Yi Liu, Zhengjie Wang, Xiang Li, Fei Kang, Xiaowei Ma, Weidong Yang, Wenhui Ma* and Jing Wang* Pages 96 - 103 ( 8 )
Peptides containing the asparagine-glycine-arginine (NGR) motif can target the tumor neovascular biomarker CD13/aminopeptidase N receptor. D-K6L9 is a tumor-selective anti-cancer peptide. To improve the capacity of NGR peptides to target tumors, we joined the NGR and D-K6L9 peptides to form NKL. Next, we linked 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to NKL and labeled it with gallium 68 (68Ga, t1/2 = 67.7 min) to form 68Ga-DOTA-NKL. This novel probe was characterized in vitro. 68Ga-DOTA-NKL was stable in phosphate buffered saline at room temperature and in human serum at 37°C. We determined that the uptake rate of 68Ga-DOTA-NKL in CD13 receptor-positive 22Rv1 tumor cells was 3.15% ± 0.04 after 2 h, and tested 68Ga-DOTA-NKL using positron emission tomography (PET)/computed tomography imaging in vivo. MicroPET imaging results revealed that 22Rv1 tumor uptake of 68Ga-DOTA-NKL was 8.69 ± 0.20, 6.61 ± 0.22, 3.85 ± 0.06, and 1.41 ± 0.23 percentage injected dose per gram of tissue (%ID/g) at 0.5, 1, 2, and 3 h postinjection (pi), respectively. The tumor-to-background contrast in the subcutaneous human prostate cancer 22Rv1 mouse model was 9.97 ± 1.90. The 68Ga-DOTA-NKL probe has combined tumor-targeting and tumor-selective properties, and may be used to diagnose CD13-positive tumors.
Anticancer peptide, CD13 receptor, NGR peptide, PET/CT imaging, tumor targeting, Tomography.
Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, Department of Nuclear Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032