia on both CT and MRI. calcified lesions on CT and MRI was 4 and 1, respectively. 5 cerebral ischemia/ anoxia, 3 brain atrophy and other 7 small lesions in the deep region of the brain were shown on MRI, which could not be found on CT. Conclusion: One. Multi-imaging techniques can increase diagnostic accuracy of the epilepsy, PET was more sensitive to find abnormality lesions, MRI was excellent in displaying structure abnormity and confirming character of the lesions, and CT have the advantage in localizing the sites and finding calcified lessons. Two. Comparative analyzing PET images with CT and MRI slice by slice suggested that there were some brain sulcus change already existed on negative CT and MRI based on PET metabolic abnormality change, which was resulted from brain tissue growth itself or early changes of encephalatrophy? It should be to do further research.

P310 Usefulness of SPECT/CT with a hybrid camera for brain metastases imaging by 99mTc-tetrofosmin L. Filippi, R. Santoni, C. Mani; R. Danieli, F. Padovano, R. Floris, O. Schillaci, Department of Diagnostic Imaging, University of Rome "Tor Vergata", Rome, Italy. Aim: To evaluate the usefulness of Tc-99m tetrofosmin (TF) scintigraphy with a hybrid (SPECT/CT) device for functional anatomical mapping (FAM) in brain metastases imaging, and to compare it with than conventional SPECT images.Materials and Methods: Thirteen patients (pts) with brain metastases (4 breast cancer, 2 melanoma, 1 laryngeal cancer, 6 lung cancer) were included. All pts underwent surgery and radiation therapy and were evaluated six months after the last radiation therapy session. Twenty minutes after TF injection (740 MBq i.v.), brain SPECT/CT was acquired. The acquisition of both anatomical and functional data by combined transmission (with CT) and emission (with SPECT) was performed during a single session in a interchangeable sequence. X-ray images were reconstructed on the nuclear medicine workstation, and CT data were integrated into nuclear medicine database. The imaging was considered true positive or true negative when it corresponded to the clinical course of the disease over a period of at least 12 months following SPECT and to the results of serial MRI.Results: SPECT was positive in 10 out of 13 pts and negative in three. All pts with TF uptake had clinical deterioration and disease persistence on MRI, while all pts with negative scans were free from disease according on follow-up. SPECT/CT had significant clinical impact in 6 out 10 pts (60%); in particular it precisely localized TF uptake in post-surgical defect in 4 cases, while in 2 cases SPECT/CT was able to detect tumor viable tissue located in the posterior fossa of the brain, a relatively small anatomical space with high physiological background.Conclusions: SPECT/CT with TF using a hybrid imaging device appears to be a reliable method for brain metastases imaging; in particular FAM seems to be of particular usefulness to more precisely characterize tumor viable tissue in areas of high physiological background.

P311 Relationship of chromogranine-a to neuronspecific enolase and 5-hydroxyindolacetic acid J. Uhrova, K. Mrazova, M. Kalousova, T. Zima; Institute of Clinical Chemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

P312 Fluorine-18-Fluorodeoxyglucose (FDG)- and Fluorine-18Fluoroethyl-L-tyrosine (FET) Positron Emission Tomography in braintumors. Initial results of a comparative study P. Mühllechner1, G. Stockhammer2, M. Gabriel1, D. Heute1, R. Moncayo1, C. Decristoforo1, I. Virgolini1, E. Donnemiller1; 1Department of Nuclear Medicine, Medical University Innsbruck, Austria, 2Department of Neurology, Medical University Innsbruck, Austria. Aim: Gliomas are the most common types of brain tumors known to accumulate the amino acid analogue O-(2-[18F]Fluoroethyl)-L-tyrosine (FET). FET-PET might be more accurate than MRI for the determination of tumor size of low grade gliomas. This study compared the accumulation of FET with that of FDG in biopsy-proven untreated as well as in histologically confirmed pretreated primary brain tumors (WHO II -III). PET results were also compared to MRI. Patients and Methods: Imaging studies were conducted in 13 patients (8 males, 5 females; mean age was 38±12 years). A retrospective analysis of data acquired 2002-2003 was carried out. Patients had had surgery, radiotherapy (R ) or chemotherapy (C ). PET imaging was done on an GE Advance PET scanner after injection of 370 MBq of 18F-FET or 185 MBq of 18F-FDG, respectively. The images were analysed by image fusion. Results: The tables show the individual results of all imaging modalities as well as the semi-quantitative evaluation using SUV.

Pt.

WHO

Tumor

no.

grade

Resection

1

II

2 3

R

C

MRI

MRI

Residual1

Signal

Recurrent2

Gd-TPA-

tumor

Enhancement

change FET

FDG

PET

PET

subtotal

-

-

yes1

SC

+

-

II

subtotal

-

-

yes1

SC

+

-

II

-

R

-

yes1,2

Gd-DTPA

+

-

4

II

-

-

-

-

SC

+

-

5

II

subtotal

R

-

yes1

SC

+

n.d.

6

II

subtotal

R

-

yes1

SC

-

-

7

II

subtotal

R

-

yes1

SC

+

n.d

8

II

total

-

-

yes2

Gd-DTPA

+

-

9

III

subtotal

R

-

yes1

SC

+

-

10

III

-

-

-

-

Gd-DTPA

+

+

11

III

-

-

-

-

SC

+

-

12

III

total

R

C

-

-

-

n.d.

13

II-IV

-

R

C

yes1, 2

Gd-DTPA

+

+

P313 Hunger and satiation in gastric pacemaker patients - a cerebral activation study: preliminary results O. S. Grosser1, C. Knippig2, S. Wolff3, J. Ricke1, P. Malfertheiner1, R. Steinke1; 1Department of Radiology and Nuclear Medicine, Magdeburg, Germany, 2Department of Gastroenterology, Magdeburg, Germany, 3 Department of Surgery, Magdeburg, Germany. Aim: Obesity is a disease increasing in prevalence with a high rate of different comorbitities. A new experimental operative therapy is the implantation of an gastric pacemaker. Gastric pacing seems to have influence on the sensation of hunger and satiation in obesity. For understanding the effect we tried to find cerebral activations correlating with stimulation pattern. Our aim was to evaluate a relationship between gastric pacing under fasting condition and cerebral activation in patients suffer from obesity.Materials and Methods: In total 7 patients (age: 44,0y+/-5,9 y, all woman) were included, with one year after gastric pacemaker implantation. All patients suffers from obesity (BMI: 42+/-4,7 kg/m2). The protocol consisted in the acquisition of full brain images, each reflecting the cellular regional cerebral perfusion (rCBF) during different activation paradigm (fasting state combined with peacemaker on/off). After arriving at a fasting state Single Photon Computer Tomography (SPECT) were acquired using Techetium-99m (99mTc)-labeled ethyl cysteinate dimer (ECD) and a Philips dual-head gamma camera with parallel collimation. SPECT images were reconstructed in axial planes according to AC-PC plane using an iterative algorithm (OS-EM) and Chang attenuation correction. Finally, images where realigned and stereotactical normalised to the MNI standard brain SPECT-Template of SPM2. Statistical analysis on brain images were conducted on a voxel-by-voxel basis using the SPM2 software package with an extent threshold of 40 voxel.Results: Fasting with activated gastric pacemaker results in a significant (p=0.01) increased rCBF. Compared to baseline SPECT-examination (fasting and gastric pacemaker deactivated) we identified an increase in cerebral perfusion in superior temporal lobule (l=left/r=right), precuneus(l/r), cingulum-post(l/r), olfactory (l/r), cingulum-anterior (l/r), superior motor area (l/r) and frontal-orbitofrontalsup (r).Conclusions: Allthough the small number of patients, our preliminary results suggest a correlation between different fasting states (with/without gastric pacing) and rCBF. In accordance with previously published reports, we conclude that under fasting gastric pacing shows elements of eating equivalent rCBF.

P314 Comparison of SUV of the pons and cerebellum in the presence of crossed cerebellar diaschisis and anatomical localization of pontine glucose metabolic activity with 18FFDG-PET/CT N. C. Nguyen1, M. H. Cooper2, W. El-Sadda1, D. Oliver3, M. M. Osman1; 1Division of Nuclear Medicine, St. Louis University, MO, United States, 2 School of Medicine, St. Louis Universtity, MO, United States, 3Cancer Center,, St. Louis University, MO, United States. Introduction: Neuronal pathways connecting both brain hemispheres with the pons (P) and the cerebellum (CR) (cortico-ponto-cerebellar-system) can be altered in the presence of supratentorial metabolic and structural changes which can be observed as crossed cerebellar diaschisis (CCD). We aimed to compare the metabolic activity in the P to that of CR in the presence of CCD and to characterize the pontine FDG uptake in normal volunteers using 18FFDG-PET/CT.Methods: 18F-FDG PET/CT scans were performed in 18 normal volunteers (NV) and 12 pre-selected patients with CCD, of those 9 had supratentorial malignancy/tumor and 3 had old cerebral infarction. CCD was present on the left in 9/12 cases and on the right in 3/12 cases. PET/CTwere retrospectively reviewed by a reader unaware of clinical information. SUVmean were obtained after a representative region of interest being drawn in bilateral halfes of the P and CR. The variablity of SUV between left and right side of the pons and cerebellum was evaluated using paired t-test.Results: In NV, the variability of SUV between left and right CR was not statistically significant (p = 0.202) compared to the more stable metabolic activity of the P (p = 0.826). In patients CCD, there was statistically significant difference between right and left CR (p ” 0.001). SUV of the P was not significantly changed in the presence of CCD (p = 0.369). With anatomical CT correlation the FDG distribution in the P appears in an unique pattern. The highest metabolic activity is concentrated in the posterior aspect of the P, in the pontine tegmentum. In this area numerous individual nuclei are found as well as neurons within the reticular formation. The metabolic activity appears less in both anterior and lateral aspects of the basilar P which corresponds to the superficial pontocerebellar and corticospinal fibers. The area of metabolic activity tapers off in the caudal P and continues further into the medulla oblongata. It is shaped like a cone with the tip being located in the posterior aspect of the medulla.Conclusions: In NV and in the presence of CCD the metabolic activity of the P is more stable compared to that of the CR, indicating that it may serve as a reliable internal reference for data normalization. The co-registered CT helps in identifying the pontine metabolic activity which demonstrates a unique pattern and shape determined by the density of nuclei and neurons relative to nerve fibers.

The semiquantitative evaluation of the studies:

P315 F-18 FET

SUV Grey Matter

SUV White Matter

SUV Tumor

Brain tumor WHO II

1.01 ± 0.12

1.22 ± 0.22

1.81 ± 0.29

Brain tumor WHO III

0.96 ± 0.12

1.15 ± 0.18

2.03 ± 0.35

Conclusions: F-18-FDG uptake of low-grade tumors is generally similar to that of normal WM, while the amino acid uptake has higher than normal GM and WM in the majority of low- and high grade tumors.

Orgasm in the female brain: a [15O]-H2O PET study. J. Georgiadis, R. Kuipers, A. Nieuwenburg, J. Pruim, R. Kortekaas; University Medical Center Groningen, Groningen, The Netherlands. Aim Female orgasm is an enigmatic and controversial part of human sexual behavior of which the underlying cerebral mechanisms are not yet identified. We aimed to advance neurosexuological knowledge by investigating orgasm-related cerebral perfusion changes. Material and Methods PET was used with [15O]-H2O as an index of regional cerebral blood flow (rCBF). Twelve subjects each received eight PET-scans (500 MBq per scan) when their clitoris was stimulated, when they imitated orgasm and when they attempted to achieve orgasm. Data acquisition was in multiple 10s-frames. Orgasms were achieved by clitoral stimulation only. The subject’s report and rectal pressure measurements determined whether orgasm had occurred. Imitation of orgasm served as a control task for the orgasmic motor output, because it involved

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Poster Presentation

Chromogranin (CgA) serves as tissue as well as serum marker of tumours originating form the neuroendocrine tissue and has highest levels in carcinoids. The aim of this study was to find out the relationship of CgA to NSE (neuron specific enolase) and 5-HIAA (5-hydroxyindolacetic acid) in patients with diagnosed carcinoid and with tumours of the gastrointestinal tract. In 73 subjects (26 men and 47 women, age 51 ± 17), following parameters were examined: CgA, NSE and 5-HIAA. ELISA was used for 5-HIAA determination, IRMA for CgA measurement and ECLIA for NSE detection. For statistical evaluation studied subjects were divided into 3 groups: group 1 - blood-donors (n=20), group 2 - patients with diagnosed carcinoid (n=38) and group 3 patients (n=15) with diagnosed tumours of the gastrointestinal tract. In group 1, physiological levels of examined markers were found (CgA<100 ng/ml). In group 2, CgA (12.2 - 847.0 ng/ml) correlated with 5-HIAA (r = 0.64, p< 0.001 ) and with NSE (r=0.67, p<0.001 ). In group 3 (24.6 1234.0 ng/ml), we found a significant negative correlation between CgA and NSE (r = - 0.27) and CgA level was not related to 5-HIAA concentration. Levels of all parameters (CgA, NSE and 5-HIAA) were increased in 20% of patients with diagnosed carcinoids and in 16% of patients with tumours of the gastrointestinal tract. Our study demonstrated that elevated CgA in patients with carcinoid is related to NSE and 5-HIAA. CgA can be elevated also in some patients with gastrointestinal tumours, however, it is not associated with NSE and 5-HIAA.

‘orgasm-like’ contractions. Of each scan the first minute of data was summed. Using Statistical Parametric Mapping (SPM), we compared reported orgasms and imitated orgasms with clitoral stimulation, a condition of heightened sexual arousal, but without orgasm. Differences in rCBF between activation and baseline scans were tested at a statistical threshold of P<0.05 (t >4.93), corrected for multiple comparisons. Results The primary finding was that female orgasm, as compared to clitoral stimulation, was mainly associated with profound decreased rCBF in the left lateral orbitofrontal cortex (OFC). The left anterior medial temporal gyrus was also deactivated. In the anterior part of the cerebellum rCBF was increased. ROI-analysis of all (de)activated clusters indicated that the OFC was the most orgasm-specific brain region. The control comparison, imitated orgasm versus clitoral stimulation, increased rCBF in the primary motor cortex and anterior cerebellum, whereas no decreased rCBF was observed. Conclusion Based on these results we conclude that decreased rCBF, particularly in the orbitofrontal cortex, is the main cerebral determinant of female orgasm. We propose that decreased rCBF in the OFC signifies low self-control during orgasm.

P316 Diagnostic value of the 111In-DTPA isotopic shuntogram: a retrospective study E. Vranken1, J. Ribeiro-Vaz2, C. Raftopoulos2, R. Lhommel1; 1Nuclear Medicine Department, Cliniques Universitaires Saint Luc, Brussels, Belgium, 2Neurosurgery Department, Cliniques Universitaires Saint Luc Université Catholique de Louvain, Brussels, Belgium. Aim: To assess retrospectively the diagnostic value of isotopic shuntography using 111In-DTPA in ventriculo-peritoneal or ventriculo-cardiac shunt malfunction. Methods and Material: Between December 2003 and February 2006, 26 shuntograms were performed in 22 patients (10 male, 12 female, ranged from 6 to 87 years). These patients were evaluated for symptoms supposed to be related to shunt malfunction. After injection of 1 mCi of 111 In-DTPA (in 1 ml) into the subcutaneous chamber of the shunt system (Delta valve, Medtronic, USA), a dynamic acquisition was performed during 2 minutes (matrix size of 64 X 64, 1 frame/s, medium energy collimator, peaks centred on 171 keV and 245 keV with a 20% energy window width), followed by early planar acquisitions (matrix size 128 x 128) upon the head (AP and lateral views), the chest and the abdomen (AP views). A normal shuntogram was defined as a complete visualisation of the shunt system, upstream and downstream of the shunt chamber, with a free diffusion of the tracer into the different cerebral ventricles and in the peritoneal cavity within the first 10 minutes post injection. In case of slow tracer progression or lack of early abdominal diffusion, late images were planned up to 6 hours p.i. Both the results of the surgical revision and the clinical follow-up were used as standard to assess our test performance.Results: Eleven of the 26 shuntograms were interpreted as a normal scan and were confirmed as true negative, based on the clinical follow-up in 10 cases and despite a surgical in one. All 14 patients with an abnormal shuntogram (n=15) underwent a shunt revision confirming a shunt dysfunction: proximal in 6 patients and distal in 8. Mean time between the shuntogram and the shunt revision was 21±22.9 d (ranging from 0 to 79 days). No false positive or false negative result was found. As such, the sensitivity, specificity, positive predictive value and negative predictive value of the 111InDTPA shuntogram was high (100%). Moreover, no adverse events were reported in relation to this well-tolerated and ambulatory procedure.Conclusions: Based on these preliminary results and in concordance with some previous reports, we concluded that the isotopic shuntography using 111In-DTPA is safe and of high diagnostic value in the management of patients with suspicion of shunt malfunction.

P317 Imaging research of functional site of midazolam in CNS in human J. Wang1, L. Wang2; 1Xijing Hospital,FMMU, Xi'an, Shaanxi, China, 2China Railway First Group Co.,Ltd.Xi'an Center Hospital,, Xi'an, Shaanxi, China. Aim: Using the application of positron emission tomography (PET) technology, examine the changes in regional cerebral glucose metabolism produced by midazolam anesthesia in volunteers, and investigate the key brain structures of effects of midazolam.Materials and Methods: Fourteen volunteers each underwent two PET scan: one scan assessed awake-baseline metabolism and the other scans assessed metabolism during midazolam anesthesia. Scans were obtained using the 18F-FDG thchnique with a SPECT with a hybrid CT and coincidence option.Results: Awake whole-brain glucose metabolic count averaged 1869.9±193.3 (means±SD), midazolam anesthesia reduced whole-brain glucose metabolic count 12% to 1631.8±174.4 (P<0.05) ; Regional cerebral glucose metabolic count also decreased throughout the brain especially thalamus, left prefrontal cortex and cingulated gyrus(P<0.01), respectively decreased33%,28% and 25%.Conclusions: Whole-brain and regional metabolism decreased significantly during midazolam anesthesia. Thalamus, left prefrontal cortex and cingulated gyrus were most sensitive to midazolam, and they are likely to be primary targets in midazolam anesthesia.

P318 Effects of playing a video game on regional cerebral flow S. Wang1, Y. Chou2, B. Yang1, S. Chen1, T. Su2; 1Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan, Taipei, Taiwan, Province of China, 2Department of Psychiatry, Taipei Veterans General Hospital, Taiwan, Taipei, Taiwan, Province of China. Objective: Video game playing is one of the most popular amusements in modern life, which involves stimuli, and requires various cognitive functions. Despite the great popularity of video games, there have been only a few studies examining the biological effects of video games on brain activity. Tc-99m ethyl cysteinate dimer (ECD) has high in vitro stability and rapid in vivo blood clearance. ECD is reliable for use in quantifying regional cerebral flow. In this study, we evaluate the effects of playing video game on regional cerebral flow using ECD brain SPECT study. Material and Methods: There were five healthy volunteers in this study (four males, mean age, 25.25±3.90y; one female, 22y). Subjects were not included in until they had been interviewed by psychiatric doctor. In the first examination, each subject would take a rest in quiet

S290

and dusky environment for twenty minutes before 99mTc ECD injection. And each subject would play the video game Dynasty Warriors 5® on Play Station 2® device for thirty minutes before 99mTc ECD injection in the second examination. SPECT imaging was performed at 30 minutes after injection of 740 MBq of 99mTc-ECD according to routine regional cerebral flow (rCBF) protocol in clinical. Two examinations were performed on each individual at least about 1 week apart. Images were then transformed into standard stereotactic space. All scans were statistically analyzed using statistical parametric mapping 2 (SPM 2) in cluster-level and statistical model of paired t-test was applied to compare the variation of rCBF distribution between first and second scans from each individual. The variations of rCBF distribution were significant if corrected p value was less than 0.05. Results: According to the result of paired t-test on SPM 2, there were significant changes on rCBF between two examinations of each individual. We found that the distribution of rCBF decreased in left inferior frontal gyrus, Brodmann area 47. Increasing area was in bilateral cerebellum and right lingual gyrus, Brodmann area 18 after each subject playing video game. Conclusion: Resting frontal, cerebellum, and occipital rCBF is significantly changed with the stimulation from playing video game. Key words: video game; 99mTc-ECD SPECT; statistical parameter mapping; rCBF distribution

P319 Affection of hypoglycemia to FDG uptake of the brain. H. Tanabe1, S. Jinnouchi2, M. Nakajo2, R. Tateno2, M. Nakajo1, Y. Nakabeppu1, M. Jinguji1; 1Department of Radiology, Kagoshima University, Kagoshima city, Japan, 2Atsuchi Memorial Clinic PET Center, Kagoshima city, Japan. Aim: It is well known that hyperglycemia decrease FDG uptake of the brain, but there are little reports how affects hypoglycemia to the uptake. We assessed the brain uptake in hypoglycemia among normal population involved FDG-PET for cancer screening and patients with cancer or suspicious malignancies.Materials and Methods: Twelve thousands seven hundreds and sixty six adults were studied with FDG-PET since June 2002 to December 2005 in our PET center. Whole body PET scan was started at one-hour post injection to collect transmission and emission data with a PET camera (AdvanceNXi, GE.). Serum blood glucose was tested just before the injection. The rate of hypo-, normal, and hyperglycemia were investigated. In hypoglycemia group, relationship between serum glucose level and standardized uptake value (SUV) of the brain was also evaluated.Results: According to the serum glucose level, they were separated four groups: 3.0% super-hyperglycemia (>150mg/dl); 9.2% semi-hyperglycemia (111~150mg/dl); 87.4% normal glucose level (70~110mg/dl) and 0.5% hypoglycemia (<70mg/dl). Hypoglycemia cases showed relative high FDG accumulation of the brain. There was a weak negative correlation between serum glucose level and SUV of the brain. Conclusion: Although the rate of hypoglycemia was only 0.5%, we should take the affection into account that hypoglycemia could increase cerebral FDG accumulation.

P320 Pre-synaptic acetylcholine system imaging [123I]-IBVM: Quantification in healthy subjects

using

O. Barret1, J. Mazere1, M. Guyot2, D. Guilloteau3, C. Prunier3, A. Lepognan3, M. Allard1; 1ERT-CNRS/Université Bordeaux 2 - CHU Bordeaux Service de Médecine Nucléaire, Bordeaux, France, 2CHU Bordeaux Service de Médecine Nucléaire, Bordeaux, France, 3CHRU Tours, Service de Médecine Nucléaire, Tours, France. Aim: Given the reports of cholinergic system deficiencies in several dementias, quantitative imaging of pre-synaptic cholinergic neurotransmission is crucial for both understanding the biology of these neurodegenerative diseases and the development of specific treatments. Here, we describe a quantitative kinetic study using SPECT with (-)-5-[123I]iodobenzovesamicol (IBVM), an analogue of vesamicol that binds to acetylcholine transporters on pre-synaptic vesicles. Materials and Methods The subjects consisted of seven healthy volunteers (mean age 75±3yr) with no neuropsychiatric disorders who gave their written informed consent. The study was approved by the Ethic committee on Human Research. [123I]-IBVM was prepared by oxidative radio-iodination of (-)-5-tributyltin precursor and purified by HPLC. Radiochemical and optical purity were checked by HPLC. SPECT imaging was performed on a dual-headed system. Subjects were given 400mg of potassium perchlorate prior to intravenous injection of 218±19MBq. 17 frames were acquired: one acquisition with 8 frames (5sec/projection) immediately after injection and three acquisitions with 3 frames (20sec/projection) at 1h, 3h and 5h post injection. The projections were pre-filtered with a Butterworth filter and attenuation corrected. Images were reconstructed using filtered backprojection with a ramp filter and a voxel size of 6.8x6.8x6.8mm3. T1-weighted MR images were acquired on a 1.5T system using a gradient-echo sequence. Data analysis was performed with PMOD. For each acquisition, the summed frames image was coregistered to the MR scan and the transformation applied to each individual frame. A Region Of Interest (sum of left/right caudate and putamen) (ROI) and a reference region (in the occipital region) were drawn on the MR scan and applied to the coregistered dynamic SPECT images. The ROI time activity curve was analysed with three reference tissue models: 3-compartment Full Reference Tissue Model (FRTM), 2-compartment Simplified Reference Tissue Model (SRTM) and Logan graphical analysis. Results:The ROI binding potential (BP), k2 and R1 kinetic parameters and the Akaike criterion (AIC) are given in the table. No significant difference is observed for BP between the models. Results for k2 agree with that found in literature (0.017±0.03), and for R1 agree within errors (1.03±0.11). No significant difference is observed for the AIC between FRTM and SRTM, with however a better parameters identifiability with SRTM. BP

k2 [min-1]

R1=K1/K1REF

AIC

Model

mean ± s.d.

mean ± s.d.

mean ± s.d.

mean ± s.d.

FRTM

3.29 ± 0.23

0.022 ± 0.007

1.23 ± 0.14

58.3 ± 12.5

SRTM

3.35 ± 0.23

0.019 ± 0.005

1.16 ± 0.14

57.1 ± 12.2

Logan

3.38 ± 0.26

-

-

-

P321 The role of brain SPECT in children with craniosynostosis E. Urbanova1, J. Jakubec2, J. Vizda1, P. Kafka1; 1Nuclear medicine, University Hospital, Hradec Kralove, Czech Republic, 2Neurosurgery, University Hospital, Hradec Kralove, Czech Republic. Aim: The exact cause of premature fusion of cranial sutures is not fully understood. The early closing can be present in one or more sutures. Primary craniosynostosis in children leads to characteristic skull deformities and prevent the constricted brain from normal growing. The treatment is only surgical to prevent development of increased intra-cranial pressure and subsequent neurological damage. Early surgery and release of craniostenosis is important to achieve optimum perfusion and improvement in the psychomotor development.Methods: During the period lasting from Februar 2004 to Februar 2006 regional cerebral blood perfusion were carried out in eight children with craniosynostosis ranging in age 12 to 24 months. Scintigraphy was performed 20 minutes after intravenous administrations 185-300MBq Tc 99m -Neurolite with dual-head gamma camera Helix equipped with low energy high- resolution collimators and body contouring. Children were in general anaesthesia by anaesthetist with proper head fixation. In babies hydration was done with intravenous infusion of normal saline solution. All data were evaluated by the processing system Xpert - Pro and visual interpretation and semiquantitative analysis was done. The results from brain scintigraphy were compared with radiological findings (Three-dimensional rendering of CT data).Results: In seven children some hemisphere deformities and mild changes in perfusion were detected, but without necessity for surgery treatment. Repeated scintigraphy was performed within the interval one year in two children. Both studies were compared, but previous mild hypo-perfusion was without progress, with the same results from CT study, so the operation was not required. One patient with the serious hypo-perfusion from craniosynostosis is after operation with eventful recovery. All children without operation will be follow up further.Conclusions: Release of craniostenosis with early surgery is essential to achieve optimum perfusion and brain development. Brain SPECT can reveal serious hypo-perfusion under closing sutures and can help in surgery timing. Until some safe techniques for prenatal diagnostic and treatment of craniosynostosis are developed 3D-CT remain the diagnostic criterion standard and brain SPECT can inform about changes in perfusion.

P25 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Neurology/Psychiatry: Receptors & Transporters P322 Different effects of risperidone and clozapine on regional cerebral blood flow in treatmen-resistant schizophrenia P. Tamayo, V. Molina, C. Montes, P. Garcia-Talavera, J. R. GarciaTalavera; University Hospital Of Salamanca, Salamanca, Spain. Introduction: The effects of clozapine and risperidone on brain activity in schizophrenia may be different, as suggested by previous studies that compared their respective patterns of activity with that found with typical antipsychotics. However, no direct comparison was performed between these two drugs. Aim: the aim of this study was to determine the regions where these drugs produce different regional cerebral blood flow (rCBF) patterns.Materials and Methods: We have studied 8 patients (4 male and 4 female with a median age of 43 years) who met DSM-IV criteria for schizophrenia with 99mTc-HMPAO-SPECT imaging at baseline (after a chronic treatment with risperidone) and a month after switching to clozapine due to lack of response to the former. The 99mTc-HMPAO was administered via i-v while the patients were performing a Stroop test, an attentional paradigm. Quantitative SPECT analysis was accomplished with the imaging software program SPM99, comparing pre and post-treatment conditions. The threshold to consider an P-value as significant was set to P<0.001 with a minimum extent of 100 voxels.Results: We have found that patients showed at baseline (while on risperidone) a higher rCBF in premotor areas of the prefontral cortex and in left hippocampus. On the other hand, activity with clozapine was higher in the anterior cingulate and inferior frontal cortices, as compared to the risperidone condition. Anterior cingulate is involved in attentional processes.Conclusions: These data suggest that clozapine and risperidone produce different rCBF patterns in schizophrenia. Clozapine may compensate better than risperidone for the functional deficits reported in schizophrenia. The increased rCBF in the anterior cingulate during an attentional test and inferior frontal cortex, as well as the decreases of perfusion in anterior hippocampus may mediate the superior antipsychotic action of clozapine.

P323 Evaluating dopamine transporter activity with 99mtc-trodat-1 spect in drug-naïve tourette’s adults D. Sun, C. Yeh, W. Huang; Tri-Service General Hospital, Taipei, Taiwan, Province of China. Objectives: Findings on imaging of dopamine transporter (DAT) activity in patients with Tourette’s syndrome (TS) remain inconclusive. The present study was carried to observe DAT activity in patients with well-controlled TS using 99mTc-TRODAT-1 single photon emission computerized tomography (SPECT).Methods: Six drug-naïve patients with TS (mean age ± SD, 21.2 ±1.5 y) were recruited. All met the criteria for TS established in the DSM-IV. Seventeen age and sex-matched healthy subjects were served as the controls. Brain SPECT were acquired 165195 min after administrating 740 MBq of 99mTc-TRODAT-1, using a double-headed camera equipped with ultra-high-resolution fan-beam collimators (Helix SPX; GE). The specific uptake ratio was calculated by subtracting the mean counts per pixel in the occipital cortex from the mean counts per pixel in the striatum, putamen or caudate nucleus and by dividing the result by the mean counts per pixel in the occipital cortex. Tic-severity scores were also measured and correlated with the specific uptake ratios.Results: No significant difference in DAT activity between patients with TS and control subjects was found in the striatum and its sub-regions. Tic-

severity scores were also not correlated with specific uptake ratios measured from the striatum and its sub-regions.Conclusions: In conjunction with previous findings, our results suggested that functional abnormality of the dopamine system in patients with TS might be evident only in its early stage. Adaptation to tic symptoms might play a role in regulating the neural system.

P324 123I-IBZM SPECT assessed striatal D2 receptor occupancy and relationship to pharmacokinetics in stabilized schizophrenic patients on olanzapine and risperidone A. M. Catafau1, M. M. Penengo2, G. Nucci3, S. Bullich4, M. Suarez-Piñera4, I. Corripio5, E. Parellada6, C. Garcia-Ribera7, J. Pavia8, D. Ros9, J. Perich10, E. Merlo-Pich11; 1Experimental Medicine, CPDM, Psychiatry CEDD, GlaxoSmithKline, & Centro de Imagen en Psiquiatria, CRC-Mar, Hospital del Mar, Barcelona, Spain, 2Centro de Imagen en Psiquiatria, CRC-Mar, Hospital del Mar, Barcelona, Spain, 3Clinical Pharmacokinetics Modelling&Simulation,Psychiatry CEDD,GlaxoSmithKline, Verona, Italy, 4 Centro de Imagen en Psiquiaria.CRC-Mar.Hospital del Mar, Barcelona, Spain, 5Serv. Psiquiatria.Hospital de Sant Pau, Barcelona, Spain, 6Serv. Psiquiatria.Hospital Clinic, Barcelona, Spain, 7Serv. Psiquiatria.Hospital del Mar, Barcelona, Spain, 8Serv. de Medicina Nuclear.Hospital Clinic, Barcelona, Spain, 9Unidad de Biofisica y Bioingenieria.Universidad de Barcelona, Barcelona, Spain, 10Dept Resonancia Magnetica,CRCMar.Hospital del Mar., Barcelona, Spain, 11Experimental Medical Sciences CPDM, Psychiatry CEDD, GlaxoSmithKline, Verona, Italy. Background: Despite extensive literature on antipsychotic (AP)-induced D2 receptor occupancy (D2RO), it is still unclear which is the D2RO associated to symptom control in chronically dosed, stabilized patients as measured by 123I-IBZM SPECT. Aims: To define the striatal D2RO in stabilized schizophrenic patients on clinically relevant doses of olanzapine (O) or risperidone (R) using 123I-IBZM SPECT, and to investigate the relationship between D2RO and plasma concentration (CP) for these AP.Methods: Stabilized schizophrenic patients (n=24, 17 M, 28.3±5.8 yrs, PANSS 44.3±7.2) at steady state of their clinically required doses of O (n=12, range 5-30 mg/d) or R (n=12, range 1.5-7 mg/d) were included. EPS were assessed using the Extrapyramidal Symptom Rating Scale (ESRS). For D2RO calculations, 123I-IBZM SPECT with MRI co-registration and the tissue ratio method was used. AP CP were measured during the SPECT scan. For R, the active moiety (R+9-hydroxyR) was considered as CP. An Emax model was tested to fit the D2RO-CP data, as D2RO=[(D2ROmax·CP)/(EC50+CP)], where D2ROmax is the maximum D2RO, and EC50 is the CP inducing 50% of the D2ROmax.Results: One subject on R was excluded from the analysis because of CP below the lower limit of quantification (5.0 ng/mL). Striatal D2RO and CP ranges were 22-84% and 8.6-89.5 ng/mL for O, and 28-75% and 9.4-60.5 ng/mL for R. Despite being stabilized patients, 42% of patients taking O and 36% of patients taking R showed CP below the lower limit of the reported optimal therapeutic range (O=20-80ng/mL, R=20-60ng/mL) (Hiemke et al., Ther Drug Monit 2004;26:156-160), and D2RO<50%. For CP within these therapeutic ranges, the model predicted D2RO range of 4778% for O (D2ROmax=100%, EC50=22.7ng/mL, r2=0.86), and of 44-64% for R (D2ROmax=83%, EC50=18.0ng/mL, r2=0.55). EPS were absent or very mild in all cases, including the only patient with D2RO>80%, who was on O.Conclusions: Stabilized schizophrenic patients with mild EPS show a wide range of both D2RO and CP when clinically effective doses of O and R were used. A D2RO-CP relationship was found, with 86% and 55% of D2RO variance explained by CP for O and R, respectively. The CP inducing D2RO=50% are in agreement with the CP in the lower limit of the reported therapeutic ranges, suggesting that using 123I-IBZM SPECT, a 50% D2RO could be associated with a clinical benefit.

P325 SPM analysis of metabolic change in women with major depression disorder - A preliminary study W. Chang1, B. Yang1, T. Su2, R. Liu3, S. Wang1; 1National PET/Cyclotron Center, Department of Nuclear medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Taipei, Taiwan, Province of China, 2Department of psychology, Taipei Veterans General Hospital, Taipei, Taiwan, Taipei, Taiwan, Province of China, 3Division of Nuclear Medicine, National YangMing University Medical School, Taipei, Taiwan, Taipei, Taiwan, Province of China. Objective: FDG PET techniques have been used in psychiatric research as a noninvasive method to study the functional changes of the brain. In this retrospective study we investigated the difference of 18F-FDG uptake by SPM between major depression and normal subjects. Subjects and Methods: Seven right-handed patients with a diagnosis of major depression, single or recurrent episode were recruited. ( Age ranged 45-66 y/o,mean ± s.d : 58 ± 6 y/o). Two patients were medication-free at the time of imaging. Of the remaining five patients were prescribed with neuroleptics. No patients received electroconvulsive therapy (ECT). Exclusion criteria included current or past Axis I diagnosis other than MDD. In control group, 10 healthy female volunteers were enrolled. (Age ranged 50-62 y/o, mean ± s.d : 53 ± 4 y/o). Health volunteers matched in aggregate for age and gender. All volunteers have no significant medical and psychiatric conditions. PET imaging was performed at 45 minutes after injection of 370 MBq of FDG. Difference of [F-18] FDG activity in the brain was analyzed by using statistical parametric mapping software (SPM2). Between-group comparisons were then performed with two sample ttest (Į= 0.005, random field theory : significant P < 0.05). RESULTS: Statistical parametric mapping analysis revealed decreased CMRglu in the in the right middle frontal gyrus (dorsolateral prefrontal cortex), right superior frontal gyrus, and left anterior cingulate cortex (uncorrected p< 0.001, cluster size = 2502). Conclusion: This small group observation demonstrates CMRglu abnormalities in the frontal and cingulate regions of cerebral cortices. These findings correlate with clinical symptoms of mood and emotions. The metabolic deficit in

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Poster Presentation

Conclusion: SPECT-IBVM quantification with data acquired during the 5h post injection is possible, whatever the model used. The results indicate that kinetic modelling using a 2compartment reference tissue model is adequate.

the right superior frontal gyrus has not been disclosed by the conventional analytic method reported previously. Further evaluation need large group study and compare with male population are needed. Key Words: depression, positron emission tomography, statistical parametric mapping

P326 The glucose metabolism changes after bilateral capsulotomy in obsessive-compulsive disorder C. Zuo1, Y. Guan1, B. Sun2; 1PET center,Huashan Hospital, Shanghai, China, 2Department of Neurosurgery, Ruijin Hospital, Shanghai, China. Objective To assess the glucose metabolism changes in regional glucose metabolism following bilateral capsulotomy in patients with medically intractable Obsessive-Compulsive Disorder (OCD). Methods 6 OCD patients underwent bilateral anterior capsulotomy. 18F-FDG PET data obtained before and after operation were subjected to SPM(statistical parameter mapping). Results The glucose metabolism decrease were found in left cingulate, caudate, thalamic nucleus medialis dorsalis, medial frontal, and right cingulated, medial frontal as well. Conclusions SPM could show the significant change of cingulate-striatum-thalamic circuits in OCD patients after operation, the findings implicate that the decreased cerebral metabolism in cingulate gyrus, striatum, and thalamus.

P327 Dysregulation of dopamine transporter methylphenidate treated tourette’s patients

binding

in

K. Ma1, C. Yeh2, W. Huang2; 1National Defense Medical Center, Taipei, Taiwan, Province of China, 2Tri-Service General Hospital, Taipei, Taiwan, Province of China. Background: Tourette’s patients (TS) are known to have disturbed central dopaminergic transmission. The dysfunction of dopamine transporter (DAT) might be related to the insensitive of methylphenidate (MPH) inhibition. We evaluated change ratios of DAT activity in TS patients after MPH treatment using Tc-99m TRADAT-1 SPECT.Methods: Seven drug-naïve patients with TS (mean age±SD, 23±6) were recruited. All met the criteria of the DSM-IV. Eight age, gender-matched healthy subjects with response to psychostimulant served as the controls. Brain SPECT were acquired 3 h after intravenous injection of 740 MBq of 99mTc-TRODAT-1, using a double-headed camera equipped with ultra-high resolution fan-beam collimators (Helix SPX; GE). All subjects received twice SPECT, i.e. the baseline and 7 d after when MPH 10 mg was taken orally 2 h before 99mTc-TRODAT-1 administration. The specific uptake ratios (SURs) in the striatum and its sub-regions were calculated as described (J Nucl Med 2003; 44: 999). Ticseverity scores were also measured and correlated with the SURs. Changes of SURs between pre- and post-MPH in both diseased or control groups were calculated by subtracting SUR values post-MPH from those of pre-MPH (i.e. SURpre - SURpost, abbreviated as “dif”), Change ratios of SUR pre- and post- MPH were calculated by the “dif” divided by “SURpre” (i.e. dif/SURpre).Results: The mean disease severity for the patient group was 25 on the Yale Global Tic Severity Scale. Significant differences for DAT binding as measured by “dif” and “dif/SURpre” were found in the right caudate nucleus, but not in the other striatal sub-regions between TS and control groups. No correlation was observed between tic severity scores and SURs measured from the striatum and its sub-regions.Conclusions: Our results suggest that a functional abnormality of the dopamine system in patients with TS might be evident by the stimulant challenging study. The underlying pathophysiology of right caudate nucleus related to developmental neuropsychiatric disorders such as TS needs further clarified.

P328 The effect of limbic system activation by procaine on brain perfusion in healthy volunteers M. Yildiz, I. Eren, S. Cerci, H. Suslu, M. Ozbek, I. Inanli; SD University Medical Faculty, Isparta, Turkey. The limbic system is an interconnected structures of cortical and subcortical brain regions. It govern emations and behavior. Procaine is a local anasthetic. Administrations of procaine cuases activation of limbic structures. Tc 99m HMPAO brain perfusion SPECT show regional cerebral blood flow. We aimed to evaluate administration of procaine on regional cerebral blood flow in healthy persons. In 19 healthy volunteers (8 female, 11 male; 24-45 years) who are right handed, not using psychotropic drugs, have not psychiatric, neurological and any physical illness, saline and immedidiatey after Tc 99m HMPAO were injected and brain perfusion SPECT was performed at baseline. All subjects were requested to abstain from caffeine and nicotine for 4 hours prior to the study. Two days after, procaine was administrationed intravenously (1.38 mg/kg) and immediately afterwards Tc 99m HMPAO were injected, and images obtained. In baseline and post procaine images, the perfusions of 30 different brain regions were evaluated. In left superior frontal, bilateral medial frontal, bilateral inferior frontal, bilateral hypocampus, bilateral nucleus caudatus, bilateral nucleus lentiformis, bilateral thalamus and bilateral anterior sinculat regions, brain perfusions were significantly increased during limbic system activation by procaine (p<0.05). Any differences in the perfusion of the other brain regions were observed after procaine infusion (p>0.05). Limbic sytem activation by procaine increases rCBF of frontal lob, hypocampus, nucleus caudatus, nucleus lentiformis and thalamus in healthy persons.

P329 Influence of limbic system activation by procaine on regional cerebral blood flow in schizophrenia patients. M. Yildiz, I. Eren, S. Cerci, H. Suslu, M. Ozbek, I. Inanli; SD University Medical Faculty, Isparta, Turkey. The limbic system refers to unite of cortical and subcortical brain regions thought to be critical in motivation and emotional expression. The intravenous administrations of procaine shows activation of limbic structures. Tc 99m HMPAO brain perfusion SPECT show regional cerebral

S292

blood flow. We aimed to evaluate administration of procaine on regional cerebral blood flow in schizophrenia patients. In 22 schizophrenia patients (9 female, 13 male; 23-44 years) (11 paranoid schizophrenia, 3 indefferented schizophrenia, 2 dysorganised schizophrenia, 6 residuel schizophrenia patients), saline and immedidiatey after Tc 99m HMPAO were injected and brain perfusion SPECT was performed at baseline. All patients were requested to abstain from caffeine and nicotine for 4 hours prior to the study. Two days after, procaine was administrationed intravenously (1.38 mg/kg) and immediately afterwards Tc 99m HMPAO were injected, and images obtained. In baseline and post procaine images, the perfusions of 30 different brain regions were evaluated. In right superior frontal(p=0.018), right medial frontal(p=0.033), left inferior frontal(0.005), bilateral nucleus caudatus(p<0.001), right nucleus lentiformis(0.015) and right insula(p=0.041) regions, brain perfusions were significantly increased during limbic system activation by procaine. Any differences in the perfusion of the other brain regions were observed after procaine infusion (p>0.05).

P330 Depression in thyroid cancer patients receiving I-131 therapy C. Sioka1, O. Giotakos2, N. Dimakopoulos1, S. Fourlis1, A. Zouboulidis1; 1417 Army Share Found Hospital, Athens, Greece, 2414 Army Hospital, Athens, Greece. AIM: The purpose of this study was to screen for depression in patients with thyroid cancer before, during, and after I-131 therapy. PATIENTS AND METHODS: Sixteen thyroid cancer patients were evaluated with a psychological assessment test [Zung Depresion Scale (ZDS) questionnaire] 3+/-1 months prior I-131 therapy, during therapy, and 3+/-1 months post therapy. The patients were designated as depressed when their score was >14 in the ZDS questionnaire and as non-depressed when their Zung Score (ZS) was ” 14. RESULTS: The average age of all patients was 50.5 years. There were 11 female and 5 male patients. We found that the incidence of depression was high in the pre-treatment (9 /12, 75.0%) and during treatment (11/16, 68.8%) periods, but it was low in the post-treatment period (2/16, 12.5%). The mean ZS suggested that patients prior to I-131 therapy had a mild depression (ZS: 16.2), which progressed to significant depression during hospitalization for I-131 therapy (ZS: 19.4). However, the same group of patients was non-depressed (ZS: 8.7) 3+/-1 months post therapy. CONCLUSION: The authors discuss the implications of these results as they pertain to screening thyroid cancer patients for depression prior and during I-131 therapy. Psychological support and short-term administration of antidepressant medications should be considered in order to help the patients endure during this difficult period. Further studies are needed to clarify the clinical significance of the depression in thyroid carcinoma patients and its impact on the efficacy of treatment and prognosis.

P331 In vivo imaging of haloperidol-induced dopamine release using [123I]FP-CIT and small animal SPECT S. Nikolaus, T. Poeppel, C. Antke, K. Kley, M. Beu, A. Wirrwar, H. Müller; University Hospital Düsseldorf, Düsseldorf, Germany. Aim: Haloperidol (HAL) increases synaptic dopamine (DA) concentrations. A suggested mode of action is the blockade of terminal presynaptic D2 autoreceptors leading to an abolition of feedback inhibition and thus to an increase of DA release. In this study, we assessed the effect of HAL on DA transporter (DAT) binding in the rat striatum using [123I]-N-[[Unsupported Character - ώ]]-fluoropropyl-2ȕ-carbomethoxy-3ȕ-(4-iodophenyl)-nortropane (FP-CIT) and a dedicated small animal SPECT.Materials and Methods: In 10 rats, DAT binding was assessed under baseline conditions (no treatment) and after pre-treatment with HAL (1 mg/kg) and vehicle (100 % ethanol). Investigations were performed in randomized order with intervals of §10 days. FP-CIT (26 MBq) was injected into the tail vein 1 h after pre-treatment with HAL or ethanol. Measurements were performed 2 h after radioligand administration with the “TierSPECT” (LEUHR, FOV: 82 mm, FWHM: 2.8 mm, sensitivity: 22 cps/MBq). Striatal regions of interest (ROI) and cerebellar reference regions (REF) were defined with the MPITool. For all conditions (Baseline, HAL, ethanol), striatal equilibrium ratios (V3''=V(ROI)/V(REF)-1) were computed as estimation for the binding potential. As Harderian and salivary glands displayed marked radioactivity accumulations, ROIs were also defined within these structures. Glandular count rates in were normalized to the cerebellum.Results: In baseline and after ethanol, striatal V3’’ was 1.21 ± 0.34 (mean ± SD) and 1.53 ± 0.83, respectively (paired t test, one-tailed, p = 0.364). After haloperidol, V3’’ decreased to 0.93 ± 0.37 (p = 0.011). Glandular ratios did not differ between pre-treatment conditions (0.071 < p < 0.43).Conclusions: Pre-treatment with 1 mg/kg haloperidol induced a 23% reduction of DAT binding relative to baseline. Glandular radioactivity accumulations did not differ between conditions suggesting that FP-CIT accumulations in these regions are nonspecific and unrelated to DAT binding. HAL has no affinity for the DAT (Ki = 13000 nM). Thus, the reduction of DAT binding may be interpreted in terms of competition between FP-CIT and endogenous DA. Our results suggest that FP-CIT might be a suitable ligand to study variations of synaptic DA concentrations from the presynaptic point of view. Findings not only have implications for the performance of DAT-SPECT in patients receiving DAergic medications but also for understanding presynaptic DAT and autoreceptor function in schizophrenia.

P332 Serotonin transporter availibility in Asperger syndrome using a novel specific SERT tracer 123 I ADAM A. Ahonen1, A. Koskela1, T. Ihalainen1, P. Nikkinen1, T. Nieminen-Wendt2, E. Kämäräinen1, M. Turunen3, T. Kauppinen1, T. Lipponen3, L. von Wendt1; 1HUCH, Div of Nuclear Medicine, Helsinki, Finland, 2HUCH, Dept of Children Neurology, Helsinki, Finland, 3HU, Dept of Radiochemistry, Helsinki, Finland. Aim: Asperger syndrome is a form of pervasive development disorder, which shares some common features with autistic disorder and is characterized by a clinical picture less grave than autism. The aetiology is still unknown, but data is accumulating to suggest contribution of genetic factors. The hyperserotoninemia common in autism occurs also in relatives of autistic

P333 Serotonin-2A binding index of the 5-HT2A receptor in dogs with anxiety disorder K. Peremans1, R. De Meester1, P. Blanckaert2, A. Dobbeleir1, E. Vandermeulen1, I. Goethals3, T. Waelbers1, F. De Vos4, K. Audenaert3; 1Faculty of Veterinary Medicine, UG, Merelbeke, Belgium, 2Faculty of Pharmaceutical Science, UG, Gent, Belgium, 3Faculty of Medicine, UG, Gent, Belgium, 4Faculty of Pharmaceutical Sciences, UG, Gent, Belgium. INTRODUCTION: The involvement of a deficient serotonergic system has been implicated in mood and behavioral disorders in both man and animals. In a former study the involvement of the serotonergic system was explored using SPET in impulsive aggressive dogs. The aim of this study was to investigate the binding index of 123I-5-I-R91150, a selective ligand for 5-HT2A receptor imaging, in dogs that were diagnosed with anxiety disorder.Materials and Methods: Nine dogs (6 M, 3 F; mean age: 40m, SD:22) with clinical overt anxiety disorder and eight normal dogs (4M, 4F) were included in the study. The binding index of the 5-HT2A receptor was measured using the selective ligand 123I-5-I-R91150. The examination was performed under general anaesthesia; with a high resolution parallel hole collimated triple head gamma camera. Serotonine2A images were reconstructed with FBP and a Butterworth-filter (cut-off 1,2 cycli/cm, order 8). Images were analysed with VOI’s drawn around fronto-, temporo, parieto-, occipitocerebral, thalamic regions and the cerebellum. Regional cerebral counts were normalised to the activity registered in the cerebellum.Results: Groups were not different concerning age (MWU=28; P=0.43) and gender distribution (Fisher Exact’s Test P=0.33). Serotonin-2A binding in the dogs with anxiety disorder was significantly lower in the left frontal (MWU=5.5; p=0.002), right frontal (MWU=0; P<0.001), left temporal (MWU=8.0; p=007), right temporal (MWU=10.5; P=0.014), right parietal MWU=12.0; P=0.021), left occipital (MWU=5.0; P=0.002) and right occipital (MWU=4.0; P=0.001) cortex. There were no differences concerning serotonin-2A binding in the left parietal cortex (MWU=21.5;P=0.17) and in subcortical regions (MWU=16.0; P=0.06). Since age is inversely related to serotonin-2A binding - although age was not significantly different between the groups - we reanalysed our data after age correction and results were identical as previously mentioned.Conclusions: This study demonstrates that SPET imaging may provide valuable information concerning the serotonergic system in dogs. Contrary to impulsive behaviour, the serotonin-2A binding index in anxious and not-impulsive dogs is lowered. This is another example of the use of the dog as a natural model for behavioural disorders.

P334 Serotonin transporters in the thalamus of Progressive Supranuclear Palsy and Parkinson’s disease Patients: a study with 123I-FP-CIT and SPECT/CT hybrid camera. L. Filippi1, C. Manni1, M. Pierantozzi2, F. Padovano1, R. Danieli3, P. Stanzione2, O. Schillaci1; 1Department of Diagnostic Imaging, University of Rome "Tor Vergata", Rome, Italy, 2Department of Neurological Sciences, Univerisity of Rome "Tor Vergata", Rome, Italy, 3Department of Diagnostic Imaging, University of Rome ", Rome, Italy. Aim: it has been demonstrated that 123I-FP-CIT single photon emission computerized tomography (SPECT) might be useful to characterize dopamine transporters loss both in Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). Our aim was to characterize the scintigraphic pattern of setonin (5-HT) neurons density in the thalamus of PD and PSP by 123I-FP-CIT, which binds with lower affinifty also to 5-HT transporters.Methods: Ten PD patients and eight and age-matched PSP patients and fifiteen age-matched healthy controls were included in this study. PD and PSP were matched also for disease duration (22 + 12 months; 24 + 6 months, respectively). All PSP and PD patients presented depression symptoms which were evaluated by using Hamilton Depression Rating Scale score. Four hour after tracer injection, SPECT/CT was obtained with a dual-headed gamma-camera coupled with a low-power X-ray system. The co-registered CT and SPECT images were then used to define regions of interest (ROI) including right and left thalamus and the cerebellum cortex. The ratio of specific [(left thalamus+ right thalamus/2) - cerebellum)] to non specific (cerebellum) binding was than calculated.Results: Visual analysis did not detect any differences in thalamus uptake between controls, PD and PSP patients. By semiquantitative analysis, the values of specific to non specific binding were not statistically (p < 0.05) different for PD (1.36 + 0.006) and PSP (1.35 + 0.008) when compared to controls (1.38 + 0.005). Moreover, thalamus to non specific binding ratio values both in PS and in PSP patients did not correlate with the Hamilton Depression Rating Scale score.Conclusions: our preliminary results suggest that 5HT-transpoter in thalamus region

might be not impaired in PD and PSP patients. Nevertheless, our findings need to be confirmed in larger series by using tracer with higher affinity for 5-HT neurons.

P335 The dopamin transporter activity (DAT) in depression and the effect of sertralin treatment (preliminary results) Z. Besenyi1, M. Árgyelán2, Z. Szabó2, S. Kéri2, Z. Janka2, L. Pávics3; 1Euromedic Diagnostics Szeged Ltd., Szeged, Hungary, 2Department of Psychiatry, University of Szeged, Szeged, Hungary, 3Department of Nuclear Medicine, University of Szeged, Szeged, Hungary. Several data suggest the role of the dopaminergic system in depression, but the results with functional imaging are contradictory. The aim of this study was to evaluate the DAT activity of untreated patients with depression and compared to healthy volunters. We also studied the effect of sertraline on dopamin transporter activity in depression.Materials and Methods: We performed overall 18 123I-FP-CIT SPECT examinations- 6 healthy controls (checked by Mini International Neuropsychiatric Interview) and 6 depressed patients (diagnosed by the instructions of DSM-IV), the inclusion criteria was a score of at least 19 on the Hamilton Depression Scale (HAM-D, 21 items). In age-matched healthy subjects and in patients baseline 123I-FP-CIT-SPECT investigations were done, in the depressed patient group the DAT SPECT imagination was repeated after 3 weeks sertraline treatment. On the transversal reconstructed SPECT slices at the level of the basal ganglia, regions of interest were fixed manually and by self-developed semiautomatic technique. The binding potential was estimated by the ratio of the specific to nonspecific activity ({mean striatal activity-mean occipital activity}/mean occipital activity.)Results: In the patients group, the median baseline binding potential was 3.35 (range: 3.02-4.04), in the control group, this value was 3.58 (range: 2.78-4.37). A Mann-Whitney U-test revealed that this difference was not statistically significant (Z=-0.32, p=0.74). In the patient group, the median binding potential after sertraline administration was 2.98 (range: 2.71-4.33), which indicates a decrease of 11.0% of FP-CIT binding. However, this alteration statistically was not significant (Wilcoxon Matched Pair Test, Z=0.31, p=0.75). Spearman’s correlation indicated no significant relationship among binding potentials, HAM-D scores, age, and education (p>0.5).Conclusions: We didn’t find any significant difference in the baseline values of DAT activity between control and untreated depressed subjects. Sertraline treatment decreased the DAT occupancy (11%) but further investigations are needed to support this finding.

P336 Striatal dopamine transporter binding measurements by Basal Ganglia Matching Tools and by QuantiSPECT G. Marotta1, R. Benti1, R. Cilia2, F. Voltini1, F. Zito1, A. Antonini2, P. Gerundini1; 1Fondazione IRCCS Ospedale Maggiore, Milano, Italy, 2 Parkinson Institute, Istituti Clinici di Perfezionamento, Milano, Italy. Objectives: The aim of this study was to compare the differences of quantitation striatal DAT binding by two different computer program, Basal Ganglia Matching Tools (BG) and QuantiSPECT (QS), using both OSEM reconstruction algorithm (Iter) and filtered backprojection (Fbp).Methods: In 65 healthy subjects (mean age 63 years, range 31-85) SPECT scans were acquired 3-4 hours after injection of 111-185 MBq of [123I]-FP-CIT, for 28 min such as 7 min per scan using a triple-headed gammacamera (Picker3000 or Irix, Philips). After Iter and Fbp reconstruction, the images were filtered with 3D-Butterworth post-filter (with order 5 and a cutoff of 0.3 cycles/pixel), attenuation corrected (Chang’s coefficient 0.12) and resliced to 2.33 mm per slice. The quantitation of striatal DAT binding was performed by Basal Ganglia Matching Tools v1.0 (www.disi.unige.it/person/IngugliaF/BasGan/), using the default parameters of threedimensional processing and by QuantiSPECT software v1.2 (GE Healthcare) using the twodimensional Crescent ROI algorithm (~12 mm thick) for the putamen uptake (PU), the putamen to caudate ratio (PCR) and the caudate uptake (CU).Results: The mean value (and SD) of BG_Fbp, BG_Iter, QS_Fbp and QS_Iter were 4.96 (0.94), 4.72 (0.95), 3.06 (0.53) and 2.83 (0.47) for PU, 0.87 (0.06), 0.86 (0.06), 0.92 (0.04) and 0.92 (0.04) for PCR, 5.70 (0.95), 5.51 (0.88), 3.33 (0.57) and 3.07 (0.51) for CU. The BG software needs a precise reorientation of the images, more in Fbp images than in Iter images, probably because of a better separation between the caudate and the putamen, as suggested in the visual evaluation. The correlations between BG_Iter versus BG_Fbp, between QS_Iter versus QS_Fbp, between QS_Fbp versus BG_Fbp and between QS_Iter versus BG_Iter were 0.93, 0.95, 0.66 and 0.73 for PU, 0.78, 0.76, 0.52 and 0.51 for PCR, 0.93, 0.95, 0.42 and 0.66 for CU; the mean paired differences (SD) were 0.25 (0.35), 0.23 (0.17), 1.90 (0.71) and 1.88 (0.61) for PU, 0.01 (0.04), 0.004 (0.03), -0.05 (0.05) and -0.07 (0.05) for PCR, 0.20 (0.35), 0.26 (0.18), 2.37 (0.76) and 2.44 (0.66) for CU. All results were statistically significant (p<0.0001).Conclusions: There was excellent correlation between the measures of quantitation of DAT binding assessed by Iter and Fbp reconstructions and all Iter measurements were lower than Fbp ones. There was weak correlation between the two different softwares, better for the putamen uptake and with Iter reconstructions. The measurements of caudate and putamen uptakes were greater (almost twofold) with Basal Ganglia Matching Tools than with QuantiSPECT.

