title: A novel site-targeted ultrasonic contrast agent with broad biomedical application.
abstract: BACKGROUND
  In this work, we report a novel targetable ultrasonic contrast agent with the potential to noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a biotinylated, lipid-coated, perfluorocarbon emulsion that has low inherent echogenicity unless bound to a surface or itself.
  
  
  RESULTS
  In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emulsion manifested significant ultrasonic backscatter until avidin was added. Avidin-induced aggregation produced a marked enhancement in backscatter from the biotinylated but not from the control emulsion. In study 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoustic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arterial thrombi were created in dogs and then exposed to antifibrin antibodies and avidin in situ. Biotinylated or control emulsion was administered either in situ or systemically. At baseline, all thrombi were undetectable with a 7.5-MHz linear-array transducer. Thrombi exposed to antifibrin-targeted contrast exhibited increased echogenicity (P < .05); control thrombi remained acoustically undetectable.
  
  
  CONCLUSIONS
  These data provide the first in vivo demonstration of a site-specific ultrasonic contrast agent and have potential for improved sensitivity and specificity for noninvasive diagnosis of thrombi and other pathological diseases.
authors.affiliation: Department of Medicine, Barnes-Jewish Hospital of St Louis, MO 63130, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Lanza
authors.forename: K D
authors.initials: KD
authors.lastname: Wallace
authors.forename: M J
authors.initials: MJ
authors.lastname: Scott
authors.forename: W P
authors.initials: WP
authors.lastname: Cacheris
authors.forename: D R
authors.initials: DR
authors.lastname: Abendschein
authors.forename: D H
authors.initials: DH
authors.lastname: Christy
authors.forename: A M
authors.initials: AM
authors.lastname: Sharkey
authors.forename: J G
authors.initials: JG
authors.lastname: Miller
authors.forename: P J
authors.initials: PJ
authors.lastname: Gaffney
authors.forename: S A
authors.initials: SA
authors.lastname: Wickline
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001360:Avidin; D001710:Biotin; D003287:Contrast Media; D004285:Dogs; D004655:Emulsions; D005263:Femoral Artery; D005337:Fibrin; D005466:Fluorocarbons; D010714:Phosphatidylethanolamines; D012542:Scattering, Radiation; D013552:Swine; D013927:Thrombosis / Q000000981:diagnostic imaging*; D014464:Ultrasonic Therapy; D014463:Ultrasonography
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D004655:Emulsions; D005466:Fluorocarbons; D010714:Phosphatidylethanolamines; D001360:Avidin; D001710:Biotin; D005337:Fibrin