Weiss Michael, Roelsgaard Klaus, Bender Dirk, Keiding Susanne
Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany.
Eur J Nucl Med Mol Imaging. 2002 Dec;29(12):1648-56. doi: 10.1007/s00259-002-0970-7. Epub 2002 Sep 24.
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 [(13)N]ammonia and [(13)N]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 [(13)N]ammonia. Model analysis showed that up to 20 min after injection the time course of [(13)N]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 [(13)N]ammonia clearance (10.25+/-1.84 ml min(-1) kg(-1)), which accounted for the formation of the circulating metabolites.
本研究的目的是开发一种建模方法，用于分析动态肝脏扫描中施用的示踪剂氮-13氨的全身动力学。该示踪剂的放射性半衰期为9.8分钟，这限制了在正电子发射断层扫描实验设置中可获得数据的时间跨度。将循环药代动力学模型应用于麻醉猪体内氨的代谢，该模型纳入了静脉注射[(13)N]氨后20分钟内动脉血和门静脉血中[(13)N]氨和[(13)N]代谢物活性的系列测量数据，以及通过门静脉和肝动脉的血流速率。模型分析表明，注射后长达20分钟，动脉血中[(13)N]氨浓度的时间进程主要由分布动力学决定（稳态分布容积为1,856±531 ml kg(-1)）。同时拟合动脉氨和代谢物血浓度可估算肝脏[(13)N]氨清除率（10.25±1.84 ml min(-1) kg(-1)），这解释了循环代谢物的形成。
