Enhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs

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dc.citation.firstpage501en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitleContrast Media & Molecular Imagingen_US
dc.citation.lastpage508en_US
dc.citation.volumeNumber7en_US
dc.contributor.authorSethi, Richaen_US
dc.contributor.authorAnanta, Jeyarama S.en_US
dc.contributor.authorKarmonik, Christofen_US
dc.contributor.authorZhong, Mengen_US
dc.contributor.authorFung, Steve H.en_US
dc.contributor.authorLiu, Xuewuen_US
dc.contributor.authorLi, Kingen_US
dc.contributor.authorFerrari, Mauroen_US
dc.contributor.authorWilson, Lon J.en_US
dc.contributor.authorDecuzzi, Paoloen_US
dc.contributor.orgSmalley Institute for Nanoscale Science and Technologyen_US
dc.contributor.orgCenter for Biological and Environmental Nanotechnologyen_US
dc.date.accessioned2015-01-05T20:03:20Zen_US
dc.date.available2015-01-05T20:03:20Zen_US
dc.date.issued2012en_US
dc.description.abstractGadolinium 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.en_US
dc.identifier.citationSethi, Richa, Ananta, Jeyarama S., Karmonik, Christof, et al.. "Enhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs." <i>Contrast Media & Molecular Imaging,</i> 7, no. 6 (2012) Wiley: 501-508. http://dx.doi.org/10.1002/cmmi.1480.en_US
dc.identifier.doihttp://dx.doi.org/10.1002/cmmi.1480en_US
dc.identifier.urihttps://hdl.handle.net/1911/78849en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.en_US
dc.subject.keywordgadolinium chelatesen_US
dc.subject.keywordMRI contrast agentsen_US
dc.subject.keywordrelaxivity enhancementen_US
dc.subject.keywordmesoporous silicon particlesen_US
dc.titleEnhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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