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

Abstract

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-PEG₂-Asp₂-PDL1P, which was labeled with nuclide ¹⁸F to obtain a new imaging agent [¹⁸F]AlF-NOTA-PEG₂-Asp₂-PDL1P. The total radiochemical yield of [¹⁸F]AlF-NOTA-PEG₂-Asp₂-PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [¹⁸F]AlF-NOTA-PEG₂-Asp₂-PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/μmol. [¹⁸F]AlF-NOTA-PEG₂-Asp₂-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 [¹⁸F]AlF-NOTA-PEG₂-Asp₂-PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy.