Preferential Effect of Synchrotron Microbeam Radiation Therapy on Intracerebral 9L Gliosarcoma Vascular Networks

Bouchet, Audrey; Lemasson, Benjamin; Duc, Géraldine Le; Maisin, Cécile; Bräuer-Krisch, Elke; Siegbahn, Albert; Renaud, Luc; Khalil, Enam A.; Rémy, Chantal; Poillot, Cathy; Bravin, A.; Laissue, Jean A.; Barbier, Emmanuel; Serduc, Raphaël

doi:10.1016/j.ijrobp.2010.06.021

Cited by 151 publications

(204 citation statements)

References 23 publications

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“…These treatment fields selectively destroy tumor tissue 2 , 3 , 4 while leaving penetrated healthy tissue unimpaired 5 , 6 . The remarkable resistance of normal tissue to microbeams has been demonstrated in various preclinical studies, beginning with neutron beams in the 1960s (Refs.…”

Section: Introductionmentioning

confidence: 99%

“…The remarkable resistance of normal tissue to microbeams has been demonstrated in various preclinical studies, beginning with neutron beams in the 1960s (Refs. 7, 8, 9, 10) to synchrotron generated photon beams in the last 25 years 2 , 5 , 6 , 11 , 12 …”

Section: Introductionmentioning

confidence: 99%

“…Manifold evidence indicates that blood vessels and their different repair efficiencies in malignant and healthy tissue are essential to explain the differential effect of microbeams 2 , 4 , 5 , 13 . Apart from that experiments demonstrate that bystander signals, 14 , 15 changes in the immune response, DNA repair, and variations in the cell cycle 16 are important for the biological response to MRT.…”

Section: Introductionmentioning

confidence: 99%

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A preclinical microbeam facility with a conventional x‐ray tube

et al. 2016

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Purpose:Microbeam radiation therapy is an innovative treatment approach in radiation therapy that uses arrays of a few tens of micrometer wide and a few hundreds of micrometer spaced planar x‐ray beams as treatment fields. In preclinical studies these fields efficiently eradicated tumors while normal tissue could effectively be spared. However, development and clinical application of microbeam radiation therapy is impeded by a lack of suitable small scale sources. Until now, only large synchrotrons provide appropriate beam properties for the production of microbeams.Methods:In this work, a conventional x‐ray tube with a small focal spot and a specially designed collimator are used to produce microbeams for preclinical research. The applicability of the developed source is demonstrated in a pilot in vitro experiment. The properties of the produced radiation field are characterized by radiochromic film dosimetry.Results:50 μm wide and 400 μm spaced microbeams were produced in a 20 × 20 mm2 sized microbeam field. The peak to valley dose ratio ranged from 15.5 to 30, which is comparable to values obtained at synchrotrons. A dose rate of up to 300 mGy/s was achieved in the microbeam peaks. Analysis of DNA double strand repair and cell cycle distribution after in vitro exposures of pancreatic cancer cells (Panc1) at the x‐ray tube and the European Synchrotron leads to similar results. In particular, a reduced G2 cell cycle arrest is observed in cells in the microbeam peak region.Conclusions:At its current stage, the source is restricted to in vitro applications. However, moderate modifications of the setup may soon allow in vivo research in mice and rats.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A preclinical microbeam facility with a conventional x‐ray tube

et al. 2016

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“…MRT involves the application of an array of spatially fractionated microbeams sourced from third generation synchrotrons, with beam widths ranging from 25 to 75 µm, and a pitch of 200-400 µm [2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…The key advantage of MRT arises from the reported increase in sensitivity of tumour tissue to the microbeam array, which differs to the observed recovery of normal tissue [9][10][11][12][13][14][15][16][17]. Radiation treatments for radioresistant tumours such as gliomas, require extremely high absorbed doses [15,16], yet with their development in sensitive brain tissue, large doses cannot be administered without significant damage.…”

