Tumor pH Imaging Using Chemical Exchange Saturation Transfer (CEST)-MRI

Abstract

Magnetic resonance imaging (MRI) is a noninvasive imaging technique that allows for physiological and functional studies of the tumor microenvironment. Within MRI, the emerging field of chemical exchange saturation transfer (CEST) has been largely exploited for assessing a salient feature of all solid tumors, extracellular acidosis. Iopamidol-based tumor pH imaging has been demonstrated to provide accurate and high spatial resolution extracellular tumor pH maps to elucidate tumor aggressiveness and for assessing response to therapy, with a high potential for clinical translation. Here, we describe the overall setup and steps for measuring tumor extracellular pH of tumor models in mice by exploiting MRI-CEST pH imaging with a preclinical MRI scanner following the administration of iopamidol. We address issues of pH calibration curve setup, animal handling, pH-responsive contrast agent injection, acquisition protocol, and image processing for accurate quantification and visualization of tumor acidosis.

Keywords: Acidosis; Cancer; Chemical exchange saturation transfer (CEST); Iopamidol; Magnetic resonance imaging (MRI); Mice; Ratiometric; Tumor; pH.