Biomedical Engineering Reference
In-Depth Information
INTRODUCTION
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 imaging—
dei ned as 'the visualisation, characterization, and measurement of biological
processes at the molecular and cellular levels' (Mankof 2007)—have been
developed.
Imaging
of endothelial adhesion molecules has been at the forefront of
this emerging i 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. h e potential benei ts for molecular
imaging of vascular endothelial adhesion molecules include the ability to diagnose
vascular inl ammation at an early stage, reveal novel pathological mechanisms and
monitor the ei 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
α
v
β
3
integrin
. VCAM-1, which is known to be
upregulated in response to several inl ammatory stimuli, plays an important role
in leukocyte tethering and therefore in the initiation of atherosclerosis and other
disease processes (Hillis and Flapan 1998). h erefore, VCAM-1 is an attractive
molecular imaging target of early vascular inl 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 trai cking and has also been implicated in
microvascular slow l ow (Benson
et al.
2007). Lastly, α
v
β
3
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, inl ammation, malignancy, infection, and immune
disorders.
Central to the paradigm of
molecular imaging
is the use of molecular 'probes' in
order to provide specii 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.
