designed nanoparticles can reveal tiny cancerous tumors
that are invisible by ordinary means of detection,
according to a study by researchers at Washington
University School of Medicine in St. Louis.
researchers demonstrated that very small human melanoma
tumors growing in mice—indiscernible from the surrounding
tissue by direct MRI scan—could be "lit up"
and easily located as soon as 30 minutes after the
mice were injected with the nanoparticles.
nanoparticles can be engineered to carry a variety
of substances, they also may be able to deliver cancer-fighting
drugs to malignant tumors as effectively as they carry
the imaging materials that spotlight cancerous growth.
of the best advantages of the particles is that we
designed them to detect tumors using the same MRI
equipment that is in standard use for heart or brain
scans," says senior author Gregory Lanza, M.D.,
Ph.D., associate professor of medicine. "We believe
the technology is very close to being useful in a
and his colleague Samuel Wickline, M.D., professor
of medicine, are co-inventors of this nanoparticle
technology. The effectiveness of the nanoparticles
in diagnosis and therapy in humans will be tested
in clinical trials in about one and a half to two
spherical nanoparticles are a few thousand times smaller
than the dot above this "i," yet each can
carry about 100,000 molecules of the metal used to
provide contrast in MRI images. This creates a high
density of contrast agent, and when the particles
bind to a specific area, that site glows brightly
in MRI scans.
this study, MRI scans picked up tumors that were only
a couple of millimeters (about one twenty-fifth of
an inch) wide.
rapidly growing tumors cause growth of new blood vessels,
which feed the tumors. To get the particles to bind
to tumors, the researchers equipped them with tiny
"hooks" that link only to complementary
"loops" found on cells in newly forming
blood vessels. When the nanoparticles hooked the "loops"
on the new vessels' cells, they revealed the location
of the tumors.
are particularly useful because of their adaptability,
according to Lanza, who sees patients at Barnes Jewish
Hospital. "We can also make these particles so
that they can be seen with nuclear imaging, CT scanning
and ultrasound imaging," Lanza says.
addition, the particles can be loaded with a wide
variety of drugs that will then be directed to growing
tumors. "When drug-bearing nanoparticles also
contain an imaging agent, you can get a visible signal
that allows you to measure how much medication got
to the tumor," Lanza says. "You would know
the same day you treated the patient and if the drug
was at a therapeutic level."
nanoparticles, drug doses could be much smaller than
doses typically used in chemotherapy, making the procedure
potentially much safer.
other side of that is you have the ability to focus
more drug at the tumor site, so the dose at the site
might be ten to a thousand times higher than if you
had administered the drug systemically," Lanza
nanoparticles also may permit more effective follow
up, because a doctor could use them to discern whether
a tumor was still growing after radiation or chemotherapy
this study focused on melanoma tumors, the researchers
believe the technology should work for most solid
tumors, because all tumors must recruit new blood
vessels to obtain nutrients as they grow.
melanoma has unique traits that make it especially
interesting as a target for nanoparticle therapy.
Melanoma has a horizontal phase, when it spreads across
the skin surface, and a vertical phase, when it goes
deep into the body and grows quickly.
melanoma has moved into its vertical phase, it is
almost untreatable because by the time the tumors
are large enough to detect, it's too late," Lanza
says. "With the nanoparticles, we believe we
would be able to see the smallest melanoma tumors
when they are just large enough to begin new blood
vessel formation. Plus, we should be able to deliver
chemotherapeutic drugs right to melanoma cells, because
melanoma tumors create blood vessels using their own
Schmieder AH, Winter PM, Caruthers SD, Harris
TD, Williams TA, Allen JS, Lacy EK, Zhang H, Scott
MJ, Hu G, Robertson JD, Wickline SA, Lanza GM. Molecular
MR imaging of melanoma angiogenesis with anb3-targeted
paramagnetic nanoparticles. Magnetic Resonance in
from the National Institutes of Health, the National
Cancer Institute and Philips Medical Systems supported
University School of Medicine's full-time and volunteer
faculty physicians also are the medical staff of Barnes-Jewish
and St. Louis Children's hospitals. The School of
Medicine is one of the leading medical research, teaching
and patient care institutions in the nation, currently
ranked third in the nation by U.S. News & World
Report. Through its affiliations with Barnes-Jewish
and St. Louis Children's hospitals, the School of
Medicine is linked to BJC HealthCare.
Washington University in St. Louis School