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e.g., Gd(III) chelates and Mn(II) chelates, and ultrasmall superparamagnetic iron oxide (USPIO).26 Gd(III) chelates of DTPA, DOTA, or their derivatives are commonly used for contrast-enhanced MRI. Both Gd(III) and Mn(II) chelates are mainly used as T1 contrast agents, whereas USPIO is used as a T2 contrast agent. These agents significantly enhance image contrast between normal tissue and diseased tissue and improve the diagnostic accuracy. Currently, contrast agents are used in approximately 30% of clinical MRI examinations. Macromolecular Gd(III) complexes have also been developed as MRI contrast agents.27,28 These agents have a prolonged blood circulation time and preferentially accumulate in solid tumors due to the EPR effect. Macro-molecular Gd(III) complexes have demonstrated superior contrast enhancement in MR angiography and cancer imaging in animal models, but are not yet approved for clinical applications.

Contrast-enhanced MRI is a useful method for noninvasive in vivo evaluation of polymeric drug delivery systems after the systems are labeled with MRI contrast agents. The real-time pharmacokinetics and biodistribution of the labeled drug delivery systems can be continuously visualized by contrast-enhanced MRI. It has a potential to provide accurate four-dimensional information of in vivo properties of the drug delivery systems.

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