Preclinical Evaluation of 68Ga-Labeled CSPG4-Targeting Peptides for PET/CT Imaging in Pancreatic and Gastric Carcinoma

  • J Med Chem. 2025 Nov 13;68(21):23335-23344. doi: 10.1021/acs.jmedchem.5c02187.
Zerong Wang  1  2  3 ,  Xiaoyu Pan  1  4  2  3 ,  Ye Li  1  5  2  3 ,  Fengsheng Zhang  1  4  2  3 ,  Linjie Bian  1  5  2  3 ,  Jindian Li  1  5  2  3
Affiliations
  • 1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 2. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
  • 3. Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai 200433, China.
  • 4. Institute of Modern Physics, Fudan University, Shanghai 200433, China.
  • 5. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
PMID: 41088886 DOI: 10.1021/acs.jmedchem.5c02187
Abstract

Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed in various solid tumors and promotes tumor progression and migration. Targeting CSPG4 therapy, such as monoclonal antibodies 9.2.27 and CAR-M, has already been in clinical trials. Database analysis further correlated elevated levels of CSPG4 with reduced overall survival in both cancers. Achieving real-time visualization of aberrant CSPG4 expression in various solid tumors remains a critical issue that needs to be addressed. To address this, we pioneered the preparation of three 68Ga-labeled PET probes targeting CSPG4, [68Ga]Ga-DOTA-LS10, [68Ga]Ga-DOTA-SH11, and [68Ga]Ga-DOTA-TH10. In pancreatic (ASPC1) and gastric (MKN45) carcinoma models, [68Ga]Ga-DOTA-TH10 showed prominent tumor uptake (ASPC1:1.63 ± 0.15%ID/g at 60 min), validated by Western blot and immunohistochemistry confirming CSPG4 overexpression. This study conducted the first PET imaging on CSPG4 expression in pancreatic Cancer and gastric Cancer models using 68Ga-labeled peptides, aiming to provide guidance for clinical real-time monitoring of its expression.

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