Validation of deconvolutional analysis for the measurement of hepatic function in dogs with toxic-induced liver disease.
The extraction of the hepatobiliary radiopharmaceutical 99mTc-mebrofenin (Choletec) by the liver can be used to evaluate the severity of hepatocellular disease. The hepatic parenchymal cells extract mebrofenin from the blood by the same active transport mechanism as bilirubin. The ability of the liver to extract 99mTc-mebrofenin is a measure of hepatic parenchymal cell function. In this study, we induced hepatocellular disease by administration of a hepatotoxic drug and compared a direct method of determining the hepatic extraction of 99mTc-mebrofenin to hepatic extraction fraction derived from deconvolutional analysis. We also compared both methods of calculating the hepatic extraction of 99mTc-mebrofenin to liver histopathology. Hepatic extraction fraction derived from deconvolutional analysis correlated very well to the direct measurement technique (R=0.922, p < 0.001). Both methods of determining hepatic extraction correlated well to quantitative histopathology, having the same correlation coefficient and p values. (R=-0.833, p=0.003). As the hepatic extraction 99mTc-mebrofenin decreased, the severity of the histopathologic lesions of the liver increased in a linear fashion. There was a significant correlation of the hepatic excretion T1/2 to quantitative histopathology (R=0.949, p < 0.001). The hepatic excretion T1/2 increased as the severity of the histopathologic lesions of the liver increased. Hepatic extraction (HEF) and excretion of 99mTc-mebrofenin are good predictors of the severity of hepatocellular damage in toxic induced liver disease. This study helps validate the premise that HEF derived from deconvolutional analysis is a good predictor of the actual first pass hepatic extraction of 99mTc-mebrofenin.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
G B
GB
Daniel
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DeNovo
A E
AE
Schultze
D
D
Schmidt
G T
GT
Smith
D000814:Aniline Compounds; D000818:Animals; D001148:Arsenamide / Q000009:adverse effects; D001663:Bilirubin / Q000097:blood / Q000378:metabolism; D001693:Biological Transport, Active; D056486:Chemical and Drug Induced Liver Injury; D004285:Dogs; D005260:Female; D005544:Forecasting; D005998:Glycine; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007098:Imino Acids / Q000008:administration & dosage; D007275:Injections, Intravenous; D016014:Linear Models; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008107:Liver Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008642:Mesenteric Veins; D015609:Organotechnetium Compounds / Q000008:administration & dosage; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D015203:Reproducibility of Results
D000814:Aniline Compounds; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C034837:technetium Tc 99m mebrofenin; D001663:Bilirubin; D005998:Glycine; D001148:Arsenamide