Development and Evaluation of Peptide-Based [ ¹⁸ F]AlF-WT12 and [ ¹⁸ F]AlF-IPB-WT12 Radiotracers for Noninvasive PD-L1 Imaging in Tumor Models

PD-L1 in the immune checkpoint pathway is expressed on various tumor cells, and multiple PD-1/PD-L1 inhibitors have been approved for treating these malignancies. However, clinical studies indicate that only 20-30% of patients benefit from immunotherapy. To address this problem, two novel peptide-based radiotracers, [¹⁸F]AlF-WT12 and [¹⁸F]AlF-IPB-WT12, were developed within the present study. Both tracers were successfully prepared, with radiochemical yields of 15-25% and 25-35%, respectively (<i>n</i> > 5), and both exhibited high molar activities (17.97-30.11 GBq/μmol and 18.09-26.46 GBq/μmol, respectively). Their evaluation using in vivo PET imaging demonstrated significantly higher accumulation of both tracers in PD-L1-expressing 4T1-hPD-L1 and A549-hPD-L1 tumors compared to CHO control tumors. Notably, the [¹⁸F]AlF-IPB-WT12 exhibited superior tumor uptake and prolonged retention time relative to [¹⁸F]AlF-WT12. Additionally, good correlations were obtained between the PET imaging results and the results obtained from biodistribution studies and immunohistochemistry studies. Together, our findings demonstrate the promise of [¹⁸F]AlF-IPB-WT12 as a tracer for noninvasive tumor imaging in clinical settings, with potential to guide immunotherapy decisions.