PNAS: Fluorescence + MR imaging probe can guide cancer surgery

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Surgery with molecular fluorescence imaging using a dual fluorescent plus a magnetic marker decreases residual cancer, improves survival and MRI-guided clinical staging, according to two studies published in the March issue of Proceedings of the National Academy of Sciences.

Roger Y. Tsien, PhD, University of California, San Diego--who shared the 2008 Nobel Prize in chemistry for his work on green fluorescent protein--and colleagues created a two-peptide structure. One peptide (activatable cell-penetrating peptide linked to nanoparticles) acts as both a fluorescent and magnetic label, and the other keeps the molecule neutral. In the presence of tumor cells, enzymes called matrix metalloproteinases (MMPs) snip off the neutralizing peptide and allow the labeled one to enter the cell. Once there, the dual probe remains for as long as four or five days delineating the margin between tumor and adjacent tissue, resulting in improved precision of tumor resection in mice.

With the new molecule, "we can not only do guided surgery, but we can show an increase in survival," said Tsien, the project's lead researcher.

The new marker not only provides a visual aid during surgery, but can be used to assess the presence of a tumor both before and afterward. Radiologists could localize tumors magnetically during a pre-operative MRI scan, surgeons could then follow the infrared map to remove all traces of glowing tumor, then radiologists could perform a post-operative MRI to ensure there's no remaining evidence of disease.

“These results should improve MRI-guided clinical staging, presurgical planning, and intraoperative fluorescence-guided surgery. The approach may be generalizable to deliver radiation-sensitizing and chemotherapeutic agents,” wrote Tsien and colleagues.

One of the drawbacks of using MMPs, however, is that they are not expressed in all cancers, and are present in some noncancerous tissues, too, including the liver and in areas of inflammation. As a result, the researchers have targeted their probe for use in surgical guidance, where an experienced surgeon can distinguish between cancerous tissue and inflamed areas elsewhere in the body.

The researchers are looking into other potential uses for their molecule, such as lighting up arterial plaques in order to identify ones most at risk of causing a stroke or heart attack. Avelas Biosciences, a new startup based in San Diego, licensed the probe technology in 2009 and hopes to have something ready for human testing within two to three years.