Development of versatile fluorescence probes for detection and imaging of heme oxygenase 1 (HO-1) activity in haemorrhage for clinical diagnostics

Heme oxygenase-1 (HO-1) is a critical enzyme for vascular health and disease and a marker of hemorrhage in ruptured coronary plaques and hemorrhagic stroke. Yet it lacks a good detection method for live cells or tissues. HO-1 imaging would add enormously to diagnostic coronary imaging.

Detection and imaging of HO-1 would allow for a full preclinical investigation of its function allowing for translation of HO-1 activity as a biomarker to improve clinical management of myocardial infarction, stroke and ruptured aortic aneurysm.

Previously funded by the BHF, we successfully incorporated coumarin in a heme analogue such that it becomes fluorescent on release by HO-1 activity. In this new proposal, the utility of a wide range of HO-1 sensitive fluorophores will be explored.

These will be easily generated by addition of an ethyne (a small and highly specific group) to the Protoporphyrin-IX ring at the alpha-carbon position.

The new probes will be evaluated spectroscopically, in cell-free systems and in cultured human and mouse cells, and then validated in an easily-imaged mouse model of hematoma. This will facilitate development of probes for clinical application in imaging and point-of-care diagnosis.