A pH-Responsive MRI Agent that Can Be Activated beyond the Tissue Magnetization Transfer Window

A terbium-based complex that displays a water exchange CEST resonance well outside the normal magnetization transfer (MT) frequency range of tissues provides a direct readout of pH values by MRI. Deprotonation of the phenolic proton in this complex results in a frequency shift of 56 ppm in a bound water molecule exchange peak between pH 5 and 8. This allows direct imaging of pH without prior knowledge of the agent concentration and with essentially no interference from the tissue MT signal. Imaging beyond the MT effect: A pH-responsive MRI contrast agent displays a water exchange peak near -550 ppm, well outside the magnetization transfer (MT) window. Additionally, the chemical shift of 56 ppm in this CEST peak is quite sensitive to changes in pH. These features enable direct imaging of pH in vivo with no masking effect from the inherent tissue MT signal.