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

• Published in: International journal of radiation oncology, biology, physics Vol. 78; no. 5; pp. 1503 - 1512
• Main Authors: Bouchet, Audrey, M.S, Lemasson, Benjamin, M.S, Le Duc, Géraldine, Ph.D, Maisin, Cécile, M.S, Bräuer-Krisch, Elke, M.S, Siegbahn, Erik Albert, Ph.D, Renaud, Luc, Khalil, Enam, Ph.D, Rémy, Chantal, Ph.D, Poillot, Cathy, M.S, Bravin, Alberto, Ph.D, Laissue, Jean A., M.D, Barbier, Emmanuel L., Ph.D, Serduc, Raphaël, Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2010; Elsevier
• Subjects: ANIMAL TISSUES; ANIMALS; BEAMS; Biological and medical sciences; BIOLOGICAL MATERIALS; BLOOD; BLOOD VESSELS; BODY; BODY FLUIDS; BRAIN; Brain - blood supply; Brain Edema; Brain Edema - diagnosis; Brain Edema - etiology; Brain Neoplasms; Brain Neoplasms - blood supply; Brain Neoplasms - mortality; Brain Neoplasms - pathology; BREMSSTRAHLUNG; Capillary Permeability; Capillary Permeability - radiation effects; CARDIOVASCULAR SYSTEM; CENTRAL NERVOUS SYSTEM; Cerebral Arteries; Cerebral Arteries - radiation effects; Cerebral Veins; Cerebral Veins - radiation effects; Cerebrovascular Circulation; Cerebrovascular Circulation - radiation effects; DIAGNOSTIC TECHNIQUES; DISEASES; Diseases of the nervous system; EDEMA; ELECTROMAGNETIC RADIATION; ENDOTHELIUM; Gliosarcoma; Gliosarcoma - blood supply; Gliosarcoma - mortality; Gliosarcoma - pathology; GROWTH FACTORS; Hematology, Oncology and Palliative Medicine; Intracerebral 9L gliosarcoma; Life Sciences; Magnetic Resonance Imaging; MAMMALS; MATERIALS; Medical sciences; Medicin och hälsovetenskap; MEDICINE; MITOGENS; Monte Carlo Method; NEOPLASMS; NERVOUS SYSTEM; Neurology; Neurons and Cognition; NMR IMAGING; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PERMEABILITY; PHOTON BEAMS; PHYSICAL PROPERTIES; PROTEINS; Radiation Tolerance; RADIATIONS; RADIOLOGY; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); RATS; Rats, Inbred F344; RODENTS; SURVIVAL TIME; SYMPTOMS; Synchrotron Microbeam radiation therapy; SYNCHROTRON RADIATION; Synchrotrons; THERAPY; Tumor Burden; tumor vasculature; Vascular diseases and vascular malformations of the nervous system; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - metabolism; VERTEBRATES; Intracerebral 9L gliosarcoma; tumor vasculature; Synchrotron Microbeam radiation therapy; Nervous system diseases; Sarcoma; Toxicity; Malignant tumor; Intracerebral; Radiotherapy; Encephalon; Vascularization; Treatment; Synchrotrons; Animal; Blood vessel; Radiation effect; Circulatory system; Gliosarcoma; Cancer; Synchrotron Microbeam radiation therapy/intracerebral 9L gliosarcoma/tumor vasculature
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2010.06.021

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 × 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 (×3.25), 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.