While ultrasound provides a less expensive and radiation-free alternative to detecting and monitoring cancer compared to technologies such as X-rays, CT scans and MRIs, the lower clarity and resolution of ultrasound has limited its use in cancer treatment. Researchers at the University of North Carolina at Chapel Hill have overcome this limitation by combining ultrasound with a contrast agent made of micro-sized bubbles that pair with an antibody produced at elevated levels by many cancers.
By binding to the protein SFRP2, the microbubble contrast agent greatly improves the resolution and tumor-detecting ability of scans produced by ultrasound. In a paper published by PLOS-ONE, UNC Lineberger Comprehensive Cancer Center members Nancy Klauber-DeMore, MD, professor of surgery, and Paul Dayton, PhD, professor of biomedical engineering, were able to visualize lesions created by angiosarcoma, a malignant cancer that develops on the walls of blood vessels.
"The SFRP2-moleculary targeted contrast agent showed specific visualization of the tumor vasculature," said Dr. Klauber-DeMore. "In contrast, there was no visualization of normal blood vessels. This suggests that the contrast agent may help to distinguish malignant from benign masses found on imaging."
Dr. Klauber-DeMore's lab was the first to discover that angiosarcoma cells produce an excess of SFRP2. Building on that discovery, her team focused on how to use the protein to better monitor the progress of the cancer within blood vessels. Using a pre-clinical model, the researchers delivered the microbubble contrast agent via intravenous injection and tracked it using ultrasound.
Since SFRP2 is expressed in many cancers -- including breast, colon, pancreas, ovarian and kidney tumors -- the technique could potentially be useful on a broad range of cancer types. Dr. Klauber-DeMore said that the next steps of her research team will involve determining how well the technique works with these other tumor types, as well as studying its effect on breast cancer.
As research indicates that the level of SFRP2 expressed by the tumors increases as the tumor develops, the team will also investigate whether the technique can be used to track tumor growth, making it useful for monitoring response to chemotherapy. They will also investigate whether it can be used to detect and visualize very small tumors.
"The question is can you develop a contrast agent that better tells you whether a tumor is malignant or benign," said Klauber-DeMore.
Since ultrasound is less expensive than commonly used imaging methods like magnetic resonance imaging (MRI), the technique could be useful in lowering the costs to patients being treated for cancer. As ultrasound is more portable than other imaging devices, it may be useful in providing treatment in rural and low-resource areas.
- James K. Tsuruta, Nancy Klauber-DeMore, Jason Streeter, Jennifer Samples, Cam Patterson, Russell J. Mumper, David Ketelsen, Paul Dayton. Ultrasound Molecular Imaging of Secreted Frizzled Related Protein-2 Expression in Murine Angiosarcoma. PLoS ONE, 2014; 9 (1): e86642 DOI: 10.1371/journal.pone.0086642
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