title: Development of N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropargylamine (18F-fluoroclorgyline) as a potential PET radiotracer for monoamine oxidase-A.
abstract: We have synthesized N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropar gylamine (18F-fluoroclorgyline) as a potential positron emission tomography (PET) radiotracer for monoamine oxidase A (MAO-A). The radiosynthesis was carried out by a 18F-fluoride-for-mesylate substitution reaction in approximately 20% radiochemical yield in specific activities of 1-2 Ci/micromol. Selectivity for MAO-A was demonstrated by the high affinity of clorgyline (IC50 = 39 nM) and lower affinity of (R)-deprenyl (IC50 > or = 100 microM) for the inhibition of 18F-fluoroclorgyline binding in vitro in rat brain membranes. The uptake of 18F-fluoroclorgyline in the rat brains was high (> 1.0% injected dose/g). The binding of 18F-fluoroclorgyline in the rat brain correlated with the distribution of MAO-A and was inhibited by preadministration of MAO-A inhibitors, clorgyline, and Ro 41-1049, whereas (R)-deprenyl, a MAO-B blocker, had no inhibitory effect. These results suggest that 18F-fluoroclorgyline is a potential PET radiotracer for MAO-A.
authors.affiliation: Franklin McLean Institute, Department of Radiology, University of Chicago, Illinois, USA. jogeshwar_mukherjee@kettheath.com
authors.forename: J
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D003010:Clorgyline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D007700:Kinetics; D008995:Monoamine Oxidase / Q000032:analysis* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D019275:Radiopharmaceuticals; D013844:Thiazoles; C085565:fluoroclorgyline; D012642:Selegiline; C063456:Ro 41-1049; D008995:Monoamine Oxidase; D003010:Clorgyline