Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents

Hepatobiliary imaging, introduced first in late 1950s with iodine 131 rose bengal, has undergone major changes since the introduction of technetium 99m-labeled agents in the late 1970s. 99mTc-labeled iminodiacetic acid (IDA) agents, with their high hepatic uptake and fast biliary excretion, provide superior image resolution in addition to supplying simultaneous physiologic parameters quantitatively. The measurement of hepatic extraction fraction by deconvolutional analysis aids in separating hepatocyte from biliary disease. Excretion half-time calculation by nonlinear least square fit provides a quantitative method of analyzing hepatobiliary function and correlates directly with the severity of disease. The measurement of gallbladder ejection fraction, ejection rate, and common bile duct bile reflux index following cholecystokinin, enables quantification of the degree of obstruction to bile flow through the common bile duct. The combined application of morphologic and physiologic parameters enables diagnosis of various hepatobiliary disease, especially in early stages. Quantitative functional parameters not only provide criteria for diagnosis, but also assist in monitoring the therapeutic benefit from drugs and interventional techniques such as endoscopic sphincterotomy or balloon dilation of the obstruction. Biliary dynamic studies with cholecystokinin assist in distinguishing common bile duct dilation without obstruction from dilation with obstruction. Methods of application of 99mTc-IDA agents in quantitative physiologic studies are reviewed and future direction of their use is proposed.