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 4-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 (30-60 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: 1) 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. 2) Elucidation of the histological basis of this phenomenon in the same animal model. 3) Determination of the in vivo myocardial tissue kinetics of Gd(ABE-DTTA) accumulation into subacute versus chronic myocardial infarct in pigs. 4) Determination of the kinetics of biodistribution of Gd(ABE-DTTA) in pigs and its clearance kinetics in rabbits. 5) Determination of Gd(ABE-DTTA) toxicity (LD50) in mice.6) 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).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
5R42HL084844-04
Application #
8287126
Study Section
Special Emphasis Panel (ZRG1-SBMI-T (10))
Program Officer
Buxton, Denis B
Project Start
2006-09-28
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$440,498
Indirect Cost
Name
Elgavish Paramagnetics, Inc.
Department
Type
DUNS #
084510499
City
Birmingham
State
AL
Country
United States
Zip Code
35226
Varga-Szemes, Akos; Simor, Tamas; Lenkey, Zsofia et al. (2014) Infarct density distribution by MRI in the porcine model of acute and chronic myocardial infarction as a potential method transferable to the clinic. Int J Cardiovasc Imaging 30:937-48
Kirschner, Robert; Varga-Szemes, Akos; Simor, Tamas et al. (2012) Acute infarct selective MRI contrast agent. Int J Cardiovasc Imaging 28:285-93