Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques
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Anderson_Polymeric nanoparticle.pdf
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Author(s)
Majmudar, Maulik D.
Yoo, J.
Keliher, Edmund J.
Truelove, J. J.
Iwamoto, Y.
Sena, B.
Dutta, P.
Borodovsky, Anna
Fitzgerald, K.
Di Carli, M. F.
Date Issued
January 2013
Journal
Circulation Research
Publisher
American Heart Association
Citation
Majmudar, M. D., J. Yoo, E. J. Keliher, J. J. Truelove, Y. Iwamoto, B. Sena, P. Dutta, et al. Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques. Circulation Research 112, no. 5 (February 28, 2013): 755-761.
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Author's final manuscript
Abstract
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 ([superscript 89]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<0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of [superscript 89]Zr-DNP in the aortic root of apolipoprotein E knock out (ApoE[superscript −/−]) mice (standard uptake value, ApoE[superscript −/−] 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 [superscript 89]Zr-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.
Description
Author Manuscript 2013 March 02.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1161/CIRCRESAHA.111.300576
