Department of Radiology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI, 48109, USA.
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, MI, 48109, USA.
Sci Rep. 2017 Mar 22;7(1):233. doi: 10.1038/s41598-017-00110-1.
In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional radiochemistry systems. In particular, the presence of bases (e.g. KCO) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesized that these limitations could be addressed through the development of alternate techniques for preparing [F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [F]fluoride from ion exchange cartridges. The new procedures are effective for fluorine-18 radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.
在相对较短的时间内，过渡金属介导的放射性氟化反应改变了 PET 放射化学领域。这些反应能够使各种底物进行放射性氟化，便于获得使用传统氟-18 放射化学难以合成的放射性药物。然而，为了将这些新反应适应于自动化放射性药物生产，人们发现它们在传统放射化学系统的限制下存在一些局限性。特别是，与氟-18 制备相关的碱（例如 KCO）和/或相转移催化剂（PTC）（例如 kryptofix 2.2.2）的存在被发现会对反应产率产生不利影响。我们假设，通过开发替代的[F]氟化物制备技术可以解决这些限制。这种方法还为洗脱液的开发提供了可能，洗脱液可以根据特定的金属催化反应的需求进行定制。在本通讯中，我们证明了各种铜盐、碱和辅助配体的溶液可用于从离子交换柱中洗脱[F]氟化物。这些新程序对氟-18 放射化学有效，并且作为概念验证，已经用于优化原本对碱敏感的铜介导的放射性氟化反应。
