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.

Mapping atomic motions with ultrabright electrons: towards fundamental limits in space-time resolution.

The long held objective of directly observing atomic motions during the defining moments of chemistry has been achieved based on ultrabright electron sources that have given rise to a new field of atomically resolved structural dynamics. This class of experiments requires not only simultaneous sub-atomic spatial resolution with temporal resolution on the 100 femtosecond time scale but also has brightness requirements approaching single shot atomic resolution conditions. The brightness condition is in recognition that chemistry leads generally to irreversible changes in structure during the experimental conditions and that the nanoscale thin samples needed for electron structural probes pose upper limits to the available sample or "film" for atomic movies. Even in the case of reversible systems, the degree of excitation and thermal effects require the brightest sources possible for a given space-time resolution to observe the structural changes above background. Further progress in the field, particularly to the study of biological systems and solution reaction chemistry, requires increased brightness and spatial coherence, as well as an ability to tune the electron scattering cross-section to meet sample constraints. The electron bunch density or intensity depends directly on the magnitude of the extraction field for photoemitted electron sources and electron energy distribution in the transverse and longitudinal planes of electron propagation. This work examines the fundamental limits to optimizing these parameters based on relativistic electron sources using re-bunching cavity concepts that are now capable of achieving 10 femtosecond time scale resolution to capture the fastest nuclear motions. This analysis is given for both diffraction and real space imaging of structural dynamics in which there are several orders of magnitude higher space-time resolution with diffraction methods. The first experimental results from the Relativistic Electron Gun for Atomic Exploration (REGAE) are given that show the significantly reduced multiple electron scattering problem in this regime, which opens up micron scale systems, notably solution phase chemistry, to atomically resolved structural dynamics.