PET imaging of phosphodiesterases in brain

Abstract

Phosphodiesterases (PDEs) regulate the intracellular concentration of the secondary messengers cGMP and cAMP thereby modulating a variety of cellular activities in brain. Eleven different families of PDEs have been identified of which at least six show significant expression in brain. Phosphodiesterase inhibitors have been evaluated clinically as potential drugs for treatment of different CNS diseases but so far, no PDE inhibitor has been registerered as a drug for treatment of a CNS disease. PET ligands have been developed and evaluated targeting PDE2,4,5, and 10 and clinical PET studies were conducted with radiolabeled PDE2, 4, and 10 inhibitors. PDEs are interesting targets for in vivo imaging with PET as both their expression level and affinity for inhibitors can be modulated. This chapter provides an overview of the development of PDE PET tracers and their application in preclinical and clinical research.