Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents

Authors

  • Peter Caravan,

    Corresponding author
    1. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 149 Thirteenth St, Charlestown, MA, 02129, USA
    • A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 149 Thirteenth St, Charlestown, MA, 02129, USA.
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  • Christian T. Farrar,

    1. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 149 Thirteenth St, Charlestown, MA, 02129, USA
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  • Luca Frullano,

    1. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 149 Thirteenth St, Charlestown, MA, 02129, USA
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  • Ritika Uppal

    1. A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 149 Thirteenth St, Charlestown, MA, 02129, USA
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Abstract

Simulations were performed to understand the relative contributions of molecular parameters to longitudinal (r1) and transverse (r2) relaxivity as a function of applied field, and to obtain theoretical relaxivity maxima over a range of fields to appreciate what relaxivities can be achieved experimentally. The field-dependent relaxivities of a panel of gadolinium and manganese complexes with different molecular parameters, water exchange rates, rotational correlation times, hydration state, etc. were measured to confirm that measured relaxivities were consistent with theory. The design tenets previously stressed for optimizing r1 at low fields (very slow rotational motion; chelate immobilized by protein binding; optimized water exchange rate) do not apply at higher fields. At 1.5T and higher fields, an intermediate rotational correlation time is desired (0.5–4 ns), while water exchange rate is not as critical to achieving a high r1. For targeted applications it is recommended to tether a multimer of metal chelates to a protein-targeting group via a long flexible linker to decouple the slow motion of the protein from the water(s) bound to the metal ions. Per ion relaxivities of 80, 45, and 18 mM−1 s−1 at 1.5, 3 and 9.4 T, respectively, are feasible for Gd3+ and Mn2+ complexes. Copyright © 2009 John Wiley & Sons, Ltd.

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