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Magnetically Targeted Microspheres for Intracavitary and Intraspinal Y-90 Radiotherapy

  • Urs O. Häfeli
  • Gayle J. Pauer
  • William K. Roberts
  • John L. Humm
  • Roger M. Macklis
Chapter

Abstract

Targeted approaches to radiotherapy using long-range ß-emitting isotopes linked to biologically selective molecules such as antibodies have shown limited success, primarily due to the relatively small amounts of radioactive material that actually reach the tumor sites. Tissuecompatible magnetic microspheres, however, can incorporate very high concentrations of radioactive material and can be maneuvered within the body through the use of an external magnetic field like that generated by a clinical MRI machine. Magnetic microspheres (MMS), 10–30 gm in diameter, were prepared from poly (lactic acid) by a solvent-evaporation method, contained 30 weight% magnetite and were loaded shortly before injection with the ß-emitting radioisotope 90Y. This radiopharmaceutical was tested in vivo in two animal models. The results from the subcutaneous mouse lymphoma model are promising and show that the locally concentrated magnetic microspheres are able to eradicate more than half of the tumors. The results from an intraspinal glioblastoma model in rats, however, failed to show a significant difference between magnetically targeted radioactive microspheres and radioactive microspheres which had not been subjected to a magnetic field. Nonetheless, both groups of radioactively treated rats lived significantly longer than animals injected with non-radioactive microspheres. Higher magnetic fields and field gradients and more susceptible, smaller magnetic microspheres might be required to achieve intraspinal magnetic targeting.

