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Simultaneous Measurement of Myocardial Oxygen Consumption and Blood Flow Using [1-Carbon-11 ]Acetate

Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine and Division of Cardiology, School of Medicine, University of California, Los Angeles, California

Correspondence: For correspondence or reprints contact: Heinrich R. Schelbert, MD, Department of Molecular and Medical Pharmacology, School of Medicine, University of California, Los Angeles, CA 90095-1735.

ABSTRACT

[1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with PET. The aim of this study was to validate, in humans, a previously proposed two-compartment model for [1-¹¹C]acetate for the noninvasive measurement of myocardial oxygen consumption (MVO₂) and myocardial blood flow (MBF) with PET. Methods: Twelve healthy volunteers were studied with [¹³N]ammonia, [1-¹¹C]acetate and PET. Myocardial oxygen consumption was invasively determined by the Pick method from arterial and coronary sinus O₂ concentrations and from MBF obtained by [¹³N]ammonia PET. Results: Directly measured MVO₂ ranged from 5.2 to 11.1 ml/100 g/min, and MBF ranged from 0.48 to 0.88 ml/g/min. Oxidative flux through the tricarboxylic acid cycle, reflected by the rate constant k₂, which correlated linearly with measured MVO₂ [k₂ = 0.0071 + 0.0074(MVO₂); r = 0.74, s.e.e. = 0.015]. With this correlation, MVO₂ could be estimated from the model-derived k₂ value by MVO₂ = 135(k₂)–0.96. The slope of this relationship was close to that previously obtained in rats and implies that the tricarboxylic acid cycle intermediate metabolite pool sizes are comparable. The net extraction (k₂) of [1-¹¹C]acetate, measured by PET, from blood into myocardium correlated closely with MBF by k₂ = 0.15 + 0.73(MBF)(r = 0.93, s.e.e. = 0.033)and, thus, provided noninvasively obtainable measures of blood flow. Conclusion: The proposed compartment model for [1-¹¹C]acetate fits the measured kinetics well and, with proper calibration, allows estimation of absolute MVO₂ rather than only an index of oxidative metabolism. Furthermore, [1-¹¹C]acetate-derived estimates of MBF are feasible.

Key Words: PET • myocardial oxygen consumption • myocardial blood flow • [1-carbon-11]acetate

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