Synthesis and Biological Evaluation of a Novel 18F-Labeled Radiotracer for PET Imaging of the Adenosine A2A Receptor

Int J Mol Sci. 2021 Jan 25;22(3):1182. doi: 10.3390/ijms22031182.

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.

Keywords: adenosine A2A receptor; fluorine-18; positron emission tomography; tozadenant.

MeSH terms

  • Animals
  • Autoradiography
  • Chemistry Techniques, Synthetic
  • Fluorodeoxyglucose F18* / chemistry
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Molecular Imaging* / methods
  • Molecular Structure
  • Positron-Emission Tomography* / methods
  • Protein Binding
  • Radioactive Tracers*
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / metabolism
  • Receptor, Adenosine A2A / chemistry
  • Receptor, Adenosine A2A / metabolism*
  • Spectrum Analysis
  • Structure-Activity Relationship

Substances

  • Radioactive Tracers
  • Radiopharmaceuticals
  • Receptor, Adenosine A2A
  • Fluorodeoxyglucose F18