MRI CEST at 1T with large µeff Ln(3+) complexes T m(3+)-HPDO3A: An efficient MRI pH reporter

Purpose: Chemical exchange saturation transfer (CEST) sensitivity relies on the prototropic exchange rate kex between the agent and the "bulk" water protons. To exploit large kex, a large frequency separation (Δω) between the pools of exchanging protons is necessary. For this reason, high magnetic fields are preferred. Herein it is shown that the use of paramagnetic CEST agents based on lanthanide (III) ions with large effective magnetic moments allows the carrying out of CEST experiments at the relatively low field strength of 1 tesla (T).

Methods: Measurements were performed on a 1T MR-scanner using continuous wave (cw)-presaturation with a spin echo sequence. ParaCEST complexes have been synthetized by mixing the ligand and Ln(III)Cl3 in a stoichiometric ratio at room temperature and pH 7.

Results: Different lanthanide chelates were investigated (Tm-, Dy-, Yb-, Eu-HPDO3A, and Eu-DOTAMGly). Ratiometric (Tm-HPDO3A) and selective detection (Eu-DOTAMGly and Tm-HPDO3A) experiments have been proven feasible in vivo.

Conclusion: In vitro experiments demonstrated the feasibility of the CEST methodology at 1T for nearly every paraCEST candidate under investigation, except for Eu-HPDO3A. Among the studied compounds, Tm-HPDO3A proved suitable for the application of a ratiometric method for assessing pH both in vitro and in vivo.