(dtpa-phe(1))-octreotide and Adenoma--Islet-Cell

Neuroendocrine tumors of the gastrointestinal tract are rare tumors that can be classified as APU-Domas (amine precursor uptake and decarboxylation). They can be subdivided into the carcinoid tumors of the gastrointestinal submucosa and the islet cell endocrine tumors of the pancreas. Although the majority of tumors that become clinically apparent are malignant, they are frequently slow growing. Despite this, neuroendocrine tumors may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better radiographic imaging and more accurate localization techniques. Medical therapies with somatostatin analogues, omeprazole, and locoregional tumor ablation have made a positive impact on curative and palliative therapy. This review updates the recent efforts made in the radiographic imaging and therapeutics of the gastrointestinal neuroendocrine tumors.

Topics: Adenoma, Islet Cell; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biogenic Amines; Carcinoid Tumor; Clinical Trials as Topic; Diagnostic Imaging; Embolization, Therapeutic; Gastrointestinal Neoplasms; Hepatic Artery; Humans; Indium Radioisotopes; Ligation; Liver Neoplasms; Octreotide; Palliative Care; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Pentetic Acid; Receptors, Somatostatin

In this review, we evaluate radiological techniques currently used to localize gastroenteropancreatic (GEP) endocrine tumors. We also describe the visualization, using intravenous administration of two isotope-labelled somatostatin analogs (123-I-Tyr3-octreotide and 111In-DTPA-octreotide), of islet cell tumors in 25 patients and carcinoids in 39 patients. The primary tumor as well as previously unrecognized distant metastases were visualized in 20 of the 25 patients (80%) and in 37 of the 39 (95%). Parallel in vitro detection of somatostatin receptors on those tumors also visualized in vivo showed that ligand binding to the tumor in vivo represents binding to specific somatostatin receptors. The detection of somatostatin receptors on tumors in vivo predicted a good suppressive effect of octreotide on hormonal hypersecretion by these tumors. It is an easy, quick and harmless procedure, valuable in the localization of primary endocrine pancreatic tumors and their often radiologically and clinically unrecognized metastases. Future prospective controlled studies comparing this procedure with other radiological investigative techniques should demonstrate its sensitivity and specificity and determine the place of somatostatin receptor imaging in the localization of GEP endocrine tumors.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Diagnostic Imaging; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Iodine Radioisotopes; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Receptors, Somatostatin

64Cu (half-life, 12.7 h; beta+, 0.653 MeV [17.4%]; beta-, 0.579 MeV [39%]) has shown potential as a radioisotope for PET imaging and radiotherapy. (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe1-octreotide (OC) was developed for imaging somatostatin-receptor-positive tumors using conventional scintigraphy. With the advantages of PET over conventional scintigraphy, an agent for PET imaging of these tumors is desirable. Here, we show that 64Cu-TETA-OC (where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) and PET can be used to detect somatostatin-receptor-positive tumors in humans.. Eight patients with a history of neuroendocrine tumors (five patients with carcinoid tumors and three patients with islet cell tumors) were imaged by conventional scintigraphy with (111)In-DTPA-OC (204-233 MBq [5.5-6.3 mCi]) and by PET imaging with 64Cu-TETA-OC (111 MBq [3 mCi]). Blood and urine samples were collected for pharmacokinetic analysis. PET images were collected at times ranging from 0 to 36 h after injection, and the absorbed doses to normal organs were determined.. In six of the eight patients, cancerous lesions were visible by both (111)In-DTPA-OC SPECT and 64Cu-TETA-OC PET. In one patient, (111)In-DTPA-OC showed mild uptake in a lung lesion that was not detected by 64Cu-TETA-OC PET. In one patient, no tumors were detected by either agent; however, pathologic follow-up indicated that the patient had no tumors. In two patients whose tumors were visualized with (111)In-DTPA-OC and 64Cu-TETA-OC, 64Cu-TETA-OC and PET showed more lesions than (111)In-DTPA-OC. Pharmacokinetic studies showed that 64Cu-TETA-OC was rapidly cleared from the blood and that 59.2% +/- 17.6% of the injected dose was excreted in the urine. Absorbed dose measurements indicated that the bladder wall was the dose-limiting organ.. The high rate of lesion detection, sensitivity, and favorable dosimetry and pharmacokinetics of 64Cu-TETA-OC indicate that it is a promising radiopharmaceutical for PET imaging of patients with neuroendocrine tumors.

