Open AccessA Novel Fluorine-18 β-Fluoroethoxy Organophosphate Positron Emission Tomography Imaging Tracer Targeted to Central Nervous System Acetylcholinesterase
Author(s) -
Shelly James,
S. Kaleem Ahmed,
Stephanie T. Murphy,
M. Braden,
Yamina Belabassi,
Henry F. VanBrocklin,
Charles M. Thompson,
John M. Gerdes
Publication year - 2014
Publication title -
acs chemical neuroscience
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.158
H-Index - 69
ISSN - 1948-7193
DOI - 10.1021/cn500024c
Subject(s) - radiosynthesis , acetylcholinesterase , tracer , chemistry , positron emission tomography , in vivo , organophosphate , central nervous system , biophysics , neuroscience , biochemistry , enzyme , biology , physics , microbiology and biotechnology , pesticide , nuclear physics , agronomy
Radiosynthesis of a fluorine-18 labeled organophosphate (OP) inhibitor of acetylcholinesterase (AChE) and subsequent positron emission tomography (PET) imaging using the tracer in the rat central nervous system are reported. The tracer structure, which contains a novel β-fluoroethoxy phosphoester moiety, was designed as an insecticide-chemical nerve agent hybrid to optimize handling and the desired target reactivity. Radiosynthesis of the β-fluoroethoxy tracer is described that utilizes a [(18)F]prosthetic group coupling approach. The imaging utility of the [(18)F]tracer is demonstrated in vivo within rats by the evaluation of its brain penetration and cerebral distribution qualities in the absence and presence of a challenge agent. The tracer effectively penetrates brain and localizes to cerebral regions known to correlate with the expression of the AChE target. Brain pharmacokinetic properties of the tracer are consistent with the formation of an OP-adducted acetylcholinesterase containing the fluoroethoxy tracer group. Based on the initial favorable in vivo qualities found in rat, additional [(18)F]tracer studies are ongoing to exploit the technology to dynamically probe organophosphate mechanisms of action in mammalian live tissues.