Proton FLASH Irradiation Using a Synchrotron Accelerator: Differences by Irradiation Positions

To establish an ultra-high dose-rate (UHDR) radiation system using a synchrotron proton beam accelerator and to compare the effects by irradiation positions on cultured cells and chick embryos.

Protons for UHDR were obtained by applying high-frequency power at much higher levels than usual to extract all protons within approximately 50 ms. Subsequently, monitoring with a Faraday cup was performed immediately after synchrotron extraction and the waveform was adjusted accordingly. Four cultured tumor lines, 2 normal cell lines, and chick embryos were used. UHDR radiation therapy (UHDR-RT) at 6 to 18 Gy (200-300 Gy/s, single exposure) and conventional dose-rate radiation therapy (Conv-RT) at 6 to 18 Gy (3 Gy/s) were administered to the 1-cm spread-out Bragg peak (SOBP) and the plateau region preceding SOBP. After irradiation, disparities in cell growth rates and cell cycle progression were assessed, and cell survival was evaluated via colony assay. Chick embryos were also examined for survival.

UHDR-RT was achieved at a range of 40 to 800 Gy/s, encompassing both plateau and peak phases. In vitro studies demonstrated similar cell-killing effects between UHDR-RT and Conv-RT in cancer cells. Significant apoptotic effects and G2 arrest were observed during the cell cycle under peak UHDR-RT conditions. The FLASH effect was not observed in normal single cells under normal atmospheric conditions. Stronger cell-killing effects were noted in V79 spheroids exposed to peak UHDR-RT than peak Conv-RT. Moreover, in chick embryos, an increase in survival rate, indicative of the FLASH effect, was observed.

The FLASH effect was also achieved with UHDR-RT using a synchrotron proton beam accelerator in chick embryos. The cell-killing effects in cancer cells were higher with peak UHDR-RT that may be due to the higher linear energy transfer at the SOBP.