Gadoteric acid

• Gd- DOTA
• Gadolinium -DOTA
• Gadoterat
• Gadoterinsäure
• Hydrogen ( 1,4,7,10- tetraazacyclododecane - 1,4,7,10- tetraacetato (4 -) ) gadolinat (1 -)
• Gadolinium ( 3) cation; 2 - [ 4,7,10 -tris ( carboxymethyl) - 1,4,7,10- tetrazacyclododec -1-yl ] acetic acid ( according to IUPAC )

V08CA02

Paramagnetic contrast agents

Template: Infobox chemical / molecular formula search available

Gadoteric acid, often referred to as Gd- DOTA, is the international non-proprietary name for a contrast agent used in magnetic resonance imaging ( MRI).

Structure and operating principle of the contrast agent

A gadoteric acid molecule contains a gadolinium ion, which is present with the aid of the strong complexing agent is 1,4,7,10 -tetraazacyclododecane -1 ,4,7,10 - tetraacetic acid ( DOTA ) in complexed form. Complexation is of great importance, since free, not complexed gadolinium ions for human or animal organisms are most toxic. The stability constant of DOTA is at a pH of 7 above 1020. Gadoteric acid is the most stable approved gadolinium complex with the longest dissociation.

Gadolinium has on the outer -shell (f- shell ) seven unpaired electrons, which gives the element a strong paramagnetism. Protons, as they occur in the water of body fluids such as, relax much more rapidly near to gadolinium. In particular, the so-called T1 - time is significantly reduced by the gadolinium. Areas in which the contrast agent accumulates, are therefore presented in T1 - weighted images brighter than other structures. Thus, the image quality of a MRI scan is significantly improved and increased the contrast between pathologies and the surrounding normal tissue.

Gadoteric acid is a non-specific contrast agent that accumulates in all organs outside the central nervous system. In the initial perfusion, the gadoteric acid spreads from the intravascular space and then passes rapidly into the extracellular space. The glomerular filtration rate ( GFR) is renal accordingly, that is excreted by the kidneys unchanged ( no metabolism, no dissociation and no retention ). Due to the fact that Gd- DOTA non- selectively distributed in the extracellular space of all extra cerebral tissue, it can not be used in specific organs. Because of its hydrophilicity can Gd -DOTA not pass intact cell membranes. Therefore, it can be found after the intravenous administration only into the intravascular space and interstitium. Because of the very low protein binding it is excreted relatively rapidly by the kidneys.

Gadoteric acid was first approved in 1989 in some European countries as a second MRI contrast agent (after gadopentetate dimeglumine (Gd - DTPA) ). As a highly polar and relatively large molecule gadoteric acid is in a healthy person will not be able cross the blood- brain barrier to overcome. However, in some diseases, such as in a glioblastoma, it can overcome the damaged blood -brain barrier and penetrate into the affected tissue. Thus, it is possible to obtain more precise information on the nature and location of the tumor. Also, the tumor in the imaging borders better off compared to the healthy tissue. The effect of overcoming the blood -brain barrier is an important diagnostic method for brain tumors.

In the human organism, the distribution half-life is about 2 to 3 minutes whereas the plasma half-life is about 90 minutes. The mean hydrodynamic diameter of approximately 5 nm, the molecule diameter is about 0.9 nm

Side effects

Gadoteric acid is very well tolerated. Uncommon ( 0.1 to 1 percent of patients), there is hypersensitivity reactions. Allergic reactions are common in patients with known intolerance to contrast media (including iodine ), asthma treatment or patients with multiple allergies. As with all gadolinium-based contrast agents can cause nausea, vomiting, skin rashes, tremors, dyspnea, bronchospasm, headache, metallic taste or heat during injection. At higher doses and pre-existing renal insufficiency or kidney disease may lead to a contrast- induced acute renal failure in rare cases. This usually occurs with a delay after 48 to 72 hours and is usually reversible. Because of the high osmolality of the solution of 1300 mOsm / kg water, the unintended extravascular injection must be avoided. In contrast to other gadolinium based contrast agents have been caused by gadoteric acid nephrogenic systemic fibrosis was observed in any of the more than 25 million patients.

Megluminat

In solution one mole gadoteric acid is added to one mole of meglumine (N-methyl -D-glucamine ). One speaks in these cases also the meglumine salt of gadoteric acid, Gadoterat meglumine, or hydrogen - [ 1,4,7,10- tetraazacyclododecane -1 ,4,7,10 - tetraacetato (4)] gadolinium- meglumine.

Trade names

Artirem (D, A, CH ) with a gadolinium concentration of 0.0025 mmol / ml in the form of Gadoterat meglumine is approved for the contrast-enhanced direct MR arthrography since 2002 ( Guerbet ). The iso-osmolar solution is injected directly into the joint space ( intra-articular ).

Dotarem (D, A, CH ) with a gadolinium concentration of 0.5 mmol / ml ( Guerbet ) has an approval for contrast medium imaging of CNS lesions, for whole-body MR - contrast examinations and contrast-enhanced MR angiography. The usual dose is 0.1 mmol / kg body weight, corresponding to 0.2 ml / kg body weight intravenously. Maximum can be administered in patients with healthy kidneys up to 0.3 mmol / kg body weight, however, is such a high dose appears only rarely.