Optimizing the efficacy of Gd-based MRI probes at high magnetic fields

GdIII complexes are in current clinical use as MRI contrast agents. Their ability to enhance the MR image is termed relaxivity and it depends upon many molecular factors, including speciation, protein binding affinity, chemical structure, and dynamic processes, such as water exchange kinetics and rotational tumbling rates. A significant portion of research in the field of contrast agent development is devoted to controlling the relaxivity (efficiency) of GdIII complexes. The structure of the chelate determines the interaction between the ion and the surrounding water molecules, and consequently the relaxivity of the complex. However, clinically used Gd-based contrast agents are low molecular weight, rapidly tumbling complexes with limited efficacy (relaxivity, r1) that decreases with the magnetic field strength. The enhancement of the efficiency of the probe is based on the structural modification of the clinical complexes, guided by a detailed understanding of the relationship between the relaxation parameters and the chemical structure.
Moreover, MRI is increasingly moving to higher fields as the majority of the scanners used in clinics operate at 1.5 – 3 T. Therefore, it is important to develop new T1 agents characterized by enhanced relaxivity over a broad range of imaging field strengths for use with current scanners. Multimeric GdIII agents with intermediate molecular weight (~2-6 kDa) have been proposed as a possible solution. The purpose of this seminar is to discuss recent results in the search for relaxivity enhancement at magnetic field strengths ≥ 1.5 T.