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

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.