ARLINGTON, Va., May 18, 2005 -- Biomedical engineers have used nanotechnology to find human melanoma tumors in mice while the growths are still invisible to conventional magnetic resonance imaging (MRI).

Earlier detection can potentially increase the effectiveness of treatment. This is especially true with melanoma, which begins as a highly curable disorder, then progresses into an aggressive and deadly disease.

A second benefit of the approach is that the same nanoparticles used to find the tumors could potentially deliver stronger doses of anti-cancer drugs directly to the tumor site with fewer side effects.

Samuel Wickline, M.D., professor of medicine, physics, biomedical engineering and cellular physiology at Washington University in St. Louis, and his colleague, Gregory Lanza, M.D., Ph.D., associate professor of medicine, have detected tumors as small as a couple of millimeters in diameter.

"This technique may be employed to noninvasively detect very small regions of angiogenesis associated with nascent melanoma tumors," the researchers reported in a recent issue of the journal Magnetic Resonance in Medicine.

To zero in on the small tumors, the researchers developed nanoparticles, thousands of which could fit in the period at the end of this sentence. Each particle was filled with thousands of molecules of the metal that is used to enhance contrast in conventional MRI scans. The surface of each particle was decorated with a substance that attaches to newly forming blood vessels, which are present at tumor sites. The goal is to create a high density of the glowing particles at the site of tumor growth so they are easily visible.

One group of mice bearing human melanoma tumors was injected with the nanoparticles and two other groups of animals were injected with other, more conventional contrast enhancers. The animals underwent MRI scans. Those injected with the nanoparticles glowed brightly at the tumor sites. The control groups showed no discernable glow.

Lanza said the nanoparticles can be made to work in other types of medical imaging, such as nuclear imaging, computed tomography (CT), and ultrasound. It may also be possible to load the nanoparticles with drugs to kill the 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," said Lanza, who treats cancer patients at Barnes Jewish Hospital. "You would know the same day you treated the patient if the drug was at a therapeutic level."

Targeting the drugs to the tumor site in this way would also allow stronger doses than would be possible if the drug were injected or delivered in some other systemic way.

The researchers believe that nanoparticles might also allow doctors to more readily assess the effectiveness of the treatment by comparing before and after pictures. Other cancer types might be accessible to this approach as well, because all tumors recruit new blood vessels as they grow.

In earlier studies, Wickline and Lanza demonstrated the use of a similar nanotechnology for detecting sites where blood-vessel plaques are just beginning to form, well before they pose a risk of heart attack or stroke.

Clinical applications of these lines of research are being explored under a $7.3 million grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health. In 1995, Wickline received a Whitaker Foundation Special Opportunity Award for cardiovascular bioengineering.

Contact:
Samuel Wickline, Washington University
Frank Blanchard, The Whitaker Foundation