Regional metabolic liver function measured in patients with cirrhosis by 2-[18F]fluoro-2-deoxy-d-galactose PET/CT

• Published in: Journal of hepatology Vol. 58; no. 6; pp. 1119 - 1124
• Main Authors: Sørensen, Michael, Mikkelsen, Kasper S., Frisch, Kim, Villadsen, Gerda E., Keiding, Susanne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2013
• Subjects: Adult; Aged; Clearance; Female; Fluorine Radioisotopes; Fucose - analogs & derivatives; Galactokinase - metabolism; Galactose; Gastroenterology and Hepatology; Humans; Liver - metabolism; Liver Circulation; Liver Cirrhosis - metabolism; Male; Middle Aged; Molecular imaging; Positron emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals; Tomography, X-Ray Computed - methods; Molecular imaging; Clearance; Galactose; Liver metabolism; Positron emission tomography
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2013.01.012

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick’s principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mLblood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157mLblood/mL liver tissue/min, which was lower than 0.274mLblood/mL liver tissue/min, previously found in healthy subjects (p<0.001), in accordance with decreased metabolic function in cirrhotic livers. Mean CoV for Kmet in liver tissue was 24.4% in patients and 14.4% in healthy subjects (p<0.0001). The degree of intrahepatic metabolic heterogeneity correlated positively with HVPG (p<0.05). A 20-min dynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring.