From the Departments of Neuroradiology (K.J.W., U.P., E.H.)
German Cancer Consortium Partner Site (K.J.W., J.P.S., O.B., U.P., E.H.), Frankfurt am Main/Mainz, Germany.
AJNR Am J Neuroradiol. 2020 Aug;41(8):1414-1422. doi: 10.3174/ajnr.A6633. Epub 2020 Jul 9.
Preclinical evidence points toward a metabolic reprogramming in () mutated tumor cells with down-regulation of the expression of genes that encode for glycolytic metabolism. We noninvasively investigated lactate and Cr concentrations, as well as intracellular pH using H/phosphorus 31 (P) MR spectroscopy in a cohort of patients with gliomas.
Thirty prospectively enrolled, mostly untreated patients with gliomas met the spectral quality criteria (World Health Organization II [ = 7], III [ = 16], IV [ = 7]; -mutant [ = 23]; wild-type [ = 7]; 1p/19q codeletion [ = 9]). MR imaging protocol included 3D P chemical shift imaging and H single-voxel spectroscopy (point-resolved spectroscopy sequence at TE = 30 ms and TE = 97 ms with optimized echo spacing for detection of 2-hydroxyglutarate) from the tumor area. Values for absolute metabolite concentrations were calculated (phantom replacement method). Intracellular pH was determined from P chemical shift imaging.
At TE = 97 ms, lactate peaks can be fitted with little impact of lipid/macromolecule contamination. We found a significant difference in lactate concentrations, lactate/Cr ratios, and intracellular pH when comparing tumor voxels of patients with -mutant with those of patients with wild-type gliomas, with reduced lactate levels and near-normal intracellular pH in patients with -mutant gliomas. We additionally found evidence for codependent effects of 1p/19q codeletion and mutations with regard to lactate concentrations for World Health Organization tumor grades II and III, with lower lactate levels in patients exhibiting the codeletion. There was no statistical significance when comparing lactate concentrations between mutant World Health Organization II and III gliomas.
We found indirect evidence for metabolic reprogramming in -mutant tumors with significantly lower lactate concentrations compared with wild-type tumors and a near-normal intracellular pH.
临床前证据表明，（）突变肿瘤细胞的代谢发生重编程，糖酵解代谢相关基因的表达下调。我们使用磷 31（P）磁共振波谱非侵入性地研究了一组脑胶质瘤患者的乳酸和 Cr 浓度以及细胞内 pH 值。
30 名符合纳入标准的脑胶质瘤患者（其中 7 名患者为世界卫生组织 2 级，16 名患者为 3 级，7 名患者为 4 级；23 名患者为 -突变型，7 名患者为 野生型，9 名患者存在 1p/19q 联合缺失）入组前瞻性研究，所有患者均未接受治疗。磁共振成像方案包括 3D P 化学位移成像和 H 单体波谱（点分辨波谱序列，TE = 30 ms 和 TE = 97 ms，优化回波间隔以检测 2-羟基戊二酸），采集肿瘤区域的信号。通过（采用水峰替代法）计算绝对代谢物浓度值。通过 P 化学位移成像测定细胞内 pH 值。
在 TE = 97 ms 时，乳酸峰可以进行拟合，几乎不受脂质/大分子污染的影响。我们发现，与 野生型胶质瘤患者相比，-突变型胶质瘤患者的肿瘤体素的乳酸浓度、乳酸/Cr 比值和细胞内 pH 值存在显著差异，-突变型胶质瘤患者的乳酸水平降低，细胞内 pH 值接近正常。我们还发现，1p/19q 联合缺失和 突变与肿瘤分级为 2 级和 3 级的患者的乳酸浓度存在依赖关系，存在联合缺失的患者乳酸水平更低。在比较 突变的 2 级和 3 级胶质瘤患者的乳酸浓度时，未发现统计学意义。
我们发现，与 野生型肿瘤相比，-突变肿瘤存在代谢重编程的间接证据，表现为乳酸浓度显著降低，细胞内 pH 值接近正常。
