90Y-DOTA-biotin
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90Y-DOTA-biotin
90Y-DOTA-biotin consists of a radioactive substance (yttrium-90) complexed by a chelating agent (DOTA), which in turn is attached to the vitamin biotin via a chemical linker. It is used experimentally in pretargeted radioimmunotherapy. Animal studies have been conducted as well as clinical studies in humans. In pretargeted radioimmunotherapy, two or three medications are applied in succession. At first, an antibody-drug conjugate is administered, which consists of a 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 ... designed to target the tumour, and a chemical marker which in the case of DOTA-biotin therapy is one of the proteins avidin and streptavidin. After a time of typically one or two days to let the antibody accumulate in the tumour, a clearing agent ma ...
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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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Radioactive
Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is considered radioactive. Three of the most common types of decay are alpha decay ( ), beta decay ( ), and gamma decay ( ), all of which involve emitting one or more particles. The weak force is the mechanism that is responsible for beta decay, while the other two are governed by the electromagnetism and nuclear force. A fourth type of common decay is electron capture, in which an unstable nucleus captures an inner electron from one of the electron shells. The loss of that electron from the shell results in a cascade of electrons dropping down to that lower shell resulting in emission of discrete X-rays from the transitions. A common example is iodine-125 commonly used in medical settings. Radioactive decay is a stochastic (i.e. random) process ...
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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 MeV with an average beta energy of 0.9336 MeV. It also produces 0.01% 1.7 MeV photons during its decay process to the 0+ state of 90Zr, followed by pair production. The interaction between emitted electrons and matter can lead to the emission of Bremsstrahlung radiation. Production Yttrium-90 is produced by the nuclear decay of strontium-90 which has a half-life of nearly 29 years and is a fission product of uranium used in nuclear reactors. As the strontium-90 decays, chemical high-purity separation is used to isolate the yttrium-90 before precipitation. Medical application 90Y plays a significant role in the treatment of hepatocellular carcinoma (HCC), leukemia, and lymphoma, although it has the potential to treat a range of tumo ...
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Chelating Agent
Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are called chelants, chelators, chelating agents, or sequestering agents. They are usually organic compounds, but this is not a necessity, as in the case of zinc and its use as a maintenance therapy to prevent the absorption of copper in people with Wilson's disease. Chelation is useful in applications such as providing nutritional supplements, in chelation therapy to remove toxic metals from the body, as contrast agents in MRI scanning, in manufacturing using homogeneous catalysts, in chemical water treatment to assist in the removal of metals, and in fertilizers. Chelate effect The chelate effect is the greater affinity of chelating ligands for a metal ion than that of similar nonchelating (monodentate) ligands for the same metal. ...
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Biotin
Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', borrowed from the German , derives from the Ancient Greek word (; 'life') and the suffix "-in" (a suffix used in chemistry usually to indicate 'forming'). Chemical description Biotin is classified as a heterocyclic compound, with a sulfur-containing ring fused ureido and tetrahydrothiophene group. A C5-carboxylic acid side chain is appended to one of the rings. The ureido ring, containing the −N−CO−N− group, serves as the carbon dioxide carrier in carboxylation reactions. Biotin is a coenzyme for five carboxylase enzymes, which are involved in the catabolism of amino acids and fatty acids, synthesis of fatty acids, and gluconeogenesis. Biotinylation of histone proteins in nuclear chromatin plays a role in chromatin stability and g ...
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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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Antibody-drug Conjugate
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are an example of bioconjugates and immunoconjugates. ADCs combine the targeting properties of Monoclonal antibody, monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue. Mechanism of action An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in or on tumor cells. Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon attaching ...
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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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Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians and deposited in the whites of their eggs. Dimeric members of the avidin family are also found in some bacteria. In chicken egg white, avidin makes up approximately 0.05% of total protein (approximately 1800 μg per egg). The tetrameric protein contains four identical subunits (homotetramer), each of which can bind to biotin (Vitamin B7, vitamin H) with a high degree of affinity and specificity. The dissociation constant of the avidin-biotin complex is measured to be ''K''D ≈ 10−15 M, making it one of the strongest known non-covalent bonds. In its tetrameric form, avidin is estimated to be 66–69 k Da in size. 10% of the molecular weight is contributed by carbohydrate, composed of four to five mannose and three N-acetylglucosamine residues The carbohydrate moieties of avidin contain at least three unique oligosaccharide structural types that are similar in structure ...
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Streptavidin
Streptavidin is a 66.0 (tetramer) kDa protein purified from the bacterium '' Streptomyces avidinii''. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin (also known as vitamin B7 or vitamin H). With a dissociation constant (Kd) on the order of ≈10−14 mol/L, the binding of biotin to streptavidin is one of the strongest non-covalent interactions known in nature. Streptavidin is used extensively in molecular biology and bionanotechnology due to the streptavidin-biotin complex's resistance to organic solvents, denaturants (e.g. guanidinium chloride), detergents (e.g. SDS, Triton X-100), proteolytic enzymes, and extremes of temperature and pH. Structure The crystal structure of streptavidin with biotin bound was reported by two groups in 1989. The structure was solved using multi wavelength anomalous diffraction by Hendrickson et al. at Columbia University and using multiple isomorphous replacement by Weber et al. at E. I. DuPont Central Research ...
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90Y-DOTA-biotin Skeletal
9 (nine) is the natural number following and preceding . Evolution of the Arabic digit In the beginning, various Indians wrote a digit 9 similar in shape to the modern closing question mark without the bottom dot. The Kshatrapa, Andhra and Gupta started curving the bottom vertical line coming up with a -look-alike. The Nagari continued the bottom stroke to make a circle and enclose the 3-look-alike, in much the same way that the sign @ encircles a lowercase ''a''. As time went on, the enclosing circle became bigger and its line continued beyond the circle downwards, as the 3-look-alike became smaller. Soon, all that was left of the 3-look-alike was a squiggle. The Arabs simply connected that squiggle to the downward stroke at the middle and subsequent European change was purely cosmetic. While the shape of the glyph for the digit 9 has an ascender in most modern typefaces, in typefaces with text figures the character usually has a descender, as, for example, in . The mod ...
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Radiopharmaceuticals
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is different from contrast media which absorb or alter external electromagnetism or ultrasound. Radiopharmacology is the branch of pharmacology that specializes in these agents. The main group of these compounds are the radiotracers used to diagnose dysfunction in body tissues. While not all medical isotopes are radioactive, radiopharmaceuticals are the oldest and still most common such drugs. Drug nomenclature As with other pharmaceutical drugs, there is standardization of the drug nomenclature for radiopharmaceuticals, although various standards coexist. The International Nonproprietary Names (INNs), United States Pharmacopeia (USP) names, and IUPAC names for these agents are usually similar other than trivial style differences. The de ...
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