Extraction efficiency and biliary excretion of hepatobiliary imaging agents in the rat perfused liver

A multitude of transitional metal complexes has recently been introduced into clinical practice as hepatobiliary imaging agents; the kinetics of these substances are often poorly understood. To gain better insight into characteristics of these different agents, we measured the extraction efficiency and mean biliary transit time of a variety of iminodiacetate derivatives in the in-situ rat perfused liver. First pass hepatic extraction efficiency averaged 59% for 99mTc N-(p-isopropylacetanilide) iminodiacetate, 73% for 99mTc N-(2,6-diethylacetanilide) iminodiacetate, 74% for 99mTc N-(3-bromo-2,4,6-trimethylacetanilide) iminodiacetate, 90% for 99mTc N-(p-butylacetanilide) iminodiacetate, and 93% for 99mTc N-pyridoxyl-5-methyltryptophan. By comparison, extraction of another organic anionic compound, 131I Rose bengal, was only 12.4%. Mean hepatocyte transit times varied from 2.3 to 7.5 min. Shorter mean transit times were observed for diortho substituted and longer mean transit times for para substituted metal complexes. Radioactivity was quantitatively recovered in bile, and excretion kinetics overall were consistent with data generated in whole animals. These studies demonstrate the value of the in-situ rat perfused liver as a screening tool to characterize hepatobiliary imaging agents.