Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques

  • Majmudar M
  • Yoo J
  • Keliher E
 et al. 
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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 ((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
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.

Author-supplied keywords

  • PET/MRI
  • atherosclerosis
  • inflammation
  • macrophage
  • molecular imaging
  • nanoparticles

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Authors

  • Maulik D. Majmudar

  • Jeongsoo Yoo

  • Edmund J. Keliher

  • Jessica J. Truelove

  • Yoshiko Iwamoto

  • Brena Sena

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