Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors
M<sub>1</sub> muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in...
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/12/2880 |
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| author | Boris D. Zlatopolskiy Felix Neumaier Till Rüngeler Birte Drewes Niklas Kolks Bernd Neumaier |
| author_facet | Boris D. Zlatopolskiy Felix Neumaier Till Rüngeler Birte Drewes Niklas Kolks Bernd Neumaier |
| author_sort | Boris D. Zlatopolskiy |
| collection | DOAJ |
| description | M<sub>1</sub> muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several <sup>11</sup>C-labeled probes. However, protocols for the preparation of <sup>18</sup>F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an <sup>18</sup>F-labeled M<sub>1</sub> mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (<i>n</i> = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an <sup>18</sup>F-labeled M<sub>1</sub> mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a <sup>18</sup>F-labeled M<sub>1</sub> selective PET tracer for experimental and diagnostic applications. |
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| last_indexed | 2024-03-10T18:57:16Z |
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| spelling | doaj.art-601a7baf02da4c3c892d1c769490d6fc2023-11-20T04:39:35ZengMDPI AGMolecules1420-30492020-06-012512288010.3390/molecules25122880Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine ReceptorsBoris D. Zlatopolskiy0Felix Neumaier1Till Rüngeler2Birte Drewes3Niklas Kolks4Bernd Neumaier5Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbH, 52428 Jülich, GermanyInstitute of Neurophysiology, University Hospital Cologne, Robert-Koch Str. 39, 50931 Cologne, GermanyInstitute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, 50931 Cologne, GermanyInstitute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbH, 52428 Jülich, GermanyInstitute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbH, 52428 Jülich, GermanyInstitute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Forschungszentrum Jülich GmbH, 52428 Jülich, GermanyM<sub>1</sub> muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer’s disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several <sup>11</sup>C-labeled probes. However, protocols for the preparation of <sup>18</sup>F-labeled mAChR-ligands have not been published so far. Here, we describe a straightforward procedure for the preparation of an <sup>18</sup>F-labeled M<sub>1</sub> mAChR agonist and its corresponding pinacol boronate radiolabeling precursor and the non-radioactive reference compound. The target compounds were prepared from commercially available aryl fluorides and Boc protected 4-aminopiperidine using a convergent reaction protocol. The radiolabeling precursor was prepared by a modification of the Miyaura reaction and labeled via the alcohol-enhanced Cu-mediated radiofluorination. The developed procedure afforded the radiotracer in a non-decay-corrected radiochemical yield of 17 ± 3% (<i>n</i> = 3) and in excellent radiochemical purity (>99%) on a preparative scale. Taken together, we developed a straightforward protocol for the preparation of an <sup>18</sup>F-labeled M<sub>1</sub> mAChR agonist that is amenable for automation and thus provides an important step towards the routine production of a <sup>18</sup>F-labeled M<sub>1</sub> selective PET tracer for experimental and diagnostic applications.https://www.mdpi.com/1420-3049/25/12/2880radiolabelingfluorine-18positron emission tomographyacetylcholine receptor agonistCu-mediated radiofluorination |
| spellingShingle | Boris D. Zlatopolskiy Felix Neumaier Till Rüngeler Birte Drewes Niklas Kolks Bernd Neumaier Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors Molecules radiolabeling fluorine-18 positron emission tomography acetylcholine receptor agonist Cu-mediated radiofluorination |
| title | Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors |
| title_full | Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors |
| title_fullStr | Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors |
| title_full_unstemmed | Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors |
| title_short | Preparation of a First <sup>18</sup>F-Labeled Agonist for M<sub>1</sub> Muscarinic Acetylcholine Receptors |
| title_sort | preparation of a first sup 18 sup f labeled agonist for m sub 1 sub muscarinic acetylcholine receptors |
| topic | radiolabeling fluorine-18 positron emission tomography acetylcholine receptor agonist Cu-mediated radiofluorination |
| url | https://www.mdpi.com/1420-3049/25/12/2880 |
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