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

Abstract

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 Lumped Constant for the Galactose Analog 2-18F-Fluoro-2-Deoxy-d-Galactose Is Increased in Patients with Parenchymal Liver Disease

“…K Ã 2gal accordingly reflects V Ã max and thus provides a measurement of the hepatic galactokinase capacity for 18 F-FDGal without the need for correction by the LC. In accordance, K Ã 2gal was significantly lower in patients with cirrhosis than in healthy subjects (3,7). These kinetic features also mean that if the same patient is followed over time, any observed changes in K The present results demonstrated the importance of applying the correct LC in PET studies in which a tracee is present in significant concentrations compared with the tracer.…”

“…In contrast, the hepatic systemic clearance of 18 F-FDGal is enzyme-determined in both patients with cirrhosis and healthy subjects (3,7). The measured hepatic systemic clearance of 18 (3,7). Since K m for galactose was similar in healthy subjects and patients with cirrhosis (Table 1), it is unlikely that K Ã m should differ between the 2 groups of subjects.…”

“…When galactose is used for measurements of hepatic metabolic function, a relatively high blood concentration of galactose is accordingly required to achieve a nearsaturated hepatic removal rate of galactose to avoid the influence of possible changes in hepatic blood flow on the estimate. In contrast, the hepatic systemic clearance of 18 F-FDGal is enzyme-determined in both patients with cirrhosis and healthy subjects (3,7). The measured hepatic systemic clearance of 18 (3,7).…”

“…The hepatic systemic clearance of 18 F-FDGal per volume of liver tissue (K Ã 1gal ; L blood/min/L of liver tissue) was calculated as the asymptote fitted to Gjedde-Patlak (15,16) representation of time-activity curve blood and time-activity curve liver using data from 6 to 20 min after the 18 F-FDGal administration (quasi-steady-state metabolism) (3,7,17).…”

How Should Lumped Constant Be Estimated for Hepatic 18F-FDG Glucose in Humans?

“…When combined with tracer studies using the galactose analog 2-18 F-fluoro-2-deoxy-D-galactose ( 18 F-FDGal) and calculation of values of -F ln(1 -E Ã 18F 2 FDGal ) from blood measurements, LC values for hepatic 18 F-FDGal-galactose were estimated; in normal pigs they were on average 0.14 (12), in healthy human subjects 0.13 (13), and in patients with cirrhosis 0.24 (14). Moreover, mean net hepatic metabolic clearance K Ã PET for 18 F-FDGal was lower in cirrhosis and with larger intrahepatic heterogeneity than in normal livers (15). This raises the question of whether LC for 18 F-FDG glucose in cirrhosis is different from that in normal liver, and with larger intrahepatic heterogeneity.…”