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Which Background is More Useful and Optimal for Detection of Head and Neck Cancer with Tc-99m MIBI SPECT ? J.W. Seok (1), I.J. Kim (1), Y.K. Kim (1), J.Y. Kim (2), S.G. Wang (2). (1) Department of Nuclear Medicine of the Pusan National University Hospital, (2) Department of Otolaryngology of the Pusan National University Hospital, Pusan, Korea. Purpose: The aim of this study was to present a method for diagnosis of head and neck cancer with Tc-99m MIBI SPECT by creating regions of interest (ROIs). Materials and Methods: Tc-99m MIBI SPECT was performed at 10 minutes after injection of 740 MBq of Tc-99m MIBI on 84 patients (71 males, 13 females, mean age=60.2yr) with the clinical suspicion for head and neck tumors. All lesions were histopathologically proven and data was analysed by creating ROIs over lesions and various backgrounds; submandibular gland (L/S), parotid gland (L/P), nuchal muscle (L/N), scalp muscle (L/Sc). Each lesion to background ratios were calculated for each patients. Results: Malignant disease were 72 patients and benign lesions were 12 patients. there was no statistically significant difference between the histopathologic results and L/S, L/P, L/N ratios (p>0.05). L/Sc ratios of malignant disease and benign lesion revealed statistical difference (p=0.00). When ROC curve analysis was used, Area under the ROC curve of L/Sc ratio was largest (AUC of L/S 0.579, AUC of L/N 0.578, AUC of L/P 0.628, AUC of L/Sc 0.986). The sensitivity and specificity of MIBI SPECT using L/Sc ratio for head and neck cancer were 98.6% and 91.7%, respectively. Conclusion: It is more helpful and objective method appling L/Sc ratio to differentiating malignant from benign lesions in head and neck.

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Multiple Myeloma imaging with 99mTc-Sestamibi and 99mTcTetrofosmin G. Villa (1), M. Carletto (1), E. Balleari (2), H. Rouhanifar (1), F. Peschiera (1), A. Piccardo (1), R. Ghio (2). (1) Nuclear Medicine, Department of Internal Medicine of the University of Genoa, Italy, (2) Emato-Oncology Unit, Department of Internal Medicine of the University of Genoa, Italy. Aim: The aim of this study was to assess the diagnostic value of 99mTc-sestamibi (MIBI) and 99m Tc-tetrofosmin (TF) in the detection on bone marrow involvment in patients suffering from multiple myeloma (MM). Both radiopharmaceuticals are routinely used in the diagnostic approach of several neoplastic diseases and a MIBI scan was recently proposed as a diagnostic tool for staging and monitoring the therapy in multiple myeloma. Materials and methods: 68 pts with MM and 42 pts with monoclonal gammopathy of undetermined significance (MGUS) were enrolled in this study. Fortynine out sixtyeight MM pts had active disease (AD), 11/68 were in complete remission (CR) and 8/68 in partial remission (PR) after chemotherapy. In all the pts a whole-body scans were obtained 10 min after the i.v. injection of 740 MBq of 99mTc-MIBI in anterior and posterior view. In 8 AD pts showing a positive 99mTc-MIBI scan and in 6 MGUS pts 740 MBq of 99mTc-TF was administered within two days with the same acquisition protocol, starting after 15 minutes from the injection. All the scans were scored semiquantitatively according to extension and intensity of tracer uptake. Results: all MGUS pts had a negative 99mTc-MIBI and 99mTc-TF scan . As to the MM pts, 54/68 pts (47 with AD, 8 with PR and 1 with CR) had a positive 99mTc-MIBI scan, while the 99m Tc-MIBI scan was negative in 14/68 pts (10 with CR, 2 with PR and 2 with AD). All the 99m Tc-TF scans in AD pts showed positive findings. No different scores were observed with the two tracers. The radioactivity ratios of the more evident bone marrow involvment or soft tissue uptake to a controlateral normal tissue (T/N) were calculated for the two tracers. Average TF T/N was mildly higher (2.17 ± 0.6), but non significantly, than MIBI T/N (2.06 ± 0.5) in AD pts. The overall sensitivity of the 99m Tc-MIBI scintigraphy was 92% while specificity was 96%. Conclusions: these results provide additional evidence indicating that 99mTc-MIBI scintigraphy closely reflects myeloma disease activity in the bone marrow, and that a negative 99mTcMIBI scan in pts with suspected MM clearly, though not absolutely, indicates absence of disease or clinical remission. Furthermore, our preliminary results suggest that 99mTc-TF and 99m Tc-MIBI are almost identical concerning their diagnostic value in detecting bone marrow involvment in MM.

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M. Georgiev-Predic (1), P. Predic (2). (1) Healt Care,Slovenj Gradec, SLO, (2) Hospital Celje, Celje, Slovenia.

H.T. Turoglu (1), F. Dede (2), T.Y. Erdil (1), S. Inanir (1). (1) Department of Nuclear Medicine of the Marmara University, Istanbul, Turkey, (2) Department of Nuclear Medicine of GATA Haydarpasa Military Hospital, Istanbul, Turkey.

Is it possible to diagnosis the metastatic sentinel node with Tc-99mMIBI

Aim:The purpose of this study was to analyse the occurrence of visualisation malignanci of sentinel node during preoperative lymphoscintigraphy in breast cancer. To precisely diagnose the metastatic sentinel node is very difficult. Methods:Preoperative lymphoscintigraphy was performed in 27 patients with breast cancer after injection of Tc-99m-MIBI. We injected 20-40 MBq Tc-99m-MIBI peritumoral. Anterior and prone lateral planar images were obtained a 2h, 4h, 6h and 20h after injection. The upetake were in region of sentinel node calculed. The sentinel node was intraoperatively indentifed and histologicali analised. Results:In 17 patients with intraoperatively detected metastatic sentinel node was in 15 patients increased upetake in sentinel node on scintigrams after 20h detected. In 10 patients with intraoperatively non detected metastatic sentinel node was in 9 patients increased upetake on scintigrams ower 2h-6h detected. Conclusion:The preliminary results indicated thed is lymphoscintigraphy with Tc-99m-MIBI is a new method for detection the preoperatively metastatic sentinel node.

Whole body blood pool scans in patients with diffuse bony metastases (super scan)

Aim: Bone metastasis is a common sequella of solid malignant tumors which can lead to various complications, including fractures, hypercalcaemia, and bone pain, as well as reduced performance status and quality of life. Bone metastases diffusely invading the bone marrow often manifest a rapid clinical course and the prognosis is very poor. The radionuclide bone scan remains an excellent modality to detect metastatic disease in patients (pts) with malignancies. When the bone scintigram reveals high diffuse skeletal activity, it may be misinterpreted as normal. In this retrospective study; we compared the whole body blood pool (WBBP) and whole body bone scans in which studies were reported as super scan and researched the diagnostic value of WBBP. Method: 14 pts (4 women, 10 men, mean age 60±11) with malignancies (prostate 65%, breast 14%, gastric 14% and lung cancers 7%) whose bone images were assessed as SS were included the study. The WBBP and bone scans were obtained 2-5 min. and 3 hrs after 740 MBq 99m-Tc-MDP injections, respectively. All images were re-evaluated. Results: In all pts, WBBP images demonstrated diffuse hyperemia on axial skeleton. Sensitivity of the WBBP for SS was 100%. Since only the cases with positive bone scan were evaluated retrospectively, the specificity of WBBP couldn’t be calculated. Discussion: Although various SS patterns (diffuse increased axial skeletal uptake, decreased visualization of the kidneys/soft tissue, faint/absent visualization of the appendicular skeleton.) were described on bone scan, some of the cases may still be interpreted as “normal”. WBBP may help to physician to reduce “false negative” reporting without causing extra radiation burden or expense as compared to routine bone scan. Conclusion: In this study WBBP was found very sensitive for SS. Potentially “false negative” circumstances such as metabolic bone disease or colony stimulating factor therapy can be differentiated also by good history taking and recognition of scintigraphic patterns.

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Application of radioguided occult lesion localisation method in subclinical recurrencies of differentiated thyroid cancer

Evaluation of Lung Cancer Using Tc99m Depreotide; A comparative study by combined application with In111 Pentetreotide

M. Turska (1), B. Maka (1), A. Sacher (1), J. Krajewska (2). (1) Clinic of Oncological Surgery, Center of Oncology, Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, (2) Dept. of Nuclear Medicine and Endocrine Oncology Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Gliwice, Poland.

G.S. Limouris (1), M. Veslemes (2), A.P. Frantzis (1), V. Voliotopoulos (1), A. Stavraka (1), L. Vlahos (1). (1) Radiology Dept, Nuclear Medicine Div, Areteion Univ Hosp, (2) Chest Clinic, Sotiris Hosp, Athens, Greece.

Clinically occult loco-regional recurrences in thyroid cancer patients can be operated by applying ROLL method (Radioguided Occult Lesion Localisation). In this method we use 99m Tc - albumin ( ALBU-RES, 100 µCi in 0,1 ml) into cytologically diagnosed lesions using ultrasound-guided technique. Afterwards, we are able to localize precisely these small tumors by means of intraoperative gamma-rays detector. Our material consists of eight thyroid cancer patients who have been operated many times and treated by iodine 131I. Six of them had local recurrence, in two – neck lymph node metastases were diagnosed. We were able to localize all the lesions (5 to 20 mm in diameter) described in ultrasound examination. All of them where pathologically proved, afterwards. Conclusions: Application of ROLL method in subclinical recurrence of differentiated thyroid cancer allows to: shrink the operation field shorten the operation time minimize the frequency of complications

Purpose: Depreotide is a somatostatin analog peptide labeled with Tc-99m. The aim of the study was to determine the sensitivity, specificity, positive and negative predictive value of Depreotide scan in patients with lung cancer as well as in combination with pentetreotide scintigraphy performed to the same cases. Materials and Methods: Twenty six patients (17 men and 9 women, age range 47 to 68) with lung cancer, detected on X-ray and CT, by biopsy confirmed, were i.v. injected with 740 MBq Tc-99m Depreotide (NeoTect, Amersham Health) and 111 MBq In-111 Pentetreotide (Octreoscan, Mallinckrodt). Both studies were performed within a time interval of roughly 10 days; Depreotide examination preceded Octreoscan. Planar and tomo-scintigraphy were done to each patient using an Elscint SPX-4 camera. Results: The outcome of the study is figured on the followingTable. sites no. of lesions parenchym 33 hilum 13 metastases 0

false (-) 12 3 2

true (+) 17 6 4

false (+) 2 3 1

true (-) 2 0 0

The sensitivity and specificity of Neotect alone was 89 % and 85 % respectively whereas in combination with Octreoscan slightly increased to 91 % and 86 %. Not marked differences were observed between primary and secondary lesions. False positives included pneumonia; atelectasia created false negative results. Conclusion: Tc-99m Depreotide scintigraphy showed an extremely high sensitivity ( 89 to 91 %), slightly increasing after the combination of In-111 Pentetreotide scan. The relative lower specificity seems to be site-dependent. The study is still in progress.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition DIAGNOSTIC ONCOLOGY: OTHERS

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How useful Octtreoscan is in Hormone-Refractory Prostate cancer patients with osseous metastases M. Koutsilieris (1), K. Milathianakis (1,2), J. Bogdanos (1,2), D. Karamanolakis (1,2), A. Stavraka (3), G.S. Limouris (3). (1) Department of Experimental Physiology, Medical School, Univ of Athens, (2) Urology Department, METAXA Anticancer Hospital of Pireaus, (3) Nuclear Medicine Division, Athens Medical Faculty, Athens and Piraeus, Greece. Introduction: The median survival for patients with hormone-refractory prostatic adenocarcinoma is less than a year, and the treatment options available are only to be seen as palliative. Prostatic cancerous cells especially in hormone-refractory disease demonstrate stronger expression of somatostatin receptors (SSTR) as compared to epithelial cells in hyperplastic noduli. Several studies have shown that a novel concept of combination therapy, using hormone ablation and Anti Survival Factor therapy (ASFt) is a promising salvage therapy for prostate cancer patients stage D3 with osseous metastases. Purpose: To evaluate the efficacy of Octreotide-scintigraphy to predict the therapeutic response to ASFt. Materials and Methods: Twelve patients with histologicaly confirmed prostatic adenocarcinoma were included in the study. All patients had stage D2 disease at the time of diagnosis, and underwent surgical (3) or pharmaceutical, i.e. gonadotrophin releasing hormone analogue [Gn-Rh a], (9) castration in combination with antiandrogenic support. After a median period of 31 months, patients failed the benefit of hormonal manipulations. At the time of biochemical progression of the disease, Octreoscan was performed. After failure of the endocrine manipulation, all patients received SST analogue treatment plus low dose dexamethasone, i.e. 30 mg Sandostatin LAR intramusculary every fourth week, dexamethasone 4mg/day p. os and a Gn-Rh analogue given i.m every month. Results: Only one patient had an initial positive Octreoscan. Of the 12 patients treated with the ASF therapy, 5 showed a complete response with a > 50% decrease of serum PSA and 10 normalized serum alkaline phosphatase value at the first 3 months. Eight patients (4 of them considered as non responders) showed a significant improvement in pain one month after induction in the study. The only patient who had an initial positive Octreoscan did not responded to the ASF therapy and died 8 months later from disseminating disease. Conclusions: The presence of SSTR detected by Octreotide-scintigraphy may predict the therapeutic response to a SST analogue as demonstrated in patients with malignant carcinoid. Our initial clinical experience with ASF therapy and hormonal ablation in patients with hormone-refractory CaP shows that Octreoscan can not predict the therapeutic response to this novel concept of combination therapy.

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Tc-99m-tetrofosmin scintigraphy in musculoskeletal tumours: The relationship between Pgp expression and tetrofosmin uptake in malignant lesions Z. Yapar (1), M. Kibar (1), A.F. Yapar (2), M. Aydin (2), S. Ozbarlas (3), A. Uguz (4), S. Zorludemir (4). (1) Department of Nuclear Medicine, Cukurova University School of Medicine, Adana, Turkey, (2) Department of Nuclear Medicine, Baskent University School of Medicine, Adana Hospital, Adana, Turkey, (3) Department of Orthopedics, Cukurova University School of Medicine, Adana, Turkey, (4) Department of Pathology, Cukurova University School of Medicine, Adana, Turkey. Aim: The aim of this study was to assess the role of Tc-99m tetrofosmin scintigraphy in the diagnosis of malignant versus benign musculoskeletal tumours and to determine the relationship between P-glycoprotein (Pgp) expression and tetrofosmin uptake in malignant lesions. Material and Methods: Forty-six patients (32 malignant, 14 benign) with various musculoskeletal lesions were studied. Each patient underwent Tc-99m methylene diphosphonate (MDP) three-phase bone scanning initially. At least two days later, dynamic and static Tc-99m tetrofosmin scans were obtained. The tetrofosmin scans were evaluated by visual and quantitative analysis. The count ratio of the lesion to the contralateral normal area (UR) was calculated from the region of interest drawn on the tetrofosmin scan. The lesions were then resected by open biopsy to obtain a histopathological diagnosis. Pgp levels were determined immunohistochemically in 22 of 32 malignant lesions. Results: A significant difference between the mean URs of benign and malignant lesions was found (1.36 ± 0.47 versus 3.35 ± 2.08, p=0.000). Visual analysis showed an accuracy of 85%, and the accuracy of the quantitative analysis was 87% regarding the threshold level of UR as 1.76. When perfusion findings were added to the evaluation criteria, the accuracies of visual and quantitative analysis were increased to 87% and 89%, respectively. The relationship between the levels of Pgp and URs of tetrofosmin was not statistically significant (r = -0.235, p = 0.2). And also the mean UR of the patients with Pgp expression was not statistically different from that of the patients without Pgp expression (3.01 ± 1.48 versus 4.27 ± 2.90, p = 0.297). Conclusion: In conclusion, visually significant tetrofosmin uptake and increased perfusion in a musculoskeletal lesion strongly suggest that the lesion is malignant (PPV: 96%). Pgp expression was not found to be a major factor that interferes with 30 min. tetrofosmin uptake in a malignant musculoskeletal lesion. However, the relatively high false-negative rate among negative results (28%) limits the value of Tc-99m tetrofosmin scintigraphy as a single diagnostic tool in differentiating between benign and malignant musculoskeletal tumours.

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n DIAGNOSTIC ONCOLOGY: OTHERS Over-expression of P-glycoprotein and Multidrug Resistance-related Protein in osteosarcoma: Correlation with Tc-99m MIBI imaging in Predicting Clinical Outcome Z. Burak (1), O. Ersoy (2), J.L. Moretti (3), G. Basdemir (2). (1) Ege University Medical Faculty Department of Nuclear Medicine, izmir, Turkey, (2) Ege University Medical Faculty Department of Pathology, izmir, Turkey, (3) Hopital Avicenne, Bobigny, Universite Paris XIII, Paris, France. Aim: Multidrug resistance (MDR) is an important prognostic factor in osteosarcoma. Most of the cytotoxic agents used in the treatment of osteosarcoma are substrates of MDR-related proteins, P-glycoprotein (Pgp) and Multidrug Resistance-associated protein (MRP). The aim of this study was to determine whether expression of Pgp and MRP predicted the survival of patients with osteosarcoma and to compare the results with kinetics of Tc-99m MIBI, a transport substrate for both Pgp and MRP. Materials and Methods: From 1998 to 2002, 29 patients (pts) (18 males, 11 males aged between 5 and 58) with osteosarcoma were studied. At the time of diagnosis, Tc-99m MIBI scintigraphy was applied by taking images at 10 min and 1 h after injection. Percent wash-out rate (WR%) of MIBI was calculated. Immunohistochemical analysis of Pgp and MRP was performed on biopsy specimens. The degree of expression of Pgp was graded from 0 to 6 and of MRP from 0 to 3. Significant expression of Pgp was defined as scores >3, for MRP expression scores >2 were defined as positive. All patients were treated by standard chemotherapy and surgery regimen. The follow-up period was up to 45 months. Pgp status, MRP levels and WR% of MIBI was analysed in relation to outcome by Kaplan-Meier method and log rank test. Results: The mean WR% of MIBI was 30.4 ± 8.4. A cut-off value of 1 SD below the mean WR% was used (22%) to discriminate cases with high and low WR%. The results of Pgp, MRP and WR% with respect to overall survival were as follows: Pgp (-) 14 pts Pgp (+) 15 pts MRP (-) 11 pts MRP (+) 18 pts WR% < 22 WR% > 22

MEAN SURVIVAL (months) 28.28 24.81 38.09 20.41 34.21 21.39

p>0.05 * p = 0.02 p> 0.05

There was a significant difference between the overall survival of patients with high and low MRP expression. Neither Pgp, nor WR% of MIBI were significantly correlated with poor outcome. Conclusion: Our series showed that the high WR% of Tc-99m MIBI and over-expression of Pgp were not correlated with poor outcome in patients with osteosarcoma. High levels of MRP appeared to be a prognostic factor as absence of this protein was associated with a favourable prognosis. These results are needed to be further investigated in large series of patients.

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Technetium-99m-MIBI scintigraphy in multiple myeloma: a sensitive index of biological activity of disease M. Myslivecek (1), J. Bacovsky (2), M. Kaminek (1), P. Koranda (1), V. Husak (1), V. Scudla (2), J. Nekula (3). (1) Dept. of Nuclear Medicine, (2) Dept. of Internal Medicine III, (3) Dept. of Radiology, University Hospital Olomouc, Czech Republic. Aim: To evaluate a role of 99mTc-MIBI scintigraphy in the detection of myeloma bone disease and myeloma lesions in soft tissues in multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS), in assessing myeloma activity, and to evaluate the relationship of different patterns of 99mTc-MIBI uptake with clinical status and stage of disease. Materials and methods: Seventy-six consecutive patients (37 men, 39 women, mean age 62 years, range 46-80 years) with MM or MGUS were divided into three subgroups: 1. Forty-two MM patients with active disease in stage II and III according to standard criteria, 2. Twelve MM patients in remission and partial remission, and 3. Twenty-two MGUS patients and MM patients in stage IA. Anterior and posterior whole-body scans were obtained 10 min after administration of 740 MBq 99mTc-MIBI. Using a semiquantitative score the diffuse bone marrow uptake was graded according to extension and intensity. Scintigraphic findings were correlated with clinical and laboratory data. Results: Among 42 MM patients in the first subgroup 38 (90%) showed 99mTc-MIBI uptake of high intensity (diffuse, focal or both patterns) while 4 exhibited physiological uptake of the tracer. All twelve MM patients (100%) in the subgroup 2 showed a negative 99mTc-MIBI scan. Eighteen MGUS and MM stage IA patients (82%) in the subgroup 3 had no pathological uptake of the radiotracer while 3 patients with MM in stage IA presented the diffuse and one both focal and diffuse pattern of 99mTc-MIBI uptake of high intensity. The uptake score correlated significantly with clinical status and stage of disease and with disease activity as determined by beta2-microglobulin (p<0,05), paraprotein (p<0,05), serum thymidinekinase (p<0,05), telopeptide–ICTP (p<0,05) and infiltration of bone marrow by plasma cells (p<0,05). Overall sensitivity and specificity of 99mTc-MIBI scintigraphy in detecting myeloma bone disease and in assessing myeloma activity were 90% and 88%, respectively. Conclusion: Whole body scanning with 99mTc-MIBI provides a simple and sensitive index of biological activity of disease. The patterns of 99mTc-MIBI uptake in patients with MM are related to both the clinical status and the stage of disease. 99mTc-MIBI scintigraphy is suggested as a useful tool for detecting and staging myeloma bone disease and soft tissues involvement. This work was supported by IGA grant, Ministry of Health, Czech Republic, NC6724-3/2001

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Is neoangiogenesis affecting Tc-99m (V)DMSA and Tc-99m MIBI uptake in breast cancer? Correlation with Calcitonin Gene Related Peptide (CGRP) immunohistochemistry V. Papantoniou (1), M. Souvatzoglou (1), M. Sotiropoulou (2), L. Nakopoulou (2), V. Valotassiou (1), A. Louvrou (3), A. Stipsanelli (1), S. Michalas (3), C. Zerva (1). (1) Department of Nuclear Medicine, (2) Department of Pathology, (3) Department of Obst. and Gyn., University of Athens, Greece. Aim: The scope of this study was to investigate if neo-vasculature represents an important factor in the accumulation of the two tracers in breast cancer and to assess its relationship with CGRP expression. Material and methods: 29 patients with histologically proven breast cancer have been submitted to consecutive (V)DMSA and MIBI scintimammography (SMM) before surgery after administration of 925-1100 MBq of each tracer. The number of blood vessels (NBV) was determined using immunohistochemical staining for CD 34 and counting the number of microvessels in two areas of their greatest density. CGRP expression was also assessed with immunohistochemical method. Tumor/background ratios (T/B) and CGRP were measured, correlated (linear regression analysis) and compared (t-test) with the number of blood vessels in invasive and pre-invasive lesions. Results: Histology identified 14 invasive carcinomas (IC) and 15 invasive associated with in situ carcinoma (IC+DCIS). The NBV was greater in IC+DCIS (in the invasive component) than in IC alone (IC+DCIS: 34,64±12,8, IC: 24,2±8,1, p<0,05). CGRP positivity was also significantly greater in IC+DCIS (20,3±10,8) than in IC alone (13,2±7,8), (p<0,05). There was no overall correlation between NBV and (V)DMSA uptake. MIBI T/B ratio was inversely correlated but not with statistical significance with NBV. A weak inverse correlation was found between NBV and (V)DMSA uptake only in IC. No overall correlation between CGRP and NBV was found whilst there was positive correlation in IC group and inverse correlation in IC+DCIS when they were separately assessed. Conclusion: The absolute number of new blood vessels is greater in IC+DCIS compared to IC, as well as the CGRP expression. The NBV does not increase (V)DMSA and MIBI uptake. The weak inverse correlation in the IC group probably reflects tumour growth and leaky ineffective microvessels. The different correlation of CGRP in IC and IC+DCIS indicates possibly its precocious role in the formation of new microvessels in DCIS as an angiogenic inducer in a situation where there is excess of CGRP and absence of neovasculature.

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In vivo Detection of Multidrug Resistance-related Protein(MRP) Expression by Tc-99m MIBI Scintigraphy in Patients with Musculoskeletal Sarcomas Z. Burak (1), O. Ersoy (2), J.L. Moretti (3), G. Basdemir (2). (1) Ege University Medical Faculty, Department of Nuclear Medicine, Izmir, Turkey, (2) Ege University Medical Faculty Department of Pathology, Izmir, Turkey, (3) Hopital Avicenne, Bobigny, Universite Paris XIII, France.

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Bone Scintigraphy Lesions of the Cranium in Patients with Cancer: Correlation to Standard Radiography J.O. Prior, S. Markl, A. Bischof Delaloye. Nuclear Medicine Division of the Centre Hospitalier Universitaire Vaudois (CHUV University Hospital), Lausanne, Switzerland.

Aim: The development of chemoresistance is one of the major clinical problems in the therapy of musculoskeletal sarcomas (MSS). The over-expression of efflux pumps, p-glycoprotein (Pgp) and Multidrug Resistance Related Protein (MRP), has been reported to be responsible in part for multidrug resistance (MDR) in bone and soft tissue sarcomas. The aim of this study was to investigate the uptake and wash-out kinetics of Tc-99m MIBI in comparison with (MRP) over-expression in patients with (MSS). Materials and Methods: Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with MSS were studied. After injection of Tc-99m MIBI, dynamic flow images of the involved area was obtained for 3 minutes and planar images were acquired at 10 min and 1 h. Tumour to background (T/B) ratios of both early and delayed images and percent washout rate (WR%) of Tc-99m MIBI were calculated. Immunohistochemical analysis of MRP was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 3. After neoadjuvant therapy, tumour response was assessed by detecting percent necrosis. Scintigraphic results were compared with MRP status and therapy response. Results: Irrespective of the MRP status, all patients showed significant perfusion and MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and MRP status. There was a positive correlation between WR% and MRP expression (r=0.556, p<0.01). WR% of MIBI was significantly higher in patients with high MRP expression than those with a low MRP score (28.8%±10.3% vs 16.6%±7.8). Therapy response was determined in 21 of 25 patients. Neither MRP expression rate nor WR% of Tc99m MIBI was found to show a significant correlation with percent necrosis in bulk tumour specimens. Conclusion: In conclusion the wash-out rate of Tc-99m MIBI was found to be in correlation with MRP expression with a significant difference being observed between patients with high and low MRP expression. Tc-99m MIBI imaging is a promising non-invasive in vivo examination that can predict the efflux function of MRP in MSS. As there is no correlation between the level of MRP expression and the extent of tumour necrosis with respect to Tc-99m MIBI results, further prospective studies are needed to evaluate the prognosis and event-free survival of patients with MSS.

Aim: To investigate the rate and outcome of correlative standard radiological examination performed in patients with cancer after a whole-body bone scintigraphy (BS) examination revealed a lesion of the cranium. Material and Methods: During the 1997-2001 period, we performed ca. 3,600 standard whole-body Tc-99m-DPD bone scintigraphy in patients with cancer searching for metastatic disease. In 125 patients, BS revealed suspicious lesions of the cranium and additional correlation with standard radiography was requested in the written BS report. We excluded patients referred from physicians outside the hospital (n=23) because of incomplete follow-up information. We studied 102 patients (50 women, 52 men, mean age 59.0±SD14.5 years) referred from 16 intra-hospital departments and obtained information on the occurrence and outcome of subsequent standard radiological examination of the cranium (X-ray or CT scan). Results: The requested correlation with standard radiography was performed in 37 (14 men, 23 women) of the 102 patients (36%), within 8.5±SD15 days. The observed BS lesions had no visible radiological counterpart in 23 subjects (62%). When radiological defects were observed, they were benign in 24% (n=9, frontal hyperostosis, Pacchioni’s granulations, osteoma) and indicative of malignant disease in 14% (n=5). A multivariate robust logistic analysis of performing the requested radiological examination showed that women were more likely than men to have the correlation done (odd-ratio OR=2.3, 95% confidence interval CI=1.0-5.3, p=0.038), independently of age (p=0.84), uniqueness of the lesion observed (no other lesion besides cranium, p=0.79) or BS report paragraph suggesting the correlation (results vs. conclusions paragraph, p=0.66). Considering the observed metastatic prevalence (1:7.5) and applying it to the 65 patients that did not have the radiological correlation, metastatic lesions to the cranium were potentially missed in 8 patients. Conclusion: The request for standard radiological correlation of a cranium lesion in BS of patients with cancer was fulfilled in one third of the cases. When performed, the radiological investigation was most of the time normal or showed benign lesions. However, in about 14% of the patients, it indicated metastatic disease. Women were twice more likely than men to have the additional radiological study performed. Since BS examination of the cranium for metastatic disease is known for its low sensitivity and specificity, performing standard radiological correlative imaging when a BS lesion is present helps to increase diagnostic accuracy. The rate of correlative examinations might be increased by calling the referring physician and asking for a copy of the follow-up correlative radiological examination.

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Preliminary study for sentinel node identification with 99mTc colloid and blue-dye in patients with endometrial cancer. E. Pelosi (1), V. Arena (1), T. Gargiulo (2), M. Bellò (1), B. Baudino (1), M. Giusti (2), L. Palladin (3), G. Bisi (1). (1) Department of Nuclear Medicine of the University of Turin, Italy, (2) Department of Gynecology, M. Vittoria Hospital, Turin, Italy, (3) Department of Anatomo-Pathology , M. Vittoria Hospital, Turin, Italy. Introduction: intraoperative lymphatic mapping and sentinel node (SN) biopsy has generated a tremendous amount of interest and is already established as part of standard practice in the surgical management of breast cancer and melanoma. To reduce extensive radical procedures and decrease morbidity in gynecologic malignancies, much effort is being focused on implementing less aggressive interventions. Objective: the purpose of our study was to determine the feasibility of SN mapping in a group of patients with endometrial cancer at early stage. Method: Between September 2000 and May 2001, 13 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral sistematic lymphadenectomy. Material: Radioactive isotope injection was performed 24 hours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic γ-scintyprobe MR 100 type 11, 99mTc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. Results: Nineteen (19) SLN were detected at lymphoscintigraphy (6 bilateral and 7 monolateral). At laparoscopic surgery were found the same locations belonging at internal iliac limph nodes (the so called “Lebeuf-Godard” area, lateral to the inferior vescical arteria, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fifteen (15) SLN result negative at histological analysis and only 4 result positive for micrometastasys (mean SLN sections=60). All the other pelvic lymph nodes result negative at histological analysis. The same SLN locations detected with γ-scintyprobe were observed during laparoscopy after patent blue dye injection. Conclusion: our preliminary data suggest that in endometrial cancer combined 99mTc-labeled colloid and vital blue-dye technique are feasible, and they represent a very promising technique to transform the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.

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Characterization of meningiomas with thallium-201 brain SPECT K. Kinuya (1), N. Kato (1), K. Nobata (1), K. Kakuda (1), S. Ishijima (2), K. Yamamoto (2), S. Itoh (2), M. Ohashi (2), S. Terahata (3). (1) Department of Radiology, Tonami General Hospital, Tonami, Japan, (2) Department of Neurosurgery, Tonami General Hospital, Tonami, Japan, (3) Department of Pathology, Tonami General Hospital, Tonami, Japan. Meningioma often has malignant nature with a high mitotic rate and rapid proliferation. It is difficult to differentiate malignant meningioma from benign ones with morphological images such as X-CT and MRI. This study was performed to investigate the feasibility of thallium201 (Tl) brain SPECT to assess histopathological character of meningiomas preoperatively. Methods: Tl SPECT images were analyzed for 59 lesions in 42 patients (15 men, 27 women; age 60.3 ± 12.8 yrs). Using early (15 min postinjection) and late (3 hr) SPECT images obtained with 111 MBq of Tl chloride, early uptake ratio (ER; lesion to normal brain count ratio), late uptake ratio (LR), and retention index (RI; ratio of LR to ER) were calculated. Histopathology was confirmed by surgical specimens for all lesions. Results: Twenty-three lesions were histologically diagnosed as malignant meningioma, which showed higher ER (7.39 ± 3.14; p<0.005) and higher LR (3.49 ± 1.19; p<0.005) than did 36 benign meningiomas (ER, 5.46 ± 2.15; LR, 2.62 ± 0.80). Benign lesions were further histopathologically classified in 19 meningotheliomatous type (ER, 6.40 ± 1.95; LR, 2.66 ± 0.76; RI, 0.43 ± 0.08), 9 psammomatous type (ER, 4.28 ± 2.50; LR, 2.51 ± 0.99; RI, 0.62 ± 0.16), 5 transitional type (ER, 4.88 ± 1.30; LR, 2.76 ± 0.85; RI, 0.59 ± 0.18), and 3 miscellaneous types (ER, 4.05 ± 0.08; LR, 2.44 ± 0.61; RI, 0.60 ± 0.16). Meningotheliomatous meningioma is the most common histological type, which showed the higher ER value than did other benign types (p<0.0005); although meningotheliomatous type could not be differentiated from malignant meningioma by means of ER, LR in malignant meningioma was significantly higher than that in meningotheliomatous type (p<0.01). LR in malignant meningioma was also significantly higher than those in benign meningiomas other than meningotheliomatous type. Meningotheliomatous type could be defferentiated from other benign types by means of RI (p< 0.005). Conclusion: Intense Tl accumulation in both early and late images is an indicator of malignant meningioma. High ER with low RI suggests that the lesion would be meningotheliomatous type; other benign types would be distinguished as relatively low ER and LR. These results indicate that Tl brain SPECT is a useful method in histologically differentiating meningioma types.

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n DIAGNOSTIC ONCOLOGY: OTHERS 111IN-DOTA-Lanreotide - Implication radionuclide Therapy in intestinal Adenocarcinoma C.F. Novotny (1), T. Traub (1), M. Raderer (2), A. Kurtaran (1), P. Angelberger (3), R. Dudczak (1), I. Virgolini (4). (1) Department of Nuclear Medicine of the Unversity of Vienna, Austria, (2) Department of Internal Medicine 1 of the Unversity of Vienna, Austria, (3) Austrian Reasearch Center Seibersdorf, (4) Department of Nuclear Medicine of the Hospital Lainz, Vienna, Austria. Aim: 111In-DOTA-lanreotide, a the somatostatin analog, which is known to bind mainly to hsstr 2 - 4, has been proved to be sucsessful in the detection of neuroendocrine tumors and thyroid carcinomas and it has already been used for radioreceptortherapy with 90Y-DOTA-lanreotide. The aim of this study was to evaluate the potential of 111In-DOTA-lanreotide to visualize primary or metastatic lesions of pancreatic, colorectal and gastric adenocarcinona, which are known to express sstr 3 and 4, in prospect of a radioreceptortherapy with 90Y-DOTA-lanreotide. Methods: After injection of 130 - 170 MBq 111In-DOTA-lanreotide, planar images and SPECT studies were performed in 36 patients with histologically or radiologically verified tumor disease, 15 patients with colorectal cancer, 7 with ventricular cancer and 14 with pancreatic cancer. All of these were adenocarcinoma with tumor grades G 2 - 3. Six patients had been pretreated with cytotoxic agents. There was no evidence of infection or inflammation. Results were compared to conventional imaging (CT, MRI, ultrasound) as well as endoscopy and surgery. Results: 111In-DOTA-Lanreotide-scintigraphy showed positive results or additional information compared to conventional methods in 8 / 15 (53%) pts. with colorectal, 5 / 7 (71%) pts. with gastric and 6 / 14 (43%) pts. with pancreatic adenocarcinoma. It showed no specific tumor uptake (false negative results or cold spots in the case of liver or lung metastases, resp.) in 7 / 15 (47%) pts with colorectal 1 / 7 (14%) pts. with gastric and in 8 / 14 (57%) pts. with pancreatic adenocarcinoma. One patient had only suspected tumor recurrence of a gastric cancer, which showed a true negative result in the study. Conclusion: 111In-DOTA-Lanreotide-scintigraphy seems to be an option for the detection / staging of ventricular cancer, it has the potential to visualize primary / metastatic colorectal and pancreatic cancer, which may lead to a radioreceptortherapy with 90Y-lanreotide in selected patients with satisfying tumor doses.

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Tl-201 SPECT In Evaluation of Intracranial Tumor Viability Ü.Ö. Akdemir (1), L.Ö. Kapucu (1), I. Egehan (2), M. Ünlü (1). (1) Department of Nuclear Medicine of the Gazi University Medical Faculty, Ankara, Turkey, (2) Department of Radiation Oncology of the Gazi University Medical Faculty, Ankara, Turkey. AIM: The aim of this retrospective study was to evaluate the value of Tl-201 SPECT imaging and to compare it with MR and CT imaging in predicting the outcome of patients treated for intracranial tumors. METHOD: In 20 patients with various intracranial tumors (14 previously operated; 8 glioblastoma multiforme, 7 astrocytoma (grade1, grade2 and grade3), 1 gliosarcoma and 4 tumors without pathological diagnosis), within 1 month after the completetion of radiotheraphy, early (15min) and delayed (3 hrs) Tl-201 SPECT imaging was performed to assess residual tumor viability. In addition to visual analysis, tumor to normal tisse uptake ratios were obtained from both early (ER) and delayed (DR) transaxial images and retention indeces (RI=(ER-DR)/ER*100) were calculated. MR (18 patients) and CT (2 patients) imagings were also performed. Status of the patients were retrospectively evaluated after a 2 years period by making telephone calls. RESULTS: Only 2 of the 20 patiens were alive at the end of 2 years. The mean time passed between Tl-201 scintigraphy and time of death was 7.1 + 4.3 months. Tl-201 SPECT revealed increased focal activity accumulation in 17 of these 18 patients (sensitivity: 94%). The single false negative case was a patient with grade 2 astrocytoma. MR and CT imaging revealed residual mass in 12, was indeterminate in 4 patients and negative in 2 of these 18 patients. All of these indeterminate and false negative patients were previously operated. Mean ER, DR and RI values were 2.68 + 1.43, 2.13 + 1.09 and 0.15 + 0.21, respectively. There was no correlation between these indices and survival times (R values were 0.364, 0.517 and 0.09 for ER, DR and RI, respectively.). The ER and RI values were higher for patients with glioblastoma multiforme. CONCLUSION: Tl-201 SPECT imaging can be used for the assessment of residual tumor viability following radiation theraphy and may be better in evaluation of post operative patients compared to MR and CT imaging.

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P_211

J. Khan, H.M. Zhuang, M. Hickeson, J.L. Alberini, L. Guan, A. Alavi. Hospital of University of Pennsylvania, Philadelphia, USA.

S. Gerali, V. Valotassiou, N.G. Sifakis, I. Koutsikos, C. Zerva. Department of Nuclear Medicine Alexandra University Hospital, Athens, Greece.

Introduction: Some reports in the literature indicate that in FDG-PET studies there is no difference between the lesions detected by the attenuation corrected (AC) images as compared to the non-attenuation (NAC) corrected images, for patients with malignant disease. We aim to address this issue in our experience. Method: We studied patients with ovarian cancer, who had FDG-PET studies done in our center (n=32). Both AC and NAC images were studied and patients were divided into three groups, patients with consistent AC and NAC images (G1), patients with more number of lesions in AC images than NAC images (G2) and patients with inconsistent images in which the difference in lesions changed the stage of disease (G3). Result: There were 21 patients in G1 (65.6%). Of these 12 (37.5%) patients had no lesions on any study. In 9 patients (28.1%) the lesions found in the studies were similar quantitatively in AC and NAC images. There were 11 patients (34.3%) who had discrepancy in the AC and NAC images. There were 6 patients in G2 (18.7%), for which the difference in the number of lesions did not affect the stage of disease (compared to G1, p=****). There were however 5 patients in G3 (15.6%), in which the discrepancy in the two images changed the stage of the disease (compared to G2 p=***). Conclusion: In our experience, the AC images are superior in detecting the number of lesions, which may also change the stage of the malignant disease. Therefore the attenuation corrected images must be obtained in every study, for correct interpretation of FDG-PET studies.

AIM: The aim of this study was to evaluate the contribution of Tc99m-MIBI in the follow-up of patients with differentiated thyroid carcinoma and the detection of metastases. MATERIAL-METHODS: We studied 32 patients (11 males, 21 females) mean age 49,7ys (range 18-83) with differentiated thyroid cancer (29 papillary, 2 Hürthle cell, 1 papillary+Hürthle cell carcinoma) who had total or nearly total thyroidectomy followed by an ablative dose of I-131 (30-200 mCi). All patients had increased serum thyroglobulin levels (mean value 64,14 ng/ml) while receiving levothyroxine therapy. Anterior and posterior images were obtained 5 min and 30 min after the intravenous injection of 15 mCi Tc99m-MIBI. The scan results were compared with those of post-therapy I-131 scans. RESULTS: 13 (40,62%) of 32 patients had positive Tc99m-MIBI and I-131 scan results, the findings concerning neck lesions and, in one case, lung lesions too. 9 (28,12%) of 32 patients had positive Tc99m-MIBI and negative I-131 scan results, the findings concerning neck lesions and, in one case, lung lesions too. 3 (9,37 %) of 32 patients had negative Tc99m-MIBI and positive I-131 scan results, the findings concerning neck lesions. 7 (21,87 %) of 32 patients had negative Tc99m-MIBI and I-131 scan results. Biopsy, U/S or CT confirmed the findings in all above patients. Finally, 22 (68,75 %) patients had positive Tc99m-MIBI scan, 16 (50 %) patients had positive I-131 scan and 25 (78,12 %) patients had positive Tc99-MIBI or I-131 scan. CONCLUSION: Tc99m-MIBI scintigraphy is a sensitive method for detecting metastases from differentiated thyroid cancer, especially neck metastases or metastases with no I-131 uptake and could be used as a complementary study since the combination of both radiopharmaceuticals (Tc99m-MIBI and I-131) increases the sensitivity of neck metastases imaging.

Malignant lesions detection by FDG-PET, Are attenuation correction images better than non-Attenuation correction Iimages ?

Tc99m-Mibi Scintigraphy in the follow-up of patients with Metastatic Differentiated Thyroid Carcinoma

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Dynamic limphoscintigraphy in diagnostic and management of postmastectomy lymphoedema

Clinical Role of Tc99m MIBI Scintigraphy in Multiple Myeloma and Comparison With Tc99m-MDP Bone Scintigraphy

M.B. Baczyk (1), J. Bieda (2), A. Wyszomirska (1), J. Sowinski (1). (1) Department of Nuclear Medicine of the University School of Medical Sciences, (2) Lymphoedema Out - patients Clinic, Poznan, Poland.

R. Erinc (1), U. Yararbas (2), K. Kumanlioglu (2), Z. Ozcan (2), M. Argon (2). (1) Marmara Nuclear Medicine Center, Istanbul, Turkey, (2) Department of Nuclear Medicine of Ege University Hospital, Izmir, Turkey.

Introduction. Postmastectomy lymphoedema develops in 20 - 36% of women after breast cancer surgery with axillary clearance. In many cases lymphoedema delays full recovery and influence physical and psychosocial well-being. Objective. The aims of the study were: to evaluate dynamics of the lymph outflow in patients after axillary clearance for breast cancer with subsequent lymphoedema to define the level of lymphatic insufficiency and its influence on effects of complex decongestive therapy (CDT) Materials and methods. The group of patient consisted of 16 women. The age of patients varied from 37 to 65 years. Dynamic lymphoscintigraphy was taken with Varicam gamma camera by Elscint. 0,5 ml of the radiotracer ( Nanocoll labelled with 99m Tc ) was injected subcutaneously between II and III metacarpal bone at the back of the hand. Subsequent acquisitions were taken every 60 sec., radioactivity over axillary, sub- and supraclavicular lymph nodes area was evaluated. Registered parameters: arrival time - the time from radiotracer injection to revealing regional lymph nodes. lymph nodes uptake - storage capacity of the radiotracer in the regional lymph nodes in %. During examination patient was doing movements of flexion and extension in the wrist to activate muscle pump. The examination was ended by final scintigraphy after 2 hours or if necessary after 5 hours by scintigraphy evaluating dermal back flow. Lymphatic insufficiency was measured in 4 steps scale by Weissleder and compared with clinical grading and effects of CDT. Results. There were three types of images registered: no axillary lymph nodes revealed and flat radioactivity curve. This corelated with severe lymphoedema in clinical grading and poor results of CDT. a few lymph nodes revealed in the axilla with marked outflow to the subclavicular lymph nodes and delayed transport of the radioactive material. It correlated with moderate lymphoedema in clinical grading and slightly better effects of CDT. direct although delayed lymph outflow to the supraclavicular lymph nodes. Those patients had clinically mild lymphoedema and achieved the best results in CDT. Conclusions. Dynamic lymphoscintigraphy helps not only to evaluate the level of lymphatic insufficiency but also to estimate remaining transport capacity and the role of muscle pump in accelerating lymph outflow. Those factors are strong predictors in the treatment efficacy. Lymphoscintigraphy should be done immediately when the first symptoms of lymphoedema occurs. The delay in proper treatment results in massive fibrosis in subcutis that compromises the lymph outflow in remain intact lymphatics.

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Effect of maximal androgen blockade on bone mineral density in men treated for prostate cancer S. Naldoken (1), S. Yazici (2), O. Adsan (2), H. Ortapamuk (1). (1) Department of Nuclear Medicine of Ankara Numune Hospital,Ankara,TURKEY, (2) Department of Urology of Ankara Numune Hospital,Ankara,Turkey. Aim In this study we evaluated the changes in bone mineral density of men with prostate cancer receiving androgen deprivation therapy. Materials&Methods Fourteen patients ( mean age 72+5.78) with histologically proven prostatic adenocarcinoma were included in the study. The main entry criteria were advanced prostate carcinoma; no prior androgen deprivation therapy and no documented bone metastases on bone scintigraphy. Exclusion criteria were a prostate specific antigen (PSA) level of 100 ng/ml, history of non-traumatic bone fracture, presence of a condition affecting the bone metabolism such as hyperthyroidism, hyperparathyroidism, hyperprolactinemia, hemochromatosis, chronic liver disease, renal dysfunction (serum creatinine >2.0 mg/dl), and treatment with calcitonin, glucocorticoids, calcium, vitamin D or metabolites, biphosphonates and thiazides. At months 0 and 6, bone mineral density (BMD) of the anteroposterior lumbar spine (L1-L4) and right hip were measured using a dual energy x-ray absorptiometer (DEXA) Hologic QDR 2000. BMD (in grams per square centimeter) at each site was compared with age and gender matched control subjects from the National Health and Examination Survey (NHANES) III normative database and expressed in standart deviation units relative to agematched men (Z score). Before beginning to androgen deprivation therapy and at 6th month of treatment, PSA, total testosterone, FSH ,LH, PTH, calcitonin, serum calcium, phosphorus and alkaline phosphatase levels were determined. Results. Five patients were treated with a long acting LHRH agonist plus an antiandrogen (bicalutamide) while 9 patients had undergone bilateral orchiectomy and received bicalutamide subsequently None of the patients had evidence of bone metasteses on bone scan. As expected, serum PSA and total testosterone levels decreased significantly at the 6th month of androgen deprivation therapy (p<0.001 and p<0.003 respectively). Serum FSH and LH concentrations concentrations were increased compared with month 0 but did not reach statistical significance (p=0.061 and p=0.184 respectively).The lumbar column, femoral neck and Ward’s triangle bone mineral density decreased significantly at month 6. Conclusion Our study demonstrated accelerated lumbar spine and femoral neck bone loss in men with prostate cancer following orchiectomy or while receiving LHRH agonist and antiandrogen therapy. We haven’t encountered any bone fractures during the study. We believe that the best method of avoiding androgen deprivation therapy associated osteoporosis is evaluation of all patients with prostate cancer with BMD measurements.

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Aim: It is known that in multiple myeloma (MM) radionuclide bone imaging is not as sensitive as conventional radiography because of destructive nature of the bone lesions. Recently, several studies with Tc99m MIBI have shown tracer uptake in myeloma tissue and suggested that Tc 99m MIBI accumulation could indicate clinical state of the disease. The purpose of this study is to investigate the clinical value of Tc99m MIBI scan (MS) and various uptake patterns and also to compare Tc99m MIBI with Tc99m MDP bone scan (BS) in patients with MM. Material & Method: Twenty-four patients (16 males, 8 females, mean age 53.3), with MM (n=23) and solitary plasmacytoma (n=1) were studied. Seventeen of 24 patients (group A) were in active state whereas 7 (group B) were in remission according to clinical and laboratory findings. MS and BS were performed in all patients within 2 weeks, respectively. Scans were evaluated visually. The uptake patterns of MS were grouped as normal (N), focal (F), diffuse (D) (showing diffuse bone marrow uptake) and diffuse+focal (D+F). Diffuse uptake was scored according to its intensity (I) and extension (E). Scores ≥3 was accepted as pathological. Results: GROUP A (active disease group) GROUP B) (remission group

F 7/17 -

Tc99m MIBI scan D F+D 2/17 7/17 (scores≥3) 4/7 (scores≤2)

(scores≥3) -

N 1

Bone Scan 17/17 (*)

3/7

2/7 (**)

(*) When MS and BS were compared, more focal lesion sites were detected in 12 patients (70.6%) in BS. Since BS could reveal arthritic, traumatic and infectious changes in bone, increased incidence of degenerative lesions and complications of primary osteoporosis in this age population caused the higher number of lesions in BS. In 3 patients (17.54%) the number of lesions was equal and 2 patients (11.6%) had more focal lesions in MS. (**) BS of 2 patients with inactive disease (2/7) showed pathological activity uptake. Radiological evaluation was normal in 1 of these patients and in the other case pathological Tc99m MDP uptake was diagnosed as an old inactive lesion. Conclusion: Tc99m MIBI is a promising oncotropic tracer in determining activity of the disease, site of active lesions, bone marrow infiltration and in the follow-up of the patients with MM. Although BS is still a valuable screening test in the evaluation of malignancies, MS is found to be a more specific imaging modality in MM cases.

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P.F. Fostitsch (1), D.A. Röhlen (1), G. Treiber (2), R. Steinke (1), H.J. Otto (1). (1) Department of Nuclear Medicine of the University of Magdeburg,Magdeburg,Germany, (2) Department of Internal Medicine of the University of Magdeburg, Magdeburg,Germany.

M. Ruchala, R. Czepczynski, M. Baczyk, J. Sowinski. Department of Nuclear Medicine of the University School of Medical Sciences, Poznan, Poland.

Somatostatin receptors are known to be expressed in a large number of human tumours and therefore they represent ideal targets for in vivo tumour imaging. Today the [111 In] labelled somatostatin derivative octreotide (Octreoscan) is the most frequently used radiopharmaceutical to determine in vivo the presence and abundance of somatostatin receptors in various tumours. The aim of our study is to assess the presence of somatostatin receptors in human liver tumours diagnosed as hepatocellular carcinoma (HCC) and to estimate the effect of therapy with octreotide (long acting release form) alone or in combination with rofecoxib on the course of the disease and on the expression of somatostatin receptors. Therefore it is planned to perform a second diagnostic scan when therapy will be finished after a six months course. Methods: Before commencing therapy thoracic and abdominal SPECT images were obtained after administration of 165-189 MBq [111 In]-Octreotide in 21 patients (4 females and 17 males; age:36-76 years) at 5, 24 and 48 h p. i. Inclusion criteria were positive ultrasound and computer tomography scans of liver tumours and bioptic diagnosis of HCC. Results: 16 patients (76,2 %) showed a high expression of somatostatin receptors in the liver. A semiquantitative analysis revealed an uptake ratio tumour(TU)/non-tumour(NTU) of 1,8 4,96 (mean: 2,72). In 5 cases (23,8 %) receptor scintigraphy was negative (uptake ratios TU/NTU of 1,20-1,25), but also these patients underwent therapy with sandostatin. Conclusions: [111-In]-octreotide scintigraphy is promising to be very useful in first line diagnosis and assessment of follow up is a promising tool for patients with HCC.

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Langerhans cell histiocytosis in children. Assessment of bone and somatostatin receptor scintigraphy in the detection of bone involvement. I. Hervás (1), P. Bello (1), A. Cañete (2), A. Saura (1), P. GonzálezCabezas (1), D. Flores (1), R. Pérez-Velasco (1), V. Castel (2), A. Mateo (1). (1) Department of Nuclear Medicine. University Hospital La Fe. Valencia. SPAIN., (2) Department of Paediatric Oncology. University Hospital La Fe. Valencia, Spain. AIM: Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve multiples sites of the body. Diagnostic imaging is of utmost importance in the management of these patients. Since now radiographic skeletal survey and bone scintigraphy (BS) have been used to assess bone involvement (both with low specificity). Magnetic resonance and CT have been used to assess visceral involvement but with the limitation that can not give information about the functional status. Recently two groups of investigators (Lastoria et al. and Calming et al.) have proposed somatostatin receptor scintigraphy (SSRS) to detect active lesions and for monitoring the response to treatment, due to the somatostatin analogue octreotide binds to the cell membrane of activated lymphocytes expressing somatostatine receptors. The aim of this study is to assess bone and somatostatine receptor scintigraphy in the detection of bone involvement in LCH in children. Visceral involvement has not been assessed due to none of the patients presented it at the moment of the SRS. METHODS: 15 scintigraphies (9 SSRS and 6 BS) were performed in four patients (3 girls and 3 boys) aged at diagnosis: 18 month- 12 years (mean age 5,8 years). The findings obtained in the scintigraphies were compared with clinical evolution and other imaging techniques. RESULTS: All the BS detected the diagnosed lesions, that decreased the uptake after the treatment. In three cases BS detected one unknown bone lesion. Two SSRS could not detect a lesion on right rib in two patients, both at the moment of diagnosis. SSRS was true negative in one patient (clinical and other imaging remission) and true positive in the other tree cases. SSRS detected two new unknown bone lesions. SRSS showed decreased uptake after treatment and increased uptake in the relapses. CONCLUSIONS: Somatostatin receptor and Bone scintigraphy can be used to detect active LCH bone lesions in children and can help in monitoring the response to treatment. Further studies are needed to confirm the diagnostic usefulness of these techniques.

