Preparation and Characterization of Small-molecule PET Probes Targeting Immune Checkpoints
Programmed cell death protein-1(PD-1)and its ligand 1(PD-L1)are key targets of immu-notherapy,and expression levels of PD-1 or PD-L1 are closely related to patients'response to immuno-therapy.Therefore,accurate detection of PD-1/PD-L1 expression level is of great clinical significance.It is essential to accurately select patients who can benefit from anti-PD-1/PD-L1 immunotherapy.In this study,based on the core structure of biphenyl methyl aryl ether as the core structure of PD-1/PD-L1 small molecule inhibitor,compound NOTA-LP was modified with metal ion chelating agent NO-TA.The precursor NOTA-LP was radiolabeled with 68 Ga and 18 F to obtain molecular probes[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP with the radiochemical purity of>95%.The radiochemical yield of[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP was 39.3±4.8%and 21.9±8.6%,respec-tively.The lipid-water partition coefficient of[68 Ga]NOTA-LP and[18 F]AlF-NOTA-LP was deter-mined to be1.53±0.04 and2.04±0.13,respectively.Stability of both probes was tested by incuba-ting the probes with PBS and mouse serum for 2 h,and the radiochemical purity of both probes was higher than 95%,indicating they are stable.The cell uptake assay confirmed that both probes could detect the expression level of PD-L1 at the cellular level.
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