Section: Introductionmentioning

confidence: 99%

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

et al. 2016

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Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta 2 O 5 nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta 2 O 5 NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta 2 O 5 NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70 keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100 keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta 2 O 5 NP distributions within 9L cancer cells. Disciplines Engineering | Science and Technology Studies Publication DetailsEngels, E., Corde, S., McKinnon, S., Incerti, S., Konstantinov, K., Rozenfeld, A., Tehei, M., . Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy. Physica Medica: an international journal devoted to the applications of physics to medicine and biology, 32 (12)

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Identification of AREG and PLK1 pathway modulation as a potential key of the response of intracranial 9L tumor to microbeam radiation therapy

Bouchet

Sakakini

Atifi

et al. 2014

Intl Journal of Cancer

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Synchrotron microbeam radiation therapy (MRT) relies on the spatial fractionation of a synchrotron beam into parallel micronwide beams allowing deposition of hectogray doses. MRT controls the intracranial tumor growth in rodent models while sparing normal brain tissues. Our aim was to identify the early biological processes underlying the differential effect of MRT on tumor and normal brain tissues. The expression of 28,000 transcripts was tested by microarray 6 hr after unidirectional MRT (400 Gy, 50 mm-wide microbeams, 200 mm spacing). The specific response of tumor tissues to MRT consisted in the significant transcriptomic modulation of 431 probesets (316 genes). Among them, 30 were not detected in normal brain tissues, neither before nor after MRT. Areg, Trib3 and Nppb were down-regulated, whereas all others were up-regulated. Twenty-two had similar expression profiles during the 2 weeks observed after MRT, including Ccnb1, Cdc20, Pttg1 and Plk1 related to the mitotic role of the Pololike kinase (Plk) pathway. The up-regulation of Areg expression may indicate the emergence of survival processes in tumor cells triggered by the irradiation; while the modulation of the "mitotic role of Plk1" pathway, which relates to cytokinetic features of the tumor observed histologically after MRT, may partially explain the control of tumor growth by MRT. The identification of these tumor-specific responses permit to consider new strategies that might potentiate the antitumoral effect of MRT.Microbeam radiation therapy (MRT) is a novel form of preclinical radiotherapy based on the spatial fractionation of an incident synchrotron beam into arrays of parallel microbeams, which are typically few tens microns wide and separated on centre by few hundred microns (for review 1 ). This unique irradiation geometry allows the deposition of hectogray doses in tumors. Remarkably, brain tumors can be palliated by MRT in small animals with limited damage to normal cerebral tissues.2,3 This differential effect relates to the radioresistance of normal brain vessels to MRT for doses up to 1,000 Gy 4,5 , whereas MRT induces a denudation of tumor vessel endothelium, a decrease in tumor blood volume, 6,7 and tumor hypoxia.7 However, other mechanisms may contribute to the differential effects of MRT on tumor vs. normal tissues, e.g., direct impact of ionising radiation on tumor cells occurring before the vascular effect 6 and communication between lethally irradiated cells in the microbeam's path and less damaged cells sited in-between.8 All biological mechanisms underlying these differential effects remain to identify.Increasing the knowledge about the differential response between normal and tumor tissue to MRT is crucial because the identification of processes highly specific for the tumor tissue could be exploited to increase tumor control without disturbing the repair and maintenance of surrounding normal brain tissues. Specific cellular and molecular responses could be used to design efficient and safe adjuvant therapies.We have recently d...

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Preferential Effect of Synchrotron Microbeam Radiation Therapy on Intracerebral 9L Gliosarcoma Vascular Networks

Cited by 151 publications

References 23 publications

A preclinical microbeam facility with a conventional x‐ray tube

A preclinical microbeam facility with a conventional x‐ray tube

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Identification of AREG and PLK1 pathway modulation as a potential key of the response of intracranial 9L tumor to microbeam radiation therapy

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