Left Ventricular Thrombus Enhancement After Intravenous Injection of Echogenic Immunoliposomes

Abstract

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. Methods and 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 (PϽ0.05). 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.

Ultrasound-facilitated thrombolysis using tissue-plasminogen activator-loaded echogenic liposomes

“…We have demonstrated specific highlighting of atheroma with intraarterial injection of anti-intercellular adhesion molecule-1-conjugated ELIP [15], as well as targeted highlighting of a left ventricular thrombus with intravenous injection of anti-fibrinogen-conjugated ELIP [16]. We have also reported entrapment of an antibiotic and of reporter genes into these ELIP with demonstration of microbial growth inhibition and gene transfection, respectively, in cultured cells [17,18].…”

“…We have previously reported development of echogenic liposomes (ELIP) for the targeted highlighting of structures [15,16] with potential for drug and gene delivery [17][18][19]. This study aimed to explore the potential of ELIP for thrombolytic loading, and to evaluate the effect of directed ultrasound exposure of the thrombolytic-loaded ELIP on effecting drug release and promoting thrombolysis.…”

Molecular Imaging of Cardiovascular Disease

“…Consequently, molecular imaging of contrast ultrasound has involved mainly molecular changes within the vascular compartment. Targeted contrast ultrasound has therefore been applied in angiogenesis, (19,20) vascular infl ammation (21,22) and thrombus formation (23) .…”

The application of antitumor drug-targeting models on liver cancer

“…As a consequence, HVJ liposomes acted pretty solid improvement on the body weight and pathological indicators of nude mice. Moreover, researchers subcutaneously inoculated human hepatoma cells into BALB/c nude mice to investigate targeted ultrasound contrast agents, and the outcome demonstrated that the agents are able to specifically enhance the targeting efficiency of hepatocellular carcinoma (Hamilton et al, 2002;LeongPoi et al, 2003).…”