A business of some heat: Molecular imaging of phosphodiesterase 5

Abstract

G-protein coupled receptors activate intracellular signaling by well-known pathways involving cyclic nucleotides or phosphatidylinositol. However, these signaling pathways (second messenger systems) have scarcely been investigated with molecular imaging techniques. This Editorial highlights a preclinical PET study by Gõmez-Vallejo and coworkers, in which the authors studied the cerebral uptake of the prototypic phosphodiesterase 5 (PDE5) inhibitor sildenafil and showed that its action manifested in elevated cGMP levels in cerebrospinal fluid of non-human primates, but their rat PET studies with [11C]sildenafil failed to show specific binding in brain. This negative PET study underlines that abundance (Bmax) of the target molecule can be decisive for success of a new ligand, and emphasizes the need for further quantitative PET studies of PDE5 as calculations suggest that it might yet be detected with a PET tracer of higher affinity than [11C]sildenafil. Read the highlighted article 'Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels' on page 403.