Cucinotta Francis A, Smirnova Olga A
University of Nevada Las Vegas, Las Vegas Nevada.
Retired.
Radiat Res. 2023 Mar 1;199(3):240-251. doi: 10.1667/RADE-22-00093.1.
A mathematical model, which describes the level of surviving lymphocytes in the blood after ultra-high (FLASH) and lower dose rates of partial-body irradiation, is developed. The model is represented by simple analytic formulae that involve a few parameters, namely, physiologic parameters (characteristics of the blood flow through the blood circulatory system and its irradiated part), a biophysical parameter (a characteristic of the blood lymphocytes radiosensitivity), and the physical parameters (characteristics of irradiation). The model predicts that the level of surviving blood lymphocytes increases as the dose rate increases and approaches the limiting level of (1 - vR), where vR is the fraction of the blood volume in the irradiated part of the blood circulatory system. The model also predicts that the level of surviving blood lymphocytes after the same exposure is higher for lower vR. It is found that FLASH irradiation in humans with doses of 10 to 40 Gy and with exposure times significantly less (<1 s) than the blood circulation time (∼60 s) leads to the maximal blood lymphocyte sparing. Simple formula, which determines effective dose rates for optimal blood lymphocyte sparing, is derived in the framework of the developed model. For the dose range specified above, the obtained modeling prediction of the range of effective dose rates for optimal blood lymphocyte sparing in humans (namely, N ≥40 Gy/s) coincides with the dose rate range in FLASH radiation therapy. It is revealed that the respective effective dose rates for mice are higher than those for humans (for the same dose range) due to the shorter blood circulation time in mice than in humans. Proceeding from the findings obtained in this paper, a hypothesis elucidating the mechanisms of the abscopal effect of FLASH radiation therapy (namely, an antitumor response on metastases located outside of irradiated part of a body) is proposed.
建立了一个数学模型，该模型描述了全身局部照射超高（FLASH）剂量率和较低剂量率后血液中存活淋巴细胞的水平。该模型由简单的解析公式表示，这些公式涉及几个参数，即生理参数（血液通过血液循环系统及其受辐照部分的特征）、生物物理参数（血液淋巴细胞放射敏感性的特征）和物理参数（辐照的特征）。该模型预测，存活血液淋巴细胞的水平随着剂量率的增加而增加，并接近极限水平（1 - vR），其中vR是血液循环系统受辐照部分的血容量分数。该模型还预测，对于较低的vR，相同照射后存活血液淋巴细胞的水平更高。研究发现，对人类进行10至40 Gy剂量的FLASH照射，且照射时间明显短于（<1 s）血液循环时间（约60 s），会导致最大程度的血液淋巴细胞 sparing。在已建立的模型框架内推导了确定最佳血液淋巴细胞 sparing有效剂量率的简单公式。对于上述剂量范围，所获得的关于人类最佳血液淋巴细胞 sparing有效剂量率范围的建模预测（即N≥40 Gy/s）与FLASH放射治疗中的剂量率范围一致。结果表明，由于小鼠的血液循环时间比人类短，相同剂量范围内小鼠的相应有效剂量率高于人类。基于本文的研究结果，提出了一个假设，以阐明FLASH放射治疗远隔效应（即对身体受辐照部位以外转移灶的抗肿瘤反应）的机制。
