A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity
Resource
BIOMATERIALS, 32(8), 2160-2165
Journal
Biomaterials
Pages
2160-2165
Date Issued
2011
Date
2011
Author(s)
Chen, Kuan-Ju
Wolahan, Stephanie M.
Wang, Hao
Hsu, Chao-Hsiung
Chang, Hsing-Wei
Durazo, Armando
Hwang, Lian-Pin
Garcia, Mitch A.
Jiang, Ziyue K.
Wu, Lily
Lin, Yung-Ya
Tseng, Hsian-Rong
Abstract
We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·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 Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA?SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA?SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA?SNPs with an r1 of 17.3 s-1 mM-1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·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 Gd3+·DTPA. A Gd3+·DOTA?SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA?SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA?SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA?SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. ? 2010 Elsevier Ltd.
Subjects
Cyclodextrin; Dynamic imaging; Gadolinium; MRI; Supramolecular Chemistry; T1-weighted Contrast Agent
Other Subjects
Adamantanes; Broad spectrum; C/N ratio; Cancer metastasis; Chelated complex; Contrast agent; Contrast to noise ratio; Dynamic imaging; Enhanced sensitivity; Ex-vivo; High field; High sensitivity; Lymph node; Mixing ratios; Molecular building blocks; MRI; MRI contrast agents; Potential tool; Relaxation rates; Relaxivity; Signal intensities; Supramolecular assemblies; Chelation; Macromolecules; Magnetic resonance imaging; Molecular biology; Molecular recognition; Nanoparticles; Paramagnetism; Gadolinium; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; adamantane; beta cyclodextrin; contrast medium; gadolinium; magnetic nanoparticle; ultrasmall superparamagnetic iron oxide; animal tissue; article; cancer diagnosis; chelation; ex vivo study; foot pad; lymphatic drainage; molecular library; molecular recognition; mouse; nonhuman; nuclear magnetic resonance imaging; priority journal; relaxation time; sensitivity analysis; signal noise ratio; supramolecular chemistry; Animals; Chelating Agents; Contrast Media; Gadolinium; Heterocyclic Compounds, 1-Ring; Magnetic Resonance Imaging; Materials Testing; Mice; Nanoparticles; Particle Size; Sensitivity and Specificity; Mus
Type
journal article
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