Evaluation of the lymphatic drainage of the thyroid tumors using lymphoscintigraphy

Introduction. Evaluation of the lymphatic drainage of a tumor is of great importance while planning the extent of the surgical treatment. Lymphoscintigraphy is one of the methods used for the assessment of the lymphatic drainage. In this study, we assessed the usefulness of lymphoscintigraphy in the preoperative evaluation of patients with thyroid tumors suspected of malignancy. Material and methods. 11 patients in whom a solitary thyroid nodule was found by the means of ultrasound examination and in whom the fine needle biopsy revealed papillary thyroid carcinoma (5 patients) or follicular nodule (6 patients). Before thyroidectomy a lymphoscintigraphy was performed. An activity of ca. 1 mCi (37 MBq) of Tc-labelled nanocolloid (Nanocoll®) was injected into the thyroid nodule with the use of a fine needle (0,35 mm diameter). The injection was supervised by the ultrasound imaging. Scintigraphy of the neck was then performed in four phases: phase 1 - 2 min. p.i., phase 2 - 1 h p.i., phase 3 - 2 h p.i., phase 4 - 3 h p.i. The images obtained were analysed for focal activity around the tumor, i.e. outside the injection site. Results. In 2 patients (18,2%) no focal activity outside the tumor was found in any phase of imaging. In the remaining 9 patients (87,8%) altogether 54 extratumoral foci accumulating the tracer were found. In 8 out of 9 patients the first focus (the sentinel node) was observed already in the early images of phase 1. In each next phase of the imaging new foci (lymphnodes) were visualised. In general the images in phase 1 revealed 20 lymphnodes, in phase 2 29 lymphnodes, in phase 3 - 50 and in phase 4 - 54 lymphnodes. Conclusion. In the majority of patients lymphoscintigraphy is able to localise the sentinel node as soon as in several minutes after injection of the tracer into the thyroid tumor. This method can be successfully used in the evaluation of the lymphatic drainage in patients operated for diagnosed or suspected thyroid carcinoma.

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Utility of gallium-67 scintigraphy to assess response to chemotherapy in patients with lymphoma A. García (1), R. González (2), S. Rodado (1), C. Rodríguez (3), V. Poblete (1), M.J. García (2), A. Soriano (1). (1) Department of Nuclear Medicine of Alarcos Hospital, Ciudad Real, Spain, (2) Department of Oncology of Alarcos Hospital, Ciudad Real, Spain, (3) Unit of Investigation of Alarcos Hospital, Ciudad Real, Spain. Aim: to evaluate the utility of Gallium-67 scans (Ga-67 s) in patients with lymphoma compared to computed tomography (CT) to assess response to chemotherapy. To study the significance of hiliar uptake in Ga-67 s in the prognosis. Materials and methods: 51 Ga-67 s undertaken in 32 patients. 13 males and 19 females with an average age of 48. 10 with Hodgkin lymphoma and 22 with non Hodgkin lymphoma. Planar and SPECT Ga-67 s were carried out 48 hours after a dose of 370 MBq of Ga-67. We defined as positive any uptake different from the physiological distribution independent of the intensity in planar studies and with an intensity similar to that of bone in SPECT studies. All the studies were evaluated with CT, LDH values in serum, clinical features and the follow up. Results: the correlation between CT and Ga-67 s results is shown in the table. Pathologic CT (group1) Negative Pathologic SPECT SPECT Negative planar Ga-67 s 5 12 Positive planar and SPECT Ga-67 s 12 TOTAL 29

Normal CT (group2) Negative Pathologic SPECT SPECT 6 7 9 22

Group 1: 18 and 11 studies corresponded to patients in partial response (PR) and complete response (CR) respectively. 18 studies (all except one with positive Ga-67 s) corresponded to patients who had recurrent o progressive disease in the follow up. Group 2: All the studies corresponded to patients in CR. 2 studies (with positive Ga-67 s) corresponded to patients with recurrent disease in the follow up. The sensitivity, specificity, PPV, NPV and accuracy of the Ga-67 s and CT were 94%, 30%, 42%, 91% and 53 %; and 100 %, 66%, 62 %, 100 % and 78% respectively. If hiliar (symmetrical or asymmetrical), mediastinum and pulmonary uptakes were considered as benign patrons and thus negative, due to post-chemotherapy changes in the Ga-67 s, the results improved to 94%, 85%, 77%, 96% and 88% respectively. Benign patrons showed better correlation with the prognosis in the group 2 compared to group 1. Conclusions: Post-chemotherapy CT and Ga-67 s had good correlation with the clinical response. The hiliar uptake associated or not with mediastinum and pulmonary uptake must be interpreted with caution in post-chemotherapy evaluation. These uptake patrons were shown to be more useful in patients with normal CT.

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Somatostatin receptor scintigraphy in patients with hepatocellular carcinoma

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Metastron and pamidronian as connected palliative therapy of osteoblastic-osteolytic breast cancer bone metastases

A scintigraphic study of bone metastases distribution in 420 patients

M.B. Baczyk (1), E. Baczyk (2), J. Sowinski (1). (1) Department of Nuclear Medicine, (2) Department of Palliative Care of the University School of Medical Sciences, Poznan, Poland.

V. Rusu, M. Rusu, G. Naum, C. Stefanescu, A.-M. Statescu, I. Raileanu, D. Hountis. Nuclear Medicine Department, Sf.Spiridon University Hospital, Iasi, Romania.

Introduction. The cancer bone metastases in 40% of patients with advanced breast cancer are detected ; osteolysis predominates in 70% of cases, but in 30% osteoblastic component is observed, that gives the possibility for use of strontium 89. Aim. The aim of this study was to evaluate the effectivness of connected therapy using strontium 89 ( osteoblastic component ) and pamidronian therapy ( osteolytic component ) in the group of breast cancer patients with multiple osteoblastic-osteolytic ( mixt ) bone metastases. Material and methods. The study included 13 patients with breast cancer and multiple bone painful metastases ( 2 or more ) detected by scintigraphy and by radiogram or CT or MRI (character of metastases). All patients have been treated with analgesic management ( NSAID + opioids ). Each patient received a standard dose 150 MBq of strontium 89 (Metastron) combined with intravenous infusion of 60 mg pamidronian (Aredia) and short low-dose steroid therapy. The bisphosphonate therapy was repeated every month. For assessment of therapy effectivness; pain relief ( VAS scale ), a reduction in analgesic requirements and motor activity ( ECOG and Karnofsky scale ) were evaluated. The group of 10 patients treated with bisphosphonate only in the same time was observed. Results. During follow-up after 4 weeks and 10 weeks of the end of strontium 89 therapy we noticed pain relief effects as follows: “good” (VAS<2) in 4 patients, “moderate” (VAS<5) in 5 patients, “no effects” (VAS>5) in 4 patients. We have observed that the analgesic requirments decreased to 30% of dose on average. The motor activity of the points evaluated according to ECOG scale increased from 3 to 2 and from 40 to 60 to Karnofsky scale. No pathological fractures, hypercalcaemia and other serious side effects with clinical manifestation were observed. The results of treatment in the group with strontium 89 and bisphosphonate were better than in the group treated with bisphosphonates only (40% “good” and “moderate” response rate, 1 case of pathological fracture). Conclusions. We conclude that connected palliative therapy using strontium 89 and bisphosphonates is effective ( 69% “good” and “moderate” response rate ) and safe for bone pain palliation in patients with multiple osteoblastic-osteolytic bone metastases from breast cancer; it also improves the quality of life.

Objectives: In the context of few literature concrete data concerning a bone metastases specific distribution related to the primary cancer type, our aim was to analyze the metastases on 9 scintigraphic well delimitate skeleton segments, in a significant number of patients. Material and method: 420 patients with cancer of breast, prostate, lung and colon were investigated through 99mTc Methylen-biphosphonate whole body scintigraphy. The presence of pathologic radiotracer uptake was qualitatively and quantitatively analyzed in order to establish the metastases distribution. Dodds and Morgan methods were used. Patient selection was realized over 2455 whole body scintigraphies effectuated between 1998 and 2001 in our Nuclear Medicine Service. The patient therapeutic status at the examination date was heterogeneous. Cases with external bone radiotherapy were excepted from the study. Planar scintigraphic images and SPECT were also realized on interest regions, when a better delimitation of metastatic sites was necessary. All selected cases were metastases with known origin primary cancer. Results: The mean number of the metastatic involved skeletal regions was significantly greater in breast and prostate cancers in comparison with lung and colon cancers (p < 0.0001). The higher metastases site frequency was the rachis, than the pelvis, the ribs and the sternum. The solitary metastasis is more frequent in breast cancer, its significant statistic elect sites being the ribs and the sternum. The skull metastases localization is more frequent in breast cancer in comparison with all other cancers (29% versus less than 15% in all other cancer types). The pelvis was more involved for the metastatic process in prostate neoplasm. Using Dodds and Morgan methods we have establish the frequency of the 9 skeleton regions involved like metastatic site. We haven’t found a significant statistic difference of the range of frequency for the analyzed cancer types. On the other hand, the highest mean anatomic sites number per patient was found in breast cancer (5.7) and prostate cancer (4.8) related to colon (3.3) and lung (3.0) cancers. Conclusions: Even some particularities were evident, in our study, between the metastases distribution in these four cancer types, the data are not sufficient to sustain the existence of a characteristic pattern related to the primary cancer origin. Metastases localization could be, however, related to the metastazation mechanism. A further study of the metastases distribution in relation with cancer chemotherapy and/or radiotherapy will follow, as well as an expert system for automatic analysis of whole body bone scintigraphy.

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CA15-3 and bone scintigraphy in the follow-up of breast cancer Z. Rajkovaca (1,2), J. Mijatovic (1), A. Matavulj (2), P. Kovacevic (2), N. Ponorac (2). (1) Department of Nuclear Medicine Clinical Center Banja Luka, (2) Department of phisiology, Medical faculty Universiti of Banja Luka, Banja Luka, Bosnia and Herzegovina. Aim: CA15-3 is the most widely used tumor marker in monitoring breast cancer patients. CA15-3 has been suggested as a marker of distant metastasis in breast cancer. Breast cancer commonly metastasizes to bones. Bone scintigraphy is commonly performed in the staging and postoperative monitoring of breast cancer. The aim of this study was to evaluate the need for bone scintigraphy as a routine staging procedure in follow-up the patients with breast cancer in relation to serum CA15-3 levels. Material and Methods: We retrospectively reviewed the case records of 162 consecutive patients (median age 51.6 years, range 27-71 years) with treated and pathologically proven breast cancer. CA15-3 was measured by radioimmunoassay. Bone scintigraphy was done 3 hours after intravenous application of 1125 MBq 99mTc dicarboxi-propan-diphosphonat (DPD). Results: In 123 (75%) patients CA15-3 was normal (5.3 - 30 U/ml). In 39 patients (25%) CA15-3 was elevated (30.1 - 240 U/ml). 53 out of 162 (35.6%) BSs demonstrated metastatic bone disease. The BS was positive in 2 of the 25 patients with CA15-3 < 10 U/ml, 17.3 % (17/98) of those with CA15-3 values between 10-30 U/ml. This resulted in negative predictive value of 83%, respectively. Positive BS was in 82% (32/39) patients with CA15-3 values > 30 U/ml which resulted in positive predictive value of 82%, respectively. Conclusion: The existence of normal CA15-3 is not sufficient to exclude the possibility of bone metastases but decrease the need for bone scintigraphy. Bone scintigraphy should be reserved for evaluation of patients with CA15-3 value < 30 U/ml and presenting symptoms suggestive of bone metastases. The serum CA15-3 value of > 30 U/ml is highly predictive of bone metastases and these patients need bone scintigraphy.

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99mTc MIBI SPET in revealing underlying neoplasms in brain hemorrhages F. Minutoli (1), F.F. Angileri (2), S. Cosentino (3), R. Lipari (3), A. Vieni (3), A. Germano’ (2), S. Baldari (3). (1) Department of Radiological Sciences, University of Messina, (2) Department of Neurological Sciences, Psychiatry and Anesthesiology, University of Messina, (3) Nuclear Medicine Unit of the Department of Radiological Sciences, University of Messina. Aim: Frequency of intraparenchymal cerebral haemorrhages (ICH) due to an underlying neoplasm (mainly malignancies) ranges between 0.8 and 7.4%. In these cases, bleeding is the first clinical sign of neoplastic disease in 9-58% of patients. Neuroimaging is not always able to clearly identify a tumour-related ICH, especially early after bleeding. We investigated the effectiveness of 99mTc MIBI SPET in early identification of tumour-related ICH. To our knowledge, there isn’t any paper concerning this issue. Material and methods: Between March 1999 and March 2001, we collected 21 consecutive patients harbouring acute onset of clinical deterioration caused by intracranial haemorrhage as demonstrated by emergency CT scan that also met the following criteria: a) clinical data (young age, negative medical history for arterial hypertension, diabetes and anticoagulant therapy) or CT findings (atypical location, irregular shape, disproportional large oedema) suggested a neoplastic haemorrhage; b) the patient didn’t have any known brain neoplasm c) a single lesion was revealed by cranial CT scan d) emergent craniotomy was not required. Pituitary haemorrhages were excluded. 15/21 patients had non-neoplastic hemorrhages (11 vascular degenerative diseases, 2 cavernous angiomas, 1 artero-venous malformation and 1 sinus rectus thrombosis) and 6/21 patients had neoplastic hemorrhages (3 metastases, 2 glioblastomas multiforme and 1 angioblastic meningioma) as diagnosed by clinical and neuroradiological (MRI and/or DSA) follow-up or direct hystological typing. All patients underwent 99mTc MIBI SPET within 48 hours from the bleeding. Images were acquired 10 min. and 3 h after iv injection of 740MBq of 99mTc MIBI. After spatial localisation of the lesion, using CT as a guide, a region of interest (ROI) was drawn encompassing the hottest part of the lesion. MIBI index was obtained as the ratio between counts in the lesion ROI and counts in its contralateral homologous “mirror image”. Early ratio (ER), delayed ratio (DR) and retention index (i.e. ratio between DR and ER) were calculated. Results: No relevant uptake was detected in both early and delayed images in all patients with non-neoplastic brain haemorrhage (ER 0.89-1.2; DR 0.89-1.18; RI 0.9-1.07) whereas abnormal uptake was revealed in all patients with tumour related ICH (ER 2-3.95; DR 1-2; RI 0.381). There was a clear cut-off in ER between the two groups. Conclusion: Despite few limitations (small number of patients, lack of bleeding low-grade gliomas), this study suggests that 99mTc MIBI SPET could be an effective noninvasive tool in early identification of tumour-related ICH.

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Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition

Assessing Salivary Function in Head and Neck Post XRT Cancer Patients

LYMPHOSCINTIGRAPHY 1

T.A. Riauka (1), S.A. Jackson (1), N. Jha (2), A.J.B. McEwan (1). (1) Department of Oncology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada, (2) Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.

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Radiation-induced xerostomia is a significant complication of radiation therapy used in the management of head and neck cancers. A clinical trial being performed at our Institute proposes to reduce the morbidity for these cancers by transferring one of the submandibular glands to the submental space such that that gland can be shielded during postoperative external radiation therapy (XRT). Over 100 patients have been enrolled into this clinical trial to date. Images were obtained on a gamma camera after i.v. injection of 350MBq of 99mTcO4. Each patient underwent 6 dynamic salivary scans (pre-surgery; post-surgery pre-XRT; as well as immediately, 3 month, 6 month, and 18 month post XRT). The scanning protocol consisted of a dynamic acquisition of 40, 30 second frames with a sialagogue (lemon juice) administered at the 12 minute mark of the scan. Regions of interest (ROI’s) for the major salivary glands were applied to each scan and time activity curves were generated from the background corrected ROI’s. Each time activity curve was used to calculate two parameters (referred to as uptake and response) to characterize the function of the gland. In addition to nuclear medicine scanning, each patient also underwent manual salivary flow collection at each of the 6 time points. For the enrolled patients, unshielded glands suffered significant loss of function post XRT (p<0.05) which was clearly demonstrated by both nuclear imaging and manual salivary flow collection. In contrast, the transferred, shielded submandibular gland retained near-normal function that was also clearly demonstrated by the two assessment methods. Maintenance of salivary function is paramount for the quality of life for head and neck cancer patients undergoing external radiation therapy. Nuclear medicine imaging provides a non-invasive, quantitative technique for assessing salivary function for this patient population.

A.. Benitez (1), A. Cortes (1), M. Fernandez (1), A. Escobedo (2), D. Azpeitia (2), E. Benito (2), A. Moreno (3), J. Mora (1), J. Martin-Comin (1). (1) S. Medicina Nuclear, Hospital Universitari de Bellvitge, (2) UFM, ICO, (3) S. Anatomia Patológica, Hospital Universitari de Bellvitge, Hospital Universitari de Bellvitge, Barcelona, Spain.

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N. Boucekkine (1), S. Boudjemai (2), R. Korso (1), A. Benzaid (2), Z. Bouhila (2), K. Belazoug (1), N. Lebkiri (1), S.E. Bouyoucef (1). (1) Department of Nuclear Medicine ,Bab El Oued Hospital,Algiers, (2) Radiopharmaceutical Laboratory ,COMENA ,Algiers. Aim: Several studies have reported that the percentage of free PSA can increase the specificity of total PSA in diagnosis of prostate cancer when serum PSA levels are mildly elevated. The aim of the present study was to evaluate the utility of measuring the percentage of free PSA in the differential diagnosis between prostate cancer (PC ) and benign prostate hyperplasia ( BPH ). Material and methods: serum total PSA levels were determined in 120 patients with BPH aged from 50 to 88 years (68 ± 10 ) and 120 patients affected by newly diagnosed , untreated primary PC aged from 50 to 91 years ( 70 ± 9 ).The diagnosis of BPH was made based on digital rectal examination , transrectal ultrasonography and histologically confirmed by biopsy or after transurethral resection of the prostate . The diagnosis of prostate cancer was achieved by echography guided biopsy. The percentage of free PSA was determined in 180 patients having their total PSA in the range of 2 – 20 ng/ml ( 120 with BPH and 60 with PC ). Total and free PSA were measured using an immunoradiometric assay. Results: No patient with BPH had a total PSA > 20 ng/ml. Over the 2 – 10 ng/ml total PSA range, the mean of total PSA values were not different between patients with BPH and PC ( 6.44 ng/ml and 6.63 ng/ml respectively ). Over the 10 – 20 ng/ml total PSA range, the difference between mean total PSA values was not significant ( 12.48 and 14.74 ng/ml respectively). Whereas the difference for mean free to total PSA ratio was highly significant ( 27 % for BPH and 9 % for PC ). The differentiation between PC and BPH was best achieved by using a cut off 14 % for the ratio of free/ total PSA. Conclusion: This study confirm that the free/ total PSA ratio improve the specificity of the differential diagnosis , gives an aid in early detection of prostate cancer and may lead to a reduction in the number of unnecessary prostate biopsy.

The aim of the work was to evaluate the results of our two years experience in the clinical application of sentinel node radioisotopic localisation and biopsy in breast cancer patients Material and method: 176 patients with breast cancer (T1N0M0) have been examined (82 non palpable). Mean age was 57 years, range 29-87. In all cases anterior and lateral breast views were obtained 2 h post administration of 1 ml of albumin nanocolloid labelled with 3 mCi (111MBq) of 99mTc. Sentinel node location was labelled on the skin and surgical detection was performed at 24 h in palpable tumours and at 4 h in non-palpable. Histopathological analysis included Hematoxiline- Eosine ( HE ), Inmunohistochemistry ( IHQ ) and PCR. Results: The SN was scintigraphically and surgically identified in 152/176 ( 86% ) and 163/176 cases ( 93% ), respectively. The SN was not scintigraphically seen in 24/176 ( 14% ) of cases, but in15 out of these 24 cases ( 63%) was surgically localised. Histology was available in 159 patients. The SN was positive in 57 (36%) and in 21 out of the 57 was the only metastatized, in 8 p other axillary lymph nodes were also involved and in 2 p metastasis were limited to the internal mammary chain. Concerning the histology method used, in 122 cases HE and PCR were performed and PCR was positive in 14 p in whom HE had been negative; in 109 p PCR and IHQ were performed, PCR was positive in 10 p in whom IHQ had been negative . Conclusion: SN radionuclide localisation and biopsy has avoided lymphadenectomy in 72% of the patients, reducing health and morbidity. PCR has modified patients staging in 24 cases.

Sentinel lymph node detection in patients with differentiated thyroid carcinoma L. Rettenbacher, H. Kaessmann, A. Hofmann, G. Galvan. Department of Nuclear Medicine, Landeskliniken Salzburg. Aim: The aim of the study was to evaluate sentinel lymph node mapping in patients with differentiated thyroid carcinoma, because regional lymph node metastases are found in two thirds of the patients with papillary thyroid carcinoma and in 25% of the patients with follicular thyroid carcinoma. Materials and Methods: Lymphoscintigraphy was performed in 15 patients with suspected differentiated thyroid carcinoma. The initial diagnoses was made by sonography, Technetium99m pertechnetate scintigraphy and fine-needle aspiration cytology. Palpation and ultrasound revealed no metastases prior to surgery. A total volume of approximately 0.5 ml of 40 MBq Tc-99m nanocolliod was divided into four aliquots and injected into the primary tumour. Planar anterior and oblique images were obtained up to 60 min after tracer administration. At surgery, first the primary tumour was removed and in cases were the intraoperative frozen section was positive for malignancy, a total or near-total thyreoidectomy was performed. The SLNs were identified and removed with the help of a hand-held gamma probe. Results: In 11 of 15 patients one or more SLNs could be visualized using lymphoscintigraphy and in 12 patients one or more SLNs were detectable intraoperatively using a gamma probe. In all 7patients with papillary thyroid carcinoma a SLN was detectable. In 3 patients with follicular carcinoma and in one patient with an adenoma no SLN was detectable with scintigraphy as well as intraoperatively using a gamma probe . In two patients we detected a SLN on the ipsi- and contralateral side. There were no false negative findings. Conclusion: These preliminary results show that the SLN detection in patients with differentiated thyroid carcinoma is possible using the intratumoural injection of Tc-99m nanocolloid.

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Poster Presentation

Clinical evaluation of measuring percent free prostate specific antigen in differentiating benign prostatic hyperplasia from prostate cancer.

Two Years Experience of Clinical Application of Radioactive Sentinel Node Localisation and Biopsy in Breast Cancer

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S. Crnkovic (1), D. Huic (1), S. Tezak (1), M. Poropat (1), D. Dodig (1), J. Jakic-Razumovic (2), J. Unusic (3). (1) Clinical Department of Nuclear Medicine and Radiation Protection, University Hospital Centre Zagreb, (2) Department of Pathology, University Hospital Centre Zagreb, (3) Clinical Department of Surgery, University Hospital Centre Zagreb.

B. Zerahn (1), T. Buhl (1), M. Hutchings (1), N. Al-Suliman (2), F. Rank (3), E. Friis (2), B. Hesse (1). (1) Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., (2) Department of Breast- and Endocrine Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., (3) Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Identification of sentinel node in melanoma and breast cancer using lymphoscintigraphy combined with gamma probe detection

Aim: We evaluated the potential of the gamma ray detecting probe in combination with lymphoscintigraphy, to detect sentinel lymph nodes (SLN) in patients with melanoma and breast cancer. Materials&Methods: A total of 50 patients were studied, 21 of them with breast cancer and 29 melanoma patients. Tc-99m HSA colloid was peritumorally injected around four corners of the breast lump, 0.3-0.5 mCi in the same volumen, and as a subcutaneous injection in melanoma patients, in 4-8 points around the primary tumor or the surgical scar of the previous excision. Dynamic, early and late static images of the lymphatic areas were acquired with the particular attention to the lateral and oblique projections, the sentinel node was scintigraphically documented and its site was marked on the skin. We confirmed the exact localization of the SLN using gamma probe both before and during the surgery. Removed nodes were histopathologically and immunohistochemically evaluated. Results: This procedure revealed SLN, matching the preoperative localization with the intraoperative gamma probe findings, in all patients.. Quantifying the radioactivity of the SLN in comparison with the background tissue, counts were apriximatelly 2-5 times higher before the surgery, and almost twice as the preoperative counts intraoperatively. In breast cancer patients, intraoperative (ex tempore) and final pathohistological diagnosis were both negative in 16 pts (76.2%), positive in 3 pts (14.3%), and false negative in 2 pts (9.5%). In 12 pts we performed complete axillary lymph node disection, finding the SLN as the only metastatic site in 4 pts (33.4%), in 7 pts (58.3%) with negative SLNs axilla nodes were also negative, and in one pt (8.3%) both SLN and further axillary lymph nodes were positive. In melanoma pts, 17 pts were true negative (58.6%), 7 pts (24.1%) true posititve, and 2 pts (6.9%) false negative. In 2 pts (6.9%) SLNs were intraoperativelly suspect, but finally negative, comprising siderophages, but not melanocytes, and in 1 pt (3.5%) suspect SLN was positive. Conclusion: Our experience indicates that preoperative lymphoscintigraphy which allows accurate identification of the SLN in association with pre- and intraoperative use of gamma probe maximise the success of sentinel node localization.

Factors associated with scintigraphic non-visualisation of sentinel nodes in breast cancer

Aim: To identify factors associated with scintigraphic non-visualisation of sentinel nodes in patients with invasive carcinoma of the breast using 99mTc-Nanocoll. Materials and methods: We studied 307 consecutive cases of sentinel node (SN) scintigraphy in patients with breast cancer. Planar scintigraphic images were obtained with a gamma camera (field-of-view 30x30 cm, acquisition time 10 minutes) in anterior and lateral projections 2 to 18 hours after tracer injection. A total dose of 20 to 110 MBq 99mTc-Nanocoll was given as either periareolar (mainly upper lateral quadrant) or peritumoral tracer injections. Factors analysed were: Location of tracer injection, patient age, tumour size, tumour location, tumour histology, tracer dose, and time between injection and imaging. In 40 patients no SN could be visualised (13.0 %). In 15 of these patients a SN was detected by probe during surgery. Results: The table below shows the number of patients in each group of variables. Relative risk (RR), 95% confidence interval in brackets, and significance level for scintigraphic nonvisualisation of a SN are shown. Significantly increased RR is indicated by **. Only peritumoral injection and age W 60 years proved to be independent variables after stratification and adjusting for confounders. Variable

n

peritumoral injection** age < 60 years tumour diameter < 15 mm upper lateral quadrant** intraductal carcinoma dose < 60 MBq < 8 hours from inj to scint

138 146 167 173 245 221 276

RR of non-visualisation of SN 1.85 (1.47-2.34), p<0.001 1.41 (1.11-1.78), p<0.02 n.s. 1.46 (1.09-1.95), p<0.03 n.s. n.s. n.s.

Variable

n

periareolar injection age W 60 years** tumour diameter W 15 mm all other regions all other types: dose W 60 MBq W 8 hours from inj to scint

169 161 140 134 62 86 31

Conclusion: Scintigraphic non-visualisation in breast cancer is more frequent in elderly patients and after peritumoral compared to periareolar injection of 99mTc-Nanocoll. Tumour location may contribute to non-visualisation too, but the data provided in this study are not conclusive. Time interval from injection to imaging, tumour histology, and tumour size were not significant factors regarding SN visualisation in this context.

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M. Papos (1), J. Varga (2), T. Sera (1), M. Lazar (1), J. Olah (2), I. Korom (2), G. Mohos (2), K. Kapitany (2), L. Pavics (1). (1) Department of Nuclear Medicine of the University of Szeged, (2) Department of Dermatology of the University of Szeged, Szeged, Hungary.

R.S. Bridwell, J. Montilla, C. Mulligan. Walter Reed Hospital, Washington DC, USA.

The value of gamma probe guidance in malignant melanoma patients

Aim: Localisation of sentinel lymph node (SLN) plays a crucial role in the planning of surgery in melanoma malignum (MM) patients. For SLN localisation the diagnostic value of the preoperative gamma camera technique and the intraoperative methods (gamma probe and blue dye staining) was analysed. Material and Methods: One hundred and twenty-two patients (71 females, 51 males, mean age: 55 years, range: 28-77 years) with MM verified by histology were involved into this study. Characterisation of primary tumour were the follows: localisation: trunk: 64, extremities: 56, neck: 2, Clark classification: I:2, II:42, III:62, IV:13, V:3, mean thickness: 1.979 mm, range: 0.228-9.956 mm. Twenty-four hours before surgery, SLN was localised visually by gamma camera technique. For intraoperative SLN localisation, gamma probe and blue dye staining methods were applied. Results: Preoperatively, 143 SLN were detected in 121/122 patients (99%). One SLN was found in 100 cases, 2 SLN were verified in 20 patients and 3 SLN in 1 patient. SLN was localised in one anatomical region in 109 cases and in two regions in 12 patients. During the intraoperative SLN mapping, gamma probe method revealed SLN in all patients (100%), altogether 153 SLN were found: one SLN in 94, 2 SLN in 25 and 3 SLN in 3 cases. Blue day method visualised SLN in 111 cases (91%). In a total, 141 SLN were detected: one SLN in 86, 2 in 21, 3 in 3 cases and 4 in one patient. In 9 cases, the stained SLN was able to localise only with the help of gamma-probe. No malignant involvement of the SLN was detected by histology in 81 patients. On the bases of clinical follow-up, the lymph node status of these patients was negative for malignancy. The SLN was found to be positive for MM involvement by histology in 41 cases. Block dissection was performed only in these patients: the histological analysis of the block lymph nodes showed malignancy in 14 cases. Conclusion: Preoperative SLN localisation is helpful for the planning of the surgery. Intraoperative gamma probe method was found to be the most accurate technique for SLN localisation in MM patients. The SLN biopsy facilitates the elective block dissection in MM patients.

Radioimmunoguided surgery in patients with lung cancer: a preliminary report of the use of a hand held intraoperative gamma probe with Tc-99m depreotide as a molecular probe.

Background: Staging of lung cancer is an important undertaking and can include invasive and non-invasive modalities. Patients with stage 1 disease after surgical resection have only a 60-80% five-year survival. It is thought that the differences in survival rates are due to an understaging of the disease. Technetium 99m depreotide is a FDA approved radiopharmaceutical for use in patients diagnosed with solitary pulmonary nodules. It differentiates tissue (benign from malignant) based on somatostatin receptor activity (receptor subtype 2,3,5). In this protocol we seek to evaluate the use of this Technetium 99m based radiopharmaceutical with the hand held intraoperative gamma probe to identify tissue that is likely to harbor metastatic disease. Procedure: Patients undergoing a diagnostic or therapeutic thoracotomy were enrolled in the protocol. Patients were injected with 20 mCi of Tc99m depreotide intravenously and imaged using SPECT techniques. Patients underwent standard operative management 18-24 hours after injection. After the tissue was removed from the body it was examined with the hand held gamma probe (CTRAK-ten second counts). The tissue was subjected to standard pathologic evaluation. Tc-99m depreotide ratios were obtained using a region of interest encompassing the parenchyma abnormality normalized to a similar area on the contralateral lung. Gamma probe count ratios were generated by dividing the total counts from the tissue by the total counts from the subcutaneous fat (background). Findings: Number of samples Image ratio Gamma count ratio range Median Standard deviation

Primary tumor Negative nodes 5 ( 4 mal, 1 benign) 10

Positive Nodes 4

1.6-8.71

0.1-1.74

1.17-1.8

3.82 .56

0.48 .26

1.52

P=0.036

Conclusion: The intraoperative gamma probe may have the ability to differentiate tissue that is more likely to harbor metastatic disease in-patients with lung cancer who undergo preoperative injection with Technetium 99m depreotide.

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n LYMPHOSCINTIGRAPHY 1 Use of lymphoscintigraphy and surgical gamma probe to determine the regional involvement in gastric cancer. N.O. Kucuk (1), M. Ozmen (2), B. Zulfikaroglu (2), G. Aras (1), M. Koc (2), A. Soylu (1), E. Ozkan (1). (1) Department of Nuclear Medicine of Ankara University,Ankara/Turkey., (2) Depertment of Surgery of Ankara Numune Hospital,Ankara/Turkey. Regional lymph node involvement is a critical stage in prognosis of gastric cancer. CT is widely used for evaluation of lymph nodes. But sensitivity and specificity of this method is low. Aim: The aim of this study was to assess the efficacy of lymphoscintigraphy to demonstrate lymphatic drainage and the value of surgical gamma probe to detect regional lymph node in gastric cancer. Material-Method: 44 patients ( 32M, 12F, age between 43-70) with gastric cancer were included in this study. Using an endoscopy, a total of 148 MBq Tc-99m Lymphoscint was injected in 4 locations peritumorally 2-3 days before the operation. Anterior, posterior and lateral images were taken at 5, 15, 30, 45 min after the injection. The surgical gamma probe was used in operable patients. Results: Extensive abdominal uptake was observed in 44 patients with lymphoscintigraphy. They evaluated as operable according to CT. All of them were undergone surgery but 34/44 were accepted as inoperable because of multiple metastasis and SGP was not used in these patients.Lymph drainage were shown with lymphoscintigraphy clearly before operation.In 10/44 patients lymph nodes were resectable, total gastrectomy and D3 lymph node dissection were made.These lymph nodes were evaluated as metastatic lymph nodes with histopathological examination.Lymph drainage were detected with SGP and lymphoscintigraphy in these patients. Conclusion:Lymphoscintigraphy by peritumoral injection via endoscopy and the use of surgical gamma probe is a promising technique for the detection of regional lymph node involvement in gastric cancer.

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Radioguided sentinel lymph node biopsy in breast cancer patients M. Lazar (1), GY. Lazar (2), T. Sera (1), M. Papos (1), A. Paszt (2), R. Hajnal-Papp (3), A. Balogh (2), L. Pavics (1). (1) Department of Nuclear Medicine, (2) Department of Surgery, (3) Department of Pathology of the University of Szeged, Szeged, Hungary. Radioguided sentinel lymph node biopsy in breast cancer patients Aim: Oncological status of axillary lymph nodes in breast cancer patients has a high prognostic value and determines the postsurgical treatment. According to the sentinel node (SN) concept the oncological status of the first draining node is representative for the other axillary nodes. SN can be localised preoperatively by gamma camera technique, and intraoperatively by vital blue dye and gamma probe techniques. The aim of the study was to determine the diagnostic value of these methods in SN localisation. Material and Methods: Twenty-one female (mean age: 50 years, range: 37-72 years) with palpable and histologically proved breast cancer (mean tumor size: 3.5 cm, range: 0.5-5 cm) were involved in the study. The day before the operation all patient underwent SN localisation using a gamma camera, after peritumoral administration of 99mTc-labelled nanocolloid. For intraoperative SN localisation vital blue dye technique and intraoperative gamma probe guidance were used. Axillary block dissection and separate histopathological analyses of SN and the axillary lymph nodes was performed in every case. Results: Gamma camera and gamma probe technique detected SN in 18/21 patients (86 %, 24 SNs), and blue dye technique showed SN also in 18/21 patients (86 %, 25 SNs), but in one case only the gamma probe method, and in another case only the blue dye technique was successful. In one patient the two methods identified different SN in the axilla. Together with these techniques SN was localised in 19/21 patients (90%, 28 SNs). The two techniques showed the same result in 15/21 patients (71 %, 17 SNs). The histological investigation of SN revealed malignant involvement in 4/19 cases (21%). Axillary malignant involvement was found in two of these patients and in one of the patients with undetected SN. All patient with negative SN histology showed also a negative axillary oncological status. Conclusion: Preoperative localisation of SN is necessary for planning the surgery. The overall sensitivity of SN detection was 90 %. The combination of intaoperative gamma probe localisation and blue dye technique could detect more SNs than one technique alone. Intraoperative localisation and histologycal analysis of SN might result the reduction of unnecessary block dissections in breast cancer patients. In patients with undetectable SN axillary block dissection should be performed.

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Impact of Sentinel Node (SN) Micrometastasis in Patients with Invasive Breast Cancer

Value of sentinel lymph node detection by using double tracer lymphoscintigraphy in squamous cell carcinoma of the head and neck

L.F. Feggi (1), L. Bergossi (2), E. Basaglia (2), G. Soliani (2), N. Prandini (1), P. Querzoli (3), E. Pozza (2), P. Carcoforo (2). (1) Nuclear Medicine , St. Anna Hospital, Ferrara, Italy, (2) General Surgery, University of Ferrara, Ferrara, Italy, (3) Pathology, University of Ferrara, Ferrara, Italy.

M. Südmeyer (1), ST. Höft (2), W. Brenner (1), W.U. Kampen (1), N. Czech (1), S. Maune (2), E. Henze (1), C. Muhle (1). (1) Clinic of Nuclear Medicine of Kiel University Hospital, (2) Clinic of Otorhinolaryngology of Kiel University Hospital, Kiel, Germany.

In early breast cancer, 25%-35% of patients had bad prognosis in spite of the absence of histologically proved nodal metastases: this could come from the presence of locoregional lymph nodes micrometastases, missed with haematoxylin-eosin (HE) staining without lymph node multiple sectioning. SN biopsy allows diagnosis of lymph node micrometastases because the SN can be submitted to HE staining and immunohistochemistry (IH) with multilevel sectioning. From November 1997 to October 2001 we performed SN biopsy in 210 breast cancer patients (T1N0M0; mean tumoral dimension:1.3 cm). Each locoregional lymph node was submitted to HE staining with IH and multilevel sectioning (100 micron interval). In our experience we studied several prognostic indexes to stage primary breast lesion: breast cancer dimension, peritumoral vascular invasion, presence of micro or macrometastasis, kind of micrometastasis. We identified 18 micrometastatic SNs in 210 patients (9%): 1 of these had non-SN metastasis; this patient had breast lesion larger than 2 cm and peritumoral vascular invasion. Other patients with SN micrometastasis showed T1 breast lesion, no peritumoral vascular invasion, undercapsular SN micrometastasis without non-SN metastases. We also identified 24 patients with SN (11,5%) macrometastases: 13 of them showed 1 or more axillary lymph nodes metastases. Prognostic meaning of presence of SN micrometastases is not clear. Many authors consider SN micrometastasis to have a lower impact when compared with SN macrometastasis; in spite of this, when we find SN micrometastasis, we perform adjuvant therapy following standard schedule of treatment. SN biopsy allows us to avoid understaging. Presence of SN micrometastasis with nSN metastases is uncommon (5,5% in our experience).A small breast lesion dimension, a good kind of SN micrometastasis (capsular/undercapsular, with better prognosis) and no peritumoral vascular invasion suggest the absence of non-SN metastases in patients with micrometastatic SN. In this kind of patients, axillary lymph nodes dissection could be avoided.

Aim: The site and number of lymphatic drainige may facilitate the therapeutic procedure in patients with head and neck tumors. The aim of this study was to determine the optimal time to identify the site of lymphatic drainage, to evaluate the contrast and the target to background ratio of sentinel lymph nodes (SLN) over a period of 24 hours. Materials and Methods: Dynamic lymphoscintigraphy was performed using a double tracer technique in a total of 31 patients. In all patients 100 MBq 99mTc-nanocolloid were injected in quadrants around the primary tumor site. Planar images from anterior, right and left lateral were obtained with a large-field-of-view gamma camera at 0.5 h, 4 h, 6 h and 24 h p.i.. Lymphatic drainage was assessed by visual inspection and assigned to six cervical compartments. In addition, evaluation of count statistics and target to background ratio was performed for each lymph node by conventional ROI(Region-of-interest)-technique. Results: Lymphatic drainage was identified in 23 patients (75%). Out of 40 detected lymph nodes (100%), 28 LN (75%) were visualized at 0.5 h, 40 LN (100%) at 4 h and 6 h and 26 LN (65%) at 24 hours p.i.. The count statistics demonstrated maximum intensity at 4 h, with decreasing values at 6 h and 24 h. The target to background ratio reached highest values at 6 h p.i.. time 0,5 h 4h 6h 24 h

SLN (n=) 28 40 40 25

target to background (ratio) 2,7 4,2 4,6 2,9

intensity (counts) 16,5 20 17,5 4

Bilateral and contralateral lymphatic drainage was most reliably detected at 4 h and 6 h p.i., but were missed in 2/31 patients (6%) on 0.5 h and 24 h scans. Conclusion: In lymphoscintigraphies using a double tracer technique, SLN can be detected less sensitive after radionuclid injection due to high background activity. Although this technique simplifies the localization of SLN to anatomical regions, recently published data indicate that lymphoscintigraphies obtained by using a gamma probe or solely peritumoral colloid injection technique further improve the sensitivity in SLN detection.

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Y.W. Chen (1), M.F. Hou (2), Y.C. Lai (1), K.L. Chang (1), C.C. Hsu (1), G.C. Liu (3). (1) Department of Nuclear Medicine of Kaohsiung Medical University, (2) Department of Gastroenterologic Surgery of Kaohsiung Medical University, (3) Department of Radiology of Kaohsiung Medical University, Kaohsiung, Taiwan..

G.L. Ross (1), T. Shoaib (1), D.S. Soutar (1), D.G. MacDonald (2), R.G. Bessent (3), H.W. Gray (3). (1) Department of Plastic Surgery, Canniesburn Hospital, Glasgow, UK, (2) Department of Oral Pathology, Glasgow Royal Infirmary, Glasgow,UK, (3) Department of Nuclear Medicine, Glasgow Royal Infirmary, Glasgow, UK.

Tc99m phytate, “in vivo calcium chelating fine colloid” agent which has been used for hepato-splenoscintigraphy previously, will be introduced to detect sentinel lymph nodes in lymphoscintigraphic mapping of breast CA. And we compare phytate with unfiltered sulfur colloid to evaluate efficiency of detection rate in this article. Patients and Methods: We collected age and stage matched two groups of patients with clinical diagnosis of breast CA. Each group has 12 females and average age is 44 +/- 3 years old. Tc99m phytate (Daiichi Radioisotope Lab, Japan) was prepared by tagging cold kit in our laboratory. Each group of patients received subdermal injection of Tc99m phytate or unfiltered Tc99m sulfur colloid in selected corners of breast lump, respectively. Activity of 0.2-0.3 mCi radiopharmaceutics with 0.5 cc. in total volume was recommended. Well-established dynamic and static vertical angle imaging protocols (Siemens E CAM, LEHR) were performed for lymphoscintigraphy. Results: Between two groups, most of breast lumps was located in the OUQ of breast and axillary sentinel lymphatic basin drainage was seen mainly. Comparison with detection rate of sentinel lymph nodes, the group of Tc99m phytate (100%) is better than unfiltered Tc99m sulfur colloid (92%). Multiple tiers of axillary lymph nodes were usually visualized in the group of Tc99m phytate. However, there was “skip” phenomenon of colloid between tiers of nodes in one case of Tc99m phytate group on the dynamic image. We intend to conduct large-scale survey to justify our findings. Conclusions: Due to convenient preparation and good detection rate, Tc99m phytate is indeed a good alternative agent for detecting sentinel lymph nodes in breast CA.

OBJECTIVES: The possible role of sentinel node biopsy (SNB) patients to upstage the clinically N0 neck in patients with oral and oropharyngeal squamous cell carcinoma was investigated. METHODS: Patients with primary untreated head and neck squamous cell carcinoma accessible to injection were enrolled into the study. Investigation was restricted to patients with clinically N0 necks. SNB was performed after radiocolloid and blue dye injection. Preoperative lymphoscintigraphy and the peroperative use of a gamma probe identified hot/radioactive sentinel nodes and visualisation of blue stained lymphatics identified blue sentinel nodes. If the sentinel node was negative there was no further treatment to the neck. If the sentinel node was positive a therapeutic neck dissection was performed. RESULTS: SNB was performed on 57 clinically N0 necks. Sentinel nodes were harvested in 50/57. Fifteen necks were upstaged by sentinel node biopsy and 35 were staged sentinel node negative. 104 sentinel nodes were harvested, 62 nodes were hot and blue, 30 nodes were hot and 12 nodes were blue only. 21/22 (95%) of positive sentinel nodes were identified as hot and 19/22 (86%) were identified as blue. There has been a mean follow up of 16 months and one patient has developed subsequent disease when the sentinel node was negative using the full pathological protocol. The sensitivity of the technique is therefore 15/16 (94%). CONCLUSIONS: SNB can be used to stage the clinically N0 patient with early nodal disease. The use of lymphoscintigraphy, radiocolloid and gamma probe are essential in the identification of sentinel nodes. Its use as a standard of care in head and neck squamous cell carcinoma requires the results of longer follow up observational trials.

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Tc99m Phytate- Another Agent Choice for Detecting Sentinel Lymph Nodes in The Lymphoscintigraphic Mapping of Breast CA

Detection of occult metastases in the sentinel lymph node by reverse transcriptase-polymerase chain reaction (RT-PCR) in earlystage melanoma patients F. Pons (1), S. Vidal-Sicart (1), S. Puig (2), M. Ortega (1), F. Martín (1), A. Vilalta (2), R. Rull (3), J. Palou (2), T. Castel (2). (1) Department of Nuclear Medicine, Hospital Clínic, University of Barcelona, (2) Department of Dermatology, Hospital Clínic., (3) Department of Surgery, Hospital Clínic, Barcelona, Spain. Sentinel lymph node (SLN) detection in early-stage Malignant Melanoma patients has been demonstrated as a very useful technique for optimising the selection of patients for lymphadenectomy. However, in a reduced number of cases false negative results are obtained, resulting in the appearance of recurrences. Aim: To study the mRNA expression of tyrosin (a melanoma associated antigen) in the SLN in order to improve the detection of occult metastases. Materials and Methods: We studied 112 patients (54 men, 58 women) suffering from Malignant Melanoma without palpable lymph nodes, Breslow’s thickness more than 0.76 mm, to be treated surgically. Lymphoscintigraphy was performed the day before surgery by injecting 74-111 MBq of Tc99m-nanocolloid in the area surrounding the lesion. Dynamic and static images were obtained. A hand-held gamma probe was used during surgery to precisely localise the SLN which was harvested and analysed. Pathologic studies included: routine histopathologic examination with hematoxilin-eosine staining (H&E), immunohistochemistry (IHC) with S100 and HMB-45 and reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase, a mRNA marker of melanoma. Patients follow-up after surgery ranged from 3 to 4.4 years. Results: SLN was positive for metastases by H&E in 22 patients (19.6 %), by IHC in 21 patients (18,6 %), and by RT-PCR in 62 patients (55.4 %). Seventeen patients died during follow-up. In 10 of these cases the results that had been obtained by H&E, IHC and RT-PCR were concordant. In the remaining 7, H&E and IHC had been negative while RT-PCR results were positive for metastases. Patients whose SLN was positive by RT-PCR had a shorter disease-free survival compared with those whose SLN was RT-PCR negative. Conclusion: H&E staining and IHC underestimate the true incidence of occult metastases in the SLN. The detection of tyrosinase mRNA by RT-PCR reflects more accurately the presence of micrometastases and it is also a prognostic factor in Malignant Melanoma patients. Supported by grant FIS 00/1023

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Sentinel node biopsy to target lymph node dissection for the clinically negative neck in head and neck cancer.

Sentinel lymph node detection in patients with head and neck malignant melanoma S. Vidal-Sicart (1), M. Ortega (1), F. Martín (1), R. Rull (2), A. Vilalta (3), F. Cuéllar (3), J. Palou (3), T. Castel (3), F. Pons (1). (1) Nuclear Medicine Department, Hospital Clínic Barcelona, Spain, (2) Surgery Department, Hospital Clínic Barcelona, Spain, (3) Dermatology Department, Hospital Clínic Barcelona, Spain. In recent years, sentinel lymph node (SLN) identification by using preoperative lymphoscintigraphy and a hand-held gamma probe in malignant melanoma (MM) patients has presented a great impact in the management of such patients. However in some areas, like head and neck, its application has some technical drawbacks. Aim: To assess the SLN identification rate in patients with head and neck MM. Method: 55 patients (25 women, 30 men) were studied. The day before surgical procedure a lymphoscintigraphy was performed by perilesional intradermal injection of albumin nanocolloid labelled with 99mTc. Dynamic and static images were obtained inmediately after injection. After 2 hours, another set of images was acquired. When the SLN was identified, it was externally marked on the skin with indelible ink. No blue dye was used in the majority of patients in order to avoid a permanent tattoo. The SLN was intraoperatively localized by using a hand-held gamma probe. Results: Lymphoscintigraphy identified the SLN in all patients (100%). A total of 90 SLNs were harvested in 51 patients. In the remaining 4 patients the SLN were not removed due to technical difficulties. In 3 of these, the SLN were within the parotid gland and in the remaining one a lymphatic tissue was harvested instead of a real node. Ten patients (19,6%) presented one or more metastatic SLN. Conclusions: SLN identification in head and neck MM patients is a relatively easy technique. However, its main drawback is the intraparotideal localization of the node and the complexity of the cervical dissection.

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Sentinel lymph node identification in breast cancer patients. Experience in 200 cases.

Sentinel node research by lymphoscintigraphy in malignant melanoma patients.

S. Vidal-Sicart (1), M. Ortega (1), G. Zanón (2), F. Martín (1), J. Pahisa (2), M. Velasco (3), G. Santamaría (3), P.L. Fernández (4), F. Pons (1). (1) Department of Nuclear Medicine, Hospital Clínic Barcelona, Barcelona, Spain, (2) Department of Gynaecology, Hospital Clínic Barcelona, Barcelona, Spain, (3) Department of Radiology, Hospital Clínic Barcelona, Barcelona, Spain, (4) Department of Pathology, Hospital Clínic Barcelona, Barcelona, Spain.

M.G. Caprio (1), A. Bracigliano (1), G. Carbone (1), C. Mainolfi (1), W. Acampa (2), G. Molea (3), M. Salvatore (1). (1) Department of Nuclear Medicine, (2) National Council of Research, Nuclear Medicine Center, (3) Plastic Surgery Division, University of Naples Federico II, Naples, Italy.

The sentinel node (SN) is the first lymph node that recieves the direct drainage from a tumour. Its study allows to assess the presence or absence of lymphatic dissemination in some tumours, in order to avoid unnecessary lymphadenectomies. Aim: To present our experience, both in validation and application stages, of the SN identification technique in breast cancer patients. Method: Two hundred patients with breast cancer (T1 or T2) divided in two groups were studied. The first 105 patients were included in the validation group (group A), and the remaining 95 patients were included in the application group (group B). All patients underwent a lymphoscintigraphy, the day before surgical procedure, by injecting nanocolloidal albumin labelled with 99mTc in or near tumoural mass. During the validation phase, the injection technique varied in several ways (subdermal, peritumoural or intratumoural) to assess which one offered the best results in our hands. During surgical procedure a hand-held gamma probe was used to accurately localize the SN and in a large proportion of cases blue dye was injected to compare both methods. In group A, lymphadenectomy was performed after SN identification in all patients. In group B, lymphadenectomy was performed only when SN was metastatic. Results: Group A (n = 105) * Group B (n = 95) T1 54 55 T2 53 40 Lymphoscintigraphic 91,4% 98,5% identification Intraoperative detection 90,4% 98,5% Sensitivity 92,3% 100% Negative predictive value 97,1% 100% False negative rate 7,6% 0%** * 107 tumours in 105 patients (2 patients had bilateral neoplasms) **In 6 months mean follow-up

Aim and background: Sentinel lymph node (SLN) is currently employed in patients with malignant melanoma (MM) with the aim to spare them from unnecessary LNs dissection. Materials and Methods: We have investigated in our institution 241 patients, 130 M, 111 F, medium age was 50 years (range 14-92). with MM (192 before and 51 after surgical biopsy); two of them had more than one melanoma lesion. In each patient an intradermic injection of approximatevely 10 MBq of Tc-99m nanocoll in 0.1 ml (Nycomed Amersham Sorin; particle size range 3 to 80 nm) was performed around to the MM lesion or surgical scare. Nanocoll quality control was performed by two different TLC systems using Silica gel and whatman n° 1 paper. The element was more in both case methanol/water (85/15 V/V), the radiochemical yield was more than 99.5%. A dynamic acquisition was performed for 20 minutes (20 frame/60 sec) and the study was concluded within 4 hours p.i. Using an external radioactive marker, the skin over the SLN was marked by china ink. Results: A total of 294 SLNs were scintigrafically identified: (117 in the inguinal, 147 in the axillae, 4 in the submandibular, 3 in the laterocervical, 23 in the other sites). In 2 patients no drainage was detected. In 43 patients more than one sentinel node was identified. In 13 patients, with lesions located in the trunk, the tracer drained towards more lymph nodes stations or usexpected lymph nodes (9 cases). Histology and immunoistochemistry diagnosed MM in 25 SLNs, (19 were positive for metastasis at hematoxilin-eosin staining, 5 at Hmb45 and 1 at CD68 immuno-staining). All 25 detected lymphatic basins were excised. In 9 of these basins there was metastatic involvement of at least another lymph node in addition to the SL. The study had follow-up for 6-62 months it suggests only one patient with histological negative SLN, was metastatic after 6 months after surgery. Conclusion: This study confirms the utility to perform scintigraphic detection of SLN in patients with MM, in fact in the majority of cases this procedure drove the surgeon to evaluate the area of drainage, which is impredictable for lesions in the trunk and may be difficult to follow using the patent blue dye procedure only. Furthermore, it indicates in approximatevely 10% of cases a dual drainage from the some lesions, mainly those localized in the trunk. Our future proposal is to compare the results obtained by the follow- up with an investigation group of patients with melanoma who haven’t been subjected to lymphoscintigraphy for the research of SL so that we can obtain more well-founded information that are pertinent to the prognostic value of this technique.

Conclusions: The identification and assessment of SN allow to perform breast cancer surgery without axillary lymphadenectomy in a selected group of patients, markedly diminishing postoperative morbidity. The results obtained in A and B groups show the neccessary learning curve of SN technique.

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M. Ortega (1), S. Vidal-Sicart (1), G. Zanón (2), F. Martín (1), G. Santamaría (3), M. Velasco (3), S. Fuertes (1), J. Pahisa (2), F. Pons (1). (1) Nuclear Medicine Department, Hospital Clinic Barcelona, Spain, (2) Gynaecology Department, Hospital Clinic Barcelona, Spain, (3) Radiology Department, Hospital Clinic Barcelona, Spain.

G. Tartaglione (1), M. Pagan (1), C. Potenza (2), A. Caggiati (2), M. Maggiore (2), F. Gabrielli (2), E. Migliano (2), F. Concolino (3), P. Ruatti (3). (1) Dept. of Nuclear Medicine, Cristo Re Hospital, Rome, Italy, (2) Dept. of Plastic Surgery, IDI, IRCCS, Rome, Italy, (3) Dept. of Oncology, IDI, IRCCS, Rome, Italy.

The most suitable injection technique in the Sentinel Lymph Node (SLN) identification in breast cancer has been extensively discussed in recent years. Some groups have noted better results with subdermic or subareolar injection than with the most frequently used, the peritumoural injection. More recently, the intratumoural radiotracer injection has also been proposed as a good alternative . Objectives: To compare in a consecutive group of patients the feasibility of identifying the SLN in lymphoscintigraphy, depending on the injection technique applied and the percentage of drainage observed in the internal mammary chain. Method: 150 patients with breast cancer (Stage T1 and T2) have been studied. The day before surgery a lymphoscintigraphy was performed by using 74-111 MBq of 99mTc-nanocolloid in one injection dose. The patients were divided into 3 groups depending on the injection technique: Group A (n=50) subdermic or subareolar, group B (n=50) peritumoural and group C (n=50) intratumoural injection. Static images at 15-30 minutes, 2 hours and so on, if necessary, were performed. When the SLN was identified in the lymphoscintigraphy it was marked on the skin. The day of the surgical procedure a hand-held gammaprobe was used to localize intraoperatively the SLN. Results: Lymphoscintigraphy identified SLN in 96% of patients in group A and C, and 88% in group B. Lymphoscintigraphy failed to identify the SLN in 10 patients, in 7 of which the tumour was larger than 3 cm. The SLN in the internal mammary chain was not identified in group A and was identified in 5 patients of group B (10%) and in 10 patients of group C (20%). Conclusions: The subdermic/subareolar injection allows the detection of SLN in a very high percentage of cases (96%), although it has the inconvenience of not detecting SLN in the internal mammary chain. The intratumoural injection identified the SLN in 96% of cases and moreover showed drainage to internal mammary chain in a significative percentage of these patients. The peritumoural injection showed a lower SLN identification percentage than those obtained with the other injection methods.

