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 <i>in vitro</i> and <i>in vivo</i>. 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.