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-A A(1,2,5)-[D-Trp(8), IAmp(9)]somatostatin and des-AA(1.5)-[Tyr(2), D-Tr p(8), IAmp(9)]somatostatin were synthesized and shown to be sst1-selec tive when tested in COS-7 cells transfected with each of the sst subty pes. In the present study, we tested the binding affinity and specific ity of the iodinatable analog in primary human tumors expressing vario us sst subtypes, selected on the basis of in situ hybridization experi ments. Des-AA(1.5)-[Tyr(2), D-Trp(8), IAmp(9)]somatostatin was found t o 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)-octreo tide have no affinity for sst1-expressing tumors, but high affinity fo r 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 poten t sst1-selective radioligands for in vivo tumor scintigraphy. (C) 1998 Elsevier Science B.V.