10P3Me: A GPC3-Targeted Peptide PET Probe for Subcutaneous and Orthotopic HCC Imaging
Chen Gong, Gangzhong Zhou, Xudong Sun, Zhencun Cui, Hange Yang, Cong Wang, Kun Wang, Xuegong Fan, Peihong Ji, Ke Wang, Jianshan Liu, Jianshan Liu, Yuhao He, Hui Wang, Hongyan Li, Yimeng Zhu, Zhimin Wang, Kuan Hu, Jiangyan Liu, Jiangyan Liu, Juan Yi, Hailong Zhang, Rui Wang
Abstract
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.