Left ventricular thrombus enhancement after intravenous injection of echogenic immunoliposomes: studies in a new experimental model.
BACKGROUND
Targeted echogenic immunoliposomes (ELIPs) for ultrasound enhancement of atheroma components have been developed. To date, ELIP delivery has been intra-arterial. To determine whether ELIPs can be given intravenously with enhancement of systemic structures, a left ventricular thrombus (LVT) model was developed.


RESULTS
In 6 animals plus 1 dose-ranging animal, the apical coronary arteries were ligated, and an LVT was produced by injecting Hemaseel fibrin adhesive through the apical myocardium. The thrombus was imaged epicardially and transthoracically at 0, 1, 5, and 10 minutes after anti-fibrinogen ELIP injections. The dose of ELIPs was varied. PBS and unconjugated ELIPs were controls. The apical thrombi were easily reproduced and clearly visible with epicardial and transthoracic ultrasound. Enhancement occurred with 2 mg anti-fibrinogen ELIPs and increased with dose. With 8 mg ELIPs, enhancement was different from control within 10 minutes (P<0.05). Rhodamine-labeled anti-fibrinogen ELIPs were seen with fluorescence microscopy of the LVT. Blinded viewing detected enhancement by 10 minutes in all animals after anti-fibrinogen ELIPs.


CONCLUSIONS
We describe an easily reproducible LVT model. Anti-fibrinogen ELIPs delivered intravenously, as a single-step process, rapidly enhance the ultrasound image of a systemic target. This allows for future development of ELIPs as a targeted ultrasound contrast agent.
Hamilton
Andrew
A
Department of Medicine, Northwestern University, Chicago, Ill 60611-2908, USA. a-hamilton@northwestern.edu
Huang
Shao-Ling
SL
Warnick
Drew
D
Stein
Adam
A
Rabbat
Mark
M
Madhav
Taruna
T
Kane
Bonnie
B
Nagaraj
Ashwin
A
Klegerman
Melvin
M
MacDonald
Robert
R
McPherson
David
D
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001161:Arteriosclerosis / Q000000981:diagnostic imaging; D003287:Contrast Media; D004285:Dogs; D004452:Echocardiography / Q000379:methods*; D005340:Fibrinogen / Q000276:immunology*; D006331:Heart Diseases / Q000000981:diagnostic imaging*; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D007275:Injections, Intravenous; D007700:Kinetics; D008081:Liposomes; D008856:Microscopy, Fluorescence; D015588:Observer Variation; D010496:Pericardium / Q000000981:diagnostic imaging; D013909:Thorax; D013927:Thrombosis / Q000000981:diagnostic imaging*
D000906:Antibodies; D003287:Contrast Media; D008081:Liposomes; D005340:Fibrinogen