Water exchange dynamics:: The key for high relaxivity contrast agents in medical magnetic resonance imaging

Current developments in medical Magnetic Resonance Imaging (MRI) call for very-high-relaxivity contrast agents. The dynamic parameters governing the relaxivity of today's (poly(amino carboxylate) complexes of Gd3+ (or other paramagnetic metals) are mainly the rates of molecular tumbling (1/tau(R)), of the exchange of the inner sphere water molecule(s) (1/tau(m)), and of electronic relaxation (1/T-1,T-2e). While it seems straightforward to freeze out rotation by attachment of the complexes to macromolecules, tuning the rates of water exchange and of electronic relaxation is less evident. Using O-17-NMR, EPR, and NMRD studies, we have gained considerable insight into the effects determining the rates and mechanisms of water exchange for monomer, dimer and polymer complexes. We present a review on the rate and mechanism of water exchange on monomeric, dimeric and polymeric Gd-III complexes. Conclusions are drawn for the design of future high-relaxivity contrast agents.