On Water and its Effect on the Performance of T1‐Shortening Contrast Agents

Abstract

AbstractThe performance of low molecular weight Gd3+ chelates as T1‐shortening contrast agents for MRI is limited by their rapid rate of molecular tumbling, which makes them very sensitive to factors that alter the rate of molecular reorientation. Unlike the interactions of these chelates with other solutes present in solution, which have been widely studied, the effect of the solvent water itself on tumbling seems to have been largely ignored. Water has long been known to adopt structures that vary from freely diffusing molecules on one extreme and a more “ice‐like” structure on the other. A variety of salts can be used to alter this “structure” of water. Relaxometric studies on inner and outersphere Gd3+ chelates were performed in the presence of both structure making and structure breaking salts. The addition of structure‐making salts to low molecular weight Gd3+ chelates was found to increase both the second‐ and outer‐sphere contributions to relaxivity. These results point to a slowing of molecular tumbling arising from an increase solvent structure and therefore microviscosity. The implication of these findings is that the performance of low molecular weight Gd3+ contrast agents is not, as generally assumed, constant in the absence of secondary interactions but may vary depending upon the nature of the solution in which it is dissolved.