Radioimmunotherapy
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Radioimmunotherapy
Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target cell. 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 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 A set of ...
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Ibritumomab Tiuxetan
Ibritumomab tiuxetan (pronounced ), sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope (either yttrium-90 or indium-111) is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group. Medical use Ibritumomab is used to treat relapsed or refractory, low grade or transformed B cell non-Hodgkin's lymphoma (NHL), a lymphoproliferative disorder, and previously untreated follicular NHL in adult patients who achieve a partial or complete response to first-line chemotherapy. The treatment should not be administered to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve. The treatment starts with an infusions of rituximab. This may be followed by an administration of indium-111 labelled ibritumomab ...
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Tositumomab
Tositumomab is a murine monoclonal antibody which targets the CD20 antigen produced in mammalian cell. It was combined with iodine-131 to produce a radiopharmaceutical for unsealed source radiotherapy, Iodine-131 Tositumomab (branded as Bexxar), for the treatment of non-Hodgkins lymphoma. It is classified as a IgG2a lambda antibody. The drug combination was developed by Corixa which was purchased by GlaxoSmithKline in 2005. It was sold for about $25,000 for one round of treatment. Bexxar competed with Zevalin, until the former's discontinuation in 2014. Clinical use A personalized regimen using Bexxar was approved for the treatment of relapsed or chemotherapy/rituxan-refractory Non-Hodgkin lymphoma in 2003. The radioactive dose was adjusted for each patient in order to maximize the radiation delivered to the tumor and minimize the exposure of other organs. Bexxar combined separate administration of unlabelled and iodine-labelled (i.e. covalently bonded to 131I) tositumomab. A ...
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Lilotomab
Lilotomab (formerly tetulomab, HH1) is a murine monoclonal antibody against CD37, a glycoprotein which is expressed on the surface of mature human B cells. It was generated at the Norwegian Radium Hospital. As of 2016 it was under development by the Norwegian company Nordic Nanovector ASA as a radioimmunotherapeutic in which lilotomab is conjugated to the beta radiation-emitting isotope lutetium-177 by means of a linker called satetraxetan, a derivative of DOTA. This compound is called 177Lu-HH1 or lutetium (177Lu) lilotomab satetraxetan (trade name ''Betalutin''). As of 2016, a phase 1/2 clinical trial in people with non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. ... was underway. References Further reading * Experimental cancer drugs Radioph ...
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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 pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few varia ...
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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 example, beta decay of a neutron transforms it into a proton by the emission of an electron accompanied by an antineutrino; or, conversely a proton is converted into a neutron by the emission of a positron with a neutrino in so-called ''positron emission''. Neither the beta particle nor its associated (anti-)neutrino exist within the nucleus prior to beta decay, but are created in the decay process. By this process, unstable atoms obtain a more stable ratio of protons to neutrons. The probability of a nuclide decaying due to beta and other forms of decay is determined by its nuclear binding energy. The binding energies of all existing nuclides form what is called the nuclear band or valley of stability. For either electron or positron emissio ...
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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 minuscule quantities arising from this decay chain in nature, 225Ac is entirely synthetic. The decay properties of actinium-225 are favorable for usage in targeted alpha therapy (TAT); clinical trials have demonstrated the applicability of radiopharmaceuticals containing 225Ac to treat various types of cancer. However, the scarcity of this isotope resulting from its necessary synthesis in cyclotrons limits its potential applications. Decay and occurrence Actinium-225 has a half-life of 10 days and decays by alpha emission. It is part of the neptunium series, for it arises as a decay product of neptunium-237 and its daughters such as uranium-233 and thorium-229. It is the last nuclide in the chain with a half-life over a day until the penulti ...
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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 has classically been considered to be a stable isotope because it has a half-life of approximately 2.01×1019 years, which is more than a billion times the age of the universe. Besides 209Bi, the most stable bismuth radioisotopes are 210mBi with a half-life of 3.04 million years, 208Bi with a half-life of 368,000 years and 207Bi, with a half-life of 32.9 years, none of which occurs in nature. All other isotopes have half-lives under 1 year, most under a day. Of naturally occurring radioisotopes, the most stable is radiogenic 210Bi with a half-life of 5.012 days. 210mBi, like 180mTa, 242mAm and some holmium isomers, is unusual for being a nuclear isomer with a half-life multiple orders of magnitude longer than that of the ground state. C ...
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Alpha Emitter
Alpha particles, also called alpha rays or alpha radiation, consist of two protons and two neutrons bound together into a particle identical to a helium-4 nucleus. They are generally produced in the process of alpha decay, but may also be produced in other ways. Alpha particles are named after the first letter in the Greek alphabet, α. The symbol for the alpha particle is α or α2+. Because they are identical to helium nuclei, they are also sometimes written as or indicating a helium ion with a +2 charge (missing its two electrons). Once the ion gains electrons from its environment, the alpha particle becomes a normal (electrically neutral) helium atom . Alpha particles have a net spin of zero. Due to the mechanism of their production in standard alpha radioactive decay, alpha particles generally have a kinetic energy of about 5  MeV, and a velocity in the vicinity of 4% of the speed of light. (See discussion below for the limits of these figures in alpha decay.) They a ...
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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 patients), rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow injection into a vein. Biosimilars of Rituxan include Blitzima, Riabni, Ritemvia, Rituenza (F.K.A. Tuxella), Rixathon, Ruxience, and Truxima. Common side effects which often occur within two hours of the medication being given include rash, itchiness, low blood pressure, and shortness of breath. Infections are also common. Severe side effects include reactivation of hepatitis B in those previously infected, progressive multifocal leukoencephalopathy, toxic epidermal necrolysis, and death. It is unclear if use during pre ...
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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. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targets, wh ...
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Non-Hodgkin's Lymphoma
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever, night sweats, weight loss, and tiredness. Other symptoms may include bone pain, chest pain, or itchiness. Some forms are slow-growing while others are fast-growing. Lymphomas are types of cancer that develop from lymphocytes, a type of white blood cell. Risk factors include immunodeficiency, poor immune function, autoimmune diseases, Helicobacter pylori infection, ''Helicobacter pylori'' infection, hepatitis C, obesity, and Epstein–Barr virus infection. The World Health Organization classifies lymphomas into five major groups, including one for Hodgkin lymphoma. Within the four groups for NHL are over 60 specific types of lymphoma. Diagnosis is by bone marrow biopsy, examination of a bone marrow or lymph node biopsy. Medical imaging is done to help with cance ...
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Fast Track (FDA)
Fast track is a designation by the United States Food and Drug Administration (FDA) of an investigational drug for expedited review to facilitate development of drugs that treat a serious or life-threatening condition and fill an unmet medical need. Fast Track designation must be requested by the drug company. The request can be initiated at any time during the drug development process. FDA will review the request and attempt to make a decision within sixty days. Purpose Fast Track is one of five Food and Drug Administration (FDA) approaches to make new drugs available as rapidly as possible: the others are priority review, breakthrough therapy, accelerated approval and Regenerative Medicine Advanced Therapy. Fast Track was introduced by the FDA Modernization Act of 1997. Requirements Fast track designation is designed to aid in the development and expedite the review of drugs which show promise in treating a serious or life-threatening disease and address an unmet medical ...
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