Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents (CA) have been routinely used for detecting tumor at an early stage. Gadolinium-based CA are the most commonly used CA in clinical MRI. There have been significant efforts to design and develop novel Gd(III) CA with high relaxivity, low toxicity, and specific tumor binding. The relaxivity of the Gd(III) CA can be increased by proper chemical modification. The toxicity of Gd(III) CA can be reduced by increasing the agents' thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific CA. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR CA tumor imaging. WIREs Nanomed Nanobiotechnol 2013, 5:1–18. doi: 10.1002/wnan.1198
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