A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity.

Abstract

We introduce a new category of nanoparticle-based T(1) MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd(3+)·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd(3+)·DOTA-encapsulated supramolecular nanoparticles (Gd(3+)·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd(3+)·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd(3+)·DOTA⊂SNPs with an r(1) of 17.3 s(-1) mM(-1) (ca. 4-fold higher than clinical Gd(3+) chelated complexes at high field strengths) was identified. T(1)-weighted imaging of Gd(3+)·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd(3+)·DTPA. A Gd(3+)·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd(3+)·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T(1)-weighted imaging after injecting Gd(3+)·DOTA⊂SNPs but not after injecting Gd(3+)·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd(3+)·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.

• Authors: Kuan-Ju Chen, Stephanie M Wolahan, Hao Wang, Chao-Hsiung Hsu, Hsing-Wei Chang, Armando Durazo, Lian-Pin Hwang, Mitch A Garcia, Ziyue K Jiang, Lily Wu, Yung-Ya Lin, Hsian-Rong Tseng
• Journal: Biomaterials (Biomaterials) Vol. 32 Issue 8 Pg. 2160-5 (Mar 2011) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 21167594 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Chelating Agents
• Contrast Media
• Heterocyclic Compounds, 1-Ring
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Gadolinium

Topics

• Animals
• Chelating Agents (chemistry)
• Contrast Media (chemistry)
• Gadolinium (chemistry)
• Heterocyclic Compounds, 1-Ring (chemistry)
• Magnetic Resonance Imaging (methods)
• Materials Testing
• Mice
• Nanoparticles (chemistry)
• Particle Size
• Sensitivity and Specificity