Implementation of ultra-high dose-rate electron beam from 6-MeV C-band linear accelerator for preclinical study

Abstract

Recent biological studies with ultra-high dose-rate (> 40 Gy/s) irradiation demonstrate the killing of tumors along with a reduction in the side-effect on normal tissues. These features can suggest the alternative radiotherapy method. The radio-biological mechanisms need to be understood, and to be applied tumor treatment. Biological validations of the ultra-high dose-rate beam are required. The 6-MeV electron linear accelerator constructed in 2015 at the Dongnam Institute of Radiological & Medical Sciences was upgraded to generate an electron beam at an ultra-high dose rate and to provide preclinical irradiation for in vitro studies of cells and small animals. The irradiation device was designed with a dual scattering foil system to achieve a uniform beam distribution with a diameter of 30 mm at a distance of 110 mm from the primary foil. The 6-MeV accelerator operating with a 6-MW pulse modulator based on a thyratron-switched pulse-forming network provides beam operation per pulse utilizing a single-board computer to control the pulse timing. The film dosimetry at a depth of 10 mm in a water phantom of the irradiation device demonstrated that a beam with an RF power of 2.5 MW and an electron-gun heating current of 2 A produced a dose per pulse of 4.22±0.12 Gy/pulse. This resulted in a dose rate of 422 Gy/s with a pulse rate of 100 Hz. The upgraded accelerator was successfully tested for preclinical use and is currently in full operation with studies being performed on the radio-biological effects of ultra-high dose-rate beam. The paper describes the design features of the ultra-high dose-rate electron beam generated from the 6-MeV accelerator and the dose measurement using the irradiation device. The design of the preclinical irradiator is also discussed.

Evaluation of Radiation Sensitivity Differences in Mouse Liver Tumor Organoids Using CRISPR/Cas9-Mediated Gene Mutation

“…Irradiation was performed using an electron beam from a 6 MeV C-band linear accelerator. 27 The irradiated cells were centrifuged, and the supernatant was aspirated. The pellets were mixed with Matrigel and plated in a 120 μL drop in the middle of one well of a pre-coated 12-well plate (Corning) with organoid expansion media with or without Nutlin-3 for 7 days.…”

Technical note: A small animal irradiation platform for investigating the dependence of the FLASH effect on electron beam parameters

“…For studying the dependence of the FLASH effect on beam parameters, as well as underlying FLASH mechanisms in vivo, a platform that is capable of varying one or more of these parameters while maintaining uniform lateral and depth-dose distributions in irradiated animals is highly desirable. However, in concerted efforts to maximize dose rates, most existing electron UHDR platforms utilize narrow, non-uniform UHDR beams, [32][33][34][35][36] which limit the performance of in vivo studies in several ways. Narrow and non-uniform UHDR beams may cause animal-to-animal differences in dose distribution due to setup uncertainties, the number of animals which can be irradiated at a time with UHDRs is generally limited to just one, and source distance cannot be used to adjust the dose rate without affecting dose distribution.…”

Optical Filter-Embedded Fiber-Optic Radiation Sensor for Ultra-High Dose Rate Electron Beam Dosimetry

“…In this study, a FORS was fabricated using a plastic scintillator, an optical filter, and a plastic optical fiber (POF) for dosimetry of ultra-high dose rate electron beams and was subsequently evaluated with electron beams from a 6 MeV LINAC at Dongnam Institute of Radiological and Medical Sciences (DIRAMS), developed as a compact LINAC system that recently implemented ultra-high dose rate electron beams for preclinical FLASH-RT studies [ 16 ]. The radiation-induced emissions (RIEs), such as Cherenkov radiation and fluorescence generated in a transmitting optical fiber, were spectrally discriminated from the light outputs of the FORS by using an optical filter.…”