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• The European Synchrotron radiation source delivers X-ray photons with a dose rate of thousands of Gy/s. • We compare alanine and ionization chamber dosimeters under ultra-high dose rates in broad beam configuration at the ESRF. • The obtained relative response r ESRF is 0.932 ± 0.027 (1σ) of the alanine pellets irradiated at the ESRF compared to the 60Co source. • The overall uncertainty of the alanine dosimeter is ≈3.1% at 2σ. The use of synchrotron X-ray sources provides innovative approaches in radiation therapy. The unique possibility to generate quasi-parallel beams promoted the development of microbeam radiation therapy (MRT), an innovative approach able to reduce damages to normal tissues while delivering considerable doses in the lesion. Accurate dosimetry in broad-beam configuration (prior to the spatial fractionation of the incident X-ray fan) is very challenging at ultra-high dose rate synchrotron sources. The available reference dosimetry protocol based on the use of a PTW PinPoint ionization chamber was compared with alanine dosimetry at the European Synchrotron Radiation Facility (ESRF) ID17 Biomedical beamline, an orthovoltage X-ray source with an average dose rate of 11.6 kGy/s. Reference dose measurements of the alanine pellets were performed at the National Centre for Radiation Research and Technology (NCRRT) 60Co facility in Egypt. All alanine dosimeters were analysed by an electron paramagnetic resonance spectrometer. We determined a relative response r ESRF = 0.932 ± 0.027 (1σ) of the alanine pellets irradiated at the ESRF compared to the 60Co facility. Considering the appropriate corrections for the ESRF polychromatic spectrum and the different field size used, our result is in agreement with the previous work of Waldeland et al. for which the utilised alanine contained the same amount of binder, and it is consistent with the works of Anton et al. and Butler et al. for which the utilised alanine contained a higher amount of binder. We confirm that alanine is an appropriate dosimeter for ultra-high dose rate calibration of orthovoltage X-ray sources. [ABSTRACT FROM AUTHOR]

• Ultrasmall theranostic nanoparticles rapidly distribute (<1 h) to target glioma. • MRI contrast enhancement can be sustained at 24 h after administration. • These nanoparticles exhibit potential chemotherapy and radiation sensitization. We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 μM. This was compared to concentrations of 10.5 ± 9.2 μM and 62.9 ± 24.7 μM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation. [ABSTRACT FROM AUTHOR]

Highlights • Preparation of dosimeter based on polymeric solution and pergascript orange. • The response of all compositions is linear in the dose range of 1–20 Gy. • Its radiation sensitivity is ≈0.066 Gy−1.cm−1 that is nearly similar to FXG dosimeter value of 0.064 Gy−1.cm−1. • PGO-P dosimeter is a water equivalent and has an energy-independent response for γ-rays of 60Co and x-ray beam of 6 and 15 MV. • The overall uncertainty is ≈4.5% at the 95% confidence level. Abstract A radiation colour former amino fluoran dye, Pergascript Orange (PGO), in a polyvinyl butyral solution containing a colour developer, hexachloroethane (HCE), was prepared and investigated for radiotherapy dosimetry of 60Co, 6 MV and 15 MV photons. PGO, a colourless dye, reacts with the acid produced upon radiation exposure of HCE, enabling the lactone ring to open and the orange colour of PGO to develop. The ring opening of PGO was confirmed by the appearance of a broad peak of OH− at 3360 cm−1, C O carboxylic peak at 1763 cm−1, and an iminium group peak at 1640 cm−1. The dose response of all prepared compositions was linear in the dose range of 1–20 Gy. Increasing HCE in the dosimeter matrix from 63 mM to 106 mM enhanced the radiation sensitivity by ≈58%. The radiation sensitivity of PGO-PVB (PGO-P) dosimeter is comparable with Fricke gel and higher than N-(Isobutoxymethyl) acrylamide polymer gel dosimeters. The experimental results reveal an energy-independent response (≈1.2% variation at 1σ) in the studied range of radiotherapy beam quality from 60Co beams to the beams from Linacs with a maximum energy of 15 MeV. Based on the theoretical study, this dosimeter is water equivalent from 80 keV to 10 MeV. The overall uncertainty was found to be 4.5% at the 95% confidence level, indicating the possibility of using PGO-P dosimeter in conventional radiotherapy dose verification. [ABSTRACT FROM AUTHOR]

