LAUSR

PURPOSE Ultra-high dose rate FLASH irradiation (FLASH-IR) has been shown to cause less normal tissue damage compared with conventional irradiation (CONV-IR), this is known as the "FLASH effect". It has attracted immense research interest because its underlying mechanism is scarcely known. The purpose of this study was to determine whether FLASH-IR and CONV-IR induce differential inflammatory cytokine expression using a modified clinical linac. MATERIALS AND METHODS An Elekta Synergy linac was used to deliver 6 MeV CONV-IR and modified to deliver FLASH-IR. Female FvB mice were randomly assigned to three different groups: a non-irradiated control, CONV-IR, or FLASH-IR. The FLASH-IR beam was produced by single pulses repeated manually with a 20-second interval (Strategy 1), or single-trigger multiple pulses with a 10 millisecond (ms) interval (Strategy 2). Mice were immobilized in the prone position in a custom-designed applicator with Gafchromic films positioned under the body. The prescribed doses for the mice were 6 to 18 Gy and verified using Gafchromic films. Cytokine expression of three pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6)] and one anti-inflammatory cytokine (IL-10) in serum samples and skin tissue were examined within 1- month post-IR. RESULTS The modified linac delivered radiation at an intra-pulse dose rate of around 1×106 Gy/s and a dose per pulse over 2 Gy at a source-to-surface distance (SSD) of 13 to 15 cms. The achieved dose coverage was 90 - 105% of the maximum dose within -20 ∼ 20 mm in the X direction and 95% within -30 ∼ 30 mm in the Y direction. The absolute deviations between the prescribed dose and the actual dose were 2.21, 6.04, 2.09 and 2.73% for 6, 9, 12 and 15 Gy as measured by EBT3 films, respectively; and 4.00, 4.49 and 2.30% for 10, 14 and 18 Gy as measured by the EBT XD films, respectively. The reductions in the CONV-IR versus the FLASH-IR group were 4.89, 10.28, -7.8 and -22.17 % for TNF-α, IFN-γ, IL-6 and IL-10 in the serum on D6, respectively; 37.26, 67.16, 56.68 and -18.95% in the serum on D31, respectively; and 62.67, 35.65, 37.75 and -12.20% for TNF-α, IFN-γ, IL-6 and IL-10 in the skin tissue, respectively. CONCLUSIONS Ultra-high dose rate electron FLASH caused lower pro-inflammatory cytokine levels in serum and skin tissue which might mediate differential tissue damage between FLASH-IR and CONV-IR. This article is protected by copyright. All rights reserved.