99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease

Harmeet M Malhi, Kuldeep K. Bhargava, Menes O. Afriyie, Irene Volenberg, Michael L. Schilsky, Christopher J. Palestro, Sanjeev Gupta

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The purpose of this study was to establish whether 99mTc-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. Conclusion: Correlation of 99mTc-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.

Original languageEnglish (US)
Pages (from-to)246-252
Number of pages7
JournalJournal of Nuclear Medicine
Volume43
Issue number2
StatePublished - 2002
Externally publishedYes

Fingerprint

Hepatolenticular Degeneration
Inbred LEC Rats
Radionuclide Imaging
Liver Diseases
Copper
Liver
Long Evans Rats
Alanine Transaminase
Histology
Serum
Multiple Abnormalities
technetium Tc 99m mebrofenin
Bilirubin
Disease Progression
Chronic Disease
Animal Models
Dasyproctidae

Keywords

  • Tc-mebrofenin
  • Liver
  • Wilson's disease

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Malhi, H. M., Bhargava, K. K., Afriyie, M. O., Volenberg, I., Schilsky, M. L., Palestro, C. J., & Gupta, S. (2002). 99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease. Journal of Nuclear Medicine, 43(2), 246-252.

99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease. / Malhi, Harmeet M; Bhargava, Kuldeep K.; Afriyie, Menes O.; Volenberg, Irene; Schilsky, Michael L.; Palestro, Christopher J.; Gupta, Sanjeev.

In: Journal of Nuclear Medicine, Vol. 43, No. 2, 2002, p. 246-252.

Research output: Contribution to journalArticle

Malhi, HM, Bhargava, KK, Afriyie, MO, Volenberg, I, Schilsky, ML, Palestro, CJ & Gupta, S 2002, '99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease', Journal of Nuclear Medicine, vol. 43, no. 2, pp. 246-252.
Malhi HM, Bhargava KK, Afriyie MO, Volenberg I, Schilsky ML, Palestro CJ et al. 99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease. Journal of Nuclear Medicine. 2002;43(2):246-252.
Malhi, Harmeet M ; Bhargava, Kuldeep K. ; Afriyie, Menes O. ; Volenberg, Irene ; Schilsky, Michael L. ; Palestro, Christopher J. ; Gupta, Sanjeev. / 99mTc-mebrofenin scintigraphy for evaluating liver disease in a rat model of Wilson's disease. In: Journal of Nuclear Medicine. 2002 ; Vol. 43, No. 2. pp. 246-252.
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abstract = "The purpose of this study was to establish whether 99mTc-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. Conclusion: Correlation of 99mTc-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.",
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AU - Palestro, Christopher J.

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N2 - The purpose of this study was to establish whether 99mTc-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. Conclusion: Correlation of 99mTc-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.

AB - The purpose of this study was to establish whether 99mTc-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. Conclusion: Correlation of 99mTc-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.

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