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Radioimmunotherapy (RIT) uses an
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
labeled with a radionuclide to deliver cytotoxic radiation to a target cell. It is a form of
unsealed source radiotherapy Radionuclide therapy (RNT, also known as unsealed source radiotherapy or molecular radiotherapy) uses radioactive substances called radiopharmaceuticals to treat medical conditions, particularly cancer. These are introduced into the body by vario ...
. In
cancer therapy Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, an antibody with specificity for a tumor-associated
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
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 A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
or is not accessible in normal cells.


History of available agents

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 Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of hematological malignancy, blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever ...
. This means they are used in patients whose lymphoma is refractory to conventional
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...
and the monoclonal antibody
rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric pa ...
.


Agents in clinical development

A set of radioimmunotherapy drugs that rely upon an alpha-emitting isotope (e.g.,
bismuth-213 Bismuth (83Bi) has 41 known isotopes, ranging from 184Bi to 224Bi. Bismuth has no stable isotopes, but does have one very long-lived isotope; thus, the standard atomic weight can be given as . Although bismuth-209 is now known to be unstable, it h ...
or, preferably,
actinium-225 Actinium-225 (225Ac, Ac-225) is an isotope of actinium. It undergoes alpha decay to francium-221 with a half-life of 10 days, and is an intermediate decay product in the neptunium series (the decay chain starting at 237Np). Except for minus ...
), rather than a
beta emitter In nuclear physics, beta decay (β-decay) is a type of radioactive decay in which a beta particle (fast energetic electron or positron) is emitted from an atomic nucleus, transforming the original nuclide to an isobar of that nuclide. For exam ...
, as the killing source of radiation is being developed. Several
phase II clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
s for the treatment of
acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...
have been carried out using alpha-emitting RITs. 90Y-FF-21101 is a monoclonal antibody against P-cadherin
radiolabel A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...
ed with
yttrium-90 Yttrium-90 () is an isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer. Decay undergoes β− decay to zirconium-90 with a half-life of 64.1 hours and a decay energy of 2.28 M ...
. It is one of several RIT treatments under investigation intending to treat
solid tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s. A
phase I clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...
began in 2015.


Other applications (non-approved indications)

Other types of cancer for which RIT has therapeutic potential include prostate cancer, metastatic melanoma,
ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...
,Zalutsky MR, Pozzi OR. Radioimmunotherapy with alpha-particle emitting radionuclides. Q J Nucl Med Mol Imaging. 2004 Dec;48(4):289-96. neoplastic meningitis,
leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
, high-grade brain
glioma A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms ...
, and metastatic colorectal cancer.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.


References


External links

*
Radioimmunotherapy.org
{{Radiation oncology Radiation therapy