UH-UK Biomedical Researchers Design Ultrasensitive Magnetic Probe to Detect Spread of Breast Cancer


London surgeon testing device for locating magnetic nanoparticles in lymph nodes
 
University of Houston and University College of London physicists have designed a handheld tool for surgeons that promises to be more accurate, cost-effective and safer than existing methods for staging and treating various cancers, including breast cancer.

Staging is the system used to determine the amount and location of cancer in the body and how much the cancer has spread.  Surgeons utilize a technique known as sentinel lymph node biopsy to find out if certain cancers have spread to the lymph nodes, with the sentinel lymph node being the first that a tumor’s metastasizing cancer cells will drain to.

To enable surgeons to more effectively locate the sentinel lymph node, teams headed by Audrius Brazdeikis, research assistant professor of physics at the Texas Center for Superconductivity at the University of Houston (TcSUH), and Quentin Pankhurst, UCL professor of physics, have developed a novel detection procedure combining nanotechnology and advanced magnetic sensing based on high-temperature superconductors.  The researchers produced the ultrasensitive magnetic probe to detect minuscule magnetic fields in the body with a $250,000 grant received in 2004 from the United Kingdom Department of Trade and Industry under the UK-Texas Bioscience Collaboration Initiative.

The probe is a supersensitive magnetometer?an instrument used to track the presence of clinically introduced magnetic nanoparticles. During breast cancer surgery, a surgeon will inject a magnetic nanoparticle dye, already approved as an imaging contrast agent by the Federal Drug Administration, into the tumor or into tissues surrounding the tumor.

The grant, which ended in 2006, required Brazdeikis and Pankhurst to show “proof of concept” by building a device and showing it worked, Brazdeikis said. An ethics committee in the UK since has approved the detection procedure for a clinical trial of women undergoing breast cancer surgery at University College Hospital, London.

“We only believe the value of biomedical research is if it is validated in a real clinical setting,” Brazdeikis said.

Dr. Michael Douek, a London surgeon who specializes in breast surgery and is a senior lecturer at UCL, is overseeing the trial and used the probe for the first time in surgery this past December. Douek, who visited Houston recently in preparation for the testing, said the ethics committee gave the hospital permission to use the probe in 10 surgeries, and after a review of those procedures, the number could increase to 100.

Brazdeikis, who heads the Biomedical Imaging Group at TcSUH, said a goal of the grant was to commercialize biomedical technology developed at universities through collaborative research.  He and Pankhurst, deputy director of the London Centre for Nanotechnology, have formed a medical devices company to bring their technology to the marketplace and patented the probe.

The UH-UK collaboration recently gained the attention of Nature Nanotechnology, a journal recently launched by Nature Publishing Group. The publication profiled the probe, marketed under the name SentiMAG™, and the spinoff company, Endomagnetics Inc., under “Research Highlights” in the January 2007 issue.

In September 2006, Endomagnetics also garnered recognition from England’s Prince Andrew, his country’s special representative for international trade and investment, who highlighted new technology developed by the nanotechnology industry at the Nano-TX ’06 conference in Dallas.

“At this conference, there is an exciting example of the early stages of this kind of progress,” the prince said, according to a transcript of his remarks. “I speak of Endomagnetics, which was developed from research funded by the UK-Texas Bioscience Collaboration Initiative at University College London and the University of Houston. The partnership has resulted in a technology used to locate lymph nodes for the staging and treatment of various forms of cancer, including breast cancers and melanomas, and some of the more disfiguring and demoralizing forms of cancer.”

Although the technology has potential for use in the staging and treatment of other cancers, including lung and prostate cancer, Douek, who has advised the researchers from the beginning of the probe’s development, said the instrument needs to be customized for the type of surgery.

“We went through a whole series of different probes over the course of a year,” he said.

Douek said he was interested in being part of the project because of his interest in magnetic resonance imaging. “This is an extension of that technology,” he said.

A surgeon holds the probe, which incorporates two sets of coils connected to a sensor. One set of coils magnetizes the magnetic particles, and the second detects the magnetic response from those particles. The sensor, known as an HTS SQUID or high temperature superconducting quantum interference device, is located in a cryogenic vessel on a cart and is submerged in liquid nitrogen that cools the sensor to 77 K, equivalent to  -320.5 F. The system uses custom-built electronics and software on a laptop computer to give the surgeon visual and audio feedback while tracking the magnetic nanoparticles in the body.

 “When breast cancer is diagnosed, and a tumor has been located,” Brazdeikis said, “a critically important issue is whether or not the cancer has spread to other parts of the body–a process that occurs via the transport of metastatic cancer cells through the lymphatic system. The surgeon looks for lymph nodes close to the cancer. They are not easy to find. The probe is a tool for the surgeon to use during the surgery to locate the sentinel lymph node.”

In the case of breast cancer, a surgeon who detects no cancer in the lymph nodes will perform a lumpectomy to remove only the tumor. If the cancer has spread, however, the surgeon will perform a more radical operation, removing not only the tumor but also the arm-pit lymph nodes.

“Our technology offers unprecedented quality and value of care benefits to patients, doctors and hospital administrators over existing procedures,” Brazdeikis said.

Existing practice calls for a breast cancer patient to receive two injections, of a radioactive isotope and a blue dye, eight to 12 hours before surgery. Later in the operating room, the surgeon uses a handheld gamma probe, aided by the visual observation of the dye, to locate the lymph node with the highest radioactivity.

The preoperative injections are necessary because during the first eight hours there is a large background signal, and after 12 hours the signal is too weak. This requires hospitalization the night before the operation, possibly increasing patient anxiety.

“Surgeons have a very small window of opportunity to measure which lymph nodes the cancer is draining to,” Brazdeikis said. 

Also, a nuclear medicine practitioner, rather than a surgeon, must inject the radioactive material, necessitating the hospital employing designated personnel in a nuclear medicine department. Hospitals must comply with increased regulations involved with using radioisotopes. And a delayed surgery may mean the hospital will have to reschedule it because of the weakened signal.

Using the current procedure, exposure to radioactive material also poses a safety concern for both the patient and the surgeon. Additionally, Douek said, “The blue dye creates a mess. It makes the whole surgery site blue.”

The UH-UCL technology not only eliminates the need for nuclear medicine personnel but also allows a surgeon to administer one injection, of the magnetic dye that takes only 10 to 15 minutes to work. If surgeries are backlogged, a patient may not have to be hospitalized while waiting, and the technology eliminates unnecessary patient and surgeon exposure to radioactivity.

“We introduce a paradigm-shifting new technology for the staging and treatment of breast cancer,” Brazdeikis said. “It will be very appealing for surgeons to take this technology into their practice.”