This renewal application builds upon the two new radio-nuclide imaging approaches which have been funded for the past 15 months in NHBI Grant HL-21751. These approaches are serial imaging after a single dose of 201T1 to distinguish between normal, viable ischemic, and infarcted myocardium and gamma imaging of radiolabeled specific antibody to cardiac myosin to identify regions of acute myocardial infarction. We have now compiled substantial evidence that redistribution of 201T1 into initial defects on serial imaging studies is primarily related to myocardial viability. Accordingly, in the present protocol we will explore methods to objectively assess the serial imaging sequence in order to determine the ischemic state, its severity and its reversibility. Regional rate of myocardial 201T1 transport and the concentration of pulmonary 201T1 relative to myocardium will be derived and determined. In addition, radiolabeled antimyosin antibody will be prepared and applied clinically. In addition to a standard gamma camera imaging, a positron emitting radiolabel, 68 Ga will be employed to allow transverse section imaging after intracoronary administration of radiolabeled antimyosin. A new dimension has been added to the evaluation of acutely ischemic or infarcted myocardium by studying the localization of 18F-, a positron emitting radionuclide and the redistribution of endogenous 19F as determined by nuclear magnetic resonance (nmr) spectroscopy. 18F- is a bone seeking agent which accumulates in acutely infarcted myocardium and allows transverse emission tomography. We will evaluate its sensitivity, its specificity and its utility in quantification of infarct size. We have also found that an easily defineable reservoir of endogenous myocardial 19F exists and is easily detected with nmr. Preliminary studies suggest that endogenous 19F is depleted from ischemic myocardial zones. We propose to further evaluate 19F redistribution and determine if a 19F leak might be detected in the peripheral blood. By elucidating the mechanisms of thallium uptake and clearance, and correlating these with fluoride uptake and antimyosin deposition, the sensitivity, specificity and clinical application of imaging the ischemic myocardium will be enhanced.
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