Purpose Microplanar X-ray beams (microbeams) originated by synchrotron sources have been delivered to the visual brain cortex regions in rodents to create microscopically narrow lesions. The effects of microbeams mimic those generated by microsurgical subpial transections (also known as multiple subpial transections) but are obtained in a low-invasive way. Methods Image-guided atlas-based microbeam cortical transections have been generated on seven 1 month-old Wistar rats. An array of 10 parallel beams of 25 microns in thickness and spaced of 200 micron center-to-center was centered on the visual cortex and deposited an incident dose of 600 Gy. Results The procedure was well tolerated by rats. After recovery, rats showed regular behavior, no sign of gross visual impairment and regular weight gain. After 3 months, rats were sacrificed and brains histologically examined. Cortical transections resembling those obtained through a surgical incision were found over the irradiated region. Remarkable sparing of the cortical columns adjacent to the transections was observed. No sign of radionecrosis was evident at least at this time point. Conclusions The visual brain cortex transected by synchrotron-generated microbeams showed an incision-like path of neuronal loss while adjacent non irradiated columns remained intact. These preliminary findings, to be further investigated also using other techniques, suggest that microbeam radiosurgery can affect the cortex at a cellular level providing a potential novel and attractive tool to study cortical function. [ABSTRACT FROM AUTHOR]

Stereotactic Synchrotron Radiotherapy (SSRT) and Microbeam Radiation Therapy (MRT) are both novel approaches to treat brain tumor and potentially other tumors using synchrotron radiation. Although the techniques differ by their principles, SSRT and MRT share certain common aspects with the possibility of combining their advantages in the future. For MRT, the technique uses highly collimated, quasi-parallel arrays of X-ray microbeams between 50 and 600 keV. Important features of highly brilliant Synchrotron sources are a very small beam divergence and an extremely high dose rate. The minimal beam divergence allows the insertion of so called Multi Slit Collimators (MSC) to produce spatially fractionated beams of typically ∼25–75 micron-wide microplanar beams separated by wider (100–400 microns center-to-center(ctc)) spaces with a very sharp penumbra. Peak entrance doses of several hundreds of Gy are extremely well tolerated by normal tissues and at the same time provide a higher therapeutic index for various tumor models in rodents. The hypothesis of a selective radio-vulnerability of the tumor vasculature versus normal blood vessels by MRT was recently more solidified. SSRT (Synchrotron Stereotactic Radiotherapy) is based on a local drug uptake of high-Z elements in tumors followed by stereotactic irradiation with 80 keV photons to enhance the dose deposition only within the tumor. With SSRT already in its clinical trial stage at the ESRF, most medical physics problems are already solved and the implemented solutions are briefly described, while the medical physics aspects in MRT will be discussed in more detail in this paper. [ABSTRACT FROM AUTHOR]

The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile. The results show that membrane related functions of calcium and 5HT are critical for true bystander effect expression. Our original inter-animal experiments used fish species whole body irradiated with low doses of X-rays, which prevented us from addressing the abscopal effect question. Data which are much more relevant in radiotherapy are now available for rats which received high dose local irradiation to the implanted right brain glioma. The data were generated using quasi-parallel microbeams at the biomedical beamline at the European Synchrotron Radiation Facility in Grenoble France. This means we can directly compare abscopal and “true” bystander effects in a rodent tumour model. Analysis of right brain hemisphere, left brain and urinary bladder in the directly irradiated animals and their unirradiated partners strongly suggests that bystander effects (in partner animals) are not the same as abscopal effects (in the irradiated animal). Furthermore, the presence of a tumour in the right brain alters the magnitude of both abscopal and bystander effects in the tissues from the directly irradiated animal and in the unirradiated partners which did not contain tumours, meaning the type of signal was different. [ABSTRACT FROM AUTHOR]