Radioimmunotherapy

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Overview

Radioimmunotherapy (RIT) utilizes an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell[1]. In cancer therapy, an antibody with specificity for a tumor-associated antigen is used to deliver a lethal dose of radiation to the tumor cells. The ability for the antibody to specifically bind to a tumor-associated antigen increases the dose delivered to the tumor cells while decreasing the dose to normal tissues. By its nature, RIT requires a tumor cell to express an antigen that is unique to the neoplasm or is not accessible in normal cells.

History of available agents

FDA approval Name Description
2002[2][3] Ibritumomab tiuxetan (Zevalin) monoclonal antibody anti-CD20 conjugated to a molecule of Yttrium-90.
2003[4] Tositumomab Iodine-131 (Bexxar) conjugates a molecule of Iodine-131 to the monoclonal antibody anti-CD20.

These medications were the first agents of what is known as radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkins lymphoma. This means they are used in patients whose lymphoma is refractory to conventional chemotherapy and the monoclonal antibody rituximab.

Other applications (non-approved indications)

Other types of cancer for which RIT has therapeutic potential include prostate cancer [5], metastatic melanoma [6], ovarian cancer [7], neoplastic meningitis [7] , leukemia [8], high-grade brain glioma [9], and metastatic colorectal cancer [10].

References

  1. Milenic DE, Brady ED and Brechbiel MW. Antibody-targeted radiation cancer therapy. Nature Rev Drug Discovery 2004; 3:488-98.
  2. http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01138.html
  3. Rao AV, Akabani G, Rizzieri DA. Radioimmunotherapy for Non-Hodgkin's Lymphoma. Clin Med Res. 2005 Aug;3(3):157-65.
  4. http://www.fda.gov/cder/biologics/products/tosicor062703.htm
  5. Smith-Jones PM. Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):297-304.
  6. Dadachova E, Nosanchuk JD, Shi L, Schweitzer AD, Frenkel A, Nosanchuk JS, and Casadevall A. Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a monoclonal antibody to melanin. Proc Natl Acad Sci USA 2004;101: 14865-70.
  7. 7.0 7.1 Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96.
  8. Burke JM, Jurcic JG. Radioimmunotherapy of leukemia. Adv Pharmacol. 2004;51:185-208.
  9. Quang TS, Brady LW. Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):972-5.
  10. Wong JY, Shibata S, Williams LE, Kwok CS, Liu A, Chu DZ, Yamauchi DM, Wilczynski S, Ikle DN, Wu AM, Yazaki PJ, Shively JE, Doroshow JH, Raubitschek AA. A Phase I trial of 90Y-anti-carcinoembryonic antigen chimeric T84.66 radioimmunotherapy with 5-fluorouracil in patients with metastatic colorectal cancer. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5842-52.

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