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Ferumoxtran-10 enhancement in orthotopic xenograft models of human brain tumors: an indirect marker of tumor proliferation?

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Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Ferumoxtran-10 belongs to the Ultra Small Particles of Iron Oxide (USPIO) class of contrast agents and induces delayed tumor enhancement in brain tumors, reflecting the trapping of iron oxide particles by the macrophages and activated microglia. The aim of the study was to compare Ferumoxtran-10 contrast enhancement in four human high-grade glioma xenograft models (TCG2, TCG3, TCG4, and U87) with different growing profiles.

Materials and methods

Fragments of human malignant glioma were orthotopically xenografted into the brain of four groups of nude mice. All mice underwent a MRI examination 24 h after intravenous administration of Ferumoxtran-10 (axial T1 SE weighted MR images). The contrast enhancement observed in the different tumor types was measured and was correlated to in vivo tumor growth and to histological parameters, such as proliferative tumor cell fraction, apoptosis, vascular density, and Perls’ staining score.

Results

A good relationship was observed: (a) between tumor-to-background contrast and proliferative index, (b) between tumor-to-background contrast and tumor growth, and (c) between tumor-to-background contrast and Perls’ staining score. The registered MR enhancement contrasts were not influenced by apoptotic index and by vascular density in these experimental xenografts.

Conclusions

Tumor contrast enhancement 24 h after intravenous Ferumoxtran-10 administration seems to be well correlated to tumor proliferative index and tumor growth and could be used as an indirect marker of tumor proliferation.

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References

  1. Antunes L, Angioi-Duprez K, Bracard S, Klein-Monhoven N, Le Faou A, Duprez A, Plénat F (2000) Analysis of tissue chimerism in nude mouse brain and abdominal xenograft models of human glioblastoma multiforme: what does it tell us about the models and about biology and therapy? J Histochem Cytochem 48:847–858

    PubMed  CAS  Google Scholar 

  2. Bellin M, Roy C, Kinkel K (1998) Lymph node metastases: safety and effectiveness of MR imaging with ultrasmall superparamagnetic iron oxide particles – initial clinical experience. Radiology 207:799–808

    PubMed  CAS  Google Scholar 

  3. Corot C, Petry KG, Trivedi R, Saleh A, Jonkmanns C, Le Bas JF, Blezer E, Rausch M, Brochet B, Foster-Gareau P, Baleriaux D, Gaillard S, Dousset V (2004) Macrophage imaging in central nervous system and in carotid atherosclerotic plaque using ultrasmall superparamagnetic iron oxide in magnetic resonance imaging. Invest Radiol 39:619–625

    Article  PubMed  CAS  Google Scholar 

  4. Dousset V, Delalande C, Ballarino L, Quesson B, Seilhan D, Coussemacq M, Thiaudiere E, Brochet B, Canioni P, Caille JM (1999) In vivo macrophage activity imaging in the central nervous system detected by magnetic resonance. Magn Reson Med 41:329–333

    Article  PubMed  CAS  Google Scholar 

  5. Enochs WS, Harsh G, Hochberg F, Weissleder R (1999) Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent. J Magn Reson Imaging 9:228–232

    Article  PubMed  CAS  Google Scholar 

  6. Fleige G, Nolte C, Synowitz M, Seeberger F, Kettenmann H, Zimmer C (2001) Magnetic labeling of activated microglia in experimental gliomas. Neoplasia 3:489–499

    Article  PubMed  CAS  Google Scholar 

  7. Kleihues P, Cavenee W (2000) Pathology and genetics of tumours of the nervous system. International Agency for Research, Lyon

    Google Scholar 

  8. Muldoon L, Manninger S, Pinkston K, Neuwelt EA (2005) Imaging, distribution, and toxicity of superparamagnetic iron oxide magnetic resonance nanoparticles in the ray brain and intracerebral tumor. Neurosurgery 57:785–796

    Article  PubMed  Google Scholar 

  9. Neuwelt E, Varallyay P, Bago A, Muldoon L, Nixon R (2004) Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours. Neuropathol Appl Neurobiol 30:456–471

    Article  PubMed  CAS  Google Scholar 

  10. Pinel S, Barberi-Heyob M, Cohen-Jonathan E, Merlin J, Delmas C, Plenat F, Chastagner P (2004) Erythropoietin-induced reduction of hypoxia before and during fractionated irradiation contributes to improvement of radioresponse in human glioma xenografts. Int J Radiat Oncol Biol Phys 59:250–259

