Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies
Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies
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DOI：
10.1088/1361-6560/aa926b
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发表时间：
2017-12-07
影响因子：
3.5
通讯作者：
Lee, Yueh Z.
中科院分区：
文献类型：
--
作者：
Bazyar, Soha;Inscoe, Christina R.;Lee, Yueh Z.
微束放射治疗（MBRT）以200-1000 μ m的射束（峰）递送100 μ m剂量的X射线（>= 100戈伊），所述射束（峰）由通常作为单个时间部分的较宽的未照射区域（谷）分隔。在同步加速器设施进行的临床前研究表明，MBRT能够消融肿瘤，同时保持正常组织的完整性。本研究的主要目的是开发一种有效的和可访问的方法，使用传统的X射线辐照器进行MBRT。然后，我们在体外和体内测试了这种新方法。使用市售的铅带和聚乙烯片，我们构建了一个准直器，该准直器将工业辐照器的锥形束转换为44个相同的束（准直器尺寸约为4 × 10 cm）。使用两种不同的辐射变色胶片（射束FWHM = 246 +/- 32 μ m;中心到中心= 926 +/- 23 μ m;峰谷剂量比= 24.35 +/- 2.10;准直器相对输出因子= 0.84 +/- 0.04）评价所产生射束的剂量测定特性。克隆形成试验证明了我们的方法在两种放射抗性小鼠肿瘤细胞系（TRP =胶质母细胞瘤; B16-F10 =黑色素瘤）中诱导放射生物学细胞死亡的能力。放射生物学当量剂量（RBE）是通过评价急性皮肤反应分级剂量的MBRT和常规放疗（CRT）计算的。正常小鼠皮肤表现出对峰值高达150戈伊剂量的耐受性。当应用RBE时，与CRT相比，MBRT显著延长了具有侧腹黑素瘤肿瘤的小鼠的存活（总体p < 0.001）。组织深处的空间分辨率损失一直是主要问题。使用我们的准直器产生的光束保持其在体内（小鼠脑组织）的分辨率和高达10厘米深的辐射变色膜。总之，初始剂量测定、体外和体内评价证实了这种经济实惠且易于复制的微束准直器在未来临床前研究中的实用性。
Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (>= 100 Gy) in 200-1000 mu m beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size approximate to 4 x 10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM = 246 +/- 32 mu m; center-tocenter = 926 +/- 23 mu m; peak-to-valley dose ratio = 24.35 +/- 2.10; collimator relative output factor = 0.84 +/- 0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP = glioblastoma; B16-F10 = melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p < 0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.