When the researchers injected the "always on" fluorescent molecule Av-0.5ROX into the peritoneum of tumor-bearing mice, fluorescence was immediately detectable and more intense than that produced by Av-3ROX immediately following its injection. However, Av-0.5ROX produced fluorescence in both tumor cells and the surrounding tissue, making it difficult to distinguish the tumor cells. In contrast, by three hours after Av-3ROX injection, the fluorescence intensity in normal tissues was less than with Av-0.5ROX , but the fluorescence intensity in tumor nodules was much higher than with Av-0.5ROX.

To confirm that Av-3ROX was primarily processed by tumor cells, the researchers performed a second experiment in mice, this time using cells that carried the gene for red fluorescent protein (RFP) to induce the initial tumors and peritoneal metastases. This approach allowed every metastasis to be detected using a camera and filter specific for RFP. The investigators then injected Av-3ROX into the peritoneum of the mice and captured fluorescent images of both Av-3ROX and RFP. Next, they compared the number of metastases identified using both compounds.


Out of 507 metastases, at least 0.8 millimeters in diameter, shown by RFP, Av-3ROX detected 465 of them, indicating a sensitivity of 92 percent. Only 2 percent of metastases identified by Av-3ROX turned out to be false positives, translating to a 98-percent tumor detection accuracy, or specificity, for this technique.

Although the data provide proof-of-concept for this type of molecular imaging technique, Av-3ROX cannot be used in people, because the avidin portion of the compound would cause an immune system reaction. Kobayashi and his colleagues 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. This compound "should not create a harmful immune response because it's based on a human protein," said Kobayashi.

The authors believe that this approach to molecular imaging holds promise as a method of optically enhancing surgical or endoscopic procedures, allowing for more complete surgical removal of metastatic disease.

For more information on NCI's Molecular Imaging Program, including Drs. Kobayashi, Choyke, and Bernardo, go to http://ccr.cancer.gov/labs/lab.asp?labid=175.

For more information about cancer, please visit the NCI website at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Researchers are from the Molecular Imaging Program, Center for Cancer Research, NCI, Bethesda, Md.; the Nuclear Medicine Department, Warren Magnuson Clinical Center, NIH, Bethesda, Md; and the Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.

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