2. Academic Validation
  3. 10P3Me: A GPC3-Targeted Peptide PET Probe for Subcutaneous and Orthotopic HCC Imaging

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

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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