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

doi:10.7538/tws.2017.30.01.0023

Abstract

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.

Key words: positron emission tomography, Alzheimer’s disease, ¹¹C-PIB

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。

关键词: 正电子发射断层扫描显像, 阿尔茨海默病, ［N-甲基-¹¹C］2-［4&prime, -(甲氨基)苯基］-6-羟基苯并噻唑

ZHANG Zheng-wei;ZHU Jian-hua;YAO Zhi-wen;GUAN Yi-hui;HUA Feng-chun. Modified Auto-synthesis and Clinical Trial of the ¹¹C-PIB as a Potential β-amyloid Imaging Agent[J]. Journal of Isotopes, 2017, 30(1): 23-28.

张政伟;朱建华;姚志文;管一晖;华逢春. 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[J]. 同位素, 2017, 30(1): 23-28.

References

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

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

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