A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety |
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| Authors: | Edgar Sawatzky Dr. Ehab Al‐Momani Ryohei Kobayashi Prof. Dr. Takahiro Higuchi Prof. Dr. Samuel Samnick Prof. Dr. Michael Decker |
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| Affiliation: | 1. Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilian University Würzburg, Würzburg, Germany;2. Experimental Nuclear Medicine, Center of Inner Medicine, University Hospital Würzburg, Würzburg, Germany |
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| Abstract: | The enzyme butyrylcholinesterase (BChE) is known to be involved in the detoxification of xenobiotics in blood plasma and is associated with the progress of neurodegenerative disorders, diabetes type 2, obesity, and diseases of the cardiovascular system. In the present study, we developed carbamate‐based inhibitors serving as positron emission tomography (PET) radiotracers with 18F and 11C as radioisotopes to visualize BChE distribution. These inhibitors are radiolabeled at the carbamate site and transfer this moiety onto BChE, which thus results in covalent and permanent radiolabeling of the enzyme. There are no comparable radiotracers for cholinesterases described to date. By ex vivo autoradiography experiments on mice brain slices and kinetic investigations, selective and covalent transfer of the radiolabeled carbamate moiety onto BChE was proven. These tracers might provide high resolution of BChE distribution in vivo to enable investigations into the pathophysiological mechanisms of diseases associated with alterations in BChE occurrence. |
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| Keywords: | carbamates inhibitors irreversible labeling isotopic labeling radiopharmaceuticals |
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