ABSTRACT
In the last two decades, magnetic resonance imaging (MRI) has evolved into one of the most powerful diagnostic modalities in clinical and biomedical imaging. MRI provides remarkable resolution, with no depth limit. To increase the signal intensity and image contrast, a reduction of the longitudinal or transverse spin relaxation time, T1 or T2, respectively, is o¹en induced by the application of suitable paramagnetic or superparamagnetic compounds, called MRI contrast agents. In today’s practice, agents that aŸect mostly the T1 relaxation time (so-called T1 agents) represent the majority of the imaging probes used. Nearly all T1 agents developed so far are compounds based on the gadolinium ion, Gd3+ (Aime et al. 2007a; Geraldes and Laurent 2009). Gd3+ is the metal of choice since it possesses the highest electron spin (S = 7/2) for a paramagnetic cation and a slow electron spin relaxation. —e e±ciency of the agent can be boosted by increasing the relaxation eŸect generated per paramagnetic center (expressed by the term relaxivity, r1) and/or by bringing many of these ions to the target. Based on theoretical considerations, an estimation of r1 ∼ 100 mM−1 s−1 per Gd3+ can be deduced as an upper limit of the attainable relaxivity, depending on the magnetic ™eld strength (Caravan et al. 1999; Toth et al. 2001; Caravan 2007). Given its intrinsic low sensitivity, MRI requires a relatively large amount of the relaxation agent to provide detectable contrast enhancement. In order to attain high amounts of Gd3+ to be delivered to
18.1 Introduction .................................................................................... 18-1 18.2 Relaxivity of Gd3+ Complexes ....................................................... 18-2
Inner Sphere Proton Relaxivity 18.3 Chelating Units for Gadolinium-Based Contrast Agents ........ 18-7
Gadolinium-Based Contrast Agents Based on Carbon Nanomaterials 18.4 “Inorganic” Bionanomaterials for MRI ..................................... 18-10
18.6 Conclusions and Perspectives .....................................................18-23 Acknowledgments ....................................................................................18-24 References ..................................................................................................18-24
the target site, various kinds of nanomaterials have been explored in the context of MRI contrast agent research. In addition to increasing the paramagnetic payload per particle, the slow rotation of nanosized systems also contributes to the increase of their relaxation e±ciency per Gd3+. —is chapter covers the basic physical-chemistry aspects related to the development of high-e±ciency MRI contrast agents, followed by a more detailed description of the diŸerent classes of gadolinium-based nano-sized imaging probes, involving both inorganic and organic bionanomaterials.
