64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model

// Xue-Di Han 1, * , Chen Liu 1, * , Fei Liu 1 , Qing-Hua Xie 1, 2 , Te-Li Liu 1 , Xiao-Yi Guo 1 , Xiao-Xia Xu 1 , Xing Yang 3 , Hua Zhu 1 and Zhi Yang 1 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing 100142, China 2 College of Chemistry, Sichuan University, Chengdu 610064, China 3 Russell H. Morgan, Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, United States * These authors contributed equally to this work Correspondence to: Hua Zhu, email: zhuhuananjing@163.com Zhi Yang, email: pekyz@163.com Keywords: prostate specific membrane antigen, neo-vasculature, gastric cancer, PET, 64Cu Received: April 14, 2017      Accepted: May 14, 2017      Published: May 26, 2017 ABSTRACT Here, we report that it’s feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64 Cu. 64 Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/μmol. It showed good stability in vitro . The specificity of 64 Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated ( n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64 Cu-PSMA-617. All those results suggested 64 Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer.