The influence of bilirubin, alcohol and certain drugs on the kinetics of 99mTc-Diethyl IDA (EHIDA) in humans

Abstract

On the basis of the mathematical analysis of 99mTc-EHIDA hepatobiliary time-activity curves of normal individuals two rate constants, one related to accumulation of radioactivity (uptake) and the other to excretion, were calculated indicating a two-compartmental model. By means of computerized fitting the rate constant of excretion (Kb), the time of maximum uptake (Tmax) and the rate constant of uptake (Ka) were calculated. In severely jaundiced patients (serum bilirubin concentrations greater than 140 mumol/l) a markedly decreased or absent uptake of 99mTc-EHIDA was observed. In moderately jaundiced patients a low Kb was invariably observed; in obstructive jaundice due to malignant disease--but not in jaundice of benign obstructive or hepatocellular origin--an increase in Ka was frequently present. This latter finding was not always present, however, and consequently kinetic studies do not unequivocally differentiate between jaundice of obstructive and hepatocellular origin. A markedly increased uptake (a high Ka) was noticed in alcoholics and patients taking phenobarbital and diphenylhydantoin possibly because of drug-induced membrane alterations. When the alcoholics developed hepatocellular injury the Ka converted to normal values. Thus, 99mTc-EHIDA kinetics may be useful in the follow-up of patients with established or suspected alcoholism by virtue of the fact that it appears to be a sensitive monitor of functional changes in hepatocyte plasma membrane properties.