Aim of the study was to evaluate the role of the lymphoscintigraphy in the identification of Sentinel Node (SN) in melanoma patients. Materials and Methods between September 1999 and November 2001, 304 consecutive patients with melanoma, tumour thickness between 0.75 and 4 mm, without clinical evidence or radiological findings of disease spreading were enrolled (T2-3N0M0). All patients underwent excissional biopsy of the lesion (excission margins, 1-3 mm) to obtain a correct staging. Within 2-3 week a lymphoscintigraphy were performed. A single dose of 30-50 MBq of Tc99m-Nanocoll, diluted in 0.2-0.3 ml, was injected intradermally on each side of the scar. A gentle massage of the area was given to obtain a fast lymphatic drainage. Patients were positioned in surgical position and a static planar acquisition (matrix 512x512, preset time 300”, LEGP collimator) in anterior or oblique projection was acquired within 5-10 min after injection. For head and neck melanomas, scans were performed as soon as possible after injection. Radioguided biopsy of SN was performed within 18 hours (elapse time was reduced to 3 hours in head and neck lesions). Intraoperative detection of the SN was always performed by perilesional intradermal injection of a vital dye (1 cc patent blue, 15 min before surgery). Results our scintigraphyc method correctly identified lymphatic ways and SN in all patients. In 80% of the patients SN location was typical. In 20% of patients (melanoma of neck, trunk and glutaeus) lymphoscintigraphy identified 2-3 lymphatic ways belonging to different lymphatic basins or to unexpected area. A quick lymphatic drainage occurs in head and neck region and the SNs are revealed after only few minutes post injection. Discordance between vital dye and lymphoscintigraphy was observed in cervical region. The overall rate of micrometastasis is 14%. We observed a metastasis rate for T2 : 3.2%, for T3a : 13.4%, for T3b : 28.3%. Conclusions lymphoscintigraphy increased accuracy in identification of SN and lymph drainage ways to various lymphatic basins or to unexpected area. Discordance between vital dye and gamma probe was observed frequently in cervical dissection, where the vital dye is inadvisable because of the very fast lymphatic drainage. The radioguided biopsy (recommended in all cases for correct identification of SN) is often performed in local anaesthesia, lowering costs and hospitalization. A strong correlation was found between the incidence of micrometastasis and primary tumour thickness.

Scintigraphyc sentinel node identification and lymphatic drainage patterns in melanoma patients. Our experience.

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Sentinel lymph node identification in breast cancer : which injection method should be used?

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C. De Gaudio (1), V. Ciliberti (1), R. Baldocchi (2), A. Marconi (2), R. Tarchi (1). (1) Nuclear Medicine Division, (2) Surgery Division, City Hospital, Lucca, Italy.

A. Hernández (1), R. Quirce (1), F.J. Pena (1), R.H. Allende (1), J.I. Banzo (1), M.G. Polavieja (2), J.M. Carril (1). (1) Servicio de Medicina Nuclear. H.U.M Valdecilla. Universidad de Cantabria. Santander. España, (2) Servicio de Cirugía General y A. Digestivo. H.U.M Valdecilla. Santander. España.

A new approach to breast nodule suspect for cancer: Sentinel Lymph Node biopsy and minimal surgery

Aim: The sentinel node biopsy provides a simple method for staging without adjunctive morbidity. As a tumour drains in a way through the lymphatic system, from the first to upper levels, the first lymph node met (SLN) will most likely be the first to be affected by metastasis. Because axillary node dissection does not improve prognosis of patients with breast cancer, SLN biopsy might reasonablely replace complete axillary dissection to stage the axilla in clinically T1N0 patients. We propose the SLN technique in staging patients affected by a breast nodule suspect for cancer. Materials and methods: In the last two years we applied SNL technique on 120 T1N0 patients. After physical examination and mammographic evaluation the patients were selected for excision. Prior to surgery all patients were submitted to lymphoscintigraphy: 11-22 MBq of 99mTc-nanocolloid (Nanocoll, Amersham-Health) were injected subdermally on cutaneous projection area of nodule; subsequently we performed two or more planar scintigrams in anterior and oblique projection 30 minutes after tracer administration. Results: in all cases (100%) we can distinguish one or two nodes. About 6 hours after lymphoscintigraphy patients undergone to surgery. Enlarged nodulectomy were performed after local anaesthesia and frozen histologic examination were performed; if nodule were cancer (96 cases, 80% in our series), in the same surgical session SLN excision and biopsy were performed at first by the aid of lymphoscintigraphy for lymphatic area determination and, intraoperatively, after the accurate localization provided by a collimate gamma probe (Neoprobe Neo-2000, Ethicon Endo-Surgery). In all 96 patients (100%) were possible to localize and excide the SLN and 22 (22.9%) of them resulted involved by metastasis; in 9 patients out of them the SLN was the only metastasis. 74 out of 96 cancerous patients (77.1%) avoided further surgical intervention as SLN resulted negative for metastasis and all of them are still free from relapse after 3-24 months. Conclusion: This new approach to breast nodule suspect for cancer showed that more than 77% of patients with cancerous breast nodule were satisfactorily treated by only an enlarged nodulectomy performed during local anaesthesia; only the 22.9% of cancerous breast nodules needed axillary dissection and in more than one third of them SLN excision resulted curative.

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Non-visualisation of sentinel node during lymphoscintigraphy: is there a pathological significance? I. Brenot-Rossi, M. Martino, J. Jacquemier, V. Moutardier, E. Charafe, N. Hassan, T. Jacob, J. Pasquier, G. Houvenaeghel. Paoli-Calmettes Institute of Marseille, Marseille, France. The aim of this study was to evaluate the relation between the non-visualization of the sentinel node (SN) during preoperative lymphoscintigraphy and the histologic status of nodes. METHODS: 238 women with T0, T1 or T2<3cm, N0 invasive breast cancer underwent sentinel lymph node biopsy procedure. All patients had intradermal and intraparenchymal injection of 4x0.1ml-10MBq 99mTc sulfur colloïd (Nano CIS Bio Schering) above and around the tumour. Anterior and lateral planar images (dynamic and static) were obtained a few minutes and 2 to 4 hours after injection. Surgery was performed 18 to 24 H. post lymphoscintigraphy. The SN were localized intra-operatively with the aid of patent blue dye and using a hand-held gamma probe. SN were analyzed by serial sections with hematoxylin and eosin, and immunohistochemical using antibody to cytokeratin. RESULTS: A sentinel node was successfully visualized on the pre-operative lymphoscintigraphy in 216 of 238 patients, with an identification rate of 90.7%. Nodes failed to visualize or showed a very low uptake on the delayed images, even after a repeat injection of radio-colloïd, in 22 patients. SN that were well identified were tumour positive in 27.7% and non-visualized sentinel nodes were involved in 54.5%; the failure to identify a hot spot increased with the number of tumour positive nodes: patients had more than 3 positive nodes in 4.1% (9/216) in the group of visualized SN, and in 36.3% (8/22) in the group of unsuccessful mapping (χ2 , P<0.0002 Fischer exact test). CONCLUSION: The lymphatic mapping, specially the failure, might contribute to predict the nodal status.

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Detection of lymphatic drainage and sentinel node in rectal cancer

Aim: To probe if the detection of lymphatic drainage and sentinel node in rectal cancer is feasible and how it would have repercussion at the staging tumor and treatment decision. Material and Methods: We performed 11 studies in 10 patients with adenocarcinoma of the rectum without metastatic disease. Two patients were studied before adyuvant treatment (aT) and 9 after. One patient was studied two times, first without aT, and the second time after. A combination of preoperative lymphatic mapping by lymphoscintigraphy and intraoperative probe detection to identify lymphatic drainage from the primary rectum tumor was realized in all of the patients. For lymphoscintigraphy 2 mililiters of nanocolloid-Tc99m , 37-74 MBq, were injected through a proctoscope in the submucosal layer underneath the tumor, the day before surgery. Patients were underwent anterior resection (8) or abdominoperineal resection (2). Eigthyfive lymph nodes were isolated ranging from 4 to 18 per specimen with a median value of 8 lymph nodes from each specimen. Cancer involvement of lymph nodes was found in 4 patients. Results: In lymphoscintigraphy no migration was observed in 4 studies (4patients), all of them performed after aT. Migration was observed in 7 studies (6 patients). In the patient with two studies the drainage pattern change after aT. Migration was observed in the first 30’ minutes in 10 studies, and in 1 performed after aT the migration time was 2h.30min. Migration into mesorectum lymph nodes was detected in the 7 studies, and also into lateral lymph nodes in 4 studies (2 studies after aT), and in lymph nodes beneath rectal tumor in 1 study performed after aT. Lymphatic dranaige by lymphoscintigraphy and intraoperative probe detection agreement in 2 studies. Regarding the correlation between metastatic regional lymph nodes and migration, it was detected in 2 of the 4. Sentinel node would not be detected intraoperatively in any patient, because of the shiny spot of injection site, which usually is very close to the sentinel node. Conclusions: In spite of the number of patients evaluated, we can conclud that preoperative lymphoscintigraphy is feasible in rectal tumors, and aberrant lymphatic drainage patterns can be observed (4/10 in our patients). In cases in wich lymphatic drainage is undetectable, several reasons would be speculated, including previus adyuvant treatment, and massive lymph node metastasis. Isolation of the sentinel node seems to be not feasible by this methodology.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition LYMPHOSCINTIGRAPHY 2

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Patient characteristics and the appearance of parasternal sentinel nodes in patients with breast cancer A. Leppänen (1), M. Leidenius (2), K. vSmitten (2). (1) Department of Nuclear Medicine, Maria Hospital, Helsinki University Hospital, (2) Breast Surgery Unit, Maria Hospital, Helsinki University Hospital. Helsinki, Finland. The aim: The aim of the study was to evaluate if patient related factors influence the visualisation of parasternal sentinel nodes in lymphoscintigraphy after a single intratumoral injection of Tc 99m labelled human albumin colloid in breast cancer. Materials and methods: The prospective, observational study included 290 consecutive patients with clinical stage T1-T2, N0 breast cancer who underwent lymphatic mapping and sentinel node biopsy between 30.5.2000 and 4.10.2001 at Breast Surgery Unit of Helsinki University Hospital. Lymphoscintigraphy was performed a median of four hours after an intratumoral injection of 80-100 MBq 99m Tc labelled human albumin colloid (Albu-Res) in 140 patients or 99m Tc albumin microcolloid (Nanocoll) in 150 patients in a volume of 0,2 ml. Anterior and lateral planar views were obtained 1-4 hours post injection. Results: 49 (17%) patients had parasternal sentinel nodes in lymphoscintigraphy. Five (2%) patients had lymphatic drainage solely to the parasternal basin. Compared to all patients the patients with parasternal sentinel nodes in the lymphoscintigraphy were younger with a median age of 53 (compared to 58 in all patients) years (p<0.005), had lower body mass index (median BMI 23, compared to 25) (p<0.01) and had more often a nonpalpable tumour (39 %, compared to 26%) (p<0.05). Tumours located in lower lateral breast segment had parasternal sentinel nodes more often (in 34 % of patients) (p<0.01) than those with upper and central tumour location. Conclusions: Parasternal sentinel nodes appear in 17 % of breast cancer patients and more often in young and lean patients with nonpalpable tumours in lower lateral breast segment.

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n LYMPHOSCINTIGRAPHY 2 Detection of clinical occult lymph node metastases by lymphoscintigraphy and sentinel node biopsy in anorectal melanoma patients M. Maccauro (1), G. Gallino (2), G. Aliberti (1), C. Villano (1), G. Savelli (1), F. Belli (2), E. Bombardieri (1). (1) Department of Nuclear Medicine, Istituto Nazionale Tumori, Milano, Italy, (2) Department of General Surgery, Istituto Nazionale Tumori, Milano, Italy. Aim: Primary anorectal melanoma is a rare and very aggressive disease. Between 0.4 and 1.6 per cent of all melanomas arise in the anorectal region and this is the most frequent site of melanoma after skin and retina. To our knowledge, this is the first report dealing with a sentinel node (SN) biopsy performed in the management of anal melanoma patients. The goal was to investigate the clinical utility of lymphoscintigraphy and SN biopsy to detect clinically occult nodal disease. Material and methods: We evaluated 4 patients; 24 hours prior surgery they received intradermally four injections of 40 MBq of 99mTc-nanocoll, around the surgical scar. We used a disposable self-lighting anoscope for a correct injection of the radiocolloid. The imaging was carried out with a 15 min dynamic γ-camera acquisition followed by a delayed 5 min acquisition. To properly identify the site of SN, a 57Co marker and flood were used. During surgery blue dye and γ-probe were used in order to detect the node involvement. Results: In all patients the lymphoscintigraphy detected a double lymphatic drainage pathway. The scintigraphic findings imaged 5 SNs in the left groin and 4 in the right groin. All identified lymphatic basins were biopsied and pathology showed metastases in two patients. These patients subsequently underwent a total lymph node dissection. At the time of writing one patients with positive SN biopsy is dead and the others are still alives. Conclusion: This study, in spite of a limited number of the observed cases, demonstrated that lymphoscintigraphy and SN biopsy are very useful in anorectal melanoma patients to detect clically occult metastases. Furthermore, early diagnosis of nodal metastases would permit to start adjuvant treatment very soon after surgery, in order to prevent the possible growth of occult disease and the spread to local or distant sites. The prognostic value of this approach has still to be investigated on a large perspective series of melanoma patients, by evaluating the disease-free interval and the survival.

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The role of lymphoscintigraphy combined with intrasurgical gamma probe in identification of sentinel node in melanoma M. Mitjavila, MA. Balsa, L. GªCañamaque, V. Torres, N. Gambí, F.J. Penín, C. Pey. Hospital Universitario de Getafe, Madrid, Spain. The biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of skin melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviate the need for lymph node dissection; a therapeutic dissection is then performed only in patients with proven nodal disease. However, many centers using the radioguided biopsy of SN omit pre-operative lymphoscintigrahy. Patients and method: In the last two years we performed dynamic SN scintigraphy in 22 patients (10 M, 12 W) with histologically proven cutaneous melanoma stages I and II (according to the American Joint Committee on Cancer staging criteria). Malignant melanoma was localized at the lower limbs (13), at the upper limbs (3) and in 6 patients at the trunk. All patients underwent preoperative lymphoscintigraphy to demonstrate the lymphatic basins at risk of metastasis disease. The injection of 99mTc nanocolloid was performed in 4 intradermal spots around the surgical scar of the primary tumor in the evening before surgery. Following injection, dynamic planar imaging were adquired until the SLN became visible. The SLNs were marked on the skin using external radioactive marker. Results: Identification of one or more (13 patients) was possible in the 22 patients. In the 6 patients with melanoma at the trunk, SNs were found in differents ganglionar groups (both axillary, 4; axillar and inguinal, 1; axillar and supraclavicular, 1). One of the SN was unable to be detected intraoperatively despite that it was visualized preoperatively. In 1 case, 2 SLNs were invaded by malignant cells. This patient underwent selective lymphadenectomy and SLN were the only malignant LN. Distant metastases were found in one patient without malignant cells in the SLN. Conclusion: The use of lymphoscintigraphy which allows accurate preoperative localization of the SN, especially in trunk melanoma, in association with the use of gamma ray detecting probe (GDP) which identify the SN before the incision, maximise the success of sentinel node localization.

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Metastatic involvement of sentinel lymph-node with lymphoscintigraphy and blue dye mapping in small breast cancer (< 10 mm)

Lymphoscintigraphy, biopsy of the sentinel lymph node and staging of coutaneous malignant melanoma

F.C. Carola (1), W. Zuccon (2), S. Martini (3), M. Barberis (3), G. Santoro (1), M. Racanelli (1), S. Catania (2). (1) Departement of Nuclear Medicine, Policlinico Mulimedica, Sesto San Giovanni, Milano, Italy, (2) Department of Senology, Policlinico Multimedica, Sesto San Giovanni, Milano, Italy, (3) Department of Patology, Policlinico Multimedica, Sesto San Giovanni, Milano, Italy.

E. Piperkova (1,3), K. Kirov (2,3), M. Dimitrova (1,3), E. Paycheva (2,3). (1) Department of Nuclear Medicine, (2) Department of Oncodermatology, (3) National Oncological Centre Hospital, Sofia, Bulgaria.

Lymphoscintigraphy associated with radioguided biopsy of sentinel lymph-node in patients with breast cancer is a simple and well-tolerated procedure by patients. The rationale of this technique is of avoiding unnecessary axillary lymph-node dissection. Aim of the work is to study correlation between smaller size of “monofocal” breast cancer (≤ 1.0 cm) and presence or absence of metastatic sentinel lymph-nodes, detected with lymphoscintigraphy and/or technique with blue dye (Patent Bleu V). Methods: we studied 88 patients (mean age 57 years, range 27-79 yr, sd ± 11.6 yr) with early and “monofocal” breast cancer of stage T1 with dimension ranging between 0.2 and 2.4 cm (mean ± sd 11.8 ± 4.4 cm). In 52/88 (59%) of patients tumor size was ≤ 1.0 cm. All patients underwent lymphoscintigraphy for sentinel lymph-node (sLN) biopsy 6-8 hours before surgery, by injecting 9 MBq of 99mTc-HSA nano-colloids (particle size 50-80 nm) in 0.2 ml of saline solution subdermally above the tumor mass. At 15 minutes to 2 hours scintigraphic images were obtained in anterior and lateral projections. Skin projection of the detected lymph-node was marked to help association technique with a gamma detecting probe during surgery. In 39/88 (44%) of patients technique with Blue dye (Patent Bleu V) was also administered in addition to subdermal radiolabeled colloid to compare blue dye mapping with lymph-node localization. After excisions all lymph-nodes were processed for histology and immunohistochemistry to study metastatic involvement. Results: we found metastatic involvement of axillary sentinel lymph-nodes excised in 13 of 88 masses (14%). In the group of 52 patients with small breast cancer (≤ 1.0 cm) only a low percentage (about 3%) of sLN (2/52) turned out to be metastatic at histology and immunohistochemestry, independently from age of the patients. Blue dye mapping was successfully correlated with lymphoscintigraphic sLN localization in 30 over 39 patients (77%) and tumor size was >10 mm in 14 pts and ≤ 10 mm in 16 pts. Conclusions: the results of our study, obtained in a quite small number of cases, demonstrate that patients with small breast cancers (≤ 1.0 cm) have low percentage (about 3%) of metastatic sentinel lymph-nodes, detected with combined technique (lymphoscintigraphy and blue dye mapping). But we need further investigations to reduce this “low percentage” to avoid axillary lymph-node dissection in small breast cancer.

The effect of elective lymph node dissection (ELND) in patients with cutaneous malignant melanoma (CMM) is still debated. The sentinel lymph node biopsy (SLNB) seems to be reasonable substitute of the ELND. The aim of this prospective study was to explore the efficacy of the lymphoscintigraphy in distinguishing SN in CMM patients, to mark their location on the skin to facilitate the surgical procedure in their detection. Material and methods: The study included 47 patients with histologically proven CMM – 23 males and 24 females. The mean age was 56.6 years (range 31-76). The CMM site was the leg (22), arm (10) and trunk (15) without any clinical data of a regional lymph node metastases. The mean Breslow thickness of the tumors was 2,96 mm (0.1-8.00 mm) and in 32 of the patients was less than 4.1 mm. The day before, all patients had lymphoscintigraphy to locate the SN on a Diacam gamma-camera (Siemens) after 99m Tc-nanocolloid 37-74 MBq injected adjacently to the primary lesion. Early and late static images were obtained with large FOV and high resolution collimator between 5-20 min and were repeted at 2nd and 4th hours. Using scintigraphic scanner with moving detector SN skin projection was defined and marked with dye to facilitate the surgical detection. The surgical procedure was carried out under general anesthesia using Patent-blue. The SN were examined histologically Results: The SLNB confirmed the 75 SN detected scintigraphicaly in 44 patients and 5 SN in 3 patients which could not be detected scintigraphically. On the early and late scans a prolonged nodal retention of the 99mTc-nanocolloid was found in the verified SN. The histologic examination cofirmed micrometastases in 11 (13.7%) SN in 7 (14.9) patients. We proposed and use the folloing TNM classification for patients with SLNB: T 1-4 N0M0 – clinically negative LN, SLNB not performed T1-4 Nsx M0 - SLN not found T 1-4 Nso M0 - SLN negative T 1-4 N2 M0 – SLN positive In conclusion the lymphoscintigraphy for a SN detection greatly facilitate the surgical procedure of SLNB and is indispensable when the primary lesion is located on the trunk, which is important for a staging and treatment strategy in CMM. A negative SLNB would preclude the presence of lymphatic malignant involvement avoiding the necessity of a total LND with accompanying morbidity

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M. Tajahuerce, A. Lara, J. Arzo, P. Boldo, M. Martin. Department of Nuclear Medicine of the Hospital Provincial de Castellon, Castellon, Spain.

N. Besseghir (1), J.F. Delaloye (2), C. Antonescu (1), F. Bonvin (1), A. Bischof Delaloye (1). (1) Department of Nuclear Medicine, Centre Hospitalier Universitaire Vaudois, (2) Department of GynecologyObstetrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Intraoperative scintigraphy as another criterion in identifying the sentinel lymph node

AIMS: Several criteria for correct identification of the sentinel lymph node have been described. Discussion of preoperative scintigraphy with the nuclear physician, skin marking, patent blue staining, use of gamma-ray detection probe and ex vivo radioactivity of excised nodes are the most common ones. Nevertheless, in some cases these criteria may be absent or not useful. The aim of this poster is to communicate the utility of intraoperative scintigraphy in identifying the sentinel lymph node when other criteria are absent or not totally useful. METHODS: Based in the use of intraoperative specimen X-Ray in breast surgery, we have indicated intraoperative scintigraphy of the specimen in several instances. RESULTS: One of these instances is when the sentinel node is close to the injection site (Figure 1) and the blue dye has not migrated. Gamma-ray probe detection will be hampered by the radioactivity from the injection site. Ex vivo activity cannot be compared with background activity because of the same reason. In these cases, intraoperative scintigraphy may comfirm correct sentinel node biopsy by comparison of the scintigraphic morphology of the specimen (Figure 2) with the preoperative images. Intraoprative scintigraphy may be also comfirmatory when, after 24 hours of injection, a low activity sentinel lymph node has been excised (Figures 1 and 2). The third situation in which intraoperative scintigraphy has been useful is when comfirmating en block excision of several close sentinel lymph nodes and ex vivo activity cannot be compared with the background (Figure 3).We would like also to underline the legal advantages of intraoperative scintigraphy of the specimen as a record of the correct sentinel node biopsy. CONCLUSIONS: In our experience intraoperative scintigraphy can be a comfirmatory exploration for correct identification of the sentinel lymph node. Besides, it may provide some medical-legal advantages.

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Value of the subareolar application of Tc-99m nanocolloid in the sentinel node detection for not precisely locally defined multifocal/centric breast carcinomas at early stages S. Maza (1), K.-J. Winzer (2), L. Geworski (1), D. Sandrock (1), A. Zander (1), D.L. Munz (1). (1) Clinic for Nuclear Medicine, University Hospital Charité, Humboldt University of Berlin, (2) Clinic for Surgery, University Hospital Charité, Humboldt University of Berlin, Germany. Aim: Due to the early diagnosis of breast carcinomas (BrCa) in the context of clinical examination and mammography screening is becoming better, more tumours are discovered at a stage, in which they are neither palpable nor identifiable by sonography. Dependent on the size of the primary tumour, 13% to 75% are multifocal/centric BrCa. Since, also in this patient group, the lymph node status represents one of the most important prognostic factors, the subareolar (SA) injection could be used for the scintigraphic detection of the sentinel nodes (SN (s)). Aim of this prospective study was to verify the clinical value of this relatively new injection technique. Materials and Methods: 8 women with a multifocal/centric BrCa and 2 women with a bioptically proven BrCa only detectable by mammography were enrolled till now. All patients were without clinical suspicion of lymph node metastases and aged between 41 and 68 years. SA injection of 40 MBq Tc-99m nanocolloid was carried out in 3 deposits/quadrant (à 0.05 ml/deposit). After application, dynamic and static lymphoscintigraphy of corresponding axillary, thoracic and cervical areas was performed in various views with a gamma camera (LEAP collimator, 256 x 256 matrix). All lymph nodes removed in the drainage area were examined by histology and immunohistochemistry. Results: An elective dissection of axillary lymph nodes was carried out in all patients. In 4 patients lymph node metastases were histologically confirmed in the SNs, all of them had a multifocal/centric BrCa (all non-SNs were tumour free). In the remaining 6 patients, lymph node metastases could be found neither in SNs nor in non-SNs. Conclusion: SA nanocolloid injection can yield reliable data in not precisely locally defined multifocal/centric BrCa at early stages.

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Delayed imaging after lymphoscintigraphy for sentinel node detection in breast cancer

Aim: This study was conducted to determine the capability of late imaging after lymphoscintigraphy (LS) for breast cancer to detect additional sentinel nodes. Methods: Our series consisted of 51 female patients (median age: 60y; range 33-84y) who were reevaluated 18 hours after LS by an anterior image of the chest. All the patients had a cT1/cT2 breast cancer and were referred by the same surgeon. Lumpectomy had already been performed before LS in 13 patients (26 %). Tc-99m-nanocolloids (Nanocoll, Amersham) was injected peritumorally (3 injections of 20MBq in 1 ml) and intradermally (10 MBq in 0.5 ml). In patients having already undergone lumpectomy, we injected 2 doses of 10 MBq/0.5 ml intradermally at both extremities of the scar. Dynamic and sequential images were acquired to identify the SN. These results were compared with the results of additional imaging on the next day. Results: The late views allowed to find 1 to 2 more nodes for a total of 17 nodes in 13 patients, seven among them were found in patients with previous lumpectomy. The new nodes were mainly located in axillary chains (8/17), but other basins like sub-clavian (5/17) or internal mammary chains (4/17) were also revealed. According to these findings, the surgical procedure and the global follow-up were changed in 4 of our patients (8 %). Conclusion: When performing LS for breast cancer, additional delayed imaging can be used to improve complementary sentinel node mapping. In our small series, 18% of the patients showed migration to additional drainage basins. Such information might have a major impact on patient management.

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Sentinel node detection in breast carcinoma. E. Pelosi (1), M. Bellò (1), B. Baudino (1), E. Arena (1), R. Bussone (2), D. Lauro (2), A. Ala (2), R. Giani (2), G. Bisi (1). (1) Department of Nuclear Medicine of the University of Turin - Italy, (2) Ist Division of Surgery, S. Giovanni Antica Sede Hospital, Turin - Italy. Introduction: the standard of care for the evaluation of axillary nodal involvement in patients with breast cancer remains complete lymph node (LN) dissection. However about 70% of patients are found to be free from metastatic disease while axillary node dissection can lead to significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. Material and methods: in a period of 18 months, we studied 201 patients with breast cancer (we excluded patients with palpable axillary nodes, patients with tumor >2.5 cm in diameter, patients with multifocal or multicentric cancer, pregnant and patients older than 80 years). Before surgery, 99mTc-labeled colloid and vital blue-dye technique was injected into the breast to identify SLN. In LN dissected at surgery, metastatic status was examined by sections at reduced intervals. Only patients with SLN histologically positive for metastases underwent axillary dissection. Result: thanks to scintigraphy we localized one or more SLN in 192 of 201 (95.5%) patients, while with both techniques the success rate was 100%. Histologically: 21% of patients showed SLN metastases (7.8% micrometastases); and 68% of them had axillary LN metastases. None of patients with negative SLN developed metastases during the follow-up period. Conclusion: at present, there is not definite evidence that negative SLN biopsy is invariable correlate with negative axillary status; however our and others study demonstrate that SLN biopsy is an accurate methods of axillary staging.

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Clinical evaluation of three gamma probes for sentinel nodes localisation in breast cancer in relation to residual activity in sentinel nodes

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition SCINTIMAMMOGRAPHY

c.c. Curtet. (nuclear medecine), C. Rousseau., J.M. Classe., R. Pioud., F. Dravet., M. Fiche., C. Sagan., J.F. Chatal., I. Resche. (1) Department of nuclear medecine, (2) Department of surgery, (3) Department of surgery, (4) Department of surgery, Nantes, France.

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Clinical evaluation of three gamma probes for sentinel nodes localisation in breast cancer in relation to residual activity in sentinel nodes. Aim: The role of the surgical gamma probe is to localise the sentinel lymph nodes (SLN) intra-operatively. The performance of 3 gamma probes (1 scintillator BgO, and 2 semi conductors CdTe, CZT) was tested in patients with breast cancer injected same day or day before. In vivo and ex vivo countings were reported and compared in SLN residual activity counted in a gamma counter. We compared these results with in vitro countings with 99m Tc source to evaluate absolute sensitivity of each probe. Material and methods: Thirty patients with infiltrative breast carcinoma were enrolled ( 7 T0, 15 T1, 8T2),. Two 0,1 ml injections of 15-20 MBq 99m Tc (100nm) sulfur colloid were administred in peritumoral space. 2 groups were defined relative to the interval between injection and peroperative radiodetection : group A 18 hours before surgery, group B 2 hours before. Only group A had lymphoscintigraphy.Patent bleue was injected in surgery room. SLN was radiodetected when Signal/ background > 2. All SLN were counted in a gamma counter (LKB) for residual activity (KBq) relative to a standart solution, and % of injected dose was determined. Standart immunohistopathological analysis was performed ;. In vitro countings were performed with 99m Tc source (1 MBq) in air and water, for spacial resolution by moving probes off axis / height cm by cm. Results: 17patients group A, and 13 patients in group B . 64 SLN were radiodetected, (5 patients with 1 SLN, 14 with 2 , 9 with 3, and 1 with 4) (100% with BgO, 89% with CdTe, andCZT), 70 % of them were bleue. For group A, 15 patients had lymphosintigraphy (95% positive).

V. Bongers (1), C. Perre (2), P. deHooge (1). (1) Department of nuclear medicine, Diakonessenhuis Utrecht, The Netherlands, (2) Department of Surgery, Diakonessenhuis Utrecht, The Netherlands.

SLN 64

BgO cps Invivo/ ex vivo

CdTe cps Invivo/ exviv

Group A 244/299 58/60 Group B 1129/1301 203/249

CZT cps Activity Injected Invivo/ SLN Dose exviv KBq (MBq) / % ID 69/63 61 37/0,18 274/459 56 34/0,16

BgO CdTe CZT Cps/KBq Cps/KBq Cps/KBq 4,4 23

0,9 4,4

0,9 8,2

99mTc-Tetrofosmin scintimammography for the detection of recurrent breast cancer

99m Tc-Tetrofosmin (99mTc-TF) scintimammography has been shown an accurate diagnostic test in patients with a symptomatic primary breast lesion and a non-diagnostic mammogram, also in patients with dense breast tissue. Since physical examination and conventional imaging modalities have their limitations in the detection of recurrent breast cancer and survival is related to the extent of the recurrent disease, complementary imaging modalities are warranted. Therefore, we evaluated the role of 99mTc-TF scintimammography for the detection of recurrent breast cancer. Patients and methods: Fifty-five women were send for scintimammography because of a clinically suspicious breast-, or chest wall recurrence and/ or evaluation of the axillary, parasternal, supraclavicular and/ or infraclavicular lymph node status. 10 minutes after intravenous injection of 700 MBq 99mTc-TF, planar breast images and images of the whole thorax were performed. Results: In this prospective study scintimammography with 99mTc-TF was diagnostic in 50 of the 55 cases. In one patient an unknown lung metastasis was detected by 99mTc-TF scintimammography and in one other patient an unknown bone metastasis of the sternum. Tumour involvement remained undetected in 1 neck node metastasis. Three cases had false positive scintimammography results with 99mTc-TF uptake in an axillary, infraclavicular, and parasternal lymphnode, respectively. A fourth patient showed 99mTc-TF uptake in the scar, which appeared cytologically to be an inflammatory lesion. Conclusion: It is concluded that 99mTc-TF scintimammography accurately detected 100% of the local recurrences independent of the extent of the preceding surgical intervention. The sensitivity and specificity of 99mTc-TF scintimammography for the detection of regional recurrent disease were 93 and 90%, respectively, and substantially higher than those of other imaging modalities.

In vitro measurements : 0 cm BgO / CdTe / CZT , FWHM (8/5/20), angular sensitivity (40°/ 40°/22°)Absolute sensitivity ( cps/KBq) Conclusion: SLN had same residual activity in group A and B.It is very important for the surgeon to know the physical parameters , and to choose the better compromise for the radiodetection.

Sentinel lymphnode detection in canine oncological patients L. Balogh (1), G. Andócs (1), J. Thuróczy (2), P. Chaudhari (4), D. Máthé (1), E. Perge (3), I. Erdélyi (2), A. Polyák (1), GY. A. Jánoki (1). (1) Fodor József National Center for Public Health, National Frédéric Joliot-Curie Research Institute of Radiobiology and Radiohygiene, Budapest, Hungary, (2) Szt. István University Faculty of Veterinary Science, Dept. of Gynaecology and Reproduction and Dept. of Pathology, Hungary, (3) National Center of Animal Health, Hungary, (4) Bhabha Atomic Research Centre, Tata Hospital Annexe, Parel, Mumbai, India. Aim: Sentinel lymphnode detection is a clinical routine in many nuclear centers in breast cancer, melanoma and other soft tissue tumor patients. Different diagnostical protocols are available concerning to the optimum particle size of applied colloids, the ideal time of imagination and intraoperative guiding after application and the mode of injection. The aim of this study was to compare the effectivity of sentinel node detection by physical examination, detection by injecting radioactive particles and the blue stain in canine oncological dog patients. Methods: Altogether 24 dog patients with the history of mammary tumors and single soft tissue tumor in the neck region underwent within 3 days fine needle biopsy, thoracal radiography and hematological examinations. Three-six hours before surgical removal of tumors 2037 MBq/0,1mL Tc-99m HSA colloid (Senti-Scint®, N.R.I.R.R., Hungary) and immediatelly before operation blue dye (1% Patent blue solution) was injected subcutaneously. Gamma camera imaging (Nucline X-ring, Mediso Ltd, Hungary) and intraoperative gamma probe (Europrobe, Eurorad) was used for localizing sentinel nodes. Removed tumors and all the localized lymphnodes were investigated by pathologists using HE stain and immunohistochemical cytokeratin detection. Results: Altogether 35 sentinel lymphnodes were found in the 24 single tumor bearing dogs what means 1,45 sentinel nodes per one tumor in a mean. Sixteen (46%) nodes of the 35 were positive by HE staining while 22 (63%) with cytokeratin immunohistochemistry. Twenty seven of the nodes (77%) were found to be painted by the blue stain intraoperatively. Thirty one of the nodes (89%) were clearly identified by gamma camera imaging and 34 (97%) were detected using the intraoperative guide and gamma camera scan. Only 8 (23%) of the nodes proved to be enlarged and palpable before and while surgery. Conclusions: Palpation, blue stain localising method and gamma camera imaging alone resulted not satisfactory data on sentinel lymphnode detection. Gamma camera studies followed by intraoperative probe guided surgery combined with blue stain seems to be the superior method for localizing sentinel lymphnodes in dogs like in human beings.

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Comparison between spiral CT and 99mTc Sestamibi scintimammography in breast cancer diagnosis A.M. Mangano (1), F. Scopinaro (1), A. De Cesare (2), G. Di Santo (1), Z. Kharrub (3), F. Monteleone (1), P. Mingazzini (4), M. Marini (2). (1) Sct. of Nuclear Medicine-Dept. Experimental Medicine and Pathology, University of Rome, Rome, Italy. Aim. In patients with acute coronary syndrome ( ACS ) daily hospital cost is higher than myocardial SPECT. Purpose of present study is to confirm improvement of decision making with Tc-99-m Tetrofosmin SPECT (TSPECT) on patients with chest pain in emergency department. Materials and Methods. We enrolled 42 consecutive patients of Sulmona general hospital emergency department. Inclusion criteria were: first attack of anterior chest pain lasting more than 20’. Exclusion criteria were a) known ACS, stable angina, valvular heart disease, cardiomyopathy b) abnormal Q wave and evolving ST elevation higher than 1 mm, d) increased serum total CPK and CPK-MB. Patients arrived within 3 hours from onset of pain had ekg, echocardiography, serum troponine I measurement, rest TSPECT. Patients observed more than 3 hours after pain onset, patients without any ecg and serum signs of acute myocardial lesions had stress TSPECT too, with single day protocol. Patients with positive TSPECT findings were admitted to intensive care and selective angiography was performed, whereas patients with negative scan were followed up at home. Results. 10/42 ( 23,8% ) patients showed positive scan, 4 of whom at rest and six after exercise. 2/10 patients showed normal coronary arteries and 8/10 showed significant stenosis, three of the latter eight patients had ACS and received e.v. thrombolysis. 40/42 did not show segmental abnormal wall motion at echocardiographic examination. 7/10 patients with positive SPECT findings had normal ecg,, one patient had aspecific ecg abnormalities of ST tract and T wave and significant stenosis of DIA coronary artery, one patient showed left BBB and the last one ekg signs of ACS and positive angiography. 32/42 (76,2%) patients had negative rest and stress TSPECT were sent home; None of them showed new chest pain attack within 6 months. 23 out of these 32 patients had normal ekg., 9/32 patients with normal scan had abnormal ekg, 7 of them showed aspecific abnormalities of ST-T waves, 2/9 patients showed negative T wave. Discussion. Concordance of TSPECT with follow up was 38/42, with concordance likelihood of 90,5 %, whereas 4/42 might be false positive and negative, though with no recurrence of pain. The presumed true negative 28/42 patients significantly lowered costs for the hospital without any risk for them. Our study, performed on the general hospital of a small town, confirms the results of larger trials. Conclusion Myocardial TSPECT is cost-effective and fits well the needs of chest pain emergency departments

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A. Spanu (1), G. Dettori (2), F. Chessa (1), A. Porcu (2), P. Cottu (2), M.B. Stochino (1), S. Nuvoli (1), A. Falchi (1), G. Madeddu (1). (1) Department of Nuclear Medicine of the University of Sassari, Sassari, Italy, (2) Department of Surgery of the University of Sassari, Sassari, Italy.

F. Cachin (1), D. Mestas (1), C. Thouly (1), A. Cayre (2), B. Geissler (1), J.C. Maublant (1). (1) Department of Nuclear Medicine of Cancer Center Jean Perrin of Clermont Ferrand, France, (2) Department of Pathology of Cancer Center Jean Perrin of Clermont Ferrand, France.

Aim: The aim of this study was to verify whether the use of SPET can increase the sensitivity of planar scintimammography in the detection of small size (V10 mm) primary breast carcinomas (BC). Materials and Methods: We studied 96 patients with breast lesions V10 mm, 72 with BC (14 T1a and 58 T1b, 42 palpable and 30 non- palpable) and 24 with benign lesions (16 palpable and 8 non-palpable). In all patients, 10 min. after 740 MBq 99mTc-tetrofosmin i.v. injection, planar scintimammography (supine and lateral views) was performed followed by SPET (360° in supine position; angular step:3°; acquisition time/frame:30 sec) using a rectangular dual-head gamma camera equipped with high-resolution, parallel-hole collimators. In all patients the scintigraphic data were related to histology. Results: SPET scintimammography was true positive in 64/72 patients with BC, while planar in 33/72 (overall sensitivity: 88.9% vs 45.8%; P<0.0005). SPET detected 10/14 T1a carcinomas and 54/58 T1b carcinomas (sensitivity: 71.4% and 93.1%, respectively), while planar 5/14 and 28/58 (sensitivity: 35.7 % vs 48.3%, respectively). The difference in sensitivity between SPET and planar imaging was statistically significant (P<0.0005) in T1b carcinomas. Moreover, SPET showed a significantly higher sensitivity in both palpable (92.8% vs 47.6%; P<0.0005) and non-palpable (83.3% vs 43.3%; P<0.005) carcinomas. SPET and planar imaging showed the same specificity value (95.8%), resulting false positive in the same patient who had a 10 mm palpable fibroadenoma. SPET showed a significantly higher overall negative predictive value and accuracy than planar (74.2% vs 37% and 90.6% vs 58.3%, respectively; P<0.0005). Conclusion: 99mTc-tetrofosmin SPET appears a highly accurate diagnostic procedure in the detection of small size primary breast carcinomas, irrespective of their palpability, improving the low sensitivity and negative predictive value of planar scintimammography. SPET scintimammography seems particularly indicated for T1b carcinoma detection, although its usefulness in T1a carcinomas should not be ignored. A larger clinical application of SPET is suggested in small size primary BC.

New automatic quantification method for 99mTc scintimammography.

The role of 99mTc-tetrofosmin SPET scintimammography in the detection of small size primary breast carcinomas

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Quantitative scintimammography with 99mTc-MIBI in the follow-up of chemotherapy of breast cancer W.Y. Ussov (1), A.A. Medvedeva (1), S. Popadic (2), J.E. Riannel (1), E.M. Slonimskaya (1), S.A. Velichko (1), S.A. Kolesnikov (1). (1) Tomsk Medical Research Center, Tomsk, Russia, (2) Institute of Oncology, Sremska Kamenica, Yugoslavia. Aim: Scintimammography (SM) has been widely proven and clinically employed as a highly specific and sensitive technique of primary and differential diagnosis of breast cancer (BC) and detection of post-mastectomy recurrencies of BC. Role of SM in the follow-up of patients under complex chemotherapy treatment hasn’t been evaluated regularily. Here we aimed to prove the abilities of MS in the follow-up of chemotherapy of ladies with BC. Methods : This was a prospective study. 21 ladies with breast cancer of stages T2-3N1-3M0 were referred for this study. All underwent planar high-resolution SM with 99mTc-MIBI (540 MBq in everybody) before and 2-3 days after neoadjuvant chemotherapy (CMF scheme). In two days later everybody underwent radical mastectomy or radical resection of breast en block with axial lymph nodes. Later on all were followed-up for as long as 2 years. {BC/Bg} (tumor to background) and {BC/Myoc} (tumor to myocardium) mean count ratios as well as volume of tumor (calculated from planar dimensions of BC on SM) were calculated and analysed for the follow-up of the chemotherapy effects on SM. Patients with stages 2 (T12N0-1M0) and 3 (T1-3N2M0) of disease were analysed separately. Results: Visual analysis of SM was not satisfactory for follow-up of BC. Quantitative changes induced by chemotherapy were as shown below (Mean ± SEM, p calculated by paired t-test) : Index Vtumor, cm3 {BC/Myoc} {BC/Bg }

Groups of pts Stage 2 (n=9) Stage 3 (n=12) Stage 2 (n=9) Stage 3 (n=12) Stage 2 (n=9) Stage 3 (n=12)

Before chemotherapy 13, 98 ± 6,34 21,82 ± 7,13 0,25 ± 0,02 0,33 ± 0,04 3,47 ± 1,12 3,28 ± 0,84

After chemotherapy 2,23 ± 0,98; p<0,001 11,72 ± 3,81; p<0,02 0,21 ± 0,032; p<0,05 0,22 ± 0,03; p<0,01 2,69 ± 1,00; p<0,05 3,11 ± 0,82; p>0,05

{BC/Myoc} index delivered adequate control of chemotherapy. In particular, no relapse of tumor was detected in the follow-up period after complex treatment when chemotherapy induced decrease of the {BC/Myoc} ratio below 0,2. Cases of mortality due to metastatic complications and recurrences (four in total) of the disease were observed only when {BC/Myoc} ratio did remain over 0,2, without significant chemotherapy-induced decrease. Conslusion: Hence the breast scintigraphy with 99mTc-MIBI can be employed for follow-up control of chemotherapy in breast cancer. Level of {BC/Myoc} count ratio after cytostatic treatment of breast cancer predicts the risk of recurrences and of metastatic progression.

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New automatic quantification method for 99mTc scintimammography.

Aim: Tumor to background (T/B) grading in scintimammography (SMM) could play an important role in the prediction of a breast tumor aggressiveness and resistance to chemotherapy. We compared the results obtained with visual reading and two quantification methods. Material and methods: Thirty seven patients (pts) with a T2 breast cancer underwent SMM before any surgical or medical treatment. Ten min. after the injection of 740 MBq of sestamibi, two prone lateral and one anterior supine 10-min views were collected in 256x256 format. All views were blindly scored according to the following scale : 0 = normal, 1 = doubtful, 2 = low intensity, 3 = medium intensity, 4 = high intensity. For each patient, the view showing at best an area of focal increased uptake was processed for T/B calculation. One method was based on the manual positioning of two small circular (10 pixels radius) regions of interest (ROI). The other method utilized an original, semi-automatic and highly reproducible approach based on the analysis of activity profile passing through the tumor and in a matching area at 15 pixels distance. Results: One patient showing no tumor uptake was excluded from analysis. When measured by the ROI approach, the T/B (m ± sd) were not significantly different, even between the group of pts with a visual score of 2 (n = 9 pts, 1.6 ± 0.3, range 1.0 - 1.9) and those with a score of 4 (n = 10 pts, 2.2 ± 0.9, range 1.2-4.0). When measured by the semi-automatic method, there was a highly significant difference between the mean T/B of these two groups (1.3 ± 0.1 for score 2 vs. 2.9 ± 1.9 for score 4, p<0.001), without any overlap between their distributions (range 1.1-1.5 for score 2 and range 1.6-7.7 for score 4). However with both methods, the T/B values of the pts with score 3 lesions were widely overlapping with those of both score 2 and score 4 lesions. Conclusion: For T/B quantification in SMM, concordance is poor between a ROI-based method and visual scoring. Our semi-automatic method is able to correctly identify low and high intensity lesions.

Date: 02.09.2002 • Time: 16:30 - 16:00 • Hall: Poster exhibition PET: OTHERS

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Lymphography causes false positive FDG-PET findings M.J. Reinhardt (1), D. Vogelgesang (2), C. Ihling (3), C. Altehoefer (4), H. Palmedo (1), T. Krause (1), A. Joe (1), H.J. Biersack (1). (1) Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany, (2) Department of Gynecology and Obstetrics, University Hospital Freiburg, Freiburg, Germany, (3) Department of Pathology, University Hospital Freiburg, Freiburg, Germany, (4) Department of Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany. Aim: FDG-PET positive pelvic and para-aortic lymph-nodes in cervical cancer are associated with lower progression-free survival and vice versa. Thus, FDG-PET results may alter therapeutic management of such patients. However, the accuracy of FDG-PET might be impaired by a preceding lymphography. Materials and Methods: In a series of 35 patients with cervical cancer stage FIGO I B and II studied with FDG-PET, two patients (31-years and 47-years old) received a lymphography 1 and 4 days before the FDG-PET study. Lymphography was performed after bipedal lymphatic application of 2 x 6 ml of the oily contrast medium Lipiodol. PET was performed 90 minutes post injection of 370 MBq F-18 FDG with photon absorption correction. Both patients were scheduled for radical hysterectomy (Wertheim-Meigs) and pelvic and para-aortic lymphadenectomy 1 week after lymphography. 74 and 42 lymph-nodes were dissected for histology. Results: Lymphography was negative in patient 1 but suggested bilateral iliac lymph-node metastases in patient 2. FDG-PET suggested a solitary lymph-node metastasis in the right obturator fossa in patient 1 and bilateral external iliac lymph-node metastases in patient 2. Histology confirmed a lymph-node metastasis in the left external iliac chain and a para-aortic micro-metastasis of patient 1 and a micro-metastasis in the left obturator fossa of patient 2. In the right obturator fossa of patient 1, where FDG-PET showed a focus with an SUV of 3.1, only granulomateous changes were seen histologically, same as with the bilateral iliacal foci of patient 2 (SUV 2.7 and 2.9). Thus, FDG-PET was correct in predicting N1-stage but for the wrong reason. These were the only false positive findings on FDG-PET images in the series of 35 patients. Conclusion: Whenever FDG-PET and lymphography were performed in the same patient to assess the extent of lymph-node metastases, lymphography should always be done after the FDG-PET study to obviate false positive results.

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Comparison of Regional FDG PET and Second Look Operation in the Patients with Ovarian Serous Adenocarcinoma without Evidence of Remnant Disease on Conventional Studies

Comparison of standardized uptake value of FDG in detecting Hodgkin disease and subtypes of non-Hodgkin’s lymphoma based on WHO/REAL classification

B.I. Kim (1), G.J. Cheon (1), S.Y. Ryu (2), C.W. Choi (1), S.M. Lim (1), S.W. Hong (1). (1) Department of Nuclear Medicine of the Korea Cancer Center Hospital, (2) Department of Obstetrics and Gynecology of the Korea Cancer Center Hospital, Seoul, Korea.

L. Guan (1), R. Elstrom (1), H.M. Zhuang (2), J.L. Alberini (2), S.J. Schuster (1), A. Alavi (1). (1) Division of Nuclear Medicine, (2) Division of Hematology/Oncology,Hospital of the University of Pennsylvania,Philadelphia, PA 19104,USA.

Objectives: FDG PET is used successfully in detection of many kinds of malignancies. In the patients of ovarian cancer, however, there is a controversy of usefulness of FDG PET. Second look operation has an important role in the decision of ovarian cancer therapy despite its invasiveness of diagnostic procedure. Any kinds of anatomical imagings have not been used successfully instead of second look operation. We evaluated the diagnostic ability of FDG PET in the patients of ovarian cancer without evidence of remnant disease on the anatomical imaging or tumor marker study, comparing to second look operation. Methods: We included 5 patients with ovarian serous adenocarcinoma, who had a history of primary operation and three cycle post-operative chemotherapy. Before second look operation, abdomino-pelvic regional FDG PET studies were performed. Intravenous hydration, diuretics and urine foley catheterization were performed before FDG PET scanning. Emission and transmission scans were acquired for 10.5 minutes and 4.5 minutes per each frame, respectively, and were reconstructed using OSEM method. If there was any focal positive finding on PET studies, biopsy was performed in second look operation. And additional blind biopsies and washing cytologies were performed. Abdomino-pelvic CT and tumor marker studies (CA-125, CA19-9) were also performed before second look operation. FDG PET scans were evaluated, compared to the pathologic results on second look operations. Results: Three of five patients were proven as having remnant disease by blind biopsies and washing cytologies of second look operations. There were no metastatic foci on peritoneal surface by visual inspection. In these three patients, FDG PET could not find any abnormal finding that could suggest remnant diseases. The other two patients were proven as no remnant disease. In one of two patients FDG PET found suspicious lesion, but subsequent biopsy revealed that there was no malignant cells. In the other one of two patients, FDG PET also could not find any abnormal findings. The sensitivity of FDG PET was 0 % (0/3), the specificity of FDG PET was 50 % (1/2) and the accuracy of FDG PET was 20 % (1/5). CT and tumor marker (CA-125 and CA19-9) studies could not find any evidence suggesting remnant disease in all patients. Conclusions: FDG PET was not expected to replace second look operation in ovarian serous adenocarcinoma when there was no evidence of remnant disease on anatomical imaging and tumor marker studies. Probably, the pattern of recurrent disease in ovarian cancer after primary operation and metabolic suppression effect of chemotherapy were inferred to affect the low sensitivity of FDG PET.

Aim: The aim of this study was to determine the difference in Standardized uptake value (SUV) in Hodgkin Disease (HD) and in Non-Hodgkin’s Lymphoma (NHL) of different histological types based on World Health Organization / Revised European-American Lymphoma (WHO/REAL) classification. Materials and Methods: 142 PET scans of 41 HD and 101 NHL patients with newly diagnosed or untreated relapsed disease were retrospectively reviewed. The maximum SUV (SUVmax) was calculated in the center of the highest region of interesting of abnormal PET images. In 101 NHL patients based on WHO/REAL classification, there were 47 diffuse large B-cell lymphomas (BCLC), 35 follicular lymphomas (FL), 12 marginal zone lymphomas (MZL) and 7 mantle cell lymphomas (MCL). Results: There were 133 positive PET and 9 negative PET (1 HD, 1FL, 6 MZL and 1 MCL). The SUV max of HD was 8.22 ± 3.18. In subtypes of NHL, the SUVmax of BCLC, FL, MZL and MCL were 10.15 ±5.70, 6.84 ± 4.50, 2.64 ± 1.84 and 10.95 ± 6.70 respectively. The average SUVmax of MZL was lowest among 4 subtypes of NHL, was significant different from other 3 subtypes of NHL (BCLC, FL and MCL), and also was significantly lower that that of HD. The average SUVmax of other 3 subtypes of NHL (LBCL, FL and MCL) was not significantly different from each other, and also was not different from that of HD. Conclusion: There is no significant difference in SUV measures among HD and different subtypes of NHL (LBCL, FL and MCL) based on WHO/REAL classification except MZL, which has low FDG uptake and may represent a distinct biological type.

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L. Guan, H.M. Zhuang, J.L. Alberini, A. Alavi. Division of Nuclear Medicine, Hospital of the University of Pennsylvania,Philadelphia, PA 19104,USA.

S. Adam (1), H. Wolff (2), E. Richter (1), M. Baehre (1). (1) Clinic of Radiotherpay and Nuclear Medicine, University Hospital Luebeck, (2) Clinic of Dermatology, University Hospital Luebeck, Luebeck, Germany.

Aim: The diagnosis of splenic involvement in lymphoma is difficult in the absence of surgical removal of spleen for histological examination. Increasingly, FDG-PET is being employed as the study of choice for the evaluation of patients with lymphoma. The aim of this study was to compare FDG-PET and CT in evaluating splenic abnormalities in patients with lymphoma in order to further validate the efficacy of the former in the assessment of involvement of this organ. Materials and Methods: One hundred and seventy-eight whole-body FDG-PET images and corresponding CT results from 130 patients with lymphoma were retrospectively analyzed. All PET studies were conducted on a dedicated PET camera. Results: In 150 studies, neither FDG-PET nor CT detected any lesions in the spleen. FDGPET and CT both detected splenic lesions in 15 cases. In 4 cases with positive splenic finding on FDG-PET, CT appeared negative. On the other hand, in 9 cases CT showed either splenomegaly or low-density lesions, while PET was interpreted as negative for an active process. The significance of this discordant observation between CT and FDG-PET remains unclear. It is conceivable that CT findings represent inactive structural changes due to previous interventions. Interestingly, Standard Uptake Values (SUV) on FDG-PET scans correlated with the CT findings. In 7 patients with focal lesions in the spleen on CT, the SUV was significantly higher than that in 8 patients with only splenomegaly without focal lesions on CT (7.26 ± 3.80 vs 3.51 ± 1.23, p < 0.05). Conclusion: These preliminary data demonstrate the efficiency of FDG-PET imaging in the assessment of splenic involvement by lymphoma. However, further validation is necessary to establish its role as the study of choice for this purpose.

