Veth Lukas, Windhorst Albert D, Vugts Danielle J
Dept. of Radiology and Nuclear Medicine Amsterdam UMC, location Vrije Universiteit, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.
Angew Chem Int Ed Engl. 2025 Jan 21;64(4):e202416901. doi: 10.1002/anie.202416901. Epub 2024 Nov 6.
The development of new tracers for positron emission tomography (PET) is highly dependent on the available synthetic tools for their radiosynthesis. Herein, we present the radiosynthesis and application of [F]trifluoroiodomethane - the first reagent for broad scope radical [F]trifluoromethylation chemistry in high molar activity. CF FI can be prepared from [F]fluoroform with 67±5 % AY and >99 % RCP. Its synthetic utility is demonstrated by the radiosynthesis of previously unprecedented F-labeled α-trifluoromethyl ketones and F-labeled trifluoromethyl sulfides, important motifs that are present in a range of bioactive compounds. Both protocols are Ru- and photo-mediated and proceed under mild reaction conditions. They show good functional group tolerance evidenced by the respective reaction scopes and make use of easily obtainable starting materials. The products can be isolated in 8.3-11.1 GBq/μmol (starting from ca. 5 GBq [F]fluoride). The applicability to PET tracer synthesis is shown by the radiolabeling of bioactive compounds, such as derivatives of probenecid and febuxostat. In a broader context, this work opens the door to the utilization of radical [F]trifluoromethylation chemistry for the radiolabeling of PET tracers in high molar activity.
正电子发射断层扫描（PET）新型示踪剂的研发高度依赖于用于其放射性合成的现有合成工具。在此，我们展示了[F]三氟碘甲烷的放射性合成及应用——这是第一种用于高摩尔活度下广泛自由基[F]三氟甲基化化学的试剂。CF FI可由[F]氟仿制备，产率为67±5 %，放射化学纯度>99 %。通过放射性合成前所未有的F标记α-三氟甲基酮和F标记三氟甲基硫化物证明了其合成效用，这些重要结构基元存在于一系列生物活性化合物中。这两种方法均由钌和光介导，且在温和反应条件下进行。从各自的反应范围可证明它们对官能团具有良好的耐受性，并使用易于获得的起始原料。产物可在8.3 - 11.1 GBq/μmol下分离（以约5 GBq [F]氟化物为起始原料）。生物活性化合物（如丙磺舒和非布司他的衍生物）的放射性标记表明了其在PET示踪剂合成中的适用性。在更广泛的背景下，这项工作为利用自由基[F]三氟甲基化化学进行高摩尔活度PET示踪剂的放射性标记打开了大门。
