Toward PET imaging of A2B adenosine receptors: a carbon-11 labeled triazinobenzimidazole tracer

Introduction A 2B adenosine receptors (ARs) are commonly defined as "danger" sensors because they are triggered during cell injury when the endogenous molecule, adenosine, increases rapidly. These receptors, together with the other receptor subtypes (A 1 , A 2A and A 3 ), exert a wide variety of immunomodulating and (cyto)protective effects, thus representing a pivotal therapeutic target for different pathologies including diabetes, tumors, cardiovascular diseases, pulmonary fibrosis and others. The limited availability of potent and selective ligands for A 2B ARs has prevented this receptor to emerge both as therapeutic and diagnostic target. Methods Recently, a new class of potent A 2B ARs antagonists was developed featuring the triazinobenzimidazole scaffold. Starting from this chemotype, we synthesized a new radiotracer, [ 11 C]-4 (1-[ 11 C]methyl-3-phenyl triazino[4,3- a ]benzimidazol-4(1 H )-one), and investigated the pharmacokinetics of this compound in vivo to define its potential use in the imaging of A 2B AR with positron emission tomography. Results [ 11 C]-4 showed a very high chemical and blood stability. Results of in vivo and ex vivo experiments underlined the ability of this molecule to bind the A 2B AR and correlated with the A 2B AR protein and gene expression data. Conclusions Although further studies are necessary, these data suggest that [ 11 C]-4 may represent a good lead compound for the development of novel selective and potent A 2B AR radiotracers, and a new option for the clinical investigation of several pathophysiological processes and chronic diseases.