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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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CD37
Leukocyte antigen CD37 is a protein that in humans is encoded by the ''CD37'' gene. Function The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic transmembrane domains. Tetraspanins mediate signal transduction events that play a role in the regulation of immune responses, cell development, activation, growth and motility. CD37 expression is restricted to cells of the immune system, with highest abundance on mature B cells, and lower expression is found on T cells and myeloid cells. CD37 is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. Alternate splicing results in multiple transcript variants encoding different isoforms. CD37 controls both humoral and cellular immune responses. CD37-deficiency in mice leads to spontaneous development on B ...
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Monoclonal Antibody
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one monoclonal antibody to two epitopes. It is possible to produce monoclonal antibodies that specifically bind to virtually any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibodies are being used on a clinical level for both the diagnosis and therapy ...
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Glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated. In proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. It is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system from reversible cytosolic-nuclear glycosylation. Glycoproteins of the cytosol and nucleus can be modified through the reversible addition of a single GlcNAc residue that is considered reciprocal to phosphorylation and the functions of these are likely to be an additional regulatory mechanism that controls phosphorylation-based signalling. In contrast, ...
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B Cell
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the 'B' stands for bursa and not bone marrow as commonly believed. B cells, unlike the other two classes of lymphocytes, T cells and ...
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Norwegian Radium Hospital
Oslo University Hospital, Radiumhospitalet ( no, Oslo universitetssykehus, Radiumhospitalet) is one of the four campuses of Oslo University Hospital in Oslo, Norway, and is dedicated to cancer treatment. This part of the hospital is the most specialized hospital in Norway for cancer therapy and research on cancer. The Norwegian Radium Hospital was an independent hospital from May 21, 1932, to 2005, when it merged with Rikshospitalet. The hospital was founded with Severin Andreas Heyerdahl as chief physician and director, and Hans L. C. Huitfeldt as chairman of the board. From 1983 to the merge with Rikshospitalet in 2005 Jan Vincents Johannessen was CEO. The Radium Hospital merged in 2005 with Rikshospitalet to create Rikshospitalet-Radiumhospitalet HF. On January 1, 2009, Rikshospitalet merged with Ullevål University Hospital and Aker University Hospital to create Oslo University Hospital Oslo University Hospital ( no, Oslo universitetssykehus; OUS) is a university hospital in ...
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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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Beta Radiation
A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus during the process of beta decay. There are two forms of beta decay, β− decay and β+ decay, which produce electrons and positrons respectively. Beta particles with an energy of 0.5 MeV have a range of about one metre in air; the distance is dependent on the particle energy. Beta particles are a type of ionizing radiation and for radiation protection purposes are regarded as being more ionising than gamma rays, but less ionising than alpha particles. The higher the ionising effect, the greater the damage to living tissue, but also the lower the penetrating power of the radiation. Beta decay modes β− decay (electron emission) An unstable atomic nucleus with an excess of neutrons may undergo β− decay, where a neutron is converted into a proton, an electron, and an electron antineutrino (the antip ...
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Lutetium-177
Naturally occurring lutetium (71Lu) is composed of one stable isotope 175Lu (97.41% natural abundance) and one long-lived radioisotope, 176Lu with a half-life of 3.78 × 1010 years (2.59% natural abundance). Thirty-five radioisotopes have been characterized, with the most stable, besides 176Lu, being 174Lu with a half-life of 3.31 years, and 173Lu with a half-life of 1.37 years. All of the remaining radioactive isotopes have half-lives that are less than 9 days, and the majority of these have half-lives that are less than half an hour. This element also has 18 meta states, with the most stable being 177mLu (t1/2 160.4 days), 174mLu (t1/2 142 days) and 178mLu (t1/2 23.1 minutes). The isotopes of lutetium range in mass number from 149 to 184. The primary decay mode before the most abundant stable isotope, 175Lu, is electron capture (with some alpha and positron emission), and the primary mode after is beta emission. The primary decay products before 175Lu are isotopes of ytterbium a ...
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DOTA (chelator)
DOTA (also known as tetraxetan) is an organic compound with the formula (CH2CH2NCH2CO2H)4. The molecule consists of a central 12-membered tetraaza (i.e., containing four nitrogen atoms) ring. DOTA is used as a complexing agent, especially for lanthanide ions. Its complexes have medical applications as contrast agents and cancer treatments. Terminology The acronym DOTA (for dodecane tetraacetic acid) is shorthand for both the tetracarboxylic acid and its various conjugate bases. In the area of coordination chemistry, the tetraacid is called H4DOTA and its fully deprotonated derivative is DOTA4−. Many related ligands are referred to using the DOTA acronym, although these derivatives are generally not ''tetra''carboxylic acids or the conjugate bases. Structure DOTA is derived from the macrocycle known as cyclen. The four secondary amine groups are modified by replacement of the N-H centers with N-CH2CO2H groups. The resulting aminopolycarboxylic acid, upon ionization of the carb ...
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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. 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 poor immune function, autoimmune diseases, ''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 examination of a bone marrow or lymph node biopsy. Medical imaging is done to help with cancer staging. Treatment depends on whether the lymphoma is slow- or fast-growing an ...
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Lutetium-177 Satetraxetan
Naturally occurring lutetium (71Lu) is composed of one stable isotope 175Lu (97.41% natural abundance) and one long-lived radioisotope, 176Lu with a half-life of 3.78 × 1010 years (2.59% natural abundance). Thirty-five radioisotopes have been characterized, with the most stable, besides 176Lu, being 174Lu with a half-life of 3.31 years, and 173Lu with a half-life of 1.37 years. All of the remaining radioactive isotopes have half-lives that are less than 9 days, and the majority of these have half-lives that are less than half an hour. This element also has 18 meta states, with the most stable being 177mLu (t1/2 160.4 days), 174mLu (t1/2 142 days) and 178mLu (t1/2 23.1 minutes). The isotopes of lutetium range in mass number from 149 to 184. The primary decay mode before the most abundant stable isotope, 175Lu, is electron capture (with some alpha and positron emission), and the primary mode after is beta emission. The primary decay products before 175Lu are isotopes of ytter ...
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Experimental Cancer Drugs
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies. A child may carry out basic experiments to understand how things fall to the ground, while teams of scientists may take years of systematic investigation to advance their understanding of a phenomenon. Experiments and other types of hands-on activities are very important to student learning in the science classroom. Experiments can raise test scores and help a student become more engaged and interested in the material they are learning, especially when used over time. Experiments can vary from personal and informal natural comparisons (e. ...
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