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dc.contributor.authorSethi, Richa
Ananta, Jeyarama S.
Karmonik, Christof
Zhong, Meng
Fung, Steve H.
Liu, Xuewu
Li, King
Ferrari, Mauro
Wilson, Lon J.
Decuzzi, Paolo
dc.date.accessioned 2015-01-05T20:03:20Z
dc.date.available 2015-01-05T20:03:20Z
dc.date.issued 2012
dc.identifier.citation Sethi, Richa, Ananta, Jeyarama S., Karmonik, Christof, et al.. "Enhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs." Contrast Media & Molecular Imaging, 7, no. 6 (2012) 501-508. http://dx.doi.org/10.1002/cmmi.1480.
dc.identifier.urihttp://hdl.handle.net/1911/78849
dc.description.abstract Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~24 m m−1 s−1 for 5–10 nm pores and ~10 m m−1 s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]3−, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24 h of continuous agitation in phosphate-buffered saline. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]3−) and, potentially, improved stability, reduced toxicity and tissue specificity.
dc.language.iso eng
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.
dc.title Enhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs
dc.type Journal article
dc.contributor.funder Cancer Prevention Research Institute of Texas
dc.contributor.funder National Institutes of Health
dc.contributor.funder Welch Foundation
dc.citation.journalTitle Contrast Media & Molecular Imaging
dc.contributor.org Smalley Institute for Nanoscale Science and Technology
dc.contributor.org Center for Biological and Environmental Nanotechnology
dc.subject.keywordgadolinium chelates
MRI contrast agents
relaxivity enhancement
mesoporous silicon particles
dc.citation.volumeNumber 7
dc.citation.issueNumber 6
dc.contributor.publisher Wiley
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1002/cmmi.1480
dc.identifier.pmcid PMC3846290
dc.identifier.pmid 22991316
dc.identifier.grantID CPRIT RP110262 (Cancer Prevention Research Institute of Texas)
dc.identifier.grantID U54CA143837 (National Institutes of Health)
dc.identifier.grantID U54CA151668 (National Institutes of Health)
dc.identifier.grantID C-0627 (Welch Foundation)
dc.type.publication post-print
dc.citation.firstpage 501
dc.citation.lastpage 508


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