Keywords

Lactic Acid Magnetic Field Gradient Magnetic Microsphere NdFeB Magnet Magnetic Target 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Gupta PK and Hung CT (1989).Magnetically controlled targeted micro-carrier systems. Life Sci. 44 175–186.CrossRefGoogle Scholar
  2. 2.
    Jain RK (1991). Invited Review: Haemodvnamic and transport barriers to the treatment of solid tumours. Int. J. Radial. Biol. 60 85–100.CrossRefGoogle Scholar
  3. 3.
    Clarke SEM (1994). Antitumor treatment: Radionuclide therapy in oncology. Cancer Treat. Rev. 20 51–71.CrossRefGoogle Scholar
  4. 4.
    Allen BJ and Blagojevic N (1996). Alpha-and beta-emitting radiolanthanides in targeted cancer therapy: The potential role of terbium-149. Nuclear Medicine Communications 17 40–47.CrossRefGoogle Scholar
  5. 5.
    Andrews JC, Walker SC, Ackermann Ri, et al (1994). Hepatic radioembolization with Yttrium-90 containing glass microspheres: Preliminary results and clinical follow up. J. Nucl. Med. 35 1637–1644.Google Scholar
  6. 6.
    Ehrhardt GJ and Day DE (1987). Therapeutic use of Y microspheres. Nucl. Med. Biol. 14 233–242.Google Scholar
  7. 7.
    Stucki G, Bozzone P, Treuer E, et al (1993). Efficacy and safety of radiation synovectomy with Yttrium-90: A retrospective long-term analysis of 164 applications in 82 patients. Brit. J. Rheumatol. 32 383–386.CrossRefGoogle Scholar
  8. 8.
    Rowlinson G and Epenetos AA (1992). Targeted delivery of biologic and other antineoplastic agents. Current Opinion in Oncology 4 1142–1148.CrossRefGoogle Scholar
  9. 9.
    Persaud RD (1988). Biting the magic bullet. Radiolabelled monoclonal antibodies: The next great step forward in the diagnosis and treatment of cancer Medical Hypotheses 27 245–251.CrossRefGoogle Scholar
  10. 10.
    Bradley EW, Chan PC and Adelstein Si (1975). The radiotoxicity of iodine-125 in mammalian cells. Effects on the survival curve of radioiodine incorporated into DNA. Radiat. Res. 64 555–563.CrossRefGoogle Scholar
  11. 11.
    Sahu SK, Kassis AI, Makrigiorgos GM, et al (1995). The effects ofIndium-111 decay on pBR322 DNA. Radiat. Res. 141 193–198.CrossRefGoogle Scholar
  12. 12.
    Humm JL, Howell RW and Rao DV (1994). Dosimetry of Auger-electron-emitting radionuclides: Report No. 3 ofAAPM nuclear medicine task group No. 6 Med. Phys. 21 1901–1915.CrossRefGoogle Scholar
  13. 13.
    Howell RW, Kassis AI, Adelstein SJ, et al (1994). Radiotoxicity of platinum-195m-labeled trans-platinum(II) in mammalian cells. Radiat. Res. 140 55–62.CrossRefGoogle Scholar
  14. 14.
    Macklis RM, Kinsey BM, Kassis AI, et al (1988). Radioimmunotherapy with alpha-particle-emitting immunoconjugates. Science 240 1024–1026.ADSCrossRefGoogle Scholar
  15. 15.
    Zalutsky MR, Garg PK, Friedman HS and Bigner DD (1989). Labeling monoclonal antibodies and F(ab’) 1 fragments with the a-particle-emitting nuclide astatine-211: Preservation of immunoreactivity and in vivo localizing capacity. Proc. Natl. Acad. Sci. USA 86, 7149–7153.ADSCrossRefGoogle Scholar
  16. 16.
    Junghans RP, Dobbs D, Brechbiel MW, et at (1993). Pharmacokinetics and bioactivity of 1,4,7,10-tetraazacyclododecane N,N’,N’’,N’’’-tetraacetic acid (DOTA)-bismuth-conjugated anti-Tac antibody for a-emitter 212 Bi therapy. Cancer Res. 53, 5683–5689.Google Scholar
  17. 17.
    Feinendegen LE and McClure JJ (1996). Workshop: Alpha Emitters for medical therapy. DOE/NE-0113.Google Scholar
  18. 18.
    Häfeli UO, Sweeney SM, Beresford BS, et al (1994). Biodegradable magnetically directed Y-microspheres: Novel agents for targeted intracavitary radiotherapy. J. Biomed. Mat. Res. 28 901–908.CrossRefGoogle Scholar
  19. 19.
    Wise DL, Fellmann TD, Sanderson JE and Wentworth RL (1979). Lactic/glycolic acid polymers. In Drug carriers in biology and medicine. Gregoriadis G (Ed), Academic Press, London, pp. 237–270.Google Scholar
  20. 20.
    Chu CC (1985). The degradation and biocompatibility of suture materials. In CRC critical reviews in bio-compatibility. Williams DF (Ed), CRC Press, Boca Raton, Vol. 1, pp. 261–322.Google Scholar
  21. 21.
    Okada H and Toguchi H (1995). Biodegradable microspheres in drug delivery. Crit. Rev. Ther. Drug Carr. Sys. 12 1–99.CrossRefGoogle Scholar
  22. 22.
    Eldridge JH, Staas JK, Chen D, et al (1993). New advances in vaccine delivery systems. Seminars in Hematology 30 Suppl. 4, 16–25.Google Scholar
  23. 23.
    Tanguay JF, Zidar JP, Phillips HR and Stack RS (1994). Current status of biodegradable stems. Cardiology Clinics 12, 699–713.Google Scholar
  24. 24.
    Hnatowich DJ, Chinol M, Siebecker DA, et al (1988). Patient biodistribution of intraperitoneally administered Y-labeled antibody J. Nucl. Med. 29 1428–1434.Google Scholar
  25. 25.
    Wang S, Quadri SM, Tang XZ, et al (1995). Liver toxicity induced by combined external-beam irradiation and radioimmunoglobulin therapy. Radiat. Res. 141 294–302.CrossRefGoogle Scholar
  26. 26.
    Herpst JM, Klein JL, Leichner PK, et al (1995). Survival of patients with resistant Hodgkin’s disease after polyclonal Yttrium-90 labeled antiferritin treatment. J. Clin. Oncol. 13 2394–2400.Google Scholar
  27. 27.
    Hopkins K, Chandler C, Bullimore J, et al (1995). A pilot study of the treatment of patients with recurrent malignant gliomas with intratumor Yttrium-90 radioimmunoconjugates. Radiother. Oncol. 34 121–131.CrossRefGoogle Scholar
  28. 28.
    Humm JL and Cobb LM (1990). Nonuniformity of tumor dose in radioimmunotherapy. J. Nucl. Med. 31 75–83.Google Scholar
  29. 29.
    Berger MJ (1971). Distribution of absorbed dose around point sources of electrons and beta particles in water and other media. J. Nucl. Med. 12 Suppl. 5, 5–23.ADSGoogle Scholar
  30. 30.
    Berger MJ (1973). Improved point kernels for electron and beta ray dosimetry. NBSIR, 73–107.Google Scholar
  31. 31.
    Häfeli UO, Sweeney SM, Beresford BA, et al (1995). Effective targeting of magnetic radioactive Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary in vitro and in vivo results. Nucl. Med. Biol. 22, 147–155.CrossRefGoogle Scholar
  32. 32.
    Tomayko MM and Reynolds CP (1989). Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother. Pharmacol. 24 148–154.CrossRefGoogle Scholar
  33. 33.
    Kooistra KL, Rodriguez M, Powis G, et al (1986). Development of experimental models for meningeal neoplasia using intrathecal injection of 9L gliosarcoma and walker 256 carcinosarcoma in the rat. Cancer Res. 46, 317–323.CrossRefGoogle Scholar
  34. 34.
    Deutsch M (1988). Medulloblastoma: Staging and treatment outcome. Int. J. Radial. Oncol. Biol. Phys. 14 1103–1107.CrossRefGoogle Scholar
  35. 35.
    Friedman HS, Oakes WJ, Bigner SH, et al (1991). Medulloblastoma tumor: Biological and clinical perspectives. J. Neuro-Oncol. 11 1–15.CrossRefGoogle Scholar
  36. 36.
    Howard MA, Grady MS, Ritter RC, et al (1989). Magnetic movement of a brain thermoceptor. Neurosurgery 24, 444–448.CrossRefGoogle Scholar
  37. 37.
    Grady MS, Howard MA, Broaddus WC, et al (1990). Magnetic stereotaxis: A technique to deliver stereo-tactic hyperthermia. Neurosurgery 27 1010–1016.CrossRefGoogle Scholar
  38. 38.
    Stabin MG (1996). MIRDOSE: Personal computer software for internal dose assessment in nuclear medicine. J. Nucl. Med. 37 538–546.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Urs O. Häfeli
    • 1
  • Gayle J. Pauer
    • 1
  • William K. Roberts
    • 1
  • John L. Humm
    • 1
  • Roger M. Macklis
    • 1
  1. 1.Radiation Oncology Department T28The Cleveland Clinic FoundationClevelandUSA

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