Noninvasive evaluation of PD-L1 expression using Copper 64 labeled peptide WL12 by micro-PET imaging in Chinese hamster ovary cell tumor model. (15th May 2021)

• Record Type: Journal Article
• Authors: Jiang, Jinquan; Li, Dan; Liu, Teli; Xia, Lei; Guo, Xiaoyi; Meng, Xiangxi; Liu, Futao; Wang, Feng; Yang, Zhi; Zhu, Hua
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 40(2021)
• Publication Date: 2021-05-15
• Subjects: PD-L1 -- 64Cu-NOTA-WL12 -- PET/CT imaging; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127901
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 64 Cu-NOTA-WL12 was a novel anti-hPD-L1 radiotracer with a high affinity, over 90% labeling yield, over 99% radiochemical purity and 20 MBq/nmol specific activity. In vitro study, the radiotracer shows good stability in saline and 5% HSA solutions. 64 Cu-NOTA-WL12 has a high binding affinity 3.012 nM which was tested by Surface Plasmon Resonance. Tumor lesion can be clearly observed from 30 min to 120 min by micro-PET/CT post-injection in PD-L1 positive tumor. All results in vivo and vitro experiments indicated that 64 Cu-NOTA-WL12 can provide a noninvasive PET strategy for PD-L1 detection. Abstract: As an indicative biomarker for immunotherapy, PD-L1 plays an important role in the clinical decision-making of the immune checkpoint blockade therapy. PET imaging through radiotracer can real-timely, quantitatively, and non-invasively assess the expression of PD-L1 in tumors. Here, we reported a copper-64 radiolabeled NOTA-WL12, 64 Cu-NOTA-WL12, and preliminarily evaluated its application in non-invasively detecting the PD-L1 expression. 64 Cu-NOTA-WL12 was produced with high radiochemical yield (>90%), radiochemical purity (>98%), and specific activity (20 MBq/nmol). 64 Cu-NOTA-WL12 showed high in vitro stability and high binding affinity to the PD-L1 (KD ≈ 3.012 nM). The micro-positron emission tomography/computerized tomography (micro-PET/CT) imaging indicated that 64 Cu-NOTA-WL12 was specifically accumulated in the tumor with PD-L1 expression. All results demonstrated that 64 Cu-NOTA-WL12 holds great potential for noninvasive evaluation of PD-L1 expression levels.