A Frequency-Selective pH-Responsive paraCEST Agent

S. James Ratnakar, Sara Chirayil, Alexander M. Funk, Shanrong Zhang, João F. Queiró, Carlos F.G.C. Geraldes, Zoltan Kovacs, A. Dean Sherry

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)21671-21676
Number of pages6
JournalAngewandte Chemie - International Edition
Issue number48
StatePublished - Nov 23 2020


  • contrast agents
  • imaging agents
  • lanthanide complexes
  • pH sensing
  • paraCEST

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)


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