Myocardial blood flow quantitation with the novel PET F Fluripidaz imaging tracer

DESCRIPTION provided by applicant Myocardial blood flow quantitation with the novel F Flurpiridaz PET imaging tracer PROECT SUMMARY Coronary artery disease CAD is the single largest cause of death in the United States Prevention early diagnosis and treatment of CAD are essential to reduce the mortality Noninvasive assessments of regional myocardial blood flow at rest and during stress have proved valuable for early diagnosis of CAD These assessments can be with a radioactive labeled myocardial perfusion imaging MPI agent using Single Photon Emission Computed Tomography SPECT or Positron Emission Tomography PET Flurpiridaz F is a novel new PET myocaridal perfusion imaging MPI agent labeled with F This agent is a structural analog of pyridaben a known mitochondrial complex MC inhibitor As mitochondria constitute to of the myocardial intracellular volume molecules that target mitochondrial proteins will be enriched and retained selectively in the myocardium In pre clinical studies flurpiridaz has shown a higher first pass extraction fraction than Tl and Tc m sestamibi at high flow rates Thus flurpiridaz can provide the opportunity to perform myocardial perfusion imaging with the improved resolution and quantification afforded by PET PET has several technical advantages over SPECT including routine measured attenuation correction which decreases the number of false positives thereby increasing specificity high spatial and contrast resolution that allows for improved detection of small perfusion defects which decreases the number of false negatives thereby increasing sensitivity and high temporal resolution that allows fast dynamic imaging of tracer kinetics The latter makes absolute quantification of MBF possible which has been shown to improve sensitivity for detection of multi vessel disease and evaluation of conditions that diffusely affect coronary circulation Flurpiridaz also could provide improved clinical utility and ease of use because of the longer half life minutes of an F based agent compared to current PET MPI agents rubidium Rb chloride nitrogen N ammonia and oxygen O water that makes delivery of unit doses from regional cyclotrons quite feasible which could not be achieved with the current shorter half live agents There is a need to optimize the acquisition and processing protocols in order to take full advantage of this andquot idealandquot MPI agent The clinical and technical research project proposed in this SBIR submission will address this optimization for the flurpiridaz imaging agent This Phase II submission is following the nearly completed SBIR Phase I grant R HL which was awarded on June Our long term objective for this project is to improve patient care and outcomes through increased diagnostic accuracy of coronary heart disease CHD maximize clinical diagnostic confidence and reduce costs by optimizing the method for flow calculation establishing quality control procedures and output for evaluation of the study standardizing the acquisition and processing protocols for Flurpiridaz F developing both relative and absolute quantitation plus measurements of myocardial blood flow MBF and coronary flow reserve CFR using the novel new cardiac imaging agent Flurpiridaz F developing an innovative Decision Support System DSS system as part of the relative quantitation which will drive an automatic structured natural language reporting system thereby increasing clinical confidence and reducing time cost and maximizing the availability of these benefits by incorporating all of this into a widely utilized and widely available commercial product the Emory Cardiac Toolbox tm ECTb PUBLIC HEALTH RELEVANCE Coronary artery disease is a major cause of death in modern industrialized countries According to the latest andquot Heart Disease and Stroke Statistics Updateandquot published by American Heart Association CAD is the single largest cause of death in the United States In million Americans were diagnosed with CAD and about died of this disease Prevention early diagnosis and treatment of CAD are essential to reduce the mortality Assessments of regional myocardial blood flow have proved valuable for early diagnosis of coronary artery disease These assessments can be performed in patients under rest and stress conditions with a radioactive labeled myocardial perfusion imaging tracer using Positron Emission Tomography PET imaging technique The tracers that are currently available for PET myocardial perfusion imaging are not practical because they require expensive onsite cyclotrons or generators Recently a novel PET imaging tracer F Flurpiridaz has been developed that has the potential for overcoming the limitations that are faced with the current PET perfusion tracers However the method for quantification of myocardial blood flow with this agent is not developed yet The overall goal of this research proposal is to develop and validate methods for relative and absolute measurement of regional myocardial blood flow for noninvasive detection of coronary artery disease using F Flurpiridaz Four Aims with specific projects are proposed in a total of patients All patients have been enrolled in Phase and Phase studies of F Flurpiridaz under the sponsorship of Lantheus Medical Imaging Successful outcome of this research is expected to enhance our ability to noninvasively diagnose and characterize coronary artery disease