Free fatty acid uptake in the myocardium and skeletal muscle using fluorine-18-fluoro-6-thia-heptadecanoic acid.

UNLABELLED: 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) has been recently introduced as a new tracer for fatty acid metabolism. Myocardial [18F]FTHA uptake is believed to reflect mainly beta-oxidation of the circulating free fatty acids (FFAs), since it is trapped in the mitochondria because subsequent steps of beta-oxidation are inhibited by sulfur heteroatom. We investigated [18F]FTHA kinetics in myocardial and skeletal muscle in vivo. METHODS: Two dynamic PET studies were performed in seven patients with stable coronary artery disease, once in the fasting state and once during euglycemic hyperinsulinemia (serum insulin approximately 60 mU/liter). The fractional [18F] FTHA uptake rates (Ki) were multiplied with serum FFA concentrations and were considered to represent FFA uptake. RESULTS: Serum FFA concentration decreased by 80% during insulin clamp. After tracer injection, rapid myocardial uptake was identified both in the fasting state and during insulin stimulation. The cardiac image quality was excellent in both occasions. In addition, femoral muscles were clearly visualized in both studies. The fractional myocardial [18F]FTHA uptake rates (Ki) in the normal myocardial regions were similar in the fasting state (0.11 +/- 0.04 ml/g/min (mean +/- s.d.) and during insulin clamp (0.12 +/- 0.03 ml/g/min; ns). The calculated myocardial FFA uptake was four times higher in the fasting state than during insulin clamp (5.8 +/- 1.7 versus 1.4 +/- 0.5 micromol/100 g/min, p < 0.005). The femoral muscle fractional [18F]FTHA uptake rates (Ki) were lower (0.0071 +/- 0.0014 ml/g/min) in the fasting state than during insulin clamp (0.0127 +/- 0.0036 ml/g/min; p = 0.03), but the estimated femoral muscle FFA uptake was three times higher in the fasting state (0.38 +/- 0.09 micromol/100 g/min) as compared to that during insulin clamp (0.12 +/- 0.05 micromol/100 g/min, p < 0.005). CONCLUSION: Fluorine-18-FTHA PET appears to be a feasible method to estimate fatty acid kinetics in myocardial and skeletal muscle. Physiologically reasonable rates of FFA uptake in myocardium and skeletal muscle were obtained. Furthermore, the uptake rates were suppressed in response to insulin both in the myocardial and femoral muscle as expected.

Fatty acid uptake is preserved in chronically dysfunctional but viable myocardium.

Glucose uptake appears preserved or even enhanced in the chronically dysfunctional but viable myocardium. However, the use of other fuels such as free fatty acids (FFA) remains unknown. We studied FFA uptake in the chronically dysfunctional but viable myocardium in seven patients with an occluded major coronary artery and a corresponding chronic wall motion abnormality but no previous infarction. Myocardial FFA uptake kinetics in the fasting state were measured with positron emission tomography (PET) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). The FFA uptake index was calculated by multiplying the fractional [18F]FTHA uptake with serum FFA concentration. Myocardial blood flow (MBF) was measured with [15O]H2O and PET. Myocardial viability was confirmed with a static 18F-labeled 2-fluoro-2-deoxy-D-glucose PET imaging and a follow-up echocardiography in the revascularized patients. Regional MBF was slightly but not significantly lower in the dysfunctional compared with normal myocardial segments (0.76 +/- 0.18 vs. 0.81 +/- 0.14 ml.min-1.g-1, means +/- SD; P = 0.16). The fractional [18F]FTHA uptake rates [0.11 +/- 0.03 vs. 0.11 +/- 0.04 ml.g-1.min-1; not significant (NS)], and the FFA uptake indexes (5.8 +/- 1.7 vs. 5.8 +/- 2.1 mumol.100g-1.min-1; NS) were similar in the dysfunctional but viable and in the normal myocardial regions. Thus, in the chronically dysfunctional but viable (collateral-dependent) myocardium, the fatty acid uptake probed by [18F]FTHA appears preserved. Taken together with preserved glucose uptake, the results indicate that there is uncoupling of substrate uptake and mechanical function in the chronically dysfunctional but viable myocardium.