Hepatic extraction efficiency of technetium-99m-mebrofenin in the dog with toxic-induced acute liver disease.

Abstract

Extraction of the hepatobiliary radiopharmaceutical 99mTc-N-(3-bromo-2,4,6-trimethyacetanilide) iminodiacetic acid (mebrofenin; Choletec, Squibb Diagnostic, Princeton, NJ) by the liver may be used as an index of hepatocellular function. The hepatic parenchymal cells extract mebrofenin from the blood using the same active transport mechanism as bilirubin. In this study, we induced hepatocellular disease by administering a hepatotoxic drug and compared the hepatic extraction efficiency (HEE), measured directly from an afferent injection of 99mTc-mebrofenin, to quantitative histopathology and to serum biochemistry analysis. The baseline HEE was 95.9% +/- 2.71% (mean +/- s.d.). Dogs that were affected by the hepatotoxic drug had reduced HEE. HEE correlated well to the severity of histologic lesions (r = -0.83, p = 0.003). HEE also correlated well to the increases in the activities of alanine aminotransferase (ALT; r = -0.85, p = 0.002) and aspartate aminotransferase (AST; r = -0.89, p = <0.001), the concentration of fasting bile acid (r = -0.97, p = <0.001), bilirubin (r = -0.92, p = <0.001) and, to a lesser degree, to the activities of alkaline phosphatase (Alk Phos; r = -0.73, p = 0.016). HEE had higher correlation coefficients to the serum biochemistry analysis than did the quantitative liver histopathology. Hepatic extraction of 99mTc-mebrofenin is a good predictor of the severity of hepatocellular damage in toxic-induced liver disease.