Zhang Xiang, Basuli Falguni, Swenson Rolf E
Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, Maryland.
J Labelled Comp Radiopharm. 2019 Mar;62(3):139-145. doi: 10.1002/jlcr.3705. Epub 2019 Feb 20.
Copper-mediated radiofluorination provides a quick and versatile approach for F-labeling of arenes and heteroarenes. However, this method is known to be base sensitive, which has been a barrier for preparative scale radiosynthesis. In this report, we provide an approach for copper-mediated radiofluorination without azeotropic drying or adding a base. [ F]Fluoride trapped on a PS-HCO Sep-Pak was quantitatively eluted with a solution of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAP·OTf) in anhydrous N,N-dimethylformamide (DMF). The eluted solution was directly used for copper-mediated radiofluorination. Twelve boronic ester substrates were tested, yielding fluorinated products in 27% to 83% radiochemical yield based on HPLC analysis. This approach was successfully applied to the radiosynthesis of [ F]flumazenil, a well-known positron emission tomography (PET) tracer for imaging central benzodiazepine receptors, with a radiochemical yield of 47%. This highly efficient protocol significantly augments the powerful copper-mediated radiofluorination approach.
铜介导的放射性氟化反应为芳烃和杂芳烃的F标记提供了一种快速且通用的方法。然而，已知该方法对碱敏感，这一直是制备规模放射性合成的一个障碍。在本报告中，我们提供了一种无需共沸干燥或添加碱的铜介导放射性氟化方法。捕获在PS-HCO Sep-Pak上的[F]氟化物用三氟甲磺酸4-二甲基氨基吡啶鎓（DMAP·OTf）在无水N，N-二甲基甲酰胺（DMF）中的溶液定量洗脱。洗脱后的溶液直接用于铜介导的放射性氟化反应。测试了12种硼酸酯底物，根据HPLC分析，放射性化学产率为27%至83%，得到了氟化产物。该方法成功应用于[F]氟马西尼的放射性合成，[F]氟马西尼是一种用于成像中枢苯二氮䓬受体的著名正电子发射断层扫描（PET）示踪剂，放射性化学产率为47%。这种高效的方案显著增强了强大的铜介导放射性氟化方法。
