Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and DTPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of 123I-Tyr3-octreotide undergoes hepatobiliary excretion, 111In-DTPAPhe1-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventional Fab-like fragments.
 ...
PMID:Radiolabeled octreotide. What lessons for antibody-mediated targeting? 128 34

A wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had been surgically removed from 31 patients by use of in vitro SS-R autoradiography with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade-malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high-grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS-Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma-camera scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]-octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R-positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS-Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.
 ...
PMID:In vitro and in vivo detection of somatostatin receptors in human malignant lymphomas. 134 40

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.
 ...
PMID:Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. 134 39

In this review, we evaluate radiological techniques currently used to localize gastroenteropancreatic (GEP) endocrine tumors. We also describe the visualization, using intravenous (IV) administration of two isotope-labeled somatostatin analogues (123I-Tyr3-octreotide and 111In-DTPA-octreotide) of islet-cell tumors in 25 patients and carcinoids in 39 patients. The primary tumor and previously unrecognized distant metastases were visualized in 20 of the 25 patients (80%) and in 37 of the 39 patients (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 that is 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.
 ...
PMID:The visualization of gastroenteropancreatic endocrine tumors. 135 84

Various tumors of neuroendocrine origin that have amine precursor uptake and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous (IV) injection of the somatostatin analogue, [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks to its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]- octreotide) was developed. This analogue is excreted mainly via the kidneys, with 90% of the dose being present in the urine 24 hours after injection. Using 111In-octreotide scintigraphy, seven of seven gastrinomas, four of seven insulinomas, one of one glucagonomas, three of three unclassified APUDomas, and none of 18 exocrine pancreatic carcinomas were visualized. Also, 19 of 19 carcinoids, 15 of 15 glomus tumors, eight of 12 medullary thyroid carcinomas, six of six small-cell lung carcinomas, four of four growth hormone-producing and six of nine clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied in visualizing breast cancer, lymphomas, and granulomas. In 39 of 50 patients with breast carcinoma, 10 of 11 patients with non-Hodgkin's lymphomas, three of three patients with Hodgkin's disease, and eight of eight patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, and also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy showed more tumor sites than did conventional imaging techniques. The results of imaging in vivo correlated with the somatostatin-receptor status on the tumors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:111In-octreotide scintigraphy in oncology. 135 91

Radioiodinated somatostatin analogues are useful ligands for the in vitro and in vivo detection of somatostatin receptors. [111In-DTPA-D-Phe1]-octreotide, a somatostatin analogue labeled with a different radionuclide, also binds specifically to somatostatin receptors in vitro. In this study we investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. After injection the radiopharmaceutical was rapidly cleared (50% decrease in maximal blood radioactivity in 4 min), predominantly by the kidneys. Excreted radioactivity was mainly in the form of the intact radiopharmaceutical. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of [111In-DTPA-D-Phe1]-octreotide in the tumors was prevented. Because of its relatively long effective half-life, [111In-DTPA-D-Phe1]-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance. This is an advantage over the previously used [123I-Tyr3]-octreotide which has a shorter effective half-life and shows high abdominal interference due to its hepato-biliary clearance. Therefore, [111In-DTPA-D-Phe1]-octreotide seems a better alternative for scintigraphic imaging of somatostatin receptor-bearing tumors.
 ...
PMID:In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats. 165 16

Increased glomerular filtration rate (GFR) is considered to be a determinant factor in the pathogeny of diabetic nephropathy. In this study we analyzed the effect of a long-acting somatostatin analog (SMS 201-995) on high GFR in type I diabetes patients. Five subjects were involved in a cross-over double blind study. All the patients had a high GFR (205 +/- 18 ml/min/1.73 m2). They were randomly submitted to a 10-hour night i.v. infusion of SMS 201-995 at a rate of 8 g/min and placebo. GFR was measured using a blood 99mTc-DTPA decay curve during the last hour of infusion. After 10-hour SMS 201-995 treatment, no statistical change was observed in GFR. However, a slight decrease was noted in four of the five subjects (183.07 +/- 22.31 vs 202.83 +/- 13.23 ml/min/1.73 m2). GFR was higher only for the patient who presented with a mild hypoglycemic reaction during the infusion, which may increase glomerular filtration by itself. All the other parameters measured remained unchanged.
 ...
PMID:Effect of long-acting somatostatin analog (SMS 201-995) on high glomerular filtration rate in insulin dependent diabetic patients. 238 55

