Physical characteristics of lanthanide complexes that act as magnetization transfer (MT) contrast agents

Rapid water exchange is normally considered a prerequisite for efficient Gd3+-based M RI contrast agents. Yet recent measures of exchange rates in some Gd3+ complexes have shown that water exchange can become limiting when such complexes are attached to larger macromolecular structures. A new class of lanthanide complexes that display unusually slow water exchange (bound water lifetimes (tau(M)(298)) > 10 mus) has recently been reported. This apparent disadvantage may be taken advantage of by switching the metal M ion from gadolinium(111) to a lanthanide that shifts the bound water resonance substantially away from bulk water. Given appropriate water exchange kinetics, one can then alter the intensity of the bulk water signal by selective presaturation of this highly shifted, Ln(3+)-bound water resonance. This provides the basis of a new method to alter MR image contrast in tissue. We have synthesized a variety of DOTA-tetra(amide) ligands to evaluate as potential magnetization transfer (MT) contrast agents and found that the bound water lifetimes in these complexes are sensitive to both ligand structure (a series of Eu3+ complexes have tau(M)(298) values M that range from I to 1300mus) and the identity of the paramagnetic Ln(3+) cation (from 3 to 800 mus for a single ligand). This demonstrates that it may be possible either to fine-tune the ligand structure or to select proper lanthanide cation to create an optimal MT agent for any clinical imaging field. (C) 2002 Elsevier Science (USA). All rights reserved.