VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint.

Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 109 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.

First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY.

Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96-0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.

Quantification of damage to plasmid DNA from 35 MeV electrons, 228 MeV protons and 300 kVp X-rays in varying hydroxyl radical scavenging environments.

The pBR322 plasmid DNA was irradiated with 35 MeV electrons, 228 MeV protons and 300 kVp X-rays to quantify DNA damage and make comparisons of DNA damage between radiation modalities. Plasmid was irradiated in a medium containing hydroxyl radical scavengers in varying concentrations. This altered the amount of indirect hydroxyl-mediated DNA damage, to create an environment that is more closely associated with a biological cell. We show that increasing hydroxyl scavenger concentration significantly reduced post-irradiation DNA damage to pBR322 plasmid DNA consistently and equally with three radiation modalities. At low scavenging capacities, irradiation with both 35 MeV electrons and 228 MeV protons resulted in increased DNA damage per dose compared with 300 kVp X-rays. We quantify both single-strand break (SSB) and double-strand break (DSB) induction between the modalities as a ratio of yields relative to X-rays, referred to as relative biological effectiveness (RBE). RBESSB values of 1.16 ± 0.15 and 1.18 ± 0.08 were calculated for protons and electrons, respectively, in a low hydroxyl scavenging environment containing 1 mM Tris-HCl for SSB induction. In higher hydroxyl scavenging capacity environments (above 1.1 × 106 s-1), no significant differences in DNA damage induction were found between radiation modalities when using SSB induction as a measure of RBE. Considering DSB induction, significant differences were only found between X-rays and 35 MeV electrons, with an RBEDSB of 1.72 ± 0.91 for 35 MeV electrons, indicating that electrons result in significantly more SSBs and DSBs per unit of dose than 300 kVp X-rays.

A study of beam position diagnostics using beam-excited dipole modes in third harmonic superconducting accelerating cavities at a free-electron laser.

We investigate the feasibility of beam position diagnostics using higher order mode (HOM) signals excited by an electron beam in the third harmonic 3.9 GHz superconducting accelerating cavities at FLASH. After careful theoretical and experimental assessment of the HOM spectrum, three modal choices have been narrowed down to fulfill different diagnostics requirements. These are localized dipole beam-pipe modes, trapped cavity modes from the fifth dipole band, and propagating modes from the first two dipole bands. These modes are treated with various data analysis techniques: modal identification, direct linear regression (DLR), and singular value decomposition (SVD). Promising options for beam diagnostics are found from all three modal choices. This constitutes the first prediction, subsequently confirmed by experiments, of trapped HOMs in third harmonic cavities, and also the first direct comparison of DLR and SVD in the analysis of HOM-based beam diagnostics.