Thirty-one patients with metastatic hormone-refractory prostatic adenocarcinoma were investigated scintigraphically with the 111In-labeled somatostatin analogue [DTPA-D-Phe1]-octreotide (OctreoScan) and with 99mTc-labeled HDP. In vitro somatostatin receptor autoradiography was performed on biopsies obtained from eight patients with hormone-refractory prostatic adenocarcinoma. In 30 of 31 patients (94%), at least one metastasis was positive at OctreoScan scintigraphy. Of the 346 lesions detected with 99mTc-labeled HDP bone scintigraphy, 128 were visualized with the OctreoScan technique, thus accounting for a 37% detection rate. Two uptakes on OctreoScan could not be identified on bone scintigraphy and were, thus, assessed as false positive. The biopsies of the eight patients disclosed a low density of receptors, localized on the tumor cells, as demonstrated with receptor autoradiography. Two patients with untreated metastatic prostatic adenocarcinoma were investigated in vivo before the start of endocrine therapy. However, none of the lesions detected by bone scintigraphy in these patients could be visualized with the OctreoScan technique. Positron emission tomography using [11C] methionine showed a decreased uptake in a metastatic index lesion in a patient treated with octreotide. It is concluded that hormone-refractory prostatic adenocarcinoma expresses somatostain receptors both in vitro and in vivo. The results obtained form the basis for the development of a new tool for in vivo characterization and of a new treatment strategy in patients with hormone-refractory prostatic adenocarcinoma.
 ...
PMID:Metastatic hormone-refractory prostatic adenocarcinoma expresses somatostatin receptors and is visualized in vivo by [111In]-labeled DTPA-D-[Phe1]-octreotide scintigraphy. 749 50

Somatostatin, a naturally occurring 14-amino acid peptide, can be thought of as an anti-growth hormone and functional down-regulator of sensitive tissue. Most neuroendocrine tumors seem to possess somatostatin receptors in sufficient abundance to allow successful scintigraphic imaging with radiolabeled somatostatin congeners. Several of these, including Indium-III-DTPA Pentetreotide (Octreoscan [Mallinckrodt Medical, St. Louis, MO]), which was approved for clinical use by the Food and Drug Administration in June 1994, have been of considerable value in scintigraphically identifying various neuroendocrine tumors. The Octreoscan compares favorably with other imaging modalities. The success of somatostatin receptor imaging in evaluating patients with suspected neuroendocrine tumors, including identifying otherwise radiographically occult lesions, has resulted in ranking somatostatin receptor imaging as the prime imaging procedure in patients with suspected neuroendocrine tumors at The Ohio State University.
 ...
PMID:Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan). 757 44

Patients with Hodgkin's or non-Hodgkin's lymphoma are staged for treatment based on the extent of known disease involvement and the histopathologic grading of the disease. Radiological techniques, including computed tomography, usually depend on estimates of lymph node enlargement and mass effects as the criterion for disease involvement. Lymphomatous tissue obtained at surgery has shown high-density somatostatin receptors. Several groups have evaluated the utility of 111In-DTPA-pentetreotide (Octreoscan, Mallinckrodt, St. Louis, MO) to detect lymphomatous tissue for more accurate staging of patients with lymphoma. The procedure is safe; both Hodgkin's and non-Hodgkins disease involvement is identified. The results, however, have not been uniformly predictive of disease involvement. Consequently, the routine use of this technique in place of currently used anatomic imaging methods is not recommended at this time. The significance of detecting somatostatin receptors in vivo in patients with malignant lymphoma requires further study.
 ...
PMID:Somatostatin-receptor imaging in lymphoma. 757 45


1 2 3 4 5 6 7 8 9 10 Next >>