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Glucocorticoids Modulate Tumor Radiation Response through a Decrease in Tumor Oxygen Consumption

Authors' Affiliations: Laboratories of ¹ Medicinal Chemistry and Radiopharmacy, ² Biomedical Magnetic Resonance, ³ Molecular Imaging and Experimental Radiotherapy, and ⁴ Pharmacology and Therapeutics, Université Catholique de Louvain, Brussels, Belgium

Requests for reprints: Bernard Gallez, CMFA/REMA, Avenue Mounier 73.40, B-1200 Brussels, Belgium. Phone: 32-2-764-7344; Fax: 32-2-764-7390; E-mail: Gallez{at}cmfa.ucl.ac.be.

Purpose: We hypothesized that glucocorticoids may enhance tumor radiosensitivity by increasing tumor oxygenation (pO₂) through inhibition of mitochondrial respiration.

Experimental Design: The effect of three glucocorticoids (hydrocortisone, dexamethasone, and prednisolone) on pO₂ was studied in murine TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO₂ (t_max, 30 min after administration), perfusion, oxygen consumption, and radiation sensitivity were studied. Local pO₂ measurements were done using electron paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo glucocorticoid administration was measured using high-frequency electron paramagnetic resonance. Tumor perfusion and permeability measurements were assessed by dynamic contrast-enhanced magnetic resonance imaging.

Results: All glucocorticoids tested caused a rapid increase in pO₂. At t_max, tumor perfusion decreased, indicating that the increase in pO₂ was not caused by an increase in oxygen supply. Also at t_max, global oxygen consumption decreased. When irradiation (25 Gy) was applied at t_max, the tumor radiosensitivity was enhanced (regrowth delay increased by a factor of 1.7).

Conclusion: These results show the potential usefulness of the administration of glucocorticoids before irradiation.

Commentary

Multiple Etiologies of Tumor Hypoxia Require Multifaceted Solutions

Mark W. Dewhirst, Isabel Cardenas Navia, David M. Brizel, Christopher Willett, and Timothy W. Secomb
Clin. Cancer Res. 2007 13: 375-377. [Full Text] [PDF]

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				M. W. Dewhirst, I. C. Navia, D. M. Brizel, C. Willett, and T. W. Secomb Multiple Etiologies of Tumor Hypoxia Require Multifaceted Solutions Clin. Cancer Res., January 15, 2007; 13(2): 375 - 377. [Full Text] [PDF]