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.