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

Journal Article · Wed Dec 01 04:00:00 EST 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.06.021· OSTI ID:21491519

Bouchet, Audrey ^[1]; Lemasson, Benjamin ^[2]; Le Duc, Geraldine ^[1]; Maisin, Cecile ^[2]; Braeuer-Krisch, Elke ^[1]; Siegbahn, Erik Albert ^[3]; Renaud, Luc ^[4]; CerCo, Toulouse ^[5]; Khalil, Enam ^[6]; Remy, Chantal; Poillot, Cathy ^[2]; Bravin, Alberto ^[1]; Laissue, Jean A ^[7]; Barbier, Emmanuel L ^[2]; Serduc, Raphael ^[1]

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1. ESRF, Grenoble (France)
2. INSERM, U836, Grenoble (France)
3. Department of Medical Physics, Karolinska Hospital, Stockholm (Sweden)
4. Universite de Toulouse, UPS, Toulouse (France) and Centre de Recherche Cerveau et Cognition (France) and CNRS
5. France
6. Faculty of Pharmacy, University of Jordan, Amman (Jordan)
7. Institute of Pathology, University of Bern (Switzerland)

Purpose: Synchrotron microbeam radiation therapy (MRT) relies on spatial fractionation of the incident photon beam into parallel micron-wide beams. Our aim was to analyze the effects of MRT on normal brain and 9L gliosarcoma tissues, particularly on blood vessels. Methods and Materials: Responses to MRT (two arrays, one lateral, one anteroposterior (2 x 400 Gy), intersecting orthogonally in the tumor region) were studied during 6 weeks using MRI, immunohistochemistry, and vascular endothelial growth factor Western blot. Results: MRT increased the median survival time of irradiated rats (x3.25), significantly increased blood vessel permeability, and inhibited tumor growth; a cytotoxic effect on 9L cells was detected 5 days after irradiation. Significant decreases in tumoral blood volume fraction and vessel diameter were measured from 8 days after irradiation, due to loss of endothelial cells in tumors as detected by immunochemistry. Edema was observed in the normal brain exposed to both crossfired arrays about 6 weeks after irradiation. This edema was associated with changes in blood vessel morphology and an overexpression of vascular endothelial growth factor. Conversely, vascular parameters and vessel morphology in brain regions exposed to one of the two arrays were not damaged, and there was no loss of vascular endothelia. Conclusions: We show for the first time that preferential damage of MRT to tumor vessels versus preservation of radioresistant normal brain vessels contributes to the efficient palliation of 9L gliosarcomas in rats. Molecular pathways of repair mechanisms in normal and tumoral vascular networks after MRT may be essential for the improvement of such differential effects on the vasculature.

• OSTI ID: 21491519
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 78; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL TISSUES
ANIMALS
BEAMS
BIOLOGICAL MATERIALS
BLOOD
BLOOD VESSELS
BODY
BODY FLUIDS
BRAIN
BREMSSTRAHLUNG
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
DIAGNOSTIC TECHNIQUES
DISEASES
EDEMA
ELECTROMAGNETIC RADIATION
ENDOTHELIUM
GROWTH FACTORS
MAMMALS
MATERIALS
MEDICINE
MITOGENS
NEOPLASMS
NERVOUS SYSTEM
NMR IMAGING
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PERMEABILITY
PHOTON BEAMS
PHYSICAL PROPERTIES
PROTEINS
RADIATIONS
RADIOLOGY
RADIOTHERAPY
RATS
RODENTS
SURVIVAL TIME
SYMPTOMS
SYNCHROTRON RADIATION
THERAPY
VERTEBRATES