Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc. Issue 33 (13th June 2018)

• Record Type: Journal Article
• Authors: Srivastava, K.; Ferrauto, G.; Harris, S. M.; Longo, D. L.; Botta, M.; Aime, S.; Pierre, V. C.
• Is Part Of: Dalton transactions. Volume 47:Issue 33(2018)
• Page Start: 11346
• Page End: 11357
• Publication Date: 2018-06-13
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c8dt01172a
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Two thulium-based paraCEST contrast agents enable detection and imaging of copper and zinc by MRI with a complete on/off response. 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 Tm 3+ ions. Upon binding to Cu +, Cu 2+, or Zn 2+, 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/ T 1 NMRD profiles, 17 O 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 : Cu 2+ and TmL : Zn 2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.