title: Syntheses and biological evaluation of (18)F-labeled 3-(1-benzyl-piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase.
abstract: We synthesized novel (18)F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[(18)F]fluoromethylbenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-ones ([(18)F]1 and [(18)F]2) and 3-[1-(4-[(18)F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-i ndol-3-yl )propan-1-one ([(18)F]3) in high yields (decay-corrected, 25%-40%) and with high effective specific activities (>37 GBq/micromol). Tissue distribution studies of the [(18)F]1 and the [(18)F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [(18)F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. yschoe@samsung.co.kr
authors.forename: Y S
authors.initials: YS
authors.lastname: Choe
authors.forename: S
authors.initials: S
authors.lastname: Oh
authors.forename: I
authors.initials: I
authors.lastname: Shim
authors.forename: S
authors.initials: S
authors.lastname: Naruto
authors.forename: D Y
authors.initials: DY
authors.lastname: Chi
authors.forename: S E
authors.initials: SE
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Choi
authors.forename: B
authors.initials: B
authors.lastname: Kim
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000201:enzymology* / Q000502:physiology; D001931:Brain Mapping; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D002800:Cholinesterase Inhibitors; D005462:Fluorine Radioisotopes; D007211:Indoles; D010880:Piperidines; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase