On-site fabrication of injectable ¹³¹I-labeled microgels for local radiotherapy

Nuclear medicine is a routine but essential clinical option for diagnostic imaging and disease treatment. Encapsulating radioisotopes in injectable biodegradable hydrogels is ideal for localizing radiation sources to target tissues or organs to achieve long-term, low-dose radiotherapy. However, difficulties in the on-site production of radioactive gels upon treatment and the unpredictable radiation level at the target region are major obstacles to their clinical use. In this study, we bypassed these limitations by developing locally injectable hydrogel microparticles based on ¹³¹I-labeled photo-crosslinkable hyaluronic acid (HA) and a microfluidic high-throughput droplet generator. This approach enabled rapid on-site production of injectable, radioactive, biodegradable (IRB) HA microgels, thus allowing their immediate therapeutic application with improved local retention and predictable radioactivity. We demonstrated the clinical utility of this comprehensive approach by preparing IRB HA microgels within 15 min and localizing them to the target tissue (rat muscle) with minimal off-target biodistribution and in vivo radioactivity that extended beyond 3 weeks.