Aim: The aim of this study was to evaluate the sensitivity and specificity of gamma camera coincidence PET (GCC-PET), the PET variant which reduces costs significantly. In a retrospective study, we investigated the diagnostic efficiency of GCC-PET in comparison to conventional diagnostic procedures in patients (P) with malignant melanoma (MM) in staging, restaging and follow-up after immunochemotherapy (IC). Materials and Methods: 52 consecutive P were investigated since October 1997 with GCCIPET and conventional morphological imaging (ultrasound, CT, MRI). 45-60 minutes after injection of 250-350 MBq 18F-FDG PET studies were performed with a double-head coincidence gamma camera (Prism 2000 XP PCD, Marconi, 19 mm crystal) in 3 bed positions with 180° rotation and 80 sec/step (corrected for decay). Data were reconstructed iteratively with implemented homogeneous absorption correction (ISA by Luig). In a total of 64 PET investigations (35 before/29 during treatment or after completion of IC) we evaluated the following regions (R) with regard to MM manifestations a) primary tumor localization, b) lung, c) liver, d) regional lymph nodes (LN) and e) others amounting to a total of 288 R. Results were verified by histological findings or a follow-up of at least 3 months. Results: The GCC-PET detected 72 of 88 proven MM manifestations (sensitivity 82 %). 16 R were proven false negative (osteolysis, partially necrotic filia, filiae < 1 cm). 189/200 R were found correctly negative (specificity 95 %). Only GCC-PET could distinguish between scar and active tissue or affected and non-affected LN in 10 cases (5/10 rp, 5/10 rn) with persistent tumor tissue after therapy. Conclusions: Even using a first generation GCC-PET system a high diagnostic accuracy in staging and restaging of P with MM was achieved. Frequently, therapeutic procedure was influenced decisively (approximately 20 % of the cases). GCC-PET was superior to conventional diagnostic procedures in reliable differentiation between scar and active tissue. PET, including GCC-PET, should accordingly play a larger role in staging and follow-up of P with MM.

Comparison of FDG-PET and CT in detecting splenic involvement in lymphoma patients

Staging, Restaging and Follow-up of Malignant Melanoma with [18F]FDG and Gamma Camera Coincidence PET

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Staging of recurrent and advanced lung cancer with FDG-PET with a coincidence gamma camera: A comparison to conventional staging methods

Accuracy of 18FDG for detecting and staging of pulmonary tumours using a dual head coincidence camera as determined by two independent observers

R. A. Schmid (1), H. Hautmann (2), B. Poellinger (3), W. Kellner (1,4), K. Brinkbaeumer (1), M. Weiss (1), K. Hahn (1), S. Dresel (1). (1) Department of Nuclear Medicine, University of Munich, (2) Department of Internal Medicine, University of Munich, (3) Department of Radiooncology, University of Munich, (4) Department of Clinical Radiology, University of Munich, Munich, Germany.

H. Stevens (1), P.F.A. Bakker (2), N.J.J. Schlosser (3), P.P. van Rijk (1), J.M.H. de Klerk (1). (1) Department of Nuclear Medicine, University Medical Center, Utrecht, The Netherlands, (2) Department of Thoracic Surgery, University Medical Center, Utrecht, The Netherlands, (3) Department of Pulmonology, University Medical Center, Utrecht, The Netherlands.

Aim: Aim of the study was to evaluate [F-18]FDG imaging of recurrent or inoperable lung cancer using a coincidence gamma camera system (hybrid PET) device. Examinations were compared to the results of conventional staging modalities. Methods: 36 patients with recurrent or primarily inoperable lung cancer (29m, 7f, age: 64.,8+/-12,0 yrs) were examined using hybrid PET (Marconi Axis Gamma-PET, 60 min p. i., 370 MBq [F-18]FDG). Studies were acquired in list mode using an axial filter anddata were reconstructed iteratively (OSEM). All patients underwent CT in multislice technique (Marconi Mx 8000). Lesions suspicious for primary or recurrent tumour were verified by biopsy; mediastinal lymph nodes were considered as malignant, when positive histology was assessed by mediastinoscopy. If no histology was to be obtained, lesions were also regarded as positive, if a diameter greater than 1cm was documented with CT and clinical course showed progression or specific therapy response. Distant metastases were diagnosed by conventional staging (CT and bone scintigraphy) and follow-up. Results: Using hybrid PET all primary lesions showed a focally elevated glucose metabolism. N1 lymph node involvement was identified in 24/26 cases (92%), N2 lymph node metastasis in 26/29 cases (90%) of and N3 disease in 11/13 (85%) . Pulmonary spread was found in 4/8 cases (50%), whereas in three patients with multiple foci with a diameter of 1,5 cm and smaller hybrid PET was false-negative. Pleural affection diagnosed by CT was seen with hybrid PET in 4/5 patients. 4/4 patients with bony metatases in conventional staging presented with positive findings in hybrid PET as well. Overall concordance with conventional staging was found in 28/36 of patients (78%). In 4/36 (11%) unknown sites of tumour were detected leading to therapeutic consequences in 3 patients. Hybrid PET would have led to an understaging in 4 cases (11%), resulting theoretically in inefficient treatment in 2 patients. Conclusion: Using hybrid PET for staging of recurrent or primarily inoperable lung cancer supplied equal (78%) or more information (11%) compared to conventional staging procedures (CT and bone scintigraphy). Using the information of hybrid PET alone, 11% of the patients would have been unterstaged. We conclude that hybrid PET of the latest generation has the potential for use as complementary staging tool in this subgroup of patients, providing supplementary information compared to conventional staging modalities.

Objectives: The accurate detection of lung carcinoma and to determine its stage remains a significant clinical problem. PET with 18F-fluordeoxyglucose (18FDG) has been shown to improve detection and staging of lung cancer and to prevent unnecessary invasive procedures. Positron imaging with dual-head gamma cameras may not be as sensitive as PET, but recent studies have shown good results with these cameras. Methods: In the present study we investigated 100 patients, 76 males and 24 females (mean age 60.7±9.4), with suspected primary bronchogenic carcinoma. 18FDG-scans were performed using a dual head coincidence camera (Vertex-MCD, ADAC) 1 hour after intravenous injection of 185 MBq 18FDG. In 46 patients attenuation correction was also performed. Two independent observers unaware of the clinical status analysed all imaging studies. TNM classification was performed after surgical staging. Results: In 44 patients with clinically suspected bronchogenic carcinoma no evidence for malignancy was found. However, in 56 patients a pulmonary neoplasm was demonstrated. At inter-observer analysis a Kappa of 0.94 (P<0.0001) was found for detection of the primary tumour and a Kappa of 0.63 (P<0.0001) for mediastinal staging. A sensitivity of 96%, a specificity of 93% and an accuracy of 95% were found for detection of pulmonary neoplasm. Assessment of lymph node involvement showed a sensitivity of 50%, specificity of 92% and an accuracy of 77%. The sensitivity of CT in assessing lymph node involvement was 36%, the specificity 86% and the accuracy 67%. The lack of sensitivity for staging lymph node involvement with the dual head camera is probably due to loss of resolution for detecting smaller malignant lesions. Attenuation correction provided more anatomical information but no differences were seen between attenuation correction and no attenuation correction for detecting lesions or lymph node involvement. Conclusion: The present study confirms earlier data showing that 18FDG-scans with dual head coincidence cameras are very useful in the detection of lung cancer and is less suitable for staging of lymph node involvement, with accuracy comparable to CT.

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R. Quirce (1), F.J. Pena (1), R.H. Allende (1), J.I. Banzo (1), J.L. Carreras (2), M.J. Garcia-Velloso (3), J.M. Carril (1). (1) Servicio de Medicina Nuclear. H.U.M.Valdecilla. Universidad de Cantabria. Santander. España, (2) Centro PET DR. Carreras. Madrid. España, (3) Servicio de Medicina Nuclear. Clínica Universitaria de Navarra. Pamplona. España.

S. Rozeboom, J. Schoenberger, M. Segmueller, C. Eilles. Department of Nuclear Medicine of the University of Regensburg, Germany.

Utility of FDG-PET in lung carcinoma with non diagnostic CT

Aim: To evaluate the utility of PET with FDG (FDG-PET) in patients with suspected or histologically proven lung cancer when CT is not diagnostic. Material and Methods: 28 FDG-PET examinations were performed in 27 patients, 3 women and 24 men, with a mean age of 58+19 years. Of the 28 FDG-PET examinations 13 were for lesion characterization: 8 solitary nodules (SPN) and 5 nodules with suspected lymph node involment. 4 were for staging , and 11 were for re-staging after therapy. In this group CT showed non conclusive findings in 10 and 1 had a negative CT whit progresive rising levels of CEA. Final diagnoses was established by histology in 9 and by clinical follow-up in 19. Malignancy was ruled out in 5 patients, all with SPN, and confirmed in the other 22. Results: Of the 8 SPN, 3 were FDG negastive (3 True Negatives -TN), 1 showed a SUV of 2.5 (malignancy was ruled out by surgery), and 4 showed high FDG uptake (4 True PositivesTP) with lymph node involvement in 2 of them (1 False Positive-FP) and also one hepatic metastase in one. Of the 5 nodules with suspected lymp node involvement, 1 showed FDG uptake with a SUV of 1.8 and no uptake in the lymph nodes (malignancy was ruled out by surgery), the other 4 showed high uptake of FDG (4 TP) with no FDG uptake in the lymph nodes of 3 (1 False Negative and 2 TN) and in the other extensive disease was detected (TP). In the 4 examinations for staging, uptake in the lymh nodes was observed (1 FP and 3 TP) and also extensive disease was detected in one. With regard to the re-staging group FDG missed two suprarenal lesions with non conclusive CT and showed new lesions in 4 examinations. FDG-PET changed the staging by CT in 21 explorations, up-staging in 16 and down-staging in 5. Conclusion: FDG-PET was in our population an useful tool for diagnosis of patiens with lung cancer when CT was not conclusive both in the initial staging and in the re-staging afther treatment.

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Clinical value of a dual-head coincidene gamma-camera in the evaluation of unknown lung lesions and lymph nodes

Aim: Aim of the study was the evaluation of the accurancy of coincidence imaging (COI) compared to dedicated PET and CT for examination of unknown lung lesions and lymph nodes and staging of the bronchial cancer. Method: Until now 22 patients (16 male/ 6 female; age 45 - 77 y) were examinated. After an overnight fasting (normoglycemia with plasma glucose level >130 mg/dl) 300-350 MBq FDG and 20 mg furosemid were injected. About 60 min. later the FDG-emission scanning for the whole-body imaging was started at the dedicated PET-scanner (lasting about 60 min.). Right after finishing the PET scan COI of the chest was started (120 min. p.i.; scan-time 30 min.). Results: Both image-techniques were interpreted visually by two experienced observers. In 16 of 22 patients a malignoma could be detected in both studies. In 5 patients with benigne lesions (e.g. hamartom, chondromas) no increased FDG-uptake was seen. All cases were confirmed histopathologically. PET-images showed a better, anatomical resolution and delineation especially in small lesions. One false-positive case was seen in PET as well as in COI. Histopathological finding was an active sarcoidosis. Conclusion: FDG-imaging by either dedicated PET and COI was superior to conventional imaging and staging. The following table summarizes sensitivity and specificity of each method (data in percent): ln-staging sensitivity CT PET COI

sensitivity

spezificity

malignoma

sensitivity

specificity

61 92 88

77 88 85

CT PET COI

100 94 91

46 80 75

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n PET: OTHERS The accuracy of FDG-PET in recurrent breast cancer D. Wong, J. Squires, K. Herrenberg. The Wesley PET Centre of The Wesley Hospital, Brisbane, Australia. Aim: To determine the accuracy of FDG-PET in the detection of recurrent breast cancer. Material and Methods: A retrospective study using a dedicated NaI PET scanner was performed in 72 consecutive women referred for a FDG-PET study for the evaluation of possible recurrent breast cancer. Follow-up was possible in 50 women. The PET findings were confirmed with other imaging modalities, biopsies and clinical follow-up for 12 months. Results: FDG-PET detected 50/56 tumour sites in 32/38 patients with tumour recurrence. Based on patients, there were 32 true positive, 10 true negative, two false positive and six false negative findings. The six false negative findings were four patients with bony/marrow metastases, one with supraclavicular nodal metastasis and one with peritoneal metastases. The two false positive findings were physiological laryngeal uptake and physiological atrial uptake. The sensitivity of FDG-PET was 84%, specificity 83% and accuracy of 84%. Conclusion: FDG-PET has a significant role in the evaluation of patients with possible recurrent breast cancer.

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Detection of recurrent breast cancer with 18FDG-PET in patients with a progressive elevation of CA-15.3 tumor marker. S.P. Suarez-Piñera (1), D.B. Delgado Bolton (2), P.C. Perez Castejon (1), J.V. Jiménez Vicioso (1), R. Ruiz (1), D. Domper (1), P.V. Pérez Vázquez (3), M. Montz (1), C.D. Carreras Delgado (2). (1) Instituto PET Dr. Carreras, Madrid, Spain, (2) Hospital Clinico San Carlos,Madrid, Spain, (3) Hospital Gregorio Marañón, Madrid, Spain. OBJECTIVES: Evaluated the role played by positron emission tomography (PET) using F 18-Fluorodeoxiglucose (FDG) in the detection of tumoral recurrence in breast cancer treated patients in apparent remission complete, whom a progressive increase of CA 15.3 have been detected and the remaining test being negative. METHODS: Retrospective study in 52 women with a history of breast cancer treated with intention to cure, underwent a whole body PET-FDG. All had a progressive increase of CA 15.3. The findings of PET-FDG were compared with the other imaging techniques, clinical follow-up (minimum of 12 months) and in those cases in which it was possible with the pathology results. RESULTS/CONCLUSIONS: In 34 patients, the PET-FDG was positive, verifying the results in 29. In 18 patients the PET was negative, and the disease was not detected by other imaging techniques in 12 of them. Sensitivity, specificity, positive predictive value and negative predictive value of the PET-FDG were 82, 71, 85 and 66% respectivily. After the PET findings, three new neoplasms were diagnosed and treatment was modified in 55% of the patients. Value of CA15.3 above 66U/ml were aaccompanied by good performance in the PET-FDG These results show how the PET-FDG is a useful test in these patients, both for its capacity to detect disease not observed with other methods as well as for the valuable information obtained from its management. These facts should lead to reconsider the need to use the PET-FDG as a first line diagnostic in these patients.

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Importance and Frequency of Unexpected FDG-PET Findings in Patients Studied for Searching Possible Malignancy S. Okay, M. Halac, C. Türkmen, S. Bozluolcay, K. Sönmezoglu. International Hospital, Departments of Nuclear Medicine, Istanbul, Turkey. Aim: We reported unexpected but atypical FDG-PET findings in 7 out of 19 (37%) patients without any diagnosed malignancy or any suspicious mass for cancer at the time of PET study. Materials and Methods: The referral reasons for FDG-PET study were suspicion of paraneoplastic syndrom in 4 pts (2 abnormal), familial cancer tendency in 9 pts (3 abnormal) and cancer phobia in the remaining 6 pts (2 abnormal). Results: Among the patients with paraneoplastic syndrom suspicion, one had an intense uptake of FDG in recto-anal region and the biopsy revealed an adenocancer. The other patient had a hypermetabolic focus in the lower lobe of the right lung, which was diagnosed as NSCLC by transbronchial biopsy. Regarding to the patients with familial cancer tendency and positive PET study, we saw two foci of increased activity in the left pelvis in the first one. No diagnostic information could be obtained due to insufficient material from the CT-guided biopsy. The patient rejected any further invasive procedure. Follow-up CT scan after 6 months showed no changes. In the second patient of this group, we noted an intense uptake of FDG in recto-anal region, which was verified as an anal inflamed fissura. The last patient of this group had a hypermetabolic focus in the left parotid region, from which FNAB revealed nonspecific chronic inflammatory changes. The FDG-PET scan was very impressive revealing numerous foci of increased FDG uptake throughout of the body in one of the patients with cancer phobia, who rejected any further possible investigation. The second patient had an increased FDG uptake in recto-anal region where an anal abscess was found. Conclusion: A whole-body FDG-PET scan is a useful method for searching any possible malignancy in suspected patients. Even in the case of no malignancy is found, it can draw the physician’s attention to unexpected region of the body where the pathological process takes place on.

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F-18 FDG Uptake in Colonic Villous Adenomas N. Arslan, F. Dehdashti, B.A. Siegel. Washington University School of Medicine, St. Louis, MO, USA. Aim: Colonic adenomas constitute 70-80% of all colorectal polyps, and their clinical significance relates primarily to their relationship with colon cancer. Endoscopic polypectomty is considered the method of choice for diagnosis and treatment of colorectal polyps for a possible subsequent malignancy. Although, colonic neoplastic adenomas have been reported to be a potential cause for false-positive findings in FDG-PET, the range of standardized uptake values (SUVs) and the histologic features of FDG-avid adenomas has not been addressed. In this study, we aimed to investigate the degree of FDG uptake within colonic villous adenomas. Material and Methods: A pathology database search was performed to identify all patients diagnosed with colonic villous adenoma between June 1,1996 and December 1, 2000. Among the patients with a diagnosis of colonic villous adenoma, patients who underwent FDG-PET up to 1 month before biopsy were included in this study. FDG-PET findings were compared with pathological features. Results: There were six patients diagnosed with villous/tubulovillous adenoma on pathology who had also FDG-PET prior to pathological evaluation. Five of these patients had focally increased FDG uptake on FDG-PET, which was considered suspicious for colon cancer. Two of the 6 patients had been referred for PET for evaluation of possible recurrent colon carcinoma because of rising CEA levels, while the others had been referred for the evaluation of other malignancies. The pathologic findings and results of the FDG-PET studies with SUVs for 4 (digital data were unavailable for the other 2) are tabulated below. No: Pathological Diagnosis 1 Villous 2 3 4 5 6

Tubulovillous adenoma Tubulovillous adenoma Villous adenoma Tubulovillous adenoma Tubulovillous adenoma

Adenoma Location Rectum adenoma Cecum Right colon Rectum Cecum

History Colon carcinoma Esophageal carcinoma Cervix carcinoma Lung carcinoma Lung nodule

Transverse Colon colon (splenic carcinoma flexura)

Tumor Size (cm) 2.5x1.5x1.3

FDG-PET Result Negative

SUV value N/A

4x3x3

Positive

N/A

4x2.5

Positive

6.1

1.5x1.3x1

Positive

3.8

1.5x9.8

Positive

4.8

Biopsy only

Positive

13.8

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n PET: OTHERS Conclusion: Given the high SUVs values (3.8-13.8) of these lesions, colonic villous adenomas may lead to false-positive findings on FDG-PET. The pathologic and metabolic features of the subsets of colonic adenomas that do and do not have increased FDG uptake needs to be further evaluated.

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Comparison of FDG-PET, Tc-99m-Tetrofosmin and Iodine-131 in the detection of thyroid cancer metastases or recitivity of local carcinoma A. Knittel, C. Alexander, C.M. Kirsch. Dept. of Nuclear Medicine; Saarland University Medical Center; D-66424 Homburg; Germany. The purpose of this study was to examine the diagnostic acurracy of FDG-PET in comparison with those of Tc-99m-Tetrofosmin and I-131 in detecting metastases or recidives of thyroid carcinoma. Methods: The study design included 62 patients with thyroid cancer who underwent iodine131 whole-body scintigraphy, Tc-99m tetrofosmin whole-body scintigraphy, and F-18 FDG positron emission tomography. The three different methods were performed within a time interval of four months. The evaluation comprised the calculation of overall and locoregional sensitivity, specificity, accuracy in comparison to patient’s histology and follow-up. Results: FDG-PET examinations gave 88 tumour sites, Tetrofosmin 28, and I-131 examinations 68 localisations. Overall sensitivity was 72 percent (28:39) for FDG-PET, 64 percent (9:14)for Tc-99m tetrofosmin, and 52 percent (16:31) for I-131 whole body scintigraphy. The specificity of the three methods respectively was 43 %, 60 %, and 62 % for FDG-PET, Tc-99m-tetrofosmin and I131 whole body scintigraphy. The locoregional sensitivity was 73 % in FDG-PET examination, 61 % in tetrofosmin and 45 % in I-131 scintigraphy. The specificity of FDG-PET was 46% in comparison to 70 % in tetrofosmin and 71 % in I-131. The corresponding values for recurrence, lymph node-, lung-, bone-, and liver metastases gave different diagnostic usefulness for the methods. Conclusion: The results demonstrate that FDG-PET and Tc-99m tetrofosmin whole-body scintigraphy are adequate additional diagnostic tools in the detection of advanced thyroid carcinoma.

Date: 02.09.2002 • Time: 16:30 - 16:00 • Hall: Poster exhibition PET: METHODOLOGICAL ASPECTS

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E. Kresnik, P. Mikosch, H.J. Gallowitsch, I. Igerc, I. Gomez, G. Kumnig, P. Lind. Dept. of Nuclear Medicine & Endocrinology, LKH Klagenfurt, Austria.

E. de Hemricourt, L.O. Dierickx, M. Van Roy, A. Vervaet, J. Vandevivere. Da Vinci PET Center-Middelheim Hospital, Antwerp, Belgium.

Emissions Tomography in the Preoperative Assessment of Thyroid Nodules in an Endemic Goitre Area

The aim of this study was to evaluate the usefulness of 18F-FDG PET in the preoperative assessment of hypofunctional or cold thyroid nodules. A total of 36 patients were examined before surgical resection. In all patients, imaging was obtained at 70 min after the intravenous administration of 180 MBq 18F-FDG. Standard uptake values (SUVs) were calculated. A total of 15 thyroid carcinomas (11 papillary, three follicular, one anaplastic), 18 thyroid adenomas (eight microfollicular, eight oxyphilic, two macrofollicular) and three patients with degenerative goitre were found. 18F-FDG uptake in oxyphilic adenoma, thyroid cancer, microfollicular adenoma, degenerative goitre and macrofollicular adenoma was 4.6±2.4, 3.6±1.9, 1.6±0.2, 1.2±0.2, and 0.9±0.1. Significant differences were observed between thyroid carcinomas and both microfollicular adenomas and degenerative goitres (p<0.05), and between oxyphilic thyroid adenomas and both microfollicular as well as degenerative goitre (p<0.05). For diagnosis of thyroid carcinoma, 100% sensitivity, 63% specificity, and 100% negative predictive value was found when a cutoff value for SUV of two was used. Our results indicate that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism. 18F-FDG PET is unlikely to successfully differentiate all benign from malignant tumours, but can help select patients who need surgery, especially if cytology is inconclusive or malignancy cannot be excluded.

Variation associated with different techniques of SUV computation : analysis of reproducibility and interobserver variability.

Aims: The use of SUV as a semi-quantitative index to measure the 18F-FDG tumoral uptake is suboptimal and depends on many parameters such as the weight (w), body surface area (BSA), maximum (max) or mean activity inside the region of interest (ROI). No authors have yet looked on the reproducibility of all these measures together. This study evaluates the variation of each type of SUV and the interobserver variability. Materials and Methods: Forthy patients scanned in our PET center were studied retrospectively. Each patient received a mean dose of 300 MBq. The images were processed with attenuation correction and OSEM. A circular ROI was drawn over the cerebellum-(Cb) (70 pixels) and the liver-(Lv) (150 pixels). Finally, different types of SUV were measured : SUVw-max, SUVw-mean, SUVBSA-max and SUVBSA-mean. Two nuclear physicians independently placed the ROIs and reported the results. Interobserver variability was expressed as mean and standard deviation of the differences. A p-value < 0.05 was considered significant for the paired t-test. Results: See table. (Cb)

(Lv)

SUV w-max w-mean BSA-max BSA-mean w-max w-mean BSA-max BSA-mean

mean (± 1 SD) 8.4 (± 1.99) 6.4 (± 1.41) 42.7 (± 8.87) 32.1 (± 6.57) 2.7 (± 0.56) 1.9 (±.0.34) 13.8 (±2.47) 9.7 (± 1.60)

range 4.5-13.1 3.5-9.7 25.0-60.5 19.9-46.7 1.7-5.0 1.0-3.0 7.9-23.4 4.7-14.1

Coeff. variat. (%) 24 22 21 21 21 18 18 17

Interobserver variability : Cb : w-max : -0.1 (± 0.79) (NS) , w-mean : -0.2 (± 0.45) (p=0.04) , BSA-max : -1 (± 3.02) (NS) , BSA-mean : -0.7 (± 1.68) (p=0.03) Lv : w-max : 0.0 (± 0.26) (NS) , w-mean : 0.0 (± 0.11) (NS) , BSA-max : 0.2 (± 1.52) (NS) , BSA-mean : 0.1 (± 0.85) (NS) Conclusion: SUV corrected for BSA indicates a lesser variation compared with SUV normalized for weight The liver shows higher reproducibility with respect to the cerebellum. The lowest variation was found for the BSA corrected SUV in the liver. Differences are however small and the interobserver variability is not statistically significant except for two measurements. A larger study is currently in progress to delineate more precisely this point.

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n PET: METHODOLOGICAL ASPECTS A complete study for oncological Standardized Uptake Value (SUV) behaviour; Consideration of time-dependency, region of interest (ROI) generation and correlation with absolute value. S. Oku (1), T. Momose (1), A. Abe (1), K. Yonekura (2), I. Yokoyama (2), M. Kameyama (1), S. Mizuno (1), Y. Kumakura, K. Ohtomo. (1) Dept. of Radiology of the University of Tokyo, Tokyo, Japan, (2) Dept. of Cardiovascular Internal Medicine of the University of Tokyo, Tokyo, Japan. Aim: Fluoro-18-deoxgyglucose positron emission tomography (FDG-PET) is considered as a useful tool for evaluation of therapeutic effect of the rectal cancer and the semi-quantification by Standardized Uptake Value (SUV) seems to replace the conventional & hazardous absolute quantification. However, there was not yet wide acceptance of a common protocol for oncological SUV. The authors thoroughly investigated time-dependency of SUV and their correlation with absolute quantification as well as with the outcome of the clinical long-time followup. Effect of the ROI generation was also examined. The purpose of the present study is to propose an optimal quantification protocol of SUV and enhance the usefulness of SUV as a prognostic indicator of cancers. Material and Methods; Fifty-two patients of the rectal cancer underwent a series of FDGPET before and after the external radiotherapy prior to the surgical operation. A dynamic study for 35 minutes of the heart immediately after the injection was used to determine the input function. Consequent dynamic acquisition for 25 minutes of the tumor lesion level was also performed. A modified Patlak’s method reported by the authors were employed to determine the absolute glucose utilization. Glucose metabolic ratio (Gmr) with four and seven time points during the second dynamic scan were used. ROI’s of various sizes and shapes; from a 4 mm circle to tumor-size-conscistent irregular shape ROI, were placed on the tumor, muscle, bladder and soft tissue and these SUV’s at t=40, 50, 55, 60 and 65 minutes were calculated and studied their quantitative steadiness. For each method, tumor SUV before radiotherapy (SUV1), SUV after radiotherapy (SUV2) and their ratio (SUV2/SUV1) were evaluated as prognostic indicator. Result: All of the examined SUV’s showed the same statistical tendency, i.e., SUV1 nor the ratio SUV2 / SUV1 displayed no statistically significant difference between the patients with and without recurrence, whereas SUV2 displayed significant difference between the patients with/without recurrence. There was a good agreement of the Gmr with four and seven time points methods. Taking the Gmr with seven points as a golden standard, SUV’s at various time points showed no statistical difference in their correlation, and at t=60, the separation between with/without recurrence was better. Given fixed t, the least quantitative variance was obtained from averaging the SUV’s of multiple small ROI’s, not from a bigger solo ROI. Conclusion: SUV at t=60, with averaging multiple smallest ROI’s, of the FDG-PET after therapy was considered to be an optimized set of parameters for SUV determination of FDGPET as a prognostic indicator.

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Neural Network Used For The Analysis Of Dynamic PET Data. L.G. Strauss (1), A. Dimitrakopoulou-Strauss (1), G. Kontaxakis (2). (1) German Cancer Research Center, (2) Univ. Politecnica de Madrid, Heidelberg, Germany, Madrid, Spain. Objectives: Calculation of the kinetic parameters for the FDG two compartment model using a multiplayer perceptron network to improve the analysis of dynamic PET data. Methods: Neural networks are very sophisticated modeling techniques, capable of modeling extremely complex functions. In particular, neural networks are non-linear, and therefore especially usefull for the analysis of tracer kinetics. The conventional iterative calculation of the parameters of the two compartment model requires experienced nuclear medicine physicians to avoid misleading results. Therefore, we try to limit the possible source of error by the use of a neural network for the data analysis. The evaluation included 150 malignant lesions from different tumor entities. PET studies were performed dynamically and a quantitative analysis was done using VOIs (volume-of-interest) and the fitting of a two compartment model using a dedicated software. The fractal dimension (FD) was calculated for each dynamic curve using a module of the PMOD software. Furthermore, several neural network models were applied to the data and optimized with regard to the results of the two compartment model. Results: The two compartment model provided the following data: vessel density (VB) and the kinetic constants K1-k4. These parameters as well as the FD were used for reference and the neural networks were optimized to obtain the best correlation. The results show that a multiplayer perceptron network with four layers provided best results. A regression ratio of 0.899 was obtained. We were able to estimate the kinetic parameters using the neural network from the raw dynamic PET data. The network accuracy is improved in the ongoing study by inclusion of further kinetic data. Conclusions: The current results show that a neural network can be used to estimate the parameters of the two compartment model. In contrast to the conventional iterative solution, the new approach provides more stable results and should therefore find preferential use for the data analysis.

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Quantification of FDG tumoral uptake : correlation between the metabolic ratio and different types of SUV.

Non Compartment Analysis Using The Fractal Dimension For the Quantification Of Dynamic PET Studies.

E. de Hemricourt, L.O. Dierickx, C. Vercauteren, M. Van Roy, A. Vervaet, J. Vandevivere. Da Vinci PET Center-Middelheim Hospital, Antwerp, Belgium.

A. Dimitrakopoulou-Strauss (1), L.G. Strauss (1), K. Mikolajczyk (2), C. Burger (3). (1) German Cancer Research Center, (2) Institute of Precision and Biomedical Engineering, (3) Clinic of Nuclear Medicine Univ. of Zuerich, Switzerland.

Aims: Standardized uptake value (SUV) as a measure of glucose metabolism is suboptimal and is highly dependent on many variables. In the past, some authors have used a metabolic ratio (MR) as another way to quantify tumoral uptake with 18F-FDG PET. This index consists of a ratio of counts measured over tumoral and non-tumoral tissues as the cerebellum, liver or brain. Contrary to the SUV, the computation of MR does not rely on data such as the patient’s weight or the BSA and on the tomographic calibration factor. Because of that, using MR instead of SUV could turn to be more useful for multicenter trial. However, no studies have focused on the correspondence between these ratios and the tumoral SUV. This study evaluates the correlation between the SUV and the MR. Materials and Methods: Forthy consecutive patients evaluated for oncological staging with FDG-PET were retrospectively studied. A histological confirmation of the tumoral lesion was obtained for every patient. Images were acquired 1 hour after injection of a mean dose of 300 MBq, then reconstructed with attenuation correction and OSEM. A ROI with a diameter of 1 cm was placed over the tumor, the cerebellum and the liver. SUV was normalized for the weight (w) and the body surface area (BSA). Mean and maximum (max) activities were measured for each ROI. The correlation between tumoral SUV and both ratios tumor/cerebellum (T/C) and tumor/liver (T/L) was studied. A p-value < 0.05 was considered significant. Results: The results are shown in table : each type of SUV is correlated to the MR. activity mean

SUVw – T/C SUVw – T/L SUVBSA – T/C SUVBSA – T/L max SUVw – T/C SUVw – T/L SUVBSA – T/C SUVBSA – T/L cc : correlation coefficient

cc 0.899 0.935 0.896 0.935 0.823 0.874 0.845 0.887

p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

Objectives: Quantification of dynamic FDG-PET studies is generally a problem. We examined the value of the fractal dimension (FD), a parameter based on the box counting (BC) procedure of the chaos theory. Methods: The evaluation included 200 malignant lesions in 159 patients with different tumor entities as well as 57 benign lesions for comparison. Malignant tumors included melanoma metastases (17 pts, 22 lesions), lymphomas (7 pts, 14 lesions), breast tumors (29 pts, 29 lesions), liver metastases from carcinoids (2 pts, 4 lesions), liver metastases from colorectal tumors (29 pts, 56 lesions), bone tumors (31 pts, 31 lesions), soft tissue tumors (44 pts, 44 lesions). Benign lesions included 2 scars (2 pts) from primary lymphomas, benign breast lesions (4 pts, 4 lesions), 36 benign bone lesions (36 pts), 15 benign soft tissue lesions (15 pts). The FDG studies were accomplished as dynamic series for 60 minutes. The evaluation of the FDG kinetics was performed using the 55-60 min SUV and the BC based FD for the timeactivity data. Results: Visual evaluation demonstrated generally different FDG uptake patterns in the SUV images and the parametric images of FD. FD estimates depended on the number of boxes and the maximum cutoff value used for calculation. Based on the discriminant analysis of all lesions, SUV alone showed a low sensitivity of 61%, but a high specificity of 91% and a diagnostic accuracy of 68%. FD demonstrated a sensitivity of 78 %, a specificity of 72 % and an accuracy of 77 %. The combination of SUV and FD was superior with respect to sensitivity and accuracy in comparison to SUV alone, and lead to a sensitivity of 71%, a specificity of 89 % and an accuracy of 75%. Conclusions: The use of the BC based FD is a reliable method for the quantification of dynamic PET studies and seems to be more robust than the SUV. The combination of SUV and BC based FD of the time activity data seems superior in comparison to SUV alone and should be preferred for the evaluation of dynamic PET studies with FDG.

Conclusion: This study shows a strong positive correlation between each SUV and the corresponding MR. Based on the correlation presented here, we think that the MR can be used in routine practice instead of the SUV for quantifying tumoral uptake. Further studies should be realized to ascertain the place of MR in this context.

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Measurement of change in tumours by 18F-FDG imaging with a hybrid camera

False positive uptake of 18FDG-fluorodeoxyglucose in the axillary brown fat lipoma (hibernoma) - case report

A.J. Green, R.J. Francis, S. Baig, R.H.J. Begent. Department of Oncology, Royal Free and University College Medical School, London, UK.

I. Makaiova (1), J. Vesely (1), S. Kovacova (1), M. Cerna (2), P. Kasan (2), E. Brabencova (2), A. Durkovsky (3), I. Holincova (1), L. Plank (4). (1) Clinic of Nuclear Medicine of the St.Elisabeth Oncological Institute and Medical Faculty University of Komensky, (2) National Institute for TBC and Respiratory Disease, (3) Department of radiology of the St. Elisabeth Oncological Institute, Bratislava, Slovenia, (4) Department of pathology FN MARTIN, Slovenia.

Aim: The use of 18F-FDG for tumour response measurement has been proposed as a major application for hybrid camera PET (HCPET). The problem of measurement of tumour can be considered in two parts: selection of the voxels containing the tumour and quantification of relevant parameters. In this study we demonstrate the use of a region growing algorithm for the generation of tumour volumes of interest (VOI) and compare measurements of uptake for use in response assessment. Methods: In a study of patients undergoing chemotherapy 9 had fully assessable FDG scans pre-treatment, after 3-4 weeks and after 3 months of chemotherapy and CT scans pre treatment and at 3 months. FDG scans followed a strict protocol, normalisation was used to account for any small variations in imaging parameters. VOI were grown from a seed point using an adaptive threshold. A total of 72 tumour VOI were assessed from 27 studies. The mean, median, maximum counts per voxel (cpv) were recorded along with the total number of voxels in the VOI. Results: In patients with progressive disease by CT assessment (by RECIST criteria) FDG imaging showed an increase (of 27%-201%) in the number of voxels identified, the median cpv did not change significantly. In patients with stable disease FDG measurements showed no clear trend. In one patient with partial response the median cpv was increased early but decreased late, the number of voxels decreased by 90% and 96% respectively; in all other patients with partial response there was a reduction in the median cpv (12-100%) at both time points, in some cases accompanied by a reduction (0%-100%) in the number of voxels. No patients showed complete response. The maximum cpv was not found to be indicative of response. The median cpv was between 97 and 100% of the mean cpv for all VOI. Conclusions: HCPET shows promise for improving the speed of assessment of response to chemotherapy. Two parameters are sufficient to measure tumour response by HCPET: the median (or the mean) cpv and the total number of involved voxels. Changes in these parameters do not always follow the same pattern and they may indicate different physiological processes. Further work is needed to investigate whether the changes seen in FDG images for the patients defined as having stable disease by CT indicate that HCPET is more sensitive to small effects.

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FDG excretion with and without application of diuretics M. Diehl, M. Manolopoulou, J.H. Risse, W.T. Kranert, C. Menzel, F. Grünwald. Department of Nuclear Mediacine, University of Frankfurt/Main, Germany. Aim: The aim of the study was to evaluate the influence of diuretics on FDG accumulation in the bladder and on FDG-elimination in FDG studies. Methods: Thirty six patients with malignant tumors were examined. Twenty patients received 0.5 mg per kg body weight furosemid i.v. prior to FDG application. Sixteen patients were examined without furosemid injection. Both groups were comparable according to age, body weight and blood glucose levels. All patients were examined in a fasted state after weight adapted, oral hydration with 900 to 1400 ml mineral water. At least 30 minutes after injection of an average of 314 MBq 18F-FDG, attenuation corrected whole-body images were acquired using a Siemens ECATExact full ring scanner. The urine volume and the activity in the urine before and after acquisition were measured. A visual determination of the intensity of FDG accumulation in the bladder was performed using a score from 1 to 4. In addition, a quantification using SUV values was done. Results: After injection of furosemid, lower activities were found in the bladder as well as a lower FDG concentration in the urine with a larger excretion volume. The results are shown in the following table.

score SUV urine volume before acquisiotion urine volume after acquisition urine activity/ml before acq. urine activity/ml after acq. total urine activity before acq. total urine activity after acq.

with furosemid 2.14 2.41 1279 ml 659 ml 67.8 kBq/ml 99.2 kBq/ml 86.7 MBq 65.4 MBq

without furosemid 3.62 5.27 523 ml 399 ml 112 kBq/ml 132 kBq/ml 58.6 MBq 52.7 MBq

Conclusion: The use of diuretics causes a larger excetion volume and a higher FDG elimination. This results in less artifacts especially in the abdominal and pelvic region and reduces radiation exposure.

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Objectives: Hibernoma is an uncommon lipoma, it is a benign tumor of brown fat. Brown fat plays an important role in heat production. Also the term hibernoma was received after resemblance to the brown fat seen in hibernating animals. This tumor most often present as painless, slowly enlarging masses. Because these lesions have a heterogeneous appearance and contain fat, they can mimic liposarcoma on CT and MRI, requiring biopsy or extirpation with histology. The ultrastrurally, the cells demonstrate numerous mitochondria, a prominent Golgi apparatus and scant rough endoplasmic reticulum. Because it is a benign lipomatous tumor, it was expected, that the 18FDG uptake will be physiologically low or only a slight positive. What was our exclusive experience, it is a content of this case report. Case report: A 42 year old women firstly surgicaly treated for the lung adenocarcinoma (T2N2Mo) in December 1997. Adjuvant chemotherapy and bilateral lung radiotherapy were performed from 1999 till 2001. It was not clear, if the lesion visible in lung region is viable or not. Therefore a PET scaning was recommended. The result of PET scaning does not show the viable lung cancer. Surprisingly, in the right axillary region there was visible a oblique mass with size 9,5x 7,0 x 3,7 cm. The standard uptake value (SUV) of this lesions was 16,0 (very high degree). The CT result can not differentiated the origin of this lesion, it was a duplex soft tissue sarcoma presumed. The surgically extirpation was performed. Two indenpedent pathologist made the histopathologic result, which was : hibernoma. Conclusion: Energetic active or agressive benign soft tissue lesion and well differentiated malignant tumors did not differ significantly concerning glucose metabolism. Therefore the result of high uptake of 18FDG in soft tissue lipoma can be not used for the differential diagnosis between benign or malignant tumor.

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Comparison of the uptake of methyl-3H-methionine (Met), O-(2-18Ffluoroethyl)-tyrosine (FET) in tumor and inflammatory cells U. Gruenwald, B. Stoeber, H. Philippi, F.C. Rau, M. Herz, H.J. Wester, M. Schwaiger, R. Senekowitsch-Schmidtke. Nuklearmedizinische Klinik, Technische Universitaet Muenchen, Munich, Germany. Aim: As recently shown in a lymphadenitis and tumor model in mice, FET, in contrast to FDG and Met, allows a differentiation between tumor and inflammation. Therefore, the aim of the study was to characterize the uptake mechanisms of the radiolabeled amino acids FET and Met in human tumor and inflammatory cells. Methods: The uptake mechanisms and kinetics of Met and FET were investigated in glioblastoma (HS683), colon carcinoma (SW707) and lymphoma cells (DHL4), granulocytes, unstimulated and stimulated macrophages and lymphocytes. Blood cells were isolated from buffy coats by density-gradient separation. Approximately 5*105 cells of each cell line were pre-incubated at 37°C in a buffered medium containing either increasing concentrations of unlabeled amino acids or concanavalin A (stimulant for lymphocytes) and LPS (stimulant for macrophages) or specific inhibitors for the amino acid transport systems L, A and ASC (BCH, MeAIB and L-serine, respectively). The cellular uptake of FET and Met was quantified 20 minutes after addition of the tracer. For kinetic studies defined concentrations of FET and Met were added and the uptake was stopped by ice-cold PBS after incubation for 0, 1, 5, 10 and 30 minutes. Results: The uptake of FET in all tumor cells investigated was 2-4fold higher than in macrophages and lymphocytes and even ten fold higher than in granulocytes. In contrast, the uptake of Met was not significantly higher in tumor cells than in inflammatory cells. The uptake in lymphocytes and macrophages was higher than in lymphoma cells. Both, FET and Met uptake was 1,5 – 2 fold higher in stimulated than in unstimulated lymphocytes and macrophages. The specific amino acid transport inhibitors reduced tracer uptake to a higher degree in tumor cells than in inflammatory cells. Met and FET uptake could be inhibited by BCH up to 80% in tumor cells, in inflammatory cells only by 30%. The kinetic studies demonstrated that the tracer uptake is dependent on the amino acid concentration and incubation time as well as on the different affinities of FET and Met for the transport systems of the investigated cells. Conclusion: The results from the lymphadenitis and tumor model in mice could be confirmed by the in vitro investigation of human cells: FET, in contrast to Met, accumulates significantly higher in tumor than in inflammatory cells. Therefore it is a promising tracer for tumor diagnosis by PET. The different uptake of FET and Met and the various affinities of FET and Met for the transport systems of the investigated cells may be explained by the expression of different subtypes of the L-transport-system.

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Standardized Uptake Value (SUV) as a prognostic indicator for rectal cancer; SUV after preoperative radiotherapy (preRT) is more important than SUV before preRT. S. Oku, T. Momose, A. Abe, S. Mizuno, Y. Kumakura, M. Kameyama, K. Ohtomo. Dept. of Radiology of the University of Tokyo, Tokyo, Japan. Aim: In the management of the rectal cancer after the combined therapy of the radiation and surgical operation, the evaluation of the prognosis is important. Although fluoro-18-deoxgyglucose positron emission tomography (FDG-PET) is considered as a useful tool for evaluation of therapeutic effect of this cancer as well as the other cancers, however, there were few articles that clearly described the appropriate procedure of the FDG-PET in order to show the best prognostic value. The purpose of the present study is to compare several quantification methods using the Standardized Uptake Values (SUV) and to determine the most appropriate parameter for the prognostic prediction and to propose the quantitative guideline of the FDGPET. Especially, the authors focused on the SUV after radiotherapy (SUV2), which has not been considered as a key quantitative value, as it was rather taken as a mere indicator of the therapeutic (radiotherapeutic) effect, not a direct indicator of the prognosis for the cancer itself. Material and Methods: Forty patients with rectal cancer in the lower rectal region (Rb) underwent two series of FDG-PET study before and after pre-operative radiothearapy. Their SUVs were calculated from FDG-PET data and compared with the result of the long-term follow-up of the patients as well as with histopathological outcomes. Results: All 40 patients had high FDG uptake before radiotherapy. The mean value of SUV before radiotherapy (SUV1) was 7.6. After radiotherapy, the mean value of SUV (SUV2) decreased to 4.2. There was a significant difference in SUV2 between the groups with and without recurrence (p<0.05), however, SUVb or SUV ratio (SUV2/SUV1) displayed no significant difference with the incidence of recurrence. Conclusion: SUV after radiotherapy was considered to be a good prognostic indicator for long-term progonosis of rectal cancer patients. SUV before radiotherapy nor SUV ratio SUV2 / SUV1 did not have the equivalent prognostic usefulness. Subsets of patients with greater SUV2 should be observed closely.

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18F FDG-PET in the follow up of colorectal cancer: relationship between CEA levels and SUV A. Bruno (1), M. Castellani (1), M. Schiavini (1), R. Casati (1), F. Colombo (1), C. Canzi (1), D. Cantalupi (2), P. Gerundini (1). (1) Department of Nuclear Medicine, IRCCS-Ospedale Maggiore, Milan, Italy, (2) Department of Nuclear Medicine, Ospedale Regionale, Aosta, Italy. Aim: A rising CEA level is an early indicator of clinical relapse after resection of colo-rectal cancer and 18FDG-PET is the most sensitive imaging modality to demonstrate recurrencies in about 70% of cases. The semiquantitative approach provided by the calculation of the Standardized Uptake Value (SUV), although controversial, is useful to confirm the visual analysis. Aim of the study was to search for a correlation between SUV, expression of the metabolic activity of tumor cells, and serum CEA values. Material and Methods: Whole Body 18FDG-PET was retrospectively evaluated in 25 patients (20 m; mean age 63±10) operated for colorectal cancer with high CEA levels (range 5.3-428 ng/ml; n.v. <5). The maximum SUV values (range 1.8-35.6), calculated on focal areas with abnormal 18FDG uptake were correlated with CEA levels in each patient. Number of metastases and volume of all lesions hystologically confirmed were also taken in account. Results: The mean volume of neoplastic lesions was 50.7 cm3±57.7 and number of localizations ranged from 1 to 3. 12/25 patients had single lesion at PET scan and the mean levels of CEA and maximum SUV were 22.1±25.5 and 9.1±8.9, respectively. In 13/25 the number of lesions ranged from 2 to 3 and CEA and maximum SUV levels were 59.6.1±115.4 and 6.9±3.5, respectively. Considering all 25 patients, the mean values of CEA and SUV were 41.6±85.6 and 7.9±6.6. No correlation was demonstrated between CEA and SUV values (r=0.09) even though in 11 patients with CEA levels <16 ng/ml (mean 9.0+3.7), the mean SUV was slightly lower (6.5+3.4) than that found in the other 14 cases (9.0+8.3; mean CEA level 67.3+109.1). Conclusion: Our preliminary data in patients with colorectal cancer surgery and increasing CEA levels show that although the highest values of CEA were observed in patients with more than one metastatic site and greatest volume of tumoral tissue, these differences were not statistically significant. Moreover, the lack of correlation between CEA and SUV values suggests that the ability of PET to localize recurrencies is not connectable with circulating CEA levels.

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P_289

M. Voth (1), B. Böhm (2), J. Scheele (2), D. Gottschild (1). (1) Department of Nuclear Medicine of Friedrich Schiller University Jena, Jena, Germany, (2) Clinic of Surgery of Friedrich Schiller University Jena, Jena, Germany.

L. Guan, A. Mehrotra, H.M. Zhuang, J.L. Alberini, A. Alavi. Division of Nuclear Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104,USA.

Whole body FDG-PET for the preoperative evaluation of patients with liver tumors

Aim: We have prospectively evaluated the importance of F-18-FDG-PET in primary and secondary liver tumors compared with CT, MRI and sonography. Extension of liver resection in primary and secondary liver tumors depends on tumor location and extrahepatic tumor manifestation. Material and Mthode: In all patients whole body FDG-PET (ECAT EXACT 47, Siemens/CTI) in a routine protocol, MRI (abdomen), CT (abdomen) and sonography (abdomen) were performed preoperatively. The interpretation of the attenuation corrected studies of the 50 patients occured blindly. Results: all cases (n=174 ) TP FN TN sonography 105 61 4 CT 118 48 4 MRI(23 pat)94 19 4 FDG-PET 137 29 2

FP 4 4 3 6

sens 63,3 71,1 83,2 82,5

colorectal ca. (n=74) TP FN TN 63 10 1 64 9 0 42 4 0 69 4 0

FP 0 1 0 1

sens 86,3 87,7 91,3 94,5

The predictive value of FDG-PET in outcome of colorectal carcinoma with or without liver metastases

Aim: The aim of this study was to determine the prognostic value of FDG-PET in colorectal cancer patients with or without liver metastases. Materials and Methods: 146 FDG-PET whole body scans of patients with colorectal cancer were retrospectively analyzed, and the results were compared to the follow-up outcome at least 1 year after the PET scan. The PET positive group were classified into 3 subgroups: liver metastases only, liver metastasis with lesions elsewhere and non-hepatic metastases only. The median survival rate of each group was calculated by Kaplan-Meier statistics method. Results: In 35 patients of negative PET, the median survival was more than 1278 days (only 7 patients were dead at follow-up time), whereas in 111 patients of positive PET, the median survival was 860 days. There was significant difference between these two survival curves (p=0.0382). In three positive PET subgroups, the median survival of liver metastases only (22 patients), liver metastasis with lesions elsewhere (38 patients) and non-hepatic metastases (51 patients) was 863 days, 775 days and 860 days respectively. There was no significant difference between any of both in the three subgroups (P>0.05). Conclusion: In colorectal cancer patients, negative PET results predict higher survival rate compared with positive PET results. There was no difference in the median survival of PET positive three subgroups (liver metastases, liver metastasis with lesions elsewhere and nonhepatic metastases).

Conclusion: A whole body FDG-PET is an efficient method for preoperative staging in primary and secondary liver tumors. It is a helpful tool for the surgeon in preparing the surgical procedure.

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M. Hoffmann (1), K. Kletter (1), A. Becherer (1), U. Jäger (2), A. Chott (3), M. Raderer (2). (1) Department of Nuclear Medicine, University of Vienna, Austria, (2) Department of Internal Medicine I, University of Vienna, Austria, (3) Department of Clinical Pathology, University of Vienna, Austria.

J. Khan, L. Guan, M. Hickeson, H.M. Zhuang, J.L. Alberini, A. Alavi. Hospital of University of Pennsylvania, Pholadelphia, USA.

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDGPET) for staging and follow-up of marginal zone B-cell lymphoma

Aim: According to recent reports, nodal marginal zone lymphoma (MZL) appears to be a distinctive lymphoma entity rather than a more advanced stage of extranodal MZL of MALTtype. We have therefore retrospectively evaluated all patients diagnosed with nodal or extranodal MZL who have been referred to our unit for imaging using 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET). Patients and methods: A total of 21 patients with a diagnosis of MZL upon referral for imaging with 18F-FDG-PET were identified. Histological reassessment of biopsy specimens confirmed the diagnosis of extranodal MZL of MALT-type in 14 patients, while a diagnosis of nodal MZL was verified in 6 patients. Lymphoma cell proliferation was assessed immunohistochemically by using a Ki-67 antibody. Whole body 18F-FDG-PET scans were performed on a GE advanced PET scanner 40 min after i.v.injection of 300-380 MBq of F18-FDG. Results: None of the patients with extranodal MZL showed focal tracer uptake within verified tumor sites. In contrast, five out of the six patients with nodal MZL showed significant FDG uptake within affected lymph nodes. These results did not simply reflect the different growth fractions of the two lymphoma entities since the proliferation indices of the two groups did not differ significantly. Conclusion: 18-FDG-PET visualizes nodal MZL in a high proportion of patients whereas FDG uptake is undetectable in extranodal MZL. Although limited by the small number of patients, this study suggests that imaging with 18F-FDG-PET might play a supportive role in the diagnostic work-up of patients with nodal MZL involvement.

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FDG-PET in the prediction of progression-free survival at 1 year (1year PFS) of patients with aggressive non-Hodgkin’s lymphoma (NHL) following anthracycline-based first-line chemotherapy (FLC) M.E. Juweid (1), G.A. Wiseman (2), Y. Menda (1), J. Vose (3), B. Link (1), M.M. Graham (1). (1) Departments of Radiology and Internal Medicine of the University of Iowa, Iowa City, Iowa, USA, (2) Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA, (3) University of Nebraska Medical Center, Omaha, Nebraska, USA. Background and Objective: The ability to accurately predict the outcome of patients (pts) with aggressive NHL following their anthracycline-based FLC could have important implications on the decision to administer additional or salvage therapy early after completion of their FLC and, hence, have a major impact on their management. In this study, we assessed the predictive ability of FDG-PET by determining its accuracy for predicting the 1-year PFS of these pts Methods: We identified all aggressive NHL pts Between between 1994 and 2001Dpts , who underwent FDG-PET within 1-3 mo following 4-8 cycles of anthracycline-based FLC their single modality and had adequate clinical, laboratory and radiological follow-up for at least 1 year after beginning of therapy or until progression. The 1-year PFS of the pts was determined based on results of their followup and/or histopathology. Results: Of 43 pts initially identified, 5 received radiotherapy shortly after their FDG-PET, hence Six of the 24 pts received involved field XRT within few weeks following their FDGPET scans and, hence, 38 pts were included in the final analysis. Of these, FDG-PET was positive in 13 and negative (you mean to tell me none of them were “indeterminate?”) in 25. 12/13 pts with positive FDG-PET disease washad histopathologically confirmed residual disease or or clinical disease progression demonstrated at FDG-positive sites in five at withina median duration timepoint of 8 mo (range, 3-10 mo) posttherapy; there was no evidence of disease1 had no evidence of progression (NEPD) in one after 26 mo of followup. In contrast, only 3/25 pts with negative FDG-PET showed disease progression, within 8-11 mo posttherapy; 22 remained with NEPD after a median duration of 15.5 mo (range 12-78 mo). The positive and negative predictive values (PPV and NPV) and accuracy of FDG-PET for 1-year PFS were 92%, 88% and 89%, respectively. In contrast, the PPV, NPV and accuracy for CT (32 pts had CT within 1 mo of FDG-PET) were 47% (9/19), 85% (11/13) and 62% (20/32), respectively. Conclusion: FDG-PET has a high accuracy for predicting 1-year PFS of pts with aggressive NHL following their anthracycline-based FLC and could, therefore, be used for potentially more accurate treatment decisions in these pts.

