The Lumped Constant for the Galactose Analog 2-18F-Fluoro-2-Deoxy-D-Galactose Is Increased in Patients with Parenchymal Liver Disease
K. S. Mikkelsen, M. Sorensen, K. Frisch, G. E. Villadsen, B. M. Bibby, S. Keiding
Journal of Nuclear Medicine
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:
... ne patients with liver cirrhosis were studied in connection with a previous study with determination of hepatic intrinsic clearance of 18 F-FDGal (V Ã max =K Ã 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 18 F-FDGal was calculated as (V Ã max =K Ã m )/(V max /K m ). On a second day, a dynamic 18 F-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 18 F-FDGal (K Ã 1gal ) from linear analysis of data (Gjedde-Patlak method). The maximum hepatic removal rate of galactose was estimated from 18 F-FDGal PET data (V PET max ) 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 from healthy subjects, K m did not differ (P 5 0.77), whereas both V max and V max /K m were significantly lower in patients (both P , 0.01). Mean LC for 18 F-FDGal was 0.24, which was significantly higher than the mean LC of 0.13 in healthy subjects (P , 0.0001). Mean K Ã 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 5 0.85). Mean hepatic V PET max 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.