Assessment of atherosclerotic plaques in the rabbit abdominal aorta with interleukin-8 monoclonal antibody-targeted ultrasound microbubbles

Abstract

In this study, we aimed to prepare a neovascularization-relevant inflammatory cytokine-targeted ultrasound contrast agent and apply it in the ultrasound imaging of atherosclerotic plaque. An interleukin-8 (IL-8) monoclonal antibody was conjugated to SonoVue microbubbles using the N-succinimidyl-3-(2-pyridyldithio)propionate cross-linking method. Then, a prepared IL-8-targeted contrast agent was used for contrast-enhanced ultrasound (CEU) to detect rabbit abdominal aorta atherosclerotic plaque and to investigate the imaging characteristics of atherosclerotic plaque with the contrast agent. We found that an IL-8 monoclonal antibody can be successfully coupled to SonoVue microbubbles with stable biological characteristics. CEU with this IL-8-targeted contrast agent can increase the atherosclerotic plaque detection sensitivity, with stronger echo, so that three more plaques were detected compared with using non-targeted SonoVue microbubbles. Thus, an inflammatory cytokine-targeting ultrasound contrast agent carrying IL-8 monoclonal antibody can provide unique advantages for researching the characteristics of atherosclerotic plaque.

Ultrasound imaging beyond the vasculature with new generation contrast agents

“…Conjugation of targeting moieties, such as antibodies or peptides, to microbubbles has been shown to have potential applications in molecular diagnosis of vascular diseases such as atherosclerosis. 64 Since the advent of echogenic nanoparticles, molecular detection of cancer in animal models with ultrasound imaging has been demonstrated. 23,58,65 Nanoparticles can first reach tumor sites via their size-dependent passive targeting, and then, with the appropriate targeting ligand, can be coupled onto cancerous cells via overexpressed markers.…”

Detection of High-Risk Atherosclerotic Plaques with Ultrasound Molecular Imaging of Glycoprotein IIb/IIIa Receptor on Activated Platelets

“…UMI can be used to detect molecular targets on the surface of activated platelets and endothelial cells that are accessible to microbubbles (MBs), including activated von Willebrand factor (vWF) for platelet adhesion 4 , 5 , vascular cell adhesion molecule-1 and P-selectin for inflammation 5 - 7 , and vascular endothelial growth factor receptor-2 and interleukin-8 for neovascularization 8 , 9 , all of which are expressed on the endothelial surface. To date, there are no reports of an atherosclerotic profile of activated platelets and thrombosis obtained by UMI.…”

Association between abdominal aortic plaque and coronary artery disease

“… 18 – 21 Currently, noninvasive imaging modalities for aortic atherosclerotic plaque detection include ultrasound, computed tomography, magnetic resonance imaging, and angiography. 1 …”

“…As the prevalence of atherosclerosis increases globally due to aging population, identifying atherosclerotic plaques will be of utmost importance for early diagnosis and intervention, which will substantially decrease the health care burden. 1 …”

“… 13 Abdominal aorta ultrasound has become a useful tool to not only screen AAA but also evaluate atherosclerotic plaques, which is noninvasive, easy to assess, cost efficient, and could be routinely used in population-based study. 1 However, the significance of abdominal aortic plaques detection by ultrasound imaging is not yet definitive.…”