A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety
| Autor: | Michael Decker, Edgar Sawatzky, Takahiro Higuchi, Samuel Samnick, Ehab Al-Momani, Ryohei Kobayashi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Fluorine Radioisotopes Carbamate medicine.medical_treatment Heterocyclic Compounds 4 or More Rings Biochemistry Isotopic labeling Mice 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Animals Humans Distribution (pharmacology) Moiety Carbon Radioisotopes General Pharmacology Toxicology and Pharmaceutics Butyrylcholinesterase Pharmacology chemistry.chemical_classification medicine.diagnostic_test Organic Chemistry Brain Kinetics 030104 developmental biology Enzyme chemistry Covalent bond Positron emission tomography Positron-Emission Tomography Acetylcholinesterase Molecular Medicine Carbamates Cholinesterase Inhibitors Radiopharmaceuticals 030217 neurology & neurosurgery |
| Zdroj: | ChemMedChem. 11:1540-1550 |
| ISSN: | 1860-7179 |
| Popis: | 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 (18) F and (11) C 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. |
| Databáze: | OpenAIRE |
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