Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?
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- 作者：Joshua M. Bryson ; Jeffrey W. Reineke ; Theresa M. Reineke
- 刊名：Macromolecules
- 出版年：2012
- 出版时间：November 27, 2012
- 年：2012
- 卷：45
- 期：22
- 页码：8939-8952
- 全文大小：662K
- 年卷期：v.45,no.22(November 27, 2012)
- ISSN：1520-5835
文摘
Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limit the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, has been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, and aggregation-resistant and have a controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, noncovalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent works in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein, and the future outlook of this field is discussed.