Researchers have created a new imaging compound that fluoresces only when processed by cancer cells. Use of this compound allowed scientists to visualize 92 percent of the very small tumors in the peritoneum - the tissue that lines the wall of the abdomen - in mice with ovarian cancer. The results were published in the March 15 Cancer Research.

The team led by Dr. Hisataka Kobayashi from the Molecular Imaging Program in NCI’s Center for Cancer Research (CCR) created a compound consisting of the protein avidin, which binds to a protein commonly found on cancer cells that have spread to the peritoneum, joined to three molecules of the fluorescent compound rhodamine X. This complex, called Av-3ROX, is taken up by a cancer cell after binding to its surface and is subsequently broken down in the lysosome. When enzymes in the lysosome break the molecule into smaller pieces, the fluorescence from rhodamine X is released, enabling the cancer cell to be detected using imaging techniques.

To verify that Av-3ROX was specifically internalized into tumor cells, the investigators used cells that carried the gene for red fluorescent protein (RFP) to induce tumors and peritoneal metastases in mice. The investigators injected Av-3ROX into the peritoneum of the mice, captured fluorescent images of both Av-3ROX and RFP, and compared the number of metastases identified using both compounds. They found that Av3-ROX had 92 percent sensitivity and 98 percent specificity for the cancer cells.

Because Av-3ROX would cause an immune system reaction in humans, the researchers are now working on a second-generation compound that joins the binding site of avidin - the part that recognizes the cancer cells - to human serum albumin. The authors believe that this approach to molecular imaging “holds promise as a method of optically enhancing surgical or endoscopic procedures,” and may allow for more complete surgical removal of metastatic disease.