PMID- 15342393
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20181130
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 64
IP  - 17
DP  - 2004 Sep 1
TI  - Molecular imaging of temporal dynamics and spatial heterogeneity of 
      hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.
PG  - 6101-8
AB  - Tumor 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.
FAU - Serganova, Inna
AU  - Serganova I
AD  - Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New 
      York, USA.
FAU - Doubrovin, Michael
AU  - Doubrovin M
FAU - Vider, Jelena
AU  - Vider J
FAU - Ponomarev, Vladimir
AU  - Ponomarev V
FAU - Soghomonyan, Suren
AU  - Soghomonyan S
FAU - Beresten, Tatiana
AU  - Beresten T
FAU - Ageyeva, Ludmila
AU  - Ageyeva L
FAU - Serganov, Alexander
AU  - Serganov A
FAU - Cai, Shangde
AU  - Cai S
FAU - Balatoni, Julius
AU  - Balatoni J
FAU - Blasberg, Ronald
AU  - Blasberg R
FAU - Gelovani, Juri
AU  - Gelovani J
LA  - eng
GR  - CA57599/CA/NCI NIH HHS/United States
GR  - CA76117/CA/NCI NIH HHS/United States
GR  - CA83084/CA/NCI NIH HHS/United States
GR  - P50 CA86438/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Radiopharmaceuticals)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 3083-77-0 (Arabinofuranosyluracil)
RN  - 69123-94-0 (2'-fluoro-5-ethylarabinosyluracil)
RN  - EC 2.7.1.21 (Thymidine Kinase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Arabinofuranosyluracil/*analogs & derivatives
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Fluorine Radioisotopes
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter/*genetics
MH  - Genetic Vectors/genetics
MH  - Glioma/*genetics
MH  - Green Fluorescent Proteins
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Luminescent Proteins/biosynthesis/*genetics
MH  - Mice
MH  - Oxygen/metabolism
MH  - Radiopharmaceuticals
MH  - Rats
MH  - Recombinant Fusion Proteins/biosynthesis/*genetics
MH  - Retroviridae/genetics
MH  - Signal Transduction/genetics/physiology
MH  - Thymidine Kinase/biosynthesis/*genetics
MH  - Tomography, Emission-Computed
MH  - Transcription Factors/*genetics
MH  - Transcriptional Activation/*physiology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2004/09/03 05:00
MHDA- 2004/10/06 09:00
CRDT- 2004/09/03 05:00
PHST- 2004/09/03 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/09/03 05:00 [entrez]
AID - 64/17/6101 [pii]
AID - 10.1158/0008-5472.CAN-04-0842 [doi]
PST - ppublish
SO  - Cancer Res. 2004 Sep 1;64(17):6101-8. doi: 10.1158/0008-5472.CAN-04-0842.