Dataset Open Access
Moldovan, Rares-Petru; Gündel, Daniel; Deuther-Conrad, Winnie; Ueberham, Lea; Kaur, Sarandeep; Otikova, Elina; Teodoro, Rodrigo; Lai, Thu Hang; Clauß, Oliver; Scheunemann, Matthias; Bormans, Guy; Kopka, Klaus; Bachmann, Michael; Brust, Peter
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Recently, we reported a novel naphthyrid-2-one based positron-emission tomography (PET) radioligand for imaging of the CB2R in the brain (<strong>[<sup>18</sup>F]5</strong>). In this study we aimed at the development of a novel <sup>18</sup>F-labeled CB2R radioligand with improved binding properties and metabolic stability. Starting from the structure of <strong>5</strong>, we developed a novel series of fluorinated derivatives by modifying the substituents at the naphthyrid-2-one subunit. Compound <strong>28</strong> (<strong>LU13</strong>) was identified with the highest binding affinity and selectivity versus CB1R (CB2R<em>K</em><sub>i</sub> = 0.6 nM; CB1R<em>K</em><sub>i</sub>/CB2R<em>K</em><sub>i</sub> > 1000) and was selected for radiolabeling with <sup>18</sup>F and biological characterization. The radiofluorination was performed starting from the corresponding bromo-precursor (<strong>31</strong>) bearing a fully deuterated <em>N</em>-alkyl chain to protect against defluorination. The in vitro evaluation of <strong>[<sup>18</sup>F]LU13 </strong>proved the high binding affinity of the radioligand towards rat (rCB2R<em>K</em><sub>D</sub> = 0.2 nM) and human (hCB2R<em>K</em><sub>D</sub> = 1.1 nM) CB2R. Metabolism studies in mice revealed a metabolic stability at 30 min p.i. with fractions of parent compound of >80% in the brain and 90% in the spleen with only trace of defluorination products detected in plasma. PET imaging in a rat model of vector-based/related overexpression in the striatum revealed a high signal to background ratio, demonstrating the ability of <strong>[<sup>18</sup>F]LU13</strong> to reach and selectively label the hCB2R in the brain. Thus, <strong>[<sup>18</sup>F]LU13 </strong>is a novel and highly promising PET radioligand for the imaging of up regulated CB2R expression under pathological conditions in the brain.</p>", "access_right": "open", "keywords": [ "cannabinoid receptor type 2", "naphthyrid-2-one", "binding affinity" ], "access_right_category": "success", "publication_date": "2022-08-09" }, "updated": "2022-08-10T12:38:36.954903+00:00", "stats": { "volume": 48422733.0, "unique_downloads": 58.0, "version_unique_downloads": 58.0, "unique_views": 291.0, "downloads": 303.0, "version_unique_views": 291.0, "version_views": 726.0, "version_downloads": 303.0, "version_volume": 48422733.0, "views": 726.0 }, "created": "2022-08-09T11:33:20.476163+00:00", "revision": 6, "id": 1381, "conceptdoi": "10.14278/rodare.1380", "conceptrecid": "1380", "links": { "badge": "https://rodare.hzdr.de/badge/doi/10.14278/rodare.1381.svg", "doi": "https://doi.org/10.14278/rodare.1381", "conceptbadge": "https://rodare.hzdr.de/badge/doi/10.14278/rodare.1380.svg", "conceptdoi": "https://doi.org/10.14278/rodare.1380", "bucket": "https://rodare.hzdr.de/api/files/c0642be8-16d1-43e4-a927-6732efebb237", "html": "https://rodare.hzdr.de/record/1381", "latest": "https://rodare.hzdr.de/api/records/1381", "latest_html": "https://rodare.hzdr.de/record/1381" } }
All versions | This version | |
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Views | 726 | 726 |
Downloads | 303 | 303 |
Data volume | 48.4 MB | 48.4 MB |
Unique views | 291 | 291 |
Unique downloads | 58 | 58 |