In Vivo Imaging of Activated Endothelium Using an Anti-VCAM-1 Magnetooptical Probe

Abstract

It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) could serve as an early marker for inflammation of the endothelium. The ability to noninvasively image VCAM-1 could thus be a useful tool to diagnose a number of inflammatory diseases at early stages. Here we demonstrate that magnetooptical nanoparticles conjugated to anti-VCAM-1 antibodies can be used to specifically detect VCAM-1 expression on endothelial cells in culture and in vivo. Elevated VCAM-1 expression was detected on cultured murine heart endothelial cells by both fluorescence and magnetic resonance, while only basal expression levels were detected on murine dermal endothelial cells. Intravital microscopy of a murine inflammatory model injected with the VCAM-1 targeted nanoparticles revealed specific labeling of the activated endothelium, with labeling kinetics yielding a maximum vessel wall signal 6 h after injection. In contrast, nontargeted nanoparticles did not exhibit any specific labeling of the endothelium. These studies suggest that the developed nanoparticle would be useful for MR and optical detection of activated endothelium.

Visualization of Vascular Inflammation in the Atherosclerotic Mouse by Ultrasmall Superparamagnetic Iron Oxide Vascular Cell Adhesion Molecule-1–Specific Nanoparticles

“…The histological assessment of the aortic root of these mice enabled the cellular detection of P03011 within early and advanced atherosclerotic plaques. In line with previous findings using Prussian blue staining for iron, [21][22][23]45,46 we detected USPIO particles in association with luminal plaque endothelial cells and macrophages. These cell types display a strong expression of VCAM-1, suggesting contrast agent accumulation in VCAM-1-expressing cells within the vessel wall.…”

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

“…Detection of early atherosclerotic signatures has recently been performed with anti-VCAM-1 (vascular adhesion molecule-1)-targeted SPIO, 145 as well as SPIO labeled with VCAM-1-specific peptides. 72 In the latter case, phage display was used to identify a VCAM-1-specific cell internalizing peptide.…”

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

“…Biodistribution studies with polymersomes, in particular, would be greatly aided by the encapsulation of an imaging agent in the vesicles; this would enable non-invasive monitoring of the location of vesicles during drug delivery without the need to sacrifice the animal. Although nanoparticles have been used with a spectrum of different imaging modalities including PET [48,49] and MRI [50][51][52], here we will focus on polymersomes that encapsulate fluorescent agents for optical imaging. Because light scattering decreases with increasing wavelength, and hemoglobin and water absorption spectra have their nadir in the near infrared (NIR) spectral region, much work has been focused on developing NIR contrast agents for in vivo imaging studies [9].…”