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

Miaomiao Chen; Chaoying Chen; Zhiwei Shen; Xiaolei Zhang; Yanzi Chen; Fengfeng Lin; Xilun Ma; Caiyu Zhuang; Yifei Mao; Haochuan Gan; Peidong Chen; Xiaodan Zong; Renhua Wu

doi:10.18632/oncotarget.17404

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Research Papers:

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

Miaomiao Chen _, Chaoying Chen, Zhiwei Shen, Xiaolei Zhang, Yanzi Chen, Fengfeng Lin, Xilun Ma, Caiyu Zhuang, Yifei Mao, Haochuan Gan, Peidong Chen, Xiaodan Zong and Renhua Wu

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Oncotarget. 2017; 8:45759-45767. https://doi.org/10.18632/oncotarget.17404

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Abstract

Miaomiao Chen1,*, Chaoying Chen2,*, Zhiwei Shen1, Xiaolei Zhang1, Yanzi Chen1, Fengfeng Lin1, Xilun Ma1, Caiyu Zhuang1, Yifei Mao1, Haochuan Gan1, Peidong Chen1, Xiaodan Zong1 and Renhua Wu1,3

1Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou 515041, China

2Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou 412000, China

3Provincial Key Laboratory of Medical Molecular Imaging, Shantou 515041, China

*These authors have contributed equally to this work

Correspondence to:

Renhua Wu, email: [email protected]

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.

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Research Papers:

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

Abstract