PET Imaging Agent for Myocardial Infarction

Project Summary Each year millions of individuals suffer from myocardial infarctionMIor heart attackDiagnosis of MI is dependent on a complex set of tests which include imagingcardiac troponin levels in plasmaand electrocardiogramViability assessment and myocardial perfusion imaging by radiolabeled tracers has the most impact on the diagnosis and risk assessment of MIHoweverperfusion scans are unable to discriminate between an ischemic region and a necrotic region because both show reduced perfusionThey also fail to differentiate an acute infarct from an event that occurred in the pastTo enable sensitive and specific imaging of acute MIHexakitIncis collaborating with University of Oklahoma health Sciences CenterOUHSCin development of fluorinelabeled fluorodeoxyglucaric acidFGAas the first agent meant for positron emission tomographyPETof acute MIPET is a superior imaging technology because of its high resolutionsensitivityand lack of attenuationOUHSC researchers have developed a novel technique of synthesizing FGA from commercially available Flabeled fluorodeoxyglucoseFDGThe reaction is quantitative and quickasof FDG is oxidatively converted into FGA withinmin of reaction that produces no side productsPreliminary PET imaging in a model of isoproterenol induced cardiomyopathy demonstrated significant uptake of FGA in infarcted myocardium as compared to the normal heartAt the same timeFGA undergoes rapid clearance from the body and does not accumulate in normal myocardium or surrounding normal organs which would otherwise create artifacts and or high background in the imagesThe specific aim of this proposed Phase I research from HexakitIncis to test a kit for FGA synthesis for detection of focal MI in a mouse coronary artery ligation modelThis model is the most acceptable representation of human MI for testing myocardial diagnostic and therapeutic agentsWe have developed a working kit of lyophilized reagentsFigbTo accomplish the following tasks we have a team with radio chemistrypharmacyPET nuclear cardiologyand interventional cardiology expertiseTaskDetermine optimal time of FGA PET imagingwith respect to FGA injectionTaskDetermine how long FGA PET remains positive post MI and compare it to Tcm MIBI perfusion imaging TaskCorrelate FGA PET findings with plasma troponin levels and histology of heart TaskDetermine the mechanistic target of FGA in cardiac cells and tissue Successful accomplishment of the above tasks will position HexakitIncto assess data and prepare for a pre IND meeting with FDA for rapid clinical translation of FGA PET in thend Phase of this STTRA specific niche for FGA PET will be in therapeutic decision makingdetermination of candidacy for revascularizationand acute assessment of revascularization success with high sensitivity and specificityIn additionFGA PET will complement existing diagnostic modalities to differentiate ischemia from necrosis in acute MIdiscriminate myocarditis from infarctionand surveillance of heart transplant rejection Project Narrative Hexakit Incproposes to develop glucaric acid labeled with radionuclide fluorineas a new imaging agent for positron emission tomographyPETof acute myocardial infarctionMIThis agent will be tested in a mouse modelBy enabling early detection of MIFlabeled glucaric acid is predicted to improve outcomes of medical therapy or surgical intervention in these patients