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The Gd3+ complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-isothiocyanatoanilide) conjugated to inulin: a potential stable macromolecular contrast agent for MRI

Authors

  • Luigi Granato,

    1. Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium
    2. CMMI - Center for Microscopy and Molecular Imaging, Gosselies, Belgium
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  • Sophie Laurent,

    1. Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium
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  • Luce Vander Elst,

    1. Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium
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  • Kristina Djanashvili,

    1. Biocatalysis and Organic Chemistry, Department of Biotechnology, Delft University of Technology, Delft, The Netherlands
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  • Joop A. Peters,

    1. Biocatalysis and Organic Chemistry, Department of Biotechnology, Delft University of Technology, Delft, The Netherlands
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  • Robert N. Muller

    Corresponding author
    1. CMMI - Center for Microscopy and Molecular Imaging, Gosselies, Belgium
    • Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Mons, Belgium
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R. N. Muller,Department ofGeneral, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 19 Avenue Maistriau, 7000 Mons, Belgium.

E-mail: robert.muller@umons.ac.be

Abstract

Reaction of DOTA–NCSA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-isothiocyanatoanilide)] with O-(aminopropyl)inulin (degree of polymerization 25) provided a chelate that formed a kinetically extremely stable Gd3+ complex. No transmetalation was observed with Zn2+. The conjugate has a relaxivity of 21.7 s−1 m m−1 at 20 MHz and 37 °C, and each molecule of the inulin carries on average 35 Gd3+ ions. The parameters governing the relaxivity of this material and of a low-molecular-weight model compound prepared by conjugation of DOTA–NCSA and propylamine were evaluated by investigation of their water 1H longitudinal relaxation rate enhancements at different magnetic fields (NMRD) and by studying variable temperature 17O NMR data. The high relaxivity of the inulin conjugate can be ascribed to the efficient slowing down of the molecular tumbling by this carrier. The rotational correlation time at 37 °C of this material is 1460 ps, whereas that of the model compound is 84 ps. Furthermore, both complexes do not interact significantly with human serum albumin, as shown by their NMRD profiles, and do not undergo transmetallation by zinc ions. The inulin conjugate thus has potential for application as a contrast agent for MRI, particularly as a blood pool agent. Copyright © 2011 John Wiley & Sons, Ltd.

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