Hyperpolarized 13C spectroscopic imaging informs on hypoxia-inducible factor-1 and myc activity downstream of platelet-derived growth factor receptor.
Hyperpolarized 13C spectroscopic imaging informs on hypoxia-inducible factor-1 and myc activity downstream of platelet-derived growth factor receptor.
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DOI：
10.1158/0008-5472.can-10-0883
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发表时间：
2010-10-01
期刊：
影响因子：
11.2
通讯作者：
Ronen SM
中科院分区：
文献类型：
--
作者：
Dafni H;Larson PE;Hu S;Yoshihara HA;Ward CS;Venkatesh HS;Wang C;Zhang X;Vigneron DB;Ronen SM
超极化 13C 磁共振波谱成像 (MRSI) 的最新发展为体内代谢成像提供了一种新方法，具有检测癌症和治疗反应的潜在应用。由于乳酸脱氢酶 (LDH) 的辅酶 NADH 的消耗，化疗诱导的细胞凋亡会减少超极化 13C 标记从丙酮酸到乳酸的通量。相比之下，我们在此表明，在 PC-3MM2 肿瘤中，用伊马替尼抑制血小板衍生生长因子受体，通过降低 LDH 本身的表达来减少超极化丙酮酸向乳酸的转化。这伴随着血管内皮生长因子和谷氨酰胺酶表达的减少，并且可能是由它们的转录因子缺氧诱导因子-1和c-Myc的表达减少介导的。我们的结果表明，超极化 13C MRSI 可以潜在地检测各种细胞信号抑制剂的分子效应，从而提供一种无辐射的方法来预测肿瘤反应。
The recent development of hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) provides a novel method for in-vivo metabolic imaging with potential applications for detection of cancer and response to treatment. Chemotherapy-induced apoptosis was shown to decrease the flux of hyperpolarized 13C-label from pyruvate to lactate due to depletion of NADH, the coenzyme of lactate dehydrogenase (LDH). In contrast, we show here that in PC-3MM2 tumors, inhibition of platelet-derived growth factor receptor with imatinib reduces the conversion of hyperpolarized pyruvate to lactate by lowering the expression of LDH itself. This was accompanied by reduced expression of vascular endothelial growth factor and glutaminase, and is likely mediated by reduced expression of their transcriptional factors hypoxia-inducible factor-1 and c-Myc. Our results indicate that hyperpolarized 13C MRSI could potentially detect the molecular effect of various cell-signaling inhibitors, thus providing a radiation-free method to predict tumor response.