Background and Aims

Synchrotron Microbeam Radiation Therapy (S-MRT) consists of Synchrotron X-rays fractionated into an array of quasi-parallel beamlets delivered in FLASH mode. S-MRT achieves excellent tumour control and normal tissue sparing. This study aimed to evaluate S-MRT efficacy in a preclinical mouse lung carcinoma model.

Methods

Lewis-lung carcinoma implanted C57BL/6J mice were treated with two cross-fired arrays of S-MRT or Synchrotron-Broad Beam (S-BB) at 11 days after implantation. An array composed of seventeen microbeams 50 µm wide, spaced 400 µm apart was employed. S-MRT peak-dose was 400 Gy with a valley-dose of 4.76 Gy (delivery 361 ms, dose-rate 991.7 Gy/s). S-BB delivered a homogeneous dose of 5.16 Gy (delivery 129 ms, dose-rate 37.0 Gy/s). In addition, mouse lungs without tumours were irradiated with S-MRT, and radiation-related effects were assessed up to 6 months post-treatment.

Results

Mice in the S-MRT group had notably smaller tumour volumes compared to the S-BB group however, there was no difference in animal survival. This was attributed to pulmonary oedema found around the S-MRT-treated tumours. A mild transient form of fluid effusion was also observed in the S-MRT-treated normal lungs. Six months after S-MRT, the lungs of healthy mice were completely absent of radiation-induced pulmonary fibrosis.

Conclusions

Our study indicates that FLASH S-MRT is a promising tool for treating mouse lung carcinoma, i.e. reducing tumour size compared to mice treated with FLASH S-BB and sparing healthy lung from pulmonary fibrosis. Future experiments should focus on optimizing S-MRT parameters to minimize pulmonary oedema and maximize its therapeutic ratio.

Background and Aims

Accurate methods for monitoring the efficacy of treatments are key in radiooncology, where the quest for imaging techniques providing in three-dimensions (3D) both high spatial and contrast resolutions is incessant. X-ray Phase Contrast-Computed Tomography (XPCI-CT) is here proposed as a label-free, full-organ, multi-scale and 3D approach to study irradiated tissues with high sensitivity.

The aim is to visualize and characterize the effects of FLASH irradiations using broad beam (BB) and spatially-fractionated microbeams (MRT) with ex-vivo XPCI-CT for virtual 3D histology.

Methods

We delivered X-ray BB and MRT on healthy lungs or on healthy and glioblastoma-bearing brains of Fisher rats; irradiations were performed at the ID17 station of the European Synchrotron Radiation Facility using a dose rate of ~14000 Gy/s. After sacrificing the animals, target organs were removed, fixed and imaged by XPCI-CT using voxel sizes down to 0.7³ µm³. Afterwards samples were analysed by histology, X-ray wide-angle scattering and fluorescence.

Results

XPCI-CT allowed the depiction of brain and lungs anatomical details down to the cellular level, the identification of tumour tissue, necrosis, calcifications and micrometric MRT-transections within brains and of radiation induced fibrosis in lungs. BB irradiations produced the largest amount of fibrotic tissue while MRT caused isolated scars with small iron accumulations and calcium deposits in damaged blood vessels. A complementary structural/chemical characterization of the detected structures was also achieved.

Conclusions

The proposed approach provides a supportive technique for 3D imaging-based virtual histology and for an accurate description of post-treatment conditions of biological tissues supplementing the capabilities of standard lab-based techniques.