Department of Neurosurgery, University of Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Germany.
Institute of Medical Radiology, University Clinic of St. Pölten, Dunant-Platz 1, 3100, St. Pölten, Austria.
Mol Imaging Biol. 2019 Aug;21(4):747-757. doi: 10.1007/s11307-018-1289-5.
Glioblastoma (GB) is one of the most vascularized of all solid tumors and, therefore, represents an attractive target for antiangiogenic therapies. Many lesions, however, quickly develop escape mechanisms associated with changes in the tumor microenvironment (TME) resulting in rapid treatment failure. To prevent patients from adverse effects of ineffective therapy, there is a strong need to better predict and monitor antiangiogenic treatment response.
We utilized a novel physiological magnetic resonance imaging (MRI) method combining the visualization of oxygen metabolism and neovascularization for classification of five different TME compartments: necrosis, hypoxia with/without neovascularization, oxidative phosphorylation, and aerobic glycolysis. This approach, termed TME mapping, was used to monitor changes in tumor biology and pathophysiology within the TME in response to bevacizumab treatment in 18 patients with recurrent GB.
We detected dramatic changes in the TME by rearrangement of its compartments after the onset of bevacizumab treatment. All patients showed a decrease in active tumor volume and neovascularization as well as an increase in hypoxia and necrosis in the first follow-up after 3 months. We found that recurrent GB with a high percentage of neovascularization and active tumor before bevacizumab onset showed a poor or no treatment response.
TME mapping might be useful to develop strategies for patient stratification and response prediction before bevacizumab onset.
胶质母细胞瘤（GB）是所有实体肿瘤中血管化程度最高的肿瘤之一，因此成为抗血管生成治疗的理想靶点。然而，许多病变很快就会产生与肿瘤微环境（TME）变化相关的逃逸机制，导致治疗迅速失败。为了防止患者因无效治疗而产生不良反应，强烈需要更好地预测和监测抗血管生成治疗的反应。
我们利用一种新的生理磁共振成像（MRI）方法，结合氧代谢和新生血管的可视化，将五个不同的 TME 隔室分类：坏死、缺氧伴/不伴新生血管形成、氧化磷酸化和有氧糖酵解。这种方法称为 TME 绘图，用于监测 18 例复发性 GB 患者接受贝伐单抗治疗后 TME 内肿瘤生物学和病理生理学的变化。
我们通过贝伐单抗治疗开始后 TME 隔室的重新排列检测到 TME 的剧烈变化。所有患者在 3 个月后的第一次随访中均显示出活跃肿瘤体积和新生血管减少，以及缺氧和坏死增加。我们发现，在贝伐单抗开始前具有高比例新生血管形成和活跃肿瘤的复发性 GB 患者的治疗反应较差或无反应。
TME 绘图可能有助于在贝伐单抗开始前制定患者分层和反应预测的策略。
