Ultra-high dose rate (FLASH) radiation therapy (RT) represents a revolutionary approach with the potential to transform radiation treatment outcomes. This paradigm-shifting approach involves delivering radiation at an ultra-high dose rate (>40 Gy/s), significantly surpassing conventional (CONV) RT dose rates. Preclinical studies have shown that FLASH RT enhances the therapeutic index by reducing damage to normal tissues while maintaining tumor treatment response, a phenomenon termed the FLASH effect. One hypothesis for the FLASH effect is a differential DNA damage and repair response. To test this hypothesis, we utilize γ-H2AX as a biomarker for DNA double-strand breaks (DSBs) and leverage super-resolution microscopy to quantify the number, size, and spatial distribution of DSBs at multiple time points following 4 Gy irradiation delivered at FLASH or CONV dose rates. We perform cluster analysis to assess DSB foci and γ-H2AX nano-foci characteristics, where super-resolution microscopy provides higher resolution than traditional confocal microscopy and more accurate quantification of the data at early time points. By leveraging super-resolution microscopy, this project aims to provide a molecular understanding of the FLASH effect, with the goal of improving RT outcomes in cancer treatment.
Gatica-Gutierrez et al. (Sun,) studied this question.