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)

The differential diagnosis and management of Cushing's syndrome remain difficult, particularly for ectopic adrenocorticotropin (ACTH) syndromes resulting from small bronchial carcinoids. We report the case of a 41-year-old man with ectopic ACTH-dependent Cushing's syndrome. Two computed tomography scans of the thorax were normal and magnetic resonance imaging of the chest showed a 6-mm hyperintense T1-weighted area close to the left pulmonary hilus, interpreted as probably vascular by the radiologists. An [111In-DTPA-D-Phe1]octreotide scintigraphy scan demonstrated a positive image for somatostatin receptors in exactly the same location and surgery confirmed the presence of a small ACTH-secreting carcinoid tumour in the upper left lung lobe which was resected. Surgery cured the hypercorticism of the patient. The differential diagnosis of Cushing's syndrome and the procedure for localisation of an ACTH source are discussed.
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PMID:Ectopic Cushing's syndrome and pulmonary carcinoid tumour identified by [111In-DTPA-D-Phe1]octreotide. 961 93

An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was relatively stable in human serum (t1/2 3.8 d for 90Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2 12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90Y radiotherapy of somatostatin receptor-positive tumours and their metastases.
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PMID:Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours. 962 Jun 21

Recent studies have shown successful therapy with the long-acting somatostatin (SM) analogues octreotide and lanreotide in patients with thyroid eye disease (TED). In one such study it was also found that response to low-dose octreotide treatment (300 microg) in these patients was correctly predicted by [111In-DTPA-D-Phe1]-octreotide scintigraphy and concluded that this parameter should be used as a predictive test of the effectiveness of treatment with nonradioactive octreotide. It has also been suggested that octreoscan-111 may be seen as a parameter of disease activity in TED. However, it remains to be clarified whether octreoscan-111 predicts the therapeutic outcome better than the clinical activity score, or magnetic resonance imaging (MRI) or finally measurement of glucosaminoglycan (GAG) in the plasma and/or urine. The exact mechanism of action of SM analogues has not yet been fully clarified. Three explanations may be offered. First, SM suppresses insulin-like growth factor 1 (IGF-1) activity and inhibits IGF-1-mediated effects. A second possible mechanism could be the direct inhibition of the release of cytokines from T-lymphocytes, and finally, SM analogues may act on target cells through specific cell surface receptors. In view of the encouraging therapeutic results reported thus far in several studies, SM analogues may provide a valuable therapeutic alternative to corticosteroids, especially in patients who cannot tolerate the latter. However, further prospective, placebo-controlled studies with a large number of patients are needed before we can reach final conclusions.
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PMID:Somatostatin analogues in the treatment of thyroid eye disease. 962 41

The somatostatin analogue [111In-DTPA-d-Phe1]-octreotide (111In-octreotide) allows scintigraphic visualization of somatostatin receptor-expressing tissue. While it is well known that a large variety of tissues express somatostatin receptors and 111In-octreotide scintigraphy has a clearly defined role in various neuroendocrine diseases, the clinical value of 111In-octreotide scintigraphy in brain tumours is still under clinical investigation. In 124 patients with 141 brain lesions (63 meningiomas, 24 pituitary adenomas, 10 gliomas WHO class I and II, 12 gliomas WHO class III and IV, 11 neurinomas and 2 neurofibromas, 7 metastases and 12 other varieties: three non-Hodgkin B-cell lymphomas, two epidermoids, one abscess, one angioleiomyoma, one chordoma, one haemangiopericytoma, one osteosarcoma, one plasmacytoma and one pseudocyst), 111In-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 110-220 MBq 111In-octreotide. Planar images of the head in four views with a 128x128 matrix and single-photon emission tomographic images (64x64 matrix) were acquired, and lesions were graded according to qualitative tracer uptake. Fifty-nine of the 63 meningiomas showed moderate to intense tracer uptake. Nine of 24 pituitary adenomas were visible; the remaining 15 did not show any tracer uptake. None of the class I and II gliomas with an intact blood-brain barrier were detected whereas 11/12 class III and IV gliomas showed 111In-octreotide uptake. None of the neurinomas or neurofibromas were positive. Five of seven metastases were classified as positive, as were the osteosarcoma, two of three non-Hodgkin B-cell lymphomas, one abscess, one angioleiomyoma, one chordoma and one haemangiopericytoma. The other varieties (one non-Hodgkin B-cell lymphoma, two epidermoids, one plasmacytoma and one pseudocyst) did not show 111In-octreotide uptake. The results demonstrate that a large variety of intracranial lesions express somatostatin receptors and therefore can be visualized by [111In-DTPA-d-Phe1]-octreotide scintigraphy. This technique can be valuable in the differentiation between meningiomas and pituitary adenomas, based on qualitative tracer uptake. [111In-DTPA-d-Phe1]-octreotide scintigraphy allows differentiation between meningiomas and neurinomas or neurofibromas and therefore provides complementary information to computed tomography or magnetic resonance imaging. Furthermore, this technique allows differentiation between scar tissue and recurrent meningiomas postoperatively and can help in non-invasive tumour differentiation of multiple intracranial lesions, which can be of value in defining the most adequate therapeutic strategy.
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PMID:Somatostatin receptor imaging in intracranial tumours. 966 88

