Gadopentetate dimeglumine

Structural formula
· 2
General
Non-proprietary name	Gadopentetate dimeglumine
other names	Gd-DTPA
Molecular formula	C 28 H 54 GdN 5 O 20
External identifiers / databases
CAS number 86050-77-3 (gadopentetate dimeglumine) 80529-93-7 (gadopentetic acid) PubChem 55466 ChemSpider 50087 DrugBank DB00789 Wikidata Q413793
Drug information
ATC code	V08 CA01
Drug class	Paramagnetic contrast agent
properties
Molar mass	938.00 g · mol -1
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
Toxicological data	9411 mg kg −1 ( LD 50 ,  rat ,  iv )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Gadopentetate dimeglumine is a drug that is used as a contrast agent in magnetic resonance imaging (MRI). It is the dimeglumine salt of gadopentetic acid ( Gd-DTPA ). The contained gadolinium ions increase the contrast in the imaging.

Structure and working principle of the contrast agent

Gadopentetic acid is a chelate complex made from gadolinium ions and the complexing agent diethylenetriaminepentaacetic acid (DTPA). The complex is extremely solid and very stable because free, uncomplexed gadolinium ions are toxic to human and most animal organisms. The complex formation constant of DTPA is above 10 ²⁰ at a pH value of 7 .

Gadolinium has seven unpaired electrons on the outer electron shell (f-shell) , which give the element a strong paramagnetism . Protons , such as those found in the water of body fluids, relax much more quickly in the vicinity of gadolinium. In particular, the so-called T ₁ time is considerably shortened by gadolinium. Areas in which the contrast agent is concentrated are therefore shown brighter in T ₁ -weighted images than other structures. This considerably improves the image quality of an MRT recording.

As a highly polar and relatively large molecule, gadopentetic acid is unable to cross the blood-brain barrier in a healthy person after it has been administered intravenously. In some diseases, such as glioblastoma , however, it can cross the damaged blood-brain barrier and penetrate the diseased tissue. In this way it is possible to obtain more precise information about the type and location of the tumor. In the imaging, the tumor is also better delineated from the healthy tissue. The effect of overcoming the blood-brain barrier is an important diagnostic tool for brain tumors.

In joint diagnostics, gadopentetate dimeglumine is administered into the interior of the joint ( intra-articular ).

Gadopentetic diffuses after intraarticular administration quickly into the bloodstream and the extracellular space . From there it is almost completely eliminated via the kidneys, the half-life is around 1.5 hours.

Side effects

Gadopentetate dimeglumine is very well tolerated. Allergic or allergic reactions rarely occur (0.1-0.01 percent of those treated). Nephrogenic systemic fibrosis can be triggered in patients with impaired renal function . Contrast media should not be administered to such patients.

Magnetic resonance imaging is safe during pregnancy . On the other hand, the administration of contrast media containing gadolinium leads to a significantly increased death rate in the newborn during or after birth with a hazard ratio (HR) of 3.7 and to an increased probability of rheumatological , inflammatory and dermatological diseases with a hazard ratio of 1, 36. For this reason, a contrast agent should not be used during pregnancy if an MRI scan is necessary.

In July 2015, the Food and Drug Administration published a recommendation that gadolinium-containing contrast media should only be used in examinations in which they provide a diagnostic advantage. The reason for this was evidence of deposits of gadolinium compounds in the brain of patients after at least four applications of the contrast medium; a possible impact on health is currently not known and is the subject of studies. In July 2017, these investigations led to the withdrawal of the EU-wide approval of gadopentetate dimeglumine and other gadolinium-containing contrast media with a linear structure. In 2019, the contrast agents were detected in German drinking water .

Development history

The diagnostic gadopentetate dimeglumine was in 1981 Schering AG by the working group of Hanns-Joachim Weinmann developed in 1988 under the name Magnevist ^® approved as the first contrast agent for magnetic resonance imaging. Although there are now a large number of different approved modifications (both to the DTPA itself and completely different gadolinium chelators), it was the most widely used contrast agent in MRI until the approval was withdrawn in 2018. At times, up to 50% of all magnetic resonance imaging in Germany was carried out with gadopentetate dimeglumine.

From 1984 to 2005 the remedy was used almost 60 million times worldwide. In 2005, Schering AG achieved sales of over EUR 300 million.

Since the patent expired at the end of 2007, cheaper generics have been introduced.

literature

• P. Reimer, R. Vosshenrich: Contrast media in the MRT. In: The Radiologist. 44/2004, pp. 273-283.
• JP Pintaske, P. Martirosian et al. a .: Comparison of the concentration-dependent relaxivities of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist) and Gadobenate Dimeglumine (MultiHance) in the blood plasma at 0.2T, 1.5T and 3T. In: RöFo - Advances in the field of X-rays and imaging processes. 177, 2005, doi: 10.1055 / s-2005-867725 .

Trade names

Monopreparations

Gado-MRT (D), Magnevist (D, CH), Magnograf (CH), MR-Lux (D, CH), Magnegita / Gadopentetat Insight (D, A, CH)

Web links

• Magnevist - A commercial preparation is developed. the history of the development of Magnevist
• L Wachsmuth: Introduction to the basics of medical physics. (PDF file; 5.25 MB)

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. ↑ Entry on gadopentetate dimeglumine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ^ H. Scholz, G. Kuschinsky, RH Böger: Pocket book of drug treatment. Springer, 2005, p. 606. ( limited preview in the Google book search)
4. ↑ KJ Murphy et al .: Adverse reactions to gadolinium contrast media: a review of 36 cases. In: American Journal of Roentgenology. 167/1996, pp. 847-849.
5. ↑ HS Thomsen et al .: Is there a causal relation between the administration of gadolinium-based contrast media and the development of nephrogenic systemic fibrosis (NSF)? In: Clinical Radiology. 61/2006, pp. 905-906.
6. ↑ Nicola Siegmund-Schulze: MRI examination during pregnancy: Contrast media can damage the child at any time. In: Deutsches Ärzteblatt . Volume 113, Issue 44, November 9, 2016, p. 1987.
7. ↑ FDA Drug Safety Communication: FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI). (Safety Announcement)
8. ^ European Medicines Agency: Gadolinium-containing contrast agents [1]
9. ↑ Katja Schmidt, Michael Bau, Gila Merschel, Nathalie Tepe: Anthropogenic gadolinium in tap water and in tap water-based beverages from fast-food franchises in six major cities in Germany. In: Science of The Total Environment. 687, 2019, p. 1401, doi : 10.1016 / j.scitotenv.2019.07.075 . (German article: MRI contrast agent detected in cola: study finds gadolinium in fast-food drinks in all German cities examined )
10. ↑ https://patents.google.com/patent/US5021236

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !