Evaluation of plasma time-activity curves of technetium-99m-mebrofenin formeasurement of hepatic function in dogs

In this study, plasma time-activity curves of Tc-99m-mebrofenin were used t o quantify hepatic function in dogs before and after induction of hepatic d amage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Pl asma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minut es following a peripheral venous injection of 111-222 MBq (3-6 mCi) of Tc-9 9m-mebrofenin. The area under the plasma time-activity curve (AUC) was calc ulated using two different methods and compared to direct measurement of th e hepatic extraction efficiency. First pass hepatic extraction efficiency o f Tc-99m-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radioph armaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, pl asma clearance and hepatic extraction efficiency determination were repeate d following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twic e daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IF). Plasma time-activity curves of Tc-99m-mebrofenin had kinetics of a two comp artment model. Area under the curve was highly correlated with hepatic extr action efficiency. The AUC integrated from 1-60 minutes (AUC60) had the bes t correlation with hepatic extraction efficiency (r(2) = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived usi ng linear regression analysis: hepatic extraction efficiency 105.583 - 3.09 9 x 10(5) * AUC60. Plasma clearance of a peripheral venous injection of Tc- 99m-mebrofenin is a simple, non-invasive, convenient method to quantify hep atic function which can be performed without a gamma camera.