Chen, Kuan-JuKuan-JuChenWolahan, Stephanie M.Stephanie M.WolahanWang, HaoHaoWangHsu, Chao-HsiungChao-HsiungHsuChang, Hsing-WeiHsing-WeiChangDurazo, ArmandoArmandoDurazoHwang, Lian-PinLian-PinHwangGarcia, Mitch A.Mitch A.GarciaJiang, Ziyue K.Ziyue K.JiangWu, LilyLilyWuLin, Yung-YaYung-YaLinTseng, Hsian-RongHsian-RongTseng2012-05-122018-07-102012-05-122018-07-102011http://ntur.lib.ntu.edu.tw//handle/246246/239190We 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.en-USCyclodextrin; Dynamic imaging; Gadolinium; MRI; Supramolecular Chemistry; T1-weighted Contrast Agent[SDGs]SDG3[SDGs]SDG6Adamantanes; 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; Musjournal article10.1016/j.biomaterials.2010.11.043http://ntur.lib.ntu.edu.tw/bitstream/246246/239190/-1/176.pdf