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)

Gamma-emitting radiopeptides are useful for scintigraphy of tumours on the basis of receptor binding. Likewise, beta-emitting radiopeptides may be used in radionuclide therapy of such tumours. As iodine-131 suggested to be suitable for this purpose, experiments were performed using three somatostatin analogues, in which the effects of coupling of a therapeutic dose of 131I to such peptides were investigated. This study deals with the radioiodination of very small amounts of peptide on a therapeutic scale, the required purification procedures after radioiodination, and the influence of high beta fluxes from 131I on a peptide during radioiodination and purification. Based on the regularly used therapeutic doses of 131I in cancer treatment and our previous experience with [111In-DTPA-D-Phe1]-octreotide, it was assumed that a minimal effective therapeutic dose of 3.7 GBq 131I has to be coupled to a maximum of approximately 100 microg peptide, representing only a slight excess of peptide over 131I. This contrasts with non-peptide radiopharmaceuticals in which high compound to radionuclide ratios are usually used. Labelling at low peptide to radionuclide ratios (low labelling yields) results in the formation of di-iodinated compounds, whereas at high peptide to radionuclide ratios (high labelling yields) mono-iodinated products of low specific activity are formed. Thus, after radioiodination the desired mono-iodinated peptide has to be separated from unreacted iodide, and from di-iodinated and unreacted peptide, as both compounds compete for the receptors. Possible radiolysis of the peptide during labelling and separation steps were investigated by irradiating 30 microgram unlabelled peptide with 370 MBq 131I in a small volume. The peptide composition of the incubation mixtures was investigated by high-performance liquid chromatography after irradiation for 30 min to 24 h. The results showed that the peptide was degraded with a half-life of less than 1 h. During the preparation of a real therapeutic dose (at much higher beta-flux) the peptide will be degraded even faster during the various steps required. In conclusion, intact mono-iodinated 131I-labelled somatostatin analogues for peptide receptor therapy will be difficult to obtain.
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PMID:Iodine-131 labelled octreotide: not an option for somatostatin receptor therapy. 866 16

Somatostatin receptor scintigraphy (SRS) was evaluated in 25 differentiated thyroid carcinoma (DTC) patients. All DTC patients had elevated thyroglobulin levels. A total body scan (TBS) was performed 4 and 24 h after injection of indium-111-DTPA-Phe-octreotide. Group 1 included 16 patients with negative 131I TBS; group 2 had 9 patients with positive 131I TBS. SRS results were compared to the results of conventional imaging methods in group 1 and to 131I TBS in group 2. 131I TBS was performed after administration of a therapeutic dose of 131I in all patients except one. SRS was positive in 20 of 25 (80%) patients. In group 1, SRS was positive in 12 of 16 patients; in the 3 patients with no previously known tumor site, SRS visualized one abnormal neck focus of uptake in two. In the other 13 patients, SRS disclosed unknown mediastinal foci in 2, but visualized less organ involvements and a smaller number of tumor sites than conventional imaging methods. In group 2, SRS was positive in 8 of 9 patients and visualized an identical (7 patients) or a smaller number (1 patient) of involved organs than 131I TBS; in 2 patients, SRS allowed the discovery of 1 abdominal and 1 bone tumor site. We suggest than SRS should guide imaging modalities in DTC patients with negative 131I TBS and be an alternative to 131I TBS in DTC patients unable to withdraw T4 treatment.
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PMID:Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patients with negative radioiodine scan. 867 74

The differential diagnosis of tumours in the skull base is often difficult. With the experience that various intracranial tumours differ in their expression of somatostatin binding sites (SBS) somatostatin receptor scintigraphy (SRS) with the somatostatin analogue octreotide can give additional information of the tumour entity. Seventy patients with various tumours of the skull base were examined with 111Indium-labelled DTPA-octreotide injected i.v.. Planar and tomographic images were obtained with a gamma camera 4-6 and 24 hours after injection. All of the meningiomas (unifocal and multifocal tumours in various locations) showed a high density of SBS whereas in none of the examined neurinomas SR were found. Pituitary adenomas revealed in only 50% SR in different concentrations and independent of the endocrine activity. SRS can help in the differential diagnosis between meningiomas and other tumours, postoperative scar or radionecrosis at the skull base. A dural infiltration with meningioma tissue ("meningeal sign") may be discriminated from a reactive hypervascularisation in lesions with a diameter > 0.5 cm. We conclude that SRS can offer additional diagnostic aspects in the pre- and postoperative management of patients with skull base tumours.
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PMID:Clinical relevance of somatostatin receptor scintigraphy in patients with skull base tumours. 873 8

Somatostatin (SRIF) receptor (sst) expression on lymphoid cells may be related to activation or proliferation of these cells. We investigated the effectiveness of sst scintigraphy in the staging of malignant lymphomas compared with conventional methods. One hundred twenty-six patients with newly diagnosed, histologically proven malignant lymphoma (54 with Hodgkin's disease [HD] and 72 with non-Hodgkin's lymphoma [NHL]) received 111In-labeled DTPA-octreotide (> 200 MBq 111In) and were assessed by planar total-body scintigraphy and single-photon emission computed tomography (SPECT) images of the upper abdomen. The sst scintigraphy was positive in 98% of HD patients. Compared with conventional methods, additional lymphomas were detected in 37%, while lesions escaped detection in 7% (all located in the abdomen); 10 HD patients were downgraded and one was upgraded. The sst scintigraphy was positive in 85% of NHL patients, but positivity did not correlate with the degree of malignancy. Additional lesions were detected in 21% of NHL patients, with false-negatives in 7% and upgrading in 13 NHL patients. The results indicate that sst scintigraphy is sensitive in patients with HD and NHL and may reveal sites of active disease undetected by conventional methods, making it a useful diagnostic tool for malignant lymphomas. Further studies should define its value in clinical management.
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PMID:The relevance of somatostatin receptor expression in malignant lymphomas. 876 95