P337 3D versus 2D quantitation of Tc-99m Trodat-1 striatal uptake in patients with Parkinson’s disease W. T. Wen, C. Y. Wen; UCSF, San Francisco, CA, United States. Objective: The study is to use a new three-dimensional voxel-based method to quantitate Tc99m Trodat-1 striatal uptake in patients clinically diagnosed to have Parkinson’s disease, and to compare it with the commonly employed two-dimensional slice-based method.Methods: Two hundred and seventy-two patients (mean age 62±4, 176 males) clinically diagnosed to have Parkinson’s disease were referred to our department for Tc-99m Trodat-1 cerebral SPECT. 92.5 MBq Tc-99m Trodat-1 was injected intravenously. SPECT of the brain was acquired approximately at 3-4 hours post injection by double-headed Varicam, at 3 degree per stop, 30 sec/stop over 360 degrees using Fan-beam collimator. A specialized head rest was used for better stabilization and prevents head movement of the patient. Quantitation of Trodat-1 uptake was performed in two steps. First ROI quantitation was performed by conventional two-dimensional

S293

Poster Presentation

persons. Our aim was to investigate SERT binding in interesting brain regions in subjects with Asperger syndrome using the novel specific SERT tracer 123 I ADAM.Methods: Serotonin transporter (SERT) SPET studies with 123 I ADAM were done for 24 patients with Asperger syndrome (aged 18 - 56 years, mean = 32 ) and 15 healthy volunteers ( aged 22 - 55 years, mean = 38 ). Imaging was carried out using a triple - head gamma camera equipped with fan beam collimator with a mean dose of 185 MBq. A template with predefined volume of interest (VOI) map for 123 I ADAM studies was used for automated registration of the scans and quantification of SERT binding. Specific binding ratios (SBRs) at five hours post injection were calculated as (counts in target region - counts in cerebellum)/counts in cerebellum. VOIs were drawn over midbrain, pons, striatum, thalamus, temporal and anterior gingulate regions.Results: The specific binding ratios for SERTs in the midbrain area at 5 h after injection were 1.79 ± 0.30 for subjects with Asperger syndrome and 1.89 ± 0.28 for healthy controls. Correspondingly, the SBRs for thalamus were 1.43 ± 0.24 and 1.39 ± 0.32 for pons 0.90 ± 0.22 and 0.97 ± 0.25, for right caudatus 1.31 ± 0.29 and 1.34 ± 0.26, and for left caudatus 1.23 ± 0.25 and 1.17 ± 0.27. No statistically significant differences were found between patients and healthy voluntary persons in midbrain or other brain regions.Conclusions: Our results do not support the previous findings of increased SERT availability in Asperger syndrome. Individual variation in SERT values both in subjects with Asperger syndrome and controls was very high. Therefore small abnormalities are difficult to uncover. However, not even any trends pointing towards abnormalities in SERT binding in Asperger syndrome were found. There are also some methodological weak points such as use of the simplified reference method with pseudoequilibrium instead of graphical method.

display over the caudates and putamens of bilateral cerebral hemispheres on 3 composite images with highest activity on the transverse slices. ROI over the occipital cortices were taken as background uptake. Secondly, using our newly developed software, semiautomatic quantitation of the voxel means of Trodat-1 uptake in the entire caudates and putamens was performed. Trodat stages were assigned using this criteria: stage 1 - unilateral reduction of putamen uptake, stage 2 - bilateral reduction of putamen uptake, stage 3 - reduced uptake in bilateral putamens plus one side of caudate, stage 4 - reduced uptake in bilateral putamens and caudates, stage 5 background uptake with caudates and putamens not well visualized.Results: The results are shown in the table. ROI quatitation of caudate-to-occipital (C/O) and putamen-to-occipital (P/O) ratios by the three-dimensional method generally gives lower estimate of the striatal Trodat-1 uptake when compared to two-dimensional method. The differences are tested with t-statistic at p<0.05. N

3D Rt C/O

2D Lt C/O

Rt P/O

Lt P/O

Rt C/O

Lt C/O

Rt P/O

Lt P/O

Stage1 26 1.88±0.03 1.87±0.03 1.58±0.02 1.50±0.03 1.94±0.03 1.93±0.03 1.66±0.02 1.58±0.03 Stage2 54 1.77±0.02 1.74±0.02 1.34±0.02 1.29±0.02 1.83±0.02 1.80±0.02 1.42±0.02 1.37±0.02 Stage3 71 1.50±0.02 1.49±0.02 1.23±0.02 1.17±0.01 1.56±0.02 1.55±0.02 1.31±0.02 1.25±0.01 Stage4 94 1.26±0.01 1.24±0.01 1.05±0.01 1.03±0.01 1.32±0.01 1.30±0.01 1.13±0.01 1.11±0.01 Stage5 27 1.02±0.05 1.05±0.05 0.98±0.05 0.98±0.04 1.08±0.05 1.11±0.05 1.06±0.05 1.06±0.04

Conclusions: Quantitation of Tc-99m Trodat-1 striatal uptake by three-dimensional versus twodimensional method results in different estimates, with the 3D method generally giving lower estimates in all stages of severity in patients with Parkinson’s disease. Whether this implies an underestimation by the 3D method or overestimation by the 2D method cannot be determined.

P338 Quantification of uptake index standard dopamine transporter spect

in

patients

with

C. Calvo, P. de la Riva, R. Iglesias, C. Ponce, N. López, J. Castro, I. Acevedo, T. Cambil, B. Rodríguez de Quesada; Hospital Virgen Macarena, Sevilla, Spain. AIM: To obtain an Uptake Index in Striatum (SI), Anterior Putamen (API) and Posterior Putamen (PPI) based on the age and sex of patients suffering with suspected Essential Tremor (ET) and unaltered Dopamine Transporter SPECT (DATSP).Materials and Methods: 315 patients were sent to the service for study with DATSP for differential diagnosis of ET versus that of Parkinson’s Disease (PD). Of these, the study included 102 patients (39 male/63 female) with an average age of 63 years and visual valuation of the images without significant alterations of radiotracer uptake. All patients received DATSP five hours after a dose of 185 MBq loflupane I123. The quantification was made on two consecutive central transaxial views, drawing geometric regions of interest (ROIs) in Striatum, Caudate Nuclei, Anterior Putamen, Posterior Putamen and Occipital. We calculated uptake index using the following formula: counts in ROIcounts in Occipital/counts in Occipital. The patients were classified into 4 age groups: 1(”50), 2(51-60), 3(61-70), 4(•71). All data was captured and recorded in Microsoft Access format, with analysis carried out using the statistical package, SPSS.Results: Table 1 shows the values obtained, expressed as the Mean and Standard Deviation (SD) for each age group. The SI obtained in the group 1(”50 years) is higher than for the other groups. As far as gender is concerned, the results within males were: SI 6,42 ± 2,18, API 9,50 ± 2,87 e PPI 7,39 ± 2,18. The results amongst females were: SI 6,05 ± 1,97, API 9,41 ± 2,70 and PPI 7,27 ± 2,24. Suggesting, there were no significant differences between both groups. Table 1

AGE GROUP

PPI

API

SI

MEAN

8,30

10,43

8,14

SD

2,62

2,68

2,35

MEAN

7,71

9,74

6,02

SD

2,37

3,03

1,33

MEAN

6,86

8,77

5,86

SD

1,80

2,00

1,77

MEAN

7,14

9,53

5,77

SD

2,22

3,17

2,09

P339 Determination of an index of protein synthesis in brain using 1-[11C]-leucine PET: Incorporation of factors for plasma large neutral amino acids and recycled tissue amino acids. O. Muzik, S. Sundaram, D. Chugani, F. Mu, T. Mangner, H. Chugani; Wayne State University, Detroit, MI, United States. Aim: The aim of this study was to assess the effect of leucine and large neutral amino acid (LNAA) plasma levels on the unidirectional uptake rate constant (K-complex) of L-[1-11C]leucine in brain and to calculate an index of protein synthesis rate (PSR) which takes into account the recycled tissue amino acid pool.Materials and Methods: Twenty-seven healthy adult volunteers (age range 20-50 years; 11 males) underwent dynamic leucine PET imaging with arterial blood sampling. Data were analyzed with a standard two-tissue compartmental model yielding the unidirectional uptake rate of leucine into tissue (K-complex = K1k3/(k2+k3)) as well as the fraction of leucine originating from exogenous sources (lamda = k2/(k2+k3)). To account for the effect of varying total LNAA plasma levels on leucine transport, the K-complex was normalized to a standard total LNAA level (K-complex'). Protein synthesis rate in brain was calculated as PSR = [K-complex'/lamda]*leucine. Finally, the K-complex was also derived noninvasively using the Patlak graphical analysis and an input function obtained from a LV ROI.Results: Plasma concentration of the sum of all LNAA (SLNAA) differed between males (981 + 86 µM) and females (850 + 76 µM, p = 0.012); however, plasma leucine concentration was similar in both genders (64 + 20 µM for males vs. 58 + 21 µM for females; p = 0.57). The whole brain value for lamda was determined as 0.64 + 0.03 and did not show a gender difference (p = 0.17). The K-complex values normalized to the SLNAA plasma concentration (K-complex') were similar in males and females (p = 0.21), as was the PSR (1.24 + 0.49µM/min in males vs. 1.29 + 0.62µM/min in females; p = 0.35). Moreover, the rank order of regional PSR values was identical with the rank order observed for the K-complex'. No relationship between plasma leucine and the K-complex' was observed (r = 0.08, p = 0.75). Finally there was a significant correlation between the PSR and the K-complex derived using the Patlak analysis (r = 0.65, p < 0.001).Conclusions: The unidirectional uptake rate constant of leucine corrected for total LNAA levels is independent of plasma leucine levels and is likely to represent a reliable index of protein synthesis. Moreover, the application of a non-invasive protocol using Patlak analysis allows calculation of an index of protein synthesis from the exogenous leucine pool with an acceptable error margin.

P26 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Neurology/Psychiatry: Dementia/Cerebrovascular P340 The influence of APOE4 genotype and educational level on regional cerebral blood flow in patients with Alzheimer’s disease P. Wu, M. Pai, N. Chiu; National Cheng Kung University Hospital, Tainan city, Taiwan, Province of China. Purpose: APOE4(+) and low education level are known risk factors of Alzheimer’s disease (AD). In this study, we used Tc-99m HMPAO SPECT to depict the influence of education and APOE4 genotypes on the regional cerebral blood flow (rCBF) of AD patients.Materials and Methods: We used Cognitive Ability Screening Instrument to determine AD severity, compared the rCBF of AD patients with APOE4(+)/low education level (LE) to APOE(-)/LE, and APOE4(+)/high education level (HE) to APOE4(-)/HE, and used Statistical Parametric Mapping 99 as the method of Statistical Image Analysis.Results: CASI scores showed no difference between two compared groups after the adjustment for age and education (i.e., z score of CASI). SPM comparisons revealed APOE4(-)/HE patients had relatively higher basal rCBF in bilateral parietal areas than did the APOE4(+)/HE patients. The rCBF of APOE4(-)/LE patients was no significantly different with APOE4(+)/LE patients.Conclusions: Our study showed that AD patients with different APOE4 genotype may have influence on rCBF in high education groups, but not in low education groups. Considering both APOE4 genotype and educational level when interpreting functional brain images may be necessary.

1 (n=15)

2 (n=18)

3 (n=34)

4 (n=35)

MEAN

7,32

9,45

6,19

SD

2,20

2,75

2,05

Total (n=102)

CONCLUSION The research shows a statistically significant difference between the SI of group 1 and the rest of the age groups. The results clearly demonstrate the necessity to establish a specific SI for patients under 50 years old and another for the remainder of the patients. With regards to gender, there were no significant statistical differences found between males and females, to justify any further research to determine a specific SI for this category.

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P341 Post-mortem human autoradiography studies on brains of Alzheimer patients and age matched controls using [125I]desmethoxy-DAA1106 and [125I]desfluoro-DAA1106 B. Gulyas1, B. Makkai2, C. Halldin1, K. Nagy2, P. Kása3, J. Anderson1, T. Suhara4, K. Suzuki4, M. Higuchi4, L. Csiba2; 1Karolinska Institute, Stockholm, Sweden, 2University of Debrecen, Debrecen, Hungary, 3 University of Szeged, Szeged, Hungary, 4National Institute of Radiological Sciences, Chiba, Japan. DAA1106 is a novel peripheral benzodiazepine receptor (PBR) ligand. The binding of 125Ilabelled DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer patients and age matched controls. Following optimisation, binding and blocking parameters with 40 pM ligand conditions were measured. N(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide and N-(5-Fluoro-2phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide were each prepared using 0.3mg of the corresponding Bu3Sn precursor, 80µl MeOH, 40µl [125I]NaI, 40µl 0.2M HCL and 40µl Chloramine-T (1mg/ml). Alzheimer (AD) brains (n = 5) were obtained from patients with clinical diagnosis of Alzheimer’s disease. Four age matched brains served as control. A post mortem neurohistological examination justified the clinical diagnosis and determined Braak grading. Frozen brains were cryosectioned, using a heavy-duty Leika cryomacrotome. The tissue cryosections (thickness 100 µm) were transferred to gelatinized glass plates. The sections were incubated for 60 min at room temperature in TRIS-HCl, HEPES, and salted HEPES buffers (pH 7.4). The ligand concentrations were 20 pM, 40 pM, 65 pM and 133 pM for desmethoxy-125I-

DAA1106, and 40 pM and 80 pM for desfluoro-125I-DAA1106. The sections were then washed in the same buffer, exposed to Kodak Biomax MR film and the autoradiograms were digitized. The quantitative measurements were done on the digitized images. Increased ligand concentrations resulted in increasing binding parameters. Optimal binding and blocking conditions were found at the lower ligand concentrations (20 and 40 pM) and using TRIS-HCL buffer. Using 40 pM ligand concentrations, on the average, the regional binding parameters for both ligands in AD brains were higher than the corresponding parameters in age matched control brains (2.33±0.20 vs 2.18±0.27 and 1.57±0.47 vs. 1.31±0.23 pM/g tissue, AD vs. control; desmethoxy-DAA respectively desfluoro-DAA). The highest binding was found in the hippocampus, thalamus, caudate nucleus, temporal and parietal cortex. The blocking effect was, on the average, 17.67 % (AD) and 11.56 % (control) for desmethoxy-DAA and 12.66 % (AD) and 9.00 % (control) for desfluoro-DAA. The highest blocking effects were found in the hippocampus (26 % and 16 %) and the temporal cortex (18 % and 17 %), followed by other cortical regions. The findings demonstrate that radiolabeled DAA1106 displays a marked binding to human brain tissue of AD patients and age matched controls in the submicromolar range. Regional binding could be markedly suppressed by cold DAA1106. DAA1106 can therefore be regarded as a prospective glia marker in human in vivo imaging studies.

Mental State Examination (initialization score > 16), (b) the DSM IV criteria and (c) the Global Deterioration Scale (5 or 6 stage). Pre and 7 month post therapy brain tomo-scintigraphy was performed with Tc-99m HMPAO. All tomographic studies were reconstructed by typical parameters of filters (Hanning) and attenuation correction (0.12 cm -1). Data from tomographic slices were obtained by using a 25% threshold. Regions of interest (ROIs) were manually drawn over the frontal and temporal lobes of the pre- and post- therapy scans in the transversal section bilaterally. The integrated number of counts over each reconstructed part, that is the number of counts Integrated Over the Volume of each part (IOV). The result of this procedure was the calculation of 2 IOV indices of each patient pre - and post - therapy, respectively. Results The activity in all post-therapy scans was obviously increased compared to the pre- therapy data. The ratio of post- over pre- therapy IOV indices used to indicate semi- quantitatively the increased concentration of activity in post- therapy scans (temporal IOV ratio: 1.6 - 3.2; frontal IOV ratio: 1.8 - 3.6 Conclusion After a 7 month treatment with memantine in FTD subjects the rCBF appears to be not only preserved but moderately improved; increased scintigraphic ratios after treatment are compatible with improvement of functional brain activity, too.

P342

Newly diagnosed mild cognitive impairment: the primary role of Brain Perfusion SPET

K. Ishii1, T. Soma2, A. K. Kono1, K. Sofue1, N. Miyamoto1, A. Sakurai3, K. Murase2; 1Hyogo Brain and Heart Center, Himeji, Japan, 2Graduate School of Medicine, Osaka University, Suita, Japan, 3Daiichi Radioisotope Laboratories, Tokyo, Japan. Purpose: The aim of this study was to investigate regional differences between morphologic and functional changes in the same patients with mild dementia with Lewy bodies (DLB), comparing with those in Alzheimer disease (AD). Subjects and methods: Twenty mild DLB patients (mean age 74.5 y. o, mean MMSE score: 22.8), 20 mild AD patients (mean age 74.1 y. o, mean MMSE score: 22.7) and 20 age and sex-matched normal volunteers (NC) underwent both F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and three-dimensional spoiled gradient echo (SPGR) magnetic resonance imaging (MRI). Fully automatic volumetry of the MRI data was used to obtain whole brain, hippocampal, occipital and striatal volumes, which were compared with the results of a similar analysis of the glucose metabolic data.Results: In DLB patients, volumetric data indicated a significant volume decrease in the striatum, while FDG-PET showed significant glucose metabolic reductions in the occipital lobe compared with those in the normal control group. In contrast, in AD patients, both hippocampal volume and glucose metabolism were significantly decreased and occipital volume and metabolism were preserved.Conclusions: Between mild DLB and AD, different morphologic and metabolic change occurs in the medial temporal lobes and occipital lobe, which demonstrates characteristic pathophysiologic difference of both diseases.

P343 Relation between brain perfusion SPECT and mini-mental state examination in Alzheimer’s disease R. Píchová1, A. Bartoš2, H. Trojanova2, J. Kukal3, O. Lang2; 1Univ. Hosp. Kralovske Vinohrady, Prague, Czech Republic, 2Charles Univ., 3rd School of Medicine, Prague, Czech Republic, 3Institute of Chemical Technology, Prague, Czech Republic. Background: Deterioration in Alzheimer´s disease (AD) can be monitored by short cognitive test such as Mini-mental state examination (MMSE) and single photon emission computerized tomography (SPECT). Aim: We compared decline of cognitive abilities and regional brain perfusion on SPECT. Patients and methods: Ten AD patients (72+-5 years; Mini-Mental State Examination score, 18.1+-5.0) underwent repeated MMSE and SPECT investigations resulting in thirty evaluations. Six elderly patients (average 73 years, range 61-83) with various nondementia diagnoses, but normal brain perfusion were considered as controls. Thirty-six SPECT scans were co-registered to a standardized template in Talairach space, generating mean ratios of uptake referenced to the cerebellum. A voxel-based correlation analysis between regional perfusion ratios and MMSEs were performed using statistical parametric mapping. The whole set of SPECT scans of AD patients were divided into three subgroups based on: 1) rate of cognitive deterioration (decline of MMSE per year - slow, medium, fast) and 2) MMSE score (mild, medium and severe form of AD).Results: MMSE score was significantly related to perfusion in segments of middle temporal lobes - left (r=0.8) and right (r=0.5). The significant correlation between MMSE score and perfusion were found in AD patients with slow and medium decline and in mild and medium form of AD.Conclusions: SPECT perfusion in temporal regions is associated with MMSE score, mainly in slow progression of AD and in mild stages of AD. This study was supported by the research project MSMT 1M0002375201.

P344 Evaluation of memantine on regional cerebral blood-flow in patients with fronto-temporal dementia (FTD) G. S. Limouris1, P. Sideras1, N. Politis2, N. Triantafyllou3, L. Lamprakos1, C. Panayides1, K. Rousopoulos1, D. Kontogeorgakos1, P. Dimitriou1, M. Lyra1, 1University of Athens-Aretaieion Hosp, A. Stavraka1, L. Vlachos4; Radiology Dept, Nucl Med Div, Athens, Greece, 2University of AthensAegineteion Hosp, Psychiatric Dept, Athens, Greece, 3University of AthensAegineteion Hosp, Neurological Clinic, Athens, Greece, 4University of Athens-Aretaieion Hosp, Radiology Dept, Athens, Greece. Aim To investigate the effect of memantine on regional cerebral blood flow (rCBF) and evaluate its diagnostic efficacy in fronto-temporal dementia. Material and Methods In 8 patients (4 m, 4f, aged 52 to 74yrs) and 8 with placebo treated subjects , aged 50-70, suffering from frontotemporal dementia (FTD) the rCBF was imaged after i.v. application of Tc-99m HMPAO (Amersham, Health) in a dosage of 740 MBq. The disease was defined according to (a) the Mini-

A. Marzullo, E. Giovannini, S. Remediani, M. Fioravanti, G. De Vincentis, R. Massa; Section of Nuclear Medicine University La Sapienza, Rome, Italy. Background: Brain perfusion scintigraphy by 99mTc-Ethyl-Cysteinate-Dimer (ECD) has been proven as useful tool in the initial diagnosis of dementia and in the differential diagnosis of the specific dementing disorder. ECD single-photon-emission-tomography (SPET) was also proposed in differential diagnosis distinguishing AD, from frontotemporal dementia (FT), vascular dementia (VD), and Lewys Body Dementia (LBD). Aim: We evaluated the diagnostic potential of ECD SPET in early detection and differential diagnosis of newly diagnosed mild cognitive impairment (MCI) patients (pts).Materials and Methods: 215 pts (115 female and 100 male, 46 to 84 y.o.) with clinical suspicion of initial dementia were examined. Clinical suspicion was categorized as follows: 35 pts with AD, 23 pts with FT, 5 pts with VD and 152 pts with undefined dementia. All pts were intravenously injected with 1110 MBq of 99mTc-ECD and 45 minutes after, SPET scans were obtained by means of a double head Anger camera (Millenium General Electric, Milwaukee, WI, USA) equipped with a high resolution low energy parallel hole collimator. Studies were obtained on a 128 x 128 matrix on a 360 deg orbit, 3 deg per step. Images were reconstructed by filtered back-projection methods applying a Butterworth filter (cut-off: 0.5, power 10) after Chang correction. Tracer distribution was evaluated on transaxial slides by qualitative and semiquantitative methods. Qualitative essay was evaluated on the basis of signal distribution in comparison with age and sex related reference database. Semiquantitative analysis was performed by considering 24 symmetrical region of interest , 12 each side. Data have been expressed as uptake ratio between singles areas and whole cerebellum mean counts. Perfusion index so obtained was considered as abnormal when < 10% than normal reference database.Results: Scintigraphic results diagnosed the 35 clinical AD pts as follow: 14 AD, 10 FT, 1 LBD, 10 inconclusive findings (UF). Of 23 initially categorized FT pts 11 were scintigraphically confirmed as FT, 6 DA, 6 UF. Of the initially 5 VD only one was scintigraphically confirmed whereas 3 were diagnosed as AD and one as LBD. Finally of the 152 clinically uncategorized pts 61 were diagnosed as AD, 37 FT, 6 VD and 3 LBD, 45 showed UF. Discussion: In our large series of studies results confirm the primary role of perfusion SPET brain study in early stages of MCI. In fact it represent a valid tool able to correctly address the therapeutical strategies in the early stages of disease.

P346 A regional cerebral blood flow study of visual hallucinations in dementia A. D. Murray1, R. T. Staff2, K. Benjamin1, C. Wiscik1, H. G. Gemmell2; 1University of Aberdeen, Aberdeen, United Kingdom, 2NHS Grampian, Aberdeen, United Kingdom. Introduction Hallucinations are one of the most common non-cognitive symptoms seen in patients with dementia and occur in 17-41% of patients with Alzheimer’s disease and 12% of patients with vascular dementia. The presence of hallucinations strongly contributes to institutionalisation, reduced patient well-being and increased the burden on carers. A possible mechanism for the origin of hallucinations in dementia is that they arise from a lesion in a particular brain region. Aim In this work we aim to test the hypothesis that, in the context of dementia, visual hallucinations are initiated by a lesion in the visual cortex . Method We imaged 91 patients who were routinely referred to for 99TcmHMPAO brain SPECT imaging as part of their work up for dementia. From this group 28 had been experiencing visual hallucinations. After reconstruction and correction for attenuation we performed a SPM group comparison between those with and without visual hallucinations using gender, age and cerebellar activity as confounding variables. Results After correcting for multiple comparisons we found a regions in the visual cortex of significantly lower perfusion in the hallucinating group than in the group without hallucinations (p<0.001 voxel level, p<0.001 cluster level). Conclusions It has been previously thought that the presence of such non-cognitive symptoms was associated with a greater level of disease severity however these results suggest that visual hallucinations in dementia are caused by defects in the visual cortex.

P347 Cerebrovascular disease is an important confounder in studies of Alzheimer’s disease and can be detected by rCBF SPECT A. D. Murray1, R. T. Staff2, K. Benjamin1, C. Wiscik1; 1University of Aberdeen, Aberdeen, United Kingdom, 2NHS Grampian, Aberdeen, United Kingdom.

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Poster Presentation

Comparison of morphologic and metabolic reduction in mild dementia with Lewy bodies and Alzheimer disease

P345

Introduction: Alzheimer’s disease (AD) is the commonest primary dementia. Cerebrovascular changes are ubiqitous in old age and may co-exist with AD (1). AD is characterised by medial temporal atrophy on magnetic resonance imaging (MRI) and by posterior temporoparietal perfusion defects on cerebral blood flow single photon emission computed tomography (rCBF SPECT) (2). White matter hyperintensities on MRI are probably caused by cerebrovascular disease and correlate with ischaemic change pathologically (3). The association between MRI changes and vascular territory defects seen on rCBF SPECT is unclear. Purpose: To measure MRI vascular changes using MRI in subjects with a clinical diagnosis of AD, and test for association between these findings and the perfusion pattern measured using rCBF SPECT. Methods: Patients: 50 patients (30 male, age range 65-91) who met research criteria for AD, were identified from our database. All patients had undergone brain MRI and rCBF SPECT imaging as part of a clinical trial in AD. MRI: was carried out on a 1.5T GE system (NVi, General Electric Medical Systems, Milwaukee, WI) and included 3D T1, T2 axial and FLAIR axial sequences. SPECT: Brain rCBF SPECT was carried out 30 minutes after intravenous injection of 500MBq 99mTchexamethyl propylene amine oxime (HMPAO) using a SMV dual headed gamma camera. After filtering and attenuation correction, mages were reconstructed in the axial, sagittal and coronal planes. Image analysis: All patients showed medial temporal atrophy on T1W MRI, consistent with AD. FLAIR images were assessed using the Schelten’s scale (4). SPECT images were categorised into two groups: AD only and mixed AD and vascular Results: All patients had some vascular changes on FLAIR MR images. Visual classification of rCBF SPECT images identified 31 in the AD only group and 19 in the mixed group. Testing for differences (Mann-Whitney) in the MR scores between these groups found significantly (p<.05) higher scores in the mixed group. Conclusions: Despite meeting criteria for AD, most patients had significant co-existing cerebrovascular changes on MRI. Schelten’s score of ischaemic lesions on FLAIR images predicts a vascular pattern of perfusion defects on rCBF SPECT. Cerebrovascular disease is an important confounder in brain imaging studies of AD and must be quantified for meaningful data analysis. References: 1. Roman GC. Journal of the Neurological Sciences 2002;203-204:7-10. 2. Jobst KA et al. International Psychogeriatrics 1998;10:271-302. 3. Fazekas F et al. Neurology 1993;43:1693-1689. 4. Scheltens P et al. J Neurol Sci 1993;114:7-12.

P348 Dynamic encephaloscintigraphy and rCBF brain SPECT in determination of blood flow abnormalities in patients with multiple infarct dementia (MID). V. S. Dekan1, A. Emelin2, V. Fokin1, G. Trufanov1, V. Lobzin2; 1Medical Military Academy, Radiology Department, Saint-Petersburg, Russian Federation, 2Medical Military Academy, Neurology Department, SaintPetersburg, Russian Federation. Purpose. The MID is one of the common brain diseases in people in the age over 60 years old. Different brain functions are affected, with devastating consequences for the patient, the patient’s family and society. Rest regional blood flow could have a strategic role in differentiating between MID patients and other dementias (Alzheimer’s disease) or normal controls. The purpose of this study was to evaluate the value of dynamic encephaloscintigraphy and rCBF brain SPECT in differentiation of MID patients and AD patients. Methods. Twenty eight patients (69,5+3,4 years) with MID, five patient with AD (mean age 73 years old) were injected with 99mTc-hexamethylpropylene amine oxime (HMPAO), one dynamic series was taken with one frame per seconds during 120 seconds followed by an rCBF SPECT study. The rCBF SPECT and dynamic images were analysed using commercial software including Patlak Plot brain dynamic curve analysis and rCBF analysis on Lassen corrected images. Results. In all MID patients multiple sites of decreased rCBF were evaluated. It was no any regions of concentration of such sites. Analysis of dynamic curves with calculation of brain perfusion index, which shows activity of tracer extraction from blood, and vessel index of brain, which shows the number of active vessels in brain tissues (calculated in per cents) was helpful in differentiating of MID and non-vessel dementia (AD). Conclusion. rCBF brain SPECT with dynamic encephaloscintigraphy in one study increase specifity for detection of vessel-related dementia and differentiation it from other types (AD). Further studies are needed to evaluate dynamic encephaloscintigraphy with rCBF brain SPECT as a diagnostic tool at the individual level.

P349 Clinical impact of positron emission tomography coincidence system in patients with atypical dementia

by

N. Paquet1, J. A. Couture1, M. Petitclerc1, F. Primeau1, V. Plante2, B. Lefebvre1; 1Hôtel-Dieu de Lévis, Lévis, PQ, Canada, 2Centre hospitalier universitaire de Québec, Québec, PQ, Canada. Objectives: Evaluate the clinical impact of FDG brain tomography (TEP)in the diagnostic and treatment of atypical dementias. Methods: Patients with cognitive decline and uncertain clinical diagnosis were referred for FDG brain tomography with a dual-head coincidence camera (MCDAC Vertex, Phillips). 3mCi FDG were injected after a > 20 minutes rest. A 50 minutes acquisition started 30 to 40 minutes later. Calculated attenuation correction was applied. The qualitative imaging diagnosis was compared to the pre-test hypothesis and to clinical follow-up. The clinician perception of the test utility was evaluated by questionnaire. Three multiple choices questions were asked: how useful was the test (very, moderately, a little or useless), what was its contribution, and the likelihood of asking it again. Results: 31 patients aged 48 to 87 y.o. (70±10 y.o.) were evaluated from March 2004 to March 2005, 17 females and 14 males. Out of these, 25 questionnaires were returned. They were referred by geriatricians(44%), neurologists(24%), gerontopsychiatrists(16%), and family physicians(16%). The clinician pre-test hypothesis were probable Alzheimer disease (AD) (16%), fronto-temporal dementia (FTD)(20%), diffuse Lewy body disease (DLBD) (8%), mild cognitive impairment (MCI) (4%), vascular dementia(12%), many different hypothesis (36%), other(4%). PET diagnosis were AD(64%), FTD(4%), DLBD(8%), mixed dementia (16%), MCI(4%),other (4%). Ninety-two percent (92%) of PET diagnosis were maintained at clinical follow-up. In 80% of the cases, the clinicians rated the test as very useful, and moderately useful in 16%. Only one was considered useless.

S296

The usefulness was attributed to increase in diagnostic certainty (48%), modification of diagnosis (18 %), modification of prognosis (9%), indication to start therapy(18%), other (6%). The referring physicians intended to ask the test again in cases of atypical dementia (93%) or before starting therapy (7%). Conclusions: FDG brain PET with dual head coincidence imaging has a significant clinical impact and is perceived as useful by the clinicians in the management of atypical dementias.

P350 Sensitivity in the diagnosis of Alzheimer’s disease using as criteria the insult of a) one and b) three of the cerebral lobes: a Tc-99m-HMPAO SPET study. G. P. Gerasimou; Ahepa Hospital, Thessaloniki, Greece. Sensitivity in the diagnosis of Alzheimer’s disease using as criteria the insult of a) one and b) three of the cerebral lobes: a Tc-99m-HMPAO SPET study. Gerasimou G P1, Papanastasiou E1, Konidari-Dedousi E1, Liaros G1, Psarrakos K1, Kosta V2, Aggelopoulou T1, Vasileiou O1, Gotzamani-Psarrakou A1, Baloyannis S2. 2nd Laboratory Nuclear Medicine1-1st Neurologic Clinic2, AHEPA University Hospital, Thessaloniki-Greece. Alzheimer’s disease (AD) is a neurodegenerative disorder affecting people aged mainly more than 65 years. Its early diagnosis can help in a better prognosis in terms of neuroprotective treatment application. The aim of this study was to evaluate the utility of Tc-99m-HMPAO SPET study in the diagnosis of AD. One hundred and eight patients with a mean age of 68.9+7.0 years were studied fulfilling the NINDSADRDA criteria for the diagnosis of AD. MMSE test has been performed to all patients and 4 groups were formed: Group A, consisting of 17 patients with a very mild disturbance of the intellectual performance, who had finally developed AD (MMSE 25-28), Group B, 37 patients with mild AD (MMSE 20-25), Group C, 34 patients with moderate AD (MMSE 11-19) and group D, 20 patients with severe AD (MMSE 0-10). Comparatively, 27 normal subjects, aged 68+3.2 years were used as controls. All subjects were submitted to cerebral blood flow (CBF) SPET study after the iv injection of 740MBq of Tc-99m-HMPAO.Using as criterion the onset of a) only one (“loose” criterion) and b) three of the lobes (“strict” criterion) in the temporoparietal regions in all groups plus normal subjects, sensitivity (S), positive and negative predictive value (PPV and NPV) were estimated. Concerning SPET data from the normal subjects, only one has presented reduced CBF in the medial left temporal cortex, considered as false positive. Concerning patients, using as criterion, the insult of only one lobe, S in the diagnosis of AD for groups A, B, C and D was 53%, 75.7%, 88.2% and 95% respectively, PPV 90%, 96.5%, 96.8% and 95% and the respective results for NPV were 76.5%, 74.3%, 86.7% and 96.3%. Using as criterion the insult of three lobes the respective results for groups A, B, C, and D were 47.1%, 73%, 85.3% and 95% for S, 88.9%, 96.4%, 96.7% and 95% for PPV and finally 74.4%, 72.2%, 83.8% and 96.3% for NPV. Tc-99m-HMPAO CBF study has its contribution to the diagnosis of AD, even in doubtful cases, on respect to the clinical evaluation of the patients.

P351 Correlation of Cerebral Blood Flow SPET findings with clinical performance, in patients with Alzheimer’s disease. G. P. Gerasimou; Ahepa Hospital, Thessaloniki, Greece. Alzheimer’s disease (AD) is a syndrome characterized by memory decline plus disturbances of other intellectual performances, like orientation, perception, calculation and praxis and finally speech. The aim of the present study is to compare cerebral blood flow (CBF) SPET findings in patients with AD, with the neuropsychological tests and clinical manifestations and evaluate the clinical impact of this procedure.Materials and Methods: One hundred and sixteen patients (42 males and 74 females, mean age 68.9+7.0 years), with AD were enrolled in the study. MMSE and CAMCOG neuropsychological tests have been performed to all patients. All subjects were injected with 740MBq of Tc99mHMPAO (Ceretec) and SPET study was performed 30min post injection in a single-headed ADAC Ȗ-camera equipment.Results: Patients with mild and moderate dementia (MMSE>20 and between 10-20 respectively) were preceding reduced CBF to the temporal and parietal and/or posterior parietal cortex-symmetrical or asymmetricalbilaterally, whilst subjects with severe dementia (MMSE<10), all the above, plus reduced activity in the frontal cortex. Patients with pre-senile onset of the disease (age<65) were most performing asymmetrical findings. A very significant correlation of the MMSE and CAMCOG scores with reduction of the CBF in the parietal, posterior parietal and frontal cortices bilaterally, plus in the medial and lateral aspects of the temporal cortex on the left hemisphere, was found. Memory recall has been correlated with reduced CBF in the medial aspect of the temporal cortices, as well as in the posterior parietal cortex bilaterally. Disturbances of perception and orientation have been correlated with reduced CBF in the temporal and parietal cortices, of attenuation and calculation with parietal and frontal cortices, of praxis with posterior parietal and lateral aspect of the temporal cortices and aphasia with reduced activity in the lateral temporal, frontal and parietal cortex on the left hemisphere. Treatment of the patients was re-evaluated according to the clinical plus CBF-SPET data. An heterogeneity of the findings, when correlated with the intellectual performance of the patients, can be attributed to multiple correlations and different stages of the disease.Conclusions: CBF-SPET study correlates well with the clinical manifestations of patients with AD and has clinical impact, contributing to the follow-up and management.

P352 Effects of electro-acupuncture on regional cerebral blood flow in normal volunteers evaluated by brain SPECT and SPM D. Kim; Kyung Hee University, Seoul, Republic of Korea. Aim: Acupuncture has been applied on the rehabilitation after stroke in Asia for thousands of years. Recently we have demonstrated that electo-acupuncture(EA) at traditional acupoints(LI 4 and LI 11) for stroke significantly increased rCBF at anterior cerebral artery territory. (Eur J Nucl Med Mol Imaging 2005;32(Suppl 1):S182) This study was performed to evaluate the effect of another well-known acupuncture point for stroke on rCBF using brain SPECT and SPM.Materials and Methods: We studied 10 normal volunteers, 5 men, 5 women, and aged 2432 years. Baseline brain SPECT images were obtained with triple head gamma camera(MultiSPECT3, Siemens, USA) after intravenous administration of 925 MBq of Tc-99m

and cbOEFBO-AI was maximum at Į = 0 (without CBV correction), and decreased with a greater Į.

Correlations between qOEF-AI vs.cbOEF-AI qOEF-AI vs. cbOEFSS-AI

qOEF-AI vs. cbOEFBO-AI

Į Slope R2

Slope R2

0.0

0.64

0.96 1.00

0.84

0.3

0.68

0.98 1.05

0.84

0.5

0.71

0.98 1.09

0.83

P353

0.7

0.73

0.98 1.13

0.82

Assessment of bone marrow cell distribution by radioactive labeling in acute ischemic stroke

1.0

0.78 0.95

P. L. Corrêa1, C. T. Mesquita1, R. M. Felix1, J. C. Azevedo1, G. B. Barbirato1, M. Mendonça1, A. Manfrim1, G. Freitas2, C. H. Falcão1, C. Gonzalez1, S. Alves3, R. Borojevic2, H. Dohman3; 1Hospital Pró-Cardíaco, Rio de Janeiro, Brazil, 2UFRJ, Rio de Janeiro, Brazil, 3Procep, Rio de Janeiro, Brazil. Stem cell transplantation has emerged as a potential therapy for the penumbra zone in ischemic stroke. The ability to track stem cell transplants in the brain by neuroimaging may be valuable in assessing the ability of these cells to engraft the damaged tissue. We evaluated the feasibility of monitoring autologous bone marrow mononuclear (ABMMN) cells implanted into the brain after acute ischemic stroke by brain scintigraphy with ABMMN labeled with 99mTc - HMPAO. Here, we report the results of our first patient submitted for the use of this technique. Case Report: A 37-year-old man was suddenly afflicted by difficulty in speaking and confusion. Neurological examination showed sensitive aphasia and apraxia, right-side hypoesthesia and right homonymous hemianopsia. His National Institute of Health Stroke Scale score was 5. MRI showed an acute ischemic infarct in the territory of the posterior branch of left middle cerebral artery.The patient and his wife agreed to participate in a protocol of ABMMN cell transplantation for acute ischemic stroke approved by the National Ethical Committee. SPECT perfusion images with 99mTc-ECD demonstrated hypoperfusion in the left temporal and posterior parietal regions. Nine days after the stroke he received 3.0 x 108 ABMMN cells delivered to the left cerebral middle artery via an intra-arterial catheter. Approximately 1 % of the ABMMN implanted cells were labeled with 150 MBq of 99mTc-HMPAO. The perfusion images were compared with SPECT views of the brain obtained eight hours after ABMMN-labeled cell delivery. These revealed intense accumulation of the ABMMN-labeled cells in the infarcted and peri-infarcted area, which were more intense than the topography of the anterior division of the middle cerebral artery, probably due to posterior branch occlusion. A whole-body scan was done and showed left brain, liver and spleen uptake. One major challenge for the development and refinement of stem cell transplantation is to map spatial distributions in situ . The described imaging approach is ideally suited for the noninvasive monitoring of cell engraftment, and permitted the observation of the implanted cells with high contrast against the host tissue. 99mTc - HMPAO can be used to track labeled ABMMN cells for in vivo cell visualization, and that brain SPECT imaging with labeled ABMMN cells is a feasible noninvasive method for studying the fate of transplanted cells in vivo. Additionally, our findings suggest the engraftment of the ABMMN cells in the brain infarcted area, a prerequisite for the success of stem cell therapy.

P354 Diagnosis of misery perfusion using noninvasive 15O-gas PET M. Kobayashi1, H. Okazawa1, T. Tsuchida2, K. Kawai3, Y. Fujibayashi1, Y. Yonekura4; 1Biomedical Imaging Research Center, University of Fukui, Fukui, Japan, 2Department of Radiology, University of Fukui, Fukui, Japan, 3 Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan, 4Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. Aim: To avoid the arterial blood sampling and complicated analyses in 15O-gas PET studies, noninvasive technique using the count-based method is a promising method for evaluation of misery perfusion. Measurement of asymmetric oxygen extraction fraction (OEF) increase in cerebrovascular disease (CVD) using count-based method was compared with quantitative OEF to evaluate whether it can correctly detect misery perfusion.Materials and Methods: Eighteen patients (61±16y) with ischemic CVD were studied for the measurement of hemodynamic parameters using the 15O-gas steady-state method. The subject also underwent H215O-PET for cerebral blood flow measurement using the bolus injection of tracer. Count-based ratio images of 15O2/C15O2 (cbOEFSS) and 15O2/H215O (cbOEFBO) were calculated and asymmetric indexes (AI) were obtained using the regions of interest drawn on the bilateral cerebral cortices. These AI were compared with AI of quantitative OEF (qOEF-AI). To remove the influence of blood volume on regional values, the cerebral blood volume (CBV) correction using counts of C15O image was applied to cbOEF because qOEF was corrected for the effect of CBV. The contribution factor for the correction was defined as variable Į, and the effect of the correction was evaluated with an assumption that this factor would useful to estimate cbOEF-AI as qOEFAI, and that Į should have an optimal value for correction of blood volume.Results: cbOEFSSAI and cbOEFBO-AI were linearly well correlated with qOEF-AI. The regression lines were y = 0.64x + 0.36 and y = 1.00x + 0.02 with the correlation coefficient of 0.98 and 0.92, respectively. cbOEFSS-AI significantly underestimated qOEF-AI (P < 0.05; paired t-test), especially with a greater AI. The difference between cbOEFBO-AI and qOEF-AI was not significant. The slope between qOEF-AI and cbOEFSS-AI was improved by the CBV correction with the increase of Į; however, that of qOEF-AI and cbOEFBO-AI was apart from the line of identity with a greater Į. The optical Į between qOEF-AI and cbOEFSS-AI was defined as 0.5 because the correlation coefficient was maximum when Į was close to 0.5. Correlation coefficient between qOEF-AI

1.19 0.77

Conclusions: cbOEFBO-AI can fairly estimate AI of OEF without CBV correction, whereas cbOEFSS-AI would require CBV correction for better estimation. The count-based method would be useful in clinical studies for the evaluation of misery perfusion in ischemic CVD with less invasive procedure.

P355 Brain perfusion in patients with arterial hypertension: relationship with cognitive function and MRI N. Y. Efimova, V. I. Chernov, I. Y. Efimova, P. I. Lukyanenok, S. V. Triss, Y. B. Lishmanov; Institute of Cardiology, Tomsk, Russian Federation. Aim: to evaluate relationship between regional cerebral blood flow (rCBF), magnetic resonance imaging (MRI) parameters and cognitive function in patients (pts) with arterial hypertension (AH).Materials and Methods: The study involved 31 patients with moderate essential hypertension investigate by SPECT with 99mTc- HMPAO, brain MRI and comprehensive neuropsychological testing. Fifteen pts without angiographic signs of carotid atherosclerosis, ischemic disease and AH, neurological and psychiatric disorders were investigated as control group. Brain SPECT slices were divided into 14 symmetrical (right and left) regions of interest per patients: inferior and superior frontal lobes, temporal, anterior and posterior parietal, occipital lobes and cerebellar hemispheres. Regional cerebral blood flow (ml/100g/min) in these regions was calculated. The presence of cortical or lacunar infarcts was evaluated. Ventricular, subarachnoidal space and sulcal enlargement, periventricular hyperintensities, deep white matter hyperintensities and index of liquor hypertension were scored. The ventricular-to-intracranial width ratio was also measured. All pts had no focal neurological symptoms.Results: MRI abnormalities were detected in 29 pts. All of them had dilatation of subarachnoidal space and disorder of liquor dynamic. Periventricular hyperintensities and ventricular enlargement were founded in 12 pts. Hypoperfused regions were revealed in 27 pts. Relationship between rCBF, MRI parameters and cognitive function was found. Deterioration of immediate verbal memory correlated well with decrease in rCBF in left posterior parietal region (R2=0.225; p=0.035), in right and left temporal regions (R2=0.20; p=0.048, R2=0.262; p=0.021, correspondingly), in left occipital region (R2=0.327; p=0.021), as well as with index of liquor hypertension (R2=0.26; p=0.015) and increase in periventricular hyperintensities degree (R2=0.16; p=0.030). Attention impairment related to diminution in cerebral perfusion in right posterior parietal region (R2=0.27; p=0.022), left superior frontal region (R2=0.33; p=0.011), right temporal region (R2=0.346; p=0.008), in right and left occipital regions (R2=0.279; p=0.02, R2=0.24; p=0.033, correspondingly) and increase in periventricular hyperintensities degree (R2=0.221; p=0.01), sulcal enlargement (R2=0.197; p=0.018). Significant correlation was shown between psychomotor slowing and worsening of rCBF in right temporal region (R2=0.21; p=0.042), left inferior frontal region (R2=0.201; p=0.047), right anterior parietal region (R2=0.352; p=0.015), as well as with increase in periventricular hyperintensities degree and sulcal enlargement (R2=0.33; p=0.003, R2=0.182; p=0.021, correspondingly). Conclusion Our results suggest that neurocognitive dysfunction in patients with arterial hypertension was connected with the decrease cerebral perfusion and MRI abnormalities.

P356 How accurately can reductions in baseline CBF and vasoreactivity detect misery perfusion in cerebrovascular disease? H. Okazawa, T. Tsuchida, Y. Arai, M. Kobayashi, T. Mori, T. Tsujikawa, Y. Yonekura, Y. Fujibayashi; University of Fukui, Eiheiji-cho, Japan. Objectives: To investigate diagnostic accuracy for misery perfusion using criteria defined by baseline cerebral blood flow (CBF) and cerebral vasoreactivity (CVR) in the acetazolamide (ACZ) challenge, patients with chronic cerebrovascular disease (CVD) were studied. Methods: 15O-water PET studies were performed in 115 patients (mean age = 64 ± 9 y) with major cerebral arterial stenoocclusive disease (> 70% stenosis) at baseline and 10 min after the ACZ injection to evaluate regional changes in rCBF. All patients also underwent 15O-gas PET studies using the steady-state method to measure total cerebral blood volume (CBV), OEF and CMRO2. Misery perfusion (stage II ischemia) was defined by the threshold determined by the mean + 2SD of OEF obtained from 15O-gas PET scans in healthy volunteers. Correlation between absolute OEF and % rCBF change in the ACZ test or asymmetry index (AI) of OEF in the affected cerebral hemispheres was evaluated. Same regions of interest were applied for all images of each patient. Diagnostic accuracy in detection of misery perfusion using the criteria determined by baseline CBF and CVR was evaluated in all patients and only in patients with occlusive lesions (>98% stenosis). Results: The mean of % increase in rCBF induced by ACZ was significant in both hemispheres of all patients with CVD although there was a subgroup of patients who showed a significant reduction of the rCBF increase in the affected hemisphere. CVR showed a weak correlation with OEF-AI but not with absolute OEF. Ten of 24 patients with misery perfusion showed a significant CVR decrease. Using criteria determined by significant decreases in CVR and baseline CBF, misery perfusion was detected with sensitivity of 42% and specificity

S297

Poster Presentation

ECD. Seven days after baseline brain SPECT, EA(GFP-91, Siemui Co, Japan) was performed at two traditional acupoints (GB 34 and GB 39) for 15 minutes. Tc-99m ECD was injected immediately after acupuncture and post-acupuncture SPECT images were obtained. Acupuncture-induced changes in rCBF were studied by SPM99 (statistical parametric mapping) with a threshold of P= 0.01.Results: GB 34 and GB 39 EA increased rCBF in both hemispheres including Rt ventral posterior cingulate cortex(Brodmann area (BA) 23), Lt superior temporal, anterior transverse temporal(BA 22, 41), Lt parastriate, peristriate(BA 18, 19), Rt occipitotemporal, angular(BA 37, 39), Lt rostral postcentral, caudal postcentral and preparietal(BA 2, 3, 5).Conclusions: GB 34 and GB 39 EA significantly increased cerebral perfusion particularly at the middle cerebral artery territory. This result was different with our previous study that LI 4 and LI 11 EA increased rCBF at the anterior cerebral artery territory. This study shows a significant correlation between the traditional acupoints for stroke and specific areas. More studies are required to evaluate the mechanism of acupuncture on cerebral blood flow and it's clinical implication.

of 95% in all patients. Patients with occlusive lesions showed higher sensitivity with slightly lower specificity. Threshold determined by baseline CBF alone provided similar diagnostic accuracy in both groups, which was more accurate than the detection by asymmetry index of OEF (OEF-AI). Conclusions: The reduced rCBF response after the ACZ challenge is not necessarily associated with misery perfusion in the affected cerebral regions of patients with CVD. The two hemodynamic parameters might interact as shown in the correlation between AI of OEF and % change in rCBF. The ACZ challenge for CVD would fairly detect cerebral regions of misery perfusion by reductions of CVR and baseline CBF.

P357 F-18-FDG MicroPET scans on transient focal ischemic rat stroke model K. Y. Chen, C. J. Chang, K. H. Wu, H. H. Liu, C. C. Chen, Y. K. Fu; Institute of Nuclear Energy Research, Taoyuan County, Taiwan, Province of China. Background: Middle cerebral artery (MCA) occlusion in rodent is a widely used experimental model of ischemic stroke. Histological studies of MCA occlusion have concentrated on the acute phase of ischemia. To depict the dynamic processes that pathophysiological events may occur over an extended period, behavior observation has been the major approach employed. Small animal Positron Emission Tomography (microPET) is a sophisticated nuclear imaging modality that affords researchers the ability to conduct both functional and molecular imaging in vivo without sacrifice the animals. The aim of this study was to evaluate the role of MicroPET scan with 18F-fluorodeoxyglucose (FDG) in the detection of the infarct regions in the MCA occluded rats.Materials and Methods: Male Sprague-Dawley rats were subjected to both common carotid arteries (CCAs) and right MCA occlusion for 60 min followed by reperfusion. Neurological scores (0-4) were assessed by behavior observations after recovered from surgery. MicroPET/18F -FDG scans were performed at 24 hours,72 hours and 96 hours after surgery. The rats were administrated 185 MBq of 18F -FDG via tail vein and images were acquired with a Concord R4 microPET. Isoflurene anesthesia was maintained during data acquisition. Uptakes of 18F-FDG in bilateral cortex to striatum areas were calculated as %ID/mL. The infarct areas were evaluated by the ratio of %ID/mL in right and left sides. The results were compared with the neurological scores.Results: There were 11 rats undergone transient MCA occlusion surgery in this study. The neurological scores varied from 0 to 4 as estimated by behavior test. Images of microPET/18F -FDG showed infarct regions were located at right side frontal cortex as expected. Uptakes of 18F-FDG in lesion areas were decreased from 0 to 15% when compared with the opposite intact side. Recovery from the lesions can be detected from the images and quantified at 24 hours,72 hours and 96 hours post ischemic procedure. Some microPET images indicated the presence of focal ischemia even the behavior findings were normal.Conclusions: Major advantage of the F-18-FDG MicroPET scan on transient focal ischemic model is durative detection of infract area. Our results revealed the F-18-FDG MicroPET technique provides a sensitive and reliable way to assess the cerebral ischemic lesion on rodents.

P27 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Neurology/Psychiatry: Movement Disorders P358 Brain 18F-FDG positron emission tomography study of kennedy disease - a preliminary study W. Chang1, T. Lai2, B. Soong2, R. Liu3, S. Wang1; 1National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taipei, 2 Taiwan, Province of China, Department of Neurology, Taipei Veterans General Hospital, Taipei, Taipei, Taiwan, Province of China, 3National Yang-Ming University Medical School, Taipei, Taipei, Taiwan, Province of China. Objective: Kennedy disease (KD) is an X-linked spinal and bulbar muscular atrophy, is a neurodegenerative disorder characterized by loss of lower motor neurons. The central nervous system was not reported to be affected by light microscopy studies. However, proton magnetic resonance spectroscopy (MRS) studies have shown significant reduction of NA/Cho and NA/Cr metabolite ratios in the primary motor cortex of the brain, and the results have challenged the previously belief. The pattern of FDG PET was not recognized before. We reviewed the PET images of 6 KD patients confirmed genetically, and the preliminary PET results are presented as follows. Method: We studied 6 patients with KD from 5 unrelated families. The age at diagnosis was ranged from 35 to 48 years. All the subjects with KD had an increased number of trinucleotide CAG repeats ranging from 44 to 48 within the exon-1 coding regions of the androgen receptor gene, (forward primer TCC AGA ATC AGT TCC AGA GCG TGC, reverse primer GCT GTG AAG GTT GCT GTT CCT CAT). Their EMG/NCS were also analyzed. The brain positron emission tomography (PET) was performed after injection of 10 mCi (370 MBq) 18FFDG.. All images were read by two experienced nuclear physicians. Results: The results of EMG/NCS consistent with sensory and motor neuronopathy and are aroused that primary motor and/or sensory cortex may involvement in KD patients. By visualized observation, the brain PET studies reveal definitively abnormal but inconsistent findings. Diffuse or multifocal cortical hypometabolic pattern can be noticed. The effected areas could include the frontal, parietal, temporal cerebral cortices and cerebellum. Even PET images disclose widespread involvement of the brain, but the findings are clinically asymptomatic. Besides, there is no relationship between disease severity and metabolic pattern in this study. Conclusion: This FDG PET study further confirms that neuronal metabolic abnormality exist in the cerebral cortices in KD patients. The PET images revealed diverse cerebral dysfunction not only located in the motor and sensory cortices. Some patient with KD may exhibit unrecognized subclinical disease process, although there have no clinical or pathological evidence. Increase in patient numbers may help elucidate the real features of cerebral dysfunction in KD. Key words: Kennedy disease; Positron emission topography, 18F-FDG Neurodegenerative disorder

S298

P359 In vivo evaluation of [11c](+/-)dihydrotetrabenazine MicroPET for the visualization of dopaminergic innervation in the rat striatum M. Collantes1, I. Peñuelas2, L. Álvarez-Erviti3, J. M. Martí-Climent2, G. Quincoces2, M. Ecay1, J. Arbizu2, J. Obeso3, J. A. Richter2; 1MicroPET Research Unit, CIMA-CUN, University of Navarra, Pamplona, Spain, 2 Nuclear Medicine Department, University Hospital, University of Navarra, Pamplona, Spain, 3Movement Disorders Laboratory, Neurosciences, CIMA, University of Navarra, Pamplona, Spain. [11C](+/-)dihydrotetrabenazine (11C-DTBZ), an in vivo marker for vesicular monoamine transporter VMAT2, has successfully been used as an excellent tracer for evaluation of PD patients. PET studies of presinaptic innervation of the dopaminergic system with 18F-DOPA can not be used for rat models of Parkinson's disease (PD) due to high peripheral decarboxylation of this radiotracer in this animals. AIM: Evaluate the utility of 11C-DTBZ for high resolution functional imaging of the dopaminergic system in the rat.Materials and Methods: 10 control animals were used (6 Wistar and 4 Sprague-Dawley rats). As an ideal internal control, striatal dopaminergic degeneration was induced in a rat by stereotaxic unilateral injection of 6hydroxydopamine (6-OHDA). Scans were performed in a Mosaic MicroPET (Philips). A 40 minutes list mode acquisition was started at the injection of 11C-DTBZ (75 MBq). Regions of interest (ROIs) were drawn over the right and left striatums and on a reference region (cerebellum) to obtain time-activity curves. For further analysis, the ROIs were placed in the summed images from the minutes 15-40, where the 11C-DTBZ uptake was evaluated.Results: High quality images with clear uptake in the striatum and low background were obtained in all the studies. The specific uptake was estimated by calculating the striatum/cerebellum concentration ratio. Striatum asymmetry (right/left) was also calculated (Table ) (Data are shown as mean ±SEM). In the unilateral 6-OHDA lesion a similar 11C-DTBZ uptake in the ipsilateral striatum as the cerebellum was seen, with a ratio lesion/cerebellum of 0.93. The non-lesioned (contralateral) striatum/cerebellum ratio was 1.94, a value similar to the total mean.Conclusions: The symmetry between striatums and the absence of uptake in the 6-OHDA lesion demonstrate the specificity of the binding. However, there are 11C-DTBZ uptake differences between rat lineages that should be considered for proper model validation. These data reveal that PET studies of 11C-DTBZ are appropriate for the visualization of dopaminergic innervation in the striatum of the rat and can be used in the evaluation of different experimental paradigms in rat models of PD.

