title: Recent advances in positron emission tomography (PET) radiotracers for imaging phosphodiesterases.
abstract: Phosphodiesterases (PDEs) are a family of enzymes that metabolically inactivate the second messengers 3',5'- cyclic adenosine monophosphate (cAMP) and/or 3',5'-cyclic guanosine monophosphate (cGMP). These two messengers regulate the extracellular signal from the plasma membrane G protein-coupled receptors (GPCRs) to the intracellular effector proteins, hence modulating a wide variety of biological processes both in the central nervous system (CNS) and peripheral tissues. Although there are many radiotracers available for positron emission tomography (PET) studies of different receptors, there are just a few tracers available for imaging studies of second messenger systems. The first reported PDE PET ligands were the 11C-labeled versions of the PDE4 inhibitors rolipram and Ro 20-1724, and, to date, PET imaging studies in human subjects have only been reported with [11C]rolipram. As a consequence of the growing interest in identifying selective PDE inhibitors as potential new therapeutic agents, new PET radiotracers for imaging specific PDEs have been described in literature as well. This article highlights these efforts on the design and evaluation of novel PET radioligands for in vivo imaging of PDEs.
authors.affiliation: Community of Research Excellence & Advanced Technology (CREATe), PET Ligand Discovery, Janssen Research & Development, Janssen-Cilag S.A., C/ Jarama 75, 45007 Toledo, Spain. iandres@its.jnj.com
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Andrés
authors.forename: Meri
authors.initials: M
authors.lastname: De Angelis
authors.forename: Jesús
authors.initials: J
authors.lastname: Alcázar
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010726:Phosphodiesterase Inhibitors; D019275:Radiopharmaceuticals; D010727:Phosphoric Diester Hydrolases