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Lung Stereotactic Arc Therapy in Mice Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion

Abstract : Purpose Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy 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 hypoxia-inducible factor 1α (HIF-1α) deletion in the endothelium on radiation-induced tissue damage. Methods and Materials The Small Animal Radiation Research Platform 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) 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 it 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, irradiation may have a strong impact on the structure and function of neighboring organs, which must be considered. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule. © 2019
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Submitted on : Monday, February 24, 2020 - 5:41:14 PM
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J. Lavigne, A. Suissa, N. Verger, M. dos Santos, M. Benadjaoud, et al.. Lung Stereotactic Arc Therapy in Mice Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion. International Journal of Radiation Oncology, Biology, Physics, Elsevier, 2019, 104 (2), pp.279-290. ⟨10.1016/j.ijrobp.2019.01.081⟩. ⟨hal-02489958⟩



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