Hyperpolarized 13C MR imaging detects no lactate production in mutant IDH1 gliomas: Implications for diagnosis and response monitoring
Hyperpolarized 13C MR imaging detects no lactate production in mutant IDH1 gliomas: Implications for diagnosis and response monitoring
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DOI：
10.1016/j.nicl.2016.06.018
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发表时间：
2016-01-01
影响因子：
4.2
通讯作者：
Ronen, Sabrina M.
中科院分区：
文献类型：
--
作者：
Chaumeil, Myriam M.;Radoul, Marina;Ronen, Sabrina M.
使用超极化[1-C-13]丙酮酸盐的C-13磁共振光谱（MRS）进行脑肿瘤的代谢成像是一种有前途的神经成像策略，在胶质母细胞瘤（GBM）模型中取得了十年的临床前成功后，目前正在多个中心进行临床试验。通常，GBM的存在与[1-C-13]丙酮酸盐产生的超极化[1-C-13]乳酸盐升高相关，对治疗的反应与超极化[1-C-13]乳酸盐下降相关。然而，迄今为止，尚未使用这种方法研究低级别胶质瘤。低级别胶质瘤中最常见的突变是异柠檬酸脱氢酶1（IDH 1）突变，除了启动肿瘤发展外，还诱导代谢重编程。特别是，突变IDH 1神经胶质瘤与低水平的乳酸脱氢酶A（LDHA）和单羧酸转运蛋白1和4（MCT 1，MCT 4），三种蛋白参与丙酮酸代谢为乳酸。因此，我们研究了超极化[1-C-13]丙酮酸的13 C MRS检测突变IDH 1胶质瘤和监测其治疗反应的潜力。我们研究了低表达LDHA、MCT 1和MCT 4的患者来源的突变IDH 1胶质瘤细胞，以及高水平表达这些蛋白的野生型IDH 1 GBM细胞。与GBM相比，突变IDH 1细胞和肿瘤产生的超极化[1-C-13]乳酸显著更少，这与它们的代谢重编程一致。此外，超极化[1-C-13]乳酸的产生不受替莫唑胺（TMZ）的化疗治疗突变IDH 1肿瘤，在GBM与以前的报告相反。我们的研究结果表明突变IDH 1胶质瘤的不寻常的代谢成像特征，当与其他临床可用的成像方法相结合时，可以用于检测体内IDH 1突变的存在。(C)2016年6月，作者。爱思唯尔公司出版
Metabolic imaging of brain tumors using C-13 Magnetic Resonance Spectroscopy (MRS) of hyperpolarized [1-C-13] pyruvate is a promising neuroimaging strategy which, after a decade of preclinical success in glioblastoma (GBM) models, is now entering clinical trials in multiple centers. Typically, the presence of GBM has been associated with elevated hyperpolarized [1-C-13] lactate produced from [1-C-13] pyruvate, and response to therapy has been associated with a drop in hyperpolarized [1-C-13] lactate. However, to date, lower grade gliomas had not been investigated using this approach. The most prevalent mutation in lower grade gliomas is the isocitrate dehydrogenase 1 (IDH1) mutation, which, in addition to initiating tumor development, also induces metabolic reprogramming. In particular, mutant IDH1 gliomas are associated with low levels of lactate dehydrogenase A (LDHA) and mono-carboxylate transporters 1 and 4 (MCT1, MCT4), three proteins involved in pyruvate metabolism to lactate. We therefore investigated the potential of 13C MRS of hyperpolarized [1-C-13] pyruvate for detection of mutant IDH1 gliomas and for monitoring of their therapeutic response. We studied patient-derived mutant IDH1 glioma cells that underexpress LDHA, MCT1 and MCT4, and wild-type IDH1 GBM cells that express high levels of these proteins. Mutant IDH1 cells and tumors produced significantly less hyperpolarized [1-C-13] lactate compared to GBM, consistent with their metabolic reprogramming. Furthermore, hyperpolarized [1-C-13] lactate production was not affected by chemotherapeutic treatment with temozolomide (TMZ) in mutant IDH1 tumors, in contrast to previous reports in GBM. Our results demonstrate the unusual metabolic imaging profile of mutant IDH1 gliomas, which, when combined with other clinically available imaging methods, could be used to detect the presence of the IDH1 mutation in vivo. (C) 2016 The Authors. Published by Elsevier Inc.