Abstract 18638: Quantification of Endothelial Activation in Atherosclerosis in vivo With Fluorine Magnetic Resonance Imaging and Spectroscopy
Endothelial activation is one of the necessary initial steps in the formation of atherosclerotic plaque that facilitates immune cell recruitment and retention. To image and quantify early markers of endothelial inflammation, we recently developed a multiplexing peptide-based targeting system for post-formulation functionalization of perfluorocarbon nanoparticles that is intrinsically quantifiable at a binding site with 19F magnetic resonance spectroscopy. The approach is now demonstrated in vivo to detect and quantify VCAM-1 in ApoE-/- mouse aorta.
Methods and Results: Anti-VCAM-1 targeting peptides were loaded onto PFC nanoparticles (260 nm) after fusion to our amphipathic peptide linker recently developed through modifications to the sequence of melittin, a component of honey bee venom. Specific targeting to VCAM-1 in vitro in mouse endothelial cells subjected to TNF-α stimulation was confirmed by confocal imaging and magnetic resonance imaging (MRI), and quantified by 19F magnetic resonance spectroscopy (MRS) (11.7T) in comparison to a 19F calibration standard. Next, ApoE-/- and control C57-BL6 mice (n ≥3/group) fed a western diet for 8 weeks, were injected i.v. with VCAM-1 targeted or non-targeted nanoparticles. After two hours, aortas were subjected ex vivo to MRS analysis (11.7T) which revealed a 4.6-fold increase in the amount of nanoparticles in aortas from the ApoE-/- mice receiving VCAM-1 targeted nanoparticles as compared with other groups (targeted vs non-targeted in ApoE -/- mice: 8.22±4.4 vs 1.78±1.2× 105 NPs/mm2, p <0.05; targeted vs non-targeted in C57-BL6 mice: 2.28±1.24 vs 2.08 ±0.98× 107 NPs/mm2).
Conclusion: The use of 19F MRI/MRS together with a flexible and rapid postformulation approach to creating ligand targeted nanoparticulate contrast agents may enhance the efficiency and breadth of molecular imaging of atherosclerosis with MRI and enable quantification of selected biomarker molecules that are important early drivers of atherosclerosis.
- © 2010 by American Heart Association, Inc.