Radiolabeling and evaluation of Cu-64-DOTA-F56 peptide targeting vascular endothelial growth factor receptor 1 in the molecular imaging of gastric cancer

Noninvasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in early diagnosis of gastric cancer. Here we reported the synthesis, radiolabeling, and evaluation of a novel Cu-64-radiolabeled peptide for noninvasive positron emission tomography (PET) imaging of VEGFR1 positive gastric cancer. The binding of modified peptide WHSDMEWWYLLG (termed as F56) to VEGER-1 expressed in gastric cancer cell BCG823 has been confirmed by immune-fluorescence overlap. DOTA-F56 was designed and prepared by solid-phase synthesis and folded in vitro. Cu-64-DOTA-F56 was synthesized in high radiochemical yield and high specific activity (S.A. up to 255.6 GBq/mmol). It has excellent in vitro stability. Micro-PET imaging of 64Cu-DOTA-F56 identifies tumor in BCG823 tumor-bearing mice, while that of F-18-FDG does not. Immunohistochemical analysis of excised BCG823 xenograft showed colocalization between the PET images and the staining of VEGFR1. These results demonstrated that Cu-64-DOTA-F56 peptide has potential as a noninvasive imaging agent in VEGFR1 positive tumors.Major Project on Drug Research and Development for the 12th Five-Year Plan of China [2012ZX09103-301-013]; National 973 Program of China [2015CB553906]; National Natural Science Foundation of China [81172083, 81371592, 81401467, 81301966, 81571705]; Beijing Natural Science Foundation [7132040, 7154188]SCI(E)PubMedARTICLEscc@bjcancer.org; pekyz@163.com113301-3310