Molecular Imaging and Biology

, Volume 13, Issue 5, pp 819–824

On the Use of Micron-Sized Iron Oxide Particles (MPIOS) to Label Resting Monocytes in Bone Marrow

Brief Article



The use of MRI to monitor immune cell infiltration into various pathologies is well established. In an effort to boost the magnetic material within immune cells, this work attempted to label resting monocytes within bone marrow, in mice, by intravenous administration of micron-sized iron oxide particles (MPIOs), similar in fashion to the administration of (U)SPIO.


MPIOs were incubated with various immune cells both in culture, and in whole blood. Flow cytometry and histology were used to analyze magnetic cell labeling. Also, MPIOs were injected intravenously into mice. In vivo, high-resolution 3-D MRI was performed on mouse legs, and signal changes were quantified. Flow cytometry and histology were used to analyze magnetic cell labeling of bone marrow resident cells.


It is demonstrated here that monocytes and neutrophils can indeed endocytose MPIOs both in cell culture and ex vivo in whole blood. However, despite rapid accumulation of MPIOs within the bone marrow following injection, MPIOs did not label monocytes or any other hematopoietic cell type in the marrow. Hypotheses are drawn to explain these results in light of recent usage of MPIOs for immune cell tracking.


Systemic administration of various MPIO formulations showed that MPIOs arrive in bone marrow rapidly following injection and remain there for at least 7 days. Data also shows slow clearance of some particles from the tissue over this period. While MPIOs can efficiently label monocytes in culture and in whole blood ex vivo, they were not found to label bone marrow resident monocytes.

Key words

MRI Iron oxide Monocytes Bone marrow 


  1. 1.
    Stoll G, Bendszus M (2010) New approaches to neuroimaging of central nervous system inflammation. Curr Opin Neurol 23(3):282–286PubMedCrossRefGoogle Scholar
  2. 2.
    Fayad ZA, Razzouk L, Briley-Saebo KC, Mani V (2009) Iron oxide magnetic resonance imaging for atherosclerosis therapeutic evaluation: still “rusty?”. J Am Coll Cardiol 53:2051–2052PubMedCrossRefGoogle Scholar
  3. 3.
    Yang Y, Yang Y, Yanasak N, Schumacher A, Hu TC (2010) Temporal and noninvasive monitoring of inflammatory-cell infiltration to myocardial infarction sites using micrometer-sized iron oxide particles. Magn Reson Med 63:33–40PubMedGoogle Scholar
  4. 4.
    Wu YL, Ye Q, Foley LM, Hitchens TK, Sato K, Williams JB, Ho C (2006) In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. Proc Natl Acad Sci USA 103:1852–1857PubMedCrossRefGoogle Scholar
  5. 5.
    Dardzinski BJ, Schmithorst VJ, Holland SK, Boivin GP, Imagawa T, Watanabe S, Lewis JM, Hirsch R (2001) MR imaging of murine arthritis using ultrasmall superparamagnetic iron oxide particles. Magn Reson Imaging 19:1209–1216PubMedCrossRefGoogle Scholar
  6. 6.
    Saleh A, Schroeter M, Ringelstein A, Hartung HP, Siebler M, Modder U, Jander S (2007) Iron oxide particle-enhanced MRI suggests variability of brain inflammation at early stages after ischemic stroke. Stroke 38:2733–2737PubMedCrossRefGoogle Scholar
  7. 7.
    Howarth SP, Tang TY, Graves MJ, King-Im JM, Li ZY, Walsh SR, Gaunt ME, Gillard JH (2007) Non-invasive MR imaging of inflammation in a patient with both asymptomatic carotid atheroma and an abdominal aortic aneurysm: a case report. Ann Surg Innov Res 1:4PubMedCrossRefGoogle Scholar
  8. 8.
    Shapiro EM, Skrtic S, Sharer K, Hill JM, Dunbar CE, Koretsky AP (2004) MRI detection of single particles for cellular imaging. Proc Natl Acad Sci USA 101:10901–10906PubMedCrossRefGoogle Scholar
  9. 9.
    Shapiro EM, Skrtic S, Koretsky AP (2005) Sizing it up: cellular MRI using micron-sized iron oxide particles. Magn Reson Med 53:329–338PubMedCrossRefGoogle Scholar
  10. 10.
    Hinds KA, Hill JM, Shapiro EM, Laukkanen MO, Silva AC, Combs CA, Varney TR, Balaban RS, Koretsky AP, Dunbar CE (2003) Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood 102:867–872PubMedCrossRefGoogle Scholar
  11. 11.
    Shapiro EM, Sharer K, Skrtic S, Koretsky AP (2006) In vivo detection of single cells by MRI. Magn Reson Med 55:242–249PubMedCrossRefGoogle Scholar
  12. 12.
    Tacke F, Ginhoux F, Jakubzick C, van Rooijen N, Merad M, Randolph GJ (2006) Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery. J Exp Med 203:583–597PubMedCrossRefGoogle Scholar
  13. 13.
    Montet-Abou K, Daire JL, Hyacinthe JN, Jorge-Costa M, Grosdemange K, Mach F, Petri-Fink A, Hofmann H, Morel DR, Vallee JP, Montet X (2010) In vivo labelling of resting monocytes in the reticuloendothelial system with fluorescent iron oxide nanoparticles prior to injury reveals that they are mobilized to infarcted myocardium. Eur Heart J 31(11):1410–1420PubMedCrossRefGoogle Scholar
  14. 14.
    Ye Q, Wu YL, Foley LM, Hitchens TK, Eytan DF, Shirwan H, Ho C (2008) Longitudinal tracking of recipient macrophages in a rat chronic cardiac allograft rejection model with noninvasive magnetic resonance imaging using micrometer-sized paramagnetic iron oxide particles. Circulation 118:149–156PubMedCrossRefGoogle Scholar
  15. 15.
    Wu YJ, Muldoon LL, Varallyay C, Markwardt S, Jones RE, Neuwelt EA (2007) In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging. Am J Physiol Cell Physiol 293:C1698–C1708PubMedCrossRefGoogle Scholar
  16. 16.
    Yoo MK, Park IY, Kim IY, Park IK, Kwon JS, Jeong HJ, Jeong YY, Cho CS (2008) Superparamagnetic iron oxide nanoparticles coated with mannan for macrophage targeting. J Nanosci Nanotechnol 8:5196–5202PubMedCrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Kevin S. Tang
    • 2
  • Bradley Hann
    • 2
  • Erik M. Shapiro
    • 1
    • 2
  1. 1.Department of Diagnostic RadiologyYale University School of MedicineNew HavenUSA
  2. 2.Department of Biomedical EngineeringYale University School of MedicineNew HavenUSA

Personalised recommendations