Construction of an Iodine-Labeled CS1001 Antibody for Targeting PD-L1 Detection and Comparison with Low-Molecular-Peptide Micro-PET Imaging

作者：Dan Li, Feng Wang, Jinquan Jiang, Xingguo Hou, Jin Ding, Zilei Wang, Yan Chen, Teli Liu, Zhi Yang, Hua Zhu · 发表于：Molecular Pharmaceutics · 年份：2022 · DOI：10.1021/acs.molpharmaceut.2c00789 · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiopharmaceutical Chemistry and Applications、Lung Cancer Treatments and Mutations

Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), the research focus in immune checkpoint regulation, play an important role in tumor immunotherapy. Inhibitors of this pathway are also the focus of tumor immunotherapy research. The PD-1/PD-L1 pathway can be blocked by selective binding to PD-L1. Clinical trials have been conducted in a variety of patients with advanced solid tumors. CS1001 is a high-affinity humanized full-length anti-PD-L1 monoclonal antibody with great clinical significance. We constructed a PD-L1-targeted radioactive molecular probe, 124/125 I-labeled full-length antibody CS1001, and evaluated its binding specificity and targeting ability to PD-L1 in tumor cells and tumor models. Additionally, a comparison study with 68 Ga-WL12, a PD-L1 targeting peptide, was conducted. The binding potency of 125 I-CS1001 to human PD-L1 was evaluated by enzyme-linked immunosorbent assay (ELISA), and the K d value was 52.1 ± 19.3 nM. The cellular uptake of 125 I-CS1001 was examined in Chinese hamster ovary cells (CHO) and CHO expressing human PD-L1 (CHO-hPD-L1). At 2 h, the uptake values of 125 I-CS1001 in CHO-hPD-L1 without blocking and in the presence of 0.1 mg non-radiolabeled CS1001 were 3.60 ± 0.08 and 0.09 ± 0.005 (%AD/2 × 10 5 cells, p < 0.001). Micro-PET imaging was performed between 8 to 192 h after injection of 124 I-CS1001 into normal KM mice and CHO-hPD-L1 and HeLa tumor models. The standard uptake value (SUV) of relevant organs in PET images was ...