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Effect of chemotherapy on the negative predictive value of FDGPET inaging in patients iwth Hodgkin Disease.

Objectives: There is controversy about the predictive value of FDG-PET in imaging NonHodgkin disease patients who have FDG-PET studies during or immediately after completion of chemotherapy. This investigation was undertaken to determine the efficacy of GDG-PET in such settings. Methods: We retrospectively reviewed 166 lymphoma patients who had FDG-PET studies with complete follow-up. One hundred thirteen patients were excluded for final analysis since patients received further treatments following FDG-PET scan. The remaining 53 patients were divided into 2 groups based on the time interval between the end of chemotherapy and FDGPET study. Group 1 had patients who had the FDG-PET scan with on-going chemotherapy or finished chemotherapy within one month prior to FDG-PET imaging, and Group 2 included patients who had the FDG-PET scan after one month of completion of chemotherapy. The follow-up results of FDG-PET unto 10 months ± 1 within first treatment, were compared to FDG-PET studies before chemotherapy. Results: In G1 patients (n=23) the follow-up results were consistent with FDG-PET results in every patient (100%). Of the 28 patients in G2, 26 patients (92.8%) showed consistence between FDG-PET scans and follow-up, and 2 patients (7.1%) with negative FDG-PET developed recurrence. The results were confirmed by clinical data. Conclusion: Our preliminary results demonstrated no significant effect of chemotherapy on the negative predictive value of FDG-PET for patients with Non-Hodgkin disease. A prospective study involving a larger patient population is needed to confirm our findings.

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Short-time Follow-up of the FDG Metabolism of Esophageal Carcinomas During Radio-Chemotherapy P. Theissen (1), P.M. Schneider (2), A. Jost (1), M. Dietlein (1), A.H. Hoelscher (2), H. Schicha (1). (1) Clinic for Nuclear Medicine, University of Cologne, (2) Clinic for Surgery, University of Cologne, Germany. Aim: To control the response of a neoadjuvante radio-chemotherapy in patients with esophageal carcinoma (EsoCa) reliable in-vivo methods are necessary. Therefore, the course of F-18-FDG metabolism was examined during a neoadjuvante radio-chemotherapy of squamous EsoCa. It was proven at what time during therapy its efficiency can be determined. Materials and Methods: 7 Patients (2 f., 5 m.) with localy exceeded but resectable EsoCa (cT3,Nx,M0) (age 56.5 years) underwent 18-FDG PET prior, 4 times weekly during, and 3 weeks after a neoadjuvante radio-chemotherapy (nRCTh). The 4 week therapy course comprized a 4 week fractioned radiation (single dose 1.8 Gy/d) and one chemotherapy course within the 1st therapy week (5-FU/Cisplatinum). All Tumours were resected 3 - 4 weeks after nRCTh by a transthoracical en-bloc esophagectomy. The PET was performed in an ECAT Exact 931 Scanner (Siemens/CTI) 69 ± 8 min after application of 370 MBq F-18 FDG. The data were analysed by maximum SUV values out of ROIs which were transfered from the pretherapeutic to the images of the later examinations. Gold standard was given by histomorphological grading of tumour regression out of the resected specimes. Results: Three types of courses of F-18 FDG accumulation could be differentiated: A: SUV deminishing > 50 % after the 1st or 2nd therapy week (n =3); B: SUV decrease > 50% after the 4th therapy week (n=3); C: no significant (< 10%) SUV decrease (n=1). Only in one patient FDG accumulation 3 weeks after the end of therapy reached the background niveau. Patients with curve type A all showed an high-grade tumour regression. Among the patients with curve type B small to moderate rates of regression occurred. The patient with curve type C showed moderate tumour regression. Conclusion: These preliminary results seem to indicate that FDG-PET relatively early during nRCTh can distinguish between patients with sufficient and with little response to nRCTh in esophageal carcinoma.

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C. Bui, P. Shreve. Department of Radiology, University of Michigan, Ann Arbor, MI, USA.

A. Versari (1), G. Lo Scocco (2), M. Lombardi (2), D. Prosperi (1), A. Fraternali (1), D. Salvo (1). (1) Department of Nuclear Medicine of S.Maria Nuova Hospital, Reggio Emilia, Italy, (2) Department of Dermatology of S.Maria Nuova Hospital, Reggio Emilia, Italy.

Aim: Determine the incidence of unsuspected extra-thoracic metastases detected by FDGPET in patients with lung cancer undergoing staging or re-staging. Materials and Methods: Clinical data on 193 patients referred for FDG-PET staging or restaging of lung cancer in an interval of over two and a half years were retrospectively analyzed to determine the incidence of unsuspected extra-thoracic metastases detected by FDGPET. All patients had undergone routine contrast enhanced helical CT of the thorax and upper abdomen within eight weeks of the FDG-PET. PET scans of the chest and upper abdomen were performed on a full ring tomograph (Siemens 921 or HR+) using 2-D emission acquisitions and segmented attenuation correction. Reports of both CT and PET under routine clinical conditions were used for comparison and the final diagnosis based on biopsy, additional imaging results or clinical course. Results: Among the 193 patients, 21 (11%) were upstaged by FDG-PET detection of distant metastases. In 15 patients, unsuspected (based on CT) bone metastases were detected in the axial skeleton. In 2 of these patients, unsuspected liver metastases were also detected and in 1 of these patients, an additional adrenal metastasis was identified. Unsuspected metastases confined to the liver were detected in 2 other patients. Soft tissue metastases in 1 patient and an isolated adrenal metastasis in another were identified which were not detected on initial CT interpretation. In 2 other patients, unsuspected upper abdominal nodal metastases in one patient and liver metastases in another were detected which subsequently proved to be metastatic melanoma and urothelial carcinoma respectively. There were 2 false negative FDG studies for hepatic metastases which were correctly detected by CT and subsequently confirmed by fine needle aspiration biopsy or by interval growth. There were presumed 3 false positive FDG studies for vertebral and rib metastases which were subsequently not confirmed by follow-up imaging. Conclusion: Addition of FDG-PET to routine CT staging or re-staging of lung cancer upstages 11% of patients to stage IV primarily due to the detection of unsuspected osseous metastases.

P_295

Metabolic Significance of the Pattern, Intensity and Kinetics of F18FDG Uptake in Malignant Pleural Mesothelioma V. H. Gerbaudo, S. Britz-Cunningham, M. F. Di Carli, C. Mauceri, D. Sugarbaker, S.T. Treves. Divisions of Nuclear Medicine and Thoracic Surgery, Brigham and Women’s Hospital, and Harvard Medical School. Aim: Malignant pleural mesothelioma is an aggressive neoplasm, in which early detection and accurate staging are known diagnostic challenges. The purpose of this study was to evaluate the significance of the pattern, intensity and kinetics of FDG uptake in mesothelioma as they compare to histopathology and surgical staging. Methods: A total of 16 patients with CT scan evidence of pleural thickening, fluid, plaques or calcification underwent FDG imaging. Eleven patients were imaged 2 hrs after the intravenous administration of 370 MBq of FDG. The remaining five patients underwent serial imaging at 45 minutes and at 2 hrs post-injection. Imaging was performed with a dual head gamma camera (ECAM Duet, Siemens) equipped with 1 inch thick (2.54 cm) NaI crystals operating in coincidence mode. Using an iterative algorithm, decay corrected whole body images were reconstructed as transaxial, sagittal and coronal images. No attenuation correction was applied. Semiquantitative analysis was performed by obtaining lesion to background ratios (L/B). The results of FDG scans were then compared to CT, to histopathologic diagnosis, and to surgical staging. Results: 12 out of 16 patients had histologically proven malignant mesotheliomas (10 epithelial & 2 sarcomatoid). Thirty-seven lesions were biopsied, and among these, 32 were found positive for tumor. Three distinct patterns of FDG uptake were observed: focal/linear, diffuse and heterogeneous. Patterns of uptake matched the extent of pleural, and parenchymal involvement observed in CT and surgery. An interesting finding was that extrathoracic metastatic lesions had significantly higher FDG avidity (L/B: 4.9 ± 2) than primary (2.73 ± 1.62) and/or nodal lesions (2.72 ± 1.03) (p < 0.001). In patients with distant spread, primary lesions were more FDG avid than in patients without spread. Serial imaging demonstrated that FDG uptake increased in all lesions over time, but at a higher rate in stage IV patients (135%), when compared to those in stage I (13%). The intensity of lesion uptake had good correlation with histologic grade (r: 0.57, p < 0.02), and excellent correlation with disease extent as defined by surgical staging (r: 0.88, p < 0.001). No significant correlation was found between histologic grade and surgical stage (r: 0.27, p < 0.35). Conclusion: These preliminary results suggest that pattern, intensity and kinetics of FDG uptake in malignant pleural mesothelioma, are good metabolic indicators of the degree of tumor aggressiveness as measured by the surgical stage, and are superior to histologic grading in this regard.

FDG-PET imaging: role in patients with melanoma

Aim: Melanoma is the most malignant of skin cancer and the most rapidly increasing cancer in white population; the mortality rate is second only to that of lung cancer. Patients with nodal metastases but no distant localizations have 20% probability to be cured by surgery. Surgery can improve survival in case of isolated distance metastases. Therefore it is important to know the extent of the disease in choosing the patients candidates to radical surgery of metastases. We evaluated the impact of FDG-PET on the management of patients with melanoma. Material and Methods: Fifty-five consecutive patients with melanoma (30 males, 25 females, mean age 53 years, range 23-81 years), studied by FDG-PET in our PET Centre from October 2000 to January 2002, were included in the evaluation. All patients were studied by conventional imaging (CT and/or MRI, ultrasound) before PET. Whole-body PET was ordered for a more accurate evaluation of the extent of the disease in patients with nodal metastases or isolated distant metastases and, sometimes, for a differential diagnosis benign lesion/metastases in patient with unclear lesion on morphologic imaging. PET studies were obtained with a 3D dedicated system (C-PET ADAC); both attenuation-corrected and noncorrected images were always evaluated. Management changes were classified as intermodality (changes between treatment modalities) and intramodality (changes within one treatment modality). Results: PET changed the clinical stage in 19 patients (35%). Changes in the patient treatment were found in 22 cases (40%), intermodality in 18 patients (33%) and intramodality in 4 (7%). In 9 patients with node metastases of unknown site melanoma, PET scan was useful to evaluate the presence of other metastatic localization but no primary site was found. Four patients with eye melanoma were studied: three cases, in follow up after surgery of eye lesion, presented high uptake metastases; a case with an unclear eye lesion (about 1 cm in diameter) had no FDG uptake: biopsy and surgery found a low metabolism melanoma. Conclusions: Our data confirm, in agreement with literature, the high impact of whole-body FDG-PET on the management of patients with melanoma contributing to a more accurate clinical staging in 35% of patients and changing the treatment decisions in 40% of cases. These values indicate important benefits in utilizing FDG-PET particularly in recurrent melanoma while it is not useful in looking for primary lesion in case of metastases of unknown site melanoma.

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Utility of 18F-fluorodeoxyglucose positron emission tomography in the management of patients with malignant melanoma after initial treatment. C. Tamas (1), L. Sarda-Mantel (1), M.F. Avril (2), F. Weil (2), A. Margulis (2), F. Semah (1), A. Syrota (1), J. Lumbroso (2). (1) Service Hospitalier Frédéric Joliot, CEA/DSV/DRM, Orsay, France, (2) Institut Gustave Roussy, Villejuif, France. Aim: In melanoma, after initial treatment, correct staging of patients is important: to confirm or rule out complete remission, or to detect tumor recurrence. The aim of this study was to evaluate the additive value of 18fluoro-deoxyglucose positron emission tomography (FDG PET) to conventional methods (clinical examination, computed tomography, ultrasound) in these settings. Methods: Twenty-nine patients were investigated. At the time of FDG-PET, according to conventional methods: 4 patients were considered in probable remission (G1), 18 had doubtful results (G2), 7 had at least 1 known tumor site (G3). FDG PET findings were compared to those of conventional methods and further evaluated by histology (n=10) or follow-up (n=19). Results: For patients’ classification (as with / without tumor sites), FDG PET was truly positive in 18 cases, truly negative in 10 cases, falsely negative in 1 G3 patient (scar uptake precluding the detection of a small nodule). FDG-PET revealed the presence of unknown tumor sites in 2/4 G1 patients, and in 3/7 G3 patients, ruled out the presence of disease in 7/18 G2 patients and confirmed suspected tumor sites in 11/18 G2 patients, revealing additional unknown tumor sites in 6 of them. The influence of FDG-PET on therapeutic management was considered positive in 22/29 (76%) patients. FDG-PET had no influence on the management of 7/29 patients. Conclusion: In this study, FDG PET showed higher sensitivity than conventional methods for detecting persistent or recurrent melanoma tumor sites after initial treatment, and was more accurate for managing further therapy.

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FDG-PET Detection of Unsuspected Extra-thoracic Metastases in Patients with Lung Cancer

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Preoperative characterisation and staging of ovarian tumours by 18-FDG with coincidence detection emission tomography (CDET) gamma camera K. Kerrou, F. Montravers, D. Grahek, N. Younsi, F. Achaïbou, C. Colombet-Lamau, V. De Beco, Y. Petegnief, J.N. Talbot. Service de Médecine Nucléaire, Hôpital Tenon, Paris, France. Objectives: The aim of this prospective study was to evaluate the role of 18-FDG PET performed with CDET gamma camera in pre operative characterisation and staging of ovarian tumours Methods: After a 6 hour fast, the patient (pt) was injected IV. with 150-250 MBq of 18-FDG and imaging (whole body scan and at least a tomoscintigram) was started 60 min. later, using Marconi, Philips Prism XP 2000 dual-head or Irix 3000 triple-head gamma cameras. Between May 2000 and January 2001, 39 pts were prospectively studied for preoperative assessment of ovarian tumours. All pts had ovarian mass discovered with ultrasonography (size range : 15 to 80 mm) and subsequent conventional imaging consisting in CT and/or MRI. All patients are currently evaluable with reference to histology after surgery. Results: The mean age of the 39 pts was 58 years (range 28 to 87). 18-FDG was true positive in 6 pts. For 3 pts 18-FDGscan detected more lesions than ultrasonography CT and MRI. 18FDG was false positive in 3 pts : 1 related to stage IV endometriosis, 1 related to peritoneal tuberculosis and one to inflammatory benign cyst. The remaining 30 patients corresponded to true negative results, benign tumours being confirmed by histology. The overall sensitivity, specificity and accuracy on a per patient basis were respectively 6/6 (100%), 30/34 (88%) and 36/39 (92%). The positive predictive value (PPV) was 6/9 (66%) but more patients are needed to accurately estimate the PPV. The negative predictive value (NPV) was 30/30 (100%). Conclusion: These results showed good performances of 18-FDG with CDET gamma camera in preoperative characterisation and staging of ovarian tumours. Thus, 18-FDG can play a major role for the choice of the adequate surgical procedure in this clinical setting.

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Application of FDG PET in Radiotherapy for High Risk Cervical Cancer Patients with Enlarged Pelvic Lymph Nodes - a Preliminary Report

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Changing Patterns of the Effects of Chemotherapy on FDG Uptake in Normal Structures of the Extracranial Head and Neck G.S. Anderson, C. Anselmi, D. Dieu, S. Gupta, A. Alavi. University of Pennsylvania, Philadelphia, USA. Aim: As FDG-PET is increasingly employed to assess response to chemotherapy and other treatments, it becomes imperative to understand whether normal structures are affected by such interventions in order to optimize the accuracy of interpretation of scans in patients with a variety of head and neck malignancies. The aim of this paper was to determine if there is an effect of chemotherapy on FDG uptake in normal structures of the head and neck that changes over time after treatment. Material and Methods: 16 patients with a history of lymphoma but prior to any treatment were compared with 62 lymphoma patients who had received chemotherapy prior to FDGPET scans. These 62 patients were then divided into groups according to the time interval between the last chemotherapy and the PET scan. SUVs were determined for normal head and neck structures, while the degree of tracer uptake was also characterized by observers as being absent, mild, moderate or intense. Structures studied included the larynx, lips, nasopharynx, oral cavity, parotid glands, sublingual glands, submandibular glands, spinal cord, palatine tonsils, pharyngeal tonsil and tongue. The location of each structure was determined using previously published atlases using MRI as a guide for identification of the structures, as well as our own as of yet unpublished data. Results: Among most structures studied, a trend toward detectable changes was noted with increased SUVs during the first two weeks after chemotherapy and then gradual return to the pre-treatment baseline value in the following months. These increases were statistically significant for the oral cavity (p=0.03) and right parotid gland (p=0.03), and borderline for the left parotid gland (p=0.07). Visual categorization of intensities demonstrated a similar trend with detectable differences in uptake between patients two weeks after chemotherapy and those without chemotherapy. Conclusion: Broadly speaking, chemotherapy appears to slightly increase FDG uptake in the region of the oral cavity and the parotid glands in the first 2 weeks following treatment. This effect could be due to inflammation after therapy.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition PET: NEW INDICATIONS

C.C. Tsai (1), C.S. Tsai (2), T.C. Chang (3), K.K. Ng (4), S. Hsueh (5), S.Y. Ma (1), T.C. Yen (1), K.Y. Tzen (1). (1) Department of Nuclear Medicine of Chang Gung Memorial Hospital, Taipei, Taiwan, (2) Department of Radiation Oncology of Chang Gung Memorial Hospital, Taipei, Taiwan, (3) Department of Gynecology Oncology of Chang Gung Memorial Hospital, Taipei, Taiwan, (4) Department of Radiology of Chang Gung Memorial Hospital, Taipei, Taiwan.

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Aim: For advanced cervical cancer, pelvic irradiation with concurrent chemotherapy is the standard treatment. Treatment failure at para-aortic lymph node (PALN) is frequently but, concerning the intestinal complication, prophylactic PALN irradiation is not routinely suggested. From previous surgical series, the lymphatic spreading is in a sequential pattern and PALN status is closely related to pelvic lymph node (PvLN) status. This prospective study evaluated the efficacy of FDG-PET for adjuvant detection of tumor metastasis and impact of radiotherapy planning among high risk patients with enlarged PvLN on MRI/CT. Materials and Methods: Patients with newly diagnosed cervical cancer scheduled to receive primary radiotherapy and meet all of the following eligibility criteria were included in the study: presence of at least one enlarged PvLN or group of small PvLN, and without suspected PALN metastasis or any lesion outside the pelvis by conventional MRI/CT. PET images were obtained using a Siemens HR+ scanner, after injection 370 MBq of FDG. Once a significant increased uptake over the metastatic upper pelvic lymph node or para-aortic lymph node is seen on FDG-PET, the irradiation field is modified accordingly. Results: FDG was taken up by 94% of the primary tumors in 16 patients. According to the FDG-PET findings, 4 patients (25%) were found to have PALN metastases, and their irradiation field changed. One patient (6%) was found to have distant metastasis proven by biopsy and changed the subsequent treatment. Four patients (25%) with metastatic PvLN detected on MRI/CT were proven to be false negative in FDG-PET. Conclusion: FDG-PET is useful in detecting PALN and distant metastases outside abdomen and pelvis. For high risk cervical cancer patients, FDG-PET is complementary to conventional imaging studies in determining the extent of tumor spreading and in adjusting the irradiation field size and changing treatment planning.

Aim: This prospective study is to investigate the association of Glut-1 expression in invasive cervical cancer (ICC) and to compare the results with preoperative FDG uptake assessed by PET and its histological findings. Materials and Methods: A FDG PET scan was performed in 154 patients with ICC (130 squamous cell carcinoma [SCC] and 24 adenocarcinoma [AdenoCa]; from FIGO staging IB to IVB prior to operation). FDG uptake was quantified by calculating standardized uptake values (SUVs). Histological sections of formalin fixed, paraffin embedded specimens from 154 primary or recurrent ICC specimens were stained for Glut-1 by using polyclonal Glut-1 antibody and the labeled streptavidin biotin procedure. The intensity (with grades 0-3, defined qualitatively) of Glut-1 immunoreactivity and percentage of the cancerous area that is positive for Glut-1 was analyzed. The levels Glut-1 expressions in this study were defined as (the intensity grade x percentage of area that is positive). Results: None of the normal cervical tissue expressed Glut-1. Overexpression of Glut-1 in both SCC and AdenoCa of the cervix was noted. There is no difference between expressions of Glut-1 for both types of cervical cancer. Also the degree of cell differentiation is correlated with the expression of the Glut-1 positive area in both SCC and AdenoCa of the cervix. There is also a positive correlation between Glut-1 expression and the SUVs. In this study, 9 of the 154 specimens (6%) showed weakly positive Glut-1 expression. After dual time point FDG PET studies of these 9 patients, 3 were recognized as having had a positive study, but 6 had poor a tumor to non-tumor uptake ratio. Conclusions: Glut-1 expression is related to FDG uptake in ICC. Glut-1 expression and FDG uptake are correlated with the degree of cell differentiation in both SCC and AdenoCa of the cervix. There is no significant difference between SUVs and Glut-1 expression in both SCC and AdenoCa for our ICC patients.

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Glut-1 expression in invasive cervical cancer T.C. Yen (1), C.H. Lai (2), Y.H. Wu (3), K.Y. Tzen (1). (1) Department of Nuclear Medicine of Chang-Gung Memorial Hospital, (2) Department of Gynecologic Oncology of Chang-Gung Memorial Hospital, (3) Institute of Human Genetics of Chang-Gung Memorial Hospital, Taipei, Taiwan.

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S. Wachter (1), A. Kurtaran (2), B. Djavan (3), A. Becherer (2), M. Mitterhauser (2), G. Dobrozemsky (4), S. Li (2), R. Dudczak (2), K. Kletter (2). (1) Department of Radiotherapy and Radiobiology, University of Vienna, (2) Department of Nuclear Medicine, University of Vienna, (3) Department of Urology, University of Vienna, (4) Department of Biomedical Engineering & Physics, University of Vienna, Vienna, Austria.

L.F. de Geus-Oei (1), H. van Laarhoven (2,3), M. Rijpkema (2), C.J. Punt (3), T.J. Ruers (4), J.O. Barentsz (2), A. Heerschap (2), F.H.M. Corstens (1), W.J.G. Oyen (1). (1) Department of Nuclear Medicine of the University Medical Center St. Radboud, (2) Department of Radiology of the University Medical Center St. Radboud, (3) Department of Medical Oncology of the University Medical Center St. Radboud, (4) Department of Surgeryof the University Medical Center St. Radboud, Nijmegen, The Netherlands.

Carbon-11-Acetate PET imaging in recurrent prostate cancer: Initial experiences at the University of Vienna

Aim: The detection of tumour sites in patients with elevated PSA after radical therapy for prostate cancer (PC) is still challenging. In this prospective study we aim to assess the clinical value of C-11 acetate whole body PET imaging in detecting clinically occult local/metastatic disease in order to choose the most appropriate therapy in these patients. Methods: In 32 clinically asymptomatic patients (age:53-86) with rising/elevated PSA after radical therapy (radical prostatectomy, radiation therapy) for PC, C-11 acetate whole body PET scans were performed. After i.v injection of 500-700 MBq C-11 acetate a whole body PET scan was performed using a full ring scanner (GE Advance). In the case of abnormal C11 acetate uptake additional radiological and nuclear medicine studies i.e. bone scan, computed tomography (CT) and /or magnetic resonance imaging (MR), were performed. In some patients histopathological confirmation was available. For a better anatomical definition of the detected foci by C-11 acetate study a 3D PET-CT/MRI image fusion was done. Results: In 7 out of 32 (24%) patients C-11 acetate PET studies demonstrated a normal distribution through the whole body PET scan (false negative results). The remaining 25 patients demonstrated, however, pathological C-11 acetate uptake suspicious for local and/or metastatic disease (76%). In 5 patients with non-diagnostic CT/MRI studies significant C-11 acetate accumulation was found in prostatic fossa. Furthermore, C-11 acetate PET study demonstrated significant lymph node involvement in 3 patients while CT/MRI were not conclusive. In 4 patients with equivocal bone scan findings C-11 acetate PET study indicated tu-activity. Conclusion: Our results demonstrate the clinical usefulness of C-11 acetate whole body PET as a promising imaging technique in order to select patients for appropriate therapy (local vs. sytemic therapy). This imaging modality may be used as first line imaging (if available) in patients with abnormal PSA after radical therapy for PC.

Correlation between Gadolinium- and 18FDG-uptake in colorectal liver metastases

Objectives: Current management of metastasized colorectal carcinoma relies on imaging methods which are generally anatomical in nature, except for 18FDG-PET. Since glucose metabolism is dependent on vascularization for glucose and oxygen supply, the assessment of tumor vasculature may be useful in colorectal cancer management, which may be characterized by dynamic contrast enhanced MRI (DCE-MRI). In this study we investigate the relationship between glucose metabolism and tumor vasculature by 18FDG-PET and DCE-MRI. Methods: 7 Patients with colorectal liver metastases underwent PET-scanning one hour after administration of 220 MBq 18FDG. Images were corrected for attenuation and reconstructed using the ordered-subsets expectation maximisation algorithm. Standardized uptake values (SUVs) of 18FDG in the whole tumor were calculated using the tumor concentration of 18FDG as measured by PET, divided by the injected dose and multiplied by body weight as a normalization factor. For DCE-MRI Gadolinium (Gd) uptake was monitored during 90 seconds postinjection using a T1-weighted sequence. To normalize data the arterial input function was determined from Gd passage in the aorta. Using a physiological pharmacokinetic model the concentration Gd versus time curves of the tumor were analyzed. The mean rate constant kep of Gd uptake in the tumor was calculated. Results: Results are shown in the table, representing SUVs versus mean values of kep. Linear regression of the mean SUV on the mean kep corrected for kep=0 shows a significant negative correlation (b=-74.48 ± 25.74; p < 0.05). Conclusion: For colorectal liver metastases a significant negative correlation is found between 18FDG-SUVs and the rate constant kep of Gd as determined from PET and DCEMRI, respectively. This may reflect a switch from aerobic to anaerobic glycolysis in tumor areas where vessels are less perfused or less permeable, inducing a higher uptake of glucose to maintain energy demand.

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FDG-PET in Lung Tumours - Correlation with Ki-67 staining, mitotic activity , and viable tumour cells

mean kep (s-1) ± sd

mean kep (s-1) ± sd corrected for kep=0 1 1.18 0.068 ± 0.029 0.068 ± 0.029 2 4.10 0.021 ± 0.013 0.021 ± 0.013 3 1.99 0.035 ± 0.029 0.041 ± 0.027 4 3.37 0.024 ± 0.027 0.042 ± 0.022 5 5.19 0.028 ± 0.041 0.033 ± 0.043 6 1.88 0.014 ± 0.032 0.052 ± 0.042 7 3.18 0.017 ± 0.041 0.049 ± 0.058 Table 1 Mean SUVs (FDG-PET) and mean values of kep (DCE-MRI)

patient

mean SUV

B. Klemenz (1), T. Göller (2), K.P. Kaiser (3), H.P. Becker (4), H. Wieler (3). (1) Department of Nuclear Medicine of the Armed Forces Hospital Ulm, Germany, (2) Department of Pathology of the Central Armed Forces Hospital Koblenz, Germany, (3) Department of Nuclear Medicine of the Central Armed Forces Hospital Koblenz, Germany, (4) Department of Surgery of the Central Armed Forces Hospital Koblenz, Germany.

Poster Presentation

Increased FDG metabolism in malignancies has been shown to be related to the expression of glucose transporters and the high activity of hexokinase in tumour cells. Recent studies reported an association of FDG uptake and the number of viable tumour cells in various malignancies. Aim of our prospective study was to evaluate the FDG-Uptake and histopathologic proliferation markers in patients (pts) with intrathoracic lesions. Materials and Methods: In 77 consecutive non-diabetic pts with suspected lung cancer whole-body FDG-PET acquisition was done 60 min after application of 350+47 MBq F-18FDG (mean+SD).. 63 male and 14 female pts were examined with a dedicated full-ring PET scanner (ECAT Exact 47, CTI Siemens). The median age was 64 years (range 19-79). Image acquisition of the lesion site was 111+21 min post injection. Image reconstruction was done with an iterative algorithm. Standardised uptake values (SUV) were ascertained with a cutoff value >2.5 suspected as malignant. SUV were corrected for partial volume effects in tumors <3cm (SUVc). Histological examination comprises the number of viable tumour cells, tumour cell mitoses, and Ki-67 positive tumour cells in 10 high power fields (HPF; dianova MIB-1). Statistical evaluation: linear regression analysis. Results: Increased FDG-uptake was demonstrated in 66/67 pts with malignant lesions (54 NSCLC, 3 SCLC, 3 sarcomas, 2 lymphomas, 2 metastases from other malignancies, 1 carcinoid tumour, 1 undifferentiated carcinoma, and 1 malignant schwannoma; sensitivity 98,5%). In one pt with low-grade sarcoma SUVc was <2.5. In contrast to this, 7 out of 10 benign tumours showed SUVc >2,5 (sarkoidosis, plasma cell granuloma, silicosis, fibrosis, chronic pneumonia, pleuritic scar, squamous cell metaplasia). FDG-PET was true negative in anthracosis, hamartoma, and fibrotic pleura tumour. The number of viable tumour cells in malignant tumours varied from 90-10.361/HPF. The range of tumour cell mitoses was 0-98/HPF, and the percentage of Ki-67-positive tumour cells in 10 HPF varied from 0 up to 83%. A significant correlation was found between FDG-uptake and the number of mitoses. No strong correlation was detected between SUVc and Ki-67-staining or the number of tumour cells, respectively. Conclusion: FDG-uptake correlates with the mitotic activity and may be a surrogate marker for biologic aggressiveness of intrathoracic malignancies. Our study confirmed the very high sensitivity of FDG-PET in the diagnostic work-up of intrathoracic lesions. However chronic inflammatory disease can produce false-positive FDG-PET results.

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M. Richter, D.L. Munz. Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Berlin, Germany.

J.N. Rini (1), K.S. Heller (2), R.F. Nunez (1), A.S. Din (1), P.V. Pugliese (1), C.J. Palestro (1). (1) Division of Nuclear Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, USA, (2) Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, New York, USA.

FDG-PET in patients with paraneoplastic syndrome of the central and peripheral nervous system

Aim: Malignant tumours sometimes express autoantibodies which are able to interact with antigens of the nervous system. The patients are symptomatic with unspecific central and peripheral neurological and psychiatric symptoms called paraneoplastic syndrome of the central and peripheral nervous system. The neurological symptoms can occur before the malignant tumour has been diagnosed. Hence, the aim of this study was to assess the clinical usefulness of FDG-PET in this clinical setting. Methods: Nine patients (5 f, aged 43 - 62 yr; 4 m, aged 61 - 66 yr) were investigated 11 times with FDG-PET from 10/99 to 12/01. All patients were suspected of having unknown primary tumours with paraneoplastic syndrome of the central and peripheral nervous system. 4 patients had only central neurological and/or psychiatric symptoms diagnosed as paraneoplastic encephalopathia (PNE). 5 patients had only peripheral motorical symptoms diagnosed as paraneoplastic syndrome with peripheral neurological symptoms (PNS). PET was performed 60 to 90 min after i.v. injection of 370 MBq 18F-FDG in a whole-body manner using an ECATEXACT-922 Scanner (CTI/Siemens). The PET data were correlated with those obtained at CT. Results: Five patients had 7 CT of the chest, abdomen and pelvis, 4 of them showing pathological results at 5 CT (4 x mediastinal, 2 x pulmonal, 1 x enlarged adrenal glands on both sides). 4 PET were inconspicuous in 3 patients (all PNS). The other 6 patients (4 x PNE, 2 x PNS) had abnormal foci (1 x cervical, 3 x mediastinal, 1 x pulmonal, 3 x abdominal) in 7 PET. Concordance between PET and CT was found in 2 patients/3 investigations (all mediastinal). In 5 patients (3 x PNE, 2 x PNS) PET yielded additional clinical information. Conclusion: Patients with PNE can benefit from FDG-PET in localizing malignant tumours. FDG-PET has to be performed early in the clinical course.

Pre-operative evaluation of thyroid nodules with FDG-PET

Aim: Approximately two-thirds of thyroid nodules are categorized as benign or malignant on the basis of fine needle aspiration biopsy (FNAB). In about one-third of cases, FNAB is indeterminate, and surgery must be performed. We undertook this investigation to determine if 18 FDG-PET can accurately differentiate benign from malignant thyroid nodules preoperatively. If 18FDG-PET can determine that a thyroid nodule is benign, unnecessary surgery may be avoided. If a tumor is known to be malignant preoperatively, a single stage, rather than a traditional two-stage total thyroidectomy can be performed. Materials & Methods: 6 patients with palpable thyroid nodules (1-4 cm in size) had 18FDGPET scans performed prior to surgical excision of their nodules. Transmission/emission imaging of the neck was performed 1 hour following intravenous injection of 185 MBq 18FDG. Thyroid uptake of 18FDG was collectively analyzed by 3 experienced readers who classified the uptake pattern as focal (limited to uptake in the nodule), diffuse (in both lobes of the thyroid), or absent (no uptake in nodule or in thyroid gland). All patients subsequently underwent thyroid lobectomy (5 patients) or total thyroidectomy (1 patient). The pattern of 18FDG uptake was compared to the pathology of the thyroid nodules. Results: Histologic evaluation of the palpable thyroid nodules demonstrated 1 Hurthle cell Ca, 1 papillary Ca in the setting of florid Hashimoto’s thyroiditis, 1 Hurthle cell adenoma, and 3 follicular adenomas. Thyroid uptake of 18FDG was focal in 3 pts (1 Hurthle cell Ca (3.8 cm) and 2 follicular adenomas (2.5 cm each)), diffuse in 1 pt (papillary Ca (1 cm)/thyroiditis), and absent in 2 pts (1 Hurthle cell adenoma (1 cm) and 1 follicular adenoma (2.5 cm)). In the patient with papillary Ca/thyroiditis, 18FDG uptake in the nodule could not be separated from diffuse uptake present in the remainder of the gland. Conclusion: Focal increased uptake of 18FDG may be seen in benign and malignant thyroid neoplasms and is nonspecific. Diffuse thyroid uptake of 18FDG is seen with thyroiditis and may preclude accurate assessment of the metabolic activity of a nodule. In this small series there were 2 thyroid nodules that did not accumulate 18FDG and they were both benign. Further work is needed to determine if lack of 18FDG uptake by thyroid nodules reliably excludes malignancy.

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M. Hofmann, A.R. Boerner, D. Otto, B. Hertenstein, G. Heil, D. Peest, A. Ganser, S. Berg, W.H. Knapp. Medical School Hannover.

S.D. Dadparvar (1), R.K. Grewal (1), I. Ahmad (2), J.Q. Yu (1), V.K. Reddy (1), C. Babaria (1), J. Mack (2). (1) Department of Nuclear Medicine of Hahnemann University Hospital, Philadelphia PA, USA, (2) Department of Radiology, Mercy Health Systems, Philadelphia PA, USA.

Defining the inflammatory status prior to bone marrow transplantation by FDG-PET

Introduction: Prior to bone marrow transplantation (BMT) in lymphoma or leukaemia the knowledge of the infectious status is highly desirable. This study deals with the pretherapeutical identification of patients with infectious lesions using [18F]-FDG PET prior to BMT or PBSCT. Methods: 1-2 weeks prior BMT 15 patients underwent [18F]-FDG PET (dedicated PET scanner Siemens ECAT EXACT 47). Pathological tracer accumulations were evaluated by means of SUV. Results: 5 of 15 patients did show pathological lesions. All of these patients had lesions located in the lung. One patient had additional lesions in the mediastine, which were confirmed to be inflammatory lymphnodes by cytology. In the CT scan these lesions had been identified as unsuspicious small lymph nodes (1-2 cm diameter). 3/5 patients did show small lesions in the lung. Two showed large lesions (>2cm). In 3/5 of patients active fungous infections were confirmed by positive sputum culture. In 2/5 Patients the lesions with SUV less than 3 were regarded to be regenerative residuals of non-active previous known bacterial infections (CRP close to normal, no clinical symptoms, sputum culture negative). All infection positive patients underwent appropriate antibiotic or antimycotic therapy before starting the conditioning regimen. Conclusion: [18F]-FDG PET is helpful in identifying the inflammatory status of patients prior to BMT especially in case of known previous infections.

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Evaluation of the Breast CA with 18FDG-PET

Introduction: 18 Fluorodeoxyglucose – positron emission tomography (18FDG-PET) is a functional imaging modality capable of identifying primary and metastatic tumors with high sensitivity and specificity. The aim of this prospective study is to evaluate the efficacy of whole body FDG-PET imaging compared to conventional Computed Tomography (CT) in initial staging, restaging, and recurrence of breast cancer. Materials and Methods: Thirty-two patients, age range of 35-80 years with a mean age of 56.9 years underwent thirty-five studies. The histopathologies included: fifteen infiltrating ductal CA, seven invasive ductal CA, six poorly differentiated Adenocarcinoma, two unknown, one fibrocystic disease and one patient with atypical hyperplasia . CT imaging was performed on all patients. The whole body PET imaging was performed 45-60 minutes following intravenous injection of an average dose of 5.18 mCi 18FDG. Twenty-nine patients underwent nine concomitant bone scans. The pathological and other radiographic correlations were also performed. Results: The 18FDG-PET studies when compared to CT revealed sensitivity of 0.93 vs. 0.46(p<0.001), specificity of 1.00 vs. 0.73(p=0.06), accuracy of 0.94 vs. 0.54 (p<0.001), positive predictive value of 1.00 vs. 0.79(p=0.01) and negative predictive value of 0.80 vs. 0.38(p=0.01). The increased efficacy of 18FDG-PET was statistically significant in all parameters and was equally significant in specificity. Conclusions: There is a significant difference in sensitivity, accuracy and predictive values of 18FDG-PET vs. conventional CT in the various stages of breast cancer. There was better detection of soft tissue and bone metastases with 18FDG-PET when compared with CT and bone scans. Therefore, we recommend 18FDG-PET for staging, restaging, and evaluation of recurrent breast cancer.

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Post-operative Image-Fusion of CT and PET data sets in recurrent Oral-Maxillo-Facial carcinoma G. Wolf (1), R.M. Aigner (1), G. Schultes (2), T. Schwarz (1), R. Nicoletti (1), M.P. Lorbach (2). (1) Division of Nuclear Medicine, Department of Radiology, Karl-Franzens-University Graz, Austria, (2) Division of oral-, maxillofacial Surgery, Karl-Franzens-University Graz, Austria. Aim: The aim was to evaluate the clinical and therapeutical value of digital image fusion of F18-FDG-PET and CT in patients with recurrent oral-maxillo-facial carcinoma. Methods: Eight patients (age 43-75, 5 male, 3 female) with suspected recurrent oral-maxillofacial carcinoma underwent CT and F18-FDG-PET (333-370 MBq). The time-interval between both diagnostic modalities varied between 1 to 8 days. The data of both imaging modalities were fused on an image work station by automatic adaptation of pixel size and slice interval. The axes were corrected semi-automatically for differences in body positions. The fused images were reconstructed in the axial, coronal and in the sagittal plane. Results: PET showed a local pathological FDG-uptake of a high intensity in the tumour in 8 / 8 patients (sensitivity 100%). CT detected the tumour in 5 / 8 patients (sensitivity 62,5 %). Image fusion of PET and CT showed the tumour in 8 / 8 ( patients (sensitivity 100%). The final diagnosis was carcinoma of the mandible in 4 / 8 patients, carcinoma of the mouth floor in 4 / 8 patients. Histology ensured malignancy in all cases. The results were path-squamouscell carcinoma, in 4 / 8 middle differentiated ( 3 mouth floor, 1 mandible), and in 4 / 8 patients high differentiated ( 3 mandible, 1 mouth floor). Conclusion: In CT in 3 / 8 patients it was not possible to discriminate between recurrent oralmaxillo-facial carcinoma and normal lesions. The reason therefore might be the limitation in the size of the lesion and the artefacts caused by the metal implants. PET showed all pathological lesions independent of metal-implants. In case of an intense FDG-uptake morphology was sometimes difficult to describe. Image fusion of both methods was helpful for better definition of exact diagnosis (dignity, topography, differentiation osseous/extraosseous). Therefore the planing of surgery (visual models) or radiotherapy (exact region) can profit from this method.

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FDG-PET Imaging in Pediatric Lymphomas C. Bui (1), B. Shulkin (1), R. Mody (2), P. Shreve (1), P. Strouse (1), L. Lahti (1). (1) Department of Radiology, University of Michigan, Ann Arbor, MI, USA, (2) Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. Aim: The purpose of this study was to examine the uptake of FDG in lymphomas presenting in childhood and to determine the potential usefulness of the technique in comparison with standard imaging modalities. Materials and Methods: 20 patients (9 HD, 11 NHL), 8-18 years of age, underwent FDGPET imaging (36 scans total). Comparison was made with Gallium scans when available (26 scans total), performed within 5 weeks (mostly within 2 weeks) of the FDG-PET scan. Results: In 9 patients studied at diagnosis before therapy, Gallium, FDG-PET and CT scans were concordantly positive for disease sites in 6. In 1 patient, the tumor accumulated FDG but not Gallium. In another patient, FDG-PET was positive before excisional biopsies of axillary and rib lesions while Gallium scan was negative 1 week after the surgical procedures. In 1 patient studied before initiation of chemotherapy but 5 weeks after complete resection of the only known site of tumor in the anterior mediastinum, there was FDG accumulation but not Gallium in the surgical bed-a false positive FDG-PET scan. In 9 patients studied during therapy, FDG-PET identified residual disease in 4, while Gallium scans were positive in 2, negative in 1 and not available in 1. In 6 patients studied after completion of therapy, FDG-PET detected residual/recurrent disease in 2 patients while Gallium scans were positive in 1 and negative in 1. In 1 patient in complete remission, the last serial Gallium scan showed resolution of thymic rebound at 9 months after completion of therapy while the last serial FDG-PET scan still showed thymic rebound at the same time. In the 10 patients with at least 1 negative FDG-PET scan during or after therapy, 8 have remained disease free from 1 to 94 months and 1 is still receiving therapy. 1 died from non-malignant causes with autopsy showing no residual lymphoma. Conclusion: FDG-PET scanning is useful for the management of pediatric patients with lymphoma. It is especially useful in patients whose Gallium´studies are negative and in whom residual disease is suspected. Additionally, FDG-PET scanning may identify those patients with residual masses whose tumor has been eradicated and do not need further therapy.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition PET: CLINICAL STRATEGIES

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M. Diehl (1), S. Graichen (1), C. Menzel (1), E. Lindhorst (2), F. Grünwald (1). (1) Department of Nuclear Medicine, University of Frankfurt/Main, Germany, (2) Department of General Surgery, University of Frankfurt/Main, Germany.

S. Roudas, T. Skvortsova, Z. Brodskaya, S. Medvedev. PET department of the Institute of the Human Brain of St.Petersburg, Russia.

Aim: Insular thyroid cancer (ITC) is a rare, poorly differentiated form of follicular thyroid cancer. The aim of the study was to evaluate the use of FDG-PET for re-staging and follow-up of ITC. Methods: Five patients with ITC ( 2 m, 3 f), tumors stages pT1 to pT4, who during TSH stimulation showed elevated tumor marker levels with a mean of 86 ng/ml were evaluated retrospectively. At least 30 min after injection of 389 MBq 18F-FDG attenuation corrected whole-body images were acquired using a Siemens ECATExact full ring scanner. One patient (# 2) underwent 4 PET studies. In one case (# 4) a histological confirmation could be obtained. PET findings were compared to the results of computed tomography (CT) and whole body iodine scan (WBI). Results: PET positive lesions were found in all five patients. patient 1 2 3 4 5

PET Hilar region both sides Sternum Right lung Left lower lung left shoulder (skin) lung, both sides Cervical, both sides Left mastoid

CT / Right lung / Lung, both sides Axillar region, both sides Cervical left side Lung, both sides

IWB no pathologic findings sternum no pathologic findings no pathologic findings no pathologic findings

Conclusion: Iodine positive and negative metastases could be detected using FDG-PET. Some of the PET positive lesions could then be verified using CT. We conclude that FDGPET is a useful method in the diagnosis and follow up of ITC. Especially this rare subtype of thyroid cancer requires this intense staging protocol, as it frequently exhibits FDG positive, iodine negative metastases which clearly worsen prognosis. ITC may serve as one example of thyroid cancer that should undergo in-vivo grading not only in radioiodine negative but also in WBI positive cases.

Positron emission tomography for diagnosis of low-grade cerebral astrocytomas

The object of the present study was to determine the usefulness of PET in reliable diagnosis and differential diagnosis of low-grade cerebral astrocytomas. Method: 93 patients with suspected low-grade glioma were investigated by PET using 11Cmethionine before any aggressive treatment. Additionally 18FDG was used in 7 patients. The diagnosis of astrocytoma grade II (including oligoastrocytoma) was confirmed in 63 patients. The tumor was excluded in 24 patients (25,8%). Nontumoral lesions included intracerebral cysts (8), ischemic lesions (6), AVM (5), encephalomyelitic foci (5). PET findings were correlated with surgery in 36 patients and with the outcomes of MR or CT imaging and clinical follow-up studies in others. Visual analysis included the determination of focal increase of 11C-methionine uptake, its extent and borders. Additionally we assessed character of distribution of the most intensive tracer uptake and its volume compared to that of the whole lesion. For quantitative analysis, a circular region of interest (10-mm diameter) was placed in the hottest area of the lesion (T). A region in contralateral unaffected cortex (C) of the same size was used as a reference. A methionine uptake index (T/C) was calculated by dividing lesion to reference activity. In all cases MRI or CT data were available during PET examination. Results: Diagnosis of low-grade glioma was based on the PET criteria established by retrospective analysis of 24 low-grade astrocytomas, which were histologically confirmed. They consisted of the T/C ratio (from 1,3 to 2,0) and the pattern of the highest methionine uptake distribution in the lesion. The PET criteria of asrtocytoma allowed to differentiate these tumors from high-grade astrocytomas. The correct classification of the astrocytomas was achieved in 91% (stepwise multigroup discriminant analysis) after the comparison of lowgrade astrocytomas with anaplastic astrocytomas and glioblastomas. The differentiation between low-grade astrocytoma and nontumoral lesions was based on the various accumulation of 11C-methionine: tumors had significantly higher uptake (mean 1,73±0,39) than nontumoral intracerebral cysts and vascular lesions (p<0,001). However differentiation between encephalomyelitic focus and low-grade astrocytoma was difficult because both pathologies were characterized by increased methionine uptake. To distinguish these lesions the PET study with 18FDG was used additionally. Encephalomyelitic foci showed the high uptake of the both tracers while low-grade astrocytomas were hypometabolic on FDG-PET scans. Conclusion PET seems to be a useful tool in diagnosis of low-grade astrocytoma. The difficulties in differentiating tumor from nontumoral cysts and vascular lesions are solved by PET with 11C-methionine supplemented by PET-18FDG when encephalitis is suspected.

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FDG-PET in insular thyroid cancer

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Comparison of 18F-fluoro-alpha-methyl tyrosine PET, FDG-PET and 201Tl SPECT in detection and differentiation of glioma N. Oriuchi (1), T. Higuchi (1), N. Khan (1), H. Ohtake (2), K. Matsubara (2), K. Endo (1). (1) Department of Nuclear Medicine of Gunma University Hospital, (2) Division of Diagnostic Radiology of Gunma University Hospital, Gunma, Japan. Aim: FDG-PET is used for detecting malignant tumors of various organs. However?because of high glucose metabolism in the normal brain, brain tumors usually show lower uptake than normal brain and malignant brain tumor sometimes can not be delineated from adjacent normal brain. The aim of this study is to evaluate diagnostic ability of 18F-labeled methyl tyrosine (FMT) in comparison to FDG-PET and 201Tl SPECT. Materials and Methods: FMT-PET, FDG-PET and 201Tl SPECT were performed in 10 patients with glioma. FMT-PET and FDG-PET were performed 50 min after injection of approximately 4 and 5 MBq/kg of body weight, respectively. Standardized uptake value was determined for quantitative comparison. 201Tl SPECT was performed 15 min and 180 min after injection of 111 MBq. Tumor-to-normal uptake ratio was calculated. Results: FDG-PET could define 8 of 10 tumor. 201Tl SPECT could detect all tumor and showed statistical difference in the tumor-to-normal ratio between low-grade (1.39+/-0.07) and high-grade tumor (1.78+/-0.27) on delayed image. FMT-PET could detect 9 of 10 tumors. FMT uptake in low-grade glima (2.01+/-0.94) was not significantly different from high-grade glioma (2.65+/-0.62). Conclusion: Both FMT-PET and 201Tl SPECT is superior to FDG-PET in detecting brain tumor. Although tumor-to-normal uptake ratio of FMT is high201Tl, uptake of FMT in glima is variable and does not seem to correlate with the histological grade.

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Prognostic Factors for Carcinoma of Unkown Primary Localized to the Neck only (CUP Syndrome) and the Role of F-18-FDG PET for Diagnosis and Therapeutic Management M. Schmuecking (1), R.P. Baum (1), P. Bank (2), E.C. Lopatta (2), S. Koscielny (3), A. Niesen (1), E. Beleites (3), T.G. Wendt (2). (1) Dept. of Nuclear Medicine, Zentralklinik Bad Berka, Germany, (2) Dept. of Radiation Oncology, University of Jena, Germany, (3) Dept. of Head and Neck Surgery, University of Jena, Germany. Aim: Treatment of patients with carcinoma of unknown primary localized to the neck only is still controversial. To determine both patient related prognostic factors and the influence of treatment parameters the records of 99 patients were analyzed retrospectively. To evaluate the role of F-18-FDG PET for diagnosis and therapy management, 33 patients with carcinoma of unknown primary localized to the neck only were analyzed prospectively. Material and Methods: Retrospective analysis. Out of 99 patients with carcinoma of unknown primary, 51 received surgery as a sole treatment. 48 were treated with a combination of surgery and radiation therapy. 8/99 patients received a F-18-FDG PET. Statistical analyses: Kaplan-Meier-plot, log-rank-test, chi-square-test. All PET studies were carried out prospectively after conventional diagnostic procedures failed to detect the primary tumor. PET findings were correlated with histology and/or clinical course of the patients. Results: Retrospective analysis: Disease specific survival (DSS) was significant longer for patients with N1/N2 vs. N3 (p=0.03), for upper nodal involvement vs. lower and/or supraclavicular nodal involvement (p=0.031) and for the absence of extracapsular spread (p=0.041). No influence of DSS was noted for grading (p=0.469), treatment volume (p=0.82) and applicated dose (>50Gy vs. <50Gy). Prospective study: FDG-PET was successful in localization of the primary tumor in 21%, most frequently in patients with lower and/or supraclavicular nodal involvement. In these patients the primary tumor was located extracervically in 72%, e.g. lung or gastric cancer. In 33% distant metastases were detected. Conclusion: The presence of ECS, the extend and localization of nodal involvement are prognostic factors in patients suffering from CUP localized to the neck only. Patients with upper nodal involvement should be treated with curative intention. The irradiation fields should cover the whole neck including the epipharynx with doses above 50 Gy, however due to small number of patients (power 1-beta<60%) our data could not prove this statement. It should be discussed to treat these patients similar to patients with head and neck cancer. Patients with lower cervical and supraclavicular metastases should be treated locally with palliative intention. However, randomized studies are warranted to identify optimal treatments and their benefits. In patients with CUP localized to the neck only, F-18-FDG PET provides important information for therapeutic management and for the delineation of the treatment volume for radiation therapy.

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T. Tomemori (1), K. Uno (1), M. Kitagawa (1), K. Nakagawa (1), K. Tomiyoshi (1), J. Wu (1), K. Takeda (2). (1) Nishidai Clinic Diagnostic Imaging Center, Tokyo, Japan, (2) Department of Radiology of Mie University School of Medicine, Mie, Japan.

U. Berner (1), A.F. Kovacs (2), C. Menzel (1), K. Bitter (2), F. Grünwald (1). (1) Department of Nuclear Medicine of the Johann Wolfgang GoetheUniversity Frankfurt, Frankfurt, (2) Department of Maxillofacial Plastic Surgery of the Johann Wolfgang Goethe-University Frankfurt, Frankfurt.

Aim: In our clinic, FDG-PET was employed for cancer screening as part of health check and FDG accumulation of thyroid gland is often observed. The aim of this study was to evaluate the usefulness of FDG-PET for detecting the thyroid cancer. Material and Methods: A total of 1747 persons who underwent whole-body FDG-PET for cancer screening or staging of tumors except for thyroid cancer was studied (mean age: 54.7 yrs). PET imaging was performed 45 min after the intravenous administration of FDG (mean dose: 277.5MBq). Each subject fasted for at least 4 hours and then ultrasound (US) study of thyroid gland was also performed for all the subjects. And the pattern of FDG accumulation in the thyroid gland was compared with the type of disease observed by US. Moreover, FDG accumulation was assessed for the subjects whose thyroid was histopathologically examined. Results: FDG accumulation in the thyroid gland was identified in 108 subjects (6.2%). Diffuse FDG accumulation was observed in 69 subjects, and localized FDG accumulation in 39 subjects. Sixty-two out of 69 subjects with diffuse FDG accumulation were diagnosed as diffuse thyroid disease such as chronic thyroiditis by US. In all the subjects who showed localized FDG accumulation, corresponding localized lesion was detected by US. The number of the subjects who histopathologically examined was 20 (5: papillary carcinoma, 9: follicular adenoma, 6: adenomatous goiter). Among them, FDG accumulation was observed in 12. Out of 12 subjects with FDG accumulation, 3 cases were malignant disease and 9 cases were benign disease. Among 8 subjects without thyroid accumulation, 2 cases were malignant disease and 6 cases were benign disease. Conclusion: In most cases with FDG accumulation, corresponding abnormalities were also detected by US. However, FDG was accumulated to benign disease as well as malignant disease of thyroid gland. FDG-PET failed to detect the malignant lesions, thus, the combination of PET and US is necessary for screening thyroid cancer.

