Indium (111In) Capromab Pendetide
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Indium (111In) Capromab Pendetide
Indium (111In) capromab pendetide (trade name Prostascint) is used to image the extent of prostate cancer. Capromab is a mouse monoclonal antibody which recognizes a protein found on both prostate cancer cells and normal prostate tissue. It is linked to pendetide, a derivative of DTPA. Pendetide acts as a chelating agent for the radionuclide indium-111. Following an intravenous injection of Prostascint, imaging is performed using single-photon emission computed tomography Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ... (SPECT). Early trials with yttrium ( 90Y) capromab pendetide were also conducted. References Radiopharmaceuticals Antibody-drug conjugates Indium compounds {{antineoplastic-drug-stub ...
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Glutamate Carboxypeptidase II
Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I), NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the ''FOLH1'' (folate hydrolase 1) gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa. GCPII is a zinc metalloenzyme that resides in membranes. Most of the enzyme resides in the extracellular space. GCPII is a class II membrane glycoprotein. It catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate (NAA) according to the reaction scheme to the right. Neuroscientists primarily use the term NAALADase in their studies, while those studying folate metabolism use folate hydrolase, and those studying prostate cancer or oncology, PSMA. All of which refer to the same protein glutamate carboxypeptidase II. Discovery GCPII is mainly expressed in four tissues of the body, including prostate epithelium, the prox ...
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Prostate Cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Only those who have male reproductive organs are able to get prostate cancer. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms ...
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Mouse
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus''). Mice are also popular as pets. In some places, certain kinds of field mice are locally common. They are known to invade homes for food and shelter. Mice are typically distinguished from rats by their size. Generally, when a muroid rodent is discovered, its common name includes the term ''mouse'' if it is smaller, or ''rat'' if it is larger. The common terms ''rat'' and ''mouse'' are not taxonomically specific. Typical mice are classified in the genus '' Mus'', but the term ''mouse'' is not confined to members of ''Mus'' and can also apply to species from other genera such as the deer mouse, ''Peromyscus''. Domestic mice sold as pets often differ substantially in size from the common house mouse. This is attributable to breeding a ...
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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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Pendetide
Pendetide (GYK-DTPA) is a chelating agent. It consists of pentetic acid (DTPA) linked to the tripeptide glycine (G) – L-tyrosine (Y) – L-lysine (K). Use The following monoclonal antibodies are linked to pendetide to chelate a radionuclide, indium-111 Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target (112Cd(p,2n) .... The antibodies selectively bind to certain tumour cells, and the radioactivity is then used for imaging of the tumours. * Indium (111In) capromab pendetide (prostate cancer) * Indium (111In) satumomab pendetide (other cancer types) References Chelating agents Chelating agents used as drugs Carboxylic acids Peptides {{pharma-stub ...
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DTPA
Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of EDTA and is used similarly. It is a white solid with limited solubility in water. Coordination properties The conjugate base of DTPA has a high affinity for metal cations. Thus, the penta-anion DTPA5− is potentially an octadentate ligand assuming that each nitrogen centre and each –COO− group counts as a centre for coordination. The formation constants for its complexes are about 100 greater than those for EDTA.J. Roger Hart "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005. As a chelating agent, DTPA wraps around a metal ion by forming up to eight bonds. Its complexes can also have an extra water molecule that coordinates the metal ion. Transition metals, however, u ...
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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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Radionuclide
A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferred to one of its electrons to release it as a conversion electron; or used to create and emit a new particle (alpha particle or beta particle) from the nucleus. During those processes, the radionuclide is said to undergo radioactive decay. These emissions are considered ionizing radiation because they are energetic enough to liberate an electron from another atom. The radioactive decay can produce a stable nuclide or will sometimes produce a new unstable radionuclide which may undergo further decay. Radioactive decay is a random process at the level of single atoms: it is impossible to predict when one particular atom will decay. However, for a collection of atoms of a single nuclide the decay rate, and thus the half-life (''t''1/2) for ...
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Indium-111
Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target (112Cd(p,2n) or 111Cd(p,n)) in a cyclotron, as recommended by International Atomic Energy Agency (IAEA). The former method is more commonly used as it results in a high level of radionuclide purity. Indium-111 is commonly used in nuclear medicine diagnostic imaging by radiolabeling targeted molecules or cells. During its radioactive decay, it emits low energy gamma (γ) photons which can be imaged using planar or single-photon emission computed tomography (SPECT) gamma cameras (primary energies (ε) of 171.3 keV (91%) and 245.4 keV (94%)) Uses in nuclear medicine When formulated as an 111InCl solution, it can be used to bind antibodies, peptides, or other molecular targeted proteins or other molecules, typically using a chelate to bind the radion ...
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Single-photon Emission Computed Tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, scintigraphy), but is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required. The technique needs delivery of a gamma-emitting radioisotope (a radionuclide) into the patient, normally through injection into the bloodstream. On occasion, the radioisotope is a simple soluble dissolved ion, such as an isotope of gallium(III). Most of the time, though, a marker radioisotope is attached to a specific ligand to create a radioligand, whose properties bind it to certain types of tissues. This marriage allows the combination of ligand and radiopharmaceutical to be carried and bound to a place of interest in the body, where ...
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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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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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