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 Sherry^1,2

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 T_2ex exchange. Phosphonate coordinating side-chains in cyclen-based complexes exclude inner sphere water and this should reduce the interfering T_2ex 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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