Aim: Oral and pharyngeal squamous cell carcinoma with metastatic lymph node involvement is treated surgically including neck dissection , postoperative radiotherapy and chemotherapy. Without metastases, resection of the primary tumor is probably curative alone, with reduced treatment related morbidity. Because the risk of occult lymph node metastases in clinical stage N0 M0 may reach more than 25 %, the discussion about the optimal therapy in these cases is still in progress. To avoid neck dissection and thus reduce postoperative morbidity, carefully preoperative staging to exclude macrometastases is recommended. The aim of this study was the evaluation of lymphoscintigraphy guided sentinel lymph node biopsy for the detection of lymphogenic micrometastases, subsequent to preoperative N0 classification using F-18-FDGPET. Materials and Methods: Between march 2000 and december 2001, thirty patients (m:f 21:9, mean 62 y, range 44-79 y) with histologically proven oral or pharyngeal squamous cell carcinoma were preoperatively be classified as N0 M0. The diagnostic procedures before surgery included clinical examination, ultrasound and computed tomography of the neck, and a whole body F-18-FDG-PET. If sentinel node biopsy showed metastatic lymph node involvement, a complete neck dissection was performed during a second operation. Results: All patients showed scintigraphically detectable sentinel lymph nodes (92 SLN, 1 to 6 SLN per patient, mean 3.1 SLN). Six SLN could not be identified during operation with the gamma probe (6.5 %). One patient had metastatic involvement of the sentinel node. Twentytwo percent of SLN’s from unilateral primaries were located contralateral. Conclusions: Radioguided sentinel node biopsy for oral and pharyngeal squamous cell carcinoma is a successful practicable procedure. To exclude macroscopic metastases preoperatively, F-18-FDG-PET has a high negative predictive value. Head and neck cancer often has lymphatic drainage to the contralateral side. Lymphoscintigraphy guided sentinel node biopsy may be more sensitive to detect lymphogenic micrometastases than unilateral neck dissection.

The evaluation of the usefulness of FDG-PET for detecting thyroid cancer

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Head and neck cancer: sentinel node scintigraphy following N0staging with F-18-FDG-PET

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Assessment of clinical utility of 18F-FDG PET in patients with head and neck cancer using a Bayesian probability analysis

Evaluation of F18 FDG dual head coincidence imaging in diagnosis of recurrent and metastatic head and neck tumors

G.W. Goerres (1), L.M. Bachmann (2), D. Schmid (1), K. Mosna-Firlejczyk (1), G.K. von Schulthess (1). (1) Division of Nuclear Medicine of the University Hospital Zurich, Zurich, Switzerland, (2) Horten Centre of the University of Zurich, Zurich, Switzerland.

H. El-Zeftawy (1), M. Dakhel (1), S. Heiba (1), S. Caruana (2), H.M. AbdelDayem (1). (1) Department of Nuclear Medicine, St. Vincent’s Catholic Medical Centers of New York, (2) Department of Surgery, St. Vincent’s Catholic Medical Centers of New York, USA.

Aim: A large number of papers have reported on accuracy of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) in patients with head and neck cancer (HNC). However, clinical usefulness of accuracy data depends on prior probabilities of the disease under study. Therefore we assessed pre-test probabilities from our database of patients with HNC that underwent PET and calculated post-test probabilities using data of a meta-analysis of the literature. Material and Methods: In a retrospective analysis of 98 patients with clinically proven HNC who underwent FDG PET between April 1999 and October 2000 we first assessed the prior probability of disease in our unit. Pre-test probabilities were estimated for initial lymph node staging. Second, we performed a systematic review with a meta-analysis of the published literature using standard methodology to generate pooled likelihood ratios for a positive and negative test result (+LR, -LR). These likelihood ratios were then combined with the prior probabilities from our hospital to determine disease probabilities for positive and negative testing. Results: Retrospective analysis of patient records revealed that additional lymph node metastases were found in 20% of our patients. The systematic review identified 24 publications that met our inclusion criteria. The pooled +LR and -LR were 16.7 (95% CI 10.8-25.8) and 0.19 (95% CI 0.13-0.26) respectively and post-test probabilities were, thus, 80.7% (95% CI 73.086.6%) for test positives and 4.53% (3.14-6.1%) for test negatives. Conclusion: In a setting with a low prior probability of additional lymph node metastases in patients with HNC staging PET is a useful test to assist the decision to rule-in or to rule-out the presence of lymph node involvement.

Accuracy of Hybrid PET systems in detection of recurrent and metastatic head and neck tumors was retrospectively evaluated in this study. METHODS: Charts of 34 patients 12 M and 13 F age ranging from 27 to 70 years (average 53) treated from head and neck tumors were reviewed. Primary tumor sites were as follows: 8 laryngeal, 7 orpharyngeal, 6 nasophgaryngeal, 5 oral cavity, 1 maxillary sinus and 7 had other head and neck lesions such as orbit, skin of the face tumors and cervical lymph nodes metastasis from an unknown primary. Pathological types were as follows: 18 squamous cell, 3 adeno, 7 undifferentiated carcinoma, 3 lymphoma, 2 sarcomas and 1 mucoepidermoid carcinoma. Material: A total of 65 F-18 FDG studies were performed, 34 baselines scans done for evaluation of treatment for detection of sites of local recurrence or metastasis, and 31 scans for later follow up, only 42 x-ray CT were performed within 3 weeks of their F-18 FDG scans and were used for comparison and correlation. 33 studies were followed by pathological examination of the detected lesions and the rest were evaluated by clinical and follow up F-18 FDG scans. F-18 FDG scan were acquired and processed as per department protocol and read blindly by at least two independent nuclear medicine physicians. Differences in interpretations were solved by consensus. RESULTS: F-18 FDG detected 42 of the 49 pathologically verified positive lesions, excluded local recurrence in 2 patients but failed to detect 7 x-ray/CT localized mediastinal lymph nodes in 3 patients. The sensitivity of F-18 FDG DHCI was 86%, specificity 100%, positive predictive value 100% and negative predictive value 40%. X-ray CT scan detected 29 of 33 pathologically verified lesions, but could not detect 2 bone metastasis and 7 cervical and hilar lymph node metastasis localized in the F-18 FDG studies. The sensitivity of the x-ray/CT studies was 72%, specificity 50%, positive predictive value 92% and negative predictive value 20%. When 42 F-18 FDG studies were interpreted in concordance with the patient’s recent x-ray/CT both studies were able to localize 30 of the 31 pathologically proven lesions and correlation excluded misinterpretation of the x-ray/CT false positive lesions. This increased the sensitivity of combined studies to 96%, specificity to 100%, and positive predictive value to 100% and negative predictive value to 80%. CONCLUSION: F-18 FDG DHCI is a reliable method for detection of locally recurrent and metastatic head and neck tumors. Correlating F-18 FDG PET with x-ray/CT findings increases the sensitivity, specificity and predictive values of both tests in detection of head and neck tumors.

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FDG-PET in the management of head and neck tumors C. Trampal (1), M. Anniko (2), H. Engler (1), B. Långström (1). (1) Uppsala University PET Centre, Uppsala, Sweden, (2) Head and Neck Department, University Hospital, Uppsala, Sweden. Aim: The aim of this study was to assess the usefulness of Positron Emission Tomography with 18F-Fluorodeoxiglucose (FDG-PET) in head and neck tumors, and to evaluate its impact in the clinical management. Material and Methods: 34 patients (21 men and 13 women, mean age 52 years) with biopsy proven cancer of head and neck region were studied (one biopsy was not conclusive). In 20 patients FDG-PET was performed for preoperative staging, being the primary tumor in the following locations: oral floor (6), base of tongue (3), hypopharynx (2), larynx (2), epipharynx (2), mandible (2), maxillary sinus (1), lip (1) and cricoid cartilage (1); in 12 patients FDG-PET was performed to detect tumor recurrence; and in 5 patients to monitoring response to radiotherapy. Whole body PET scan was performed 60 minutes after iv administration of 400 MBq FDG, using a ECAT EXACT HR+. PET results were validated with histopathological findings, anatomic imaging and clinical follow-up. Results: All the primary tumors but one (n=19) were detected by FDG-PET, either visually or using SUV as semiquantitative index (mean SUV was 7.75, range 2.8-14.5). The only tumor not detected was a 4 millimetres lesion in the tongue. The tumor with not conclusive biopsy showed high FDG uptake, but was a benign cartilaginous tumor. In addition, FDG-PET detected 10 regional nodal metastases in 8 patients. No distant metastases were demonstrated. In the patients with suspicion of tumor recurrence (n=12), FDG-PET demonstrated local recurrence in 5, distant recurrence in 6 (3 in cervical nodes, 2 in oral floor and 1 in the lungs) and was negative in 1. FDG-PET performed to verify treatment response (n=5) was negative for residual disease in all of them. FDG-PET influenced the clinical management in 11 patients (32.3%), suggesting appropriate treatment strategy (n=8) or avoiding unnecessary surgery (n= 3). In the last 3 cases, PET saved the cost of surgical procedures, which was calculated to be higher than the cost of PET imaging in all the patients included in this study. Conclusion: FDG-PET is a functional non invasive technique useful in staging primary head and neck carcinomas as well as in detecting tumor recurrence, specially in areas often equivocal by anatomic imaging, and in monitoring treatment response. In addition, FDG-PET may influence in selecting appropriate therapeutic management and may be cost-effective, by reducing the cost of patient treatment.

Comparison of 99mTc-MIBI and 18F-Fluorodeoxyglucose in lung tumors using a coregistration imaging system (CT/CDET) J.L. Alberini (1), M. Wartski (2), C. Corone (1), L. Mabille (2), J. Cerrina (3), E. Dulmet (4), V. De Montpreville (4), P. Dartevelle (3), A.P. Pecking (1). (1) Department of Nuclear Medicine, Centre Rene Huguenin, SaintCloud, France, (2) Department of Nuclear Medicine, Centre Marie Lannelongue, Le Plessis Robinson, France, (3) Department of Thoracic Surgery, Centre Marie Lannelongue, Le Plessis Robinson, France, (4) Department of Pathology, Centre Marie Lannelongue, Le Plessis Robinson, France. Objectives: Compare the performance of 99mTc-MIBI-SPECT and 18F Fluorodeoxy-glucose (FDG-CDET) using coregistration imaging system with Computed Tomography and Coincidence Detection Emission Tomography (CT/CDET) in the diagnosis and mediastinal staging of lung tumors. Patients and Methods: 29 patients (22 males; mean age = 64 y) with lung tumor, recently detected by Xray and confirmed by helical CT (n=25) or previously treated by 3 courses of chemotherapy (n=4), were included in a prospective study. FDG-CDET and MIBI-SPECT were acquired on the same day, on a dual head gamma camera (Millenium VG) equipped with a CT (Hawkeye, General Electric, Millwaukee, USA). CT scans were used for correction attenuation on FDG images but not for mediastinal staging because no contrast enhancement was performed. Results were compared to histologic findings : 24 patients had malignant tumors and 5 patients had benign tumors. In order to decrease the number of false negative results for the mediastinal staging, FDG-CDET and CT results were associated and the higher stage of both methods was retained. Results: Sensitivities and specificities of MIBI-SPECT were respectively 39 % and 33 % for the lung tumor and mediastinal staging. Sensitivities and specificities of FDG-CDET were respectively 87 % and 76 % for the lung tumor and mediastinal staging. Sensitivity and specificity of FDG-CDET and helical CT combined results for the mediastinal staging were 92 % and 75 %. False negative mediastinal lymph nodes results of FDG-CDET were observed in tumors in contact with mediastin and there was no false negative result for peripheric tumors. All pulmonary lesions but one (0.8*0.3 cm) were detected by CT used on the CT/CDET system. Performances of FDG-CDET were better than those of CT to assess mediastinal stage. Conclusion: This study suggests that FDG-CDET is better than MIBI-SPECT for a routine use in diagnosis of lung tumors even if its performances were lower than those published using dedicated Positron Emission Tomography. Coregistration imaging system CT/CDET was useful to correct images from attenuation and to be sure than FDG uptake corresponded to the tumor or enlarged lymph node visualized by helical CT.

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COMPARISON OF FDG AND CT SENSITIVITY IN HIGH, LOW AND INTERMEDIATE NHL AND HD

M. Halac (1), H. Akman (2), C. Türkmen (1), K. Kuzucu (2), S. Okay (1), S. Bozluolcay (1), K. Sönmezoglu (1). (1) International Hospital, Nuclear Medicine and, (2) Radiology Departments, Istanbul, Turkey.

Pathology Calcification

FDG-PET in The Evaluation of Focal Pulmonary Abnormalities.

Aim: We evaluated the value of FDG-PET in radiographically indeterminate focal lung masses. A total of 36 patients with indeterminate masses on chest X-ray CT were referred to our PET imaging facility between October 2000 and November 2001. There were 27 male (75%) and 9 female (25%) with an average age ± SD of 62±12 (range from 37 to 78). Of the patients, 26 were meeting the radiologic criteria of “SPN” with a size 0.8-4 cm. Materials and Methods: FDG-PET scanning was performed in a full-ring dedicated PET scanner (Siemens ECAT EXACT), after IV injection of 10-15 mCi FDG. PET scans were interpreted by two nuclear medicine physicians with the knowledge of CT results and clinical history. Areas of increased activity over background were interpreted as positive. Results: Final diagnosis was determined by histology (n=25), serial imaging (n=6) or clinical follow-up with a median duration of 6 months (n=5). There were 24 (67 %) malignant, 12 (33 %) benign lesions. FDG-PET had a sensitivity of 100 %, specificity of 67 %, PPV of 85.7 %, NPV of 100 %, and accuracy of 88.8 % in differentiating malignant from the benign lesions. There were 4 false positives including 3 granulomas and 1 aspiration pneumonia. No false negative is found. PET revealed 5 extra lesions that were not seen on CTs, of which 3 had been verified as malignant including 1 surrenal, 1 contralateral lung, and one ipsilateral diaphragmatic pleura. In addition, 2 suspected lesions on CTs (1 liver, 1 contralateral lung) for metastasis were truly shown as benign by PET. Regarding to mediastinal staging, FDG-PET led to upstaging in 3 patients and downstaging in 2 patients. Conclusion: FDG-PET is not an excellent technique in the evaluation focal lung masses because of suboptimal specificity. However, its sensitivity and PPV are excellent and therefore it appears useful in the subset of patients in whom a positive result would alter clinical management.

Sensitivity of FDG above the Diaphragm High grade NHL 96.3% Intermediate NHL 93.1% Low grade NHL 95.2% HD 98%

Sensitivity of CT above the Diaphragm 76.7% 73.3% 75.3% 91.5%

Sensitivity of FDG below the Diaphragm 86% 85.7% 82.6% 83.4%

Sensitivity of CT below the Diaphragm 87.5% 82.7% 85.2% 92.6%

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M. Dakhel (1), M.M. Aladdin (2), H. El-Zeftawy (1), R. Perone (2), S. Heiba (1), H.M. Abdel-Dayem (1). (1) Department of Nuclear Medicine, St. Vincent’s Catholic Medical Centers of New York, (2) Department of Radiology, St. Vincent’s Catholic Medical Centers of New York, USA.

A. Castagnoli (1), V. Briganti (1), E. Costanzo (1), P. Ferri (1), G. Gallini (1), M. Matteini (1), L. Rigacci (2), F. Bernardi (2), L. Vaggelli (1). (1) UO Medicina Nucleare, Azienda Ospedaliera di Careggi, (2) Dipartimento di Ematologia, Azienda Ospedaliera di Careggi- Università degli Studi, Firenze, Italy.

Impact of hybrid F18 FDG PET scan on initial staging of various types of malignant lymphoma compared with CT scans

OBJECTIVES: The aim of this retrospective study was to validate the clinical value of F18FDG PET imaging acquired on dual head gamma camera coincidence imaging system with attenuation correction (DHGCCI AC) in initial staging of Malignant Lymphoma. The results of F18-FDG and CT studies were evaluated in the low, intermediate and high-grade nonHodgkin’s Lymphoma (NHL) and Hodgkin’s Disease (HD). METHODS: 53 patients with malignant lymphoma (9 HD, 44 NHL) were retrospectively evaluated. Patients had F-18 FDG and CT studies for initial staging. The results of the F18FDG and CT imaging regarding detection of lymph node groups involved, and staging of the disease was compared with each other. The NHL patients were divided into three groups according to working group pathology classification. RESULTS: In 44 NHL patients FDG detected 264 lesions, 164 lesions in high grade lymphoma (104 above, 60 below the diaphragm), and 48 lesions in the intermediate grade lymphoma (30 above and 18 below the diaphragm), 53 lesions in low grade lymphoma patients (34 above and 19 below the diaphragm). The CT detected 154 lesions (56 above and 98 below the diaphragm), 38 lesions (14 above and 24 below the diaphragm) and 46 (17 above and 29 below the diaphragm) in high, intermediate and low grade lymphoma respectively. In 9 patients with HD the F18-FDG detected 53 lesions and the CT 48 lesions. In NHL the FDG upstaged 9 patients and CT upstaged 6 patients. The CT detected 18 lesions that were not seen in FDG. 15 of these lesions were in the abdomen. Sensitivity of FDG and CT are in the Table. FDG detected 44 lesions that were not seen in the CT, 34 of these lesions were above the diaphragm. CONCLUSION: The FDG PET scan with DHGCCI AC appears to be an accurate method of initial staging of HD and all pathological subgroup of NHL. Due to the limitation of hybrid PET, the CT detected more lesions below the diaphragm than the FDG, while the FDG detected more lesions above the diaphragm.

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2-[18-F]fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) in post-treatment restaging in Hodgkin’s Disease (HD)

Background: Computed tomography (CT) is still the main imaging modality for staging in the post-therapy setting where residual masses are found ; notwithstanding CT it is often unable to differentiate residual disease from fibrosis. Aim: to evaluate the role of the 18FDG-PET in the posttreatment evaluation of patients with HD in comparison with computed tomography (CT). Patients and Methods: Twenty-nine patients recruited for 18FDG-PET evaluation between june1999 and december 2000 were included in this study, The characteristics of patients at diagnosis were the following: 17 were female and 12 male; 2 were stage I, 15 were stage II, 8 stage III and 4 stage IV. Eighteen patients (62%) were treated with chemotherapy and radiotherapy and 11 were treated only with chemotherapy. 18FDG-PET and CT were performed in 21 patients during follow-up or at the end of therapy to evaluate the remission and in 8 cases 18 FDG-PET was performed because of a doubt of relapse upon radiological examination. 18 FDG-PET was performed with a dedicated scanner 45-60 min after tracer dose injection( 370 MBq/ 70 Kg). Results: We have observed agreement between 18FDG-PET and CT in 16 cases out 29 (52%). In particular in 4 cases the two procedures were both positive for the presence of disease and two patients experienced relapse; in 9 cases both techniques were negative and confirmed clinical remission. In the remaining 16 patients the two procedures were discordant: in 4 patients out of 16 CT was negative and 18FDG-PET positive. Three patients out of these 4 experienced a relapse while the fourth patient was free from disease upon lymph nodes biopsy (false positive 18FDG-PET). In twelve patients out of 16 discordant cases 18FDG-PET was negative and CT positive (in 8 of these cases the CT study showed a suspiciuos mass in the mediastinum): in all these cases after a median follow-up of 24 months (range 13 – 31 months) we have not observed relapse. In our overall experience twenty-one 18FDG-PET were negative and no relapse was observed in this subset of patients. The sensitivity was 100% and 40% and specificity was 87% and 42% for 18FDG-PET and CT respectively. Conclusions: Our results, even if the follow-up is still brief and the series is short, seems to confirm that FDG-PET is a very sensitive tool in assessing remission in HD and of particular value in the assessement of residual massess (in particular mediastinum) showed by CT.

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I. Buchmann (1), M. Bommer (2), B. Neumaier (1), M. Bentz (2), G. Glatting (1), P. Möller (3), F. Leithäuser (3), J. Kotzerke (1), S.N. Reske (1). (1) Department of Nuclear Medicine of the University of Ulm, Germany, (2) Department of Hematology of the University of Ulm, (3) Department of Pathology of the University of Ulm, Germany.

I. Gayed (1), R. Iyer (2), W. Sureshbabu (1), H. Macapinlac (1), D.A. Podoloff (1). (1) Department of Nuclear Medicine, University of TexasM.D. Anderson Cancer Center, (2) Department of Radiology, University of Texas-M.D. Anderson Cancer Center, Houston, Tx-USA.

[18F]3’-deoxy-3’-fluorothymidine - PET in NHL patients: Whole-body imaging and correlation with tissue proliferation index

Purpose. The nucleoside 3’-deoxy-3’-fluorothymidine (alovudine) is an antiviral agent accumulating in proliferating cells. We prospectively evaluated the biodistribution of the PET tracer [18F]3’-deoxy-3’-fluorothymidine (FLT) and its value in measuring the proliferation activity of non-Hodgkin lymphomas (NHL). Methods. Eight patients (7 male, 1 female) with indolent NHL (2), NHL in transformation (3) or aggressive NHL (3) were examined. Patients received initial staging or restaging with an intervall of at least 10 weeks between therapy and PET. Mean doses of 324 ± 165 MBq FLT were injected intravenously. Static PET scans were performed 50-70 min after application. Maximum standardized uptake values (SUV) of organs and NHL tumor tissues were calculated. Proliferation rates were evaluated by Ki-67 immunostaining of biopsies (7 lesions) or aspiration smears (4 lesions). Results. Tracer accumulated physiologically in bones with hematopoietic marrow and in the liver and was renally excreted. SUV of organs 1 hrs p.i. were: bone with hematopoietic marrow (vertebrae; ribs; pelvis; sternum), 9.9 ± 4.7; liver, 5.2 ± 1.0; kidneys, 4.0 ± 1.7; spleen, 3.0 ± 1.2; bone without hematopoietic marrow (lower humeri/femora), 1.9 ± 1.1; lungs, 0.8 ± 0.3. Range of maximum lymphoma SUV of FLT was 3 to 7 for the indolent group and 5 to 16 in the transformation/aggressive group. For all patients including one having large cell anaplastic B-cell lymphoma with marked sclerosis, the correlation coefficient was 0.57 (p = 0.06). For 7 patients with non-sclerotic NHL, the correlation coefficient of intratumoural FLT uptake and tissue proliferation index was 0.95 (p < 0.0001). Conclusion. FLT-PET was effective in imaging NHL and in measuring tissue proliferation in patients with indolent NHL, NHL in transformation and aggressive NHL. FLT-PET might be less appropriate for evaluating tumor proliferation in vivo in case of marked sclerosis within the lymphoma lesion.

Evaluation of Positron Emission Tomography As The Sole Required Procedure for Staging Melanoma

The yield of conventional imaging modalities used in combination with positron emission tomography (PET) in staging cancer patients needs to be reconsidered for better cost-effective management of patients. Aim: To investigate the additive value of computerized tomography (CT) to FDG PET scans in staging melanoma. Methods: Whole body FDG PET and CT scans from 34 melanoma patients performed within 1 month interval were evaluated. PET scans were interpreted by an experienced nuclear medicine physician with no knowledge of the clinical or other imaging findings. Lesions with SUV > 2.5 were considered malignant and below 2.5 as benign. An experienced radiologist also blindly interpreted CT of the chest, abdomen and pelvis in 28 patients, the chest in 3 patients, and the abdomen and pelvis in 3 additional patients. Site of lesions and basins of lymph node metastases were recorded. The findings were compared with follow-up, other imaging modalities, and/or biopsy results for accurate staging of the patients. The average follow-up time was 4.0 months. Results: A total of 120 lesions were detected using PET and 98 using CT in 32 patients. Two patients had innumerable metastases using both modalities, so they were excluded from the total number of lesions. The performance of PET versus CT in the chest and abdomen/pelvis is as follows: PET CT Chest Abdomen/Pelvis Chest Abdomen/Pelvis True Positive 25 16 19 13 False Positive 2 0 6 2 True Negative 40 35 34 34 False Negative 11 1 13 3 Sensitivity 69% 94% 59% 81% Specificity 95% 100% 85% 94% Positive Predictive Value 93% 100% 76% 87% Negative Predictive Value 78% 97% 72% 92% The difficulty of PET in detecting nodules less than 1 cm in the lungs was the main reason for lower sensitivity in the chest. On the other hand, PET identification of melanoma metastases in the abdomen and pelvis was extremely good. Conclusion: CT abdomen and pelvis may be used only for more accurate anatomical localization of lesions found with FDG PET scans, when required for surgical resection, rather than for the initial staging of melanoma patients.

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M. Simo, F. Lomena, X. Setoain, J.R. Garcia, G. Perez, J.M. Costansa, J. Setoain, F.M. Domenech-Torne, I. Carrio. CETIR.UNITAT PET.Barcelona, Spain.

H.W. Hendel (1), N. M. Jensen (2), I. Kanstrup (1), J. Herrstedt (2). (1) Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, University of Copenhagen, Denmark, (2) Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.

Objectives: The purpose of the study was to retrospectively investigate how 18F-FDG wholebody studies influenced clinical therapeutic decision in a series of patients with suspected recurrence of renal cell carcinoma. Methods: 19 consecutive patients (14 male, 5 female) underwent whole-body 18F- FDG PET (GE ADVANCE) after 6-8 hours fast. All patients had suspected recurrence of renal cell carcinoma based on elevated CEA levels and /or inconclusive X-ray, bone scan, CT or MR examinations. PET results were confirmed by surgical resection or clinical follow-up. Management change because of PET examination was considered if surgery was made possible, or if systemic treatment was implemented due to disseminated disease. Results: PET scans detected tumor recurrence in 9/19 (47%) patients and were negative in 10/19 (53%) patients. A total of 22 lesions were detected in the 9 patients: 7 lesions in bone, 6 in lung, 2 mediastinal and 7 abdominal. 13 of these 22 lesions were not seen by other imaging techniques. Based on PET results, 2/9 patients were operated on and 7/9 underwent chemotherapy because of unresectable recurrence or spread disease. Conclusion: Whole-body FDG examinations detect lesions in >40% of patients with suspected recurrence of renal cell carcinoma and have major impact on clinical decision making in these patients. (EUREKA FIT0700002000693).

Experience with Dual Head Gamma Camera 18F-FDG-PET in the Detection of Suspected Recurrent Epithelial Ovarian Carcinoma

Aim: The aim of this retrospective study in patients with epithelial ovarian cancer was to evaluate PET in the following two situations: CA 125 levels are elevated and clinical investigation plus conventional imaging does not confirm recurrence. A single metastatic site is diagnosed, and the patient is suitable for operation if additional tumor spread is absent. Patients: 23 PET scans were performed in 21 patients (mean age 54 years) with epithelial ovarian cancer, who had received first line chemotherapy. Eight scans were performed due to elevated CA 125 (group 1) and 15 scans concerned operability (group 2). Eleven patients underwent surgery (histological biopsy) the rest were evaluated by ultrasound, CT, and/or histological biopsy. Methods: Whole body PET (from the neck to the knees) was performed using a dual head gamma camera equipped with MCD facility (Forte, ADAC) after injection of 140 MBq 18FFDG 1 hour prior to scanning with the patient in the fasting state for 6 hours. Visualized evaluation was performed on transversal, frontal and sagittal sections and in the 3-dimensional cine mode. Focally increased 18F-FDG activity outside the regions of physiologically increased activity was considered pathologic. The results of PET scans were compared with findings at operation (11 patients) or results of other imaging techniques and clinical course was used as arbiter. Results: 14 of 23 PET scans were considered true positive or true negative. Nine of 23 PET scans were considered false positive or false negative. Two of the 5 false negative scans were found in patients with peritoneal carcinosis only. The overall sensitivity and specificity were 64% and 56%. Accuracy in group 1 and 2 were 50% and 67% respectively. Conclusion: Although the diagnostic accuracy may vary depending on the clinical application, 18F-FDG PET is basically a suitable method for detecting relapsed ovarian cancer. PET has the same problems as other imaging modalities in detection of microscopic disease.

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Impact of whole-body 18F-FDG PET on the management of patients with suspected recurrence of renal cell carcinoma

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K. Murakami, K. Nasu, S. Nawano, H. Ikeda, H. Fukukita. Department of Radiology, National Cancer Center Hospital East.

L. Joerg (1), F. Kurz (2), B. Wieser (1), R. Klug (2), M. Heinisch (1), E. Rechberger (1), P.J. Panholzer (1), M. Aufschnaiter (2), W. Langsteger (1). (1) Department of Nuclear Medicine, PET Center BHS Linz, Austria, (2) Department of Surgery, BHS Linz, Austria.

Efficacy of FDG-PET for detecting lymph node metastases from colorectal cancer

Introduction: Some recent reports indicated the usefulness of whole body FDG-PET for evaluating hepatic metastases or recurrence of colorectal cancer. But only a few studies mentioned about clinical efficacy of FDG-PET for lymph node metastases, though N factor have great influence on therapeutic procedure. Objectives: To assess the utilization of FDG-PET in detection of lymph node metastases from colorectal cancer. Methods: The study included 20 patients with suspected lymph node swelling (8mm<) on CT or unusual elevated CEA. Patients with regional lymphadenopathy only were excluded in this study because limited regional lymph node metastasis does not influence the surgical management. All patients underwent whole-body FDG-PET (300MBq; GE medical system ADVANCE scanner), abdominal/pelvic CT, and pelvic MRI. The results were confirmed histopathologically after surgical resection in all cases. Results: Lymph node metastases were pathologically confirmed in 11 of 20 patients. Truepositive scans were obtained with PET in 10 and with CT in 9 cases (sensitivity 90.9% and 81.8%, respectively). True negative scans were obtained with PET in 6 and with CT in 3 cases (specificity 66.7% and 33.3%, respectively). In three patients with positive CT findings, PET showed no RI uptake, which turned out to be reactive lymphadenopathy on histology. In three cases with positive both PET and CT findings, lymph nodes swelling proved to be inflammation in two cases. In these cases, elevated CRP was existed before surgery and abscess accompanied by primary tumors were proved pathologically. Conclusion: FDG-PET is feasible for differentiation between metastatic and reactive lymph node swelling, though careful estimation may be needed in patients with elevated CRP.

18F-FDG PET for Staging of Rectal Carcinoma: Comparison with Histology and Conventional Imaging Modalities

Aim: 18F fluoro - deoxy - glucose (FDG) positron emission tomography (PET) has been successful used to image recurrent colorectal cancer. The aim of this preliminary study was to evaluate the potential usefulness of FDG PET in patients with primary carcinoma of the rectum. Materials and Methods: In a prospective study overall 43 patients with primary rectal carcinoma were included. In group A (20 patients) FDG PET was compared postoperatively with histopathological findings. In group B (23 patients) only conventional imaging modalities (CIM) which included computed tomography (CT), endorectal ultrasonography and chest X - ray were compared with FDG PET. The final diagnosis was based on operative, histopathological findings and/or clinical follow up. Results: Primary: Overall, PET was able to detect the primary tumor in 97,7 % (42/43 pts); one patient had previously undergone polypectomy. N Staging: In group A FDG PET depicted lymph node metastases in only one of five patients (sensitivity 20 %); in group B among nine patients with CIM positive lymph node metastases FDG PET was positive in five patients (5/9 pts: sensitivity 55,6 %). M Staging: With regard to distant metastases FDG PET was positive in 5/43 patients (11,6 %), whereas CIM was only positive in 4/43 patients (one false - negative patient with cervical lymph node metastasis). Conclusion: Our preliminary results show that regarding the primary tumor FDG PET has a very high sensitivity in patients with rectal carcinoma. Due to the vicinity to the primary tumor FDG PET is only of limited value for detecting lymph node metastases. Concerning distant metastases the sensitivity compared with CIM might be higher in FDG PET. Further studies in a larger series of patients are needed to verify this suggestion.

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C. Turkmen (1), M. Halac (1), H. Akman (2), S. Okay (1), T. Özer (2), S. Bozluolcay (1), K. Sönmezoglu (1). (1) International Hospital, Departments of Nuclear Medicine and, (2) Radiology, Istanbul.

K. Uno, T. Tomemori, J. Wu, K. Tomiyoshi. Nishidai Clinic Diagnostic Imaging Center,Tokyo,Japan.

Clinical Value of FDG-PET in Recurrent Colorectal Cancer

Aim: We have evaluated the clinical value of positron emission tomography (PET) with 18Ffluoro-2-deoxyglucose (FDG) in pts with suspected recurrent colorectal cancer (CRC). Material and Methods: A total of 31 pts with suspected CRC recurrence based on elevated CEA levels and/or inconclusive CT /MR examinations were studied by FDG-PET. There were 20 (65 %) male, and 11 (35 %) female (age range: 29-74 yrs mean: 57±11 yrs). The pts were classified in two groups. Group I is consisted of 8 pts with elevated serum CEA levels but negative CT scans. Group II included 23 pts with suspected inconclusive lesions on CT/MR. Results: The final diagnosis was based on pathological findings (n=9), or clinical and radiological follow-up with a median duration of 5.9 months (n=22). In Group I, PET scans demonstrated 15 lesions (3 intrahepatic and 12 extrahepatic) in 6 (75%) pts, of whom 4 were operated and recurrence was proven histologically; 2 pts were inoperable because of extensive disease. Regarding to 2 (25%) pts with normal PET imaging in the first group, one is currently disease free with a 14 months follow up period; the other one was found a local recurrence by colonoscopy (musinous adenocancer) 4 months after PET study. In the second group, FDG-PET studies confirmed tumor recurrence in 16 (70%) pts (2 local, 6 lymphatic, 8 hepatic and 4 pulmonary) and ruled out a recurrence in 7 (30%) pts. Of the PET confirmed recurrence disease, 7 were found as a resectable disease (5 pts with liver metastasis, 1 patient with local relapse, 1 patient with lung lesion). In the patient with lung lesion, pathological examination surprisingly revealed a NSCLC. The remaining 9 pts had unresectable disease, 2 of which were died during follow-up period. Conclusion: Whole-body FDG-PET scan is a useful method for the detection of local relapse and distant recurrence of CRC. It is also enable to detect coexistent secondary malignancy, which may affect clinical management.

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Screening and early diagnosis using FDG-PET

Aim: Screening and Early Diagnosis using FDG-PET Whole body Positron Emission Tomography with F-18 FDG has a recognized role in tumor imaging. Because seamless scanning of the whole body is possible, FDG-PET can be employed as a useful tool for cancer screening. Since our PET clinic opened on October 2, 2000, we have focused on cancer screening for asymptomatic patients using FDG-PET, EBT, US and MRI. We also perform differential diagnosis, staging, and recurrence detection for patients referred to us from hospitals across Japan. Materials and Methods: Over a period of 17 months, 838 male and 674 female (mean age 54.4+/-10.1 year, range 28-85) 340 symptomatic patients and 1172 asymptomatic patients were studied. We administered 0.125MBq/kg of FDG to the patients, all of who had fasted for at least 4 hours prior to receiving the FDG. Scanning commenced within 30-45 minutes of receiving the FDG using a whole body PET camera (Posicom HZL m-power). For the group undergoing cancer screening, emission images were acquired and reconstructed without attenuation correction. For the other patients transmission and emission images were acquired and reconstructed both with and without attenuation correction. We evaluated the utility of screening with PET for early cancer diagnosis by comparing PET results with final screening outcomes. Results: A total of 21 malignant tumors (1.4%) were found in the screening group. PET was positive in 14 cases and negative in 7 cases. The 8 positive cases were comprised of one esophagus carcinoma, two lung cancers, two breast cancers, two renal cancers, two rectal cancer, two sigmoid colon cancers, and three thyroid cancers. The 7 negative cancers were comprised of one thyroid cancer, one lung cancer, one gastric cancer, one bladder cancer, one prostate cancer, and two esophageal cancers. For those patients suspected of bearing tumors there were 33 true positive cases, one true negative case, two false positive cases, and two false negative cases. In two cases we detected double cancers with PET. Various benign tumors were also detected in the asymptomatic group. The benign tumors were comprised of a pituitary tumor, a parotid tumor, thyroid adenomas and an adenoma of the pancreas. It was important to both understand the physiological uptake of FDG and to recognize the relationship of benign lesions and inflammation in order to avoid false positive interpretation. In our data high gastric uptake of FDG was seen in 20% of the cases, this uptake being associated with H. Pylori infection. Conclusion: We conclude that FDG-PET can be used to detect a variety of cancers in their curable stages despite the limitation in differentiating between benign and malignant lesions.

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Tc-99m-HMPAO Brain SPECT in patients with epilepsy, treated with Topiramate A. Klissarova (1), D. Minchev (2). (1) Department of Nuclear Medicine of the Medical Universityof Varna, Varna, Bulgaria, (2) Department of Neurology of the Medical University of Varna, Varna, Bulgaria.

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Brain PET and SPECT in children with cortical dysgenesis and epilepsy S.A. Asenbaum (1,2), M. Feucht (3), G. Zettinig (1), A. Becherer (1), K. Kletter (1). (1) Department of Nuclear Medicine, University of Vienna, (2) Department of Neurology, University of Vienna, (3) Department of Neuropsychiatry of children and adolescents, University of Vienna; Vienna, Austria.

Aim: Tc-99m HMPAO-Brain SPECT is a popular method for detection of the regional cerebral blood flow. Topiramate is used in patients with epilepsy since it increases the brain GABA, homocarcinosine and pyrrolidinone. The aim of the study is to assess the regional cerebral blood flow in hypoperfusion areas before and after the treatment with Topiramate in patients with epilepsy and to compare the scintigraphic results with the frequency and intensity of the seizures. Methods: Subject to the study were 20 patients with epilepsy (mean age 22) who were treated with Topiramate. All the patients underwent brain SPECT study with 740-MBq- HMPAO before treatment and on the 30th day from it. Brain perfusion was detected by means of the indices calculated as follows: hypoperfusion areas in temporal lobe to referent zone of the cerebellum. The brain perfusion increase in hypoperfusion areas was calculated in per cent. The frequency and intensity of the seizures were followed-up in all the patients for 6 months. Results: An approximately 10% increase in brain perfusion was established in 15 patients who also showed a decrease in the seizure intensity and frequency. About 5% increase in brain perfusion was detected in 2 patients who did not show significant improvement from the treatment. In three patients there were no changes in brain perfusion and the physical status. Conclusions: Treatment with Topiramate increases brain pefusion in 75% of the cases and reduces the frequency and intensity of seizures in patients with epilepsy, which is likely to be due to neuronoprotective effect of the drug. Our studies suggest that Tc99m-HMPAO SPECT can be useful for assessment of the treatment effect and for the prognosis of the frequency and intensity of the seizures in patients with epilepsy.

Cortical dysgenesis is one cause of epilepsy in childhood. In intractable epilepsy surgical intervention is one therapeutic approach. The aim of the study was to determine the benefit of nuclear medicine in preoperative evaluation of malformations of cortical development (MCD) with respect to epileptic focus . Methods: 17 patients (pts; 12m, 3-17y) with intractable partial seizures were investigated during preoperative evaluation with either 99mTc HMPAO SPECT (ictal:7, interictal: 10) or 18F FDG (n=4) and 11C Methionine (MET) PET (preoperative n= 5, postoperative n=3). MRI led to diagnosis initially, which was confirmed histologically in 5 pts. Focal cortical dysplasia (FCD) was evident in 12 children, polymicrogyria in 3 and band heterotopia in 2 children. Studies were evaluated visually and compared with MRI retrospectively. Postoperative outcome was classified according to Engel criteria.. Results: Excellent results were obtained for ictal SPECT. A correct lateralization was found in all investigated pts (with FCD), showing an extended area of increased tracer uptake with relative maximum in the region of the MCD. -Interictal SPECT allowed a focus lateralization in 9 pts demonstrating extended areas with hypoperfusion. A correct focus localization, defined by region with maximal reduced HMAPO uptake in comparison with MRI, was possible in 5 pts with FCD. Heterotopia could be clearly delineated within white matter region in one pt, 2/3 pts with polymicrogyria demonstrated abnormal cortical configuration. -FDG PET was normal in one child, revealed extended areas of hypometabolism surrounding the MCD in 2 pts. Displaced activity of normal gray matter could be seen in one pt with heterotopia, in accordance with MRI. -MET PET demonstrated elevated aminoacid transport in 3/5 pts (with FCD) and was normal in the remaining. Postoperative MET PET revealed no abnormal MET uptake postoperatively in 3 pts with unclear hyperintensities on MRI, but excellent outcome measures (grade IA). Conclusion: In a very high percentage important information concerning the epileptic focus could be obtained from all applied nuclear medicine methods. But in the majority of the cases abnormalities exceeded the boundaries of the MRI lesion clearly. Only MET PET delineated an epileptogenic area in more than half of the pts. Therefore the importance of MET PET in MCD has to be investigated in further studies more intensively.

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K. Borbély (1), A. Balogh (2), M. Neuwirth (3), P. Halász (4), M. Tóth (1), V. Juhos (2), A. Sólyom (1). (1) National Institute of Neurosurgery, (2) SzentIstván Hospital, (3) Bethesda Children’s Hospital, (4) National Institute of Psychiatry and Neurology, Budapest, Hungary.

A.F. Maes, W. Van Paesschen, P. Dupont, I. Van Lierde, L. Mortelmans. UZ Gasthuisberg, Leuven, Belgium.

Contribution of ictal/postictal rCBF SPECT pattern model in localizing epileptogenic foci: a retrospective study

Objectives: RCBF SPECT has been proved to be a sensitive and specific method in the presurgical evaluation of patients with complex partial seizures (CPS). Ictal minus interictal rCBF analysis is a routine part in the assessment of epileptogenic foci. During ictal studies patients might have secondary generalizations or rCBF changes might appear not only in the epileptogenic area. The precise note of the time of the tracer injection for SPECT is the key in interpreting the brain perfusion changes. We studied ictal/postictal rCBF patterns in the brain tissue within, adjacent to, and remote from the epileptogenic foci in 64 patients with CPS. Methods: The assessment included neurological examination, ictal semiology, interictal and ictal electrophysiological recording, MRI, and neuropsychological evaluation. Baseline, ictal and/or postictal SPECT studies were carried out with a standard technique for each patient. SPECT data were analysed visually and by a special region of interests (ROIs) program. Circular ROIs were placed over the basal ganglia, thalamus, frontal, temporal, parietal, occipital cortex, and cerebellum. ROIs were normalized to the whole brain average. The statistical analysis was considered significant at P<0.05. MRI was positive in 46 patients, while in 18 cases there were no abnormalities. SPECT results were compared to electrophysiological and surgical findings. Results: The baseline SPECT demonstrated a significant hypoperfusion (P<0.05) in the epileptogenic area (EA) in 37/64 (57.81%) cases. 54/64 (84.38%) of the ictal studies showed a marked hyperperfusion (P<0.005) in the EA with low cerebellar tracer uptake (P<0.05). In 26/64 (40.63%) patients the early postictal studies demonstrated moderate or high tracer uptake in the EA (P<0.05) with diffuse perfusion abnormalities in the surrounding tissue. Late postictal studies (14/64, 21.88%) showed hypoperfusion (P<0.05) in the EA with moderate or high tracer uptake in the surrounding tissue. The results of the ictal/postictal studies correlated well with the electrophysiological, and surgical data. Conclusions: Ictal SPECT presents precise localization of the EA, and particularly useful in patients with normal MRI. Surgical resection of ictal onset zone identified by ictal SPECT and concordant electrophysiological recording appears to have a good postsurgical outcome. Ictal SPECT may provide better localization of EA than other imaging methods, especially in case of multifocal laesions. The sensitivity and reliability of postictal SPECT might be improved by applying the perfusion pattern model, and by noting the precise time of injection for SPECT studies.

De novo cryptogenic multifocal refractory febrile status epilepticus in the young adult.

Background: Status epilepticus (SE) is a common neurological emergency. In around 10 percent, the etiology of SE is not clear (cryptogenic SE). Aim: To describe a syndrome of de novo cryptogenic multifocal refractory febrile SE in the young adult. Methods: Retrospective chart review. Results: We describe six young adults with an unremarkable previous medical history who presented with de novo partial SE. All had an ill-defined febrile illness in the week preceding SE. Investigations were unable to reveal the underlying etiology. Brain biopsy obtained during SE in two patients was normal. SE proved refractory to conventional antiepileptic drug (AED) treatment and anesthesia was required. Seizures during SE or ensuing epilepsy were multifocal on PET FDG imaging and ictal and interictal SPECT imaging. There was evidence of hippocampal sclerosis (HS) in four patients, which was bilateral in three, and probably secondary to seizures. Outcome was poor in all cases: one patient died during the course of SE, and the other five developed refractory multifocal partial epilepsy. Three patients were cognitively impaired and one was physically disabled because of critical illness polyneuropathy. One of these patients died a sudden unexpected death in epilepsy (SUDEP) and one drowned during a seizure. Brain autopsy in two of the deceased patients showed changes secondary to seizure. Conclusions: De novo cryptogenic multifocal refractory febrile SE in the young adult appears to be a distinct SE syndrome with poor prognosis.

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CEREBROVASCULAR

SPM analysis of perfusion and perfusion reserve in patients with internal carotid artery (ICA) stenosis before and after revascularization

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K.H. Hwang, H.Y. Lee, D.S. Lee, C.W. Oh, J.S. Yeo, J.-K. Chung, M.C. Lee. Seoul National University College of Medicine, Seoul, Korea.

Fully automated quantification of regional cerebral blood flow with three-dimensional stereotaxic ROI template: validation of the method using MRI R. Takeuchi (1), Y. Yonekura (2), J. Konishi (3). (1) Department of Internal Medicine, Nishi-Kobe Medical Center, Kobe, JAPAN, (2) Biomedical Imaging Research Center, Fukui Medical University, Fukui, JAPAN, (3) Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Aim; We have lately constructed a „Three-dimensional stereotaxic ROI template (3DSRT-t)“ on the anatomically standardized CBF SPET images and reported its usefulness to objectively estimate rCBF (Eur J Nucl Med, 2002). We further developed a fully automated quantification Windows software (3DSRT) whose anatomically standardization engine and ROIs for quantification was transplanted from SPM99 and 3DSRT-t, respectively. Using 3DSRT we could automatically quantify rCBF values of 536 ROIs, which was grouped into 12-paired segments (1, superior frontal; 2, middle and inferior frontal; 3, primary sensorimotor; 4, parietal; 5, angular; 6, temporal; 7, occipital; 8, pericallosal; 9, lenticular nucleus; 10, thalamus; 11, hippocampus; 12, cerebellar hemisphere) and calculate the area-weighted average for each of the 24 segments based on the rCBF in each of the ROI in only a few minutes. In this study, we tried to justify the delineation of 3DSRT using 3D-MRI. Materials and Methods; All examinations were performed using a 1.5 T MR unit (Magnetom, Siemens, Erlangen, Germany) with a circulatory-polarized head coil. Threedimensional imaging with fast spin-echo sequence was used in transverse orientation with the following parameters: repetition time, 3400 ms; echo time, 120 ms; flip angle, 180 degree; slab-thickness, 8 mm; number of slab, 8; number of partition, 8; matrix size, 216 x 256; pixel size, 0.93 x 0.90 mm; number of slice, 144-160. We inspected T2-weighted 3D-MRI of 10 patients (3 women and 7 men; age range, 58-83 yr-old) with localized infarcted area: putamen, 13; thalamus, 3; posterior limb of internal capsule, 2; anterior limb of internal capsule, 1; precentral artery territory (segment 2), 1. The position of their central sulcus in the primary sensorimotor area (segment 3) were also inspected. Results; All positions of the 20 lesions showed strict concordance with the ROI delineation of 3DSRT. Among the 280 pairs of the ROI of the segment 3, central sulci were identified in the 200 pairs and located in the midst of the 194 (97%) paired ROIs. Conclusion: The ROI delineation of 3DSRT was justified by the analysis of 3D-MR images. 3DSRT is expected to enable fully automated objective estimation of CBF SPET images.

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2-year follow-up of arteriovenous malformations (AVM) after gamma knife therapy (GKT): A com-parison of 15O-water PET and digital subtraction angiography (DSA) K. Setani (1), O. Sabri (1), M. Schreckenberger (1), B. Huffmann (2), W.M. Schaefer (1), M. Mull (3), J.M. Gilsbach (2), M. Zimny (1), U. Buell (1). (1) Department of Nuclear Medicine of the RWTH University Aachen, (2) Department of Neurosurgery of the RWTH University Aachen, (3) Department of Neuroradiology of the RWTH University Aachen. Aim: GKT is a non-invasive form of therapy for cerebral AVM of up to 10 cm3. Aims of this study were: 1) To detect and follow up haemodynamic changes in the AVM and the neighbouring cerebral parenchyma up to 24 months after therapy; 2) To investigate to what extent reduced perifocal rCBF is due to neuronal deafferentiation or hypoxic damage. Materials and Methods: A total of 24 patients with cerebral AVM were examined with PET and DSA prior to GKT, 17 of these were re-examined after 6 months, 14 of these were reexamined after 12 months, and 7 of these were re-examined after 24 months. Acquisition was done with 3 scans of 1500 MBq 15O water administered i.v. for 120 seconds. In addition to visual assessment, the relevant areas (angioma nidus, perifocal cerebral parenchyma) were defined as ROIs to allow quantification of the dynamic rCBF changes in these areas. The rCBF was normalised to the global CBF. The results were then compared with the AG findings. Results: In the 7 patients re-examined after GKT, nidus rCBF was reduced by 69±8% (p<0.0005) (Table 1). Five patients showed near-total AVM obliteration which was confirmed by AG, while another 2 showed residual nidus perfusion. Four of the 7 patients showed a reduced perifocal perfusion (rCBF) prior to GKT which was further reduced after 24 months after GKT (-14%), with 2 patients showing an improved rCBF (-8%). Tab. 1 Cortex-normalised AVM perfusion of 7 patients within 24 months after GKT pre-GKT mean±SD

2.90±0.62

6 months post-GKT 1.86±0.39

12 months post-GKT 1.04±0.21

2 years post-GKT 0.89±0.26

Conclusion: Evidence of the haemodynamic effectiveness of GKT was a significant reduction (69%) in nidus perfusion 24 months after GKT. First results already indicate a slight improvement of perifocal rCBF in several cases pointing at deafferentiation. PET and AG findings agree regarding nidus obliteration.

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Objective: While perfusion and perfusion reserve could have been evaluated on basal/acetazolamide 99mTc HMPAO SPECT in cerebrovascular occlusive disease, objective quantification is necessary for an assessment of the efficacy of the revascularization. In this study we adopted the SPM method to quantify basal perfusion and reserve on basal/acetazolamide SPECT in assessment of the patients who underwent bypass surgery for ICA stenosis. Methods: Ten patients (51±15 yr) with ICA stenosis were enrolled. 99mTc HMPAO basal/acetazolamide perfusion SPECT images were performed before and after superior temporal artery - middle cerebral artery anastomosis. After spatial and count normalization to cerebellar activity, basal perfusion and perfusion reserve were compared with those of 20 agematched normal controls and postoperative changes of regional perfusion and reserve were assessed by paired t-test on SPM method. Mean pixel values of each brain region were calculated using probabilistic anatomical map of lobes/gyri and ICA territory. Perfusion reserve was defined as the % changes after acetazolamide over basal counts. Results: Basal perfusion and perfusion reserve were significantly decreased in involved ICA territory. In group analysis, postoperative improvement of perfusion and perfusion reserve was observed in grafted ICA territory. Improvement of the perfusion reserve was most prominent in superior temporal and angular gyrus, nearest to the anastomosis sites. In individual analysis, the ranges of postoperative perfusion changes at acetazolamide SPECT were –1.4 % to 34% in the grafted ICA territory and –7% to 48% in parietal lobe. This improvement showed correlation with preoperative impairment of perfusion reserve (Pearson’s r=-0.72, p=0.02). Perfusion reserve also improved ranging from –3 % to 13%. Conclusion: Using SPM quantification method on basal/acetazolamide 99mTc HMPAO SPECT, the perfusion and perfusion reserve could be assessed before revascularization and so could the efficacy of the bypass surgery.

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Brain SPECT imaging and cognitive functioning in coronary artery bypass patients V. Chernov, N. Efimova, I. Efimova, SH. Akhmetov, YU. Podoksenov, YU. Vecherskiy, YU. Lishmanov. Institute of Cardiology, Tomsk, Russia. Purpose: The aim of this study was to evaluate cerebral perfusion and cognitive functions in cardiac patients (pts) following coronary artery bypass graft surgery(CABG). Methods:36 pts (34 males and 2 females, mean age 53+4) underwent CABG with cardiopulmonary bypass (CPB) (20 pts ) and off-pump surgery using the Octopus stabilisation system(16 pts ),were included in the study . All pts underwent brain SPECT scanning, standard neurologist examination and comprehensive neuropsychological testing 1day before, and 1014 days after surgery. Results: CABG with CPB followed by the decrease in regional cerebral blood flow (an average from 47,6+1,6 to 41,7+1,5 ml/100g/min in left hemispheric brain and from 48,1+1,7 to 43,5+1,6 ml/100g/min in right hemispheric (p<0,05)) in all the pts. In the group of Octopus off-pump coronary pts no significant postoperative declines of cerebral perfusion were found. Measures of immediate verbal memory, delayed memory and learning showed a significant decrease after surgery with CPB an average on 22,4% (p=0,033), 38,5% (p=0,033), 23,6% (p=0,00005), respectively. In the less degree negative impact of CABG on all the kind of memory was noted after coronary revascularisation using Octopus system. Particulary, significantly deterioration memory (more than 20%) was found only in 55% pts. In this pts decrease in regional cerebral blood flow was shown in 6-11%. Conclusion: Our results suggest that the coronary revascularisation on beating heart helps to prevent or significantly to diminish impairment of cerebral perfusion and neuropsychological status of pts. Brain SPECT is useful technique for evaluation of cerebral perfusion in cardiac pts following coronary artery bypass graft surgery.

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n CEREBROVASCULAR Comparative correlations of Brain Perfusion SPECT indices, CT volume and Neurological scores with clinical outcome in Acute Ischemic Stroke A. Serena (1), J.M. Nogueiras (1), E. Corredera (2), J. Outomuro (1), A. Ortega (2), J. Romero (2), L. Campos (1). (1) Department of Nuclear Medicine. Hospital Meixoeiro., (2) Department of Neurology. Hospital Meixoeiro, Vigo, Spain. Aim: To compare the diagnostic yield of CT and Perfusion SPECT on admission and the prognostic value of several SPECT indices on clinical outcome. Methods: 25 patients with ischemic stroke were assessed on admission (<24h.) by CT, 99mTc-HMPAO-SPECT and Neurological scales (Scandinavian-NSP, SNSLP, Barthel Index). Control CT scan on days 3-7 with planimetry of infarct volume. A second SPECT and Neurological scores on days 30-60. Infarct size and severity on SPECT were assessed: a) Visually: added individual scores in 22 areas (graded 1 to 4; subcortical weighted x 2-3 factor) gave a “Total Weighted Score”; spatial extent by the “number of areas” involved; B) By semiquantitative counts-based indices: hemispheric activity-curves were generated with symmetrical ROIs over 24 transaxial slices and “% hemispheric counts deficit”, “average asymmetry index” and a (virtual:zero-perfusion) “cortical volume loss” -by a modified Mountz technique- calculated. Results: Sensitivity: First CT (5,2+/-4,2h.) was positive (hypodensity) in 24% patients, 36% if indirect signs included. No statistical difference in infarct volume, study delay or neurological scores on admission between CT-positive or negative cases. Initial SPECT (18,2+/-6,6h.) positive (hypoperfusion) in 75%, 83% if doubtful cases included; 27% of pure subcortical infarcts were undetected but only 9% of those with cortical involvement. Localization: kappa: 0,725 between SPECT findings on admission and those on control CT. Extent and severity: good correlation between count-based and visual indices (r:>0,719), the latter correlated slightly better with clinical-scales. Both predicted similarly (Rho>0,739) infarct size in CTdiagnostic scan. Early-Outcome: 6 patients died during immediate follow-up. Statistical differences with survivors in SPECT (<24h) indices and CT-infarct size (mean 5 days), not in neurological scores on admission. Long-term Outcome: Correlation of initial SPECT indices with follow-up functional scores (SNSLP, Barthel index; mean 37 days) only significant for visual SPECT indices (Rho:–0,560 to –0,620). Nevertheless the best predictor of functional status at discharge was the Barthel Index on admission. In multiple lineal regression analysis only the CT-infarct volume and the global weigthed score slightly improve outcome prediction. Conclusions: 1) Early SPECT has good sensitivity and accurate infarct size prediction so can be a useful tool for deciding thrombolytic therapy; 2) Visual scores perform as well as more complex indices; 3) Infarct volume seems to be a critical determinant in vital outcome; other factors (strategic localization, etc) might influence long-term functional status.

