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Radioimmunotherapy
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Radioimmunotherapy
Schematic of radioimmunotherapy (RIT)
Other namesRIT
ICD-9-CM92.28
MeSHD016499

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Withdrawn (2014)[6]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Withdrawn (2015)[7]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

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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)

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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

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