Hepatic Galactose Metabolism Quantified in Humans Using 2-18F-Fluoro-2-Deoxy-d-Galactose PET/CT

Abstract

Accurate quantification of regional liver function is needed, and PET of specific hepatic metabolic pathways offers a unique method for this purpose. Here, we quantify hepatic galactose elimination in humans using PET and the galactose analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) as the PET tracer. Eight healthy human subjects underwent (18)F-FDGal PET/CT of the liver with and without a simultaneous infusion of galactose. Hepatic systemic clearance of (18)F-FDGal was determined from linear representation of the PET data. Hepatic galactose removal kinetics were determined using measurements of hepatic blood flow and arterial and liver vein galactose concentrations at increasing galactose infusions. The hepatic removal kinetics of (18)F-FDGal and galactose and the lumped constant (LC) were determined. The mean hepatic systemic clearance of (18)F-FDGal was significantly higher in the absence than in the presence of galactose (0.274 ± 0.001 vs. 0.019 ± 0.001 L blood/min/L liver tissue; P < 0.01), showing competitive substrate inhibition of galactokinase. The LC was 0.13 ± 0.01, and the (18)F-FDGal PET with galactose infusion provided an accurate measure of the local maximum removal rate of galactose (V(max)) in liver tissue compared with the V(max) estimated from arterio-liver venous (A-V) differences (1.41 ± 0.24 vs. 1.76 ± 0.08 mmol/min/L liver tissue; P = 0.60). The first-order hepatic systemic clearance of (18)F-FDGal was enzyme-determined and can thus be used as an indirect estimate of galactokinase capacity without the need for galactose infusion or knowledge of the LC. (18)F-FDGal PET/CT provides an accurate in vivo measurement of human galactose metabolism, which enables the quantification of regional hepatic metabolic function.