title: 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.
authors.affiliation: Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552.
authors.forename: K C
authors.initials: KC
authors.lastname: Rosenspire
authors.forename: M S
authors.initials: MS
authors.lastname: Haka
authors.forename: M E
authors.initials: ME
authors.lastname: Van Dort
authors.forename: D M
authors.initials: DM
authors.lastname: Jewett
authors.forename: D L
authors.initials: DL
authors.lastname: Gildersleeve
authors.forename: M
authors.initials: M
authors.lastname: Schwaiger
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003891:Desipramine / Q000494:pharmacology; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D005069:Evaluation Studies as Topic; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011849:Radioactive Tracers; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D011849:Radioactive Tracers; C065363:3-hydroxyephedrine; D004809:Ephedrine; D003891:Desipramine