title: Synthesis of some 11C-labelled MAO-A inhibitors and their in vivo uptake kinetics in rhesus monkey brain.
abstract: Five potential MAO-A inhibitors--harmine, N-methyl-harmine, harmaline, brofaromine, and clorgyline--were labelled with 11C and their brain kinetics evaluated in vivo in rhesus monkey using PET. The compounds were synthesized by alkylation with 11C methyl iodide and obtained in 48-89% radiochemical yield within 40 to 45 min synthesis time and with specific radioactivities in the region of 0.49-2.4 Ci mumol-1 (18-87 GBq mumol-1) at the end of synthesis. The kinetic pattern after administration of MAO-A inhibitors was comparable to that seen in the tracer study when using 11C-brofaromine, 11C-harmaline, or 11C-clorgyline, although the magnitude of uptake markedly increased in the case of brofaromine and harmaline. Both 11C-methylharmine and 11C-harmine showed a significant washout in the inhibition studies. The kinetics of brain uptake with and without MAO-A inhibition is compatible with a significant fraction of the tracer bound to MAO-A for 11C-methylharmine and 11C-harmine, whereas 11C-brofaromine, 11C-harmaline, or 11C-clorgyline did not seem to show specific enzyme binding.
authors.affiliation: Uppsala University Pet Centre, University Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bergström
authors.forename: G
authors.initials: G
authors.lastname: Westerberg
authors.forename: T
authors.initials: T
authors.lastname: Kihlberg
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D008253:Macaca mulatta; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors