MRA contrast selection expands with new compounds

February 11, 2006

Contrast agents that can aid MRA examinations have been on the market for more than 15 years. Historically, radiologists could choose from a wide range of agents that, once injected intravenously, would flow through the extracellular space. They would then be excreted from the body relatively rapidly. These extracellular contrast agents are now being joined by a new class of blood pool, or intravascular, contrast agents that bind with molecules in the blood and stay in the circulation for longer.

Contrast agents that can aid MRA examinations have been on the market for more than 15 years. Historically, radiologists could choose from a wide range of agents that, once injected intravenously, would flow through the extracellular space. They would then be excreted from the body relatively rapidly. These extracellular contrast agents are now being joined by a new class of blood pool, or intravascular, contrast agents that bind with molecules in the blood and stay in the circulation for longer.

- Extracellular contrast. Most extracellular MRA contrast agents are based on gadolinium chelates. These compounds all shorten T1 relaxation times to a certain degree, improving visualization of blood vessels and vascular pathology during MRA. Because the chelates are reasonably small molecules, they will stay in the vasculature for only a short period of time before leaking out and being eliminated in the body.

Most extracellular MRA contrast agents are available as 0.5 M solutions. These include Doterem (gadoterate meglumine or Gd-DOTA, Guerbet), Magnevist (gadopentate or Gd-DTPA, Schering), and Omniscan (gadodiamide or Gd-DTPA-BMA, GE Healthcare).

Schering also markets a 1 M formulation, Gadovist (gadobutrol or Gd-BT-DO3A). The higher concentration means that MRA can be performed with a smaller contrast bolus. This may improve the quality of studies and permit perfusion imaging.

- Intravascular agents. Intravascular, or blood pool, MR contrast agents are made from smaller molecules than those used for extracellular contrast. Once in the bloodstream, they bind reversibly with albumin in blood plasma to form a larger structure that is essentially trapped in the vasculature. This increases the longevity of blood pool agents in the body considerably and, as a result, also increases the time available for imaging. The large size of the chelate-albumin combination also means that the agent has a greater impact on the relaxation times of water molecules. This should result in shorter T1 relaxation times and so greater efficacy per unit dose than extracellular agents.

Vasovist (gadofosveset trisodium or diphenylcyclohexyl phosphodiester-Gd-DTPA, Schering) became the first intracellular MRA contrast agent to receive marketing approval in October 2005. The agent is currently available throughout Europe and is awaiting clearance from the U.S. Food and Drug Administration before launching to the U.S. market.

Other blood pool agents are at various stages of development. Most, but not all, are likely to be based on Gd chelates. Alternative options under consideration include agents made from superparamagnetic iron oxide particles. Such agents would have quite different pharmacokinetics compared with the Gd compounds, inducing some changes to T2 relaxation times as well as T1 shortening.

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