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Issue 33, 2018
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Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc

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Abstract

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.

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

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Publication details

The article was received on 26 Mar 2018, accepted on 17 May 2018 and first published on 23 May 2018


Article type: Paper
DOI: 10.1039/C8DT01172A
Citation: Dalton Trans., 2018,47, 11346-11357
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    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 and V. C. Pierre, Dalton Trans., 2018, 47, 11346
    DOI: 10.1039/C8DT01172A

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