Synthesis and Preliminary Evaluation of FAPα Targeted Tracer 131I-FAPI-03
Using N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine)as scaffold,we prolonged the linker with serine to obtain a FAPI derivative ATE-FAPI-03,which was subsequently labeled with 131I by electrophilic substitution.Then the in vitro stability,Log P value,binding affinity,targeting properties and biodistribution behavior of 131I-FAPI-03 was evaluated.Results show that 131I-FAPI-03 was lipophilic and stable in vitro,capable of specifically binding to FAPα-positive U87MG cells fast with a major proportion trapped intracellularly.After 10 min of incubation,131I-FAPI-03 showed a specific binding rate of(22.00±0.35)%,and the binding rate increased with the incubation time,to a peak of(37.5±0.83)%at 180 min.However,the FAPα-negative MCF-7 cells exhibited very low uptake of 131I-FAPI-03 at any time point.The IC50 measured by the competition assay indicated significant binding property of 131I-FAPI-03.Biodistribution studies revealed that 131I-FAPI-03 could rapidly accumulate in tumor sites with an uptake of(14.90±3.21)%ID/g at 5 min post injection.At 2 h post injection,131I-FAPI-03 displayed the highest tumor-to-muscle ratio of 43.7±16.7.All above results provided important reference for the development of novel FAPα-targeting tracers.
国家科技期刊平台
NSTL
万方数据
