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Lung stereotactic arc therapy in mice: development of radiation pneumopathy and influence of HIF-1α endothelial deletion.

PURPOSE: Stereotactic body radiation therapy (SBRT) offers good lung local tumor control by the administration of a high dose per fraction in small volumes. SBRT preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional HIF-1α deletion in the endothelium on radiation-induced tissue damage.

METHODS AND MATERIALS: The Small Animal Radiation Research Platform (SARRP) was used to create a mouse model of focal irradiation of the lung using arc therapy. HIF-1α conditional deletion was obtained by crossing mice expressing Cre Recombinase under the endothelial promoter VE-cadherin (VECad-Cre+/+ mice (1)) with HIF-1α floxed mice.

RESULTS: Lung stereotactic arc-therapy allows thoracic wall sparing and long-term studies. However, isodose curves showed that neighboring organs received significant doses of radiation, as revealed by ipsilateral lung acute red hepatization and major gene expression level modifications. Conditional HIF-1α deletion reduced acute lung edema and tended to diminish neutrophil infiltrate, but had no impact on long-term global tissue damage.

CONCLUSIONS: Arc therapy for focal high-dose irradiation of mouse lung is an efficient model for long-term studies. However, it is possible that irradiation may have a strong impact on the structure and function of neighboring organs which have to be taken into account. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule.

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