Synthesis and Biological Evaluation of a Novel 18 F-Labeled Radiotracer for PET Imaging of the Adenosine A 2A Receptor.

The adenosine A _2A receptor (A _2A R) has emerged as a potential non-dopaminergic target for the treatment of Parkinson's disease and, thus, the non-invasive imaging with positron emission tomography (PET) is of utmost importance to monitor the receptor expression and occupancy during an A _2A R-tailored therapy. Aiming at the development of a PET radiotracer, we herein report the design of a series of novel fluorinated analogs ( TOZ1 - TOZ7 ) based on the structure of the A _2A R antagonist tozadenant , and the preclinical evaluation of [ ¹⁸ F] TOZ1 . Autoradiography proved A _2A R-specific in vitro binding of [ ¹⁸ F] TOZ1 to striatum of mouse and pig brain. Investigations of the metabolic stability in mice revealed parent fractions of more than 76% and 92% of total activity in plasma and brain samples, respectively. Dynamic PET/magnetic resonance imaging (MRI) studies in mice revealed a brain uptake but no A _2A R-specific in vivo binding.