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).
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