title: Pharmacodynamics of streptavidin-coated cyanoacrylate microbubbles designed for molecular ultrasound imaging.
abstract: OBJECTIVE
  To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging.
  
  
  METHODS
  Biodistribution of MBs was analyzed in tumor-bearing mice using gamma-counting, immunohistochemistry, flow cytometry, and ultrasound. Further, vascular endothelial growth factor receptor 2-antibody coupled MBs were used to image tumor neovasculature.
  
  
  RESULTS
  After 1 minute >90% of MBs were cleared from the blood and pooled in the lungs, liver, and spleen. Subsequently, within 1 hour a decent reincrease of MB-concentration was observed in the blood. The remaining MBs were removed by liver and spleen macrophages. About 30% of the phagocytosed MBs were intact after 48 hours. Shell fragments were found in the kidneys only. No relevant MB-accumulation was observed in tumors. In contrast, vascular endothelial growth factor receptor 2-specific MBs accumulated significantly within the tumor vasculature (P < 0.05).
  
  
  CONCLUSIONS
  The pharmacokinetic behavior of streptavidin-coated cyanoacrylate MBs has been studied. In this context, the low amount of MBs in tumors after >5 minutes is beneficial for specific targeting of angiogenesis.
authors.affiliation: Department of Diagnostic Radiology, Ruprecht-Karls University, Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.forename: Bernd
authors.initials: B
authors.lastname: Morgenstern
authors.forename: Peter
authors.initials: P
authors.lastname: Hauff
authors.forename: Michael
authors.initials: M
authors.lastname: Reinhardt
authors.forename: Jochen
authors.initials: J
authors.lastname: Huppert
authors.forename: Mathias
authors.initials: M
authors.lastname: Maurer
authors.forename: Eva C
authors.initials: EC
authors.lastname: Woenne
authors.forename: Sebastian
authors.initials: S
authors.lastname: Doerk
authors.forename: Gesa
authors.initials: G
authors.lastname: Ladewig
authors.forename: Juergen W
authors.initials: JW
authors.lastname: Jenne
authors.forename: Stefan
authors.initials: S
authors.lastname: Delorme
authors.forename: Lars
authors.initials: L
authors.lastname: Grenacher
authors.forename: Peter
authors.initials: P
authors.lastname: Hallscheidt
authors.forename: Guenter W
authors.initials: GW
authors.lastname: Kauffmann
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003287:Contrast Media / Q000493:pharmacokinetics*; D003487:Cyanoacrylates / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D009928:Organ Specificity; D019809:Streptavidin / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014463:Ultrasonography
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D003487:Cyanoacrylates; D019809:Streptavidin