Abstract
A series of N-fluoroethylpiperidinyl (1), N-fluoroethylpiperidinemethyl (2) and N-fluoroethylpyrrolidinyl (3) esters were synthesized and examined as new (18)F-labeled radiotracers for measuring brain cholinesterase activity. The fluoroethyl group, instead of methyl group, results in slower in vitro enzymatic cleavage rates and higher selectivity for AChE. Based on metabolism in mouse blood and PET time-activity curves in rats, two radiotracers were identified as potential candidates for further in vivo evaluation in higher species.
Publication types
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Comparative Study
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Evaluation Study
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholinesterase / metabolism*
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Animals
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Brain / diagnostic imaging
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Brain / metabolism
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Cerebral Cortex / diagnostic imaging
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Cerebral Cortex / metabolism*
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Corpus Striatum / diagnostic imaging
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Corpus Striatum / metabolism*
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Electrophorus
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Esters / blood
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Esters / chemistry*
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Esters / pharmacokinetics*
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Female
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Horses
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Hydrolysis
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Isotope Labeling / methods
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Metabolic Clearance Rate
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Mice
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Piperidines / blood
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Piperidines / chemistry*
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Piperidines / pharmacokinetics*
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Protein Binding
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Pyrrolidines / blood
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacokinetics*
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Radionuclide Imaging
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Radiopharmaceuticals / blood
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
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Tissue Distribution
Substances
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Esters
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Piperidines
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Pyrrolidines
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Radiopharmaceuticals
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Acetylcholinesterase