This molecular imaging methodology could facilitate development of new targeted therapies not only for breast cancer, but also for certain types of ovarian, prostate, and lung cancers that may be aggravated due to HER2.
The conventional method requires biopsies of tumors that have been removed from the body; however, these samples may not represent the overall characteristics of the tumor and may not accurately estimate HER2 expression. In addition, there are currently no means to evaluate how long a therapeutic agent takes to affect the targeted tumors and how long the effects last.
In the study, researchers attached the radioactive nuclide flourine-18 to an HER2-binding variant of a small protein known as an Affibody molecule. Positron Emission Tomography (PET) scans can detect the Affibody compound and allow researchers to visualize breast cancer tumors with HER2 protein in mice. These molecules can also be engineered to specifically bind to other targets for cancer diagnosis and therapy.
The researchers implanted human breast cancer cells - expressing either very high or high levels of HER2 - under the skin of mice to show that this method of imaging can be used to monitor changes in HER2 expression after treatment. Researchers then intravenously injected the HER2-targeting Affibody compound and performed PET imaging three to five weeks after tumors had formed. Four doses of the drug 17-DMAG were administered, which decreases HER2 expression, spaced 12 hours apart. 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.
MEDICA.de; Source: Society of Nuclear Medicine