Abstract 1732: Specific In Vivo Imaging of Macrophages in Atherosclerosis With a Targeted Multimodal Magnetofluorescent Nanoparticle
OBJECTIVE: Macrophages play a critical role in atherogenesis. Conventional magnetofluorescent nanoparticles (MNFP) are taken up predominantly but not exclusively by macrophages. We sought to image specifically macrophage distribution in atheroma in vivo using a derivatized MFNP (MFNP-gly) targeted to activated human macrophages. In addition, we compared the cellular distribution of MFNP-gly and conventional MFNP.
METHODS: Cholesterol-fed 28 week-old apoE−/− mice (n=8) were injected with MFNP-gly (15 mg Fe/kg), or saline (n=3). A subset of MFNP-gly mice (n=3) was co-injected with a spectrally-distinct conventional MFNP to compare macrophage specificity of each agent. Mice were sacrificed 24h later for ex vivo aortic fluorescence reflectance imaging (FRI) and histology. For MRI, mice received MFNP-gly at 30 mg Fe/kg followed by in vivo T2*-weighted MRI (9.4 Tesla, echo time 4.7 ms, in-plane resolution 125x125 um).
RESULTS: FRI revealed focal accumulation of MFNP-gly in atheroma (target to background ratio 5.8 ± 0.9 vs 1.3 ± 0.2 saline; p<0.05). Compared to conventional MFNP, MFNP-gly had a more restricted spatial distribution (FIG 1⇓). Immunohistochemistry showed selective MFNP-gly co-localization with macrophages (arrow) whereas MFNP co-localized with both macrophages (arrowhead) and smooth muscle cells (*) (FIG 1⇓). On in vivo MRI, MFNP-gly enhanced the T2 contrast between aortic root plaque and blood (white arrows, FIG 2⇓).
CONCLUSIONS: MFNP-gly is a macrophage-selective nanoparticle for optical and in vivo MR imaging of atherosclerosis. This agent is promising for studying macrophages in atherogenesis and assessing anti-macrophage therapies in living animals.