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August 12, 2015

Tiny Magnets Used to Detect Metastatic Breast Cancer

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    Metastasis occurs when cells are shed from primary breast cancer tumor and establish a new tumor at a distant site. CWRU researchers developed a probe that binds to fibrin-fibronectin protein complexes in high-risk tumors. Fibronectin is expressed in high-risk (aggressive) cancer and not in normal tissue, so MRI imaging is able to distinguish metastases from normal tissue. [Lu Lab, CWRU]

    Metastasis—the spread of cancer from its point of origin to a more distant organ—is of critical concern for most tumor types, but of particular importance for breast and prostate cancers. Early detection of rogue cells is vital for treatment options to be most effective, yet has had limited success previously.

    Now researchers at Case Western Reserve University (CWRU), funded by a grant from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a division of the National Institutes of Health, have shown that magnetic resonance imagining (MRI) can be used to detect the earliest signs of breast cancer recurrence and fast growing tumors. 

    "MRI has a wide array of diagnostic applications and shows promise in breast cancer detection and treatment monitoring," said Richard Conroy, Ph.D., director of NIBIB Division of Applied Science and Technology. "The technique used by researchers in this study enables very early detection of metastatic spread, which would allow adaptation of treatment more quickly and hopefully lead to better outcomes in the future."

    The findings from this study were published online today in Nature Communications through an article entitled “MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent.”

    The investigators used a biochemical approach combined with MRI to detect specific molecular signals that differentiate micrometastases from normal cells. Specifically, they developed a special contrast solution that contained a five amino acid long peptide coupled to a microscopic magnet. The amino acid chain was chosen for its affinity to bind to protein matrix structures surrounding cancer cells called fibrin-fibronectin.  

    "We showed with this technique that we can detect very tiny tumors of just a few hundred cells," explained senior author Zheng-Rong Lu, Ph.D., professor of biomedical engineering at CWRU. "Our imaging technology has the potential to differentiate aggressive tumors from low-risk tumors. These are two things that potentially can make a big impact on clinical practice and also management of cancer."

    Dr. Lu and his team collected images depicting metastases where breast cancer had spread beyond the original tumors. Metal molecules within the contrast solution are magnetized during the MRI process and enhance the image wherever the molecules of solution bind with the targeted protein.

    "The primary tumor sends signals to distant tissue and organs to prepare the soil for metastasis," Dr. Lu said. "By also binding with the magnetically tagged peptide, the biomarker is enhanced, generating enough signal for MRI detection of small, high-risk cancer and micrometastases."

    Using mice which they previously injected with breast cancer cells, the CWRU scientists were able to observe micrometastases in lung, liver, lymph node, adrenal gland, bone, and brain tissue. Moreover, using high-resolution fluorescence cryoimaging, the researchers were able to prove that their contrast peptide bound almost exclusively to fibrin-fibronectin complexes, producing a strong and prolonged image enhancement.

    Dr. Lu and his team had previously determined that their newly developed contrast agent was safe in animals and readily cleared from tissues—essential data for the method to be moved into human clinical trials, which they expect to do in the next few years. 

    "The recurrence rates of some forms of breast cancer and the consequence of metastatic cancer make these efforts urgent and important," noted Dr. Lu. "We think this targeted approach holds great promise for earlier imaging of high-risk cancers in the clinic. It could also become useful as a non-invasive way to assess breast cancer treatment progress."

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