title: Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques.
abstract: BACKGROUND
  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).
  
  
  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 ((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 (89)Zr-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 (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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St., Boston, MA 02114, USA.
authors.forename: Maulik D
authors.initials: MD
authors.lastname: Majmudar
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Keliher
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Truelove
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Brena
authors.initials: B
authors.lastname: Sena
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.forename: Anna
authors.initials: A
authors.lastname: Borodovsky
authors.forename: Kevin
authors.initials: K
authors.lastname: Fitzgerald
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D003911:Dextrans; D004195:Disease Models, Animal; D018450:Disease Progression; D005240:Feasibility Studies; D008264:Macrophages / Q000000981:diagnostic imaging* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes; D012680:Sensitivity and Specificity; D015040:Zirconium
chemical_list: D001057:Apolipoproteins E; D003911:Dextrans; D011868:Radioisotopes; D015040:Zirconium