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dc.contributor.authorVider, Jelenaen_US
dc.description.abstractTumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor and host tissue-specific processes. To study the dynamics and spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging of hypoxia-induced HIF-1 transcriptional activity in tumors in living mice. This approach uses a novel retroviral vector bearing a HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion) and a constitutively expressed "beacon" reporter gene (DsRed2/XPRT). C6 glioma cells transduced with this multireporter system revealed dose-dependent patterns in temporal dynamics of HIF-1 transcriptional activity induced by either CoCl2 or decreased atmospheric oxygen concentration. Multicellular spheroids of C6 reporter cells developed a hypoxic core when >350 microm in diameter. 18F-2'-fluoro-2'deoxy-1beta-D-arabionofuranosyl-5-ethyl-uracil (FEAU) PET revealed spatial heterogeneity of HIF-1 transcriptional activity in reporter xenografts in mice as a function of size or ischemia-reperfusion injury. With increasing tumor diameter (>3 mm), a marked increase in HIF-1 transcriptional activity was observed in the core regions of tumors. Even a moderate ischemia-reperfusion injury in small C6 tumors caused a rapid induction of HIF-1 transcriptional activity, which persisted for a long time because of the inability of C6 tumors to rapidly compensate acute changes in tumor microcirculation.en_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.publisher.placeUnited States of Americaen_US
dc.relation.ispartofjournalCancer Researchen_US
dc.subject.fieldofresearchCancer Cell Biologyen_US
dc.titleMolecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.en_US
dc.typeJournal article
dc.type.descriptionJournal Articles (Refereed Article)en_US
gro.facultyGriffith Health Facultyen_US
gro.hasfulltextNo Full Text

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