Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

177Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model

Version 1 : Received: 21 May 2024 / Approved: 23 May 2024 / Online: 23 May 2024 (10:36:26 CEST)

How to cite: Park, B.-N.; An, Y.-S.; Kim, S.-M.; Lee, S.-J.; Park, Y.-J.; Yoon, J.-K. 177Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model. Preprints 2024, 2024051497. https://doi.org/10.20944/preprints202405.1497.v1 Park, B.-N.; An, Y.-S.; Kim, S.-M.; Lee, S.-J.; Park, Y.-J.; Yoon, J.-K. 177Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model. Preprints 2024, 2024051497. https://doi.org/10.20944/preprints202405.1497.v1

Abstract

This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate syn-thase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in se-rum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment sig-nificantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, en-hanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This ap-proach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.

Keywords

Radioimmunotherapy; ATP synthase; 177Lu; Angiogenesis; Gastric cancer

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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