Cerium(III), Europium(III), and Ytterbium(III) Complexes with Alcohol Donor Groups as Chemical Exchange Saturation Transfer Agents for MRI

Abstract

Lanthanide(III) complexes of macrocycles 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane (THED) and (1S,4S,7S,10S)-1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (S-THP) were studied as chemical exchange saturation transfer (CEST) agents for magnetic resonance imaging (MRI) applications. The four hyperfine-shifted alcohol protons of these Ln(III) complexes gave rise to a single (1)H resonance in wet d(3)-acetonitrile that was separated from the bulk water resonance (Delta omega) by 8 ppm (Ce), 2 ppm (Nd), 7 ppm (Eu), or 17 ppm (Yb). A CEST peak corresponding to the alcohol protons was observed for all Ln(THED)(3+) or Ln(S-THP)(3+) complexes except Nd(III) at low water concentrations (<1%). In 100% aqueous buffered solutions, the CEST hydroxyl peak is observed for the Eu(III), Ce(III), and Yb(III) complexes over a range of pH values. The optimal pH range for the CEST effect of each complex is related to the pK(a) of the hydroxyl/water ligands of the complex. Optimum pH values for the CEST effect from alcohol proton exchange are pH = 6.0 for Ce(S-THP)(3+), pH = 4.5 for Eu(THED)(3+), and pH = 3.0 for Yb(S-THP)(3+).