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Link to our work on the arXiv: https://pubmed.ncbi.nlm.nih.gov/37352867/
This work has been published in the journal Physics in Medicine and Biology.
Recent numerous small animal studies (e.g. Friedl et al 2022) that observed normal tissue sparing under ultrahigh dose rate irradiation at greater than 40 Gy/s have ignited an immense interest in the radiotherapy community. The clinical translation of this ‘FLASH effect’ could potentially lead to a significant reduction of patient radiotoxicities associated with conventional dose rates. Against such a backdrop, modeling approaches that harness radiobiological principles to explain mechanisms driving this effect have also surfaced in recent literature. They range from models of processes of oxygen diffusion leading to transient oxygen reduction (Pratx and Kapp 2019), sparing of immune cells in models of radioimmune responses (Jin et al 2020), to studies of how ultra-high dose rates minimize induction of pro-inflammatory genes and persistent DNA damage (Favaudon et al 2014).
In a recent work that we presented in the 65th American Association of Physicists in Medicine Annual Meeting, we showed that upon solving a series of coupled differential equations that arose from chemical kinetics of radicals and other interacting biochemical molecules, the area-under-the-curve of harmful radicals correlated strongly with many biological endpoints (e.g. TGF-β1, leg contracture of the mice subjects, and plasma level of cytokine IL.-6.) of various FLASH experiments. Our work suggests strongly that the enhanced normal-tissue sparing of the FLASH effect is at least partially related to the resulting reduced exposure of tissues to harmful radicals. The figure on the right shows part of the web of biochemical pathways that underpin our mathematical model, with R being a generic carbon-based molecule, GSH: gluthathione, X: either lipid or DNA.
We hope that our paper inspires future works that will develop our understanding of how the chemical reaction dynamics of peroxyl and superoxide radicals potentially enacts an important and universal role in the FLASH effect, ultimately helping us to know how ultra-high dose rate radiotherapy can benefit patients!