4.6 Article

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

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00004.2008

Keywords

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

Funding

  1. NIDDK NIH HHS [1 R01 DK-074419-01, R01 DK074419] Funding Source: Medline

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Metabolism of galactose is a specialized liver function. The purpose of this PET study was to use the galactose analog 2-[F-18] 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 (CO)-O-15 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, K-FDGal,K- was 332 - 481 ml blood . min(-1) .l(-1) tissue in experiments with approximately firstorder 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 mu mol . 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 ( K dual FDGal) or the single arterial input ( K arterial FDGal). 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.

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