This study aimed to evaluate whether high-energy X-rays (HEXs) of the PARTER (platform for advanced radiotherapy research) platform built on CTFEL (Chengdu THz Free Electron Laser facility) can produce ultrahigh dose rate (FLASH) X-rays and trigger the FLASH effect. Materials and methods: EBT3 radiochromic film and fast current transformer (FCT) devices were used to measure absolute dose and pulsed beam current of HEXs. Subcutaneous tumor-bearing mice and healthy mice were treated with sham, FLASH, and conventional dose rate radiotherapy (CONV), respectively to observe the tumor control efficiency and normal tissue damage. Results: The maximum dose rate of HEXs of PARTER was up to over 1000 Gy/s. Tumor-bearing mice experiment showed a good result on tumor control (p < 0.0001) and significant difference in survival curves (p < 0.005) among the three groups. In the thorax-irradiated healthy mice experiment, there was a significant difference (p = 0.038) in survival among the three groups, with the risk of death decreased by 81% in the FLASH group compared to that in the CONV group. The survival time of healthy mice irradiated in the abdomen in the FLASH group was undoubtedly higher (62.5% of mice were still alive when we stopped observation) than that in the CONV group (7 days). Conclusion: This study confirmed that HEXs of the PARTER system can produce ultrahigh dose rate X-rays and trigger a FLASH effect, which provides a basis for future scientific research and clinical application of HEX in FLASH radiotherapy.

The ultrahigh dose-rate (FLASH) radiotherapy, which is efficient in tumor control while sparing healthy tissue, has attracted intensive attention due to its revolutionary application prospect. This so-called FLASH effect has been reported in preclinical experiments with electrons, kilo-voltage X-rays, and protons, thus making FLASH a promising revolutionary radiotherapy modality. High energy X-ray (HEX) should be the ideal radiation type for clinical applications of FLASH due to its advantages in deep penetration, small divergence, and cost-friendly. In this work, we report the first implementation of HEXs with ultrahigh dose-rate (HEX-FLASH) and corresponding application of in vivo study of the FLASH effect produced by a high-current (10 mA), high-energy (6-8 MeV) superconducting linac. Joint measurements using radiochromic film, scintillator and Fast Current Transformer device validated that a maximum dose rate of over 1000 Gy/s was achieved in the mice and the mean value within several square centimeters keeps higher than 50 Gy/s within a depth of over 15 cm. The performance of the present HEX can satisfy the requirement of the FLASH study on animals. Breast cancer (EMT6) inoculated into BAL b/c mice was found efficiently controlled by HEX-FLASH. The radio-protective effect of normal tissue was observed on the C57BL/6 mice after thorax/abdomen irradiation by HEX-FLASH. Theoretical analyses of cellular response following HEX-FLASH irradiation based on the radiolytic oxygen depletion hypothesis were performed to interpret experimental results and future experiment design. This work provided the first demonstration of the FLASH effect triggered by HEX, which paved the way for future preclinical research and clinical application of HEX-FLASH.

No abstract

China Academy of Engineering Physics terahertz free electron laser (CAEP THz FEL,CTFEL) is the first THz FEL oscillator in China,which is jointly built by CAEP,Peking University and Tsinghua University.It is designed as a high-repetition-rate and high-duty-cycle linac-based FEL facility. This THz FEL mainly consists of a gallium arsenide (GaAs) photocathode high-voltage direct current (DC) gun,a superconducting radio frequency (RF) linac,a planar undulator,and a quasi-concentric optical resonator. The DC gun provides a high-brightness electron beam with the bunch charge of about 100 pC and the repetition rate of 54.167~MHz.The normalized emittance of the electron beam is less than 10m,and the energy spread is less than 0.75%.A 24-cell superconducting RF accelerator provides an effective field gradient of about 10 MV/m and energizes the electron beam to 6-8~MeV.The beam then goes through the undulator and generates the spontaneous radiation,which is reflected back and forth in the optical resonator and then stimulated by the electron beam. The first stimulated saturation of CTFEL in the macro-pulse mode was obtained in August,2017.In this paper,the THz spectrum is measured by a Fourier spectrometer (Bruker VERTEX 80 V).The macro-pulse energy is measured by an absolute energy meter from Thomas Keating Instruments.The longitudinal beam length is preliminarily calculated by the auto-correlation curve from the time-domain signal of the spectrometer.The macro-pulse duration is captured by a GeGa cryogenic detector from QMC Instrument.The measurement results indicate that the terahertz laser frequency is continuously adjustable from 2 THz to 3 THz.The macro-pulse average power is more than 10 W and the micro-pulse power is more than 0.3 MW.The single-pass gain is larger than 2.5%. This facility is now working in macro-pulse mode in the first step,also called step one.The minimum macro-pulse duration is about 50s and the maximum is about 2 ms.The macro-pulse repetition is 1 Hz or 5 Hz.The typical pulse duration and repetition rate are 1 ms and 1 Hz,respectively.In the middle of 2018,the duty cycle will upgrade to more than 10% as step two.And the continuous wave (CW) operation will be obtained in step three by the end of 2018.The spectrum adjustment range will also be expanded to cover from 1 THz to 4 THz by then. Some application experiments have been carried out on the platform of CTFEL.This facility will greatly promote the development of THz science and its applications in material science,chemistry science,biomedicine science and many other cutting-edge areas in general.

No abstract