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Magnetic-Field-Dependent 1H Relaxivity Behavior of Biotin/Avidin-Based Magnetic Resonance Imaging Probes

Authors

  • Dr. Kirti Dhingra Verma,

    Corresponding author
    1. Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
    2. Department of Radiology, Case Center for Imaging Research, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH (USA)
    • Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
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  • Dr. Anurag Mishra,

    1. Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
    2. Department of Chemistry, Durham University, South Road, Durham (United Kingdom)
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  • Dr. Jörn Engelmann,

    1. High Field MR Center, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
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  • Michael Beyerlein,

    1. Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
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  • Prof. Dr. Martin E. Maier,

    1. Institute for Organic Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 18, Tübingen (Germany)
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  • Prof. Dr. Nikos K. Logothetis

    Corresponding author
    1. Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
    2. Imaging Science and Biomedical Engineering, University of Manchester, Manchester (United Kingdom)
    • Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, Tuebingen (Germany)
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Abstract

One major challenge in noninvasive mapping of various molecular targets is their inherently low in vivo concentration coupled with the insensitivity of imaging modalities, such as the widely used magnetic resonance imaging (MRI). Development of agents with high sensitivity and specificity is of paramount importance for structural and functional noninvasive imaging. The design, synthesis, and physiochemical characterization of two gadolinium-based contrast agents (CAs) for MRI, the sensitivity of which was optimized by exploiting the well-established biotin–avidin amplification strategies, are reported. The relaxivity of these agents showed a large increase if bound to avidin; specifically, the first compound showed an approximately 1000 % increase in transverse proton relaxivity (r2p), whereas the second compound had an approximately 250 % r2p increase. The increase in r2p was magnetic field independent in the range of 1.5–16.4 T whereas the longitudinal proton relaxivity (r1p) showed strong field dependence. The CAs were further characterized by measuring luminescence lifetimes and emission spectral changes upon addition of avidin to their Eu3+ analogues. The difference in relaxation rate behavior of both complexes was explained on the basis of hydration number modulation and the “global/internal motion concept”. The association constant of these CAs with avidin was found to be in the range of approximately 1015M−1, which shows that the coupling of biotin to Gd-DO3A did not affect its affinity for binding to avidin (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid).

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