A concentration-independent method to measure exchange rates in PARACEST agents

W. Thomas Dixon, Jimin Ren, Angelo J M Lubag, James Ratnakar, Elena Vinogradov, Ileana Hancu, Robert E. Lenkinski, A. Dean Sherry

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Abstract

The efficiency of chemical exchange dependent saturation transfer (CEST) agents is largely determined by their water or proton exchange kinetics, yet methods to measure such exchange rates are variable and many are not applicable to in vivo measurements. In this work, the water exchange kinetics of two prototype paramagnetic agents (PARACEST) are compared by using data from classic NMR line-width measurements, by fitting CEST spectra to the Bloch equations modified for chemical exchange, and by a method where CEST intensity is measured as a function of applied amplitude of radiofrequency field. A relationship is derived that provides the water exchange rate from the X-intercept of a plot of steady-state CEST intensity divided by reduction in signal caused by CEST irradiation versus 1/ω1 2, referred to here as an omega plot. Furthermore, it is shown that this relationship is independent of agent concentration. Exchange rates derived from omega plots using either high-resolution CEST NMR data or CEST data obtained by imaging agree favorably with exchange rates measured by the more commonly used Bloch fitting and linewidth methods. Thus, this new method potentially allows access to a direct measure of exchange rates in vivo, where the agent concentration is typically unknown.

Original languageEnglish (US)
Pages (from-to)625-632
Number of pages8
JournalMagnetic Resonance in Medicine
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2010

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Keywords

  • CEST
  • PARACEST
  • Saturation transfer
  • Temperature dependent linewidths
  • Water exchange rate

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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