ARLINGTON, Va., Nov. 26, 2002 – Bioengineers have used nanotechnology to see where blood-vessel plaques are just beginning to form, well before they pose a risk of heart attack or stroke.

The noninvasive technology pinpoints plaque formation before it can be detected by any other means, said Samuel Wickline, M.D., professor of medicine and biomedical engineering at Washington University School of Medicine and a leader of the study.

Earlier detection of blood-vessel plaques raises the possibility of earlier treatment and a higher likelihood of success.

Wickline and his colleagues packaged targeting molecules and signalling atoms inside extremely tiny capsules, or nanoparticles, that can be safely injected into the bloodstream.

The targeting molecules are attracted to a protein (avb3) found in rapidly developing capillaries, which appear at sites of plaque formation. The signalling atoms of gadolinium glow brightly under magnetic resonance imaging (MRI). The nanoparticles are designed to collect at sites of plaque formation and signal their location.

The researchers injected these nanoparticles into 13 rabbits, nine of which had eaten high-cholesterol diets for almost three months. The other four rabbits had eaten normally.

All of the animals then underwent MRI scans of the abdominal aorta, the largest artery in the body. Those fed the high-cholesterol diet displayed gadolinium signals twice as bright as those of the other rabbits.

Autopsies confirmed that the high-cholesterol rabbits were developing capillaries around the aorta, while the other rabbits were not.

"You can load these nanoparticles with whatever you want," Wickline said. "The targeting agent allows us to select where the particle goes, and then we can either add an imaging agent, like gadolinium, or a drug, like plaque stabilizing medications or anticancer agents."

Collaborator Patrick Winter, Ph.D., of Washington University Medical School presented results of the study at this month's meeting of the American Heart Association in Chicago.

Technology used in the study has been licensed to a spin-off company, KEREOS Inc., co-founded by Wickline and Gregory Lanza, M.D., Ph.D., assistant professor of medicine and biomedical engineering and co-leader of the nanoparticle research.

Wickline and colleagues Salvatore Sutera, Ph.D., and Sandor Kovacs, M.D., Ph.D., received a Special Opportunity Award for cardiovascular bioengineering in 1995 from The Whitaker Foundation.

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