title: Evaluation of 3-[18F]fluoro-alpha-fluoromethyl-p-tyrosine as a tracer for striatal tyrosine hydroxylase activity.
abstract: 3-[18F]Fluoro-alpha-fluoromethyl-p-tyrosine (3-F-FMPT) was evaluated as a tracer for CNS tyrosine hydroxylase (TH) activity in rodents and in a rhesus monkey. Results of in vitro experiments using rat striatal homogenates showed that the introduction of fluorine into the 3-phenyl position did not significantly alter the ability of FMPT to act as a TH-activated L-aromatic amino acid decarboxylase (L-AAAD) inhibitor. These studies further showed that 3-F-FMPT-induced L-AAAD inhibition was dose-dependent. Furthermore, striatal homogenates prepared from rats pretreated with the potent TH inhibitor alpha-methyl-p-tyrosine was found to have diminished 3-F-FMPT-induced L-AAAD inhibition. However, despite these promising in vitro results, the biodistribution of this compound in mice showed low brain uptake and fast clearance through the kidneys. A PET study using a Rhesus monkey injected with 3-[18F]F-FMPT confirmed the results obtained in mice, i.e. negligible brain uptake but high localization in the bladder. We conclude that 3-[18F]F-FMPT would not be useful as a tracer for cerebral TH activity.
authors.affiliation: Department of Medical Physics, University of Wisconsin, Madison 53719, USA.
authors.forename: O T
authors.initials: OT
authors.lastname: DeJesus
authors.forename: D
authors.initials: D
authors.lastname: Murali
authors.forename: R
authors.initials: R
authors.lastname: Kitchen
authors.forename: C
authors.initials: C
authors.lastname: Endres
authors.forename: T R
authors.initials: TR
authors.lastname: Oakes
authors.forename: S E
authors.initials: SE
authors.lastname: Shelton
authors.forename: L
authors.initials: L
authors.lastname: Freund
authors.forename: D
authors.initials: D
authors.lastname: Houser
authors.forename: H
authors.initials: H
authors.lastname: Uno
authors.forename: J E
authors.initials: JE
authors.lastname: Holden
mesh_terms: D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008253:Macaca mulatta; D008297:Male; D008781:Methyltyrosines / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D005462:Fluorine Radioisotopes; D008781:Methyltyrosines; C107830:3-fluoro-alpha-fluoromethyltyrosine; D014443:Tyrosine; C040511:alpha-monofluoromethyl-4-tyrosine; D014446:Tyrosine 3-Monooxygenase