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人类脑胶质瘤中缺氧与血管生成的体内关系:一项多模态影像学研究。

In Vivo Relationship Between Hypoxia and Angiogenesis in Human Glioblastoma: A Multimodal Imaging Study.

机构信息

Normandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.

Department of Neurosurgery, University Hospital of Caen, Caen, France.

出版信息

J Nucl Med. 2017 Oct;58(10):1574-1579. doi: 10.2967/jnumed.116.188557. Epub 2017 Jun 8.

DOI:10.2967/jnumed.116.188557
PMID:28596159
Abstract

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. Twenty-three GBM patients were assessed by F-fluoromisonidazole (F-FMISO) PET and conventional and perfusion MRI before surgery. The level and location of hypoxia (F-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 F-FMISO uptake and the volumes of the high CBV regions and the contrast-enhancement regions. A significant correlation was found between hypoxia and hypervascularization, especially for their maximum values (volume of maximal tumor hypoxia vs. relative CBV: = 0.61, = 0.002) and their volumes (hypoxia vs. hypervascularization: = 0.91, < 0.001). A large proportion of the high CBVs collocated with hypoxia (81.3%) and with contrast enhancement (46.5%). 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.

摘要

多形性胶质母细胞瘤(GBM)是最常见和侵袭性最强的原发性脑肿瘤。这种侵袭性部分归因于肿瘤缺氧和血管生成这两种紧密相关的现象,尽管在人类脑肿瘤中很少有体内数据。本研究旨在使用多模态成像技术,在接受 GBM 治疗的患者中进行体内和原位研究缺氧和血管生成。23 名 GBM 患者在手术前接受 F-氟代米索硝唑(F-FMISO)PET 和常规及灌注 MRI 评估。通过肿瘤与血液(T/B)比值评估缺氧(F-FMISO 摄取)、血管生成(脑血容量 [CBV])和血管通透性(钆注射后对比增强)的水平和位置。通过重叠分析 F-FMISO 摄取量和高 CBV 区域以及对比增强区域的体积来评估肿瘤缺氧和血管生成之间的空间关系。发现缺氧与高血管生成之间存在显著相关性,特别是在它们的最大值(最大肿瘤缺氧体积与相对 CBV: = 0.61, = 0.002)和它们的体积(缺氧与高血管生成: = 0.91, < 0.001)方面。高 CBV 与缺氧(81.3%)和对比增强(46.5%)的大部分区域重叠。这些结果支持缺氧和血管生成之间紧密关联的假说。我们的研究结果表明,尽管肿瘤血管生成增加,但人类 GBM 中的肿瘤氧合仍然不足。

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