Design Chemical Exchange Saturation Transfer Contrast Agents and Nanocarriers for Imaging Proton Exchange in Vivo

Chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) enables the imaging of many endogenous and exogenous compounds with exchangeable protons and protons experiencing dipolar coupling by using a label-free approach. This provides an avenue for following interesting molecular events in vivo by detecting the natural protons of molecules, such as the increase in amide protons of proteins in brain tumors and the concentration of drugs reaching the target site. Neither of these detections require metallic or radioactive labels and thus will not perturb the molecular events happening in vivo. Yet, magnetization transfer processes such as chemical exchange and dipolar coupling of protons are sensitive to the local environment. Hence, the use of nanocarriers could enhance the CEST contrast by providing a relatively high local concentration of contrast agents, considering the portion of the protons available for exchange, optimizing the exchange rate, and utilizing molecular interactions. This review provides an overview of these factors to be considered for designing efficient CEST contrast agents (CAs), and the molecular events that can be imaged using CEST MRI during disease progression and treatment, as well as the nanocarriers for drug delivery and distribution for the evaluation of treatments.