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In Vivo Relationship Between Hypoxia and Angiogenesis in Human Glioblastoma: A Multimodal Imaging Study
The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2017-10-01 , DOI: 10.2967/jnumed.116.188557
Keven Ferreira da Ponte , David Hassanein Berro , Solène Collet , Jean-Marc Constans , Evelyne Emery , Samuel Valable , Jean-Sébastien Guillamo

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. This aggressiveness is in part attributed to the closely interrelated phenomena tumor hypoxia and angiogenesis, although few in vivo data exist in human brain tumors. This work aimed to study hypoxia and angiogenesis, in vivo and in situ, in patients admitted with GBM using multimodal imaging. Methods: Twenty-three GBM patients were assessed by 18F-fluoromisonidazole (18F-FMISO) PET and conventional and perfusion MRI before surgery. The level and location of hypoxia (18F-FMISO uptake, evaluated by tumor-to-blood [T/B] ratio), vascularization (cerebral blood volume [CBV]), and vascular permeability (contrast enhancement after gadolinium injection) were analyzed. The spatial relationship between tumor hypoxia and angiogenesis was assessed by an overlap analysis of the volume of 18F-FMISO uptake and the volumes of the high CBV regions and the contrast-enhancement regions. Results: A significant correlation was found between hypoxia and hypervascularization, especially for their maximum values (volume of maximal tumor hypoxia vs. relative CBV: r = 0.61, P = 0.002) and their volumes (hypoxia vs. hypervascularization: r = 0.91, P < 0.001). A large proportion of the high CBVs collocated with hypoxia (81.3%) and with contrast enhancement (46.5%). Conclusion: These results support the hypothesis of a tight association between hypoxia and angiogenesis. Our results suggest that there is insufficient tumor oxygenation in human GBM, despite increased tumor vascularization.



中文翻译:

缺氧与人类胶质母细胞瘤血管生成之间的体内关系:多模式成像研究。

多形胶质母细胞瘤(GBM)是最常见和侵略性的原发性脑肿瘤。这种侵略性部分归因于肿瘤缺氧和血管生成的密切相关现象,尽管人脑肿瘤中几乎没有体内数据。这项工作旨在通过多模态成像研究入院的GBM患者体内和原位的缺氧和血管生成。方法:23例GBM患者在手术前接受18 F-氟代咪唑(18 F-FMISO)PET以及常规和灌注MRI检查。缺氧的程度和位置(18分析了F-FMISO摄取量,通过肿瘤与血液[T / B]比率,血管化(脑血容量[CBV])和血管通透性(注射g后的造影剂增强)进行了评估。通过对18 F-FMISO摄取量与高CBV区和造影剂增强区的体积进行重叠分析,评估了肿瘤缺氧与血管生成之间的空间关系。结果:发现缺氧与血管过度之间存在显着相关性,尤其是它们的最大值(最大肿瘤缺氧量与相对CBV的关系:r = 0.61,P = 0.002)和它们的体积(缺氧与血管过度形成:r = 0.91,P<0.001)。大部分高CBV与缺氧(81.3%)和对比度增强(46.5%)并存。结论:这些结果支持了缺氧与血管生成之间紧密联系的假设。我们的结果表明,尽管肿瘤血管形成增加,但人GBM中的肿瘤氧合不足。

更新日期:2017-10-02
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