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Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging

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Abstract

The purpose of this study was to determine the cellular distribution and degradation in rat liver following intravenous injection of superparamagnetic iron oxide nanoparticles used for magnetic resonance imaging (NC100150 Injection). Relaxometric and spectrophotometric methods were used to determine the concentration of the iron oxide nanoparticles and their degradation products in isolated rat liver parenchymal, endothelial and Kupffer cell fractions. An isolated cell phantom was also constructed to quantify the effect of the degradation products on the loss of MR signal in terms of decreased transverse relaxation times, T2*. The results of this study show that iron oxide nanoparticles found in the NC100150 Injection were taken up and distributed equally in both liver endothelial and Kupffer cells following a single 5 mg Fe/kg body wt. bolus injection in rats. Whereas endothelial and Kupffer cells exhibited similar rates of uptake and degradation, liver parenchymal cells did not take up the NC100150 Injection iron oxide particles. Light-microscopy methods did, however, indicate an increased iron load, presumably as ferritin/hemosiderin, within the hepatocytes 24 h post injection. The study also confirmed that compartmentalisation of ferritin/hemosiderin may cause a significant decrease in the MRI signal intensity of the liver. In conclusion, the combined results of this study imply that the prolonged presence of breakdown product in the liver may cause a prolonged imaging effect (in terms of signal loss) for a time period that significantly exceeds the half-life of NC100150 Injection iron oxide nanoparticles in liver.

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References

  • Allkemper T, Bremer C, Matuszewski L, Ebert W, Reimer P (2002) Contrast-enhanced blood-pool MR angiography with optimized iron oxides: effect of size and dose on vascular contrast enhancement in rabbits. Radiology 223:432–438

    PubMed  Google Scholar 

  • Bauer WR, Hiller KH, Roder F, Rommel E, Ertl G, Haase A (1996) Magnetization exchange in capillaries by microcirculation affects diffusion-controlled spin-relaxation: a model which describes the effect of perfusion on relaxation enhancement by intravascular contrast agents. Magn Reson Med 35:43–45

    CAS  PubMed  Google Scholar 

  • Berg T, Blomhoff R (1983) In: Rickwood D (ed) Iodinated density gradient media: a practical approach. IRL Press, Oxford, pp 173–174

  • Berry MN, Friend DS (1969) High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol 43:506–520

    CAS  PubMed  Google Scholar 

  • Bjornerud A, Briley-Saebo K, Johansson LO, Kellar KE (2000) Effect of NC100150 injection on the (1)H NMR linewidth of human whole blood ex vivo: dependency on blood oxygen tension. Magn Reson Med 44:803–807

    Article  CAS  PubMed  Google Scholar 

  • Bjornerud A, Johansson LO, Briley-Saebo K, Ahlstrom HK (2002) Assessment of T1 and T2* effects in vivo and ex vivo using iron oxide nanoparticles in steady state-dependence on blood volume and water exchange. Magn Reson Med 47:461–471

    Article  CAS  PubMed  Google Scholar 

  • Blomhoff R, Drevon CA, Eskild W, Helgerud P, Norum KR, Berg T (1984) Clearance of acetyl low density lipoprotein by rat liver endothelial cells. Implications for hepatic cholesterol metabolism. J Biol Chem 259:8898–8903

    CAS  PubMed  Google Scholar 

  • Chen F, Ward J, Robinson PJ (1999) MR imaging of the liver and spleen: a comparison of the effects on signal intensity of two superparamagnetic iron oxide agents. Magn Reson Imaging 17:549–556

    Article  CAS  PubMed  Google Scholar 

  • Chouly C, Pouliquen D, Lucet I, Jeune JJ, Jallet P (1996) Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. J Microencapsul 13:245–255

    CAS  PubMed  Google Scholar 

  • Clement O, Siauve N, Cuenod CA, Vuillemin-Bodaghi V, Leconte I, Frija G (1999) Mechanisms of action of liver contrast agents: impact for clinical use. J Comput Assist Tomogr 23:S45–S52

    PubMed  Google Scholar 

  • Dupas B, Berreur M, Rohanizadeh R, Bonnemain B, Meflah K, Pradal G (1999) Electron microscopy study of intrahepatic ultrasmall superparamagnetic iron oxide kinetics in the rat. Relation with magnetic resonance imaging. Biol Cell 91:195–208

    Article  CAS  PubMed  Google Scholar 

  • Eskild W, Smedsrod B, Berg T (1986) Receptor mediated endocytosis of formaldehyde treated albumin, yeast invertase and chondroitin sulfate in suspensions of rat liver endothelial cells. Int J Biochem 18:647–651

    Article  CAS  PubMed  Google Scholar 

  • Gillis P, Koenig SH (1987) Transverse relaxation of solvent protons induced by magnetized spheres: application to ferritin, erythrocytes, and magnetite. Magn Reson Med 5:323–345

    CAS  PubMed  Google Scholar 

  • Gossuin Y, Roch A, Muller RN, Gillis P (2000) Relaxation induced by ferritin and ferritin-like magnetic particles: the role of proton exchange. Magn Reson Med 43:237–243

    Article  CAS  PubMed  Google Scholar 

  • Johansson AG, Skogh T (1994) Different elimination of circulating IgA immune complexes in rat and guinea pig. Blood clearance, organ distribution and cellular uptake in the liver. Int Arch Allergy Immunol 103:36–43

    CAS  PubMed  Google Scholar 

  • Kjeken R, Mousavi SA, Brech A, Gjoen T, Berg T (2001) Fluid-phase endocytosis of 125I-iodixanol in rat liver parenchymal, endothelial and Kupffer cells. Cell Tissue Res 304:221–230

