{{Infobox interventions | Name = Radioimmunotherapy | Image = Radioimmunotherapy schematic.png| Caption = Schematic of radioimmunotherapy (RIT)| ICD10 = | ICD9 = {{ICD9proc|92.28}} | MeshID = D016499 | Synonyms = RIT| }} '''Radioimmunotherapy''' (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell.<ref>{{cite journal |last1=Milenic |first1=Diane E. |last2=Brady |first2=Erik D. |last3=Brechbiel |first3=Martin W. |title=Antibody-targeted radiation cancer therapy |journal=Nature Reviews Drug Discovery |date=June 2004 |volume=3 |issue=6 |pages=488–499 |doi=10.1038/nrd1413 |pmid=15173838|s2cid=22166498 |url=https://zenodo.org/record/1233515 }}</ref> 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== {{expand list|date=February 2011}} {| class="wikitable" ! Name !! Description !! FDA status !! EMA status |- | Ibritumomab tiuxetan (Zevalin) || monoclonal antibody anti-CD20 conjugated to a molecule that chelates Yttrium-90. || Approved (2002)<ref>[https://web.archive.org/web/20021113021831/http://www.fda.gov/OHRMS/DOCKETS/ac/01/slides/3782s2_02_idec/index.htm FIbritumomab Tiuxetan (Zevalin™) Radioimmunotherapy of Non-Hodgkin’s Lymphoma]</ref><ref>Rao AV, Akabani G, Rizzieri DA. Radioimmunotherapy for Non-Hodgkin's Lymphoma. Clin Med Res. 2005 Aug;3(3):157-65.</ref> || Authorised (2004)<ref>{{cite web |title=Zevalin |url=https://www.ema.europa.eu/en/medicines/human/EPAR/zevalin |website=European Medicines Agency |date=8 December 2017 |accessdate=8 November 2020}}</ref> |- | Iodine (<sup>131</sup>I) tositumomab (Bexxar) || links a molecule containing Iodine-131 to an anti-CD20 monoclonal antibody || Approved (2003)<ref>[https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/tosicor062703L.htm Tositumomab and Iodine I 131 Tositumomab – Product Approval Information – Licensing Action<!-- Bot generated title -->]</ref> <br /> Withdrawn (2014)<ref name=Timmerman2013>{{cite web | url = http://www.xconomy.com/national/2013/08/26/why-good-drugs-sometimes-fail-in-the-market-the-bexxar-story/ | title = Why Good Drugs Sometimes Fail: The Bexxar Story| work = Xconomy| date = 2013-08-26}}</ref> || Orphan drug (2003)<br /> Withdrawn (2015)<ref>{{cite web |title=EU/3/03/136 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu303136 |website=European Medicines Agency |date=12 December 2005 |accessdate=8 November 2020}}</ref> |- | Lutetium (<sup>177</sup>Lu) lilotomab satetraxetan (Betalutin) || combination of lutetium-177 and an anti-CD37 monoclonal antibody || Fast track (2020)<ref>{{cite news |title=FDA grants fast track status to Betalutin for marginal zone lymphoma |url=https://www.healio.com/news/hematology-oncology/20200629/fda-grants-fast-track-status-to-betalutin-for-marginal-zone-lymphoma |work=Healio |date=29 June 2020}}</ref> || Orphan drug (2020)<ref>{{cite web |title=EU/3/20/2280 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202280 |website=European Medicines Agency |date=19 August 2020 |accessdate=8 November 2020}}</ref> |}
<sup>131</sup>I tositumomab and <sup>90</sup>Y 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.<ref>{{cite journal |last1=Bodet-Milin |first1=Caroline |last2=Kraeber-Bodéré |first2=Françoise |last3=Eugène |first3=Thomas |last4=Guérard |first4=François |last5=Gaschet |first5=Joëlle |last6=Bailly |first6=Clément |last7=Mougin |first7=Marie |last8=Bourgeois |first8=Mickaël |last9=Faivre-Chauvet |first9=Alain |last10=Chérel |first10=Michel |last11=Chevallier |first11=Patrice |title=Radioimmunotherapy for Treatment of Acute Leukemia |journal=Seminars in Nuclear Medicine |date=March 2016 |volume=46 |issue=2 |pages=135–146 |doi=10.1053/j.semnuclmed.2015.10.007 |pmid=26897718}}</ref><ref>{{cite journal |last1=Pandit-Taskar |first1=Neeta |title=Targeted Radioimmunotherapy and Theranostics with Alpha Emitters |journal=Journal of Medical Imaging and Radiation Sciences |date=December 2019 |volume=50 |issue=4 |pages=S41–S44 |doi=10.1016/j.jmir.2019.07.006 |pmid=31451417 |url=https://www.jmirs.org/article/S1939-8654(19)30348-0/fulltext|doi-access=free |url-access=subscription }}</ref>
