Ultra-stable radioactive microspheres enabled by radiation-induced graft polymerization for imaging-guided intra-arterial brachytherapy

Abstract Intravascular brachytherapy requires advances in radio-embolization technologies that combine brilliant radiostability efficacy with a facile and green synthesis route. We report a hybrid-integrated radioactive microsphere strategy using phosphorylcholine-modified lutetium-177 coordinated polymeric microspheres ( 177 Lu-PCMs) that were fabricated via radiation-induced graft polymerization for imaging-guided locoregional intravascular brachytherapy. The underlying formation mechanism of 177 Lu-PCMs is elucidated using first-principles computations and density functional theory calculations and 177 Lu loading mechanisms was investigated with Near-edge and extended X-ray absorption fine structure spectroscopy. The engineered 177 Lu-PCMs exhibit excellent mechanical properties, good hydrophilicity, and controlled sphere diameter. These features provide advantages of ultra-stable and ultra-selective embolic radio-theranostics, which is demonstrated in different preclinical rodent models and isolated human liver tumor tissues. During locoregional intra-arterial brachytherapy, 177 Lu-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 may offer a new avenue for the development of a highly innovative and translational approach for precision intravascular brachytherapy.