Researchers have developed a new type of imaging compound that allows them to visualize viable breast cancer cells that have spread to the lungs in mice. The compound binds to a protein called HER2, which is found on the surface of some breast cancer cells, and it glows, or fluoresces, only when taken inside living cells. This method of targeting and activation allowed researchers to detect specific types of live cancer cells in a mouse model of breast cancer. The study, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and in Japan, appeared online Dec. 7, 2008, in Nature Medicine.

Previously developed fluorescent compounds that are activated inside the body's cells have the limitation that, once they are turned on, they continue to fluoresce even after they diffuse to new locations, making it difficult to distinguish viable tumor cells from normal tissue or dead or damaged tumor cells. The research team, led by Hisataka Kobayashi, M.D., Ph.D., at the Molecular Imaging Program of NCI's Center for Cancer Research (CCR), in collaboration with Yasuteru Urano, Ph.D., at the University of Tokyo, created an imaging compound that is turned on only when it is inside a living cell and stops fluorescing when it leaves the cell, as would happen when the cell dies or becomes damaged. The compound also can be engineered to target specific types of cancer cells.

"Imaging compounds designed by our concept may have applications in the clinic," said Kobayashi. "These compounds may allow clinicians to monitor a patient's response to cancer therapy by allowing them to visualize whether a drug hits its target and whether hitting the target leads to shrinkage of the tumor. With additional research and extensive testing in humans, these compounds may also be adapted for use in endoscopy procedures and for use as a surgical aid to improve removal of tumors."
The team created the activatable, cancer-targeting compound by joining a drug called trastuzumab (Herceptin), which is an antibody that binds to HER2 and is used to treat HER2-positive breast cancer, to a modified version of a small fluorescent complex known as BODIPY. This complex fluoresces only under acidic conditions, such as those found inside cellular structures called lysosomes, which are sac-like compartments inside cells that contain enzymes that break down large molecules the cell does not need. When the activatable BODIPY-antibody compound encounters a HER2-positive breast cancer cell, the trastuzumab portion binds to HER2 proteins on the cell's surface, and then the cell takes the HER2-activatable complex inside. When this complex is processed inside the cell and enters the acidic environment of a lysosome, BODIPY becomes activated and fluoresces.

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