Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques

RATIONALE:Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention. OBJECTIVE:To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS AND RESULTS:Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling (Zr-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%, P