Non-Targeted Effects of Synchrotron Radiation: Lessons from Experiments at the Australian and European Synchrotrons

Abstract

Studies have been conducted at synchrotron facilities in Europe and Australia to explore a variety of applications of synchrotron X-rays in medicine and biology. We discuss the major technical aspects of the synchrotron irradiation setups, paying specific attention to the Australian Synchrotron (AS) and the European Synchrotron Radiation Facility (ESRF) as those best configured for a wide range of biomedical research involving animals and future cancer patients. Due to ultra-high dose rates, treatment doses can be delivered within milliseconds, abiding by FLASH radiotherapy principles. In addition, a homogeneous radiation field can be spatially fractionated into a geometric pattern called microbeam radiotherapy (MRT); a coplanar array of thin beams of microscopic dimensions. Both are clinically promising radiotherapy modalities because they trigger a cascade of biological effects that improve tumor control, while increasing normal tissue tolerance compared to conventional radiation. Synchrotrons can deliver high doses to a very small volume with low beam divergence, thus facilitating the study of non-targeted effects of these novel radiation modalities in both in-vitro and in-vivo models. Non-targeted radiation effects studied at the AS and ESRF include monitoring cell–cell communication after partial irradiation of a cell population (radiation-induced bystander effect, RIBE), the response of tissues outside the irradiated field (radiation-induced abscopal effect, RIAE), and the influence of irradiated animals on non-irradiated ones in close proximity (inter-animal RIBE). Here we provide a summary of these experiments and perspectives on their implications for non-targeted effects in biomedical fields.

Radiation-Induced Rescue Effect: Insights from Microbeam Experiments

“…Moreover, as mentioned in Section 4.1 above, there has been research into MRT using microbeam radiations [ 76 ]. Interestingly, Fernandez-Palomo et al further remarked that MRT could operate under the FLASH-mode with doses delivered within a few milliseconds and at ultrahigh dose rates (up to 16 kGy s −1 ), which could help spare normal tissues while efficiently eradicating local tumors [ 13 ]. As both the spatial fractionation provided by MRT and the ultrahigh dose rate of FLASH inflict lower toxicity to normal tissues, it is pertinent to examine the resultant sparing effect on normal tissues and the potentially improved tumor control of the FLASH-mode MRT when compared to conventional irradiation.…”

“…Interested readers are referred to published reviews on RIBE (see, e.g., refs. [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]).…”

Synchrotron x-ray spectra characterisation for radiation therapy applications at the ESRF - ID17 biomedical beamline

“…MRT exploits the dose-volume effect [7,8], a phenomenon in which mature biological tissues tolerate high microbeam doses in the order of hundreds of Gy better than broad beam doses of only a few Gy. MRT has shown remarkable results in numerous preclinical studies compared to conventional radiotherapy, thanks to increased tolerance of healthy tissues and increased effectiveness in limiting tumour development [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”