P360 123I-FP-CIT specific striatal binding assessed by SPET in PARK2 and PARK8-linked Parkinson’s Disease R. Benti1, I. U. Isaias2, G. Marotta1, S. Goldwurm2, R. Cilia2, M. Carletto1, A. Antonini1, M. Rognoni1, P. Gerundini1, M. Gasparini1; 1IRCCSOspedale Maggiore, Milano, Italy, 2Istituti Clinici di Perfezionamento, Milano, Italy. 123I-FP-CIT striatal binding was assessed by mean of brain SPET to characterise the dopaminergic degeneration in two common forms of genetic parkinsonism: PARK8 and PARK2. Methods: SPET data obtained in these forms of genetic PD were compared with a group of patients with Idiopathic Parkinson’s Disease (IPD) who tested negative for both genetic mutations. 123I-FP-CIT SPECT studies were obtained using a dedicated gamma camera in 7 patients with familial parkinsonism carrying a mutation on the gene locus PARK2 (chromosome 6q25.2-27) and in 10 patients with a mutation on the gene locus PARK8 (Gly2019Ser mutation) and in 16 IPD patients with no mutation in the same loci. PARK2 patients had mean age 50±15ys and disease duration15±6ys; PARK8 patients had mean age 62±14 and disease duration 9±3ys; IPD patients had mean age 60±9ys and disease duration 8±5ys. Specific Striatal Binding (SSB) of FP-CIT was calculated in a 2.54 cm thick reference section including striatal structures and occipital cortex as non-specific reference, after iterative reconstruction (OS-EM algorithm), 3D filtering and reorientation of SPECT sections. Results: UPDRS III motor score was 27.5±17.6, 21.6±6.6 and 21.0±9.0 in PARK2, PARK8 and IPD. Mean SSB values in putamen were 0.58±23, 0.65±0.18 and 0.61±0.20 in PARK2, PARK8 and IPD respectively. Mean SSB values in caudate were 0.91± 0.35 1.05±0.25 and 1.06±0.31 in the same groups. We found no differences between SSB values and UPDRS III motor score in PARK2, PARK8 and IPD. Side UPDRS III score and contralateral SSB values in caudate and putamen were significantly correlated in all groups studied.Conclusions: We found comparable degrees of dopamine transporter loss in both PARK8 and PARK2 patients, with asymmetrical striatal involvement consistent with clinical asymmetries. 123I-FP-CIT striatal binding was similar in patients with both forms of genetic parkinsonism vs. IPD. Disease duration in PARK2 patients was longer vs. both PARK8 and IPD (p=0.01) and therefore a greater DAT loss might been expected in PARK2 group, suggesting a slower rate of SDAT density decrement in PARK2 course versus PARK8 and IPD.

P361 An assessment of the stability of Specific Binding Ratios for DaTSCAN with different geometries. G. Shabo, A. G. Kettle, M. J. O'Doherty; Canterbury, United Kingdom.

Kent & Canterbury Hospital,

Aim This study demonstrates the effects of the camera positioning and the applied image reconstruction methods on measured Specific Binding Ratios (SBRs). Materials & Methods Using the GE Healthcare supplied striatal brain phantom filled with 123I solutions as per the supplied instructions, tomographic data sets were acquired at different radii of rotation. Reconstruction was performed by filtered backprojection, with or without Chang attenuation correction and additionally by iterative reconstruction. Analysis by the Southampton method to estimate the SBRs for the left and right striata was performed on the reconstructed transverse slices. Analysis was performed by a single operator 3 times to gauge reproducibility of the software. Results Results showed a trend for the measured SBRs to numerically increase as the radius of rotation increased. From our clinically best radius obtainable from a typical patient,

12.5 cm to a radius of 18.5 cm which represents a worst case set up for a ‘difficult’ patient SBRs calculated rose from 5.40 to 6.50 when reconstruction was by filtered backprojection. For iterative reconstruction the equivalent values are 4.96 and 5.80. Applying the Chang attenuation correction scales these figures by approximately 18%. Conclusion Reliance on the Specific Binding Ratios to categorise DaTSCAN results and monitor disease progression in the clinical setting, a department needs to perform imaging with reproducible geometry. To accommodate all patient builds the centre of rotation chosen will not be optimal for best qualitative image acquisition. Reconstruction algorithm influences measured Specific Binding Ratios and local normal ranges will be required for a department’s preferred methodology.

Conclusions. Striatal uptake indexes in the PD all > MSA , but ns. There is no asymmetrical uptake of DAT-scan in PD comparatively to MSA as shown in previous studies. Moreover antero-posterior indexes are the same in PD and MSA (eg C/P). Striatal ratios decrease more rapidly at follow up in MSA group comparatively to PD group, but ns. The semi-quantitative method is reproducible. Differentiating PD from MSA patients, at early stage or at follow up, is impossible with DAT-scan. The size of our population and the absence of anatomical references to draw perfect striatal ROI induce methodological skew. Nevertheless DAT-scan data alone is insufficient to make an individual diagnosis between PD and MSA, for that it is necessary to associate imaging data of dopamine transporters and of D2 receptors.

P362

P364

Impact of scatter and attenuation correction on 123I-FP-CIT quantification

Quantitation of digitized (DATSCAN) imaging for accurate differentiation of parkinsonism and essential tremor

A. Dobbeleir, H. Ham, I. Goethals; University Hospital, Ghent, Belgium.

M. Lyra1, D. Pappas2, B. Kostakis1, C. Chatzigiannis1, C. Skouroliakou1, J. Jordanou1, L. Vlahos1, G. Limouris1; 1Athens University, A' Radiology Department, Athens, Greece, 2Airforce General Hospital 251, Athens, Greece.

P363 Is I 123FP-CIT(DAT-scan) brain SPECT usefull to differentiate multiple system atrophy (MSA) from idiopathic Parkinson’s disease (PD) at early stage of the disease or during follow up ? N. Chany-Mac Dougall, L. P. Collombier, G. Castelnovo, J. R. Hauet, V. Boudousq, P. O. Kotzki, P. Labauge; CHU de Nîmes, Nîmes, France. Is I 123FP-CIT(DAT-scan) brain SPECT usefull to differentiate multiple system atrophy (MSA) from idiopathic Parkinson's disease (PD) at early stage of the disease or during follow up ? Background : Diagnosis between PD and MSA is difficult especially at early stage. It is based on the clinical features and there is a considerable overlap between these diseases. Objectives. We used DAT-scan brain SPECT to estimate differences between MSA and PD at early stage and during follow up. Methods. 2 DAT-scan SPECT were performed : 1 at diagnostic time and 1 during follow up, in 17 patients with PD and 16 with MSA. Imaging was done with 3 heads camera SPECT : 3 hours after IV of 148 MBq DAT-scan. Manual ROI were drawn by 4 readers on 8 added transaxial slices showing the greatest striatal uptake (18,4 mm). 7 regions of interest (ROI) : right, left caudatus (RC, LC), right,left putamen (RP, LP), entire right, left striatum (RS, LS), occipital cortex (OC). 6 indexes calculated as the ratio of mean count rate eg (RC-OC)/OC. Asymmetry (high/low uptake for C, P, S) and antero-posterior indexes (RC/RP , LC/LP) were calculated. The same set of ROI was used to analyze the two SPECT of each patient. Results. Semi-quantitative method is concordant between the 4 readers : excellent interindividual correlations with intra-class correlation coefficient > 0,97. Mean indexes of 4 readers:

Indexes

RC

LC

RP

LP

RS

LS

PD

1.94 ± 0.65

1.96 ± 0.74

1.32 ± 0.64

1.34 ± 0.70

1.52 ± 0.60

1.52 ± 0.66

MSA

1.84 ± 1.05

1.79 ± 0.97

1.26 ± 0.86

1.30 ± 0.91

1.45 ± 0.90

1.45 ± 0.90

ns

ns

ns

ns

ns

ns

Asymmetry indexes: PD = 0.89, MSA = 0.88 and antero-posterior indexes PD = 1.64, MSA = 1.64 Variation of indexes are exposed in next table.Time between 2 spect in year is : 1.50 for PD, 1.56 for MSA.

Variation in %

RC

LC

RP

LP

RS

LS

Median value PD

- 9.86

- 15.04

-17.10

- 7.93

- 10.33

- 9.92

Median value MSA

- 17.31

-9.64

- 30.08

- 14.56

- 22.58

- 18.49

ns

ns

ns

ns

ns

ns

AIM: To extract parameters by digitized processing of [123I]-FP-CIT (DATSCAN) images to differentiate between parkinsonism and essential tremor (ET).Methods:. DATSCAN is a cocaine analogue that binds to presynaptic dopamine. Imaging of dopamine transporters, situated in the membrane of dopaminergic neurons could detect degeneration of the dopaminergic nigrostriatal pathway. Datscan imaging studies have shown the ability to detect loss of striatal dopamine transporters. This would allow distinguishing Parkinson’s from Essential tremor. It is valuable to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using the digitized data of Datscan imaging. [123I]-FP-CIT SPECT imaging was conducted in a study of 24 patients with a diagnosis of Parkinsonism compared with 10 ET diagnosed cases. All patients were scanned during a 12-month period. Using Datscan, we have imaged the striatal dopamine transporters in our two groups of patients. Degeneration of the nigrostriatal pathway was found scintigraphically in the first group. In second group of 10 subjects no degeneration was found scintigraphically. We analysed the image data producing a dicom format image file. We have transferred the dicom images in a PC and saved in an uncompressed bitmap format in order to be processed by Interactive Data Language (IDL) tools. Oval ROIs are created around the striatum while rectangular ROIs include caudate and putamen uptake data. Via IDL we integrated an array oriented language and a graphical display technique by profiles of the regions of interest data. Quantitative profile indices were extracted and ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen imaging and compared with ratios obtained in 3 volunteer healthy controls. Striatal uptake ratio and profiles were graded from normal up to 4 abnormal levels. Group of ET subjects covered the 1 and 2 abnormal grades.Conclusions: Quantitative processing of Datscan images is a useful diagnostic test in the differential diagnosis of tremor disorders. Semi-quantitative analysis of specific: non-specific caudate and putamen uptake were consistent with the results of visual inspection and clinical diagnosis.Our results show that quantitative analysis of Datscan images provides an objective way to extract and interpret image data. The performance of a pattern recognition program can aid to detect parkinsonism in early stage.

P365 123I FP-CIT SPECT and 99mTc HM-PAO SPECT combined use in patients with associated movement and cognitive disorders S. Nuvoli1, V. Agnetti2, A. Nieddu3, K. Paulus2, M. E. Solinas1, A. Falchi1, F. Chessa1, A. Spanu1, G. Madeddu1; 1Nuclear Medicine DPT, University of Sassari, Sassari, Italy, 2Neurology DPT, University of Sassari, Sassari, Italy, 3 Geriatric DPT, Policlinico Sassarese, Sassari, Italy. AIM: We investigated the usefulness of brain SPECT with 123I FP-CIT and 99mTc HM-PAO in patients with associated movement and cognitive disorders.Materials and Methods: We enrolled consecutively 30 patients, 20 males and 10 females, aged 37 to 82 yrs (65±9) all affected by associated movement and cognitive disorders: 12 had advanced Parkinson’s disease (PD) (Hoehn & Yahr scale: 2.0±0.39; range: 2-3), 5 parkinsonism (P), 6 advanced Alzheimer Dementia (AD), 4 Lewy body dementia (LBD), 2 psychiatric catatonia (PC) and 1 vascular tremor (VT). Mini Mental State Examination (MMSE) was low only in AD cases. CT and/or MR had normal or aspecific findings in 16 cases and gliosis in the remaining 14. In all patients 123I-FP-CIT (DaTscan, Amersham-GE) SPECT was performed by dual head gamma camera with fan beam collimators (180°, 128x128 matrix size, zoom factor 1, 30 sec frame time, 3° angular step). At qualitative analysis SPECT was classified as normal (striatal omogeneous and symmetrical tracer uptake) or pathological (striatal symmetrical or asymmetrical uptake defects); the patients also underwent SPECT with 99mTc HM-PAO (Ceretec, Amersham-GE) after 740 MBq i.v. injection using the same gamma camera and protocol acquisition.Results: 123I- FP-CIT SPECT was pathological in 18/30 cases (all 12 PD, 3 LBD, 2/5 P, 1/1 PV) and normal in the remaining 12 (6/6 AD, 3/5 P, 1 LBD, 2/2 PC). Nine PD patients had involvement of both putamen (4 patients also one caudate) and the remaining 3 only one putamen; bilateral putamen involvement was also ascertained in 3 LBD and in 1 P, while monolateral in the remaining 3 patients. Bilateral defects at 99mTc HM-PAO SPECT were present in all 6 AD (4 temporo-parietal, 2 fronto-temporal) in 8/12 PD (5 temporo-parietal, 2 fronto-parietal) and in all 3 LBD (temporo-occipital). Diffuse hipoperfusion cortical areas were ascertained in all P while multifocal areas in the only VT case. Both SPECT were normal in the 2 PC cases.Conclusions: these data seem to demonstrate that the combined use of receptorial and perfusion brain SPECT was useful to correctly evaluate the patients with associated movement and cognitive disorders, in our cases. In particular, it was possible to detect or exclude an associated dementia in advanced PD with cognitive abnormalities, while MMSE was uneffective, as well as to identify or exclude an associated PD in LBD and AD patients with movement disorders. These results are expecially important to planning the most appropriate therapy.

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Purpose: It is well known that partial volume effect has a huge effect on quantification values of small organs as the striatum. We investigated the additional influence of scatter and attenuation correction on striatal uptake for three quantitative methods.Methods: Twenty 123I-FP-CIT studies were performed with a 20% energy window centred around 159 keV and 2 scatter windows (11% below and 9% above this window). A 50cm long catheter filled with 740 kBq 123I was fixed on the canthometal level. Forty views/head of 45 sec each were acquired on a triple-head gamma camera equipped with fanbeam collimators. The studies were reconstructed without and with triple energy scatter correction. Attenuation correction was applied using a linear attenuation coefficient of 0.12 cm-1 for non-scatter corrected studies and 0.15 cm-1 after scatter correction. In 10 patients the delimiting ellipse was put inside, on and outside the fixed catheter corresponding to a variation of 8 mm radius in each direction. For each reconstruction three quantifications were applied: the classical (striatum-cortical)/ cortical ratio, a resolution independent method (total striatal counts / mean brain counts per ml) and an absolute expressing the total striatal uptake in % of the injected activity.Results: The classical method was insensitive to attenuation correction. Mean values of 1.91, 1.99, 1.95 and 1.97 were obtained without attenuation, ellipse in, on and outside the catheter. The resolution independent method provided values of 98.4, 136.4, 131.7 and 126.4. The absolute method was of course radius dependent: 0.257, 0.552, 0.571 and 0.598 % of injected activity. Scatter correction had the biggest effect on the classical method. The mean value incremented from 1.72 to 3.15 (83%). Resolution independent method incremented from 116 to 158 (36%). Using a camera sensitivity factor of 6770 counts/µCi.scan without and 5010 after scatter correction, the mean absolute difference was 10.2% for the absolute method.Conclusions: The classical method is insensitive to attenuation but very sensitive to scatter correction. The resolution independent method is insensitive to the size of the attenuation ellipse but sensitive to scatter correction. The absolute method needs adequate scatter and attenuation correction.

P366 Usefulness of 123I-Ioflupano SPECT in the evaluation of monolateral resting tremor of recent appearance S. Nuvoli1, V. Agnetti2, K. Paulus2, F. Chessa1, A. Spanu1, G. Madeddu1; 1Nuclear Medicine DPT, University of Sassari, Sassari, Italy, 2Neurology DPT, University of Sassari, Sassari, Italy. AIM: we employed 123I-Ioflupano SPECT in patients with monolateral tremor of recent appearance in whom a differential diagnosis between Parkinson’s Disease (PD) and Essential Tremor (ET) may often be uncertain at clinical examination.Materials and Methods: Ninety-four consecutive patients, 43 males and 51 females, aged 26 to 85 yrs (65±10), with the only neurologic sign represented by monolateral resting tremor for 1-13 mths, were enrolled; a family history of PD (FPD) was ascertained in 26/94 patients. PD in the early stage was suspected in all patients on the basis of accepted criteria (Hoehn & Yahr scale: 1.0±0.23; range: 1-2). No patient had alterations in both CT or MR and had ever received specific therapy. In all patients SPECT was performed 3-4 hrs after 148 MBq 123I- Ioflupano (DaTscan, Amersham-GE) i.v. injection by a dual head gamma camera with fan beam collimators (180°, 128x128 matrix size, zoom factor 1, 30 sec frame time, 3° angular step). SPECT was classified as normal (striatal omogeneous and symmetrical tracer uptake) or pathological (striatal symmetrical or asymmetrical uptake defects); putamen/occipital (p/o) and caudate/occipital (c/o) ratios normalized with phantom and compared to age matched normal controls ( C ) were also calculated.Results: SPECT was pathological in 53/94 (56.4%) cases confirming PD clinical diagnosis. A monolateral putamen uptake deficit was ascertained in 33/53 patients, 7 of whom FPD, in concordance with the clinically evidenced site; moreover, p/o ratio (3.95±1.27) in the involved putamen was significantly lower than both controlateral one (7.1±1.23, (p<0.001) and C (8.25±3.70; p<0.00002). Uptake defects were bilateral in the remaining 20/53 pathological cases including 4 FPD, while a monolateral lesion were clinically suspected; p/o ratio was significantly lower (p<0.001) than C in both left (3.46±1.53) and right (3.01±1.97) putamen. All 53 patients classified as PD underwent L-Dopa therapy. SPECT resulted normal in 41/94 (43.6%) patients, 15 of whom FPD, with no difference in both p/o and c/o ratio in respect of C; all these cases were classified as affected by ET.Conclusions: In patients affected by monolateral resting tremor of recent appearance as the only neurological sign 123I-Ioflupano SPECT seems to be able to clarify uncertain clinical diagnosis of PD, also giving useful information on a correct disease extension. Furthermore, the procedure proved effective to differentiate PD from ET in our cases, including FPD patients, thus permitting to accurately select the patients to be submitted or not to L-Dopa therapy.

P367 Ioflupane 123I (DatSCAN): Does age alter the report? C. Dick1, P. Kemp2, A. Hoffmann2, L. Bolt2; 1Dorset County Hospital, Dorchester, United Kingdom, 2Southampton University Hospital, Southampton, United Kingdom. Aim:Parkinsons disease primarily results in a loss of dopaminergic neurons in the ventro-lateral putamen. Ageing also results in a normal uniform loss of dopaminergic neurons in the basal ganglia. This normal ageing of the brain may interfere with the diagnostic certainty of specific dopaminergic neuronal imaging agents. We aim to determine if the normal loss of neurons from the nigrostriatal pathways due to ageing influences the diagnostic certainty of Ioflupane 123I (DatSCAN) in patients referred for imaging in suspected Parkinsons disease.Materials and Methods: A prospective study of 180 consecutive patients referred for diagnosis of Parkinsons disease was performed. This included 100 neurology and 80 psychiatry referrals. All patients had imaging with Ioflupane 123I (DatSCAN) performed using a dual head gamma camera and our standard processing. Images were reported and scored from 1-4 (1 normal, 4 abnormal), individually by two clinicians experienced in Ioflupane 123I (DatSCAN) reporting. This was performed on two separate occasions with agreement on the final scoring. The data was comparatively analysed by age group, referral pattern and result.Results: One hundred and eighty consecutive patients were included in the study with a mean age of 75 (40-90). Ninety percent of all patients had a diagnostic scan including: 100% in age groups 40-50/50-60, 85% 60-70, 88% 70-80 and 91% of patients in the 80-90 age group. There was no significant statistical difference between the results in the 60-90 year old age groups or based on the referral pattern. Ten percent of the scans returned an equivocal result however, there was no statistical difference between these results based on the patients age group.Conclusions: Although 90% of scans were diagnostic, 10% of scans had an equivocal result. The reasons behind this are unclear but may be due to: early pre-clinical Parkinsons disease, unmasking in drug induced Parkinsons disease or a mixed dementia (e.g. Lewy Body Dementia + Vascular Disease). We are currently undertaking further work in this area. In the elderly age group (80-90), 91% of patients had a conclusive scan. These results do not show any relationship between the overall diagnostic certainty of the scan and the age of the patient. In conclusion, Ioflupane 123I (DatSCAN) is a reliable, interpretable imaging agent with clinically beneficial results for all groups of patients regardless of age.

P368 Interobserver variability in the interpretation of DaTSCAN SPECT A. Nafati1, G. Gnanasegaran2, J. Buscombe1, A. Hilson1; 1Royal Free Hampstead NHS Trust, London, United Kingdom, 2Guy’s and St Thomas’ Hospital, London, United Kingdom. Parkinson Syndrome is characterised by loss of striatal dopaminergic neurons. DaTSCAN is very useful in the differentiation of PS from other movement disorders with no striatal degeneration such as essential tremor. Interpretation of images is usually done by visual assessment which is observer dependent. The objective was to test the degree of inter-observer agreement in the diagnosis of Parkinson Syndrome by visual interpretation of DaTSCAN SPECT. Methods: Thirty-one patients presented with clinical manifestations of Parkinson Syndrome were referred by neurologists to the Nuclear Medicine Department between June 2002 and June 2005. They included 19 males and 12 females, aged 19 to 84 years, mean age 55.3 ±15. All patients have normal anatomical imaging (CT and or MRI). DaTSCAN SPECT imaging was performed 1-6 years after onset of symptoms using a triple head gamma camera, 3 hours after injecting

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approximately 185 MBq of 123I-ioflupane (DaTSCAN™). Visual assessment of reconstructed transaxial slices with no attenuation correction applied was performed independently by three experienced nuclear medicine physicians who were blind to patients clinical data. The images were classified into 4 grades. Grade 1, normal, included images with striatal symmetric intense tracer uptake (two commas). Grade 2 was characterised by unilateral reduced putamen uptake (a comma and a full stop). Images with bilateral reduction of putamen uptake (two full stops) were classified as Grade 3 and those with bilateral severe reduction of striatal tracer uptake resulting in high background activity were put in Grade 4. The results were analysed in pairs using kappa statistic as a measure of agreement. Results: Moderate inter-observer agreement was found between the first and the second observers (kappa 0.41) and between the first and the third observers (kappa 0.45). Good inter-observer agreement was found between the second and the third observers (kappa 0.67). The average kappa coefficient value for all the observers is 0.51 which corresponds to ‘moderate’ strength of agreement. Conclusion: Nuclear medicine specialists can achieve moderate inter-observer agreement in the diagnosis of Parkinson Syndrome by visual interpretation of DaTSCAN™ SPECT images.

P369 Subgroups of Parkinson’s disease (PD) on brain perfusion SPECT image and comparison of neuropsychological test between subgroups Y. Jeong, J. Cha, S. Kim, J. Kim, D. Kang; Dong-A University Medical Center, Busan, Republic of Korea. Aim : It was well known that cerebral blood perfusion was normal or diffuse hypoperfusion in the majority of patients with PD. Some studies reported decreased perfusion in the occipital lobe in PD patients with dementia. Actually we interpreted image of brain perfusion SPECT image of PD patients in the clinical situation, we observed a variety of cerebral perfusion patterns in patients with PD. So we performed brain perfusion SPECT and neuropsychological test - that was used for screening test - clinically to the patients with PD and analyzed the correlation of both results. Material & Methods : One hundred forty one patients (M : 49, F : 92, mean age : 63 ± 10 yrs) who diagnosed as PD clinically were performed Tc-99m HMPAO brain perfusion SPECT. The brain perfusion images were analyzed using by SPM (SPM99, Matlab 6.5). We classified 141 patients into 6 groups (normal, frontal, temporal, occipital, diffuse and unclassified) according to the hypoperfusion areas. All patients were evaluated neuropsychological test (Seoul Neuropsychological Screening Battery, SNSB) before 2 weeks from SPECT exams. Then we compared data of perfusion SPECT and neuropsychological test between each groups. Results : There was normal cerebral blood perfusion in 25 (18%) of 141 patients with PD, decreased perfusion on the frontal lobe in 30 patients (21%), the temporal lobe in 26 patients (18%), the occipital lobe in 15 patients (11%), diffuse area in 36 patients (26%) and unclassified in 9 patients (6%). Among all 80 items of neuropsychological test, there was statistically significant difference in the false positive at recall between normal perfusion group and frontal group (p = 0.016). Also there was statistically significant difference in the COWATanimal between normal perfusion group and diffuse group (p = 0.047). Other items showed no significant difference between every group. Conversely, there was no difference in status of brain perfusion according to items of neuropsychological test. Conclusion : Unlikely previous reports, various perfusion state were found in patients with PD. We were able to classify perfusion state into several groups. A few neuropsychological test was correlated with status of brain perfusion between subgroups of PD on SPECT. So it will not be able to know the reason only using neuropsychological test why brain perfusions were different between patients. It should be considered about various information of patients including clinical symptom.

P370 Differences of brain perfusion SPECT images in patient with Parkinson’s disease (PD) with and without frontal lobe dysfunction Y. Jeong, J. Cha, S. Kim, J. Kim, D. Kang; Dong-A University Medical Center, Busan, Republic of Korea. Aim : PD is a neurodegenerative disorder that represents cognitive impairment as well as motor symptoms. PD patients were performed neuropsychological test, as the screening test, to know cognitive alterations. Some PD patients showed low score in items reflected frontal lobe function in the neuropsychological test. In this study, we performed brain perfusion SPECT to know difference in PD patients with and without frontal lobe dysfunction, revealed by neuropsychological test. Material & Methods : PD patients were evaluated using neuropsychological test (the Seoul Neuropsychological Screening Battery, SNSB) and they were divided 2 groups - PD with frontal lobe dysfunction (64 patients) and without frontal lobe dysfunction (71 patients) as the results of neuropsychological test. This selection was based on the items, phonemic total score and color reading, in neuropsychological test. These 135 patients were performed Tc-99m HMPAO brain perfusion SPECT within 1 week after neuropsychological test. And we analyzed brain perfusion in both groups using SPM (SPM99, Matlab 6.5). Results : In neuropsychological test, the items that reflected function of frontal lobe were 29. Fourteen of 29 items showed significant low score statistically that were; fist-edgepalm, alternating hand movement, COWAT-animal, phonemic total score, number of correct response(word / color), response time(word / color), time-per-item(word), number of error(color), correct response time(color) and interference score (p<0.05). Brain perfusion SPECT image revealed significantly decreased cerebral blood perfusion in the inferior and medial frontal gyri of both frontal lobes (Brodmann area 25 and 47), orbital gyrus of Lt. frontal lobe (Brodmann area 11), Lt. anterior cingulated gyrus (Brodmann area 24) in patients with frontal lobe dysfunction compared to age matched healthy controls (P=0.01). Conclusion : As a general rule, brain perfusion SPECT image showed normal brain perfusion or diffusely decreased perfusion in patient with PD. But some cases demonstrated focal hypoperfusion in specific sites according to clinical symptoms. We found the results of neuropsychological test were well correlated with status of brain perfusion SPECT in PD patients with frontal lobe dysfunction.

Interand intra-observer agreement and image reconstruction effects on visual and quantitative assessment of DaTSCANs. G. Shabo, A. G. Kettle, M. J. O'Doherty; Canterbury, United Kingdom.

Kent & Canterbury Hospital,

Aim Idiopathic Parkinson’s disease and Parkinson-plus syndromes are severe degenerative diseases with debilitating consequences. They can be easily confused with benign conditions, especially benign essential tremor, in a significant number of cases. Therefore, DaTSCAN is a valuable diagnostic imaging tool to distinguish parkinsonian from non-parkinsonian disorders. This study aims to compare visual and quantitative interpretation of DaTSCANs, to evaluate the effects of various reconstruction methods on quantification of DaTSCANs and to look at the possibility of establishing ‘ranges’ to segregate normal from abnormal scans. Materials & Methods Three nuclear physicians of different levels of experience (trainee, newly appointed consultant and an experienced consultant) blinded to clinical details reviewed retrospectively the first 53 consecutive DaTSCANs out of 170 performed in our department of Nuclear Medicine between 2002 and 2006 to look at the consistency of visual interpretation within and between the three clinicians. This review was carried out on two occasions separated by several weeks. Scans were read either as parkinsonian, normal or equivocal. Our standard DaTSCAN imaging protocol uses dual-head ADAC Forte gamma camera with VXGP collimator and a tight radius of rotation, usually 12.5 - 14 cm. The iterative algorithm applied on the oblique transverse sections, without attenuation correction, is the reconstruction method. The semi-automated Southampton method was used for quantification of patient data sets, generating values called Specific Binding Ratios (SBRs) for comparison. To try and distinguish a “normal” range for SBRs, projection data were reconstructed by filtered backprojection and OSEM with and without Chang attenuation correction. Results Inter-observer visual interpretation variability showed moderate agreement (Kappa values 0.50 - 0.56 for three observers). Intra-observer visual assessment variability showed moderate to good agreement (Kappa values 0.56 - 0.74 for three observers) with best value achieved by the most experienced clinician. Most disagreements were mainly with equivocal scans (4 out of 53 scans for each observer). When ‘ranges’ for parkinsonian, normal and equivocal cases were produced with each reconstruction method, there was a significant overlap between normal and abnormal scans. SBR values for an individual patient varied with reconstruction technique applied. Iterative algorithm and Chang attenuation correction gave rise to slightly higher values. Conclusion Quantification did not bring a significant change in reporting DaTSCANs. The visual assessment is at least as good as the quantitative assessment. ‘Ranges’ could not be established to reliably segregate parkinsonian and normal scans. Quantification is a useful adjunct but not indispensable.

P372 Cognitive correlates of nigrostriatal dysfunction in de novo Parkinson’s disease (PD) F. Nobili1, S. Morbelli2, A. Mignone3, A. Brugnolo1, P. Calvini4, G. Abbruzzese5, G. Rodriguez1; 1Clinical Neurophysiology, University of Genoa, Genoa, Italy, 2Nuclear Medicine, Galliera Hospital, Genoa, Italy, 3 Nuclear Medicine (DIMI), University of Genoa, Genoa, Italy, 4Dept. of Physics (INFN), University of Genoa, Genoa, Italy, 5Dept. of Neurology, University of Genoa, Genoa, Italy. Aim: PD can affect some aspects of cognition in the early stages. However, the impact of nigrostriatal dysfunction on cognitive failure has been poorly investigated.Methods: Twelve drug-naïve patients (6 males; mean age:67.2±6.4) with de novo PD (1999-NINDS criteria; mean motor UPDRS score:11.5±4.1; mean symptoms duration:10.2±5.0 months) and a prevalent akinteic-rigid syndrome, underwent 123I-Ioflupane SPECT. Acquisition started 180’-240’ after injection of 185 MBq 123I-Ioflupane; 120 projections were acquired with a 2-head camera (LEHR collimators) giving 2.5-3.0 million counts. Images were reconstructed with a customized OSEM algorithm. Tridimensional Volumes of Interest (VOIs) were automatically drawn on the striatum by means of an original algorithm (BasGan: Neuroimage 2005;26(Suppl 1): S39 (686 TPM)). Striatum uptake was normalized as: (Basal Ganglia uptake-occipital uptake)/ occipital uptake. Values were compared with those from 10 patients with essential tremor (2 males; mean age:64.7±8.3). Neuropsychological evaluation included tests for sustained attention (visual search), ideomotor speed and shifting attention (trailmaking A and B, TMT-A and B), phonologic verbal fluency (letters), logic reasoning (Raven’s PM47), episodic verbal memory (word list), visuospatial abilities (constructional apraxia). Scores were compared with Italian normative values. Because of the high correlation among uptake in the 4 BG (mean r value = 0.79) and of the small number of patients, correlation was assessed between mean uptake among the four BG and score (corrected for age and education) on each test.Results: Reduced scores were found in 6/12 patients: 6 on TMT-A, of whom 5 on TMT-B, 3 on constructional apraxia and 1 on verbal memory. BG uptake was abnormally low in all patients in the putamen of the clinically most affected hemisphere, in 11 patients in the contralateral putamen and in ipsilateral caudate, in 10 patients in the contralateral caudate. A significant positive correlation was found between BG uptake and TMT-B (p<0.01), constructional apraxia (p<0.01) and TMT-A (p<0.05). Correlation trends (r= 0.28-0.39) were also found with visual search, Raven’s matrices and words list learning, but not with verbal fluency.Conclusions: It is confirmed that a part of patients with de novo PD without dementia shows impairment in some cognitive domains. BG failure is strictly reflected by ideomotor slowness and a reduced shifting attention which points to an impairment of connections between BG and frontal lobes structures involved in movement planning and performance. However, the correlation with a visuospatial task suggests a wider involvement of networks engaged in spatial management.

P373 Cerebral blood flow distribution is normal in patients with de novo Parkinson’s disease (PD) S. Morbelli1, F. Nobili2, N. Girtler2, A. Mignone3, A. Piccardo1, P. Calvini4, G. Abbruzzese5, G. Rodriguez2; 1Nuclear Medicine, Galliera Hospital,

Genoa, Italy, 2Clinical Neurophysiology (DiSEM), University of Genoa, Genoa, Italy, 3Nuclear Medicine (DIMI), University of Genoa, Genoa, Italy, 4 Dept. of Physics (INFN), University of Genoa, Genoa, Italy, 5Dept. of Neurology, University of Genoa, Genoa, Italy. Aim. A reduced regional Cerebral Blood Flow (rCBF) has been reported in several regions in PD patients without dementia. However, most of them had a long disease duration and received dopaminergic treatment. The present work assesses rCBF in drug-naive patients with de novo PD. Methods. Thirteen consecutive patients (7 females, mean age:66.2±6.9 yrs.) with de novo PD (1999-NINDS criteria; mean motor UPDRS:11.2±4.0; mean symptoms duration:9.8±4.9 months) and a prevalent akinteic-rigid syndrome underwent 123I-Ioflupane SPECT and 99mTc-ECD SPECT. Dementia was excluded with ADL and IADL questionnaires and neuropsychological evaluation. Two groups of controls were used: 10 patients with essential tremor (8 females; mean age:64.7±8.3) were the control group for 123I-Ioflupane SPECT; 13 healthy subjects (6 females; mean age:69.8±5.1) were the control group for 99mTc-ECD SPECT. Brain SPECTs were acquired with a 2-head gamma camera (LEHR collimators). The 120 projections were reconstructed by a customized OSEM algorithm. Tridimensional Volumes of Interest (VOIs) were automatically drawn on the striatum by means of an original algorithm (BasGan: Neuroimage 2005;26(Suppl 1): S39 (686 T-PM)). Striatum uptake was normalized as: (Basal Ganglia uptake-occipital uptake)/ occipital uptake. Voxel-based comparison between 99mTcECD SPECT of PD patients and controls was performed with SPM2 (height threshold: p=0.01; clinically most affected hemisphere on the same side). Results. 123I-Ioflupane uptake was significantly (p<0.001) lower in all basal ganglia in PD group in comparison to controls. In the clinically most affected hemisphere, caudate uptake was 1.99±0.67 and putamen uptake was 0.68±0.3. In the less affected hemisphere corresponding values were 2.37±0.81 (caudate) and 1.19±0.64 (putamen). Values in controls were (left and right hemisphere, respectively): 4.19±0.7 and 4.23±0.69 (caudate) and 3.52±0.63 and 3.66±0.72 (putamen). The caudate uptake was below the mean -2 SDs of controls in 13/13 cases for the putamen of the clinically most affected hemisphere, in 12/13 cases in the most affected caudate and in the less affected putamen and in 11/13 cases in the less affected caudate. No difference was found between CBF distribution of PD patients and controls. Conclusion. These data show that CBF distribution is still normal in early PD without dementia at the same time when significant a impairment can be shown in the presinaptic nigrostriatal endings. The reduced rCBF reported in the literature that has been observed after several years of PD together with the present data support the Braak & Braak staging of PD and their “ascending” caudal-rostral theory.

P374 Benefit of [123I]FP-CIT SPET in the clinical diagnosis of Drug-Induced Parkinsonism (DIP) I. Pasquin1, S. Ottaviani2, M. Zuffante1, D. Grigolato1, M. Tinazzi3, P. G. Giorgetti1; 1Operative Unit of Nuclear Medicine Ospedale Civile Borgo Trento, Verona, Italy, 2Operative Unit of Neurology Ospedale Civile Borgo Trento, Verona, Italy, 3Operative Unit of Neurology Ospedale Civile Borgo Trento; Department of Neurological Sciences and of Vision University of Verona, Verona, Italy. Aim: Aim of this study is to evaluate the clinical benefit of FP-CIT Imaging in Differential Diagnosis between Drug-Induced Parkinsonism (DIP) and Idiopathic Parkinson’s Disease (IPD). Patients and Methods: We studied with DaTscan-SPET 30 patients initially diagnosed as possible DIP, receiving neuroleptic (NL) therapy. Clinical assessment was performed by a neurologist trained in movement disorders and the diagnosis was considered when at least two of the three basic parkinsonian signs ( rest tremor, rigidity and bradykinesia) were present. UPDRS motor score (part III) was used to quantify motor symptoms in the off-state. DaTscan-SPET images were acquired using a triple-head camera (IRIX-Philips), 110 MBq of 123I FP-CIT 3-4 hours from injection. For this purpose only visual assessment was used to promptly diagnose DIP from IPD. Results and Discussion: 22 pts. had a Normal SPET (Group 1) and 8 an Abnormal one (Group 2). Between pts. of Group 1 and Group 2 statistical differences were found in the duration of symptoms, of psychiatric disease and UPDRS motor score (10+/- 4,5 vs. 18,6+/-15) in a range of 3-32. DIP develops when more than 80 % of striatal dopamine postsynaptic receptors are blocked in a reversible way, so that recovery occurs usually 3-18 months after the NL drug is stopped. But in a minority of patients symptoms worsen or reappear after some months: a new diagnosis of IPD was made in these cases, all with an abnormal SPET (Group 2), almost 27% of the total. In fact pts. of Group 2 had probably an idiopathic subclinical dopamine deficiency, the degree of which determines how easily DIP developes since NL treatment is started.Conclusions: Symptoms of our pts. are similar, just in 2 cases DIP being easily distinguishable for typical oro-facial diskynesia and acatysia. Moreover DIP diagnosis is not often easy also in relation to unknown pharmacological history.Therefore DaTscan-SPET is a quick, useful tool to early differentiate symptoms related only to interfering drugs from symptoms due to nigrostriatal degeneration, since management and prognosis are quite different.

P28 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Radiopharmacy/Radiochemistry: Technetium P375 Preparation, in vitro and in vivo Evaluation of 99mTc-7HYNIC-taxol as a Tumor Imaging Agent O. D. Awh1, D. S. Rha1, J. Y. Park1, T. S. Lee2, T. H. Choi2, K. S. Woo2, W. S. Chung2, G. J. Cheon2, C. W. Choi2, S. M. Lim2; 1Yonsei university, Wonju, Republic of Korea, 2Korea Institute of Radiological and Medical Science, Seoul, Republic of Korea. Taxol has been used in the treatment of breast, ovary and lung cancers. To evaluate the feasibility of 99mTc-7-HYNIC(hydrazino nicotinamide)-taxol as a tumor imaging agent, it was synthesized, and its biodistribution and gamma camera image were obtained in B16-F10 melanoma bearing C57BL6 mice. 7-t-BOC-HYNIC-taxol was synthesized through six steps, and

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Poster Presentation

P371

7-HYNIC-taxol was finally obtained by t-BOC deprotecting from 7-t-BOC-HYNIC-taxol. The product was purified by column chromatography. 99mTc-7-HYNIC-taxol complex from 7HYNIC-taxol was prepared by labeling with 99mTc in the presence of SnCl2·2H2O and tricine. The biochemical behaviors of the complex such as in vitro stability and lipophilicity, in vitro transchelation were investigated. The biodistribution and in vivo image of 99mTc-7-HYNICtaxol were obtained in C57BL6 mice bearing B16-F10 melanoma. After 1, 6 and 24 hr postinjection, the weight and radioactivity of each organ were measured and gamma camera image was obtained. The total synthetic yield of 7-HYNIC-taxol was 42.6%. Radiolabeling yield of 99mTc-HYNIC-taxol was 99.9%. 99mTc-7-HYNIC-taxol was stable at 37°C for 24 hrs. 99mTc7-HYNIC-taxol was slightly more soluble in water than in organic solvent. The binding ability of 99mTc-7-HYNIC-taxol to serum proteins was 39.9%. In vivo transchelation test, the 99mTc-7HYNIC-taxol retained over 86% of radiochemical purity after incubation with DTPA or cysteine. 99mTc-7-HYNIC-taxol was intravenously administered to C57BL6 mice bearing B16-F10 melanoma at footpad. Tumor/blood ratios were 1.17, 26.0, and 2.87, and tumor/muscle ratios were 12.2, 168, and 15.0 at 1 h, 6 h and 24 h post injection, respectively. The gamma camera image was obtained at 6 h post injection showed selectively localized in tumor. 99mTc-7HYNIC-taxol showed high stability and was selectively localized in B16-F10 melanoma. These results suggest that 99mTc-7-HYNIC-taxol can be used as tumor imaging agent.

P376 Labelling of N,N-Dimethyltryptamine for imaging serotonin receptors C. O. Cañellas1, A. B. Pomilio2, A. A. Vitale2, J. Ciprian-Ollivier2, J. M. Knez1, S. I. Gomez1, N. Nevares3, F. G. Calcagno4, H. Glait4; 1Tecnonuclear S.A., Buenos Aires, Argentina, 2Buenos Aires University, Buenos Aires, Argentina, 3National Atomic Energy Comission, Buenos Aires, Argentina, 4Nuclearvet, Buenos Aires, Argentina. The structure of some indolealkyamines such as N,N-dimethyltryptamine, bufotenin, etc., is similar to that of serotonin, which plays an important role in the central nervous transfer system. These compounds are also known to have an affinity for the serotonin receptors. Labelled indolealkylamines with radionuclides could be interesting compounds for the study of the serotonin action mechanism and the in vivo receptor assay in the brain. In a previous work N,NDimethyltryptamine (N,N-DMT) was synthesized and identified by 1H- and 13C-NMR and MS. The aim of this work was to label N,N-DMT with 131I and 99mTc and evaluate its biological behaviour in inbred rabbits and in vitro studies. This compound was labelled in position 2 with 131I/chloramine-T, and further with 99mTc/tin (II) tartrate giving rise to a [99mTc(V)]-biscomplex. Radiochemical purity was determined by paper chromatography and chloroform:acetic acid (9:1) as a solvent when labelling with iodine and by ITLC using MEK and saline for technetium labelling. In this case a cysteine challenge and a protein binding were also performed. Biodistribution was evaluated in inbred rabbits with a 30 sec image adquisition up to 60 min, being brain, liver, heart, and bladder areas of interest. Data were processed at 120, 180, 240 and 360 minutes. Blood samples were taken at different times post administration of the labelled compounds. Radiochemical purity was higher than 90% for both labelled compounds, which showed to be both hydrosoluble and neutral. The cysteine challenge showed that 17% of 99mTc is removed by cysteine at 1 h and 14% is bounded to albumin at 2h. An amount of 20±2.2 %I.D [131I]-N,N-DMT was taken by brain after 5 min and 70.1±5.5 %I.D by bladder after 60min, whereas 15.2±1.5% I.D [99mTc]-N,N-DMT was taken by brain after 10 min and 78.6±5.5 %I.D by bladder (60 min). Brain was removed 60min after radioactivity administration and cerebral cortex, cerebellum, medulla oblongata, olfactory bulb and olfactory peduncle homogenates were measured in a gamma counter being 77.2±3.5 % and 18.2±2.3% the percentages of technetium activity retained by the olfactory bulb and peduncle respectively. These results showed that both labelled N,N-DMT were relatively highly accumulated in the brain and their accumulations were retained, indicating the feasibility of examining serotonin receptor in human brain in vivo. Pretreatment studies with monoamine oxidase inhibitor in animals to enhace the proportion of the radioactivity in receptor-rich fractions are in progress.

P377 Inhibiting role of aryl substituents on the aminolytic reactivity of activated Tc-99m complexes comprising a 3,4diaminobenzoate backbone O. Calderon Sanchez1, A. Mohammed1, C. Bauer2, M. Wolf2, B. Wängler2, W. Mier1, R. Mocelo3, U. Haberkorn1, M. Eisenhut2; 1University of Heidelberg, Heidelberg, Germany, 2German Cancer Research Center, Heidelberg, Germany, 3Facultad de Química - Universidad de La Habana, Habana, Cuba. Preformed Tc-99m chelates with an activated ester function are useful for the gentle labeling of proteins (precomplexation route). With this background a series of new heterobifunctional ligands deriving from 2,3,5,6-tetrafluorophenyl (TFP) 3,4-diamino-benzoates (OC1, OC3, OC4) were synthesized. Their corresponding Tc-99m complexation and protein-conjugation characteristics were elucidated, and compared with the results previously reported using 2,3,5,6tetrafluorophenyl N-(S-benzoylthioacetyl)glycylglycyl-p-aminobenzoate (OC2). The reaction temperatures and the reaction time markedly influenced complexation yields. Compared with OC2 the Tc-99m-chelate formation with OC1 and OC4 was more effective, showing radiochemical yields of 60 and 70% within 20 min, respectively. Owing to steric hindrance the complexation of OC3 did, however, not exceed 10%. Non-carrier added Tc-99m complexes were conjugated at pH 10 with the anti EGF-receptor monoclonal antibody MAb425, resulting in labeling yields of 14% for Tc-99m-OC1 and 7% for Tc-99m-OC4 after incubating for 20 min at 30°C. Increasing the temperature to 40°C improved these results by 14% and 3%, respectively. As compared with Tc-99m-OC2, which provides the chelating substituent at the 4-phenyl position only, the application of 3,4-phenyl substituents proved less efficiently for protein conjugation. The influence of the meta positioned R-CO-NH substituent which is participating in complex formation explains the reduction of reactivity at the electrophilic center of the activated ester function. The 3,4-diaminobenzoate backbone may, however, be attractive for an alternative design of novel Tc-99m N2S2 or N3S complexes, because they show excellent complexation characteristics.

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P378 Flow Cytometry usefulness as a final quality control of labelled leukocytes with tc99m-HMPAO È. Torrent1, B. Soriano1, C. Palacio2, M. Boronat3, S. Aguadé3, J. Castell3; 1Radiopharmacy Unit, Nuclear Medicine department. Vall Hebron Hospital, Barcelona, Spain, 2Flow Cytometry Unit. Vall Hebron Hospital, Barcelona, Spain, 3Nuclear Medicine department. Vall Hebron Hospital, Barcelona, Spain. Introduction The Flow Cytometry (FC) is an useful method which provides us the granulocytes viability and the full blood count report of the labelled leukocytes with Tc99m-HMPAO (LLTHMPAO) using an small volume of sample (50µL) exempted from radioprotection controls (<10MBq). Aim To evaluate the usefulness of the final quality control of LLTHMPAO by using the FC method. Methods The final control of LLTHMPAO was performed by using FC in 49 patients (21 female), with mean age of 48 years (range 2-82 years) recollected during 6 months (from May to September 2005). The reasons of leukocyte scan in our serie was to evaluate infection activity in joint protesis (n=17), osteopathies (n=11), inflammatory bowel disease (n=17), vascular pathologies (n=2), fever of unknown origin (n=1), abdominal abscess (n=1). Besides the usual controls, the blood count report (leukocytes, erythrocytes and platelets), the count of the leukocyte subpopulations (lymphocytes, monocytes and neutrophils) and the granulocyte viability were determinated by FC. The final verification of gammagraphic results were confirmed by the other complementary proves (radiography, biopsy, bacteriology) and/or clinical course (minimum 6 months) to establish the true positives (TP), true negatives (TN), false positives (FP) and false negatives (FN) results. Finally the calculated parameters by FC were compared with the gammagraphic results. Results Gammagraphic results: 17 TP, 26 TN, 1 FP, 2 FN and 3 no concluded results.

TP

TN

FC data:

Labelling efficiency (%)

median

x±sd

median

x±sd

54.5

53.9±7.9

55.5

54.5±8.9

Total cells (cellsx106)

946

836±330

587

685±319

Red-cells (cellsx106)

234

243±98

218

220±101

Platelets (cellsx106)

380

387±235

246

322±201

Leukocytes (cellsx106)

179

206±99

126

143±75

Lymphocytes (%)

17.6

20.4±9.7

27.8

26.3±8.9

Monocytes (%)

8.6

8.2±2.4

7.8

8.7±4.3

Granulocytes(%)

73.5

70±10.7

62.7

63.1±10.3

Granulocytes viability(%)

97.5

97.4±1.3

97.8

97.6±1.5

x=mean, sd= standard deviation No significant correlation were found between the labelling efficiency and total cell, red-cell, platelet and leukocyte counts. Conclusion The FC is an useful and feasible method for the final quality control of LLTHMPAO which provides us the full blood count report and the leukocyte viability. Therefore the labelling method not affect the leukocyte viability and the TP labelling efficiency is similar between to TP and TN, with no linear relation between the labelling efficiency and the final blood counts.

P379 Evaluation of radiolabelled inh as specific mycobacterial lesion imaging in humans A. K. SINGH1, A. Bhatnagar1, J. Verma2; 1Inmas, Delhi, India, 2Patent Office, Delhi, India. Introduction: There is an urgent need of specific radiopharmaceuticals to detect and locate Mycobacterial lesions. Conventional modalities have their proven utility but they suffer from one or other drawbacks. The present work is based on radionuclidic imaging technique using 99mTcINH complex to detect and locate TB at an early stage in any anatomical site.Materials and Methods: Isoniazid (INH) was chosen because it is a specific anti-tubercular drug (interacts specifically with mycolic acid of Mycobacterium) shows selective uptake in live Mycobacteria sensitive to INH. After complexation of INH with Tc-99m using indirect labelling approach (Patent pending), Labelling efficiency, in-vitro and in-vivo stability blood kinetics, organ distribution were studied in balb/c mice and New Zealand White Rabbits at different time interval up to 24hrs. Post labeled biological activity of INH was studied by Colony Forming Unit (CFU) assay of M.tuberculosis, on solid media (Middlebrook 7H10 Agar, DIFCO). Thigh model of localized TB lesion was prepared in four rabbits by injecting 500µl of 3 x 108 cells/ml of Mycobacterium tuberculosis (Clinical Human Isolate) live bacteria in growing phase. The localization kinetics was studied in the animal model by injecting 70-75MBq of 99mTc-INH intravenously in the ear of rabbit and the images were taken with a Gamma-camera at different time intervals.Results: Labeling efficiency of 99mTc-INH was found to be >95%. Only 2-3.5% of the tracer leached out from the complex even at 24 hrs in serum at 37oC, confirming its high stability. Blood kinetics studies exhibited biphasic pattern and 50% of 99mTc-INH cleared from the blood within 5 min of the post administration of tracer. Organ distribution studies suggests the renal route of excretion. No gastric/thyroid activity was noted suggesting the high labeling efficiency and in-vivo stability. The number of colonies grown were found to be same in 99mTcINH and native INH thereby suggesting no loss in biological activity of INH after labeling. Cold

P380 Biodistribution of 99mTc-dextran-70 radiopharmaceutical in rat A. Ramirez-Navarro, L. Fernández-Maza, M. Arcocha, M. A. Muros, M. Bellón, M. Vera, M. Cañadas, J. M. Llamas-Elvira; H. U. Virgen de las Nieves, Granada, Spain. Biodistribution of 99mTc-DEXTRAN-70 Radiopharmaceutical in Rats Iintroduction. Dextrans are glucose polymers, whose versatility has led to their application in numerous fields. 99mTc-labelled dextrans have been proposed as possible substitutes for human albumin and labelled red blood cells in angiography and cardiac pool studies. Objectives. To assess the biodistribution in rats of a preparation of 99mTc-labelled dextran-70. Material and Methods. multidoses vials were prepared with the following composition per vial: 20mg of dextran-70, ascorbic acid, gentisic acid and Cl2Sn·2H2O. Labelling was carried out by adding 370-555 MBq of pertechnetate in a volume of 1.5 ml of 0.9% NaCl solution per vial. After 15 minutes of incubation at room temperature, we determinated the RCP by chromatography. For the chromatographic method ITLC-SG was employed as stationary phase and 0.01N HCl as mobile phase in order to separate colloids; chromatography in paper (Watmman 17MM) and acetone as mobile phase to obtain free pertechnetate. The radiochromatograph scanner employed was miniGita Raytest, isotopenmebgeräte GmbH. Ten Wistar rats were administered with an 18 MBq dose of 99mTc-dextran via cannula in jugular vein. Whole-body images were obtained at 10, 30 and 60 minutes post-injection. Areas of interest were marked and the indexes were calculated for heart to lung, spleen, liver and kidney. The animals were then killed and blood, heart, lung, spleen, liver, kidney, muscle and bone were extracted. Organs and tissues were weighed and the activity they contained was measured. Indexes were obtained for the activity per gram of blood versus the activity per gram of the different organs, and the percentage of activity was calculated with respect to the total activity administered. Results are expressed as means ± standard deviation. Results.

TIME(min)

Heart/Lung

Heart/Spleen

Heart/Kidney

10

2,43±0,27

2,29±0,34

0,87±0,05

30

2,19±0,21

1,62±0,36

0,56±0,05

60

2,16±0,22

1,69±0,45

0,46±0,05

blood

Heart

Lung

Spleen

Liver

Ïndex blood/

1

2,66±0,68

1,51±0,26

2,10±0,39

2,13±0,25

% Dose

1,05±0,20

0,38±0,12

0,57±0,05

0,69±0,14

0,48±0,08

Discussion. At 30 minutes of the administration of the radiopharmaceutical, the activity indexes of the different organs stabilised, remaining practically constant at 60 minutes. In all cases, the blood/organ index obtained after the killing of the animal showed that the activity remained predominantly in the blood. This finding was confirmed by calculations of the percentage of the administered dose present in each organ. However, a high renal uptake was observed, showing an activity that was even higher than that found in the blood.

P381 Human microvascular endothelial binding of 125I- and 99mTc-native and glycated low-density lipoprotein - potential for imaging atherosclerosis? G. Sobal, E. J. Menzel, H. Sinzinger; Vienna, Austria.

Medical University of Vienna,

Aim: Modification of low-density lipoprotein (LDL) plays a key role in the formation of atherosclerotic plaques and the resulting damage to the arterial wall. Native (n), glycated (g) and glycoxidated (go) LDL was labeled with 125I or 99mTc and the labeling efficiency/binding was compared for potential use in imaging analysis of atherosclerotic lesions (PPAR gamma receptors). Materials and Methods: The radiolabeling with 99mTc was performed by sodium dithionite method, with 125I by chloramine T method. The number of specific receptors for nLDL, gLDL or goLDL on human microvascular endothelial cells as well as Kds using either 125I- or 99mTc-labeled LDL-modifications were assessed.Results: Specific activity of labeled modified LDLs was a much higher (for goLDL 20 times higher) than of nLDL. Gel filtration of labeled LDLs revealed, however, that 99mTc-g/go LDL is significantly degraded by the labeling. No fragmentation of 99mTc-nLDL and all 125I LDL forms was seen. Binding studies using both 125I and 99mTc-nLDL indicated weak binding affinity (Kd 10-7mol/L) to human microvascular endothelial cells. The binding affinity of the cells for 125I-g/goLDL was significantly higher (Kd 10-9mol/L) and could still be increased by preactivation of the endothelial cells with TNFĮ. Incubation with 99mTc-goLDL, however, did not result in specific binding of the ligand, possibly a consequence of the fragmentation of the lipoprotein during the labeling. Scatchard evaluation of 99mTc-gLDL binding, while showing specific high binding affinity to the endothelial cells, revealed the presence of very few binding sites only for this LDL-modification. This is in contrast to the results obtained with 125I-gLDL, showing a much higher membrane density of scavenger receptors for this ligand.Conclusions: We conclude, that from the methodological point of view (labeling) for in-vitro binding studies as well as for potential in-

vivo imaging only 125I-gLDL-modifications should be used, while nLDL may be applied both in 125I- and 99mTc-labeled form.

P382 A New tridentate N,S,S-donor bifunctional chelating agent for the labeling with [M(CO)3]+(M=Tc, Re) cores Y. Hong, K. Choi, S. Choi; Daejeon, Republic of Korea.

Korea Atomic Energy Research Institute,

In order to develop a new chelating system for the radiolabeling with [99mTc(CO)3]+ precursor, we prepared a tridentate ligand containing an aromatic amine and two thioether. Furthermore, the chelator was conjugated to glucosamine and radiolabeled with [99mTc(CO)3]+ precursor. Material and Methods 2,6-bis(carboxymethylthiomethyl)-prydine were prepared as follows; To a solution of thioglycolic acid in dry DMF, at - 10C, sodium hydride(3 eq.) was added in portion and remained for 15 min. When the mixture turned to slightly pale yellow suspension, 2,6bis(bromomethyl)prydine (0.5 eq.) was added and stirred at 0C for 4 hrs. After quenching and neutralizing sodium hydride using methanol and 0.1N HCl solution, the product was separated by precipitation using acetone. 2,6-bis(glucoseamidomethylthiomethyl)prydine was synthesized by the conventional method for amide formulation using DCC. For the formulation of [99mTc(H2O)3-complexes, a ligand vial (10-5M) in PBS buffer (0.02M, pH= 7.4) was prepared followed by the injection of [99mTc(H2O)3(CO)3]+ precursor and incubation at 75 C for 30 min. The complexes were analyzed by a reverse-phase HPLC with a linear gradient method using 0.1% TFA in water and 100% acetronitrile over 30 min. Results A tridentate N,S,S-donor bifunctional chelating agent, 2,6-bis(carboxymethylthiomethyl)-prydine, was prepared by the simple synthetic approach. Reaction of the compound with the 99mTc(CO)3-precursor produced a single product in high radio-labeling efficiency(>98%). The radiolabeled complex of 2,6bis(glucoseamidomethylthiomethyl)prydine was also formulated a single product. It was predicted that the 99mTc(CO)3-complexes were formulated in a similar tridentate manner via the aromatic amine and two thioether of the ligand. Conclusion We prepared a potential N,S,Sdonor bifunctional chelating agent, 2,6-bis(carboxy methylthiomethyl)-prydine for the labeling with [M(CO)3]+(M=Tc, Re) cores to form a tridentate cationic complex. The compound can be applied for the conjugation to biomolecules. Furthermore, the synthesized glucose derivative will be evaluated as a tumor imaging agent.

P383 Preparation of a Crysamine G derivative and its bifunctionalization with L-Cysteine for the labeling with [M(CO)3]+(M=Tc, Re) cores Y. Hong, O. Choi, S. Choi; Daejeon, Republic of Korea.

