VALIDATION OF [1-C-11]ACETATE AS A TRACER FOR NONINVASIVE ASSESSMENT OF OXIDATIVE-METABOLISM WITH POSITRON EMISSION TOMOGRAPHY IN NORMAL, ISCHEMIC, POSTISCHEMIC, AND HYPEREMIC CANINE MYOCARDIUM

Extraction and clearance kinetics of [1-11C] acetate were examined in 65 experiments in 30 open-chest dogs. Twenty-nine studies were performed at control, 13 during ischemia, eight after reperfusion, 13 during dipyridamole-induced hyperemia, and two during alteration of cardiac workload. [1-11C] Acetate was injected directly into the left anterior descending coronary artery, and myocardial tissue-time activity curves were recorded with a gamma probe. The single-pass extraction fraction averaged 64.2±9.7% in control, 65.3±9.1% in ischemia, 70.0±4.4% in reperfusion, and 46.5±7.4% in dipyridamole-induced hyperemia groups. 11C clearance was biexponential in all cases. The rate constant k1 for the first rapid clearance phase correlated closely with myocardial oxygen consumption (r=0.94) in control, ischemia, reperfusion, and dipyridamole-induced hyperemia groups. Monoexponential fitting of only the first linear part of the clearance curve yielded the rate constant kmono, which also correlated with myocardial oxygen consumption (r=0.96). Arterial lactate concentrations and the amount of free fatty acid oxygen equivalents consumed by the myocardium were shown to have a small but statistically significant impact on the relation between [1-11C] acetate clearance rate constants and myocardial oxygen consumption. The fraction of 14CO2 activity contributing to overall 14C activity leaving the myocardium after simultaneous injection of [1-14C] acetate (n=24) was relatively high in all cases (97.4±2.5% in control, 89±2.6% in ischemia, 94.1±3.5% in reperfusion, and >99% in dipyridamole groups), indicating that externally measured 11C clearance corresponds to CO2 production and thus to tricarboxylic acid cycle activity. In conclusion, the results validate the use of [1-11C]acetate as a tracer of oxidative myocardial metabolism for use with positron emission tomography.