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Sarrp irradiator

Manufactured by Xstrahl
Sourced in United Kingdom

The SARRP (Small Animal Radiation Research Platform) is a specialized irradiator designed for pre-clinical research applications. It is capable of delivering precise and targeted radiation doses to small animal models, enabling researchers to study the effects of radiation on biological systems.

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5 protocols using sarrp irradiator

1

SMSM-167 and Radiotherapy for U87-Luc Tumors

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Example 23

Study Aim

To evaluate efficacy of SMSMs in Subcutaneous U87-Luc Brain Tumor Model in combination with radiotherapy

Experimental Design

Subcutaneous U87-Luc Brain Tumor Model in Ncr Nude Mice: tumor inoculation on Day 0; compound treatment initiation at 100 mm3 (Day 0), twice daily by oral gavage; radiotherapy treatment on Day 3. The radiotherapy treatment (10 Gy) was conducted using Image Guided Small Animal Radiation Research Platform (SARRP) irradiator (Xstrahl Limited, GU15 3YL).

Experimental Groups

The experimental groups used in this study are shown in the table below. Results are shown in FIGS. 24A and 24B.

Treatment 1
Group# MiceTreatment 1ScheduleTreatment 2Treatment 2 Schedule
Group 15NoneNAVehicleBID from Day 0 for the
duration of the study
Group 25NoneNASMSM-167, BID from Day 0 for the
5 mg/kgduration of the study
Group 3510 GyDay 3VehicleBID from Day 0 for the
duration of the study
Group 4510 GyDay 3SMSM-167,BID from Day 0 for the
5 mg/kgduration of the study

The examples and embodiments described herein are for illustrative purposes only and various modifications or changes suggested to persons skilled in the art are to be included within the spirit and purview of this application and scope of the appended claims.

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2

Evaluating Anti-VEGFR2 and Anti-Dll4 Antibodies in Tumor Radiotherapy

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Animals with tumors approximately 100 mm3 in the chamber were administered with either anti-mouse vascular endothelial growth factor receptor 2 (VEGFR2) antibody [27 mg/kg; clone DC101 (37 (link)), BioXCell], anti-mouse Dll4 antibody (39 (link)) twice per week at a dose of 5 mg/kg (in two doses on the initial day of imaging and 3 days later), or one of two radiation treatments. For the radiation treatments, mice were anesthetized under inhalation with isoflurane and placed in an imaging-guided small animal radiation research platform (SARRP) irradiator (Xstrahl Ltd). A Cone Beam CT (computerized tomography) scan of each mouse was obtained, and the treatment was planned using MuriPlan (Xstrahl Ltd). The SARRP was used to deliver 15 Gy of x-rays (220–kilovolt peak copper-filtered beam with half-value layer of 0.93 mmCu) to the tumor at 2 Gy/min. This was given either in a single dose or at five daily fractionations of 3 Gy of x-ray radiation to the tumor. Dosimetry of the irradiator was performed as previously described (66 (link)).
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3

Small Animal Irradiation Protocols

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EBRT treatments (220 kVp X-rays; half-value layer of 0.93 mmCu; 2 Gy/min; 14 mm × 7 mm field at the isocentre) were given using a small animal radiation research platform (SARRP) irradiator, (Xstrahl Ltd, Camberley, Surrey, UK). Dosimetric measurements for this collimator were performed using EBT3 film (Ashland ISP Advanced Materials, Wayne, NJ) that was calibrated against absolute measurements following the recommendations of the report of the American Association of Physicists in Medicine Task Group 61 [13] (link). MR images were used to identify and delineate the tumour volume using a custom made cradle [12] , which allowed animals to be transported and mounted on the SARRP irradiator with minimal movement between procedures. A cone beam CT (CBCT) image was acquired using the SARRP and co-registered with the MR image using in-house MATLAB® (MathWorks, Natis, MA, USA) software based on the Modality Independent Neighbourhood Descriptor (MIND) algorithm for multi-modal deformable registration to compensate for the non-linear spatial distortions inherent in MR imaging [14] (link) (see Supplementary Fig. 1). Treatment planning and subsequent beam delivery was performed using Muriplan (Xstral Ltd, Camberley, Surrey, UK) [15] (link), with segmentation performed using the CBCT image; and targeting and planning using the combined MRI-CBCT image.
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4

Precise Image-Guided Tumor Irradiation in Mice

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Mice were anesthetized under inhalation with isoflurane and placed in an imaging‐guided small animal radiation research platform (SARRP) irradiator (Xstrahl Ltd). A cone beam CT image of each mouse was obtained, and the treatment was planned using Muriplan (Xstrahl Ltd) to ensure uniformity of dose across the tumor while sparing the surrounding normal tissue. This was achieved using a coronal arc beam with the isocenter positioned a few millimeters above the glass window with a beam at an angle of 65° to the vertical and the mouse rotated through 360° horizontally. To achieve full coverage of the tumor, a 4 mm × 10 mm field size (defined as the isocenter and the long axis parallel to the mouse) was chosen. The SARRP was used to deliver 15 Gy of X‐rays (220 kVp copper‐filtered beam with HVL of 0.93 mmCu) to the tumor at ~2 Gy per minute; this was given either in a single fraction or five daily fractionations of 3 Gy X‐ray radiation to the tumor. Dosimetry of the irradiator was performed as previously (Hill et al, 2017 (link)). A visualization of the planned dose distribution is presented in Appendix Fig S4.
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5

Dietary Fiber Modulation of Radiation Toxicity

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At six to 7 weeks of age, C57BL/6 female mice started receiving either a low-fibre (0.2% cellulose) or high-fibre diets including 5% psyllium, 5% psyllium plus 10% RS or 5% psyllium plus 10% inulin for a maximum time of 9 weeks followed by normal chow for another 12 weeks. All diets are isocaloric, approximately 4 kcal/g, and details of the diet formulae are listed in Supplementary Table S5 (Research Diets Inc, USA). For acute toxicity experiment, two and a half weeks after commencing the modified diets, mice were treated supine with 10, 12 or 14 Gy of X-rays (220 kVp, 13.0 mA copper filtered beam with a measured half-value layer (HVL) of 0.84 mmCu) to the lower abdomen, including the lower small intestine using a SARRP irradiator (Xstrahl Ltd, Camberley, UK). For late toxicity experiments, 2 weeks after commencing the modified diets, mice were treated supine using a SARRP with 5 Gy for 5 consecutive days, using a 356° arc treatment and 8.5-mm collimator, with the isocentre positioned at the posterior caudal bladder wall covering the lower large intestine, to avoid the small intestine. In both experiments, small and large intestines were collected using the ‘Swiss roll technique’ described in (Moolenbeek and Ruitenberg, 1981) [67 (link)].
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