University: Institute of Radiopharmaceutical Cancer Research, Department of Research and Development ROTOP Pharmaka Ltd, University Hospital of North Norway, The Arctic University of Norway
Authors: Thu Hang Lai, Magali Toussaint, Rodrigo Teodoro, Sladjana Dukić-Stefanović, Mathias Kranz, Winnie Deuther-Conrad, Rareş-Petru Moldovan and Peter Brust
Journal: IJMS – International Journal of Molecular Sciences
Impact Factor: 4.556 (What is the IF?).
TITLE: Synthesis and Biological Evaluation of a Novel 18F-Labeled Radiotracer for PET Imaging of the Adenosine A2A Receptor
ABSTRACT: The adenosine A2A receptor (A2AR) 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 A2AR-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 A2AR antagonist tozadenant, and the preclinical evaluation of [18F]TOZ1. Autoradiography proved A2AR-specific in vitro binding of [18F]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 A2AR-specific in vivo binding