Improved FBX chemical dosimeter system with enhanced radiochemical yield for reference dosimetry in radiobiology and radiotherapy research

Radiation dosimetry plays important role in the reproducibility of radiobiology experiments, in the replicability of results, as well as in the successful and safe use of radiotherapy procedures. The consistency and accuracy of the applied dosimetry methods pre-define the outcomes of these applications. This paper presents a version of the well-known ferrous sulphate – benzoic acid – xylenol orange (FBX) chemical dosimeter with improved sensitivity, accuracy and precision. Sensitivity is increased due to a slight modification in composition and the preparation procedures. We use stock solutions for the preparation of the dosimeter solution, which consists of 1 mM ferrous sulphate and 16 mM benzoic acid with 0.25 mM xylenol orange added post-irradiation. The nonlinear response to the absorbed dose of this system is eliminated by the increased ferrous sulphate concentration, permitting the calculation of the absorbed dose by a linear relationship between the absorbed dose and the optical absorbance of the solution. The measured chemical yield of our dosimeter is 9.08⋅10−6mol/J for 6 MV photon beams and 6.42⋅10−6mol/J for 250 kVp x-rays. This is a 24% enhancement over the original FBX solution, which permits a finer dose resolution. The accuracy and precision of our method is assured by a well-designed and consistently used practice. A custom designed multipurpose PMMA slab phantom was used for irradiation in reference conditions. This phantom can be used for irradiation in reference conditions of dosimetric solutions, dosimetric films and chemical or biological samples. The combined standard uncertainty of this system is 1.12%, which can be improved by using an appropriate temperature correction factor. Furthermore, a working protocol has been established which allows dosimetry measurements using less than 1 mL dosimetric solutions

Analysis of Ionizing Radiation Induced DNA Damage by Superresolution dSTORM Microscopy

The quantitative detection of radiation caused DNA double-strand breaks (DSB) by immunostained γ-H2AX foci using direct stochastic optical reconstruction microscopy (dSTORM) provides a deeper insight into the DNA repair process at nanoscale in a time-dependent manner. Glioblastoma (U251) cells were irradiated with 250 keV X-ray at 0, 2, 5, 8 Gy dose levels. Cell cycle phase distribution and apoptosis of U251 cells upon irradiation was assayed by flow cytometry. We studied the density, topology and volume of the γ-H2AX foci with 3D confocal microscopy and the dSTORM superresolution method. A pronounced increase in γ-H2AX foci and cluster density was detected by 3D confocal microscopy after 2 Gy, at 30 min postirradiation, but both returned to the control level at 24 h. Meanwhile, at 24 h a considerable amount of residual foci could be measured from 5 Gy, which returned to the normal level 48 h later. The dSTORM based γ-H2AX analysis revealed that the micron-sized γ-H2AX foci are composed of distinct smaller units with a few tens of nanometers. The density of these clusters, the epitope number and the dynamics of γ-H2AX foci loss could be analyzed. Our findings suggest a discrete level of repair enzyme capacity and the restart of the repair process for the residual DSBs, even beyond 24 h. The dSTORM superresolution technique provides a higher precision over 3D confocal microscopy to study radiation induced γ-H2AX foci and molecular rearrangements during the repair process, opening a novel perspective for radiation research

An evaluation of the various aspects of the progress in clinical applications of laser driven ionizing radiation

There has been a vast development of laser-driven particle acceleration (LDPA) using high power lasers. This has initiated by the radiation oncology community to use the dose distribution and biological advantages of proton/heavy ion therapy in cancer treatment with a much greater accessibility than currently possible with cyclotron/synchrotron acceleration. Up to now, preclinical experiments have only been performed at a few LDPA facilities; technical solutions for clinical LDPA have been theoretically developed but there is still a long way to go for the clinical introduction of LDPA. Therefore, to explore the further potential bio-medical advantages of LDPA has pronounced importance. The main characteristics of LDPA are the ultra-high beam intensity, the flexibility in beam size reduction and the potential particle and energy selection whilst conventional accelerators generate single particle, quasi mono-energetic beams. There is a growing number of studies on the potential advantages and applications of Energy Modulated X-ray Radiotherapy, Modulated Electron Radiotherapy and Very High Energy Electron (VHEE) delivery system. Furthermore, the ultra-high space and/or time resolution of super-intense beams are under intensive investigation at synchrotrons (microbeam radiation and very high dose rate (> 40 Gy/s) electron accelerator flash irradiation) with growing evidence of significant improvement of the therapeutic index. Boron Neutron Capture Therapy (BNCT) is an advanced cell targeted binary treatment modality. Because of the high linear energy transfer (LET) of the two particles (7Li and 4He) released by 10BNC reaction, all of the energy is deposited inside the tumour cells, killing them with high probability, while the neighbouring cells are not damaged. The limited availability of appropriate neutron sources, prevent the more extensive exploration of clinical benefit of BNCT. Another boron-based novel binary approach is the 11B-Proton Fusion, which result in the release of three high LET alpha particles. These promising, innovative approaches for cancer therapy present huge challenges for dose calculation, dosimetry and for investigation of the biological effects. The planned LDPA (photons, VHEE, protons, carbon ions) at ELI facilities has the unique property of ultra-high dose rate (> Gy/s-10), short pulses, and at ELI-ALPS high repetition rate, have the potential to develop and establish encouraging novel methods working towards compact hospital-based clinical applications. © 2017 IOP Publishing Ltd and Sissa Medialab srl