¹⁸ F-Labeling Chemistry in Aqueous Media

¹⁸ F-Labeled molecular tracers and subsequent positron emission tomography are indispensable molecular imaging tools in medical diagnosis and research. The preparation of ¹⁸ F-labeled molecular tracers involves critical steps such as the ¹⁸ F-labeling reaction, work-up, and ¹⁸ F-product purification, which are governed by ¹⁸ F-labeling chemistry. Since direct incorporation of ¹⁸ F in aqueous media exhibits many advantages in practice, this Review summarizes the existing ¹⁸ F-labeling methods in aqueous media, which are sorted by atoms forming chemical covalent bonds with F. The Review is focused on the respective reaction mechanism, the water effect and the applications of these methods for the development of ¹⁸ F-radiopharmaceuticals. The research progress on aqueous nucleophilic labeling methods using [¹⁸ F]F^- as the ¹⁸ F source has been mainly discussed.