    Article  PubMed  CAS  Google Scholar 

  11. Pinel S, Chastagner P, Merlin J, Marchal C, Taghian A, Barberi-Heyob M (2006) Topotecan can compensate for protracted radiation treatment time effects in high grade glioma xenografts. J Neurooncol 76:31–38

    Article  PubMed  CAS  Google Scholar 

  12. Plénat F, Vignaud J, Guerret-Stocker S, Hartmann D, Duprez K, Duprez A (1992) Host–donor interactions in healing of human split-thickness skin grafts onto nude mice: in situ hybridization, immunohistochemical and histochemical studies. Transplantation 53:1002–1010

    Article  PubMed  Google Scholar 

  13. Roggendorf W, Strupp S, Paulus W (1996) Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol 92:288–293

    Article  PubMed  CAS  Google Scholar 

  14. Rosset A, Spadola L, Ratib O (2004) OsiriX: an open-source software for navigating in multidimensional DICOM images. J Digit Imaging 17:205–216

    Article  PubMed  Google Scholar 

  15. Saini S, Edelman R, Sharma P, Li W, Mayo-Smith W, Slater G, Eisenberg P, Hahn P (1995) Blood-pool MR contrast material for detection and characterisation of focal hepatic lesions: initial clinical experience with ultrasmall superparamagnetic iron oxide (AMI-227). Am J Roentgenol 164:1147–1152

    CAS  Google Scholar 

  16. Schroeter M, Saleh A, Wiedermann D, Hoehn M, Jander S (2004) Histochemical detection of ultrasmall superparamagnetic iron oxide (USPIO). Magn Reson Med 52:403–406

    Article  PubMed  Google Scholar 

  17. Taillandier L, Antunes L, Angioi-Duprez K (2003) Models for neurooncological preclinical studies: solid orthotopic and heterotopic grafts of human gliomas into nude mice. J Neurosci Methods 125:147–157

    Article  PubMed  Google Scholar 

  18. Varallyay P, Nesbit G, Muldoon L, Nixon R, Delashaw J, Cohen J, Petrillo A, Rink D, Neuwelt E (2002) Comparison of two superparamagnetic viral-sized iron oxide particles Feruxomides and Ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors. Am J Neuroradiol 23:510–519

    PubMed  Google Scholar 

  19. Zimmer C, Wright SC, Engelhardt RT, Johnson GA, Kramm C, Breakefield XO, Weissleder R (1997) Tumor cell endocytosis imaging facilitates delineation of the glioma-brain interface. Exp Neurol 143:61–69

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank S. Pizzagalli, D. Muriel, B. Cunin, D. Meng and C. Taine for excellent technical assistance, and C. Maire for expert help in the preparation of this manuscript.

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Authors and Affiliations

  1. Service de Neuro-Radiologie, Hôpital Central, CHRU Nancy, Nancy, France

    Stéphane Kremer & Serge Bracard

  2. Laboratoire d’Histopathologie Expérimentale et Moléculaire – EA 4001, Faculté de Médecine, Vandoeuvre-lès-Nancy, France

    Sophie Pinel, Pierre-Olivier Védrine, Aude Bressenot & François Plénat

  3. Service d’ORL, Hôpital Central, CHRU Nancy, Nancy, France

    Pierre-Olivier Védrine

  4. Service d’Anatomie et Cytologie Pathologiques, Hôpital de Brabois, CHRU Nancy, Vandoeuvre-lès-Nancy, France

    Aude Bressenot & François Plénat

  5. Laboratoires Guerbet, Roissy, France

    Philippe Robert

  6. Service de Radiologie 2, Centre Hospitalier et Universitaire de Strasbourg, avenue Molière, Hôpital de Hautepierre, 67098 , Strasbourg Cedex, France

    Stéphane Kremer

Authors
  1. Stéphane Kremer
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  2. Sophie Pinel
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  3. Pierre-Olivier Védrine
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  4. Aude Bressenot
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  5. Philippe Robert
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  6. Serge Bracard
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  7. François Plénat
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Corresponding author

Correspondence to Stéphane Kremer.

Additional information

Stéphane Kremer and Sophie Pinel have equally contributed to this work.

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Kremer, S., Pinel, S., Védrine, PO. et al. Ferumoxtran-10 enhancement in orthotopic xenograft models of human brain tumors: an indirect marker of tumor proliferation?. J Neurooncol 83, 111–119 (2007). https://doi.org/10.1007/s11060-006-9260-8

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  • DOI: https://doi.org/10.1007/s11060-006-9260-8

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