基于NEPTIS Perform模块的Aβ显像剂18F-AV45的自动化合成

Automated Synthesis of Aβ Imaging Agent 18F-AV45 Based on NEPTIS Perform Module

  • 摘要: 为满足临床应用需求,利用NEPTIS perform合成模块,研发自动化合成Aβ显像剂18F-AV45的合成工艺。在NEPTIS perform模块上,编写合成18F-AV45的运行程序,经冷实验调试运行成功后,以前体AV105为原料,与18F进行亲核取代反应,制得18F中间体。中间体经盐酸水解、碱中和制得18F-AV45粗产品,经固相萃取、半制备高效液相色谱(HPLC)分离纯化、富集,最后经无菌过滤器制得18F-AV45注射液,对产品质量进行分析。结果表明,该合成工艺全过程总耗时约60 min,未衰减校正放化产率为(32.1±2.1)%(n=5),放化纯度>98%,外观颜色、pH、体外稳定性及细菌内毒素、残留溶剂均符合要求。采用NEPTIS perform 合成模块一步法自动合成18F-AV45,工艺简单,重现性好,所得产品质量符合规定,满足临床研究要求。

     

    Abstract: To meet the clinical application requirements, the Aβ-Amloid imaging agent 18F-AV45 was synthesized automatically using NEPTIS perform synthesis module .In the pre-written program, the AV105 was used as precursor to obtain the 18F-intermediate through nucleophilic substitution reaction with 18F, followed by hydrolysis with hydrochloric acid, neutralization with base to obtain the crude product of 18F-AV45, which was next purified by solid-phase extraction and semi-preparative high-performance liquid chromatography (HPLC). Finally, 18F-AV45 injection solution was obtained through sterile filtration, followed by quality control analysis. The average production time of 18F-AV45 preparation was 60 min, the no-corrected efficiency was (32.1±2.1)% (n=5), the radiochemical purity was over 98%, and the appearance color, pH value, in vitro stability, bacterial endotoxin, and residual solvents all met the requirements. 18F-AV45 could be synthesized automatically and simply by NEPTIS perform module with good repeatability and the product meets the requirements for clinical use.

     

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