A wide variety of neuroendocrine tumours express somatostatin receptors, and can be visualized by radiolabelled somatostatin analogue scintigraphy. To investigate the value of [111In]-octreotide scintigraphy (Octreoscan), 48 patients (37 with proven carcinoid, pancreatic endocrine and medullary carcinoma of thyroid tumours, 11 with neuroendocrine syndromes multiple endocrine neoplasia (MEN-I) and Zollinger-Ellison syndrome (ZES) were examined with 111In-DTPA-D-Phe1-octreotide. Scintigrams were obtained at 24 and 48 h, and the results were compared with CT and magnetic resonance imaging (MRI). Thirty-five of 48 patients had positive [111In]-octreotide scintigraphy (23/25 (92%) carcinoids, 8/9 (89%) PETs, 4/11 (36%) MEN-I & ZES). Of the 42 lesions located by conventional imaging techniques, 37 (88%) were also identified by Octreoscan. Unexpected lesions (40 sites), not detected by CT or MR imaging were found in 24/48 (50%) patients. [111In]-octreotide scintigraphy has a higher sensitivity for tumour detection, and is superior to MR imaging and CT scanning in the identification of previously unsuspected extraliver and lymph node metastases. It may also be helpful for the localization of clinically suspected tumours in patients with MEN-I and ZES.
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PMID:Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. 966 53

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.
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PMID:Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings. 1004 54

Granulomatous diseases can be visualized in vivo after the injection of indium-111-DTPA-octreotide (111In-pentetreotide), a radiolabelled somatostatin analogue. We evaluated whether somatostatin receptor imaging reflects disease activity, whether certain scintigraphic characteristics can predict the disease prognosis and whether repeat scintigraphy correlates with the clinical course in patients with sarcoidosis. 111In-pentetreotide was injected in 46 patients and images were obtained 24 h later. Known mediastinal, hilar and interstitial disease was recognized in 36 of 37 patients. Also, such pathology was found in seven other patients who had normal chest X-rays. In five of these, somatostatin receptor imaging pointed to interstitial disease. Frequently, accumulation of radioactivity in parotid glands and supraclavicular lymph nodes was found. Neither the degree of radioactive accumulation in the thorax nor a specific pattern of pathological uptake was correlated with disease severity or clinical course. The degree of uptake of radioactivity in the parotid glands was correlated with significantly higher serum angiotensin-converting enzyme (ACE) levels. Somatostatin receptor imaging was repeated in 13 patients. In five of six patients in whom chest X-ray monitored improvement of disease activity, the pentetreotide scintigram also showed a decrease in pathological uptake. In two of five patients in whom the chest X-ray was unchanged, but serum ACE concentrations had decreased and lung function improved, normalization on pentetreotide scintigrams was found. It is concluded that: (1) somatostatin receptor imaging can demonstrate active granulomatous disease in patients with sarcoidosis; (2) pathological uptake of radioactivity in the parotid glands during somatostatin receptor imaging is correlated with higher serum ACE concentrations; (3) the value of somatostatin receptor imaging in the follow-up of patients with sarcoidosis will have to be determined in a prospective longitudinal study.
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PMID:Somatostatin receptor imaging in patients with sarcoidosis. 972 78

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.
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PMID:Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy. 981 48

In vitro studies have shown that gastroenteropancreatic tumors, with the exception of insulinomas, have a high density of somatostatin receptors and can be imaged in vivo using somatostatin receptor scintigraphy (SRS) with either [123I-Tyr3]octreotide or [111In DTPA,DPhe1]octreotide. However, the sensitivity in relation to conventional imaging studies (ultrasound, CT, MRI, angiography) remains unclear. To address this question, we performed a prospective study of 80 patients with gastrinomas where SRS was compared with other conventional imaging techniques for detecting extrahepatic gastrinomas or liver metastases. Extrahepatic gastrinomas were identified by SRS in 58 percent of patients, whereas conventional imaging studies detected gastrinomas in 9 percent to 48 percent of patients. In detecting hepatic metastases in 24 patients with histologically-proven metastases, SRS was positive in 92 percent; ultrasound, CT or angiography in 42 percent to 62 percent; and MRI in 71 percent of patients. These results are compared with other studies in detecting gastrinomas as well as series including other PETs, excluding insulinomas, with insulinomas alone, and with carcinoid tumors. An analysis of the ability of SRS to identify gastrinomas found in different sites at surgery was performed. The role of endoscopic ultrasound (EUS) in detecting various PETs, in comparison to that of SRS, is yet to be established, particularly for extrapancreatic PETs. Therefore, the results of EUS in various studies containing patients with PETs are compared to those with SRS and conventional imaging studies. These data suggest that EUS is the first choice of localization methods for detecting insulinoma, which is an intrapancreatic tumor in almost all cases. In other PETs there still is not sufficient data to establish the relative roles of EUS and SRS.
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PMID:Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors. 982 78

Scintigraphy with 111In-DTPA-octreotide (111In-octreotide) enables the localization of tumours with somatostatin receptors on their cell membranes, of which pituitary adenomas are an example. Trans-sphenoidal excision of such tumours is sometimes incomplete and the detection of post-surgical residues is a difficult diagnostic task. In this study, we used 111In-octreotide SPET to visualize pituitary adenomas and their minimal residues. In positive cases, the indirect demonstration of the presence of somatostatin receptors may be decisive for the planning of treatment. 111In-octreotide SPET was able to visualize adenomas in 21 of 27 patients (77.7%) (10 GH-secreting, 10 PRL-secreting and 1 non-secreting). Repeat SPET after the recurrence of clinical symptoms and hormone hypersecretion revealed intense 111In-octreotide uptake by residues in 8 of 10 patients (4 GH-secreting and 6 PRL-secreting). Magnetic resonance imaging was positive in only 3 of these 10 patients. Our results suggest that 111In-octreotide SPET, in combination with other imaging modalities, is useful in the diagnosis and follow-up pituitary adenomas. It ensures better selection of patients for treatment with somatostatin analogues, both pre- and post-operatively, and assists in the development of personalized treatment plans.
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PMID:Pituitary adenomas: the role of 111In-DTPA-octreotide SPET in the detection of minimal post-surgical residues. 988 2


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