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 (P_13C = 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.

中文翻译：

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用于无创 pH 传感的 [1,5-13C2]Z-OMPD 的 SABRE-SHEATH 超极化


超极化 （HP） ¹³C 标记探针正在成为有前途的体内 pH 值成像试剂。特别是 HP [1,5-13 C₂]Z-OMPD （Z-4-甲基-2-氧戊-3-烯二酸） 除了能够检测局部肿瘤酸化外，最近还被用于同时报告肾灌注、过滤和 pH 稳态。在以前的研究中，溶出动态核极化用于超极化 Z-OMPD。在这里，我们率先通过 SABRE-SHEATH（通过屏蔽中的可逆交换进行信号放大，使对准转移到异核）实现 [1,5-13 C₂]Z-OMPD 的超极化，这相对简单和快速，并有望具有高度可扩展性。使用 SABRE-SHEATH，我们在 Z-OMPD 的标记 C-1 和 C-5 位置上在 1.1 T 处实现了 ∼3950 和 ∼2400 的增强值（P_13C = 0.4 和 0.25%）。使用 B3LYP 理论水平的密度泛函理论计算来研究 Z-OMPD 在铱基极化转移催化剂上的可能结合模式。实验和理论结果表明，与催化剂的赤道结合模式（其中 Z-OMPD 在 C-1 和 C-5 羧酸盐位置与催化剂结合）是最稳定的复合物。HP 信号用于测量 Z-OMPD 化学位移与 pH 值的函数关系，显示 pH 值 4–11 范围内发生 ∼3 ppm 的变化。这项工作为开发一种简单、低成本的超极化技术来对 pH 值进行成像奠定了基础。