    Article  CAS  PubMed  Google Scholar 

  • Knook DL, Sleyster EC (1977) Preparation and characterisation of Kupffer cells from rat and mouse liver. In: Wisse E, Knook DL (eds) Kupffer cell and other liver sinusoidal cells. Elsevier/North-Holland, Biomedical Press, Amsterdam, pp 273–288

  • Koenig SH, Kellar KE (1995) Theory of 1/T1 and 1/T2 NMRD profiles of solutions of magnetic nanoparticles. Magn Reson Med 34:227–233

    CAS  PubMed  Google Scholar 

  • Laakso T, Artursson P, Sjoholm I (1986) Biodegradable microspheres. IV: Factors affecting the distribution and degradation of polyacryl starch microparticles. J Pharm Sci 75:962–967

    CAS  PubMed  Google Scholar 

  • Majumdar S, Zoghbi SS, Gore JC (1990) Pharmacokinetics of superparamagnetic iron-oxide MR contrast agents in the rat. Invest Radiol 25:771–777

    CAS  PubMed  Google Scholar 

  • McCourt PA, Smedsrod BH, Melkko J, Johansson S (1999) Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors. Hepatology 30:1276–1286

    CAS  PubMed  Google Scholar 

  • Pouliquen D, Le Jeune JJ, Perdrisot R, Ermias A, Jallet P (1991) Iron oxide nanoparticles for use as an MRI contrast agent: pharmacokinetics and metabolism. Magn Reson Imaging 9:275–283

    CAS  PubMed  Google Scholar 

  • Reimer P, Bader A, Weissleder R (1998) Preclinical assessment of hepatocyte-targeted MR contrast agents in stable human liver cell cultures. J Magn Reson Imaging 8:687–689

    CAS  PubMed  Google Scholar 

  • Rety F, Clement O, Siauve N, Cuenod CA, Carnot F, Sich M, Buisine A, Frija G (2000) MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection. J Magn Reson Imaging 12:734–739

    CAS  Google Scholar 

  • Seglen PO (1976) Preparation of isolated rat liver cells. In: Prescott DM (ed) Methods in cell biology, vol XIII. Academic Press, New York, pp 29-83

  • Sibille JC, Kondo H, Aisen P (1988) Interactions between isolated hepatocytes and Kupffer cells in iron metabolism: a possible role for ferritin as an iron carrier protein. Hepatology 8:296–301

    CAS  PubMed  Google Scholar 

  • Skotland T, Sontum PC, Oulie I (2002) In vitro stability analyses as a model for metabolism of ferromagnetic particles (Clariscan), a contrast agent for magnetic resonance imaging. J Pharm Biomed Anal 28:323–329

    Article  CAS  PubMed  Google Scholar 

  • Smedsrod B, Pertoft H, Eriksson S, Fraser JR, Laurent TC (1984) Studies in vitro on the uptake and degradation of sodium hyaluronate in rat liver endothelial cells. Biochem J 223:617–626

    PubMed  Google Scholar 

  • Smedsrod B, Pertoft H, Eggertsen G, Sundstrom C (1985) Functional and morphological characterization of cultures of Kupffer cells and liver endothelial cells prepared by means of density separation in Percoll, and selective substrate adherence. Cell Tissue Res 241:639–649

    CAS  PubMed  Google Scholar 

  • Wang YX, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11:2319–2331

    CAS  PubMed  Google Scholar 

  • Weisskoff RM, Zuo CS, Boxerman JL, Rosen BR (1994) Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med 31:601–610

    CAS  PubMed  Google Scholar 

  • Weissleder R, Papisov M (1992) Pharmaceutical iron oxides for MR Imaging. Rev Magn Reson Med 4:1–20

    Google Scholar 

  • Wisner ER, Amparo EG, Vera DR, Brock JM, Barlow TW, Griffey SM, Drake C, Katzberg RW (1995) Arabinogalactan-coated superparamagnetic iron oxide: effect of particle size in liver MRI. J Comput Assist Tomogr 19:211–215

    CAS  PubMed  Google Scholar 

  • Wisse E, Doucet D, Van Bossuyt H (1991) A transmission electron microscopic study on the uptake of AMI-25 by sinusoidal liver cells. In: Wisse E (ed) Cells of the hepatic sinusoid, vol. 3. Kupffer Cell Foundation, the Netherlands, pp 534–539

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Authors and Affiliations

  1. Amersham Health, Oslo, Norway

    Karen Briley-Saebo, Derek Grant & Grete Mørk Kindberg

  2. Department of Radiology, National Hospital, Oslo, Norway

    Atle Bjørnerud

  3. Department of Diagnostic Radiology, Uppsala University Hospital, Uppsala, Sweden

    Karen Briley-Saebo & Håkan Ahlstrom

  4. Department of Biology, University of Oslo, Oslo, Norway

    Trond Berg

  5. Amersham Health, Nydalen 0401, PO Box 4220, Oslo, Norway

    Karen Briley-Saebo

Authors
  1. Karen Briley-Saebo
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  2. Atle Bjørnerud
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  3. Derek Grant
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  4. Håkan Ahlstrom
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  5. Trond Berg
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  6. Grete Mørk Kindberg
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Correspondence to Karen Briley-Saebo.

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Briley-Saebo, K., Bjørnerud, A., Grant, D. et al. Hepatic cellular distribution and degradation of iron oxide nanoparticles following single intravenous injection in rats: implications for magnetic resonance imaging. Cell Tissue Res 316, 315–323 (2004). https://doi.org/10.1007/s00441-004-0884-8

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  • DOI: https://doi.org/10.1007/s00441-004-0884-8

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