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The Role of Urgent Cerebral Blood Flow SPECT for Determination of Operative Indication and Prediction of Outcome in Major Subarachnoid Hemorrhage T. Inagaki (1), K. Saito (2), S. Irie (2), S. Suzuki (3), T. Aburano (4), N. Shuke (4), K. Hokin (1). (1) Department of Neurosurgery of Sapporo Medical College, Sapporo, Japan, (2) Kushiro Neurosurgical Hospital, Kushiro, Japan, (3) Hoshigaura Hospital, Kushiro, Japan, (4) Department of Radiology of Asahikawa Medical College, Asahikawa, Japan. Aim: The aim of this study was to clarify the clinical role of urgent cerebral blood flow (CBF) SPECT in major subarachnoid hemorrhage by investigating the relationships of the SPECT findings to clinical outcome retrospectively. Materials and Methods: Forty-six patients with major subarachnoid hemorrhage (World Federation of Neurosurgical Societies Grade 4 and 5), who were admitted to the hospital within 24 hours after the onset and had no serious postoperative complications such as delayed ischemic neurological deficits, were studied. In these patients, 29 patients had radical clipping operation and 17 patients, whose Glasgow Coma Scale was 3, had conservative therapy. CBF SPECT with Tc-99m HMAPO (740 MBq) was performed immediately after the admission. Quantitation of regional CBF was done by the Patlak plot method. Hemispheric and basal gangliar CBFs were compared with an index of clinical outcome, the Glasgow Outcome Scale (GOS), at 3 months after the onset. In the patients with internal carotid and middle cerebral arteries aneurysms, CBF in the affected side was adopted for the comparison; while in those with anterior cerebral and vertebrobasilar arteries aneurysms, mean CBF of bilateral sides was adopted. Results: The patients were classified into 5 groups arranged in order of increasing severity according to the GOS: good recovery (GR), 6; moderate disability (MD), 8; severe disability (SD), 7; vegetative state (VS), 8; death (D), 17. The mean hemispheric CBF of GR, MD and SD groups (41.55±1.50 ml/100g/min, n=21) was significantly different from that of VS and D groups (31.18±1.51 ml/100g/min, n=26, p<0.0001), although there were no significant differences between neighboring groups. The mean basal gangliar CBF of GR, MD and SD groups (61.07±2.88 ml/100g/min, n=21) was significantly different from that of VS and D groups (19.48±3.03 ml/100g/min, n=26, p<0.0001), and there were significant differences between neighboring groups (p<0.05). All patients whose basal gangliar CBF were below 40 ml/100g/min had unfavorable outcome, VS or D. Conclusion: The findings of urgent CBF SPECT on admission was significantly correlated with clinical outcome of major subarachnoid hemorrhage. Basal gangliar CBF showed more significant correlation than hemispheric CBF. Patients whose basal gangliar CBF is greater than 40 ml/100g/min could be expected to have good prognosis by radical operation.

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Evaluation of the dual table ARG method to quantify two sequential rCBFs in a single SPET session with IMP S. Nishizawa (1), T. Tsuchida (2), Y. Yonekura (1). (1) Biomedical Imaging Research Center, Fukui Medical University, Fukui,Japan, (2) Department of Radiology, Fukui Medical University, Fukui, Japan. Aim: Recent reports indicate importance of cerebrovascular reserve capacity (CVR) in patients with occlusive diseases of major cerebral artery to predict a risk for stroke and select a surgical candidate. The dual table ARG method was recently introduced to test CVR with two sequential rCBFs in a single IMP-SPET session. The method uses a fixed distribution volume (Vd) and a standard input function (SIF) calibrated by a single arterial blood sample. To calculate the second rCBF, two look-up tables are used to cope with an effect of radioactivity from the first dose of IMP. We evaluated the method with simulation and patient studies. Materials and Methods: Simulation studies were performed to evaluate errors caused by (1) a rCBF change during measurement, (2) a difference between an individual and a fix Vd values and (3) the scan length. We generated simulation curves with first rCBF from 20 to 60 ml/100g/min, Vd from 27 to 33 ml/ml and a change of second rCBF by –25% to +50%. Data were analyzed with a Vd value of 30. Twenty patients were studied with two injections of IMP and frequent arterial blood sampling. Reproducibility of sequential rCBFs was evaluated in 9 patients studied without a challenge test. Reliability was tested in 20 patients by comparing rCBFs by the method with those by the two-compartment model analysis using a non-linear least squares fitting. We generated a SIF and optimized time for calibration by comparing with an individual input function. Results: Errors caused by (1) were less than 4 %, which was seen at a low flow area for the second rCBF. Errors by both (1) and (2) were largest at a high flow area for the second rCBF, and those were affected by (3) with an increasing error in longer scan length. From those studies, we chose a scan protocol of 25 min for the first and 15 min for the second with a diamox injection at 15 min. In the patient study, a mean absolute error was 6.4% for the reproducibility and 5.0% for the reliability. The optimal time for calibration of SIF was 29 min with a mean absolute error of 7.5%. Conclusion: The dual table ARG method with 40 min scan is practical as a routine clinical test to quantify rCBF and CVR.

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Cerebral blood flow measurements by Tc-99m ECD and phase contrast MR M. Hosono, K. Machida, N. Honda, T. Takahashi, A. Kashimada, O. Murata, H. Osada, M. Ohmichi, N. Ohtawa. Department of Radiology, Saitama Medical Center, Kawagoe, Japan. Aim: Cerebral blood flow (CBF) can be measured by either phase contrast magnetic resonance imaging (PCMR) or radionuclide imaging. The purpose of this study was to examine correlation and agreement of CBF values measured by the two methods. Materials and Methods: Twenty-five subjects were enrolled in this study (M:F=19:6 , Age: 62±14 years). Subjects underwent PCMR and 99mTc-ECD (ECD) imaging within 3 days. All subjects had normal neurological findings at the time of the CBF measurements and no subject received neurosurgical intervention prior to this study. By PCMR, the blood flow of the bilateral internal carotid arteries (ICs) and the basilar artery (BA) was measured with a 1.5 T MR imaging unit (Signa Horizon, GE). The volume of the cerebrum was calculated from 3-D images of the brain by an imaging workstation (Advantage Windows, GE), then converted into weight with a specific gravity of 1.05. Total CBF (TCBF) was determined as the sum of flows in the bilateral ICs and the BA, then mCBF was obtained as a division of TCBF by the cerebrum weight. On the other hand, CBF measurements with ECD were performed by obtaining sequential anterior views of the head and thorax after bolus infusion of the tracer on the basis of Patlak plot analysis as reported previously, in short, regions of interest were placed on the aortic arch and the bilateral cerebral hemispheres, and then, a graphical analysis of Patlak was conducted. CBF values by PCMR and ECD were compared by linear regression analysis and Bland-Altman analysis. Results: On MR, the volume of cerebrum was 1125.2±113.8 ml, and TCF and mCBF were determined by PCMR to be 552.0±113.7 ml/min and 46.7±6.3 ml/100g/min (coefficient of variation, CV 13.8%), respectively. Whereas on ECD imaging, mCBF was 40.7±4.6 ml/100g/min (CV 11.6%). By comparing CBF values of the two methods, mCBF by ECD (X) and TCBF by PCMR(Y) showed a correlation of Y=3.3X+407, R=0.14, whereas mCBF by ECD (X) and mCBF by PCMR(Y) showed a good correlation of Y=1.225X-2.23, R=0.81. The difference of mCBF values between the two methods was 13.2±11.5%. Conclusion: These studies show that there were good correlation and agreement between mCBF values determined by PCMR and by ECD. ECD has a CV better than that of PCMR for mCBF determination. CBF values quantified by the two different modalities may be more reliable.

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Regional cerebral blood flow with Tc 99 m ECD SPECT in the prefrontal area as progression marker of Alzheimer´s disease in patients with mild cognitive impairment R. De Juan (1), M. Encinas (1), A. Barabash (2), P. Gil (3), A. Marcos (4), C. Fernandez (2), J.A. Cabranes (1). (1) Department of Nuclear Medicine, San Carlos University Hospital, Madrid, Spain, (2) Research Department, San Carlos University Hospital, Madrid, Spain, (3) Geriatrics Department, San Carlos University Hospital, Madrid, Spain, (4) Neurology Department, San Carlos Univeristy Hospital, Madrid, Spain. Aim: To find early functional neuro-imaging markers, which predict progression of mild cognitive impairment ( MCI ) to Alzheimer’s disease ( AD ). Methods: A prospective study with 42 patients who met MCI criteria according to the International Psychogeriatric Association and the Alzheimer´s Disease Co-operative Study was carried out. Functional neuro-imaging with Tc 99m ECD SPECT was performed, calculating regions of interest in cerebellum, frontal, temporal and parietal lobes as well as in parahippocampal region in transversal and coronal projections. After a follow-up period of at least 12 months ( ranging from one to three years ), a new neuro-psychologic assessment was performed to make a second diagnosis. The patients were divided into two groups: Group 1: 21 patients who developed AD according to DSM-IV and NINCDS-ADRDA criteria. Group 2: 21 patients who kept their initial diagnosis of MCI. In the statistical analysis, T test for mean difference and ROC curves were performed for quantitative variable analysis. Results: Group 1 patients showed a significantly reduced ( 8 to 10% less, 0, 001 < p < 0,03 ) regional cerebral blood flow ( rCBF ) when compared with Group 2 in the following cortex areas studied in transversal projection: right and left prefrontal ( rPF & lPF ), right and left motor frontal ( rMF & lMF ), temporal superior, mid and postero-inferior gyrii right and left ( rTe & lTe ) and frontoparietotemporal right and left ( rFPT & lFPT ). The left temporal postero-lateral ( lTPL ) area was studied in coronal projections. ROC curve analysis shows for a cut off value of 0.87 a sensibility of 70% and a specificity of 71% in the right prefrontal cortex and for a cut off value of 0.86 a sensibility of 79% and specificity of 76%. Conclusions: 1) The reduction of rCBF is statistically significant between the two groups of patients in the following areas rPF, lPF, rF, lF, rTe, lTe, rFTP, lFTP and lTPL 2) The reduction of rCBF in the right and left prefrontal cortex may be useful in predicting progression to AD in patients with MCI.

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Adult moyamoya syndrome: Long term clinical experience with routinely performed pre- and postoperative evaluation of cerebral perfusion and vasodilatory capacity using 99mTc-ECD SPECT prior and after acetazolamide provocation D.A. Roehlen (1), M. Goertler (2), T. Blaser (2), R. Steinke (1). (1) Department of Nuclear Medicine of the University of Magdeburg, Magdeburg, Germany, (2) Department of Neurology of the University of Magdeburg, Magdeburg, Germany. Aim: Moyamoya disease as a very uncommon cerebrovascular disease is characterised by progressive bilateral stenoses in the territories of the internal carotid arteries and other arteries of the circle of Willis followed by abnormal parenchymal collateralisation. Patients suffered from a variety of ischaemic events ranging from transient ischaemic attacks to stroke but also in a smaller extent from haemorrhage and aneurysms. Today therapy of choice is surgical revascularisation of the perfusion compromised brain tissue by means of external/internal carotid anastomoses. Therefore it is essential to determine the cerebral perfusion pattern as this has a significant influence on surgical preoperative decisions. Single-photon emission computed tomography using 99mTc-ethyl-cystein-dimer (ECD) before and after administration of acetazolamide is a proven diagnostic technique that can be routinely performed in most centres to assess cerebral blood flow (CBF) reserve. Here we present the first report of the results of long-term follow up studies in patients with adult moyamoya syndrome before and after external/internal carotid bypass surgery. Material and Methods: Ten patients who suffered from adult moyamoya syndrome were studied prior to and after acetazolamide provocation. Cerebral perfusion was measured by 99m Tc-ECD SPECT and data were reconstructed into transversal, coronal and sagittal slices for review and compared with findings of previous imaging examinations. Furthermore a semiquantitative evaluation of perfusion was obtained by calculation of the tracer uptake ratio between regions of interest and cerebellum. Six to twelve months after uni- or bilateral bypass surgery the SPECT examinations were repeated to assess whether there was a significant improvement of cerebral perfusion and vasodilatory capacity in the affected territories recognisable. Results: At baseline study all patients showed significant perfusion defects with areas of vascular compromise and diminished vasodilatory capacity that cross normal vascular territories of the major cerebral arteries. In general at postoperative state the repeated SPECT examination demonstrated the improvement of CBF reserve in areas diagnosed to be at risk and as expected no major change in infarcted areas. Conclusion: Our long term experience suggest that 99mTc-ECD SPECT combined with acetazolamide provocation is one the most valuable routinely diagnostic techniques for planning and predicting outcome of surgical interventions in patients with moyamoya syndrome.

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The value of Tc-99m HMPAO brain SPECT and MR imaging in neuro-Behçet’s disease N. Cengiz (1), M. Sahin (2), B. Kirtiloglu (2), O. Yapici (2), T. Basoglu (2). (1) Department of Neurology, Faculty of Medicine, 19 Mayis University, Samsun, Turkey, (2) Department of Nuclear Medicine, Faculty of Medicine, 19 Mayis University, Samsun, Turkey. Behçet’s disease is a systemic disorder of unknown cause that may include CNS in addition to ocular, articular, vascular, mucocutaneus and GI involvement. In our study, we investigated the utility of Tc-99m HMPAO brain SPECT in patients with Behçet’s syndrome showing CNS involvement. Patients and Methods: Ten patients (9 men, aged 22-45 yr) with neuro-Behçet’s syndrome, fulfilling the criteria of the International Study Group for Behçet’s Disease, were included in the study. MR imaging was performed according to a standard protocol with a 0.5 T imager. Brain SPECT data was obtained using a single head gamma camera after 555 MBq Tc-99m HMPAO injection. Image reconstruction was performed by filtered backprojection and the data was preprocessed with Butterworth filters without attenuation correction. Transaxial slices were re-oriented parallel to orbitomeatal line to obtain sagittal and coronal reconstructions. Cerebellar activity was chosen to normalize the brain slices. Brain SPECT images were evaluated visually. Results: Brain SPECT showed hypoperfused areas in 6 of 11 (54%) patients. Pathological basal ganglia and cerebellar perfusion findings were not present. Two of 5 patients with normal brain SPECT findings had basal ganglia and white matter involvement on MR imaging while the others were normal. MR imaging findings were abnormal in 7 of 11 (63%) patients. MR imaging showed brain stem, basal ganglia and white matter abnormalities in these patients. None of the patients had gray matter lesions on MR imaging. In 2 of 4 patients with normal MR findings, hypoperfusion was present on brain SPECT. Conclusion: Tc-99m HMPAO Brain SPECT demonstrated cerebral cortex lesions while MR imaging showed brain stem, basal ganglia and white matter lesions. Therefore, brain SPECT may act as a complemantery modality to increase the detection rate of affected regions in patients with Behçet’ disease.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition NEUROTRANSMISSION IMAGING

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Mitochondrial disorders: is complex I/IV deficiency sufficient to elicit dopaminergic dysfunction? M.J. Reinhardt (1), M. Minnerop (2), A. Joe (1), K. Tatsch (3), C. Kornblum (2), U. Wuellner (2), H.J. Biersack (1). (1) Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany, (2) Department of Neurology, University Hospital Bonn, Bonn, Germany, (3) Department of Nuclear Medicine, LMU Munich, Munich, Germany. Aim: Decreased activity of complex I/IV of the mitochondrial respiratory chain is linked to the pathogenesis of dopaminergic cell loss in Parkinson’s disease. Several compounds that inhibit complex I/IV activity induce a Parkinsonian syndrom in humans and non-human primates. Thus, the question arises whether complex I/IV deficiency itself is sufficient to elicit dopaminergic dysfunction in humans. Materials and Methods: Dopamine transport function was determined in 15 patients (10 female, 5 male; aged 49 ± 11 years) with histologically confirmed mitochondrial disorder and reduced complex I/IV activity by means of 123I-Ioflupan (DaTSCAN®, Amersham Health, Ismaning, Germany) brain SPECT. SPECT-images were obtained 3 to 4 hours after i.v. injection of 185 MBq 123I-Ioflupan. Quantitative evaluation was done by calculating the specific striatal binding with ROI technique. Mean specific to non-specific binding ratio of patients was compared with that of 15 sex matched healthy controls in the age of 61 ± 13 years. All investigations were performed after approval of the local ethical committee and after obtaining informed consent from each patient. Results: Mean specific to non-specific binding ratio of the radiotracer in the striatum of patients and controls was 3.92 ± 0.66 and 3.23 ± 0.50 (n.s.), in the nucleus caudatus it was 4.46 ± 0.76 and 3.64 ± 0.53 (n.s.), and in the putamen it was 3.66 ± 0.82 and 3.02 ± 0.56 (n.s.). Thus, mean specific to non-specific binding ratio of patients was not significantly different from that of controls. Conclusion: Impairment of mitochondrial complex I/IV activity is not sufficient to elicit significant dopaminergic dysfunction in humans.

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O. Schillaci, C. Manni, M. Pierantozzi, L. Brusa, V. Picardi, R. Danieli, P. Stanzione. University Tor Vergata, Rome, Italy.

P.F. Kao (1), H.S. Wang (2), C.S. Lu (3), K.Y. Tzen (1), T.C. Yen (1), S.P. Wey (4), G. Ting (4). (1) Department of Nuclear Medicine, Chang Gung Memorial Hospital and University, (2) Department of Pediatric Neurology, Chang Gung Children Hospital and Chang Gung University, (3) Movement Disorder Unit, First Department of Neurology, Chang Gung Memorial Hospital and University, (4) Institute of Nuclear Energy Research, Atomic Energy Council.

[Tc-99m]TRODAT-1 SPET imaging of striatal dopamine transporter binding in patients with Tourette’s syndrome.

Aim: Asymmetry at the onset is a clinical feature of Parkinson’s disease (PD). A good correlation between clinical asymmetry and PET metabolic findings asymmetry has been reported in early PD. Presynaptic SPET tracers have been used to assess dopaminergic fibres reduction in the basal ganglia (BG) of PD. An asymmetric tracer (t) uptake (u) was demonstrated in PD but not in essential tremor, multiple system atrophy (MSA) and progressive supranuclear palsy. A correlation between clinical and tu asymmetry might probably distinguish advanced PD from MSA patients: we studied whether in early PD patients tu asymmetry parallels clinical asymmetry helping to distinguish PD from other parkinsonisms. Material and Methods: At the onset of a rigid-akinesic parkinsonian syndrome 13 patients were evaluated and then assigned to the PD group or to the atypical parkinsonism (AP) group on the basis of their clinical response to apomorphine test and three months levodopa therapy. According to their response to pharmacological assessment, six were assigned to the PD group and seven to the AP group. UPDRS clinical scores for rigidity and bradykinesia were separately evaluated and an asymmetry index was calculated as the difference between the two sides, for both symptoms. SPET was performed four hours after the injection of 185 MBq of I-123FPCIT, using a dual head gamma-camera fitted with high resolution collimators. After reconstruction, the five transaxial slices showing the highest u in the BG were summed. In each summed image five ROIs were drawn: left and right caudate, left and right lenticular and occipital cortex. Caudal and lenticular data were normalised as percentage of occipital uptake. Asymmetry index was calculated for caudate and lenticular as the difference between the normalised data of each side. Results: A significant (p< 0.04) correlation (Spearman rank order correlation r= 0.94) was found between bradykinesia asymmetry index and asymmetry index of lenticular uptake in the PD group. No correlation was found for rigidity in PD group and no correlation was found in the AP group. Conclusion: Our data suggest that I-123 FPCIT u at the level of lenticular nucleus may represent an early sign distinguishing PD from other forms of AP and confirm the presence of an early asymmetry as detected by metabolic PET studies. This early differential diagnosis is relevant as regarding to the large different prognosis between the two parkinsonian forms.

[Aim: The authors used [99mTc]TRODAT-1 SPET to examine whether patients with Tourette syndrome (TS) have higher than normal striatal dopamine transporter (DAT) densities, as suggested by previous post-mortem findings. Materials and Methods: Twelve adults (9M,3F, 28 ±9.6 y/o) with TS and 12 age- and sexmatched normal controls (NC) were included in the study. In all cases, SPET imaging were performed 4hr after i.v. injection 925MBq of [99mTc]TRODAT-1. The SPET imaging were performed with a Siemens MultiSPECT3 gamma cammera.with fan-beam collimators and 128 x 128 matrix size. SPET images were reconstructed using a filtered back-projection with RampButterworth filter, cut-off 0.3, order 10, and Chang’s attenuation corrected. The counts/pixel of caudate/occipital (C/O), putamen /occipital (P/O), and caudate/putamen (C/P) ratios were calculated. Results: There was no statistically significant difference between TS and NC on all of the right and left C/O and P/O ratios (P> 0.05, pair t-test). Also the C/P ratios were not significant different. The striatal/occipital ratios were 2.56 ±0.41 for NC and 2.61 ±0.46 for TS patients, respectively. Conclusion: Based on this preliminary study results, the post-mortem findings of DAT increased in TS patients cannot be demonstrated by [99mTc]TRODAT-1 SPET. However, further study with more patients is needed.

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Lack of gender differences in striatal dopamine D2 receptor binding in drug-naive schizophrenic patients: An IBZM-SPECT study. F. Lomena (1), E. Parellada (2), A.M. Catafau (3), M. Bernardo (2), M. Font (2), F. Gutierrez (2), J. Pavia (1). (1) Department of Nuclear Medicine, Hospital Clinic, (2) Department of Psychiatry, Hospital Clinic, (3) Department of Nuclear Medicine, Hospital Sant Pau. Barcelona. Spain. Lack of gender differences in striatal dopamine D2 receptor binding in drug-naive schizophrenic patients : An IBZM-SPECT study Aim: Differences in clinical course, antipsychotic treatment response and outcome of schizophrenia could be related to gender anatomical and functional cerebral differences. Data concerning gender differences in striatal dopamine D2 receptor binding of schizophrenic patients is still controversial. The aim of our study was to asses gender differences in the striatal dopamine D2 receptor binding in drug-naive schizophrenic patients, using 123-I-IBZM SPECT. Methods: Seven male and 8 female patients with DSM-IV criteria for schizophrenia or schizophreniform disorder were included in this study. All patients were first-episode, drug-naive schizophrenics and they were inpatients in a state of acute psychosis. Patients were clinically evaluated using the Brief Psychiatric Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impresion Scale (CGI). Brain SPECT were performed 90 minutes after the i.v. injection of 185 MBq of 123-I-IBZM using a doubled head rotating gammacamara fitted with fam bean collimators. Semiquantitive analysis was performed drawing irregular regions of interest on basal ganglia and frontal cortex, using an automatic process. Basal ganglia / frontal cortex ratios (BG/FC) and laterality index (LI = right BC/FC divided by left BC/FC) were obtained. Shapiro-Wilks test was carried out to asses the normality of variables. A Mann-Whitney test was applied to check for differences between male and female patients for demographic chararacteristics, psychopathological scale scores and BC/FC and LI. Spearman’s correlation was used to asses the relationship of BG/FC with age, duration of illness, and psychopathological scale scores. Results: Male and females did not differ in age (26+5,6 vs 26+6,4 years), duration of illness (1282+2832 vs 1154+2856 days) or in psychopathological scale scores (BPRS: 55,1+8,2 vs 53,4+16,8; PANSS: 100,6+15,1 vs 95,6+32,1; CGI: 5,7+0,8 vs 5,5+0,9). No significant differences were found in global (1,79+0,13 vs 1,81+0,10), left (1,8+0,1 vs 1,8+0,1) , right (1,8+0,1 vs 1,8+0,1) BC/FC or LI (1,0+0,0 vs 1,0+0,0) between males and females. No correlation was found between BG/FC and age, duration of illness or psychopathological scale scores. Conclusions: In our drug-naive schizophrenic patients, there were not gender differences in IBZM striatal uptake. This data does not support previous reports of left lateralized striatal D2 receptor binding assymmetry in male schizophrenic patiens.

99mTc-TRODAT SPECT investigations in parkinsonians L. Pavics (1), GY. Dibo (2), M. Argyelan (1), B. Kanyo (2), A. Lancz (2), L. Csernay (1). (1) Department of Nuclear Medicine of the University of Szeged, (2) Polyclinic of Neurology of the University of Szeged, Szeged, Hungary. Aim: The diagnosis of Parkinson’s disease still depends on clinical criteria. The visualisation of the dopaminergic system might decrease the rate of misdiagnosis. The aim of our study was to evaluate the clinical value of 99mTc-TRODAT SPECT in parkinsonism. Material and Methods: Ten patients with Parkinson’s disease ( 4 women, 6 men, age: 60 y SD11 y, range: 46-78 y, Hoehn Yahr: 1.5-2), 6 patients with Parkinson sy with other etiology (2 women, 4 men, age: 67 y SD 7 y, range: 56-74 y, Hoehn Yahr: 1.5-2.5) were investigated by 99mTc-TRODAT SPECT. As control group served 8 normal volunteer (3 women, 5 men, age: 36 y SD 14 y, range: 22-58 y). The SPECT images were visually and semi-quantitatively evaluated. ROI-s were placed on the frontal , occipital lobes , and on the cerebellum as reference regions, and for the analysis of the specific uptake of the striatum on the nucleus caudatus, and anterior - posterior putamen. From the ROI data activity uptake ratios were calculated. Results: Comparing the Striatum/Frontal, Striatum/Occipital, Striatum/Cerebellar ratios, the parkinsonians group significantly differed (p< 0.001) from the control group (1.18 SD 0.19 vs. 1.79 SD 0.21; 1.54 SD 0.34 vs. 2.12 SD 0.27; 1.61 SD 0.29 vs. 2.13 SD 0.45). The best separation between the two groups was found using the frontal lobe as reference region. Analysing the different striatal areas at the nucleus caudatus, anterior and posterior putamen the ratios in the patients differed also significantly from the controls. According to the ratios there was not possible to distinguish the Parkinson’s disease patients from the parkinsonians with other etiology. In Parkinson’s disease in relation to the time elapsed from the appearance of the clinical manifestation a tendency of decrease of the ratios were observed. By the visual evaluation a decreased striatal 99mTc-TRODAT uptake were observed with relatively speared nucleaus caudatus accumulation in 6/10 Parkinson’s disease patients and in 4/6 other parkinsinonians. Conclusion: 99mTc-TRODAT SPECT is an effective tool in the evaluation of patients with Parkinson syndrom. The reference region plays important role in the semi-quantitative evaluation of the SPECT data. According to our results the evaluation of the dopamin transporter status alone is not sufficient for the differentiation of the etiology of parkinsonism.

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Poster Presentation

Correlation between clinical and I-123 FPCIT SPET asymmetry may characterize Parkinson’s disease in early stage

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W.S. Huang (1), K.H. Ma (1), Y.H. Chou (1), C.Y. Chen (1), J.C. Liu (1), S.P. Wey (2), G. Ting (2). (1) Tri-Service General Hospital, National Defense Medical Center, (2) Institute of Neclrar Energy Research, Taipei, China.

J.S. Kim (1), J.H. Kang (2), M.C. Lee (2), J.H. Im (2), H.K. Lee (1), D.H. Moon (1). (1) Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, (2) Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Serotonin Transporter Imaging Using I-123-ADAM SPECT In Healthy And Parkinsonian Primates

Objectives: Serotonin transporters (SERT) play a major role in modulating serotonergic neuronal function. The study was undertaken to image central SERT using 123I-ADAM SPECT in healthy and parkinsonian (PD) primates. Methods: Two healthy and a 6-OHDA induced PD monkeys (Macaca cyclopis) were studied. Duplicate SPECT, at least 2 wk apart, of each monkey were obtained after 123I-ADAM (180 MBq) injection for 4 h using a dual-headed camera equipped with ultrahigh resolution fanbeam collimators (GE, Millennium VG Hawkeye). Except for visual inspection, specific uptake ratios (SUR) of midbrain (MB), thalamus (TH) and striatun (ST), using cerebellum as reference were measured. Results: By visual inspection, there was discernable uptake of 123I-ADAM in the MB, TH, and ST. Cerebellum had little uptake. The SUR of MB, TH and ST appeared reaching equilibrium at 210 min after injection. The averaged SUR of MB, TH and ST in healthy monkeys at equilibrium were 2.9, 2.1 and 1.6. A comparable SUR of MB was found in the PD monkey (2.8), but decreased in TH and ST (1.5 and 0.7). No major side effect was found during and after imaging. Conclusion: The brain distribution of 123I-ADAM in monkeys appears correlated with the known distribution of SERT. The decreased SUR of TH and ST in the PD monkey is consistent with the postmortem study, suggesting that PD might also affect SERT in TH and ST.

P_353

Dopamine transporter imaging (DaT Scan) in midbrain tremor Z. Malek (1), E. Itti (1), P. Remy (2), E. Evangelista (1), G. Fenelon (2), J.P. N’Guyen (3), P. Cesaro (2), M. Meignan (1). (1) Department of Nuclear Medicine, H. Mondor Hospital/Paris XII University, Creteil, FR, (2) Department of Neurology, H. Mondor Hospital/Paris XII University, Creteil, FR, (3) Department of Neurosurgery, H. Mondor Hospital/Paris XII University, Creteil, France. Aim: Midbrain tremor is a rare condition, in which a postural and resting tremor occurs within weeks or months following a lesion of the contralateral upper midbrain. Although its exact pathophysiology is unknown, it has been shown with positron emission tomography (PET) that this tremor might be related to a lesion of the nigrostriatal dopaminergic pathway. The aim of this study was to assess dopamine transporter density using single photon emission tomography (SPET) and FP-CIT in this kind of tremor. Material and Methods: A 45-year-old man without previous history of neurological disease, suffered a sudden right hemiplegia with a left IIIrd cranial nerve palsy due to a midbrain haemorrhage. Several weeks later, while motor deficit improved, he developed a tremor in the right arm. The tremor was present at rest, at posture and during movement with a low frequency (56 Hz). Patient received potassium iodide orally to block the thyroid before intravenous injection of 153 MBq [123I]-FP-CIT (DaT Scan, Amersham Health, Pantin, FR). Brain SPET was performed 3 h later using a dual-head camera, equipped with high-resolution collimators, in 128×128 matrices and for a total imaging time of 45 min. Quantification of striatal uptake was performed using circular regions of interest, drawn over the caudate nucleus, putamen and occipital cortex. The ratio of specific striatal uptake to non displaceable uptake was calculated as an estimate of the dopamine receptor binding potential (BP). Right and left BP values were compared to those from a 71-year-old control subject, who was referred for essential tremor. Results: In the patient, the tracer uptake was markedly decreased in the left striatum, ipsilateral to the midbrain lesion, compared to the right striatum: respectively, caudate = 1.01 and 1.64 ; putamen = 0.42 and 1.76. By comparison, tracer uptake was symmetrical in the control subject: BP = 1.75 and 1.86 in the right and left caudate, respectively and BP = 1.80 and 1.71 in the right and left putamen. Conclusion: SPET FP-CIT can demonstrate unilateral striatal dopaminergic denervation in midbrain tremor and may serve to indicate L-DOPA treatment in this condition, as previously suggested by PET studies.

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Movement disorders associated with focal midbrain lesion: Correlation with clinical and I-123 IPT SPECT findings

Aim: Midbrain lesion may produce a variety of movement disorders including tremor, dystonia, and parkinsonism. The anatomical and functional basis of the movement disorder associated with the midbrain lesion is still unclear. The purpose of this study was to correlate focal midbrain lesions with clinical and I-123 IPT SPECT findings. Material and Methods: Five patients (age 25 to 69 years, 3 men and 2 women) who presented with movement disorder associated with discrete focal midbrain lesion on the brain MRI were included. We reviewed the clinical characteristics of movement disorders and the brain MRI findings in all patients. I-123 IPT SPECT was performed in all patients and 9 normal controls to evaluate the integrity of the nigrostriatal dopaminergic system and striatal specific binding ratios were also calculated. Results: Patients consisted of 2 with parkinsonism, 1 with midbrain tremor, 1 with hemidystonia, and 1 with micrographia as the only manifestation. In all patients, movement disorders were confined to the limbs contralateral to the focal midbrain lesions. The causes of midbrain lesion were trauma (n=2), rupture of AVM (n=1), cerebral infarction (n=1), and encephalitis (n=1). The latency between the midbrain injury and the onset of movement disorder varied from 1.5 months to 2 years (mean 6.7 months). Specific binding ratios (1.6 ±1.4) of ipsilateral striatum to the midbrain lesion were significantly lower than those of contralateral side (3.3 ±0.99) and normal control (3.5 ±0.5) (p<0.05). All of five patients had lesions involving substantia nigra on MRI and two of these with resting tremor had also lesions involving the red nucleus. Bradykinesia and rigidity were mild or absent in these two patients, despite severely decreased specific binding ratios (mean 0.55) of ipsilateral striatum. Conclusion: Movement disorders associated with focal midbrain lesion were related to the damage of ipsilateral nigrostriatal dopaminergic system. However, the severity and nature of movement disorder were variable and not correlated with striatal specific binding ratio of I123 IPT.

P_355

Investigating Dopaminergic Neurotransmission with 123I-FP-CIT and 123I-IBZM SPECT: Comparability of Modern SPECT Systems P.T. Meyer, B. Sattler, T. Lincke, A. Seese, O. Sabri. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. Introduction: With 123I-FP-CIT and 123I-IBZM SPECT increasingly gaining access into routine patient care, the comparability of the results of different SPECT systems in the quantification of receptor binding is important for accurate clinical decision making and for the translation of imaging results between institutions (e.g., in follow-up studies or multi-centre trials). We investigated if ligand binding measures acquired by different modern SPECT systems are directly comparable or -if necessary- transferable. Patients and Methods: Using a triple-headed gamma camera (MultiSpect3 [MS], Siemens) and a dedicated brain SPECT camera with an annular scintillation crystal (Ceraspect [CS], DSI), we conducted phantom (n=4) and patient (n=26 123I-IBZM, n=23 123I-FP-CIT) studies. The phantom contained three cylinders of 2.8cm and 2cm diameter each, filled with iodine123 solutions giving target to background count rate ratios (T/BG) in the range 0:1-9:1. Reconstruction was done by filtered back projection using a Butterworth filter. Standard ROI templates were used for data analyses. Results: In phantom studies, the T/BG ratios recovered by both systems were highly correlated to the true T/BG ratios (R?>0.97) with the slope of a linear regression analysis being 0.861.17 and 0.41-0.52 (less steep for smaller target cylinders and T/BG ratios < 3.5) for the CS and the MS, respectively. Both systems showed a high linear correlation with each other (R?>0.95, slope=0.43-0.51, no significant effect of the target size). A similar inter-system correlation was found in 123I-FP-CIT patient studies (R?=0.80 [0.65; 0.82], slope=0.39 [0.43; 0.43] for the striatum [caudate; putamen] to occipital reference region uptake ratio) but not in 123 I-IBZM patient studies (R?=0.31, slope=0.37; striatum to frontal reference region uptake ratio). Conclusion: Therefore, at this stage a linear transformation of striatal uptake ratios between different SPECT systems appears to be not feasible in ligands with relatively low specific to unspecific binding like 123I-IBZM, while it appears to be achievable for ligands with high specific binding like 123I-FP-CIT. It has to be evaluated if this can be done with sufficient accuracy for clinical purposes using the present method or if methodological adaptations are necessary.

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D.G. Solis (1), R. Alvarez (1), J. Luis (1), J. López (1), R. Alberca (2), P. Mir (2), R. Vazquez (1). (1) U.D. Medicina Nuclear., (2) S. Neurologia. H.U. Virgen del Rocio. Seville. Spain.

L. Collombier (1), G. Castelnovo (2), V. Boudousq (1), M. Vergé (1), P. Labauge (2), P.O. Kotzki (1). (1) Department of Nuclear Medicine of CHU de Nîmes, Nîmes, France, (2) Department of Neurology of CHU de Nîmes, Nîmes, France.

Regions of interest standardization for quantitative analysis of 123I-FP-CIT brain Spect

Aim: Spect imaging of dopamine transporters using 123-I-FP-CIT has shown promise as a clinically useful tool to diagnose and evaluate the severity of Parkinson´s disease (PD). However, accurate methods for quantification of the striatal density of dopamine transporters are needed. It has been shown that 123-I-FP-CIT Spect quantification is affected by the type and size of the regions-of-interest (ROI). The aim of this study was to analyze how ROI`s characteristics modify the results of quantitative analysis of 123-I-FP-CIT brain Spect. Materials and Methods: We performed quantitative analysis of the 123-I-FP-CIT Spect scans obtained in 5 subjects with normal uptake, 5 patients suffering of mild PD (H&Y=1) and 5 patients with moderate-severe PD (H&Y=2-4). Transaxial slices oriented along the orbitomeatal line were reconstructed and 3 images were obtained by summing 1, 3 and 5 slices with the most intense uptake, yielding final slices of thickness of 4.4, 13.2 and 22 mm respectively. Two types of ROI were used on each of these 3 slices: a) ROI were manually drawn over right and left caudatus nucleus, putamen and the entire striatum using a color scale with 90%, 80%, 60% and 40% isocontour cutoff boundaries por delineation. An occipital cortex ROI was used as a reference (nondisplaceable activity). b) predetermined ROI templates, of 4 different sizes, derived from the average data calculated in normal uptake studies were placed in the patients`s scans. Thus, a total of 144 ROI`s for each study were analyzed. Specific striatal binding indexes was calculated as: (striatal ROI uptake – occipital ROI uptake)/occipital ROI uptake. Results: The values of specific estriatal indexes showed strong variability depending on the type and size of ROI. The larger ROI and thicker slice yielded smaller specific/non-specific index. Intra-individually maximum ratios between specific binding indexes obtained with different ROI types (highest/lowest values for each subject)

Estriatum Caudatus nucleus Putamen

Normal uptake group mean range 2.3 2.0-2.5 2.0 1.7-2.5 2.0 1.9-2.3

Pathologic uptake group mean range 2.9 2.5-3.8 1.9 1.7-2.4 3.8 2.0-6.6

p p<0.05 n.s. (p=0.3) p<0.05

Value of (123 I) FP-CIT to estimate importance of degeneration of nigrostriatal pathway in patients with presynaptic Parkinsonism.

Aim of the study: Clinical diagnosis of parkinsonian syndromes despite clinicals criterias is sometimes difficult. We used (123 I) FP-CIT SPECT (FPCS) to confirmed and estimate the degeneration of the nigrostriatal pathway in patients with suspected presynaptic parkinsonian syndromes (PPS). Material and Methods: 25 patients : 19 to 79 years (66.8±13.5) were examined by FPCS. Clinical diagnosis based on neurological findings and usual parkinsonians syndromes criterias. Imaging was done with a 3 heads camera, 120x45’’x128.128 projections. SPECT was performed 3 hours after IV of 148 MBq (123 I) FP-CIT (FPC : Amersham). After reconstruction, transaxial slices of 0.23 cm thickness were added four by four in function of FPC uptake. 3 regions of interest (ROI) was drawn on the transaxial slice showing the greatest striatal uptake : ROI on right striatal (RS), left striatal(LS), and occipital cortex(OC). 2 indexes were calculated : (RS –OC)/OC and (LS-OC)/OC (average count per pixel). Result was considered abnormal if 1 or the 2 indexes < 2. Results: Pathology Abnormal Normal effective

Parkinson 5 1 6

MSA 6 3 9

Lewy 1 1 2

PSP 2 0 2

Dystonia 0 2 2

FTD 1 1 2

Other 1 1 2

Discussion: Surprisingly, 3 patients with suspected multiple system atrophy (MSA) has normal results. Reevaluation of clinical status invalidate the diagnosis in one patient (cognitive impairment, evidence of stroke disease) but not for the others. We follow up closely (clinical and FPCS) the two patients. Our results confirm that imaging of presynaptic nigrostriatal dopaminergic neurons is not able to distinguish Parkinson’s disease (PD) from Parkinsonians syndromes (PS). To differentiate PD from PS, it’s necessary to explore these patients with radioligands binding to D2 receptors.

Specific binding indexes between normal and pathologic uptake studies were most clearly separated by using 13.2 mm slice and the ROI template with isocontour cutoff ≤ 60%. Conclusion: ROI size and slice thickness are significant factors affecting measurement of the striatal uptake of 123-I-FP-CIT. Methodological standardization of ROI must be considered when quantitative analysis is performed.

Evaluation of dopamine transporters using 123I-FPCIT: comparison of methods to analyze SPECT results C. Pettinato (1), S. Fanti (2), M. Dondi (3), V. Malfatti (2), S. Zoboli (3), M. Contin (4), M. Marengo (1), C. Bergamini (1), N. Monetti (2). (1) Fisica Sanitaria - Policlinico S.Orsola - Malpighi, (2) Medicina Nucleare Policlinico S.Orsola - Malpighi, (3) Medicina Nucleare - Ospedale Maggiore, (4) Clinica Neurologica, Bologna, Italy. Aim: recent studies reported the capability of 123I-FPCIT SPECT to evaluate dopamine transporters in patients with movement disorders. Several techniques were suggested for semiquantitative measurement of 123I-FPCIT uptake, on the basis of specific to non specific ratio. Aim of this study was to compare the results of different methods to analyze defects of 123IFPCIT uptake. Materials and methods: 123I-FPCIT SPECT was performed in 12 patients with Parkinson’s disease (PD) and in 4 patients with essential tremor (ET). Images were analyzed using 3 different methods: a) visual analysis (0=normal; 0.5=near normal, minimal abnormalities; 1=mild reduced uptake at one or both putamen; 2=severely reduced uptake at both putamen; 3=reduced uptake at caudate and putamen); b) large rectangular ROIs (including entire striatum); c) small irregular ROIs (manually drawn; different for putamen and caudate nucleus). All evaluations were carried out by 3 different operators. Results: The use of small irregular ROIs resulted more affected by operator-dependency, while methods based on visual analysis and large rectangular ROIs showed the higher reproducibility. Visual analysis resulted very effective in distinguishing between PD and ET (given scores ≥1 as PD we had 16/16 correct diagnosis); large rectangular ROIs failed in a relevant number of cases (with a 50% value as cut-off point we had 7/12 correct diagnosis of PD and 4/4 correct diagnosis of ET). The use of small ROIs did not allow to identify a cut-off value enabling to effectively distinguish PD and ET. Conclusions: Application of 123I-FPCIT SPECT in routine clinical studies requires a reliable and reproducible technique to evaluate the scan. Our data indicate visual analysis as the more effective method, while the use of ROIs, although enabling a semi-quantitative evaluation of defects, was not successful for differential diagnosis. Large ROIs were not accurate in PD patients with normal uptake at caudate nuclei: this fact may increase overall values for ratio. Small ROIs resulted significantly operator dependent, probably due to small dimensions of analyzed structures.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition PSYCHIATRY

P_359

The regional cerebral blood flow differences between depressed and dysthymic patients M. Kula (1), A. Tutus (1), A.S. Gonul (2), A. Bilgin (2), M. Cayci (1), A. Oguz (2). (1) Erciyes University, School of Medicine, Department of Nuclear Medicine, (2) Erciyes University, School of Medicine, Department of Psychiatry, Kayseri, Turkey. Aim: Dysthymic disorder is classified as distant category in DSM-IV, separately from major depressive disorder. A number of studies support the idea that dysthymic disorder is biologically similar major depressive disorder. However, relatively high doses of antidepressants are needed for treatment, which may give an impression that dysthymia may have differences from major depression on biological point of view. We aimed to test the hypothesis that regional cerebral blood flow (rCBF) of dysthymic patients might be different from those of depressed patients. Material and methods: Ten patients (7 M, 3 F; 28.15 ± 4.30) who met the DSM-IV criteria for dysthymic disorder and 10 patients (6 M, 4 F; 36.50 ± 8.60) with major depressive disorder included in the study. Control group consisted of 12 ages and sex matched healthy volunteers (8 M, 4 F; 34.0 ± 5.85). All the patients had been free of psychotropic medications for at least 2 weeks before brain SPECT study. The SPECT imaging was performed after 20 minutes following the injection of 550 MBq Tc-99m HMPAO. A semiquantitative method was used for the analysis. Results: There was significant group effect on rCBF values (F [20,132]=6.42 p<0.001). Both dysthymic and depressed patients had lower rCBF values than those of controls in the right and left superior frontal cortex (F [2,32]=13.30 p<0.001 and F [2,32]=44.42 p<0.001, respectively). Dysthymic patients have a higher rCBF values that those of depressive patients and controls (F [2,32]=13.40 p<0.001) in the cingulate gyrus. Dysthymic patients also had higher rCBF values than controls in the left caudate nucleus (F [2,23]=4.80 p<0.01). Conclusion: These finding suggest that dysthymic and depressed patients showed similar rCBF pattern in the frontal cortex, but not in the subcortical area. Different patterns of cerebral blood flow between these patient groups may explain differences in symptom profile and response to antidepressants.

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Poster Presentation

P_357

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99mTc ECD SPECT functional brain imaging in early diagnosis of fronto-temporal dementia.

SPECT evaluation of regional cerebral blood flow in schizophrenic patients after substitution of haloperidol by risperidone

J.H.M. Misko (1), M.B. Barcikowska (2), A.P. Pfeffer (2), K.C. Czyzewski (2), T.G. Golebiowski (2), T.G. Gabryelewicz (2), A.W. Wlodarski (1), J.S. Szychiewicz (1), M.K. Koprowski (1). (1) Department of Nuclear Medicine of the Central Rail Hospital, Warsaw, Poland, (2) Department of Neurodegenerative Disorders of the PAN/CSK MSWiA Hospital, Warsaw, Poland.

S. Crnkovic (1), R. Petrovic (1), V. Medved (2), I. Sain (2), M. Poropat (1), D. Dodig (1). (1) Clinical Department of Nuclear Medicine and Radiation Protection, University Hospital Centre Zagreb, (2) Clinical Department of Psychiatry, University Hospital Centre Zagreb, Zagreb, Croatia.

Fronto-Temporal Dementia (FTD) is a degenerative disorder of the brain. Clinical diagnosis in its early stage is difficult, especially differential diagnosis with Alzheimer’s Disease (AD), but it is very important due to differences in treatment. We know that typical for FTD abnormalities in regional cerebral blood flow (rCBF) are located in anterior part of the brain. The aim of our study was to determine the initial changes in frontal and temporalregional cerebral blood flow (rCBF) in early FTD using 99mTc-ethyl cysteinate dimer (ECD) SPECT. Methods: rCBF was noninvasively measured using 99mTc ECD SPECT in 20 patients complaining of mild cognitive impairment with probability of FTD (clinical symptomatology with or without signs of mild frontal atrophy in CT) and Mini Mental State Examination score more than 19 (mean age 62,5y.). Control group consists of 10 volunteers (mean age 61y.) without psychoneurological and neurological symptoms and without atrophy and focal changes in CT and SPECT neuroimaging. ECD uptake was measured in 6 pairs of cortical Regions of Interest (ROI) drawn on a four slices (slice thickness 6 mm) located about 5 cm above orbito-meatal plane: 3 pairs of ROI located in anterior part of the brain (anterior frontal, posterior frontal, anterior temporal) and 3 pairs in the posterior part of the brain (posterior temporal, parietal, occipital). A semiquantitative analysis of ECD was made in all ROIs referred to three regions: cerebellum (A), subcortical nucleuses (B) and pons (C). 2 patients from FTD group were excluded due to severe bilateral reducing of coefficients A,B and C in temporo-parietal regions (below 2SD of mean value in control group) typical for AD. Results: We found a significant difference, between FTD and control group, in the tracer uptake in the anterior part of the brain. The most prominent reduction in rCBF was observed, in all three coefficients, in anterior and posterior part of the frontal lobes and anterior part of temporal lobes (p<0,01), mild reduction was observed in the posterior part of the temporal lobes (p<0,05). Conclusion: In patients with symptoms of early stage of FTD we can enhance probability of appropriate diagnosis by using ECD SPECT – SPECT pattern of early FTD shows significant bilateral perfusion defects in the anterior part of the brain (frontal lobes and anterior part of temporal lobes) with mild CBF reduction in posterior part of temporal lobes and normal perfusion in parietal and occipital lobes.

P_361

Quantitative global assessment of cerebral perfusion changes via 3D perfusion isosurface in patients with dementia of Alzheimer type using Iodine-123-IMP SPECT. K. Utsunomiya (1), I. Narabayashi (1), Y. Ogura (1), T. Komori (1), I. Adachi (1), A. Stundzia (2), P. Dufort (2), M. Ichise (3). (1) Department of Radiology of Osaka Medical College, Takatsuki, Japan, (2) Advanced Biologic Corp., Toronto, Canada, (3) National Institute of Mental Health, Bethesda, USA. Objectives: To evaluate the use of 3D perfusion isosurface measures as a new method for providing a rapid overall quantitative assessment of global cerebral blood flow (gCBF) compared to the conventional 2D ROI method. Methods: Changes in fifteen patients with dementia of Alzheimer type (DAT) treated with donepezil hydrochloride therapy [mean age - 71.4 yrs, mean Mini-Mental State Examination (MMSE) score - 18.3] were evaluated. Iodine-123-IMP SPECT baselines were acquired before treatment. SPECT Iodine-123-IMP data was subsequently re-acquired for each subject at a mean interval of 10 months. For tracer uptake quantification, Iodine-123-IMP SPECT data was normalized using the autoradiography protocol. Perfusion isosurfaces at 20, 30, 40, and 50 [ml/min/100g] were generated in 3D using BrainGuide software. Associated with each isosurface value, BrainGuide also generated 1) the surface area associated with a isosurface value, 3D-PSA, 2) the volume of brain tissue enclosed by the selected isosurface, 3D-PSV, 3) the derived ratio, 3D-PSR = 3D-PSA / 3D-PSV, and 4) the integral of total blood flow within the enclosed isosurface, 3D-PSEV. Results: In follow up SPECT, a statistically significant increase in gCBF was indicated by 3D perfusion isosurface measures (p<0.01). Although no significant change in rCBF was observed in any region of the 5 cases using the conventional 2D ROI method, 3D perfusion isosurface measures revealed increased 3D-PSA, 3D-PSIV, and 3D-PSEV in 3 cases and decreased 3D-PSA, 3D-PSIV, and 3D-PSEV in 2 cases. All cases showed a tendency to be correlated to MMSE score changes. Conclusion: 3D perfusion isosurface measures may prove to be a set of useful techniques for rapid, quantitative, clinical assessment of the global progress of DAT in patients and the efficacy of treatments.

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Aim: Since non-uniformity of regional cerebral blood flow (rCBF) findings before and especially after different conventional and atypical antipsychotic treatments is a reality, the aim of our study was to evaluate and compare rCBF changes in schizophrenic patients treated with haloperidol after being replaced by risperidone. Materials&Methods: Thirteen female patients (mean age 34 years, range19-50) who fully met DSM-IV criteria for schizophrenia were included in the study. Patient symptoms were assessed using Positive and Negative Scale for Schizophrenia (PANSS) on the day of the first SPECT examination while they were on haloperidol, and this protocol was repeated after 8week risperidone treatment. The SPECT imaging was performed after 20 minutes following injection of 740 MBq of Tc-99m-ECD using a three-headed gamma camera. A visual analysis was performed from the SPECT images. For the semiquantitative analysis of the data, rectangular regions of interest were drawn over upper and lower frontal, temporal, parietal and occipital regions, as well as basal ganglia and thalami, using the whole brain as the reference. We performed intrasubject analysis of the same regions between two SPECT studies. Results: Only one patient had normal SPECT studies, both before and after replacement of antipsychotics. Differences in rCBF patterns were most significant in frontal and temporal cortical region, and in basal ganglia. In frontal region we usually detected hypoperfusion, while in temporal region and in basal ganglia, hyperperfusion. In 6 of 13 patients rCBF was normalised after the second SPECT study, after substitution of haloperidol with risperidone, which as well correlated to improvement of clinical symptoms (almost in all cases patterns of hyperperfusion). In 7 of 13 patients rCBF pattern remained the same as in the first SPECT study, and in 5 of 13 patients we found some new perfusion changes, usually hypofrontality. Conclusion: Our results support that mostly frontal, temporal and basal ganglia patterns of rCBF in schizophrenic patients change with 8-week risperidone treatment, which is associated also with clinical improvement of both positive and negative symptoms, representing different brain activity in a response to risperidone. These findings encourage the use of SPECT in the clinical management of these patients and for individual estimation of different antipsychotic effects.

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FDG-PET Scan in Drug-Naïve Schizophrenia Y.C. Chang (1), M.C. Hsiao (2), C.C. Tsai (1), C.Y. Liu (2), K.Y. Tzen (1), T.C. Yen (1). (1) Departments of Nuclear Medicine of Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, (2) Departments of Psychiatry of Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. Aim: It was proposed that the cortical-striatal-thalamic circuits might be involved in the cognitive dysfunction in schizophrenia. There were few data focusing in drug-naïve schizophrenia (DNS). The aim of this study was to determine whether there was glucose metabolic rate (GMR) change in the brain cortices, basal ganglia, or limbic system in DNS pts by FDG-PET scan. Post-therapy cerebral GMR changes were also evaluated. Material and Methods: 10 DNS pts (age range: 16-43 yrs; mean 26.3±8.5 yrs; 1M, 9F), and 5 age-matched normal controls (NL) (age range: 19-42 yrs; mean 20.3±9.0 yrs; 3M, 2F) were enrolled in this study. The psychopathology was interviewed by the Standardized Clinical Assessment for Neuropsychiatry of World Health Organization, the diagnosis of schizophrenia was based on the DSM-IV criteria, and the severity psychosis was valued by the Positive and Negative Syndrome Scale. All pts received FDG-PET scan and 6 of them had a post-therapy scan after receiving a fixed dose of haloperidol (10mg/day) therapy for 4 wks. All FDGPET brain scan was performed with 5 mCi of FDG injected intravenously. Image acquisition with Siemens HR+ scanner began 40 min after injection. 5-mm circular regions of interest were used to sample radiotracer uptake in the selected cerebral regions on 6 matched axial slices, and average GMRs were calculated. Data was evaluated using Wilcoxon Signed Ranks Test. Results: In comparison, there was no statistically significant difference of the GMRs between DNS and NL. However, there was significantly decreased GMRs in the bilateral medial frontal gyrus, left inferior frontal gyrus, left anterior rectal gyrus and right middle frontal gyrus in post- than pre-therapy DNS pts (p<0.05). Conclusion: Our results suggested no significant GMR change in DNS but significantly lower GMR in frontal cortices in post- than pre-treatment DNS pts. It might imply that frontal cortices probably played a role in the pathogenesis of schizophrenia.

