The paper is to study pharmacologic characteristics of 18F-FP-β-CIT (18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18F-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 18F-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 18F-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 18F-FP-β-CIT is very safe. So 18F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity.
LI XiaominxCHEN ZhengpingWANG SongpeiTANG JieLIN YansongZHU Zhaohui2FANG Ping
This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition coefficients were determined in n-octanol and phosphate buffer (PB) (pH 7.0 and pH 7.4). 6-Hydroxydopamine (6-OHDA) left-sided lesioned Parkinsonian rats were established and validated by rotational behavior tests. Biodistribution in vivo in mice, autoradiography in normal and hemi-Parkinsonian rat brains, and toxicity test were performed. The results showed that partition coefficients were 34.14 (pH 7.0) and 56.41 (pH 7.4), respectively. Biodistribution exhibited rapid uptake and favorable retention in the mice brains. The major radioactivity was metabolized by the hepatic system. The autoradiography showed that 18F-FECNT was highly concentrated in striatum, and that the left and the right striatal uptake were symmetrical in normal SD rat brains. In left-sided lesioned PD rat brains, the striatal uptake of 18F-FECNT bilaterally decreased in comparison with normal rats. No significant uptake was visible in the 6-OHDA lesioned-sided striatal areas. The results demonstrated that 18F-FECNT binds to DAT was specific. Toxicity trial displayed that the acceptable dose per kilogram to mice was 625 times greater than that to human. These indicate that 18F-FECNT is a potentially safe and useful DAT PET imaging agent in the brain.
