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

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.