Epel Boris, Sundramoorthy Subramanian V, Krzykawska-Serda Martyna, Maggio Matthew C, Tseytlin Mark, Eaton Gareth R, Eaton Sandra S, Rosen Gerald M, Kao Joseph P Y, Halpern Howard J
Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA.
Department of Biochemistry, School of Medicine, University of West Virginia, Morgantown, WV 26506, USA.
J Magn Reson. 2017 Mar;276:31-36. doi: 10.1016/j.jmr.2016.12.015. Epub 2016 Dec 31.
Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of H,N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with l-buthionine sulfoximine (BSO) markedly altered the kinetic images.
硫醇氧化还原状态是影响癌症治疗成败的一个重要生理参数。快速扫描电子顺磁共振（RS EPR）是一种新技术，在体外研究中已显示出比传统连续波EPR更高的信噪比。在此，我们使用RS EPR获取活体小鼠肿瘤硫醇氧化还原状态的快速三维图像。这项工作首次展示了H,N-取代二硫键连接的二硝基氧化物（PxSSPx）自旋探针与细胞内谷胱甘肽反应动力学的体内RS EPR图像。裂解速率与细胞内谷胱甘肽浓度成正比。在C3H小鼠的FSa纤维肉瘤肿瘤模型中证明了其可行性。与其他体内和细胞模型研究类似，用L-丁硫氨酸亚砜胺（BSO）处理小鼠降低细胞内谷胱甘肽浓度会显著改变动力学图像。
