Skip to main content

Radioimmunotherapy (RIT)

  • Chapter
  • First Online:
Radiopharmaceuticals for Therapy

Abstract

Immunotherapy is a therapeutic modality that utilizes the antibody–antigen mechanism to enhance or suppress the immune response for management of a range of disorders (Baxevanis et al., Crit Rev Clin Lab Sci 46(4):167–189, 2009; King et al., QJM 101(9):675–683, 2008; Krüger et al., Histol Histopathol 22(6):687–669, 2007; Matzku and Zöller, Drugs Aging 18(9):639–664, 2001). Antibodies are glycoproteins produced by lymphocytes to combat infection and foreign organisms utilizing a system that has evolved over millions of years to protect animals from environment insults (Scott et al., Nature Rev Cancer 12:278–287, 2012). As part of the immune regulatory system, antibodies are also widely used as vaccines for treating or preventing infections as one of the most important disease control tools in medicine. Antibodies are also are being developed for use against other diseases, including cancers and virus-based diseases. In this chapter, the biology and function of antibodies and antigens are first described in detail, as a basis for the introduction of the development and use of radioimmunotherapy (RIT), where therapeutic radioisotopes are attached to targeting antigens as a unique strategy to deliver ionizing radiation to the target site. The basics of some key clinical disorders such as lymphomas are also described, since their treatment with radiolabeled antibodies represents a spectacular success in this field.

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 EPUB and 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 159.99
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

References

  • Ahlskog J, Paganelli G, Neri D. Vascular tumor targeting. Q J Nucl Med Mol Imaging. 2006;50:296–309.

    PubMed  CAS  Google Scholar 

  • Anand P, Kunnumakara AB, Sundaram C. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008;25(9):2097–116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Azinovic I, DeNardo GL, Lamborn KR, et al. Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies. Cancer Immunol Immunother. 2006;55:1451–8.

    Article  PubMed  CAS  Google Scholar 

  • Barendswaard EC, Humm JL, O’Donoghue JA. Therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft. J Nucl Med. 2001;42:1251–6.

    PubMed  CAS  Google Scholar 

  • Baxevanis CN, Perez SA, Papamichail M. Cancer immunotherapy. Crit Rev Clin Lab Sci. 2009;46(4):167–89.

    Article  PubMed  CAS  Google Scholar 

  • Behr TM, Sgouros G, Vougiokas V, et al. Therapeutic efficacy and dose limiting toxicity of Auger-electron versus beta emitters in radioimmunotherapy with internalizing antibodies: evaluation of 125I-versus 131I-labeled CO17-1A in a human colorectal cancer model. Int J Cancer. 1998;76:738–48.

    Article  PubMed  CAS  Google Scholar 

  • Berenson A. Market forces cited in lymphoma drugs’ Disuse. New York Times, 14 Jul 2007.

    Google Scholar 

  • Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9:653–60.

    Article  PubMed  CAS  Google Scholar 

  • Caron PC, Schwartz MA, Co MS. Murine and humanized constructs of monoclonal antibody M195 (anti-CD33) for the therapy of acute myelogenous leukemia. Cancer. 1994;73:1049–56.

    Article  PubMed  CAS  Google Scholar 

  • Chatal JF, Mahé M. Therapeutic use of radiolabelled antibodies. In: Murray IPC, Ell PJ, editors. Nuclear medicine in clinical diagnosis and treatment. Edinburgh: Churchill Livingstone; 1998. p. 1101–14.

    Google Scholar 

  • Dillman RD. Monoclonal antibody therapy. In: Oldman RK, editor. Principles of cancer biotherapy. 4th ed. Norwell: Kluwer Academic Publishers; 2003. p. 329–90.

    Chapter  Google Scholar 

  • Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27–31.

    Article  PubMed  CAS  Google Scholar 

  • Goldenberg DM. The role of radiolabeled antibodies in the treatment of non-Hodgkin’s lymphoma: the coming of age of radioimmunotherapy. Crit Rev Oncol Hematol. 2001;39:195–201.

    Article  PubMed  CAS  Google Scholar 

  • Goldenberg DM, Sharkey RM. Advances in cancer therapy with radiolabeled monoclonal antibodies. Q J Nucl Med Mol Imaging. 2006;50:248–64.

    PubMed  CAS  Google Scholar 

  • Goldenberg DM, Gaffar SA, Bennett SJ, et al. Experimental radioimmunotherapy of a xenografted human colonic tumor (GW-39) producing carcinoembryonic antigen. Cancer Res. 1981;41:4354–60.

    PubMed  CAS  Google Scholar 

  • Goldsmith SJ. Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin Nucl Med. 2010;40:122–35.

    Article  PubMed  Google Scholar 

  • Griffiths GL, Govindan SV, Sgouros G, et al. Cytotoxicity with auger electron- emitting radionuclides delivered by antibodies. Int J Cancer. 1999;81:985–92.

    Article  PubMed  CAS  Google Scholar 

  • Humm JL. A microdosimetric model of astatine-211 labeled antibodies for radioimmunotherapy. Int J Radiat Oncol Biol Phys. 1987;13:1767–73.

    Article  PubMed  CAS  Google Scholar 

  • Humm JL. Problems and advances in the dosimetry of radionuclide targeted therapy. In: Bihl S, Luise M, Bihl H, Wannenmacher M, editors. Systemic radiotherapy with monoclonal antibodies, options and problems. Berlin/Heidelberg/Germany: Springer; 1996. p. 37–66.

    Chapter  Google Scholar 

  • Kaminski MS, Zasadny KR, Francis IR, et al. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993;329:459–65.

