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.

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

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.

Last Modified: 15.10.2024