MYOCARDIAL UPTAKE OF THE FATTY-ACID ANALOG 14-FLUORINE-18-FLUORO-6-THIA-HEPTADECANOIC ACID IN COMPARISON TO BETA-OXIDATION RATES BY TRITIATED PALMITATE

The fatty acid tracer 14-F-18-fluoro-6-thia-heptadecanoic acid (FTHA) is a metabolically trapped tracer of exogenous fatty acid utilization. The objectives of this study were to determine the relationship of FT HA uptake to changes in perfusion and fatty acid oxidation and to conf irm the retention of FTHA in the mammalian heart. Methods: Six pigs wi th extracorporeal perfusion of the left anterior descending artery (LA D) and cannulation of the LAD vein were studied. The extraction fracti on (EF) of FTHA, measured from LAD arterial and venous blood samples, was compared to beta-oxidation rates, determined by water production f rom tritiated palmitate. After a baseline period, changes in FTHA EF w ere measured in 15-min periods of hyperemia, control (baseline Row rat e) and lactate infusion. After the lactate infusion, FTHA infusion was terminated, and a 15-min washout period was observed. Results: Beta-o xidation rate was unchanged from the baseline period during the hypere mic and control periods. With lactate infusion, the expected myocardia l preference for lactate was noted, with a decline in exogenous fatty acid oxidation. Fluorine-18-FTHA EF paralleled the changes in beta-oxi dation, with a decrease in EF during lactate infusion. Increase in per fusion was associated with a decrease in FTHA EF, compared to control, such that the product of flow and extraction 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 sa mples suggested that the majority of tissue radioactivity was protein- bound. Conclusion: In the extracorporeally perfused mammalian heart, F THA EF declined during suppression of beta-oxidation with lactate infu sion and alteration in perfusion without change in fatty acid oxidatio n rate. The linear relationship of FTHA EF with fractional water produ ction from tritiated palmitate further confirms a correlation of the u ptake of FTHA with fatty acid beta-oxidation rate and supports the uti lity of FTHA in the noninvasive 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.