Volume 8, Number 4, 237-244, DOI: 10.1007/s11307-006-0042-7

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The Effect of Insulin on the Intracellular Distribution of 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic Acid in Rats

Xiuli Ci, Frédérique Frisch, François Lavoie, Pascale Germain, Roger Lecomte, Johan E. van Lier, François Bénard and André C. Carpentier

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Abstract

Purpose  

The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA).

Procedures  

Mitochondrial retention and intracellular lipid incorporation of [18F]FTHA were compared to that of [14C]-2-bromopalmitate or [14C]palmitate during hyperinsulinemic clamp vs. saline infusion in male Wistar rats.

Results  

Mitochondrial 18F activity was increased in the heart (1.7 ± 0.4 vs. 0.5 ± 0.1% ID/g, P < 0.05), whereas it was reduced in the liver (1.1 ± 0.3 vs. 1.8 ± 0.4% ID/g, P < 0.05) during insulin vs. saline infusion, respectively. Mitochondrial [14C]-2-bromopalmitate activity was affected by insulin in a similar way in both tissues. The fractional esterification of [18F]FTHA into triglycerides was impaired compared to [14C]palmitate in both tissues, and [18F]FTHA was insensitive to the shift of esterification of fatty acids into complex lipids in response to insulin.

Conclusions  

[18F]FTHA is sensitive to insulin-induced modifications of free fatty acid oxidative metabolism in rats but is insensitive to changes in nonoxidative fatty acid metabolism.

Key words  PET tracer - Small animal - Pharmacokinetic - 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid - Biodistribution - Lipid metabolism - Free fatty acid

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