Atherosclerosis
Atherosclerosis is a chronic inflammatory response in the walls of arteries, resulting in the formation of multiple plaques. Soft (or vulnerable) plaque may rupture, causing the formation of a thrombus (blood clot) that will rapidly slow or stop blood flow. When this occurs in a coronary artery, the result may be myocardial infarction, or heart attack. Similar events occur also in the arteries to the brain, intestines, kidneys, legs, etc.
This condition is the leading cause of death in the Western world, yet there is still no noninvasive way to diagnose vulnerable plaque prone to rupture. The decisions on vascular intervention and stenting are still largely based on vessel narrowing, even though it is known that most flow-disrupting events occur at locations with less than 50% narrowing.
Apoptosis plays a significant role in early vascular-injury response and in influencing the progression of the disease and ultimately plaque erosion. Therefore, molecular imaging of apoptosis can detect and quantify the presence of vulnerable plaque.
Studies with pre-clinical Aposense probes demonstrated the ability to detect and label vulnerable plaque in vivo, as well as ex vivo in human carotid artery samples excised at endarterectomy.
Imaging of human atherosclerotic plaques ex-vivo: Aposense binds to plaques in human carotid arteries following removal by endardarectomy (A), confirmed histologically by H&E staining (B) and Sudan staining (C)
Atherosclerotic plaques imaged by Aposense in a pre-clinical studies: Fluorescence-labeled Aposense probe following intravenously administration accurately labels vulnerable plaque in the aortic arch of ApoE-deficient mouse (A) (X10), as histologically confirmed by H&E staining (B) and oil Red-o staining (C).
IN-intima LC-lipid core FC-fibrous cap L-lumen
Ischemic Heart Disease
Death of myocardial cells by apoptosis occurs in various stages of heart disease, from the slow-progressing congestive heart failure to the acute myocardial infarction. The ability to visualize, localize and quantify the amount of ongoing cell death in the heart muscle may have important implications for patient management in the preventive, acute and post-acute settings of heart disease.
To illustrate, Aposense molecular probes were tested in preclinical models of apoptosis in a beating heart.
A. Mice were subjected to transient occlusion of the left coronary artery, followed by intravenous administration of the Aposense probe. As shown, a distinct region of bright Aposense signal was observed, in correlation with the region of the myocardium subjected to the ischemia / reperfusion insult.
B. Mice were subjected to the transient coronary occlusion, followed by intravenous administration of the Aposense probe, with concomitant intravenous administration of a pan-caspase inhibitor. Accordingly, no uptake of the Aposesne probe was observed, in correlation with the inhibition of the apoptotic death process by the caspase inhibitor.
Images are courtesy of Dr. L. Hofstra and C.Reutelingsperger from the University Hospital, Maastricht, Netherlands
[18F]-ML-10 is an investigational agent, not yet approved for use outside clinical trials