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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



Contrast agents to prevent heart attacks and strokes


12 May 2006

US researchers have prepared compounds that detect the presence of an enzyme linked to heart attacks and strokes.

Alexei Bogdanov at the University of Massachusetts and colleagues developed a contrast agent (a substance that improves tissue visibility in medical images) based on a gadolinium complex. The contrast agent is activated by the enzyme myeloperoxidase (MPO), reported to be responsible for atherosclerosis, or hardening of the arteries.

MPO contrast agent

Atherosclerosis involves the build up of cholesterol and lipid deposits on artery walls. These deposits, or plaques, contain high levels of MPO; Bogdanov's goal was to develop a sensing agent to highlight MPO-rich areas and so detect the plaques. Early detection of plaques is important since ruptured plaques can release fragments that cause clots to form. Clots can block the arteries or, if they become dislodged, pass into the heart or brain and lead to heart attacks or strokes.

"MPO activation enables the agent to give off a much brighter signal in diseased areas that lasts longer than those of conventional, non-specific, agents"
Bogdanov's contrast agents react in the presence of MPO, forming larger molecules which display more clearly in magnetic resonance imaging (MRI) scans. 'MPO activation enables the agent to give off a much brighter signal in diseased areas that lasts longer than those of conventional, non-specific, agents,' said Bogdanov. The compounds have shown no substantial toxicity in tests in vivo and, although there is a need for formal toxicity tests, the future looks promising, he said.

Hongzhi Xie from the Los Alamos National Laboratory in the USagreed. 'The current study on MR [magnetic resonance] contrast agents can be developed to identify MPO-rich areas and detect atherosclerotic vulnerable plaque [for] imaging and diagnosis,' said Xie.

Elinor L Richards

References

M Querol, J W Chen and A A. Bogdanov Jr, Org. Biomol. Chem., 2006, 4, 1887
DOI: 10.1039/b601540a