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Orthovoltage X-Rays Exhibit Increased Efficacy Compared with γ-Rays in Preclinical Irradiation
Cancer Research ( IF 11.2 ) Pub Date : 2022-08-03 , DOI: 10.1158/0008-5472.can-22-0656
Brett I Bell 1, 2 , Justin Vercellino 1, 2 , N Patrik Brodin 1 , Christian Velten 1 , Lalitha S Y Nanduri 1 , Prashanth K B Nagesh 3 , Kathryn E Tanaka 2 , Yanan Fang 2 , Yanhua Wang 2 , Rodney Macedo 1 , Jeb English 1, 2 , Michelle M Schumacher 1, 2 , Phaneendra K Duddempudi 4 , Patrik Asp 1 , Wade Koba 5 , Shahin Shajahan 1 , Laibin Liu 1 , Wolfgang A Tomé 1, 6 , Weng-Lang Yang 1 , Richard Kolesnick 3 , Chandan Guha 1, 2
Affiliation  

Radionuclide irradiators (137Cs and 60Co) are commonly used in preclinical studies ranging from cancer therapy to stem cell biology. Amidst concerns of radiological terrorism, there are institutional initiatives to replace radionuclide sources with lower energy X-ray sources. As researchers transition, questions remain regarding whether the biological effects of γ-rays may be recapitulated with orthovoltage X-rays because different energies may induce divergent biological effects. We therefore sought to compare the effects of orthovoltage X-rays with 1-mm Cu or Thoraeus filtration and 137Cs γ-rays using mouse models of acute radiation syndrome. Following whole-body irradiation, 30-day overall survival was assessed, and the lethal dose to provoke 50% mortality within 30-days (LD50) was calculated by logistic regression. LD50 doses were 6.7 Gy, 7.4 Gy, and 8.1 Gy with 1-mm Cu-filtered X-rays, Thoraeus-filtered X-rays, and 137Cs γ-rays, respectively. Comparison of bone marrow, spleen, and intestinal tissue from mice irradiated with equivalent doses indicated that injury was most severe with 1-mm Cu-filtered X-rays, which resulted in the greatest reduction in bone marrow cellularity, hematopoietic stem and progenitor populations, intestinal crypts, and OLFM4+ intestinal stem cells. Thoraeus-filtered X-rays provoked an intermediate phenotype, with 137Cs showing the least damage. This study reveals a dichotomy between physical dose and biological effect as researchers transition to orthovoltage X-rays. With decreasing energy, there is increasing hematopoietic and intestinal injury, necessitating dose reduction to achieve comparable biological effects. Significance: Understanding the significance of physical dose delivered using energetically different methods of radiation treatment will aid the transition from radionuclide γ-irradiators to orthovoltage X-irradiators.

中文翻译:

与 γ 射线相比,正电压 X 射线在临床前照射中表现出更高的功效

放射性核素辐照器(137Cs 和 60Co)通常用于从癌症治疗到干细胞生物学的临床前研究。出于对放射性恐怖主义的担忧,有一些机构倡议用较低能量的 X 射线源取代放射性核素源。随着研究人员的转变,关于 γ 射线的生物效应是否可以用正电压 X 射线重现的问题仍然存在,因为不同的能量可能会引起不同的生物效应。因此,我们试图使用急性辐射综合症的小鼠模型来比较具有 1 毫米铜或 Thoraeus 过滤的正电压 X 射线和 137Cs γ 射线的效果。全身照射后,评估 30 天的总体生存率,并通过逻辑回归计算 30 天内引起 50% 死亡率的致死剂量 (LD50)。1mm Cu 过滤的 X 射线、Thoraeus 过滤的 X 射线和 137Cs γ 射线的 LD50 剂量分别为 6.7 Gy、7.4 Gy 和 8.1 Gy。对接受同等剂量照射的小鼠的骨髓、脾脏和肠道组织进行比较表明,1毫米Cu过滤的X射线损伤最严重,导致骨髓细胞结构、造血干细胞和祖细胞群的减少最大。肠隐窝和 OLFM4+ 肠干细胞。经过 Thoraeus 过滤的 X 射线引发了中间表型,其中 137C 的损伤最小。这项研究揭示了随着研究人员转向正电压 X 射线,物理剂量和生物效应之间的二分法。随着能量的减少,造血和肠道损伤不断增加,需要减少剂量才能达到类似的生物效应。意义:了解使用能量不同的放射治疗方法传递的物理剂量的重要性将有助于从放射性核素 γ 辐照器过渡到正电压 X 辐照器。
更新日期:2022-08-03
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