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M. Milcinski (1), B. Novak (2), M. Grmek (1), M. Kocmur (2). (1) Department of Nuclear Medicine, University Medical Centre, (2) University Clinic for Psychiartry, Ljubljana, Slovenia.

I. Savitcheva, H. Engler, B. Långström. Uppsala University PET Centre, Uppsala, Sweden.

Aim of our study was to evaluate regional cerebral blood flow (r-CBF) in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF. Methods: Clinical criteria for schizophrenia according to ICD-10 were met. Psychiatric status and severity of disease in each patient were evaluated with a semistructured psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed after 99mTc-ECD application. So far, r-CBF was measured in 9 first-episode schizophrenic patients 2-7 (~5.2) days after the beginning of antipsychotic treatment and 8-15 (average 10.4) weeks later. Quantitative analysis of r-CBF in comparison with cerebellum as reference region was performed. Global brain perfusion and calculated values of r-CBF in both examinations in each patient were compared. Results: Decrease in perfusion in comparison to cerebellum was detected in left (90 %) and right (93 %) frontal lobes in addition to global brain hypoperfusion. Increase in perfusion between the first and the second investigation was significant (p<0.05) for both frontal regions (left 94 %, right 97 %). Global increase in perfusion was noted on second scan. Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with increase of r-CBF. Conclusions: Despite low number of patients included in our study so far, our findings are in concordance with some studies that found left frontal hypoperfusion in patients with firstepisode schizophrenia. Increase in brain perfusion in frontal lobes was observed after 10 weeks of drug treatment. Significant amelioration of r-CBF correlates with clinical improvement.

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition NEUROLOGY/PSYCHIATRY: OTHERS

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Brain 99mTc-ECD SPECT imaging in Machado Joseph diseaseIndian experience S. Rao, J. Desai, B. Sharma, D. Sarnath, V.R. Lele. Department of Nuclear Medicine, Jaslok Hospital & Research Centre, Mumbai, India. Machado Joseph disease (MJD) is a relatively uncommon variety of autosomal dominant Spino Cerebellar Ataxia (SCA) with a genetic mutation on chromosome 14q. There are no reports on findings of 99m-Tc- Ethyl Cysteinate Dimer (ECD) Single Photon Emission Computed Tomography (SPECT) in this disorder. Objectives: To investigate the possible abnormalities with ECD SPECT in patients with MJD and correlate the findings with Magnetic Resonance Imaging (MRI), clinical symptomatology and molecular characteristics of the MJD gene mutation (Expansion of CAG repeats within chromosome 14q). Methods: 5 patients (4 male, 1 female) with mean age of 30 years and genetically proven MJD (SCA-3) and 2 patients with non-MJD SCA were studied along with 10 normals (5 male, 5 female) with 99mTc-ECD SPECT using Triple head gamma camera, and MRI. Images were analysed visually and semi quantitatively. Results: All SPECT scans were abnormal. Abnormalities were predominantly in the cerebellum, especially in the vermis, frontal lobes (superior and middle, 5/5 patients) temporal lobes (medial and lateral 5/5) and brain stem. Unilateral Basal ganglia abnormalities were seen in 2/5 patients. MRI showed cerebellar vermian abnormalities in all patients but no abnormalities in other brain regions. There was no clinical evidence of frontal or temporal dysfunction in these patients. 2 patients with non MJD SCA also showed abnormalities in the cerebellar vermis but not in other areas on SPECT. There was no correlation of the severity of SPECT abnormalities with the duration and severity of clinical symptoms or the number of CAG repeats on genetic studies. Conclusion: 99mTc-ECD SPECT reveals multiple sub clinical abnormalities in patients with MJD, more than those seen on MRI, especially in the frontal and temporal lobes. These findings are similar to those reported using 99mTc-HMPAO in MJD. These findings may be helpful for a better understanding of the pathophysiology of this disease.

Multitracer PET investigations in Parkinson’s disease and parkinsonism

Introduction: More than 15% of the patients, which are initially considered to have an idiopathic Parkinson’s disease, demonstrate with time more extensive degenerative processes in the brain. Therefore, utility of tools allowing correct early diagnosis in those patients is obvious. We have used 11C-L-DOPA for detection of the presynaptic dopaminergic degeneration and 18F-FDG for estimation of the regional brain metabolic rate in patients with “parkinsonism”. Methods: Glucose metabolic rate and dopadecarboxylase activity were investigated in 47 patients (26 men, 21 women, age range 29-77 years) with “parkinsonism” with unclear etiology or vague response to DOPA treatment. All patients underwent PET kinetic investigations with FDG and 11C-L-DOPA. Results and discussions: Decreased dopadecarboxylase activity (DDA) in dorsal parts of putamen indicated presynaptic dopaminergic degeneration and lack of metabolic alterations in the brain allowed to confirm idiopathic Parkinson’ disease in 11 patients. Multiple system atrophy (MSA) was suggested in 13 patients, which showed diminished DDA and significant reduction of metabolism in striatum, pons and cerebellum. In 6 patients with decreased DDA and reduction of metabolic rate in the parietal and primary visual cortex, diffuse Lewy’s body (DLBD) disease was considered the cause of Parkinson’s syndrome. 13 patients showed considerable reduction of the metabolism in different cortical and subcortical regions, which were not completely compatible with MSA or DLBD but suggested more extensive degenerative process than only idiopathic Parkinson’s disease (corticobasal degeneration, Parkinson’s disease+dementia etc.). In 4 patients, normal DDA and lack of significant metabolic alterations allowed to exclude degenerative process in the brain. Conclusions: Use of double tracer study (FDG and DOPA) in patients with Parkinson’s syndrome allows an estimation of the dopadecarboxylase activity in striatum and global and regional brain metabolism. This makes it possible to distinguish between idiopathic Parkinson’ disease and Parkinson+ syndrome.

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FDG-PET Scan in Vascular Parkinsonism K.Y. Tzen (1), Y.C. Chang (1), C.S. Lu (2), T.C. Yen (1), W.J. Lin (3), J.T. Chen (3). (1) Department of Nuclear Medicine of Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, (2) Department of Neurology of Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, (3) Institute of Nuclear Energy Research, Taoyuan, Taiwan. Aim: Vascular parkinsonism (VP) is thought to be a distinct parkinsonian syndrome associated with vascular lesions. The lesions were small in size and located in deep lacunar areas and/or at subcortical white matter. In our previous study, dopamine transporter in VP was relatively reserved. For further investigation on the pathogenesis of its neurological symptoms and signs, we used FDG-PET to study the glucose metabolic rate (GMR) changes in these VP pts. Material and Methods: Seven VP pts (age range: 48-85 yrs; mean age: 69.1±13.2 yrs), 4 age-matched Parkinson’s disease (PD) pts (age range: 59-73 yrs; mean age: 68.3±6.3 yrs), and 5 age-matched normal controls (NL) (age range: 51-64 yrs; mean age: 56.2±5.3 yrs) were enrolled in this study. The inclusive criteria for VP were: (1) clinical symptoms of lower body parkinsonism; (2) multiple cerebral vascular changes in bilateral basal ganglia and/or white matter; (3) no obvious stroke history; (4) no or poor response to anti-Parkinson drugs; (5) exclusion of other degenerative diseases or administration of drugs that can induce parkinsonism. PD was defined by the criteria for possible diagnosis of PD by Gelb et al. The NLs were free from any neurological or psychiatric disease. The FDG-PET scan was performed with injection of 5 mCi of FDG intravenously. Images were taken with Siemens HR+ scanner 40 min after injection. 5-mm circular regions of interest were used to sample radiotracer uptake (SUV) in the selected basal ganglia and thalamus regions on two matched axial slices and average GMRs were calculated. Mann-Whitney test was applied in this study. Results: The SUVs in VP pts were statistically significant lower in bilateral basal ganglia and thalamus regions than in NLs and PD pts (p<0.01). There was no significant difference in GMR in the basal ganglia and thalamus regions as compared PD with NLs (p>0.05). Conclusion: Brain GMR evaluation was valuable in differentiating VP from PD and normals. The clinical neurological symptoms and signs for VP might be related to striatal-thalamo-cortical dysfunction rather than dopamine neuronal damage.

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Poster Presentation

Brain perfusion SPECT: Early effect of treatment in first-episode of schizophrenia

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Sympathetic myocardial innervation in Parkinson’s disease and multiple system atrophy G. Berding (1), C.H. Schrader (2), T. Peschel (2), J. van den Hoff (1), H. Kolbe (2), R. Dengler (2), W.H. Knapp (1). (1) Department of Nuclear Medicine, University Medical School, Hannover, Germany, (2) Department of Neurology, University Medical School, Hannover, Germany. Aim: Orthostatic hypotension (OH) can be found in Parkinson’s disease (PD) and multiple system atrophy (MSA). Histopathologic studies indicated sympathetic myocardial denervation as underlying cause in PD, but not in MSA. Preliminary studies assessing myocardial innervation with [123I]MIBG suggest that both diseases can be differentiated in vivo. However, imaging and pharmacokinetic properties of [123I]MIBG are not optimal for quantification. We employed [11C]HED, which shows selective neuronal uptake-1 and offers the possibility of quantification based on kinetic modelling of PET data. The aim was to confirm MIBG results in cases with clinically established diagnosis, and get a first impression if denervation in PD patients without OH or with short duration of disease is detectable. Materials and Methods: Seven patients (3 female, 4 male, mean age 60±7) were investigated. Two suffered from probable MSA for 3.5 and 4 years, and 5 from probable PD for a mean period of 7 (2-16) years. OH was present in both MSA and 3 PD patients. Dynamic PET studies were acquired for 45 min after i.v. injection of 400 MBq [11C]HED (Hydroxyephedrine) using a dedicated full ring scanner. For quantitative analysis the left ventricular myocardium was delineated using an automated rendering procedure. Mean myocardial influx of HED in the first 5 min (K1) was calculated based on an 1-compartment model and using an input function generated from the cavum of the left ventricle. Results: In MSA K1-values of 0.384 and 0.450 min-1 were obtained. In one patient with PD for 10 years and OH myocardial uptake was too low for quantitative analysis. Two PD patients with OH and 6 and 16 years duration of disease showed mean K1-values of 0.359 and 0.198. In one PD patient, ill for 3 years without OH, K1 was 0.363 min-1. Only in one patient with PD for 2 years and no OH K1 was in the range of values observed in MSA (0.400 min-1). Conclusion: All patients with established PD for at least 3 years could be separated from those with MSA based on sympathetic innervation measurement even in the absence of OH – although the differences were small in some cases. However, one case of early PD without OH could not be separated. We conclude that the diagnostic value of the method especially in early stages of disease has still to be evaluated.

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A new approach for Alzheimer’s Disease and Frontal Lobe Dementia diagnosis and classification based on combined SPECT intensity and gradient features M.M.E. Pagani (1,2), V.A. Kovalev (3), R. Lundqvist (4), H. Jacobsson (2), S.A. Larsson (2), L. Thurfjell (4). (1) Institute of Neurobiology and Molecular Medicine,CNR,Rome,Italy, (2) Section of Nuclear Medicine, Dept. of Hospital Physics and Dept. of Medical Radiation Physics, Stockholm University, Stockholm, Sweden, (3) Institute of Engineering Cybernetics, Belarus National Academy of Sciences, Minsk, Belarus; Max Planck Institute of Cognitive Neuroscience, Leipzig, Germany, (4) Centre for Image Analysis, Uppsala University, Uppsala, Sweden. Aim: Alzheimer Disease (AD) and Frontal Lobe Dementia (FLD) show characteristic patterns of regional cerebral blood flow (rCBF). Compared to normal individuals, these patterns often superimpose with those of the aging brain. The aim of this study is to develop a new method for improved classification and recognition of AD and FLD. Materials and Methods: 46 AD and 7 FLD patients and 34 normal controls (CTR) were included in the study. rCBF was assessed by 99m-Tc-HMPAO and using a three-headed gamma camera. A standardised brain atlas was used to define volumes of interest (VOIs) corresponding to the brain lobes. The intensity mean of the signal and its histogram, the intensity gradient mean and its histogram and the orientation of the gradient angle were computed for each VOI and tested separately as features (image descriptors) to classify the different groups. The normalized combined 5D co-occurrence matrices, relative to such features, were then computed for each VOI and their abilities to recognise the group to which each individual belonged were investigated. Statistical analyses were performed after preliminary features discrimination by two-sided t-test. K-means clustering was used to classify the image sets into categories. The recognition of a scan into a class was performed by computing the Euclidean distance between its 5D features value and the centres of classes (groups) under consideration as assessed by averaging the features computed over the class member feature element-byelement. Results: In the correct classification of the AD-CTR groups, the intensity gradient histogram in the temporo-parietal lobes was the most useful feature (91.3% of accuracy). FLD and CTR were better classified by the intensity histogram (frontal and occipital lobes) and the intensity gradient mean (frontal, temporal, parietal lobes) (97.6%). For AD and FLD the intensity histogram in the frontal, parietal and occipital lobes classified the groups with the highest accuracy (84.9%). 5D co-occurrence matrices recognised correctly 97.5% of the AD-CTR individuals, 100% of the FLD-CTR subjects and 98.1% of the AD-FLD patients. Conclusion: The proposed approach combining biological data and mathematical methods diagnosed and classified AD and FLD patients with a high accuracy. This was achieved increasing the dimensional resolution of SPECT data utilising additional features, possible to be extracted by the same SPECT data pool, other than the mere uptake signal intensity.

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T. Tang (1), S. Minoshima (2), P. Laloux (3), J. George (1), A. Robert (4), M. Ossemann (3), T. Vander Borght (1). (1) Department of Nuclear Medicine, Université Catholique de Louvain, Belgium, (2) Department of Radiology, University of Washington, Seattle, USA, (3) Department of Neurology, Université Catholique de Louvain, Belgium, (4) Department of Medical Statistics, Université Catholique de Louvain, Belgium.

B. Palumbo (1), L. Parnetti (2), D. Siepi (1), A. Bianchi (1), S. Messina (1), A. Lanari (2), S. Amici (2), V. Gallai (2), R. Palumbo (1). (1) Institute of Nuclear Medicine of the Department of Radiological Sciences of the University of Perugia, Italy, (2) Department of Neurosciences of the University of Perugia, Italy.

Aim: Previous studies demonstrated that three dimensional surface stereotactic projection (3D-SSP) technique improves diagnostic performances of FDG-PET and rCBF-SPET for the diagnosis of Alzheimer disease (AD). In this study, we evaluated in AD patients the relationship between cerebral perfusion in different cortical areas and cognitive function using a multiple regression analysis. Materials and methods: 24 patients (mean age: 74±5 years old; ranges: 66-83) diagnosed with a probable AD using the NINCDS-ADRDA criteria were included in the study. The MMS mean score was 19±6 (ranges: 5-28). SPET studies were acquired 1h after injection of 740 MBq ECD on a triple-head camera equipped with LEUHR collimators. Images were reconstructed by FBP and automatically quantified using 3D-SSP. rCBF was normalized to the thalamic or mean cortical activity. Multiple regression analysis between the MMS scores and activity into 13 predefined “Broadman” ROIs for each hemisphere was performed. Results: Using the activity normalized to the thalamus, multiple regression showed the strongest correlation between the MMS score and rCBF in the right parietal cortex (r=0.61; p=0.002), then in decreasing order, in the left parietal, the right temporal, the right occipital and the left temporal cortices (see table). As rCBF in each of the later cortical regions correlated significantly with that of the right parietal cortex, only the correlation between the MMS and right parietal perfusion was statistically valid (Simpson paradox). Activity normalised to the mean cortical activity provided a less significant correlation between MMS score and parietal rCBF.

Aim: Neuron Specific Enolase (NSE) is a glycolitic enzyme found in neurons and neuroendocrine cells that is considered an index of organic neuronal damage and a biochemical marker for brain ischemia; a relevant increase of CSF concentration of NSE was observed in several neurological diseases, including acute stroke. Data on Alzheimer’s disease and vascular dementia are more controversial. We measured CSF concentration of NSE in patients suffering either from vascular dementia or from Alzheimer’s disease and in control subjects. Materials and Methods: We studied 72 subjects; 37 patients were affected by probable Alzheimer’s disease (AD) according to NINCDS-ADRDA criteria, 20 by subcortical vascular dementia (VaD) according to DMS-IV R criteria and 15 were healthy age-matched controls referred to Urology Department for minor surgical problems requiring spinal anaesthesia. CSF NSE was measured by a solid phase two-site immunoradiometric assay (ELSA-NSE, CIS bio International-Schering). Results: CSF NSE levels were significantly higher in AD (mean±SD: 23.14±7.9 ng/ml) with respect to controls (mean±SD: 7.8±2.4 ng/ml, p<0.001) and to VaD (mean±SD: 14.92±3.8 ng/ml, p<0.001); NSE was also significantly increased in VaD patients as compared to controls (p<0.01). Conclusion: Our results support the role of NSE as a marker of active injury of the central nervous system, being this enzyme significantly altered in all dementia patients with respect to controls. Furthermore the continuous neuronal destruction typically present in AD could explain the relevant increase of NSE. On the other hand the significant increase of NSE observed in VaD, although less relevant than in AD, could be due to the ongoing neuronal degeneration reported in subcortical vascular dementia.

Parietal perfusion is correlated with the MMS score in Alzheimer disease

Multiple regression between MMS and rCBF normalized to the thalamus MMS R. Par. r-Pearson .609 p-value .002

L. Par. .531 .008

R. Temp. L. Temp. R. Occ. L. Occ. .509 .406 .416 .381 .011 .049 .043 .066

L. Front. R. Front. .252 .246 .235 .247

Conclusion: MMS score correlates with the right parietal perfusion and the later correlated with other associative posterior cortices, especially on the right side. As thalamic activity is commonly spared in AD, normalization to that regions is better than global normalization for such analysis. Automated 3D-SSP method of ECD-SPET provides a valid assessment of the pattern and severity of cortical perfusion abnormalities in patients with AD.

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CSF Neuron Specific Enolase as a biological marker of Alzheimer’s disease and subcortical vascular dementia

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n NEUROLOGY/PSYCHIATRY: OTHERS Imaging of cerebral blood flow abnormalities in mild cognitive impairment and Alzheimer’s disease A. Varrone (1), S. Pappatà (1), A. Postiglione (3), G.A. Carlesimo (4), V. Sansone (2), A.R. Sorrentino (2), M. Quarantelli (1), A. Soricelli (1,2), M. Salvatore (2). (1) National Research Council, IBB, Napoli, Italy (2) Dep. of Biomorphological and Functional Sciences, University "Federico II" of Napoli, Italy (3) Dep. of Clinical and Experimental Medicine, University "Federico II" of Napoli, Italy (4) IRCCS S. Lucia of Roma, Italy Previous studies in patients with mild cognitive impairment (MCI) demonstrated reduced volume of entorhinal cortex and hippocampus and impaired metabolism or perfusion in temporoparietal cortex, hippocampus and posterior cingulate cortex suggesting the involvement of these regions in early stages of Alzheimer’s disease (AD). Aim: The aim of this study was to evaluate cross-sectionally regional cerebral blood flow (rCBF) differences among aged controls, MCI and AD patients. Materials and Methods: Six healthy controls (3M, 3F, age 62±10 yrs), 9 MCI patients (5M, 4F, age 71±6 yrs) and 11 AD patients (7M, 4F, age 65±9 yrs) with mild-to-moderate disease (MMSEW16, mean 19±3) were studied with 99mTc HMPAO SPET. Images were analysed with statistical parametric mapping (SPM’99), using proportional scaling and a threshold of uncorrected p<0.01 for voxel height and p<0.05 for cluster extent. A priori analysis with small volume correction on posterior cingulate and precuneus was conducted in MCI patients. Results: When MCI patients were compared to controls significant reduction of relative rCBF was observed only with SVC analysis in posterior cingulate cortex (-2, -31, 40; 0, -35, 42). In AD patients significant reduction of rCBF was observed in left posterior cingulate (-2, -23, 42) right posterior cingulate (8, -49, 26), left and right precuneus (-12, -53, 36; 18, -60, 34) and left parietal cortex (-51, -43, 26; -34, -62, 49) compared to controls. Direct comparison of AD to MCI patients revealed a more marked reduction of rCBF in left precuneus (-12, -47, 39; -40, -70, 40), left parietal cortex (-57; -44; 22) left temporal cortex (-60, -64, 4; -53, -58, 2; -59, -61, -7), left parahippocampal gyrus (-28, -24, -12; -18, -43, 2) and left lingual gyrus (26, -66, 0) of AD patients. Conclusion: These preliminary data suggest a mild impairment of rCBF in posterior cingulate cortex of MCI patients compared to controls. A more marked reduction of rCBF in left parietal cortex, left lateral and medial temporal cortex was observed in AD compared to MCI patients, suggesting a possible early involvement of these brain regions in AD. Longitudinal follow-up of MCI patients is required to evaluate the specific role of these regions in the conversion of MCI to AD.

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Frequency of Subclinical Hyperthyroidism in Dementia N. Döbert (1), C. Menzel (1), N. Hamscho (1), L. Frölich (2), U. Berner (1), F. Grünwald (1). (1) Dept. of Nuclear Medicine of the University Hospital Frankfurt/ Main, (2) Dept. of Psychiatry of the University Hospital Frankfurt/ Main, Germany. Aim: Subclinical hyperthyroidism is one of the most likely reasons for the developement of secondary dementia. Kalmijn et al. recently described increased TPO antibodies in patients with dementia of Alzheimer type (DAT). Methods: We examined thyroid parameters (TSH, FT3, FT4, thyroid peroxidase (TPO) antibodies, TSH-receptor antibodies, microsomal antibodies) in 51 patients (m:f = 21:30, age: 31 - 95 years) with clinical suspicion of dementia. In addition to psychiatric diagnostics, rCBFSPECT (Tc-99m-HMPAO, n = 37 examinations) and/ or rCGU-PET (F-18-DG, n = 24 examinations) were performed. 10 patients underwent both procedures. Results: Suppressed TSH values were found in 17/51 patients (33 %), in 13 cases endogenous and in 4 cases caused by treatment with thyroid hormons. Four patients showed up with a tracer distribution typical for DAT in FDG-PET. Using rCBF-SPECT, in one patient a pattern typical for progressive DAT was found, in 3 patients a frontal lobe hypoperfusion. Another 6 patients (12 %) had low normal TSH values (0.3 - 0.5 mU/l), with FDG-PET in 2 cases a DAT was detected. In contrast to the paper of Kalmijn et al., thyroid antibodies did not correlate with a dementia of Alzheimer type. Only 2 patients with a typical FDG-PET result for DAT showed an increase of TPO antibodies. Three patients had increased thyroid antibody values without any imaging evidence of a dementia of Alzheimer type. Conclusion: Low TSH values were found in more than 45% (23/51) of the patients with clinical suspicion of dementia. Thyroid antibody values were not increased in most of the cases with DAT. References: Kalmijn S, et al. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol 2000; 53: 733-737

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Brain Perfusion SPET in Alzheimer’s Disease has equivalent diagnostic power as MRI

Prognostic value of brain Spect with Tc99m-HMPAO and ApoE genotype in patients with memory impairment

K. Machida (1), N. Honda (1), M. Hosono (1), H. Matsuda (2), T. Matsumoto (3), M. Oshima (4), A. Kashimada (1), T. Takahashi (1), H. Osada (1). (1) Department of Radiology, Saitama Medical Center, Kawagoe, Japan, (2) Department of Radiology, National Center for Neurology and Psychiatry, Kodaira, Japan, (3) National Institute of Radiological Sciences, Chiba, Japan, (4) Department of Radiology, Teikyo University, Tokyo, Japan.

J. Lopez (1), D.G. Solis (1), R. Alberca (2), E. Montes (2), R. Alvarez (1), P. Gomez (1), A. Gutierrez (1), R. Vazquez (1). (1) U.D. of Nuclear Medicine, (2) Department of Neurology. University Hospital Virgen del Rocio. Seville. Spain.

Aim: Both brain perfusion single photon emission computed tomography (bSPET) and magnetic resonance imaging of the brain (bMRI) is effective for differentiating dementias. The purpose was to compare the diagnostic performance of bSPET with that of MRI by modified receiver operating characteristics curve (ROC) analysis. Material and Methods: Fifty-seven cases were selected out of 99 cases from four institutions. Selection criteria were; definite diagnosis by experts, almost equal number of cases with normal and Alzheimer’s Disease (AD), single source as far as possible, and dementias other than AD were all included regardless of the source. Consequently, thirty-two cases were from one particular institution. There were 22 cases of normal, 19 of Alzheimer’s disease (AD), 8 of multi-infarct dementia (MID), and 8 of other dementias. In the first experiment (E1), ten nuclear medicine physicians (NMPs) interpreted bSPET images. In the second experiment (E2), three board-certified neuroradiologists (NRs) interpreted. The participants independently rated each of the diagnoses listed on a reporting form according to a 5-point confidence scale (score 1 to 5). The clinical information, including patient’s age, gender, handedness, MMSE score, and focal neurological deficits, if any, was provided. Since the number of the cases was small in some diseases, grouping was necessary. Three groups were formed as normal, dementia of any type (abnormal), and AD or MID (AD/MID). When several diseases were present in one group, a score of the group by each of the participants was defined as the maximum of the scores assigned to the diseases within the group. Two groups to compare were selected and a frequency histogram of the first group was generated. The scores (SS) of the second group were converted to (6 - SS) and another histogram was created to proceed to usual ROC analysis. Area under the ROC curve (Az) was calculated and compared. Results: Mean Az (SD) of discriminating abnormal from normal was 0.714 (0.13) for the NMPs in E1, 0.771 (0.01) for NRs in E2, respectively. Mean Az (SD) of discriminating AD/MID from normal was 0.671 (0.12), 0.714 (0.01). There was no significant difference between NMPs and MRs in the above. Mean Az’s of the experienced NMPs were greater (p<0.035) than that of NRs in discriminating AD/MID from normal. Conclusion: Differential diagnosis of dementia with bSPET read by NMPs has comparable diagnostic power as MRI read by NRs.

Aim: Perfusion brain Spect would be useful in subjects with memory loss to identify who will progress to Alzheimer´s disease (AD). However, a high rate of non-specific for AD Spect abnormalities can be found in these patients and the typical bilateral temporo-parietal hypoperfusion pattern is more specific, but not sensitive. In other hand, the ApoE epsilon4 allele has proven to have a high predictive value for AD. The aim of this study was to determine the prognostic value of both parameters in subjects with a memory disturbance to predict its progression to AD. Materials and Methods: 85 patients (31 male and 54 female; age 66± 9.5 years), that were seen in the Unit of Dementia of our Hospital complaining of memory disturbance, have been studied. They did not meet the clinical criteria for dementia. Mean follow-up was 2.4 years. At least a brain SPECT with Tc99m-HMPAO was performed in all patients. Bilateral posterior temporo-parietal hypoperfusion was considered as a positive result. Apo E genotyping was also performed. Results: Mean MMSE score for the first visit was 24±4. During the follow-up period, 20 out of 85 patients developed AD. An Apo E4 allele was present in 25 subjects (29%), of which 12 (48%) evolved into AD. In 14 out of the 85 patients (16%), brain SPECT showed bilateral temporo-parietal hypoperfusion; in 46 (54%) non AD-typical perfusion defects were found, and in 25 (29%) the study was normal. Among the 20 patients that evolved into AD, 12 showed bilateral temporo-parietal hypoperfusion; non-specific abnormalities were detected in 6 and the SPECT imaging was normal in 2. In this AD patient group, a positive Apo E4 plus an abnormal SPECT was found in 7 subjects. A positive Apo E4 was also found in 5 patients with a non diagnostic brain SPECT. Conclusions: The capability to predict the progression to AD in patients with memory impairment may increase if diagnosis is based upon the jointly use of perfusion brain SPECT and Apo E genotyping.

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Acute encephalitis, cognition and SPECT - a case report R. Pichova (1), O. Lang (1), R. Rusina (2), A. Javurkova (2). (1) Department of Nuclear Medicine, University Hospital Kralovske Vinohrady, Prague, Czech republic, (2) Department of Neurology, Charles University, 3rd Medical Faculty, Prague, Czech republic.

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The Clearance Rates of In-111 DTPA from CSF Vary with Different Sites of CSF Blockade. F.C. Wong, E. Kim, M. Groves, C. Conrad, I. McCutcheon, D. Podoloff. Dept. of Nuclear Medicine of the Univ. of Texas M. D. Anderson Cancer Center, Houston, TX, USA..

Aim: The aim of our work is to present a case report of using brain perfusion single photon emission computed tomography (SPECT) together with cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) including neuropsychological evaluation in patients during acute phase of encephalitis. Materials and methods: A 56-y-old lady was admitted with acute frontal headache, abulia, bradypsychia. Generalized seizures with focal onset succeeded. Signs of aphasia, right-sided hemiparesis and meningeal irritation progressively developed. Electroencephalography (EEG), CSF analysis, polymerase chain reaction (PCR) and neuropsychological evaluation as well as MRI and brain perfusion SPECT with 99mTc HMPAO and fan-beam collimators using dual-head gammacamera were performed. Results: Focal epileptic activity above the right temporal lobe was visible on EEG. CSF analysis revealed hyperproteinorachia and mononuclear pleiocytosis, PCR of herpesviridae were negative. T2 and almost T1 hyperintense lesions were detected by MRI six days after the onset, compatible with hemorrhagic encephalitis. Brain perfusion SPECT showed regional hypoperfusion predominantly in the left orbitofrontal area, thalamus, basal ganglia and less in the both parietal lobes. Neuropsychological disorders manifested as anosognosia, dynamic aphasia, dysexecutive syndrome, stereotypias and reduced text comprehension, fluctuating disorientation and desinhibition with gatismus. Conclusion: The cognitive profile and the evolution of our patient correlated better with the brain perfusion SPECT findings comparing to MRI. This case report supports the usefulness of perfusion imaging in acute inflammatory brain disease for more appropriate goal oriented early rehabilitation.

Objectives: CSF blockade is a contra-indication for intrathecal therapy for potentially decreased efficacy and increased toxicity from loculation. It is an occasional finding with cisternogram and Ommayogram, especially with cancer patients. However, conventional cisternogram and Ommaygram are typically qualitative studies. They do not directly answer the question whether CSF blockade indeed result in lower efficacy and higher toxicity from loculation. This study is designed to evaluate the patterns of CSF blockade with the clearance rates of In-111 DTPA, based on whole-body CSF imaging. Methods: This is a retrospective survey of 229 consecutive patient studies referred to our clinic for In-111 DTPA cisternogram (lumbar injection) or Ommaygram (via Ommaya reservoir) from 1997 to 2002. Typically 0.5 mCi of In-111 DTPA was injected. Four whole-body anterior and posterior scans were acquired by a dual-head gamma camera in 1-2, 4-6, 18-22 and 24-28 Hours. Geometric-mean images were generated to account for different depth of the CSF compartments. Effective half-lives (Te) of In-111 in the entire CSF pathway were calculated and contrasted with CSF blockade. CSF blockade was determined based on persistent visualization of In-111 and persistent non-visualization of distal pathways. Planar images were acquired on selected cases for verification. Studies with CSF leakage or ventriculopertoneal shunting were excluded. Results: 3/32 cisternograms showed T-spine blockade and fast Te (3, 4, 5.5 Hr) while those (29/32) without block showed slower Te (15.3 +/- 4.2 Hr). Blockade at the catheter tip (5/146) on Ommayogram also exhibited fast Te( 8.1+/- 3.0 Hr); blockade at the ventricular outlet (2/146) showed slow Te (20, 35Hr) compared with those without block (116/146, Te=15.6 +/5.1 Hr). Blockade at the C-spine (4/146) and T-spine (19/146) on Ommayogram were associated with a wide range of Te (17.8+/- 2.6 Hr and 14.9 +/- 6.8 Hr, respectively). Conclusion: Whole-body cisternogram and Ommayogram allow more comprehensive evaluation of drugs in the CSF flow and its retention, which is correlated with exposure to intrathecal medication. This approach allows identification of different patterns of CSF blocks which are actually associated with wide ranges of clearance rates. The traditional teaching of CSF block as an absolute contra-indication may need to be revised. As long as there is substantial beneficial exposure of the CSF space to the medication for the intended therapy and there no excessive exposure in the blocked area, intrathecal therapy may still be advisable. Semi-quantitative whole-body imaging of CSF (as presented in our study) will then be essential for such determination.

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H. Kaya, S. Erdogan, T.A. Balci, H. Kömek. Department of Nuclear Medicine, Medical Faculty of Dicle University, Diyarbakir, Turkey.

L. Ruffini (1), E. Ferrante (2), G. Biscontini (1), C. Rossetti (1). (1) Nuclear Medicine Department of Niguarda Hospital, (2) Neurology Department of Niguarda Hospital, Milan, Italy.

Estimation of regional cerebral blood flow with Tc-99m HMPAO brain SPECT in fibromyalgia

Aim: Fibromyalgia (FM) is a disorder characterised by chronic generalised musculoskeletal pain and fatigue. No specific reason for this type of pain can be found. Because of some reports about the presence of regional cerebral blood flow (rCBF) abnormality in FM, we also aimed in this study to define if there is an abnormality in brain blood flow in patients with FM. Materials and methods: Subjects included 14 women with FM and a control group of 17 normal female of comparable age and education levels. We performed Tc-99m HMPAO brain SPECT to all patients. Perfusion of 19 different cerebral cortical regions, pons, right-left caudate nuclei and right-left hemithalamus were analysed by semiquantitative technique using transverse scan sections on the Tc-99m HMPAO brain perfusion SPECT. Results: In addition to some alterations of regional cerebral blood flow, the main finding was significantly increased rCBF in the left caudate nucleus of FM patients compared with control subjects (p<0.004). Conclusion: Our study also corroborated the presence of regional cerebral blood flow alterations in FM. However, versus the findings of the other researchers, we found increased rCBF in the left caudate nucleus.

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Role of radionuclide cisternography in the diagnosis of spontaneous intracranial hypotension

Spontaneous intracranial hypotension (SIH) is a rare syndrome characterized by intense postural headaches elicited or exacerbated by the upright position and relieved only by recumbent position. SIH is associated with low cerebrospinal fluid (CSF) pressure. A CSF leak may be the cause of SIH but it has rarely been demonstrated. Aim: Aim of the study was to define the role of radionuclide cisternography (RNC) in SIH diagnosis algorythm. Materials and methods: Four patients with SIH were studied from 1998 to 2002. All patients underwent radionuclide cisternography and brain MRI. RNC was performed after injection at the lumbar level L4-L5 of 111In-DTPA (30 MBq). Imaging was performed 2, 4 and 24 hours after tracer injection. Cranial, thoracic and abdominal images were acquired after 10 minutes of standing position. Results: Physical and neurological examination, cranial CT and routine laboratory studies were normal. Lumbar puncture showed clear CSF and no RBCs. All cultures were negative. Brain MRI showed minimal signs of diffuse linear thin meningeal gadolinium enhancement along cerebral and cerebellar convexity. Patients were treated symptomatically with bed rest and analgesics. Because of continuing postural headache associated with vomiting and vertigo patients were submitted to the radionuclide study. RNC showed direct signs of CSF leakage in 3 pts: diffusion of tracer into the extra-arachnoid space at the dorsal level 6 hrs after injection in 1 patient, asymmetric image at the dorsal vertebral level in 1 patient and diffuse activity near the spine in 1 patient. Only indirect signs of CSF hypotension were demonstrated in 1 patient with early accumulation of radioactivity in the bladder and activity reduction over cerebral convexities after 24 hours suggesting rapid uptake of the tracer into the circulation. Patients were treated with strict bed rest and i.v. saline infusion. Conclusion: Radionuclide cisternography plays a central role in the diagnosis of SIH. MRI findings suggest the diagnosis that is confirmed only by RNC showing direct signs of CSF leakage or indirect signs of CSF hypotension.

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n NEUROLOGY/PSYCHIATRY: OTHERS Auditory cortex activation after pure sounds stimulation

Date: 02.09.2002 • Time: 14:30 - 16:00 • Hall: Poster exhibition

M.C. Migueis (1), M.F. Botelho (2), C.M. Gomes (2), J. Neto (3), M.J. Cunha (3), A. Paiva (1), J. Lima (3), J.J.P. de Lima (2). (1) Ear Nose and Throat Service - HUC, (2) Biophysics Department, IBILI - Faculty of Medicine, (3) Nuclear Medicine Service - HUC, Coimbra, Portugal.

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Objectives: The evaluation of neuro-anatomical responses at auditory cortex, after stimulation with pure sounds of 500 Hz, 1000 Hz and 4000 Hz, with a sound pressure level of 70 dB, during 15 minutes comparing to a basal study, obtained with no stimulation. The neuronal responses were assessed by single photon emission tomography (SPET), using regional cerebral blood flow (rCBF) as parameter. Material and Methods: Seven normal-hearing adults were studied before and after auditory stimulation. The subjects were stimulated monaural (right ear) and the stimuli were delivered through earphone with the contralateral ear occluded with a foam earplug. The patients kept a vein line with saline in order to ensure that were unaware of tracer administration. Five minutes after the initiation of a continuous auditory stimulus, 629 to 925 MBq of 99mTc-ECD (ethyl cysteinate dimmer) were injected over a 30 sec period in the venous line. The subjects were scanned for 20 minutes using a dedicated gamma camera (Neurocam-GE Electric), 1.5 hour after injection. The study was approved by the Ethics Committee and all the subjects included signed an informed consent. Results: Despite our small sample, the results suggested that there are differences in the activation areas with the different stimuli. The main difference appears to be for 500 Hz stimulus which activate only the homolateral temporal areas. For higher frequencies (1000 and 4000 Hz) the same temporal areas seems to be bilaterally involved. Conclusions: Our data suggest that SPECT functional cerebral blood flow imaging can be useful tool in the study of the responsiveness to auditory stimuli.

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PEDIATRICS

In-111 Pentetreotide versus bone scintigraphy (PS and BS) in the detection of bone metastases (BM) of neuroblastoma (NB) M.E. Juweid, Y. Menda, D. Bushnell, M.S. O’Dorisio, M. Blake, M.M. Graham. Departments of Radiology and Pediatrics of the University of Iowa College of Medicine, Iowa City, Iowa, USA. Background and Objective: The assessment of BM is an integral part of staging of children with NB. Although BS is a widely accepted tool for this purpose, it can still underestimate the extent of these metastases (Brodeur et. al. JCO 1993). PS has been successfully shown to image NB. The purpose of this study was to compare PS with BS for detecting BM of NB. Methods: Eight patients (pts) with NB underwent both PS and BS for staging/restaging of their disease. The sensitivity and specificity of PS and BS were compared by retrospectively and blindly interpreting the images and comparing the results with the findings of histopathology, other conventional imaging methods and subsequent clinical followup. Results: In 5/8 pts, both PS and BS were negative for BM. Radiographic bone surveys (RBS) were also negative in these pts except in one who showed a suspicious tibial lesion, but a CTguided biopsy failed to show evidence of disease. These pts remained without clinical evidence of BM after a median duration of 15+ mo (range 6-19 mo). In the remaining 3 pts, both BS and PS were positive for BM. However, in all three patients, PS showed a greater number of skeletal lesions with greater conspicuity compared with BS. Overall, a total of 29 skeletal lesions were detected using PS versus only 7 using BS. The additional presumed BM detected by PS were predominantly focal and asymmetric (in the extremities), thereby highly suggestive of BM rather than bone marrow metastases. Moreover, in one of the 3 pts, PS showed only BM, confirmed by RBS, with no apparent concomitant bone marrow involvement seen in the other 2 pts. No false-positive lesions were seen on BS or PS. Conclusion: Compared with BS, PS appears to be more sensitive and at least as specific for detecting BM and should therefore be utilized as an adjunctive approach in the assessment of NB pts. A comparison between PS and MIBG scintigraphy in this setting is warranted.

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Functional brain abnormality in MSA evaluated by Tc-99m HMPAO SPECT and statistical parametric mapping (SPM).

Quantitative evaluation of Tc-99m MDP uptake by growth plate in children with growing pains

M. Kameyama, T. Momose, A. Abe, S. Oku, S. Mizuno, Y. Kojima, K. Ohtomo. Department of Radiology, School of Medicine, the University of Tokyo, Tokyo, Japan.

M. Yilmaz (1), Y.Z. Celen (1), S. Zincirkeser (1), M. Karaoglan (2). (1) Department of Nuclear Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey, (2) Department of Pediatrics, Gaziantep University School of Medicine, Gaziantep, Turkey.

AIM: We evaluate functional brain abnormality in patients with multiple system atrophy (MSA). Materials and Methods: We performed Tc-99m HMPAO SPECT and analyzed regional cerebral blood flow (rCBF) data by statistical parametric mapping (SPM). Twenty-two patients with MSA (16 with olivopontocerebellar atrophy (OPCA) type and 6 with striatonigral degeneration (SND) type) and eleven normal control subjects were studied. Thirty minutes of SPECT data acquisitions were performed fifteen minutes after intravenous injection of 740 MBq of Tc-99m HMPAO. All transaxial images obtained were transformed into normal standard brain and smoothed. The rCBF distribution pattern of MSA group was compared with that of Normal control (N). And difference of rCBF distribution of SND type and OPCA type was also analyzed. In addition, we compared cortical CBF distribution of MSA patients with mild cognitive impairment and that of MSA patients without cognitive impairment. Results: Hypoperfusion in cerebellum, brain stem and frontal cortex were detected in MSA. Hypoperfusion in frontal cortex was detected both in MSA with and without cognitive impairment. There was no significant correlation between the degree of cognitive impairment and the degree of decreased perfusion in the frontal cortex. Striatal hypoperfusion was not detected even in the patients with SND, though all of them had striatal D2 receptor abnormalities in posterior part of putamen, which were detected on positron emission tomography (PET). Conclusion: SPM analysis demonstrated hypoperfusion in cerebellum, brain stem and frontal cortex in MSA. This rCBF pattern differs from that in patients with other types of parkinsonism, such as Parkinson’s disease, progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD) and diffuse levy body disease (DLBD) and other types of dementing conditions such as Alzheimer’s disease or fronto-temporal dementia (FTD).

Aim: Growing pains are recurrent, typically bilateral leg pains in children and are diagnosed by excluding all other possible causes. In this study, we aimed to evaluate quantitatively growth plate uptake of Tc-99m MDP in children with growing pains. Materials and methods: Eighteen children (11 M, 7 F; aged 6-12 yr) with growing pains were included in the study. They had been referred for bone scan to rule out an underlying bone pathology. Patients with bone and joint pathologies such as osteomyelitis, arthritis and history of trauma were excluded. Control group (n=15) was selected among the age-matched subjects without pain and abnormality in their lower extremities. Posterior planar image of the both knees was obtained 2-3 hr after injection of 7.4 MBq/kg Tc-99m MDP in addition to whole body bone imaging. A rectangular regions of interest (ROIs) were drawn over distal femoral growth plate (GP) and femoral diaphysis (D) of the more painful leg, and then for background activity (B) over soft tissue next to diaphysis. Mean counts were used to calculate the ratio between GP and D after subtracting background counts, and this was termed as growth plate index (GPI); (GPI=GP counts-B counts / D counts-B counts x 100). GPI values in growing pain group were compared to those in control group. Results: Visual evaluation of the bone scans was within normal limits. The mean GPI was 15.39±1.55 (range, 12.32 to 17.55) and 13.22±1.90 (range, 9.13 to 15.97) in growing pain and control groups, respectively. The difference between the two groups was statistically significant (p<0.05). Conclusion: Quantitative assessment of growth plate uptake of Tc-99m MDP may help to confirm the diagnosis of growing pains in children.

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Even in newborns and infants F-15 diuresis renography provides additional diagnostic information in cases of equivocal F+20 diuresis renograms M. Heinisch (1), M. Riccabona (2), L. Joerg (1), B. Wieser (1), E. Rechberger (1), P. Panholzer (1), W. Langsteger (1). (1) Department of Nuclear Medicine and Endocrinology, PET Center Linz, St. Vincent´s Hospital Linz, (2) Department of Pediatric Urology, St. Vincent´s Hospital Linz, Linz, Austria. Aim: To evaluate the results of F-15 diuresis renography (F-15 DR) in newborns/infants with equivocal renogram patterns on F+20 diuresis renograms (F+20 DR). F-15 DR is recommended in cases of equivocal results of F+20 DR, as thus a reduction of equivocal results can be achieved. However, if these findings can be applied to examinations in newborns/infants, too, is not entirely clear yet. Materials and Methods: 12 kidneys in 11 patients (mean age 8.9 months) with hydronephrosis (unilateral n=10, bilateral n=1) and equivocal renogram patterns on F+20 DR were further examined by F–15 DR performed on the following day. Hydration: intravenously, 15ml/kg. Tracer: Tc99m-MAG3, weight-adjusted dosage according to EANM recommendations. Furosemide:1mg/kg, 20 min p.i. (F+20), respectively 15min ante tracer injection (F-15). Calculation of Emax = elimination index (F+20 renograms) and T1/2 = elimination half-time (F-15 renograms). Renograms were scored according to O´Reilly. Results: The equivocal renogram patterns on F+20 DR were type IIIb in 11 cases and suspect Homsy-sign in one case. Applying the recommended cut-off values of Emax for F+20 DR (Emax < 7: obstructed, 7 14: not obstructed) 2 kidneys were to be considered as obstructed, 3 as not obstructed and 7, still, as equivocal. As to the F-15 renograms, applying the recommended cut-off value for T1/2 (20 min), 9 kidneys were to be considered as obstructed and 3 as not obstructed, respectively. Renogram patterns in the F-15 studies correlated well to the calculated figures: In none of the patients with prolonged T1/2 ( T1/2 >30 min: n=7, 30>T1/2> 20 min: n=2) an exponential-shaped renogram pattern in the washout phase could be observed. As compared to the visually interpreted F+20 DR, F-15 DR downgraded 3 kidneys (equivocal˜not obstructed), upgraded 8 (equivocal˜obstructed) and revealed obstruction in one case with Homsy-sign. As compared to the results of Emax-calculation in F+20 DR, F-15 DR downgraded one kidney (equivocal˜not obstructed), upgraded 7 (equivocal˜obstructed, n=6 and not obstructed˜obstructed, n=1) and was in accordance in 4 cases (not obstructed n=2, obstructed n=2). Conclusion: Even in newborns/infants F-15 diuresis renography delivers valuable additional information in cases of equivocal F+20 renograms. Thus it may help to more accurately separate those patients who probably require a very short follow-up interval -if not immediate surgical intervention- from those, for whom a longer follow-up intervall may be sufficient.

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Varability of 99mTc MAG3 renography Tmax and T1/2 values due to age and time of diuretic administration in pediatric patients. N. Yildirim, N.I. Karabacak, E. Cingi. Department of Nuclear Medicine of Gazi University Faculty of Medicine, Ankara, Turkey. AIM: The aim of this study was to assess normal ranges of (tmax and t ? ) and to evaluate the effects of age and time of diuretic administration on these parameters in a selected pediatric population (age under 6 year) with normal renograms.METHOD: A total of 87 kidneys with normal renograms were evaluated in four groups where 30 studies had F+0 diuretic renography protocol. Group 1: Under 2 years old and with F+0 diuretic protocol (n=21,mean age 13.7 months), Group 2: Under 2 years old and with F+20 or no diuretic administration (n=20, mean age 3.8 years old),Group 3: 2-6 years old and with F+0 diuretic protocol (n=20, mean age 14.4 months), Group 4: 2-6 years old and with F+20 or no diuretic administration (n=26,mean age 4.2 years old). After adequate hydration, standart MAG3 renal images were obtained for 40 minutes. Tmax, T1/2, were determined by using regions of interest (ROIs) over the cortex and renal background. RESULTS: The mean tmax and t1/2 values and 2 standart deviations for all groups were as follows; Group 1: 2.4±0.94 and 7.0±2.6, Group 2:2.9±0.88 and 6.2±2.7, Group 3: 2.5±0.76 and 5.2±1.5, Group 4:2.9±0.92 and 5.2±1.7 respectively. When compared with ANOVA, significant differences existed between tmax values between group 1 and 2 (p<0.001) as well as group 3 and 4 (p=0.001). For t1/2 values; there were significant differences between group 1 and 3 (p<0.001) as well as group 2 and 4 (p= 0.004). CONCLUSION: F+0 diuretic renography shortens the tmax values significantly in pediatric subjects and needs to be taken into consideration for this protocole for the evaluation of concentration function. Our findings also suggest that t1/2 values are relatively prolonged in children under 2 years old when compared with the older age group both in F+0 and F+20 protocoles most likely due to renal immaturity. These physiological variables must be taken into consideration during the interpretation of the diüretic renograms in pediatric population.

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A. Aydin (1), B. Degirmenci (2), C. Tasci (2), A. Soylu (3), R. Bekis (2), M. Turkmen (3), H. Durak (2), S. Kavukcu (3). (1) Department of Nuclear Medicine of the Gazi Osman Pasa University of Tokat, Turkey, (2) Department of Nuclear Medicine of the Dokuz Eylul University of Izmir, Turkey, (3) Department of Pediatri of the Dokuz Eylul University of Izmir, Turkey.

E. Gencoglu (1), G. Moray (2), M. Haberal (2). (1) Department of Nuclear Medicine of Baskent University Medical Faculty, Ankara, TURKEY, (2) Department of Surgery of Baskent University Medical Faculty, Ankara, Turkey.

Tc-99m MAG3 diuretic scintigraphy to evaluate congenital hydronephrosis in neonates and infants

AIM: To differentiate non-obstructive hydronephrosis from obstruction is an important point in clinical management in children within neonatal and early infancy periods. Since kidney dismaturation is a major problem in neonates and infants, we investigated the diagnostic value of Tc-99m MAG3 diuretic scintigraphy in neonates and children within early infancy period. METHOD:Twenty-six children (22 boys, 4 girls) were included in the study. Thirteen of them were neonates (mean age: 25.5 ± 5 days),13 of them were in early infancy period (mean age:6.6 ± 3 months). Unilateral hydronephrosis had been documented in all children ultrasonographically. Megaureter was present in 3 children. All children were well hydrated and urinary catheter was placed before Tc-99m MAG3 study. Dynamic images were obtained for 30 minutes after iv bolus injection of Tc-99m MAG3 (10mci/kg). At the 20th minute diuretic (furosemide;1mg/kg) was injected. Time-activity curves were obtained using standard software programe. The evaluation was as follows: 1)Non-obstructive pattern (NO), if more than 50% of activity in the renal pelvis is clearanced within 10 minutes. 2)Equivocal pattern (E), if the 50% of activity in the renal pelvis is clearanced up to 20 minutes 3)Obstructive pattern(O), if more than 50% of activity in the renal pelvis persists or gradually increasing activity is present in the renal pelvis at the 20 minute after iv diuretic injection. RESULTS: Tc-99m MAG3 scans were evaluated as NO, E and O in 14, 5 and 7 children respectively. Uretero-pelvic junction (UPJ) stenosis was found in 4, UPJ and vesicoureteral junction (VUJ) stenosis in 1, VUJ stenosis in 2 of 7 children with O. UPJ stenosis was present in 4 of 5 children with E. 13 of 14 children with NO were followed-up at least one year without evidence of obtruction in the urinary tract.The remaining child was operated for correction of vesicoureteral reflux. CONCLUSION: This study indicates that Tc-99m MAG3 diuretic scintigraphy is a useful method for differentiation of non-obstructive hydronephrosis from obstruction in neonates and early infancy periods.

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The value of quantitative Tc-99m DTPA scintigraphy for assessing pediatric renal transplant recipients

Aim: Kidney transplantation is the most effective therapy for children with end-stage renal failure. The post-transplantation period is a critical time for pediatric recipients because various complications which lead to graft dysfunction may arise during this time. Early diagnosis of rejection, acute tubular necrosis, toxisity of cyclosporin A , infection and planning a suitable therapy are very important in these patients. The aim of this study was to evaluate the value of serial quantitative Tc-99m DTPA scintigraphy for detecting and monitoring complications in pediatric renal transplant recipients. For this purpose we compared scintigraphic results to the results of fine needle aspiration biopsy. Materials and Methods: 18 pediatric patients that underwent renal transplantation (5F, 13M, mean age at transplantation was 13.6± 1.4 years) were studied. The median follow-up period after the transplantation was 4 years. Total 87 renal scintigraphies with Tc-99m DTPA were carried out in these patients during this period.The basal scintigraphy was performed 3 days after the transplantation. A large-field-of-view single-head gamma camera with a low-energy all-purpose collimator was used for image acquisition. Immediately after bolus injection of 259 MBq of Tc-99m DTPA anterior dynamic imaging was performed. The vascular and renographic phases were then evaluated quantitatively. The quantitative parameters used were perfusion index (PI), time to maximum activity (Tmax), time to half of maximum activity (T1/2 ), and glomerular filtration rate (GFR). Graft kidney aspiration biopsy was performed in all cases that showed abnormal scintigraphic parameters, and then scintigraphic results and biopsy results were compared. Results: In 9/18 pediatric recipients, scintigraphic findings were normal throughout the study. In the other 6 patients, scintigraphic results that were agreed biopsy results were abnormal in the early post-operative period. The renal graft biopsies from these six patients showed 4 acute rejection episodes and 2 acute tubular necrosis attacks. Four of these 6 patients’ scintigraphic parameters returned to normal levels after these complications and normal values remained constant throughout the follow-up period. In the 3/18 recipients that had shown normal scintigraphic findings previously, exhibited abnormal PI, Tmax, T1/2, and GFR values in the late post-transplantation period and these parameters gradually deteriorated in the serial scintigraphies. In these patients, graft biopsies showed chronic rejection. Conclusion: Based on these findings, we conclude that serial quantitative Tc-99m DTPA scintigraphy is a useful method for the detecting and monitoring complications in pediatric patients that underwent renal transplantation.