Journal Article

Emergence of a barium metal-organic framework for mitigating off-target effects of alpha radionuclide therapy

Yang, Yuanyou, Liu, Ning, Guo, Yuqi, Lyu, Jie, Qiu, Long, Geng, Junshan, Liao, Jiali, Li, Feize, Shi, Shilong, Chen, Xijian, Xiao, Qian, Zhang, Jinsong

2026

Overview

Ra, an alpha-emitting radionuclide with a half-life of 3.63 d, holds significant promise in cancer therapy. However, like many other medical alpha-emitters, the development of Ra radiopharmaceuticals has long been impeded by dosimetry limitation caused by the off-target toxicity, which is tightly related to the secondary radioactivity biodistribution. In this work, we propose leveraging radionuclide trap preorganized in nanoscale barium-based metal-organic framework (AEMOF-6) to overcome the off-target effects of Ra therapy. Functional side chains with high binding affinity towards Ra and its decay daughters were preinstalled inside the cavity of nanoscale AEMOF-6, constructing radionuclide trap capable of inhibiting the radioactivity leaking effectively. The Ra-labeled radiopharmaceutical Ra-AEMOF-6@CS demonstrates effective radioactivity localization ability, significant antitumor efficacy, and favorable biosafety. It was obtained with a radiochemical yield of 92.87% and a radiochemical purity of 94.75%, maintaining over 87% stability throughout the observation period. Integrated micro-PET/CT and micro-SPECT/CT imaging, complemented by biodistribution analyses, validated the robust stability and radioactivity localization capability of the AEMOF-6@CS nanocarrier . A dose-dependent antitumor effect accompanied by excellent biosafety was observed, achieving complete tumor eradication in 20%, 40%, and 60% of mice at 36 d after injection of 18.5, 37.0, and 55.5 kBq of Ra-AEMOF-6@CS, respectively. This discovery provides a potential approach to address the challenges of radioactivity migration of Ra radiopharmaceuticals radionuclide trap preorganized in nanoscale MOFs, which can also be beneficial to other alpha-emitting radiopharmaceuticals.

• Publisher: Ivyspring International Publisher
• Subject: Alpha Particles - therapeutic use / Animals / Barium - chemistry / Cell Line, Tumor / Female / Humans / Metal-Organic Frameworks - chemistry / Mice / Mice, Inbred BALB C / Neoplasms - radiotherapy / Radioisotopes / Radiopharmaceuticals - administration & dosage / Radiopharmaceuticals - chemistry / Radiopharmaceuticals - pharmacokinetics / Radiopharmaceuticals - pharmacology / Radiopharmaceuticals - therapeutic use / Research Paper / Tissue Distribution