mRNA expression may overestimate the number of receptors present, depending on the technique used [PR-polymerase chain reaction, Northern blot, in-situ hybridization]. [Data from Plöckinger U. Biotherapy. Best Practice & Research Clinical
Endocrinology & Metabolism 2007; Vol. 21, No. selleck screening library 1, pp. 145-162] In a study examining 81 functioning and non-functioning GEP NETs the large parte of the tumours expressed SSTRs 1, 2, 3 and 5, while SSTR 4 was detected only in a small minority . Somatostatin receptors have been extensively mapped in different pancreatic tumours by means of autoradiography, reverse-transcription polymerase chain reaction, in situ hybridization and immunohistochemistry; SSTRs 1, 2, 3 and 5 are usually expressed in pancreatic NETS. Pancreatic insulinomas had heterogeneous SSTRs expression while 100% of somatostatinomas expressed SSTR 5 and 100% gastrinomas and glucagonomas expressed SSTR 2 . Somatostatin (SST) is a natural peptide hormone secreted in various parts of the human body, including the
digestive tract, able to inhibit the release of numerous endocrine hormones, including insulin, glucagon, and gastrin. The biological effects of somatostatin are mediated through its specific receptors (SSTR 1-5) with a high degree of sequence similarity (39-57%) and which have been cloned in the early 1990s. They all bind natural peptides, somatostatin for 14, somatostatin 28 and cortistatin with similar high affinity (nM range). However, endogenous somatostatin short
half-life in circulation find more (1-3 min), makes it difficult to use it continuously and has resulted in the development of synthetic analogues. By the early 1980s a number of short synthetic analogues of somatostatin including SMS201-995 (octreotide), RC-160 (vapreotide), BIM 23014 (lanreotide), and MK 678 (Selleck ARN-509 Seglitide) were developed. These cyclic octapeptides are more resistant to peptidases and their half-lives and hence their biological activities are substantially longer than native somatostatin (1.5-2 h vs 1-2 min) . The development of a depot formulation of octreotide, Sandostatin LAR (Novartis) (long-acting repeatable), administered up to 30-60 mg once every 4 weeks has to a large extent eliminated the need for daily injections. Lanreotide (Somatuline; Ipsen, Slough, UK), a long-acting somatostatin analogue administered every 10-14 days, has a similar efficacy to octreotide in the treatment of carcinoid tumors, but its formulation is easier and more comfortable for patients to use . A new slow-release depot preparation of lanreotide, Lanreotide Autogel (Ipsen), is administered subcutaneously up to 120 mg once a month . Native SST and its synthetic analogues show different affinity for the five specific receptor subtypes [9, 10, 15]. Native SST binds all the five receptor subtypes (SSTRs 1-5).