Determinants of [¹³N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model

Abstract.

The aim of this study was the development of a modelling approach for the analysis of the systemic kinetics of the tracer nitrogen-13 ammonia administered for dynamic liver scanning. The radioactive half-life of this tracer is 9.8 min, which limits the time span in which data are available in a positron emission tomography experimental setting. A circulatory pharmacokinetic model was applied to the metabolism of ammonia in anaesthetised pigs, which incorporated data from serial measurements of [¹³N]ammonia and [¹³N]metabolite activity in arterial and portal venous blood together with blood flow rates through the portal vein and through the hepatic artery obtained over 20 min after intravenous injection of [¹³N]ammonia. Model analysis showed that up to 20 min after injection the time course of [¹³N]ammonia concentration in arterial blood is primarily determined by distribution kinetics (steady-state volume of distribution 1,856±531 ml kg^–1). Simultaneous fitting of arterial ammonia and metabolite blood concentrations allowed for estimation of the hepatic [¹³N]ammonia clearance (10.25±1.84 ml min^–1 kg^–1), which accounted for the formation of the circulating metabolites.