Radioimmunotherapy

Radioimmunotherapy uses 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.

Radioimmunotherapy
Other namesRIT
ICD-9-CM92.28
MeSHD016499

History of available agents
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U.S. FDA approvalNameDescription
2002[2][3]Ibritumomab tiuxetan (Zevalin)monoclonal antibody anti-CD20 conjugated to a molecule that chelates Yttrium-90.
2003[4]Iodine (131I) tositumomab (Bexxar)links a molecule containing Iodine-131 to an anti-CD20 monoclonal antibody.
It was withdrawn in 2014.[5]

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

Agents in clinical development

A set of radioimmunotherapy drugs that rely upon an alpha-emitting isotope (e.g., bismuth-213 or, preferably, actinium-225), rather than a beta emitter, as the killing source of radiation is being developed. The most developed drug is directed to treating acute myeloid leukemia and is in patient clinical trials (as of the fourth quarter of 2010).

FF-21101(90Y) is a monoclonal antibody against P-cadherin radiolabeled with yttrium-90 (90Y).[6][7]

Other applications (non-approved indications)

Other types of cancer for which RIT has therapeutic potential include prostate cancer,[8] metastatic melanoma,[9] ovarian cancer,[10] neoplastic meningitis,[10] leukemia,[11] high-grade brain glioma,[12] and metastatic colorectal cancer.[13]

References
  1. Milenic DE, Brady ED and Brechbiel MW. Antibody-targeted radiation cancer therapy. Nature Rev Drug Discovery 2004; 3:488-98.
  2. FIbritumomab Tiuxetan (Zevalin™) Radioimmunotherapy of Non-Hodgkin’s Lymphoma
  3. Rao AV, Akabani G, Rizzieri DA. Radioimmunotherapy for Non-Hodgkin's Lymphoma. Clin Med Res. 2005 Aug;3(3):157-65.
  4. Tositumomab and Iodine I 131 Tositumomab - Product Approval Information - Licensing Action
  5. "Why Good Drugs Sometimes Fail: The Bexxar Story". 2013-08-26.
  6. Strategia Therapeutics Initiates a Phase 1 Clinical Trial of the Radioimmunotherapeutic “FF-21101" For FUJIFILM in Patients with Advanced Cancers
  7. A Phase 1 Dose-escalation Study of Radio- Labeled Antibody, FF-21101(90Y) for the Treatment of Advanced Cancer
  8. Smith-Jones PM. Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):297-304.
  9. 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.
  10. Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96.
  11. Burke JM, Jurcic JG. Radioimmunotherapy of leukemia. Adv Pharmacol. 2004;51:185-208.
  12. 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.
  13. 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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