Purpose
To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons, and carbon ions.
Methods
This study presents measurements of the oxygen consumption in sealed, 3D‐printed water phantoms during irradiation with x‐rays, protons, and carbon ions at varying dose rates up to 340 Gy/s. The oxygen measurement was performed using an optical sensor allowing for noninvasive measurements.
Results
Oxygen consumption in water only depends on dose, dose rate, and linear energy transfer (LET) of the irradiation. The total amount of oxygen depleted per 10 Gy was found to be 0.04% atm ‐ 0.18% atm for 225 kV photons, 0.04% atm ‐ 0.25% atm for 224 MeV protons, and 0.09% atm ‐ 0.17% atm for carbon ions. Consumption depends on dose rate by an inverse power law and saturates for higher dose rates because of self‐interactions of radicals. Higher dose rates yield lower oxygen consumption. No total depletion of oxygen was found for clinical doses.
Conclusions
FLASH irradiation does consume oxygen, but not enough to deplete all the oxygen present. For higher dose rates, less oxygen was consumed than at standard radiotherapy dose rates. No total depletion was found for any of the analyzed radiation types for 10 Gy dose delivery using FLASH.
Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.
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