Preparation of 4‐[11C]methylmetaraminol, a potential PET tracer for assessment of myocardial sympathetic innervation

The false adrenergic neurotransmitter [11C]meta‐hydroxyephedrine ([11C]HED) is currently the PET tracer of choice for assessment of myocardial sympathetic innervation. The molecule is metabolised in the 4‐position of the aromatic ring. The resulting radiolabelled metabolites need to be measured in order to obtain an arterial input function. Our aim was the development of a PET tracer with an increased metabolic stability relative to [11C]HED. We selected 4‐methylmetaraminol as a candidate molecule for radiolabelling with 11C (t1/2 20.4 min). Our radiosynthetic approach towards 4‐[11C]methylmetaraminol involved a palladium‐catalyzed cross‐coupling reaction of a protected 4‐trimethylstannyl derivative of metaraminol with [11C]methyl iodide followed by removal of the protective groups. 4‐[11C]methylmetaraminol was obtained in a final decay‐corrected radiochemical yield of 20–25% within a synthesis time of 60–80 min. The specific radioactivity at the end of the synthesis ranged from 18–37 to GBq/μmol. The unlabelled reference molecule, 4‐methylmetaraminol, was prepared in a 5‐step synthesis starting from metaraminol. A biological evaluation of 4‐[11C]methylmetaraminol is in progress and the results will be reported elsewhere.