March 2001

From University of Pennsylvania Medical Center

Breast cancer detection technique uses fluorescent molecules

Penn researcher describes 'minimally invasive' test at national meeting

A detection technique for early-stage breast cancer that literally tracks and illuminates cancerous cells will be announced Wednesday by a scientist at the University of Pennsylvania School of Medicine, on behalf of a group of researchers from Penn, Harvard University and Washington University.

Britton Chance, MD-PhD, an emeritus professor of biochemistry and biophysics at Penn, will discuss the technique in his report on current molecular beacon research at the annual meeting of the American Physical Society in Seattle. His work focuses on sensitive optical methods to detect those beacons, which are hidden deep in cancers inside breast tissue.

The research borrows from the radar techniques of the 1940s as well as contemporary CD and cell phone technology.

It relies on tricarbo-cyanine, a well-known contrast agent traditionally used for testing liver function. In the current study, the tricarbo-cyanine is adminstered into the bloodstream and accumulates in the breast tissue. It is imaged by sending very short pulses of red light through subsurface tumors to co-register with magnetic resonance imaging (MRI). Chance and his colleague, Ata Akin, PhD, of Drexel University, now propose using a hand-held, near-infra-red sensor they've been developing to pick up the light pulses. "This is an example of minimally invasive imaging where small amounts of a biochemical can make a definitive diagnosis," Chance says. The procedure, which he describes as a "stealth probe," was developed in collaboration with Ralph Weissleder, PhD, of Harvard and Penn researchers Ponzy Lu, PhD; Jerry D. Glickson, PhD, and Alan M. Gewirtz, MD.

Fluorescent tricarbo-cyanine molecules that are cloaked by a peptide are administered into the bloodstream and travel to the breast, where they begin searching for cancer cells. When they locate malignant cells, they enter. Then enzymes in the tumor cells respond by opening the peptides covers. When the covers are removed, the glowing tricarbo-cyanine molecules emit a signal powerful enough to be picked up by a circle of tiny laser diodes on the sensor -- an optical imaging device that is, itself, smaller than a CD disc.(The sensors are acquired from manufacturers that also supply CD players.)

Finding a way to defeat breast cancer by homing in on malignant cells before they can begin to metasticize is one of the most tantalizing goals of medical science. Traditional mammography, which is still considered the best method of detection in the field, is far from fail-safe; even yearly X-rays can miss beginning tumors. And although recent innovations -- including computer-aided detection (CAD), which re-checks mammograms for accuracy, digital mammograms, and MRI scans -- are hopeful advances, just this month the Institute of Medicine exhorted scientists to make greater efforts to devise more effective technology.

The optical imaging technique that Chance and his colleagues are proposing has already been tested with a limited number of women, and will soon enter phase-II trials at Penn and in two other laboratories and four pharmaceutical companies: Dartmouth University, under Brian Pogue, PhD, and the University of California, Irvine, under Bruce Tromberg, PhD. The companies include: Phillips, Siemens, ART, and Imaging Diagnostic Systems, Inc.

"In our preliminary test," Chance says, "We had a success rate in the percentage range of the high 80s." He notes that an animal-model study that evaluated the procedure for use in detecting prostate cancer, which was conducted by Steven Jacques, PhD, of the University of Oregon, has also had positive results.

In searching for breast cancer cells, the procedure could offer advantages beyond being minimally invasive. Because the procedure does not have the limitations that mammography has in its capacity to examine dense breast tissue, it could be used on women under 40 who have a family history of breast cancer. "And the proposed hand-held unit has outreach possibilities for underserved populations of women who can't get to a clinic or hospital for an X-ray," Chance said.

The study was conducted in collaboration with Weissleder and Sam Achilefu, PhD, of Washington University. Others who worked on the study are Vasilis Ntziachristos, PhD; Mitchell D. Schnall, MD, and Joseph Culver, PhD, all of Penn, and Eva M. Sevick-Muraca, PhD, of Texas A&M University. The work was funded by the National Institutes of Health through the Unconventional Innovations Program and other Cancer Institute grants.












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