T2 Exchange Agents: a New Class of Paramagnetic MRI Contrast Agent That Shortens Water T2 by Chemical Exchange Rather Than Relaxation

Exchange of water molecules between the frequency-shifted inner-sphere of a paramagnetic lanthanide ion and aqueous solvent can shorten the T-2 of bulk water protons. The magnitude of the line-broadening T-2 exchange (T-2exch) is determined by the lanthanide concentration, the chemical shift of the exchanging water molecule, and the rate of water exchange between the two pools. A large T-2exch contribution to the water linewidth was initially observed in experiments involving Eu3+-based paramagnetic chemical exchange saturation transfer agents in vivo at 9.4 T. Further in vitro and in vivo experiments using six different Eu3+ complexes having water exchange rates ranging from zero (no exchange) to 5 x 10(6) s(-1) (fast exchange) were performed. The results showed that the exchange relaxivity (r(2exch)) is small for complexes having either very fast or very slow exchange, but reaches a well-defined maximum for complexes with intermediate water exchange rates. These experimental results were verified by Bloch simulations for two site exchange. This new class of T-2exch agent could prove useful in the design of responsive MRI contrast agents for molecular imaging of biological processes. Magn Reson Med 66:1697-1703, 2011. (C) 2011 Wiley Periodicals, Inc.