[11 C]Acetate rest–stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats

• Published in: Nuclear medicine and biology Vol. 39; no. 2; pp. 287 - 294
• Main Authors: Croteau, Etienne, Gascon, Suzanne, Bentourkia, M'hamed, Langlois, Réjean, Rousseau, Jacques A, Lecomte, Roger, Bénard, François
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2012
• Subjects: [11C]Acetate, Cardiovascular reserve; Acetates; Animals; Antibiotics, Antineoplastic - pharmacology; Carbon Radioisotopes; Case-Control Studies; Congestive heart failure; Coronary Circulation - drug effects; Coronary Circulation - physiology; Dobutamine; Doxorubicin - pharmacology; Heart Failure - diagnostic imaging; Heart Failure - physiopathology; Myocardial oxygen consumption; Myocardial perfusion; Myocardial Perfusion Imaging - methods; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; Positron-Emission Tomography - methods; Radiology; Rats; Rest–stress study; Small-animal PET imaging; Small-animal PET imaging; Rest–stress study; [ 11C]Acetate, Cardiovascular reserve; Dobutamine; Congestive heart failure; Myocardial perfusion; Myocardial oxygen consumption; [11C]Acetate, Cardiovascular reserve
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2011.07.010

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 (MVO2 ) in rats. Doxorubicin cardiotoxicity was used to test the usefulness of this approach for the assessment of congestive heart failure. Methods [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. Results Validation of the protocol showed a good correlation between the MBF and MVO2 ( r2 =.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 MVO2 reserve (treated 1.8±0.4 vs. controls 2.3±0.3; P =.02). Conclusions 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.