Abstract
This study describes an [(11)C]acetate rest-stress method to obtain an indirect estimate of myocardial blood flow (MBF) and myocardial oxygen consumption (MVO(2)) in rats. Doxorubicin cardiotoxicity was used to test the usefulness of this approach for the assessment of congestive heart failure. [(11)C]Acetate rest-stress studies have been used in clinical research to assess the capacity of the coronary arteries to respond to stress. In this article, we used this approach to assess the cardiotoxicity of doxorubicin in a rat model. The method was first validated in a group of healthy rats and then used to follow the effect of doxorubicin chemotherapy on cardiac function. The effect of doxorubicin on myocardial perfusion and oxygen consumption reserve was measured at rest and under dobutamine stimulation. Validation of the protocol showed a good correlation between the MBF and MVO(2) (r(2)=.68). The doxorubicin-treated group showed a significant (P=.04) decrease in cardiovascular perfusion reserve at 1.3±0.2 compared with the control animals at 1.6±0.2. Similar results were obtained for the MVO(2) reserve (treated 1.8±0.4 vs. controls 2.3±0.3; P=.02). We describe an [(11)C]acetate PET rest-stress protocol for the assessment of congestive heart failure in rats and its application to the follow-up of cardiotoxicity under doxorubicin chemotherapy. This is a rapid and reliable approach to the measurement of cardiac perfusion and oxygen consumption reserve that could be applied to the development of new strategies to reduce the cardiotoxicity of anthracycline.
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