Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
J Labelled Comp Radiopharm. 2024 Jul;67(9):324-329. doi: 10.1002/jlcr.4113. Epub 2024 Jun 6.
A new automated radiosynthesis of [C]2-(2,6-difluoro-4-((2-(N-methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([C]K2), a radiopharmaceutical for the glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)-compliant synthesis of [C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33 min from end of bombardment, and the production method provides 2.66 ± 0.3 GBq (71.9 ± 8.6 mCi) of [C]K2 in 97.7 ± 0.5% radiochemical purity and 754.1 ± 231.5 TBq/mmol (20,382.7 ± 6256.1 Ci/mmol) molar activity (n = 3). Batches passed all requisite quality control testing confirming suitability for clinical use.
一种新的 [C]2-(2,6-二氟-4-((2-(N-甲基苯磺酰胺基)乙基)硫代)苯氧基)乙酰胺 ([C]K2) 的自动化放射合成方法被报道，[C]K2 是一种用于谷氨酸 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 受体的放射性药物。虽然已经描述了手动合成方法，但这些方法不适合用于常规生产更大批次的 [C]K2，以用于 (前)临床 PET 成像应用。为了满足我们的功能神经影像学合作者对成像剂的需求，在此，我们报告了一种符合现行良好生产规范 (cGMP) 的 [C]K2 合成方法，使用商业合成模块。新的合成方法完全自动化，并已验证可用于临床。从结束轰炸开始，总合成时间为 33 分钟，生产方法提供 2.66±0.3GBq（71.9±8.6mCi）的 [C]K2，放射化学纯度为 97.7±0.5%，摩尔活度为 754.1±231.5TBq/mmol（20,382.7±6256.1Ci/mmol）（n=3）。所有批次均通过了所有必需的质量控制测试，证实了其适合临床使用。
