title: Advanced characterization and refinement of poly N-butyl cyanoacrylate microbubbles for ultrasound imaging.
abstract: We aimed to develop and characterize poly n-butylcyanoacrylate (PBCA) microbubbles (MBs) with a narrow size distribution. MBs were synthesized by established emulsion polymerization techniques, size-isolated by centrifugation and functionalized for molecular imaging by coating their surface with streptavidin. The physical and acoustic properties of the parent solution, different-size isolated populations and functionalized MBs were measured and compared. As expected from negative zeta potentials at pH 7, cryo scanning electron microscopy showed no aggregates. In phantoms MBs were destructible at high mechanical indices and showed a frequency-dependent attenuation and backscattering. The MBs were stable in solution for more than 14 weeks and could be lyophilized without major damage. However, for injection, small needle diameters and high injection rates are shown to be critical because both lead to MB destruction. In summary, when being handled correctly, size-isolated PBCA MBs are promising candidates for preclinical functional and molecular ultrasound imaging.
authors.affiliation: Department of Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Stanley
authors.initials: S
authors.lastname: Fokong
authors.forename: Monica
authors.initials: M
authors.lastname: Siepmann
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Georg
authors.initials: G
authors.lastname: Schmitz
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Jessica
authors.initials: J
authors.lastname: Gätjens
mesh_terms: D002498:Centrifugation; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis*; D004355:Drug Stability; D004659:Enbucrilate / Q000737:chemistry*; D005434:Flow Cytometry; D005612:Freeze Drying; D045423:Microbubbles; D008855:Microscopy, Electron, Scanning; D019809:Streptavidin / Q000737:chemistry; D014463:Ultrasonography
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D019809:Streptavidin; D004659:Enbucrilate