title: Evaluation of plasma time-activity curves of technetium-99m-mebrofenin for measurement of hepatic function in dogs.
abstract: In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes 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 two different 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 two-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 determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.
authors.affiliation: Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville 37901, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Matwichuk
authors.forename: G B
authors.initials: GB
authors.lastname: Daniel
authors.forename: R C
authors.initials: RC
authors.lastname: DeNovo
authors.forename: A E
authors.initials: AE
authors.lastname: Schultze
authors.forename: D E
authors.initials: DE
authors.lastname: Schmidt
authors.forename: K E
authors.initials: KE
authors.lastname: Creevy
mesh_terms: D000465:Algorithms; D000814:Aniline Compounds; D000818:Animals; D019540:Area Under Curve; D001148:Arsenamide / Q000009:adverse effects; D002251:Carbon Tetrachloride / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D004283:Dog Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D004285:Dogs / Q000378:metabolism / Q000502:physiology*; D005369:Filaricides / Q000009:adverse effects; D005500:Follow-Up Studies; D005998:Glycine; D007098:Imino Acids / Q000008:administration & dosage / Q000097:blood; D007275:Injections, Intravenous; D016014:Linear Models; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008107:Liver Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000662:veterinary; D008642:Mesenteric Veins; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000097:blood; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000097:blood; D012997:Solvents / Q000009:adverse effects
chemical_list: D000814:Aniline Compounds; D005369:Filaricides; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012997:Solvents; D002251:Carbon Tetrachloride; C034837:technetium Tc 99m mebrofenin; D005998:Glycine; D001148:Arsenamide