Hyperpolarized Y-EDTMP complex as a chemical shift-based NMR sensor for pH at the physiological range.

Yttrium (III) complexes are interesting due to the similarity of their chemistry with gadolinium complexes that are used as contrast agents in nuclear magnetic resonance (NMR) spectroscopy or imaging (MRI). While most of the paramagnetic Gd-based MRI contrast agents are T or T relaxation-based sensors such as Gd-complexes for zinc or pH detection, a number of diamagnetic Y-complexes rely on changes in the chemical shift for potential quantitative MRI in biological milieu. Y, however, is a challenging nucleus to work with in conventional NMR or MRI due to its inherently low sensitivity and relatively long T relaxation time. This insensitivity problem in Y-based complexes can be circumvented with the use of dissolution dynamic nuclear polarization (DNP) which allows for several thousand-fold enhancement of the NMR or MRI signal relative to thermal equilibrium signal. Herein, we report on the feasibility of using hyperpolarized Y-complexes with phosphonated open-chain ligands, Y-EDTMP and Y-DTPMP, as potential chemical shift-based pH NMR sensors. Our DNP-NMR data show that hyperpolarized Y-DTPMP has an apparent pK ~ 7.01 with a 4 ppm-wide chemical shift dispersion with the signal disappearing at pH below 6.2. On the other hand, pH titration data on hyperpolarized Y-EDTMP show that it has an apparent pK of pH 6.7 and a 16-ppm wide chemical shift dispersion at pH 5-9 range. In comparison, the previously reported hyperpolarized pH NMR sensor Y-DOTP has a pK of 7.64 and ~ 10-ppm wide chemical shift dispersion at pH 4-9 range. Overall, our data suggest that hyperpolarized Y-EDTMP is better than hyperpolarized Y-DOTP in terms of pH sensing capability at the physiological range.