Radioimmunotherapy

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Template:Infobox interventions Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell.[1] It is a form of unsealed source radiotherapy. 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

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Name Description FDA status EMA status
Ibritumomab tiuxetan (Zevalin) monoclonal antibody anti-CD20 conjugated to a molecule that chelates Yttrium-90. Approved (2002)[2][3] Authorised (2004)[4]
Iodine (131I) tositumomab (Bexxar) links a molecule containing Iodine-131 to an anti-CD20 monoclonal antibody Approved (2003)[5]
Withdrawn (2014)[6]		 Orphan drug (2003)
Withdrawn (2015)[7]
Lutetium (177Lu) lilotomab satetraxetan (Betalutin) combination of lutetium-177 and an anti-CD37 monoclonal antibody Fast track (2020)[8] Orphan drug (2020)[9]

131I tositumomab and 90Y ibritumomab tiuxetan 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. Several phase II clinical trials for the treatment of acute myeloid leukemia have been carried out using alpha-emitting RITs.[10][11]

90Y-FF-21101 is a monoclonal antibody against P-cadherin radiolabeled with yttrium-90.[12] It is one of several RIT treatments under investigation intending to treat solid tumors.[13] A phase I clinical trial began in 2015.[14]

Other applications (non-approved indications)

Other types of cancer for which RIT has therapeutic potential include prostate cancer,[15] metastatic melanoma,[16] ovarian cancer,[17] neoplastic meningitis,[17] leukemia,[18] high-grade brain glioma,[19] and metastatic colorectal cancer.[20]

Components of the extracellular matrix and the tumor microenvironment can also be targeted by radioimmunotherapy, such as Netrin-1 [21] (an axon guidance protein) and FAP (a marker for cancer associated fibroblasts).[22]

References

Template:Reflist

External links

Template:Radiation oncology

  1. ↑ Script error: No such module "Citation/CS1".
  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. ↑ Script error: No such module "citation/CS1".
  5. ↑ Tositumomab and Iodine I 131 Tositumomab – Product Approval Information – Licensing Action
  6. ↑ Script error: No such module "citation/CS1".
  7. ↑ Script error: No such module "citation/CS1".
  8. ↑ Script error: No such module "citation/CS1".
  9. ↑ Script error: No such module "citation/CS1".
  10. ↑ Script error: No such module "Citation/CS1".
  11. ↑ Script error: No such module "Citation/CS1".
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  13. ↑ Script error: No such module "Citation/CS1".
  14. ↑ A Phase 1 Dose-escalation Study of Radio- Labeled Antibody, FF-21101(90Y) for the Treatment of Advanced Cancer
  15. ↑ Smith-Jones PM. Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):297-304.
  16. ↑ 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.
  17. ↑ a b Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96.
  18. ↑ Burke JM, Jurcic JG. Radioimmunotherapy of leukemia. Adv Pharmacol. 2004;51:185-208.
  19. ↑ 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.
  20. ↑ 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
  21. ↑ Kryza D, Wischhusen J, Richaud M, Hervieu M, Sidi Boumedine J, Delcros JG, Besse S, Baudier T, Laval PA, Breusa S, Boutault E, Clermidy H, Rama N, Ducarouge B, Devouassoux-Shisheboran M, Chezal JM, Giraudet AL, Walter T, Mehlen P, Sarrut D, Gibert B.From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors. EMBO Mol Med. 2023 Apr 11;15(4):e16732. doi: 10.15252/emmm.202216732. Epub 2023 Mar 6. PMID: 36876343
  22. ↑ Marko Magdi Abdou Sidrak, Maria Silvia De Feo, Ferdinando Corica, Joana Gorica, Miriam Conte, Luca Filippi, Orazio Schillaci, Giuseppe De Vincentis, and Viviana Frantellizzi1,Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review Int J Mol Sci. 2023 Feb; 24(4): 3863. Published online 2023 Feb 15. doi: 10.3390/ijms24043863
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