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^99mTc-Mebrofenin Scintigraphy for Evaluating Liver Disease in a Rat Model of Wilson’s Disease

¹ Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
² Division of Nuclear Medicine, Long Island Jewish Medical Center, New Hyde Park, New York
³ The National Center for the Study of Wilson’s Disease, St. Luke’s–Roosevelt Hospital Center, New York, New York
⁴ Division of Hepatology and Transplant Institute, Mount Sinai School of Medicine, New York, New York

View larger version (165K): [in a new window]   FIGURE 1. (A) Histologic analysis of tissues in LEA rat liver showed completely normal histology. (B) Liver in LEC rats showed multiple abnormalities, including bile duct proliferation and fibrosis as seen here in portal area (P), as well as apoptosis (curved arrows), fatty change (solid straight arrow), and polyploidy (open arrow), which refers to abnormally enlarged nuclei containing multiple DNA copies. Inset shows metaphase (arrow) indicating increased mitotic activity.

View larger version (63K): [in a new window]   FIGURE 2. Mebrofenin imaging shows kinetics of hepatic mebrofenin uptake and excretion in representative rats. Sequential images from same animal are shown. (A) LEA rat shows prompt mebrofenin clearance from liver, such that at 20 min after mebrofenin injection, significant amount of activity had cleared. (B) LEC rat shows considerably longer retention of mebrofenin activity in liver. In this animal, exceptionally large amount of activity was present in liver even at 60 min after mebrofenin injection. Arrowhead indicates splenic site of mebrofenin injection.

View larger version (20K): [in a new window]   FIGURE 3. Representative hepatic time–activity curves derived from mebrofenin imaging. Data are from 1 LEA rat (A) and 1 LEC rat (B). For superior graphic representation, data are restricted to initial 20 min after mebrofenin administration. Mebrofenin activity declined earlier in LEA rat than in LEC rat.

View larger version (19K): [in a new window]   FIGURE 4. Mebrofenin-handling parameters were internally consistent, showing excellent positive correlation between Tpeak of mebrofenin uptake and T1/2 peak (T1/2) of mebrofenin retention in liver. = LEA rats; • = LEC rats.

View larger version (18K): [in a new window]   FIGURE 5. Correlation between hepatic copper content and graded evaluation of liver histology. Data are from all LEC and LEA rats studied. Highly significant association existed between these parameters. Additional relationships were observed between hepatic copper and other parameters. These findings indicate that comparison of mebrofenin-handling parameters with selected parameters of liver disease in LEC rats would be useful. = LEA rats; • = LEC rats.