Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T1 contrast agents
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Open Access
- 28 January 2009
- journal article
- research article
- Published by Wiley in Contrast Media & Molecular Imaging
- Vol. 4 (2), 89-100
- https://doi.org/10.1002/cmmi.267
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.Keywords
This publication has 63 references indexed in Scilit:
- The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomainMagnetic Resonance Imaging, 2008
- Relaxometric and Modelling Studies of the Binding of a Lipophilic Gd-AAZTA Complex to Fatted and Defatted Human Serum AlbuminChemistry – A European Journal, 2007
- Optimized Relaxivity and Stability of [Gd(H(2,2)-1,2-HOPO)(H2O)]- for Use as an MRI Contrast Agent1Inorganic Chemistry, 2007
- Highly Soluble Tris-hydroxypyridonate Gd(III) Complexes with Increased Hydration Number, Fast Water Exchange, Slow Electronic Relaxation, and High RelaxivityJournal of the American Chemical Society, 2007
- Probing the Water Coordination of Protein‐Targeted MRI Contrast Agents by Pulsed ENDOR SpectroscopyChemphyschem, 2005
- High-field pulsed EPR and ENDOR of Gd3+ complexes in glassy solutionsApplied Magnetic Resonance, 2005
- The Impact of Rigidity and Water Exchange on the Relaxivity of a Dendritic MRI Contrast AgentChemistry – A European Journal, 2002
- Lipari-Szabo approach as a tool for the analysis of macromolecular gadolinium(III)-based MRI contrast agents illustrated by the [Gd(EGTA-BA-(CH2)12)] n n + polymerJBIC Journal of Biological Inorganic Chemistry, 2001
- Gd(DOTP)5‐ outer‐sphere relaxation enhancement promoted by nitrogen basesMagnetic Resonance in Medicine, 1993
- Nuclear relaxation in macromolecules by paramagnetic ions: a novel mechanismJournal of Magnetic Resonance (1969), 1975