Specific in vivo binding to the norepinephrine transporter demonstrated with the PET radioligand, (S,S)-[11C]MeNER

(S,S)-2-(α-(2-Methoxyphenoxy)benzyl)morpholine (MeNER), an O-methyl analog of the selective and potent norepinephrine transporter (NET) inhibitor, (S,S)-reboxetine, and its less active enantiomer, (R,R)-MeNER, have each been radiolabeled by O-methylation of their corresponding phenolic precursors in good yields from [11C]methyl iodide or [11C]methyl triflate. Radiochemical purities were >99% and specific radioactivity at time of injection was about 74 GBq/μmol. Autoradiographic examination of (S,S)-[11C]MeNER binding to human brain slices post mortem indicated specific binding in a brain region including the locus coeruleus. PET examination of both [11C]MeNER enantiomers in a cynomolgus monkey demonstrated a higher specific binding of the (S,S)-enantiomer with ratios of 1.4-1.6 in the lower brainstem, mesencephalon and thalamus to striatum. Pretreatment with the NET ligand, desipramine, decreased the specific binding of (S,S)-[11C]MeNER. Labeled metabolites of [11C]MeNER were all more polar. (S,S)-[11C]MeNER is a good lead compound in the search for a selective radioligand for quantitation of NET in the human brain in vivo