Abstract
Phosphodiesterase 4B (PDE4B) plays a critical role in cAMP hydrolysis and is highly expressed in brain regions associated with neuroinflammation and central nervous system (CNS) disorders. Selective PDE4B radioligands hold significant potential for elucidating disease mechanisms, such as those in Parkinson's disease and schizophrenia, and enabling target occupancy measurements. In this study, we developed [ (18) F]P4B-2412, a novel PDE4B-selective radioligand, and evaluated its utility for positron emission tomography imaging (PET). [ (18) F]P4B-2412 was synthesized in high radiochemical yield (27.2%), excellent radiochemical purity (99%), and favorable molar activity (66.2 ± 2.5 GBq/μmol. In vitro autoradiography and dynamic PET imaging demonstrated high specificity for PDE4B in rodent brain regions, with blocking studies confirming negligible interaction with PDE4D. [ (18) F]P4B-2412 also exhibited robust in vitro and in vivo metabolic stability. These results establish [ (18) F]P4B-2412 as a promising PET imaging agent for visualizing PDE4B activity, offering a valuable tool for investigating neuroinflammation and advancing CNS drug development.