177 Lu‐labeled amidoxime‐functionalized biodegradable microspheres for transarterial radioembolization of hepatocellular carcinoma
Xingliang Liu, Gang Wang, Zhenwen Zhao, Haoyu Wang, Hongyu Chen, Xiao Xu, Jingdong Li, Hongjuan MaAbstract
Purpose
Transarterial radioembolization (TARE) is an important locoregional therapy for hepatocellular carcinoma (HCC). However, clinically used yttrium‐90 ( 90 Y) microspheres are non‐biodegradable and provide limited imaging capability, while biodegradable polymeric microspheres prepared using conventional radiolabeling strategies often exhibit poor radionuclide stability.
Experimental design
We designed a biodegradable radiometal‐chelating microsphere based on amidoxime‐functionalized polylactic acid microspheres (PLA‐g‐PAO‐Ms) engineered via electron beam‐induced graft polymerization.
Results
The PLA‐g‐PAO‐Ms exhibited a high Lu 3+ loading capacity (33.83 mg g −1 ) and underwent controlled biodegradation in vitro after approximately 20 d. Cell Counting Kit‐8 (CCK‐8) assays confirmed favorable cytocompatibility, with both LO2 and HepG2 cell viabilities exceeding 90% after 72 h, showing no significant difference from the control group ( p > 0.05); by contrast, free Lu 3+ (50 mg·L −1 ) significantly reduced HepG2 viability to 51.4% ( p < 0.001). In a rat orthotopic liver tumor model, the intra‐arterial administration of 177 Lu‐labeled 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 d. Biodistribution analysis revealed selective tumor accumulation of 8.79 ± 1.74 %ID g −1 , significantly higher than that in normal liver ( 1 ± 0.54 %ID g −1 ) and other organs ( P < 0.001 ), whereas free 177 LuCl 3 showed minimal tumor uptake ( 0.30 ± 0.28 %ID g −1 ) with predominant non‐target organ accumulation.
Conclusion
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 for HCC.