Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University.
Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University; School of Medicine, West Virginia University.
J Vis Exp. 2021 Mar 11(169). doi: 10.3791/61692.
Radiation dosimetry is critical in the accurate delivery and reproducibility of radiation schemes in preclinical models for high translational relevance. Prior to performing any in vitro or in vivo experiments, the specific dose output for the irradiator and individual experimental designs must be assessed. Using an ionization chamber, electrometer, and solid water setup, the dose output of wide fields at isocenter can be determined. Using a similar setup with radiochromic films in the place of the ionization chamber, dose rates for smaller fields at different depths can also be determined. In vitro clonogenic survival assays of cancer cells in response to radiation treatment are inexpensive experiments that provide a measure of inherent radio-sensitivity of cell lines by fitting these data with the traditional linear-quadratic model. Model parameters estimated from these assays, combined with the principles of biologic effective doses, allows one to develop varying fractionation schedules for radiation treatment that provide equivalent effective doses in tumor-bearing animal experiments. This is an important factor to consider and correct for in comparing in vivo radiation therapy schedules to eliminate potential confounding of results due to variance in the delivered effective doses. Taken together, this article provides a general method for dose output verification preclinical animal and cabinet irradiators, in vitro assessment of radio-sensitivity, and verification of radiation delivery in small living organisms.
辐射剂量学在具有高度转化相关性的临床前模型中精确提供和重现辐射方案中至关重要。在进行任何体外或体内实验之前,必须评估辐照器和个别实验设计的特定剂量输出。使用电离室、静电计和固体水设置,可以确定等中心宽野的剂量输出。使用类似的设置,将电离室替换为放射性色迹胶片,还可以确定不同深度的较小野的剂量率。针对癌细胞对放射治疗的反应的体外克隆存活分析是一种廉价的实验,通过将这些数据拟合到传统的线性二次模型中,提供了细胞系固有放射敏感性的衡量标准。从这些分析中估计的模型参数,结合生物有效剂量的原则,可以为放射治疗制定不同的分割方案,为荷瘤动物实验提供等效的有效剂量。在比较体内放射治疗方案以消除由于有效剂量传递的差异而导致的结果混淆时,这是一个需要考虑和纠正的重要因素。综上所述,本文提供了一种用于临床前动物和机箱辐照器的剂量输出验证、体外放射敏感性评估以及小型活体生物中放射传递验证的通用方法。