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Chemical-exchange saturation transfer (CEST) agents are a new class of MRI contrast agents that offer a number of advantages over conventional Gd(3+) agents. Over the past few years, a variety of small-molecule CEST agents responsive to physiological conditions, such as pH and temperature, have been designed and their imaging applications have been reported. One of the major drawbacks of current small-molecule CEST agents is their relatively low sensitivity. The advantages of using macromolecular and nanosized systems with large numbers of exchangeable groups to improve contrast sensitivity are highlighted in this brief review. Although this approach has been shown to amplify contrast sensitivity, other limitations, including relatively small chemical-shift differences between the exchanging species and bulk water and less than optimal proton exchange rates, still exist. By addressing these issues, it is anticipated that CEST agents will find useful applications in the detection of specific biomarkers of disease.

Advantages of macromolecular to nanosized chemical-exchange saturation transfer agents for MRI applications