Korea Atomic Energy Research Institute,

Synthetic strategies for the bifunctionalization of stilbene, a derivative of crysamine G, with cysteine for the transition metal coordination are reported. Organometalic technetium complexes were synthesized and investigated to evaluate the feasibility for the imaging of amyloid plaque of Alzheimer’s patients. Material and Methods In order to prepare a crysamine G derivative, {[3cysteinemethyl]phenylvinyl}-2-hydroxybenzoate methyl ester(stillben) was prepared in seven steps. The bifunctionalization of the derivative with cysteine was accomplished by the reaction with L-cysteine preconditioned using sodium methoxide in methanol under nitrogen atmosphere at room temperature. The organometallic precursor, [99mTc(H2O)3(CO)3]+ and [NEt]2[ReBr3(CO)3] were prepared according to the reported procedures. The radiolabeling was accomplished as follows: A ligand vial (10-5M) in PBS buffer (0.02M, pH= 7.4) was prepared and flushed with nitrogen. The [99mTc(H2O)3(CO)3]+ precursor was injected into the prepared ligand vial followed by incubation at 75 C for 30 min and cooled in ice bath. The macroscopic complex was prepared by the equimolar reaction with the ligand and rhenium precursor under a slightly alkaline pH condition. Electrophoresis was performed to examine the electric charge of the 99mTc(CO)3-complex. The complexes were analyzed by a reverse-phase HPLC (TEAP buffer:methanol, X-tera column, waters). Results The bifunctionalization of stillben with cysteine was accomplished by the simple synthetic approach. Reaction of the compound with the organometallic precursor [M(CO)3] core produced a neutral single product in high yield(>98%) and stability at room temperature over 6 hrs. HPLC analysis of the 99mTc(CO)3-complex showed similar retention times as for the corresponding macroscopic Re(CO)3-complex. It revealed that the 99mTc(CO)3-complex is identical structure to that of rhenium analogue. Conclusion Synthetic strategies of stilbene and its bifunctionalization with cysteine were established. The radioactive-labeled compound, a neutral complex suitable to cross the blood brain barrier by diffusion, was prepared in high radiochemical yield. Furthermore, the synthesized stillben and its cysteine derivative can be applied for the development of diagnostic agent for amyloid plaque of Alzheimer’s patients.

P384 Cell function and distribution of radioactivity among blood components after labelling equine leucocytes with 99mTcSnF colloid M. Abushhiwa1, N. S. Salehi2, R. Slocombe3, P. Finnin4, C. Whitton5, I. Caple5; 1The faculty of veterinary Science, University of Melbourne, Werribee, 3030, Australia, 2Royal Melbourne Hospital, Parkville, Australia, 3 faculty of veterinary sceince, the University of Melbourne, werribee, 3030, Australia, 4The faculty of Veterinary Science, the University of Melbourne,, Werribee, 3030, Australia, 5The Faculty of Veterinary Science, The University of Melbourne, Werribee,3030, Australia. Aims: 1) to develop a method for the efficient labelling of equine leucocytes with 99mTc-SnF colloid 2) to investigate the phagocytic activity and labelling retention of labelled leucocytes 3); to determine the distribution of radioactivity between granulocytes and monocytes.Methods: Labelling of leukocytes: Whole blood was collected from normal horses and divided equally into control (A) and labelled (B) samples. In each sample, erythrocyte sedimentation was allowed to

S303

Poster Presentation

abscess was visible at the site of injection of bacteria in rabbits. Lesions could be visualised in all four rabbits as early as 2 hours post administration (abscess/muscle ratio 2.0: 1.0) which Increased to (abscess/muscle ratio 3.5: 1.0) at 4 hours and was maintained till 24. The results of animal study suggest that 99mTc-INH is a viable, specific and cost effective agent for diagnosis of tuberculosis. Incited by the animal studies efficacy was evaluated in human subjects, results thus obtained further confirmed its utility for Mycobacterial lesion detection.

proceed for 30-45 min at room temperature (RT°C) and Leukocyte rich plasma (LRP) was then collected. Then 360 MBq of 99mTc-SnF colloida was added to LRP (B), and both samples were slowly rotated for 25 min at RT°C. Leukocytes were collected by centrifugation (1500 rpm/ 10 min/ RT°C) and pelleted cells were resuspended to a final concentration of 1.0x106 viable cells/ml in Krebs solution. Phagocytic activity: Freshly opsonised zymosan was added to control and labelled leukocytes (0.2mg/ml), mixed and incubated at 37°C for 2 hrs. Aliquots (100 µl) of the suspensions were centrifuged onto microscope slides using a cytocentrifuge (300rpm/5min/RT°C) and the slides were stained with Giemsa stain. The percentage of leukocytes that had phagocytosed at least one zymosan particle was determined by counting a minimum of 500 cells per slide. Labelling retention: Cells were labelled as previously described and 1 ml aliquots were taken at 3, 6, 8 and 9 hrs post-labelling. Each aliquot was centrifuged to pellet the leukocytes (1500 rpm/ 10 min/ RT°C) and the radioactivity in the supernatant and pellet was determined using a dose calibrator. Labelling of leukocyte subpopulations: Granulocytes and monocytes were separated using a double density gradient of Histopaque 1077b and Histopaque 1119 b. Labelled cells were layered onto the density gradient and centrifuged (340g/30min/RT°C). Radioactivity of granulocyte and monocyte layers was then measured.Results: Labelled equine leukocytes had a phagocytic activity of 93.7± 0.6% (control = 94.6±0.3%). The labelled cells retained 94.6 ± 1.6 of the radioactivity for at least 9hrs postlabelling. Of the total leukocyte radioactivity, 67.18 ± 1.75% was associated with granulocytes and 32.81 ± 1.73 % was associated with monocytes.Conclusions: Labelling of equine leukocytes with 99mTc-SnF colloid did not affect phagocytic activity and the labelled leukocytes retained a high proportion of the radiolabel for at least 9 hrs post-labelling. The percentage of radioactivity in equine granulocytes was higher than monocytes, indicating that this radiopharmaceutical may be more efficient for localising acute inflammation than chronic inflammation. aRadpharma scientific bSigma

P29 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Radiopharmacy/Radiochemistry: Radiopharmaceuticals

PET-

P385 Synthesis and evaluation of a 18F-labelled ȕ-galactosidase substrate as potential probe for in vivo visualization of Lacz gene expression with PET S. Celen1, T. de Groot1, C. Deroose2, C. Terwinghe1, A. Verbruggen1, G. Bormans1; 1Laboratory for Radiopharmaceutical Chemistry, UZ Gasthuisberg, Leuven, Belgium, 2Nuclear Medicine, UZ Gasthuisberg, Leuven, Belgium. Aim. Gene therapy holds great promise for the treatment of various diseases, including cancer, cystic fibrosis and immunodeficiency. However, a major obstacle to widespread implementation is the need to verify successful transfection in a spatial and temporal way. Many promising methods are being developed to image gene expression by including a reporter gene in tandem with the therapeutic gene. One of the most widely used reporter genes is the LacZ gene, which encodes the bacterial ȕ-galactosidase enzyme. For its in vitro detection, several substrates (e.g. ONPG) are available. In vivo imaging of ȕ-gal expression would further extend the use of this reporter system. The purpose of this study was to develop and evaluate a 18F-labelled ȕ-gal substrate for in vivo visualization of LacZ gene expression with PET. Methods. Precursor (1) was synthesized by glycosylation of 2-nitro-resorcinol with acetobromo-Į-D-galactose. Labelling with 18F was done by alkylation of (1) with [18F]fluoroethyl triflate in acetone at 90 °C in the presence of NaOH. Subsequent deprotection of the sugar hydroxy groups with NaOH and preparative RP-HPLC purification yielded 2-nitro-3-[18F]fluoroethoxy phenyl ß-Dgalactopyranoside (2). Log P, the in vitro affinity for ȕ-gal, uptake in LacZ transduced cells and biodistribution in mice of (2) were studied. Results. (1) was efficiently labelled with [18F]fluoroethyl triflate, yielding 59 % of the desired compound (2). In an in vitro test with ȕgal, (2) was fully hydrolysed within 15 min. Although the log P value was rather low (-0.8), cell uptake of (2) in lentiviral vector transduced cells was 7.4 fold higher than in control cells. Tissue distribution in normal mice showed some brain uptake at 2 min and 60 min p.i. Compound (2) was cleared from plasma mainly by the renal pathway. Conclusion. A derivative of the ȕ-gal substrate ONPG was synthesized and labelled with [18F]fluoroethyl triflate to obtain (2) that was evaluated as a potential probe for in vivo visualization of LacZ gene expression with PET. (2) was found to be a good substrate of ȕ-gal and its uptake in LacZ expressing cells was higher as compared to control cells. Work is in progress to evaluate the in vivo behaviour in mice expressing LacZ using µPET. This study was funded in part by the EC-FP6-project DiMI, LSHB-CT-2005-512146-

P386 Metabolism of LBT-999, [11C]-LBT-999 and [18F]-LBT-999, a selective ligand for PET examination of the dopamine transporter M. Schollhorn-Peyronneau1, W. Saba1, H. Valette1, C. Coulon1, M. Ottaviani1, F. Hinnen1, S. Demphel1, S. Chalon2, P. Emond2, F. Dolle1, J. Deloye3, D. Guilloteau2, M. Bottlaender1; 1Service Hospitalier Frédéric Joliot, DRM/DSV CEA, Orsay, France, 2Inserm U619, Tours, France, 3 Cyclopharma, Clermont-Ferrand, France. Aim: LBT-999 is a high affinity and selective dopamine transporter(DAT) ligand. LBT-999 has first been labeled with carbon-11 and then with fluorine-18 for PET studies in baboons. The conversion of radioactivity data obtained in PET to ligand-receptor kinetics, often estimated by a model, must take into account the intact fraction of the radiotracer in plasma as a function of time. A better understanding in the biotransformation of the tracer allows a better determination of the metabolite-corrected plasma curve. The aim of this study was to investigate the in vitro metabolism of LBT-999 in order to propose a metabolic pathway. The in vivo metabolism was studied in baboon after i.v. administration of [11C] or [18F]-LBT-999.Materials and Methods:

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The in vitro metabolism of LBT999 was carried out using rat and human liver microsomes and cDNA-expressed human P450 enzymes. Microsomal incubations were analysed by electrospray LC/MS and LC/MS/MS for kinetics and structural studies.Following i.v. administration of radiolabeled ligand in baboon, metabolic profiles were determined by radioactive HPLC. The fraction of labeled unchanged radiotracer was quantified using either the chromatographic profile and/or a calibration curve of [18F]-LBT-999.Results: The in vitro oxidation of LBT-999 in rat and human hepatic microsomes led to the formation of at least four metabolites more polar than LBT-999. Based on their structural elucidation by LC/MS/MS, the major routes of metabolism proposed were (a) hydroxylation of the phenyl ring or tolyl-hydroxylation (m/z=348), (b) Ndealkylation (m/z=260), (c) N-dealkylation and tolyl-hydroxylation (m/z=276), (d) Hydroxylation of the nortropane moiety with loss of water (m/z=330). In vivo results showed different HPLC metabolic pattern when using [11C]-LBT-999 or [18F]-LBT-999 as radioligand. These differences in the nature and in the amounts of metabolites and unchanged radioligand may be explained by the presence of labeled [11C]-metabolites, that are not labeled any more with [18F], such as N-dealkylated products. For [18F]-LBT-999, a large fraction of the radioactivity was detected in the proteins fraction after plasma sample acetonitrile precipitation. This radioactivity was increased as a function of time and was not observed with [11C]-LBT999. [18F]-LBT-999 was rapidly and extensively metabolized in baboons as only 25 % of the radiotracer remained unchanged 30 minutes after administration.Conclusions: In vitro experiments demonstrated the formation of hydroxylated and dealkylated products. In vivo results suggested a rapid and high metabolism in the liver, that may contributes, depending on the radioisotope, in variations observed in PET studies.

P387 Double Tracer Autoradiography with 18FDG/64Cu-ATSM and Cell Proliferation in tumor M. Oh1, T. Tanaka1, M. Kobayashi2, T. Furukawa3, S. Fujieda1, Y. Fujibayashi2; 1Department of Otorhinolaryngology, University of Fukui, Fukui, Japan, 2Biomedical Imaging Research Center, University of Fukui, Fukui, Japan, 3Molecular Imaging Center, National Institute of Radiological Science, Chiba, Japan. Aim: Copper chelate, Cu(II)-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is retained in hypoxic tumor. In general, hypoxic region of tumor is considered as resistant to chemotherapy and radiotherapy, and the cell proliferating area of tumor is sensitive to the therapies. Does it mean the cells in 64Cu-ATSM accumulated area don’t proliferate? In our previous study we showed Ki67 positive cells for proliferating cells were not mostly appeared in the high accumulation area of 64Cu-ATSM. In this study, we investigated correlation between cell proliferation and accumulation of 64Cu-ATSM in tumor by BrdU, one of the proliferation makers, and compared with 18FDG.Materials and Methods: C57BL/6 mice bearing subcutaneous LLC1 tumors were injected intravenously with 64Cu-ATSM, 18FDG and bromodeoxyuridine(BrdU). After 1 hour, they were sacrificed and their tumors were extirpated. After dual-tracer autoradiography of 64Cu-ATSM and 18FDG, tumors were fixed in 10% buffered formaldehyde and embedded in paraffin. The paraffin embedded block were cut to 5µm-thick sections and stained with anti- BrdU antibody. Autoradiographic images were divided to 4 levels by uptake level of each tracer. BrdU positive cells of 15 high-power fields were counted at each level of autoradiographic images.Results: In dual-tracer autoradiography, 64CuATSM mainly accumulated at the edge of the tumors. On the other hand, the highest uptake region of 18FDG was present within 64Cu-ATSM region. Most of the high uptake region of 64Cu-ATSM did not overlap with the high uptake region of 18FDG. Since BrdU incorporates into DNA during the S-shape of the cell cycle, BrdU positive cells showed proliferating cells. In immunostaining with BrdU, more positive cells were in the high uptake region of 64Cu-ATSM than the low uptake region of the tracer. Therefore, the number of BrdU positive cells was positively correlated with 64Cu-ATSM uptake. In addition, most BrdU positive cells were shown in the low uptake region of 18FDG than in the high uptake region of the tracer. The number of the cells negatively correlated with 18FDG uptake. Thus, cell proliferation appeared to occur in the high uptake region of 64Cu-ATSM or in the low uptake region of 18FDG.Conclusions: The high accumulation of 64Cu-ATSM was different from the high accumulation of 18FDG. BrdU showed the cells actively proliferated in the high uptake region of 64Cu-ATSM. There seems to be dissociation of Ki67 and BrdU. We need to be careful to interpret `proliferation maker`.

P388 Ion trap mass spectrometry in the qualitative analysis of [18F]MPPF J. Muhonen, T. Lipponen, K. Bergström; Finland.

Helsinki University, Helsinki,

Aim. Mass spectrometry (MS) offers an easy and fast technique to get exact qualitative information such as molecular mass of the molecule. In addition, ion trap mass spectrometry allows possibility for further isolation and fractionation of a certain molecule when MSn is used. This is useful especially when the product and the by-products of the radiosynthesis are identified and the position of [18F]fluorine is located. A particular challenge for the radiosynthesis of 18F-labelled serotonin receptor HT1A ligand 4-[18F]fluoro-N-[2-[1-(2methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (p-[18F]MPPF) are the 18Flabelled by-products. In this study the ion trap mass spectrometry with electron spray ionisation technique (ESI-MS) was tested for the qualitative analysis of the p-[18F]MPPF and the byproducts of the p-[18F]MPPF synthesis. Materials and Methods. The quality and fractionation of the precursor 4-nitro-N-[2-[1-(methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-MPPNO2) and the product reference were measured by ESI-MS with a direct infusion technique. Molecule peaks were identified first by MS and then isolated and fractionated by MS2 and further MS3. A reverse phase (C18) liquid chromatography (LC-ESI-MS) method was developed for p-MPPF and it was used in the analysis of the product and the by-products of the p-[18F]MPPF synthesis. Radiosynthesis of the p-[18F]MPPF was done according to the earlier method (1) starting from the inactive precursor of p-MPPNO2. Results. Correct molecular masses for p-MPPNO2 and p-MPPF were obtained by ESI-MS. In addition, the fractionations of the molecules were reasonable when MS2 and MS3 were tested. The LC-MS method was used successfully for the qualitative analysis of the p-[18F]MPPF and the by-products of the

P389 Automated microwave supported synthesis of Ga-68 labeled peptides for tumor imaging B. Wängler1, M. Schäfer1, A. Runz1, H. Hauser1, J. Schuhmacher1, U. Haberkorn2, M. Eisenhut1; 1Deutsches Krebsforschungszentrum, Heidelberg, Germany, 2Ruprecht-Karls-Universität, Heidelberg, Germany. In the last years there is an increasing demand for radiolabeled peptides for tumor imaging in nuclear medicine. The synthesis of Ga-68 labeled radiotracers such as DOTA-TOC and the bombesin analogue BZH3 (DOTA-Bom) at the German Cancer Research Center (DKFZ) is based on the use of a Ge-68/Ga-68 generator system (J. Schuhmacher et al. Appl. Rad. Isot. 1981; 32: 31) already developed in 1981. The aim of this work was the construction of a fully automated synthesis module for the rapid and convenient preparation of the radiotracers. The main focus herein was to reduce the radiation load of the operator and to obtain reproducible yields. The implementation of a laboratory microwave for the labeling step - as recommended by I. Velikyan et al. Bioconjug. Chem. 2004; 15: 554 - should shorten the synthesis time and enhance the chemical and radiochemical purity. The synthesis module was assembled from parts of a kit developed by NuKam (Fürstenfeldbruck, Germany) and a laboratory microwave (CEM, Kamp-Lintfort, Germany). The generator is eluted with 5.5M HCl (flow: 3mL/min) and the [Ga68]GaCl4- is trapped on an anion exchange resin (AG-1X8, BioRad, München, Germany). 95±3% of the Ga-68 activity was trapped on the anion exchange resin. After drying the resin in a continuous helium flow, 84±3% of the activity was eluted with 200±14µL of aqua ad iniectabilia into the reaction vessel containing the precursor and buffer. The optimal pH range of 4.1 to 4.8 was maintained using Hepes buffer and small amounts of NaOH. The module was optimized with regard to the very small volumes by using a HPLC injection valve which reduced the amount of HCl coeluted with the radionuclide from the anion exchanger. Possible ionic impurities such as [Ga-68]Ga3+ were removed with a SepPak C-18 or C-8 cartridge (Waters, Eschborn, Germany). The radiolabeled peptide was eluted from the cartridge with 1.5 mL ethanol. After ethanol evaporation the product was transferred into isotonic saline and filtered sterile. This module setup allowed labeling of several DOTA peptide derivatives with high yields and purity. In the case of Ga-68-DOTA-TOC, for example, radiochemical yields of 98.1±0.7% were obtained after 2 minutes at 95°C. The radiotracers were produced in high specific activities and good yields with or without a further purification step after synthesis times of 8 or 19 min, respectively.

P390 N-[11C]Methylamino derivatives of 4-hydroxy-2(1H)quinolones as new PET radioligands for the glycine-binding site of NMDA receptors T. Fuchigami1, T. Haradahira2, T. Okauchi2, J. Maeda2, T. Suhara2, K. Suzuki2, F. Yamamoto1, T. Mukai1, M. Maeda1; 1Faculty of Pharmaceutical Sciences, Kyusyu University, Fukuoka, Japan, 2Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. Aim: We have recently developed a PET radioligand, 4-acetoxy-[11C]L-703,717 (AcL703), for detection of the cerebellar glycine-binding site of NMDA receptors, and have just recently performed a first human trial. In human brain, AcL703 showed the highest uptake in the cerebellum. The radioactivity concentration in the cerebellum, however, was insufficient to visualize the cerebellar NMDA receptors by PET, indicating poor brain penetration of AcL703. In this study, in order to further develop a PET radioligand for the glycine/NMDA receptors with high brain uptake characteristic, we synthesized several N-[11C]methylamino derivatives of 4hydroxy-2(1H)-quinolones and examined for their brain uptakes in mice. Material and Methods: Amino groups (NH2, NHMe, or NMe2) were introduced into the terminal phenyl moieties of 4-hydroxy-2(1H)-quinolones (L-703,717 and L-701,315) in place of the methoxy group or hydrogen. The C-11 labeled compounds were obtained by N-[11C]methylations of the corresponding des-methyl precursors with [11C]methyl triflate. In vitro binding characteristics were assessed on rat brain cryosections. In vivo brain uptakes were examined in mice after intravenous injection. Results: The in vitro binding characteristics (IC50, regional brain distribution, and specific binding) were not significantly altered by the introduction of the amino groups, compared with the corresponding methoxy groups. Plasma protein bindings of the labeled compounds were measured by an ultrafiltration method to be 98% and 70% of total for the methoxy and N-methylamino derivatives of L-701,315, respectively. The reduced protein binding of the amino derivative may be due to the decreased acidity and/or lipophilicity. The brain uptakes of the amino derivatives were found to be higher than those of the methoxy derivatives. Conclusion: 4-Hydroxy-2(1H)-quinolones are all acidic with pKa values of around 5, and more amenable to bind with blood proteins than non-acidic compounds. The introduction of basic amino group may increase the pKa value and therefore might reduce unsuitable protein bindings, expecting increase in brain uptake of the amino derivatives of 4-hydroxy-2(1H)quinolones. This hypothesis was strongly supported by the present studies, and, among the amino derivatives tested, 3'-N-[11C]methylamino-L-701,315 had the most suitable brain uptake characteristics for further in vivo evaluation with PET.

P391 Uptake of two sigma ligands and FDG in tumor and inflammation: a microPET study A. van Waarde1, J. Doorduin1, E. F. J. de Vries1, K. Ishiwata2, R. A. Dierckx1, P. H. Elsinga1; 1Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands,

2 Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

Aim: The common PET tracer 18F-FDG is not tumor-specific. Accumulation of 18F-FDG in other cells, e.g. active macrophages, leads to false-positive lesions and is a pitfall in therapy control with 18F-FDG-PET after chemotherapy. Sigma receptors are strongly overexpressed in most human and rodent tumors. We therefore intended to examine whether radiolabeled sigma ligands are more tumor-specific than 18F-FDG. Methods: The sigma ligands 11C-SA4503 (sigma-1 subtype-selective) and 18F-FE-SA5845 (non-subtype selective) were prepared by reaction of 11C-methyl iodide and 18F-fluoroethyl tosylate with the appropriate 4-O-methyl compound. 18F-FDG was produced by the Hamacher method. The tracers were administered to male Wistar rats that bore a C6 glioma in the right shoulder and also had sterile inflammation in the left calf muscle, induced by injection of 0.1 ml of turpentine. Twenty-four hours after administration of turpentine, the rats received an i.v. bolus of PET tracer (50-100MBq). Wholebody images were made with a microPET Focus 220 scanner, 20-60 min after tracer injection. Results: 18F-FDG was taken up avidly both by the tumor and by the inflamed leg, as expected. After injection of 11C-SA4503 or 18F-FE-SA5845, the tumor was visible but not the inflammation. However, these sigma ligands produced a much lower tumor-to-muscle contrast than 18F-FDG. 18F-FE-SA5845 and 18F-FDG visualized the majority of the tumor volume with exception only of necrotic areas, but accumulation of 11C-SA4503 was limited to a very thin rim at the outside of the tumor mass. The same highly characteristic pattern of 11C-SA4503 accumulation was recently observed by our group in a clinical PET study of lung cancer patients. Conclusion: Sigma ligands are more tumor-selective but unfortunately also much less sensitive than 18F-FDG in our animal model. Sigma-1 receptors may be expressed only at the outside of a tumor lesion where actively dividing cells are present.

P392 Improvement in the quantitative PET detection after absolute calibration using 18F-FDG national primary standard C. Giliberti1, L. Strigari2, M. Capogni3, M. Benassi2, M. D'Andrea2, A. Fazio3, M. Criscuoli4, P. De Felice3; 1ISPESL National Institute of Occupational Safety and Prevention, Rome, Rome, Italy, 2Laboratorio di Fisica Medica e Sistemi Esperti, Regina Elena National Cancer Institute, Rome, Rome, Italy, 3ENEA-Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti, C.R. Casaccia, P.O. Box 2400 - I-00100 Rome (Italy)., Rome, Italy, 4IRMET, Torino, Italy. Aim Positron Emission Tomography (PET) plays an important role in the staging of cancer by showing the functional activity of neoplasms respect to normal tissues; in particular, [18F]Fludeoxyglucose ([18F]FDG) allows their detection as regions of increased metabolic activity. The lack of anatomical reference structures and the poor spatial resolution of the PET systems make the interpretation of images difficult. Recently, the potential of integrated PET/CT systems in the definition of the target volume in radiotherapy planning has been demonstrated, allowing to provide both anatomical and functional images in a single imaging session. Within this context, a growing request for 18F calibration of activity calibrators, important to optimise the detection of the lesions, is coming from nuclear medicine centres; it provides the development of the 18F national primary standard. Material and methods The 18F national primary standard has been developed utilizing the 4ʌȕ Liquid Scintillation Spectrometry Method with 3H-Standard Efficiency Tracing (CIEMAT/NIST method), where the counting efficiency İ18F(P) of a Liquid Scintillation Counting system for the nuclide 18F, as function of the quench parameter P is obtained from the experimentally measured counting efficiency İ3H(P) for the tracer nuclide, 3H, by means of a theoretical calculation. The measurements were performed using 18F produced by Amersham Health in the Cyclotron of the EC-JRC in Ispra. An INMRIENEA portable well-type Ionization Chamber was calibrated, established as a Secondary Standard Measurement System and transported in a PET centre, located in Torino (Italy); a suitable calibration procedure for 18F calibrator has been applied and the local PET instrumentation has been calibrated by comparison. Corresponding calibration factors were calculated as ratios of reference activity values and IC readings, which in turn were obtained from reference activity concentration and solution mass values. Results Presently at Ispra, 18F activity measurements (both as raw material and FDG synthesis) are performed with an uncertainty lower than 2%. Well-type ionisation chambers were calibrated by using the standard source and the calibration factors have been evaluated for different masses, source geometry and self-absorption effects. The calibration of scanner PET showed that administrated activity to patients was under-estimated respect to the activity reference. PET images has been analyzed to evaluate changes in Specific Uptake Values after calibration. Conclusion Results underline that calibration is quite important for the detection of lesions as regions of increased metabolic activity and in particular for uptakes quantification studies.

P393 How much 18FDG is needed to scan a given number of oncologic patients with PET/CT? A. Speranza1, A. Varrone1, A. Venetucci2, G. Storto1, M. Panico1, A. Russo1, L. Pace2, M. Salvatore2; 1cnr-ibb, Napoli, Italy, 2Università di Napoli "Federico II", Napoli, Italy. Aim 18F-FDG PET scan is a rising methodological examination in the diagnostic clinical routine imaging whose costs are proportional to economical investment for setting up PET unit as well as to the monthly expenditure due to personnel salary, electrical energy and 18FDG costs for production or purchase. In particular the 18F-FDG related costs can play a dominant role in determining the amount of monthly cost to afford for the PET unit management. Therefore, the calculation of the right amount of 18F-FDG needed for a given number of patients to be scanned may permit a better tuning of cost management. We aimed at evaluating the 18F-FDG demand for a given number of patient to scan and for several scan duration time. Materials & Methods To quantify the amount of 18F-FDG demand it is important to know the following data:a) injected activity for each patient;b) time interval between 18F-FDG administration and scan;c) scan duration time (SDT). Injected activity depends on patient body weight and age. The EANM guide-lines in PET oncology suggests that activity for adults can range between 111-555 MBq (370MBq) and that recommended interval of time between 18F-FDG administration and scan is of 60 minutes. Scan duration time significantly depends on the kind of scanner and acquisition

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Poster Presentation

radiosynthesis and sensitivity of the LC-MS was noticed to be sufficient. Conclusion. The LCESI-MS is a useful instrument for characterizing the products after synthesis of 18F-labelled tracers as p-[18F]MPPF. In addition, this study showed that it may be possible to measure the specific radioactivity of 18F-labelled tracer by a quantitative LC-ESI-MS method. 1. Le Bars D. et al. Nucl Med Biol 1998; 25: 343-350

mode (2-3D). The kind of PET crystal used (BGO/LSO) for emission and the kind of source used (68Ge/CT) for transmission can considerably modify SDT, which range 55-13 minutes according to literature data. Regarding this data and to our own experience with the (GE PET/CT LS Discovery Scanner) we generate an algorithm calculating the 18F-FDG demand with respect to number of patient (NP) and SDT of 20, 30 and 40 minutes; calculations were carried-out taking into account average injection dose and interval between administration and scanning as EAMN guide-lines. Results. The table shows average FDG demand according to NP and SDT. The activities is in GBq.

.

NP2 NP3 NP4 NP5 NP6

NP7

NP8

NP9

NP10 NP11

NP12

SDT20

1,19 1,80 2,72 3,80 4,92

6,57

8,51

10,45 13,40 16,82

20,01

SDT30

1,26 2,12 3,28 4,83 6,88

9,58

13,12 17,69 23,60 31,17

40,98

SDT40

1,47 2,55 4,20 6,79 10,05 14,80 22,21 31,20 43,78 >43,78 >>43,78

Conclusion 18F-FDG demand increase exponentially with the number of patients to scan. Therefore, the number of scheduled patients and the PET scanners performance are the factors determining 8F-FDG demand, which has large impact on monthly costs of a PET centre.

P394 Stability of Fluorotrialkylsilanes as Prosthetic groups for Instant Labelling of Biomolecules with Fluorine-18 U. Choudhry1, K. Martin1, D. Mainard1, S. C. G. Biagini2, P. J. Blower3; 1University of Kent, Biosciences Dept, Canterbury, Kent CT2 7NJ, UK, United Kingdom, 2University of Kent, Physical Sciences, Canterbury, Kent, CT2 7NJ, UK, United Kingdom, 3Kings College London, Division of Imaging Sciences, London, UK, United Kingdom. Background: Current methods for 18F labelling of peptides for PET imaging are timeconsuming and complex. More efficient (preferably single step) methods, analogous to 99mTc kits, are required because of the short half-life (110 min) of 18F. It has been suggested [1] that single-step nucleophilic fluorination with fluoride ions may be possible using silicon-fluorine chemistry. Aims: This work aims to identify suitable alkyl groups to include in the required alkoxytrialkylsilane, in order to achieve the fastest radiolabelling (nucleophilic displacement of alkoxide by fluoride) and optimal kinetic stability of the Si-F bond (and hence optimal in vivo stability). Material & Methods: Four model trialkylfluorosilanes were synthesised and evaluated using HPLC and NMR to determine rates of formation and hydrolysis of Si-F bonds: ButPh2SiF, Ph3SiF, ButMe2SiF, and Me2PhSiF. The fluorosilanes were incubated in 1:1 phosphate buffered saline (pH 7.4):acetonitrile solution, and in 1:1 acetate buffer (pH 5):acetonitrile, 1:1 bicarbonate buffer (pH 8.5 and 11). Results: Rapid Si-F bond formation (within 5 minutes at 40oC) on reaction of trialkylalkoxysilanes with fluoride was confirmed by NMR and HPLC in all cases, showing that rapid fluorination is feasible. However, only ButPh2SiF showed sufficient hydrolytic stability at 40oC to allow feasibility of imaging studies. At pHs 5 and 7.5 hydrolysis of ButPh2SiF was not detectable even at 6 h. In alkaline conditions its hydrolysis was more rapid: at pH 8.5 it was below 15% at 2 h, and at pH 11 it was complete before 1.75 h. Conclusion: The hydrolysis of the Si-F bond to give a hydroxysilane and fluoride is base-catalysed but is slow at acidic, neutral and mildly basic pH. The rate of Si-F bond formation from alkoxysilane is fast enough for radiolabelling within a few minutes. Steric hindrance is a requirement to ensure adequate kinetic stability of the Si-F bond, and the tbutyldiphenylalkoxysilane group has therefore been selected for further development as a prosthetic group for single step labeling with 18F- ions straight from the cyclotron. Reference 1 Walsh JC, et al. J Labelled Comp Radiopharm 1999; 42(suppl): S1-S3.

P395 The synthesis of the stable substrate for imaging HSV-1 TK expression and biological study G. An, T. Choi, H. Ahn K. Lee, B. Moon, S. Lim, G. Chon, H. Rhee, K. Chun; Korea Institute of Radiological & Medical Science, Seoul, Republic of Korea. Background: The development of effective and stable compounds for use in tumor imaging is one of the most important interest in the field of radiopharmaceuticals and nuclear medicine. In last decade, interest in the study of the 5-iodo-2’-deoxyuridine analogues has grown exclusively since the potential antitumor therapeutic agents. methods The replacement of the furanose oxygen by a carbon gives the nucleoside increased in vivo stability. Radioiodinated carobcyclic IUdR analogue was evaluated for monitoring of HSV1-TK (herpes simplex virus type 1 thymidine kinase) gene transduced MCA hepatoma cells and wild-type MCA cells. The synthetic route employed cyclopentadiene as a starting material and proceed in good yield through 8 steps which contain Pd(0)-catalyzed coupling reaction and radioiodination as key reactions. Carbocyclic tin precursor was radioiodinated with I-124 This radioiodinated compound was purified with reverse phase HPLC system. Cellular uptake was determined at fixed MCA and MCA-TK cell density for 12 hr incubation. . Results The synthesis of trialkyltin precursor for iodination was achieved from cyclopentadiene in 37 % overall yield and iodination was employed in high yield. Specific radioactivity of radiocarbocyclic IUdR analogue was approximately 6x10-5 mCi/mg. The MCA-TK uptake of radiocarbocyclic IUdR analogue was about 2 times higher than MCA uptake at 12 hr incubation. conclusion The synthesis of carrier free carbocyclic IUdR analogue is currently under investigation. We hope this synthetic protocol can be a useful method for the synthesis of other carbocyclic radiopharmaceuticals. These results suggest that radioiodinated carbocyclic IUdR analogue can be applied to monitoring of HSV1TK gene expression.

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P30 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Radiopharmacy/Radiochemistry: Antibodies/Proteins/Peptides P396 Preparation and evaluation of In-111 ttda-herceptin for radioimmunoimaging agent T. Luo, I. Tang, H. Yang, W. Lin, Y. Fu; Institute of Nuclear Energy Research, Taoyuan, Taiwan, Province of China. Herceptin has been identified as a highly specific affinity humanized antibody for Her-2/neu type breast cancer in clinical. In this report, Herceptin linked with 3,6,10-tri(carboxymethyl)-3,6,10triaza- dodecanedioic acid (abbreviated as TTDA) was used to label with In-111 radioisotope. Different reaction conditions were tested to find the better labeling results checked with radiochemical purity. The experimental results showed that better labeling yield could be achieved at pH 7 buffer and the temperature setting at room temperature or 37oC or 50oC. We also used MCF-7, breast cancer cell line, to test the radioimmunoactivity and internalization of In-111 TTDA-Herceptin. It revealed that In-111 TTDA-Herceptin could bind to MCF-7 and part of activity could enter into the cancer cell through internalization. Animal imaging experiments with BALB/c mice implanted with MCF-7 showed that the uptake of tumor site was seen at 3 hr post- injectied In-TTDA-Herceptin. We suggest that In-111 TTDA-Herceptin could be potentially used as a radioimmunoimaging agent in the future.

P397 Target affinity, specificity and internalisation of an anti-CD33scfv expressed by Pichia pastoris for radioimmunotherapy of acute myeloid leukaemia L. M. Emberson, A. J. Weeks, P. J. Blower, P. J. Nicholls; University of Kent, Canterbury, Kent, United Kingdom. CD33 is a cell surface glycoprotein expressed on cells of myelomonocytic lineage, leukaemic cells, but not haematopoietic stem cells, and therefore has become a popular target for new immunotherapeutic approaches to treat leukaemia. Radiolabelled anti-CD33-mAbs such as 213Bi-labelled HuM195 have already been developed for radioimmunotherapy of acute myeloid leukaemia. However, the biokinetics of whole antibodies are not well-matched with the short half-life of alpha emitters (213Bi, 211At). Therefore, the methylotrophic yeast Pichia pastoris expression system was used with strain KM71H, as shake-flask cultures, to produce an antiCD33 single chain variable fragment (scFv), for conjugation to a therapeutic radionuclide. Analysis of the binding and specificity of the scFv for target antigen using flow cytometry and Biacore analysis demonstrated specific binding of the scFv to CD33, both on the surface of human leukaemic cell lines HL-60 and U937, and in soluble form. The thermal stability of the scFv was tested by incubation in human serum at 37°C for 0-10 days. Flow cytometry analysis of aliquots removed each day showed no decrease in functionality over time. As a baseline for comparison to the radiolabelled scFv, cell proliferation/viability and DNA synthesis inhibition studies have been performed with the unlabelled scFv. These assays have shown that the scFv has no effect on the growth/proliferation of HL60 or U937 cells. For the radiolabelled scFv to be most effective in vivo, internalisation into the target cell is essential. HL60 and U937 cells pulse labeled with anti-CD33-mAb or anti-CD33-scFv, and analysed at various timepoints up to 6hrs using flow cytometry, showed that the scFv is internalised at a rate comparable to whole antibody. Preliminary microscopy data supports these findings. This anti-CD33-scFv has demonstrated specific and high affinity binding to target antigen, and other characteristics necessary for therapeutic applications, and therefore warrants further evaluation as a vehicle for targeted radionuclide therapy.

P398 Preliminary biodistribution study of 131I-labelled and 99mTctricarbonyl-labelled anti-MUC1 trivalent antibody S. Schoonooghe1, I. J. G. Burvenich2, P. Blanckaert2, F. De Vos2, N. Mertens1; 1Flanders Institute of Biotechnology, Ghent, Belgium, 2 University of Ghent, Ghent, Belgium. Aim: MUC1 is a transmembrane epithelial mucin at the luminal surface of glandular epithelia. Its highly expressed and underglycosylated form on carcinomas and metastatic leasions is a potential target for radioimmunotherapy. The monoclonal antibody PH1 binds PAPGS, contained within the tandem repeat of the linear MUC1 core protein. A trivalent anti-MUC1 tribody was developed to target this repetitive cancer associated form of MUC1. The aim of this study was to investigate the in vitro stability and pharmacokinetics of 99mTc-tricarbonyl-labelled mono-, biand trivalent anti-MUC1 antibodies and compare the results to their iodinated counterparts.Materials and Methods: The (His)6-labelled PH1 antibodies (mono-, 50 kDa; bi-, 75 kDa; trivalent, 100 kDa) were affinity-purified from HEK293T supernatant. 99mTc-tricarbonyllabelled PH1 antibodies were prepared using IsoLink Carbonyl Labeling Agent (Mallinckrodt). PH1 antibodies were radio-iodinated using the Iodo-Gen method. After purification over a Sephadex PD-10 column, radiochemical purity and stability were evaluated with HPLC. Biodistribution studies of 99mTc-tricarbonyl- and 131I-labelled PH1 antibodies were performed in NMRI mice. Animals were sacrificed at 1min, 1h, 3h, 6h, 24h, and 48h post-injection.Results: Typical labelling efficiencies were between 30-50% with 99mTc-tricarbonyl and between 6070% with 131I. After PD10 elution, radiochemical purity remained > 98% after 24h at room temperature in PBS. With 99mTc-tricarbonyl (n = 3), the blood activity at 24 h was 1,00 ± 0,24 %ID/g for trivalent PH1, 1,27 ± 0,25 %ID/g for bivalent PH1 and 0,45 ± 0,04 %ID/g for Fab PH1. With 131I (n = 1), the preliminary biodistribution study showed a blood activity of 1.95 %ID/g for trivalent PH1, 0.56 %ID/g for bivalent PH1 and 0.51 %ID/g for Fab PH1. With 99mTc-tricarbonyl all PH1 antibodies showed high liver and kidney uptake (10-20%ID/g at 24 h post injection), with highest kidney uptake observed with Fab (> 30% ID/g). This liver and kidney uptake was not observed with the radio-iodinated counterparts. However, radio-iodinated

P399 Production of 227Th-labelled radioimmunoconjugates, assessment of antigen binding ability and stability in vitro. J. Borrebaek1, J. Dahle2, K. B. Melhus2, C. Krogh2, Ø. S. Bruland2, R. H. Larsen1; 1Algeta ASA, Oslo, Norway, 2The Norwegian Radium Hospital, Oslo, Norway. Aim Radioimmunoconjugates with beta-emitters are currently utilized for therapy against CD20 positive B-cell lymphoma. Conjugating monoclonal antibodies with alpha-emitting nuclides may further enhance the effectiveness of radioimmunotherapy in some settings. We have evaluated the possibility of constructing radioimmunoconjugates by using the novel therapeutic candidate alpha-emitter 227Th, which has a beneficial physical half-life of 18.7 days and can be produced in good yield and with adequate purity from a generator system utilizing the parent nuclide 227Ac (half-life of 21 years). Materials and Methods The bifunctional chelator p-SCN-BenzylDOTA was used as a linker to connect 227Th to the two monoclonal antibodies, Rituximab (MabThera) and Trastuzumab (Herceptin). To determine the immunoreactive fractions, binding studies were performed with CD20 and Her/2 positive cells, respectively, with or without antigens pre-saturated with unlabelled antibody. To evaluate stability the radioimmunoconjugates were incubated in 80% bovine serum at 37°C. Unbound activity was separated from the conjugate using gel filtration at different timepoints of incubation. Percent stability was calculated as percent of 227Th activity in the antibody-containing fractions versus the total activity initially applied. Results The overall labelling yield spanned from 6 to 17 %. The radioimmunoconjugates demonstrated specific antigen binding, with relevant immunoreactive fractions, which could be blocked by pre-incubation with unlabelled antibody. The in vitro stability testing at 37°C in serum demonstrated high stability of the radioimmunoconjugates over several weeks. Conclusions These data indicate that this novel radioimmunoconjugate possesses the desirable properties, in terms of stability and immunoreactivity, for utilization in cancer therapy.

P400 Optimization of radiolabelling efficiency of [ DOTA0,Tyr3] octreotate with 177Lu, 90Y, 111In M. Ocak1, L. Kabasakal2, E. Uslu3, C. Decristoforo4, S. Mut2, I. Uslu2; 1Istanbul University,Pharmacy Faculty,Department of Pharmaceutical Technology, Istanbul, Turkey, 2Istanbul University,Cerrahpasa Medicine Faculty,Department of Nuclear Medicine, Istanbul, Turkey, 3Istanbul University,Cerrahpasa Medicine Faculty, Department of Biochemistry, Istanbul, Turkey, 4Clinical Department of Nuclear Medicine, Inssbruck Medical University, Inssbruck, Austria. Receptor targeted scintigraphy using radiolabeled somatostatin analogs has been used with great success to obtain in vivo presence of somatostatin receptors on somatostatin expressing tumours. Nowdays a new and fascinating application of radiolabelled somatostatin analogs is radionuclide therapy. For this purpose 177Lu, 90Y and 111In have been used to label somatostatin analogs for peptide receptor radionuclide therapy. And also, it has been shown somatostatin analogue [ DOTA0,Tyr3] octreotate (DOTATATE) has a higher affinity for the somatostatin receptor subtype 2 as compared with [ DOTA0,Tyr3] octreotide (DOTATOC). AIM: The aim of this study was to determine the optimal parameters for the radiolabelling DOTATATE with 177Lu, 90Y and 111In in our laboratory conditions.Methods: The labeling DOTATATE with 177LuCl3( 0.05 M HCl) was carried out in sodium ascorbate/gentisic acid buffer (pH 3.5, 4, 4.5, 5, 5.5), at different temperatures (80ºC, 100 ºC) and incubation periods (10 min., 20 min., 30min.) For labeling DOTATATE with 90YCl3 and 111InCl3( 0.05 M HCl) were studied in asetat gentisin asid buffer (pH 3.5, 4, 4.5, 5, 5.5), at 100 ºC and different incubation periods (10 min., 20 min., 30min.). Radiolabeling efficiency of the radiolabeled peptide was studied at room temperature and instant ITLC was performed with mobil phase Na-citrate pH 5.Results: The best condition of labeling efficiency of DOTATATE with 177Lu has been found in pH 4-4.5 at 80 ºC, 20 min (94.08%, 95.49% respectively). The best condition of labeling efficiency of DOTATATE with 90Y have been found in pH 4-4.5 at 100 ºC, 20 min (96.17±0.33 %, 94,39±1,68 %respectively). The best condition of labeling efficiency of DOTATATE with 111In have been found in pH 44.5 at 100 ºC, 30 min (94.63±1.21 %, 96.66±1.14% respectively) .Conclusions: Results suggested that radiolabeling efficiency of DOTATATE different for each radionuclide and with 177Lu, 90Y, 111In it is controlled by the pH, temperature and incubation time.

P401 Preparation and characterization of 99mTc radiolabeled glycosylated somatostatin as potential imaging agent for somatostatin receptor positive tumours C. He1, S. Zhai2, Y. Shen1, C. Hu1, L. Zhao2, H. Cui1, J. Du1; 1Department of Iosotpes, China Institute of Atomic Energy, Beijing, China, 2Medical Isotope Research Center, Peking University, Beijing, China. Aim: Glycosylated somatostatin-14 (somatostatin-dextran) has shown an enhanced in vivo stability and retained high affinity to all five somatostatin receptor subtypes. The aim of this study was to prepare 99mTc radiolabel somatostatin-dextran conjugate and test it as a potential imaging agent for somatostatin receptor positive tumours. Materials and Methods: Somatostatin-14 and new synthesized chelator MAG2-Lys were coupled to periodate activated dextran-10. The linkage was stabilized by reductive amination to yield somatostatin-dextranMAG2Lys (SMS-Dex10-MAG2Lys) conjugate. The SMS-Dex10-MAG2Lys was then

radiolabeled with 99mTc using sodium tartrate as a transchelator. The radiolabeled conjugate was purified and characterized by HPLC. The specific biding of 99mTc radiolabeled conjugate was tested in vitro on rat brain cortex membranes by competition against somatostatin-14. The in vivo pharmacokinetic and tumour uptake of radiolabeled conjugate was evaluated in nude mice bearing human pancreatic tumour. Results: The SMS-Dex10-MAG2Lys showed high somatostatin receptor binding affinity, i.e. in the same nM range as the reference ligand somatostatin (IC50 ~ 1.0 nM). Under the optimum conditions, the labelling efficiency of 99mTcMAG2Lys-Dex10-SMS was approximately 40-50%. The biodistribution showed that the excretion of the conjugate was mainly through liver and kidneys. The half-life of conjugate in blood was 2.4 h. The accumulation of radioactivity in the tumour was 1.25% ID/g at 4 h after injection and remained almost constant within 24 h. In all other organ systems the radioactivity was more rapidly eliminated. 99mTc-MAG2Lys-Dex10-SMS was selectively localized in tumour at 4 h imaging. Conclusions: The results suggest the possible potential of 99mTcMAG2Lys-Dex10-SMS as a somatostatin receptor positive tumours imaging agent. This work was supported in part by the National Natural Science Foundation of China (30370421) and the President Foundation of China Institute of Atomic Energy.

P402 Elimination and retention of 177Lu-DOTA-octreotate in perfused rat kidney F. Trejtnar1, A. Laznickova1, M. Laznicek1, H. R. Maecke2; 1Charles University, Faculty of Pharmacy, Hradec Kralove, Czech Republic, 2 University Hospital, Basel, Switzerland.

REJECTED BY AUTHOR P403 Multiple DOTA chelates conjugated to octreotate strongly diminish the tumour localisation. W. Mier1, K. Graham1, S. Kraemer1, C. Beck1, M. Eisenhut2, U. Haberkorn1; 1Radiologische Klinik, Heidelberg, Germany, 2Deutsches Krebsforschungszentrum, Heidelberg, Germany. Aim: The use of tumour specific-peptides in the therapy and diagnosis of malignant disease is a modality that has recently shown rapid progress. To improve the efficiency in the diagnosis and treatment of disseminated occult disease, the use of chelator-oligomers together with carrier substances such as tumour specific peptides represents an attractive prospect. Using a stepwise synthesis strategy the defined synthesis of Tyr3-octreotate conjugated to up to nine DOTA ligands per peptide could be performed (1). The peptide derivatives retain a relatively high receptor binding affinity. The aim of this study was the investigation of the effect of the large chelator moiety on the biodistribution of these peptides.Materials and Methods: Four (DOTA)nTATE (n = 1,3,6,9) derivatives were labelled with In-111. The products were analyzed by RPHPLC. No uncomplexed radiometal could be determined after 30 min at 60 °C. At 1 h post injection biodistribution experiments were performed by systemic application (injection via the tail vein) in nude mice bearing the SSTR positive AR4-2J tumours.Results: It was found that the biodistribution of these peptides is dominated by the DOTA chelates. At 1 h p.i. all of the compounds investigated revealed high uptake in the kidneys. The highest value in the kidneys was observed for the DOTA-trimer conjugate. Consequently, a substantially decreased uptake in the tumour and the SSTR-positive tissues had to be observed (%ID/g tumour: DOTATOC = 8.90; (DOTA)3TATE = 3.57; (DOTA)6TATE = 0.50 and (DOTA)9TATE = 0.45).Conclusions: Due to the hydrophilicity of the chelator-oligomers a relative large uptake into kidneys could be expected. However, the complete loss of tumour uptake for (DOTA)6TATE and (DOTA)9TATE is surprising because of their high SSTR affinity. This result reveals that the receptor affinity is not the predominant factor controlling accumulation in the tumour. This data shows the necessity of a balanced polarity charge of the SSTR affine peptides for therapeutic applications. Reference: (1) Mier W, Graham KAN, Wang Q et al. Synthesis of peptide conjugated chelator oligomers for endoradiotherapy and MRT imaging. Tetrahedron Lett 2004; 45: 5453-5.

P404 Preclinical pharmacokinetic comparison of glucose-125ITyr3-octreotate with DOTA-125I-Tyr3-octreotate A. Laznickova1, M. Petrik1, L. Melicharova1, M. Laznicek1, M. R. Zalutsky2; 1Charles University, Faculty of Pharmacy, Hradec Kralove, Czech Republic, 2Duke University Medical Centre, Durham, NC, United States. Aim: Targeted radionuclide imaging and treatment of the cancers of neuroendocrine origin are based upon the interaction of radioligands with somatostatin receptors in the target tissue. Radioiodinated somatostatin derivatives represent promising group of such agents. Recently it has been shown that NH2-terminal carbohydration leads to an improvement of the peptide receptor affinity and its retention in the tumour (1). In this study, preclinical analysis of distribution profiles and elimination pathways of radioiodinated glucose-Tyr3-octreotate (125Igluc-tate) is presented in comparison with that of another promising targeting iodinated radiopharmaceutical, DOTA-125I-Tyr3-octreotate (125I-DOTA-tate).Materials and Methods: For radiolabelling of somatostatin analogues under study with 125I, chloramine-T method was used. Biodistribution was determined in male Wistr rats after administration of the peptides in a dose of 1 µg/kg. Internalisation properties of somatostatin analogues were determined in rat pancreatic carcinoma AR42J cells.Results: Specific internalization by sstr2 - expressing AR42J rat pancreatic carcinoma cells in vitro and radioactivity accumulation of 125I-gluc-tate in somatostatin receptor-rich organs (the pancreas and adrenals) were significantly higher in comparison with 125I-DOTA-tate. Plasma radioactivity-time decrease was similar for both agents. Whereas 125I-DOTA-tate was excreted mostly by urine, 125I-gluc-tate was eliminated parly by urine nad partly by feces. The liver accumulation of radioactivity was significantly higher and radioactivity uptake in the kidney was significantly lower for 125I-gluc-tate in comparison with 125I-DOTA-tate up to 48 hr after dosing. HPLC analysis of radioactivity in the urine confirmed the predominant elimination of the parent peptides in urine 2 hrs after dosing

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Poster Presentation

PH1 antibodies showed higher stomach uptake between 1-3 h post injection. All other organ activity remained below the blood activity, with exception of the spleen.Conclusions: These preliminary data suggest that 99mTc-tricarbonyl is not the ideal isotope for the PH1 antibodies due to high kidney uptake and retention in the liver. However, this might be reduced by using basic amino acids (e.g. Lysine) or other radiometals. Also, the clearance of 131I-labelled PH1 molecules differed from that of 99mTc-tricarbonyl-labelled PH1 molecules. These results warrant further investigation of 131I-labelled PH1 molecules as MUC1 detecting radiotracers.

whereas 24 and 48 hrs after administration, the eliminated radioactivity was mostly in the form of low molecular weight metabolites. Rat liver perfusion experiments showed higher bile clearance of 125I-gluc-tate when compared with 125I-DOTA-tate.Conclusions: In summary, 125I-gluc-tate exhibited higher uptake in somatostatin receptor-rich organs with lower uptake in the kidney. For that reason radiohalogenated gluc-tate may be promissing ligand for targeted radiotherapy for instance in case when labelled with short living 211At. [1] Vaidyanathan, G., Friedman, H.S., Affleck, D.J., Schottelius, M., Wester H.-J., Zalutsky M.R.: Specific and highlevel targeting of radiolabeled octreotide analogues to human madulloblastoma xenografts, Clin. Canc. Res. (2003) 9, 1868-1876

P405 The assess of capability of some compounds to reduce the renal retention of radiolabelled somatostatin analogues M. Laznicek, A. Laznickova, J. Cihlo; Kralove, Czech Republic.

Faculty of Pharmacy, Hradec

The aim. Targeted peptide radionuclide therapy represents a promising technique for the treatment of neuroendocrine tumours and their metastases. However, high and long term renal retention of radioactivity is a major dose-limiting factor in this therapy owing to the possible renal radiation toxicity. The aim of this study was to test selected compounds in order to assess their capability to diminish the renal retention of 111In-DOTA-Tyr3-octreotate (In-DOTA-tate) in rats and in the proximal tubule-derived opossum kidney (OK) cells. The approach is centered on the possible blockade of receptor-mediated endocytosis via the megalin-cubilin system in the kidney. Methods. In-DOTA-tate was administered to male Wistar rats in the dose of 1 µg/kg. For the inhibition of receptor-mediated endocytosis, groups of animals were pretreated 15 min before the peptide dosing with lysine (1g/kg intravenously, and 1g/kg p.o.), maleate (400 mg/kg i.v.) cytochrom C (50 mg/kg i. v.), gentamicin (10 mg/kg i.v.) and cyclosporine A (100 mg/kg i.v.). 24 hours after In-DOTA-tate administration, distribution of radioactivity in selected organs and tissues of rats were determined. Radioactivity in the kidney of pretreated animals was compared with that of a control group. Radioactivity accumulation in organs with a high density of somatostatin receptors (namely the adrenals and pancreas) served as an endogenous marker of the affinity of In-DOTA-tate to somatostatin receptors. Results. In all groups of animals, no statistically significant changes of radioactivity accumulation in the adrenals were determined. It is known from literature that aminoacid solution is able to reduce renal uptake of radiolabelled peptides. In agreement with that, renal radioactivity was inhibited by lysine (to 34% after intravenous administration and to 71% after peroral administration). Maleate reduced renal uptake of radioactivity to 26% (maleate inhibits a variety of renal transport systems by inhibiting the citric acid cycle in tubular cells and reduces ATP supply). cytochrom C (interacts with megalin receptors and decreases renal accumulation for example aminoglycosides), gentamicin (is intrenalized by megalin transport system in renal proximal tubules) and cyclosporine A (an inhibitor of P-glycoprotein-mediated transport), did not significantly change renal radioactivity uptake after In-DOTA-tate administration. The results obtained in animals were compared with that of uptake kinetics by OK cells. Conclusion. Our results demonstrated that renal uptake of In-DOTA-tate was significantly reduced by a pre-treatment of animals with lysine and maleate. No other compound under study (cytochrom C and gentamicin) exhibited a significant capability to inhibit renal accumulation of somatostatin analogues.

