Researchers have created a new imaging compound in mice that selectively binds to certain cancer cells and glows, or fluoresces, only when processed by these cells. This cancer-specific fluorescence allowed the investigators to successfully visualize very small tumors in the peritoneum — the tissue that lines the wall of the abdomen — in mice with ovarian cancer. The sensitivity — or ability to accurately detect small clusters of tumor cells — of this approach was 92 percent. The study, conducted by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and colleagues, appears in the March 15, 2007 issue of Cancer Research.

"The virtue of this study is that other fluorescent compounds have been tested for the detection of small clusters of cancer cells that might otherwise be missed during surgery, but those have drawbacks, including being always fluorescent thereby making it difficult to distinguish tumor cells from normal tissue. This study points to a potential solution to this problem," said NIH Director Elias A. Zerhouni, M.D.

"A fluorescent imaging compound that is specific for cancer cells holds great promise for the treatment of cancers, such as ovarian and pancreatic cancer, which often metastasize widely before diagnosis. In the coming years, as cancer research is increasingly based on an understanding of tumors down to a detailed molecular level, advanced imaging will be a key component of essentially every study," said NCI Director John E. Niederhuber, M.D.

The researchers, led by Hisataka Kobayashi, M.D., Ph.D., from NCI's Molecular Imaging Program in the Center for Cancer Research, created a compound to be tested only in mice that consisted of the protein avidin, which binds to another protein commonly found on the surface of cancer cells that potentially can spread, or metastasize, to the peritoneum. They joined this compound to three molecules of the fluorescent compound rhodamine X. In this new compound, which they called Av-3ROX, the rhodamine X molecules are unable to fluoresce. However, when Av-3ROX is taken up by cancer cells after binding to them, it is broken down in sac-like compartments inside the cells called lysosomes. When enzymes in the lysosomes break the compound into smaller pieces, the rhodamine X is released and is able to fluoresce.

"Conventional imaging methods such as nuclear isotopes, MRI, or CT use contrast agents that make a signal whether they are bound or unbound to a cancer cell," said Kobayashi. "Our method will make a signal only from cancer cells. It's cancer-specific imaging."

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.