Nikolaj Worm Ørntoft

Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

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The aim was to develop a method for quantification of hepatobiliary uptake and secretion of conjugated bile acids using PET and the (11)C-labeled conjugated bile acid analog [N-methyl-(11)C]cholylsarcosine ((11)C-CSar).

METHODS: Six pigs (13 experiments) underwent dynamic (11)C-CSar PET of the liver with measurements of hepatic blood perfusion and (11)C-CSar concentrations in arterial, portal and hepatic venous blood. In three pigs (seven experiments) bile was collected from a catheter in the common hepatic duct (CHD). PET data were analyzed by a two-tissue compartmental model with calculation of rate constants for transport of (11)C-CSar between blood, hepatocytes and intra- and extra-hepatic bile ducts. PET results were validated against invasive blood and bile measurements.

RESULTS: Directly measured secretion rate of (11)C-CSar into bile was equal to removal rate from blood at steady state. Hepatocytes accordingly did not accumulate bile acids but simply facilitated transport of bile acids from blood into bile against a measured concentration gradient of 4,000 from blood to bile. In experiments with catheter in CHD, rate constant for secretion of (11)C-CSar from hepatocytes into bile was 25% of that in experiments without a catheter (P < 0.05) which we interpreted as mild cholestasis caused by the catheter. The catheter caused an increased backflux of (11)C-CSar from hepatocytes to blood and hepatic blood flow was 25% higher than in experiment without catheter. The capacity of the overall transport of (11)C-CSar from blood into bile, as quantified by intrinsic clearance, was significantly lower in experiments with catheter than in pigs without catheter (P < 0.001). PET and blood measurements correlated significantly (P < 0.05).

CONCLUSION: In vivo kinetics of hepatobiliary secretion of conjugated bile acids can now be determined by dynamic (11)C-CSar PET.

OriginalsprogEngelsk
TidsskriftThe Journal of Nuclear Medicine
Vol/bind57
Nummer6
Sider (fra-til)961-966
ISSN0161-5505
DOI
StatusUdgivet - jun. 2016

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