P406 Comparative evaluation of two novel, Bombesin-like peptides for prostate cancer detection E. Gourni1, P. Bouziotis1, M. Paravatou1, C. Zikos2, G. Loudos3, M. Fani2, E. Livaniou1, S. Xanthopoulos1, S. C. Archimandritis1, A. D. Varvarigou1; 1NCSR Demokritos, Athens, Greece, 2Biomedica Life Sciences SA, Athens, Greece, 3National Technical University of Athens, Athens, Greece. Aim: Aim of the present work is the evaluation of the complexes two novel Bombesin (BN)-like peptides form with radiometals, to investigate their possible use in prostate cancer detection. The first derivative is: Gly-Gly-Cys-Aca-BN[2-14] (BN1.1) where Aca: 6-amino-hexanoic acid and pyroglutamic acid in the bombesin molecule has been replaced by the chemical group Gly-GlyCys-Aca, bearing amino-acid combination capable of complexing a variety of radiometals. The other derivative under study is: Gly-Gly-Cys-Aca-BN[7-14] (BN1.1p). The last was chosen because GRP and bombesin share amidated C terminus sequence homology in the final 7 amino acids. Materials and methods: The peptide derivatives were synthesized by the SPPS method, according the Fmoc strategy, their 185/187Re complexes were formed via the precursor rhenium gluconate and were identified by RP-HPLC, ESI-MS and 1H- and 13C-NMR. Radiolabeling with 99mTc was performed via the precursor 99mTc-MDP. The stability of the radiolabeled species was examined with time. The ability of the new peptide to tag cancer cells was evaluated in an epithelial prostate cancer cells (PC3) culture. Initially, we examined whether the BNderivatives, as well as their 185/187Re complexes inhibit [125I-Tyr4]-BN binding. In vitro studies followed, to determine the efficiency of internalization of the 99mTc-BN like peptides and the degree of the residualization of 99mTc into the cells as a function of time. Studies of the in vivo behavior and of the pharmacokinetic properties of the 99mTc-labeled derivative were assessed in normal mice and in prostate cancer models. Autoradiographic studies on human cancer sections are in progress. Results: Spectroscopic data indicated the formation of a monomer. Chromatographic analysis showed for both derivatives, that 99mTc labeling led to the formation of a single radioactive species in high yield (>98%), stable with time. Biodistribution studies indicated that both derivatives present specificity for the cancer cells studied and get rapidly internalized into the prostate cancer cells. The in vivo behavior of the radiolabeled products, as evaluated in normal mice, presented high uptake in pancreas, while body elimination took place mainly via the urinary system in the case of 99mTc-BN1.1 and through the hepatobiliary in the case of 99mTc-BN1.1p. Satisfactory tumor images were obtained with both radiolabeled peptides. Conclusions: The above preliminary results indicate that the new Bombesin derivatives are promising for human cancer studies. #

P407 Primary evaluation of cRGDfK-S-Cys-99mTc(CO)3 for integrin targeting and tumor angiogenesis imaging

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D. Psimadas1, M. Fani1, C. Zikos1, P. Bouziotis2, E. Gourni2, S. Xanthopoulos2, S. C. Archimandritis2, A. D. Varvarigou2; 1Biomedica Life Sciences SA, Athens, Greece, 2NCSR Demokritos, Athens, Greece. Aim: Primary tumor growth and metastasis are angiogenesis dependent. The increased expression of Įv integrins on activated endothelial and tumor cells, but not on quiescent endothelial cells, suggest the potential suitability of radiolabeled antagonists of this adhesion receptor for cancer imaging and/or therapy. RGD peptides, which are recognized by these integrins and are radiolabeled via the precursor [99mTc(H2O)3(CO)3]+ through different bifunctional chelating agents (BFCAs), have been previously evaluated by our group. In this study we introduce a new BFCA in an RGD peptide and we evaluate the radiochemical and radiopharmacological properties of the new derivative. Material and methods: This study was performed on the cyclic pentapeptide cRGDfK (Arg-Gly-Asp-D-Phe-Lys), which was synthesized by employing the SPPS method, according to the F-moc strategy. On the Nİ-amino group of the Lys of cRGDfK we have conjugated the BFCA S-Cys on resin. This chelator binds the 99mTc-tricarbonyl precursor in a tridentate way all three water molecules being replaced, when radiolabeled. The effect of heating time and peptide concentration on the radiolabeling was studied. In vitro stability of the radiolabeled derivative was assessed: a) at different time-points, b) in the presence of an excess of His and Cys and c) in human serum. In vitro internalization and efflux studies in cancer cells, and autoradiography in slices from various human cancers, were performed. The in vivo behavior and the pharmacokinetics of the radiolabeled product were studied in normal mice. Results: Labeling of cRGDfK-S-Cys led to the formation of a single product (>98%). The study of the effect of heating time and peptide concentration on the radiolabeling showed that for >20 min heating, even at low concentrations, high radiolabeling was obtained (>85%). In vitro stability studies showed cRGDfK-S-Cys-99mTc(CO)3 to remain stable for 24 h, at RT or when incubated with a 1000-fold excess of His and Cys at 37oC. Incubation with human serum showed quite good stability. The radiolabeled compound internalizes rapidly in cancer cells (plateau at ~15min). The study of the in vivo behavior of the derivative showed that cRGDfK-S-Cys-99mTc(CO)3 has fast blood clearance and is eliminated rapidly by both the urinary and the hepatobiliary system. Conclusion: This novel, Tc-labeled RGD derivative has noteworthy in vitro and in vivo stability and good internalization behavior in cancer cells in vitro. Evaluation of this compound on tumor-bearing animals, already in progress, is expected to demonstrate that it is a promising agent for imaging primary and metastatic tumors. #

P408 Membrane extraction - a new method for purification of labeled compounds T. M. Trtic-Petrovic1, K. Kumric1, E. Koumarianou2, S. Archimandritis2, J. Comor1; 1Vinca Institute of Nuclear Science, Belgrade, Serbia and Montenegro, 2NCSR Demokritos, Athens, Greece. The aim of this study was to investigate the applicability of supported liquid membrane (SLM) extraction for cleaning the labeled compound from the free radionuclide. In this particular case the extraction of the radio-lanthanide 177Lu with di(2-ethylhexyl) phosphoric acid (DEHPA) was investigated and this technique was applied as a clean-up procedure for the separation of the labeled peptide 177Lu-DOTA-lanreotide from free 177Lu(III). 177Lu was produced by direct neutron activation of 176Lu (in the form of oxide, Lu2O3) in the research nuclear reactor at NCSR Demokritos, Athens, Greece. After the dissolution of the irradiated target the radioactive concentration was 1.1 GBq·cm-3 and the specific activity of 177Lu was 793 MBq·mg-1. Radiolabeling of the DOTA-lanreotide conjugate was performed following a procedure slightly different than described in literature [1]. 177Lu and DOTA-lanreotide were mixed in the molar ratio of 1:1.7, and incubated at 60oC for 60 min. The radiochemical purity of the labeled 177LuDOTA-lanreotide was determined by gradient HPLC analysis. The free 177Lu(III) was removed from 177Lu-DOTA-lanreotide applying SLM extraction using flat microporous poly(tetrafluoroethene) PTFE membrane laminated on polyester fleece with 5% DEHPA as the carrier. The volume of labeled 177Lu-DOTA-lanreotide was 0.3 cm3, and was not changed after the SLM extraction procedure. The time needed to accomplish the clean-up procedure in the miniaturized membrane contactor with flat membrane was 10 min only. The radiochemical purity of the purified 177Lu-DOTA-lanreotide determined by gradient HPLC analysis was higher than 99% even if the initial purity after the labeling procedure was only about 50% [2]. In contrast to flat membrane based contactors, hollow fiber membranes have very large surface to volume ratio and their effectiveness is expected to be even higher. In order to compare the performance of these two membranes, the extraction efficiency of a polypropylene hollow fiber membrane based contactor made of a single fiber was used for the extraction of lutetium under the same conditions. From the obtained results it is evident that the hollow fiber based extraction process is faster and more efficient than the extraction based on flat membranes. In general, a SLM extraction based clean-up procedure is fast, simple, reliable, and it does not change the sample volume. Also, it can be easily automated in order to reduce the radiation dose received by the personnel. 1. S. Banerjee, et al, Nucl. Med. Biol. 31 (2004) 753. 2. K. Kumric, et al, Sep. Purif. Technol., in press.

P409 DOTA-oligomers for the improved derivatisation of proteins. S. Kraemer1, C. Beck1, M. Eisenhut2, U. Haberkorn1, W. Mier1; 2 Deutsches 1Radiologische Klinik, Heidelberg, Germany, Krebsforschungszentrum, Heidelberg, Germany. Aim: In addition to the tissue specific uptake, the therapeutic success of a tumour specific agent is determined by the cytotoxic effect that can be attained per carrier molecule. The number of receptors expressed on the tumour tissue is limiting the amount of conjugate, that can be administered. If the protein causes pharmacological effects, only very small amounts of protein may be tolerated. Hence the efficacy of the conjugate is determined by the number of the ßemitters per carrier molecule. In addition to the efforts being made to ameliorate the targeting of the protein, the transport capacity of the carrier should thus be increased. We have recently developed a strategy for the conjugation of several DOTA chelates per peptide carrier (1).Materials and Methods: The syntheses of four different p-nitrobenzoyl-[Lys(Mtt)]n-resins (n = 1,3,6,9) was performed by Fmoc solid-phase peptide synthesis on a Rink Amide AM Resin using HBTU/DIPEA activation. After selectively removing the Mtt-protecting groups with 2%

P410 68Ga-labelled peptide inhibitor of vascular adhesion protein1/semicarbazide sensitive amine oxidase as potential PET tracer for inflammation imaging T. A. Pöyhönen1, S. Salomäki2, P. Virsu1, P. Lankinen3, T. J. Mäkinen3, A. Autio1, G. G. Yegutkin4, J. Knuuti1, S. Jalkanen4, A. Roivainen1; 1Turku PET Centre, Turku University Hospital, Finland, 2Turku PET Centre and Department of Chemistry, University of Turku, Finland, 3Orthopaedic Research Unit, University of Turku, Finland, 4MediCity Research Laboratory and National Public Health Institute, University of Turku, Finland. Aim: To evaluate a new peptide radiopharmaceutical targeting vascular adhesion protein1/semicarbazide sensitive amine oxidase (VAP-1/SSAO) for in vivo imaging of inflammation.Materials and Methods: DOTA-conjugated linear peptide was labelled with 68Ga. The in vitro stability was tested by incubating 68Ga-DOTA-peptide in buffer solution at RT and in human blood at 37°C for 4 h. Samples were taken during incubation at 15 min, 45 min, 75 min, 2 h, 3 h and 4 h (n=3/each time point), and analysed by radio-HPLC. After i.v. injection of 68Ga-DOTA-peptide into a normal rat, samples of plasma (n=6/each time point) and urine (n=4/each time point) obtained 15 min, 30 min, 60 min and 120 min after tracer injection, were subjected to radio-HPLC analysis for the evaluation of in vivo degradation of the peptide. Competetive enzyme assays and cellular binding assays were performed using Chinese hamster ovary (CHO) cells stably transfected with human VAP-1. Biodistribution and biokinetics of 68Ga-DOTA-peptide were studied in vivo by dynamic PET imaging of healthy, adult SpragueDawley rats (n=12) and of rats with experimental bone infection/inflammation (n=6). Wholebody distribution measures were also verified ex vivo using normal rats (n=24).Results: 68GaDOTA-peptide remained stable both in the buffer solution and in human plasma at RT or +37°C, respectively, for at least 4 h as demonstrated by repeated radio-HPLC analyses. The analysis of rat plasma samples showed that the percentages (mean±SD) of unchanged peptide were 62±1.3%, 46±3.1%, 31±9.0% and 16±19% at 15 min, 30 min, 60 min and 120 min after tracer injection, respectively. Accordingly, the in vivo half-life of intact 68Ga-DOTA-peptide in rat blood circulation was 26 min. The radio-HPLC analysis of rat urine samples revealed 81±13% of intact peptide, which seemed to be constant during the whole 120 min examination. In vitro competitive enzyme assays revealed that the inhibitory potency of the peptide retained also after its DOTA-conjugation. Cellular binding of 68Ga-DOTA-peptide to VAP-1 transfected CHO cells was significantly higher compared to CHO cells transfected with the vector only (p=0.016). Biodistribution in Sprague-Dawley rats showed rapid blood clearance and fast renal excretion. When osteomyelitic rats were injected with 68Ga-DOTA-peptide, the infected/inflamed tibia were clearly delineated by PET imaging with a high target-to-background ratio (range 1.73.4).Conclusions: 68Ga-DOTA-peptide shows promising in vitro and in vivo characteristics indicating its potential for inflammation imaging. The findings make 68Ga-DOTA-peptide an attractive candidate for further evaluation as diagnostic imaging agent in experimental models of inflammation.

seem to have high receptor affinity; they might be potential new candidates for molecular imaging and internal radiotherapy of tumours overexpressing the RCCK2 receptors.

P31 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Radiopharmacy/Radiochemistry: Miscellaneous P412 Dosimetric evaluation of the polyphosphonate; PEI-MP labeled with 117mSn, 186Re and 99mTc as potential diagnosis/therapeutic bone agents M. F. Botelho1, J. R. Zeevaart2, I. C. Dormehl3, W. K. A. Louw2, F. Caramelo1, L. F. Metello4, C. M. Gomes1, M. Neves5, C. Sena6, A. M. Abrantes1, Z. I. Kolar7, G. C. Krijger7, R. J. Milner8, F. Schneeweiss9; 1Biophysics/Biomathematics Institute, IBILI, Faculty of Medicine, Coimbra, Portugal, 2Radiochemistry, NECSA, Pretoria, South Africa, 3AEC Institute for Life Sciences, University of Pretoria, Pretoria, South Africa, 4Institute for Health Technologies of Porto, Porto, Portugal, 5Nuclear Technology Institute, Sacavem, Portugal, 6Institute of Physiology, Faculty of Medicine, Coimbra, Portugal, 7Radiochemistry Department, Interfaculty Reactot Institute, Delft, The Netherlands, 8Department Small Animal Clinical Science, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States, 9Forschungszentrum Jülich GmbH, Labor für Strahlenbiologie im GB Sicherheit und Strahlenschutz, Julich, Germany. Introduction: Because of the physical characteristics of 117mSn (13.6 d half-life, conversion electrons) and 186Re (3.7 d half-life, 1.1MeV ȕ-) they can be used as agents for secondary bone cancer treatment. In continuation of previous studies [1] we present here the results obtained with the 10-30 kDa fraction of the water-soluble polymer polyethyleneimine, functionalised with methylene phosphonate groups (PEI-MP) and labelled with these radionuclides and studied in rats. Tests with PEI labeled with 99mTc were also performed to evaluate the potencial use as a diagnose agent.Materials and Methods: Normal Wistar rats were injected, in the tail vein, with an average activity of 11-13 MBq 117mSn-PEI-MP (20 rats), 186Re-PEI-MP (22 rats), 186ReO4(8 rats) and 99mTc (5 rats) respectively. We also injected CD1 rats (5) that have gallbladder in order to evaluate potencial enterohepatic cycle. Half of them were sacrificed 2.5 h after injection and the others after 4 h. The organs were counted in a well counter to determine the biodistibution. Absorbed doses in the main organs were then calculated according to the MIRD recommendation using OLINDA software.Results: PEI-MP shows high dose for bladder and kidney for all tested radionuclides (99mTc, 117mSn, 186Re). Heart shows also a considerable dose. Perenate shows lower doses for all the analyzed organs maintaining bladder and kidneys as target organs. This results are consistent with biodistibution which show moderate reticuloendothelial uptake, reasonable bone-uptake and considerable uptake in the bladder wall. At 4 h 186Re-PEI-MP shows rapid clearance of all organs had taken place as confirmed by the 2.5 h study which indicated considerable and early excretion in the urine and little bone uptake. 186ReO4- showed at 4 h uptake in the stomach, bladder and urine. As expected doses for 99mTc are much lower, however the bladder is the target organ. Discussion/Conclusion: The dosimetric evaluation shows that the target organs are kidneys and bladder whatever the metal. Besides low uptake in normal bone and consequently, low dose more research must be done using animal models of human osteosarcoma. The study with 186ReO4- which showed a different biodistibution confirmed that the 186Re-PEI-MP complex remains in fact in the blood plasma.117mSn-PEI-MP is a more promising agent than 186Re-PEI-MP as the latter shows no bone uptake. References: [1] Zeevaart JR, Louw W, Wagener JM, Botelho F, Gomes C, Abrunhosa A, Metello L, Kolar Z, Dormehl I [2004] W. J. Nucl. Med. 3:237

P413

P411

The Preliminary study of binding of 90Y and 99mTc labelled phosphonates on hydroxyapatites.

Synthesis and assessment of new radioligands of cholecystokinin/gastrin receptors in xenograft nude mice.

E. Iller, D. Pawlak; Radioisotope Centre Polatom, Otwock, Poland.

S. Brillouet, O. Caselles, S. Silvente-Poirot, B. Mestre, J. Nalis, L. Dierickx, C. Picard, G. Favre, M. Poirot, F. Courbon; Claudius Regaud, Toulouse, France. Aim: Somatostatin receptor scintigraphy has been proven a valuable tool for staging endocrine tumors. However, its sensitivity and accuracy in metastatic medullary thyroid cancer (MTC) or small cell lung cancer (SCLC) is limited by the poor and inconstant expression of these receptors. The CCK-2 (cholecystokinin)/gastrin receptors (RCCK2) are overexpressed in 90% of MTC and 60% in SCLC but not in corresponding healthy tissues. They represent an ideal target for the diagnosis and internal radiotherapy of these tumours. The objective of this original work is to assess the effectiveness of new radioligand CCK4 peptides for RCCK2 targeting in preclinical models.Materials and Methods: Derivatives of CCK8 and CCK4 peptides coupled to new synthetized chelating agents have been developed and labelled with 111Indium. Nude mice, bearing tumors from the human SCLC cell line NCI-H69, the human MTC cell line TT and NIH3T3 cell line, were intravenously injected with 10 MBq of radiolabelled peptide. Scintigraphy of these various peptides were performed 1h and 24 h post injection : a dynamic acquisition of zoomed planar images was performed using a gamma camera equipped with low energy high resolution collimators. Images analysis was done on a Xeleris workstation. Thereafter biodistribution studies (%ID/g tissue ) were performed.Results: We elaborated the conditions of radiolabelling leading to a radiochemical purity > 85%. Scintigraphic studies of xenograft mice showed significant tumour uptake with a high target to non target ratio. Images at 1h post injection were found to be more affected by non specific uptake. Ex vivo studies confirmed the efficiency of RCCK2 targeting with the new radiolabelled CCK4 analogs. A biodistribution study showed physiological distribution (stomach, pancreas), renal excretion (gallbladder, kidneys) and tumor uptake at 24 h post injection.Conclusions: These new radiopeptides CCK

Aim. The aim of work is investigation of binding kinetics of phosphonic complexes of radionuclides on hydroxyapaptites as well as determination of the correlation between obtained results with the biodistribution study of these complexes. Materials and methods. The three type of hydroxyiapatites (HA) which a molar ratio of Ca/P were 1.67, 1.76 and 1.86 have been synthesized. Each types of HA have been divided on three sieve fractions <50 µm, 50-100 µm and >100 µm of particle diameters. In our study the complexes MDP (methylenediphosphonic acid), EDTMP (ethylenediaminopentamethylenephosphonic acid) and DTMP (diethylenetriaminepentamethylenephosphonic acid)with 90Y and 99mTc were investigated. To the preparation of complexes 2 GBq of 99mTc or 6 GBq of carrie-free 90Y were added to 1 ml of water solution contain 10 mg of ligand. The solution was incubated during about 30 minutes at RT. The radiochemical purity for labelled phosphonates were determined by TLC or HPLC methods. For perform of the binding kinetics study 1 ml of a solution contain 0,04 µmole of the radiolabelled ligands was added to 10 mg of HA. The reaction mixture was shacked during 10, 30 and 90 minutes at RT next centrifuged and washed too times of 1 ml of saline. For determination of binding of phosphonic complexes with HA the radioactivity of collected water fraction was measured. Results and conclusion. The results shown that the binding of examinated complexes on HA depend on a concentration of Ca in hydroxyapatites and particle diameters. The binding is decreasing in order 99mTc-EDTMP, 99mTc-MDP, 99mTc-DTMP, 90Y-EDTMP. After 10 minutes incubation at RT up to 90 % of radioactivity is adsorbed on surface of hydroxyapatites.

S309

Poster Presentation

TFA in DCM, tris-tBu-DOTA was attached to the lysine side chains. The products were detached from the resins and deprotected by TFA treatment. After HPLC purification, the aromatic nitro groups were converted into amino groups by catalytic hydrogenation using a 20% Pd/C catalyst. The reaction of the amines with thiophosgene yielded the corresponding isothiocyanates.Results: We were able to synthesize p-isothiocyanatobenzoyl-[Lys(DOTA)]n-amides with one, three, six or nine lysine spacers in acceptable yields (6-31% overall) at high purity. As the best results for the hydrogenation step can be obtained with a heterogene catalyst the reductions had to be performed in solution. Preparative HPLC was required to obtain the pure intended compounds. The purity of the desired products was determined by HPLC and ESI mass spectrometry.Conclusions: The synthesis of multimeric chelators is challenging. It could be shown that DOTA oligomers can be obtained by solid phase synthesis protocols. The activation with thiophosgene can be performed in solution to yield the activated isothiocyanates. These products are stable when stored at -18 °C. Conjugation and labelling reactions with tumour targeting proteins are currently in progress. Reference: (1) Mier W, Graham KAN, Wang Q et al. Synthesis of peptide conjugated chelator oligomers for endoradiotherapy and MRT imaging. Tetrahedron Lett 2004; 45: 5453-5.

P414 How to increase the yield of carrier-free 177Lu from neutron irradiated 176Yb? D. Pawlak, J. Parus, R. Mikoáajczak, M. Zuchlinska; Radioisotope Centre Polatom, Otwock, Poland. Aim. The aim of work is to demonstrate the possibility of obtaining carrier-free 177Lu in one lot sufficient for therapeutical use. Materials and methods. Highly enriched 176Yb (minimum 95%) will be used as target for irradiation in a nuclear reactor in thermal neutron flux not lower than 2*1014 ncm-2s-1. Cooling time of 24 hours will allow a conversion of 177Yb into 177Lu. Microgram quantities of 177Lu will be separated from milligram amount of Yb with the use of ion exchange columns of different dimensions and filled with various cationic exchangers. As an eluent Į-hydroxyisobutyric acid (HIBA) will be used in a gradient mode. The effect of a number of factors on a separation efficiency such as pH, flow rate, grain-size, eluent concentration, length of column will be disscussed in detail. Results and conclusion. Carrier-free 177Lu of a few microgram quantity ( ~ 10 GBq) should be obtained in one batch. The purity of the isotope obtained will be checked by conjugating it with one of typical ligands.

P415 Development of albumin radionuclide therapy of tumors

188Re-microspheres

for

V. M. Petriev1, T. P. Ryzhikova1, T. A. Tarasova1, N. A. Demidova1, V. G. Skvortsov1, D. V. Stepchenkov2, N. G. Baranov3; 1State Institution Medical Radiological Research Center, Obninsk, Russian Federation, 2 State Scientific Center of the Russian Federation – Institute for Physics and Power Engineering, Obninsk, Russian Federation, 3SState Scientific Center of the Russian Federation – Institute for Physics and Power Engineering, Obninsk, Russian Federation. Alternative treatment method of liver metastases is the internal radionuclide therapy with the use of the glass 90Y-microspheres. These microspheres possess high stability and good efficiency of treatment of a primary or metastatic liver cancer. Despite the fact that these spheres have shown good results in treatment of patients, their high density is serious disadvantage. In addition, the absence of Ȗ-component in 90Y radiation spectrum does not allow monitoring of preparation behavior in organism. 188W/188Re generator of up to 185 GBq activity allows obtaining of 188Re eluate, which specific activity is up to 10 GBq/ml. Optimal nuclear and physical characteristics of 188Re (half-life period - 17 hours, Ȗ-component of 0.155 MeV energy, ȕparticles of the maximal energy 2,1 MeV) allow the therapeutic absorbed doze development in a tumor, get scintigraphic image and investigate pharmacokinetic characteristics of a preparation in an organism. The purpose of this work is the development of 188Re-microspheres of human serum albumin (HAM) which size is 15-30 microns - potential radiopharmaceuticals for radionuclide therapy of liver metastases. As a result of research it has been shown, that under the boiling of reacting mixture with 8 mg SnCl2 within 1 hour the percentage of 188Re inclusion into microspheres structure is 68.6; 83.1 and 88.6% at pH 3; 5 and 7, correspondingly. The maximal level of 188Re binding with HAM (97-98%) has been obtained in 24 hours at pH5. The level of 188Re binding with HAM during the first minutes of reaction practically does not depend on SnCl2 concentration in the range of 2 up to 16 mg. The regular increase of 188Re binding amount with HAM under the growth of SnCl2 concentration in reagent is observed in 1 hour, and this tendency remains till 24 hours. The level of 188Re binding with HAM higher than 95% is marked in 24 hours under SnCl2 concentration in 12-16 mg range. 188Re binding reaction rate with HAM naturally increases with the increase of SnCl2 concentration in reagent. Thus, the results obtained testify to the prospects of 188Re-HAM creation - potential radiopharmaceuticals for treatment of tumours.

P416 188Re(V)DMSA as a core complex for synthesis of phosphonate derivatives for treatment of bone metastases U. Choudhry1, P. J. Blower2; 1University of Kent, Biosciences Dept, Canterbury, Kent CT2 7NJ, UK, United Kingdom, 2King’s College London, Division of Imaging Sciences, London, UK, United Kingdom. Bisphosphonate 186/188Re complexes show promise clinically for treatment of bone metastases in prostate cancer. However, target-to-background ratios are lower than in 99mTc bone scans and there is considerable soft tissue retention, and there is great potential for improvement of targeting and dosimetry. The complexes are inhomogeneous, unstable in vivo and structurally illdefined, because while the bisphosphonate group is effective for bone targeting, it is a poor rhenium chelator. Because of its excellent in vivo stability and ease of synthesis, we have previously used 188Re(V)DMSA as a bifunctional chelate for peptide labelling. Moreover, 188Re(V)DMSA is an intrinsically bone targeting complex, and its chemical structure and biodistribution are identical to the technetium analogue. Our aim is to improve the targeting and dosimetry of 186/188Re bone agents by synthesising bifunctional bisphosphonate conjugates in which the rhenium-chelating function is DMSA rather than the bisphosphonate group. The work may also generate improved 99mTc-bone imaging agents. Methods: A series of monophosphonate derivatives were prepared first to demonstrate the feasibility. 188Re(V)DMSA was converted to its bis(anhydride) by treatment with 1-ethyl-(3-(3dimethylaminopropyl)carbodiimide hydrochloride (EDC), followed by reaction with a series of aminophosphonates to prepare phosphonate conjugates. Alternatively, conjugates were prepared directly from 188Re(V)DMSA in water by activation with EDC. The analogy between 188Re and 99mTc was checked by radio-HPLC. Results: The conjugates could be synthesised either as single-isomer (syn-endo) or mixed isomers, by using non-aqueous or aqueous conditions, respectively. The reaction could be controlled to give either the cyclised imide product or the ring-opened form, depending on temperature and use of primary or secondary amine. All conjugates and their isomers were identifiable by 1H and 31P NMR, IR spectrometry and HPLCelectrospray mass spectrometry. They were separable by HPLC and therefore can be subjected individually to in vivo evaluation to select the optimal complex. Conjugation chemistry of the 188Re and 99mTc chemistry proceeded analogously. The products were stable in serum and

S310

bound strongly to hydroxyapatite. We conclude that the 188Re(V)DMSA core and its 99mTc analogue represent an attractive basis for synthesis of stable, well-defined bisphosphonate conjugates from which optimal bone targeting agents may be developed.

P417 Development of stationary tungsten-188/rhenium-188 generator of high activity and set of cold kits intended for radiotherapy on the basis of rhenium-188 eluate N. Baranov1, D. Stepchenkov1, V. Petriev2, Y. Minko1, A. Semenova1, E. Sulim1, V. Poddubienko1, M. Zinchenko1, V. Skvortsov2; 1SSC RF - IPPE, Obninsk, Russian Federation, 2MRRC RAMS, Obninsk, Russian Federation. Aim. 188W/188Re generator has good prospects in nuclear medicine thanks to the application of Rhenium-188 compounds in beta-radiation therapy. In the process of development of high active (1Ci and higher) 188W/188Re generator the possibility of meeting the medical requirements has been considered. Development of such generator will allow obtain eluate of high concentration activity - more than 100mCi/ml, which gives the possibility to create new cold kits, which composition would allow get labeled compound with high radionuclide yield in clinical conditions within short time period. Materials and methods. With the aim to develop such generator the process of tungsten and rhenium adsorption has been studied with the use of oxides of yttrium, zirconium, tin, aluminum and nano-structured aerogel (Al2O3 * H2O) as an adsorbents. 188W of high specific activity (7.7Ci/g) obtained by irradiation of tungsten-186 oxide in SM reactor of Dimitrovgrad was used as the mother radionuclide. Sorption properties in tungsten have been studied. Tungsten concentration in eluate comprises 1*10-2 up to 18 10-3% of rhenium activity. Results. Aluminum oxide in [[Unsupported Character - Н]]+-form has been determined as the most effective and practically feasible sorbent. Rhenium distribution factor on aluminum oxide in the presence of tungsten is 1.2 in this case. At present a stationary generator of 4Ci activity has been developed and loaded allowing obtain sodium perrhenate with 188Re of 300mCi/ml concentration activity and higher for creation of radiopharmaceuticals providing the needed therapeutic dose. Eluate specification is as follows: - 188Re radionuclide yield - 80%;- 188W radionuclide concentration - not more than 1*10-3%;- aluminum concentration - not more than 5.0microg/ml;- total inactive impurities concentration - not more than 10.0microg/ml;- radiochemical purity not less than 99.0%. Work on creation of radiopharmaceuticals intended for treatment of metastases, rheumatoid arthritis and other diseases, has been performed. With the use of eluate from 188W/188Re generator cold kits has been fabricated based on hydroxyethylidene diphosphonic acid (HEDP) and albumin microspheres (HAM) of 10-20 micron diameter. Research results have shown that Rhenium-188 binding with HEDP and HAM reaches 95% within 1 hour. Radiopharmaceutical high stability remains within 2-3 days. Conclusion. Development of stationary 188W/188Re generator and cold kits allows at lesser expenses supply hospitals with open radionuclide sources for betaradiation therapy of malignant tumors.

P418 A cationic dextran conjugate as a potential candidate for local pretargeted therapy of tumors S. Zhai1, Y. Shen2, C. Hu2, L. Zhao1, C. He2, J. Du1; 1Medical Isotope Research Center, Peking University, Beijing, China, 2Department of Isotopes, China Institute of Atomic Energy, Beijing, China. Aim: 99mTc radiolabeled cationic dextran and avidin have shown selective accumulation in superficial bladder tumors by intravesical instillation compared to normal tissue. The aim of this study was to synthesis a cationic dextran-avidin conjugate in order to further explore the possibility to treat superficial bladder tumors locally with 90Y radiolabeled biotin in two-step approach (first cationic dextran-avidin and then 90Y radiolabeled biotin). Materials and Methods: Dextran-40 was oxidized with sodium periodate and subsequently reacted with lysine and avidin. The conjugate was then stabilized by reducing Schiff bases with sodium cyanoborohydirde and purified with a Sephadex G25 column. The concentration of avidin in final conjugate was determined by spectrophotometric method. The cationic dextran-avidin conjugate was then tested for the affinity towards to biotin with a 90Y radiolabeled DOTA-biotin by fast protein liquid chromatography and by the spectrophotometric method known as HABA assay based on the use of 4-hydroxazobenzene-2-carboxylic acid. The stability of final 90Ybiotin-avidin-dextran conjugate was tested in saline and human serum. Results: The high purity of cationic dextran-avidin conjugate was achieved with 80% yield. 90Y-DOTA-biotin binding towards to cationic dextran-avidin conjugate determined by FPLC showed that about 85% of 90Y-biotin was bound to cationic dextran-avidin conjugate at 1:4 molar ratios. The cationic dextran-avidin conjugate retained complete affinity for 90Y radiolabeled biotin. The 90Y-biotinavidin-dextran conjugate was stable in saline and human serum. Conclusions: The results suggest the possible potential of cationic dextran-avidin conjugate as a candidate for further studies in local pretargeted therapy of tumors. This work was supported in part by the National Natural Science Foundation of China (30370421) and the President Foundation of China Institute of Atomic Energy.

P419 Microbiological monitoring during radiopharmaceuticals in hospitals

the

preparation

of

P. V. Okletey, E. M. W. van de Garde, J. F. Verzijlbergen; St. Antonius Hospital, Nieuwegein, The Netherlands. Background: Determination of sterility of radiopharmaceuticals before patient administration is often not possible due to relatively short shelf- and half-life of these products. Microbiological monitoring entails regularly controlling for the presence of micro-organisms during preparation of radiopharmaceuticals and could provide information on the quality of preparation environment. Aim: Goal of this study was to establish "alert" and "action" levels based on quantification of a "steady-trend" level in number of present micro-organisms.Materials and Methods: During daily preparation of radiopharmaceuticals, a settle plate (tripticase Soya-agar;

P420 Streptavidin may be used to link antisense DNAs with carriers for improved cellular delivery K. Nakamura1, Y. Wang2, X. Liu2, N. Kitamura1, A. Kubo1, D. J. Hnatowich2; 1Keio University School of Medicine, Tokyo, Japan, 2 University of Massachusetts Medical School, Worcester, MA, United States. Objective: Recent results from these laboratories and others suggest that antisense DNAs should be complexed with transfecting agents as carriers to improve intracellular delivery. The large number of available and potentially useful carriers are limited only by difficulties in preparing the DNA/carrier complexes. We are investigating streptavidin as a linker between biotinylated carriers and biotinylated antisense DNAs requiring only simple mixing for preparation. If successful, a large number of these carriers could be prepared and tested quickly to help identify the rules governing intracellular transport, hopefully leading to improved antisense targeting. This study was performed in cell culture to evaluate the effectiveness of DNA/carrier complexes prepared in this manner.Methods: The model carriers for these studies include 10 mer Tat, 9 mer polyarginine and cholesterol. The biotinylated peptides were purchased as such while the cholesterol was biotinylated in house. As is usual in these laboratories, the model target was the mdr1 mRNA of Pgp in KB-31 (Pgp+), KB-G2 (Pgp++) and TCO-1 (Pgp++) cells targeted by an 18 mer AS DNA. The DNA was purchased both as the biotinylated uniform phosphorothioate and phosphodiester and, because it was considered important to place the radiolabel on the DNA in the complex, with a primary amine on one end for conjugation with MAG3 and radiolabeling with 99mTc. Preparation thereafter of the 1 : 1 carrier : DNA constructs followed simple mixing with the carrier to the steptavidin or the radiolabeled DNA to the streptavidinpeptides/cholesterol construct at a 1 :1 molar ratio. SE HPLC confirmed that each preparation was successful. All cell studies were performed at various times over 24 h, at 50 nM at 37 oC and, in all cases results were compared to the identical DNAs added at identical molar concentrations but without the carrier (i.e. “naked”).Results: No evidence of cellular toxicity by growth delay was observed in any study. Regardless of carrier, almost all cellular accumulations, whether with phosphorothioate or phosphodiester DNA, whether in KB-31, KB-G2 or TCO-1 cells and at all times, showed positive ratios of accumulation compared to naked ranging between 1.1 and 1.5. Conclusions: Using Tat, polyarginine and cholesterol as carriers, the preparation of DNA/carrier complexes were greatly simplified using streptavidin as linker over covalent conjugations. Although the carriers and cells selected for this study were only models of what should be possible, it is encouraging that increased accumulations over naked was observed in almost all cases.

peptide stability in serum. At the levels determined, this preclinical study did not reveal a targeting of the hepatocytes. However, the peptide is circulating in the blood at concentration that is high enough to prevent infections with the virus. It can be speculated that the peptide is protected against degradation due to an association via its lipophilic end to serum proteins. Consequently, the peptide is a promising candidate for future clinical applications, e.g. prevention of HBV reinfection after liver transplantation. Reference: (1) Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptidesderived from the large viral surface protein. J Virol. 2005; 79: 1613-22.

P422 Microbiological contamination during the reconstitution of cold kits in a radiopharmacy unit. J. Martinez Soler1, A. Laut Martinez1, E. Torres Manosa1, Y. Said Criado1, A. Valades MIranDA1, D. Garcia Chica1, M. Bellon Guardia2, M. De Arcocha2, J. Llamas Elvira2; 1Radiopharmacy Unit of Hospital Virgen De Las Nieves, Granada, Spain, 2Nuclear Medicine Departement of Hospital Virgen De Las Nieves, Granada, Spain.

REJECTED BY AUTHOR P423 Assessment of serum levels of interleukin-6 and tnf-alpha and leptin in hyperthyroid and hypothyroid patients A. Ramirez-Navarro, M. Arcocha, L. Fernández-Maza, M. A. Muros, M. Bellón, M. Vera, M. Cañadas, J. M. LLamas-Elvira; H. U. Virgen de las Nieves, Granada, Spain. Introduction: The relationship between thyroid hormone changes and proinflammatory cytokines such as IL-6 and TNF-Į are not well known. Serum levels of cytokines may indicate activity levels of immune functions. The another hand, Leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. The action of thyroid axis components on leptin secretion has not been completely understood. Objectives. To measure serum concentrations of the proinflammatory cytokines interleukin-6 and TNF-Į and leptin in patients with thyroid disease coursing with hyper- or hypothyroidism, and to study possible alterations in the plasma levels of these parameters and their relationship with circulating thyroid hormone levels. Material and Methods. the serum of 29 hyperthyroid patients, 29 hypothyroid patients and 20 euthyroid control patients was analysed. Levels of TSH, FT4, IL-6, TNF-Į and leptin were determined in all sera. All measurements were made using IRMA or RIA techniques. Statistical analysis: A descriptive analysis was performed, calculating means and standard errors of the mean. The Student’s t test for independent samples was used to compare means, regarding p < 0.05 as significant. Results.

TSH

FT4

IL-6

uIU/ml

ng/dl

pg/ml

3,43±0,25

43,34±8,82

Hypothiroids patients 29 32,11±3,28

0,52±0,04

13,17±2,04

Controls patients

1,26±0,06

17,01±3,17

n Hyperthyroid patients

29 0,05±0,01

20 2,16±0,37 t-test controls

P421

IL-6

The potential of hepatitis B virus (HBV) entry inhibitors for the development of hepatotropic tracers. 1

2

1

3

4

W. Mier , S. Urban , H. Eskerski , J. Petersen , M. Eisenhut , U. Haberkorn1; 1Radiologische Klinik, Heidelberg, Germany, 2 Universitätsklinikum, Heidelberg, Germany, 3Universitätsklinikum, Innere 4 Deutsches Medizin, Hamburg Eppendorf, Germany, Krebsforschungszentrum, Heidelberg, Germany. Aim: Chronic infection with the human hepatitis B virus (HBV) is still a major health problem to the world’s population today. Interference with HBV infection by externally applied fragments of viral surface proteins that interfere with receptor interaction or membrane fusion might allow the development of novel antiviral strategies that interfere with the hepadnaviral entry process, as has been shown for gp-41-derived T 20-peptides in HIV-therapy.Materials and Methods: We have recently demonstrated that peptides encompassing the 47 terminal amino acids of the Nterminal part of a major envelope protein block HBV infection of primary human hepatocytes with surprising efficacy, at already picomolar concentrations, probably by sustained inactivation of a receptor on hepatocytes (1). The biodistribution of the I-125-labelled peptide was determined in RAG-2 mice bearing hepatocytes susceptible to infection with HBV. The stability of the peptide was determined in human serum.Results: A tyrosine bearing derivative of the peptide Myr-GQNLSTSNPLGFFPDHQLDPAFRANTANPDWDFNPNKDWTPDANKVGCONH2 was obtained by Fmoc solid phase synthesis. The peptide was labelled with 125-I using the Chloramine-T method. No significant increase of the I-125-labelled peptide was determined in mice bearing infection susceptible hepatocytes at 1 h post injection. The peptide was cleared by the kidneys that were the major sites of accumulation. However, a high concentration (5.1 %ID/g at 1 h post injection) was found in the blood. The biological half live of the peptide was > 60 h in human serum.Conclusions: Using the labelled lipopeptide we investigated the organ distribution with respect to a specific targeting to the transplanted hepatocytes, as well as the

p= 0,02

Hyperthyroids

vs

t-test hypothyroids vs controls p= 0,291

TNF-Į

p=0,886

p= 0,720

LEPTIN

p= 0,121

p= 0,245

Conclusion. Thyroid status had no influence on serum levels of leptin. No relationship was found between thyroid hormone levels and leptin levels in serum. Serum levels of TNF-Į also showed no relationship. However, markedly higher plasma IL-6 levels were observed in the hyperthyroid patients than in the hypothyroid and control patients.

P424 Control of labelling efficiency of radiopharmaceuticals: Retrospective validation of modified procedures

99mTc-

P. Komarek1, I. Komarkova2, L. Polivkova2; 1Institute for Postgraduate Medical Education, Prague, Czech Republic, 2State Institute for Drug Control, Prague, Czech Republic. Control of labelling efficiency of 99mTc-radiopharmaceuticals: Retrospective validation of modified procedures The labelling yield and/or radiochemical purity testing of products prepared from licensed labelling kits should be performed on each preparation. Methods to determine labelling efficiency are given in instructions for use accompanying the kit. Any deviation from these instructions has to be validated. Aim: The purpose of this study is to evaluate modified procedures of labelling efficiency control and their suitability for routine preparation of 99mTc-radiopharmaceuticals. Materials and methods: Kits produced by both

S311

Poster Presentation

90 mm) was placed as close as possible to the centre of the LAF preparation chamber. On completion of the preparation, gloved fingerprints from dominant hand of the preparer were impressed in a subsequent settle plate. The duration of preparation, date, and name of technologist were noted. Subsequently, settle plates were incubated at 30 degrees Celsius for 7 days and colony-forming units (cfu's) were counted at day 3 and 7. The number of cfu's per hour was calculated and a cumulative sum was obtained. The cumulative sum starts with 1 and increases with an ascending factor (AF) when colony's are forming and decreases with a descending factor (DF) when not, whereas DF = average local preparatory time(hr)/4, and AF = 1-DF.Results: Within 12 months a total of 239 preparation periods were monitored with an average preparatory time of 76 minutes. The average number of cfu's/hr was 0.34 (SD 1.9) for the settle plate in the preparation chamber and 1.48 (SD 2.92) for the gloved fingerprint impressions. There were generally non-pathogenic strains normally associated with skin-flora. The cumulative sum showed a steady-trend below 1 for the settle plate in the preparation chamber. The cumulative sum for fingerprints showed a steady-trend when number of cfu's > 2 were counted as colony forming. Discussion: The general GMP (Annex 1) limit of < 1 cfu/4 hours was achievable for settle plates in the preparation chamber. The values for fingerprint impressions exceeded this limit probably due to handling of non-sterile lead-shielded syringe holders. For fingerprints impressions an "alert" level of > 2 cfu's for more than 2 consecutive days and an "action" level of > 2 cfu's for more than 3 consecutive days are considered appropriate to detect future changes in microbiological environment quality and preparation circumstances. Moreover, microbiological monitoring is a valuable tool in training technologists in sterile handling of radiopharmaceuticals.

local and foreign manufacturers, authorised for and most frequently used in the Czech Republic, were chosen to be controlled: MDP, DMSA, MAG3, DTPA; Hepatate II, LyoMAA, LeukoScan, Cardio-Spect, Brain-Spect, Senti-Scint, Nano-Albumon. Kits were evaluated using control methods in line with the Ph.Eur., technical leaflets or their modifications by procedures applying planar chromatography, solvent extraction and membrane filtration. Modification of chromatography procedures consisted of the choice of stationary phases and used solvents. For radiopharmaceuticals evaluated by solvent extraction method, the amount of “free” 99mTc was determined. Due to time factor it is not possible to apply planar chromatography carried out in several solvents or HPLC method (e.g. HM-PAO) prior to administration of radiopharmaceuticals to patients. Validation comprised 100, and 150 labelled kits, respectively. Radioactivity of chromatograms was detected by proportional counter and/or NaI(Tl) well counter. Measured values of labelling efficiency or content of “free” 99mTc were statistically processed and are shown in charts for each radiopharmaceutical. Results: All labelled kits show labelling efficiency over 95 %. When the results fell bellow the set limit of radiochemical purity, the control was repeated. For all batches of individual kits the labelling efficiency complied with specifications of Ph.Eur. and Technical leaflets. Results obtained by modified methods for routine employment were also within the set specification limits. Chromatographic methods: 99mTc-MDP 99,9 %, 99mTc-DMSA 99,3 %, 99mTc-DTPA 99,9 %, 99mTc-MAG3 97,1 %, 99mTc-sulesomab 98,7 %, 99mTc-Sn-colloid 99,4 %, 99mTc HSA-nanocolloid 99,7 %, 99mTcHSA colloid 99,1 %, 99mTc-MAA 99,6 %. Solvent extraction method (“free” 99mTc): 99mTcHM-PAO 8,7 %, 99mTc-MIBI 4,5 %. Membrane filtration method: 99mTc-MAA 99,8 %. Presented charts of individual preparations show value range within the set specifications, which confirms validation of method for routine use. Conclusion: Based on retrospective validation of results, authors consider routinely used methods for preliminary assessment of radiochemical purity and/or content of “free” 99mTc to be fully confirmative.

P427 In vitro uptake studies in a neuroendocrine tumour cell line with PET O. C. Neels1, P. L. Jager1, K. P. Koopmans1, E. G. E. de Vries2, I. P. Kema3, P. H. Elsinga1; 1University Medical Center, Department of Nuclear Medicine and Molecular Imaging, Groningen, The Netherlands, 2University Medical Center, Department of Medical Oncology, Groningen, The Netherlands, 3University Medical Center, Department of Pathology and Laboratory Medicine, Groningen, The Netherlands.

Reduction of renal toxicity in In-111-dotatoc treatment: an animal study

Aim: To study the uptake and decarboxylation of [18F]FDOPA with different inhibitors in a neuroendocrine cell line.Materials and Methods: [18F]FDOPA was incubated in the neuroendocrine human pancreas cell line BON for several durations up to the effect of amino acid decarboxylase with the blocking agent Carbidopa in amino acid rich HAM/DME (1:1) culture medium containing 10% foetal calf serum in comparison with amino acid free enriched phosphate buffer (PBS-GMC). Uptake of tracer was determined for different concentrations of Carbidopa (0.02-0.08 mM) for an incubation period of 60 minutes in PBS-GMC. The LAT1uptake system was studied by the use of the specific blocker 2-Aminobicyclo[2.2.1]heptane-2carboxylic acid (BCH) at different concentrations (0.03-20 mM) in PBS-GMC over an incubation period of 15 minutes. Radioactivity was measured in a gamma counter and vitality of cells was assessed by the trypan blue method. Results and conclusion: Uptake in culture medium both with and without Carbidopa was lower than 2% per million cells. In enriched phosphate buffer a maximum of uptake of 15 % per million cells was reached after 15 min. A difference in uptake depending on the concentration of Carbidopa was not observed. Uptake of [18F]FDOPA is blocked by addition of BCH in low concentrations (0.1 mM). The in vitro uptake mechanism of [18F]FDOPA in the neuroendocrine cell line BON is not affected by Carbidopa but easily inhibited by BCH suggesting that uptake reflects uptake rather than dopamine synthesis through decarboxylation.

Y. Lin, C. Chen; Chunghsing University, Taichung, Taiwan Republic of China.

P32 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

P425

Aim: Renal toxicity has been reported in the treatment with a high dose of Y-90 DOTA Tyr3octreotide (DOTATOC). Renal protection is necessary in treatments with Y-90 DOTATOC. In this study, we compared the effectiveness of three kinds of amino acids, D-lysine (lysine), Larginine (arginine) and histidine, on renal protection in healthy rats and tried to determine which one was the most effective.Materials and Methods: Twenty SD healthy male rats were divided into 4 groups: lysine, histidine, arginine, and control. The rats were injected with a dose of 400 mg/kg of amino acid or 2 ml of phosphate-buffered saline (PBS) (as control) intraperitoneally. All rats were sacrificed at 4 hrs after the injection of 1 MBq In-111-DOTATOC. Samples of the kidney were taken and weighed carefully. The counts of radioactivity were measured by a gamma counter and renal concentrations were calculated and expressed as percent injected dose per gram (% ID/g).Results: All three kinds of amino acids effectively reduced renal uptake of DOTATOC when compared to the control group. Among these three amino acids, lysine had the best reduction rate (56.8%). Lysine was also significantly more effective than histidine (reduction rate = 36.3%) and arginine (reduction rate = 30.3%). Furthermore, histidine was more effective than arginine in reducing renal uptake of DOTATOC, but no statistical difference was noted.Conclusions: Among these three amino acids, lysine had the best reduction rate of renal uptake of DOTATOC. Histidine was more effective than arginine but no statistical difference was noted.

P426 Biodistribution of doubly radiolabeled pretargeted radioimmunotherapy.

liposomes

for

M. Mougin-Degraef, E. Jestin, C. Bourdeau, C. Sai-Maurel, P. Le Saec, P. TheDrez, J. Barbet, A. Faivre-Chauvet; Institute of Cancer Research, Nantes, France. Aim: We have developed methods to label preformed liposomes, with a high specific radioactivity, in order to target them to cancer cells. The tumor targeting is obtained by using a pretargeting system with a monoclonal bispecific antibody (BsmAb). Liposome formulations were evaluated in vivo to confirm radiolabeling stabilities and to obtain favorable pharmacokinetics parameters. Then, we have tested the capacity of these liposomes to target tumor cells in xenografted nude mice model.Materials and Methods: Distearoylphosphatidylcholine (DSPC)/cholesterol liposomes incorporating 1,5% DTPAderivatized phosphatidylethanolamine and 5 to 8% of DSPE-PEG2000 were prepared in arginine containing buffers. Radiolabeling of liposome surface was obtained by binding In-111 to DSPEDTPA. The aqueous phase was labeled by an original active loading of radioiodinated BoltonHunter reagent which reacts with the pre-encapsulated arginine. In vivo radiolabeling stabilities were tested by a pharmacokinetic study in mice and by an HPLC radiochromatographic control to check the integrity of the liposomes. The feasibility of in vivo tumor pretargeting was studied in nude mice xenografted with human colorectal adenocarcinoma cells, which express CEA and doubly radiolabeled liposomes (500 nmol) injected 24h after anti-ACExanti-DTPA-In BsmAb (100 micrograms).Results: Surface radiolabeling yield is up to 75 % until 44 MBq/micromol. lipids and the active loading was efficient (encapsulation yield >60 %) and stable (>85 % after 24h in serum 37degrees). With the two radiolabeling methods, the liposomes are stable at 4degrees in buffer for 6 days (stability >90 %). The pharmacokinetic behavior of doubly radiolabeled liposomes is strongly dependant on the formulation. The blood clearance with the best formulation is 0,18ml/h compared to a conventional formulation (1,01ml/h). The BoltonHunter reagent coupled to arginine is quickly eliminated by kidneys (clearance 5,26ml/h). The better formulation was used to achieve the tumor pretargeting studies. The tumor uptake after bispecific antibody injection (active targeting) was 7,6±1,4 % DI/g of tumor at 24h versus 4,0±1,8 % for the passive targeting. These results are significant (p<0,05) between active and passive targeting, at 24 and 48h. Conclusions : We have developed a new liposomes radiolabeling method based on an active-loading approach to obtain high specific activity (2.8 GBq/micromol. lipids). Moreover, the rapid renal elimination of the Bolton-Hunter reagent is an advantage to envisage a therapeutic use with high specific activities. In vivo, the correlation between the two tracers permits to confirm the integrity of the liposomes. Animal studies have demonstrated the feasibility of tumor pretargeting with radiolabeled liposomes and BsmAb.

S312

Radiopharmacy/Radiochemistry: Halogens P428 Iodine-124 produced by the Te-124(p,n)I-124 Specific activity and Te(IV) determination

reaction:

A. T. Yordanov, A. Anzellotti, S. Rizvi, R. Ylimaki, M. Kiselev; Molecular, Sterling, VA, United States.

IBA

Iodine-124 (124I) is an attractive isotope of iodine due to its complex radioactive decay scheme and convenient half-life (4.18 d). With the increasing use of positron emission tomography (PET) in nuclear medicine, medical oncology, pharmacokinetics and drug metabolism, 124I-labeled radiopharmaceuticals could be most useful for PET imaging.1 Furthermore, the 4.18 d half-life would permit their use in PET facilities far away from the radionuclide production centers. Limited availability of this radionuclide so far has been a hindrance to its wider development and clinical use. Sodium [124I]iodide is already reportedly used for diagnosis and treatment planning in thyroid disease. Also [124I]m-iodobenzylguanidine ([124I]MIBG) is a promising PET tracer for cardiovascular imaging and for diagnosis/treatment planning in malignant diseases such as neuroblastoma, paraganglioma, pheochromocytoma, and carcinoid. The achievement of a radiopharmaceutical preparation possessing the optimal specific activity and radiochemical purity always requires a radiohalogen starting material with no-carrier-added (NCA) specific activity as close to the theoretical carrier-free (CA) specific activity as possible. Another important characteristic of 124I batches would be a minimal Te(IV) content, since it is widely believed that Te(IV) can potentially interfere with radioiodination reactions. We have tested batches of 124I produced by the 124Te(p,n)124I reaction and have estimated their specific activity and Te(IV) content. References: (1) Glaser, M.; Luthra, S.K.; Brady, F., Int. J. Oncology, 2003, 22, 253-267.

P429 Changing the injection medium of [123I]IBZM to increase its shelf life: a bioequivalence study J. Booij1, K. de Bruin1, A. G. M. Janssen2; 1University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands, 2GE Healthcare, Eindhoven, The Netherlands. Aim: [123I]iodobenzamide ([123I]IBZM) is a selective SPECT tracer for dopamine D2 receptors (D2Rs). [123I]IBZM is frequently used to assess striatal D2R binding in the differential diagnosis of parkinsonism. Parkinsonian syndromes, such as multiple system atrophy, are characterized by loss of D2Rs. By contrast, there is no loss in Parkinson’s disease patients. Apart from routine clinical studies, [123I]IBZM is frequently used to assess release of endogenous dopamine in scientific studies. [123I]IBZM is routinely produced at GE Healthcare (Eindhoven, The Netherlands). However, its relatively short shelf life may interfere with the distribution to remote centers. Therefore, the shelf life of IBZM has recently been improved by changing the vehiculum, by introducing gentisic acid as a stabilizer in the injection medium. This procedure improves the radiochemical stability of [123I]IBZM. In this study, we evaluated whether the new injection medium (presence of gentisic acid) of [123I]IBZM has influenced its binding to D2R in-vivo.Materials and Methods: To compare directly the binding kinetics of the “traditionally” prepared [123I]IBZM (IBZM-1; ascorbic acid as stabilizer) and [123I]IBZM produced by the new formulation (IBZM-2; gentisic acid as stabilizer), distribution studies were performed with both IBZM-1 and IBZM 2 in groups of male Wistar rats (n = 7 per group) up to 2 h after intravenous injection. Groups of rats were sacrificed 5 min, 15 min, 1 h and 2 h after injection. In blocking experiments, rats received 5 min prior to injection of the radiotracer the D2R antagonist haloperidol, and 2 h after injection of the radiotracer rats were sacrificed. Then, several brain regions (including striatum and cerebellum) and pieces of various peripheral tissues were excised and weighted, and activity was assayed. The amount of radioactivity was expressed as percentage of injected dose, multiplied by body weight in grams, per gram tissue. Finally, striatal-to-

P430 N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[131I]iodo-5methoxybenzyl)acetamide: a potent iodinated radioligand for peripheral benzodiazepine receptor in brain M. Zhang1, J. Maeda1, K. Kumata1, J. Noguchi1, T. Haradahira1, T. Suhara1, C. Halldin2, K. Suzuki1; 1National Institute of Radiological Sciences, Chiba, Japan, 2Karolinska Institute, Stockholm, Sweden. Introduction The peripheral benzodiazepine receptor (PBR) density was increased in the injured brain, and this increase has been used as an indicator of neuronal damage and several neurodenerative disorders such as Alzheimer’s disease. We have previously developed two PET ligands [11C]DAA1106 and [18F]FEDAA1106 for PBR imaging in the human brain. Using DAA1106 as a lead compound, we designed two novel iodinated ligands: N-(5-fluoro-2phenoxyphenyl)-N-(2-iodo-5-methoxybenzyl)acetamide (1) and N-(2,5-dimethoxybenzyl)-N-(5iodo-2-phenoxyphenyl)acetamide (2). Here, we report the chemical synthesis and in vitro binding affinities of 1 and 2 to PBR, labeling of 1 and 2 using [131I]I, and distribution of [131I]1 and [131I]2 in the rat brain. Chemistry Two tributylstannyl analogues, the precursors of [131I]1 and [131I]2, were prepared from the commercial compounds in 6 steps. Reaction of the tributylstannyl compounds with I2 afforded 1 and 2 in high chemical yields of >90%, respectively. Labeling of 1 or 2 using 131I was performed by treatment of the tributylstannyl precursor with [131I]NaI and H2O2 in AcOH for 5 min. After the reaction, the radioactive mixture was applied onto a semi-preparative HPLC system. The corresponding radioactive fraction was collected and the solvents were removed by nitrogen flow at room temperature. The obtained residue was dissolved in saline containing 10% ethanol to give the [131I]1 or [131I]2 formulation. Using HPLC and radio-TLC, the identity of [131I]1 or [131I]2 was confirmed by comparison with the non-radioactive samples, and their radiochemical purities in the final products were determined to be >99%. Evaluation The in vitro binding experiments using quantitative autoradiography on the rat brain sections determined that 1 displayed a similar affinity to PBR with PK11195 but 2 had a weak potency to PBR. The ex vivo autoradiography showed [131I]1 and [131I]2 had a considerably high uptake in the rat brain. In the brain treated by [131I]1, a significantly high radioactivity was observed in the olfactory bulb and choroids plexus, two high PBR density areas in the rodent brain. Co-injection with non-radioactive DAA1106 exhibited a statistically significant reduction of [131I]1 radioactivity in the brain regions. This finding suggested that [131I]1 had high specific binding to PBR in the rat brain, especially in the olfactory bulb and choroids plexus. On the other hand, [131I]2 did not show an obvious distribution pattern relative to PBR in the brain. In conclusion, this study has succeeded in developing a promising iodinated ligand [131I]1 which has a high specific binding for PBR in the rat brain.

P33 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Physics 1: PET and PET/CT P431 Attenuation Coefficients in Brain PET Studies: comparison between CT data and ȕ+ external sources methods. M. Casale1, B. Alfano2, M. Comerci2, A. A. Russo2, M. Salvatore2; 1Health Physics School, Napoli, Italy, 2Italian National Research Council, Institute of Biostructure and Bioimaging, Napoli, Italy. AIM The use of CT data instead of ȕ+ sources transmission scan in PET-CT, has been validated, so far, in terms of accuracy, precision and dose only for whole-body studies. Aim of this study was to compare the two alternative methods, in brain studies, taking into account the following parameters: the systematic error of the attenuation coefficients, introduced by the conversion function used by the scanner; the noise on the measure depending on the CT tube current; the noise on the measure carried-out with the external sources in different experimental conditions. MATERIALS AND METHODS The transmission scans have been carried-out with the Discovery LS PET/CT scanner (GE medical Systems, Milwaukee, Wis.). The software of this system transforms the CT numbers (CT(HU)) to linear PET attenuation coefficients (cm-1), through a bi-linear function, with two different angular coefficients for negative and positive CT(HU).We estimated the accuracy of the conversion from CT(HU) to attenuation coefficients at 511 keV energy, in the case of distilled water at T=20°C using a cylindrical phantom. The CT was performed with Vmax=140kV and 0.5 s tube rotation time, at different tube currents (10, 20 40, 80mA); the transmission scans were carried-out, without moving the phantom, with the two 207 MBq 68Ge rod sources, at different transmission acquisition times (1, 5, 7, 15, 20, 30, 60min).We repeated many external source transmission scans at short acquisition times to evaluate a systematic error that we found when acquisition time was shorter than 30 minutes. All the coefficients were obtained averaging 87451 voxels in the central volume of the phantom. RESULTS The obtained value of the attenuation coefficient, using the CT method, is 0.09226 cm-1, which differs less than 1% from the expected value 0.093 cm-1, used in the conversion function of our scanner. The values obtained with the different currents differs less than 0.05%. Using the external source acquisition with a transmission scan of 60 minutes and a blank scan of 30 minutes, we measured an attenuation coefficient of 0.09501±0.00002 cm-1 (mean±standard error). In the transmission acquisitions of 2 and 7 minutes we obtained respectively 0.0772±0.0006 and 0.0928±0.0005 cm-1 (mean±standard deviation). The mean values of the coefficients vs. acquisition time are reported in the table.

