An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

Ibahim, Mohammad Johari; Crosbie, Jack; Yang, Yuqing; Zaitseva, Marina; Stevenson, A. W.; Rogers, Peter A. W.; Paiva, Premila

doi:10.1371/journal.pone.0100547

Cited by 45 publications

(28 citation statements)

References 30 publications

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“…Recently, Ibahim et al . conducted serial cell irradiation studies to evaluate the equivalence between synchrotron MRT and conventional BRT, and reported that BRT doses of 3.4 ± 0.1 Gy were radiobiologically equivalent to a peak microbeam dose of 112 Gy (25 µm wide spaced, 175 µm on center) using clonogenic assays on EMT6.5ch cells (43), which is much lower than the integrated MRT dose. On the other hand, the in vitro cell radiation study could not truly represent in vivo irradiation where possible bystander effects and vascular network factors might greatly influence the final efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…It is still debatable which dose level of broad-beam radiation can be used for a comparison with the MRT study. The dose level of 10 Gy was chosen for BRT in the study mainly because it has been widely used in small animal studies with single-fraction conventional radiation (38, 43, 44). Our study showed that 10 Gy of BRT led to a survival extension similar to MRT.…”

Section: Discussionmentioning

confidence: 99%

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Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

et al. 2015

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

et al. 2015

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“…It remains unresolved as to the choice of radiation doses for the comparative investigation of the effects of MRT and CRT (18). In our recent work, we found that the integrated dose was not a useful indicator of the biological equivalence of MRT and CRT treatment and the MRT valley dose alone does not determine the acute cellular response to MRT (29). Future in vitro and in vivo studies based on the biological equivalence of MRT and CRT are warranted.…”

Section: Gene Expression and Pathway Analysis After Mrtmentioning

confidence: 90%

In Vitro Study of Genes and Molecular Pathways Differentially Regulated by Synchrotron Microbeam Radiotherapy

et al. 2014

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The aim of this study was to identify genes and molecular pathways differentially regulated by synchrotron-generated microbeam radiotherapy (MRT) versus conventional broadbeam radiotherapy (CRT) in vitro using cultured EMT6.5 cells. We hypothesized (based on previous findings) that gene expression and molecular pathway changes after MRT are different from those seen after CRT. We found that at 24 h postirradiation, MRT exerts a broader regulatory effect on multiple pathways than CRT. MRT regulated those pathways involved in gene transcription, translation initiation, macromolecule metabolism, oxidoreductase activity and signaling transduction in a different manner compared to CRT. We also found that MRT/CRT alone, or when combined with inflammatory factor lipopolysaccharide, upregulated expression of Ccl2, Ccl5 or Csf2, which are involved in host immune cell recruitment. Our findings demonstrated differences in the molecular pathway for MRT versus CRT in the cultured tumor cells, and were consistent with the idea that radiation plays a role in recruiting tumor-associated immune cells to the tumor. Our results also suggest that a combination of MRT/CRT with a treatment targeting CCL2 or CSF2 could repress the tumor-associated immune cell recruitment, delay tumor growth and/or metastasis and yield better tumor control than radiation alone.

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“…As a result, a uniform dose distribution inside the tumor is reached ( 37 ) while the surrounding normal tissue out of the “cross-firing” range still receive largely MRT radiation pattern of peaks and valleys. In a synchrotron-MRT study Ibahim et al (38) reported that valley dose is closely correlated with cell survival, but valley dose alone does not determine the observed radiobiological effects. Our study shows that the tumor EUD (a=−10) and minimum/valley tumor dose have the highest linear associations (R 2 =0.7923, F-stat=15.26*; R 2 =0.7636, F-stat=12.92*, respectively) with tumor treatment response (Fig 7 and S1 Table).…”

Section: Discussionmentioning

confidence: 99%

Conventional dose rate spatially-fractionated radiation therapy (SFRT) treatment response and its association with dosimetric parameters – A preclinical study in a Fisher 344 rat model

Rivera

Kierski

Kasoji

et al. 2020

Preprint

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2728 Abstract 29 Purpose: To identify key dosimetric parameters that have close associations with tumor treatment 30 response and body weight change in SFRT treatments with a large range of spatial-fractionation 31 scale at dose rates of several Gy/min. 32 Methods: Six study arms using uniform tumor radiation, half-tumor radiation, 2mm beam array 33 radiation, 0.3mm minibeam radiation, and an untreated arm were used. All treatments were 34 delivered on a 320kV x-ray irradiator. Forty-two female Fischer 344 rats with fibrosarcoma tumor 35 allografts were used. Dosimetric parameters studied are peak dose and width, valley dose and 36 width, peak-to-valley-dose-ratio, volumetric average dose, percentage volume directly irradiated, 37 and tumor-and normal-tissue EUD. Animal survival, tumor volume change, and body weight 38 change (indicative of treatment toxicity) are tested for association with the dosimetric parameters 39 using linear regression and Cox Proportional Hazards models.

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An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

Cited by 45 publications

References 30 publications

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

In Vitro Study of Genes and Molecular Pathways Differentially Regulated by Synchrotron Microbeam Radiotherapy

Conventional dose rate spatially-fractionated radiation therapy (SFRT) treatment response and its association with dosimetric parameters – A preclinical study in a Fisher 344 rat model

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