Majmudar, MaulikYoo, JeongsooKeliher, EdmundTruelove, JessicaIwamoto, YoshikoSena, BrenaDutta, ParthaBorodovsky, AnnaFitzgerald, KevinDi Carli, MarceloLibby, PeterAnderson, DanielSwirski, FilipWeissleder, RalphNahrendorf, Matthias2019-09-212013Majmudar, Maulik D., Jeongsoo Yoo, Edmund J. Keliher, Jessica J. Truelove, Yoshiko Iwamoto, Brena Sena, Partha Dutta, et al. 2013. “Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques.” Circulation Research 112 (5): 755–61. https://doi.org/10.1161/circresaha.111.300576.0009-73300069-41851524-4571http://nrs.harvard.edu/urn-3:HUL.InstRepos:41384204Rationale: 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-89-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<0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of Zr-89-DNP in the aortic root of apolipoprotein E knock out (ApoE(-/-)) mice (standard uptake value, ApoE(-/-) mice versus wild-type controls, 1.9+/-0.28 versus 1.3+/-0.03; P<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased Zr-89-DNP plaque signal (P<0.05) and inflammatory gene expression (P<0.05). Conclusions: Hybrid PET/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy. (Circ Res. 2013;122:755-761.)en-USJournal Article2019-09-2110.1161/CIRCRESAHA.111.300576