title: Synthesis and biological evaluation of 1-(4-[18F]fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine for in vivo studies of acetylcholinesterase.
abstract: We synthesized and evaluated 1-(4-fluorobenzyl)-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (4-FDP), which is an analog of donepezil. The 4-[(18)F]FDP was prepared by reductive alkylation of debenzylated donepezil with 4-[(18)F]fluorobenzaldehyde in high radiochemical yield (decay-corrected, 40-52%) and with high effective specific activity (30-38 GBq/micromol). Tissue distribution studies in mice demonstrated nonspecific distribution of the 4-[(18)F]FDP in brain regions, suggesting that this radioligand may not be a suitable agent for in vivo studies of acetylcholinesterase (AChE), despite its potent in vitro biological activity.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Center for Clinical Research, Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Y S
authors.initials: YS
authors.lastname: Choe
authors.forename: H
authors.initials: H
authors.lastname: Sugimoto
authors.forename: S E
authors.initials: SE
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Hwang
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Kim
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D000077265:Donepezil; D005462:Fluorine Radioisotopes; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C422186:1-(4-fluorobenzyl)-4-((5,6-dimethoxy-1-oxoindan-2-yl)methyl)piperidine; D005462:Fluorine Radioisotopes; D007189:Indans; D010880:Piperidines; D019275:Radiopharmaceuticals; D000077265:Donepezil; D000110:Acetylcholinesterase