Abstract
Purpose
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 (r 2=0.83, p<0.0001 and r 2=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-α, r 2=0.72, p<0.0001 and r 2=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r 2=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r 2=0.70, p<0.001).
Conclusion
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.
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Acknowledgements
We thank Wilmar de Graaf for his assistance in the histology analysis and Jaap Rip (Department of Vascular Medicine) for his assistance with triglyceride assays.
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Veteläinen, R.L., Bennink, R.J., de Bruin, K. et al. Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model. Eur J Nucl Med Mol Imaging 33, 1107–1114 (2006). https://doi.org/10.1007/s00259-006-0125-3
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DOI: https://doi.org/10.1007/s00259-006-0125-3