A Single PARACEST MRI Contrast Agent for Accurate in vivo pH Measurements

Introduction: pH is a physiological indicator of tumor lesions and other pathological abnormalities in soft tissues. MRI has shown tremendous potential for noninvasive in vivo pH measurements, though formidable challenges exist regarding sensitivity, accuracy and/or the need of a second pHunresponsive agent as control. Endogenous Chemical Exchange Saturation Transfer (CEST) and PARAmagnetic CEST (PARACEST) contrast agents have been successfully applied to measure pH, although a second pH-unresponsive agent is still required for accurate measurements. A single contrast agent with a pH-responsive and pH-unresponsive PARACEST effect has been developed to achieve pH measurements with a single agent. Herein we propose a single contrast agent with two PARACEST effects that have opposite dependencies on physiological pH, which possesses the ideal characteristics for MRI-based pH measurements to assess tumors and other pathologies.