PET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS, A receptors are expressed mainly within the neurons of the basal ganglia. Alterations in A receptor function and expression have been noted in movement disorders, and in Parkinson's disease pharmacological A receptor antagonism leads to diminished motor symptoms. Although A receptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation of A receptors in extrastriatal CNS tissue, and this has been successfully quantitated using positron emission tomography (PET) imaging and A receptor-binding radioligands. Several radioligands for PET imaging of A receptors have been developed in recent years, and A receptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammation . This review article provides a brief overview of A receptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances in A receptor-targeting PET imaging studies.