Combination Radionuclide Therapy Using ¹⁷⁷Lu- and ⁹⁰Y-Labeled Somatostatin Analogs

Abstract

Peptide receptor-targeted radionuclide therapy of somatostatin receptor-expressing tumors is a promising application of radiolabeled somatostatin analogs. Suitable radionuclides are ⁹⁰Y, a pure, high-energy β-emitter (2.27 MeV), and ¹⁷⁷Lu, a medium-energy β-emitter (0.5 MeV) with a low-abundance γ. Methods: Lewis rats, each bearing both a small (approximately 0.5 cm²) and a large (7–9 cm²) somatostatin receptor-positive rat pancreatic CA20948 tumor in their flanks, were used. We investigated the radiotherapeutic effects of [⁹⁰Y-tetraazacyclododecanetetraacetic acid (DOTA),Tyr³]octreotide, [⁹⁰Y-DOTA,Tyr³]octreotate, [¹⁷⁷Lu-DOTA,Tyr³]octreotate, and the combination of ⁹⁰Y- and ¹⁷⁷Lu-labeled analogs at the same tumor radiation dose (60 Gy). Results: Radiotherapeutic effects of the ⁹⁰Y- and ¹⁷⁷Lu-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% ¹⁷⁷Lu- plus 50% ⁹⁰Y-analogs were superior to those in animals treated with either ⁹⁰Y- or ¹⁷⁷Lu- analog alone. In smaller tumors, the ⁹⁰Y 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 ¹⁷⁷Lu alone to go completely into remission. Conclusion: This study shows the superior antitumor effects of the combination of ¹⁷⁷Lu- and ⁹⁰Y-somatostatin analogs when compared with either ⁹⁰Y- or ¹⁷⁷Lu-analog alone in animals bearing tumors of various sizes.