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Intravenous MRI contrast agents

Intravenous MRI contrast agents include chelates of paramagnetic ions, both ionic and nonionic. The particulates, sequestered in the liver, spleen, and lymph nodes, the intravascular agents, confined to the blood pool, and tumour specific agents are discusses separately (see bottom). 

NOTE: This article has been transferred from mritutor.org and was last updated in March 5, 1996. Review and edit pending. 

Paramagnetic metal ions suitable as MR contrast agents are all potentially toxic when injected IV at or near doses needed for clinical imaging. With chelation of these ions, acute toxicity is reduced and elimination rate is increased thereby reducing the chance of long term toxicity.

Ionics

Chelates of paramagnetic ions Cr and Gd with EDTA were first used however EDTA was of relatively low stability resulting in toxicity in animals 1. Chelates with a higher stability constant have since been used successfully such as Gd-DTPA .

Gd-DTPA was the first intravenous MR contrast agent to be approved for human use (Magnevist, Berlex Labs). Gd has a large magnetic moment, exceeded only by Dysprosium(III) and Holmium(III), explaining its paramagnetic properties at low concentrations. This large magnetic moment is related to its seven unpaired orbital electrons. Gd-DTPA has similar pharmacokinetics as iodinated contrast agents. It is distributed in the intravascular and extracellular fluid spaces, does not cross an intact blood-brain-barrier, and is excreted rapidly by glomerular filtration 2.

Nonionics

The development of nonionic contrast agents for MRI has paralleled that for iodinated contrast materials. Ionic chelates are also hyperosmolar and some of their side effects may be attributed to this property.

Gadodiamide

Gadodiamide (Omniscan, Winthrop Pharm.) is a nonionic complex with two-fifths of the osmolality of Gd-DTPA. It has a median lethal dose of 34 mmol/kg resulting in a safety ratio of 2-3 times that of Gd-DOTA, and 3-4 times that of Gd-DTPA. No abnormal serum bilirubin levels occur, however elevated serum iron levels occurred with an incidence of 8.2% in one study of 73 patients.The efficacy of this contrast is similar to that of Gd-DTPA 3.

Gadoteridol 

Gadoteridol (Prohance, Squibb) is the third intravenous contrast agent on the market. It is a low osmolar, nonionic contrast as is Gadodiamide. Indications for use and efficacy are similar to the other agents 4.

Intravenous MRI contrast agent safety

Intravenous MRI contrast agent safety and Nephrogenic systemic fibrosis are discussed separately. 


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