Somatostatin mediates its actions through five different
somatostatin receptor subtypes, sst1-sst5. Recently, the
somatostatin analogs des-AA1,2,5-[D-Trp8, IAmp9]
somatostatin and des-AA1,5-[Tyr2, D-Trp8, IAmp9]
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-AA1,5-[Tyr2, D-Trp8, IAmp9]
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 Tyr3-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.