^18F-FECNT的生物分布特性及小动物PET显像研究

Biodistribution and microPET imaging of ^18F-FECNT as a dopamine transporter imaging agent

目的探讨多巴胺转运蛋白（DAT）显像剂^18F-N-（2-氟乙基）-2β-甲酯基-3β-（4-氯苯基）去甲基托烷（FECNT）的体内生物分布特性，并进行小动物PET显像研究，以评价其临床应用潜力。方法自制^18F-FECNT注射液，进行正常小鼠脑内分布、DAT阻断实验、正常和单侧帕金森病（PD）模型大鼠小动物PET脑显像。结果正常ICR小鼠在给药后5，15，30，60，120，180min的进脑量分别达2．22，1．20，1．02，0．78，0．71，0．67百分注射剂量率（％ID）。给药后5～60min内，药物在纹状体（ST）部位浓聚，纹状体／小脑（ST／CB）比值在5，15，30，60min时分别为2．56，3．47，2．78，1．63。120min后ST的放射性浓度下降至与其他脑组织相近。脑内DAT经β-CFF阻断的小鼠，其ST未见放射性浓聚。正常大鼠小动物PFT显像图中ST显影清晰（ST／CB=2．18±0．16，n=3），双侧对称；PD模型大鼠未损毁侧ST放射性浓聚（ST未损毁侧／CB=2．01±0．23，n=3），而损毁侧ST放射性摄取不明显，与小脑相当（ST损毁侧／CB=1．04±0．05）。结论^18F-FECNT能透过无损的血脑屏障浓聚于ST，对DAT具有高亲和性与特异性，是一种有临床应用潜力的DAT显像剂。

Objective 2β-carbomethoxy-3β-（4-corophenyl）-8-（2-^18F-iluoroethyl） nortropane （^18F- FECNT ） is a recently developed dopamine transporter （DAT） imaging agent. The aim of this study was to evaluate its brain biodistribution and to assess its usefulness in quantitation of DAT density in normal and hemiparkinsonian rats. Methods Six groups of mice （5 mice each group） received ^18F-FECNT were sacrificed at indicated time post injection. Different brain regions （cortex, hippocampus, striatum, cerebellum） were removed, weighed, and countered. DAT blocking effect was investigated in mice pretreated with 2β- Carbomethoxy-3β- （4-fluorphenyl） tropane （β-CFT） at before ^18F-FECNT injection. MicroPET scans were performed in both normal and unilaterally 6-hydroxydopamine-lesioned rats. Results The brain uptake of ^18F-FECNT was 2.22, 1.20, 1.02, 0.78, 0.71, and 0.67 percent injection dose （% ID） at 5, 15, 30, 60, 120, and 180 min post injection. Radioactivity concentration of the striatum, the target region, was the highest in the brain regions and decreased quickly from 5 to 60 min and reached to background at 120 min of post injection. The striatum/cerebellum ratio was 2.56, 3.47, 2.78, 1.63, 0.97, and 0.88 at 5, 15, 30, 60, 120, and 180 rain, respectively, post injection. The selective striatum uptake of iSF.FECNT decreased dramatically to the background when the DAT was blocked with β-CFT. The striatum of normal rats in micro- PET exhibited symmetrical （ left/right = 1.00 ± 0.05 ） and the highest uptake of radioactivity （ striatum/cerebellum =2.18 ±0.16 at 5- 125 min, n =3 ）. As for the hemiparkinsonian rats, nonsymmetrical [ unlesioned striatum/cerebellum vs lesioned striatum/cerebellum = 2.01 ± 0.23 （ n = 3 ） vs 1.04 ± 0.05 ] and the highest uptake of radioactivity were also noted. Conclusions The results suggest that ^18F-FECNT rapidly passes through blood-brain barrier and locates in stiatal region with high affinity and selectivity to DAT. It is a potential radiotracer to assess the in vivo DAT density in Parkinson＇s disease.