In Vivo 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(2A)) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS, A(2A) receptors are expressed mainly within the neurons of the basal ganglia. Alterations in A(2A) receptor function and expression have been noted in movement disorders, and in Parkinson's disease pharmacological A(2A) receptor antagonism leads to diminished motor symptoms. Although A(2A) 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(2A) receptors in extrastriatal CNS tissue, and this has been successfully quantitated using in vivo positron emission tomography (PET) imaging and A(2A) receptor-binding radioligands. Several radioligands for PET imaging of A(2A) receptors have been developed in recent years, and A(2A) receptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammation in vivo. This review article provides a brief overview of A(2A) receptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances in A(2A) receptor-targeting PET imaging studies.