Back to Search
Start Over
Longitudinal and multimodal in vivo imaging of tumor hypoxia and its downstream molecular events.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2009 Aug 18; Vol. 106 (33), pp. 14004-9. Date of Electronic Publication: 2009 Jul 31. - Publication Year :
- 2009
-
Abstract
- Tumor hypoxia and the hypoxia-inducible factors (HIFs) play a central role in the development of cancer. To study the relationship between tumor growth, tumor hypoxia, the stabilization of HIF-1alpha, and HIF transcriptional activity, we have established an in vivo imaging tool that allows longitudinal and noninvasive monitoring of these processes in a mouse C51 allograft tumor model. We used positron emission tomography (PET) with the hypoxia-sensitive tracer [(18)F]-fluoromisonidazole (FMISO) to measure tumor hypoxia over 14 days. Stabilization of HIF-1alpha and HIF transcriptional activity were assessed by bioluminescence imaging using the reporter constructs HIF-1alpha-luciferase and hypoxia response element-luciferase, respectively, stably expressed in C51 cells. Interestingly, we did not observe any major change in the level of tumor hypoxia throughout the observation period whereas HIF-1alpha levels and HIF activity showed drastic temporal variations. When comparing the readouts as a function of time we found a good correlation between HIF-1alpha levels and HIF activity. In contrast, there was no significant correlation between the [(18)F]-FMISO PET and HIF readouts. The tool developed in this work allows for the longitudinal study of tumor hypoxia and HIF-1alpha in cancer in an individual animal and will be of value when monitoring the efficacy of therapeutical interventions targeting the HIF pathway.
- Subjects :
- Animals
Cell Line, Tumor
Disease Models, Animal
Humans
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Luciferases metabolism
Mice
Misonidazole analogs & derivatives
Misonidazole pharmacology
Models, Biological
Neoplasm Transplantation
Positron-Emission Tomography methods
Response Elements
Time Factors
Transcription, Genetic
Hypoxia
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 106
- Issue :
- 33
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 19666490
- Full Text :
- https://doi.org/10.1073/pnas.0901194106