A Multipurpose Fluorescent Molecule Guides Cancer Surgery

Researchers at the University of California San Diego (UCSD; USA) developed the novel molecular label, which works in two ways. First, it tags the cancer cells with a fluorescent marker that highlights the tumors for identification and removal during surgery; second, it contains a magnetic marker that can be used to evaluate the disease via magnetic resonance imaging (MRI).

The molecule is composed of a two-peptide structure; one peptide acts as both a fluorescent and magnetic label and the other keeps the molecule neutral. When in the presence of tumor cells, enzymes called matrix metalloproteinases (MMPs) snip off the neutralizing peptide and allows the labeled one to enter the cell. Once there, the dual probe remains active for as long as four or five days. During that time the peptide fluoresces in the near-infrared (IR) range, which has wavelengths long enough to make their way through layers of opaque human tissue, helping surgeons find hidden tumor cells. However, the new marker not only provides a visual aid during surgery, it can also be used to assess the presence of a tumor both before and after surgery. Radiologists can localize tumors magnetically during a preoperative MRI scan, surgeons then follow the IR map to remove all traces of the glowing tumor, and radiologists can then perform a postoperative MRI to ensure there is no remaining evidence of disease.

In studies in mice, the researchers were able to find and remove 90% more residual cancer cells than was possible with visible light alone; depending on the type of cancer, they were able to increase the animals' long-term survival rates by as much as fivefold. The researchers hope they may be able to add yet another feature to their molecule, a third peptide branch that becomes toxic in the presence of bright light. Thus, at the end of the surgery, the surgeon could shine a bright light that targets the fluorescent molecule and turns it phototoxic, killing all residual cells. The researchers are also looking into other potential uses for their molecule, such as lighting up arterial plaques to identify those most at risk of causing a stroke or heart attack. The study describing the new molecular label was published in the March 2010 issue of the Proceedings of the [U.S.] National Academy of Sciences (PNAS).

"With the new molecule, we can not only do guided surgery, but we can show an increase in survival,” said lead author Roger Tsien, Ph.D., a biochemist at UCSD who shared the 2008 Nobel Prize in chemistry for his work on green fluorescent protein.

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