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Abstract #3590

A new class of pH-responsive paraCEST agents for MRI

James S Ratnakar1, Sara Chirayil1, Alexander M Funk1, Zoltan Kovacs1, and A Dean Sherry1,2

1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Department of Chemistry, University of Texas at Dallas, Richardson, TX, United States

Many paraCEST agents have reduced sensitivity in vivo due to the reduction of the T2 relaxation of bulk water by T2ex exchange. Phosphonate coordinating side-chains in cyclen-based complexes exclude inner sphere water and this should reduce the interfering T2ex effects. In the new complexes reported here, a combination of phosphonate and hydroxypropyl pendant arms were incorporated to take advantage of the CEST signal from the Ln-bound OH. Protonation of the coordinating phosphonates results in a shift in the resonance frequency of Ln-bound OH CEST. These agents display several attractive features for imaging tissue pH in vivo by CEST MRI.

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