Skip to main content

Targeted Tumor Therapy with “Magnetic Drug Targeting”: Therapeutic Efficacy of Ferrofluid Bound Mitoxantrone

  • Chapter
  • First Online:
Ferrofluids

Part of the book series: Lecture Notes in Physics ((LNP,volume 594))

Abstract

The difference between success or failure of chemotherapy depends not only on the drug itself but also on how it is delivered to its target. Biocompatible ferrofluids (FF) are paramagnetic nanoparticles, that may be used as a delivery system for anticancer agents in locoregional tumor therapy, called “magnetic drug targeting”. Bound to medical drugs, such magnetic nanoparticles can be enriched in a desired body compartment (tumor) using an external magnetic field, which is focused on the area of the tumor. Through this form of target directed drug application, one attempts to concentrate a pharmacological agent at its site of action in order to minimize unwanted side effects in the organism and to increase its locoregional effectiveness.

Tumor bearing rabbits (VX2 squamous cell carcinoma) in the area of the hind limb, were treated by a single intra-arterial injection (A. femoralis) of mitoxantrone bound ferrofluids (FF-MTX), while focusing an external magnetic field (1.7 Tesla) onto the tumor for 60 minutes. Complete tumor remissions could be achieved in these animals in a dose related manner (20% and 50% of the systemic dose of mitoxantrone), without any negative side effects, like e.g. leucocytopenia, alopecia or gastrointestinal disorders.

The strong and specific therapeutic efficacy in tumor treatment with mitoxantrone bound ferrofluids may indicate that this system could be used as a delivery system for anticancer agents, like radionuclids, cancer-specific antibodies, anti-angiogenetic factors, genes etc.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alksne JF, Fingerhut A, Rand R. Magnetically controlled metallic thrombosis of intracranial aneurysms. Surgery 1966; 60: 212–218.

    Google Scholar 

  2. Hilal SK, Michelsen WJ, Driller J, Leonard E. Magnetically guided devices for vascular exploration and treatment. Radiology 1974;113: 529–534.

    Google Scholar 

  3. Ram, W. and Meyer, H. Heart catheterization in a neonate by interacting magnetic fields. A new and simple method of catheterguidance. Catheterization and Cardiovascular Diagnosis, 22: 317–319, 1991.

    Article  Google Scholar 

  4. McNeil, R. G., Ritter, R. C., Wang, B. et al. Functional design features and initial performance characteristics of a magnetic-implant guidance system for stereotactic neurosurgery. IEEE Transactions on Biomedical Engineering, 42: 793–801, 1995.

    Article  Google Scholar 

  5. Luborsky, F.E. Recent advances in the removal of magnetic foreign bodies from the esophagus, stomach and duodenum with controllable permanent magnets. Am. J. Roentg. Rad. Ther. Nucl. Med., 1964.

    Google Scholar 

  6. Weissleder R, Hahn PF, Stark DD et al. MR imaging of splenic metastases: ferrite-enhanced detection in rats. AJR 1987; 149: 723–726.

    Google Scholar 

  7. Weissleder R, Stark DD, Engelstad BL et al. Superparamagnetic iron oxide: pharmacokinetics and toxicity. AJR 1989;152: 167–173.

    Google Scholar 

  8. Weissleder R, Elizondo G, Wittenberg J, Lee AS, Josephson L, Brady TJ. Ultra-small superparamagnetic iron oxide. An intravenous contrast agent for assessing lymph nodes with MR imaging. Radiology 1990;175: 494.

    Google Scholar 

  9. Taupitz M, Wagner S, Hamm B, Dienemann D, Lawaczeck R, Wolf KJ. MR lymphography using iron oxide particles. Detection of lymph node metastases in the VX2 rabbit tumor model. Acta Radiol. 1993; 34: 10–15.

    Google Scholar 

  10. Hardingham JE, Kotasek D, Sage RE, Eaton MC, Pascoe VH. Detection of circulating tumor cells in colorectal cancer by immunobead-PCR is a sensitive prognostic marker for relapse of disease. Molec. Med. 195;1: 789–794.

    Google Scholar 

  11. Mitamura Y, Wada T, Keisuke S. A ferrofluidic actuator for an implantable artificial heart. Artif. Organs 1992; 16(5): 490–495.

    Article  Google Scholar 

  12. Alexiou, C., Arnold, W., Klein, R.J. et al. Locoregional cancer treatment with Magnetic Drug Targeting. Cancer Res 2000; 60: 6641–6648.

    Google Scholar 

  13. Alexiou, C., Arnold, W., Hulin, P. et al. Magnetic mitoxantrone nanoparticle detection by histology, X-ray and MRI after magnetic tumor targeting. JMMM 2001;255: 187–193.

    ADS  Google Scholar 

  14. Alexiou, C., Schmidt, A., Klein, R.J. et al. Magnetic drug targeting: Biodistribution and dependency on magnetic field strength. JMMM in press.

    Google Scholar 

  15. Lübbe AS, Bergemann C, Huhnt W et al. Preclinical experiences with magnetic drug targeting: tolerance and efficacy. Cancer Res 1996; 56: 4694–4701.

    Google Scholar 

  16. Ho, A. D., Del Valle, F., Haas, R. et al. Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin’s lymphoma. Semin. Oncol., 17: 14–18, 1990.

    Google Scholar 

  17. Hiddemann, W., Buchner, T., Heil, G. et al. Treatment of refractory acute lymphoblastic leukemia in adults with high dose cytosine arabinoside and mitoxantrone (HAM). Leukemia., 4:637–640, 1990.

