Acute-infarct selective cardiac MRI contrast agent

DESCRIPTION provided by applicant The overall goal of this project is to demonstrate the ability of our acute myocardial infarct selective paramagnetic contrast agent Gadolinium ABE DTTA to differentiate between acute and chronic infarcts in a reliable manner using contrast enhanced magnetic resonance imaging ceMRI In our Phase I data we have shown that Gd ABE DTTA exclusively highlights acute infarcts by causing signal hyper enhancement but contrary to presently used contrast agents it does not cause hyper enhancement in week old infarcts A reliable noninvasive diagnostic differentiation between acute and older myocardial infarcts could be used to make decisions about which vessels and in what order should be reopened or bypassed by an interventional cardiologist or a cardiac surgeon in a patient with myocardial infarction MRI contrast agents presently used in the clinic are unable to make such differentiation Using a conventional MRI contrast agent to highlight all infarcts followed by an appropriate minimum time period to allow for this agent to clear from the heart muscle minutes and subsequently using Gd ABE DTTA one would elucidate which infarct area is due to a new acute infarction Using a canine model of myocardial infarction in the Phase I project we proved with statistical significance the ability of Gd ABE DTTA to show such differentiation In preparation for commercialization the objectives of Phase II are Investigation of the infarct age time frame for the disappearance or the decay of the affinity of Gd ABE DTTA to the myocardial infarct in the pig model of reperfused infarct Elucidation of the histological basis of this phenomenon in the same animal model Determination of the in vivo myocardial tissue kinetics of Gd ABE DTTA accumulation into subacute versus chronic myocardial infarct in pigs Determination of the kinetics of biodistribution of Gd ABE DTTA in pigs and its clearance kinetics in rabbits Determination of Gd ABE DTTA toxicity LD in mice Quantitative comparison of the effect of high dose of Gd ABE DTTA on Nephrogenic Systemic Fibrosis to that of FDA approved Gd DTPA PUBLIC HEALTH RELEVANCE A significant number of heart patients suffer a second heart attack after the first infarction was treated either by angioplasty or by bypass surgery It would be important to the cardiologist to be able to distinguish on the MRI image between the old and new infarct A reliable noninvasive diagnostic differentiation between acute and older infarcts could be used to make decisions about which vessels and in what order should be reopened or bypassed by an interventional cardiologist or a cardiac surgeon in a patient with multiple myocardial infarction MRI contrast agents presently used in the clinic are unable to make such differentiation The overall goal of this project is to demonstrate the ability of our acute myocardial infarct selective paramagnetic contrast agent Gadolinium ABE DTTA to differentiate between acute and chronic infarcts in a reliable manner using contrast enhanced magnetic resonance imaging ceMRI