N-[(18)F]Fluoroethylpiperidinyl, N-[(18)F]fluoroethylpiperidinemethyl and N-[(18)F]fluoroethylpyrrolidinyl esters as radiotracers for acetylcholinesterase.
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.
Shao
Xia
X
Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Butch
Elizabeth R
ER
Kilbourn
Michael R
MR
Snyder
Scott E
SE
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004593:Electrophorus; D004952:Esters / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D006736:Horses; D006868:Hydrolysis; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D010880:Piperidines / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D011485:Protein Binding; D011759:Pyrrolidines / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D004952:Esters; D010880:Piperidines; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D000110:Acetylcholinesterase