Skip to main content
SpringerLink
Log in

Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro

  • Experimental
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

To evaluate the capacity of human monocytes to phagocytose various approved iron oxide based magnetic resonance (MR) contrast agents and to optimize in vitro labeling of these cells. Human monocytes were incubated with two superparamagnetic iron oxide particles (SPIO) as well as two ultrasmall SPIO (USPIO) at varying iron oxide concentrations and incubation times. Iron uptake in monocytes was proven by histology, quantified by atomic emission absorption spectrometry and depicted with T2* weighted fast field echo (FFE) MR images at 1.5 T. Additionally, induction of apoptosis in iron oxide labeled monocytes was determined by YO-PRO-1 staining. Cellular iron uptake was significantly (P<0.01) higher after incubation with SPIO compared with USPIO. For SPIO, the iron oxide uptake was significantly (P<0.01) higher after incubation with the ionic Ferucarbotran as compared with the non-ionic Ferumoxides. Efficient cell labeling was achieved after incubation with Ferucarbotran at concentrations ≧500 μg Fe/ml and incubation times ≧1 h, resulting in a maximal iron oxide uptake of up to 50 pg Fe/cell without impairment of cell viability. In vitro labeling of human monocytes for MR imaging is most effectively obtained with the approved SPIO Ferucarbotran. Potential subsequent in vivo cell tracking applications comprise, e.g. specific targeting of inflammatory processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Anzai Y, Blackwell KE, Hirschowitz SL, Rogers JW, Sato Y, Yuh WT, Runge VM, Morris MR, McLachlan SJ, Lufkin RB (1994) Initial clinical experience with dextran-coated superparamagnetic iron oxide for detection of lymph node metastases in patients with head and neck cancer. Radiology 192:709–715

    CAS  PubMed  Google Scholar 

  2. Daldrup-Link HE, Rummeny EJ, Ihssen B, Kienast J, Link TM (2002) Iron-oxide-enhanced MR imaging of bone marrow with non-Hodgkin’s lymphoma: differentiation between tumor infiltration and hypercellular bone marrow. Eur Radiol 12:1557–1566

    Article  PubMed  Google Scholar 

  3. Gellissen J, Axmann Ch, Prescher A, Bohndorf K, Lodemann KP (1999) Extra- and intracellular accumulation of ultrasmall superparamagnetic iron oxides (USPIO) in experimentally induced abscesses of the peripheral soft tissues and their effects on magnetic resonance imaging. Magn Reson Imaging 17:557–567

    Article  CAS  PubMed  Google Scholar 

  4. Dousset V, Gomez C, Petry KG, Delalande C, Caille JM (1999) Dose and scanning delay using USPIO for central nervous system macrophage imaging. MAGMA 8:185–189

    Article  CAS  PubMed  Google Scholar 

  5. Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF (2001) Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation 103:415–422

    CAS  PubMed  Google Scholar 

  6. Bulte JW, Ma LD, Magin RL, Kamman RL, Hulstaert CE, Go KG, The TH, de Leij L (1993) Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles. Magn Reson Med 29:32–37

    CAS  PubMed  Google Scholar 

  7. Weissleder R, Cheng HC, Bogdanova A, Bogdanov A Jr (1997) Magnetically labeled cells can be detected by MR imaging. J Magn Reson Imaging 7:258–263

    CAS  PubMed  Google Scholar 

  8. Sipe JC, Filippi M, Martino G, Furlan R, Rocca MA, Rovaris M, Bergami A, Zyroff J, Scotti G, Comi G (1999) Method for intracellular magnetic labeling of human mononuclear cells using approved iron contrast agents. Magn Reson Imaging 17:1521–1523

    Article  CAS  PubMed  Google Scholar 

  9. Foster-Gareau P, Heyn C, Alejski A, Rutt BK (2003) Imaging single mammalian cells with a 1.5 T clinical MRI scanner. Magn Reson Med 49:968–971

    Article  PubMed  Google Scholar 

  10. Wang YX, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11:2319–2331

    Article  CAS  PubMed  Google Scholar 

  11. Weissleder R, Elizondo G, Wittenberg J, Rabito C, Bengele H and Josephson L (1990) Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 175:489–493

    CAS  PubMed  Google Scholar 

  12. Jung CW (1995) Surface properties of superparamagnetic iron oxide MR contrast agents: ferrumoxides, ferrumoxtran, ferrumoxisil. Magn Res Imag 13:675–691

    Article  CAS  Google Scholar 

  13. Weissleder R, Stark D, Engelstad B, Bacon B, Compton C (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. Am J Roentgenol 152:167–173

