¹⁷⁷Lu-Labeled Amidoxime-Functionalized Biodegradable Microspheres for Transarterial Radioembolization of Hepatocellular Carcinoma*

Abstract: Transarterial radioembolization (TARE) has become an important locoregional therapy for hepatocellular carcinoma (HCC). However, the clinically used yttrium-90 ( ⁹⁰ Y) microspheres are non-biodegradable and provide limited imaging capability, while biodegradable polymeric microspheres prepared through conventional radiolabeling strategies often exhibit poor radionuclide stability. Here, we report a biodegradable radiometal-chelating microsphere based on amidoxime-functionalized polylactic acid microspheres (PLA-g-PAO-Ms) engineered via electron-beam-induced graft polymerization. The resulting PLA-g-PAO-Ms exhibit a high Lu ³⁺ loading capacity (33.83 mg g ^-1 ) and undergo controlled biodegradation in vitro after approximately 20 days. In a rat orthotopic live tumor model, intra-arterial administration of ¹⁷⁷ Lulabeled PLA-g-PAO-Ms ( ¹⁷⁷ Lu-PLA-g-PAO-Ms) resulted in pronounced tumor suppression with sustained in vivo radionuclide retention for at least 14 days. Notably, the radiometal chelation strategy enables tunable specific radioactivity of the microspheres through modulation of coordination conditions, offering precise control over therapeutic dose deposition. These findings suggest that PLA-g-PAO-Ms provide a biodegradable microsphere system capable of stable radiometal incorporation and effective tumor suppression following intra-arterial administration, offering a promising approach for interventional radionuclide therapy of HCC.