验证生产中枢神经系统穿透性 KRASG12c 抑制剂 [11C]AZD4747 的良好生产规范程序

IF 0.9 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS Journal of labelled compounds & radiopharmaceuticals Pub Date : 2023-12-20 DOI:10.1002/jlcr.4079

Miguel A. Cortés González, Antonia A. Högnäsbacka, Christer Halldin, Magnus Schou

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摘要

AZD4747 是一种 KRASG12C 抑制剂，最近的研究表明它能有效穿过非人灵长类动物的血脑屏障。本研究开发了符合 GMP 标准的 [11C]AZD4747 生产方法，以便在人类受试者中进行 PET 研究。经过验证的程序可将[11C]AZD4747制成注射溶液，放射性收率高（1656 ± 532 MBq），放射化学纯度高（100%），合成结束时的摩尔活度为 77 ± 13 GBq/μmol。最终产品的质量控制令人满意，符合所有验收标准。

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Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor

AZD4747 is a KRAS^G12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [¹¹C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [¹¹C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

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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.