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

The false adrenergic neurotransmitter [C-11]meta-hydroxyephedrine ([C-11]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 [C-11]HED. We selected 4-methylmetaraminol as a candidate molecule for radiolabelling with C-11 (t(1/2) 20.4min). Our radiosynthetic approach towards 4-[C-11]methylmetaraminol involved a palladium-catalyzed cross-coupling reaction of a protected 4-trimethylstannyl derivative of metaraminol with [C-11]methyl iodide followed by removal of the protective groups. 4-[C-11]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/mumol. The unlabelled reference molecule, 4-methylmetaraminol, was prepared in a 5-step synthesis starting from metaraminol. A biological evaluation of 4-[C-11]methylmetaraminol is in progress and the results will be reported elsewhere. Copyright (C) 2002 John Wiley Sons, Ltd.