The
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.
In this study, MRI scans picked up tumors that were
only a couple of millimeters (about one twenty-fifth
of an inch) wide.
Small, 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.
Nanoparticles 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.
In 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."
Using nanoparticles, drug doses could be much smaller
than doses typically used in chemotherapy, making the
procedure potentially much safer.
"The 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
says.
The 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
treatments.
Although 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.
Nevertheless, 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.
"Once 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 cells."
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 Medicine
, 2005;53:621-627.
Funding from the National Institutes of Health, the
National Cancer Institute and Philips Medical Systems
supported this research.
Washington 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 |
