Microbeam Radiation-Induced Tissue Damage Depends on the Stage of Vascular Maturation

Sabatasso, Sara; Laissue, Jean A.; Hlushchuk, Ruslan; Graber, Werner; Bravin, A.; Bräuer-Krisch, Elke; Corde, Stéphanie; Blattmann, H.; Gruber, Guenther; Djonov, Valentin

doi:10.1016/j.ijrobp.2011.03.018

Cited by 58 publications

(68 citation statements)

References 30 publications

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“…The CAM vasculature recovered rapidly and only small defects were detectable in the capillary plexus 24 h after 300 Gy MBI. The vascular pattern appeared similar to that of the non-irradiated CAMs [15]. Microscopic and ultrastructural observations showed a destruction of the plexus of immature capillaries in the irradiated zone while the capillaries were preserved in between (Fig.…”

Section: Microbeam Radiation-induced Damage Depends On the Vascular Msupporting

confidence: 57%

“…A CAM is an almost pure avian vascular system in which immature vessels, lacking periendothelial coverage, mature within few days to vessels with such coverage [15]. CAMs cultivated in Petri dishes were irradiated with microplanar beams (width,~25 mm; interbeam spacing,~200 mm) at entrance doses of 200 Gy.…”

Section: Microbeam Radiation-induced Damage Depends On the Vascular Mmentioning

confidence: 99%

“…Uni-or bidirectional MRT reduced or even stopped the growth of tumors such as the EMT6 murine mammary carcinoma [7], an aggressive mouse model of squamous cell carcinoma [8], and of 9L intracerebral gliosarcoma in rats [3,9e12]. The tolerance of normal tissues to microbeam irradiation (MBI) was surprisingly high in the rat skin [13], fast-growing immature tissues such as the duck brain in ovo [14], the chick chorioallantoic membrane (CAM) [15] and, the in vivo cerebella of normal, suckling SpragueeDawley rat pups [16], as well as adult rat and mouse brains [3,5,17,18] and in normal weanling piglet cerebella [19,20] (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

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Effects of microbeam radiation therapy on normal and tumoral blood vessels

et al. 2015

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Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.

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Section: Microbeam Radiation-induced Damage Depends On the Vascular Msupporting

confidence: 57%

Section: Microbeam Radiation-induced Damage Depends On the Vascular Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of microbeam radiation therapy on normal and tumoral blood vessels

et al. 2015

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“…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%

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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“…MRT delivers high doses, e.g., Ͼ 100 Gy, of synchrotrongenerated X-rays through arrays of 25 -500 μ m-wide parallel microbeams separated by 200 -2000 μ m (center to center of the beam openings) (Serduc et al 2006, Sabatasso et al 2011. Th e high fl ux synchrotron radiation is delivered extremely rapidly, usually within 1 s, to target volume, thereby avoiding smear out of beam collimation caused by tissue movement.…”

Section: Introductionmentioning

confidence: 99%