Combination radionuclide therapy using 177Lu- and 90Y-Labeled somatostatin analogs

Peptide receptor-targeted radionuclide therapy of somatostatin receptor-express in g tumors is a promising application of radiolabeled somatostatin analogs. Suitable radionuclides are Y-90, a pure, high-energy beta-emitter (2.27 MeV), and Lu-177, a medium-energy beta-emitter (0.5 MeV) with a low-abundance gamma. Methods: Lewis rats, each bearing both a small (approximately 0.5 cm(2)) and a large (7-9 cm(2)) somatostatin receptor-positive rat pancreatic CA20948 tumor in their flanks, were used. We investigated the radiotherapeutic effects of [Y-90-tetraazacyclodoclecanetetraacetic acid (DOTA),Tyr(3)]octreotide, [Y-90-DOTA, Tyr(3)]octreotate, [Lu-177-DOTA,Tyr(3)]octreotate, and the combination of Y-90- and Lu-177-labeled analogs at the same tumor radiation dose (60 Gy). Results: Radiotherapeutic effects of the Y-90- and Lu-177-labeled analogs were found in the rat tumor model. In these animals bearing tumors of different sizes, the antitumor effects of the combination of 50% Lu-177- plus 50% Y-90-analogs were superior to those in animals treated with either Y-90- or Lu-177- analog alone. In smaller tumors, the Y-90 radiation energy was not completely absorbed in the tumor, whereas in larger tumors the increased number of clonogenic tumor cells at the fixed level of absorbed dose may account for the failure of Lu-177 alone to go completely into remission. Conclusion: This study shows the superior antitumor effects of the combination of Lu-177- and Y-90-somatostatin analogs when compared with either 90Y- or Lu-177-analog alone in animals bearing tumors of various sizes.