Impact of Mouse Strain and Sex when Modeling Radiation Necrosis

Abstract

Background: Murine models are among the most common type of preclinical animal models used to study the human condition, but a wide selection of different mice is currently in use with these differences potentially compromising study results and impairing the ability to reconcile interstudy results. Our goal was to determine how the train and sex of the mice selection would affect the development of radiation necrosis in our murine model of radiation-induced cerebral necrosis. Methods: We generated this model by using a preclinical irradiator to irradiate a sub-hemispheric portion of the brain of mice with single-fraction doses of 80 Gy. Eight possible combinations of mice made up of two different with two substrains each(BALB/cN, BALB/cJ, C57BL/6N, and C57BL/6J) and both sexes were irradiated in this study. Radiation necrosis development was tracked up to eight weeks with a 7T Bruker MRI utilizing T2-weighted and post-contrast T1-weighted imaging. MRI results were compared to and validated with the use of histology which utilized a scale from 0-3 in ascending order of damage. Results: Both time post-irradiation and strain (BALB/c vs C57BL/6) were significant factors affecting radiation necrosis development. Sex was in general not a statistically significant parameter in terms of radiation necrosis development. Conclusion: Mouse strain thus need to be considered when evaluating the results of necrosis models. However, sex does not appear to be a variable needing major consideration.

Three discipline collaborative radiation therapy (3DCRT) special debate: FLASH radiotherapy needs ongoing basic and animal research before implementing it to a large clinical scale

“…Specifically, in the context of radiobiological preclinical studies, radiation responses are highly dependent on the choice and source of cell lines, the choice of animal species and often the specific animal strain within the species, and the immune status of the animal model. 44,45 We believe therefore, that we are now at a point where additional exploratory preclinical research is going to be inefficient (in our opponents' own estimate, it will take "a generation"!) compared to targeted preclinical studies that are more directly informed by clinical insights.…”

“…Furthermore, despite impressive advances such as organoid models and patient‐derived xenografts, these preclinical systems, especially small‐animal preclinical systems (where the vast majority of preclinical FLASH research is being performed), can still only offer a limited recapitulation of a human patient. Specifically, in the context of radiobiological preclinical studies, radiation responses are highly dependent on the choice and source of cell lines, the choice of animal species and often the specific animal strain within the species, and the immune status of the animal model 44,45 . We believe therefore, that we are now at a point where additional exploratory preclinical research is going to be inefficient (in our opponents’ own estimate, it will take “a generation”!)…”