Acquisition

µaverage

Acquisition

µaverage

Time(min)

(cm-1)

Time(min)

(cm-1)

2

0.0782

7

0.0925

2

0.0772

7

0.0927

2

0.0775

7

0.0922

2

0.0767

7

0.0932

2

0.0767

7

0.0925

2

0.0772

7

0.0936

CONCLUSIONS The results obtained for the negative CT(HU) suggest that the error introduced by the CT attenuation correction method can be constrained below the noise introduced by the measured attenuation correction also with low dose CT.

P432 Evaluation of the count recovery coefficient of a whole-body PET/CT scanner in 3D mode image T. Tsujikawa1, H. Okazawa1, H. Ohtsuka2, N. Morita2, H. Nishitani2; 1University of Fukui Biomedical Imaging Research Center, Fukui, Japan, 2 University of Tokushima Faculty of Medicine, Tokushima, Japan. We evaluated the count recovery coefficient (RC) of PET/CT in 3D mode using cylindrical and spherical phantoms. Method: Diameters of the cylindrical phantoms were 5,6,7,8,9,10,11,12,14,17,19,21,26,31,36,46mm, in which 18F-FDG (4200 Bq/ml, SUV max = 1.32) was contained. Images were acquired by use of PET/CT combined with a dedicated fullring lutetium oxyorthosilicate (LSO) scanner and 16-multidetector row CT scanner (Aquiduo 16 ; Toshiba) for 2 min in 3D mode and reconstructed by use of ordered-subset expectation maximization (OSEM) with different parameters (iteration, subset, Gaussian filter) 4-14-8, 8-148, 4-42-8, 4-14-4, 8-14-0, 8-14-16. And we compared the RC curve of cylindrical phantoms with some spherical ones which have some of the same diameters. Result: RC curves of the cylindrical ones are shown in Fig.1, which indicates it is not iteration and subset but gaussian filter that influence RC, and they are lower than of the spherical one. RC decreases seriously in the diameter lower than 20mm. Conclusion: We should evaluate RC of each PET/CT scanner and understand the characteristics for correct diagnosis.

P433 Comparison of noise equivalent count rates and image noise for different phantom length K. Shimizu1, K. Matsumoto1, E. Watanabe1, K. Kitamura2, S. Yamamoto3, K. Murase4, M. Senda1; 1Institute of Biomedical Research and Innovation, Kobe, Japan, 2Shimadzu Corporation, Kyoto, Japan, 3Kobe City College of Technology, Kobe, Japan, 4Osaka University, Suita, Japan. Aim: It is widely recognized that noise equivalent count (NEC) rates is easily able to evaluate image quality from count statistics. However, the NEC may be unable to evaluate image quality of each slice when it is different types of phantom length because there is contribution of scatter and random from activity outside the scanner field of view (FOV). The purpose of this study was to compare NEC and coefficient of variation (COV) of reconstruction image using different types of phantom length. Materials & methods: A PET scanner, CTI-Siemens ECAT EXACT HR+, was used to scan images of two types of phantom, a uniform 20 cm tall cylindrical phantom (20 cm diameter), and a uniform 70 cm tall cylindrical phantom (20 cm diameter) filled in 11C. The scatter fraction measurement of 20 cm and 70 cm tall phantom were performed following the National Electrical Manufacturers Association (NEMA) NU 2-1994 Standard and NEMA NU 22001, respectively. The NEC measurement was performed following the NEMA NU 2-2001 procedure. The data were reconstructed using a ramp filter with a Gaussian filter (6 mm FWHM), corrected for dead-time, random, attenuation, and scatter. The quality of the reconstructed images was evaluated with the COV (S.D./mean for the pixel within a 18 cm region of interest). Results: The peak NEC of 20 cm tall phantom was approximately four times higher than 70 cm tall phantom. Furthermore, this occurs at approximately two higher activity concentration (12.8 vs. 6.3 kBq/ml). As for the image quality of all slices, although the COV showed a linear relationship with the NEC in double logarithmic plot within a given experiment, the quality of the reconstructed images was dependent on the phantom length and slice number. Conclusion: Our preliminary data suggested that the NEC may be able to evaluate image quality. However, image quality of each slice can not evaluate only in the NEC because the NEC is dependent on scatter and random from activity outside the FOV.

P434 Influence of attenuation correction on PET image quality M. Nishio1, S. Kojima2, S. Tamai1, A. Nakagawa2, T. Tamaki3, H. Iwata1; 1Nagoya PET Imaging Center, Nagoya-shi, Aichi, Japan, 2GE Yokogawa Medical Systems, Hino-shi, Tokyo, Japan, 3Nagoya Kyoritsu Hospital, Nagoya-shi, Aichi, Japan. Aim The aim of this study was to examine the influence of attenuation correction methods on PET image quality. Material and Methods A PET/CT system (GE Discovery LS), IEC body phantom and NEMA scatter phantom were used. The background region of the body phantom was filled with an activity of 5.3 kBq/mL. The four hot spheres were filled with an activity concentration of 4 times that of the background. The largest two spheres were filled with water only. The lung insert was placed in the center of the phantom. The line source of the scatter

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Poster Presentation

cerebellum ratios were calculated. Differences between groups were analyzed with ANOVA.Results: In both groups, striatal uptake was fast, resulting in high striatum-tocerebellum ratios at 2 h post-injection. At all studied time-points, these ratios were not significantly different between IBZM-1 and IBZM-2. Moreover, the blocking experiment confirmed in-vivo binding to D2R for “both” radiotracers. Finally, the excretion of radioactivity as assessed by activity in liver and kidneys was not statistically significantly different between IBZM-1 and 2.Conclusions: This study showed that the improved shell life of [123I]IBZM by introducing another vehiculum in the production process, did not influence the in-vivo binding to D2R in rats.

phantom was filled with 116MBq. The CT tube parameters were 140KV and 40mA. Transmission scan time was 2, 6 and 240 min with rod source (about 300MBq). Emission scan time was 20 min. Images were reconstructed by OSEM with 1~4 iterations and 28 subsets with respect to each attenuation correction, MAC240, CTAC, SAC6 and SAC2. According to the image quality measurement protocol of NEMA NU 2-2001, the pixel values on each image were examined. The values by MAC240 were used as standard values. Results The %Contrast with hot spheres (%C-h) and %Background variability (%BGV) by CTAC were little less than those of MAC240. The %Contrast with cold spheres (%C-c) was about 2 points higher than those of MAC240. The %BGV , %C-h and %C-c by SAC6 were little less, about 1 point lower and 1 point higher than those of MAC240, respectively. With SAC2, the %BGV, %C-c and %C-h were about 3 points higher, 6 points lower and 5 points higher than those of MAC240, respectively. The %C-h by SAC2 was about 6 points higher than those of SAC6. The average %relative error by CTAC, SAC6 and SAC2 were about 1, 7 and 9 points higher than those of MAC240, respectively. However, variability of relative errors by CTAC, SAC6 and SAC2 were about 0.9, 1.9 and 4.0 times compared to those of MAC240, respectively. The results show that these measured values were influenced by statistical variation of µ values as well as the number of iterations. Conclusion The image quality by SAC depended on transmission scan time or was affected by changes in rod source activity. There was not much difference between those by CTAC and MAC240. However, reconstruction convergence and attenuation correction errors by CTAC were kept lower than those of MAC240 due to smaller statistical variation of µ values.

P435 Image quality assessment of different reconstructions on PET images: A phantom study

iterative

L. Zabalza1, J. M. Marti-Climent1, E. Prieto1, M. Gómez2, P. Lecumberrri2, H. Bustince2, J. Arbizu1; 1Nuclear Medicine Service, University Hospital of Navarra, Pamplona, Spain, 2Mathematics and Computers Science Department, Public University of Navarra, Pamplona, Spain. Quality of PET images depends on the algorithm employed on the sinograms reconstruction. For small structures, where partial volume effect plays an important role, the recovered value is also influenced by the reconstruction method. Aim: To investigate PET image quality depending on the OSEM iterative reconstruction parameters (number of iterations and subsets) in a phantom simulating the brain, by means of different figures of merit.Materials and Methods: A Jaszczak phantom (h= 18,6cm, diameter= 21,6cm) was acquired in a HR+ PET scanner. Spheres, with diameters between 31,2 and 9,8 mm, had a concentration of 26,6 Bq/ml, while the background phantom had 5,5 Bq/ml. A 3D emission scan of 20 minuntes (total trues = 300 Mcounts) was followed by a 5 minutes transmission scan. Attenuation correction was done after transmission segmentation. Different combinations of the number of iterations-subsets were chosen for the OSEM reconstruction: (2-4), (2-8), (2,-16), (2-32), (3-4), (3-8), (3-16), (3-32), (4,-32), (6,-32), y (8-32). A 4,9 mm postreconstruction filter was used, and the scatter correction was applied. Different algorithms were implemented in Matlab in order to coregister the reconstructed studies with a synthetic image that simulated the real phantom radioactivity distribution, and to evaluate the following figures of merit, by means of a 3 dimensional definition of volumes of interest (VOI): 1) Recovery coefficient (RC)= ratio of the mean sphere concentration value to the real value. 2) Image noise defined as the coefficient of variation (CV)= 100 x (standard deviation divided by the mean measured value). This figure was evaluated in a 10 mm diameter VOI both in the background and inside the biggest sphere. 3) Contrast= [(measured sphere concentration/background measured concentration)-1] / [(real sphere concentration/real background concentration)-1].Results: CR and Contrast were stable when the effective iterations (EI = iterations x subsets) were greater than 48, for the six spheres, with mean values of RC = 0,62 and Contrast =0,52; ranging from 0,41 to 0,80, and 0,25 and 0,75, respectively. From lower to higher EI values, image noise increased in the background from 1,45 to 5,15; while in the biggest sphere ranged between 1,1 and 1,9. For 48 EI, CV was 2,7 and 1,4 for the background and sphere regions respectively.Conclusions: Results showed that 48 effective iterations in the OSEM reconstruction optimized the contrast and differences between real and measured radioactivity concentration, with a small increase in the noise evaluation, in a cylindrical phantom simulating the brain.

P436 The role of the updating coefficient of the ML-EM algorithm in PET image reconstruction A. Gaitanis1, G. Kontaxakis2, G. Panayiotakis3, G. Spyrou4, G. Tzanakos5; 1Foundation for Biomedical Research of the Academy of Athens / University of Patras, Department of Medical Physics, Athens, Greece, 2 Universidad Politécnica de Madrid E.T.S.I. Telecomunicación, Dpto. Ingeniería Electrónica, Madrid, Spain, 3University of Patras, Department of Medical Physics, Patras, Greece, 4Foundation for Biomedical Research of the Academy of Athens, Athens, Greece, 5University of Athens, Department of Physics, Athens, Greece. Aim: We have studied certain properties of the maximum likelihood expectation maximization (ML-EM) algorithm for iterative image reconstruction in positron emission tomography (PET). The principal aim of the work has been the development and evaluation of a new stopping criterion for this algorithm.Materials and Methods: We developed and used a software platform based on Monte-Carlo techniques, which simulates the emission of gamma rays in the source and their detection in the tomograph, it subsequently computes the transition matrix and also generates projection data for reconstruction. A single-ring tomograph has been simulated with 128 detector crystals on the ring, which has 15 cm radius and a field of view (FOV) of 20x20 cm2. For the present study the digital Hoffman brain phantom was used. The 2D images were reconstructed over a 64×64, 128×128 256x256 and 512x512 grid. In order to investigate the problem of the deterioration of the image quality after a number of iterations, we have studied the statistical properties of the updating coefficients in the ML-EM algorithm. For the further study of these properties, patient images (transverse slices) from a Siemens Biograph 6 PET scanner were used. Using these images we created projection data for image reconstruction and the behavior of the updating coefficient was analyzed.Results: The results of this study show that the values of the updating coefficients for the non-zero reconstructed pixels follow a distribution composed of a peak region around unity, which becomes progressively narrower as the iteration

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proceeds, and also a tail below unity, which corresponds to that part of the image that is far from being completely reconstructed. This tail is pushed to high values (around to unity) as the iterations progress. We find that the minimum and average values of the tail are related to the quality of the image. In particular for optimally reconstructed image these values are independent of the number of counts and of the image size. Furthermore, if the image counts are more than 4 million, the minimum and average ǻx values are almost the same in each kind of image (patient data or phantom image).Conclusions: The use of a stopping criterion of ML-EM algorithm based on its updating coefficient in PET image reconstruction is discussed.

P437 Utilization of deconvolution

coregistered

pet/ct

images

for

image

A. L. Kesner, M. Dahlbom, S. Huang, D. H. S. Silverman; University of California, Los Angeles, Los Angeles, CA, United States. Aim: Inherent image degradation and resolution limitations add a source of inaccuracy when quantifying activity with PET. With a priori knowledge that this blurring can be approximated by a convolution function, we aimed to develop a method to correct regional activity concentration values for partial volume and other blurring effects utilizing geometrical information gained by the fusion of a PET/CT volume.Materials and Methods: Both PET and CT scans were acquired using a bulb calibration phantom (10:1 activity ratio) and then fused together. The CT scan was segmented using region growing algorithms so as to segment each of the bulbs from the background. Tests were based upon approximating the blurring inherent in a PET scan through convolution of the phantom image with an effective blurring kernel. The true regional activity values for each organ ROI (region of interest) were estimated through iterative adjustments converging to match the convolution of the estimated true ROI value with the observed PET scan ROI value. Corrective multiplication factors were applied at each iteration to the estimated “true” organ activity. This corrective factor was calculated by blurring the estimated “true” organ and vicinity, and then comparing the mean ROI uptake to the ROI uptake in the actual PET image. Iterations continued until the two values were within 1% of each other. As a measure of accuracy we were able to compare corrected bulb activity values with their known concentrations.Results: The mean normal absolute error between the corrected PET measurements and the true measurements (|PET-true|/true) was 0.94 ± 0.05 (mean ± SD, range: 0.85-0.1.03). Before the correctional methods were applied, the mean error for bulb uptake measurements had a value of 0.59 ± .11 (range: 0.39-0.71). This measure of accuracy improved for 100% of the bulb measurements.Conclusions: We developed a practical method for accomplishing estimated recovery of some of the PET information lost by typical image degradation processes. By utilizing PET/CT image co-registration for a bulb phantom, we diminished average error in the pixel intensity distribution matrix typically arising in acquiring whole body PET images, by more than three-fourths of its uncorrected level.

P438 Effects to the SUV using by high energy X-ray and 137Cs for attenuation correction in PET/CT imaging Y. Jeong, D. Kang; Dong-A University Medical Center, Busan, Republic of Korea. Aim : Not only the X-ray CT but 137Cs transmission data are used for the attenuation correction in Philips GEMINI PET/CT scanner. It is known that maxSUV value with corrected attenuation using low energy, less than 100kVp, 100mAs, CT X-ray was larger than using 137Cs. Recently, the use of CT with high energy can used for diagnostic purpose is on the increase. Since many previous studies evaluated with low energy CT X-ray and 137Cs, we investigated the effect to maxSUV value using by high energy X-ray and 137Cs for attenuation correction. Material & Methods : Eight patients were performed PET/CT scan after 1hour intravenous injection of 18FFDG. Initially CT scan was done (120kVp, 130mAs) and immediately 137Cs (662keV, 20mCi) transmission image was acquired. Following them, PET scan was complete. The 3D-RAMLA method was used for image reconstruction. There was no abnormal hypermetabolic lesion in PET images of all patients. The maxSUV values were measured in 10 regions that showed normal metabolism in all 8 patients - apex and base of Rt. lung, ascending aorta above carina level, S8 and S6 of liver, lower pole of the spleen, T7 spine body and adjacent paraspinal muscle, Lt. femoral head and iliopsoas muscle anterior to the femoral head. Results : Totally 80 regions were studied in 8 patients. The mean value of maxSUV was 1.01±0.55 using by high energy X-ray for attenuation correction and 0.98±0.51 using by 137Cs. There was no significant difference in maxSUV values between both attenuation correction methods (p=0.303). In the Bland-Altman analysis showed ranges of limit of agreement were -04 to 0.4. In 10 regions for evaluated maxSUV values, no regions revealed significant differences between both attenuation correction methods. (p>0.05) Conclusion : Since there was no significant difference in the values of maxSUV using by high energy X-ray and 137Cs and range of limit of agreement was so narrow, it will be able to use same normal ranges at interpret for PET images corrected attenuation with both methods in clinical situation.

P439 Impact of Ge-68-based correction on PET imaging

versus

CT-based

attenuation

J. A. van Dalen, E. P. Visser, W. V. Vogel, F. H. M. Corstens, W. J. G. Oyen; Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Aim: Transmission (Tx) scans are used in PET to correct for attenuation. For standalone PET this is typically done using Ge-68 sources, for PET-CT using CT. Since PET scanners measure 511 keV photons, standalone PET suffers from emission contamination during a Tx-scan. Although methods exist to correct for emission contamination, it is not, or insufficiently implemented in clinical PET scanners. Therefore, this issue remains important in (semi)quantitative PET studies, especially when quantitative values are compared across imaging systems. This issue becomes even increasingly relevant since an increasing number of institutions proceed from a standalone PET to a hybrid PET-CT scanner. Here, we systematically studied the effects of attenuation correction (AC); In particular, the recovery of activity

P440 Assessment of scattered photons on the quantification of small animal pet studies P. Aguiar1, C. Tsoumpas2, J. Pavía3, C. Falcón4, A. Cot1, K. Thielemans5, D. Ros1; 1Unitat de Biofísica. Universitat de Barcelona, Barcelona, Spain, 2 Division of Clinical Sciences, Faculty of Medicine, Imperial College, London, United Kingdom, 3Servei de Medicina Nuclear. Hospital Clinic., Barcelona, Spain, 4Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain, 5Hammersmith Imanet Ltd, part of GE Healthcare, London, United Kingdom. Aim: To study the contribution of scatter components and to assess their effect on the quantification of relative changes in small animal PET scanner.Methods: Monte Carlo (MC) techniques were used to simulate small animal PET studies. MC simulation allows us to store photons in separate files according to the number of Compton scattering events undergone by the photon: single, double or multiple scatter. Simulation included scatter in the subject and detectors. Scatter in scanner was not incorporated. A simple whole body mouse phantom was employed to simulate 18F-FDG brain studies. A value of 100 was assigned to the whole phantom with exception of the left side of the brain, where an index of 20 was applied to simulate cerebral ischemia. Simulation mimics a dedicated small animal PET scanner with four planar LSO detectors in perpendicular positions. The low energy in the energy window was fixed at 150keV, 250keV, 350keV and 450keV to assess the influence of energy window size on the values of scatter fraction. Total (TSF) , Single (SSF), Double (DSF) and Multiple scatter fractions (MSF) were calculated as the ratio of scattered photons to total detected coincidences. Reconstructed images were obtained (for 250keV minimum energy) using 3D iterative algorithms included in the STIR library (http://stir.hammersmithimanet.com). 128 iterations and 8 subsets were applied and attenuation correction was included. The contrast, (ratio of mean counts in the lesion and in the contralateral area) was calculated. Finally, the contrast recovery (CR), defined as the ratio (in %) of the calculated to the theoretical contrast was obtained.Results: The table summarizes the scatter fractions for different values of the low energy window and CR when total photons were used (TSF), and when single (SSF), single and double (DSF) or all scattered photons (MSF) were removed from the total photons. Our findings show that the scatter fractions increase with the size of the energy window. The Table shows that the ratio SSF/TSF varies from 91.2% for 150keV to 97.8% for 450keV minimum energy, thereby indicating that SSF represents an important contribution of the scatter fraction in the subject. CR increases by 10% when correction for scattered photons is performed.

TSF (%)

SSF (%)

DSF (%)

MSF (%)

150keV

9.1

8.3

0.6

0.2

250keV

8.4

7.8

0.5

0.1

350keV

6.4

6.1

0.3

0.0

450keV

4.5

4.4

0.1

0.0

CR(%)

66.7%

76.2%

76.5%

76.6%

Conclusions: 1) Scatter correction improves quantification of relative changes. 2) Scatter correction algorithms based on single scatter approximations could be a highly accurate approach for a dedicated small animal PET scanner.

P442 Investigation of parallax effect within ring of a whole body PET B. Demir1, M. Demir2, S. Sager2, M. Halac2, A. Ahmed2, I. Uslu2; 1Science Faculty, Istanbul, Turkey, 2Cerrahpasa, Istanbul, Turkey. Purpose: Ring geometry influences the detection sensitivity of PET detectors and it has a direct bearing on quality of images. This problem is known as parallax effect. The purpose of this study is to investigate the parallax effect in a whole body PET.Materials and Methods: Measurements were performed in a whole body PET (Siemens Biograph-6 model HI-RES) using Na-22 positron emitter point source. A special phantom was designed by plexglass as to dimensions of PET ring. This phantom allows the movement of Na-22 source along three axes (X=horizontal, Y=vertical, Z=depth). The plexglass phantom was placed in PET ring and then, the location of Na-22 source on the phantom was changed along the each axis. Thus, true and random counts of Na-22 for all position in the PET ring were determined. In addition to in-air measurements with Na-22 source, we measured the parallax effect of PET in a tissue equivalent body phantom using F-18 sourcelesion.Results: In-air measurement, there were important alterations for true counts when the location of Na-22 source went away from FOV centre to each direction. True counts at 15 cm off-centre was high 11.8% compared to FOV centre and true counts at 15 cm off-centre of 4 cm depth was low 18.1% compared to FOV centre. In tissue equivalent body phantom measurements, there were also significant alterations for the image shapes and FWHM of F-18 source-lesion when the location of F-18 lesion went away from FOV centre to each direction. Conclusion: We observed that the parallax effect within PET ring increased with increasing of distance from FOV centre.

P443 Respiratory motion correction in PET with gated PET/CT data J. E. Iglesias1, S. Kimiaei2; 1Karolinska Institute, Stockholm, Sweden, 2 Hermes Medical Solutions, Stockholm, Sweden. Objectives: To present a novel approach for correction of respiratory motion in PET using data from gated CT.Methods: Prior to the PET acquisition, gated CT images along a respiratory cycle are acquired in several respiratory phases (bins). The acquired CT images are co-registered using the “demons” deformable algorithm [Thirion 98] to one or several reference phase frames. Gated PET data, in corresponding respiratory bins, is then acquired and the data of each bin is transformed to corresponding reference phase frame using the vector fields calculated previously from the CT data set. The transformed PET images from every phase are then summed to obtain a compensated image.Results: The method was applied on one data set acquired from separate CT and PET units. The data set belongs to a patient with a tumor in his right lung. The reduction in the deviation of the center of gravity of the lesion between the corrected and non-corrected image set and the gated data used as reference is shown in table 1. The lesion’s volume (delimited by using a threshold equal to a 33% of the maximum voxel value in the tumor) decreases by approximately 33%. The maximum voxel value in the tumour region increased from 3097 prior to correction, to an average of 3390 after correction (3500 in the gated image).Conclusions: In this preliminary study, it was shown that the information from a set of respiratory gated CT images can be used to compensate for respiratory movements in gated PET. The studies performance was limited by the fact that the PET and CT data were acquired by two different units. With data from a hybrid PET/CT, where the two data sets are already coregistered, the proposed method should provide an even better result.

Distance between the centers of gravity of the reference frame and the corrected / uncorrected

P441 High sensitivity multi-pinhole animal-SPECT/CT submillimetre resolution allows absolute in quantification

positron emission tomography PET. Full benefit of small animal imaging can only be achieved by in vivo quantification of radiotracers which allows to follow physiological processes over time in the same animal or to compare quantitatively different tracers. Due to the high sensitivity obtained by multi-pinholes the scanning time can be kept low which allowed dynamic acquisitions. We investigated the capabilities of the new four headed multi-pinhole SPECT/CT system.Methods: The camera (NanoSPECT/CT, Bioscan Inc., Washington D.C.) consists of four detectors, each outfitted with a with an interchangeable 9-pinhole aperture, giving a total of 36 pinholes. The scanning mode is helical for both modalities. A number mice and rats was scanned with a variety of tracers emitting photons at different energies ranging from I-125 (24 keV) to I131 (364 keV). Fifteen rats with different levels of renal damage were scanned with Tc-99mDMSA (Dimercaptosuccinic acid) and sacrificed immediately after scanning. The kidneys were removed and measured in a gamma counter. 2 rats were injected with Tc-99m-MAG3 (Mercaptoacetyltriglycerin) and dynamic SPECT-CT images were acquired with a scanning time of 50 seconds per frame.Results: The helical scanning mode allows a user-selectable axial field of view of 16 to 290 mm. High quality SPECT/CT images were acquired with all radionuclides. The resolution for SPECT was found to be in the submilimetre range. Images could be quantified absolutely to determine tumour uptake or kidney-uptake respectively. A very strong linear correlation between the determined activity in vivo and ex vivo was found. Approximation of organ and tumour size is feasible on CT. The dynamic scans with Tc-99m-MAG3 allowed reconstructing a renogram. Iodine-scans in mice allowed a straight forward separation of the two thyroid lobes.Conclusions: The NanoSPECT/CT is a highly accurate tool to follow physiological processes in the same animal over time with different tracers. It allows a precise determination of size and absorbed activity in vivo. This was found in numerous small-animal scans performed with an array of tracers.

image

with vivo

F. Forrer1, B. Bernard1, N. U. Schramm2, J. W. Hoppin2, C. Lackas2, R. Valkema1, E. P. Krenning1, M. De Jong1; 1Erasmus MC, Rotterdam, The Netherlands, 2Research Centre Juelich, Juelich, Germany.

Reference phase number

0

5

9

Lesion deviation prior to correction (mm)

9.3

4.1

6.0

Lesion deviation after correction (mm)

3.0

1.3

2.1

Aim: Multi-pinhole single photon emission computed tomography (SPECT) achieved emerging influence on preclinical research. The spatial resolution of pinhole-SPECT is higher than in

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Poster Presentation

concentration and activity distribution.Materials and Methods: In a Jaszczak phantom, 7 hollow spheres (11-60 mm) were filled with 150 kBq/ml FDG. Activity in the background was 15 kBq/ml. Multiple scans were acquired on a standalone PET (Siemens ECAT EXACT 47) and a PET-CT (Siemens Biograph 2) until 1% of the initial concentration remained. The activity concentration in the spheres and background was measured from the reconstructed images and compared to the actual concentration. For standalone PET, the emission scans were reconstructed using Tx-data acquired directly after each emission acquisition (hot Tx), but also using Tx-data acquired when only 0.1% of the initial activity was left (cold Tx). The uniformity within the spheres was investigated by profile-analysis.Results: For both scanners, background activity concentration was recovered on all scans. For PET-CT, the concentration in the big spheres (>16 mm) was also recovered. For the smaller spheres, recovery was insufficient due to partial volume effects. For standalone PET, using cold Tx in the 3D mode, the recovery of the spheres (>16 mm) was 20% lower than the actual concentration. Using hot Tx, underestimation of activity concentration was up to > 50%. For 5 kBq/ml or more, non-uniformities within the biggest spheres were up to 35%, 12% and 5%, when using standalone PET with hot Tx, cold Tx and using PET-CT, respectively.Conclusions: Due to contamination of the AC by emission photons, the standalone PET, using Ge-68 rod sources, suffers from bias in the recovery of relatively high activity concentrations and uniformity. This bias is not observed using the PET-CT scanner. Especially when patients get follow-up PET scans on both a standalone PET and a PET-CT, this phenomenon may impact on image interpretation.

P444 Comparative anatomical accuracy of interactive automated rigid registration between CT and FDG-PET

and

G. Wolz, A. Nömayr, T. Hothorn, J. Hornegger, W. Bautz, W. Römer, T. Kuwert; University of Erlangen-Nürnberg, Erlangen, Germany. Aim: The purpose of this study was to compare the anatomical accuracy of interactive (ILR) and automated linear registration (ALR) of separately acquired X-ray computed tomography (CT) and positron emission tomography (PET) data sets.Methods: Independently acquired PET and helical CT data from 22 tumor patients were registered manually using a commercially available software tool. ILR was performed separately for the thorax and the abdomen using physiological FDG uptake in several organs as a reference. In addition, ALR with Mirada 7D was also performed on all of the patients. For both registration methods, the distances between the representation of 53 malignant lesions on PET and CT were measured in X-, Y-, and Z-direction with reference to a common coordinate system (X-, Y-, Z-distances).Results: The percentage of lesions misregistered by less than 1.5 cm was in X-direction 91% for ILR and 89% for ALR; in Y-direction 85% and 68%; in Z-direction 72% and 51%, respectively. The average X-, Y- and Zdistances for ILR ranged from 0.58+/- 0.55cm (X-direction) to 1.17 +/- 1.66cm (Z-direction). For ALR, the average X-, Y- and Z-distances varied between 0.66 +/- 0.61 cm (X-direction) and 1.81 +/- 1.37 cm (Z-direction). Mixed effects analysis of the absolute X-, Y- and Z-distances revealed a significantly better alignment for ILR compared to ALR (p < 0.05) in the Zdirection.Conclusions: For the majority of malignant lesions, manual image registration with the possibility to separately align different body regions was more accurate than the automated approach. Registration errors were greater in the Z-direction due to non-rigid body transformations caused, e.g., by breathing.

P445 Experimental comparison of FDG-PET volumes determined by two segmentation methods. D. Huglo1, M. Vermandel2, N. Betrouni2, J. Rousseau2, C. Vasseur3, M. Steinling1; 1Hôpital Huriez, Lille, France, 2ITM, Lille, France, 3LAGIS, Villeneuve d'Ascq, France. The aim of this study was to compare FDG-PET volumes measured with a segmentation method using fuzzy logic (FLM) to the usual segmentation method by thresholding (TM).Materials and Methods: Two series of acquisitions with or without background activity were performed on PET-Advance (GEMS) with the parameters usually used: six spheres of 0.5/1.0/2.0/4.0/8.0/16.0mL filled with the same FDG solution, or eight 40mL cylinders of solution with progressive radioactive concentrations. TM was performed using the workstation Vision (SMV-GEMS) with a threshold of 30% of the peak activity of the object (sphere or cylinder). The object volume was the product of the number of voxels with an activity higher than threshold by the voxel volume. FLM, developed and validated for MRI, was adapted for PET. A fuzzy region was generated around a manual or automatic ROI (here the same than for the first method). Each voxel was divided and for each sub-voxel a membership degree was assigned, between 0 (out of the object) and 1 (inner contour, certainly in the object). The object volume was the product of the number of voxels with a membership value higher than 0.5 by the voxel volume. Results : Initially, volumes were underestimated by FLM compared to TM (or real volumes), but with less overestimation for small spheres (mean relative error for four acquisitions : +1.3% vs. +9.8% for 4mL, -5.2% vs. +31.3% for 2mL, +25.9% vs. +56.7% for 1mL and +101.9% vs. +166.8% for 0.5mL), smaller SD and less overestimation with the decrease of contrast (mean relative error [SD] for three acquisitions of cylinders for FLM : 15.6% [6.0], -12.8% [1.3], -10.1% [1.4] versus -5.8% [9.5], +0.7% [3.8], +5.9% [3.5] for TM). The underestimation was lower with FLM and membership value of 0.4: -5.6% [4.5], -2.0% [2.2], -1.1% [2.6] with the initial ROI and -0.2% [3.8], +2.0% [1.5], +3.9% [3.9] with a threshold of 0.20% for the ROI.Conclusions: If some improvements are still possible, FLM seems already a promising method for the determination of volumes in PET, less dependent of contrast, size or operator than TM.

P446 Phantom studies of factors influencing FDG-PET detection of sub-centimeter pulmonary lesions K. J. Nichols, J. N. Rini, E. V. Moroni, C. J. Palestro; Long Island Jewish Medical Center, New Hyde Park, NY, United States. Aims: Some investigations of FDG-PET pulmonary nodule detection have found reduced accuracy for lesions < 1 cm. While it is well known that relative radioactive concentrations cannot be compared for lesions of size < twice system spatial resolution, lesion detection may not demand precise concentration quantitation. This study was conducted to investigate the circumstances under which it is feasible to reliably detect sub-centimeter pulmonary lesions by FDG-PET.Materials and Methods: In order to design appropriate phantom experiments, a retrospective chart review was conducted of 126 patients who underwent FDG-PET imaging for evaluation of lung nodules. Lesion size was found to be 2.7±2.1 cm, with 23 lesions < 1 cm for which target-to-background ratio (T:B) ranged from 1.0 to 29.0. Using a commercially available phantom (Nuclear Associates) with 8 cylindrical chambers of sizes 0.4-2.2 cm in 6 cm of Plexiglas, and mean radioactive concentration of 0.04 MBq/ml, spatial resolution of a coincidence-PET system (“Solus,” Philips Medical Systems) was measured to be 0.55 cm. With this same phantom, unusually low and high T:Bs were simulated by inserting 1 cm long sources of inner diameter 0.4 cm, with T:B ranging from 0.0 to 32.0, into various combinations of cylinders. A wide range of clinically realistic counts were acquired, and transaxial slices were sampled over the entire extent of Plexiglas inserts to simulate lower T:B near the end of the Plexiglas insert and higher T:B at the middle of the Plexiglas insert. 1550 potential lesion sites were assessed, 1406 of which were of normal concentration, 91 of which were more intense and 16 of which were less intense than mean concentration. Three experienced observers independently read all PET images blinded to knowledge of the amount of radioactive concentration within the phantom chambers.Results: By ROC curve analysis, accuracy was 72±3% to detect unusually bright 0.4 cm objects, 88±4% to detect unusually dim objects, and 86±4% to detect either unusually bright or unusually dim objects. Accuracy was significantly

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greater for T:B > 12.0 versus T:B < 12.0 (83±5% versus 72±3%, p < 0.0001). McNemar’s test indicated that there were no significant differences between observers’ readings.Conclusions: Lesions smaller than system spatial resolution are detectable if their activity is sufficiently high, suggesting that lesions must be both too small and too low in activity in order to be visually undetectable.

P447 Comparison on two-dimensional and three-dimensional imaging characteristics and quality of a whole body PET-CT scan A. Fernandez Leon1, C. Gamez1, A. Benitez1, C. Lorenzo1, C. Massuet2, D. AlvarezZ3; 1Idibell. Hospital de Bellvitge. Unitat PET., Barcelona, Spain, 2Idibell. Hospital de Bellvitge. Medicina Preventiva., Barcelona, Spain, 3General Electric Medical Systems, Barcelona, Spain. The aim of the study was to compare the clinical utility and imaging quality of a whole body PET-CT scan in three-dimensional (3D) and two-dimensional (2D) modes. The study group consisted of 60 patients (56 +/-15 yrs) with a suspected diagnosis of primary or recurrent malignancy consecutively scheduled for PET. Three sequential PET-CT scans (GE Healthcare, Discovery ST) were performed 50 min after 260-530 MBq 18FDG i.v. of each patient. Every subject was studied in three standard modes: 2D (3 or 4 min/ bed depending on patient weight over or under 70 Kg), long 3D (3 or 4 min/bed) and short 3D acquisition (1.5 or 2 min/bed). In order to avoid the influence of chronology in sequential studies, patients were included consecutively in 6 groups, including all the order possibilities. PET data were reconstructed using iterative algorithm and one single attenuation correction CT was applied for the three studies in each patient. Two blinded observers analyzed the images and quality assessment was based on 4 items quantification (1 to 5 with 5 best punctuation): Image free of artifacts (IFA), Qualitative signal to noise (QSN), Lesion detectability (LD) and Overall image quality OIQ). Overall tStudent test for appeared samples was applied in order to detect significant differences between different acquisition modes. Our results showed that in the 2D acquisition method improved significantly (p<0.01) the image quality in comparison on 3D in IFA and OIQ. No differences were observed in QSN (mean differences not significant between 2D and long 3D) and LD (2D versus long 3D).

P448 Impact of the attenuation and scatter correction methods on hot and cold contrasts obtained with the philips gemini petscanner. A. E. J. J. Seret1, T. Nguyen1, C. Bernard2; 1University of Liege, Liege, Belgium, 2CHU - University of Liege, Liege, Belgium. Aim. To compare the performance in terms of contrast of the Philips Gemini PET-scanner when the four possible combinations of the available scatter and attenuation correction methods are used. Material and methods. Three inserts made of plexiglas, 7 hot rods (4-20 mm) in cold background, 7 cold rods (6-25 mm) in hot background and a grid, were introduced in a 20 cmdiameter cylindrical phantom while leaving a volume free from any object. The phantom was filled with an aqueous solution of 100 MBq 18FDG. Data were reconstructed using the 3D RAMLA method provided with the scanner. Attenuation was corrected using transmission data obtained either with the cesium source (trac) or with the build-in CT scanner (ctac). Scatter was corrected using either the non-uniform background (nubg) or the single scatter simulation (sss) method. Contrasts for the hot and the cold rods were measured by drawing ROIs on the adequate reconstructed slice regions and using standard formula. Results. With all correction methods, the contrast reached a maximum plateau for the hot rods of 13 mm diameter or larger but was only maximum for the largest (25 mm diameter) cold rods. Both for the cold and hot rods, the contrasts were always : trac-sss = ctac-sss > trac-nubg > ctac-nubg. A detailed analysis showed that sss leaved much less counts in the cold regions than nubg. Moreover, with sss, the number of counts in cold regions was nearly independent from the attenuation correction method. In contrast, nubg combined with ctac generated more counts than the three other method combinations (ctac-sss, trac-sss, trac-nubg) both in the hot and in the cold regions. Conclusion. The larger contrast on cold and hot rods indicates a better scatter correction with the sss method than with the nubg method. The higher number of counts obtained with ctac-nubg and the fact that both attenuation correction methods combined with sss give the same results suggest that the tail fitting done in nubg depends strongly on the attenuation map through automatic contour drawing. In conclusion, the single scatter simulation method improves markedly the contrast of PET images obtained with the Philips Gemini PET scanner. This is very important for PET-FDG oncological studies.

P449 Differences of FDG distribution between the whole body panel and dedicated brain panel in brain image of GEMINI PET/CT scanner Y. Jeong, D. Kang; Dong-A University Medical Center, Busan, Republic of Korea. Aim : We found that FDG uptake of frontal area was more than other brain regions visually in brain PET images of healthy people using GEMINI PET/CT scanner (Philips, USA). We performed PET/CT scanning using brain phantom with same protocol. We also acquired the same results for visual and count analysis. This result stood up against the universal knowledge that glucose metabolism of occipital area was higher than frontal area. This study was to know whether there was any change in count of brain PET image according to the kinds of panel quantitively in normal healthy people. Material & Methods : Brain PET image was acquired in 40 people without neurological problem after 1hour 18F-FDG injection intravenously. Twenty people (54 ± 6.6 yrs) of 40 were scanned with a dedicated brain panel, another 20 people (52.0 ± 6.0 yrs) were scanned with a whole body panel. We drew regions of interest (ROI) on the frontal, occipital lobes and the cerebellum and measured maximum counts. Then we calculated the ratio

P34 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Physics 2: SPECT and SPECT/CT P450 Comparison of lung image fusion of CT with normal respiration versus breath hold perfusion SPECT Y. Ogura, T. Komori, F. Aga, M. Hayashi, I. Adachi, I. Narabayashi; Osaka Medical College, Takatsuki, Japan. [Aim] We have developed a non-rigid method, called the LungGuide Image Fusion Method (LGIFM), to rapidly register and fuse lung CT images with perfusion SPECT images. This study investigated the accuracy of LG-IFM by comparing image fusion of normal respiration (NR) SPECT and breath hold (BH) SPECT with breath hold CT. [Material and Methods] Lung CT and 99mTc-MAA perfusion SPECT were performed for 36 patients whose post-scan diagnoses included embolism, emphysema and lung cancer. Same patient perfusion SPECT was acquired by alternating between NR and BH every 15 seconds. The CT protocol was standard breath hold. These data were transferred to the LungGuide workstation via DICOM where image coregistration and fusion was performed. The results were visually-qualitatively evaluated by 3 radiologists and graded as 1) no significant differences; 2) minor differences; and 3) significant differences between NR and BH SPECT image fusion with BH CT. [Results] In the upper and middle lung fields, 35 of 36 cases (97 ± 3%) showed no significant image fusion differences (1) and 1 of 36 cases (3 ± 3%) showed minor differences (2). In the lower field, 29 of 36 cases (81 ± 7%) were found to have no significant differences (1); 2 of 36 cases (6 ± 4%) showed minor differences (2); and 5 of 36 cases (14 ± 6%) showed significant differences (3). The image registration and fusion typically took about 60 seconds (Intel P4 1.5 GHz).[Conclusion] In many patients, repeated BH during perfusion SPECT is not possible due to the impaired condition of their lungs. LG-IFM was found to be a viable and clinically useful alternative technique for nonrigid image fusion of NR lung perfusion SPECT with CT.

P451 Review of imaging parameters and image artifacts for SPECT/CT myocardial perfusion studies A. M. Celler; University of British Columbia & Vancouver Coastal Health Authority, Vancouver, BC, Canada. Objectives Increased popularity of the combined SPECT-CT systems calls for a systematic evaluation of both acquisition protocols and image reconstruction parameters. In order to optimize quality and quantitative accuracy of images produced by these complex cameras the user needs to fully understand their principles of operation and be aware of potential pitfalls and artifacts. Such vigilance is becoming increasingly important as imaging procedures tend to be more and more automated and some of the problems may easily go unnoticed, potentially changing the outcome of the study. In this work we review the acquisition and data processing procedures, recommend additional quality control tests, suggest an evaluation method for the acquired data and discuss optimized image reconstruction techniques. Methods Different aspects of the myocardial perfusion studies ranging from patient positioning, acquisition parameters to reconstruction method and use of quantitative corrections (resolution recovery (RR), attenuation (AC) and scatter (SC) corrections) were investigated. Twenty seven thorax phantom experiments were performed with normal heart and heart with defects, and with and without additional cold and hot water bags attached around the phantom to model large patients, breasts and acquisitions with arms positioned along the body. Studies included truncation and misalignment of the CTbased attenuation maps and the emissions data. Clinically relevant Tc-99m activity levels were used with heart to body ratio equal to 1:5-6. Acquired data were reconstructed using FBP and iterative OSEM with different combination of corrections using manufacturers’ and our software. Results The study confirmed our previous results that AC and RR are essential for an accurate diagnostic assessment of myocardial perfusion studies. Further increase in quantitative accuracy is achieved by adding SC to the reconstruction (the relative errors for the myocardium and the body were 2% and 4%, respectively). More complex reconstructions obviously require more iterations to get full benefit from these corrections. In general, attenuation map quality has only limited effect on the quality of the emission images and some streaks and map artifacts can be tolerated. However, misalignments of the maps and the emission data, as well as some cases of map truncation create wrong activity distributions and substantial artifacts. Conclusion The most important conclusion from this study is that SPECT/CT system, with careful acquisition and proper image reconstruction, creates high quality quatitatively accurate images. At the same time, due to increased complexity of the imaging procedure the potential for artifacts and erroneous images creation is relatively high.

P452 Comparison of three reconstruction techniques in myocardial SPECT: standard FBP, iterative OSEM and OSEM with CT-low dose attenuation correction C. Pasquali1, E. De Ponti1, M. Arosio2, L. Guerra2, M. Musarra2, G. Di Pisa3, A. Crespi1, C. Messa3; 1A.O. S. Gerardo - Medical Physics, Monza, Italy, 2A.O. S. Gerardo - Nuclear Medicine, Monza, Italy, 3A.O. S. Gerardo Nuclear Medicine, University of Milano-Bicocca, Monza, Italy. Aim Different techniques are used to reconstruct cardiac SPECT and in the last years new algorithms were introduced to avoid artefacts due to primary photon attenuation: breast, diaphragmatic and thoracic wall attenuation cause in fact regional variations in myocardial activity that are not related to myocardial perfusion. The aim of this study is to compare two no attenuation corrected (nAC) SPECT images with images corrected for attenuation with low-dose CT (AC). Materials and Methods A hybrid SPECT-CT system, GE Hawkeye, was used. 50 patients referred to cardiac SPECT studies for cardiovascular disease were included. SPECT imaging was performed using standard two day cardiac acquisition protocol, and CT was acquired immediately after each SPECT section without moving the patient and with the same system. Three sets of transaxial images were reconstructed on GE Xeleris workstation: nAC SPECT emission data reconstructed in two different ways, FBP and iterative technique OSEM, and a third set of OSEM low CT-AC images. For a quantitative analysis Bull’s-eye images, divided into 17 segments, were produced for each set of clinical acquisition. For clinical inspection analysis, nAC FBP, nAC OSEM and AC OSEM rest/stress images were presented in a random sequence to 3 expert readers, blinded to reconstruction type and to all clinical information. Images were visually analyzed using the same 17 segments of Bull’s eye. Furthermore they interpreted each study overall by use of a 4-point scoring system (from normal to abnormal) and results were compared with clinical reports. Results Preliminary results, using Bull’s eye method, show there are no differences (<10%) in anterior, lateral and apical segments. The only difference higher than 15% was found in the inferior and infero-septal segments between AC and nAC, notably marked in medio-basal zone. Visual inspection analysis is ongoing, but initial results show that differences in the inferior wall between AC and nAC images are relevant in patients with BMI>30, being AC images results closer to clinical report than nAC. Conclusion Use of low dose CT images for attenuation correction in cardiac SPECT modifies the imaging of tracer distribution, particularly in the inferior segments and probably in relation with several patients’ characteristics as gender and BMI.

P453 The simultaneous correction for attenuation and scatter without transmission scan in thallium-201 myocardial perfusion SPECT M. Onoguchi1, T. Takayama1, K. Nakajima1, M. Yamada1, T. Miyati1, N. Motomura2; 1Kanazawa University, Kanazawa, Japan, 2Toshiba Medical Systems, Otawara, Japan. Aim: We devised a new correction method that combined attenuation correction using a difference of intrinsic dual-energy between lower energy emissions (71keV) and higher energy emissions (167keV) without transmission scan and Compton scatter correction using tripleenergy window (TEW) method for 71keV because of enhancing a difference of intrinsic dualenergy in 201TlCl (201Tl), and applied to cardiac phantom and myocardial perfusion SPECT studies. Material and methods: Attenuation coefficients ratio and counts ratio for 71keV/167keV were calculated from SPECT data acquired by energy window of 71keV and 167keV, respectively. Defects with the same thickness were inserted on the inner surface of a myocardial phantom at 2 difference locations: anterior (ANT) and inferior (INF). The myocardial perfusion SPECT studies was performed with 201Tl using the same protocol that we use for patients. The images reconstructed by non-attenuation-scatter (A(-)S(-)), only scatter (A(-)S(+)) and attenuation-scatter (A(+)S(+)) correction were compared by visual and quantitative analysis, respectively. Results: The adequate attenuation coefficients ratio and counts ratio for 71keV/167keV were 2.277 and 5, respectively. In the normal myocardial phantom, the INF wall was improved by attenuation-scatter (A(+)S(+)) correction, and the whole of the myocardial wall was uniform. In the ANT and INF defect wall phantom, the tracer distribution except defect wall were uniform, and the all defects were clearly detected. In patients with known or suspected CAD, defect regions were clearly discriminated by technique, the detectability for CAD was improved. Conclusion: It is suggested that a new correction method that combined attenuation correction using a difference of intrinsic dual-energy and Compton scatter correction using tripleenergy window (TEW) method for 71keV is useful in 201Tl myocardial perfusion SPECT studies. This may reduce both of attenuation and scatter artifacts, and allow the more accurate assessment of patients with known or suspected CAD.

P454 Diagnostic benefits of dual-modality integrated imaging system SPECT/CT by hybrid camera Infinia Hawekey - own experiences M. Gorska-Chrzastek1, M. Bienkiewicz2, J. Kusmierek1; 1Department of Nuclear Medicine of the Medical University, Lodz, Poland, 2Department of Procedure Quality Control and Radiological Protection, Medical University, Lodz, Poland. Abstract: Integrated system for combined radioisotope (SPECT) and x-ray (CT) tomograms, by use of single device - with no necessity for changing patient position, provides better precision of fusion than traditional method of image fusion from two different diagnostic modalities. Aim: Assessment of additional value of hybrid SPECT/CT imaging compared with SPECT scintigraphy alone.Materials and Methods: Studies acquisitions were performed with use of hybrid device SPECT/CT Infinia Hawkeye GE-combining dual-detector gamma camera with a low-dose X-ray tube attached to the same gantry. Comparison of combined SPECT/CT and single SPECT images was made for all SPECT acquisitions performed in the first year of

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of counts in the frontal and occipital respectively compared to the cerebellum. Results : In the group with whole body panel, the ratios of frontal and occipital lobes compared to the cerebellum were 1.4 ± 0.1, 1.3 ± 0.1, respectively. The ratio between the frontal lobe and cerebellum was larger than occipital lobe in 14 of 20 people. The ratio of the occipital lobe was larger than the frontal lobe in 2 people. And 4 people showed the same value in both ratios. In the group with dedicated brain panel, the ratios of frontal and occipital lobes compared to the cerebellum were 1.3 ± 0.1, 1.5 ± 0.5, respectively. The ratio between the occipital lobe and cerebellum was larger than frontal lobe in 13 of 20 patients. The ratio of the frontal lobe was larger than the occipital lobe in 2 patients. And 5 patients showed the same value in both ratios. Fisher’s exact test revealed there was significant difference in the counts according to using the dedicated brain panel or not (p<0.001). Conclusion : Without using the dedicated brain panel, the count of frontal lobe was higher than occipital lobe in brain PET image of the GEMINI PET/CT scanner. So we recommend using the dedicated brain panel to get the image showed more even and normal distribution of FDG.

operation of new device. Field of view of tomographic study (CT)-was usually narrower than one in scintigraphy (SPECT), as restricted to ROI defined on scintigraphic preview or existing X-ray tomograms. Assessment was based on 103 consecutive studies, performed in various clinical situations: - 10 brain studies (suspicion of primary or recurrent tumor) - 14 studies of parathyroid (hyperparathyroidismus) - 49 studies of thorax or abdomen in search for foci of malignant growth - 23 bloodpool liver studies (diagnostics of haemangioma) - 26 bone scintigraphy procedures (different indications) - 1 abdomen study in diagnostics of gastric bleeding. Visual analysis of images on Xeleris workstation was performed separately for SPECT alone and fused SPECT/CT.Results: Assessment of single scintigraphic SPECT study, providing information on radiotracer uptake in 3 planes, allows for diagnosis of pathology, better recognition of its characteristics and localization-than planar study. Initial assessment of fused SPECT/CT images indicates that there is: • better anatomical localisation of SPECT-detected lesions-in all studies with positive result • a possibility of differentiating sites of pathological with physiological radiotracer uptake - in all cases of studies in abdomen and pelvis and in 8 liver studies for the diagnosis of haemangioma • better detection of small lesions in sites difficult for diagnosis-5 cases of small parathyroid adenoma and 5 haemangiomas • easier localisation of the site of greatest activity of radiopharmaceutical in structures of pathological nature, better localisation of site for biopsy or planning of appropriate therapeutic options-in 8 cases of glioma recurrence.Conclusions: Preliminary findings from year of application confirm diagnostic benefits of assessment of fused images from hybrid device SPECT/CT vs. SPECT analysis alone, especially when better localisation of lesions (including small ones in sites difficult for diagnosis) and differentiating sites of pathological with physiological radiotracer uptake are concerned.

P455 Acquisition parameters for oncologic imaging with a new spect/multislice ct scanner. R. Núñez, W. Erwin, A. Stachowiak, M. Mar, H. Macapinlac; Anderson Cancer Center, Houston, TX, United States.

UT MD

Objectives: To optimize the acquisition parameters of a new SPECT/Multislice CT scanner to be used for Oncologic Imaging.Materials and Methods: The scanner is a combination of a dual detector gammacamera and a 6 slice CT scanner, using the same gantry and couch. Medical physicists from different sections in the division of Diagnostic Imaging in addition to technical personnel from the vendor company, assisted and supervised the implementation of the best acquisition parameters for this new type of scanner. For the CT component of the scanner the idea was to use similar -if not identical- parameters to what is already being used by other CT scanners throughout the division. For SPECT imaging, attenuation corrected iterative construction is standard.Results: For SPECT acquisition; we use 128 views over 360 deg (64 views per head with a 180 deg gantry rotation). 128 x 128 matrix (4.8 mm per pixel). For 21 sec/view (for 99mTc-MDP bone scan; and increasing for other radiopharmaceuticals such as 67Gallium citrate with 25 sec/view, or even 60 sec/view for a 99mTc-CEA monoclonal antibody scan) in a step and shoot mode, non-circular orbit. The energy windows for 99mTc radiopharmaceuticals is 140 KeV/15% (photopeak), 109-130 KeV (for the Compton scatter). Axial FOV: 38.7 cm. For the CT acquisition; 130 KeV, 90 mAs (using CARE which is a Dose mAs Reduction Algorithm). Collimation of 6x20 mm, pitch 1.2, rotation speed of 0.6 seg per 360 degree rotation. Time of 9.42 sec, and a scan length of 38.7 cm. For the CT reconstruction; for diagnostic CT 2.5 mm slice thickness, 2.0 mm slice reconstruction increment, 36 cm FOV (bone, soft-tissue and lung reconstructions). For attenuation correction CT, 5 mm slice thickness, 5 mm slice reconstruction increment, 50 cm FOV (smooth filtering for attenuation correction map). For SPECT reconstruction; Iterative reconstruction , 126 subsets, 8 iterations, 3D resolution recovery, 55 mm Gaussian 3D for 99mTc,(varying according to the specific radiopharmaceutical being image, such as 8.4 mm for 67-Gallium citrate or 9.6 mm for 111-In) post-reconstruction filter.Conclusions: The use of this new SPECT/Multislice CT scanner, using optimized acquisition and reconstruction parameters has produced high quality SPECT and CT images. The availability in a single study of AC and Non AC high quality SPECT images, together with diagnostic quality CT images and SPECT/CT fused images, combining function and form has the potential to become a leading technique in oncologic imaging.

P456 Application of CT attenuation correction on lesion detection in SPECT imaging J. D. Birchall1, K. R. Blackwell2, R. H. Ganatra2, K. Griffith2, A. C. Perkins2, R. M. Smith2; 1Nuclear Medicine Department, Derbyshire Royal Infirmary, Derby Hospitals NHS Foundation Trust, Derby, United Kingdom, 2 Department of Medical Physics, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom. Aim Attenuation correction (AC) of SPECT studies can improve the accuracy of the detection and localisation of activity at different depths within the body. Low dose CT instead of a conventional rod source for this purpose offers the additional advantage of fusing the functional study to the anatomical image. We have assessed this technology in a series of patients undergoing SPECT/CT imaging. Materials and Methods Over a 12-month period, in 44 patients, we assessed CT AC performed on a dual headed gamma camera/CT system (GE Hawkeye). For the region of pathological uptake the effect of AC on the count rate from was compared with that of the same region in the non-AC image and expressed as a ratio (AC/NAC). Results Over all of the studies the effect of CT AC was to increase the AC/NAC ratio by a factor of 3.19 (Mann-Whitney U test p<0.0001). For the 28 99mTc studies the AC/NAC ratio increase was 3.64 (p<0.0001). Not unsurprisingly we found there was significant correlation between the AC/NAC ratio and depth of lesion from skin surface being for all radionuclides (r=0.535, p<0.0002) and for Tc99m (r=0.76, p<0.0001). Conclusion We conclude that hybrid SPECT with CT attenuation correction improves the definition of pathological radionuclide uptake and should be utilised where available to assist in the patient’s management . This was in agreement with clinical findings and supports the use of CT AC for SPECT imaging where available.

P457 Anatomical accuracy of hybrid SPECT/CT in the lower spine

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A. Nömayr, W. Römer, D. Strobel, W. Bautz, T. Kuwert; University of Erlangen-Nürnberg, Erlangen, Germany. Aim: The anatomical accuracy of hardware-based registration of skeletal single-photon emission tomography (SPECT) and X-ray computerized tomography (CT) has as yet not been studied. The aim of this study was to evaluate this variable in the lower spine for a newly introduced hybrid SPECT/ spiral-CT camera.Methods: In 22 patients referred for degenerative joint disease or tumors, whole-body bone scintigraphy including hybrid SPECT/ spiral-CT of the lower spine was performed. Subsequent analyses were performed on these pairs of images as well as on data sets obtained after using a rigid automated fusion procedure in addition. Two observers independently measured the distances between the visually determined centers of gravity of the CT and SPECT representation of the fourth and fifth lumbar vertebral body in X-, Y-, and Zdirection (X-, Y-, and Z-distances).Results: The distances determined by the two observers for the two vertebral bodies correlated significantly and were averaged for further analysis. For hybrid SPECT/ spiral-CT without consecutive automated registration, the mean X-, Y-, and Zdistances were 1.6 ± 1.9 mm, 1.7 ± 1.3 mm, and 0.9 ± 0.5 mm, respectively. Additional automated registration lowered these values to 1.2 ± 0.9 mm, 1.1 ± 0.7 mm, and 0.8 ± 0.4 mm, respectively. The difference for the Y-distance proved statistically significant (p < 0.05). Additional automated registration significantly reduced the number of subjects in whom at least one of the distances determined was greater than the SPECT pixel size of 4.6 mm from 14 % (n=3) to 0 % (p < 0.05).Conclusions: Hardware-based fusion between skeletal SPECT and CT offers a nearly perfect data match in the lower spine. The additional use of a tool for automated rigid registration has the potential to reduce the error of alignment even further and may be useful in patients with reduced compliance leading to movements between the two examinations.

