Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

The G protein-coupled adenosine A2B receptor is suggested to be involved in various patholog-ical processes accompanied by increased levels of adenosine as found in inflammation, hypoxia, and cancer. Therefore, the adenosine A2B receptor is currently in the focus as a novel target for cancer therapy as well as for noninvasive molecular imaging via positron emission tomography (PET). Aiming at the development of a radiotracer labeled with the PET radionuclide fluorine-18 for imaging the adenosine A2B receptor in brain tumors, one of the most potent and selective an-tagonists, the xanthine derivative PSB-603, was selected as a lead compound. As initial biodis-tribution studies in mice revealed a negligible brain uptake of [3H]PSB-603 (SUV3min: 0.2), struc-tural modifications were performed to optimize the physicochemical properties regarding blood-brain barrier penetration. Two novel fluorinated derivatives bearing a 2-fluoropyridine (7) and a 4-fluoropiperidine (8) moiety have been synthesized, and their affinities for the four adenosine receptor subtypes were determined in competition binding assays. Both compounds showed high affinity towards the adenosine A2B receptor (Ki (7) = 9.97 ± 0.86 nM; Ki (8) = 12.3 ± 3.6 nM) with moderate selectivities versus the other adenosine receptor subtypes.