Effects of Synchrotron X-Ray Micro-beam Irradiation on Normal Mouse Ear Pinnae

Potez, Marine; Bouchet, Audrey; Wagner, Jeannine; Donzelli, Mattia; Bräuer-Krisch, Elke; Hopewell, J. W.; Laissue, Jean A.; Djonov, Valentin

doi:10.1016/j.ijrobp.2018.02.007

Cited by 21 publications

(23 citation statements)

References 34 publications

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“…In addition, a recently published study demonstrated that the irradiated normal tissue surrounding the tumor is highly tolerant of MRT. 9 Different components of the tumor-bearing normal tissue, including cutis, subcutis, cartilage, blood, and lymphatic vessels, demonstrated no significant short-and long-term morphologic alteration by 400 Gy MRT. High normal tissue tolerance has been reported recently during experiments employing BB FLASH radiation therapy.…”

Section: Discussionmentioning

confidence: 94%

“…The irradiations were performed on the ID17 biomedical beamline at the European Synchrotron Radiation Facility (ESRF, France) with synchrotron x-rays, as described previously. 9 Ten to 11 days after tumor implantation, mice were separated into MRT-treated, uniform BB-treated, and nonirradiated (control) groups. The mice were placed vertically, with the head retained by a tooth bar and muzzle clamp.…”

Section: Dosimetry and Irradiationmentioning

confidence: 99%

“…Proliferating Ki67-positive cells were counted among a random selection of 100 nuclei stained with DAPI. T cells, NK cells, and macrophages were evaluated by a scoring system of 1 to 4, adapted from, 9 representative of the approximate number of immunostained cells (CD4 and CD8: 1, <5%; 2, 5%-12%; 3, 13%-20%; 4, >20%; NK cells and macrophages: 1, <10%; 2, 10%-20%; 3, 21%-40%; 4, >40%) ( Fig. E1; available online at https://doi.org/10.1016/ j.ijrobp.2019.08.027).…”

Section: Image Acquisition and Analysismentioning

confidence: 99%

“…Moreover, normal tissues showed only limited damage in response to the very high peak doses deposited by microbeams. 8,9 The mechanisms and the chronology underlying the MRT-induced antitumor response are not well understood, but studies have reported preferential effects of MRT on immature over mature blood vessels, 10-12 a differential gene expression between MRT and uniform broad beam (BB) irradiation regarding cell death, [13][14][15] and effects on immune and inflammatory responses. [16][17][18] To gain a better understanding of the mechanisms involved in the efficiency of MRT, a melanoma model was selected.…”

Section: Introductionmentioning

confidence: 99%

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Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms

Potez

Fernández-Palomo

Bouchet

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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Synchrotron microbeam radiation therapy (MRT) is a unique treatment that spatially distributes the x-ray beam into several microbeams of very high dose.MRT significantly delays tumor regrowth compared with uniform radiation therapy. The underlying mechanisms include tumor vascular disruption, senescence, and inflammatory and antitumor Purpose: Synchrotron microbeam radiation therapy (MRT) is a method that spatially distributes the x-ray beam into several microbeams of very high dose (peak dose), regularly separated by low-dose intervals (valley dose). MRT selectively spares normal tissues, relative to conventional (uniform broad beam [BB]) radiation therapy. Methods and Materials: To evaluate the effect of MRT on radioresistant melanoma, B16-F10 murine melanomas were implanted into mice ears. Tumors were either treated with MRT (407.6 Gy peak; 6.2 Gy valley dose) or uniform BB irradiation (6.2 Gy). Results: MRT induced significantly longer tumor regrowth delay than did BB irradiation. A significant 24% reduction in blood vessel perfusion was observed 5 days after MRT, and the cell proliferation index was significantly lower in melanomas treated by MRT compared with BB. MRT provoked a greater induction of senescence in melanoma cells. Bio-Plex analyses revealed enhanced concentration of monocyteattracting chemokines in the MRT group: MCP-1 at D5, MIP-1a, MIP-1b, IL12p40,

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Section: Discussionmentioning

confidence: 94%

Section: Dosimetry and Irradiationmentioning

confidence: 99%

Section: Image Acquisition and Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms

Potez

Fernández-Palomo

Bouchet

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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“…13,15 In principal, modern clinical linacs can be made suitable for FLASH therapy, but this requires substantial modification to these clinically optimized systems. 16,17 Moreover, while synchrotrons, notable for their superior beam intensities, 14,18,19 and high-energy cyclotron-accelerated protons are also capable of achieving the requisite dose rates, 20 limited accessibility and high costs remain barriers to their widespread application.…”

Section: Introductionmentioning

confidence: 99%

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

Bazalova‐Carter

Esplen

2019

Medical Physics

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Purpose By means of Monte Carlo (MC) simulations and indirect measurements, we have evaluated the maximum dose rates achievable with conventional x‐ray tubes and related them to FLASH therapy dose rates of >40 Gy/s. Methods Monte Carlo models of two 160 kV x‐ray tubes, the 3‐kW MXR‐160/22 and the 6‐kW MXR‐165, were built in the EGSnrc/BEAMnrc code. The dose rate in a water phantom placed against the x‐ray tube surface, located at 3.7 and 3.5 cm from the focal spot for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively, was calculated with DOSXYZnrc. Dose delivered with the 120‐kV beam in a plastic water phantom for the MXR‐160/22 was measured and calculated. Gafchromic EBT3 films were placed at 15 and 18 mm depths in the plastic water phantom that was irradiated with a low tube current of 0.2 mA for 30 s. Results The maximum 160‐kV phantom surface dose rate was determined to be FLASH capable, calculated as (114.3 ± 0.6) Gy/s and (160.0 ± 0.8) Gy/s for the MXR‐160/22 and MXR‐165 x‐ray tubes, respectively. The dose rate in a 1‐cm diameter region was found to be (110.6 ± 2.8) Gy/s and (151.9 ± 2.6) Gy/s and remained FLASH capable to depths of 1.4 and 2.0 mm for the MXR‐160/22 and MXR‐165 x‐ray tube, respectively. The 120‐kV dose profiles measured with EBT3 films agreed with MC simulations to within 3.6% for regions outside of heel effect and at both measurement depths; this presented a good validation data set for the simulations of phantom surface dose rate using the 160‐kV beam. Conclusions We have indirectly determined that, with a careful experimental design, conventional x‐ray tubes can be made suitable for use in FLASH radiotherapy and dosimetry experiments.

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Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy

Griffin

Ahmed²,

Amendola

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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While the workshop was co-sponsored by the NCI and RSS, the comments in this report are strictly the opinions of the co-authors and does not constitute endorsement of these results and/or treatments by the NCI and RSS or consensus of all the co-authors on each of the points. This report is designed to stimulate further formal research and development to explore the future clinical application of these novel therapies and not for implementation into routine clinical practice.

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Effects of Synchrotron X-Ray Micro-beam Irradiation on Normal Mouse Ear Pinnae

Cited by 21 publications

References 34 publications

Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms

Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms

On the capabilities of conventional x‐ray tubes to deliver ultra‐high (FLASH) dose rates

Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy

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