@article{77140da84ca64e0ebcf4c299556e1b43,
title = "Synthesis and Initial Characterization of a Selective, Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer",
abstract = "The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.",
keywords = "carbamate, enzyme kinetics, fluorine-18, positron emission tomography, radiotracers",
author = "Christian Gentzsch and Matthias Hoffmann and Yasuhiro Ohshima and Naoko Nose and Xinyu Chen and Takahiro Higuchi and Michael Decker",
note = "Funding Information: This work was supported by the German Research Council (Deutsche Forschungsgemeinschaft DFG; grants DE 1546/6‐3 for M.D. and HI 1789/3‐3 for T.H.). M.H. was supported by the German Academic Scholarship Foundation (“Studienstiftung des deutschen Volkes”) with a PhD scholarship. C. G. and M. H. were supported by the MuTaLig COST Action (active participation at the 3rd Working Group Meeting, Paris). We gratefully acknowledge Professor Oksana Lockridge (University of Nebraska Medical Center) for providing BChE. Open access funding enabled and organized by Projekt DEAL. h Funding Information: This work was supported by the German Research Council (Deutsche Forschungsgemeinschaft DFG; grants DE 1546/6-3 for M.D. and HI 1789/3-3 for T.H.). M.H. was supported by the German Academic Scholarship Foundation (?Studienstiftung des deutschen Volkes?) with a PhD scholarship. C. G. and M. H. were supported by the MuTaLig COST Action (active participation at the 3rd Working Group Meeting, Paris). We gratefully acknowledge Professor Oksana Lockridge (University of Nebraska Medical Center) for providing hBChE. Open access funding enabled and organized by Projekt DEAL. Publisher Copyright: {\textcopyright} 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH",
year = "2021",
month = may,
day = "6",
doi = "10.1002/cmdc.202000942",
language = "English",
volume = "16",
pages = "1427--1437",
journal = "ChemMedChem",
issn = "1860-7179",
publisher = "John Wiley and Sons Ltd",
number = "9",
}
