Labelling, molecular modelling and biological evaluation of vardenafil: a potential agent for diagnostic evaluation of erectile dysfunction.
99mTc-tricarbonyl-vardenafil was specifically radiosynthesized for diagnostic evaluation of erectile dysfunction with a radiochemical yield ~97.2%. It was stable in saline up to 15h and in serum for more than 6h. The radiocomplex was lipophilic with a partition coefficient ~1.32 and plasma protein binding 72-76%. Its structure was determined using molecular mechanics and confirmed by NMR. In-silico docking to its target PDE5enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC50was 0.7nM. Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction were performed. The results strongly suggested that99mTc-tricarbonyl-vardenafil is a good candidate to image erectile dysfunction in humans.
Labelled Compounds Department, Atomic Energy Authority, 13759 Cairo, Egypt; Faculty of Pharmacy, Division of Pharmacology and Pharmacotherapy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland. Electronic address: elkawyo@gmail.com.
O A
OA
El-Kawy
Faculty of Pharmacy, Division of Pharmacology and Pharmacotherapy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland.
J A
JA
García-Horsman
Faculty of Pharmacy, Division of Pharmacology and Pharmacotherapy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland.
R K
RK
Tuominen
D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D016903:Drug Monitoring / Q000379:methods; D007172:Erectile Dysfunction / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D062105:Molecular Docking Simulation; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods; D014018:Tissue Distribution; D000069058:Vardenafil Dihydrochloride / Q000737:chemistry* / Q000493:pharmacokinetics*
D058986:Phosphodiesterase 5 Inhibitors; D019275:Radiopharmaceuticals; D000069058:Vardenafil Dihydrochloride; D013667:Technetium
Biological evaluation; Erectile dysfunction; Labelling; Technetium-99m; Tracer; Vardenafil