SABRE-SHEATH Hyperpolarization of 1,5-13C2Z-OMPD for Noninvasive pH Sensing

Hyperpolarized (HP) 13C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-13C2]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD. Here, we pioneered the hyperpolarization of [1,5-13C2]Z-OMPD via SABRE-SHEATH (signal amplification by reversible exchange in shield enabling alignment transfer to heteronuclei), which is relatively simple and fast and promises to be highly scalable. With SABRE-SHEATH, we achieve enhancement values of ∼3950 and ∼2400 at 1.1 T (P13C = 0.4 and 0.25%) on the labeled C-1 and C-5 positions of Z-OMPD. Density functional theory calculations at the B3LYP level of theory were used to investigate possible binding modes of Z-OMPD on the iridium-based polarization transfer catalyst. The experimental and theoretical results suggest that the equatorial binding mode to the catalyst, where Z-OMPD binds to the catalyst at both C-1 and C-5 carboxylate positions, is the most stable complex. The HP signals were used to measure the Z-OMPD chemical shift as a function of pH showing an ∼3 ppm shift across pH 4-11. This work lays a foundation for the development of a simple, low-cost hyperpolarization technique to image pH.Hyperpolarized (HP) 13C-labeled probes are emerging as promising agents to noninvasively image pH in vivo. HP [1,5-13C2]Z-OMPD (Z-4-methyl-2-oxopent-3-enedioic acid) in particular has recently been used to simultaneously report on kidney perfusion, filtration, and pH homeostasis, in addition to the ability to detect local tumor acidification. In previous studies, dissolution dynamic nuclear polarization was used to hyperpolarize Z-OMPD. Here, we pioneered the hyperpolarization of [1,5-13C2]Z-OMPD via SABRE-SHEATH (signal amplification by reversible exchange in shield enabling alignment transfer to heteronuclei), which is relatively simple and fast and promises to be highly scalable. With SABRE-SHEATH, we achieve enhancement values of ∼3950 and ∼2400 at 1.1 T (P13C = 0.4 and 0.25%) on the labeled C-1 and C-5 positions of Z-OMPD. Density functional theory calculations at the B3LYP level of theory were used to investigate possible binding modes of Z-OMPD on the iridium-based polarization transfer catalyst. The experimental and theo