Park Bok-Nam, An Young-Sil, Kim Su-Min, Lee Su-Jin, Park Yong-Jin, Yoon Joon-Kee
Department of Nuclear Medicine & Molecular Imaging, Ajou University School of Medicine, Worldcup-ro 164, Suwon 16499, Republic of Korea.
Antibodies (Basel). 2024 Jun 27;13(3):51. doi: 10.3390/antib13030051.
This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope Lu using DOTA as a chelating agent. Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in serum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. Lu-DOTA-ATPS mAb treatment significantly 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 Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, enhanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This approach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
本研究调查了一种用于靶向肿瘤血管生成的新型放射免疫疗法策略。我们使用DOTA作为螯合剂，通过用放射性同位素镥标记抗三磷酸腺苷合酶（ATPS）单克隆抗体（mAb）来开发一种放射性药物复合物。镥- DOTA - ATPS单克隆抗体在血清中显示出高标记效率（99.0%）和稳定性。MKN - 45癌细胞表现出最高的细胞摄取，未标记的ATPS单克隆抗体可特异性阻断这种摄取。在小鼠中，镥- DOTA - ATPS单克隆抗体在肿瘤中显著蓄积，第7天时肿瘤摄取为16.0±1.5%ID/g。镥- DOTA - ATPS单克隆抗体治疗以剂量依赖方式显著降低了MKN - 45细胞的活力。在异种移植肿瘤模型中，这种放射免疫疗法策略导致显著的肿瘤生长抑制（82.8%）。此外，将镥- DOTA - ATPS单克隆抗体与抗血管生成药物舒尼替尼联合使用，增强了舒尼替尼在小鼠模型中的治疗效果。我们的研究成功开发了镥- DOTA - ATPS单克隆抗体，一种靶向肿瘤血管的放射免疫治疗剂。这种方法无论是作为单一疗法还是与其他抗癌药物联合使用，在抑制肿瘤生长方面都显示出巨大的前景。