<sup>90</sup>Y-FF-21101 is a monoclonal antibody against P-cadherin radiolabeled with yttrium-90.<ref>{{cite journal |last1=Subbiah |first1=Vivek |last2=Erwin |first2=William |last3=Mawlawi |first3=Osama |last4=McCoy |first4=Asa |last5=Wages |first5=David |last6=Wheeler |first6=Catherine |last7=Gonzalez-Lepera |first7=Carlos |last8=Liu |first8=Holly |last9=Macapinlac |first9=Homer |last10=Meric-Bernstam |first10=Funda |last11=Hong |first11=David S. |last12=Pant |first12=Shubham |last13=Le |first13=Dao |last14=Santos |first14=Elmer |last15=Gonzalez |first15=Jose |last16=Roszik |first16=Jason |last17=Suzuki |first17=Takeaki |last18=Subach |first18=Ruth Ann |last19=Madden |first19=Timothy |last20=Johansen |first20=Mary |last21=Nomura |first21=Fumiko |last22=Satoh |first22=Hirokazu |last23=Matsuura |first23=Tadashi |last24=Kajita |first24=Masamichi |last25=Nakamura |first25=Eri |last26=Funase |first26=Yuichi |last27=Matsushima |first27=Satoshi |last28=Ravizzini |first28=Gregory |title=Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90 Y-FF-21101 Monoclonal Antibody in Solid Tumors |journal=Clinical Cancer Research |date=18 August 2020 |volume=26 |issue=22 |pages=1078–0432.CCR–20-0037 |doi=10.1158/1078-0432.CCR-20-0037 |pmid=32816889|doi-access=free }}</ref> It is one of several RIT treatments under investigation intending to treat solid tumors.<ref>{{cite journal |last1=Zaheer |first1=Javeria |last2=Kim |first2=Hyeongi |last3=Lee |first3=Yong-Jin |last4=Kim |first4=Jin Su |last5=Lim |first5=Sang Moo |title=Combination Radioimmunotherapy Strategies for Solid Tumors |journal=International Journal of Molecular Sciences |date=8 November 2019 |volume=20 |issue=22 |pages=5579 |doi=10.3390/ijms20225579 |pmid=31717302 |pmc=6888084|doi-access=free }}</ref> A phase I clinical trial began in 2015.<ref>[https://clinicaltrials.gov/ct2/show/NCT02454010 A Phase 1 Dose-escalation Study of Radio- Labeled Antibody, FF-21101(90Y) for the Treatment of Advanced Cancer]</ref>
==Other applications (non-approved indications)== Other types of cancer for which RIT has therapeutic potential include prostate cancer,<ref>Smith-Jones PM. Radioimmunotherapy of prostate cancer. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):297-304.</ref> metastatic melanoma,<ref>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.</ref> ovarian cancer,<ref name="Radioimmunotherapy">Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96.</ref> neoplastic meningitis,<ref name="Radioimmunotherapy" /> leukemia,<ref>Burke JM, Jurcic JG. Radioimmunotherapy of leukemia. Adv Pharmacol. 2004;51:185-208.</ref> high-grade brain glioma,<ref>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.</ref> and metastatic colorectal cancer.<ref>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</ref>
Components of the extracellular matrix and the tumor microenvironment can also be targeted by radioimmunotherapy, such as Netrin-1 <ref>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 </ref> (an axon guidance protein) and FAP (a marker for cancer associated fibroblasts).<ref>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</ref>
==References== {{Reflist|2}}
==External links== * {{MeshName|Radioimmunotherapy}} * [http://www.radioimmunotherapy.org Radioimmunotherapy.org] {{Webarchive|url=https://web.archive.org/web/20170423213106/http://radioimmunotherapy.org/ |date=2017-04-23 }}
{{Radiation oncology}}
Category:Radiation therapy