title: Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi.
abstract: OBJECTIVE
  New targeted microbubbles directed to the GPIIb IIIa receptor have been developed. The objective was to determine whether targeting microbubbles to clots would enhance ultrasound imaging. Systematic studies were designed to determine whether in vitro methodology is an acceptable predictor of in vivo efficacy.
  
  
  METHODS
  Bioconjugate ligands were inserted into lipid-coated membranes of perfluorocarbon gas microbubbles and binding studies performed on activated platelets immobilized on cell culture plates. Targeted microbubble binding to clots in a flow through chamber was also assessed. Finally, microbubble binding studies on arteriolar and venular clots in a mouse cremasteric muscle model were conducted.
  
  
  RESULTS
  Binding studies on platelet-immobilized plates demonstrated an affinity for targeted microbubbles versus untargeted microbubbles. Semiquantitative light obscuration techniques helped to measure extent of targeted microbubble binding. Targeted microbubbles similarly bound to platelet clots in the flow model. Finally, studies in the mouse model confirmed binding of targeted microbubbles in both venules and arterioles.
  
  
  CONCLUSIONS
  The use of receptor selective targeted microbubbles improved binding to vascular thrombi in both in vitro and in vivo settings.
authors.affiliation: ImaRx Therapeutics, Inc., Tucson, Arizona 85719, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Schumann
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Christiansen
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Quigley
authors.forename: Thomas P
authors.initials: TP
authors.lastname: McCreery
authors.forename: Robert H
authors.initials: RH
authors.lastname: Sweitzer
authors.forename: Evan C
authors.initials: EC
authors.lastname: Unger
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.forename: Terry O
authors.initials: TO
authors.lastname: Matsunaga
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005466:Fluorocarbons; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010784:Photomicrography; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D013927:Thrombosis / Q000000981:diagnostic imaging*; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex