PET and SPECT imaging of apoptosis in vulnerable atherosclerotic plaques with radiolabeled Annexin A5.

Atherosclerosis still represents killer number one in industrialized nations, and is starting to have increased impact in developing countries. Atherosclerotic plaques are the net result of a complex interplay between vascular cholesterol deposition, inflammatory activity and extracellular matrix formation. The result is luminal narrowing of arteries, which may ultimately lead to compromised blood flow to essential body organs, most notoriously to the heart. Most of the cardiovascular events that are caused by atherosclerosis, such as acute myocardial infarction or stroke, are the result of a transition of so-called stable atherosclerotic plaques to vulnerable plaques, that are prone to rupture. The direct consequence of atherosclerotic plaque rupture is exposure of thrombogenic plaque constituents to the blood, leading to instant local thrombus formation. The formation of this localized thrombus may ultimately result in sudden obstruction of blood flow and consequent infarction of distal tissue. Clinical risk profiling methods, such as the Framingham and Procam risk scores, are reasonable predictors of myocardial infarction over a 10-year time-span. However, the challenge remains to identify those patients with a very high risk of suffering from myocardial infarction in the coming months. Imaging may provide the necessary diagnostic information to identify such individuals. The transition of stable atherosclerotic plaques to vulnerable plaques is typically heralded by inflammation, thinning of the overlying fibrous cap, and the presence of a large necrotic core. Apoptosis is linked to all of these features of plaque vulnerability, and may, therefore, provide uniquely useful targets for the identification of plaque vulnerability. In recent years, a number of molecular imaging technologies have been developed to image apoptosis, which will be discussed in this review. Further development of apoptosis imaging technologies may aid us in the years to come in the quest to identify patients with critical cardiovascular risks, to treat myocardial infarction in its imminent, instead of its evident phase.

Cardiovascular molecular imaging of apoptosis.

INTRODUCTION: Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. APOPTOSIS AND MOLECULAR IMAGING: Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. AIMS: This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies.