Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors.
Evaluation of LDH-A and glutaminase inhibition in vivo by hyperpolarized 13C-pyruvate magnetic resonance spectroscopy of tumors.
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DOI：
10.1158/0008-5472.can-13-0465
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发表时间：
2013-07-15
期刊：
影响因子：
11.2
通讯作者：
Gillies RJ
中科院分区：
文献类型：
--
作者：
Dutta P;Le A;Vander Jagt DL;Tsukamoto T;Martinez GV;Dang CV;Gillies RJ
超极化13 C磁共振波谱（MRS）提供了一个独特的机会，以检测实时代谢通量作为一种手段来测量体内代谢治疗反应。在这里，我们表明，药理学抑制乳酸脱氢酶A抑制超极化13 C-丙酮酸转化为乳酸在小鼠异种移植的P493人淋巴瘤。相比之下，丙氨酸氨基转移酶抑制剂降低13 C-丙酮酸向丙氨酸的转化，而不影响丙酮酸向乳酸的转化。这些结果说明了监测生物标志物对抗代谢治疗反应的真实的时间的能力，为临床开发成像生物标志物以监测代谢药效学铺平了道路。
Hyperpolarized 13C magnetic resonance spectroscopy (MRS) provides a unique opportunity to detect real-time metabolic fluxes as a means to measure metabolic treatment responses in vivo. Here we show that pharmacological inhibition of lactate dehydrogenase A suppressed the conversion of hyperpolarized 13C-pyruvate to lactate in murine xenografts of P493 human lymphoma. In contrast, a glutaminase inhibitor reduced conversion of 13C-pyruvate to alanine without affecting conversion of pyruvate to lactate. These results illustrate the ability to monitor biomarkers for responses to anti-metabolic therapy in real time, paving the way for clinical development of imaging biomarkers to monitor metabolic pharmacodynamics.