Oral formulation: A mixture of MnCl 2, alanine and vitamin D3, designated as CMC-001, and is currently undergoing phase 3 clinical trial for oral intake.įollowing i.v. Intravenous formulation: Mangafodipir trisodium, manganese–dipyridoxyl diphosphate chelate (MnDPDP manganese-5, 5’-bis(phosphate) sodium salt, which is commercially available and used for slow injection (in Europe) or bolus injection (in the US). Manganese based MR contrast agents are used in two forms: FORMULATION OF MANGANESE BASED MR CONTRAST AGENTS This article discusses the development and use of both intravenous (i.v.) and oral manganese based contrast agents, including their formulation, preclinical evaluations, pharmacokinetics and clinical applications.Ģ. As hepatocytes are rich in mitochondria, Mn 2+ is an excellent contrast agent for MR imaging of the liver and other mitochondria rich organs like pancreas and kidneys. Biologically manganese is involved in mitochondrial function of cells, and thus the more mitochondria in the tissue, the higher its uptake. When used as a contrast agent, manganese ion (Mn 2+) belongs to the same group of paramagnetic ions as gadolinium (Gd 3+) and copper (Cu 2+), which are capable of shortening the T1 of water protons, thus increasing the signal intensity of T1 weighted (T1w) Magnetic Resonance (MR) images but manganese has also a minor T2 effect which reduces the signal intensity. In contrast to many other minerals in the body, manganese is actively excreted via hepatocytes into the bile, and only minimal amounts are excreted via the kidney. The main route of manganese absorption is the gastrointestinal tract, but in man, rats and mice less than 5% of the oral intake is absorbed. Manganese is also present in many intracellular organelles, especially mitochondria, where it has an important metabolic function as a coenzyme in protein synthesis. Therefore it is involved in oxidation–reduction processes, phosphorylation, fermentation, and in the synthesis of cholesterol, fatty acids and mucopolysaccharides. Manganese is also a cofactor in a variety of enzymes including pyruvate carboxylase, superoxide dismutase, glutamine synthetase and alkaline phosphates. Manganese is interchangeable with other ions such as cobalt, zinc and nickel in the activation of enzymes. The highest concentrations of manganese are found in the liver (22–38 µmol/kg) and pancreas, and lesser quantities in kidneys (11–16 µmol/kg). In man, the normal whole body content of Mn is 220–360 µmol, with a daily turn over of 90–140 µmol, and up to 25% stored in the skeleton which is not readily accessible. Manganese (Mn 2+) is an essential trace element that plays an important role in various aspects of metabolism in humans, animals, plants and microorganisms. formulation can be used for focal pancreatic lesions. Manganese based MR contrast agents are particularly suitable for detection of focal liver lesions due to their uptake by the mito¬chondria rich hepatocytes, and biliary delineation due to their biliary excretion it can provide useful information in diffuse liver lesions. administration exposes all the organs, whereas oral ingestion exposes only the enterohepatic circulation. The main reported clinical difference between the two formulations is that i.v. The compositions, preclinical studies and pharmacokinetics of both form¬ulations are discussed. formulation is a manganese–dipyridoxyl diphosphate chelate which is commer¬c¬ially available whereas the oral formulation is a mixture of MnCl2, alanine and Vitamin D3, which is currently under clinical trials. This paper discusses the development and clinical applications of positive manganese based MR contrast agents, including both intrave¬nous (i.v.) and oral formulations.
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