# Transformative Technology for FLASH Radiation Therapy
## FLASH Studies with Laser-Driven Particle Sources Developed at Lawrence Berkeley National Laboratory
### Laser-Driven Particle Sources for Preclinical Radiobiological Studies of the FLASH Effect  
Laser-driven (LD) particle sources may soon become adequate complements to RF-driven accelerators for basic radiobiological research of the FLASH effect [74]. Access to conventional experimental and medical machines has been rather limited for this type of research [75] while the steady increase in the available compact LD particle sources has already started to open up new experimental options for systematic radiobiological studies. The majority of radiobiological studies with LD particle sources has been conducted in view of potential future applications in radiotherapy, in particular with protons and heavier ions. As such, an appreciable number of in vitro studies and one in vivo study [76] have been conducted to investigate the radiobiological effectiveness of LD protons [77; 78; 79; 80; 81; 82; 83; 84; 85; 86; 87; 88]. Fewer radiobiological studies were so far conducted with LD electrons [89; 90; 91; 92; 93; 94]. The only in vivo study found no difference in tumor-growth delay when comparing LD electrons and RF accelerated electrons [91]. The proposal of using very-high-energy electrons (VHEE), with energies in the range of 150-250 MeV for radiotherapy [95], has sparked renewed interest in the dosimetric properties and the potential for new radiotherapy protocols using compact LWFA electron sources [96; 97; 98]. So far, no differential sparing effect of normal tissue was reported from radiobiological studies with LWFA electrons. While the dose rate was not always specified in publications, it can be assumed that samples were irradiated at ultra-high IDR due to the LD particle acceleration mechanisms, as mentioned above. So far, the majority of radiobiological studies with LD particle beams were conducted using in vitro cell cultures and at atmospheric \(\sim\)20% oxygen levels. Magnetic transport beamlines have been implemented at a few laser facilities to transport LD protons to a dedicated sample site and apply a three-dimensional dose profile for in vivo studies with small animals, for which tumor models have been developed [99; 100; 101; 102]. In a preliminary study at the 40-Joule BELLA petawatt laser proton beamline, it was demonstrated for the first time that LD protons delivered at ultra-high IDR can indeed induce the differential sparing of normal versus tumor cells in vitro for total doses \(\geq\)7 Gy [88]. In that study, normal and tumor prostate cells in 1 cm-diameter custom cell cartridges were irradiated with LD protons of 2-8 MeV at an IDR of 10\({}^{7}\) Gy/s. After acceleration from a tape-drive target, the proton bunch was transported with a compact active plasma lens beamline [103] to the cell sample site located outside the vacuum chamber (Figure 10a). An integrating current transformer (ICT) was implemented for the online beam charge measurements. The dosimetry was performed with calibrated radiochromic films attached to every cell sample. With 1 Gy applied per laser shot, total dose values up to \(>\)30 Gy were accumulated by operating the LD proton beamline at 0.2 Hz. A significant sparing of normal prostate cells compared to prostate tumor cells was observed after irradiation with LD protons (Figure 10b). The main proton beam parameters for this study are summarized in Table 3.  
Figure 10: Figure adapted from Ref. [88]. (**a**) Schematic depiction of the laser-driven proton beamline at the BELLA PW laser with tape-drive target, active plasma lens, dipole magnet, integrating current transformer (ICT), cell sample, radiochromic film, and scintillator. (**b**) Cell survival fraction of human prostate cancer cells (PC3) and normal human prostate cells (RWPE1) after irradiation with laser-driven protons. ([PERSON], et al.