Ultrasound is used as a primary diagnostic technique for the detection
of deep venous thrombosis, The purpose of this study is to describe t
he development of a new thrombus-specific ultrasound contrast agent: T
he linear hexapeptide lysine-glutamine-alanine-glycine-aspartate-valin
e) was synthesized and coupled to a lipid moiety. The targeted lipid w
as then incorporated irate the lipid blend for the contrast agent Aero
somes (ImaRx, Tucson, AZ, USA).The lipid blend was used to entrap perf
luorobutane microbubbles. The microbubbles were sited and studied in v
itro for acoustic stability, binding to blood clot, and ultrasound enh
ancement in vitro of blood clot. The results showed the mean size of t
he specific ultrasound contrast agent (MRX-408) was about 2.0 mu m. Th
e microbubbles appeared as smooth spherical structures, Microscopy sho
wed that the targeted bubbles bound to blood clot whereas control, non
targeted bubbles did not bind to blood clot. In vitro acoustic study s
howed similar stability of the microbubbles compared with control micr
obubbles,The targeted microbubbles enhanced blood clot in vitro wherea
s nontargeted microbubbles did not enhance clot. Thus this promising n
ew thrombus-specific ultrasound contrast agent cooed potentially impro
ve detection of thrombosis by ultrasound and might be useful for disti
nguishing between new and old thrombosis, In vivo studies are in progr
ess. (C) 1998 by Excerpta Medica, Inc.