1: Cancer Res. 2006 Oct 1;66(19):9698-9704.

Mechanism of Reoxygenation after Antiangiogenic Therapy Using SU5416 and Its
Importance for Guiding Combined Antitumor Therapy.

Ansiaux R, Baudelet C, Jordan BF, Crokart N, Martinive P, Dewever J, Gregoire V,
Feron O, Gallez B.

Laboratory of Biomedical Magnetic Resonance, Laboratory of Medicinal Chemistry
and Radiopharmacy, Laboratory of Pharmacology and Therapeutics, and Laboratory
of Molecular Imaging and Experimental Radiotherapy, Universite Catholique de
Louvain, Brussels, Belgium.

Emerging preclinical studies support the concept of a transient "normalization"
of tumor vasculature during the early stage of antiangiogenic treatment, with
possible beneficial effects on associated radiotherapy or chemotherapy. One key
issue in this area of research is to determine whether this feature is common to
all antiangiogenic drugs and whether the phenomenon occurs in all types of
tumors. In the present study, we characterized the evolution of the tumor
oxygenation (in transplantable liver tumor and FSAII tumor models) after
administration of SU5416, an antagonist of the vascular endothelial growth
factor receptor. SU5416 induced an early increase in tumor oxygenation [measured
by electronic paramagnetic resonance (EPR)], which did not correlate with
remodeling of the tumor vasculature (assessed by CD31 labeling using
immunohistochemistry) or with tumor perfusion (measured by dynamic contrast
enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration
(measured by EPR) was responsible for this early reoxygenation. Consistent with
these unique findings in the tumor microenvironment, we found that SU5416
potentiated tumor response to radiotherapy but not to chemotherapy. In addition
to the fact that the characterization of the tumor oxygenation is essential to
enable correct application of combined therapies, our results show that the
long-term inhibition of oxygen consumption is a potential novel target in this
class of compounds. (Cancer Res 2006; 66(19): 9698-704).

PMID: 17018628 [PubMed - as supplied by publisher]

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