[177Lu-DOTA0, Tyr3]octreotate for somatostatin receptor-targeted radionuclide therapy

Receptor-targeted scintigraphy using radiolabeled somatostatin analogs such as octreotate is being used with great success to demonstrate the in vivo presence of somatostatin receptors on various tumors, A new and promising application for these analogs is radionuclide therapy, Radionuclides suitable for this application include the Auger electron-emitter In-111 and the beta -emitters Y-90 (high energy) and Lu-177 (low energy), We investigated [DOTA(0), Tyr(3)]octreotate, labeled with the lanthanide Lu-177, in biodistribution and radionuclide therapy experiments using male Lewis rats bearing the somatostatin receptor-positive rat CA20948 pancreatic tumor. Biodistribution studies in Lewis rats showed the highest uptake in the rat pancreatic CA20948 tumor and sst(2)-positive organs which include the adrenals, pituitary and pancreas, of [Lu-177-DOTA(0),Tyr(3)]octreotate In comparison with Y-88- and In-111-labeled analogs. Kidney uptake of [Lu-177-DOTA(0),Tyr(3)]octreotate could be reduced by approximately 40% by co-injection of 400 mg/kg D-lysine, in radionuclide therapy studies, a 100% cure rate was achieved in the groups of rats bearing small (less than or equal to 1 cm(2)) CA20948 tumors after 2 doses of 277.5 MBq or after a single dose of 555 Ft Bq [Lu-177-DOTA(0),Tyr(3)]octreotate. A cure rate of 75% was achieved after a single administration of 277.5 MBq, In rats hearing larger (greater than or equal to 1 cm(2)) tumors, 40% and 50% cure rates were achieved in the groups that received I or 2 277.5 MBq injections of [Lu-177-DOTA(0),Tyr(3)]octreotate, respectively, After therapy with [Lu-177-DOTA(0),Tyr(3)]octreotide in rats bearing small tumors, these data were 40% cure after injection with 277.5 MBq and 60% cure after 2 repeated injections, In conclusion, [Lu-177-DOTA(0),Tyr(3)]octreotate has demonstrated excellent results in radionuclide therapy studies in rats, especially in animals bearing smaller tumors. This candidate molecule shows great promise for radionuclide therapy in patients with sst,-expressing tumors, (C) 2001 Wiley-Liss, Inc.