{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:46:10Z","timestamp":1784864770376,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development FUND and S\u00e4chsische Aufbau Bank","award":["100226753"],"award-info":[{"award-number":["100226753"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A2A adenosine receptors (A2A-AR) have a cardio-protective function upon ischemia and reperfusion, but on the other hand, their stimulation could lead to arrhythmias. Our aim was to investigate the potential use of the PET radiotracer [18F]FLUDA to non-invasively determine the A2A-AR availability for diagnosis of the A2AR status. Therefore, we compared mice with cardiomyocyte-specific overexpression of the human A2A-AR (A2A-AR TG) with the respective wild type (WT). We determined: (1) the functional impact of the selective A2AR ligand FLUDA on the contractile function of atrial mouse samples, (2) the binding parameters (Bmax and\u00a0KD) of [18F]FLUDA on mouse and human atrial tissue samples by autoradiographic studies, and (3) investigated the in vivo uptake of the radiotracer by dynamic PET imaging in A2A-AR TG and WT. After A2A-AR stimulation by the A2A-AR agonist CGS 21680 in isolated atrial preparations, antagonistic effects of FLUDA were found in A2A-AR-TG animals but not in WT. Radiolabelled [18F]FLUDA exhibited a KD of 5.9 \u00b1 1.6 nM and a Bmax of 455 \u00b1 78 fmol\/mg protein in cardiac samples of A2A-AR TG, whereas in WT, as well as in human atrial preparations, only low specific binding was found. Dynamic PET studies revealed a significantly higher initial uptake of [18F]FLUDA into the myocardium of A2A-AR TG compared to WT. The hA2A-AR-specific binding of [18F]FLUDA in vivo was verified by pre-administration of the highly affine A2AAR-specific antagonist istradefylline. Conclusion: [18F]FLUDA is a promising PET probe for the non-invasive assessment of the A2A-AR as a marker for pathologies linked to an increased A2A-AR density in the heart, as shown in patients with heart failure.<\/jats:p>","DOI":"10.3390\/ijms23031025","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T08:09:20Z","timestamp":1642493360000},"page":"1025","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-Invasive Assessment of Locally Overexpressed Human Adenosine 2A Receptors in the Heart of Transgenic Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-2325","authenticated-orcid":false,"given":"Daniel","family":"G\u00fcndel","sequence":"first","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-8979","authenticated-orcid":false,"given":"Thu Hang","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"},{"name":"Department of Research and Development, ROTOP Pharmaka Ltd., 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sladjana","family":"Dukic-Stefanovic","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-0567","authenticated-orcid":false,"given":"Rodrigo","family":"Teodoro","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3062","authenticated-orcid":false,"given":"Winnie","family":"Deuther-Conrad","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-3857","authenticated-orcid":false,"given":"Magali","family":"Toussaint","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-1271","authenticated-orcid":false,"given":"Klaus","family":"Kopka","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technical University Dresden, 01069 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-7945","authenticated-orcid":false,"given":"Rare\u015f-Petru","family":"Moldovan","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boknik","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology and Toxicology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Medical Faculty, Martin Luther University of Halle-Wittenberg, 06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6986-485X","authenticated-orcid":false,"given":"Ulrich","family":"Gergs","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology and Toxicology, Martin Luther University of Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Neumann","sequence":"additional","affiliation":[{"name":"Institute for Pharmacology and Toxicology, Martin Luther University of Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-7058","authenticated-orcid":false,"given":"Peter","family":"Brust","sequence":"additional","affiliation":[{"name":"Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, 04813 Leipzig, Germany"},{"name":"The L\u00fcbeck Institute of Experimental Dermatology, University Medical Center Schleswig-Holstein, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s40256-019-00345-5","article-title":"Adenosine and the Cardiovascular System","volume":"19","author":"Reiss","year":"2019","journal-title":"Am. 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