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.
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.
Choe
Y S
YS
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. yschoe@samsung.co.kr
Oh
S
S
Shim
I
I
Naruto
S
S
Chi
D Y
DY
Kim
S E
SE
Lee
K
K
Choi
Y
Y
Kim
B
B
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
D002800:Cholinesterase Inhibitors; D005462:Fluorine Radioisotopes; D007211:Indoles; D010880:Piperidines; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase