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Free Fatty Acid Uptake in the Myocardium and Skeletal Muscle Using Fluorine-18-Fluoro-6-Thia-Heptadecanoic Acid

Departments of Nuclear Medicine, Medicine and Clinical Physiology, and Radiochemistry Laboratory, University of Turku, Turku; Turku PET Centre, Turku, Finland

Correspondence: For correspondence or reprints contact: Maija T. Mäki, MD, Turku PET Centre, University of Turku, FIN-20520, Turku, Finland.

ABSTRACT

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 60 mU/liter). The fractional [¹⁸F] FTHA uptake rates (K_i) were multiplied with serum FFA concentra tions 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 (K_i) 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 /xmol/100 g/min, p < 0.005). The femoral muscle fractional [¹⁸F]FTHA uptake rates (K_i) 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 /u.mol/100 g/min) as compared to that during insulin clamp (0.12 ± 0.05 µmol/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.

Key Words: free fatty acids • fluorine-18-fluoro-6-thia-heptade-canoic acid • muscle • myocardium • PET

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