In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement
In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement
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DOI：
10.1016/s0735-1097(98)00607-x
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发表时间：
1999-03-01
影响因子：
24
通讯作者：
McPherson, DD
中科院分区：
文献类型：
--
作者：
Demos, SM;Alkan-Onyuksel, H;McPherson, DD
目的本研究的目的是将声反射脂质体靶向体内的动脉粥样硬化斑块进行超声图像增强。本研究评估了针对动脉粥样硬化斑块和血栓不同成分的抗体偶联的脂质体在体内靶向和增强超声图像的能力。方法以磷脂和胆固醇为原料，采用脱水/复水方法制备脂质体。抗体与N-琥珀酰亚胺基-3-(2-吡啶二硫)丙酸酯进行硫代化，形成硫醚键连接蛋白和磷脂。将脂质体与抗纤维蛋白原、抗细胞间黏附分子-1(anti-ICAM-1)偶联。在尤卡坦迷你葡萄酒模型中，动脉粥样硬化是通过挤压损伤一条颈动脉和一条股动脉以及摄入高胆固醇饮食而形成的。斑块形成后，注射生理盐水、非偶联脂质体和抗体偶联脂质体后，用20 MHz血管内超声导管和7.5 MHz经血管线性探头对动脉进行成像。结果结合脂质体保留了其声反射特性，并对其靶结构提供了超声图像增强。与抗纤维蛋白原结合的脂质体与血栓和动脉粥样硬化的纤维部分结合，而与抗ICAM-1结合的脂质体结合在动脉粥样硬化早期。(C)1999年由美国心脏病学会颁发。
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 br 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. (C) 1999 by the American College of Cardiology.