Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging

Abstract

Carbon-11-meta-hydroxyephedrine is a new radiotracer developed for mapping the sympathetic nerves of the heart. Carbon-11-meta-hydroxyephedrine is synthesized by direct N-methylation of metaraminol with [11C]methyl iodide in dimethyl formamide/dimethyl sulfoxide and purified by semi-preparative reversed-phase HPLC. Total synthesis time is 45 min from end-of-bombardment. Carbon-11-meta-hydroxyephedrine is produced in 40%-50% corrected radiochemical yield with a specific activity of 900 Ci/mmol. Routine radiochemical and chemical purity are 95% and 98%, respectively. Biodistribution studies in rats show high myocardial uptake. Pretreatment with desipramine, a drug known to selectively block neuronal uptake, results in a 92% decrease in tracer accumulation in the myocardium. Metabolic studies in guinea pigs show less than 5% metabolites in heart tissue 30 min after intravenous injection suggesting that [11C]meta-hydroxyephedrine is suitable for kinetic modeling. These preliminary results support this new tracer as a clinical agent for neuronal imaging of the heart.