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Physics 3: Software and Methods P458 Comparison of the current techniques used for the denoising of scintigraphic images M. Kirkove, A. Seret; University of Liege, Liege, Belgium. Aim. Several techniques for denoising images contaminated by Poisson noise were compared in terms of gain in signal-to-noise ratio (SNR) and preservation of resolution and contrast. Materials and methods. Wavelet methods recently developed to denoise Poisson noise limited images were compared to the traditional low-pass filter methods. The two following classes of wavelet denoising techniques for photon limited imaging were considered. The first is based on the representation in Haar wavelets: the original image is modeled by a piecewise-constant function defined on a partition of dyadic squares. There are some variants: a translation invariant version («Hereditary TI Haar» estimation) and the possibility of including wedges in the partition («Wedgelets» estimation). The second class is based on the idea of applying a first operator, called «variance stabilisator», allowing to transform the Poisson noise into white Gaussian noise. The Haar-Fisz transform provides such operator. Denoising of the Gaussian noise is performed by using either thresholding or Bayesian wavelet methods. The Bayesian method developed by Pizurica appeared to be the most powerful and was used in this work. In total, six methods were compared : the Metz and Hanning filters, Hereditary TI Haar and Wedgelets, the combination of the Haar-Fisz transform with the most classical thresholding methods (HFTThr) or with the method of Pizurica (HFTPiz). The study was conducted on various images whose noise-free part was known: images simulating capillary line source, images of various SNRs of the Hoffman brain and Shepp-Logan phantoms. Results. Concerning the gain in SNR, the best methods were Metz and HFTPiz which provided a gain of 12.3 and 11.3 db in average, the other methods allowed a gain of less than 10 db. The preservation of the resolution depended strongly on the background. For a non-null background, the resolution was preserved by the filters, increased by HFTPiz and the Wedgelets method and decreased by the two other methods. For a null background, the resolution was preserved by HFTThr and decreased by the other methods. The contrast provided by Metz and HFTThr was larger and that provided by HFTPiz was more or less identical to the original one. The visual aspects of the denoised images must also be considered. Artefacts in form of oscillations are generated by the filter methods, HFTThr generates line artefacts and the Hereditary TI Haar and Wedgelets methods present staircasing artefacts. Conclusion. Among the tested methods, the HFTPiz method appears to be the best method.

P459 IIR-Grid: A heterogeneous grid environment for automatic and large-scaled tasks of Iterative Image Reconstruction L. Pan1, G. Kontaxakis2, A. Dimitrakopoulou-Strauss1, K. Mikolajczyk3, C. Burger4, U. Haberkorn1, L. G. Strauss1; 1German Cancer Research Center, Heidelberg, Germany, 2Technical University of Madrid, Madrid, Spain, 3 Warsaw University of Technology, Warsaw, Poland, 4University of Zuerich, Zuerich, Switzerland. Aim: The study established a heterogeneous grid environment, IIR-Grid, for large-scaled iterative image reconstruction (IIR) tasks that are high computationally time-consuming in static and dynamic PET studies. The environment can implement the distributed computation of the IIR tasks at multi-tasks level and inner-task level as well as the distributed storage of image data in different image databases.Materials and Methods: The environment is built as a cross-platform java application integrated into the PMod software (PMOD Technologies Ltd., Adlisvil, Switzerland). Based on a flexible and customizable reconstruction parameter templates mechanism, we have implemented a fully automatic process of image reconstruction tasks. One machine in the grid, which plays the role of task producer and server, periodically downloads the sinogram data from the remote ftp server of the ECAT HR+ system. Once one reconstruction data set is available for reconstruction, the scanner will match the data set with the templates according to the header information of the data files and creates the reconstruction mission description files. The other computers in the grid, which play the role of task consumer, search for a task in the queue and participate in the distributed computation of image reconstruction. Besides, for the more time-consuming tasks like reconstruction of dynamic PET data, the system

P460 Fractal texture analysis of lung scan in diagnosis of pulmonary embolism: K. Hwang1, Y. Kim1, S. Choi2, D. Choi, M.D.3, M. Yoon1, W. Choe1; 1 Department of Nuclear Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea, 2Department of Radiology, Gachon University Gil Medical Center, Incheon, Republic of Korea, 3Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea. Introduction Although diagnosis of pulmonary embolism is very important in the patient management, the conventional lung scan is only diagnostic in a minority of cases and indeterminate in a majority. Fractal texture analysis is a popular method to analyze images. We investigated whether the fractal texture analysis of lung scan is helpful in interpreting lung scans in patients with suspected pulmonary embolism. Materials and Methods We retrospectively reviewed 41 lung perfusion scan images of patients who were suspected of pulmonary embolism (18 high probability, 17 low probability and 6 intermediate probability). Corresponding CT angiographic images were also reviewed. Bilateral oblique lung perfusion scan images were segmented with a minimum rectangular box including the each entire lung. The fractal dimension of the segmented oblique lung images were calculated by fractal analysis algorithm in image-J software. The calculated values of fractal dimension of oblique lung perfusion scan images were compared between the images of high and low probability and between the images of intermediate probability with embolism(+) CT angiography and embolism(-) CT angiography. Results The calculated fractal dimension values of high probability lung images were significantly lower than those of low probability ones (p < 0.05). In the images of intermediate probability, the fractal analysis also effectively divided them into two positive and negative groups which were matched well with the corresponding CT angiographic findings. Conclusion The fractal texture analysis of perfusion lung scan is useful in the diagnosis of pulmonary embolism. Further studies including larger numbers of lung scan images of intermediate probability using more advanced algorithms are warranted.

P461 Development of training software for nuclear medicine imaging V. Fidler1, K. Škaliþ2, S. Fidler3, M. Medved1, I. Slodnjak4, S. Škaliþ2, M. Dimic5; 1Xlab Research, Ljubljana, Slovenia, 2Oncology Institute, Ljubljana, Slovenia, 3Faculty of Computer and Information Science, Ljubljana, Slovenia, 4Clinical Center, Ljubljana, Slovenia, 5High School of Health Care, Ljubljana, Slovenia. Introduction Individual teaching and training of acquisition and processing of Nuclear Medicine (NM) images and patient studies is highly desired for all beginners of different specializations in the field. Aim Development of realistic imaging & processing software for simulating the acquisition of planar static, dynamic and gated as well as SPET and PET studies for all clinical protocols could replace in great extent the on-site training in NM departments. Methods Interactive software was developed to cover all subsequent steps in performing and analysis of any NM imaging study: - inserting or selecting a patient in/from the database with clinical protocol, acquisition, instrumental and personnel settings, - simulating persistence display, performing acquisition and recording of images with simultaneous display of all relevant count, time and frames data, displaying the randomly generated acquired images from archived patient study for each displayed intermediate time, - analyzing with standard clinical processing protocols on the extensive set of NM patient studies (normal and different pathology) - creating study report by special report ”engine” with printout, archiving and distributing coded report to the addressed institution, department’s server and telemedicine Internet server. Results Nuclear medicine teaching & training Windows software (MedicView) was developed with full functionality of standard clinical systems and covers all steps in the acquiring of image data (planar, SPECT and PET), patient database functions, standard and special clinical processing protocols, reporting, local and global network archiving and connectivity. Clinical acquisition and processing protocols were quality evaluated by several IAEA and EU interlaboratory evaluation projects. Training software was already effectively applied to the teaching program in High Radiology School (training hours in NM departments can be reduced to one quarter, rest of hours in the computer lab) and is planned also for training in postgraduate courses and in IAEA technology workshops. Conclusions Present developed system covers training of the acquisition and processing (including reporting and communication) of NM studies and can be effectively applied in the NM teaching program. New modules will be added for teaching clinical indications for studies, pharmacology and imaging technology.

P462 Influence of source size, voxel size, source-to-background ratio and edge definition criteria on SPECT volume quantitation.

I. Printzipas, M. Kotzassarlidou, T. Kalathas, A. Makridou, N. Salem; “TheAGENION” Cancer Institute, Thessaloniki, Greece. Aim: In diagnostic and oncological medicine, SPECT is an important acquisition mode for in vivo 3-D imaging of radiopharmaceuticals. When the intention is to measure volume of a specific organ, it is convenient to make preliminary phantom studies of an object of similar shape and size. Absolute quantitation by SPECT is feasible and has been shown to be a clinically reliable and useful technique. A number of factors influence the accuracy of estimation of source volume with SPECT imaging. The purpose of this study is to evaluate the influence of source size, voxel size, source-to-background ratio (SBR) and edge definition criteria on SPECT volume quantitation.Materials and Methods: The first step of the study included determination of the slice thickness and the voxel size for 64x64 and 128x128 matrix during SPECT acquisition. Six (6) plastic cylindrical sources of known volumes (1.7 - 13ml) were filled with an activity concentration of 825kBq/ml (22.3µCi/ml) of Tc-99m pertechnetate and fixed into a cylindrical Jaszczak phantom, filled with nonradioactive water. Two SPECT acquisitions of the above phantom were performed (64x64 matrix, 15 sec/frame over 360o and 128x128 matrix, 15sec/frame over 360o) on a SOPHA DST-Xli Ȗ-camera. In order to study the influence of the source-to-background ratio, one source (10ml, 592 kBq/ml Tc-99m pertechnetate) was positioned in a cylindrical phantom filled with radioactive water. SBR of 0, 1.5, 5 and 9.6 were applied. SPECT acquisition of the above phantom was performed only for 128x128 matrix (128 frames, 10sec/frame over 360o). Source’s volume was measured for 50%, 70% and 80% count threshold. Projections were reconstructed using filtered backprojection. Attenuation correction was applied.Results: Measured volumes were overestimated in most cases. The 128x128 matrix showed better accuracy in all cases and as the source volume was increasing, accuracy was improved. In larger sources (>6ml), 70% count threshold showed better estimation of the source volume. The increase of background radiation influenced volume estimation and, while a 70% threshold was satisfactory in zero or low background radiation, the use of 80% count threshold improved volume estimation in larger SBR.Conclusions: SPECT volume determination is more accurate in volumes larger than 5ml. The combination of 128x128 matrix size with 70% count threshold is good for calculating volumes in the presence of low background radiation (SBR<5). As the SBR increases, a larger threshold must be applied.

P463 Generation of voxel phantoms to investigate the effect of statistical noise on image analysis programs A. J. Green, R. H. J. Begent; University College London, London, United Kingdom. Aim: In order to bring a new image analysis method into clinical use it is necessary to validate the program which realises the algorithm, and to define its range of useful operation. An important factor in nuclear medicine is the statistical noise inherent in the images. We describe the development of a tool to generate 3 dimensional software phantoms of known configuration with defined statistical noise characteristics, for amalysis program validation.Methods: A computer program was developed (using the IDL development environment) to allow users to define the configuration of a 3D phantom consisting of an elliptical cylinder and a set of elliptical cylinders and ellipsoids with set activity densities relative to the first cylinder. A voxel phantom of this source distribution is generated; this is transformed into a cumulative density function matrix which is normalised to give a cumulative probability density matrix. This matrix is sampled with a pseudo random number sequence to obtain a count density matrix which is transformed into an image of known statistical noise characteristics. The program allows a series of low count density images to be generated during the creation of a high count density image. The generated images, and the noise free phantom image, are saved as DICOM files for importing into the program to be validated. A series of test images was created. The count density ratios were compared with the input parameters. The statistics were compared with the theoretical (Poisson) statistics. The NEMA uniformity statistic (((Nmax-Nmin)/(Nmax+Nmin)) x 100%) was calculated for each volume. A voxel phantom containing spherical lesions was created for initial testing of a volume of interest (VOI) growing program for use in FDG imaging. The images were passed to the VOI program and the characteristics of the grown images were compared to the noise free images.Results: The program produced images with correctly positioned objects in 32x32x32, 64x64x64 and 128x128x128 voxel matrices. The images exhibited Poisson statistics. Uniformity improved with increased total counts in line with theoretical predictions. For the VOI growing program the accuracy of the grown volume and the estimate of total lesion counts was seen to improve with increasing count density. Discussion: We have developed a nuclear medicine voxel phantom creation program which allows the effect of statistical noise to be investigated in isolation from other factors (e.g. scatter and attenuation). This program will contribute to the validation of image analysis programs.

P464 Accuracy assessment of fast dynamic volumetric measurements with a three-headed SPECT system E. Vanzi1, A. Pupi1, M. T. De Cristofaro1, V. Orlando2, A. R. Formiconi1; 1 University of Florence, Florence, Italy, 2GE Healthcare, Milan, Italy. The clinical impact of SPECT measurements of dopamine receptor density is hampered by the low capability of SPECT to recover activity concentration ratios (ACRs) [1]. In [2] we proposed a method for acquiring and processing data when three-headed systems are used in Dynamic SPECT (DSPECT). We showed that when few regions of interest (ROI) are concerned, three views data sets may be sufficient to reconstruct ROI contents directly from projections. This phantom study evaluates the accuracy of our DSPECT method to recover ACRs in selected brain regions. To this aim an Alderson striatal phantom (www.rsdphantoms.com) was filled with striatal/background ratios of 6:1, 9:1, 28:1 (this is the range of the expected ACRs with dopamine system tracers). The temporal sampling of the DSPECT was settled as to comply with the count statistics of clinical SPECT studies with dopaminergic tracers. A total of 120 time points were acquired. The gamma-camera used for this study was an Irix (Philips). Briefly, the striatal and background ROIs were drawn on the basis of an X-ray CT of the phantom. The coregistration matrix between X-ray-CT and SPECT was obtained with Neurostat (http://128.95.159.66/~Download/) with the use of the images of a conventional SPECT acquisition on a 360 degree rotation. The ACRs of these ROIs were derived both from the DSPECT acquisition and from the conventional SPECT EM reconstruction. The influence of a segmentation error up to 20% of the striatal volume was also evaluated. The ACRs obtained with

S319

Poster Presentation

will divide one task at multi-tasks level according to the acquired frames. Subsequently, the merger function of server combines the sub-result files to a final image file and distributes it to the multiple image databases in the grid.Results: The distributed image reconstruction server was tested and evaluated on a heterogeneous local area network environment including PCs, Mac Systems (Apple Computer Inc., Cupertino, CA, USA) and Linux systems. We did a series of experiments at different arriving rates of data files to simulate the different situations including the smooth and outburst stream. Even in the most crowded phase, the system can finish the data reconstruction created by a middle-scaled PET lab in less than an hour using all calculating resources.Conclusions: The distributed nature of image reconstruction makes itself very suitable for grid computation. Our IIR-Grid achieved the target of totally automatic and quick processing of image reconstruction though phases of automatic data scanning, data-template matching, task distribution, task calculation, distributed storage of images.

EM reconstruction were 3.2, 4.9 and 15.9 respectively at the points of 6:1, 9:1 and 28:1. At the same points with DSPECT the ACRs were 6.2+/-0.6, 9.0+/-0.9 and 27.2+/-2.6. The segmentation error gave greater changes in DSPECT ACRs (up to 15% for a 20% error) than in EM ACR values (up to 5%). Therefore, fast DSPECT is feasible and accurate in the clinical examination of the dopaminergic system. This holds on a wide range of ACR values. This approach can be fruitful in disease progression monitoring, in developing new radiopharmaceuticals for SPECT imaging of the dopaminergic system and in clinical trials of dopaminergic drugs. [1] M. Soret, P. M. Koulibaly et al.: J. Nucl. Med., 44(7):1184-1193,2003. [2] E. Vanzi, A. R. Formiconi et al.: IEEE Trans. Med. Imag., 23(3):363-373,2004.

P36 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

P465

D. Thers, J. Cussonneau; Subatech, Nantes, France.

The use of the NCAT phantom to simulate the performance of lung ventilation-perfusion spect versus conventional planar VQ scanning

Gamma detection with liquid xenon has been studied at Subatech for two years, with the goal of improving PET (Positron Emission Tomography) imaging and diagnostic. The key idea is to integrate in a liquid xenon proportional chamber recent progresses made with gaseous devices, for detecting both ionization and scintillation. The ionization contribution will be detected by a PIM/Micromegas device, developed at Subatech, immersed in liquid xenon for the first time and the scintillation contribution will be detected by a new type of gaseous photomultiplier, particularly suited for covering large areas, and developed at the Weizmann Institute of Sciences. Simulations of image characteristics obtained with such a detector have been performed and confirm the interest of a research effort around liquid xenon for PET. They demonstrate the potentiality to reduce injected activity and exposure time in human-body PET diagnostic when considering a large camera containing ~100 litres of liquid xenon. But, the technical difficulties associated to the xenon liquefaction (T ~ -110° C) and purification on a large volume put strong constrains, for which a dedicated development has to be pursued. We report on the construction of a first small prototype adapted for nuclear medical imaging associated to ȕ immunotherapy. The proposed imaging technique is based on the measurement of the emitter location in the 3 dimensions with a few mm spatial precision using ȕ+Ȗ coincidences. It will also allow an accurate dosimetry along the therapy process. A new generation of camera and an ad hoc radio-nuclide are then the foundations of this proposition: the incident direction of the third Ȗ-ray emitted quasi simultaneously with the ȕ+ decay of the 44Sc radio-nuclide is measured by a liquid xenon Compton telescope (LXeComp). The innovative LXeComp/44Sc couple should be particularly interesting when associated to research in ȕ immunotherapy/dosimetry with 47Sc/44mSc. We review the major ideas initiating the experimental feasibility of this novel medical imaging technique. After this demonstration step, we foresee to submit in two years a new research program for the construction of a second prototype based on a larger liquid xenon Compton camera dedicated to the small animal imaging.

M. J. Guy, R. J. Morton, P. J. Hinton; The Royal Surrey County Hospital, Guildford, United Kingdom. Aim One possible approach to improving the sensitivity and specificity of conventional planar Ventilation-Perfusion (VQ) studies is the use of SPECT. However, the exceptionally low detected counts typically found in such studies will limit the theoretical advantages of SPECT. In order to investigate the extent of these limitations and optimise the SPECT acquisition parameters, a simulation tool, combining the NCAT mathematical cardiac-torso phantom and a fast simulation of the gamma camera detector, has been developed. Using this tool the sensitivity and specificity of 99m-Tc Ventilation-Perfusion (VQ) SPECT versus planar scans can be evaluated and the optimal SPECT parameters determined. Materials and Methods The NCAT phantom was used to generate activity distributions in the lung and airway volumes. Multiple spherical ‘defects’ were added interactively to the lung perfusion activity distributions, simulating Pulmonary Emboli (PE). The size, severity (partial or complete obstruction) and position of each PE were controlled by the user. If required, respiratory motion was then added using the NCAT software tools. An analytical routine was developed to perform a basic simulation of gamma camera projections formed from the NCAT 3-D activity and attenuation output files. The algorithm included an estimation of the GE Infinia gamma camera’s pointspread function with Low Energy General Purpose collimators, photon attenuation and Poisson noise. It did not include photon scatter or any interactions in the detector as these components were not thought to play a significant role in this initial application. The simulated datasets were reconstructed and compared with traditional eight-view planar data. Results and Conclusions The simulation tool has been shown to produce clinically realistic lung ventilation and perfusion scans. The user has full control over the size, placement and severity of the simulated PE ‘defects’ and other parameters, such as the number of projections and count density. Unlike a full Monte-Carlo based simulation, the algorithm used to generate the final projection dataset is complete within a couple of minutes on a standard desktop PC. By relying on simulated data to initially evaluate VQ SPECT, prolonged studies involving large numbers of patients could be avoided. It is envisaged that the results of this study will be applied to a small patient study to verify the optimum VQ SPECT settings for the Infinia camera. Additional applications of this tool include staff training in the technical reporting of lung nuclear medicine scans and the development of fully- or partially-automated algorithms for reporting VQ SPECT studies.

P467 +

Nuclear medical imaging using ȕ Ȗ coincidences from radio-nuclide with liquid xenon as detection medium

44

Sc

P468 Transmission imaging using an uncollimated uniform sheet source A. van Aswegen, J. A. van Staden, H. du Raan, M. G. Lötter, C. P. Herbst, A. C. Otto; University of the Free State, Bloemfontein, South Africa.

REJECTED BY AUTHOR P469

P466 Feasibility study of respiratory (RE) gating (GAT) of 99m-Tc HMPAO labelled leukocytes scintigraphy (LEUKO) without external respiratory device: LEUKO-REGAT project D. Daou, N. Kaci, M. Tawileh, A. Benada, C. Coaguila; Hospital, AP-HP, Paris, France.

Physics 4: Instrumentation and Quality Control

Lariboisiere

Aim: Static renal parenchyma scintigraphy imaging using 99m-Tc HMPAO labelled leukocytes over the abdomen and the chest is realized without consideration of the patient respiratory motion along the acquisition. We developed a method that synchronises the images to the patient respiratory motion. This method presents the advantage of being purely based on image processing without further need of any external device. In this study, we aimed to verify the feasibility of this method in patients addressed for 99m-Tc HMPAO labelled leukocytes scintigraphy.Materials and Methods: The study included 8 patients addressed for 99m-Tc HMPAO labelled leukocytes scintigraphy for the work-up of osteo-articular disease. The developed method processes dynamic planar acquisitions of 99m-Tc HMPAO labelled leukocytes (50 ms per frame during 400 seconds per view, matrix 128x128 pixels, anterior and posterior views over the abdomen and chest). The acquired dynamic images allow the generation of a respiratory signal curve based on a pure image processing method (no external device). Then this signal is used to create a mean respiratory cycle by analogy to what is done with ECG gating for cardiac imaging. The generated mean respiratory cycle sequence allows the generation of a ciné mode study after the normalization of all phase images to the highest activity image (avi mode), a reference image corresponding to the end expiratory respiratory cycle (Reference image), and a summed image of the overall acquisition time (Summed non-realigned image). In parallel, a rigid registration algorithm allows the registration of the images and the generation of a summed realigned image of the overall acquisition time ((Summed realigned image) The quality of the obtained images was evaluated visually by 2 observers.Results: Mean±SD of age, weight, and height were 62±15 years, 73±25 Kg, and 168±12 cm. And 6 patients were male. In all patients and in all 8 views, the processing method allowed the generation of good respiratory curves corresponding to the acquired images. These curves allowed the generation of good quality cine mode imaging sequence, reference images and summed realigned image.Conclusions: Respiratory gating of 99m-Tc HMPAO labelled leukocytes is feasible in all evaluated patients and in the anterior and posterior views of the chest and the abdomen. The study of its additional value and impact on the clinical performances of static 99m-Tc HMPAO labelled leukocytes is warranted.

Improvement of spatial resolution in In-111 imaging using a low-energy general purpose collimator A. Kojima1, S. Kawamura2, Y. Inoue2, K. Okada2, M. Matsumoto1, S. Tomiguchi1, Y. Yamashita1; 1Kumamoto University, Kumamoto, Japan, 2 Saiseikai Kumamoto Hospital, Kumamoto, Japan. Indium-111 (In-111) decays by electron capture and emits two gamma rays with almost equal abundance, 171 keV (90%) and 245 keV (94%). Since these energies require the use of a medium-energy (ME) collimator, In-111 imaging results in relatively poor spatial resolution. The aim of this study was to investigate the improvement in spatial resolution of In-111 imaging using a low-energy collimator instead of a ME collimator.Materials and Methods: A line source, a sheet source with multiple defects, and a sheet source with hot distributions were imaged with In-111 and some patients with In-DTPA (cisternography). Planar imaging was performed using a dual-head gamma camera equipped with a low-energy, general-purpose (LEGP) collimator (<170 keV). Two 20% energy windows, W171 and W245 were set at the 171 keV-photopeak and 245 keV-photopeak respectively. Scatter correction (SC) by the triple energy window (TEW) method was performed for the W171 images alone and, the SC and collimator-penetration correction (CPC) by the blurring filter for the W245 images. Furthermore, the corrected (W171 + W245) images were generated. The same data acquisitions with the ME collimator (<300 keV) were also performed and these images were compared to ones with the LEGP collimator.Results: The W245 images with the LEGP collimator had a large amount of septal penetration, but the W245 images with the CPC showed the equal spatial resolution to the W171 images with the LEGP collimator. All the LEGP collimator images (W171, W245with the CPC, W171+ W245with the CPC) were superior to the ME collimator images on spatial resolution. However, the imaging count rates (sensitivity) of the LEGP collimator images were ~ 20% lower than the ME collimator images. In the patient’s study, the LEGP collimator images did not cause any imagedistortion and showed better spatial resolution than the ME collimator images.Conclusions: The CPC for the 245 keV gamma ray allows the use of the LEGP collimator in In-111 imaging instead of the ME collimator. This advantage can provide a more qualitative and quantitative assessment of the In-111 accumulation.

P470 Which collimator should be used for myocardial perfusion SPECT, HR or GP? A. Gustafsson1, J. Gretarsdottir2; 1Department of Radiation Physics, Linköping, Sweden, 2Department of Medical Physics and Engineering, Göteborg, Sweden.

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FWHM(mm) Postfilter

None

Matrix

64

Butterworth f=0.5cm-1, p=5 128

64

128

Collimator

HR

GP

HR

GP

HR

GP

HR

GP

L-mode z=1.28

14.6

15.5

10.7

13.9

17.4

18.8

15.8

17.9

H-mode z=1.00

18.1

18.8

11.5

13.3

20.0

20.6

16.5

17.7

Conclusions: The resolution is degraded using GP collimator. This degradation can partly be compensated by increasing the matrix size. The highest contrast to noise ratio was achieved using the HR collimator.

P471 Automated detection and correction of SPECT quality assurance phantom axis orientation errors K. J. Nichols, E. V. Moroni, C. J. Palestro; Long Island Jewish Medical Center, New Hyde Park, NY, NY, United States. Aims: SPECT system quality assurance tests include periodic evaluation of multi-purpose Plexiglas phantoms. Documenting that cameras perform SPECT studies well can be problematic due solely to difficulty in reliably aligning phantom physical axes with some cameras’ axes of rotation, as misalignment can lead to incorrectly reduced assessment of resolution and contrast. This investigation was conducted to test new methods to detect and correct automatically phantom positioning and axis misalignment.Materials and Methods: Algorithms were devised to provide evidence of phantom axis misalignment, manifested as the appearance of axis precession in cines of original projection images. Input data to algorithms consisted of the original projection images (counts = 42±17 M counts; range = 2-90 M counts), shown to users as a cine display from which a visual impression of precession could be judged. Phantom sides were tracked at each projection based on a 20% threshold of maximum phantom counts, the 2D count profiles of which were fit linearly to measure slopes of the phantom sides per projection. First order harmonic fits to derived slopes provided information as to azimuthal orientation tilt angles, which were subsequently used to correct transaxial reconstructions of phantoms. These were reprojected to form equivalent projection images which were also shown to observers, enabling them to judge the extent to which algorithms succeeded in reorienting phantom images automatically. Data were processed for fixed-tilt-angle detector systems (N=13), variable-tiltangle detector systems (N=9), and 3 phantoms for axes purposefully aligned by 0° - 9°. Two observers graded cinematic displays independently of original and corrected projection data for evidence of precession on a 5-point scale as “none,” “slight,” “noticeable,” “significant” or “severe.”Results: Agreement between observers was kappa = 0.69 (“good” agreement). Observers consistently judged data with precession angles measured to be greater than 2° to be “noticeable” or “significant.” Precession was significantly greater for variable-tilt-angle than fixed-tilt-angle detector systems (1.9°±0.3° versus 0.8°±0.3°; p < 0.0001). For simulations of 0° 9° offsets, the algorithms correctly found misalignment angles to within ±0.5°. In all cases review of cine displays of corrected re-projected data were judged to show “none” or “slight” residual precession artifact, and further quantification of residual tilt angle was less than ±0.5°, even for the 2 M count phantom.Conclusions: Data provided by standard commercially available multi-purpose Plexiglas phantoms are sufficiently predictable to permit execution of automated algorithms for reliable detection and correction for suboptimal phantom orientation.

P472 Influence of the line source width on the spatial resolution measurements of gamma camera P. I. Trindev, N. Ozturk, A. Atanasov; Medical University, Sofia, Bulgaria. Spatial resolution (SR) is a subject of regular quality control (QC) because it is one of the basic parameters to indicate the gamma camera (GC) performance. The SR is assessed trough the FWHM (full width of half maximum) of the profile image of the line source (LS). Usually it is recommended to use a LS with a very small diameter in order to diminish the measurement error. Next requirement refers to the number of matrix pixels that encompass FWHM - at least 10 pixels. We decided to check if there is any influence of the LS internal diameter upon results. Phantom commonly used to measure SR is PLES (Parallel lines equally spaced). Commercially

available PLES phantom consists of lead strips 30mm wide separated by 1mm slit. We developed our own slit phantom with adjustable width of the slit. The phantom consists of 3 lead blocks 100x20x50 (LxWxT) and 3 pairs of inserts. The inserts are plastic sheets with calibrated thickness 0,25mm, 0,5mm and 1mm respectively. The phantom is irradiated from a syringe with activity solution (99mTc) positioned under each slit. The syringes are carefully shielded. A shielding is especially important when intrinsic resolution is measured, because without collimator GC is very sensitive to a scattered radiation. The phantom is placed under the crystal at a close proximity. The separation between 2 LS is fixed at 20mm (the width of the lead block) so the size of the pixel can be accurately defined independently from the zoom factor used. Results from the measurement of the SR with different width of the slit demonstrate a significant difference - up to 67%. At least 3 conclusions stem from this result: 1.The change of SR within time should be tracked with a fixed size slit (or with the same PLES phantom). 2.A comparison between the SR of 2 gamma cameras should be carried out with the same phantom. 3.A SR at different locations of detector field is assessed with a PLES phantom. How far can we rely that the size along a single slit and among all slits is the same?

P473 How wide is that curve? An analysis of errors in determining the width of Gaussian curves. A. Britten; St Georges Hospital, London, United Kingdom. Introduction. Measurement of the full width at half or tenth maximum (FWHM and FWTM), is frequently used to characterise Gaussian curves, for example to measure the spatial resolution of gamma cameras or gamma probes. Commonly accepted good practice would be to take ten data samples in the FWHM, with 10,000 counts in the peak. However, this may not be achievable due to sampling and count rate or time limitations. Aims. To determine the errors in the FWHM and FWTM due to sampling with 20, 10 and 5 points in the FWHM, at peak counts from 10,000 to 61. Methods. Simulation of Gaussian curves with poisson noise allowed 110 trials of FWHM and FWTM calculation, at different sampling intervals and peak counts. The effects of sourceaperture misalignment, peak fitting, and the differences between image and single point detectors were investigated. Results. Accurate and precise measures of FWHM and FWTM (less than 1 % absolute error, coefficient of variation CoV less than 2 %) can be achieved even with 5 samples in the FWHM and down to 1615 peak counts, as long as the peak is fitted. CoV rises relatively rapidly below 1615 peak counts, with FWHM systematically underestimated by up to 5 % at low peak counts.Conclusions: Good accuracy and precision in estimating curve widths can be achieved with lower quality sampling and statistics than previously recommended. This is important to know when performing Quality control procedures in Nuclear Medicine, and may save time and effort. This knowledge is useful when designing appropriate assessment methods for gamma cameras and gamma probes.

P474 Quantitative gamma-only imaging of multi-well culture plates with a phosphorimager A. J. Weeks1, D. Lloyd1, P. J. Blower2; 1University of Kent, Canterbury, United Kingdom, 2King's College London, London, United Kingdom. The phosphorimager is a digital autoradiography system for quantitative imaging of radioactivity distribution in two-dimensional samples in contact with a phosphor screen. Its typical use is for detecting relatively short-range particulate radiation, and as such it provides <0.1 mm resolution if the range of the emissions allows. We wish to report a novel application for the instrument in which it can be used to image gamma emissions from multi-well plates, in order to quantify radioactivity in the wells. This is useful in order to measure radionuclide uptake in cultured cells in a multi-well plate format. Aims: to devise a collimator to minimise cross-talk between wells, determine the linearity and sensitivity of response of the system for non-contact imaging of gamma emitting radionuclides and produce a calibration curve. Methods: A set of lead templates was designed with circular apertures of diameter 5 mm, to underlay the centre of each well of a twenty-four well microtitre plate with circular wells of diameter 15 mm. The templates were stacked to give a collimator of varying thickness from 1 to 8 mm. The multi-well plates were filled with activites of In-111 ranging from 0 to 0.8 MBq, (0 to 1.6 MB/ml) with the same volume in each well. The plates were then imaged for 2 min using a MS storage phosphor screen. The screen was subsequently analysed using a Perkin Elmer Cyclone system. Regions of interest were drawn and analysed using OptiQuant software. Results: The response was linear within the range 0 MBq/well to at least 0.8 MBq/well. Cross talk between cells was adequately damped (to 1.3% in adjacent wells) by a lead thickness of 3mm or more for 5 mm circular apertures, whereas a thickness of 1 mm was inadequate. Conclusion: In addition to its conventional applications in contact imaging of gels, chromatograms and animal/tissue sections, the phosphorimager is a useful and relatively inexpensive device for quantitative collection and analysis of gamma emitting radionuclide distribution in multi-well plates not in contact with the phosphor screen, fulfilling the same role as a gamma camera would in this setting.

P475 Cyclotron-vault activation after a long-term usage H. Bammer1, M. Bichler2, U. Sahm3, P. Reuland3, K. Kletter4; 1GE Healthcare Technologies, Milwaukee, WI, United States, 2Atomic Institute of the Austrian Universities, Vienna, Austria, 3EURO PET GmbH, Freiburg, Germany, 4Medical University Vienna, Clinics for Nuclear Medicine, Vienna, Austria. Introduction: Medical cyclotrons are in operation since the 1950s (1). The use leads to an activation of the surrounding wall. At the EURO-PET installation in Freibug/Germany and at the General Hospital of Vienna/Austria a "PETtrace" (GE Healthcare Technologies, Waukesha, WI, USA) is in routine use since 1996 and 1997, respectively. Beam energies are 16,4 MeV, targetconfigurations are (6 targets): 18F2, 11C, 18F, 15O, 13N, 18F. It is situated in a vault made from normal concrete. At the Vienna installation additional neutron-shields (moderating polyethylene) are added. The knowledge about the activation of vaults housing such type of particle accelerators is crucial for decommissioning plans.Materials and Methods: Several samples of cylindric shape were cut out of the wall-concrete. Significant positions for the neutron-flux were

S321

Poster Presentation

Aims: Parameters that influence the image quality in gamma camera scintigraphy often seem to be chosen without an accurate evaluation. High resolution (HR) collimator and 64 matrix are usually recommended for myocardial perfusion studies. This choice may not be obvious. A general purpose (GP) collimator with higher sensitivity allows a shorter acquisition time for same count density. A matrix size of 64 over the whole area of a large field of view gamma camera gives a pixel size of 8.4 mm. This decreases the advantage of the resolution gained using a HR collimator. The aim of this study was to investigate whether a GP collimator can be used for myocardial scintigraphy with a preserved image quality. The acquisition time could then be shortened to minimize patient motion artifacts.Materials and Methods: All acquisitions were done in both H- and L-mode with a GE VG Millenium gamma camera, equipped with a HR or GP collimator. The system resolution and sensitivity were measured in a cylindrical water phantom with and without a line source respectively. An anatomical cardiac phantom was used to evaluate the image quality. All images were reconstructed with filtered back projection. The contrast was evaluated in a profile through the cardiac phantom in a slice with a defect and the noise was evaluated in a ROI drawn within the myocard in a slice without a defect.Results: The resolution for different pixel sizes and collimators is shown in table 1 below. The higher resolution in L-mode depends on the reduced pixel size because of the zoom factor. Corrected for the difference in pixel size, H-mode gives a slightly better resolution for a central placed line source. The sensitivity was 63 counts/s/MBq for the HR collimator and 122 counts/s/MBq for the GP collimator. In slices reconstructed with a Butterworth filter the contrast to noise ratio reached maximum at a cut off frequency 0.5 cm-1 for both collimators and was highest for the HR collimator for all measured frequencies. Table1.

chosen: 1) In beam direction, 2) in 90° direction and 3) underneath the targets. Activation measurements were performed with a high purity germanium detector (HPGe) with a multichannel-analyzer (Canberra). Standards for the calibration of the detector were made.Results: The halflifes of most of the nuclides are below 100 days, except 152Eu, 134Cs and 60Co. The activityconcentrations in concrete were found to be close to or below 1 kBq/kg. Special PE absorbers at the Vienna installation have lead to significant reductions. There, after a depth of ~10cm the activity concentrations drop to ¼ of the max-values.Conclusions: Most activityconcentration values are below limits in the EURATOM directive (1).Therefore little issues or problems during a decommissioning of the accelerator and its vault are expected. Due to the short halflifes of most of the nuclides, after a waiting period of ~1 year no activites of those should be found. The values are higher in standard concrete vaults compared to such with polyethylene absorbers mounted. Literature: (1) Council Directive 96/26/Euratom of 13 May 1996 (2) Radiation data from de-commissioning the original Hammersmith cyclotron (1985). B. Mackay (3) High yield [18F]F2 productions on a commercial cyclotron. SNM 2004; Helen Björk, Jan-Olof Bergström, Bruce Mackay, Nigel Steel, Eine Södergren and Anders Uppfeldt (4) Predicting Long-Lived, Neutron-Induced Activation of Concrete in a Cyclotron Vault; L. R. Carroll. (5) Fast-Neutron Activation and Ultimate Decommissioning of a Cyclotron Vault: 19811995 J. Cehn, Lewis Carroll, et.al. (6) Residual Long-lived Radioactivity Distribution in Inner Concrete Wall of a Cyclotron Vault.Health Physics. 67(6):621-631, December 1994. Kimura et al

P37 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Physics 5: Probes and Small Cameras P476 How to perform accurate intraoperative monitoring of leakage during hyperthermic isolated limb perfusion using Tc-99m labelled human serum albumin and a collimated gamma detector K. Perisinakis, S. Koukouraki, O. Zoras, N. Karkavitsas; Hospital of Heraklion, Heraklion, Greece.

University

Aim: The aim of the study was to investigate parameters affecting accuracy of intraoperative monitoring of leakage during hyperthermic isolated limb perfusion (HILP) using Tc-99m labelled human serum albumin and a collimated scintillation detector.Materials and Methods: HILP aims to deliver regionally high doses of toxic chemotherapeutic agents that could be extremely hazardous if administered systemically. Leakage into the systemic circulation during HILP is mandatory in order to interrupt perfusion when leakage reaches untolerable levels. In the current study, Tc-99m labelled HSA was used as the radioactive tracer for continuous intraoperative external monitoring of perfusate leakage by means of collimated NaI(Tl) scintillation detector in four patients undergoing HILP. The radiation detector was connected to a singlechannel analyzer and the level of exposure over the heart was continiuously recorded via a stripchart recorder. All devices were mounted on a home-made mechanically articulated mobile stand. Following surgical isolation of the treated limb, a dose of 0.05 MBq/kgr body weight Tc99m labelled HSA was injected in the systemic circulation. Following stabilization, the baseline exposure over the heart was recorded. A ten-fold dose of Tc-99m labelled HSA was then injected into the perfusion circuit. Leakage was determined by monitoring the % difference in the exposure over the heart from the baseline. Introduction of the chemotherapy agent into the isolated limb circulation was permitted only if leakage was below 2%/15min. The effects of detector positioning, rate-averaging time constant, extracorporeal circuit flow rate and limb temperature on leakage determination were investigated.Results: Positioning of the collimated radiation detector over the heart is crucial for the accurate determination of leakage during HILP. Appropriate orientation of the shielded detector should ensure exclusion of photons emitted from the perfusion circuit. The estimated total perfusate leakage over 1.5 h of treatment was <6% in all treated patients. Leakage was increased with increasing limb temperature or increasing flow rate. The rate averaging time constant should be above 5s to achieve a low statistical error of leakage monitoring. To compensate for the in vivo decay of Tc-99m HSA, leakage values should be corrected for the effective radioactive tracer decay rate.Conclusions: Appropriate detector alignment, ratemeter settings and leakage correction for the nominal in vivo decay of the radiotracer may considerably enhance the efficacy of leakage monitoring during HILP procedures using Tc-99m labelled human serum albumin and a collimated external radiation detector.

P477 System for the continuous leakage monitoring during perfusion of an extremity based on a portable gammacamera S. Vidal-Sicart1, A. Orero1, A. Muxi1, J. Duch1, N. Roé1, N. Pavón2, F. Pons1, J. Pavía1; 1Nuclear Medicine Department (CDI). Hospital Clinic Barcelona, Barcelona, Spain, 2GEM Imaging, Valencia, Spain. Introduction: The treatment by means of perfusion of an extremity with Tumour Necrosis Factor (TNF) and melphalan can bear a high degree of systemic toxicity if there is leakage from the blood territory of the extremity to the systemic vascular territory. Classically, the passing of blood from a territory to another one has been controlled by means of the administration of a radiotracer and its monitoring with an external detector. Objective: To develop the appropriate software to carry out the monitoring, using a portable gammacamera adapted for intraoperative use as an external detector.Materials and Methods: The Sentinella S102 gammacamera (GEM Imaging, Valencia, Spain) was used with a light support to facilitate its handling in an operation theatre. The program is written in MATLAB programming environment, and it allows the perfusion monitoring during the operation. Two 99mTc-Albumin doses were used ( 0.74 MBq in systemic vascular territory; 7.4 MBq in the extremity). The program takes as a reference the measure in the precordial zone before TNF is perfunded. The variations of activity are monitorized every 30 seconds. They are expressed in percentage leakage and they are visualized on the screen of a portable computer. The maximum leakage allowed after TNF administration is of 6 %. It has been tested with five patients.Results: This system has allowed our centre to obtain

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the European homologation, thanks to the monitoring and the in situ measurement of the percentage leakage. The values that have been obtained as basal measures are around 1000 cps. and the observed leakage varied between 0.5 % and 6 %.Conclusions: Software has been developed that allows the monitoring of a perfusion of an extremity. The monitoring allows knowing at any time the total percentage of leakage since the beginning of the perfusion. The portability of the system allows its movement and utilization in an operation theatre in a comfortable and simple way.

P478 Suitable applications for a portable mini gamma camera A. R. McDowell; Royal Free Hospital, London, United Kingdom. The Dilon 6800 Gamma Camera is a mobile device for the high-resolution imaging of small, low-activity objects. Its intended use is scintimammography. We have made a study, using various phantoms, for other suitable applications including sentinel node work and imaging of small bones. Phantoms were used to show resolution and sensitivity of small and low activity objects devised to correlate to clinical images. The collimator provided was a High Efficiency collimator with septa length of 2.0cm and septa thickness of 0.03 cm. The results show a very high sensitivity camera at 184 cps/MBq. The resolution is very good at the camera face (3.9mm) but drops off rapidly with distance from the camera face (12.4mm at 10cm). Phantom images show good contrast and detail. This camera shows high contrast-detail performance, improving on images from standard large field-of-view cameras. The resolution at the camera face is achieved without loss to the sensitivity. The small field of view and mobility of the arm means that the camera can be positioned close to the skin taking advantage of the high resolution and sensitivity at this point. Therefore, this camera is an improvement for surface work such as sentinel node and small bone imaging.

P479 Evaluation of 2 intraoperative radiodectection of 18F FDG C. Curtet1, T. Carlier2, F. Kraeber-Bodere2; France, 2University Hospital, Nantes, France.

gamma 1

probes

for

Inserm U 601, Nantes,

Objectives: We investigated the feasibility of surgical gamma probes for detection of 18F-FDG in recurrent,or residual tumors visualised by PET-scan before surgery. We tested 2 gamma probes equipped with scintillators for studying performance measurements regarding sensitivity, shielding, and spatial resolution. Methods: We investigated 2 probes Gammasup (Clerad), and Modelo 2(Novelec) with respectively collimated CsI(Tl), and BgO scintillators, and a window setting 511 keV ± 10%. NEMA guidelines (NU3-2004) were used for testing performance measurements. Sensitivity in air and water was tested with a 1.2 MBq 18F-FDG point source along the probe’s axis at 10 and 30 mm depth. For the sensitivity in water, we used a bath container filled with 4.2 L with the probe positioned with its tip touching the water surface. Sensitivity to scatter was performed by positioning the point source at 90 degrees from the probe's axis at 50 mm, both touching the water surface. The volume sensitivity to distributed activity in a scatter medium was performed by adding 18F-FDG (20 kBq/mL) in the container without additional point source. Sensitivity through side shielding in air used the point source positioned horizontally from the probe’s axis at 50mm. Spatial resolution was achieved by moving the probes laterally from -90 to + 90 mm, at 0, 10 and 20 mm depth from the point source. Results: Sensitivity results were expressed in cps/MBq, spatial resolution FWHM in mm

Sensitivity

/ Air (10/30 mm Water (10/30 mm Volume

sensitivity

to

Shielding

distance

depth)

depth)

distributed activity

CsI(Tl)

89 / 39

63 / 17

17

8

BgO

814 / 241

1484 / 374

187

114

Sensitivity in water to volume sensitivity to distributed activity in a scatter medium ratio was 106 for CsI(Tl) and 88 for BgO. Spatial resolution in water at 0/10/20mm depth were 20/29/41 mm for CsI(Tl), and 21/36/55 for BgO. Conclusion: The CsI(Tl) probe appeared to better discriminate true events from background. Indeed, the CsI(Tl) probe showed a better spatial resolution and sensitivity performance measurements as compared to BgO. We demonstrate the feasibility of high energy photon detection with conventional scintillator subject to appropriate collimation.

P480 High resolution small animal imaging with a mouse sized camera G. K. Loudos1, S. Majewski2, A. Weisenberger2, R. Wojcik2, N. Sakellios1, K. Nikita1, N. Uzunoglou3, A. Varvarigou4; 1Nuclear Imaging Medical group, Biomedical Simulations and Imaging Applications Laboratory, School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece, 2Thomas Jefferson National Accelerator Facility, Newport News, VA, United States, 3School of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece, 4 Institute of Radioisotopes-Radiodiagnostic Products, National Center for Scientific Research "Demokritos", Athens, Greece. In terms of collaboration between the Detector Group of Thomas Jefferson National Accelerator Facility (US), the Institute of Radioisotopes and Radiodiagnostic Products (IRRP) of N.C.S.R. “Demokritos” and the Biomedical Simulations and Imaging Applications Laboratory (BIOSIM), National Technical University of Athens (Greece), a mouse sized camera optimized for Tc99m imaging has been developed. The detector was built in Jefferson Lab and transferred in Greece,

P481 Development and Evaluation of MollyQ; a micro-SPECT scanner D. Wyper1, D. Dewar2, J. Patterson1, H. F. Stoddart3, H. A. Stoddart3, D. 1 Martin3; Southern General Hospital, Glasgow, United Kingdom, 2 University of Glasgow, Glasgow, United Kingdom, 3Neurophysics Corporation, Boston, MA, United States. Aim: The objective was to develop and evaluate a micro-SPECT scanner. The MollyQ-50™ is a novel design of scanner based on the same principles as the Neurofocus clinical section scanner. It was designed for studies on rats and has a 50 mm FOV. There are two other scanners in the series - the MollyQ-30™ is optimum for imaging mice and has a FOV of 30 mm and the MollyQ-175™ has a 175 mm FOV and is used for primates. They are section scanners using the focusing collimator principle. The MollyQ-50™ has eight detectors that traverse the object being scanned so that each covers half the field of view.Methods: Many phases of the design presented challenges of miniaturisation - none more so than fabrication of the collimator. Image reconstruction and display algorithms have been developed. Evaluation of performance required construction of customised phantoms as well as scanning of animals on the MollyQ scanner with selected ligands of known anatomical distribution and comparison of results with anatomical 7Tesla MRI scans.Results: Collimators 2.5cm thick and with over 10,000 converging conical holes were constructed. These will be illustrated and scans will be demonstrated. Early glitches in the software have been successfully overcome and this now runs reliably, with a range of options for image display and transfer. Initially problems were encountered with phantom scans. These turned out to be due to absorption of iodine in perspex [despite pre-treatment with potassium iodide]. Later scans confirmed sub-millimetre resolution.Conclusions: The instrument has the capacity for high performance pre-clinical drug discovery studies.

P38 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Physics 6: Brain P482 Development of quantitative follow-up processing method for brain 99mTc ECD SPECT V. Fidler1, T. Milanez2, P. Rogelj3, I. Slodnjak2, S. Fidler4, K. Škaliþ5, J. Kobal2, M. Medved1; 1Xlab Research, Ljubljana, Slovenia, 2Clinical Center, Ljubljana, Slovenia, 3Faculty for Electrotehnics, Ljubljana, Slovenia, 4 Faculty of Computer and Information Science, Ljubljana, Slovenia, 5 Oncology Institute, Ljubljana, Slovenia. Introduction Brain scintigraphy with SPECT 99mTc ethyl-cysteinate dimer (ECD) is functional and highly sensitive procedure for the detection of regional cerebral blood perfusion and functional brain status. Aim Development of the quantitative evaluation of the follow-up of the patient’s brains functional status. Methods The initial and follow-up SPECT studies were performed at the same acquisition and instrumental conditions. The following subtraction method was applied to both studies (second minus first study) in order to find the global and regional differences in the radiotracer accumulation: both studies were geometrically registered using the method of point similarity measures, normalised by maximal regional intensity (in cubes of 3x3x3 pixels), segmented into high intensity (“grey matter”) regions and subtracted voxel by voxel. The global change of accumulation was computed by summing of all statistically (one standard deviation) different regional values in the positive direction (increased accumulation) and in the negative direction (decreased accumulation). Applying this criterion the influence of the regional uncertainties (due to the randomness of radioactive decay, registration error, patient movement, computing errors) was mostly eliminated. The regional differences were displayed on the top of the first study (fusing first study with the positive or negative differences). Method was evaluated in a group of clinically well defined patients and in Jaszczak phantom studies. Results Registration, normalization, segmentation and subtraction method for the two subsequent SPECT studies (matrix 128x128) takes 5 minutes of computing time at minimum. For quality control of all these steps the set of parametric images are computed (correlation coefficient and difference in displaced and rotated Jaszczak phantom for registration, standard error of maximal regional activity for normalization, starting segmentation intensity for ”grey” matter from the minimum of the histogram’s valley between ”white” and ”grey” peaks and by visual inspection of the segmented tomograms). The results of the difference analysis in a group of patients with different brain functional status have shown good correlation with the relevant neurological tests. Discussion Applied subtraction method in the 99mTc ECD SPECT follow-up analysis showed a good correlation with neurology clinical tests and is moderately time consuming in the data processing.

P483 Iterative reconstruction using OSEM algorithm with scatter and attenuation correction analysis of the striatal 123 dopaminergic receptors density with I-IBZM brain SPECTCT. V. Camacho, M. Estorch, A. Flotats, J. Fuertes, A. Rodríguez-Revuelto, E. Rivera, M. Quera, I. Carrió; Hospital de Sant Pau, Barcelona, Spain. Aim: Filtered back-projection (FBP) is the most commonly used reconstruction method for brain SPECT images. The iterative reconstruction technique such as an ordered subsetsexpectation maximization (OSEM) algorithm can easily incorporate various physical models of attenuation and scatter correction and improve the quality of images in brain SPECT. The aim of the study was to evaluate the effect of the iterative reconstruction using OSEM algorithm with scatter and attenuation correction analysis of the striatal dopaminergic D2 receptors density with 123 IBZM brain SPECT-CT.Materials and Methods: 123IBZM brain SPECT-CT was performed in 14 healthy volunteers with a hybrid system (dual head gamma camera with low resolution Xray tube) GE Medical System Millennium VG-Hawkeye. Brain SPECT-CT data were acquired 90 min. after i.v. administration of 185 MBq 123I-IBZM. The images were reconstructed using conventional FBP method and OSEM algorithm that include scatter and attenuation correction. ROIs for the basal ganglia and the occipital and frontal cortex were placed on three consecutive oblique slices that contained the maximum 123I-IBZM uptake. D2 receptors density measurement was obtained by basal ganglia/occipital cortex (BG/OC) and basal ganglia/frontal cortex (BG/FC) uptake ratios.Results: The mean values BG/OC and BG/FC ratios were higher in OSEM algorithm (2.0157+/-0.301 and 2.0279+/- 0.344) than in FBP reconstruction (1.8696+/0.345 and 1.7125 +/-0.248), p<0.001. No relationship was observed in striatal D2 receptors density between occipital and frontal cortex reference ROIs.Conclusions: OSEM algorithm reconstruction method with scatter and attenuation correction can be employed for clinical applications to measure the striatal dopaminergic D2 receptors density with 123I-IBZM brain SPECT-CT. No differences were observed between occipital and frontal cortex reference ROIs.

P484 Quantitative analysis and reproducibility 18 transporter imaging using [ F]FPCIT

of

dopamine

J. Kim1, S. Oh1, S. Chung2, M. Lee2, D. Chi3, D. Moon1; 1Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 2Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, 3Department of Chemistry, Inha University, Incheon, Republic of Korea. Aim: To find optimal quantification method for the clinical application of [18F]FPCIT PET, we assessed the relationship and test/retest reproducibility of dopamine transporter (DAT) binding potential (BP) measured by non-invasive analytic methods.Materials and Methods: Eleven early stage Parkinson's disease patients (H&Y stage 1 or II, M/F:5/6, age: 61±8yrs) and 10 normal controls (M/F: 6/4, age: 54±11yrs) underwent dynamic PET scan during 120 min after bolus injection of [18F]FPCIT (185 MBq). Of these, 5 normal controls and 5 patients also underwent retest PET scan 2-14 days after the 1st PET scan. Striatal BP was measured by 4 non-invasive quantification methods (two parameter multilinear reference tissue model, MRTM2; original multilinear reference tissue model, MRTMo; specific striatal binding to non-specific occipital binding ratios on 90 min and 110 min delayed image, SNBR90 and SNBR110, respectively). The correlation and the test/retest reproducibility of BP measured by 4 analytic methods were evaluated. Results: In normal controls, striatal BPs measured by MRTM2 were 5.0±0.9 in both putamens and caudate nuclei. In Parkinson's disease patients, BPs of ipsilateral and contrlateral caudate nuclei were 2.7±1.2 and 2.3±0.9, respectively and BPs of ipsi- and contralateral putamens were 1.5±0.7 and 0.9±0.4, respectively. Striatal BPs measured by all 4 methods in Parkinson's disease patients were significantly lower than those in normal controls (P<0.001). In Parkinson's patients, striatal BPs were more decreased in contralateral side than ipsilateral side (P<0.01) and in putamens than caudate nuclei (P<0.05). BPs measured by MRTMo, SNBR90, and SNBR110 were significantly correlated (r>0.97, P<0.001) with those measured by MRTM2. However, BPs measured by MRTMo, SNBR90, and SNBR110 were lowered than those measured by MRTM2 in normal controls (9.3%, 16.3%, 5.2%, P<0.005, respectively). BPs measured by SNBR110 were higher than those measured by MRTM2 in Parkinson's disease patients (10.7%, P=0.005). There was no significant test/retest difference in all 4 methods (P>0.1). The test/retest variability of all 4 methods ranged from 5.6 to 12.1% in caudate nuclei and putamens with high test/retest reliability (ICC>0.93). There was no difference of variability or reliability among the analytic methods. Conclusion: [18F]FPCIT PET was useful for demonstrating the DAT loss in early stage Parkinson's disease patients. All 4 non-invasive analytic methods for measuring the striatal BP showed high reproducibility and reliability. Considering its methodological simplicity, specific to non-specific binding ratio on 120 min image after injection of [18F]FPCIT might be useful quantification method for the clinical application of [18F]FPCIT PET.

P485 Assessment of spm analysis in 99mtc-hmpao brain spect studies D. Pareto1, P. Aguiar2, J. Gispert1, C. Falcón2, A. Cot2, F. Lomeña3, J. Pavía3, D. Ros2; 1Institut Alta Tecnologia - PRBB, Barcelona, Spain, 2Unitat Biofísica. Fac. Medicina. Universitat Barcelona, Barcelona, Spain, 3Servei Medicina Nuclear. Hospital Clínic, Barcelona, Spain. Aim: To study the performance of SPM to detect changes in regional blood flow (rCBF) in both hypo/hyperperfused situations and with/without correction for degradations in 99mTc-HMPAO SPECT brain studies. Methods: The Zubal phantom was used to model the rCBF. Values of 100, 25 and 4 were assigned respectively to grey, white matter and cerebral spinal fluid to simulate the relative concentrations. A non-uniform attenuation map was obtained (attenuation coefficient

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Poster Presentation

where it was initially evaluated with phantoms. The system is being used for dynamic studies in small animals, in order to assess the performance of new radiolabeled biomolecules for oncological studies. The performance of a gamma camera, sized particularly for imaging mice, is described. The active area of the detector is approximately 48 mm x 96 mm. It is based on two flat-panel Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMT), a pixellated NaI(Tl) scintillator and a copper-beryllium (CuBe) parallel-hole collimator. The system has been developed to optimize both sensitivity and resolution for in vivo imaging of small animals injected with technetium compounds. Results in planar mode show that spatial resolution is ~1.5mm on the detector surface, while average energy resolution is 15%. Sensitivity was measured ~130counts/min/µCi. In a typical mouse study, this leads to 13,000-65,000 counts per minute, which is a satisfactory number, in order to perform dynamic studies. Results from the in vivo dynamic studies of mice injected with 100µCi of Tc99m-MDP and Tc99m-DTPA have been performed and quantified results are presented. System's performance is currently being evaluated, using a 1mm pinhole collimator. Moreover, the system is being assessed in SPECT mode as well. Finally tumor bearing nude mice are being imaged using novel derivatives and results will be presented as well. This study indicates that a mouse sized camera is a suitable tool for the performance of dynamic studies with high resolution in small animals.

0.014mm-1 for brain tissue and 0.03mm-1 for bone). Foci of 15, 20 and 25mm in diameter were placed in the corpus cingulus. Two groups were considered: control studies and studies with changes of (in %) -50,-25,-15,+15,+25 and +50 in the foci. SimSET Monte Carlo package was employed to obtain simulated projections. A fan-beam collimator with focal 355mm and hole side 0.866mm was included. Projections were reconstructed using OSEM algorithm (10 subsets, 8 iterations), without corrections (NC) and with attenuation correction, collimator/detector response correction and an ideal scatter compensation (C). The reconstruction parameters were: 64x64 matrix size and 4.16mm pixel size. Statistical Parametrical Maps of rCBF were obtained with SPM2. Both basal and activated images were previously normalized to the SPECT template space and smoothed with a three dimensional Gaussian filter of 10mm FWHM. Differences were evaluated with a Compare Population (1scan/1subject) design using pFWE<0.05. Results: The table shows the sample size needed to detect the foci. As expected, this value increases when the activation factor or focus diameter decreases.

