Mangafodipir

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Structural formula
Structure of Mangafodipir
General
Non-proprietary name Mangafodipir
other names
  • Mn-DPDP
  • N , N '-bis (pyridoxal-5-phosphate) ethylenediamine- N , N ' -diacetic acid
  • Teslascan (brand name)
Molecular formula C 22 H 28 MnN 4 O 14 P 2
External identifiers / databases
CAS number 119797-12-5
PubChem 3086672
ChemSpider 2343239
DrugBank DB06796
Wikidata Q423624
Drug information
ATC code

V08 CA05

Drug class

Paramagnetic contrast agent

properties
Molar mass 689.36 g mol −1 as Mn-DPDP
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

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

Indication and application

The use of Mangafodipir as contrast agents in nuclear spin tomography is essentially at lesions of the liver indicated. It can also be used on lesions of the pancreas . In many cases it is used to diagnose liver metastases . Even non-malignant changes, such as those of the pancreas in Caroli's syndrome , can be better diagnosed with the help of this contrast agent.

The substance is given intravenously before the MRI . After about 15 to 20 minutes, the maximum accumulation in the parenchyma of the liver is reached and held for about four hours.

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

Structure and working principle of the contrast agent

Manganese 2+ ions have five unpaired electrons on their outer electron shell, which makes them highly paramagnetic . When administered intravenously, free manganese ions are neurotoxic to humans and many other organisms and damage the central nervous system . However, complexation with a chelator can drastically reduce toxicity. In the case of Mangafodipir, dipyridoxyl diphosphate (DPDP or Fodipir), a complexing agent based on two molecules of pyridoxine (vitamin B6), is used.

As contrast agents shorten manganese 2+ ions, the T 1 - relaxation time , which is why T 1 -weighted images appear brighter in the magnetic resonance imaging at the points at which Mangafodipir has enriched. Mangafodipir is specifically absorbed by the hepatocytes in the liver. Liver metastases are produced by other types of cells that mangafodipir cannot take up. In this way Mangafodipir enhances the contrast in magnetic resonance imaging: the liver metastases appear in T 1 significantly -weighted images darker than the healthy liver tissue. In the case of T 2 -weighted images, this contrast enhancement by mangafodipir is not given.

Pharmacokinetics

Mangafodipir is metabolized by dephosphorylation , whereby the manganese ions are released by exchange with zinc ions in the plasma. The manganese released in this way is absorbed as soon as it first passes through the liver, which is why it cannot develop its neurotoxic effect.

The released manganese and dipyridoxyl diphosphate are excreted differently from the body. The mean initial plasma half-life of the manganese ions is less than 20 minutes. They are mainly taken up by the liver, pancreas, kidneys and spleen . The initial plasma half-life of the ligand is about 50 minutes. Almost all of it is excreted in the urine and a small part in the stool within 24 hours . In contrast, only about 15 to 20 percent of the manganese is eliminated in the urine in the first 24 hours. Most of the remainder is excreted in the stool over the next four days.

Side effects

The most common undesirable side effects after administration of Mangafodipir are headache , nausea , reddening of the skin and a feeling of heat. This affects around 1 to 10% of patients.

For pregnant or lactating patients Mangafodipir should not be used, as well as in patients with a pheochromocytoma or severe liver and kidney disease.

In the model organism color rat , a teratogenic effect could be determined at a dose that is slightly higher than the usual clinical dose . The rat fetuses showed increased malformations of the skeletal system.

Therapeutic effects

As a contrast medium, Mangafodipir should only have diagnostic properties and no side effects or therapeutic properties. Mangafodipir also shows therapeutic effects in various model organisms. For example, it protects the myocardium against oxidative stress triggered by reactive oxygen species . It stabilizes the lysosomal and mitochondional membranes and thus prevents apoptosis .

In addition, mangafodipir shows an anti-tumor and liver protective effect in animal experiments. In color mice , for example, the survival rate for acute liver failure induced by paracetamol could be improved preventively and curatively.

Mangafodipir apparently has a similar effect to superoxide dismutases in vivo .

Mangafodipir is not approved for therapeutic use.

