SOMATOSTATIN RECEPTOR-BINDING PEPTIDES LABELED WITH TC-99M - CHEMISTRY AND INITIAL BIOLOGICAL STUDIES

The synthesis of peptides which possess a high affinity for the somato statin receptor and contain a chelator for the radionuclide technetium -99m is described. The target compounds were designed such that they w ould form stable, oxotechnetium(V) chelate complexes in which the site of metal coordination was well defined and remote from the receptor-b inding region. Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Pe ptide oxorhenium complexes and Tc-99m complexes eluted closely upon HP LC analysis. The receptor-binding affinities of both the free and rhen ium-coordinated species were measured in vitro. The binding affinities of the free peptides (K-i's in the 0.25-10 nM range) compared favorab ly with [DTPA]octreotide (K-i = 1.6 nM), which, as the indium-lll comp lex, is already approved for somatostatin receptor (SSTR)-expressing t umor imaging in the United States and Europe. Furthermore, the rhenium -coordinated peptides had binding affinities which, in many cases, wer e higher than those of the corresponding free peptides, with several c omplexes having a K-i's of 0.1 nM. Some of the more potent SSTR-bindin g peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The Tc-99m-labeled peptides prepared i n this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, b ecause they are low molecular weight peptides, expected pharmacokineti cs characterized by rapid tracer excretion from the body resulting in high-contrast images.