title: Carbon-11 and Fluorine-18 Radiolabeled Pyridopyrazinone Derivatives for Positron Emission Tomography (PET) Imaging of Phosphodiesterase-5 (PDE5).
abstract: The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDE5 represents an important therapeutic and/or prognostic target, but noninvasive assessment of PDE5 expression is lacking. The purpose of this study was to develop and evaluate pyridopyrazinone derivatives labeled with carbon-11 or fluorine-18 as PDE5-specific PET tracers. In biodistribution studies, highest PDE5-specific retention was observed for [11C]-12 and [18F]-17 in the lungs of wild-type mice and in the myocardium of transgenic mice with cardiomyocyte-specific PDE5 overexpression at 30 min postinjection. In vivo dynamic microPET images in rats revealed that both tracers crossed the blood-brain barrier but brain retention was not PDE5-specific. Both [11C]-12 and [18F]-17 showed specific binding to PDE5 in myocardium of transgenic mice; however [18F]-17 showed significantly higher PDE5-specific inhibitable binding than [11C]-12.
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , BE-3000 Leuven, Belgium.
authors.forename: Rufael
authors.identifier: 0000-0002-7420-2495
authors.initials: R
authors.lastname: Chekol
authors.affiliation: Department of Imaging and Pathology, KU Leuven , and Nuclear Medicine, UZ Leuven, BE-300 Leuven Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gheysens
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , BE-3000 Leuven, Belgium.
authors.forename: Muneer
authors.initials: M
authors.lastname: Ahamed
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , BE-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Cleynhens
authors.affiliation: Department of Cardiovascular Sciences, UZ Leuven, KU Leuven , 3000 Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.affiliation: Discovery Sciences, Janssen Pharmaceutica, R&D , B-2340 Beerse, Belgium.
authors.forename: Greet
authors.initials: G
authors.lastname: Vanhoof
authors.affiliation: Department of Cardiovascular Sciences, UZ Leuven, KU Leuven , 3000 Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , BE-3000 Leuven, Belgium.
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.affiliation: Laboratory of Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , BE-3000 Leuven, Belgium.
authors.forename: Guy
authors.identifier: 0000-0002-0335-7190
authors.initials: G
authors.lastname: Bormans
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D066244:Proton Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5