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Myocardial Uptake of the Fatty Acid Analog 14-Fluorine-¹⁸-Fluoro-6-Thia-Heptadecanoic Acid in Comparison to Beta-Oxidation Rates by Tritiated Palmitate

Departments of Medicine (Cardiology), Radiology (Nuclear Medicine)and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; Department of Radiology, Duke University, Durham, North Carolina

Correspondence: For correspondence or reprints contact: Charles K Stone, MD, Cardiology Section, H6/317 Clinical Sciences Center, 600 Highland Avenue, University of Wisconsin Madison, Madison, WI 53792-3248.

ABSTRACT

The objectives of this study were to determine the relationship of FTHA uptake to changes in perfusion and fatty acid oxidation and to conlirm the retention of FTHA in the mammalian heart. Methods: Six pigs with extracorporeal perfusion of the left anterior descending artery (LAD) and cannulation of the LAD vein were studied. The extraction fraction (EF) of FTHA measured from LAD arterial and venous blood samples, was compared to beta-oxidation rates, determined by water production from tritiated palmitate. After a baseline period,changes in FTHA EF were measured in 15-min periods of hyperemia, control (baseline flow rate) and lactate infusion. After the lactate infusion, FTHA infusion was terminated, and a 15-min washout period was observed. Results: Beta-oxidation rate was unchanged from the baseline period during the hyperemic and control periods. With lactate infusion, the expected myocardial preference for lactate was noted, with a decline in exogenous fatty acid oxidation. Fluorine-¹⁸-FTHA EF paralleled the changes in beta-oxidation, with a decrease in EF during lactate infusion. Increase in perfusion was associated with a decrease in FTHA EF, compared to control, such that the product of flow and extractionn was maintained. A linear relationship of FTHA EF to fractional tritiated water production was found. Washout analysis confirmed minimal washout of tracer at 15 min after termination of infusion. Organic solvent extraction of tissue samples suggested that the majority of tissue radioactivity was protein-bound. Conclusion: In the extracorporeally perfused mammalian heart, FTHA EF declined during suppression of beta-oxidation with lactate infusion and alteration in perfusion without change in fatty acid oxidation rate. The linear relationship of FTHA EF with fractional water production from tritiated palmitate further confirms a correlation of the uptake of FTHA with fatty acid beta-oxidation rate and supports the utility of FTHA in the non invasive determination of fatty acid oxidation rate. Furthermore, the trapped nature of the tracer may allow the use of graphical analysis for the quantification of beta-oxidation rates.

Key Words: fatty acid tracer • 14-fluorine-18-fluoro-6-thia-heptade-canoic acid • myocardial metabolism • fatty acid metabolism • fatty acids

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