Abstract 16189: 99mTc-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 Trastuzumab (Trz) with injections after 3 or 4 injections of Dox. Myocardial uptakes of 99mTc-Duramycin were analyzed by micro SPECT/CT imaging and gamma counting. LVEF was quantified by echocardiography. Plasma levels of Troponin I were measured. Cardiac damage was confirmed by pathology.
Results: A single injection of 5 or 10 mg/kg Dox reduced LVEF compared with control (67.9 ± 2.7 %, p<0.05: and 60.6 ± 2.5 % vs 75.2 ± 2.3 %, p<0.01) and increased myocardial uptake of 99mTc-Duramycin uptake in %ID/g by gamma counting (0.074 ±0.011, p<0.01: and 0.097 ± 0.029 vs 0.047 ± 0.006, p<0.01). In multiple injection models, the combination of 3 or 4 injections of Dox and Trz reduced LVEF compared with control (65.9 ± 1.3 %, p<005: and 60.9 ± 2.9 % vs 74.3 ± 1.7 %, p<0.05) and increased 99mTc-Duramycin uptake (0.084 ± 0.010, p<0.05: and 0.089 ± 0.020 vs 0.048 ± 0.009, p<0.05). Although there was no significant difference in LVEF between Dox injection 2, 3, or 4 times and control (74.6 ± 0.7 %, 74.2 ± 2.6 %, 72.9 ± 5.4 % and 74.3 ± 1.7 %), 99mTc-Duramycin uptake showed a significant increased with Dox (0.081 ± 0.015, p<0.05: and 0.076 ± 0.017, p<0.05: and 0.076 ± 0.015 vs 0.048± 0.009, p<0.05).
Conclusion: 99mTc-Duramycin detects cardiotoxicity of anti-cancer drug at an early stage in this rat model.
Author Disclosures: T. Nakahara: None. A.D. Petrov: None. T. Tanimoto: None. N. Haider: None. N. Narula: None. F. Chaudhry: None. J.A. Mattis: None. K.Y. Pak: None. G. Sahni: None. A. Tiersten: None. A. Bhardwaj: None. P.P. Sengupta: None. M.R. Dweck: None. H.W. Strauss: None. J. Narula: None.
- © 2016 by American Heart Association, Inc.