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Radioactive antibody fragment may help scientists identify artery deposits

Date:
March 29, 2012
Source:
American Heart Association
Summary:
Creating a tiny, radioactive antibody fragment may help scientists identify artery deposits most likely to burst and cause a heart attack. A non-invasive system uses miniature antibodies to detect a molecule that identifies the vulnerable deposits. Researchers plan clinical trials to determine the safety and efficacy of the new imaging technique.

Creating a radioactive antibody fragment may allow scientists to identify fat and debris deposits in artery walls that are most likely to rupture and cause heart attacks , according to a new study in Circulation: Research, an American Heart Association journal.

Of the more than 17 million annual cardiovascular deaths worldwide, most result from ruptured plaque .

"The detection of vulnerable coronary plaques is a major clinical challenge because it would allow preventive patient management prior to a heart attack," said Alexis Broisat, Ph.D., the study's lead author and a post-doctoral fellow at the University of Grenoble in France. "In clinical practice, there is currently no early, reliable and noninvasive tool allowing such detection."

The researchers created radioactive antibody fragments called nanobodies that attached to particles in artery plaque called vascular cell adhesion molecule-1 (VCAM1).

"Nanobodies constitute a promising new class of radiotracers for cardiovascular imaging," Broisat said.

Ongoing inflammation in a plaque deposit is a crucial sign that the plaque may rupture, and VCAM1 plays a major role in the inflammation process.

In laboratory tests, the radioactive nanobodies were attracted to VCAM-1.

In animal tests, researchers injected a solution containing the radioactive particles into the blood stream of mice with artery plaques. They then used a single-proton emission computed tomography (SPECT/CT) imaging scan to detect the radioactive particles.

The nanobodies attached to VCAM-1 expressing tissues. Following radiolabeling, some of the nanobodies remained stable in the laboratory and in mouse blood for six hours. This allowed imaging of the mice up to three hours after nanobody injection. These scans revealed plaques in the animals' aortic arches.

If approved for human use, physicians can inject nanobodies into patients to determine if they are at risk of plaque rupture.

"The early detection of trouble looming ahead could trigger steps for intervention, possibly involving the aggressive modulation of risk factors," according to an editorial accompanying the report by Matthias Nahrendorf, M.D., Ph.D., Jason R. McCarthy, Ph.D., and Peter Libby, M.D., of Harvard Medical School in Boston, Mass.

Before the imaging concept can be used regularly, researchers must conduct toxicology studies, produce clinical-quality material and determine whether the radiotracer technique is safe, beneficial and cost effective.

Broisat and his colleagues are planning clinical studies of the radiotracer technique to address these issues, including whether the anti-VCAM1 nanobodies can trigger adverse immune system reactions in people.

Broisat's co-authors are: Sophie Hernot, Ph.D.; Jakub Toczek, M.Sc.; Jens De Vos, M.Sc.; Laurent M. Riou, Ph.D.; Sandrine Martin, Ph.D.; Mitra Ahmadi, Ph.D.; Nicole Thielens, Ph.D.; Ulrich Wernery, Ph.D.; Vicky Caveliers, Ph.D.; Serge Muyldermans, Ph.D.; Tony Lahoutte, M.D., Ph.D.; Daniel Fagret, M.D., Ph.D.; Catherine Ghezzi, Ph.D.; and Nick Devoogdt, Ph.D.


Story Source:

The above story is based on materials provided by American Heart Association. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Broisat, S. Hernot, J. Toczek, J. De Vos, L. M. Riou, S. Martin, M. Ahmadi, N. Thielens, U. Wernery, V. Caveliers, S. Muyldermans, T. Lahoutte, D. Fagret, C. Ghezzi, N. Devoogdt. Nanobodies Targeting Mouse/Human VCAM1 for the Nuclear Imaging of Atherosclerotic Lesions. Circulation Research, 2012; 110 (7): 927 DOI: 10.1161/CIRCRESAHA.112.265140

Cite This Page:

American Heart Association. "Radioactive antibody fragment may help scientists identify artery deposits." ScienceDaily. ScienceDaily, 29 March 2012. <www.sciencedaily.com/releases/2012/03/120329170429.htm>.
American Heart Association. (2012, March 29). Radioactive antibody fragment may help scientists identify artery deposits. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2012/03/120329170429.htm
American Heart Association. "Radioactive antibody fragment may help scientists identify artery deposits." ScienceDaily. www.sciencedaily.com/releases/2012/03/120329170429.htm (accessed September 2, 2014).

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