淀粉样蛋白显像剂11C-PIB的自动化制备优化及临床初步应用

Modified Auto-synthesis and Clinical Trial of the 11C-PIB as a Potential β-amyloid Imaging Agent

  • 摘要: 采用国产自动化碘代甲烷仪,通过氢化锂铝/四氢呋喃(LAH/THF)还原法制得的11C-碘代甲烷(11CH3I),在线转换成活性更高的11C-三氟磺酸甲酯(11CH3OTf),通入锥形反应瓶内,和1.0 mg PIB前体6-OH-BTA-0丁酮溶液在盐冰浴条件下反应,利用改进的HPLC方法纯化产品,并对最终产品进行质量控制。用昆明小鼠进行急性毒性试验,并行4例临床AD患者及1例正常人PET/CT显像。结果表明,改进后的自动化制备工艺,最终得到可供注射的11C-PIB 10%乙醇溶液,改进后使用前体原料更少,产率稳定。改进后的11C-PIB制备路线稳定可靠,初步临床研究表明,制备的11C-PIB显像剂可以用于阿尔茨海默病诊断。

     

    Abstract: The auto-synthesis method was developed for the on-line preparation of amyloid-beta (Aβ) plaques image agent 11C-PIB. A intermediate, 11CH3OTf, made from 11CH3 which was produced from 11CO2 with LAH/THF, was bubbled into 1.0 mg precursor 6-OH-BTA-0 butanone solution in salt-ice condition. The final crude product was then purified though prep-HPLC to get purified product. The human images were obtained in four cases of AD and 1 normal volunteer. The total synthesis process took about 35 minutes. The synthesis yield (EOS) was (25±5)% (not correct), the radiochemical purity over 98%, and the specific activity about 5.55 GBq/μmol. The modified automated preparation of 11C-PIB was verified in producing 11C-PIB of high radiochemical purity and synthesis yield in a short time. The results showed that this promising product could be used in clinical imaging.

     

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