Goethe University Frankfurt, Institute of Neuroradiology, Schleusenweg 2-16 (Haus 95), 60528 Frankfurt/M, Germany.
Neuro Oncol. 2011 Dec;13(12):1349-63. doi: 10.1093/neuonc/nor132. Epub 2011 Sep 2.
Bevacizumab shows unprecedented rates of response in recurrent glioblastomas (GBM), but the detailed mechanisms are still unclear. We employed in vivo magnetic resonance spectroscopic imaging (MRSI) and quantitative magnetic resonance imaging to investigate whether bevacizumab alters oxygen and energy metabolism and whether this effect has antitumoral activity in recurrent GBM. (31)P and (1)H MRSI, apparent diffusion coefficient (ADC), and high-resolution T2 and T2' mapping (indirect marker of oxygen extraction) were investigated in 16 patients with recurrent GBM at 3 Tesla before and 1.5-2 months after initiation of therapy with bevacizumab. Changes of metabolite concentrations and of the quantitative values in the tumor and normal appearing brain tissue were calculated. The Wilcoxon signed-ranks test was used to evaluate differences for tumor/edema versus control as well as changes before versus after commencement of therapy. Survival analyses were performed for significant parameters. Tumor T2', pH, ADC, and T2 decreased significantly in patients responding to bevacizumab therapy (n = 10). Patients with at least 25% T2' decrease during treatment showed longer progression-free and overall survival durations. Levels of high-energy metabolites were lower at baseline; these persisted under therapy. Glycerophosphoethanolamine as catabolic phospholipid metabolite increased in responders. The MRSI data support the hypothesis that bevacizumab induces relative tumor hypoxia (T2' decrease) and affects energy homeostasis in recurrent GBM, suggesting that bevacizumab impairs vascular function. The antiangiogenic effect of bevacizumab is predictive of better outcome and seems to induce antitumoral activity in the responding GBMs.
贝伐单抗在复发性脑胶质瘤（GBM）中显示出前所未有的反应率，但详细机制仍不清楚。我们采用体内磁共振波谱成像（MRSI）和定量磁共振成像来研究贝伐单抗是否改变氧和能量代谢，以及这种效应在复发性 GBM 中是否具有抗肿瘤活性。在 3T 磁共振扫描仪上，对 16 例复发性 GBM 患者进行了（31）P 和（1）H MRSI、表观扩散系数（ADC）以及高分辨率 T2 和 T2' 图谱（氧提取的间接标志物）检测，在开始贝伐单抗治疗前和治疗后 1.5-2 个月进行检测。计算肿瘤和正常脑组织中代谢物浓度和定量值的变化。采用 Wilcoxon 符号秩检验评估肿瘤/水肿与对照以及治疗前与治疗后之间的差异。对有意义的参数进行生存分析。对贝伐单抗治疗有反应的患者（n=10），肿瘤 T2'、pH、ADC 和 T2 显著降低。在治疗过程中 T2' 至少降低 25%的患者，无进展生存期和总生存期更长。基线时高能代谢物水平较低；这些在治疗过程中持续存在。作为分解代谢磷脂代谢产物的甘油磷酸乙醇胺在应答者中增加。MRSI 数据支持贝伐单抗诱导相对肿瘤缺氧（T2' 降低）并影响复发性 GBM 能量平衡的假设，表明贝伐单抗损害血管功能。贝伐单抗的抗血管生成作用是预后良好的预测指标，并且似乎在应答性 GBM 中诱导抗肿瘤活性。
