title: Synthesis of carbon-11- and fluorine-18-labeled 1-methyl-4-piperidyl-4'-fluorobenzoate and their biodistribution in mice.
abstract: Carbon-11- and fluorine-18-labeled forms of 1-methyl-4-piperidyl-4'-fluorobenzoate were prepared as potential in vivo substrates for brain acetylcholinesterase. The 1-methyl-4-piperidyl-4'-[18F]fluorobenzoate was prepared by aromatic nucleophilic substitution using the nitro precursor and no-carrier added [18F]fluoride ion. The 1-[11C]methyl-4-piperidyl-4'-fluorobenzoate was synthesized by N-[11C]methylation of the appropriate nor-methyl precursor. Biodistribution studies in mice showed high brain uptake of these radiotracers followed by a fast washout with no significant retention of radioactivity in areas of high acetylcholinesterase enzymatic activity. This is contrasted with 1-[11C]methyl-4-piperidylacetate, which is rapidly trapped in brain tissues through hydrolysis by AChE. Further in vivo and in vitro studies demonstrated that 1-methyl-4-piperidyl-4'-fluorobenzoate was not a substrate for AChE, and thus not suitable as an in vivo radiotracer for studying this enzyme in the brain.
authors.affiliation: Laboratory for Radiopharmaceutical Chemistry, K.U. Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Bormans
authors.forename: P
authors.initials: P
authors.lastname: Sherman
authors.forename: S E
authors.initials: SE
authors.lastname: Snyder
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D001565:Benzoates; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D010880:Piperidines; C102686:1-methyl-4-piperidyl 4'-fluorobenzoate; C102687:1-methyl-4-piperidyl acetate