Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi.
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.
Schumann
Patricia A
PA
ImaRx Therapeutics, Inc., Tucson, Arizona 85719, USA.
Christiansen
Jonathan P
JP
Quigley
Rachel M
RM
McCreery
Thomas P
TP
Sweitzer
Robert H
RH
Unger
Evan C
EC
Lindner
Jonathan R
JR
Matsunaga
Terry O
TO
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*
D003287:Contrast Media; D005466:Fluorocarbons; D008024:Ligands; D019039:Platelet Glycoprotein GPIIb-IIIa Complex