Synthesis and Biological Evaluation of a Novel 18F-Labeled Radiotracer for PET Imaging of the Adenosine A2A Receptor.
Thu Hang LaiMagali ToussaintRodrigo TeodoroSladjana Dukić-StefanovićMathias KranzWinnie Deuther-ConradRareş-Petru MoldovanPeter BrustPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- pet imaging
- positron emission tomography
- computed tomography
- magnetic resonance imaging
- resting state
- white matter
- contrast enhanced
- pet ct
- binding protein
- cerebral ischemia
- functional connectivity
- single cell
- high fat diet induced
- high resolution
- type diabetes
- smoking cessation
- stem cells
- magnetic resonance
- adipose tissue
- multiple sclerosis
- risk assessment
- photodynamic therapy
- mesenchymal stem cells
- skeletal muscle
- diffusion weighted imaging
- subarachnoid hemorrhage
- molecular docking
- replacement therapy
- human health
- fluorescence imaging