Biomedical Engineering Reference
In-Depth Information
Annexin A5 as an Imaging Biomarker of Cardiovascular Disease
Annexin A5, a plasma protein, has strong affinity for phosphatidylserine (PS) - a
plasma cell membrane phospholipid. Coupling of Annexin A5 to contrast agents
enables in vivo visualization of apoptotic cell death, which is manifested by exter-
nalization of PS (Laufer et al.
2008
). These imaging studies have provided novel
insight into the extent and kinetics of apoptosis in cardiovascular disease.
Furthermore, Annexin A5 imaging has proven to be a suitable imaging biomarker
for the evaluation of apoptosis-modifying compounds and plaque stabilizing strate-
gies. Annexin A5 not only binds to exteriorized PS, but is also internalized through
an Annexin A5-specific mechanism indicating that Annexin A5 imaging can also
be used to visualize inflammation and cell stress. This will enable a better under-
standing of pathological processes underlying cardiovascular diseases.
Cardiovascular MRI
Cardiovascular MRI has recently emerged as a powerful tool for detecting cardiovas-
cular biomarkers and has an important role, particularly in visualizing several revers-
ible and irreversible myocardial tissue changes (Schulz-Menger and Abdel-Aty
2008). It has potential applications in nonischemic and inflammatory cardiomyopa-
thies. Cardiac MRI is helpful in making a differential diagnosis between ischemic
and dilated cardiomyopathy, identifying patients with myocarditis, diagnosing car-
diac involvement in sarcoidosis and Chagas' disease, identifying patients with
unusual forms of hypertrophic cardiomyopathy, and defining the sequelae of ablation
treatment for hypertrophic obstructive cardiomyopathy (Sechtem et al.
2007
).
Myocardial Perfusion Imaging
Myocardial perfusion imaging (MPI) is used as a primary screen to identify the
presence of coronary artery disease (CAD) as evidenced by detection of areas of
poor blood flow in the heart that can be caused by the formation of plaques that
block the normal flow of blood to the heart. A pharmacologic stress agent is used
to increase blood flow through coronary arteries temporarily during stress testing
in order to more strikingly define areas of the heart that receive poor blood flow.
The adenosine A2A receptor is the receptor subtype responsible for coronary vaso-
dilation, or the widening of blood vessels.
Stedivaze (apadenoson) is a potent agonist of the A2A and offers improved
selectivity over other adenosine receptor subtypes (A1 and A2B). Phase II studies
suggest that Stedivaze produces ample coronary vasodilatory activity needed for
cardiac stress MPI and has a pharmacokinetic profile that will allow it to be admin-
istered as a fixed dose bolus injection. Because of its improved selectivity for the
A2A receptor subtype and its optimal pharmacokinetic profile, Stedivaze may offer
improved tolerability over other adenosine receptor agonists currently marketed for
use in pharmacologic stress MPI. Stedivaze is in phase III clinical development
by Clinical Data Inc for use as a pharmacologic agent for MPI with the goals of
demonstrating equal efficacy and improved tolerability compared to adenosine.
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