School of Medicine

Cardiovascular imaging study targets high-risk artery plaque 

Jan. 12, 2014 — An international team that includes UC Irvine Health researchers is testing a novel sugar-based tracer contrast agent to be used with positron emission tomography (PET) imaging to help detect dangerous inflammation and high-risk atherosclerotic plaque inside vessel walls that can cause acute heart attacks and strokes. 

Their findings, reported Jan. 12 in Nature Medicine, discuss the possible advantage of the proposed imaging agent, fluorodeoxymannose (FDM), a sugar-based tracer, over fluorodeoxyglucose (FDG), the current glucose-based tracer used widely in patients undergoing PET imaging.

“Our pre-clinical testing shows that by PET imaging the radiotracer FDM may potentially offer a more targeted strategy to detect dangerous, high-risk plaques and inflammation that may be associated with serious cardiovascular events,” said the study's principal author, Dr. Jagat Narula, director of cardiovascular imaging at Mount Sinai Hospital in New York City and associate dean of global health at Mount Sinai's Icahn School of Medicine.

Glucose, which forms the main source of energy for the human body, has been traditionally used for the identification of atherosclerosis in the radio-labeled form FDG. A known biomarker for high inflammation in arterial plaque is the presence of an abundant level of macrophage cells. Macrophage-rich inflammation lining the artery walls filled with plaque is known to be associated with increased risk of heart attack and stroke. Macrophage cells have a very high metabolic demand for sugars and are dependent on the exogenous source of sugars, which is why  sugar-based tracers are used to identify the inflamed, or dangerous, plaques.

“Although the research team’s investigations of the FDM tracer shows that it performs comparably to the traditional FDG tracer, it is expected that the new sugar tracer may have an advantage to more specifically target inflammation because the plaque infiltrating macrophages develop mannose receptors (MRs),” added Narula, formerly the chief of cardiology at UC Irvine Health School of Medicine.

Jogeshwar Mukherjee, PhD, and his UC Irvine Health team of radiochemists had labeled the FDM with fluorine-18, which, like glucose, enters the cells through glucose transporters. The current study results show that mannose is taken up by a specific subset of macrophage cells dwelling in high-risk plaques that have developed the mannose receptors. This finding may represent the theoretical advantage of FDM over FDG tracers. These macrophages called “M2” are noted within atherosclerotic plaques; they tend to overly express MRs, and are especially common in inflamed and hemorrhagic arterial lesions.

In the study FDG and FDM were compared using PET imaging in atherosclerosis animal models. While uptake of each tracer within atherosclerotic plaques and macrophage cells were similar, according to the researchers the experimental FDM tracer showed at least a 25 percent higher FDM uptake advantage due to MR-bearing macrophages.

“The FDM binds to MR-bearing macrophages while FDG does not bind to the MR receptors. This specific binding provides clinically relevant avenue why FDM uptake in high-risk plaques should be further investigated, said Dr. Zahi Fayad, director of Mount Sinai's Translational and Molecular Imaging Institute and co-author of the study. Researchers also observed FDM uptake occurred in the presence of atherosclerosis and almost none in non-atherosclerosis control models.

“We are excited about our possibly sweeter imaging breakthrough, but further research and clinical trial testing will need to confirm its potential advantage,” said Narula. “The labeling of FDM is cumbersome and the yield of radiolabeled material is extremely low; the labeling methodology would need to be perfected,” Mukherjee added.