(99mT)c-duramycin Imaging Detects Cancer Therapy Related Cardiac Dysfunction Before a Decrease in Lvef

Background: Although the remission rate of cancer has increased, cardiotoxicity due to cancer therapy remains a major problem. Detection of cardiotoxicity prior to a decrease in left ventricular functions (LVEF) or an enzyme leak should allow preservation of normal ventricular function. Previous studies suggest that injury to the cardiomyocyte is associated with increased expression of phosphatidylethanolamine (PE) on the cell membrane. In this study we evaluated 99mTc labeled -Duramycin, an agent that binds with nanomolar affinity to membrane bound PE, as an early marker of sarcolemmal cell membrane damage caused by cardiotoxicity of doxorubicin. Method: 54 male Sprague-Dawley rats were divided into 9 groups. We tested duramycin in both a single injection model (5 or 10 mg/kg of Doxorubicin (Dox), or vehicle) and in a multiple injection model, where rats received injections of 2.5mg/kg of Dox every other day for 2, 3, or 4 injections, or vehicle. Two other groups received single dose of 10mg/kg of Trastu...