Development of 8-bicycloalkyl-CPFPX derivatives for PET imaging of A1 adenosine receptors

Abstract

8-Cyclopentyl-3-(3-[¹⁸F]fluoropropyl)-1-propylxanthine ([¹⁸F]CPFPX) is an established radioligand for PET imaging of A₁ adenosine receptors (A₁R), but its application is complicated by rapid peripheral metabolism. To identify A₁R ligands with improved properties, several new CPFPX derivatives were developed and evaluated by preclinical in vitro studies. The most promising compound showed significantly improved A₁R affinity and selectivity compared to CPFPX and no formation of lipophilic metabolites. In addition, the corresponding radioligand [¹⁸F]1-NBX exhibited a high passive permeability and an A₁R-specific distribution pattern with low non-specific binding in autoradiographic studies with rat brain slices. These findings identify [¹⁸F]1-NBX as a promising candidate for further preclinical evaluation as potential PET tracer for A₁R imaging.

Humpert, S.; Schneider, D.; Bier, D.; Schulze, A.; Neumaier, F.; Neumaier, B.; Holschbach, M.

8-Bicycloalkyl-CPFPX derivatives as potent and selective tools for in vivo imaging of the A₁ adenosine receptor

European journal of medicinal chemistry 2024, 271, 116380.