Blood‐Pool and Targeting MRI Contrast Agents: From Gd‐Chelates to Gd‐Nanoparticles

Abstract

Magnetic resonance imaging (MRI) is a powerful and noninvasive diagnostic technique of the human anatomy, physiology, and pathophysiology on the basis of superior spatial resolution and contrast. MRI is useful in providing anatomical and functional images of the human body. A large number of MRI techniques are performed employing gadolinium III [GdIII] complexes to enhance image contrast by increasing the water proton relaxation rate in the body. Despite their wide and successful application in clinic, however, conventional GdIII‐based low‐molecular weight contrast agents (CAs) are mostly extracellular contrast agents (ECCAs) exhibiting rapid extravasation from the vascular space. As a result, the time window for imaging is considerably reduced, thus limiting acquisition of high‐resolution images. To overcome such limitations inherent to ECCAs, the necessity and the demand for the development of a new class of MRI CAs with functions including blood‐pool and organ (or tumor)‐targeting have risen recently. This microreview deals with our recent efforts on the design and the synthesis of new Gd‐chelates and Gd nanoparticles (GdNPs) for use as blood‐pool and organ/tumor‐targeting MRI CAs. We also consider properties such as high r1 relaxivity and high thermodynamic, kinetic, and biostabilities.

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 ­Years of Studies

“…[14,29] On the other hand, the general assumption is that blood-pool CAs (contrast agents suited to analysis of blood vessels: angiography) are very hydrophilic, high-molecular-weight molecules, so they have longer intravascular residence times due to limited diffusion through the capillary walls. [30] Finally, structural elements, the character of additional groups or moieties in the ligand, and the charge of the complex are considered in depth in the case of targeting an agent to the lymph or to crossing the cell membranes of the blood-brain barrier. [31] …”

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

“…23 Different types of Gd-containing contrast agents have been approved by the European Medicines Agency (EMEA) and the US Food and Drug Administration (FDA) ( Table 1) for use in MRI as a contrast agent to provide improved images of organs and tissues.…”

Hybrid Nanoparticles for Cancer Imaging and Therapy

“…MRI provides excellent spatial resolution, high soft tissue contrast, and unlimited penetration depth, but is intrinsically insensitive [32]. Therefore, large doses of contrast enhancement agents such as Gd(III) chelates are used in clinical scans to enhance the contrast between normal and diseased tissues [60]. The effectiveness of Gd(III)-containing NMOFs as T 1 -weighted contrast agents was first demonstrated by Lin and coworkers [52,53,61].…”