1 In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center, West Virginia University , Morgantown, West Virginia.
2 Department of Biochemistry, West Virginia University School of Medicine , Morgantown, West Virginia.
Antioxid Redox Signal. 2018 May 20;28(15):1365-1377. doi: 10.1089/ars.2017.7329. Epub 2017 Dec 20.
A key role of the tumor microenvironment (TME) in cancer progression, treatment resistance, and as a target for therapeutic intervention is increasingly appreciated. Among important physiological components of the TME are tissue hypoxia, acidosis, high reducing capacity, elevated concentrations of intracellular glutathione (GSH), and interstitial inorganic phosphate (Pi). Noninvasive in vivo pO, pH, GSH, Pi, and redox assessment provide unique insights into biological processes in the TME, and may serve as a tool for preclinical screening of anticancer drugs and optimizing TME-targeted therapeutic strategies. Recent Advances: A reasonable radiofrequency penetration depth in living tissues and progress in development of functional paramagnetic probes make low-field electron paramagnetic resonance (EPR)-based spectroscopy and imaging the most appropriate approaches for noninvasive assessment of the TME parameters.
Here we overview the current status of EPR approaches used in combination with functional paramagnetic probes that provide quantitative information on chemical TME and redox (pO, pH, redox status, Pi, and GSH). In particular, an application of a recently developed dual-function pH and redox nitroxide probe and multifunctional trityl probe provides unsurpassed opportunity for in vivo concurrent measurements of several TME parameters in preclinical studies. The measurements of several parameters using a single probe allow for their correlation analyses independent of probe distribution and time of measurements.
The recent progress in clinical EPR instrumentation and development of biocompatible paramagnetic probes for in vivo multifunctional TME profiling eventually will make possible translation of these EPR techniques into clinical settings to improve prediction power of early diagnostics for the malignant transition and for future rational design of TME-targeted anticancer therapeutics. Antioxid. Redox Signal. 28, 1365-1377.
肿瘤微环境 (TME) 在癌症进展、治疗耐药性以及作为治疗干预的靶点方面的关键作用越来越受到重视。TME 的重要生理成分包括组织缺氧、酸中毒、高还原能力、细胞内谷胱甘肽 (GSH) 浓度升高和间质无机磷酸盐 (Pi)。非侵入性体内 pO2、pH、GSH、Pi 和氧化还原评估提供了对 TME 中生物过程的独特见解，并可能成为临床前抗癌药物筛选和优化 TME 靶向治疗策略的工具。最新进展：在活组织中有合理的射频穿透深度，以及在功能性顺磁探针的开发方面取得的进展，使得基于低场电子顺磁共振 (EPR) 的光谱学和成像成为非侵入性评估 TME 参数的最适当方法。
在这里，我们概述了与提供有关化学 TME 和氧化还原 (pO2、pH、氧化还原状态、Pi 和 GSH) 的定量信息的功能顺磁探针结合使用的 EPR 方法的现状。特别是，最近开发的双功能 pH 和氧化还原氮氧自由基探针和多功能三苯甲基探针的应用为在临床前研究中进行几种 TME 参数的体内同时测量提供了前所未有的机会。使用单个探针测量多个参数允许独立于探针分布和测量时间对它们进行相关分析。
临床 EPR 仪器的最新进展以及用于体内多功能 TME 分析的生物相容性顺磁探针的开发最终将使这些 EPR 技术能够转化为临床环境，从而提高对恶性转化的早期诊断的预测能力，并为未来合理设计针对 TME 的抗癌治疗方法提供帮助。抗氧化。氧化还原信号。28，1365-1377。
