Evaluation of new radiotracers for in vivo imaging of brain adenosine receptors

Positron emission tomography (PET) is an imaging technique to visualize processes in the living body ("in vivo"). With this minimal invasive method, we study the brain, and we need radioactively labeled molecules (radioligands), which must be tailored to analyze proteins such as receptors.

Adenosine receptors, especially type A₁ and A_2A, are found throughout the body and are involved in a variety of processes; they also play a major role in the brain. Cerebral A₁ and A_2A adenosine receptors are involved in the regulation of locomotion, sleep-wake rhythms, anxiety, memory function, and perception (among others). Thus, they are also associated with the pathogenesis of various diseases. The examination of these receptors with PET may therefore provide fundamental insights into brain function and the development of diseases such as Alzheimer's disease, Parkinson's disease, epilepsy and depression. It therefore has the potential to become a promising tool for the diagnosis of these diseases.

Several radioligands have been evaluated for PET-based imaging of these adenosine receptors. A fluorine-18 labeled tracer (8-cyclopentyl-3-(3-[¹⁸F]fluoropropyl)-1-propylxanthine ([¹⁸F]CPFPX)) based on a xanthine structure has found application in human imaging of A₁ adenosine receptors and was developed several years ago at Forschungszentrum Jülich. [¹⁸F]CPFPX binds with high affinity and selectively to brain A₁ adenosine receptors. In medicinal chemistry (nuclear chemistry, INM-5), binding affinity and metabolic stability is further improved in new tracer candidates. For in vivo imaging of cerebral A_2A adenosine receptors, on the other hand, there is not yet an ¹⁸F-labeled tracer that is routinely used in humans. For this, the radioligand needs to cross the blood-brain barrier and should not be degraded too quickly to send signals from the brain.

In cooperation with the medicinal chemistry (INM-5; Institute of Neuroscience and Medicine), we are evaluating new radioligands in PET measurements to what extent they offer the properties necessary for medical imaging in humans.

More information under https://www.sciencedirect.com/science/article/abs/pii/S0223523421000635?via%3Dihub [1]

[1] „Reprinted from European Journal of Medicinal Chemistry, Volume 214, Dana R. Renk, Marcel Skraban, Dirk Bier, Annette Schulze, Erika Wabbals, Franziska Wedekind, Felix Neumaier, Bernd Neumaier, Marcus Holschbach, Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A_2A receptor ligands (2021), with permission from Elsevier."

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