Eur J Nucl Med

Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours.

Adams S. Baum R. Rink T. Schumm-Drager PM. Usadel KH. Hor G.
Department of Nuclear Medicine, University Medical Center, Frankfurt/Main, Germany.
Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.

Somatostatin receptor scintigraphy using [111In-DTPA0]RC-160 in humans: a comparison with [111In-DTPA0]octreotide.

Breeman WA. van Hagen PM. Kwekkeboom DJ. Visser TJ. Krenning EP.
Department of Nuclear Medicine, University Hospital "Dijkzigt", Rotterdam, The Netherlands.
Somatostatin receptor-positive lesions can be visualized by scintigraphy using [111In-DTPA0]octreotide. Recently, there have been reports of differences in receptor binding between somatostatin receptor subtypes and between somatostatin analogues, such as RC-160 and octreotide, as well as of differences in internalization between the somatostatin receptor subtypes. The possibility that certain somatostatin receptor-positive tissues and tumours which do not bind octreotide may bind and internalize RC-160 would open new scintigraphic or radiotherapeutic applications of radiolabelled RC-160. We investigated the metabolism and tissue distribution of [111In-DTPA0]RC-160 in comparison with [111In-DTPA0]octreotide in four patients after injection of 250 MBq (10 microgram) of these radiopharmaceuticals. Patient 1 had a metastatic follicular thyroid carcinoma, patient 2 a metastatic medullary thyroid carcinoma, patient 3 tuberculosis and patient 4 an insulinoma. The plasma clearance of the [111In-DTPA0]RC-160 was slower than that of [111In-DTPA0]octreotide, with 5% and 2%, respectively, of the initial plasma radioactivity remaining at 10 h p.i. The urinary excretion of [111In-DTPA0]RC-160 was initially also slower than that of [111In-DTPA0]octreotide, but the cumulative excretion of radioactivity was not significantly different at 48 h p.i. Approximately 80% of injected radioactivity was cleared in the urine, while in one patient 20% of the injected dose was recovered in the faeces. The slower clearance of [111In-DTPA0]RC-160 resulted in a higher background in all organs studied i.e. liver, spleen, kidneys and lungs, at 24 h p.i. Although the target to background ratio with [111In-DTPA0]octreotide was higher, no differences were found between the two analogues with regard to their sensitivity in detecting lesions in these four patients. We conclude that although only four subjects were studied, [111In-DTPA0]RC-160 does not appear to have additional value for scintigraphy and is associated with higher background activity.

In vivo evaluation of a lead-labeled monoclonal antibody using the DOTA ligand.

Year 1998
Milenic DE. Roselli M. Brechbiel MW. Pippin CG. McMurray TJ. Carrasquillo JA. Colcher D. Lambrecht R. Gansow OA. Schlom J.
Laboratory of Tumor Immunology and Biology, National Cancer Institute, The National Institutes of Health, Bethesda, MD 20892, USA.
The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with 203Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-125I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the 203Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as immunoscintigraphy studies. Such data highlight the stability of a lead radionuclide in the DOTA ligand. The suitability of this chelation chemistry for labeling radioimmunoconjugates with a lead radionuclide now makes its application in nuclear medicine a feasible proposition.

Focal fluorine-18 fluorodeoxyglucose accumulation in inflammatory pancreatic disease.

Year 1998
Shreve PD.
Department of Nuclear Medicine, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
Focal 2-deoxy-2[fluorine-18]fluoro-D-glucose (FDG) uptake on positron emission tomography (PET) in a pancreatic mass has been reported as a specific finding for pancreatic carcinoma. Inflammatory conditions of the pancreas and associated clinical circumstances yielding similar findings have not yet been fully defined. Among 42 patients studied by attenuation-corrected FDG PET for pancreatic disease, 12 with focal FDG uptake in the pancreas were identified as having no underlying neoplasm based on surgical findings, biopsy results, and long term clinical and imaging follow up. Focal FDG accumulation in the pancreas with standardized uptake values ranging from 3.4 to 11.2 on FDG PET was ultimately found to be related to inflammation rather than neoplasm. This occurred in pancreatic masses in which clinical and laboratory evidence of acute pancreatitis was equivocal or entirely lacking, as well as in the setting of acute pancreatitis and after recovery from acute pancreatitis. Inflammation can give rise to focal FDG uptake in the same intensity range as pancreatic neoplasm, even when clinical, laboratory and computed tomographic findings suggestive of an inflammatory etiology are equivocal or absent.