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 2-18F-fluoro-2-deoxy-d-galactose (18F-FDGal) as the PET tracer. Methods Eight healthy human subjects underwent 18F-FDGal PET/CT of the liver with and without a simultaneous infusion of galactose. Hepatic systemic clearance of 18F-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 18F-FDGal and galactose and the lumped constant (LC) were determined. Results The mean hepatic systemic clearance of 18F-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 18F-FDGal PET with galactose infusion provided an accurate measure of the local maximum removal rate of galactose (Vmax) in liver tissue compared with the Vmax 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 18F-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. Conclusion 18F-FDGal PET/CT provides an accurate in vivo measurement of human galactose metabolism, which enables the quantification of regional hepatic metabolic function.

Background & Aims There is a clinical need for methods that can quantify regional hepatic function noninvasively 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 for this purpose and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Methods Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick’s principle. From blood measurements, hepatic systemic clearance (Ksyst, l blood/min) and hepatic intrinsic clearance (Vmax/Km, l blood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, ml blood/ml liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient of variation (CoV, %) using parametric images of Kmet. Results 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 0.157 ml blood/ml liver tissue/min, which was lower than 0.274 ml blood/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). Conclusions 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 assessment of patients with liver disease as well as treatment planning and monitoring.

The high prevalence of dizziness, tinnitus and taste disturbances reported by cochlear implant recipients necessitates that assessment of symptoms related to inner ear and chorda tympani damage are included when evaluating operative results.

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: Nine 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. 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. PET is an excellent noninvasive tool for in vivo studies of metabolic processes. The PET tracers used may be natural substrates radiolabeled with positron-emitting isotopes such as 11 C. However, analogs of natural substrates are commonly used, a well-known example being the glucose analog 18 F-FDG used for studies of glucose metabolism. Using an analog tracer is advantageous when its metabolism is simpler, such as the metabolism of 18 F-FDG, which, unlike that of glucose, essentially stops after 6-phosphorylation. Fewer kinetic parameters are thus required in the kinetic model fitted to the dynamic PET data. An important disadvantage of using an analog tracer is that it may differ from the natural substrate in its affin...

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