title: The lumped constant for the galactose analog 2-18F-fluoro-2-deoxy-D-galactose is increased in patients with parenchymal liver disease.
abstract: The galactose analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) is a suitable PET tracer for measuring hepatic galactokinase capacity in vivo, which provides estimates of hepatic metabolic function. As a result of a higher affinity of galactokinase toward galactose, the lumped constant (LC) for (18)F-FDGal was 0.13 in healthy subjects. The aim of the present study was to test the hypothesis of a significantly different LC for (18)F-FDGal in patients with parenchymal liver disease.
  
  
  METHODS
  Nine patients with liver cirrhosis were studied in connection with a previous study with determination of hepatic intrinsic clearance of ¹⁸F-FDGal (V*(max/K*(m)). The present study determined the hepatic removal kinetics of galactose, including hepatic intrinsic clearance of galactose (V(max)/K(m)) from measurements of hepatic blood flow and arterial and liver vein blood galactose concentrations at increasing galactose infusions. LC for ¹⁸F-FDGal was calculated as (V*(max)/K*(m))/(V(max)/K(m)). On a second day, a dynamic ¹⁸-FDGal PET study with simultaneous infusion of galactose (mean arterial galactose concentration, 6.1 mmol/L of blood) and blood samples from a radial artery was performed, with determination of hepatic systemic clearance of ¹⁸F-FDGal (K*(+gal) from linear analysis of data (Gjedde-Patlak method). The maximum hepatic removal rate of galactose was estimated from ¹⁸F-FDGal PET data (V(max)(PET)) using the estimated LC.
  
  
  RESULTS
  The mean hepatic V(max) of galactose was 1.18 mmol/min, the mean K(m) was 0.91 mmol/L of blood and the mean V(max)/K(m) was 1.18 L of blood/min. When compared with values of healthy subjects, K(m) did not differ (P = 0.77), whereas both V(max) and V(max)/K(m) were significantly lower in patients (both P < 0.01). Mean LC for ¹⁸LF-FDGal was 0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects (P < 0.0001). Mean K*(+gal) determined from the PET study was 0.019 L of blood/min/L of liver tissue, which was not significantly different from that in healthy subjects (P = 0.85). Mean hepatic V(max)(PET) was 0.57 mmol/min/L of liver tissue, which was significantly lower than the value in healthy subjects (1.41 mmol/min/L of liver tissue (P < 0.0001).
  
  
  CONCLUSIONS
  Disease may change the LC for a pet tracer, and this study demonstrated the importance of using the correct LC.
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kasper S
authors.initials: KS
authors.lastname: Mikkelsen
authors.forename: Michael
authors.initials: M
authors.lastname: Sørensen
authors.forename: Kim
authors.initials: K
authors.lastname: Frisch
authors.forename: Gerda E
authors.initials: GE
authors.lastname: Villadsen
authors.forename: Bo M
authors.initials: BM
authors.lastname: Bibby
authors.forename: Susanne
authors.initials: S
authors.lastname: Keiding
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D003627:Data Interpretation, Statistical; D005260:Female; D005643:Fucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005690:Galactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D016014:Linear Models; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000000981:diagnostic imaging / Q000378:metabolism; D008107:Liver Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014680:Veins / Q000378:metabolism
chemical_list: D019275:Radiopharmaceuticals; D005643:Fucose; C049289:2-deoxy-2-fluorogalactose; D005690:Galactose
keywords: cirrhosis; clearance; hepatic removal kinetics; liver function; positron emission tomography