TY - JOUR
T1 - An integrated method for reproducible and accurate image-guided stereotacti cranial irradiation of brain tumors using the small animal radiation research platform
AU - Baumann, Brian C.
AU - Benci, Joseph L.
AU - Santoiemma, Phillip P.
AU - Chandrasekaran, Sanjay
AU - Hollander, Andrew B.
AU - Kao, Gary D.
AU - Dorsey, Jay F.
N1 - Funding Information:
Address all correspondence to: Jay F. Dorsey, MD, PhD, Department of Radiation Oncology, Perelman Center for Advanced Medicine, TRC2W, 3400 Civic Center Blvd, Philadelphia, PA 19104. E-mail: [email protected] 1The authors acknowledge the support of Dr Ann Kennedy and the grant submitted by Drs Cameron Koch and Costas Koumenis, which funded the purchase of the Small Animal Radiation Research Platform used in the experiments described in this article. B.C.B. was supported by the Radiation Biology training grant C5T32CA009677. J.L.B. was supported by the SUPERs grant 5 R25 CA140116-03. J.F.D. was supported by a Burroughs Wellcome Career Award for Medical Scientists (1006792). This work was supported by the National Institutes of Health (RC1 CA145075 and K08 NS076548-01). A patent application for the novel stereotactic mouse restrainer is in preparation. Received 5 March 2012; Revised 23 May 2012; Accepted 24 May 2012 Copyright © 2012 Neoplasia Press, Inc. Open access under CC BY-NC-ND license. 1944-7124/12 DOI 10.1593/tlo.12136
PY - 2012/8
Y1 - 2012/8
N2 - Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT's resultant histologic and BBB changes, may aid future brain tumor research.
AB - Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT's resultant histologic and BBB changes, may aid future brain tumor research.
UR - http://www.scopus.com/inward/record.url?scp=84865484225&partnerID=8YFLogxK
U2 - 10.1593/tlo.12136
DO - 10.1593/tlo.12136
M3 - Article
C2 - 22937174
AN - SCOPUS:84865484225
SN - 1936-5233
VL - 5
SP - 230
EP - 237
JO - Translational Oncology
JF - Translational Oncology
IS - 4
ER -