Hepatobiliary transport kinetics of the conjugated bile acid tracer (11)C-CSar quantified in healthy humans and patients by Positrion Emission Tomography (PET).

Ørntoft NW, Munk OL, Frisch K et al.

Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.

Journal of hepatology. Feb 2017.

Hepatobiliary secretion of bile acids is an important liver function. Here, we quantified the hepatic transport kinetics of conjugated bile acids using the bile acid tracer [N-methyl-(11)C]cholylsarcosine ((11)C-CSar) and PET.Nine healthy subjects and eight patients with varying degrees of cholestasis were examined with (11)C-CSar PET and measurement of arterial and hepatic venous blood concentrations of (11)C-CSar.Results are presented as median (range). The hepatic intrinsic clearance was 1.50 (1.20-1.76) mL blood/min/mL liver tissue in healthy subjects and 0.46 (0.13-0.91) in patients. In healthy subjects, the rate constant for secretion of (11)C-CSar from hepatocytes to bile was 0.36 (0.30-0.62) min(-1), 20 times higher than the rate constant for backflux from hepatocytes to blood (0.02, 0.005-0.07 min(-1)). In the patients, rate constant for transport from hepatocyte to bile was reduced to 0.12 (0.001-0.27) min(-1), 2.3 times higher than the rate constant for backflux to blood (0.05, 0.04-0.09). The increased backflux did not fully normalize exposure of the hepatocyte to bile acids as mean hepatocyte residence time of (11)C-CSar was 2.5 (1.6-3.1) min in healthy subjects and 6.4 (3.1-23.7) min in patients. The rate constant for transport of (11)C-CSar from intrahepatic to extrahepatic bile was 0.057 (0.023-0.11) min(-1) in healthy subjects and only slightly reduced in patients 0.039 (0.017-0.066).This first in vivo quantification of individual steps involved in the hepatobiliary secretion of a conjugated bile acid in humans provided new insight into cholestatic disease.Positron emission tomography (PET) using the radiolabelled bile acid ((11)C-CSar) enabled quantification of the individual steps of the hepatic transport of bile acids from blood to bile in man. Cholestasis reduced uptake and secretion and increased backflux to blood. These findings improve our understanding of cholestatic liver diseases and may support therapeutic decisions.

Pubmed

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