_Applied sciences_  
_Review_  
**Non-Targeted Effects of Synchrotron Radiation: Lessons from Experiments at the Australian and European Synchrotrons**  
**[PERSON] 1,\({}^{\ddagger}\), [PERSON] 2,\({}^{\ddagger}\), [PERSON] 1, [PERSON] 2,\({}^{\ddagger}\) and [PERSON] 1,3,4,*  
\({}^{1}\) Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland;  
[EMAIL_ADDRESS] (C.F.-P); [EMAIL_ADDRESS] (V.D.)  
\({}^{2}\) School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 15780 Athens, Greece; [EMAIL_ADDRESS]  
\({}^{3}\) Peter MacCallum Cancer Centre, Division of Radiation Oncology, 305 Grattan St, Melbourne,  
VIC 3000, Australia  
\({}^{4}\) [PERSON] Department of Oncology, The University of Melbourne, Melbourne, VIC 3010, Australia  
\({}^{*}\) Correspondence: [EMAIL_ADDRESS] (A.G.G.); [EMAIL_ADDRESS] (O.A.M.)  
\({}^{\ddagger}\) These authors contributed equally to this work.  
**Featured Application: The characteristics of X-rays generated at the synchrotron facilities in Australia (the Australian Synchrotron) and France (the European Synchrotron Radiation Facility) share common features which provide the basis for development of new modalities for cancer radiotherapy treatment. In addition to the empirical optimization of the physical configurations of the radiation, research is now focused on the underlying radiobiological mechanisms, especially in the context of systemic \"non-targeted effects\".**  
**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.  
**Keywords:** synchrotron radiation; microbeam radiotherapy (MRT); FLASH; non-targeted effects; radiation-induced bystander effect (RIBE); radiation-induced abscopal effect (RIAE); Australian Synchrotron (AS); European Synchrotron Facility (ESRF)