Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI

// Miaomiao Chen 1, * , Chaoying Chen 2, * , Zhiwei Shen 1 , Xiaolei Zhang 1 , Yanzi Chen 1 , Fengfeng Lin 1 , Xilun Ma 1 , Caiyu Zhuang 1 , Yifei Mao 1 , Haochuan Gan 1 , Peidong Chen 1 , Xiaodan Zong 1 and Renhua Wu 1, 3 1 Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou 515041, China 2 Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou 412000, China 3 Provincial Key Laboratory of Medical Molecular Imaging, Shantou 515041, China * These authors have contributed equally to this work Correspondence to: Renhua Wu, email: rhwu@stu.edu.cn Keywords: liver cancer, pH imaging, breast cancer, ioversol, CEST MRI Received: January 24, 2017     Accepted: April 03, 2017     Published: April 25, 2017 ABSTRACT Extracellular pH (pH e ) 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 pH e 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 pH e imaging in an MMTV-Erbb2 transgenic mouse breast cancer model, which is often used in CEST pH e studies. Furthermore, in vivo ioversol CEST MRI, we were able to map relative pH e and differentiate between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests pH e may be a useful biomarker for human liver cancer.