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

  • J Med Chem. 2025 Sep 25;68(18):19714-19725. doi: 10.1021/acs.jmedchem.5c02081.
Gong Chen  1 ,  Gangzhong Zhou  2 ,  Xudong Sun  1 ,  Zhencun Cui  3 ,  Hange Yang  1 ,  Cong Wang  1 ,  Kun Wang  2 ,  Xuegong Fan  1 ,  Peihong Ji  1 ,  Ke Wang  1 ,  Jianshan Liu  1 ,  Yuhao He  1 ,  Hui Wang  4 ,  Hongyan Li  4 ,  Yimeng Zhu  5 ,  Zhimin Wang  5 ,  Kuan Hu  2 ,  Jiangyan Liu  3 ,  Juan Yi  1 ,  Hailong Zhang  1 ,  Rui Wang  1  2
Affiliations
  • 1. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
  • 2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 3. Department of Nuclear Medicine, The Second Hospital of Lanzhou University & The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730030, P. R. China.
  • 4. Gansu Isotope Laboratory, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
  • 5. PET/CT Center of Gansu Provincial Hospital & The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou, Gansu 730050, P. R. China.
PMID: 40916346 DOI: 10.1021/acs.jmedchem.5c02081
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 Kd 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.

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