Automatic synthesis of a phosphodiesterase 4B (PDE4B) radioligand and PET imaging in depression rodent models.

Abstract

Phosphodiesterase 4B (PDE4B) is an enzyme that hydrolyzes cyclic adenosine monophosphate (cAMP), a critical signaling molecule involved in various cellular processes. Dysregulated PDE4B activity has been implicated in psychiatric diseases like depression and schizophrenia. In this report, a PDE4B-targeted PET tracer, [¹⁸F]PF-06445974, was synthesized using an automated synthesis module. [¹⁸F]PF-06445974 demonstrated high brain specificity, robust uptake, and excellent stability. In vivo metabolic studies confirmed that its radioactive metabolites did not cross the blood-brain barrier, and no abnormal bone uptake was observed in PET imaging. Furthermore, PET studies and quantitative autoradiography revealed significantly increased expression of PDE4B in the hippocampus and cortex of depression model rats compared to normal controls. The findings highlight the potential of in vivo PDE4B PET imaging as a valuable tool for monitoring PDE4B changes in depression, providing insights into its pathophysiological processes and paving the way for clinical translational research in this domain.