MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging (MRI) has developed into one of the most versatile techniques in clinical imaging and biomedical research by providing non-invasively high resolution, three-dimensional anatomical and contrast-enhanced images of living tissue. The two most common groups of contrast-enhancing agents are gadolinium-based complexes and magnetic nanoparticles. Both types of contrast agents shorten locally the relaxation time of bulk water protons via rapid exchange of water molecules employing inner- or outer-sphere magnetic interactions to provide T1-, T2-, or T2*-based contrast enhancement. The quest for disease-specific and individualized approaches to imaging requires contrast agents with a relatively high sensitivity and has propelled the development of novel functional or target-specific agents. With this aim, the shift properties of paramagnetic complexes other than gadolinium have been exploited for designing new types of contrast agents with highly specific reporter functionalities. The particularly beneficial chemical shift properties of thulium (III) and their thermal sensitivity, therefore, have stimulated the development of novel thulium (III)-based contrast agents for MR imaging. An important group of such agents is formed by those that generate contrast based on the transfer of saturated magnetization from the contrast agent or from water molecules interacting with a lanthanide shift reagent to the bulk water (chemical exchange saturation transfer (CEST) agents). Magnetization saturation is created using either exchangeable protons of the paramagnetic thulium (III) chelate complex (paraCEST agents), or using water molecules that interact with a thulium shift reagent encapsulated in a liposomal carrier (lipoCEST agents). Various strategies have already been devised to modulate the CEST effect in response to a physiologically meaningful parameter, such as pH, metabolite concentration, or enzyme activity. MR...
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