title: Design and characterization of targeted ultrasound microbubbles for diagnostic use.
abstract: Targeted ultrasound (US) contrast agents represent, because of their size (1 to 5 μm), a unique class of diagnostic imaging agents enabling true vascular imaging of conditions like inflammation and tumor angiogenesis. The objective of this study was to develop technology for preparing targeted microbubbles with binding and acoustic properties compatible with diagnostic use. Phosphatidylcholine (PC) was shown to represent the most favorable wall material. Various thiolated peptide binders were effectively conjugated to PC-based microbubbles containing maleimide functionalized lipids (95:5) without the need for biotin-streptavidin or antibody technology. By optimizing the technology, specific targeting of the inflammatory target E-selectin and the angiogenic target VEGFR2 in the presence of 100% serum was achieved. Increased phospholipid chain length from 18 carbons to 22 carbons improved the stability of the microbubbles during US exposure, without compromising binding or acoustic properties.
authors.affiliation: Omegatri AS, Oslo, Norway.
authors.forename: Astrid Hilde
authors.initials: AH
authors.lastname: Myrset
authors.forename: Hege Brincker
authors.initials: HB
authors.lastname: Fjerdingstad
authors.forename: Ragnar
authors.initials: R
authors.lastname: Bendiksen
authors.forename: Bente Elisabeth
authors.initials: BE
authors.lastname: Arbo
authors.forename: Roger Malerbakken
authors.initials: RM
authors.lastname: Bjerke
authors.forename: John Henrik
authors.initials: JH
authors.lastname: Johansen
authors.forename: Mari Ann
authors.initials: MA
authors.lastname: Kulseth
authors.forename: Roald
authors.initials: R
authors.lastname: Skurtveit
mesh_terms: D000162:Acoustics; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000737:chemistry*; D019040:E-Selectin / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging; D010743:Phospholipids / Q000737:chemistry; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D003287:Contrast Media; D019040:E-Selectin; D010743:Phospholipids; D040301:Vascular Endothelial Growth Factor Receptor-2