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 2-18F-fluoro-2-deoxy-D-galactose ( 18F-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 18F-FDGal was 0.13 in healthy subjects. The aim of the present study was to test the hypothesis of a significantly different LC for 18F-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 (VV/max=K/m). The present study determined the hepatic removal kinetics of galactose, including hepatic intrinsic clearance of galactose (Vmax/Km) 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)/(Vmax/K m). On a second day, a dynamic 18F-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+ 1gal) from linear analysis of data (Gjedde-Patlak method). The maximum hepatic removal rate of galactose was estimated from 18F-FDGal PET data (VPETmax) using the estimated LC. Results: The mean hepatic Vmax of galactose was 1.18 mmol/min, the mean Km was 0.91 mmol/L of blood, and the mean Vmax/K m was 1.18 L of blood/min. When compared with values from healthy subjects, Km did not differ (P 5 0.77), whereas both Vmax and Vmax/Km were significantly lower in patients (both P , 0.01). Mean LC for 18F-FDGal was 0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects (P , 0.0001). Mean K+ 1gal 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 VPETmax 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. © 2014 SNMMI; all rights reserved.