TARGETING PEPTIDES FOR PLEURAL CAVITY TUMOR-RADIOTHERAPY - SPECIFICITY AND DOSIMETRY OF RE-188-RC-160

Re-188-RC-160, a radiolabeled somatostatin analogue, is being explored for its potential as a local/regionally administered radiotherapeutic agent targeting somatostatin receptor-positive tumors, In studies in vitro and in vivo, Re-188-RC-160 was found to bind to somatostatin rec eptor-positive cells (NCI-H69, human small cell lung carcinoma), but n ot to binding-negative cells (Raji, Burkitt's lymphoma). The comparati ve binding of Re-188-labeled RC-160 [cyclic NH2-(D)-Phe-Cys-Try-(D)-Tr p-Lys-Val-Cys-Trp-NH2] or CTOP [cyclic NH2(D)-Phe-Cys-Try-(D)-Trp-Orn- Thr-Pen-Thr-ol], a mu-opioid receptor antagonist used a negative contr ol compound, was also determined in vitro and in vivo using NCI-H69 ce lls as targets. Re-188-RC-160 demonstrated higher net binding in vitro and in vivo compared to Re-188-RC-CTOP, and in vitro its binding coul d be reduced by excess unlabeled RC-160 whereas binding of Re-188-CTOP could not be reduced. Using another somatostatin receptor-positive hu man tumor line, ZR-75-1, a substantial amount of the cell-bound Re-188 -RC-160 was found to be internalized, Dose estimates for Re-188-RC-160 in animals containing NCI-H69 tumors indicated that with three serial injections therapeutic doses greater than 60 Gy can be achieved.