Radioimmunotherapy
Encyclopedia
Radioimmunotherapy uses an antibody
labeled with a radionuclide
to deliver cytotoxic radiation to a target cell. 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.
These medications were the first agents of radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkins lymphoma. This means they are used in patients whose lymphoma is refractory to conventional chemotherapy
and the monoclonal antibody rituximab
.
Actinium Pharmaceuticals (www.actiniumpharmaceuticals.com) is developing a set of radioimmunotherapy drugs that rely upon an alpha particle-emitting isotope (e.g., Bi-213 or, preferably, Ac-225), rather than a beta emitter, as the killing source of radiation. The most developed drug is directed to treating acute myeloid leukemia and is in patient clinical trials (as of the fourth quarter of 2010).
, metastatic melanoma
, ovarian cancer
, neoplastic meningitis
, leukemia
, high-grade brain glioma
, and metastatic colorectal cancer
.
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
labeled with a radionuclide
Radionuclide
A radionuclide is an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide, in this process, undergoes radioactive decay, and emits gamma...
to deliver cytotoxic radiation to a target cell. 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
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
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
| U.S. FDA approval | Name | Description >- | 2002 |
Ibritumomab tiuxetan Ibritumomab tiuxetan Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for some forms of B cell non-Hodgkin's lymphoma, a lymphoproliferative disorder and thus affects the lymphatic system... (Zevalin) |
CD20 CD20 B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity.... conjugated to a molecule Molecule A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge... that chelates Yttrium-90 Yttrium-90 Yttrium-90 is a medically significant isotope of yttrium.It emits beta rays of 2.3 MeV.Yttrium-90 is a decay product of Strontium-90 which makes up about 5% of the Nuclear daughter isotopes when Uranium is fissioned.... . >- | 2003 |
Iodine (131I) tositumomab Tositumomab Tositumomab is a drug for the treatment of follicular lymphoma. It is a IgG2a anti-CD20 monoclonal antibody derived from immortalized mouse cells.... (Bexxar) |
links a molecule Molecule A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge... containing Iodine-131 Iodine-131 Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical... to the monoclonal antibody anti-CD20 CD20 B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity.... . |
These medications were the first agents of radioimmunotherapy, and they were approved for the treatment of refractory non-Hodgkins lymphoma. This means they are used in patients whose lymphoma is refractory to conventional chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and the monoclonal antibody rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
.
Actinium Pharmaceuticals (www.actiniumpharmaceuticals.com) is developing a set of radioimmunotherapy drugs that rely upon an alpha particle-emitting isotope (e.g., Bi-213 or, preferably, Ac-225), rather than a beta emitter, as the killing source of radiation. The most developed drug is directed to treating acute myeloid leukemia and is in patient clinical trials (as of the fourth quarter of 2010).
Other applications (non-approved indications)
Other types of cancer for which RIT has therapeutic potential include prostate cancerProstate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, metastatic melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
, ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
, neoplastic meningitis
Neoplastic meningitis
Neoplastic or malignant meningitis, also described with the older term meningitis carcinomatosa is the development of meningitis due to the infiltration of the subarachnoid space with cancer cells...
, leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, high-grade brain glioma
Glioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, and metastatic colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
.