    CAS  Google Scholar 

  14. Clarke SE, Weinmann HJ, Dai E, Lucas AR, Rutt BK (2000) Comparison of two blood pool contrast agents for 0.5-T MR angiography: experimental study in rabbits. Radiology 214:787–794

    CAS  PubMed  Google Scholar 

  15. Reimer P, Engelhardt M, Mahler M, Tombach B (2003) Führt das Eisen-basierte Blutpool-Kontrastmittel SH U 555 C zu Signalveränderungen in den Nieren? Ergebnisse einer Plazebo-kontrollierten MRA Studie. RöFo 1(Suppl 1):237

    Google Scholar 

  16. Chambon C, Clement O, Le Blanche A, Schouman-Claeys E and Frija G (1993) Superparamagnetic iron oxides as positive contrast agents: in vitro and in vivo evidence. Magn Reson Imaging 11:509–519

    Article  CAS  PubMed  Google Scholar 

  17. McLachlan SJ, Morris MR, Lucas MA, Fisco RA, Eakins MN, Fowler DR, Scheetz RB, Olukotun AY (1994) Phase I clinical evaluation of a new iron oxide MR contrast agent. J Magn Reson Imaging 4:301–307

    CAS  PubMed  Google Scholar 

  18. Idziorek T, Estaquier J, De-Bels F, Ameisen JC (1995) YOPRO-1 permits cytofluorometric analysis of programmed cell death (apoptosis) without interfering with cell viability. J Immunol Methods 185:249–258

    Article  CAS  PubMed  Google Scholar 

  19. Deigner HP, Claus R, Bonaterra GA, Gehrke C, Bibak N, Blaess M, Cantz M, Metz J, Kinscherf R (2001) Ceramide induces aSMase expression: implications for oxLDL-induced apoptosis. FASEB J 15:807–814

    Article  CAS  PubMed  Google Scholar 

  20. Kinscherf R, Deigner HP, Usinger C, Pill J, Wagner M, Kamencic H, Hou D, Chen M, Schmiedt W, Schrader M, Kovacs G, Kato K, Metz J (1997) Induction of manganese superoxide dismutase by oxidized-LDL—its relevance in atherosclerosis of humans and heritable hyperlipidemic rabbits. FASEB J 11:1317–1328

    CAS  PubMed  Google Scholar 

  21. Bowen CV, Zhang X, Saab G, Gareau PJ, Rutt BK (2002) Application of the static dephasing regime theory to superparamagnetic iron-oxide loaded cells. Magn Reson Med 48:52–61

    Article  CAS  PubMed  Google Scholar 

  22. Daldrup-Link HE, Rudelius M, Oostendorp RAJ, Settles M, Piontek G, Metz S, Heinzmann U, Rummeny EJ, Schlegel J, Link TM (2003) Targeting of hematopoietic progenitor cells with MR contrast agents. Radiology 228:760–767

    PubMed  Google Scholar 

  23. Matuszewski L, Wall A, Persigehl T, Schwindt W, Tombach B, Fobker M, Poremba C, Heindel W, Bremer C (2003) Cell tagging with superparamagnetic iron-oxide particles: impact of hydrodynamic diameter and coating on labeling efficiency. Mol Imaging 2:268

    Google Scholar 

  24. Brillet PY, Clément O, Bessoud B, Luciani A, Siauve N, Cuénod CA (2003) Use of two superparamagnetic iron oxide particles (SPIO) for tumoral imaging: in vitro and in vivo studies. Eur Radiol 13(Suppl 1):439

    Google Scholar 

  25. Fleige G, Seeberger F, Laux D, Kresse M, Taupitz M, Pilgrimm H, Zimmer C (2002) In vitro characterization of two different ultrasmall iron oxide particles for magnetic resonance cell tracking. Invest Radiol 37:482–488

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Diagnostic Radiology, Technical University Munich, 81675, Munich, Germany

    Stephan Metz, Marcus Settles, Ernst J. Rummeny & Heike E. Daldrup-Link

  2. Institute of Anatomy and Cell Biology, Ruprecht-Karls-University, Heidelberg, Germany

    Gabriel Bonaterra

  3. Department of Pathology, Technical University Munich, 81675, Munich, Germany

    Martina Rudelius

Authors
  1. Stephan Metz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriel Bonaterra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martina Rudelius
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marcus Settles
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ernst J. Rummeny
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Heike E. Daldrup-Link
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan Metz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Metz, S., Bonaterra, G., Rudelius, M. et al. Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol 14, 1851–1858 (2004). https://doi.org/10.1007/s00330-004-2405-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-004-2405-2

Keywords

Search

Navigation