Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model |
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| Affiliation: | 1. Department of Radiology and Nuclear Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;4. Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran;1. Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, PR China;2. Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, PR China;3. CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Centre for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China;4. College of Life Sciences, University of Science and Technology of China, Hefei 230026, PR China;5. China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, PR China;1. Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), 11365-3486, Tehran, Iran;2. Department of Clinical Biochemistry, School of Medical Sciences, Tarbiat Modares University (TMU), Tehran, Iran;3. Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, Iran;4. Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran |
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| Abstract: | Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC50 = 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide 64Cu. 64Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14–16 GBq/μmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. 64Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by human lung adenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after 64Cu-NOTA-Nb6 administration. The study revealed that 64Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, 64Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging. |
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| Keywords: | Heavy chain-only antibody (HCAb) PD-L1 Lung cancer PET/CT imaging |
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