Lab Anim Res.  2014 Jun;30(2):64-72. 10.5625/lar.2014.30.2.64.

Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model

• Lee SH
• Kim JY
• Lee KC
• Nam JS
• Choi J
• Lee SH
• Sung KH
• Ahn SH

• KMID: 1707445
• DOI: http://doi.org/10.5625/lar.2014.30.2.64

Abstract

This study was conducted to assess the feasibility of image guided radiotherapy (IGRT) for orthotopic 4T1 mouse mammary tumor using linear accelerator (LINAC). Eighteen Balb/C mice were inoculated with 4T1 cells on left mammary fat pad and nine of them were irradiated using LINAC. Tumors, planning target volumes (PTV), bowels adjacent to tumors, bones and lungs were delineated on planning CT images. IGRT plans were generated to irradiate prescription dose to at least 90% of the PTV and then compared with conventional 2-dimensional plans with anterior-posterior and posterior-anterior beams with 5 mm margins (2D AP/PA plan). Homemade dose-build-up-cradle was designed to encompass mouse bed for homogeneous dose build up. To confirm the irradiated dose, tumor doses were measured using diode detector placed on the surface of tumors. Plan comparison demonstrated equivalent doses to PTV while sparing more doses to normal tissues including bowel (from 90.9% to 40.5%, median value of mean doses) and bone marrow (from 12.9% to 4.7%, median value of mean doses) than 2D AP/PA plan. Quality assurance using diode detector confirmed that IGRT could deliver 95.3-105.3% of the planned doses to PTV. Tumors grew 505.2-1185.8% (mean 873.3%) in the control group and 436.1-771.8% (mean 615.5%) in the irradiated group. These results demonstrate that LINAC-based IGRT provides a reliable approach with accurate dose delivery in the radiobiological study for orthotropic tumor model maintaining tumor microenvironment.

Keyword

Image guided radiotherapy; 4T1 mouse mammary tumor; orthotopic tumor model; dose-build-up cradle

MeSH Terms

Adipose Tissue
Animals
Bone Marrow
Lung
Mice*
Particle Accelerators
Prescriptions
Radiotherapy*
Tumor Microenvironment

Figure

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  Figure 1 Mouse bed and dose-build-up cradle made of acrylic plate. (A) Three acrylic plates of 30 cm×30 cm×0.6 cm on anterior direction and two on posterior direction were attached together. U-shaped pillar was made of Styrofoam. (B) When a mouse is laid on mouse bed, the body of the mouse is naturally extended because of the slope.

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  Figure 2 (A) Two tissue-equivalent boluses of 2 cm-thickness located on the mouse bed in dose-build-up cradle. (B) Dose measurement points of bolus. The numbers of 1, 2 and 3 indicate the surface, center and bottom of bolus, respectively.

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  Figure 3 Axial, sagittal and coronal view of 2 dimensional anterior-posterior/posterior-anterior plan. Field margin was 5 mm from planning target volume. It is shown that a part of bowel adjacent to tumor is included within the treatment field.

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  Figure 4 Axial, sagittal and coronal view of image guided radiation therapy plan. Field margin was 5 mm from planning target volume. The volume of irradiated bowel is reduced because of adjustment of beam direction and appropriate beam shaping with multileaf collimators.

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  Figure 5 (A) Cone beam CT images were fused with digitally reconstructed radiogram generated from planning CT images to confirm the tumor location. (B) Open-field portal vision image obtained by electronic portal imaging device just before the treatment, which shows well matched tumor location. (C) In vivo tumor dosimetry using diode detector placed on the tumor surface.

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  Figure 6 An example of dose volume histogram of 2-dimensional anterior-posterior/posterior-anterior (2D AP/PA) field plan and image guided radiation therapy (IGRT) plan. In IGRT plan, tumor dose is higher and that of the bowel, bone and bladder is lower as compared with 2D AP/PA field plan.

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  Figure 7 An example of density profile of the treatment field using electronic portal image. Rapid dose fall off occurs within ±2 mm from the treatment field edge.

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  Figure 8 Tumor growth delay and metastatic lung nodules. (A) Primary tumor growth measured by electronic calipers in vivo. (B) Primary tumor volume after necropsy on day 28. (C) Metastatic lung nodules observed at necropsy on day 28.

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  Figure 9 Simultaneous treatment of tumors inoculated on the thigh. Mice were obliquely positioned to reduce the irradiated dose to normal tissue of abdomen. Five mice were treated simultaneously.

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