title: 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.affiliation: Department of Molecular and Medical Pharmacology, California NanoSystems Institute (CNSI), Crump Institute for Molecular Imaging (CIMI), University of California, Los Angeles, 570 Westwood Plaza, Building 114, Los Angeles, CA 90095-1770, USA.
authors.forename: Kuan-Ju
authors.initials: KJ
authors.lastname: Chen
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Wolahan
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Chao-Hsiung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Hsing-Wei
authors.initials: HW
authors.lastname: Chang
authors.forename: Armando
authors.initials: A
authors.lastname: Durazo
authors.forename: Lian-Pin
authors.initials: LP
authors.lastname: Hwang
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Garcia
authors.forename: Ziyue K
authors.initials: ZK
authors.lastname: Jiang
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
authors.forename: Yung-Ya
authors.initials: YY
authors.lastname: Lin
authors.forename: Hsian-Rong
authors.initials: HR
authors.lastname: Tseng
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012680:Sensitivity and Specificity
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium