Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc

K. Srivastava, G. Ferrauto, S. M. Harris, D. L. Longo, M. Botta, S. Aime, V. C. Pierre

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-βAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of transition metals. Both complexes function as paraCEST agents in the absence of copper and zinc, with the positively charged Tm-DOTAm-py being more sensitive than the neutrally charged Tm-DOTAm-βAla-py. In each case, the CEST signal arises from amide protons rather than from a water molecule coordinated to Tm3+ ions. Upon binding to Cu+, Cu2+, or Zn2+, the exchange rate of the amide protons increases substantially, resulting in a complete loss of the CEST signal. This efficient mode of action along with the lack of inner-sphere water molecules both in the presence and absence of transition metals was confirmed by 1/T1 NMRD profiles, 17O NMR measurements, and molecular modelling simulations. Neither complex is selective for copper over zinc. Both form either a 1:1 TmL:Cu+ or a 2:1 TmL:Cu2+ and TmL:Zn2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.

Original languageEnglish (US)
Pages (from-to)11346-11357
Number of pages12
JournalDalton Transactions
Issue number33
StatePublished - 2018

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© 2018 The Royal Society of Chemistry.


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