Abstract 5044: Antitumor activity comparison of two somatostatin receptor ligands radiolabeled with Lutetium-177 (SSO110 and DOTA-TATE) alone or combined with chemotherapy in mice bearing AR42J SST2-positive tumors

Abstract

Abstract Only a limited number of studies have compared the therapeutic effects of repetitive cycles of radiolabeled somatostatin (SST) analogues or assessed potential synergy of these analogues with chemotherapy agents. Hence, a comparison was conducted in an in vivo AR42J tumor model with an SST2 antagonist, [177Lu]Lu-satoreotide tetraxetan ([177Lu]LuSSO110), and a SST2 agonist, [177Lu]Lu-DOTA-TATE. The efficacy of treatment combining [177Lu]Lu-satoreotide tetraxetan with capecitabine plus temozolomide was also assessed. Swiss Nude mice were xenografted with AR42J tumor cells. For the evaluation of the tumor response to radiation therapy, animals received one weekly dose of [177Lu]LuSSO110 or [177Lu]Lu-DOTA-TATE for four consecutive weeks. For combined treatments, animals received one weekly dose of [177Lu]LuSSO110 at 20 MBq for four consecutive weeks in association with daily doses of capecitabine and temozolomide (CAPTEM). Weekly treatment for four consecutive weeks with [177Lu]LuSSO110 at 15 MBq revealed a significantly reduced tumor growth, with 68 days to reach a tumor volume of 850 mm3, compared to [177Lu]Lu-DOTA-TATE at 15 MBq or 30 MBq, with, respectively, 43 days and 48 days. This was associated with a 3.5 fold higher tumor uptake of [177Lu]LuSSO110 (15 MBq) compared to [177Lu]Lu-DOTA-TATE, with no or mild effects on body weight, hematological toxicity, or renal toxicity. In AR42J tumor-bearing mice treated once a week for four consecutive weeks, [177Lu]LuSSO110 (15 MBq) associated with CAPTEM regimen did not significantly increase the median time to reach a tumor volume of 1000 mm3 as compared to treatment with [177Lu]Lu-satoreotide alone: 50.7 vs 42.2 days, respectively. The association of the two treatments only led to mild weight losses. Repeated administrations of [177Lu]LuSSO110 were able to potentiate peptide receptor radionuclide therapy with a higher tumor uptake and longer median survival compared to [177Lu]Lu-DOTA-TATE. The The combination of [177Lu]Lu-satoreotide with capecitabine and temozolomide did not show any synergy, but no antagonism was observed either. Citation Format: Olivier Raguin, Marcel Krüger, Peggy Provent, Funda Cay, Elodie Marie dit chatel, Marie Lux, Stéphane Lezmi, Florence Meyer-Losic, Pascale Plas, Ben Pais, Cyril Berthet. Antitumor activity comparison of two somatostatin receptor ligands radiolabeled with Lutetium-177 (SSO110 and DOTA-TATE) alone or combined with chemotherapy in mice bearing AR42J SST2-positive tumors. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5044.