Microbeam evolution: from single cell irradiation to pre-clinical studies

Abstract

Purpose: This review follows the development of microbeam technology from the early days of single cell irradiations, to investigations of specific cellular mechanisms and to the development of new treatment modalities in vivo. A number of microbeam applications are discussed with a focus on pre-clinical modalities and translation towards clinical application.

Conclusions: The development of radiation microbeams has been a valuable tool for the exploration of fundamental radiobiological response mechanisms. The strength of micro-irradiation techniques lies in their ability to deliver precise doses of radiation to selected individual cells in vitro or even to target subcellular organelles. These abilities have led to the development of a range of microbeam facilities around the world allowing the delivery of precisely defined beams of charged particles, X-rays, or electrons. In addition, microbeams have acted as mechanistic probes to dissect the underlying molecular events of the DNA damage response following highly localized dose deposition. Further advances in very precise beam delivery have also enabled the transition towards new and exciting therapeutic modalities developed at synchrotrons to deliver radiotherapy using plane parallel microbeams, in Microbeam Radiotherapy (MRT).

Keywords:

• Microbeam
• DNA damage
• MRT
• bystander effects of radiation

Acknowledgements

E. B. K. and all authors want to acknowledge Prof Jean Laissue for his vital contribution in the field of MRT.

Disclosure statement

The authors report no conflict of interest.

Notes on contributors

Dr Mihaela Ghita is a Postdoctoral Research Assistant at Centre for Cancer Research and Cell Biology (CCRCB), in the Radiation Biology group led by Prof Prise. Her research focuses on in vitro and in vivo studies of targeted and non-targeted radiation induced effects aiming to enable the fine tuning of pre-clinical models to the specific tumor biology.

Dr Cristian Fernandez-Palomo is a Postdoctoral Fellow at University of Bern and studies the effects of Synchrotron radiation to improve the treatment of skin cancer using spatially fractionated microbeams to increase the normal tissue tolerance to the radiotherapy treatment.

Hisanori Fukunaga is a PhD student in the Radiation Biology Group within the CCRCB led by Prof Prise. His research focuses on Radiobiological Implications of the Fukushima nuclear accident and radiation-induced effects on spermatogenesis.

Dr Pil M. Fredericia is a Postdoctoral Fellow at Technical University of Denmark, Institute for Nuclear Technologies. Her work is focusing on quantification of radiation induced DNA damage following intracellular Auger cascade.

Dr Giuseppe Schettino is Principal Research Scientist in the Radiation Dosimetry Group at the NPL. His main research interest is in radiation biology, advanced radiotherapy, and dosimetry. He is leading UK initiatives for standardization of dosimetry and QA processes for pre-clinical radiotherapy and radiobiology research.

Dr Karl T. Butterworth is a Lecturer in Translational Radiation Biology in the Advanced Radiotherapy Group within the CCRCB. His research group is focused on translational studies using in vivo models for pre-clinical radiotherapy and imaging. His work focuses on developing novel radiation based strategies to overcome radioresistance and minimize toxicities in normal tissues.

Dr Elke Brauer Krisch is the Project Leader for Microbeam Radiation Therapy (MRT) at European Synchrotron Radiation Facility, Direction of Experiments. Her research interests are focused on in vivo effects as well as dosimetric aspects of MRT.

Dr Stephen McMahon is a Queen’s Research Fellow within the CCRCB. His work focuses on the development of predictive models of radiation response, taking into account factors such as irradiation geometry, radiation quality, and intrinsic cellular radiosensitivity.

Prof Kevin M. Prise is Deputy Director of CCRCB, Professor of Radiation Biology and Head of the Radiation Biology Group at Queen’s University Belfast. His research group is multidisciplinary with strong expertise in both radiation physics and radiation biology and is working in areas related to both radiation protection and radiotherapy.

Additional information

Funding

H. F. is funded by a fellowship from the International Exchange and Research Grant of Marubun Research Promotion Foundation, Japan. K. T. B. and K. M. P. would like to acknowledge the UK Department of Health [DOH 091/0205] for supporting their work.