Improved pH measurements with a single PARACEST MRI contrast agent

The measurement of extracellular pH has potential utility for assessing the therapeutic effects of pH-dependent and pH-altering therapies. A PARAmagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agent, Yb-DO3A-oAA, has two CEST effects that are dependent on pH. A ratio derived from these CEST effects was linearly correlated with pH throughout the physiological pH range. The pH can be measured with a precision of 0.21 pH units and an accuracy of 0.09 pH units. The pH measurement is independent of concentration and T₁ relaxation times, but is dependent on temperature. Although MR coalescence affects the CEST measurements, especially at high pH, the ratiometric analysis of the CEST effects can account for incomplete saturation of the agent's amide and amine that results from MR coalescence. Provided that an empirical calibration is determined with saturation conditions, magnetic field strength and temperature that can be used for subsequent studies, these results demonstrate that this single PARACEST MRI contrast agent can accurately measure pH.