Synthesis and Preliminary Biological Assessment of Fluorosulfonyl-containing Small-molecular PET Probe Targeting PD-L1
A number of research data have demonstrated that the effect of anti-tumor immunotherapy is positively correlated with the expression level of programmed cell death protein ligand 1(PD-L1)in tumors.Positron emission computed tomography(PET)imaging using radionuclide-labeled probes is a-ble to precisely determine the level of PD-L1 expression in vivo.Here,a novel small-molecule com-pound 8 targeting PD-L1 was synthesized by introducing fluorosulfonyl group into the scaffold of bi-phenyl small-molecule inhibitor.The structure of compound 8 was characterized by MS and 1H/13C/19F NMR characterization.Compound 8 showed good inhibit activity to the interaction of PD-1/PD-L1 with IC50 values of 237.2±9.37 nM measured by homogeneous time-resolved fluorescence.In vivo ex-periments showed that compound 8 had good biocompatibility.Small-molecule PET probe[18F]8 was synthesized by"18F-19F"ion exchange of fluorosulfonyl group in over 79％radio-conversion and nearly 98％radio-chemical yield with high stabilitye in both PBS and mouse serum.For[18F]8,the lipid-water partition coefficient was 1.87±0.19.The maximum uptake of probe[18F]8 reached 2.23±0.05％AD in mouse melanoma cells B16-F10 and the uptake could be significantly blocked by com-pound 8(0.24±0.21％AD).Thus,the simple,rapid,high-yield labeling method and good affinity for PD-L1 provide the basis for PET imaging of probe[18F]8.
PD-L1fluorosulfonyl groupsmall-molecule PET probeaffinity18F-19F
万方数据
维普