    Article  PubMed  CAS  Google Scholar 

  • Kawashima H. Radioimmunotherapy: a specific treatment protocol for cancer by cytotoxic radioisotopes conjugated to antibodies. Scientific World Journal. 2014;49:2061.

    Google Scholar 

  • King J, Waxman J, Stauss H. Advances in tumour immunotherapy. QJM. 2008;101(9):675–83.

    Article  PubMed  CAS  Google Scholar 

  • Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7.

    Article  PubMed  CAS  Google Scholar 

  • Kozak RW, Atcher RW, Gansow OA. Bismuth-212-labeled anti-TAC monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy. Proc Natl Acad Sci. 1986;83:474–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Krüger C, Greten TF, Korangy F. Immune based therapies in cancer. Histol Histopathol. 2007;22(6):687–96.

    PubMed  Google Scholar 

  • Küppers R. Molecular biology of Hodgkin’s lymphoma. Adv Cancer Res. 2002;44:277–312.

    Article  Google Scholar 

  • Matzku S, Zöller M. Specific immunotherapy of cancer in elderly patients. Drugs Aging. 2001;18(9):639–64.

    Article  PubMed  CAS  Google Scholar 

  • Michel RB, Andrews PM, Rosario AV, et al. 177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo. Nucl Med Biol. 2005;32:269–78.

    Article  PubMed  CAS  Google Scholar 

  • Müschen M, Rajewsky K, Bräuninger A, et al. Rare occurrence of classical Hodgkin’s disease as a T cell lymphoma. J Exp Med. 2000;191:387–94.

    Article  PubMed  PubMed Central  Google Scholar 

  • Postema EJ, Boerman OC, Oyen WJ, et al. Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma. Eur J Nucl Med. 2001;28:1725–35.

    Article  PubMed  CAS  Google Scholar 

  • Sautter-Bihl ML, Herbold G, Bihl H. Minimal residual disease: a target for radioimmunotherapy with 131I-labeled monoclonal antibodies? Some dosimetric considerations. Recent Results Cancer Res. 1996;141:67–75.

    Article  PubMed  CAS  Google Scholar 

  • Schlom J, Colcher D, Siler K, et al. Tumor targeting with monoclonal antibody B72.3: experimental and clinical results. Cancer Treat Res. 1990;51:313–35.

    Article  PubMed  CAS  Google Scholar 

  • Schroff RW, Foon KA, Beatty SM, et al. Human antimurine immunoglobulin responses in patients receiving MoAb therapy. Cancer Res. 1985;45:879–85.

    PubMed  CAS  Google Scholar 

  • Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012;12:278–87.

    Article  PubMed  CAS  Google Scholar 

  • Seitz V, Hummel M, Marafioti T, et al. Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease. Blood. 2000;95:3020–4.

    PubMed  CAS  Google Scholar 

  • Sharkey RM, Brenner A, Burton J, et al. Radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response? J Nucl Med. 2003;44:2000–18.

    PubMed  CAS  Google Scholar 

  • Tosato G, Magrath IT, Koski IR, et al. B cell differentiation and immunoregulatory T cell function in human cord blood lymphocytes. J Clin Invest. 1980;66(2):383–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trikha M, Yan L, Nakada MT. Monoclonal antibodies as therapeutics in oncology. Curr Opin Biotechnol. 2002;13:609–14.

    Article  PubMed  CAS  Google Scholar 

  • Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol. 2010;10:317–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weiss LM, Chan JKC, MacLennan K, et al. Pathology of classical Hodgkin’s disease. In: Mauch PM, Armitage JO, Diehl V, Hoppe RT, Weiss LM, editors. Hodgkin’s disease. Philadelphia: Lippincott Williams & Wilkins; 1999. p. 101–20.

    Google Scholar 

  • White CA, Berlfein JR, Grillo-Lopez AJ. Antibody-targeted immunotherapy for treatment of non-Hodgkin’s lymphoma. Curr Pharm Biotechnol. 2000;1:303–12.

    Article  PubMed  CAS  Google Scholar 

  • Winter G, Harris WJ. Humanized antibodies. Trends Pharmacol Sci. 1993;14:139–43.

    Article  PubMed  CAS  Google Scholar 

  • Wiseman GA, White CA, Sparks RB. Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. Crit Rev Oncol Hematol. 2001;39:181–94.

    Article  PubMed  CAS  Google Scholar 

  • Witzig TE. Radioimmunotherapy for patients with relapsed B-cell non- Hodgkin lymphoma. Cancer Chemother Pharmacol. 2001;48:91S–5.

    Article  Google Scholar 

  • Zalutsky MR, Schuster JM, Garg PK, et al. Two approaches for enhancing radioimmunotherapy: a emitters and hyperthermia. In: Bihl SML, Bihl H, Wannenmacher M, editors. Systemic radiotherapy with monoclonal antibodies, options and problems. Berlin/Heidelberg/Germany: Springer; 1996. p. 101–22.

    Chapter  Google Scholar 

  • Zola H, Swart B. The human leucocyte differentiation antigens (HLDA) workshops: the evolving role of antibodies in research, diagnosis and therapy. Cell Res. 2005;15:691–4.

    Article  PubMed  CAS  Google Scholar 

  • Zola H, Swart B, Nicholson I, et al. CD molecules 2005: human cell differentiation molecules. Blood. 2005;106(9):3123–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer India

About this chapter

Cite this chapter

Knapp, F.F.(., Dash, A. (2016). Radioimmunotherapy (RIT). In: Radiopharmaceuticals for Therapy . Springer, New Delhi. https://doi.org/10.1007/978-81-322-2607-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-81-322-2607-9_9

  • Published:

  • Publisher Name: Springer, New Delhi

  • Print ISBN: 978-81-322-2606-2

  • Online ISBN: 978-81-322-2607-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics