Non-Invasive Assessment of Locally Overexpressed Human Adenosine 2A Receptors in the Heart of Transgenic Mice.

A adenosine receptors (A-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 [F]FLUDA to non-invasively determine the A-AR availability for diagnosis of the AR status. Therefore, we compared mice with cardiomyocyte-specific overexpression of the human A-AR (A-AR TG) with the respective wild type (WT). We determined: (1) the functional impact of the selective AR ligand FLUDA on the contractile function of atrial mouse samples, (2) the binding parameters ( ) of [F]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 A-AR TG and WT. After A-AR stimulation by the A-AR agonist CGS 21680 in isolated atrial preparations, antagonistic effects of FLUDA were found in A-AR-TG animals but not in WT. Radiolabelled [F]FLUDA exhibited a of 5.9 ± 1.6 nM and a of 455 ± 78 fmol/mg protein in cardiac samples of A-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 [F]FLUDA into the myocardium of A-AR TG compared to WT. The hA-AR-specific binding of [F]FLUDA in vivo was verified by pre-administration of the highly affine AAR-specific antagonist istradefylline. Conclusion: [F]FLUDA is a promising PET probe for the non-invasive assessment of the A-AR as a marker for pathologies linked to an increased A-AR density in the heart, as shown in patients with heart failure.