Mangafodipir

Mn - DPDP
N, N'-bis (pyridoxal -5-phosphate ) ethylenediamine -N, N' -diacetic acid
Teslascan (brand name)

V08CA05

Paramagnetic contrast agents

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Mangafodipir, as an abbreviation of Mn - DPDP, is the international non-proprietary name of a contrast agent for magnetic resonance imaging (MRI ), on the basis of divalent manganese. It is sold under the brand name Teslascan of GE Healthcare.

Indication and Application

The use of Mangafodipir as contrast agents in nuclear spin tomography, is indicated generally in lesions of the liver. In addition, it can also be used in lesions of the pancreas. In many cases it is used for the diagnosis of liver metastases. Not malignant changes, such as the pancreas in Caroli 's syndrome, may be diagnosed using this contrast medium more.

It is administered intravenously before the MRI. After about 15 to 20 minutes, the maximum of accumulation is achieved in the parenchyma of the liver and held for about four hours.

In the European Union, the dose administered to the patient is usually 0.5 ml per kilogram of body weight.

Structure and operating principle of the contrast agent

Mangan2 ions have on their outer electron shell five unpaired electrons, making them highly paramagnetic. Free manganese ions are neurotoxic when intravenous administration to humans and many other organisms and cause harm to the central nervous system. However, upon complexation with a chelator that toxicity can be reduced drastically. In the case of Mangafodipir is Dipyridoxyldiphosphat ( DPDP or fodipir ), a complexing agent on the basis of two molecules of pyridoxine (vitamin B6 ) is used.

As contrast agents shorten Mangan2 ions, the T1 relaxation time, which is why T1-weighted images appear in the MRI at the points at which Mangafodipir has enriched brighter. Mangafodipir is specifically taken up by the hepatocytes in the liver. Liver metastases are formed from other cell types that Mangafodipir can not record. In this way reinforced Mangafodipir contrast in magnetic resonance imaging: the liver metastases appear much darker than the healthy liver tissue in T1 - weighted images. At T2 - weighted images, this contrast enhancement is not given by Mangafodipir.

Pharmacokinetics

Mangafodipir is metabolised by Dephosphorylisierung, the manganese ions are released by exchange with zinc ions in the plasma. The thus liberated manganese is directly recorded in the first pass through the liver, so it can not exert its neurotoxic effect.

The liberated manganese and Dipyridoxyldiphosphat are excreted from the body differently. The mean initial plasma half-life of manganese ions is less than 20 minutes. They are taken up mainly by the liver, pancreas, kidneys and spleen. Initial plasma half-life of the ligand is about 50 minutes. He is excreted within 24 hours, almost entirely in the urine and to a small extent on the chair. However during the first 24 hours, only about 15 to 20 percent of the manganese is eliminated via urine. The largest portion of the remaining residue is excreted in the next four days on the chair.

Side effects

Place it in unwanted side effects after administration of Mangafodipir most commonly headache, nausea, redness of the skin and a sensation of heat one. Of about 1 to 10% of patients are affected.

In pregnant or lactating patients may Mangafodipir not be used, not as in patients with pheochromocytoma or severe liver and kidney disease.

In the model organism pet rat a teratogenic effect was observed at a dose that is slightly higher than the clinically normal doses. The rat fetuses showed enhanced malformations of the skeleton system.

Therapeutic effects

As a contrast agent Mangafodipir should only have diagnostic properties and no side effects or therapeutic properties. However Mangafodipir shows in various model organisms and therapeutic effects. There, for example, protects the myocardium against oxidative stress, which is triggered by reactive oxygen species. It stabilizes lysosomal membranes and mitochondionalen and prevents apoptosis.

In addition Mangafodipir shows in animal experiments, an anti -tumor and the liver protective effect. Thus, for example in color mice, the survival rate in paracetamol -induced acute liver failure, improved preventive and curative.

Mangafodipir in vivo has obviously an effect similar to superoxide dismutases.

For therapeutic applications Mangafodipir is not allowed.

History of development

Mangafodipir was developed in the early 1980s. The first clinical trials were conducted in the early 1990s. The European Commission granted on 22 May 1997, GE Healthcare drug approval.