PT - JOURNAL ARTICLE AU - Michael Sørensen AU - Ole Lajord Munk AU - Nikolaj W. Ørntoft AU - Kim Frisch AU - Kasper Jarlhelt Andersen AU - Frank Viborg Mortensen AU - Aage Kristian Olsen Alstrup AU - Peter Ott AU - Alan F. Hofmann AU - Susanne Keiding TI - Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by <sup>11</sup>C-Cholylsarcosine PET AID - 10.2967/jnumed.115.171579 DP - 2016 Jun 01 TA - Journal of Nuclear Medicine PG - 961--966 VI - 57 IP - 6 4099 - http://jnm.snmjournals.org/content/57/6/961.short 4100 - http://jnm.snmjournals.org/content/57/6/961.full SO - J Nucl Med2016 Jun 01; 57 AB - The aim of this study was to develop a method for the quantification of hepatobiliary uptake and secretion of conjugated bile acids with PET and the 11C-labeled conjugated bile acid analog [N-methyl-11C]cholylsarcosine (11C-CSar). Methods: Six pigs (13 experiments) underwent dynamic 11C-CSar PET of the liver with simultaneous measurements of hepatic blood perfusion and 11C-CSar concentrations in arterial, portal, and hepatic venous blood. In 3 pigs (7 experiments), bile was collected from a catheter in the common hepatic duct. PET data were analyzed with a 2-tissue compartmental model with calculation of rate constants for the transport of 11C-CSar among blood, hepatocytes, and intra- and extrahepatic bile ducts. PET results were validated against invasive blood and bile measurements. Results: The directly measured rate of secretion of 11C-CSar into bile was equal to the rate of removal from blood at steady state. Accordingly, hepatocytes did not accumulate bile acids but simply facilitated the transport of bile acids from blood to bile against a measured concentration gradient of 4,000. The rate constant for the secretion of 11C-CSar from hepatocytes into bile in experiments with a catheter in the common hepatic duct was 25% of that in experiments without a catheter (P &lt; 0.05); we interpreted this result to be mild cholestasis caused by the catheter. The catheter caused an increased backflux of 11C-CSar from hepatocytes to blood, and hepatic blood flow was 25% higher than in experiments without the catheter. The capacity for the overall transport of 11C-CSar from blood to bile, as quantified by intrinsic clearance, was significantly lower in experiments with the catheter than in those without the catheter (P &lt; 0.001). PET and blood measurements correlated significantly (P &lt; 0.05). Conclusion: The in vivo kinetics of hepatobiliary secretion of conjugated bile acids can now be determined by dynamic 11C-CSar PET.