Animal Models in Microbeam Radiation Therapy: A Scoping Review

Abstract

Background: Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres. Objective: This scoping review was conducted to map the available evidence and provide a comprehensive overview of the similarities, differences, and outcomes of all experiments that have employed animal models in MRT. Methods: We considered articles that employed animal models for the purpose of studying the effects of MRT. We searched in seven databases for published and unpublished literature. Two independent reviewers screened citations for inclusion. Data extraction was done by three reviewers. Results: After screening 5688 citations and 159 full-text papers, 95 articles were included, of which 72 were experimental articles. Here we present the animal models and pre-clinical radiation parameters employed in the existing MRT literature according to their use in cancer treatment, non-neoplastic diseases, or normal tissue studies. Conclusions: The study of MRT is concentrated in brain-related diseases performed mostly in rat models. An appropriate comparison between MRT and conventional radiotherapy (instead of synchrotron broad beam) is needed. Recommendations are provided for future studies involving MRT.

Animal Models for Radiotherapy Research: All (Animal) Models Are Wrong but Some Are Useful

“…Stripay and colleagues [ 13 ] review the role of CSI showing how it has improved with advances in conformal techniques and is now being incorporated into preclinical models, suggesting that this approach may be used to address outstanding questions relating to the benefits of dose boosting following chronic treatment. Fernandez-Palomo et al [ 14 ] review the current evidence for microbeam radiotherapy (MRT) in animal models. This approach uses spatially-modulated modulated microscale beam geometries delivered at high peak dose and dose rate, and has shown equivalent levels of tumour control compared to conventional beam deliveries, but with reduced toxicity in normal tissues.…”

Complete Remission of Mouse Melanoma after Temporally Fractionated Microbeam Radiotherapy

“…This spatial arrangement of the radiation beam allows a sharp transition between high peak-dose deposition in the microbeam path (typically 300-800 Gy) and the region between these microbeams (valley), which typically receives 1-10% of the peak dose [4]. These doses are delivered in a single fraction at ultra-high dose rates (up to 16,000 Gy/s in the European Synchrotron) [4]. As a result, MRT induces extremely low normal-tissue radiation toxicity, which is attributed, in part, to the rapid delivery of radiation (<200 ms), and this is known as the "FLASH" effect [5].…”

“…Synchrotron Microbeam Radiation Therapy (MRT) is a preclinical approach of spatial fractionation that has been found to obtain superior tumour control in different animal models relative to a homogenous radiation field [ 1 , 2 , 3 ]. Synchrotron-based MRT uses a multi-slit collimator to spatially fractionate synchrotron X-rays into an array of microbeams that range from 20 to 100 μm in width, which are spaced by 50–500 μm from beam centre to beam centre [ 4 ]. This spatial arrangement of the radiation beam allows a sharp transition between high peak-dose deposition in the microbeam path (typically 300–800 Gy) and the region between these microbeams (valley), which typically receives 1–10% of the peak dose [ 4 ].…”

“…Synchrotron-based MRT uses a multi-slit collimator to spatially fractionate synchrotron X-rays into an array of microbeams that range from 20 to 100 μm in width, which are spaced by 50–500 μm from beam centre to beam centre [ 4 ]. This spatial arrangement of the radiation beam allows a sharp transition between high peak-dose deposition in the microbeam path (typically 300–800 Gy) and the region between these microbeams (valley), which typically receives 1–10% of the peak dose [ 4 ]. These doses are delivered in a single fraction at ultra-high dose rates (up to 16,000 Gy/s in the European Synchrotron) [ 4 ].…”

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model

“…Ongoing technological developments provide new charged particle acceleration methods that yield beams with parameters, such as ultrahigh dose rate, pulsed operation and extremely small non-divergent beams. Examples are laserdriven particle beam therapy (8), FLASH therapy (9), Micro Beam therapy (10) and combined modalities (11). Prior to human application, it is essential to establish the safety of a novel modality and to define the potential toxicity profile and the basic pathomechanism of action.…”