Labelling, molecular modelling and biological evaluation of vardenafil: a potential agent for diagnostic evaluation of erectile dysfunction

• Published in: Applied radiation and isotopes Vol. 118; pp. 258 - 265
• Main Authors: El-Kawy, O.A., García-Horsman, J.A., Tuominen, R.K.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2016
• Subjects: Biological evaluation; Erectile dysfunction; Labelling; Technetium-99m; Tracer; Vardenafil; Labelling; Erectile dysfunction; Vardenafil; Biological evaluation; Tracer; Technetium-99m
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2016.09.023

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 PDE5 enzyme was performed. The radiocomplex inhibitory activity was assessed and its IC50 was 0.7nM. Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction were performed. The results strongly suggested that 99mTc–tricarbonyl–vardenafil is a good candidate to image erectile dysfunction in humans.
•Labelling method of vardenafil with technetium 99m using tricarbonyl precursor is investigated and described.•The radiocomplex was lipophilic with a partition coefficient ~1.32, and its plasma protein binding was 72-76%.•Structure prediction and docking result of the labelled complex to its target the phosphodiesterase enzyme type 5. The complex has an optimal fit with a binding energy of −117.39 Kcal/ mole.•The radiocomplex inhibitory activity was assessed and its IC50 was 0.7nM. Labelling did not affect the biological behaviour of the original molecule.•Biodistribution in normal rats and biological evaluation in rat models of erectile dysfunction strongly suggested that the tracer could be used in monitoring the effectiveness of drugs used to treat erectile dysfunction.