L222	Novel PET tracers for plaque imaging.
M.Schäfers
Dept. of Nuclear Medicine, University Hospital, Münster, DE.

Cardiovascular diseases are the most common cause of death and disability in industrialised countries. Most of the morbidity and mortality is due to atherosclerosis of the coronary arteries, resulting in coronary heart disease (CHD) and its principal manifestations, angina pectoris, myocardial infarction, sudden cardiac death and heart failure. The main pathologic feature of atherosclerosis is the atherosclerotic lesion. It develops in a course of a series of highly specific cellular and molecular responses of the vessel wall to injury. The potentially most dangerous lesions are unstable and prone to rupture. These plaques are often of lesser stenosis severity and thus would sometimes not impair blood flow at rest or during exercise. At autopsy, they are characterised by a thin fibrous cap overlying cell-rich regions with a central core of extracellular lipid. Rupture of those plaques mainly occurs in their shoulder where active macrophages accumulate and apoptosis may occur. The activated macrophages and mast cells locally destabilise the plaque shoulder by secreting a variety of matrix-degrading proteolytic enzymes such as metalloproteinases. Magnetic resonance imaging (MRI) techniques have recently been used to assess plaque components such as lipid cores, fibrous caps, calcification and intra-plaque hemorrhage in experimental models. The value of this imaging technique to predict future coronary events based on plaque morphology has not been examined so far. Therefore, there is a great need for non-invasive diagnostic techniques that discriminate vulnerable from stable plaques within coronary arteries, to early identify patients at high risk of major acute coronary events. Since techniques such as MRI are based on morphological analysis of plaque structure, composition and size, none of them is able to elucidate the characteristic metabolic profile of potentially unstable (vulnerable) plaques. Positron emission tomography (PET) provides the most sensitive and selective means for imaging molecular interactions non-invasively in the living body and could therefore prove a potent approach to the identification of the metabolically active plaque that is vulnerable to rupture. Targets for PET imaging are among enzymes (e.g. matrix-metalloproteinases, caspases) and receptors, whose expression an activation destabilizes the plaque and increase the risk for plaque rupture and subsequent lifetheatening events. Different strategies for developing new radiopharmaceuticals for imaging the vulnerable plaque and first results will be presented.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.