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基于氘代氢可逆交换的 [1-¹³C]丙酮酸高极化活体代谢成像。

In Vivo Metabolic Imaging of [1- C]Pyruvate-d Hyperpolarized By Reversible Exchange With Parahydrogen.

机构信息

Division of Medical Physics, Department of Radiology, Medical Center, Faculty of Medicine, University of Freiburg, Killianstr. 5a, 79106, Freiburg, Germany.

German Cancer Consortium (DKTK), partner site Freiburg and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

出版信息

Angew Chem Int Ed Engl. 2023 Sep 4;62(36):e202306654. doi: 10.1002/anie.202306654. Epub 2023 Jul 25.

DOI:10.1002/anie.202306654
PMID:37439488
Abstract

Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non-invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra-fast and low-cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1- C]pyruvate-d for injection in 6 minutes. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1- C]pyruvate-d polarized to ≈11 % (residual 250 mM methanol and 20 μM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

摘要

利用(HP)吡咯烷酮进行代谢磁共振成像(MRI)正成为一种用于诊断、分期和监测癌症和其他疾病治疗反应的非侵入性技术。然而,临床上用于生产 HP 吡咯烷酮的方法——溶解动态核极化,相当复杂且缓慢。信号放大可逆交换(SABRE)是一种基于快速化学交换的超快、低成本方法。在这里,我们首次不仅展示了体内应用,还展示了 SABRE 的代谢 MRI。我们提出了一种新的常规方法,可在 6 分钟内生产用于注射的水相 HP [1- C]吡咯烷酮-d。注射溶液无菌、无毒、pH 值中性,含有 ≈30 mM [1- C]吡咯烷酮-d,极化度 ≈11 %(残留 250 mM 甲醇和 20 μM 催化剂)。它是通过快速溶剂蒸发和金属过滤获得的,我们在本文中详细介绍了该方法。这一成果使得 HP 吡咯烷酮 MRI 能够为广大生物医学领域提供快速的活体代谢成像。

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