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http://dx.doi.org/10.25673/85390
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DC Field | Value | Language |
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dc.contributor.author | Gündel, Daniel | - |
dc.contributor.author | Lai, Thu Hang | - |
dc.contributor.author | Dukic-Stefanovic, Sladjana | - |
dc.contributor.author | Teodoro, Rodrigo | - |
dc.contributor.author | Deuther-Conrad, Winnie | - |
dc.contributor.author | Toussaint, Magali | - |
dc.contributor.author | Kopka, Klaus | - |
dc.contributor.author | Moldovan, Rareş-Petru | - |
dc.contributor.author | Boknik, Peter | - |
dc.contributor.author | Hofmann, Britt | - |
dc.contributor.author | Gergs, Ulrich | - |
dc.contributor.author | Neumann, Joachim | - |
dc.contributor.author | Brust, Peter | - |
dc.date.accessioned | 2022-05-06T07:46:49Z | - |
dc.date.available | 2022-05-06T07:46:49Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/87342 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/85390 | - |
dc.description.abstract | 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 KD) 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 ± 1.6 nM and a Bmax of 455 ± 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. | eng |
dc.description.sponsorship | Publikationsfonds MLU | - |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.ddc | 610 | - |
dc.title | Non-invasive assessment of locally overexpressed human adenosine 2A receptors in the heart of transgenic mice | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | International journal of molecular sciences | - |
local.bibliographicCitation.volume | 23 | - |
local.bibliographicCitation.issue | 3 | - |
local.bibliographicCitation.publishername | Molecular Diversity Preservation International | - |
local.bibliographicCitation.publisherplace | Basel | - |
local.bibliographicCitation.doi | 10.3390/ijms23031025 | - |
local.openaccess | true | - |
local.accessrights.dnb | free | - |
Appears in Collections: | Open Access Publikationen der MLU |
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ijms-23-01025.pdf | 2.58 MB | Adobe PDF | ![]() View/Open |