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使用可回收全氟铱信号放大试剂通过可逆交换催化剂对小鼠中[1-C]丙酮酸的代谢感应的活体检测。

In vivo Metabolic Sensing of Hyperpolarized [1-C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst.

机构信息

Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, 9800 Medical Center Drive, Rockville, Maryland, 20850, United States.

Center for Cancer Research, National Cancer Institute, Bethesda, 10 Center Drive Maryland, 20814, United States.

出版信息

Angew Chem Int Ed Engl. 2024 Oct 21;63(43):e202407349. doi: 10.1002/anie.202407349. Epub 2024 Jul 29.

Abstract

Real-time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non-invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost-effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 1.2-fold increase in [1-C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy-metal-containing catalyst from the hyperpolarized [1-C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE-SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3-fold decrease in hyperpolarization potency. This proof-of-concept study encourages wider adoption of SABRE hyperpolarized [1-C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases.

摘要

实时可视化体内代谢过程为癌症和代谢紊乱等情况提供了关键的见解。代谢磁共振成像 (MRI) 通过超极化放大丙酮酸分子的信号,实现了代谢通量的非侵入性监测,有助于了解疾病进展和治疗反应。通过可逆交换进行信号放大 (SABRE) 提供了一种比溶解动态核极化更简单、更具成本效益的替代方案,消除了对昂贵设备和复杂程序的需求。我们首次在人类胰腺癌异种移植模型中进行了体内代谢感应的演示,并与健康小鼠进行了比较。一种新型全氟铱 SABRE 催化剂在氟化溶剂和甲醇混合物中的应用促成了这一突破,使 [1-C]丙酮酸 SABRE 超极化的信号增加了 1.2 倍。全氟部分允许轻松分离含有重金属的催化剂和超极化的 [1-C]丙酮酸靶标。全氟催化剂表现出可回收性,通过后续的超极化循环保持 SABRE-SHEATH 活性,在前两个循环后最小化活性损失。值得注意的是,该催化剂的活性至少保持了 10 个循环,超极化势降低了 3.3 倍。这项概念验证研究鼓励更广泛地采用 SABRE 超极化 [1-C]丙酮酸 MR 来研究体内代谢,有助于诊断癌症和其他疾病的阶段并监测治疗反应。

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