Blood-pool and targeting MRI contrast agents: From Gd-Chelates to Gd-nanoparticles

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 [Gd^III] 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 Gd ^III-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. A new family of BPCAs and tumor-targeting MRI CAs are provided and characterized by a neutral Gd-chelate, [Gd(H₂O)(L)], where chelates (L) are DTPA-conjugates of ferrocenyldiamines (1), diaminobiphenyls (2), and DOTA-conjugates of tranexamates (3) and liver-targeting CAs by gold nanoparticles coated with GdL (Au@GdL). Tumor-targeting is achieved by GdL-RGD conjugation and GdO nanoparticles.