Topics: Adenoma, Islet Cell; Aged; Animals; Carcinoid Tumor; Female; Gastrointestinal Neoplasms; Humans; Indium Radioisotopes; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Papio; Pentetic Acid; Radiation Dosage; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Tomography, Emission-Computed

The distribution and elimination characteristics of the 111In-labelled somatostatin analogue OctreoScan111 were studied in 23 patients with malignant tumours. The substance exhibited a rapid blood elimination following a bi-phasic pattern. The initial part of the elimination curves showed a t1/2a of between 0.27 and 3.6 h. The patients investigated had creatinine clearance rates ranging from 33 to 124 ml/min. However, within this range, no apparent correlation was found between the OctreoScan111 elimination rate and kidney function. Also no correlation was observed between the amount of administered activity and the elimination rate of OctreoScan111. The serum radioactivity of 6 patients was analyzed with respect to molecular size. These experiments showed that OctreoScan111 circulated unbound in serum. About 3% of the radioactivity, most probably representing 111In-chloride of DTPA-111In-chloride, circulated protein-bound. The elimination of OctreoScan111 radioactivity in urine displayed a bi-phasic pattern. Size separation of the radioactivity appearing in the urine after 24 h showed a higher molecular weight when compared with OctreoScan111, indicating the existence of a metabolite of the injected substance. The results obtained are discussed in the light of a potential role for the substance in systemic radiotherapy.

Topics: Adenoma, Islet Cell; Adult; Aged; Carcinoid Tumor; Chromatography, Gel; Endocrine Gland Neoplasms; Female; Half-Life; Humans; Indium Radioisotopes; Kidney; Male; Middle Aged; Molecular Weight; Neoplasms; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Thyroid Neoplasms

Somatostatin (SRIF) receptors are present in a variety of human tumors such as pituitary and endocrine pancreatic tumors, brain tumors, small cell lung cancers and malignant breast tumors. The 111In-labeled SRIF analog SDZ 215-811 (OctreoScan 111) binds with a high affinity to somatostatin receptors and exhibits SRIF-like biological properties, as demonstrated by the inhibition of growth hormone release from pituitary cells. We report here the in vitro characterization of SDZ 215-811 and the in vivo imaging of an islet cell tumor grown in rats using [111In]SDZ 215-811. In vitro autoradiographies revealed a high density of SRIF receptors on the pancreatic tumor tissue. As early as 5 min after intravenous injection of [111In]SDZ 215-811 into tumor-bearing rats, the tumors were clearly localized by gamma-camera scintigraphy. Even 24 h post injection, the islet cell tumor was still detectable. The radioligand was mainly cleared from the circulation via the kidneys, with a rapid alpha-phase (t1/2 = 5.6 min) and a slow elimination phase (t1/2 = 7.3 h). Biodistribution studies revealed a relatively high accumulation of radioactivity in the kidneys, but low uptake into the liver and the intestine. High uptake of [111In]SDZ 215-811 was observed for the tumor tissue (0.92 +/- 0.07% ID/g; 1 h post injection). Interestingly, a tumor load of 0.14 +/- 0.01% ID/g was still measured after 24 h. The tumor/blood ratio was 4.93 after 24 h, indicating specific accumulation of radioactivity in the islet cell tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma, Islet Cell; Animals; Indium Radioisotopes; Iodine Radioisotopes; Octreotide; Pancreatic Neoplasms; Pentetic Acid; Radionuclide Imaging; Rats; Receptors, Somatostatin; Tissue Distribution