A Novel Peptide-Based PD-L1 PET Tracer: Design, Synthesis, and Preclinical Imaging Validation

作者：Meilian Zhang, Ye Dong, Chunwei Mo, Zihao Chen, Yanjiang Han, Meng Wang, Haoran Liang, Yongshuai Qi, Yun Zhu, Ganghua Tang, Baomin Xi, Penghui Sun · 发表于：ACS Medicinal Chemistry Letters · 年份：2025 · DOI：10.1021/acsmedchemlett.5c00448 · 被引用次数：1 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiopharmaceutical Chemistry and Applications、Peptidase Inhibition and Analysis

PD-L1 (programmed death ligand 1), the primary ligand of PD-1 (programmed death 1), is widely expressed across various tumor types. In this study, we developed a novel PET probe, [ 18 F]AlF-Asp 2 -TPP-1, for noninvasive imaging of PD-L1 expression. The probe was synthesized with a radiochemical yield of 13.7%, high radiochemical purity (>95%), and a molar activity exceeding 2.4 GBq/μmol. Stability assays confirmed excellent stability both in vitro and in vivo . Dynamic PET imaging over 90 min revealed rapid tracer accumulation in tumors and other organs within 15 min postinjection. Tumor uptake was 2.48 ± 0.05% ID/g, 1.81 ± 0.20% ID/g, and 0.96 ± 0.09% ID/g at 30, 60, and 90 min, respectively. Collectively, these results suggest that [ 18 F]AlF-Asp 2 -TPP-1 is a promising PET imaging agent for monitoring PD-L1 expression in tumors and may serve as a valuable tool for guiding PD-L1-targeted immunotherapy.