Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27606, United States.
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.
Anal Chem. 2023 May 23;95(20):7822-7829. doi: 10.1021/acs.analchem.2c04817. Epub 2023 May 10.
Hyperpolarization modalities overcome the sensitivity limitations of NMR and unlock new applications. Signal amplification by reversible exchange (SABRE) is a particularly cheap, quick, and robust hyperpolarization modality. Here, we employ SABRE for simultaneous chemical exchange of parahydrogen and nitrile-containing anticancer drugs (letrozole or anastrozole) to enhance N polarization. Distinct substrates require unique optimal parameter sets, including temperature, magnetic field, or a shaped magnetic field profile. The fine tuning of these parameters for individual substrates is demonstrated here to maximize N polarization. After optimization, including the usage of pulsed μT fields, the N nuclei on common anticancer drugs, letrozole and anastrozole, can be polarized within 1-2 min. The hyperpolarization can exceed 10%, corresponding to N signal enhancement of over 280,000-fold at a clinically relevant magnetic field of 1 T. This sensitivity gain enables polarization studies at naturally abundant N enrichment level (0.4%). Moreover, the nitrile N sites enable long-lasting polarization storage with [N] over 9 min, enabling signal detection from a single hyperpolarization cycle for over 30 min.
极化方式克服了 NMR 的灵敏度限制，开辟了新的应用。可逆交换信号放大（SABRE）是一种特别廉价、快速和强大的极化方式。在这里，我们利用 SABRE 同时对氘化氢和含腈抗癌药物（来曲唑或阿那曲唑）进行化学交换，以增强 N 极化。不同的底物需要独特的最佳参数集，包括温度、磁场或形状磁场分布。在这里，我们演示了对各个底物的这些参数的微调，以最大化 N 极化。经过优化，包括使用脉冲 μT 场，可以在 1-2 分钟内对常见抗癌药物来曲唑和阿那曲唑上的 N 核进行极化。极化可以超过 10%，在临床相关的 1 T 磁场下，N 信号增强超过 280000 倍。这种灵敏度增益使得在自然丰度的 N 富集水平（0.4%）下进行极化研究成为可能。此外，腈基 N 位能够实现长时间的极化存储，[N]超过 9 分钟，从而能够在单个极化循环中进行超过 30 分钟的信号检测。
