Posted on November 3rd, 2011 by msequeira
A new technology for detecting breast cancer cells is making waves – nanomagnetic waves. Melding nanomedicine and magnetic imaging, researchers at the University of New Mexico Health Sciences Center, the UNM Cancer Center, Senior Scientific and Sandia National Labs have pioneered a detection strategy that has several potential advantages over conventional x-ray mammography. Their new method, described in the current issue of BioMed Central’s open-access journal Breast Cancer Research, uses tumor-targeted magnetic nanoparticles that are detected by ultra-sensitive magnetic coils. The technology could eventually improve screening for a disease that affects 207,000 American women each year.
“Our results suggest that this approach is a very promising first step toward the development of novel magnetic-based cancer detection in patients,” said UNM Associate Professor of Cell Biology & Physiology Helen Hathaway, PhD, a UNM Cancer Center researcher and lead author of the paper.
To create the new detection method, researchers developed a magnetic nanoprobe, made up of tiny iron oxide nanoparticles attached to antibodies for HER-2, a protein that is overexpressed in about 30 percent of breast cancers. HER-2 is one of the best known biomarkers for breast cancer and is typically associated with aggressive forms of the disease. Released into model tumor systems, the antibody-tagged magnetic nanoparticles fastened themselves to HER-2 receptors on the surface of breast cancer cells. Though this research was specific to HER-2 breast cancers, the team sought to develop both a universal magnetic nanoprobe and a universal method of attaching tumor-targeting peptides or antibodies to nanoparticles in anticipation of future biomarker discoveries and the flexible application of their technology to other types of cancer.
After allowing time for the nanoprobes to bind to breast cancer cells (typically on the order of 100,000 nanoparticles per cell), researchers introduced a brief magnetizing pulse to set up a uniform magnetizing field across the sample. Within this field, magnetic particles line up in the same direction, a phenomenon that physicists call a “magnetic moment.” The magnetic moment decays at a predictable rate once the magnetizing field is removed. Researchers measured that decay using extremely sensitive magnetic coils known as SQUID. Because the amount of decay has a linear relationship to the number of tumor-bound nanoparticles, researchers are able to mathematically determine the number of cancer cells within the tumor. Signals from unbound particles are not detected by the system – which makes it potentially more precise than MRI in identifying the location of cancer cells.
In a final phase of the reported research, the team tested the sensitivity of their system using a clay breast model similar to the “breast phantom” used to evaluate mammography. (Both clay and the human body are transparent to low-frequency magnetic fields, so the clay model accurately simulates typical breast geometry and magnetic behavior.) Nanoparticle-labeled cells were embedded in the synthetic breast at various depths and concentrations for detection by the new magnetic method.
“We were able to accurately pinpoint 1 million cells at a depth of 4.5 centimeters,” said Dr. Hathaway. “This is about 1000 times fewer cells than the size at which a tumor can be felt in the breast, and 100 times more sensitive than mammography.” The system’s success at that depth is crucial because the human breast has an average thickness of 4.4 centimeters. While the sensitivity gains may not translate fully in the more complicated environment of the actual human breast, Dr. Hathaway cautioned, the system offers clear advantages for women with dense, scarred or augmented breasts. These tissue types pose some barriers to accurate mammographic imaging, but are transparent to the nanomagnetic detection method.
The new method has other potential benefits over mammography. Though screening mammography is a powerful tool in detecting breast cancer early – when treatment is often most effective – mammograms fail to find an estimated 10 to 25 percent of breast cancers. Research results to-date suggest that the UNM team’s technology, with its greater sensitivity, may pave the way for earlier detection of breast cancer tumors, as well as more accurate detection in certain women. Further, x-ray mammography is unable to distinguish between benign and malignant tumors (a biopsy is needed to rule out or confirm cancer), resulting in many “false positives.” The new system could reduce the false positive rate – in principle, the magnetic coils only detect nanoparticles that are bound to cancer cells – thereby easing the mental health toll and potential for overtreatment.
Beyond detecting breast cancer tumors, the technology could be further refined to predict disease progression and monitor the effectiveness of treatment. Both of these additional applications have the potential to improve patient survival.
“Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors” was published online in Breast Cancer Research on October 28, 2011. Authors include Helen J. Hathaway (UNM Department of Cell Biology & Physiology, UNM Cancer Center), Kimberly S. Butler (UNM Department of Pathology), Natalie L. Adolphi, (UNM Department of Biochemistry & Molecular Biology, UNM Cancer Center), Debbie M. Lovato (UNM Department of Pathology), Robert Belfon (UNM Department of Cell Biology & Physiology), Danielle Fegan (Senior Scientific, LLC), Todd C. Monson (Sandia National Labs), Jason E. Trujillo (UNM Department of Pathology), Trace E. Tessier (Senior Scientific, LLC), Howard C. Bryant (Senior Scientific, LLC), Dale L. Huber (Sandia National Labs), Richard S. Larson (UNM Health Sciences Center), and Edward R. Flynn (Senior Scientific, LLC, UNM Cancer Center).
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