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues, 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2-2.0 nM) and low (Kd 5-15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using 123I-OCT and/or 123I-Tyr-3-OCT and/or 111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either 123I-OCT/123I-Tyr-3-OCT (four of five), 123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or 123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues: 123I-OCT, 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which 111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.
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PMID:In vitro and in vivo studies of three radiolabelled somatostatin analogues: 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-D-Phe-1-OCT. 878 Nov 46

Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.
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PMID:The diagnostic utility of somatostatin receptor scintigraphy in oncology. 878 66

With the technique of in vivo somatostatin (SRIF) receptor (sst) scintigraphy a variety of human sst-positive tumours can be visualised 24-48 h after intravenous injection of the radiolabelled (SRIF) analogue [111In-DTPA-D-Phe1]octreotide. This rather long residence time of radioactivity on tumours suggests that the radioligand is internalised by the tumour cells; literature data for normal pituitary and pancreatic islet cells agree with this. Internalised SRIF has been found to be associated with cytoplasmic organelles, especially the Golgi apparatus, lysosomes and secretory granules. We have found that mouse AtT20 and primary cultures of human growth-hormone-secreting pituitary adenoma cells internalised a high amount of radio-iodinated [Tyr3]octreotide. Since octreotide binds with high affinity to the sst2 and sst5 subtypes and because both sst subtypes are expressed in these cells, one or both subtypes may be involved in this process. We also found that unlabelled octreotide, SRIF-14 or SRIF-28 can increase the internalisation of the radioligand. These observations, together with other studies on the manipulation of sst expression, may help to optimise the uptake of radioligand in in vivo sst scintigraphy in humans and improve the potential effect of radiotherapy with radiolabelled (subtype-specific) SRIF analogues.
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PMID:Internalisation of isotope-coupled somatostatin analogues. 881 57

The aim of the present study was to selectively target a beta-emitter-labelled octreotide analogue to somatostatin (SRIF)-receptor-expressing tumours and to evaluate the feasibility of SRIF-receptor-mediated radiotherapy by delivering a lethal dose of radiation to the tumour. The most promising compound in a series of DTPA-coupled octreotide analogues was DTPA-benzyl-acetamido-D-Phe1, Tyr3-octreotide (SDZ413). In vitro, SDZ413 binds with nanomolar affinity to SRIF-receptors (IC50 = 4.0 nM) and inhibits growth hormone release from primary cultures of rat pituitary cells with an IC50 of 7.2 nM. Biodistribution studies with [90Y]SDZ413 demonstrated a fast and significant SRIF-receptor-specific accumulation of the labelled conjugate (tumour/muscle ratio after 24 h: 52/1). [90Y]SDZ413 was effective in the radiotherapy of SRIF-receptor-positive tumours in a nude mouse model. A single treatment with [90Y]SDZ413 led to a significant decrease (25%) of tumour mass. This effect was mediated by the intact radioligand, since treatment with [90Y]SDZ978, a derivative of SDZ413 which does not bind with high affinity to SRIF-receptors or with the unlabelled SDZ413 alone, failed to affect tumour growth. These results suggest that receptor-targeted radiotherapy with a 90Y-labelled octreotide analogue represents a new strategy for the treatment of SRIF-receptor-positive tumours that have been previously diagnosed with OctreoScan111 (pentetreotide).
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PMID:Somatostatin analogues for somatostatin-receptor-mediated radiotherapy of cancer. 881 61

Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.
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PMID:Somatostatin receptor: scintigraphy and radionuclide therapy. 881 72

We evaluated a hand-held scintillation detector for intra-operative localisation of somatostatin-receptor-positive tumours in situ, and after excision, as an addition to preoperative scintigraphy with [111In-DTPA-Phe1]octreotide. Using the hand-held detector, the suspect tumour/normal tissue ratio R(in situ) between measurements was calculated for 23 patients with neuroendocrine tumours. The count rates of excised tumour and normal tissue were also measured ex vivo and their ratio R(ex vivo) was calculated. In midgut carcinoid (MC) patients (all scintigraphy positive), 4/29 macroscopically identified tumours gave false R(in situ). Tumour/blood 111In activity (T/B) ratios measured in a gamma counter were all high (27-650). In patients with medullary thyroid carcinoma (8/10 scintigraphy positive), misleading R(in situ) were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in MC patients. 2/4 patients with endocrine pancreatic tumours (EPTs) had positive scintigraphy, reliable intra-operative measurements, and very high T/B ratios (910-1,500). 1 patient with a gastric carcinoid had correct R(in situ) and R(ex vivo), with high T/B ratios (71-210). 1 patient with sporadic insulinoma had negative scintigraphy and 1 patient with neuroendocrine carcinoma of the uterus also had low T/B ratios. In most cases, in situ measurements added little information to preoperative scintigraphy and surgical findings. The very high T/B ratios seen in MC tumours and some EPTs seem promising for future radiotherapy via somatostatin receptors.
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PMID:Radioisotope-guided surgery in patients with neuroendocrine tumours. 881 80


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