The preclinical pharmacological study of dopamine transporter imaging agent ~(18)F-FP-β-CIT

摘要

The paper is to study pharmacologic characteristics of ~(18)F-FP-β-CIT (~(18)F-N-(3-fluoropropyl)-2β- car-bomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of ~(18)F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that ~(18)F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that ~(18)F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that ~(18)F-FP-β-CIT is very safe. So ~(18)F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.