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

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, [¹⁸F]-AlF-Asp₂-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 [¹⁸F]-AlF-Asp₂-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.