Open AccessInfluence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium‐ and manganese‐based T 1 contrast agents
Author(s) -
Caravan Peter,
Farrar Christian T.,
Frullano Luca,
Uppal Ritika
Publication year - 2009
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.267
Subject(s) - manganese , gadolinium , chemistry , rotational correlation time , chelation , metal ions in aqueous solution , metal , linker , ion , field (mathematics) , molecule , nuclear magnetic resonance , magnetic field , analytical chemistry (journal) , computational chemistry , inorganic chemistry , organic chemistry , physics , mathematics , quantum mechanics , computer science , pure mathematics , operating system
Simulations were performed to understand the relative contributions of molecular parameters to longitudinal ( r 1 ) and transverse ( r 2 ) 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 r 1 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 r 1 . 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 m M −1 s −1 at 1.5, 3 and 9.4 T, respectively, are feasible for Gd 3+ and Mn 2+ complexes. Copyright © 2009 John Wiley & Sons, Ltd.