Molecular Magnetic Resonance Imaging with Gd(III)-Based Contrast Agents: Challenges and Key Advances

In an era of personalized medicine, the clinical community has become increasingly focused on understanding diseases at the cellular and molecular levels. Magnetic resonance imaging (MRI) is a powerful imaging modality for acquiring anatomical and functional information. However, it has limited applications in the field of molecular imaging due to its low sensitivity. To expand the capability of MRI to encompass molecular imaging applications, we introduced bioresponsive Gd(III)-based magnetic resonance contrast agents (GBCAs) in 1997. Since that time, many research groups across the globe have developed new examples of bioresponsive GBCAs. These contrast agents have shown great promise for visualizing several biochemical processes, such as gene expression, neuronal signaling, and hormone secretion. They are designed to be conditionally retained, or activated, in vivo in response to specific biochemical events of interest. As a result, an observed MR signal change can serve as a read-out for molecular events. A significant challenge for these probes is how to utilize them for noninvasive diagnostic and theranostic applications. This Perspective focuses on the design strategies that underlie bioresponsive probes, and describes the key advances made in recent years that are facilitating their application in vivo and ultimately in clinical translation. While the field of bioresponsive agents is embryonic, it is clear that many solutions to the experimental and clinical radiologic problems of today will be overcome by the probes of tomorrow.