Department of Medical Biophysics, Western University, London, ON, Canada.
General Electric Healthcare, Toronto, ON, Canada.
Tomography. 2020 Sep;6(3):290-300. doi: 10.18383/j.tom.2020.00024.
This study shows the use of hyperpolarized C magnetic resonance spectroscopic imaging (MRSI) to assess therapeutic efficacy in a preclinical tumor model. C-labeled pyruvate was used to monitor early changes in tumor metabolism based on the Warburg effect. High-grade malignant tumors exhibit increased glycolytic activity and lactate production to promote proliferation. A rodent glioma model was used to explore altered lactate production after therapy as an early imaging biomarker for therapeutic response. Rodents were surgically implanted with C6 glioma cells and separated into 4 groups, namely, no therapy, radiotherapy, chemotherapy and combined therapy. Animals were imaged serially at 6 different time points with magnetic resonance imaging at 3 T using hyperpolarized [1-C]pyruvate MRSI and conventional H imaging. Using hyperpolarized [1-C]pyruvate MRSI, alterations in tumor metabolism were detected as changes in the conversion of lactate to pyruvate (measured as Lac/Pyr ratio) and compared with the conventional method of detecting therapeutic response using the Response Evaluation Criteria in Solid Tumors. Moreover, each therapy group expressed different characteristic changes in tumor metabolism. The group that received no therapy showed a gradual increase of Lac/Pyr ratio within the tumor. The radiotherapy group showed large variations in tumor Lac/Pyr ratio. The chemo- and combined-therapy groups showed a statistically significant reduction in tumor Lac/Pyr ratio; however, only combined therapy was capable of suppressing tumor growth, which resulted in low endpoint mortality rate. Hyperpolarized C MRSI detected a prompt reduction in Lac/Pyr ratio as early as 2 days post combined chemo- and radiotherapies.
本研究展示了利用超极化 13C 磁共振波谱成像（MRSI）评估临床前肿瘤模型的治疗效果。 13C 标记的丙酮酸用于根据沃伯格效应监测肿瘤代谢的早期变化。高级恶性肿瘤表现出增加的糖酵解活性和乳酸产生，以促进增殖。使用啮齿动物神经胶质瘤模型来探索治疗后乳酸产生的改变，作为治疗反应的早期成像生物标志物。将 C6 神经胶质瘤细胞手术植入啮齿动物体内，并将其分为 4 组，即无治疗、放疗、化疗和联合治疗。使用 3T 磁共振成像对动物进行连续成像，使用超极化 [1-C]丙酮酸 MRSI 和常规 H 成像。使用超极化 [1-C]丙酮酸 MRSI，可以检测肿瘤代谢的变化，表现为乳酸向丙酮酸的转化率变化（以 Lac/Pyr 比值表示），并与使用实体瘤反应评估标准检测治疗反应的常规方法进行比较。此外，每种治疗组的肿瘤代谢都表现出不同的特征变化。未接受治疗的组显示肿瘤内 Lac/Pyr 比值逐渐增加。放疗组的肿瘤 Lac/Pyr 比值变化较大。化疗和联合治疗组的肿瘤 Lac/Pyr 比值均有统计学显著降低；然而，只有联合治疗能够抑制肿瘤生长，从而导致低终点死亡率。超极化 13C MRSI 在联合化疗和放疗后仅 2 天即可检测到 Lac/Pyr 比值的迅速降低。
