Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

Lee, David Y.; Chunta, John L.; Park, Sean S.; Huang, Jiayi; Martínez, Álvaro; Grills, I.S.; Krueger, S.A.; Wilson, George D.; Marples, Brian

doi:10.1016/j.ijrobp.2013.04.034

Cited by 27 publications

(22 citation statements)

References 20 publications

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“…In the second line (d-f), growth of U87MG tumor cells in the basal ganglia of a untreated mouse without central tumor necrosis and normal contrast enhancement is shown micro-CT-derived tumor volumes and histological analyses in a rat glioma model [5]. Micro-CT imaging of brain tumor growth in live mice has been reported sporadically [9][10][11][12] and most notably in combination with other modalities (e.g. PET) [9][10][11]24].…”

Section: Discussionmentioning

confidence: 93%

“…Micro-CT imaging of brain tumor growth in live mice has been reported sporadically [9][10][11][12] and most notably in combination with other modalities (e.g. PET) [9][10][11]24]. Interestingly, a clinical CT scanner has been used to verify the presence of intracerebral tumors in live mice [25], but the authors did not seem to try to perform volumetric analyses of these data.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor volumetry of micro-CT images was performed by drawing the outlines of the contrasted regions of interest (ROIs) in coronar sections using OsiriX freeware. Subsequently the volume of interest (VOI) was ascertained by applying a wrapping calculation to the previously measured regions of interest [10,11]. Tumor diameter of micro-CT images was measured according to the RANO criteria using OsiriX (i.e.…”

Section: Bioluminescence Imaging (Bli)mentioning

confidence: 99%

“…Thus few studies describe the use of micro-CT for in vivo imaging of orthotopic glioma xenografts in rats [5][6][7][8] as a stand alone technique or in combination with other techniques. Likewise, only few studies report the use of this method in live mice [9][10][11][12] and there is a lack of data regarding the diagnostic accuracy of micro-CT imaging of orthotopic glioma in live mice.…”

Section: Introductionmentioning

confidence: 99%

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In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging

et al. 2015

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Small animal imaging is of increasing relevance in biomedical research. Studies systematically assessing the diagnostic accuracy of contrast-enhanced in vivo micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/γc(-/-) mice (n = 27) underwent intracerebral implantation of 2.5 × 10(6) GFP-Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI) to detect tumor growth and afterwards repeated contrast-enhanced (300 µl Iomeprol i.v.) micro-CT imaging (80 kV, 75 µAs, 360° rotation, 1,000 projections, 33 s scan time, resolution 40 × 40 × 53 µm, 0.5 Gy/scan). Presence of tumors, tumor diameter and tumor volume in micro-CT were rated by two independent readers. Results were compared with histological analyses. Six mice with tumors confirmed by micro-CT received fractionated irradiation (3 × 5 Gy every other day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor volume was 30 ± 33 mm(3), and the smallest detectable tumor measured 360 × 620 µm. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21 after tumor implantation had a sensitivity and specificity of 0.90 and 1.0, respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro-CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor growth in live mice is feasible at high sensitivity levels and with excellent inter-rater agreement and allows visualization of radiation effects.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Bioluminescence Imaging (Bli)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging

et al. 2015

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“…Tumor volumetry was performed by contouring contrast-enhancing regions of interest (ROIs) in coronal sections. Subsequently the volume of interest (VOI) was ascertained by applying a wrapping calculation to the previously measured regions of interest [33, 34]. …”

Section: Methodsmentioning

confidence: 99%

Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology

et al. 2016

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PurposeThere is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated.Materials and Methods2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18).ResultsTumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively.ConclusionClinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice.

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Improving control of high‐grade glioma by ultra‐hyper‐fractionated radiotherapy

Fròsina

2022

J of Neuroscience Research

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Ionizing radiation is a mainstay of high‐grade glioma therapy. The current standard radiotherapeutic schedule involves a total 60 Gy split in 2.0 Gy fractions delivered on weekdays for six weeks. Thereafter, almost invariably the tumor relapses and progresses. In vitro studies have demonstrated that the therapeutic effectiveness of ionizing radiation towards high‐grade glioma cells is greatly increased by splitting the total dose in fractions ten times smaller [0.1–0.5 Gy instead of standard 2.0 Gy—ultra‐hyper‐fractionated radiotherapy (ultra‐hyper‐FRT)]. Recently, it became possible to consistently translate this therapeutic effect to the animal setting, by using glioma‐initiating cell‐driven faithful animal modeling. A re‐analysis of the literature reporting radiotherapeutic clinical trials also suggests that the lower the average fraction size, the higher is the achievable overall survival of patients. However, average fraction sizes ≤ 0.5 Gy have never been thoroughly investigated in the clinics. We propose to study in the clinical setting the therapeutic effect of an ultra‐hyper‐FRT schedule promptly extending the conventional radiation component of the current guidelines (“Stupp”) therapeutic protocol.

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Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

Cited by 27 publications

References 20 publications

In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging

In vivo micro-CT imaging of untreated and irradiated orthotopic glioblastoma xenografts in mice: capabilities, limitations and a comparison with bioluminescence imaging

Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology

Improving control of high‐grade glioma by ultra‐hyper‐fractionated radiotherapy

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