Abstract Body

FLASH radiation therapy has been shown to reduce normal tissue side effects in multiple animal models. At the same time, other studies observed no or very limited sparing effects. This suggests that the onset of the FLASH tissue sparing effect depends on multiple parameters, including physics parameters such as average dose rate, instantaneous (per pulse) dose rate and dose, but also on the microenvironment, e.g. oxygen concentrations, and the tissue being irradiated. So far, the experimental results still paint a heterogeneous picture and the exact mechanisms why extremely high dose rates cause less tissue damage is still not fully understood.

I will discuss several of the models that have been proposed to explain the mechanisms of FLASH tissue sparing. Common aspects and potential interplay effects will be discussed, starting with track structure Monte Carlo simulations, resulting chemical reactions, effects of oxygen and other reactants, up to potential impacts of blood supply.

Background and Aims

There has been increasing evidence of the protective effect of ultra-high dose rate (FLASH) irradiation on different normal tissues recently. Here we intend to verify the FLASH effect of proton irradiation of the intestine, brain and skin.

Methods

For the partial abdominal irradiation, 6-8-week-old C57BL/6j mice and Rag1^-/-/C57 mice were exposed to FLASH (120-130 Gy/s) or conventional dose rate (CDR, ~0.4 Gy/s) proton irradiation of 16 Gy or 16.2 Gy.

For the brain irradiation, 10-12 weeks C57BL/6j mice received a single dose of 10 Gy whole brain irradiation. BrdU was injected to label the proliferating neural stem/progenitor cells in the hippocampus.

To study radiation-induced skin injury, Indian ink was injected intracutaneously into the skin of FVB/N mice the day before irradiation. The distance between the two ink dots was measured with a vernier caliper.

Results

Long-term observation (278 days) of the C57BL/6j mice after 16.2 Gy abdominal irradiation showed no significant survival difference between the FLASH and CDR groups (Figure A). The survival of Rag1^-/-/C57 mice in the 16 Gy FLASH group was lower than that of the 16 Gy CDR group (Figure B). No significant difference was observed in the number of the BrdU labeled cells within the subgranular zone of the hippocampus. Skin contraction after 25 and 27 Gy was significantly greater in mice receiving conventional irradiation compared to FLASH groups (Figure C).

Conclusions

Proton FLASH irradiation protection was observed in skin tissue. However, no significant FLASH sparing effect was observed for intestine and brain.

Abstract Body

FLASH radiation therapy has been shown to reduce normal tissue side effects in multiple animal models. At the same time, other studies observed no or very limited sparing effects. This suggests that the onset of the FLASH tissue sparing effect depends on multiple parameters, including physics parameters such as average dose rate, instantaneous (per pulse) dose rate and dose, but also on the microenvironment, e.g. oxygen concentrations, and the tissue being irradiated. So far, the experimental results still paint a heterogeneous picture and the exact mechanisms why extremely high dose rates cause less tissue damage is still not fully understood.

I will discuss several of the models that have been proposed to explain the mechanisms of FLASH tissue sparing. Common aspects and potential interplay effects will be discussed, starting with track structure Monte Carlo simulations, resulting chemical reactions, effects of oxygen and other reactants, up to potential impacts of blood supply.

Background and Aims

There has been increasing evidence of the protective effect of ultra-high dose rate (FLASH) irradiation on different normal tissues recently. Here we intend to verify the FLASH effect of proton irradiation of the intestine, brain and skin.

Methods

For the partial abdominal irradiation, 6-8-week-old C57BL/6j mice and Rag1^-/-/C57 mice were exposed to FLASH (120-130 Gy/s) or conventional dose rate (CDR, ~0.4 Gy/s) proton irradiation of 16 Gy or 16.2 Gy.

For the brain irradiation, 10-12 weeks C57BL/6j mice received a single dose of 10 Gy whole brain irradiation. BrdU was injected to label the proliferating neural stem/progenitor cells in the hippocampus.

To study radiation-induced skin injury, Indian ink was injected intracutaneously into the skin of FVB/N mice the day before irradiation. The distance between the two ink dots was measured with a vernier caliper.

Results

Long-term observation (278 days) of the C57BL/6j mice after 16.2 Gy abdominal irradiation showed no significant survival difference between the FLASH and CDR groups (Figure A). The survival of Rag1^-/-/C57 mice in the 16 Gy FLASH group was lower than that of the 16 Gy CDR group (Figure B). No significant difference was observed in the number of the BrdU labeled cells within the subgranular zone of the hippocampus. Skin contraction after 25 and 27 Gy was significantly greater in mice receiving conventional irradiation compared to FLASH groups (Figure C).

Conclusions

Proton FLASH irradiation protection was observed in skin tissue. However, no significant FLASH sparing effect was observed for intestine and brain.