Abstract 10600: PET/MR Imaging of Inflammation In Atherosclerotic Plaque With a Novel Dextran Nanoparticle

Abstract

Background: Plaque macrophage content likely predicts the risk of plaque rupture. Dextran-coated nanomaterials are readily engulfed by inflammatory macrophages in atherosclerotic lesions and can be used as molecular imaging probes. We hypothesize that nanoparticle-based hybrid PET/MR imaging of macrophages will allow non-invasive assessment of inflammatory activity within atherosclerotic plaques.

Methods and Results: We systematically developed dextran nanoparticles (DNP) through iterative synthesis and here tested a lead compound. The DNP is composed of short dextran strands crosslinked to form a 13.3 nm diameter nanoparticle with a blood half-life of 3.9 hours. It was subsequently labeled with Zirconium-89 (89Zr) via desferroxamine chelation for in vivo PET imaging. 89Zr-DNP or fluorochrome-labeled DNP were injected in C57BL/6 and ApoE-/- mice 24-48 hours prior to in vivo imaging or flow cytometry analysis of excised aortas. PET/MR fusion was facilitated using external fiducial markers. Flow cytometry of aortas excised from ApoE -/- mice showed uptake of DNP predominantly within macrophages as compared to neutrophils and lymphocytes (76.7% vs 11.8% and 0.7%, p<0.05). Mean fluorescent intensity was significantly higher within macrophages compared to neutrophils and lymphocytes (MFI 4.2x104 vs 0.08x104 vs 0.02x104, p<0.001). DNP signal colocalized with macrophages as assessed by CD11b and DAPI staining on immunohistochemistry. In vivo PET imaging of ApoE -/- mice revealed signal enhancement in the aortic root identified by MRI (Figure). Aortas excised from ApoE -/- had significantly higher percent injected dose per gram tissue as compared to controls (2.1±0.41 vs 0.63±0.14, p<0.01), corroborated by enhanced signal in the aortic root on autoradiography exposure and Oil-Red-O staining.

Conclusion: Hybrid PET/MR imaging using a novel dextran nanoparticle enables non-invasive assessment of inflammatory activity within atherosclerotic plaques.