Magma

, Volume 1, Issue 3–4, pp 134–139 | Cite as

Complete elimination of the hepatobiliary mr contrast agent Gd-EOB-DTPA in hepatic dysfunction: An experimental study using transport-deficient, mutant rats

  • Andreas Muhler
  • Ronald P. J. Oude Elferink
  • Hanns-Joachim Weinmann
Papers

Abstract

Mutant Wistar rats (TR rats) are characterized by a defect in the canalicular transport system for organic anions in the hepatocytes. Anionic hepatobiliary contrast agents for X-ray and MR imaging usually depend on this transport system for biliary secretion. The current study investigated in rats whether Gd-EOB-DTPA, a hepatocyte-directed MR contrast agent, can be completely eliminated in the absence of biliary excretion, and whether urinary elimination may compensate for the hepatic dysfunction. In TR/t- rats elimination of Gd-EOB-DTPA almost completely depended on renal excretion: following intravenous administration of 25µmol kg−1 Gd-EOB-DTPA only 2.4±0.4% of the injected dose underwent biliary excretion. Nevertheless only 2% of a 10-fold higher dose (250µmolkg−1 Gd-EOB-DTPA) was still detected in the body 24 hours p.a., and less than 0.5% 7 days p.a. (no statistically significant differences as compared to values in control rats). In TR rats, renal and liver signal intensities on T1-weighted MR images returned to baseline within 24 hours following administration of 25µmol kg−1 Gd-EOB-DTPA. In control rats, return to baseline values was observed already 6 hours after injection of the contrast agent. In conclusion, the hepatobiliary MR contrast agent Gd-EOB-DTPA is effectively and completely cleared from the body even in the virtual absence of biliary excretion. The urinary elimination pathway is able to fully compensate for the deficient hepatic transport system.

Keywords

liver mr contrast agent gadolinium contrast agent elimination transport systems 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mühler A, Clement O, Vexler V, Berthezene Y, Rosenau W and Brasch RC (1992)Radiology 184 207–213.PubMedGoogle Scholar
  2. 2.
    Clement O, Mühler A, Vexler VS, Kuwatsuru R, Berthezene Y, Rosenau W and Brasch RC (1993)JMRI 3 71–77.PubMedGoogle Scholar
  3. 3.
    Clement O, Mühler A, Vexler V, Berthezene Y and Brasch RC (1992)Invest Radiol 27 612–619.PubMedGoogle Scholar
  4. 4.
    Schuhmann-Giampieri G, Schmitt-Willich H, Press WR, Negishi C and Weinmann H-J (1992) Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system.Radiology 183 59–64.PubMedGoogle Scholar
  5. 5.
    Weinmann H-J, Schuhmann-Giampieri G, Schmitt- Willich H, Vogler H, Frenzel T and Gries H (1991)Magn Res Med 22 222–228.Google Scholar
  6. 6.
    Jansen P (1987)Hepatology 7 71–76.Google Scholar
  7. 7.
    Oude Elferink RPJ, Ottenhoff R, Liefting W, Haan J and Jansen PLM (1989)J Clin Invest 84 476–483.PubMedGoogle Scholar
  8. 8.
    Oude Elferink RPJ, Haan Jd, Lambert KJ, Hagey LR, Hofmann AL and Jansen PLM (1989)Hepatology 9(6): 861–865.PubMedGoogle Scholar
  9. 9.
    Jansen PLM and Oude Elferink RPJ (1988)Seminars of Liver Disease 8 168–178.Google Scholar
  10. 10.
    Jansen PLM and Oude Elferink RPJ (1993) InHepatic transport and bile secretion: physiology and pathophysiology (N Tavoloni & PD Berg Eds) pp. 721–731. New York: Raven Press.Google Scholar
  11. 11.
    Arias IM, Che M, Gatmaitan A, Levelle C, Nishida T and Pierre MS (1993)Hepatology 17 318–329.PubMedGoogle Scholar
  12. 12.
    Klaassen CD and Watkins JB (1984)Pharmacol Reviews 36(1): 1–67.Google Scholar
  13. 13.
    Meijer DKF (1989) InHandbook of Physiology (SG Schultz, JG Forte, BB Rauner Eds) Bethesda, Maryland, USA: American Physiological Society.Google Scholar
  14. 14.
    Mühler A, Freise CE, Kuwatsuru R, Rosenau W, Liu T, Montorovitch J, Clement O, Vexler V, Mahboubi S, Lang P, Roberts JP and Brasch RC (1993)Radiology 186 139–146.PubMedGoogle Scholar
  15. 15.
    Clement O, Mühler A, Vexler VS, Rosenau W, Berthezene Y, Kuwatsuru R and Brasch RC (1992)Radiology 185 163–168.PubMedGoogle Scholar
  16. 16.
    Marchal G (1993) personal communication.Google Scholar
  17. 17.
    Rocklage SM, Quay SC and Worah D (1988)Diagn. Imaging Intern. Suppl Nov: 78–79.Google Scholar
  18. 18.
    Shaw D (1992) Mn-DPDP: clinical development of the first liver-specific MRI contrast agent.Third special topic seminar of the European Magnetic Resonance Forum: New developments in contrast agent research. Hamburg, Germany.Google Scholar
  19. 19.
    Grant D, Holtz E and Zech K (1993) Biodistribution and excretion of 54Mn and 14C labelled MnDPDP in rats and dogs (abstract).10th Annual Scientific Meeting of the ESMRMB Rome, Italy: p. 251.Google Scholar
  20. 20.
    Marchal G, Ni Y, Zhang X, Yu J, Lodemann KP and Baert AL (1993)J Comp Ass Tomogr 17(2): 290–296.Google Scholar
  21. 21.
    Lamirande E de and Plaa GL (1979)Toxic Appl Pharmacol 49 257–263.PubMedGoogle Scholar
  22. 22.
    Lamirande E de and Plaa GL (1978) Role of manganese, bilirubin and sulphobromophtalein in manganese-bilirubin cholestasis in rats.Proc Soc Exp Biol Med 158 283–287.PubMedGoogle Scholar
  23. 23.
    Vogl TJ, Pegios W, McMahon C, Balzer J, Waitzinger J, Pirovano G and Lissner J (1992)AJR 158 887–892.PubMedGoogle Scholar
  24. 24.
    Pirovano G, Lorusso V, Tirone P and Rosati G (1993)JMRI 3 155.Google Scholar

Copyright information

© Chapman & Hall 1993

Authors and Affiliations

  • Andreas Muhler
    • 1
  • Ronald P. J. Oude Elferink
    • 2
  • Hanns-Joachim Weinmann
    • 1
  1. 1.MRI Contrast Media Research, Schering AGBerlinGermany
  2. 2.Department of GastroenterologyUniversity of AmsterdamAmsterdamThe Netherlands

Personalised recommendations