Abstract 1729: MSR-Targeted Immunomicelles-Mediated MRI Enhancement of Atherosclerosis is Associated With Macrophage Content of Atherosclerotic Plaques and Inhibited by Monoclonal Antibodies to MSR.
Introduction: Gadolinium immunomicelles(Gd-IM), which are micelles linked to a specific antibody targeting macrophage scavenger receptor(MSR), have been shown to greatly improve in-vivo assessment of atherosclerosis & macrophages using MRI. The goals here were:(1) to evaluate whether there is a relationship between macrophage density of atherosclerotic plaques & MRI enhancement of plaques using Gd-IM targeting MSR;(2) to investigate whether monoclonal antibodies(mAbs) to MSR would inhibit Gd-IM from providing MRI enhancement of atherosclerosis
Methods: ApoE-/-mice were imaged at baseline & intervals after tail injection of Gd-IM(n=9), untargeted micelles n=9 or standard Gd-DTPA n=4. A group n=4 of mice were pre-injected with anti-MSR mAbs prior to imaging with Gd-IM. Immunohistochemis-try(IHC) & various pathological analyses were performed
Results: Using targeted Gd-IM the signal intensity(SI) increase of atherosclerosis post-contrast was avg of 1.79±0.1(79% enhancement) at 24-hrs. See Figures⇓ for complete results. Using the macrophage-stained IHC sections, there was a correlation between the number of macrophages per HPF & the MRI SI observed in the atherosclerotic aorta R2=0.75 p<0.01-Graph1. In the mice that were pre-injected with mAbs to MSR, the MRI changes were much lower than using Gd-IM alone p<0.001-Graph2
Conclusions: The MRI signal intensity using Gd-IM as the contrast agent is related to macrophage content. Monoclonal antibodies to MSR significantly impeded Gd-IM from providing MRI enhancement of plaque. Gd-IM shows promising results for in-vivo assessment of atherosclerosis & detection of high-macrophage density typical of high-risk plaques