Iwamoto Keisuke S, Sandstrom Robert E, Bryan Mark, Liu Yue, Elgart S Robin, Sheng Ke, Steinberg Michael L, McBride William H, Low Daniel A
Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California.
Triplet State Technology LLC, Longview, Washington.
Adv Radiat Oncol. 2021 Jan 16;6(3):100645. doi: 10.1016/j.adro.2021.100645. eCollection 2021 May-Jun.
The clinical efficacy of radiation therapy is mechanistically linked to ionization-induced free radicals that cause cell and tissue injury through direct and indirect mechanisms. Free radical reaction dynamics are influenced by many factors and can be manipulated by static weak magnetic fields (WMF) that perturb singlet-triplet state interconversion. Our study exploits this phenomenon to directly increase ionizing radiation (IR) dose absorption in tumors by combining WMF with radiation therapy as a new and effective method to improve treatment.
Coils were custom made to produce both homogeneous and gradient magnetic fields. The gradient coil enabled simultaneous in vitro assessment of free radical/reactive oxygen species reactivity across multiple field strengths from 6 to 66 G. First, increases in IR-induced free radical concentrations using oxidant-sensitive fluorescent dyes in a cell-free system were measured and verified. Next, human and murine cancer cell lines were evaluated in in vitro and in vivo models after exposure to clinically relevant doses of IR in combination with WMF.
Cellular responses to IR and WMF were field strength and cell line dependent. WMF was able to enhance IR effects on reactive oxygen species formation, DNA double-strand break formation, cell death, and tumor growth.
We demonstrate that the external presence of a magnetic field enhances radiation-induced cancer cell injury and death in vitro and in vivo The effect extends beyond the timeframe when free radicals are induced in the presence of radiation into the window when endogenous free radicals are produced and therefore extends the applicability of this novel adjunct to cancer therapy in the context of radiation treatment.
放射治疗的临床疗效在机制上与电离诱导的自由基相关,这些自由基通过直接和间接机制导致细胞和组织损伤。自由基反应动力学受多种因素影响,并且可被干扰单重态-三重态相互转换的静态弱磁场(WMF)所调控。我们的研究利用这一现象,通过将WMF与放射治疗相结合,直接增加肿瘤中的电离辐射(IR)剂量吸收,作为一种改善治疗的新的有效方法。
定制线圈以产生均匀和梯度磁场。梯度线圈能够在体外同时评估6至66 G的多个场强下自由基/活性氧物质的反应性。首先,在无细胞系统中使用对氧化剂敏感的荧光染料测量并验证IR诱导的自由基浓度的增加。接下来,在体外和体内模型中评估人源和鼠源癌细胞系在暴露于临床相关剂量的IR并结合WMF后的情况。
细胞对IR和WMF的反应取决于场强和细胞系。WMF能够增强IR对活性氧形成、DNA双链断裂形成、细胞死亡和肿瘤生长的影响。
我们证明,磁场的外部存在在体外和体内均增强了辐射诱导的癌细胞损伤和死亡。这种效应不仅在辐射存在时诱导自由基的时间范围内存在,还延伸到内源性自由基产生的时间段,因此扩展了这种新型癌症治疗辅助手段在放射治疗背景下的适用性。