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

摘要

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 ¹H resonance in wet d3-acetonitrile that was separated from the bulk water resonance (Δω) 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 pKa 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⁺.