Evaluation of 111In-DOTA-F56 peptide targeting VEGFR1 for potential non-invasive gastric cancer xenografted tumor mice Micro-SPECT imaging |
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| Affiliation: | 1. Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266000, PR China;2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, PR China;3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China;1. China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China;2. School of Pharmacy, Tianjin Medical University, Tianjin 300070, China;3. Centre de recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France;1. Division of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Republic of Korea;2. Department of Crop Science and Biotechnology, Dankook University, Cheonan 31116, Republic of Korea;3. Department of Biological Sciences, Chonbuk National University, Jeonju 54896, Republic of Korea;4. Forest Biomaterials Research Center, National Institute of Forest Science (NIFS), Jinju 52817, Republic of Korea;1. Department of Oncology, Division of Oncological Imaging, University of Alberta, Edmonton, AB T6G 2R3, Canada;2. Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg 69120, Germany;3. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada |
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| Abstract: | Non-invasive imaging of vascular endothelial growth factor receptor 1 (VEGFR1) remains a great challenge in the early diagnosis of tumors, especially in gastric cancer. Here, we designed and evaluated a novel 111In-DOTA-F56 peptide as a radioactive analogue of F56 (peptide WHSDMEWWYLLG) to bind VEGFR1. It was obtained by radiolabeling DOTA-F56 with 111InCl3 with 98% radiochemical purity and 1.4 ± 0.4 GBq/µmol specific activity. 111In-DOTA-F56 was obtained by the reaction of DOTA-F56 (10 µg) with 111InCl3 in pH 4.0 sodium acetate buffer at 85 °C for 20 min. 111In-DOTA-F56 shows good stability in 0.01 M Phosphate Buffered Saline (PBS) and 5% Human Serum Albumin (HSA). 111In-DOTA-F56 has a high binding affinity for human gastric cancer BGC-823 cells. Bio-distribution studies of 111In-DOTA-F56 were performed in nude mice xenografted with human gastric cancer BGC-823 cells and the results revealed tumor uptake accumulation. A blocking dose of DOTA-F56 significantly reduced the tumor uptake of 111In-DOTA-F56. Tumors were observed with Micro-SPECT images, and the uptake in the tumor increased with time from 4 h to 24 h. The MIP of the Micro-SPECT also showed that the excess DOTA-F56 can specifically block 111In-DOTA-F56 in a mouse tumor model. We successfully synthesized the 111In-DOTA-F56 VEGFR1-targeted peptide as a non-invasive molecule with fine radiochemical properties. Micro-SPECT indicates tumor uptake, which can be further blocked by excess of the F56 peptide, indicating that 111In-DOTA-F56 peptide has potential for early detection of VEGFR1 positive gastric cancer and is worthy of further clinical investigations. |
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| Keywords: | DOTA-F56 VEGFR1 Micro-SPECT imaging Gastric cancer |
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