99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease.
The purpose of this study was to establish whether (99m)Tc-mebrofenin could noninvasively assess liver function in Wilson's disease.


METHODS
Long-Evans Cinnamon (LEC) rats, which reproduce Wilson's disease with copper toxicosis, and their normal counterparts, Long-Evans Agouti (LEA) rats, were studied. Scintigraphic findings were correlated with biliary mebrofenin excretion and residual organ counts and with hepatic copper content, histology, copper excretion capacity, and liver test results.


RESULTS
Serum alanine aminotransferase (ALT) levels were elevated in some LEC rats, whereas serum bilirubin levels were normal. Liver histology was normal in LEA rats, whereas LEC rats showed multiple abnormalities. Mebrofenin was incorporated rapidly in LEA rats, with a mean time to peak liver activity of 80 +/- 30 s, followed by prompt biliary excretion of the tracer. In LEC rats, the mean time to peak activity, 283 +/- 190 s, was significantly longer (P = 0.001). The time to half of peak activity, indicating tracer clearance, was significantly greater in LEC rats than in LEA rats (1,825 +/- 1,642 s vs. 524 +/- 82 s, P = 0.002). Hepatic mebrofenin handling correlated with hepatic copper content, histologic grade, copper excretion capacity, and serum ALT.


CONCLUSIONS
Correlation of (99m)Tc-mebrofenin handling with liver morphology, function, and copper accumulation in LEC rats suggests that mebrofenin scintigraphy can be useful for noninvasively monitoring disease progression and therapeutic response in Wilson's disease. Although the data were obtained in an animal model of Wilson' disease, these biochemical parameters likely reflect liver damage in general, suggesting that there may be a role for mebrofenin scintigraphy in other chronic liver diseases as well.
Malhi
Harmeet
H
Marion Bessin Liver Research Center, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 11040, USA.
Bhargava
Kuldeep K
KK
Afriyie
Menes O
MO
Volenberg
Irene
I
Schilsky
Michael L
ML
Palestro
Christopher J
CJ
Gupta
Sanjeev
S
D000410:Alanine Transaminase / Q000097:blood; D000814:Aniline Compounds; D000818:Animals; D001663:Bilirubin / Q000097:blood; D002570:Ceruloplasmin / Q000032:analysis; D003300:Copper / Q000378:metabolism; D005998:Glycine; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D007098:Imino Acids; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D020332:Rats, Inbred LEC; D020318:Rats, Long-Evans; D012709:Serum Albumin / Q000032:analysis
D000814:Aniline Compounds; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012709:Serum Albumin; D003300:Copper; D002570:Ceruloplasmin; D000410:Alanine Transaminase; C034837:technetium Tc 99m mebrofenin; D001663:Bilirubin; D005998:Glycine