Development and Preclinical Evaluation of the Novel Peptide-Based Tracer 68Ga-PDT01 for Noninvasive PET Imaging of PD-L1 Expression.

Programmed death-ligand 1 (PD-L1) is a key mediator of tumor immune evasion and plays a critical role in tumor immunodiagnosis and immunotherapy. We developed a PD-L1-targeted peptide PET tracer, 68Ga-PDT01, incorporating a 2-substituted naphthyl group and 5-(trifluoromethyl)nicotinic acid to enhance tumor uptake and retention. 68Ga-PDT01 exhibited moderate binding affinity (KD = 304 ± 26 nM) and specific uptake in PD-L1-positive cells, which was blocked by excess unlabeled peptide. PET imaging demonstrated clear tumor visualization in multiple subcutaneous tumor models with tumor-to-muscle ratios >6.00 at 1 h postinjection. Tracer uptake increased ∼3.16-fold following cisplatin-induced PD-L1 upregulation, indicating sensitivity to dynamic PD-L1 modulation. These findings suggest that 68Ga-PDT01 enables accurate, noninvasive assessment of PD-L1 expression and holds translational potential for guiding PD-L1-targeted diagnosis and therapeutic monitoring.