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The work of Jacek Capala
may have implications
in breast cancer research

Imaging Technique Allows Researchers to Monitor Protein Changes in Mouse Tumors

by Barbara Kram, Editor
A new imaging technique can monitor, in living mice, the HER2 protein found in above-normal amounts in many cases of breast cancer as well as some ovarian, prostate and lung cancers. This new approach, once validated in mice and pending further experiments, could provide a real-time noninvasive method for identifying tumors in humans who express HER2 and who would be candidates for targeted therapy directed against this protein. It may also provide real-time information that will help clinicians optimize treatment for individual patients. The study, published in the July 2009 issue of The Journal of Nuclear Medicine, was conducted by researchers at the National Cancer Institute (NCI) and the National Institute of Biomedical Imaging and Bioengineering, both parts of the National Institutes of Health.

The HER2 protein is overexpressed (produced at higher-than-normal levels) in approximately 20 percent to 25 percent of breast cancers. Tumors that overexpress HER2 are more aggressive and more likely to recur than tumors that do not overexpress the protein. Targeted therapies directed against HER2 can slow or stop the growth of tumors that overexpress it.

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Currently, HER2 expression is measured in biopsy specimens - that is, in tumor samples that have been removed from the body. However, expression of HER2 in these samples may not accurately represent HER2 expression in the tumor as a whole. Moreover, follow-up biopsies are not routinely performed after the initial diagnosis, and there are no means to evaluate how long a targeted therapy takes to reach its target, how effective it is, and how long its effects last.

In this study, the research team used an imaging compound that consists of a radioactive atom (fluorine-18) attached to an Affibody molecule, a small protein that binds strongly and specifically to HER2. Affibody molecules, developed by Affibody AB, Bromma, Sweden, are much smaller than antibodies and can reach the surface of tumors more easily. The radioactive atom allows the distribution of the Affibody molecules in the body to be analyzed by positron emission tomography (PET) imaging.

The research team first used the radiolabeled Affibody molecule to visualize tumors that expressed HER2 in mice. The mice were injected under the skin with human breast cancer cells that varied in their levels of HER2 expression, from no expression to very high expression. After three to five weeks, when tumors had formed, the mice were injected with the Affibody molecule and PET images were recorded. The levels of HER2 expression as determined by PET were consistent with the levels measured in surgically removed samples of the same tumors using established laboratory techniques.

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