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The precise molecular location of gadolinium atoms has a significant influence on the efficacy of nanoparticulate MRI positive contrast agents

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The precise molecular location of gadolinium atoms has a significant influence on the efficacy of nanoparticulate MRI positive contrast agents

Content Provider	Royal Society of Chemistry (RSC)
Author	Davis, Thomas P. Lowe, Andrew B. Esser, Lars Elst, Luce Vander Muller, Robert N. Laurent, Sophie Li, Yang Boyer, Cyrille
Copyright Year	2014
Abstract	In this work, we studied the influence of the structure of macromolecular ligands on the relaxivity of gadolinium contrast agents constructed as nanoparticle systems. Macromolecular ligands were assembled as single-molecule nanoparticles in the form of either discrete core cross-linked star polymers or hyperbranched polymers. 1-(5-Amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraaza-cyclododecane (DO3A–tBu–NH2) chelate was incorporated into different parts (arms, cores, and end-groups) of the polymeric structures using activated ester/amine nucleophilic substitutions, deprotected and complexed with Gd3+. The relaxivity properties of the ligated Gd3+ agents were then studied to evaluate the effect of macromolecular architecture and Gd3+ placement on their behavior as discrete nanoparticle magnetic resonance imaging (MRI) contrast agents. The precise placement of Gd3+ in the polymeric structures (and therefore in the nanoparticles) proved to be critical in optimizing the performance of the nanoparticles as MRI contrast agents. The relaxivity was measured to vary from 11 to 22 mM−1 s−1, 2–5 times higher than that of a commercial DOTA–Gd contrast agent when using a magnetic field strength of 0.47 T. The relaxivity of these nanoparticles was examined at different magnetic fields from 0.47 T to 9.4 T. Finally, the residence time of the coordinated water (τM) and the rotational correlation time of the final molecule (τR) were evaluated for these different nanostructures and correlated with the polymeric architecture.
Starting Page	2592
Ending Page	2601
Page Count	10
File Format	HTM / HTML PDF
ISSN	17599954
Volume Number	5
Issue Number	7
Journal	Polymer Chemistry
DOI	10.1039/c3py01676e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Ester Nucleophilic aromatic substitution Magnetic resonance imaging Nanoparticle DOTA MRI contrast agent Magnetic field Rotational correlation time
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Bioengineering Biomedical Engineering Polymers and Plastics

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