Development and evaluation of PET ligands for the in vivo visualisation of phosphodiesterase type 5 (PDE5).

Phosphodiesterases are enzymes that break down the signaling molecules cGMP and cAMP. The phosphodiesterase subtype 5 (PDE5) is the target for treatment of erectile dysfunction with the well known PDE5 inhibitor sildenafil (Viagra). PDE5 has been found to be upregulated in lungs in pulmonary hypertension and in the heart in myocardial diseases. Both pathologies may benefit from treatment with PDE5 inhibitors. This project aims to synthesize radiolabelled tracers that specifically bind to PDE5. The radiation emitted upon decay of the radionuclides is detected by a dedicated scanner (PET camera) that thus allows visualizing the spatial distribution of PDE5 in the body and more specifically in the lung and myocardium. Within this project new PDE5 tracers will be evaluated in animal models of lung and cardiac disease in order to establish whether they allow to detect pathologically increased PDE5 expression. As for PET examinations extremely low mass amounts of radiolabelled tracers are administered, the technology can be rapidly translated to human application so that ultimately the tracer will be evaluated in patients with lung and/or cardiac disease. This will allow to select patients that have an increased PDE5 expression and may thus benefit from therapy with PDE5 inhibitors and to monitor pharmacological therapy with PDE5 inhibitors.

Keywords:Tracer, Radiopharmaceutical, PDE5, PET, Phosphodiesterases

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences