Gadolinium(III)-based blood-pool contrast agents for magnetic resonance imaging: status and clinical potential

Blood-pool MRI contrast agents have enormous potential to aid sensitive magnetic resonance detection and yield definitive diagnostic data of cancer and diseases of the cardiovascular system. Many attempts have been initiated to design macromolecular gadolinium (Gd[III]) complexes as magnetic resonance imaging blood-pool contrast agents, as macromolecules do not readily diffuse across healthy vascular endothelium, and remain intravascular. Although extremely efficacious in detecting and characterizing pathologic tissue, clinical development of these agents has been limited by potential toxicity concerns from incomplete Gd(III) clearance. Recent innovative technologies, such as reversible protein-binding contrast agents and biodegradable macromolecular contrast agents, may be valuable alternatives that combine the effective imaging characteristics of an intravascular contrast agent and the safety of clinically approved low-molecular-weight Gd(III) chelates.