Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model.
OBJECTIVE
This study evaluated the utility of non-invasive assessment of hepatobiliary function by 99mTc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis.


METHODS
Male Wistar rats (250-300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. 99mTc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T(peak)) and the time required for peak activity to decrease by 50% (T(1/2peak)). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology.


RESULTS
MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T(peak), T(1/2peak) prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p<0.05). There was a strong, significant correlation between the severity of steatosis (histopathology, hepatic triglyceride content) and the 99mTc-mebrofenin uptake rate (r2=0.83, p<0.0001 and r2=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-alpha, r2=0.72, p<0.0001 and r2=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r2=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r2=0.70, p<0.001).


CONCLUSIONS
Hepatobiliary function assessed by 99mTc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients.
Veteläinen
Reeta L
RL
Department of Surgery, Academic Medical Center, Meibergdreef 9, IWO-1, 1105 AZ Amsterdam, The Netherlands.
Bennink
Roelof J
RJ
de Bruin
Kora
K
van Vliet
Arlène
A
van Gulik
Thomas M
TM
D000814:Aniline Compounds; D000818:Animals; D001659:Biliary Tract / Q000000981:diagnostic imaging / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005998:Glycine; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007098:Imino Acids / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008111:Liver Function Tests / Q000379:methods*; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D000814:Aniline Compounds; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C034837:technetium Tc 99m mebrofenin; D005998:Glycine