Atherosclerosis is largely an asymptomatic disease where plaques
develop over decades and symptoms do not appear until greater than 70%
of a vessel is occluded. This results in significant risk of
severe cardiovascular events such as stroke or myocardial infractions,
highlighting the need for early, non-invasive diagnosis of the disease.
Researchers at Stanford University have demonstrated for the first
time the use of a dual optical and PET/CT activity-based probe to detect
atherosclerotic plaques. The study is published in the October issue of
the Journal of Nuclear Medicine
‘The use of a dual optical and PET/CT activity-based probe to detect atherosclerotic plaques has been demonstrated by researchers.’
Matthew Bogyo, one of the lead authors of the study explains,
"This collaborative study with Zhen Cheng and Michael McConnell provides evidence that these probes have potential benefits for
non-invasive imaging of atherosclerotic plaque inflammation, potentially
leading to the application of this probe in the clinic to help identify
patients at high risk of developing premature atherosclerosis."
Macrophages are cellular mediators of vascular inflammation and are
involved in the formation of atherosclerotic plaques. These immune cells
secrete proteases such as matrix metalloproteinases and cathepsins that
contribute to disease formation and progression. In this study,
activity-based probes (ABPs) targeting cysteine cathepsins were used in
mouse models of atherosclerosis to non-invasively image activated
macrophage populations using both optical and PET/CT methods. The probes
were also used to topically label human carotid plaques, demonstrating
similar specific labeling of activated macrophage populations.
The study demonstrates that ABPs targeting the cysteine cathepsins
offer a rapid, non-invasive way to image atherosclerotic disease
progression and plaque vulnerability.
Bogyo notes, "What's novel about this is the fact that these probes
provide accurate detection of lesions undergoing high levels of
inflammatory activity and extracellular matrix remodeling. They not only
enable early disease detection, they can provide real-time monitoring
of therapeutic responses and clinical drug efficacy."
He sees broader uses for the probes in the future. "The probes show
efficacy in a variety of imaging modalities, including fluorescence,
PET/CT, and topical application of the probe to fresh frozen murine and
human tissue sections. These tools further demonstrate that the future
of molecular imaging and nuclear medicine will be focused on agents that
allow specific targeting of disease-associated proteins or markers that
allow monitoring of disease onset, progress and response to therapeutic