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Preclinical model of stereotactic ablative lung irradiation using arc delivery in the mouse:fractionation effect
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Edité par CCSD ; Frontiers media -
International audience. Purpose: pre-clinical modelling of radiation-induced lung damage is being challenged by emerging radiation therapies, such as stereotactic body radiation therapy. The aim of the present study was to implement previously published data on focal lung irradiation in mice using different fractionation schedules, with the objective of developing lung fibrosis in a time lapse that is compatible with the lifespan of a rodent.Methods and materials: the left lungs of C57BL/6JRj mice were exposed to ionizing radiation using arc therapy and 3 x 3 mm beam collimation. Three-fraction schedules delivered in 1 week were used with 20, 28, 40 and 50 Gy doses per fraction. Lung tissue opacification, global histological damage and the numbers of type II pneumocytes and club cells were assessed 6 months post-exposure, together with the gene expression of several lung cells and inflammation markers.Results: administration of 3 x 40 or 3 x 50 Gy generated focal lung fibrosis after 6 months, with tissue opacification visible by cone beam computed tomography, tissue scarring and consolidation, decreased club cell numbers and a reactive increase in the number of type II pneumocytes.Conclusions: a fractionation schedule using an arc-therapy-delivered 3 fraction/1 week regimen with 3 x 3 mm beam collimation was complex but feasible, with satisfying image-guided animal repositioning. Such a schedule generates focal lung fibrosis within 6 months when using 40 or 50 Gy per fraction. A comparison with previously published laboratory data suggests that, in this focal lung irradiation configuration, administrating a Biological Effective Dose ≥ 1000 Gy should be recommended to obtain lung fibrosis within 6 months.
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