In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement

• Published in: Journal of the American College of Cardiology Vol. 33; no. 3; pp. 867 - 875
• Main Authors: Demos, Sasha M., Alkan-Onyuksel, Hayat, Kane, Bonnie J., Ramani, Kishin, Nagaraj, Ashwin, Greene, Rodney, Klegerman, Melvin, McPherson, David D.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.1999; Elsevier Science
• Subjects: Animals; Antibodies - administration & dosage; Arteriosclerosis - complications; Arteriosclerosis - diagnostic imaging; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Arteries - diagnostic imaging; Drug Carriers; Endothelium, Vascular - diagnostic imaging; Endothelium, Vascular - metabolism; Femoral Artery - diagnostic imaging; Fibrinogen - immunology; Image Enhancement; Injections, Intra-Arterial; Intercellular Adhesion Molecule-1 - immunology; Liposomes - administration & dosage; Liposomes - chemistry; Medical sciences; Swine; Swine, Miniature; Thromboembolism - diagnostic imaging; Thromboembolism - etiology; Ultrasonography, Interventional - methods; BAP; DPPG; PC; ATH; DTT; MPB-PE; ICAM-1; SPDP; Sonography; Liposome; Cardiovascular disease; Exploration; Endovascular route; Vascular disease; Vertebrata; Mammalia; Atherosclerotic plaque; Animal; Atherosclerosis; Echography; Artiodactyla; Minipig; Technique; Ungulata; Contrast media
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(98)00607-X

OBJECTIVES The purpose of this study was to target acoustically reflective liposomes to atherosclerotic plaques in vivo for ultrasound image enhancement. BACKGROUND We have previously demonstrated the development of acoustically reflective liposomes that can be conjugated for site-specific acoustic enhancement. This study evaluates the ability of liposomes coupled to antibodies specific for different components of atherosclerotic plaques and thrombi to target and enhance ultrasonic images in vivo. METHODS Liposomes were prepared with phospholipids and cholesterol using a dehydration/rehydration method. Antibodies were thiolated for liposome conjugation with N-succinimidyl 3-(2-pyridyldithio) propionate resulting in a thioether linkage between the protein and the phospholipid. Liposomes were conjugated to antifibrinogen or anti–intercellular adhesion molecule-1 (anti–ICAM-1). In a Yucatan miniswine model, atherosclerosis was developed by crush injury of one carotid and one femoral artery and ingestion of a hypercholesterolemic diet. After full plaque development the arteries were imaged (20-MHz intravascular ultrasound catheter and 7.5-MHz transvascular linear probe) after injection of saline, unconjugated liposomes and antibody conjugated liposomes. RESULTS Conjugated liposomes retained their acoustically reflective properties and provided ultrasonic image enhancement of their targeted structures. Liposomes conjugated to antifibrinogen attached to thrombi and fibrous portions of the atheroma, whereas liposomes conjugated to anti–ICAM-1 attached to early atheroma. CONCLUSIONS Our data demonstrate that this novel acoustic agent can provide varying targeting with different antibodies with retention of intravascular and transvascular acoustic properties.