在线自动化制备多巴胺转运蛋白显像剂^(11)C-β-CFT

Automated on-line preparation of ^(11)C-β-CFT, a dopamine transporter imaging agent

目的建立适于在线自动化制备多巴胺转运蛋白显像剂11C-甲基N-2β-甲基酯3β-(4氟-苯基)托烷(β-CFT)的方法。方法将11C碘代甲烷转换成11C三氟甲基磺酰甲烷(Triflate甲烷),与前体-2β甲基酯-3β(4-氟苯基)去甲基托烷(norβCFT)反应,在线转移到反相C18柱上纯化,最后将11CβCFT洗脱于收集瓶。正常大鼠给药后不同时间处死,测定其生物分布。2例帕金森病(PD)患者分别用11CβCFT和多巴胺D2受体显像剂11C-雷氯必利(Raclopride)显像。结果在线自动化制备的11CβCFT放化纯>98%,比活度>2TBqmmol,校正合成效率为(92.4±3.1)%,从11C-碘代甲烷到11CβCFT的合成时间为4min。放射性在正常大鼠体内主要分布于肝、肾和脑;颅内纹状体摄取放射性最高,与小脑的比值在5、15、30min分别为2.15、4.18和3.15。2例PD患者显像结果表明,11CβCFT对PD的诊断比11C-Raclopride灵敏。结论在线自动化制备11C-β-CFT效率高,速度快,放化纯高。初步显像结果表明,其可满足临床需要。

Objective To develop an automatic synthesis method for the on-line preparation of dopamine transporter imaging agent, 11C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl)-tropanel ( 11C-β-CFT). Methods A mid-product, 11C-methyl triflate made from 11C-methyl iodide, was bubbled into 0.1 mg precursor, nor-β-CFT, to get 11C-β-CFT. The final product, 11C-β-CFT, was then purified through C-18 column, the column was eluted by 10 ml water twice and then by ethanol. The biodistribution of 11C-β-CFT was studied in SD rats. The human images were obtained in 2 cases of Parkinson's disease (PD), and the results were compared with that of 11C-Raclopride imaging. Results The whole synthesis process took about 4 min from 11C-methyl iodide to 11C-β-CFT. The synthesis yield (end of bomardment) was (92.4±3.1)%, the radiochemical purity over 98%, and the specific radioactivity was more than 2 TBq/mmol. 11C-β-CFT was mainly concentrated in liver, kidney and brain in SD rats. High uptake in striatum was noticed in the rat brain. The uptake ratios of striatum to cerebellum were 2.15, 4.18, 3.15 at 5, 15, 30 min after injection. 11C-β-CFT was found more sensitive than 11C-Raclopride in the early diagnosis of PD. Conclusions The automated on-line preparation method was verified in producing 11C-β-CFT of high radiochemical purity and synthesis yield for a short period of time. The product can be used in clinical imaging.