This work demonstrates the development of novel pH-responsive contrast agents, highlighting potential improvements in extracellular pH imaging using CEST methods.
Motivation: Development of diamagnetic CEST MRI agents that ratiometrically determine pH response and overcome limitations of the current CT contrast agents repurposed for CEST imaging of pH. Goal(s): Concentration independent, metal free ratiometric assessment of extracellular pH. Approach: Design and chemical synthesis of contrast agents and technology development involving CEST methods on 600 MHz NMR Varian spectrometer Results: We have designed a series of agents and performed CEST NMR studies of 25 mM solutions of the agents and identified a lead agent that is diamagnetic and harbors a pH unresponsive sulfonamide and pH responsive amide moiety and can be used for ratiometric pH assessment. Impact: We have incorporated a pH-unresponsive and a pH-responsive functional group in a small organic molecule to generate a ratiometric, concentration independent approach of extracellular pH assessment with CEST methods without any metal addition to be used for imaging bacterial infections.
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Patkulkar et al. (2025) studied this question.
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