A Frequency-Selective pH-Responsive paraCEST Agent

Angew Chem Int Ed Engl. 2020 Nov 23;59(48):21671-21676. doi: 10.1002/anie.202008888. Epub 2020 Oct 6.

Abstract

Paramagnetic chemical exchange saturation transfer (paraCEST) agents are well-suited for imaging tissue pH because the basis of CEST, chemical exchange, is inherently sensitive to pH. Several previous pH-sensitive paraCEST agents were based on an exchanging Ln3+ -bound water molecule as the CEST antenna but this design often added additional line-broadening to the bulk water signal due to T2 exchange. We report herein a pH-sensitive paraCEST agent that lacks an inner-sphere water molecule but contains one Ln-bound -OH group for CEST activation. The Yb3+ complex, Yb(1), displayed a single, highly shifted CEST peak originating from the exchangeable Yb-OH proton, the frequency of which changed over the biologically relevant pH range. CEST images of phantoms ranging in pH from 6 to 8 demonstrate the potential of this agent for imaging pH. Initial rodent imaging studies showed that Gd(1) remains in the vascular system much longer than anticipated but is cleared slowly via renal filtration.

Keywords: contrast agents; imaging agents; lanthanide complexes; pH sensing; paraCEST.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry*
  • Coordination Complexes / chemistry*
  • Hydrogen-Ion Concentration
  • Lanthanoid Series Elements / chemistry*
  • Ligands
  • Luminescent Agents / chemical synthesis
  • Luminescent Agents / chemistry*
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure

Substances

  • Contrast Media
  • Coordination Complexes
  • Lanthanoid Series Elements
  • Ligands
  • Luminescent Agents