Precision radiation oncology · 2026
177Lu-labeled amidoxime-functionalized biodegradable microspheres for transarterial radioembolization of hepatocellular carcinoma.
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Liu Xingliang, Wang Gang, Zhao Zhenwen, Wang Haoyu, Chen Hongyu, Xu Xiao, Li Jingdong, Ma Hongjuan
Аннотация
PURPOSE: Transarterial radioembolization (TARE) is an important locoregional therapy for hepatocellular carcinoma (HCC). However, clinically used yttrium-90 (90Y) 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 Lu3+ 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 Lu3+ (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 177Lu-labeled PLA-g-PAO-Ms (177Lu-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 177LuCl3 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.
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 Lu3+ 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 Lu3+ (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 177Lu-labeled PLA-g-PAO-Ms (177Lu-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 177LuCl3 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.