Researchers investigating how to make PET imaging even sweeter

January 13, 2014

An international research team led by Mount Sinai Heart at Icahn School of Medicine at Mount Sinai, is testing its novel sugar-based tracer contrast agent to be used with positron emission tomography (PET) imaging to help in the hunt for dangerous inflammation and high-risk vulnerable atherosclerotic plaque inside vessel walls that causes acute heart attacks and strokes.

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

"Our pre-clinical testing shows that PET imaging with 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," says Jagat Narula, MD, PhD, the principal investigator for the study who serves as Director of the Cardiovascular Imaging Program at The Mount Sinai Hospital, and Associate Dean of Global Health at Icahn School of Medicine at Mount Sinai.

Glucose forms the source of main energy supply in the human body and in the radiolabeled form FDG it has been traditionally used for the identification of atherosclerosis. Valentin Fuster, MD, PhD, the Director of the Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, was one of the earliest investigators to use FDG for the detection of atherosclerosis.

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, and that's why the sugar-based tracers are able to identify the inflamed or dangerous plaques," according to Dr. Fuster.

"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)," according to Dr. Narula.

Co-author Jogeshwar Mukherjee, PhD, and his team of radiochemists at the University of California, Irvine had labeled the FDM with Fluorine-18, which like glucose enters the cells through glucose transporters. The current study results show mannose is taken up by a specific subset of macrophage cells that dwell in high-risk plaques, which have developed the mannose receptors. This may represent the theoretical advantage of FDM over the FDG tracer. These macrophages called "M2" within atherosclerotic plaques, 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 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," says study co-author Zahi Fayad, PhD, the Director of the Translational and Molecular Imaging Institute at Icahn School of Medicine at Mount Sinai. 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," stresses Dr. Narula.

"The labeling of FDM is cumbersome and the yield of radiolabeled material is extremely low; the labeling methodology would need to be perfected," Dr. Mukherjee cautions.

Explore further: Noninvasive 18F-fluoride PET can identify culprit coronary plaques

Related Stories

Noninvasive 18F-fluoride PET can identify culprit coronary plaques

November 12, 2013
(HealthDay)—Combined positron emission tomography (PET) and computed tomography (CT) using the radioactive tracer 18F-sodium fluoride (18F-NaF) can identify ruptured and high-risk coronary plaques, according to a study ...

Macrophage proliferation appears to drive progression of atherosclerosis

August 11, 2013
New insights into the development of vulnerable atherosclerotic plaques could lead to better treatment or prevention of heart attacks and strokes. In a report being published online in Nature Medicine, researchers at the ...

Unique study shows efficacy of imaging technology in evaluating heart drug dalcetrapib

September 13, 2011
Researchers from Mount Sinai School of Medicine have for the first time used several imaging techniques to prove the efficacy of a promising new treatment for atherosclerosis—the build-up of plaque in artery walls that ...

New classification system for cardiomyopathy

December 3, 2013
Leading cardiologists at The Mount Sinai Hospital have contributed to the development of a new classification system called MOGE(S) for cardiomyopathies, the diseases of the heart muscle which can lead to heart enlargement ...

Recommended for you

Manipulating a type of brain cell gets weight loss results in mice

July 28, 2017
A new study has found something remarkable: the activation of a particular type of immune cell in the brain can, on its own, lead to obesity in mice. This striking result provides the strongest demonstration yet that brain ...

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.