Engineering Radioactive Microspheres for Intra-Arterial Brachytherapy Using Radiation-Induced Graft Polymerization

Intravascular brachytherapy requires advances in radio-embolization technologies that combine brilliant radiostability efficacy with a facile and green synthesis route. A hybrid-integrated radioactive microsphere strategy using phosphorylcholine-modified lutetium-177 coordinated polymeric microspheres (Lu-177-PCMs) is reported that are fabricated via radiation-induced graft polymerization for imaging-guided locoregional intravascular brachytherapy. The underlying formation mechanism of Lu-177-PCMs is elucidated using first-principles computations and density functional theory calculations, and Lu-177 loading mechanisms are investigated with Near-edge and extended X-ray absorption fine structure spectroscopy. The engineered Lu-177-PCMs exhibit excellent mechanical properties, good hydrophilicity, and controlled sphere diameter. These features provide advantages of ultra-stable embolic radio-theranostics, which is demonstrated in different preclinical rodent models and isolated human liver tumor tissues. During locoregional intra-arterial brachytherapy, Lu-177-PCMs can be visualized via SPECT to validate the in vivo biodistribution and retention in real time, achieving precise delivery, effective anti-cancer treatment, and a distinguished safety profile without degradation, ectopic embolization, and adverse reactions. Therefore, this study offer a new avenue for the development of a highly innovative and translational approach for precision intra-arterial brachytherapy.