Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery

Jameel A. Feshitan, Fotis Vlachos, Shashank R. Sirsi, Elisa E. Konofagou, Mark A. Borden

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 10 5 ± 3.0 × 10 5 Gd(III)/μm 2 after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r 1) and transverse (r 2) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM -1s -1, respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalBiomaterials
Volume33
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Blood-brain barrier opening
  • Cavitation
  • DOTA
  • Lanthanide
  • Perfluorobutane
  • Phospholipid

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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