猫多巴胺转运蛋白PET脑显像研究

Study on PET Brain Imaging of ^(18)F-FP-β CIT in Cats

目的:制备多巴胺转运蛋白显像剂^(18)F-FP-βCIT[^(18)F-N-(3-氟丙基)-2β-甲酯基-3β-(4’-碘苯基)去甲基托烷],并进行猫PET脑显像。材料和方法:^(18)F-FP-βCIT的制备应用一步法:用K_(222)催化发生亲核氟化反应,得到^(18)F-FP-βCIT。PET显像仪器为Siemens ECAT HR^+ PET仪,3只健康正常猫进行^(18)F-FP-βCIT PET脑动态显像,观察纹状体体区放射性计数随时间的变化,并进行半定量分析。结果:^(18)F-FP-βCIT总放化合成时间为60～90min,时间校正后放化产率为2％～10％,放化纯度平均为96.3％,tR=3.38±0.20min。PET显像示早期(15min内)猫脑皮质及纹状体可见显影,随显像时间延长,脑皮质放射性减退,而纹状体显影更为清晰,30min纹状体/小脑比值达2.59±0.16,60min、90min及120min时此比值分别为2.73±0.23、2.52±0.13、2.08±0.11。结论:^(18)F-FP-βCIT是一种理想的PET多巴胺转运蛋白显像剂,可利用PET进行猫的脑受体方面的研究。

Purpose: To develop[^(18)F]N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane (^(18)F-FP-βCIT) as dopamine transporter (DAT) imaging agent and to study the regional brain DAT uptake in health cat using ECAT HR^+ PET scanner. Materials and Methods: ^(18)F-FP-βCIT was prepared based on nucleophilic fluorination of mesylate with K^(18)F/K_(222)(Kryptofix) via single-step method. Dynamic scans were carried out at 15min, 30min, 60min, 90min and 2h after injection of 22.2～55.5MBq ^(18)F-FP-βCIT. The changes of distribution of ^(18)F-FP-βCIT in brain with time elapse were observed, and striatum/cerebellum ratio was calculated. Results: The total radiochemical synthesis time was 60～90min, the overall radiochemical yield from stating synthesis was 2%～10%. The radiochemical purity was 96.3% by HPLC. In early stage(within 15min), ^(18)F-FP-βCIT accumulation in cortical, striatum, thalamus, and cerebellum was showed clearly. The radioactivity in cortical, thalamus and cerebellum exhibited decrease with time. The radioactivity mainly accumulated in striatum areas. The striatum-to-cerebellum ratio was 2.59±0.16 at 30min, 2.73±0.23 at 60min, 2.52±0.13 at 90min and 2.08±0.11 at 120min. Conclusiou: These results show that ^(18)F-FP-βCIT is a valuable PET imaging agent for dopamine transporter. Some brain receptor research on cat may be carried out with clinical PET scanner.