Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.
Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer.
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DOI：
10.1016/j.ijrobp.2016.07.008
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Lu B
中科院分区：
文献类型：
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作者：
Du S;Lockamy V;Zhou L;Xue C;LeBlanc J;Glenn S;Shukla G;Yu Y;Dicker AP;Leeper DB;Lu Y;Lu B
利用小动物放射研究平台（SARRP）在基因工程小鼠肺癌模型中实施临床立体定向体部放射治疗（SBRT）。本研究使用多结节Kras驱动的自发性肺肿瘤的小鼠模型。高分辨率锥形束计算机断层扫描（CBCT）成像用于识别和靶向外周肿瘤结节，而对侧肺中的脱靶肺结节用作未照射对照。CBCT成像有助于定位肿瘤，促进高精度照射，并监测肿瘤生长。SBRT计划、处方剂量和对正常组织的剂量限制遵循RTOG方案设定的指南。采用免疫组织化学方法观察照射后肿瘤的病理变化。在肺癌的基因工程小鼠模型中，使用SARRP系统的图像引导辐射递送有效地定位和精确地治疗肺癌。免疫组化数据证实了SBRT精确递送至靶向肺结节。每周分3次给予60戈伊剂量显著降低了增殖指数Ki-67，并增加了照射肺结节中切割的caspase-3染色的细胞凋亡。使用SARRP平台进行肺癌小鼠SBRT的剂量学规划和递送是可行的。这使得临床前研究能够为涉及SBRT的临床试验提供理论基础，特别是当与免疫治疗剂联合使用时。
To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and target peripheral tumor nodules, whereas off-target lung nodules in the contralateral lung were used as a nonirradiated control. CBCT imaging helps localize tumors, facilitate high-precision irradiation, and monitor tumor growth. SBRT planning, prescription dose, and dose limits to normal tissue followed the guidelines set by RTOG protocols. Pathologic changes in the irradiated tumors were investigated using immunohistochemistry. The image guided radiation delivery using the SARRP system effectively localized and treated lung cancer with precision in a genetically engineered mouse model of lung cancer. Immunohistochemical data confirmed the precise delivery of SBRT to the targeted lung nodules. The 60 Gy delivered in 3 weekly fractions markedly reduced the proliferation index, Ki-67, and increased apoptosis per staining for cleaved caspase-3 in irradiated lung nodules. It is feasible to use the SARRP platform to perform dosimetric planning and delivery of SBRT in mice with lung cancer. This allows for preclinical studies that provide a rationale for clinical trials involving SBRT, especially when combined with immunotherapeutics.