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

Abstract 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 ( 177 Lu‐PCMs) is reported that are 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 are 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 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 offer a new avenue for the development of a highly innovative and translational approach for precision intra‐arterial brachytherapy.