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 (). The present study determined the hepatic removal kinetics of galactose, including hepatic intrinsic clearance of galactose () 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 ()/(). 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 () from linear analysis of data (Gjedde–Patlak method). The maximum hepatic removal rate of galactose was estimated from ¹⁸F-FDGal PET data () using the estimated LC. Results: The mean hepatic of galactose was 1.18 mmol/min, the mean was 0.91 mmol/L of blood, and the mean was 1.18 L of blood/min. When compared with values from healthy subjects, did not differ (P = 0.77), whereas both and / 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 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 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.