An Integrated Method for Reproducible and Accurate Image-Guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform

Baumann, Brian C.; Benci, Joseph L.; Santoiemma, Phillip P.; Chandrasekaran, S.; Hollander, Andrew; Kao, Gary D.; Dorsey, Jay F.

doi:10.1593/tlo.12136

Cited by 35 publications

(45 citation statements)

References 13 publications

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“…The light emission is highly localized to the tumor inoculation site, confirming the absence of tumor dissemination to other areas such as the spine. As reported previously [35], we verified that our tumor models closely recapitulated histological phenotypes consistent with those of human GBM; and we provide a representative T2-weighted MRI image of an implanted orthotopic GBM tumor in Figure 5C.…”

Section: Resultssupporting

confidence: 87%

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

et al. 2013

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Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

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Section: Resultssupporting

confidence: 87%

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

et al. 2013

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“…A representative histological section of an orthotopically placed GBM tumor used in our experiments is shown in Figure 3(b); the cellular atypia and hyperchromaticity of the tumor tissue is evident in comparison with adjacent normal brain tissue. Orthotopic xenografts of U251 cells in mice have been shown in our laboratory and by others to recapitulate the relevant pathobiological features of human GBM; 39 thus, such preclinical models can provide valuable prognostic insight into behavior and response of these tumors to treatment. BLI imaging was successfully used to serially monitor tumor growth in orthotopic models (Figs.…”

Section: Resultsmentioning

confidence: 95%

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

Sun¹,

Joh²,

Al-Zaki³

et al. 2016

j biomed nanotechnol

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109

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The treatment of glioblastoma multiforme, the most prevalent and lethal form of brain cancer in humans, has been limited in part by poor delivery of drugs through the blood-brain barrier and by unclear delineation of the extent of infiltrating tumor margins. Nanoparticles, which selectively accumulate in tumor tissue due to their leaky vasculature and the enhanced permeability and retention effect, have shown promise as both therapeutic and diagnostic agents for brain tumors. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been leveraged as T2-weighted MRI contrast agents for tumor detection and imaging; and gold nanoparticles (AuNP) have been demonstrated as radiosensitizers capable of propagating electron and free radical-induced radiation damage to tumor cells. In this study, we investigated the potential applications of novel gold and SPION-loaded micelles (GSMs) coated by polyethylene glycol-polycaprolactone (PEG-PCL) polymer. By quantifying gh2ax DNA damage foci in glioblastoma cell lines, we tested the radiosensitizing efficacy of these GSMs, and found that GSM administration in conjunction with radiation therapy (RT) led to ~2-fold increase in density of double-stranded DNA breaks. For imaging, we used GSMs as a contrast agent for both computed tomography (CT) and magnetic resonance imaging (MRI) studies of stereotactically implanted GBM tumors in a mouse model, and found that MRI but not CT was sufficiently sensitive to detect and delineate tumor borders after administration and accumulation of GSMs. These results suggest that with further development and testing, GSMs may potentially be integrated into both imaging and treatment of brain tumors, serving a theranostic purpose as both an MRI-based contrast agent and a radiosensitizer.

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“…This set-up consists of a single, anterior 225kV, 15mA x-ray beam with a 0.15mm Cu at an SSD of 35cm that is designed to accurately reproduce the internal radiation dose distribution in mice that were used in previous studies [21,22,27]. The dosimetry and shielding of this system has been tested extensively [28]. The dose of radiation is a single fraction delivered via single AP (anterior-posterior) approach.…”

Section: Methodsmentioning

confidence: 99%

Radiation mitigating properties of the lignan component in flaxseed

et al. 2013

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BackgroundWholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy.MethodsWe evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival.ResultsFLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60–73.3% survival in mice fed 10%-20% FLC initiated 24–72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet.ConclusionsDietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.

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An Integrated Method for Reproducible and Accurate Image-Guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform

Cited by 35 publications

References 13 publications

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme

Radiation mitigating properties of the lignan component in flaxseed

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