| March 14, 2001
Breast Cancer Detection Technique
Uses Fluorescent Molecules To Track and Illuminate Malignant
Cells
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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