Chen Miaomiao, Chen Chaoying, Shen Zhiwei, Zhang Xiaolei, Chen Yanzi, Lin Fengfeng, Ma Xilun, Zhuang Caiyu, Mao Yifei, Gan Haochuan, Chen Peidong, Zong Xiaodan, Wu Renhua
Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou 515041, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou 412000, China.
Oncotarget. 2017 Jul 11;8(28):45759-45767. doi: 10.18632/oncotarget.17404.
Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8, by a ratiometric method. Then we verified the feasibility of this technique and the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse breast cancer model, which is often used in CEST pHe studies. Furthermore, in vivo ioversol CEST MRI, we were able to map relative pHe and differentiate between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests pHe may be a useful biomarker for human liver cancer.
细胞外pH值(pHe)降低与肿瘤生长、侵袭、转移和化疗耐药相关,可通过化学交换饱和转移(CEST)磁共振成像(MRI)检测到。在此,我们证明了碘海醇CEST MRI可用于实现肝癌微环境的pHe成像。在体外研究中,我们首先探究了碘海醇信号是否依赖于pH值,并通过比率法计算了碘海醇的CEST效应与pH值在6.0至7.8范围内的函数方程。然后,我们通过在常用于CEST pHe研究的MMTV-Erbb2转基因小鼠乳腺癌模型中进行pHe成像,验证了该技术和方程在体内的可行性。此外,在体内碘海醇CEST MRI中,我们能够在McA-RH7777大鼠肝癌模型中绘制相对pHe图并区分肿瘤组织和正常组织。这表明pHe可能是人类肝癌的一个有用生物标志物。