Evaluation of 64Cu radiolabeled anti-hPD-L1 Nb6 for positron emission tomography imaging in lung cancer tumor mice model. Issue 4 (15th February 2020)

• Record Type: Journal Article
• Authors: Jiang, Jinquan; Zhang, Meixin; Li, Guanghui; Liu, Teli; Wan, Yakun; Liu, Zhaofei; Zhu, Hua; Yang, Zhi
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 4(2020)
• Publication Date: 2020-02-15
• Subjects: Heavy chain-only antibody (HCAb) -- 64Cu-NOTA-Nb6 -- PD-L1 -- Lung cancer -- PET/CT imaging; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.126915
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 64 Cu-NOTA-Nb6 was a novel anti-hPD-L1-specific Molecular probe with a high affinity for potential hPD-L1 targeted non-invasive PET/CT imaging 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. 64 Cu-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 64 Cu-NOTA-Nb6 administration. The study revealed that 64 Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. 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 64 Cu. 64 Cu-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. 64 Cu-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 64 Cu-NOTA-Nb6 administration. The study revealed that 64 Cu-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, 64 Cu 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.