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MRI of ICAM-1 Upregulation After Stroke: the Importance of Choosing the Appropriate Target-Specific Particulate Contrast Agent

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Abstract

Purpose

Magnetic resonance imaging (MRI) with targeted contrast agents provides a promising means for diagnosis and treatment monitoring after cerebrovascular injury. Our goal was to demonstrate the feasibility of this approach to detect the neuroinflammatory biomarker intercellular adhesion molecule-1 (ICAM-1) after stroke and to establish a most efficient imaging procedure.

Procedures

We compared two types of ICAM-1-functionalized contrast agent: T 1-shortening gadolinium chelate-containing liposomes and T 2 (*)-shortening micron-sized iron oxide particles (MPIO). Binding efficacy and MRI contrast effects were tested in cell cultures and a mouse stroke model.

Results

Both ICAM-1-targeted agents bound effectively to activated cerebrovascular cells in vitro, generating significant MRI contrast-enhancing effects. Direct in vivo MRI-based detection after stroke was only achieved with ICAM-1-targeted MPIO, although both contrast agents showed similar target-specific vascular accumulation.

Conclusions

Our study demonstrates the potential of in vivo MRI of post-stroke ICAM-1 upregulation and signifies target-specific MPIO as most suitable contrast agent for molecular MRI of cerebrovascular inflammation.

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Acknowledgments

We gratefully acknowledge funding from the Netherlands Organization for Scientific Research (NWO; VIDI 917.76.347) and the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreements no. 201024 and no. 202213 (European Stroke Network).

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Yalelaan 2, 3584 CM, Utrecht, the Netherlands

    Lisette H. Deddens, Geralda A. F. van Tilborg, Annette van der Toorn, Kajo van der Marel & Rick M. Dijkhuizen

  2. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, N-laag, room b2.06, PO Box 513, 5600 MB, Eindhoven, the Netherlands

    Leonie E. M. Paulis & Gustav J. Strijkers

  3. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB, Utrecht, the Netherlands

    Louis van Bloois & Gert Storm

  4. Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, PO Box 1234, New York, NY, 10029, USA

    Willem J. M. Mulder

  5. Department of Molecular Cell Biology and Immunology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, the Netherlands

    Helga E. de Vries

Authors
  1. Lisette H. Deddens
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  2. Geralda A. F. van Tilborg
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Correspondence to Rick M. Dijkhuizen.

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Deddens, L.H., van Tilborg, G.A.F., van der Toorn, A. et al. MRI of ICAM-1 Upregulation After Stroke: the Importance of Choosing the Appropriate Target-Specific Particulate Contrast Agent. Mol Imaging Biol 15, 411–422 (2013). https://doi.org/10.1007/s11307-013-0617-z

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