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Nano-sized MRI contrast agents with dendrimer cores.

Kobayashi H, Brechbiel MW

Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA. Kobayash@mail.nih.gov

Gadolinium-based MRI contrast agents (CAs) can be effective at a approximately 100-fold lower concentration of Gadolinium ions in comparison to the concentration of Iodine atoms required for CT imaging. Therefore, a number of dendrimer based macromolecular MRI CAs of various sizes and properties prepared employing relatively simple chemistry are readily available that can provide sufficient contrast enhancement for various applications. Molecules up to 20 nm in diameter behave differently in the body depending on their size. Even if these molecules possess similar chemical properties, small changes in size can greatly impact their pharmacokinetics. Changes in molecular size up to 15 nm in diameter altered permeability across the vascular wall, excretion route, and recognition by the reticuloendothelial system. Smaller sized polyamidoamine (PAMAM) dendrimer-based contrast agents, i.e., less than 3 nm in diameter, easily "leak" across the vascular wall resulting in rapid perfusion throughout the body. Contrast agents 3-6 nm in diameter were quickly excreted through the kidney indicating these agents to be potentially suitable as functional renal contrast agents. Contrast agents 7-12 nm in diameter were retained in circulation and were better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polypropylenimine diaminobutane (DAB) dendrimer cores quickly accumulated in the liver and potentially have use as liver contrast agents. Larger hydrophilic agents have suitable characteristics for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

Published 12 December 2005 in Adv Drug Deliv Rev, 57(15): 2271-86.
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