A PEI-Based Surface Strategy for Robust <b> ¹⁷⁷ </b> Lu Incorporation into Biodegradable Chitosan Microspheres: A Potential Platform for Hepatocellular Carcinoma Radioembolization

While lutetium-177 ( 177 Lu) holds immense promise as a theranostic radionuclide for image-guided radioembolization of hepatocellular carcinoma, its translation into effective biodegradable microsphere platforms has been critically hindered by the lack of stable and efficient carriers capable of robustly incorporating the radionuclide while maintaining biodegradability. To bridge this gap, we herein develop biodegradable chitosan microspheres engineered with an aminated surface via sequential grafting of poly(glycidyl methacrylate) (PGMA) and polyethylenimine (PEI) to establish a robust Lu(III) binding capacity as a pivotal carrier for future 177 Lu-based radioembolization. The aminated microspheres exhibit good sphericity, favorable in vitro dispersion, and a gradual biodegradation profile. They exhibit a high Lu(III) adsorption capacity of 70.55 mg·g –1 at 333 K, corresponding to an estimated theoretical specific activity of up to 2.07 MBq per individual CPPs- 177 Lu microsphere. These results demonstrate the potential of PEI-functionalized chitosan microspheres as biodegradable carriers for further investigation into 177 Lu-based transarterial radioembolization.