A selective analog for the somatostatin sst1-receptor subtype expressed by human tumors

Somatostatin mediates its actions through five different somatostatin receptor subtypes, sst1-sst5. Recently, the somatostatin analogs des-AA(1,2,5)-[D-Trp(8), IAmp(9)]somatostatin and des-AA(1.5)-[Tyr(2), D-Trp(8), IAmp(9)]somatostatin were synthesized and shown to be sst1-selective when tested in COS-7 cells transfected with each of the sst subtypes. In the present study, we tested the binding affinity and specificity of the iodinatable analog in primary human tumors expressing various sst subtypes, selected on the basis of in situ hybridization experiments. Des-AA(1.5)-[Tyr(2), D-Trp(8), IAmp(9)]somatostatin was found to have a high affinity, comparable to that of the natural somatostatin-28, for sst1-expressing tumors such as prostate cancers. However, it had no affinity for tumors expressing the sst2, sst3, or sst5 subtypes. For comparison, the somatostatin analogs octreotide or Tyr(3)-octreotide have no affinity for sst1-expressing tumors, but high affinity for sst2- and sst5-expressing tumors and intermediate affinity for sst3-expressing tumors. These data represent the first characterization of a sst1-selective analog in human tumors; it may be of potential use in the therapy of sst1-expressing tumors as an antiproliferative agent, as well as providing a lead compound for the development of more potent sst1-selective radioligands for in vivo tumor scintigraphy. (C) 1998 Elsevier Science B.V.