Research Projects

Gadolinium(III) complexes (Gd) are used as MRI contrast agents (CAs) in approximately 40–50% of MRI scans performed worldwide for contrast enhancement. However, recent studies indicate that patients with severe renal impairment cannot safely use Gd-based CAs, and concerns regarding the long-term effects of retained Gd are further limiting their clinical usefulness. This has created a demand for Gd-free MRI contrast agents, driving a new direction in medicinal chemistry. MRI contrast agents based on first-row transition metals such as iron (Fe) have emerged as promising alternatives. Among these, CAs that are activated by analytes through redox changes referred to as smart MRI Cas. It functions via modulating the oxidation or spin state of the paramagnetic center. These agents exhibit varying r1 relaxivity in response to metabolite molecules (analytes) found in tumour cells. However, only a few such smart contrast agents have been reported to date, and none have yet been approved for clinical trials. To address this, we propose the synthesis of mononuclear Fe(II/III) complexes featuring multidentate ligands with redox-responsive groups. These groups are designed to trigger contrast enhancement via redox activity and spin crossover mechanisms. The redox-responsive CAs aim to exploit the redox-imbalanced environment of tumour cells such as elevated reactive oxygen species (ROS) and related redox processes. Additionally, glucose will be conjugated to these complexes to enhance the delivery of MRI contrast agents to tumour cells. This approach is analogous to the use of radiolabelled glucose and amino acids in nuclear medicine for targeting cancer. This step is crucial for promoting cellular uptake of the contrast agent and enabling imaging of the intracellular environment. Our proposed Fe(II/III) complexes thus offer both technical and safety advantages. Finally, the in vitro and in vivo efficacy of these Fe-based MRI contrast agents will be evaluated using various cancer cell lines and tumour-bearing mouse models.