Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 37, Issue 7, Pages 2584-2597Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X16671965
Keywords
Hypoxia; oxygenation; glioblastoma; magnetic resonance imaging; positron emission tomography; rat
Categories
Funding
- Centre National de la Recherche Scientifique (CNRS)
- Universite de Caen-Normandie (UCN)
- Conseil Regional de Basse-Normandie (CRBN)
- Elen Fund
- European Union-Fonds de Developpement Regional (FEDER)
- l'Europe s'engage en Basse-Normandie
- French National Agency for Research (ANR IMOXY) ['ANR-11-BSV5-004']
- French National Agency for Research ('Investissements d'Avenir') [ANR-11-LABEX-0018-01]
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The partial pressure in oxygen remains challenging to map in the brain. Two main strategies exist to obtain surrogate measures of tissue oxygenation: the tissue saturation studied by magnetic resonance imaging (StO2-MRI) and the identification of hypoxia by a positron emission tomography (PET) biomarker with 3-[F-18]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([F-18]-FMISO) as the leading radiopharmaceutical. Nonetheless, a formal validation of StO2-MRI against FMISO-PET has not been performed. The objective of our studies was to compare the two approaches in (a) the normal rat brain when the rats were submitted to hypoxemia; (b) animals implanted with four tumour types differentiated by their oxygenation. Rats were submitted to normoxic and hypoxemic conditions. For the brain tumour experiments, U87-MG, U251-MG, 9L and C6 glioma cells were orthotopically inoculated in rats. For both experiments, StO2-MRI and [F-18]-FMISO PET were performed sequentially. Under hypoxemia conditions, StO2-MRI revealed a decrease in oxygen saturation in the brain. Nonetheless, [F-18]-FMISO PET, pimonidazole immunohistochemistry and molecular biology were insensitive to hypoxia. Within the context of tumours, StO2-MRI was able to detect hypoxia in the hypoxic models, mimicking [F-18]-FMISO PET with high sensitivity/specificity. Altogether, our data clearly support that, in brain pathologies, StO2-MRI could be a robust and specific imaging biomarker to assess hypoxia.
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