Investigational nanoparticle approved for clinical trials

A new imaging agent may light up dangerous plaque in arteries, and Mallinckrodt radiologist Pamela K. Woodard, MD, led the team that designed the nanoparticle researchers hope to use to identify patients at high risk of stroke.

Woodard, principal investigator, and colleagues at the University of California, Santa Barbara, in collaboration with Texas A&M University, jointly developed the imaging agent now approved for evaluation in people by the Food and Drug Administration (FDA).

“This is the first receptor-targeted nanoparticle agent for cardiovascular imaging approved for investigational use in humans,” says Woodard, professor of radiology and of biomedical engineering. “Starting with bench research, then developing and testing the agent and taking it through the FDA process into human patients has involved an extensive team of basic scientists, clinical researchers, and clinicians.”

In patients with atherosclerosis, plaque accumulates on the inner walls of arteries that deliver blood to the body. According to Woodard, also director of Mallinckrodt’s Center for Clinical Imaging Research, these plaques can be stable or progress to a vulnerable phase in which they rupture, leading to stroke or heart attack.

With current technology, researchers can’t tell whether the plaque is vulnerable or stable, and so can’t distinguish high-risk patients who need surgery from low-risk patients who can be treated with medication alone.

The new nanoparticle is unique in how it is targeted, according to Yongjian Liu, PhD, assistant professor of radiology and co-investigator on the project. Previous research demonstrated that a receptor called NPR-C is present on the surface of cells that line blood vessels and is increased in atherosclerotic plaque. So the investigators added a small molecule to the nanoparticle that seeks out and binds to NPR-C, specifically targeting the particle to potentially dangerous plaque.

Once the imaging agent illuminates plaque in any of the body’s arteries, it can be detected with positron emission tomography (PET). Researchers recently began testing the safety of the nanoparticle in healthy individuals. They next will focus on patients with atherosclerosis who already are scheduled to undergo surgery to remove plaque from their carotid arteries.

“In this way, we’ll be able to see whether the areas that light up in the image because of our nanoparticles are the same areas that contain vulnerable plaque, as assessed from the surgeries,” Woodard says. “Once we show success imaging the carotid arteries, we will evaluate the nanoparticle agent in other vessels such as the coronary arteries, which represent a greater challenge because of their smaller size and complex motion.”