10P3Me: A GPC3-Targeted Peptide PET Probe for Subcutaneous and Orthotopic HCC Imaging

Hepatocellular carcinoma (HCC) remains a growing global health threat, necessitating the development of precise molecular probes for its prevention, early diagnosis, and treatment. Glypican-3 (GPC3) is highly expressed in various HCC subtypes and exhibits minimal expression in normal liver tissue, making it a promising biomarker for early-stage HCC diagnosis. Herein, we report a novel cyclic peptide molecular probe, 10P3Me, exhibiting high binding affinity for GPC3, with a K_d of 93.8 nM. In PET-imaging studies, 10P3Me showed pronounced tumor-targeting ability in GPC3-positive models, reaching a peak uptake of 5.61%ID/mL at 1 h post-injection, 3.8-fold higher than in GPC3-low models. 10P3Me also displayed robust targeting in an orthotopic HepG2-LUC liver tumor model, enabling accurate localization of intrahepatic lesions. Biodistribution revealed selective tumor accumulation over normal liver, achieving a tumor-to-liver uptake ratio of 8.28 at 1 h. These findings highlight 10P3Me as a promising probe for molecular imaging of GPC3-positive HCC.