From bench to imagingMolecular imaging with contrast ultrasound and targeted microbubbles☆
Section snippets
Targeting strategies and imaging protocols
Several strategies have been used to target ultrasound contrast agents to regions of disease (Figure 1). The first strategy simply takes advantage of inherent chemical or electrostatic properties of the microbubble shell that promote retention of microbubbles within diseased organs. For example, certain disease states involve upregulation of receptors that are capable of binding either albumin or lipid components of the microbubble shell.1 A second and more selective strategy relies on the
Imaging inflammatory responses
Acute and chronic inflammatory responses play an important role in many cardiovascular diseases such as atherosclerosis, ischemia-reperfusion injury, myocarditis, and transplant rejection. A critical component of inflammation is the activation and recruitment of freely circulating leukocytes in the blood pool, which relies upon a series of cellular and molecular events that can be targeted (Figure 3).5, 6 Initial leukocyte capture and rolling are mediated primarily by the selectin family of
Molecular imaging of angiogenesis
There has been a recent surge of interest in techniques to image angiogenesis for the purpose of tumor imaging. To meet their metabolic demand, tumors promote their own vascular supply by creating an imbalance between angiogenic stimulators and inhibitors.18 The ability to image angiogenesis may be useful for diagnosing neoplasms, for detecting metastases, and for assessing susceptibility or response to novel antiangiogenic tumoricidal therapies. For cardiovascular disease, assessment of
Detection of intravascular thrombus
The need to improve the diagnostic accuracy of ultrasound for detecting vascular or intracardiac thrombi has led to the development of thrombus-targeted microbubbles. The ability to bind a high concentration of microbubbles to the surface of clots may also have therapeutic potential. Destruction of microbubbles in proximity to blood clots by exposure to high acoustic power ultrasound has been shown to improve the efficacy of chemical thrombolytic therapy and can even result in clot lysis in the
Summary and future directions
The relatively new field of molecular imaging will likely play an important role in both the clinical and research settings. Preliminary studies have demonstrated that CEU can be used for this purpose and that ultrasound contrast agents can be effectively targeted to inflammation, angiogenesis, and thrombus. There are ongoing efforts to improve both the targeting efficiency of microbubbles and the ultrasound detection methods. It is quite likely that targeted agents can also be used for
Acknowledgements
The author has indicated he has no financial conflicts of interest.
References (28)
Targeted delivery of gas-filled microspheres, contrast agents for ultrasound imaging
Adv Drug Deliv Rev
(1999)- et al.
Optical and acoustical dynamics of microbubble contrast agents inside neutrophils
Biophys J
(2001) - et al.
Development of inherently echogenic liposomes as an ultrasonic contrast agent
J Pharm Sci
(1996) - et al.
In vivo targeting of acoustically reflective liposomes for intravascular and transvalvular ultrasonic enhancement
J Am Coll Cardiol
(1999) - et al.
In vitro studies of a new thrombus-specific ultrasound contrast agent
Am J Cardiol
(1998) - et al.
Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles
Ultrasound Med Biol
(2003) - et al.
Microbubble persistence in the microcirculation during ischemia-reperfusion and inflammationintegrin- and complement-mediated adherence to activated leukocytes
Circulation
(2000) - Dayton PA, Pearson D, Clark J, et al. Ultrasonic enhancement of αvβ3-expressing cells with targeted contrast agents....
- et al.
Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes
Circulation
(2000) Adhesion receptors of the immune system
Nature
(1990)
Molecular mechanisms of leukocyte recruitment in the inflammatory process
Cardiovasc Res
Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo
J Clin Invest
Non-invasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles
Circulation
Non-invasive imaging of myocardial reperfusion injury using leukocyte-targeted contrast echocardiography
Circulation
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Supported by grants from the National Institutes of Health (R01-DK063508), Bethesda, Md, and the American Heart Association Mid-Atlantic Affiliate, Baltimore, Md.