15mm

20mm

25mm

activation factor (%)

activity region. This effect leads to an underestimation of the radioactivity concentration of objects smaller than two to three times the spatial resolution of the scanner. Iterative reconstruction algorithms, such as OSEM, can incorporate a detector response characterizing by collimator geometry and an intrinsic resolution of detector. Detector response correction (DRC) improves SPET resolution; these algorithms would reduce the collimator dependency in radioactivity concentration. We implemented the OSEM-DRC reconstruction with rotationalbased slab-by-slab incremental blurring algorithm. SPET projection data for the brain perfusion images were generated using Monte Carlo simulation and the Zubal brain phantom, which included the effect of photon attenuation, Compton scattering, and blurring caused by the detector response. The photon energy was assumed to be 140keV. The radioactivity ratio of gray matter (GM) and white matter (WM) was assumed to be 4:1. The simulated projection data were 128 x 128 matrix (pixel size: 2.50 mm) for 120 angles using ultra high-resolution collimator (UHR), high-resolution collimator (HR), and general all-purpose collimator (GAP). The respective spatial resolution, which was varied as a function of distance d, was 6.9, 9.1 and 13.1 mm FWHM at d=13 cm. The sensitivity ratio of UHR:HR:GAP was 1.00:1.78:4.00. The OSEM reconstruction was performed with and without the DRC. Attenuation correction was incorporated into the detection probability of OSEM-DRC calculated from the assumed µ-map. Scatter corrections was performed the TEW method. Butterworth filter was used as a prefilter. The DRC improved the image resolution and contrast, especially for the image using the GAP collimator. The image resolution and contrast using the GAP with the DRC were comparable to that using the UHR and HR. However the S/N of images using the GAP with the DRC was superior to that using HR and UHR. Pixel values in the GM region were increased overall by the DRC, whereas those in the WM region were decreased. The increase rates in the GM were 5.82, 10.1 and 12.4% for the UHR, HR and GAP, respectively; whereas those in the WM were -11.5, 12.8 and -11.2%, respectively. Our simulation results suggested that the DRC was reasonably successful in reducing collimator dependency for cerebral blood flow imaging using SPET.

C

NC

C

NC

C

NC

-50

4

6

3

4

4

4

-25

5

8

5

7

4

6

-15

9

15

8

10

7

8

15

11

20

9

11

5

10

25

6

11

6

6

5

7

P39 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

50

5

6

4

6

3

4

Radionucl.Therapy/Dosimetry - Clinical: mIBG and Peptides

Conclusions: Our findings show that correction for degradations diminishes the number of pairs needed to detect changes in rCBF. This diminution is more important for low values of the activation factor and for small foci. Our results also suggests differences between hyper and hypoperfusion situations, especially when no corrections are included in reconstruction.

P486 How to improve image registration protocols of ictal and interictal SPECT images? 1

2

2

2

2

P. Nikkinen , O. Sipilä , E. Salli , K. Van Leemput , J. Hämäläinen , E. Gaily3, A. Ahonen1; 1HUSLAB, Helsinki University Central Hospital, Helsinki, Finland, 2HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland, 3Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. Subtraction of ictal and interictal SPECT images can assist in evaluation of epileptogenic region. Before the subtraction, the images must be registered. For better anatomical localization of the focus the SPECT images can also be registered with the MR images. We compared different registration protocols using an in-house developed software package, based mainly on the ITK software library. Methods: Ictal (ICT) and interictal (INT) Tc-99m-ECD SPECT imaging was performed for 8 patients using a Philips/Picker Prism 3000XP gamma camera with a Gd-153 transmission source. The STEP/SSP protocol was used for reconstruction and transmission imaging based attenuation correction of the images. Conventional images with ML-EM iterative reconstruction and Chang attenuation correction were also obtained. The voxel size was 2.0×2.0×3.56 mm3. MR images (voxel size 1.0 mm3) were acquired with 1.5 T Siemens Magnetom Vision using a T1 weighted 3D MPRAGE sequence. For STEP/SSP and conventional data three registration protocols were compared: 1) ICT to MR and INT to MR: interictal SPECT images were registered separately with MR images, 2) ICT to MR and ICT to INT: ictal SPECT images were registered with MR images and thereafter interictal images were registered with ictal SPECT images, 3) ICT to INT: registration of ictal and interictal SPECT images only. The rigid registration method was based on mutual information (MI) metric, calculation of which was implemented according to the method proposed by Mattes et al. The following parameters were used: number of resolution levels 3, number of bins 40, number of samples 40000. For ICT to INT SPECT registration the number of samples was 20000. After registrations the ICT-INT subtraction images were obtained using normalization to mean counts. Results. The registration protocols were evaluated using transformation and rotation parameters and visually comparing the subtraction images. For the transmission imaging corrected STEP/SSP images there was no significant difference between the three protocols. In the conventional images an ellipse outside the patients skull is fitted for attenuation correction, which can lead into difficulties in SPET to MR registration. The misalignment in registration protocol 1 caused artefacts in some subtraction images. This could be avoided by rescaling the images by using 10% LT. Conclusions. According to our preliminary results the transmission imaging based STEP/SSP attenuation correction assist in SPECT to MR registration. However, in conventional SPET image registrations the results were satisfactory and can be used for clinical purposes.

P487 Reduction of collimator dependency in CBF using iterative reconstruction algorithm incorporating detector response correction for SPET T. N. Yokoi1, K. Yoshioka2, Y. Takahashi2, S. Teraoka3, H. Shinohara4; 1 Bioimaging Laboratory, Inc, Kyoto, Japan, 2Osaka University School of Medicine, Osaka, Japan, 3Daiichi Radioisotope Laboratories, Ldt, Tokyo, Japan, 4Tokyo Metropolitan University, Tokyo, Japan. A low spatial resolution of SPECT scanner is mainly due to the limited collimator resolution. The low spatial resolution introduces the loss of high radioactivity caused by spill-out toward surrounding low-activity regions, as well as the relatively small spill-in from adjacent low

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P488 Targeted therapy with radio-labelled analogues: our clinical experience.

somatostatine

F. Perniciaro, A. Herberg, S. Baldari, S. Russo, M. Martino, S. Pulizzi, A. Restuccia, A. Vadalà, S. Baldari; Nuclear Medicine, Policlinico "G.Martino", Messina, Italy. Aim Various compounds such as 111In-pentetreotide, 90Y-DOTATOC, 177Lu-DOTATATE and 90 Y-DOTA-lanreotide have been proved to be an effective and safe treatment in neuroendocrine tumours. We report our clinical experience using 111In-pentetreotide and 90Y-DOTATOC. Materials and methods Between Genuary 2005 and March 2006 we have treated 13 patients (seven males and six females; mean age 58 years, range 38-67 years) with histologically confirmed cancers expressing sst2 receptors, as documented by OctreoScan. Our series included four lung carcinoid, three pancreatic NET, 1 rinopharinx NET, four unknown origin NET, 1 medullary thyroid cancer. All patients had documented residual disease or recurrence after conventional treatment. Disease extent is assessed by computed tomography (CT) or magnetic resonance (MRI). Renal function is assessed by renal scintigraphy. Four patients have been treated with repeated cycles of 111In pentetreotide and with 90Y-DOTATOC, nine patients have been treated with 90Y-DOTATOC alone. Three patients received a second treatment of 90YDOTATOC. The patients previously injected with 111In pentetreotide received a mean activity of 7200 MBq (range 6700-7700 MBq) for treatment, and a mean cumulative activity of 21400 MBq (range 21100-21700 MBq). For each treatment an activity of 70 mCi of 90Y-DOTATOC was administered with amino acids for renal protection, except for one patient with multiple bone metastases who received 125 mCi of 90Y-DOTATOC. The patient had previously been treated with three cycles of 111In-pentetreotide and two cycles of 186Re-HEDP and autologous peripheral blood stem cells had been collected before 90Y-DOTATOC therapy. Results After administration of 90Y-DOTATOC no acute reaction was observed, except grade I-II gastrointestinal toxicity (nausea and vomiting), due to aminoacid infusion, in five of thirteen patients. No haematological toxicity was observed in twelve of thirteen patients. The patient who received 125 mCi of 90YDOTATOC had grade IV haematologic toxicity and autologous stem cell reinfusion was performed. Cromogranine A levels reduced significatively in 60% of patients. No renal toxicity was observed at renal scintigraphy after treatment. Follow-up is now available in four of thirteen patients and show stable disease (SD). All patients are scheduled for revaluation with TC or MRI after three cycles of 90Y-DOTATOC. Conclusion Our preliminary results show that the treatment with 111In-pentetreotide and/or 90Y-DOTATOC is safe and determines reduction of Cromogranine A levels. Evaluation of objective response and subjective benefits is ongoing.

P489 The phase II clinical trial of targeting therapy using hepama-1 in patients with HCC

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i-

S. L. Chen1, B. L. Li1, H. Xie2, L. Xu3, G. j. Nu3, S. Fan3, Q. X. Fan3; 1 zhongshan Hospital, Institute of Nuclear Medicine,Fudan University, Shanghai, China, 2Institute of Biochemistry, Shanghai, China, 3First hospital, Henan Medical University, Zhengzhou, China. Purpose: Approval for the use of 131I-hepama-1 McAb (DGDK-1) in Phase II clinical trial was obtained from Chinese State Drug & Food Administration (SFDA). Therapeutic efficacy and toxicity of 131I-hepama-1 in HCC patients were studied in this First Stage of Phase II Clinical Trial.Methods: Twenty-four patients (21 men, 3 women, age range 37-67y, KPS•60) with unresectable HCC volunteered to take part in the First Stage of Phase II Clinical Trial. The intranvenous injection of radiolabelled antibody was 10mg and the McAb was radiolabeled with 131 I 1480-2960 MBq(40-80mCi, 0.8 mCi/kg). Efficacy was assessed and responses were defined according to WHO criteria for measuring solid tumors. The objective response rate (ORR) was assessed as the primary endpoint in this clinical study. Confirmation of response required a

P490 Optimal timing of radioimmunotherapy adjuvant to cytoreductive surgery for the treatment of peritoneal carcinomatosis of colonic origin F. Aarts, M. Koppe, T. Hendriks, J. van Eerd, W. J. G. Oyen, F. H. M. Corstens, R. P. Bleichrodt, O. C. Boerman; Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Introduction: Peritoneal carcinomatosis (PC) occurs in 5-50% of the patients with colorectal carcinoma. In part of these patients no further distant metastases are present. Without treatment the median survival of these patients is 6 months. In order to improve survival, extensive surgical procedures in combination with intraperitoneal chemotherapy are performed. Combining these treatment modalities resulted in a median 2-year survival rate of 60%. Radioimmunotherapy (RIT) could be an effective treatment modality for small volume disease, and therefore holds promise as adjuvant therapy after Cytoreductive Surgery (CS) of PC. The aim of this study was to determine the effects of adjuvant RIT in combination with CS as a treatment for PC of colonic origin in rats. In addition, the optimal timing of RIT in relation to CS was determined.Methods: PC was induced by intraperitoneal injection of 2x106 CC-531 rat colon carcinoma cells in Wag/Rij rats. Rats underwent Exploratory Laparotomy (EL), CS alone or CS + RIT at different time intervals following surgery. RIT consisted of i.p injected 177Lu-labeled anti-CC531 antibody MG-1 (0.15 mg/rat, 1.5 mCi/rat) administered directly postoperative (RIT-ǻT=0), 4 days after surgery (RIT-ǻT=4) or 14 days after surgery (RIT- ǻT=14). Survival was the primary outcome parameter.Results: Both CS and RIT were well tolerated. Median survival of the rats that underwent EL and CS alone was only 29 days and 36 days respectively (P=0.04). Median survival of the rats that were treated with CS + RIT-ǻT=0, or CS + RIT-ǻT=4 and CS + RITǻT=14 was 77 days (P=P<0.0001), 52 days (P=0.0012) and 45 days (P=0.0002), respectively. When compared to monotherapy, EL and CS, there was a highly significant improved survival in rats that received the combined treatment of CS + RIT (P=0.0004). Moreover, there was a significant difference in survival between CS + RIT groups; RIT-ǻT=0 vs RIT-ǻT =14, P=0.008. There was no difference in survival between groups RIT-ǻT=0 vs RIT-ǻT=4 (P=0.10) or RITǻT=4 vs RIT-ǻT=14 (P=0.56). Thus, when applied in combination with CS, RIT is most effective when administered directly following surgery.Conclusions: This study rats with PC shows that RIT, when applied directly after cytoreductive surgery, is effective in the treatment of PC of colorectal origin. In this adjuvant setting, optimal timing of the administration of the radiolabeled monoclonal antibodies is essential.

P491 Impact of two cycles of peptide receptor radionuclide therapy (PRRT) on renal function as determined by repeated Tc-99m DTPA/GFR measurements: comparison between Y-90 DOTATATE and Lu-177 DOTA-TATE V. Prasad, R. P. Baum; Zentralklinik Bad Berka, Bad Berka, Germany. Renal function impairment is one of the major possible adverse effects in patients with metastasized neuroendocrine tumors (NET) treated by PRRT. Aim: To determine the impact of PRRT on glomerular filtration rate (GFR) after two cycles of Y-90-DOTA-TATE (Y90) as compared to Lu-177-DOTA-TATE (Lu177).Methods: Group A: patients treated with Y90, Group B: patients treated with Lu-177. Group A1: 24 patients (age 60.5±11a), injected with 4.00± 0.72 GBq of Y90 (1st cycle). Group A2: 16 patients (age 62.2±9.4a, followed up after a total of 7.8 GBq±0.82 GBq of Y90 (after 2nd cycle). Group B1: 14 patients (age 62.2±10.6 years) received 4.8± 0.8 GBq Lu177 (1st cycle). Group B2: 6 patients (age 58.5±12a were followed up after receiving 9.57±1.5 GBq of Lu177 (after 2nd cycle). GFR was determined in each patient using 110-185 MBq of Tc-99m DTPA prior to and 3-4 months after therapy. Normalised/absolute values for GFR pre/post PRRT were compared (paired T-test).Results: In group A1 there was a fall of normalized GFR value by 2% vs. 16% in group A2. The fall in absolute GFR value was 2 ml/min in group A1 and 7 ml/min in group A2. Baseline normalized/absolute GFR values was 1.02/87.5 ml/min in subgroup A1 and and 86.5 ml/min in A2. The fall in both, the absolute and normalized GFR values was not significant after the 1st cycle (p=0.555), but was significant (p= 0.007) after the 2nd cycle of PRRT. In group B1 there was a fall of normalized GFR value by 10% vs. 8% in group B2. The fall in absolute GFR value was 7.7ml/min in group B1 and 9.7ml/min in group B2. Baseline normalized GFR values was 0.86 and 0.89 in subgroups B1 and B2 respectively. Baseline absolute GFR value was 78.3 ml/min and 81 ml/min in subgroups B1 and B2. The fall in the absolute GFR values was significant after the 1st cycle (p=.009) but was not significant (p=0.486) after the 2nd cycle of PRRT. The fall in normalized GFR value was not significant in both the subgroups (p=0.07 after 1st cycle and p=0.49 after 2nd cycle).Conclusions: The impact of Y-90-DOTA-TATE on renal function is more pronounced as compared to Lu-177-DOTA-TATE. A higher activity of Lu-177 DOTA-TATE can be used in patients with lower than normal GFR values without detrimental effect. Normalized GFR value is more appropriate for follow-up of patients as compared to the absolute GFR values.

P492 Usefulness of combined application of radiolabeled and longacting somatostatin analogues in patients with somatostatin receptor expressing malignancies M. Gabriel, D. Heute, U. Andergassen, D. Kendler, M. Rodrigues, C. Decristoforo, T. Traub-Weidinger, E. Von Guggenberg, I. Virgolini; University Clinic of Nuclear Medicine, Innbruck, Austria. AIM: To evaluate the efficiency of the sequential treatment regime, established at our department, using radiolabeled somatostatin analogues and long-acting “cold” somatostatin analogues in patients with metastatic endocrine tumors. MATERIAL and METHODS: Twenty-five patients (10f/15m), mean age 59a, age-range from 21 to 81a were treated by using 90 Y- or 177Lu-labeled compounds. The time interval between each cycle of the radionuclide therapy was at least 10 weeks. Each patient patient received an i.m. injection (20-30 mg) of a long-acting somatostatin analogue one day and four weeks after i.v. treatment with the radiopharmaceutical. Diagnosis of patients; small-bowel carcinoid (n=8), neuroendocrine pancreatic tumor (n=11), pulmonary carcinoid (n=1), colonic carcinoid (n=1), carcinoid unknown primary with liver metastases (n=3) and one patient with non-medullary thyroid carcinoma. Clinical symptoms caused by functional tumors were found in 13 patients. Sixteen patients were treated with 90Y-DOTA-TOC and 4 patients with 177Lu-DOTA-TATE. Four patients received both 90Y-DOTA-TOC and 177Lu-DOTA-TATE and one female patient with a neuroendocrine pancreatic tumor was even treated with 90Y-DOTA-Lanreotide, 90Y-DOTA-TOC and 177Lu-DOTA-TATE (accumulated activity of 34 GBq during 12 cycles from 2000 to 2006). She further received more than 50 individual doses of long-acting octreotide. RESULTS: Tumor-related symptoms (flush, diarrhoe) early diminished in all patients with functional tumors (n=13). Partial remission was observed in 8 patients (4 secreting and 4 non-secreting tumors), stable disease in 15 patients (8 secreting and 7 non-secreting tumors), and progressive disease in either one patient with secreting and one patient with non-secreting tumor. The 55-year old patient who received all three compounds has shown no side effects of this treatment regime and progression free survival is yet more than five years. CONCLUSIONS: The concept of combined treatment regime using radiolabeled and “cold” somatostatin analogues was well tolerated in all patients with promising objective treatment response. Furthermore, early symptom relief was observed in patients with functional tumors. Cold analogues might also provide protection of severe side effects of radionuclide therapy.

P493 Results of 90Y-DOTA TATE therapy in patients with neuroendocrine tumors - own experience J. Kunikowska1, L. Krolicki1, P. Ochman1, R. Mikolajczak2, D. Pawlak2, A. Hubalewska3, A. Sowa-Staszczak3, M. Kobylecka1, J. Maczewska1; 1 Warsaw Medical Academy, Warsaw, Poland, 2ORBI Polatom, Swierk, Poland, 3Nuclear Medicine Unit, Chair of Endocrynology, JU Medical College, Cracow, Poland. Neuroendocrine tumors compose approximately 2% of gastrointestinal track carcinomas. In 80’s expression of somatostatin receptors on that type cells was discovered. That discovery gives possibility for using it in diagnosis and in therapy. The aim of the study was to assess response of targeted radionuclide therapy using radiolabelled somatostatin analog 90Y [DOTA0, D-Phe1, Tyr3] octreotate (DOTATATE).Materials and Methods: 10 patients with diffuse neuroendocrine tumors were enrolled (5 woman, 5 men, avg. age 59,7 +/- 11,3). Before therapy blood tests for hematology, kidney and liver function, CoA were done. All patients underwent CT scans and scintigraphy with 99mTc-HYNIC-TATE. Treatments of 90Y [DOTA0, D-Phe1, Tyr3] octreotate (DOTATATE) were repeated 4-6 weeks apart up to total calculated doses - 200 mCi/m2 ; per one course we usually used 100 mCi. Mixed amino acids infusion over 8 hours was used for kidney protection.Results: 1. Regression of disease was observed in 5 patients- decreasing of size and number of metastases in imaging methods and decreasing CoA level (PR) 2. Stable disease was observed in 3 patients- stable size and number of metastases in imaging methods and decreasing CoA level (SD) 3. 2 patients died. No nephrotoxity was observed. WBC and PLT level was stable during therapy in 3 pts (pts without chemotherapy). In 1 pts with very diffuse disease, after therapy decrease of PLT level was observed: on onset of therapy 220 x 103/ mm3, after first course 47 x 103/ mm3; 2 months after the begining of therapy patients died (patient with lots of chemotherapy in past, last course month before radioisotope therapy). In 6 pts leucopenia was observed (WBC level < 4 x103/ mm3) but serious neutropenia < 2 x 103/ mm3, was observed in 2 pts with previous chemiotherapy. PLT level decreased in 5 pts, but thrombopenia was observed only in 1 patient (with chemotherapy in past)Conclusions: 1. PR and SD were observed in 8/10 patients with diffuse neuroendocrine tumors. 2. In patients after chemotherapy we must often tests hematological parameters; The length of period between chemotherapy and radioisotope therapy, is still is question . 3. Mixed amino amid infusion is good protection for kidney. This study was supported in part by Research Grant for Scientific Research (3666/P.05-6/05) from Ministry of Health and Ministry of Education.

P494 Estimation of cure after somatostatin-receptor based radionuclide therapy in patients with disseminated midgut carcinoids in the liver P. Bernhardt, E. Mehrara, L. Kölby, H. Ahlman, E. Forssell Aronsson; Göteborg University, Göteborg, Sweden. Introduction: Metastases of midgut carcinoid tumours can often be restricted to the liver for long periods. Using systemic radionuclide therapy, e.g. 177Lu-DOTA-Tyr3-octreotate or 90YDOTA-Tyr3-octreotide, the aim is to cure liver metastases of different size, and avoid severe side effects. Using high energetic electron emitters, e.g. 90Y, the smallest metastases will receive too low absorbed doses for cure. However, cross-irradiation from surrounding normal tissues may increase the absorbed dose to these small tumours, leading to cure. Large tumours can be difficult to cure due to impaired vascular supply and low uptake, as well as high numbers of hypoxic

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repeated imaging study 3 months after treatment using CT and AFP mensurate. Nuclear imaging was performed to document the biodistribution of the 131I radioactivity in the tumor sites and the whole body. MIRDOSE 3.0 was utilized for the estimation of the radiation-absorbed organ doses. Adverse experiences were graded using the WHO Toxicity Criteria. Thyroid function tests were performed at baseline, at 4 and 12 weeks after the start of therapy.Results: The results of CT scan showed objective response rate of 62.5% (partial response 62.5%, no change 12.5%, and progressive disease 25.0%) in all patients. Biodistribution study demonstrated excellent localization of the radioactivity in tumors. In 14 (58.3%)of these patients, the HCC lesions were visualized by SPECT. Radioimmunoimaging demonstrated that the highest tumor/liver ratio was 5.6:1 at day 5. Among 12 serum AFP patients, 8 cases (66.6%) AFP levels decreased obviously. Fourteen patients with clinical staging II survived averagely 6.5 months, and the median survival was 5.0 months. Ten patients with clinical staging III survived averagely 4.8 months, and the median survival was 3.8 months. No patient had any evidence of fever, severe side effect and impairments on important organs. The most obvious adverse side effect was mild and reversible bone marrow suppression.Conclusion: radioimmunotherapy with 131I-hepama-1 was well tolerated and can be used systemically to treat refractory tumors of the HCC.

cells. Our aim was to study the influence of tumour burden, cross-irradiation from normal tissues, and variable activity concentrations on metastatic cure after radionuclide therapy in a patient with liver metastases of a midgut carcinoid tumor (primary tumor and regional metastases removed by surgery).Methods: A model to calculate the metastatic cure probability (MCP) was developed. The distribution of metastases in the MCP model was based on the authentic distribution of liver metastases in a patient with a primary midgut carcinoid. The influence of cross-irradiation was assessed by calculating MCP for various tumor-to-normal-tissue activity concentration ratios (based on patient studies). The influence of variable activity concentrations was calculated by assuming that the activity concentration in tumors was an inverse power law function of tumor mass (based on animal studies). The absorbed dose to the largest tumour and liver to obtain MCP=0.99 was calculated for the electron emitters 103mRh, 177Lu and 90Y with mean energies of 39, 147 and 935 keV, respectively. Similar calculations were also performed for the alpha emitter 225 Ac.Results: The MCP model demonstrated that tumour burden, cross-irradiation and variable activity concentration greatly influenced MCP. Selecting the most optimal radionuclide the tolerance dose to normal tissue will limit the use of electron emitters with high energy. From this study electron emitters with energies below 150 keV, e.g. 177Lu, and alpha emitters were best suited for radionuclide therapy.Conclusions: Today, the risk of kidney failure after systemic administration of radiolabelled somatostatin analogues limits the cure rate for carcinoid metastases in the liver. However, this study demonstrates that with reduced kidney activity concentration increased cure rates were possible to achieve with 177Lu-DOTA-Tyr3-octreotate. The reduced kidney activity concentration can be achieved by effective blockade of kidney uptake or by reduced administration of activity to the liver.

P495 Repeated Treatment with I-131-MIBG in metastatic Neural Trest tumors

Patients with

H. Balink1, M. G. E. H. Lam2, J. M. H. de Klerk3, P. P. van Rijk2; 1MCL, leeuwarden, The Netherlands, 2University Medical Center Utrecht, Utrecht, The Netherlands, 3Meander Medical Center, Amersfoort, The Netherlands. Aim: Meta-iodo-benzyl-guanidine (MIBG) labelled with I-131 is used for (palliative) treatment of tumors originating from the neural crest. In a retrospective analysis the clinical files of patients with neuroendocrine tumors treated with I-131-MIBG in the UMCU, were reviewed in order to assess the therapeutic response and potential adverse effects.Methods: 20 patients (15 with metastatic carcinoid, 1 metastatic medullary thyroid carcinoma (MTC/MENII), 3 metastatic pheochromocytoma, 1 multicentric paraganglioma) treated with I-131-MIBG over a 16-year period of time, were included in this analysis. Twelve patients were treated with I-131-MIBG alone, 8 received additional therapy (7 octreotide and one patient 5-FU and streptozotocine). A total of 57 I-131-MIBG doses were administered (mean cumulative dose 19,5 GBq, range 3,744,4 GBq).Results: No patient showed a complete tumor response. Overall survival during the study period was 55 %. Stable disease was found in 20 % of patients treated with I-131-MIBG alone and 35 % of patients with additional therapy, reflecting the disease severity. However subjective response (symptomatic relief) was reported ‘good’ for 60 % of patients, ‘moderate’ for 15 %, and ‘none’ for 20 % of patients. (Due to lack of complaints, response evaluation was not possible in one patient). Objective response (laboratory) was not in all patients congruent with subjective response; one patient with good palliation showed persistent increased serotonine in thrombo’s, another patient with moderate response showed a dramatic decline in 5-HIAA’s in urine. Toxicity was limited to nausea during treatment with a single dose of 7.4 GBq. Haematological toxicity was confined to a temporary decline in platelet counts in 4 patients (43 % mean decline). Instead of the usual mild and transient hepatic dysfunction, two patients died after developing hepatic coma. One patient (with MTC/MEN II) died a few weeks after the first I-131-MIBG therapy of 7.4 GBq, most probably related to the fast progression of severe liver metastasis on CT. The second patient died from acute liver-cell necrosis and hepato-renal syndrome 8 days after the fifth I-131-MIBG administration (cumulative dose 22,2 GBq). Progressive liver metastasis on CT, previous I-131- administrations and concomitant continuous use for more than a year of (radiosensitizing!) 5-FU, contributed to the toxicity.Conclusions: In general I-131-MIBG therapy delivers symptomatic relief and hormonal improvement in patients with metastatic neuroendocrine tumors with minimal toxicity. The decision to treat with I-131MIBG in case of severe liver metastasis should be taken with caution.

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Radionucl.Therapy/Dosimetry-Clinical: Radioimmunotherapy P496 In-111 ibritumomab tiuxetan (In-111 Zevalin) biodistribution images are necessary: not knowing may be dangerous. H. R. Balon1, D. Fink-Bennett1, O. Lang2; 1W. Beaumont Hospital, Royal Oak, MI, United States, 2Charles University, Prague, Czech Republic. Aim: Y-90 ibritumomab tiuxetan (Zevalin®, Y-90 ZEV) has been approved in the USA for over 4 years for the treatment of relapsed/refractory low grade follicular CD20 positive B-cell nonHodgkin’s lymphoma (NHL). Until Aug 2005, at least 2 sets of whole body biodistribution (BD) images with In-111 ibritumomab tiuxetan (In-ZEV) were required by FDA before Y-90 ZEV therapy (Tx) could be performed. Currently only one scan at 48-72 h is required in the USA. In many European countries no BD imaging is required. We present four unusual In-111 ZEV biodistribution images that resulted in a change in pt. managementMaterials and Methods: All pts were pretreated with an infusion of rituximab (250 mg/m2) and received 185 MBq In-111 ZEV i.v. Whole body biodistribution scans were obtained 24 and 48 h later.Results: Two pts had unusual scan findings that did not warrant withholding therapy: Pt. 1 was found to have a large hepatic cyst occupying the majority of the right hepatic lobe. Because of the uncertainty about the potential destructive effect of beta radiation on the cyst wall integrity, the cyst was aspirated (600 ml) before proceeding with Y-90 ZEV Tx. Pt. 2 had increased lung uptake (less than liver), corresponding to known atelectasis and pleural effusion. The effusion was aspirated before planned Y-90 ZEV Tx, but Tx was not given due to rapid clinical deterioration. Pt.3 had

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abnormal BD (excessive bone marrow uptake throughout the entire skeleton despite <25% marrow involvement on biopsy), Y-90 ZEV Tx was not given to avoid irreversible marrow suppression. Pt 4 had abnormal BD (no blood pool, intense renal uptake at 24h). Since the HAMA titer was negative, the abnormal BD was believed to be due to poor In-111 radiolabeling technique rather than true altered BD. Y-90 ZEV Tx was withheld, however.Conclusions: In-111 ZEV biodistribution images are important. Their performance in our 4 pts resulted in clinical management changes that optimized the safety of Y-90 ZEV therapy administration. .

P497 Our experience of therapy with high dose In111-DTPA-D-Phe Octreotide in patients with neuroendocrine tumors. E. M. Trivizaki, B. G. Moshogiannis, S. P. Saranti, L. A. Iordanidou, K. M. Pateniotis, E. S. Matselas, A. T. Georgakopoulos, P. T. Koutsiouba; Metaxa’s Memorial Cancer Hospital, Piraeus, Greece. Radiolabeled somatostatin analogs represent an interesting approach for the treatment of Somatostatin positive tumors such as neuroendocrine tumors. In 111 Octreotide in high activities has been suggested for radionuclide therapy. The aim of this study is to assess the therapeutic effect of In111 Octreotide in patients with sst-expressing tumors. Patients and method: from July 2003 to January 2006, 13 pts with neuroendocrine tumors and refractory disease, received high activities of In111 Octreotide. There were 6 male and 7 female with age ranged 35-77 years(m.a.54,5 y). 8/13 pts had carcinoid 3/13 pts had medullary Ca 1/13 pts had Prostate Ca and 1/13 pts had a malign pheocromocytoma. All patients had previously received local or general palliative treatments. Each patient received a total dose of 22 GBq, divided in 4 cycles, with 4 weeks interval between every cycle. Treatment was given using an infusion pump. Between every cycle toxicity was measured using blood and urine tests, renal, hepatic and bone marrow function. Response to therapy was assessed considering changes in tumor size, tumor marker levels and symptoms.Results: no significant adverse reactions or toxicity were observed. No one patient had complete response. No one patient presented tumor regression. 7/13 pts had CTassessed tumor progression. 6/13 pts had a period of tumor stability with no growth in tumor size. 3/13 pts responded with a reduction in tumor markers (CT and 5HIAA) during the treatment period. 2/13 pts presented a pain relief.Conclusions: we conclude that high activity In111Octreotide is well tolerated with low toxicity. This therapy could offer symptom palliation in some patients and disease stability for a period, especially in these patients with low tumor load.

P498 Radioimmunotherapy with anti-CD antibodies in patients with NHL Our experience with 90Y-Zevalin in Northern Greece. I. Iakovou1, K. Badiavas1, D. Chatzopoulos1, M. Papachristou2, N. Karatzas1; 1Nuclear Medicine dept, Aristotle University,Papageogioy hsp, Thessaloniki, Greece, 2Shering Hellas, Athens, Greece. Objectives: To present the experience of our nuclear medicine department personel in preparing, handling and administrating the first Yttrium-90 ibritumomab tiuxetan (Zevalin®) treatments in Northern Greece.Methods: Zevalin therapy included an i.v infusion of rituximab (250 mg/m2) to clear peripheral B-cells and optimize biodistribution of the radiolabelled murine antibody. After 8 days another i.v infusion of rituximab (250 mg/m2) was performed, followed by an i.v dose of 90Y-Zevalin. The preparation of the radiopharmaceutical is a staight forward but demanding procedure, consisting of labelling rituximab, being part of a complex kit, with 90Y. Quality control of the radiopharmaceutical was performed with ITL-chromatography. Labelling procedure and quality control takes approximately 45 min. Five patient with CD20 + follicular Bcell NHL were referred to our department for the appropriate treatment. Therapy criteria were met for all patients at the time of their referral.Results: Depending on their peripheral blood status, three patients with CD20 + follicular B-cell NHL were given a 0.4 mCi/Kg and in one case 0.3 mCi/Kg dose of 90Y-Zevalin. Treatment was not given to one patient because of low white blood cell count the day of labelling. Not only storing and handling temperature conditions but also minute technical details were blamed for the only unsuccessful labelling procedure (QC < 65%) leading us to reorder the radiopharmaceutical. The radiochemical purity was high (97% at least) in the rest 5/6 labellings. One of the four patients administered the therapy died after 20 days. Two of the rest showed significant improvement with no special adherent effects and severe myelotoxicity was noticed in one patient, faced with growth factors treatment. Our experience concerns a 4 to 11 month period of follow up.Conclusions: 90Y-Zevalin provides an alternative treatment for patients with rituximab relapsed or refractory CD20 + follicular B-cell NHL. We would like to emphasise the need of the last peripheral blood test to be done in the morning of 90Y-Zevalin labelling procces, in order to avoid the needless use of the cold rituximab kit. This way the whole cost loss can be limited just to the 90Y price. Although we had a false labelling, the process is reproducible and provides a consistent quality product for patient administration. The problems of the mislabelling were faced and solved.

P499 Preliminary results showing effectiveness of Y90Ibritumomab-Tiuxetan (Zevalin) in patients with relapsed or refractory CD20 positive NHL: PET-CT is of great value in showing treatment response S. Kohlfuerst, I. Igerc, P. Lind; LKH Klagenfurt, Klagenfurt, Austria. Aim: Y90 Zevalin is indicated in the treatment of patients with relapsed or refractory (radio-, chemotherapy or Rituximab treatment) CD 20 + NHL. One way to enhance the effectiveness of monoclonal antibodies is to chelate radionuclides such as Y 90, a high energy beta emitting radioisotope delivering most of its radiation over a pathlength to 5mm. The aim was to look for tumor response using 18F-FDG PET-CT for treatment response as a combined imaging modality showing morphological changes (CT: tumor size, necrosis) and functional (PET: FDG uptake, SUV) information concerning tumor viability. Patients and methods: Up to now 6 patients (age 46 to 71 years) received Y90 Zevalin as a single dose (726 to 1185 MBq). Treatment schema includes one infusion of 250 mg/m² of Rituximab on day 1, another one on day 8 followed by Y90 Zevalin i.v. (11 to 15 MBq/kg). All patients underwent a baseline PET-CT scan

P41 — Monday, October 02, 2006, 2:30 pm - 4:00 pm, Poster Exh.Area

Radionucl.Therapy/Dosimetry - Clinical: Thyroid, Bone Pain Palliation & Miscellaneous 1 P500 Increase of Thyroglobulin after 131-I treatment is related to the absorbed dose. P. L. O. C. Bourgeois; Jules Bordet, Brussels, Belgium. Background: The ablation of thyroid tissues has been related (more than 20 years ago) to the absorbed dose (AA: in Gys) and (more recently) to the Tg variation (D5/D0) observed 5 days after the 131-I administration. Aims of the study: To evaluate the evolution of Tg after treatment, the relation between AA and Tg variation and their respective interestsMaterials and Methods: In 29 patients (13 men, 16 women; age ranging from 25 to 75 years: 2 staged IV: 4 with anti Tg antibodies and 3 of these 4 with Tg < 0.3 ng/ml at D0: given activities ranging from 1.05 to 7.73 GBq; 5 with one or more previous 131-I treatments: one patient under dialysis), Tg measured at D0 (TgD0: ranging from < 0.3 to 615 ng/ml) have been compared to Tg values obtained 3 (D3) and 7 (D7) days later. The variations Dx/D0 have been analyzed in function of the AA calculated on the basis of the scintigraphic imagings obtained at D3 and D7 and normalized for TgD0 (AA/TgD0 in Gy/ng-ml).Results: - D3/D0 (ranging from 4 to 102.7 and > 20 in 8) was the highest in 12 patients and D7/D0 (ranging from 7.9 to 300 and > 20 in 5) in 7: in 3, no significant variations were observed at D3 and D7 and in other 7, the (increased) ratios D3/D and D7/D0 were quite the same (ranging from 1.6 to 71.9 and > 20 in one case). - among the 3 patients with Tg < 0.3 ng/ml at D0, all had Tg becoming detectable at D3 but 2 had Tg returning < 0.3 ng/ml at D7.AA/TgD0 were respectively at least 62.7 (follow-up at one year: ablation), 123 and 213 Gy/ng-ml. - the patient under dialysis had Tg at D0 = 1.5, at D3 = 1.6 and at D7 = 13.8. AA/TgD0 was 108.7 Gy/ng-ml and ablation was observed after one year - one woman to whom 131-I was given 4 years after operation had Tg = 0.9 at D0, increasing to 9.8 at D3 with a AA/TgD0 = 130. - when the 2 previous cases and the 4 with antibodies are excluded from the analysis, the following correlation was found: Dmax/D0 = 1.1 + (0.79 x AA/TgD0) (R = 0.823)Conclusions: The maximum of Tg release after treatment is observed at variable times and is related to the absorbed dose.

P501 Intraoperative brachytherapy with I-125 sealed sources for patients with non-small cell lung cancer O. Lang1, A. Vlachova2, J. Votruba3, I. Kleisner2, M. Mala1, J. Fanta1; 1 Charles Univ., 3rd School of Medicine, Prague, Czech Republic, 2Univ. Hosp. Kralovske Vinohrady, Prague, Czech Republic, 3Hospital Na Homolce, Prague, Czech Republic. Objectives: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in developed countries. Limited resection is associated with high frequency of locoregional recurrence. Intraoperative brachytherapy seems to be an effective therapeutic approach. We present our initial experience with this technique.Methods: We treated 4 patients, 3 men (63, 60 and 71 y old) and 1 woman (74 y old). Stages of tumors were T1-2N0M0, T2N2M0, T2N2MX and T4N1MX, respectively. Surgery was performed by experienced thoracic surgeon. Brachytherapy was accomplished with sealed source of I-125 in the form of seeds (RapidStrand, Amersham Health, model 6711). Each seed consists of welded titanium capsules containing I-125 adsorbed onto a silver rod. Seeds are carried in an absorbable braid at a fixed distance of 1 cm. We used seed activity from 0.450 to 0.575 mCi to deliver 100 to 120 Gy to the tissue at 0.5 cm. Ten braids with seeds were sewn into the vicryl mesh 1 cm apart in a laminar flow hood immediately before surgery.Results: One pneumonectomy and three lobectomies with one lymphadenectomy were performed. The mesh with I-125 seeds was applied as a whole (1 pt, lung surface) or cut into two parts (2 pts, mediastinum and tumor resection bed) or three parts (1 pt, mediastinum, tumor bed and thoracic wall). There were no infectious complications or any early radiation complication. The dose rate during mesh preparation was aroud 8 µSv/hour, the procedure lasted 30 to 40 minutes. Dose rate at a distance of 20 cm from the mesh was 25 to 27 µSv/hour, the insertion and suture of mesh at surgery did not exceed 20 minutes. At 24 h post surgery the dose rate over the site of surgery ranged from 7 to 12 µSv/hour at 30 cm and from 0.5 to 1 µSv/hour at1 meter. The calculated dose until complete decay will be approximately 6 mSv at 10 cm from the thorax.Conclusions: Based on our preliminary data we conclude that a flat source of radiation using I-125 seeds could be easily prepared without infectious complications. The mesh with seeds could be modified during surgery to cover the presumed tumor spread. There were no early radiation complications. The radiation dose rates during preparation and application of the mesh were acceptable. This work was supported by the Internal Grant´s Agency of Czech Ministry of Health - NR 8528-5/2005.

P502 Enhancement results of In-111-DTPA- Octreotide Therapy by Ultrasound -microbubbles M. Lyra, G. Limouris, D. Kontogeorgakos, N. Dimitropoulos, S. Drosos, G. Papanikolos, L. Vlahos; Athens University, A' Radiology Department, Athens, Greece. Aim:To improve the action of In-111 Octreotide therapy by Ultrasound application after contrast micro bubbles insertion in the tumor tissues. Ultrasound interaction with microbubbles provokes them to oscillate, resonate and eventually to be disrupted by the ultrasound energy.Methods: 32 patients, suffering of neuroendocrine tumors, were treated by In-111 Octreotide, through hepatic artery catheterization radionuclide infusion. Scintigraphic images of the tumor area were taken after the administration of the radiopharmaceutical. Liver displays a strong affinity for taking up the microbubbles. 18 hrs post infusion 2,4ml contrast agent Sonovue was injected i.v. in a concentration of 45mgr per ml followed by flash of 5ml sodium chloride. A 2nd dosage repeated 10 min later. In sonovue, gas used is Sulphur HexaFluoride and is contained in a phospholipids surface layer. The bubble behaves isothermally, but its radius violently changes and its coating controls the way in which respond to ultrasound. Ultrasound beam of an HDI-ATL 3000 system and a broadband convex transducer 2- 4 MHz frequency and a max pulse repetition frequency 0.05%, operating at maximal Mechanical Index 0.9-1, was applied externally to the treatment area for a total time of 12 to 16 minutes. Restriction in the duration of ultrasound examination was necessary due to the In-111 radiation burden of the examiner. Scintigraphic images were obtained after the described procedure. Uptake measurements were performed to the images taken before and after the ultrasound application in order to explore the differences on the relative activity and the target area In-111 redistribution.Results: Semiquantitative measurements give a Tumor Enhancement Ratio (TER) and pattern differentiation of the mean counts on tumor selective regions after microbubbles sonoporation. This shows induced acceleration of intracellular motion of the receptors in the tumor compared to that before the microbubbles ultrasound application.Conclusions: Ultrasound -microbubbles application increases and differentiates the uptake and distribution of In-111 Octreotide by somatostatin receptor positive tumors. Microbubbles sonoporation for cell permeabilization enhancement leads to a statistical significant peptide internalization increase, for the benefit of the treated patient. Adjunctive tumour treatment by In-111-Octreotide and contrast micro bubbles activated by ultrasound is more effective than simple In-111-Octreotide infusion.

P504 Yttrium 90 microspheres in the treatment of hepatic metastases: a comparison of FDG-PET and CT imaging in assessment of response to treatment T. Szyszko, J. Nadarajah, S. Khan, P. Tait, H. Wasan, N. Habib, A. AlNahhas; Hammersmith Hospital NHS Trust, London, United Kingdom. PURPOSE: The purpose of this study was to evaluate the clinical value of computed tomography as compared to FDG-PET imaging in evaluating the response of patients with hepatic metastases treated with yttrium 90 microspheres.Materials and Methods: 18 patients with unresectable hepatic metastases were treated with yttrium 90 microspheres from June 2004 to January 2006. In 17 cases the tumour volume was less than 50% of the liver. CT and FDG-PET imaging was undertaken before treatment and at 6 weeks after treatment to assess response.Results: FDG-PET results were available for 14 patients. 10 of the14 patients showed initial improvement on the FDG-PET imaging and on the measured SUV values. This correlated with tumour markers. Two showed a mixed response. One showed disease progression and one was unchanged. CT results were available for 13 patients and showed a variable response: 6 of the 13 showed that the liver lesions were unchanged; 2 showed improvement, 3 showed progression and 2 showed a mixed response. These were the same two patients who showed a mixed response on FDG-PET. On subsequent follow up imaging at 6 months in the first 8 patients, there was evidence of disease progression on both FDG-PET and CT imagingConclusions: FDG-PET imaging is more sensitive than computed tomography in assessment of response to treatment with yttrium 90 microspheres.

P505 Preparation and Quality Control Macroaggregates for Radiosynoviorthesis

of

166

Ho-Boro-

M. Kropacek1, F. Melichar1, J. Srank1, M. Mirzajevova1, M. Klejzarova1, O. Kraft2, R. Kasparek2, J. Zahlava3, A. Chodacki4; 1Nuclear Physics Institute, Rez near Prague, Czech Republic, 2Dept. of Nuclear Medicine University Hospital, Ostrava-Poruba, Czech Republic, 3Dept. of Nuclear Medicine University Hospital, Plzen, Czech Republic, 4Dept. of Nuclear Medicine University Hospital, Chomutov, Czech Republic. Objectives Radiosynoviorthesis (RSO) by intra-articular injection of beta-emitting radionuclides appears to be a reliable alternative way for surgical synovectomy, which is easy-to-perform without harmful side effects for the treatment of inflammatory rheumatoid, as well as degenerative joint diseases. It is possible to repeat this therapy with similarly good results as the first therapy. 166Ho is a ȕ-emitter (Eȕmax=1.84 MeV, T1/2=26.7 hours) with a mean and a maximum penetration of ȕ-particles in the soft tissue of 2.2 mm and 8.7 mm. 166Ho also releases Ȗ-photons (81 keV, 1380 keV). In this paper we present our experiences with preparation and quality control of 166Ho-Boro-Macroaggregates (166Ho-BMA)within the scope of clinical study.Methods: Non-radioactive macroaggregates (Ho-BMA) were prepared by reacting the aqueous solution of Ho(NO3)3 pentahydrate with sodium borohydride solution in 0.2 M NaOH. Particles of Ho-BMA grow during vigorous hydrogen generation. Ho-BMA were then centrifuged 3 min at 2000 rpm, washed repeatedly with distilled water and finally dried at 105°C. Ho-BMA were consequently milled using ball mill and then using homogeniser working at 70.000 rpm in order to obtain particles of 1-15 microns. Particle size distribution was verified using Laser Particle Size Analyser. Consequently 120 mg of Ho-BMA was irradiated in screwed Titanium ampoules in the LWR-15 nuclear reactor (8-10 MW) at the neutron flux 1013-1014 neutrons.cm-24.s-1 for 45-105 minutes in order to attain approximately 17-40 GBq of 166Ho at the

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(Biograph®LSO, Siemens MS, third generation dual slice spiral CT) prior to treatment, and if possible a posttherapy PET-CT. The morphological CT results according to the IWRC (Int.Workshop Response Criteria) of the NCI (Nat.Cancer Institute) were compared with the combined PET-CT findings using additionally SUV calculations to decide therapy response.Results: Four patients out of 6 were able to undergo a follow up PET-CT. One patient died 2 weeks after Zevalin therapy due to progression of the NHL, one patient was lost to follow up. The 4 patients with follow-up PET-CT showed a great variability in tumor size and a wide range of treatment changes (in- or decrease in the lesions’ size and necrotic features) visible in the CT. Referring to the IWRC criteria (lymphnode size <1.5cm is required for complete remission (CR) 2 patients were classified as partial remission (PR), but showed CR in PET-CT. One patient showed partial response referring to the tumor lesions regarding tumor shrinkage and SUV decrease. The 4 th patient showed no change in tumor size and a slightly decrease in the SUV and was therefore classified as stable disease. Conclusions: As shown in other tumor entities in the follow up of patients in oncology the metabolic information obtained from F18FDG-PET CT provides more accurate and earlier information of therapy response following Y90 Zevalin treatment than the anatomical CT results.

end of bombardment. The irradiated samples were allowed to cool 24 hours and then were dispersed in 6 ml of saline (0.9% NaCl). Final suspension was prepared using ultrasound. After dispensing into the glass vials, suspension was thermally sterilised in autoclave. Prior administration, radiochemical purity, radionuclide purity, apyrogenicity as well as pH value were verified in quality control laboratory.Results: In the scope of clinical study that was carried out on 20 patients we prepared 6 batches of 166Ho-Macroaggregates. Totally we supplied 30.5 GBq radioactivity of 166Ho calculated at the time of calibration. We didn’t obtain any analytical result out of specification and all batches were released for injection.Conclusions: Routine methods for preparation and quality control of 166Ho-Macroaggregates provided reproducible results and at the moment allow producing enough radioactivities for five patients within one production run. The therapeutic and adverse effects of the application of 166Ho-Macroaggregates were evaluated in a prospective clinical trial in patients suffering from chronic synovitis of the knee joints.

P506 Radioiodine breast uptake in non lactation young women with differential thyroid cancer: is it avoidable? H. H. Shi1, X. Zhang2, S. Chen1, Y. Gu1, W. Liu1, W. Zhu1; 1Zhongshan Hospital, Fudan University, Shanghai, China, 2Department of Foreign Language,Shanghai I&C Foreign Language School, Shanghai, China. Aims: To find a reasonable method to avoid breast uptake radioiodine in young women with differential thyroid cancer using 131Iodine therapy. To minimize the side effect of radiation to the breast and to maximize benefit patients from the radioiodine therapy.Materials and Methods: Ninety four female (age from 23 to 68 years old, average 42 years) patients with differential thyroid cancer accepted radioiodine therapy after thyroidectomy. All those patients’ clinical data and whole-body radioiodine scanning imaging were reviewed. The radioiodine whole body scan was performed at 48h, 72h and 72h later after patients took 131-iodine (50mCi to 200mCi).Results: No patients had history of pregnant or breast feeding in the past half year. The TSH level was all more than 30µU/ml when the patients took 131-iodine for therapy. Eleven patients’ breast uptake radioiodine was found by whole body scan. The age of those patients range from 25 to 46 years old and average 38 years old. Analyzed those patients menstrual history, nine out of eleven patients took radioiodine in the follicular stage or later. And the whole body scan was taken about in the premenstrual stage in those patients. Breast uptakes were found in the second time or third time whole body scan imaging in 5 patients but not in the first time whole body scan imaging. The breast uptakes radioiodine showed in the first time scan imaging were much intense than that showed uptakes only in the third times whole body scan imaging. The other 2 patients showed breast uptake radioiodine took 131-iodine in premenstrual stage.Conclusions: In order to avoid breast uptakes and get the best therapy results using radioiodine for young female patients with differential thyroid cancer, it would be better taking radioiodine in the first half of their menstrual circle.

P507 Ten years results of yttrium-90 radiosynoviorthesis in chronic knee synovitis of different origin M. Szentesi, S. Takács; Semmelweis Univ., Chair of Rheumatology and Physiotherapy, Budapest, Hungary. Authors report on the results of Yttrium-90 radiosynoviorthesis in chronic synovitis of the knee joint. Study objectives: Examination of anti-inflammatory effect of 90-Yttrium injection. Patients and Methods: Out of these 617 patients 366 suffered from rheumatoid arthritis, 51 ankylosing spondylitis, 39 other seronegative spondylarthritis, 144 suffered from inflamed osteoarthritis , 3 hydrops articulorum intermitterns, 3 synovitis villonodularis, 11 from chronic traumatic synovitis . Evaulation was based on the criteria as described by Müller, Rau and Scütte the score system was developed by the authors.Results: In the first ten 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 patients with ankylosing spondylitis and at 55% of patients with osteoarthritis. Ten years after radiosynoviorthesis 72% of patients did not need another punction.Conclusions: Radiosynoviorthesis is as effectiv method of treating chronic synovitis as surgical synovectomy. Even after a ten-years period 71% the findings were rated as excellent or good. 72% of the patients do not need another punction even after a ten years 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 I-II.

P508 Histological and arthroscopical changes after y-90 isotope treatment in chronic synovitis M. Szentesi, I. Berkes; Semmelweis Univ., Chair of Rheumatology and Physiotherapy, Budapest, Hungary. Background: 4000 patients suffering from chronic synovitis were treated by Yttrium-90 / Y-90/ radiosynoviorthesis / RSO /. Results were recorded with 70-80% as very good or good. Objectives: our work aimed at examinig arthroscopic and tissue changes as a result of successful radiosynoviorthesis.Methods: 40 patients of them suffering from Rheumatoid Arthritis /RA/ were examined by arthroscop and arthroscopic-biopsy before Y-90 RSO, and ½-1 year or two years after the treatment.Results: Before the treatment: The membrane is hyperaemic with grape-like clusters proliferating. The surface was covered with several layers of synoviocyst with a diffuse inflammatory infiltration beneath. After the treatment: Half a year later, no grape-like clusters proliferating, the surface became silk-like. The surface was covered with one layer of synoviocysts, inflammatory infiltration decreased, signs of fibrosis could be seen. The histological picture remained unchanged even 1-2 years later. No damages in cartilage could be seen. Spectral analysis did show no Y in the synovial membrane and cartilage.Conclusions: RSO was effective in 70-80% Parallel to the improvement of the clinical pinture the macroscopic and microscopic signs of inflammation were decreasing. membrane or cartilige contained no Y deposits. References: Szentesi M., Bene É., Berkes I., Hehl I.: A chronicus synovitisek Y-90 kezelésének hatására bekövetkez[[Unable to Display Character: ő]] szövettani változások. Hung. Rev. Sports. Med. 29; 3-4: 246-247. 1988. Szentesi M., Berkes I., Tanka D., Hehl I.,

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Neumark T. Macroscopic and microscopic changes following Yttrium-90 radiosynoviorthesis in rheumatoid arthritis. Hung. Rev. Sports. .Med. 35. 2:107-116. 1994. M. Szentesi, I. Berkes, É. Bene, E. Piroska, D. Tanka : Y-90 radiosynoviorthesis and it's advantages over synovectomy obtained by chemotherapy using osmium acid. Proceedings of IV. Prague Rheumatological Symposium. 128. 1989. Szentesi M., Bene É., Berkes I., Tanka D.: Histological and arthroscopical changes after Y-90 isotope treatment in chronic synovitis. Proceedings of 4.th.Interscience World Conference on Inflammation. Geneva Switzerland. 393. 1991. M. Szentesi, S. Takács, I. Berkes: Histological and arthroscopycal changes after Y-90 isotope treatment in chronic synovitis European Journal of. Nucl. Med.and Molecular Imaging 29. Suppl.1. S202. 2002. M. Szentesi, S. Takács, I. Berkes: Histological and arthroscopycal changes after Y-90 isotope treatment in chronic synovitis Abstracts book. APLAR X. 1. 1. 12. 2002.

P509 Ultrasound monitoring of the synovial thickness after 166holmium-phytate radiosynoviorthesis - four-years results.(phase i-iia, comparative, randomized, single-blind, placebocontrolled study with increasing dosage) M. Szentesi, S. Takács, I. Buday, M. Nyitrai, E. Nagy, P. Géher, Z. Farbaki; Semmelweis Univ., Chair of Rheumatology and Physiotherapy, Budapest, Hungary. 166-Holmium-phytate has a: radiation type beta energy maximum: 1.84 MeV; and radiation type gamma, energy maximum: 0.66 MeV; soft tissue penetration: maximum 8.4 mm; /average: 3.3 mm /; half-life: 26.9 hours; particle size: 0.6-2 µm Study objectives: measur the synovial thickness after 166-Holmium radiosynoviorthesis by sonography.Methods: Phase I-II, randomized, simple-blind, placebo-controlled comparative study using increasing dosage. 31 patients suffering from chronic synovitis, rheumatoid arthritis, or seronegative spondylarthritis were examined. Patients: Gender (male/female): 12-19; Diagnosis (RA / SNSA): 21 / 10; Stage of knee joint x-ray (I / II): 7/24; Duration of synovitis (years): 7.9; Duration of disease (years): 5.72; Number of punctures before the Ho-166 treatment: 18.76; Number of steroid injections before the treatment: 18.85. The protocol commenced with screening. The patients were selected according to inclusion and exclusion criteria. Patients were randomly distributed into four treatment arms: Group I. 185 MBq 166Holmium phytate injectable suspension and 40 mg of 1 ml triamcinolone acetonide, and 1 ml of lidocaine injection 1 % Group II. 555 MBq 166 Holmium phytate injectable suspension, and 40 mg of 1 ml triamcinolone acetonide and 1 ml of lidocaine 1 % Group III. 925 MBq 166Holmium phytate injectable suspension and 40 mg of 1 ml triamcinolone acetonide and 1 ml of lidocaine 1 %. Group IV. Solely 40 mg of 1 ml triamcinolone acetonide and 1 ml of lidocaine injection 1 %. There were 48 month follow-up period after the administration of the isotope. We measured the quantity of the synovial fluid and the thickness of the synovia before the treatment, and the 14th, 28th days and 3, 6, 9, 12, 24, 36 and 48 months after the treatment. We measured the synovial thickness the following locations: In the midline, lateral and medial, by the condylus of femur medial and lateral.Results: The thickness of the synovia decreased significantly in the Group II. (555 MBq) and III. (925 MBq). After a transient improve (the steroid effect) the thickness of the synovia began to rise in the Group I. (185 MBq) and in the control group. We find a significant correlation between the synovial thickness and the clinical improvenes.Conclusions: The 166-Holmium-phytate is an effective new radiopharmacon in the treatment of synovitis. We detect the clinical improvement by sonography. The effective dose is 555-925 MBq.

P510 Serum thyroglobuline at the time of remnant ablation in predicting clinical outcome in patients with low risk differentiated thyroid carcinoma A. Akgun, O. Erdim, B. Yazici, Z. Ozcan, H. Ozkilic; Ege University Medical Faculty Department of Nuclear Medicine, Izmir, Turkey. Aim: Serum thyroglobulin (Tg) is accepted as the best means for detecting the presence of normal and/or malignant thyroid tissue. In the current study we investigated the value of initial serum Tg (after T4 withdrawal) at the time of remnant ablation after near/total thyroidectomy in comparison with the follow-up Tg values obtained at 6-12 months after ablation. It is aimed to review the clinical significance of initial Tg values in assessing the clinical outcome in patients with differentiated thyroid carcinoma. Material-methods: A total of 474 patients with low-risk differentiated thyroid carcinoma were included. Those patients with thyroglobulin autoantibodies and extra-cervical metastases were excluded. There were 402 papillary, 59 follicular, 11 Hurtlecell, and 2 mixed carcinomas. The age range was 16-82 and the female/male ratio was 392/82. All patients underwent total or near/total thyroidectomy followed by radioiodine ablation for the remnant tissue. The initial Tg levels at the time of ablation were classified as <2 (group1), 2-10 (group2), 10-30 (group 3), >30 ng/ml (group 4). The distribution of the patients was as follows; group 1: 216 (45.5%), group 2: 126 (26.5%), group 3: 81 (17.1%), group 4: 51 (10.7%). 6-12 months after ablation follow-up Tg measurements and total body I-131 scans were performed. Results: Clinical records including the laboratory and imaging data were reviewed and outcome was categorized as total remission, state of Tg (+) - Iodine (-), recurrence and cervical metastases. Second RAI treatment was required in 34 pts (12, 4, 12 and 7 respectively in groups 1-4) without a significant difference among the groups. The highest remission rate (93.1-94.5 %) was achieved in group1 and 2. Tg (+) - Iodine (-) disease was noted in 20 pts with a majority in group 4 (14/20). Only 1 recurrence was noted in group in 1. There were a total 15 cases with cervical metastases in which 10 of them were group 4 pts. Conclusion: It is showed that remission rate improves in agreement with decreasing initial Tg levels. The occurrence of cervical metastatic involvement or disease progression should be evaluated in patients with Tg> 30 ng/ml. Therefore it is suggested that initial Tg-levels at the time of remnant ablation may be helpful in predicting clinical outcome in low-risk differentiated thyroid carcinoma patients.