A business of some heat1: molecular imaging of phosphodiesterase 5. Issue 2 (January 2016)

• Record Type: Journal Article
• Authors: Cumming, Paul
• Is Part Of: Journal of neurochemistry. Volume 136:Issue 2(2016)
• Page Start: 220
• Page End: 221
• Publication Date: 2016-01
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13453
• Languages: English
• ISSNs: 0022-3042

Abstract

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 Gómez‐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 page403 .