PET Aids in Cancer Treatment
Reported July 07, 2009
(Ivanhoe Newswire) Molecular imaging methodology could promote development of new targeted therapies for certain types of breast, ovarian, prostate, and lung cancers that may be aggravated by the HER2 protein, which is often associated with very aggressive cancer.
Researchers successfully used position emission tomography (PET) and a specially-developed radioactive compound in mice to image HER2 in breast cancer cells before and after a novel treatment aimed at decreasing HER2 expression.
Much new research has focused on therapies targeted to HER2. This protein is over-expressed in approximately 20 percent of breast cancers and in some ovarian, prostate and lung cancers. Tumors that have an excess of HER2 protein are more aggressive and are more likely to recur than tumors that do not over-express the protein.
“Obtaining an accurate assessment of the HER2 expression levels in breast cancer tumors is absolutely essential to know whether treatment aimed at reduction of the protein levels in tumor cells is effective,” Jacek Capala, senior author of the study and investigator for the radiation oncology branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD, is quoted as saying. “Our study indicates that PET could be a powerful tool both to identify patients who might benefit from targeted molecular therapies and to manage their care by measuring response to treatment. As research into HER2 therapies continues, similar techniques could be developed for other cancers over-expressing different proteins.”
The imaging technique developed in the study represents a breakthrough in measuring HER2 expression. The conventional method requires biopsies of tumors that have been removed from the body. These samples may not represent the overall characteristics of the tumor and may not accurately estimate HER2 expression. Currently there is no way to evaluate how long a therapeutic agent takes to affect the targeted tumors and how long the effects last.
In this study, the researchers implanted human breast cancer cells expressing either high or very high levels of HER2 under the skin of mice. They attached the radioactive nuclide flourine-18 to an HER2-binding variant of a small protein known as an Affibody molecule. They injected the HER2-targeting Affibody compound intravenously and performed PET imaging three to five weeks after tumors had formed. PET scans were able to detect the Affibody compound and allow researchers to visualize breast cancer tumors with HER2 protein.
Four doses of the drug 17-DMAG were administered at 12-hour intervals. PET scans were performed before the treatment and after each dose. The researchers found that HER2 expression was reduced by 71 percent in mice bearing tumors with very high levels of HER2 protein and by 33 percent in mice bearing tumors with high levels of the protein, compared to the levels measured before treatment and to tumors that did not receive the treatment. Researchers believe these Affibody molecules can also be engineered to specifically bind to other targets for cancer diagnosis and therapy.
SOURCE: The Journal of Nuclear Medicine, July 2009