Integrins as Targets for Imaging

In an effort to image angiogenesis, Mulder and collaborators have created MR-detectable and fluorescent liposomes that are targeted to avb3 integrin on neovasculature.36 The MR contrast agent Gd-DTPA-bis(stearylamide) was incorporated into PEGylated liposomes covalently coupled to RGD peptide. It was observed that the liposomes effectively brought about an increase in signal on T1-weighted images. Injection of these lipidic nanoparticles in nude mice with subcu-taneously implanted LS174 human colon adenocarcinoma led to the ability to specifically image the vascular endothelial cells in the tumor. Ex vivo fluorescence confirmed that RGD liposomes specifically interacted with tumor endothelium associated with neovasculature.

In a study reported by Lanza, paramagnetic molecular imaging of angiogenesis was accomplished in vivo with avb3-targeted lipid encapsulated perfluorocarbon nanoparticles of about 250 nm.37 A Vx-2 carcinoma tumor in New Zealand rabbits was imaged with a 1.5-T MRI system with either nontargeted or avb3-targeted nanoparticles. An eight-fold greater contrast enhancement was achieved with the targeted nanoparticles. In the second part of the study, pacli-taxel loaded nanoparticles were targeted to tissue factor (TF) proteins on vascular smooth muscle cells with a specific TF antibody. The TF-targeted paclitaxel particles inhibited cell proliferation while delivery of nanoparticles to targeted cells was confirmed with fluorine spectroscopy.

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