Molecular imaging by micro-CT: specific E-selectin imaging

Abstract

The primary goal of this study was to design a fluorescent E-selectin-targeted iodine-containing liposome for specific E-selectin imaging with the use of micro-CT. The secondary goal was to correlate the results of micro-CT imaging with other imaging techniques with cellular resolution, i.e., confocal and intravital microscopy. E-selectin-targeted liposomes were tested on endothelial cells in culture and in vivo in HT-29 tumorbearing mice (n=12). The liposomes contained iodine (as micro-CT contrast medium) and fluorophore (as optical contrast medium) for confocal and intravital microscopy. Optical imaging methods were used to confirm at the cellular level, the observations made with micro-CT. An ischemia-reperfusion model was used to trigger neovessel formation for intravital imaging. The E-selectintargeted liposomes were avidly taken up by activated endothelial cells, whereas nontargeted liposomes were not. Direct binding of the E-selectintargeted liposomes was proved by intravital microscopy, where bright spots clearly appeared on the activated vessels. Micro-CT imaging also demonstrated accumulation of the targeted lipsomes into subcutaneous tumor by an increase of 32±8 HU. Hence, internalization by activated endothelial cells was rapid and mediated by E-selectin. We conclude that micro-CT associated with specific molecular contrast agent is able to detect specific molecular markers on activated vessel walls in vivo.

Functionalization of nano-emulsions with an amino-silica shell at the oil–water interface

“…5 E-selectin peptides graed on liposome surface, 6 or 2-deoxy-D-glucose onto gold NPs 7 have also shown interesting accumulation in cancer cells due to their enhanced glucose consumption. Specic targeting of pancreatic ductal adenocarcinoma can be performed through plectin-1 targeted peptides (PTP) at the surface of hybrid iron oxide/polymeric NPs.…”

High-Resolution CT for Small-Animal Imaging Research

“…The advances in synthesizing nanoparticle contrast agents (Hainfeld et al, 2006;Jackson et al, 2011;Mukundan et al, 2006;Rabin et al, 2006) have enabled high-resolution rodent studies using micro-CT. As imaging probes, these nanoparticlebased contrast agents have also opened the door for molecular CT imaging using various targeting strategies (Chanda et al, 2011;Cormode et al, 2010;Ghann et al, 2012;Popovtzer et al, 2008;Reuveni, 2011;Wyss et al, 2009). A liposomaliodinated (Lip-I) contrast agent has been used to image the tumor microenvironment with exquisite detail (Ghaghada et al, 2011;Moding et al, 2012).…”

The role of imaging and molecular imaging in the early detection of metabolic and cardiovascular dysfunctions

“…Molecular imaging agents have been designed for MR, 89-91 nuclear, 92,93 optical, 94,95 computed tomography 96 and ultrasound imaging. 97,98 The agents are classically designed as activatable or targeted agents.…”

“…The first strategy for targeted imaging is to add targeting moieties on the surface of iron oxide nanoparticles directed against known targets on the cell surface, such as a(v)b3 integrin, 106,109 E-selectin 95,96,110,111 or vascular cell addition molecule. 112 In addition to being specific, such contrast media also benefit from biological amplification through cellular trapping.…”