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

Richa Sethi, Jeyarama S. Ananta, Christof Karmonik, Meng Zhong, Steve H. Fung, Xuewu Liu, King Li, Mauro Ferrari, Lon J. Wilson, Paolo Decuzzi

Research output: Contribution to journalArticle

41 Scopus citations

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 60MHz, they exhibited longitudinal relaxivities of ~24m m-1s-1 for 5-10nm pores and ~10m m-1s-1 for 30 - 40nm 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 3days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24h 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.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalContrast Media and Molecular Imaging
Volume7
Issue number6
DOIs
StatePublished - Nov 2012

Keywords

  • Gadolinium chelates
  • Mesoporous silicon particles
  • MRI contrast agents
  • Relaxivity enhancement

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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