Two requirements of gadolinium based contrast agents (GBCAs) designed for use in MRI include high stability and high relaxivity. Stability is important because gadolinium is toxic to biological systems, and so it must be bound to an organic ligand to form a gadolinium complex. Relaxivity is important because it is a marker for the ability of GBCAs to enhance signal intensity on the MR image and is a prerequisite of technical efficacy of MRI contrast.1
In terms of stability, gadolinium complexes available on the market fall into two major classes based on their chemical structures: the linear and the macrocyclic agents (Please see article Gadolinium Presence in the Brain and Body). The macrocyclic complex is the most stable class of GBCA.2 The three macrocyclic agents available in Canada are illustrated in Figure 1.
While molecular structure plays a large role in the stability of GBCAs, molecular structure also influences relaxivity, which is characterized by the ability of the gadolinium complex to enhance relaxation rates of nearby water protons. Factors that influence this relaxation rate include the number of water molecules that are bound to the gadolinium ion at a time (hydration number, q), the lifetime of the water molecule in the inner sphere of the gadolinium (τM), and the rotational correlation time of the contrast agent (τR).1
One approach for increasing relaxivity is to improve interaction of water molecules in the second coordination shell of the gadolinium ion.3 This strategy has been implemented in the design of Gadovist® using additional hydroxyl groups, which increases the number of water molecules in the second hydration shell through hydrogen bonding. This leads to better interaction of bulk water with the contrast agent and helps generate the high relaxivity of Gadovist (Figure 1).
- De León-Rodríguez LM, Martins AF, Pinho MC, et al. Basic MR relaxation mechanisms and contrast agent design. J Magn Reson Imaging. 2015;42(3):545-565.
- Frenzel T, Lengsfeld P, Schirmer H, et al. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37°C. Invest Radiol. 2008;43:817-828.
- Botta M. Second Coordination Sphere Water Molecules and Relaxivity of Gadolinium(III) complexes: Implications for MRI Contrast Agents. Eur J Inorg Chem. 2000;399-407.