Synthesis and biological evaluation of a novel 18F-labeled radiotracer for PET imaging of the adenosine A2A receptor

Abstract

The adenosine A_2A receptor (A_2AR) 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_2AR-tailored therapy. Aiming at the development of a PET radiotracer, we herein report the design of a series of novel fluorinated analogs (<b>TOZ1-TOZ7</b>) based on the structure of the A_2AR antagonist <b>tozadenant</b>, and the preclinical evaluation of [¹⁸F]<b>TOZ1</b>. Autoradiography proved A_2AR-specific in vitro binding of [¹⁸F]<b>TOZ1</b> 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_2AR-specific in vivo binding.