目标:最近,剂量输送技术随着无滤波器平坦化光束(FFF)而迅速发展,高剂量率的生物学效应是一个令人感兴趣的问题。我们假设使用现代线性加速器获得的不同剂量率的FFF光束对TME具有不同的影响。
方法:建立B16-F10黑色素瘤同系肿瘤模型,将小鼠随机分为2种不同的剂量(2Gy和10Gy)和3种不同的剂量率(1Gy/min,6Gy/min,和14Gy/min)与对照组一起。在RT后的第七天进行安乐死,收集心内血液进行彗星试验。收集肿瘤并进行组织形态学和免疫组织化学检查。使用SPSS软件版本23(SPSSInc.,芝加哥,IL,美国)。
结果:日生长速率均匀,在每种剂量的所有三种剂量率中,肿瘤体积之间没有观察到差异。血液单核细胞脱氧核糖核酸(DNA)损伤不受剂量或剂量率的影响。在TME组织形态学检查中,10Gy臂中有丝分裂的数量较少,而多态性评分更大。然而,不同的剂量率对有丝分裂数或多态性评分无影响.炎症的严重程度,TME中的细胞密度,免疫组织化学标记物的表达在所有剂量和剂量率之间具有可比性。
结论:在我们涉及B16-F10同系肿瘤模型的研究中,用FFF束获得的不同剂量率对肿瘤体积没有影响,血液单核细胞DNA损伤,或TME参数。然而,为了充分了解新技术的生物学影响,我们的研究应通过替代临床前设置进行验证.
OBJECTIVE: Recently, dose delivery technology has rapidly evolved with flattening filter-free beams (FFF), and the biological effects of high dose rates are a matter of interest. We hypothesized that FFF beams at different dose rates obtained with modern linear accelerators have different effects on the TME.
METHODS: The B16-F10 melanoma syngeneic tumor model was established, and mice were randomized to 2 different doses (2 Gy and 10 Gy) and 3 different dose rates (1 Gy/min, 6 Gy/min, and 14 Gy/min) along with the control group. Euthanasia was performed on the seventh day after RT, and intracardiac blood was collected for a comet assay. Tumors were harvested and examined histomorphologically and immunohistochemically. Statistical analyses were performed using SPSS software version 23 (SPSS Inc., Chicago, IL, USA).
RESULTS: The daily growth rate was uniform, and no difference was observed between tumor volumes across all three dose rates for each dose. Deoxyribonucleic acid (DNA) damage in blood mononuclear cells was not affected by dose or dose rate. In the TME histomorphological examination, the number of mitosis is less in the 10 Gy arm, whereas the pleomorphism score was greater. Nevertheless, varying dose rates had no effect on the number of mitosis or the pleomorphism score. The severity of the inflammation, cell densities in the TME, and expression of immunohistochemical markers were comparable across all doses and dose rates.
CONCLUSIONS: In our study involving the B16-F10 syngeneic tumor model, varying dose rates obtained with FFF beams had no effect on tumor volume, blood mononuclear cell DNA damage, or TME parameters. However, in order to fully understand the biological impacts of novel techniques, our study should be validated with alternative preclinical setups.