提出了一种改进的生物学加权函数（IBWF），从现象学上将微剂量线性能量概率密度分布与最常用的哺乳动物细胞系的体外克隆细胞存活（存活分数=10％）的相对生物学有效性（RBE）联系起来。即中国仓鼠肺成纤维细胞(V79)。IBWF,旨在作为快速RBE评估的简单而强大的工具，以比较粒子治疗光束中的不同暴露条件，通过迭代全局拟合过程确定，目的是在暴露于1H至238U的各种类型离子的情况下，将RBE计算与文献体外数据之间的平均相对偏差降至最低。通过使用单个独立于粒子和能量的函数，对于跨越近五个数量级（液态水中0.2至15000keV/µm）的无限制线性能量转移（LET）范围的颗粒，可以在线性能量与克隆细胞存活之间建立明确的相关性。IBWF衍生的RBE值与公布的体外数据之间的平均偏差为~14%。还将IBWF结果与使用修改的微剂量动力学模型(修改的MKM)进行的相应计算(V79细胞系的体外RBE10)进行比较。此外，包括用小鼠体内早期肠耐受性的参考生物加权函数(BWF)计算的RBE值用于比较,并进一步探索BWF结果与体外RBE之间的潜在相关性,如先前研究中报道的。结果表明，在离子重于20Ne的情况下，修饰的MKM在复制V79细胞系的体外实验RBE10方面具有局限性。此外，由于不同的建模端点，对于重于2H的离子，使用参考BWF和IBWF评估的RBE值之间发现了明显的偏差。最后,IBWF通过处理10个不同设施（8个临床设施和2个研究设施）中的19个1H和12C束中的8个不同微剂量计实验测量的线性能量密度分布，被不变地应用于计算RBE值。尽管探测器之间存在差异,辐照设施，光束轮廓(原始或展开布拉格峰)，最大光束能量,光束传输（被动或主动扫描），能量降解系统(水，PMMA,聚酰胺或低密度聚乙烯)，在计算机模拟的微剂量光谱的情况下，发现获得的基于IBWF的RBE趋势与相应的趋势非常吻合。
An improved biological weighting function (IBWF) is proposed to phenomenologically relate microdosimetric lineal energy probability density distributions with the relative biological effectiveness (RBE) for the in vitro clonogenic cell survival (surviving fraction = 10%) of the most commonly used mammalian cell line, i.e. the Chinese hamster lung fibroblasts (V79). The IBWF, intended as a simple and robust tool for a fast RBE assessment to compare different exposure conditions in particle therapy beams, was determined through an iterative global-fitting process aimed to minimize the average relative deviation between RBE calculations and literature in vitro data in
case of exposure to various types of ions from 1H to 238U. By using a single particle- and energy- independent function, it was possible to establish an univocal correlation between lineal energy and clonogenic cell survival for particles spanning over an unrestricted linear energy transfer (LET) range of almost five orders of magnitude (0.2 to 15000 keV/µm in liquid water). The average deviation between IBWF-derived RBE values and the published in vitro data was ~14%. The IBWF results were also compared with corresponding calculations (in vitro RBE10 for the V79 cell line) performed using the modified microdosimetric kinetic model (modified MKM). Furthermore, RBE values computed with the reference biological weighting function (BWF) for the in vivo early intestine tolerance in mice were included for comparison and to further explore potential correlations between the BWF results and the in vitro RBE as reported in previous studies. The results suggest that the modified MKM possess limitations in reproducing the experimental in vitro RBE10 for the V79 cell line in
case of ions heavier than 20Ne. Furthermore, due to the different modelled endpoint, marked deviations were found between the RBE values assessed using the reference BWF and the IBWF for ions heavier than 2H. Finally, the IBWF was unchangingly applied to calculate RBE values by processing lineal energy density distributions experimentally measured with 8 different microdosimeters in 19 1H and 12C beams at 10 different facilities (8 clinical and 2 research ones). Despite the differences between the detectors, irradiation facilities, beam profiles (pristine or spread out Bragg peak), maximum beam energy, beam delivery (passive or active scanning), energy degradation system (water, PMMA, polyamide or low density polyethylene), the obtained IBWF-based RBE trends were found to be in good agreement with the corresponding ones in
case of computer-simulated microdosimetric spectra.
