Theranostic application of 131I-labeled anti-glypican-3 antibody for targeted radioimmunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal malignancy and a leading cause of cancer-related mortality worldwide, largely due to its asymptomatic progression and the limited therapeutic efficacy available for advanced stages. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is overexpressed in approximately 70-80% of HCC cases while remaining absent in healthy liver tissue, making it an ideal theranostic target. In this study, we developed a novel 131I-labeled anti-GPC3 antibody. This radiopharmaceutical was synthesized with a high labeling yield (~93%) and demonstrated robust in vitro stability (with >81% radiochemical purity retained at 120 h). In vitro MTT assays revealed dose-dependent cytotoxicity, with cell viability significantly reduced to 27.7% at a dose of 6 μCi. In vivo evaluation in a spontaneous HCC mouse model confirmed strong GPC3 expression restricted specifically to tumor tissues. Biodistribution analysis further revealed preferential tumor accumulation (~1.3% injected dose per gram) with minimal radioactivity in non-target organs. Collectively, these findings demonstrate the feasibility and therapeutic potential of 131I-GPC3 as a targeted theranostic radiopharmaceutical for HCC and other GPC3-expressing malignancies.