CAMEL has pioneered the development and application of Chemical Exchange Saturation Transfer (CEST) MRI for in vivo studies with exogenous contrast agents. We have developed methods to synthesize CEST MRI contrast agents, have pioneered the development of CEST MRI methods for pre-clinical studies, and have started clinical trials to translate CEST “from bench to bedside”. We especially focus on methods that can detect two CEST signals, where one signal is responsive to a biomarker while the other signal is an unresponsive ‘control’ signal, which greatly facilitates quantitative imaging. We also specialize in fast CEST MRI acquisition methods and rapid analysis methods that can precisely and accurately measure in vivo biomarkers. Our research provides a new paradigm for molecular imaging that can impact precision medicine.
CAMEL has developed a non-invasive imaging method that can measure tumor acidosis, known as acidoCEST MRI. We have performed many pre-clinical studies with acidoCEST MRI to measure the extracellular pH in tumor models. These studies have shown that faster-growing tumors are typically more acidic; tumors with high levels of proteins involved in glycolysis metabolism are more acidic; the same tumor type can have different levels of acidity when growing in different locations in the body; therapies can alter the level of acidosis within 4 hours of initiating treatment; baking soda can neutral tumor acidosis but not in all cases. We have recently started a clinical trial that measures tumor acidosis in breast cancer patients. One of our CEST MRI contrast agents is already clinically approved, which greatly facilitates our clinical study. Also, we have developed CEST MRI protocols that are safe to use with clinical MRI scanners.
CAMEL has developed a method known as catalyCEST MRI that detects the catalytic activities of enzymes in vitro and in vivo. To date, we have detected the activities of caspase-3, cathepsin-B, urokinase Plasminogen Activator; kallikrien-6; transglutaminase; gamma glutamyl transferase; esterases; sulfatases; phosphatases; and reductases. We have used the same methodology to detect the metabolite nitric oxide. We have measured Michaelis-Menten kinetics parameters using catalyCEST MRI. We have used catalyCEST MRI to detect enzyme activities in mouse xenograft models of human cancers. We have developed many CEST agents with innovative features to accomplish these catalyCEST MRI studies: contrast agents with two CEST effects, with one enzyme-responsive CEST signal and an unresponsive “control” signal”, so that a ratio of CEST signals can improve quantitative imaging and detection specificity; contrast agents with a modular design that conjugates the enzyme-responsive ligand to the CEST MRI contrast agent through a linker, which facilitates the development of new agents; polymeric versions of our agents to improve detection sensitivity; non-metallic CEST agents that have outstanding biocompatibility, which facilitates clinical translation.