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

43 Citations (Scopus)

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 1 2012

Fingerprint

Microbubbles
Magnetic resonance
Surgery
Lipids
Ultrasonics
Magnetic Resonance Imaging
Imaging techniques
Chelation
Lipid bilayers
Sonication
Biocompatible Materials
Cavitation
Biomaterials
Protons
Ligands
Ions
Ultrasonography
Lipid III
Theranostic Nanomedicine
Lipid Bilayers

Keywords

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

ASJC Scopus subject areas

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

Cite this

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery. / Feshitan, Jameel A.; Vlachos, Fotis; Sirsi, Shashank R.; Konofagou, Elisa E.; Borden, Mark A.

In: Biomaterials, Vol. 33, No. 1, 01.01.2012, p. 247-255.

Research output: Contribution to journalArticle

Feshitan, Jameel A. ; Vlachos, Fotis ; Sirsi, Shashank R. ; Konofagou, Elisa E. ; Borden, Mark A. / Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery. In: Biomaterials. 2012 ; Vol. 33, No. 1. pp. 247-255.
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