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Biodistribution of the Fatty Acid Analogue ¹⁸F-FTHA: Plasma and Tissue Partitioning Between Lipid Pools During Fasting and Hyperinsulinemia

¹ Turku PET Centre, University of Turku, Turku, Finland; ² Medical Sciences Branch, SSSUP, Pisa, Italy; ³ PET Centre, Institute of Clinical Physiology, CNR National Research Council, Pisa, Italy; ⁴ Department of Surgery, University of Turku, Turku, Finland; ⁵ Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy; and ⁶ Department of Medicine, University of Turku, Turku, Finland

Correspondence: For correspondence or reprints contact: Patricia Iozzo, MD, PhD, Turku PET Centre, P.O. Box 52, University of Turku, Turku, Finland. E-mail: patricia.iozzo{at}ifc.cnr.it

Alterations of free fatty acid (FA) metabolism in several organs are implicated in the pathogenesis of chronic disorders. The aim of this study was to investigate the biodistribution and partitioning of the FA analog, 14(R,S)-¹⁸F-fluoro-6-thia-heptadecanoic acid (¹⁸F-FTHA), across different lipid pools in plasma and in metabolically important organs and its response to insulin. Methods: Eight anesthetized pigs were studied during fasting or euglycemic insulin stimulation. Plasma samples from the carotid artery, hepatic vein, and portal vein were collected at 10 and 40 min after ¹⁸F-FTHA injection via indwelling catheters. The animals were then sacrificed and tissue biopsies rapidly obtained from the heart, brain, liver, subcutaneous and visceral fat, pancreas, intestine, and skeletal muscle. Radioactivity was assessed in the FA, phospholipid, and triglyceride or glycerol ester pools. Results: The tissue-to-plasma intact ¹⁸F-FTHA ratio was high in all tissues, with the highest values being in the heart and liver; ¹⁸F-FTHA accumulated in the brain to a significant extent. Hyperinsulinemia was associated with higher plasma ¹⁸F-FTHA clearance (P < 0.05) and lower labeled triglyceride appearance (P 0.01) than those associated with fasting, indicating faster tissue removal and suppressed hepatic triglyceride release. Tracer retention was enhanced in skeletal muscle, pancreas, and visceral fat (P < 0.05 vs. fasting). Under both study conditions, tissue radioactivity was greatly accounted for by glycerol ester. Conclusion: ¹⁸F-FTHA is a promising tracer in PET imaging of metabolically important organs, which are currently inaccessible in vivo. Physiologic hyperinsulinemia enhances plasma tracer clearance in fat, skeletal muscle, and pancreas.

Key Words: ¹⁸F-FTHA • insulin • fatty acid metabolism • brain • PET

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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