The new agent works by binding to micro-calcifications produced in breast cancers. Though scientists cant explain exactly why these calcifications occur, studies show that the calcifications in malignant breast tumors contain a higher proportion of a particular calcium salt called hydroxyapatite. In benign tumors, the predominant calcium salt is calcium oxalate.
By homing in on hydroxyapatite, we can target these malignant cells with a high degree of specificity, and that has the potential to improve the patients outcome, Frangioni says.
The contrast agents are designed using a combination of bisphosphonate, a type of drug used to strengthen bone, with a near-infrared fluorophore. When used with optical tomography, an imaging method that transmits near-infrared light through the body, doctors can reconstruct a three-dimensional image of tissues deep inside the breast, highlighting areas where malignant tumors appear.
The agent also may be used during surgery to pinpoint the location of hydroxyapatite, and therefore the breast cancer cells themselves, Frangioni notes.
His group began working to develop agents to target hydroxyapatite six years ago, but efforts were stalled by the inability to manufacture large quantities of the agent.
It was a chemical catch22, he says. Bisphosphonates are insoluble in anything but water, but to prepare large quantities of the substance for our studies, we need to perform the reaction in the absence of water.
Last year, Frangionis chemistry group, led by Bhushan, went back to the drawing board and devised a scheme that allowed them to synthesize the agents sans water. Once the compound was completely assembled, the researchers found a way to then make it water soluble.
Recent studies by the lab proved that the new agent works well in
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26-Mar-2007