title: Biodistribution of the fatty acid analogue 18F-FTHA: plasma and tissue partitioning between lipid pools during fasting and hyperinsulinemia.
abstract: 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)-(18)F-fluoro-6-thia-heptadecanoic acid ((18)F-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 (18)F-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 (18)F-FTHA ratio was high in all tissues, with the highest values being in the heart and liver; (18)F-FTHA accumulated in the brain to a significant extent. Hyperinsulinemia was associated with higher plasma (18)F-FTHA clearance (P < 0.05) and lower labeled triglyceride appearance (P <or= 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.
  
  
  CONCLUSIONS
  (18)F-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.
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Letizia
authors.initials: L
authors.lastname: Guiducci
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Järvisalo
authors.forename: Jan
authors.initials: J
authors.lastname: Kiss
authors.forename: Antti
authors.initials: A
authors.lastname: Viljanen
authors.forename: Alexandru G
authors.initials: AG
authors.lastname: Naum
authors.forename: Tapio
authors.initials: T
authors.lastname: Viljanen
authors.forename: Timo
authors.initials: T
authors.lastname: Savunen
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Piero A
authors.initials: PA
authors.lastname: Salvadori
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
mesh_terms: D000818:Animals; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D006946:Hyperinsulinism / Q000378:metabolism*; D050356:Lipid Metabolism; D013552:Swine; D014018:Tissue Distribution
chemical_list: D005227:Fatty Acids; D005462:Fluorine Radioisotopes; C071178:14-fluoro-6-thiaheptadecanoic acid