Contrast Ultrasound and Targeted Microbubbles: Diagnostic and Therapeutic Applications for Angiogenesis

Abstract

Angiogenesis represents the formation of new capillaries from existing vasculature, and as such plays a critical role in the response to ischemia in the setting of chronic coronary artery and peripheral vascular disease. Recent technological advances in non-invasive imaging modalities now allow the molecular imaging of angiogenesis. One such technique is contrast-enhanced ultrasound using microbubbles targeted against molecular markers of the angiogenic process. The ability to non-invasively image the angiogenic process would be useful in risk stratifying patients with arterial occlusive disease and would aid in the evaluation of new therapies to promote angiogenesis in ischemic cardiac and skeletal muscle. Furthermore, ultrasound technologies have also been developed that allow targeted angiogenic gene therapy using high-power ultrasound and DNA-bearing microbubbles. This review will focus specifically on recent advances in (1) contrast-enhanced ultrasound molecular imaging techniques for the evaluation of angiogenesis and (2) ultrasound-mediated gene delivery for therapeutic angiogenesis, techniques that have potential for translation to clinical practice.

Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines

“…Gene therapy using this technology has gained significant momentum in recent years (Smith et al, 2011;Chen et al, 2012;Sirsi & Borden, 2012;Smith & Land, 2012). In summary, we propose that P. aeruginosa ExoT possesses attractive anti-cancer properties that make it an attractive cancer drug candidate.…”

Ultrasound-targeted cardiovascular gene therapy

“…33,[62][63][64][65][66][67][68][69] Of particular interest for this chapter is the delivery of plasmids in the cardiovascular setting for exogenous gene therapy. Table 17.1 and Table 17.2 outline the major studies of UMGD in different animal models of cardiac and vascular disease respectively, and summarize the major similarities and differences of the UMGD techniques studied to date.…”

Molecular Imaging of Angiogenesis in Cardiac Regeneration

“…Cardiac ultrasound is a widely used technique that has several advantages over the previously described imaging modalities, e.g., lack of ionizing radiation, routine accessibility, and superior spatial resolution compared to SPECT and PET [33]. Hitherto tissue perfusion assessed by ultrasound has been used as an endpoint reflecting angiogenesis; however, an increase in perfusion does not necessarily reflect angiogenic activity [34].…”

“…Hitherto tissue perfusion assessed by ultrasound has been used as an endpoint reflecting angiogenesis; however, an increase in perfusion does not necessarily reflect angiogenic activity [34]. For more detailed imaging, targeted microbubbles can be used as contrast agents in a technique known as contrast-enhanced ultrasound (CEU) [33]. Microbubbles that target integrins or VEGFRs reflect angiogenesis in a more direct manner than perfusion imaging [34, 35].…”

“…Microbubbles loaded with therapeutic agents can be dissolved by high acoustic pressures after accumulation at the region of interest, thus enabling targeted drug delivery. Additionally, it is hypothesized that a combination of targeted imaging and drug release via microbubbles is possible [33, 88, 89]. …”