Ln(III)-DOTAMGIY complexes: A versatile series to assess the determinants of the efficacy of paramagnetic chemical exchange saturation transfer agents for magnetic resonance imaging applications

Rationale and Objectives: Paramagnetic Ln-DOTAMGly complexes (Ln not equal La, Lu, and Gd) are the prototypes of a novel class of contrast agents for magnetic resonance imaging based on chemical exchange saturation transfer (CEST). Their ability to reduce the water signal intensity depends on the interplay of several physicochemical properties of the agent and instrumental parameters. This study aims to identify possible routes for their optimization Methods: Saturation transfer (ST) has been measured in vitro at 7.05 T as a function of pH, temperature, and concentration of the agent. Results: Large saturation transfer effects have been observed upon irradiating the coordinated water protons (for Ln = Pr, Nd, Eu, and Th). The comparison of the results obtained by irradiating water versus amide protons allows the set-up of ratiometric methods through which the ST response can be made independent on the concentration of the agent. Conclusions: The modulation of the magnetic properties along the lanthanide series allows an in-depth understanding of the determinants of ST effect and provides useful insights for the design of more efficient agents.