PRECLINICAL EXPERIENCE WITH RE-188-RC-160, A RADIOLABELED SOMATOSTATIN ANALOG FOR USE IN PEPTIDE-TARGETED RADIOTHERAPY

The clinical potential of radiolabeled peptides such as octreotide and VIP has been widely established for tumor localization. Radiotherapy based on the tumor binding potential of the peptides and the radiotoxi c effects of beta- or alpha-emitting radionuclides is an extension of such applications. Rhenium-188 (T-1/2 16.9hr, beta(max)(-) 2.1 MeV) co upled to the analogue RC-160 has been used to establish the feasibilit y of treating tumors with radiolabeled peptides, and our experience wi th this approach is summarized. In three different experimental Rimer models (human prostate, mammary gland and small cell lung carcinomas) in nude mice, treatment resulted in significant reduction or eliminati on of tumor burden. Two routes of administration were used: intra-lesi onal injection (prostate carcinoma) and intra-cavity injection (mammar y and SCLC). Re-188-labeled negative control peptides bound to tumor- cells to a low extent and did not exhibit therapeutic benefit. RC-160 by itself did not result in therapeutic benefit. Tumors which did not bind Re-188-RC-160 did not evidence a therapeutic benefit. Uncoupled R e-188 (control) was rapidly excreted via the urinary bladder and did n ot accumulate in either tumors or normal tissues even following direct injection. Instant radiolabeling kits containing 200 mu g of RC-16O w ere labeled with <3000 MBq of Re-188 in 30 minutes with no need for su bsequent purification. These studies establish the conceptual feasibil ity of targeted radiotherapy based on the local or regional administra tion of radiolabeled peptides.