Development history

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

further reading

  • S. Maurea, C. Mollica, M. Imbriaco, M. Fusari, L. Camera, M. Salvatore: Magnetic resonance cholangiography with mangafodipir trisodium in Caroli's disease with pancreas involvement. In: Journal of the pancreas Volume 11, Number 5, 2010, pp. 460-463, PMID 20818116 .
  • SN Gandhi, MA Brown, JG Wong, DA Aguirre, CB Sirlin: MR contrast agents for liver imaging: what, when, how. In: Radiographics: a review publication of the Radiological Society of North America, Inc Volume 26, Number 6, 2006 Nov-Dec, pp. 1621-1636, doi: 10.1148 / rg.266065014 , PMID 17102040 .
  • BM Yeh, RS Breiman, B. Taouli, A. Qayyum, JP Roberts, FV Coakley: Biliary tract depiction in living potential liver donors: comparison of conventional MR, mangafodipir trisodium-enhanced excretory MR, and multi-detector row CT cholangiography – initial experience. In: Radiology Volume 230, Number 3, March 2004, pp. 645-651, doi: 10.1148 / radiol.2303021775 , PMID 14990830 .
  • W. Schima, R. Függer: Evaluation of focal pancreatic masses: comparison of mangafodipir-enhanced MR imaging and contrast-enhanced helical CT. In: European radiology Volume 12, Number 12, December 2002, pp. 2998-3008, doi: 10.1007 / s00330-002-1531-y , PMID 12439582 .
  • MP Federle, JL Chezmar, DL Rubin, JC Weinreb, PC Freeny, RC Semelka, JJ Brown, JA Borello, JK Lee, R. Mattrey, AH Dachman, S. Saini, B. Harmon, M. Fenstermacher, RE Pelsang, SE Harms, DG Mitchell, HH Halford, MW Anderson, CD Johnson, IR Francis, JG Bova, PJ Kenney, DL Klippenstein, GS Foster, DA Turner: Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the US multicenter phase III clinical trials (safety). In: Journal of magnetic resonance imaging: JMRI Volume 12, Number 1, July 2000, pp. 186-197, PMID 10931579 .
  • M. Federle, J. Chezmar, DL Rubin, J. Weinreb, P. Freeny, UP Schmiedl, u. a .: Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the US Multicenter phase III clinical trials. Efficacy of early imaging. In: Journal of magnetic resonance imaging Volume 12, Number 5, November 2000, pp. 689-701, PMID 11050638 .
  • D. Mathieu, C. Coffin, H. Kobeiter, F. Caseiro-Alves, A. Mahfouz, A. Rahmouni, T. Diche: Unexpected MR-T1 enhancement of endocrine liver metastases with mangafodipir. In: Journal of magnetic resonance imaging: JMRI Volume 10, Number 2, August 1999, pp. 193-195, PMID 10441024 .
  • P. Jynge, H. Brurok, A. Asplund, R. Towart, H. Refsum, JO Karlsson: Cardiovascular safety of MnDPDP and MnCl2. In: Acta radiologica (Stockholm, Sweden: 1987) Volume 38, Number 4 Pt 2, July 1997, pp 740-749, PMID 9245970 .
  • Y. Ni, G. Marchal: Clinical implications of studies with MnDPDP in animal models of hepatic abnormalities. In: Acta radiologica (Stockholm, Sweden: 1987) Volume 38, Number 4 Pt 2, July 1997, pp 724-731, PMID 9245968 .
  • NM Rofsky, JP Earls: Mangafodipir trisodium injection (Mn-DPDP). A contrast agent for abdominal MR imaging. In: Magnetic resonance imaging clinics of North America Volume 4, Number 1, February 1996, pp. 73-85, PMID 8673718 .

Web links

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. Jump up ↑ S. Maurea, C. Mollica, M. Imbriaco, M. Fusari, L. Camera, M. Salvatore: Magnetic resonance cholangiography with mangafodipir trisodium in Caroli's disease with pancreas involvement. In: Journal of the pancreas Volume 11, Number 5, 2010, pp. 460-463, PMID 20818116 .
  3. ↑ a b c d New Zealand Medicines and Medical Devices Safety Authority: TESLASCAN - Mangafodipir trisodium ( Memento of February 7, 2013 in the Internet Archive ). Retrieved July 8, 2011.
  4. ↑ a b c European Public Assessment Report (EPAR) - TESLASCAN - EPAR summary for the public. (PDF; 285 kB) European Medicines Agency, April 2007
  5. ↑ The Elixirs of Life. ( Memento of April 11, 2011 in the Internet Archive ) (PDF; 1.1 MB) In: MaxPlanckForschung 3, 2003, pp. 47–51.
  6. ↑ a b J. Crossgrove, W. Zheng: Manganese toxicity upon overexposure. In: NMR in biomedicine Volume 17, Number 8, December 2004, pp. 544-553, doi: 10.1002 / nbm.931 . PMID 15617053 . (Review).
  7. ↑ mr-tip.com: Teslascan. Retrieved July 8, 2011
  8. ↑ A. Laskar, S. Miah, RG Andersson, W. Li: Prevention of 7β-hydroxycholesterol-induced cell death by mangafodipir is mediated through lysosomal and mitochondrial pathways. In: European journal of pharmacology Volume 640, number 1-3, August 2010, pp. 124-128, doi: 10.1016 / j.ejphar.2010.04.046 . PMID 20452343 .
  9. ↑ A. Laurent, C. Nicco, C. Chéreau, C. Goulvestre, J. Alexandre, A. Alves, E. Lévy, F. Goldwasser, Y. Panis, O. Soubrane, B. Weill, F. Batteux: Controlling tumor growth by modulating endogenous production of reactive oxygen species. In: Cancer Research Volume 65, Number 3, February 2005, pp. 948-956, PMID 15705895 .
  10. ↑ a b S. Bedda, A. Laurent, F. Conti, C. Chéreau, A. Tran, J. Tran-Van Nhieu, P. Jaffray, O. Soubrane, C. Goulvestre, Y. Calmus, B. Weill, F. Batteux: Mangafodipir prevents liver injury induced by acetaminophen in the mouse. In: Journal of Hepatology Volume 39, Number 5, November 2003, pp. 765-772, PMID 14568259 .
  11. ^ JO Karlsson, H. Brurok, R. Towart, P. Jynge: The magnetic resonance imaging contrast agent mangafodipir exerts antitumor activity via a previously described superoxide dismutase mimetic activity. In: Cancer research Volume 66, Number 1, January 2006, p. 598; author reply 598, doi: 10.1158 / 0008-5472.CAN-05-2053 . PMID 16397277 .
  12. ↑ H. Brurok, JH Ardenkjaer-Larsen, G. Hansson, S. Skarra, K. Berg, JO Karlsson, I. Laursen, P. Jynge: Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties? In: Biochemical and biophysical research communications Volume 254, Number 3, January 1999, pp. 768-772, PMID 9920816 .
  13. ↑ Diagnosia: Teslascan 0.01 mmol / ml infusion solution. ( Memento of February 23, 2014 in the Internet Archive ) Retrieved July 9, 2011.