An Improved HPLC Separation Method for TSPO Radioligand [11C]ER176 Clinical Production

IF 0.9 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Journal of labelled compounds & radiopharmaceuticals Pub Date : 2024-04-19 DOI:10.1002/jlcr.4093

Kang-Po Li, Hancheng Cai

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引用次数: 0

Abstract

Mitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [¹¹C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [¹¹C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [¹¹C]ER176 using a reverse phase semi-preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [¹¹C]ER176 was collected around 8.5–9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [¹¹C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.

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一种用于 TSPO 放射性配体 [11C]ER176 临床生产的改进型 HPLC 分离方法

线粒体膜转运蛋白18 kDa（TSPO）在活化的小胶质细胞中表达增加，被确定为神经炎症成像的一个可信靶点。[11C]ER176与TSPO特异性结合，已被开发为TSPO PET成像的第三代放射性配体，与前代产品相比，它在量化神经炎症方面具有更好的潜力。在本研究中，我们开发了一种自动放射合成技术，并改进了 HPLC 纯化方法，用于 [11C]ER176 的临床生产。改进后的高效液相色谱分离法被集成到[11C]ER176的自动化生产中，采用反相半制备高效液相色谱柱，使用等度泵和甲醇与50 mM乙酸铵的混合物作为流动相。与[11C]ER176 相对应的馏分在 8.5-9.0 分钟左右收集完毕，不会受到附近杂质的污染。自动生产过程在轰击结束（EOB）后耗时约 30 分钟，最终产品[11C]ER176 的质量符合当前美国药典和 FDA CGMP 要求的所有临床使用规范。

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来源期刊

Journal of labelled compounds & radiopharmaceuticals 医学-分析化学

CiteScore

3.30

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Labelled Compounds and Radiopharmaceuticals publishes all aspects of research dealing with labeled compound preparation and applications of these compounds. This includes tracer methods used in medical, pharmacological, biological, biochemical and chemical research in vitro and in vivo. The Journal of Labelled Compounds and Radiopharmaceuticals devotes particular attention to biomedical research, diagnostic and therapeutic applications of radiopharmaceuticals, covering all stages of development from basic metabolic research and technological development to preclinical and clinical studies based on physically and chemically well characterized molecular structures, coordination compounds and nano-particles.