Multimodal liposomes for SPECT/MR imaging as a tool for in situ relaxivity measurements

Authors

  • Anke de Vries,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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    • The first two authors contributed equally to this paper.

  • Maarten B. Kok,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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    • The first two authors contributed equally to this paper.

  • Honorius M. H. F. Sanders,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • Klaas Nicolay,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • Gustav J. Strijkers,

    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
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  • Holger Grüll

    Corresponding author
    1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
    • Department of Bio-molecular Engineering, Philips Research Eindhoven, the Netherlands
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H. Grüll, Eindhoven University of Technology, Department of Biomedical Engineering, Biomedical NMR Den Dolech 2 (N-laag 2.62) 5600 MB Eindhoven, the Netherlands. E-mail: h.gruell@tue.nl

Abstract

One of the major challenges of MR imaging is the quantification of local concentrations of contrast agents. Cellular uptake strongly influences different parameters such as the water exchange rate and the pool of water protons, and results in alteration of the contrast agent's relaxivity, therefore making it difficult to determine contrast agent concentrations based on the MR signal only. Here, we propose a multimodal radiolabeled paramagnetic liposomal contrast agent that allows simultaneous imaging with SPECT and MRI. As SPECT-based quantification allows determination of the gadolinium concentration, the MRI signal can be deconvoluted to get an understanding of the cellular location of the contrast agent. The cell experiments indicated a reduction of the relaxivity from 2.7 ± 0.1 m m−1 s−1 to a net relaxivity of 1.7 ± 0.3 m m−1 s−1 upon cellular uptake for RGD targeted liposomes by means of the contrast agent concentration as determined by SPECT. This is not observed for nontargeted liposomes that serve as controls. We show that receptor targeted liposomes in comparison to nontargeted liposomes are taken up into cells faster and into subcellular structures of different sizes. We suggest that the presented multimodal contrast agent provides a functional readout of its response to the biological environment and is furthermore applicable in in vivo measurements. As this approach can be extended to several MRI-based contrast mechanisms, we foresee a broader use of multimodal SPECT/MRI nanoparticles to serve as in vivo sensors in biological or medical research. Copyright © 2011 John Wiley & Sons, Ltd.

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