title: Synthesis and preliminary evaluation of [18F]FEtP4A, a promising PET tracer for mapping acetylcholinesterase in vivo.
abstract: N-[18F]Fluoroethyl-4-piperidyl acetate ([18F]FEtP4A), an analog of [11C]MP4A for mapping brain acetylcholineseterase (AchE) activity, was prepared by reacting 4-piperidyl acetate (P4A) with [18F]fluoroethyl bromide ([18F]FEtBr) using a newly developed automated system. Preliminary evaluation showed that the initial uptake of [18F]FEtP4A in the mouse brain was > 8% injected dose/g tissue. The distribution pattern of [18F]FEtP4A in the brain was striatum>cerebral cortex>cerebellum within 10-120 min post-injection, which reflected the distribution rank pattern of AchE activity in the brain. Moreover, chemical analysis of in vivo radioactive metabolites in the mouse brain indicated that 83% of [18F]FEtP4A was hydrolyzed to N-[18F]fluoroethyl-4-piperidinol ([18F]FEtP4OH) after 1 min intravenous injection. From these results, [18F]FEtP4A may become a promising PET tracer for mapping the AchE in vivo.
authors.affiliation: Department of Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Akio
authors.initials: A
authors.lastname: Tsuchiyama
authors.forename: Terushi
authors.initials: T
authors.lastname: Haradahira
authors.forename: Kenji
authors.initials: K
authors.lastname: Furutsuka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Takayo
authors.initials: T
authors.lastname: Kida
authors.forename: Junko
authors.initials: J
authors.lastname: Noguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000085:Acetates / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D005462:Fluorine Radioisotopes; C469347:N-fluoroethyl-4-piperidyl acetate; D010880:Piperidines; D000110:Acetylcholinesterase