Evaluation of plasma time-activity curves of technetium-99M-mebrofenin for measurement of hepatic function in dogs.

C. L. Matwichuk
G. B. Daniel
Robert C. DeNovo Jr., University of Tennessee, Knoxville
A. E. Shultze
D. E. Schmidt
K. E. Creevy

Abstract

In 9 healthy dogs in which hepatic damage was induced using using a hepatotoxic agent, plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 min following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using 2 methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a 2-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency measurements were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg i.v. twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg i.p.). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a 2 compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1 to 60 min (AUC60) had the best correlation with hepatic extraction efficiency (r=0.978). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis. It is concluded that plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to measure hepatic function without a gamma camera. Accession Number: 20002210034