N-(4-(di-tert-butyl[18F]fluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide ([18F]SiFAN+Br−): A novel lead compound for the development of hydrophilic SiFA-based prosthetic groups for 18F-labeling

18F-labeled compounds play a major role in the development of new in vivo imaging agents for Positron Emission Tomography (PET), a non invasive imaging modality depicting the biodistribution of radioactive compounds in humans. Recently we reported a new method for the introduction of fluorine-18 into a range of organic molecules exploiting the very fast 18F–19F isotope exchange of fluorosilanes (termed SiFA compounds). Here, we wish to report the labeling of the first charged SiFA molecule N-(4-(di-tert-butylfluorosilyl)benzyl)-2-hydroxy-N,N-dimethylethylammonium bromide (SiFAN+Br−) serving as a lead compound in the development of SiFA-based prosthetic groups of reduced lipophilicity for biomolecule labeling. Mild conditions for synthesis of [18F]SiFAN+Br− and an easy purification procedure using simple C-18 solid phase cartridge have been developed yielding the [18F]SiFAN+Br− in radiochemical yields of 34% (non-decay corrected) within 40 min. A series of kinetic experiments were performed that show high isotopic exchange rate constants. Low activation energy (15.7 kcal/mol) and a large preexponential factor (7.9 × 1013 M−1 s−1) were calculated for the isotopic exchange reaction from a corresponding Arrhenius plot. For comparison, the 18F-fluorination of ethyleneglycol-di-p-tosylate via the formation of a carbon–18F bond showed a 1.3 kcal/mol higher activation energy and a much lower preexponential factor of 2.9 × 109 M−1 s−1. Moderate hydrophilicity (log D = 0.44), stability in aqueous media at pH up to 7.4 and a high specific activity of [18F]SiFAN+Br− (SA = 20.4 GBq/μmol, 0.55 Ci/μmol) make this charged SiFA compound useful for the development of novel SiFA-based 18F-labeling synthons.