Synthesis and preclinical evaluation of a novel molecular probe [18F] AlF-NOTA-PEG2-Asp2-PDL1P for PET imaging of PD-L1 positive tumor

Immunotherapy has brought great benefits to cancer patients, but only some patients benefit from it. Noninvasive, real -time and dynamic monitoring of the effectiveness of immunotherapy through PET imaging may provide assistance for the treatment plan of immunotherapy. In this study, we designed and synthesized a new targeted PD-L1 peptide NOTA-PEG(2)-Asp(2)-PDL1P, which was labeled with nuclide F-18 to obtain a new imaging agent [F-18]AlF-NOTA-PEG(2)-Asp(2)-PDL1P. The total radiochemical yield of [F-18]AlF-NOTA-PEG(2)-Asp(2)-PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [F-18]AlF-NOTA-PEG(2)-Asp(2)-PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/mu mol. [F-18]AlF-NOTA-PEG(2)-Asp(2)-PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro, it can specifically targets B16F10 tumor with PD-L1 expression, and had a relatively high retention in tumor, a relatively fast clearance in vivo and a higher tumor-to-non-target ratio, all of which could make [F-18]AlF-NOTA-PEG(2)-Asp(2)-PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy.