The lumped constant for the galactose analog 2-18F-fluoro-2-deoxy-D-galactose is increased in patients with parenchymal liver disease

J Nucl Med. 2014 Apr;55(4):590-4. doi: 10.2967/jnumed.113.125559. Epub 2014 Mar 3.

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).

Conclusion: Disease may change the LC for a pet tracer, and this study demonstrated the importance of using the correct LC.

Keywords: cirrhosis; clearance; hepatic removal kinetics; liver function; positron emission tomography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Data Interpretation, Statistical
  • Female
  • Fucose / analogs & derivatives*
  • Fucose / pharmacokinetics
  • Galactose / analogs & derivatives*
  • Galactose / pharmacokinetics
  • Humans
  • Linear Models
  • Liver Circulation
  • Liver Cirrhosis / diagnostic imaging
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis, Alcoholic / diagnostic imaging
  • Liver Cirrhosis, Alcoholic / metabolism
  • Liver Diseases / diagnostic imaging*
  • Liver Diseases / metabolism
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacokinetics*
  • Veins / metabolism

Substances

  • Radiopharmaceuticals
  • Fucose
  • 2-deoxy-2-fluorogalactose
  • Galactose