title: Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.
abstract: Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.
authors: a  Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|b  Biomedical Imaging Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Hong
authors: H
authors: Yuan
authors: c  Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Lei
authors: L
authors: Zhang
authors: b  Biomedical Imaging Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Jonathan E
authors: JE
authors: Frank
authors: c  Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Christina R
authors: CR
authors: Inscoe
authors: d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Laurel M
authors: LM
authors: Burk
authors: d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Mike
authors: M
authors: Hadsell
authors: a  Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|b  Biomedical Imaging Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|e  Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|g  Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Yueh Z
authors: YZ
authors: Lee
authors: c  Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Jianping
authors: J
authors: Lu
authors: d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|e  Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|f  Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|g  Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Sha
authors: S
authors: Chang
authors: c  Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|d  Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.|g  Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors: Otto
authors: O
authors: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy*; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage; D006657:Histones / Q000032:analysis; D006801:Humans; D008297:Male; D051379:Mice; D037742:Nanotubes, Carbon; D011829:Radiation Dosage; D011878:Radiotherapy / Q000295:instrumentation
chemical_list: D006657:Histones; D037742:Nanotubes, Carbon; C475961:gamma-H2AX protein, mouse