=====Tumor hipoxia===== Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy. IV injections of [[perfluorocarbon]] (PFC) emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors ((Feldman LA, Fabre MS, Grasso C, Reid D, Broaddus WC, Lanza GM, Spiess BD, Garbow JR, McConnell MJ, Herst PM. Perfluorocarbon emulsions radiosensitise brain tumors in carbogen breathing mice with orthotopic GL261 gliomas. PLoS One. 2017 Sep 5;12(9):e0184250. doi: 10.1371/journal.pone.0184250. eCollection 2017. PubMed PMID: 28873460. )). ===== Hypoxia in glioma ===== Hypoxia plays an important role in the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet [[Glioma]]s develop within a mechanically challenged microenvironment that is characterized by a dense [[extracellular matrix]] (ECM) that compromises vascular integrity to induce [[hypoxia]] and activate [[HIF1A]]. Hypoxia is a key driver for infiltrative growth in experimental [[glioma]]s. ===== Hypoxia in glioblastoma ===== The [[microenvironment]] of [[hypoxia]] is an important factor contributing to the development of glioblastoma (GBM) It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. Thiepold et al in a study reveal an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients ((Thiepold AL, Luger S, Wagner M, Filmann N, Ronellenfitsch MW, Harter PN, Braczynski AK, Dützmann S, Hattingen E, Steinbach JP, Senft C, Rieger J, Bähr O. Perioperative cerebral ischemia promote infiltrative recurrence in glioblastoma. Oncotarget. 2015 May 4. [Epub ahead of print] PubMed PMID: 25966341. )). During the last decade, experimental evidence has demonstrated the important role of hypoxia, which leads to neuronal cell death and angiogenesis, in the mechanisms of seizure precipitation and recurrence. [[Macrophage]] infiltration is associated with [[glioblastoma]] GBM invasion, but the mechanisms remain unclear. Hypoxia microenvironment modulates the biological behaviors of both tumor cells and infiltrating immune cells, including macrophages. In a study, Wang et al., analyzed the effects of hypoxia and [[macrophage]]s on the invasion of GBM cells and its potential mechanisms. They found that both hypoxia and macrophage supernatant promoted GBM cells invasion and matrix metalloproteinase (MMP)-9 expression, and hypoxia modulated the invasive activity of GBM cells by upregulating their [[CCR5]] expression. The supernatant of hypoxic macrophages also showed a greater pro-invasion effect than normoxic macrophages through the elevated secretion of CCL4. Moreover, they found that interferon regulatory factor-8 (IRF-8) was possibly involved in the hypoxia-modulated CCL4 expression of macrophages. Taken together, the present study found that macrophages promoted GBM invasion by the CCL4-CCR5 axis, and hypoxia enhanced the interaction between these two types of cells by upregulating both CCL4 and CCR5 expression, respectively. The results of the present study suggested that hypoxia would be a potential target for the development of immune therapies of GBM ((Wang Y, Liu T, Yang N, Xu S, Li X, Wang D. Hypoxia and macrophages promote glioblastoma invasion by the CCL4-CCR5 axis. Oncol Rep. 2016 Oct 13. doi: 10.3892/or.2016.5171. PubMed PMID: 27748906. )). ---- FMISO or [[fluoromisonidazole]] is used as a [[PET]] [[radiotracer]] for imaging [[hypoxia]] when labeled with [[fluorine 18]] see [[18F fluoromisonidazole positron emission tomography]]