1: Int J Radiat Oncol Biol Phys. 2005 Nov 1;63(3):901-10. 

Early reoxygenation in tumors after irradiation: determining factors and
consequences for radiotherapy regimens using daily multiple fractions.

Crokart N, Jordan BF, Baudelet C, Ansiaux R, Sonveaux P, Gregoire V, Beghein N,
DeWever J, Bouzin C, Feron O, Gallez B.

Laboratory of Medicinal Chemistry and Radiopharmacy, Universite Catholique de
Louvain, Brussels, Belgium.

PURPOSE: To characterize changes in the tumor microenvironment early after
irradiation and determine the factors responsible for early reoxygenation.
METHODS AND MATERIALS: Fibrosarcoma type II (FSaII) and hepatocarcinoma
transplantable liver tumor tumor oxygenation were determined using electron
paramagnetic resonance oximetry and a fiberoptic device. Perfusion was assessed
by laser Doppler, dynamic contrast-enhanced MRI, and dye penetration. Oxygen
consumption was determined by electron paramagnetic resonance. The interstitial
fluid pressure was evaluated by the wick-in-needle technique. RESULTS: An
increase in oxygen partial pressure was observed 3-4 h after irradiation. This
increase resulted from a decrease in global oxygen consumption and an increase
in oxygen delivery. The increase in oxygen delivery was due to radiation-induced
acute inflammation (that was partially inhibited by the antiinflammatory agent
diclofenac) and to a decrease in interstitial fluid pressure. The endothelial
nitric oxide synthase pathway, identified as a contributing factor at 24 h after
irradiation, did not play a role in the early stage after irradiation. We also
observed that splitting a treatment of 18 Gy into two fractions separated by 4 h
(time of maximal reoxygenation) had a greater effect on tumor regrowth delay
than when applied as a single dose. CONCLUSION: Although the cell cycle
redistribution effect is important for treatment protocols using multiple daily
radiation fractions, the results of this work emphasize that the oxygen effect
must be also considered to optimize the treatment strategy.

PMID: 16199320 [PubMed - indexed for MEDLINE]