    Google Scholar 

  18. Freund, M., Wunsch-Zeddies, S., Schafers, M. et al. Prednimustine and mitoxantrone (PmM) in patients with low-grade malignant non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), and prolymphocytic leukemia (PLL). Ann. Hematol., 64: 83–87, 1992.

    Article  Google Scholar 

  19. Bistner SI, Ford RB, Raffe MR (eds.). Kirk and Bistner’s Handbook of Veterinarian Procedures and Emergency Treatment, Ed 6, p. 907. Philadelphia: W.B. Saunders Co., 1995.

    Google Scholar 

  20. Stephens, F. O. Why use regional chemotherapy? Principles and pharmacokinetics. Reg Cancer Treat., 1: 4–10, 1988.

    Google Scholar 

  21. Link, K.H., Kornmann, M., Formenti, A. et al. Regional chemotherapy of nonresectable liver metastases from colorectal cancer — literature and institutional review. Langenbecks Arch. Surg., 384: 344–353, 1999.

    Article  Google Scholar 

  22. v. Scheel, J.: Invasive procedures for antineoplastic chemotherapy. In: Naumann et al. (eds.): Head and Neck Surgery. Stuttgart, New York: Thieme, 1998.

    Google Scholar 

  23. Gerlowski, L.E. and Jain, R.K. Microvascular permeability of normal and neoplastic tissues. Microvascular Research 31: 288–305, 1986.

    Article  Google Scholar 

  24. Swistel AJ, Bading JR and Raaf JH Intraarterial versus intravenous Adriamycin in the VX2 tumor system. Cancer (Phila.) 53: 1397–1404, 1984

    Article  Google Scholar 

  25. Senyei, A., Widder, K., and Czerlinski, C. Magnetic guidance of drug carrying microspheres. J. Appl. Physiol., 49: 3578–3583, 1978.

    Article  ADS  Google Scholar 

  26. Goodwin, S., Peterson, C., Hoh, C., Bittner, C. Targeting and retention of magnetic targeted carriers. J. Magn. Magn. Mater., 194: 132–139, 1999.

    Article  ADS  Google Scholar 

  27. Bergemann, C., Müller-Schulte, D., Oster, J., à Brassard, L., Lübbe, A.S. Magnetic ionexchange nano-and microparticles for medical, biomedical and molecular biological applications. J. Magn. Magn. Mater.,194: 45–52, 1999.

    Article  ADS  Google Scholar 

  28. Lübbe, A. S., Bergemann, Ch., Huhnt, W., Fricke, T., Riess, H., Brock, J. W., and Huhn, D. Preclinical experiences with magnetic drug targeting: tolerance and efficacy. Cancer Research, 56: 4694–4701, 1996.

    Google Scholar 

  29. Lübbe, A. S., Bergemann, Ch., Riess, H. et al. Clinical experiences with magnetic drug targeting: a phase I study with 4’-epidoxorubicin in 14 patients with advanced solid tumors. Cancer research, 56: 4686–4693, 1996.

    Google Scholar 

  30. Taupitz, M., Wagner, S., Hamm, B., Dienemann, D., Lawaczeck, R. and Wolf, K.J. MR Lymphography using iron oxide particles. Detection of lymph node metastases in the VX2 rabbit tumor model. Acta Radiologica, 34:10–15, 1993.

    Article  Google Scholar 

  31. Widder, K.J., Senyei, A.E. and Scarpelli, D.G. Magnetic microspheres: a model system for site specific drug deleivery in vivo. Proc. Soc. Exp. Biol. Med. 58: 141–146, 1978.

    Google Scholar 

  32. Bacon, B.R., Park, D. D., Saini, S., Groman, E. V., Hahn, P. F., Compton, C. C., and Ferrucci, J. T. Ferrite particles: A new magnetic resonance imaging contrast agent. Lack of acute or chronic hepatoxicity after intravenous administration. J. Lab. Clin. Med., 110: 164–171, 1987.

    Google Scholar 

  33. Rummeny, E., Weissleder, R., Stark, D. D., Elizondo, G. and Ferrucci, J. T. Magnetic resonance tomography of focal liver and spleen lesions. Experiences using ferrite, a new RES-specific MR contrast medium. Radiologe 28: 380–386, 1988.

    Google Scholar 

  34. Häfeli, U.O., Pauer, G.J., Roberts, W.K., Humm, J.L. and Macklis, R.M. Magnetically targeted microspheres for intracavitary and intraspinal Y-90 radiotharpy. In: U. Häfeli and W. Schütt (eds.), Scientific and clinical applications of magnetic carriers, pp 501–516, New York and London: Plenum press, 1997.

    Google Scholar 

  35. Jordan, A., Scholz, R., Wust, P. et al. Effects of magnetic fluid hyperthermia (MFH) on C3H mammary carcinoma in vivo. Int. J. Hyperthermia, 13: 587–605, 1997.

    Article  Google Scholar 

  36. Partridge, M., Phillips, E., Francis, R., Li, S.R. Immunomagnetic seperation for enrichment and sensitive detection of disseminated tumour cells in patients with head and neck SCC. J. Pathol., 189: 368–377, 1999.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Alexiou, C., Schmid, R., Jurgons, R., Bergemann, C., Arnold, W., Parak, F.G. (2002). Targeted Tumor Therapy with “Magnetic Drug Targeting”: Therapeutic Efficacy of Ferrofluid Bound Mitoxantrone. In: Odenbach, S. (eds) Ferrofluids. Lecture Notes in Physics, vol 594. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-45646-5_12

Download citation

  • DOI: https://doi.org/10.1007/3-540-45646-5_12

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-43978-3

  • Online ISBN: 978-3-540-45646-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics