Amplifying the Sensitivity of Zinc(II) Responsive MRI Contrast Agents by Altering Water Exchange Rates

Jing Yu, André F. Martins, Christian Preihs, Veronica Clavijo Jordan, Sara Chirayil, Piyu Zhao, Yunkou Wu, Khaled Nasr, Garry E. Kiefer, A. Dean Sherry

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase the rate of water exchange to improve MRI detection sensitivity. These new sensors exhibit fine-tuned water exchange properties and, depending on the individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two sensors in particular demonstrate optimized parameters and, therefore, show exceptionally high longitudinal relaxivities of about 50 mM-1 s-1 upon binding to Zn(II) and human serum albumin (HSA). This value demonstrates a 3-fold increase in r1 compared to that displayed by the original sensor, GdDOTA-diBPEN. In addition, this study provides important insights into the interplay between structural modifications, water exchange rate, and kinetic stability properties of the sensors. The new high relaxivity agents were used to successfully image Zn(II) release from the mouse pancreas in vivo during glucose stimulated insulin secretion.

Original languageEnglish (US)
Pages (from-to)14173-14179
Number of pages7
JournalJournal of the American Chemical Society
Volume137
Issue number44
DOIs
Publication statusPublished - Nov 11 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

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