Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate

Charles K. Stone, Robert A. Pooley, Timothy R DeGrado, Britta Renstrom, Robert J. Nickles, Stephen H. Nellis, A. James Liedtke, James E. Holden

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The fatty acid tracer 14-18F-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 FTHA uptake to changes in perfusion and fatty acid oxidation and to confirm 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 betaoxidation 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 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 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 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.

Original languageEnglish (US)
Pages (from-to)1690-1696
Number of pages7
JournalJournal of Nuclear Medicine
Volume39
Issue number10
StatePublished - Oct 1998
Externally publishedYes

Fingerprint

Fluorine
Palmitates
Fatty Acids
Lactic Acid
Perfusion
Arteries
margaric acid
Water
Hyperemia
Catheterization
Radioactivity
Veins
Swine

Keywords

  • 14-fluorine-18-fluoro-6-thia-heptadecanoic acid
  • Fatty acid metabolism
  • Fatty acid tracer
  • Fatty acids
  • Myocardial metabolism

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate. / Stone, Charles K.; Pooley, Robert A.; DeGrado, Timothy R; Renstrom, Britta; Nickles, Robert J.; Nellis, Stephen H.; Liedtke, A. James; Holden, James E.

In: Journal of Nuclear Medicine, Vol. 39, No. 10, 10.1998, p. 1690-1696.

Research output: Contribution to journalArticle

Stone, CK, Pooley, RA, DeGrado, TR, Renstrom, B, Nickles, RJ, Nellis, SH, Liedtke, AJ & Holden, JE 1998, 'Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate', Journal of Nuclear Medicine, vol. 39, no. 10, pp. 1690-1696.
Stone, Charles K. ; Pooley, Robert A. ; DeGrado, Timothy R ; Renstrom, Britta ; Nickles, Robert J. ; Nellis, Stephen H. ; Liedtke, A. James ; Holden, James E. / Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate. In: Journal of Nuclear Medicine. 1998 ; Vol. 39, No. 10. pp. 1690-1696.
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title = "Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate",
abstract = "The fatty acid tracer 14-18F-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 FTHA uptake to changes in perfusion and fatty acid oxidation and to confirm 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 betaoxidation 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 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 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 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.",
keywords = "14-fluorine-18-fluoro-6-thia-heptadecanoic acid, Fatty acid metabolism, Fatty acid tracer, Fatty acids, Myocardial metabolism",
author = "Stone, {Charles K.} and Pooley, {Robert A.} and DeGrado, {Timothy R} and Britta Renstrom and Nickles, {Robert J.} and Nellis, {Stephen H.} and Liedtke, {A. James} and Holden, {James E.}",
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T1 - Myocardial uptake of the fatty acid analog 14-fluorine-18-fluoro-6- thia-heptadecanoic acid in comparison to beta-oxidation rates by tritiated palmitate

AU - Stone, Charles K.

AU - Pooley, Robert A.

AU - DeGrado, Timothy R

AU - Renstrom, Britta

AU - Nickles, Robert J.

AU - Nellis, Stephen H.

AU - Liedtke, A. James

AU - Holden, James E.

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N2 - The fatty acid tracer 14-18F-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 FTHA uptake to changes in perfusion and fatty acid oxidation and to confirm 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 betaoxidation 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 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 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 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.

AB - The fatty acid tracer 14-18F-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 FTHA uptake to changes in perfusion and fatty acid oxidation and to confirm 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 betaoxidation 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 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 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 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.

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KW - Fatty acid tracer

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