Dr. Senckenberg Institute of Neurooncology, Goethe-University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt, Germany.
J Neurooncol. 2010 Aug;99(1):49-56. doi: 10.1007/s11060-009-0098-8. Epub 2009 Dec 25.
Bevacizumab is an anti-vascular endothelial growth factor (VEGF) antibody with activity against recurrent malignant glioma inducing high rates of objective responses as assessed by magnetic resonance imaging (MRI). However, the mechanisms of the anti-tumor action of bevacizumab are controversial. In particular, it is unclear whether and when bevacizumab induces hypoxia in gliomas. Vascular normalization with hyperperfusion and enhanced oxygen delivery to the tumor has been suggested as an alternative mechanism. We analyzed diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in 18 consecutive patients with recurrent malignant glioma before and after exposure to bevacizumab. Stroke-like lesions with diffusion restriction on DWI and corresponding ADC decrease were induced by bevacizumab within the previously enhancing tumor area in 13 of 18 patients. These lesions were detectable as early as 4 weeks after initiation of therapy and were maintained for up to 80 weeks. In one patient, an ADC-decreased lesion was biopsied, and histology showed atypical necrosis and nuclear hypoxia-inducible factor 1alpha upregulation but no tumor recurrence. Normalized regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were analyzed in selected patients. Both parameters were decreased in responders with diffusion-restricted lesions. Within the tumor bed, bevacizumab induces diffusion-restricted lesions in the presence of reduced rCBF and rCBV. The cause of these alterations is unclear but may involve atypical necrosis and chronic hypoxia.
贝伐单抗是一种抗血管内皮生长因子（VEGF）的抗体，对复发性恶性胶质瘤有活性，可通过磁共振成像（MRI）评估达到高比例的客观缓解率。然而，贝伐单抗的抗肿瘤作用机制仍存在争议。特别是，贝伐单抗是否以及何时会导致胶质瘤缺氧仍不清楚。血管正常化伴高灌注和肿瘤供氧增加被认为是一种替代机制。我们分析了 18 例连续复发性恶性胶质瘤患者在接受贝伐单抗治疗前后的弥散加权成像（DWI）和表观弥散系数（ADC）图。在 18 例患者中的 13 例中，贝伐单抗在先前增强的肿瘤区域内诱导了具有弥散受限的中风样病变，在 DWI 上出现弥散受限，相应的 ADC 降低。这些病变早在治疗开始后 4 周即可检测到，并持续长达 80 周。在一名患者中，对一个 ADC 降低的病变进行了活检，组织学显示非典型坏死和核缺氧诱导因子 1α上调，但没有肿瘤复发。在选定的患者中分析了区域性脑血流（rCBF）和区域性脑血容量（rCBV）。在有弥散受限病变的反应者中，这两个参数均降低。在肿瘤床内，贝伐单抗在 rCBF 和 rCBV 降低的情况下诱导弥散受限病变。这些改变的原因尚不清楚，但可能涉及非典型坏死和慢性缺氧。
