Radioimmunotherapy | |
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![]() Schematic of radioimmunotherapy (RIT) | |
Other names | RIT |
ICD-9-CM | 92.28 |
MeSH | D016499 |
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.
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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[5] Withdrawn (2014) [6] |
Orphan drug (2003) Withdrawn (2015) [7] |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.
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 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]
Radioimmunotherapy | |
---|---|
![]() Schematic of radioimmunotherapy (RIT) | |
Other names | RIT |
ICD-9-CM | 92.28 |
MeSH | D016499 |
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.
![]() |
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.
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 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]