Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multi-institutional research project.
BACKGROUND
Recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation.


METHODS
The present article will introduce a multi-institutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Würzburg, Germany.


RESULTS
The joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined.


CONCLUSIONS
Besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation.
Department of Radiotherapy and Radiation Oncology, Medical Faculty, University of Technology, Dresden, Germany.
Daniel
D
Zips
Markus
M
Adam
Michael
M
Flentje
Axel
A
Haase
Michael
M
Molls
Wolfgang
W
Mueller-Klieser
Cordula
C
Petersen
Christine
C
Philbrook
Peter
P
Schmitt
Oliver
O
Thews
Stefan
S
Walenta
Michael
M
Baumann
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015687:Cell Hypoxia; D006801:Humans; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010101:Oxygen Consumption; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins