Automated Radiosynthesis of [¹⁸F]FMeNER-D₂ Using the Simplified One-Pot ¹⁸F-Fluoromethylation Method

(S,S)-2-(α-(2-[¹⁸F]Fluoro[dideutero]methoxyphenoxy)benzyl)morpholine ([¹⁸F]FMeNER-D₂), which is used to image the norepinephrine transporter in the brain via positron emission tomography (PET), is typically radiosynthesized by O-fluoromethylating norethylreboxetine (NER) with [¹⁸F]bromofluoromethane-d₂ using a fully automated ¹⁸F-labeling synthesizer with a two-pot unit. We simplified the automated radiosynthesis of [¹⁸F]FMeNER-D₂ through the use of a straightforward one-pot method to prepare [¹⁸F]fluoromethyl-d₂-tosylate as the fluoromethylating agent (avoiding the need to azeotropically dry [¹⁸F]F^- in advance), which was then reacted with NER. The reaction conditions were optimized, with [¹⁸F]FMeNER-D₂ synthesized using an ¹⁸F-labeling synthesizer equipped with a one-pot unit. As a result, a synthesis time, radiochemical yield based on total [¹⁸F]F^-, molar activity, and radiochemical purity of 66 ± 4.7 min (n = 7), 9.0% ± 0.8% (n = 3), 130-275 GBq/μmol (n = 7), and > 97% (n = 7), respectively, were obtained at the end of synthesis. In conclusion, we successfully synthesized [¹⁸F]FMeNER-D₂ using a simplified one-pot, fully automated, ¹⁸F-fluoromethylation method in an ¹⁸F-labeling synthesizer.