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The cardiac contractile work is fundamental to maintain heart’s tissue perfusion. Adenosine Triphosphate (ATP) is the main chemical fuel used for this purpose. Almost 90% of ATP in the healthy heart is synthesised through the FAO, while the remaining 10% is produced via the glycolysis pathway. In the Heart Failure (HF) syndrome a switch between these two pathways has been reported: in the early stages of HF the FAO/glycolysis relative rates are unchanged, while in the advanced ones there is a downregulation of the FAO pathway strongly linked to disease’s progression and severity. Thus, assessing the FAO rate would improve patients monitoring and therapy effectiveness. FAO imaging using Positron Emission Tomography (PET) allows its absolute quantification through a tracer labelled with radioactive nuclides, for instance 11C or 18F. Metabolically trapped probes are particularly interesting because they undergo the FAO generating a radioactive metabolite, which is trapped in the mitochondria reflecting the oxidation rate. A novel PET candidate has been designed to be taken up by the myocardium as a conventional fatty acid and would be a FAO substrate; the β-oxidation cycle is then expected to generate a reactive difluoroketone which would be trapped inside the mitochondria and its emitted radioactivity would reflect the FAO rate.
Collaborators:
Astrazeneca
CIC biomaGUNE