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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / metabolism*
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Animals
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Biotransformation
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Brain / enzymology*
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Brain / physiology
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Brain Mapping
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / pharmacology
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Drug Stability
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Fluorine Radioisotopes
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Indoles / chemical synthesis*
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Indoles / pharmacokinetics
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Indoles / pharmacology
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Male
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Mice
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Mice, Inbred ICR
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Piperidines / chemical synthesis*
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Piperidines / pharmacokinetics
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Piperidines / pharmacology
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / pharmacokinetics
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Radiopharmaceuticals / pharmacology
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Tissue Distribution
Substances
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Cholinesterase Inhibitors
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Fluorine Radioisotopes
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Indoles
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Piperidines
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Radiopharmaceuticals
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Acetylcholinesterase