Imaging of cardiac metabolism using radiolabelled glucose, fatty acids and acetate.

The heart metabolizes a wide variety of substrates such as free fatty acids, glucose, lactate, pyruvate, ketone bodies and amino acids, but under normal conditions, free fatty acids and glucose are the major sources of energy. In contrast, in ischaemia with less than normal delivery of oxygen, oxidative metabolism of free fatty acids is decreased and exogenous glucose becomes the preferred substrate and the production of energy mainly depends on anaerobic glycolysis. These metabolic changes under various pathophysiological conditions of the myocardium stress the importance of metabolism for the function of the heart and allow metabolic imaging of important cardiovascular diseases. For the detection of cardiac energy metabolism, three different tracers have been developed and validated; namely radiolabelled glucose, fatty acids and acetate. [18F]-fluorodeoxyglucose (FDG) is a glucose analogue and the initial uptake of [18F]-fluorodeoxyglucose is almost identical to that of glucose. After uptake, [18F]-fluorodeoxyglucose undergoes phosphorylation but, unlike glucose-6-phosphate, FDG-6-PO4 does not undergo further metabolism and remains trapped in the myocardium. This trapping of FDG allows imaging of FDG by positron-emission-tomography and single photon emission computed tomography (SPECT) cameras. Use of FDG for assessing acute and chronic ischaemic syndromes has been studied, but it is mainly used in clinical practice to assess dysfunction of viable myocardium, which has the ability to improve in function. FDG data have been shown to adequately predict regional and global function improvement after revascularization of patients with chronic left ventricular dysfunction and coronary artery disease (CAD). They can also be a powerful predictor of prognosis in these patients. Fatty-acid metabolism can be studied after labelling with 1-123. Beta-methyl iodine phenylpentadecanoic acid is a structurally modified fatty acid, which is used to trace uptake of fatty acids in the myocardium. Similarly to the case with FDG distinct uptake patterns have been observed in patients with CAD, and preliminary data concerning detection of myocardial viability assessment of prognosis are available. Interesting data suggest that fatty-acid imaging is the most sensitive technique for assessing metabolic changes in patients with hypertrophic cardiomyopathy. [11C]-Acetate immediately enters the tricarboxylic-acid (TCA) cycle and metabolism of [11C]-acetate is dependent solely on the TCA-cycle activity. Because the TCA-cycle activity is directly coupled to myocardial oxygen consumption, clearance rates of [11C]-acetate are used to assess regional myocardial consumption of oxygen. [11C]-acetate imaging has been validated for normal subjects and patients with CAD and appears to be as effective as use of FDG for assessing viability. The unique feature of this technique is to measure the regional consumption of oxygen non-invasively. Thus myocardial metabolic imaging is a promising approach for achieving direct insight into the processes underlying functional abnormalities of the myocardium.