Strategies for the development of gadolinium-based 'q'-activatable MRI contrast agents.

The emergence and rapid development of activatable contrast agents (CAs), whose relaxivity changes in response to the variation of a specific marker in the surrounding physiological microenvironment, have expanded the scope of MRI beyond anatomical and functional imaging to also convey information at the cellular and molecular level. The essence of an activatable MRI CA is the difference in relaxivity before and after a change in a physiological variable: the larger the difference, the better the CA. In this review, strategies for the design of activatable gadolinium CAs, with a switching mechanism based on the modulation of hydration (q), sensitive to common variables in the physiological microenvironment, such as pH, light, redox and metal ions, are illustrated and discussed.