ABSTRACT
In clinical practice, medical imaging techniques such as X-ray angiography, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound have been used to diagnose diseases of the vascular system by identifying structural abnormalities. However, in recent years, opportunities for molecular imagingde ned as ‘the visualisation, characterization, and measurement of biological processes at the molecular and cellular levels’ (Manko 2007)—have been developed. Imaging of endothelial adhesion molecules has been at the forefront of this emerging eld and has attracted great interest for two main reasons: (1) they play an important pathological role in a variety of disease conditions, including atherosclerosis, cancer, and autoimmune disease, and (2) these molecules are accessible to blood-borne contrast agents. e potential bene ts for molecular imaging of vascular endothelial adhesion molecules include the ability to diagnose vascular in ammation at an early stage, reveal novel pathological mechanisms and monitor the e cacy of therapeutic interventions in drug development. To date, a variety of endothelial adhesion molecules have been successfully imaged, including vascular cell adhesion molecule 1 (VCAM-1, CD106), intracellular adhesion molecule 1 (ICAM-1, CD54), E-selectin (CD62E, endothelial leukocyte adhesion molecule 1) and αvβ3 integrin. VCAM-1, which is known to be upregulated in response to several in ammatory stimuli, plays an important role in leukocyte tethering and therefore in the initiation of atherosclerosis and other disease processes (Hillis and Flapan 1998). erefore, VCAM-1 is an attractive molecular imaging target of early vascular in ammation. E-selectin is another important mediator of early rolling recruitment of leukocytes to the endothelium and can also serve as a molecular imaging marker of endothelial activation. ICAM-1 plays a key role in leukocyte tra cking and has also been implicated in microvascular slow ow (Benson et al. 2007). Lastly, αvβ3 integrin is expressed on small blood vessels in cancer and atherosclerosis and has been shown to mediate leukocyte-endothelial interaction, for example, following ischemia-reperfusion injury (Ichioka et al. 2007). Angiogenesis plays a pivotal role in a number of disease states, including ischemia, in ammation, malignancy, infection, and immune disorders. Central to the paradigm of molecular imaging is the use of molecular ‘probes’ in order to provide speci c contrast. Such molecular ‘probes’ have many synonyms, including tracers, nano-and micro-particles, and contrast agents (Massoud and Gambhir 2003), but the majority share two fundamental components: (1) the actual contrast agent (tautologous to a ‘signaling element’) and (2) the targeting ligand. A variety of techniques have been used for molecular imaging to date and are listed in Table 1. In this chapter, each imaging modality is explored in turn, highlighting the opportunities and limitations of each for the development of molecular imaging techniques that can visualize endothelial adhesion molecules.
