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

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

Author information

1
Normandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
2
Department of Neurosurgery, University Hospital of Caen, Caen, France.
3
Department of Neuroradiology, University Hospital of Caen, Caen, France.
4
Normandie University, UNICAEN, INSERM, Inserm UMR-S U919, Caen, France.
5
Normandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France jeansebastien.GUILLAMO@chu-nimes.fr.
6
Department of Neurology, University Hospital of Caen, Caen, France; and.
7
Department of Neurology, University Hospital of Nimes, Nimes, France.

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. 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.

KEYWORDS:

18F-FMISO PET; MRI; angiogenesis; glioblastoma; hypoxia

PMID:
28596159
DOI:
10.2967/jnumed.116.188557
[Indexed for MEDLINE]
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