Octreotide

Lamberts, Steven W. J.; Lely, Aart-Jan van der; Herder, Wouter W. de; Hofland, Leo J.

doi:10.1056/nejm199601253340408

Cited by 1,058 publications

(721 citation statements)

References 79 publications

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“…SSTRs are overexpressed by a variety of neuroendocrine tumors and frequently by tumors of the nervous system, 1-4 making somatostatin analogs, such as OC, 5 attractive candidates for tumor targeting. 111 In-labeled DTPA-OC (OctreoScan) was the first radiopeptide routinely used in the clinic for imaging SSTR-positive tumors by scintigraphy.…”

mentioning

confidence: 99%

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

Froidevaux

Eberlé

Christe

et al. 2002

Intl Journal of Cancer

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Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTRexpressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes 67 Ga and 68 Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suit- SSTRs are overexpressed by a variety of neuroendocrine tumors and frequently by tumors of the nervous system, 1-4 making somatostatin analogs, such as OC, 5 attractive candidates for tumor targeting. 111 In-labeled DTPA-OC (OctreoScan) was the first radiopeptide routinely used in the clinic for imaging SSTR-positive tumors by scintigraphy. 6 -10 A new generation of somatostatin analogs, incorporating the macrocyclic chelator DOTA instead of DTPA, have been developed, which ensure better stability of the radiometal-peptide complex. After labeling with 90 Y (␤ --emitter 2.28 MeV, t 1 ⁄2 64.1 hr) or 111 In (␥-emitter, Auger-and conversionelectron emitter, 0.5-245 keV, t 1 ⁄2 67.9 hr), they showed improved biodistribution and tumor uptake in animal models [11][12][13] and their clinical utility as diagnostic and therapeutic tools was confirmed in patients. 14 -18 These findings prompted us and others to develop somatostatin analogs suitable for PET, which offers higher sensitivity and resolution than SPECT, making it possible to visualize very small metastatic lesions, including tumor deposits in regional draining lymph nodes. Several strategies have been studied to develop a somatostatin analog-based PET tracer using different positronemitting radionuclides. Wester et al. 19 successfully labeled OC with 18 F, but despite specific accumulation in the tumor, this radioligand was of limited clinical application, owing to fast tumor washout, high liver uptake and, hence, insufficient visualization of abdominal tumors. Various 64 Cu-labeled somatostatin analogs were synthesized which showed favorable biodistribution in animal models 20,21 and good performance for PET imaging in patients; 22 however, the use of 64 Cu relies on the availability of a cyclotron.Another interesting positron emitter is 68 Ga (t 1 ⁄2 68 min, ␤ ϩ 88%), which is produced by a 68 Ge/ 68 Ga generator available at most PET centers and is not dependent on a cyclotron. Gallium as radiometal is of even broader interest in nuclear medicine because it is also available as 67 Ga (t 1 ⁄2 78 hr), which is not only a ␥-emitter useful for tumor diagnosis (␥-camera scintigraphy, SPECT) but also an emitter of Auger (0.1-8 keV) and conversion (80 -90 keV) electrons, which makes it attractive for internal radiotherapy. 23 The radiotoxicity of 67 Ga has been demonstrated in vitro in a lymphoma cell line 24 and myeloid leukemic blasts. 25 The use of a low-energy emitter might increase the therapeutic index because most of the electrons deposit their energy within the target, i.e., the tumor, thereby min...

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confidence: 99%

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

Froidevaux

Eberlé

Christe

et al. 2002

Intl Journal of Cancer

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“…hSSTR2 is the receptor subtype to which the currently marketed analogue, octreotide, binds with highest affinity (Lamberts et al, 1996). Vapreotide (RC160) and lanreotide (BIM23014) bind to hSSTR5 with higher affinity than octreotide.…”

Section: Discussionmentioning

confidence: 99%

“…Vapreotide (RC160) and lanreotide (BIM23014) bind to hSSTR5 with higher affinity than octreotide. Lanreotide, but not vapreotide, also binds to hSSTR2 with higher affinity than octreotide, and all three analogues have a lower affinity for the other three subtypes (O'Carroll et al, 1994;Lamberts et al, 1996). Some reports have suggested that vapreotide (RC160) is associated with tyrosine phosphatase activity but octreotide is not (Todisco et al, 1994), although on the basis of the subtype specificity of the analogues, it is difficult to explain this.…”

Section: Discussionmentioning

confidence: 99%

“…They couple to G-protein a subunits, which variously inhibit the activity of adenyl cyclase (Gal/2), prevent intracellular calcium rises (GaO) and may also stimulate the activity of protein phosphatases (Buscail et al, 1995), leading to the abrogation of intracellular stimulatory signals and transmodulation of tyrosine kinase-type receptors, for example, the epidermal growth factor receptor (Pinski et al, 1994). The receptor subtypes also have different biochemical characteristics, including variable binding affinities for somatostatin 14 (SS14), somatostatin 28 (SS28), which is involved in the regulation of colonic motility (Bitar and Kothary, 1994), and synthetic analogues (Raynor et al, 1993;Lamberts et al, 1996). Subtype 5 is the only receptor that has a higher relative binding affinity for SS28 than SS14 (O'Carroll et al, 1993).…”

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confidence: 99%

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Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae

Laws

Gough²,

Evans³

et al. 1997

Br J Cancer

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Summary Somatostatin analogues may be useful novel agents in the systemic treatment of advanced colorectal cancer, as somatostatin inhibits proliferation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour and mucosal samples respectively, but in 75% (9/12) of early-stage tumours (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) of late-stage tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (X2 with Yates' correction). There was also reduced expression of hSSTR5 in samples of metastatic tumour (11%, 1/9) compared with all tumour samples (56%, 18/32) 0.025>P>0.01 (X2 with Yates' correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2 expression is retained after malignant transformation in colonic epithelium and, although it may potentially be a target for antiproliferative therapy, its ubiquitous expression militates against this. hSSTR5 warrants investigation as a tumour suppressor.

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“…This selectivity is probably the result of different somatostatin receptor (SSTR) populations mediating the secretion of different hormones (Rossowski and Coy, 1994;Patel, 1999;Portela-Gomes et al, 2000). In contrast to the natural SST somatostatin-14, octreotide does not bind with the same affinity to all five SSTR subtypes (Reisine and Bell, 1995;Lamberts et al, 1996). In the rat and rhesus monkey, but not in humans, octreotide is also more potent than somatostatin-14 (Bauer et al, 1982;Patel and Srikant, 1994).…”

Section: Introductionmentioning

confidence: 99%

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

Robben

Brom

Mol

et al. 2006

Research in Veterinary Science

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The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 lg octreotide were studied in healthy dogs in the fasting state (n = 7) and in dogs with insulinoma (n = 12).Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred.Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased.Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.

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Octreotide

Cited by 1,058 publications

References 79 publications

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma

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