title: N-[18F]fluoroethylpiperidin-4-ylmethyl butyrate: a novel radiotracer for quantifying brain butyrylcholinesterase activity by positron emission tomography.
abstract: In Alzheimer's disease, cerebral cortical butyrylcholinesterase (BChE) activity is reported to be elevated. Our aim was to develop a novel (18)F-labeled tracer for quantifying cerebral BChE activity by positron emission tomography. With in vitro screening of N-[(14)C]ethylpiperidin-3- and 4-ylmethyl esters, N-[(14)C]ethylpiperidin-4-ylmethyl butyrate was selected as a lead for (18)F-labeling, affording N-[(18)F]fluoroethylpiperidin-4-ylmethyl butyrate. The (18)F-labeled butyrate showed the required properties for in vivo BChE measurement, that is, the lipophilic nature of the authentic ester, high specificity to BChE, a moderate hydrolysis rate, and the hydrophilic nature of the metabolite.
authors.affiliation: Department of Medical Imaging, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ikota
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukushi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okamura
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Arano
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry; D002091:Butyrylcholinesterase / Q000032:analysis* / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D006801:Humans; D006868:Hydrolysis; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D013379:Substrate Specificity; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002087:Butyrates; D005462:Fluorine Radioisotopes; C492885:N-fluoroethylpiperidin-4-ylmethylbutyrate; D010880:Piperidines; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase