Synthesis and Biological Evaluation of a Novel F-18-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 [F-18]TOZ1. Autoradiography proved A(2A)R-specific in vitro binding of [F-18]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.

Automated summary

The research focuses on developing a PET radiotracer for monitoring the expression and occupancy of the non-dopaminergic target A(2A) receptor in Parkinson's disease therapy. Novel fluorinated analogs are designed and evaluated in preclinical studies, showing specific in vitro binding to A(2A)R but no specific in vivo binding in dynamic PET/MRI studies.