title: Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery.
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(-1)s(-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.
authors: Department of Chemical Engineering, Columbia University, NY 10027, USA.
authors: Jameel A
authors: JA
authors: Feshitan
authors: Fotis
authors: F
authors: Vlachos
authors: Shashank R
authors: SR
authors: Sirsi
authors: Elisa E
authors: EE
authors: Konofagou
authors: Mark A
authors: MA
authors: Borden
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D007668:Kidney / Q000000981:diagnostic imaging; D008051:Lipid Bilayers / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D045423:Microbubbles; D013388:Succinimides / Q000737:chemistry; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; C502492:DOTA-NHS; D008051:Lipid Bilayers; D013388:Succinimides; D005682:Gadolinium