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Am J Physiol Gastrointest Liver Physiol 295: G27-G36, 2008. First published May 15, 2008; doi:10.1152/ajpgi.00004.2008
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LIVER AND BILIARY TRACT

Hepatic uptake and metabolism of galactose can be quantified in vivo by 2-[18F]fluoro-2-deoxygalactose positron emission tomography

Michael Sørensen,1,2 Ole Lajord Munk,1 Frank Viborg Mortensen,3 Aage Kristian Olsen,1 Dirk Bender,1 Ludvik Bass,4 and Susanne Keiding1,2

1PET Center, 2Department of Medicine V, and 3Department of Surgery L, Aarhus University Hospital, Aarhus, Denmark; and 4Department of Mathematics, University of Queensland, Brisbane, Australia

Submitted 3 January 2008 ; accepted in final form 14 May 2008

Metabolism of galactose is a specialized liver function. The purpose of this PET study was to use the galactose analog 2-[18F]fluoro-2-deoxygalactose (FDGal) to investigate hepatic uptake and metabolism of galactose in vivo. FDGal kinetics was studied in 10 anesthetized pigs at blood concentrations of nonradioactive galactose yielding approximately first-order kinetics (tracer only; n = 4), intermediate kinetics (0.5–0.6 mmol galactose/l blood; n = 2), and near-saturation kinetics (>3 mmol galactose/l blood; n = 4). All animals underwent liver C15O PET (blood volume) and FDGal PET (galactose kinetics) with arterial and portal venous blood sampling. Flow rates in the hepatic artery and the portal vein were measured by ultrasound transit-time flowmeters. The hepatic uptake and net metabolic clearance of FDGal were quantified by nonlinear and linear regression analyses. The initial extraction fraction of FDGal from blood-to-hepatocyte was unity in all pigs. Hepatic net metabolic clearance of FDGal, KFDGal, was 332–481 ml blood·min–1·l–1 tissue in experiments with approximately first-order kinetics and 15.2–21.8 ml blood·min–1·l–1 tissue in experiments with near-saturation kinetics. Maximal hepatic removal rates of galactose were on average 600 µmol·min–1·l–1 tissue (range 412–702), which was in agreement with other studies. There was no significant difference between KFDGal calculated with use of the dual tracer input (KdualFDGal) or the single arterial input (KarterialFDGal). In conclusion, hepatic galactose kinetics can be quantified with the galactose analog FDGal. At near-saturated kinetics, the maximal hepatic removal rate of galactose can be calculated from the net metabolic clearance of FDGal and the blood concentration of galactose.

liver physiology; Michaelis-Menten kinetics; liver function; clearance; galactokinase



Address for reprint requests and other correspondence: M. Sørensen, PET Center, Aarhus Univ. Hospital, DK-8000 Aarhus, Denmark (e-mail: michael{at}pet.auh.dk)







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