Hyperpolarized 89 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 ³⁺ -based MRI contrast agents are T ₁ or T ₂ relaxation-based sensors such as Gd ³⁺ -complexes for zinc or pH detection, a number of diamagnetic Y ³⁺ -complexes rely on changes in the chemical shift for potential quantitative MRI in biological milieu. ⁸⁹ Y, however, is a challenging nucleus to work with in conventional NMR or MRI due to its inherently low sensitivity and relatively long T ₁ relaxation time. This insensitivity problem in ⁸⁹ 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 ⁸⁹ Y-complexes with phosphonated open-chain ligands, ⁸⁹ Y-EDTMP and ⁸⁹ Y-DTPMP, as potential chemical shift-based pH NMR sensors. Our DNP-NMR data show that hyperpolarized ⁸⁹ Y-DTPMP has an apparent pK _a  ~ 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 ⁸⁹ Y-EDTMP show that it has an apparent pK _a 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 ⁸⁹ Y-DOTP has a pK _a of 7.64 and ~ 10-ppm wide chemical shift dispersion at pH 4-9 range. Overall, our data suggest that hyperpolarized ⁸⁹ Y-EDTMP is better than hyperpolarized ⁸⁹ Y-DOTP in terms of pH sensing capability at the physiological range.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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