Abstract
The simultaneous detection of multiple enzyme activities can improve the specificity of disease diagnoses. We therefore synthesized and characterized a diamagnetic chemical exchange saturation transfer (CEST) MRI contrast agent that can simultaneously detect two enzyme activities. Sulfatase and esterase enzymes cleave the ligands of the CEST agent, releasing salicylic acid that can be detected with CEST MRI. Importantly, both enzymes are required to activate the agent to produce a CEST MRI contrast, and the CEST agent was stable without enzyme treatment. These results established that this diamagnetic CEST MRI contrast agent is a platform technology with a modular design that can be potentially exploited to detect other combinations of enzyme activities, which can expand the armamentarium of contrast agents for molecular imaging.