Responsive gadolinium(III) complex-based small molecule magnetic resonance imaging probes: Design, mechanism and application

Magnetic resonance imaging (MRI) is a molecular imaging technology that has been widely adopted in biomedical and clinical diagnostics fields owing to its capability of deep tissue imaging with high spatiotemporal resolution. Responsive small molecule MRI contrast agents, known as MRI probes, are of particular interest for the detection and visualisation of target analytes in vitro and in vivo, thus expanding MRI’s capability into the molecular imaging regime. Each of the responsive MRI probe selectively responds to corresponding target analyte and then gives the magnetic resonance (MR) signal change for this analyte detection. In this work, advances in developing responsive MRI probes based on gadolinium(III) (Gd(III)) complexes are systematically summarized. Specifically, we first introduce the strategies in developing Gd(III) complex probes through different response mechanisms, and then discuss the progresses in developing Gd(III) complex-based resposnvie MRI probes for different target analytes, including biologically relevant cations, anions, pH, biomolecules and redox homeostasis. Responsive bimodal probes, such as MRI-fluorescence probes, MRI-PET probes, and MRI-SPECT probes are then briefly outlined. The applications of Gd(III) complex-based responsive probes in in vivo and in vitro MRI are also included. Current limitations and future research directions in developing Gd(III) complex probes for MR analysis and imaging are also proposed. It is anticipated that this work will promote the ongoing research on developing Gd(III) complex-based MRI probes and their applications in understanding the bioactive analytes’ pathophysiological processes.