Xiao W, Wang L, Scott T, Counsell R E, Liu H
School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada.
Pharm Res. 1999 Mar;16(3):420-6. doi: 10.1023/a:1018881904228.
Atherosclerosis is the underlying factor leading to such cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction. The early detection of atherosclerotic plaques is considered to be crucial for successful prevention and/or therapeutic and dietary intervention of CVD. Current diagnostic practice, on the other hand, can only detect the problem at an advanced stage. The purpose of this study was to examine the potential of using a radiolabeled cholesterol ester analog/acetylated low density lipoprotein (AcLDL) conjugate as a diagnostic agent for the early and non-invasive detection of atherosclerosis and for the monitoring of the effects of drug therapy.
Cholesteryl iopanoate (CI), a cholesterylester analog, was synthesized, radiolabeled, and incorporated into AcLDL. Early atherosclerotic lesions were induced in New Zealand White rabbits. 125[-CI/AcLDL was injected intravenously at 2 microCi/kg. Blood samples were taken at different time intervals after injection and clearance of the injected drug from blood was studied. The rabbits were sacrificed after 72 hours and the distribution of radioactivity in various organs was investigated. Aortae of both atherosclerotic lesion and control rabbits were removed for Sudan IV staining and autoradiography in order to confirm the formation of the atherosclerotic lesion and localization of radioactivity.
The injected drug was found to be cleared from blood following a two compartment model. Radioactivity in the atherosclerotic aorta was found to be about 8 times higher than that in normal aorta, suggesting that the proposed diagnostic probe was selectively taken up by the atherosclerotic lesion. The autoradiography and staining confirmed that the localization of the proposed probe was superimposed with the atherosclerotic lesion site.
The results suggested that incorporation of CI into AcLDL resulted in the selective localization of CI at the atherosclerotic plaque areas. CI/AcLDL labeled with appropriate radioisotope has the potential to be used as a probe for visualization of early atherosclerotic lesion using scintigraphy technology.
动脉粥样硬化是导致中风、动脉瘤和心肌梗死等心血管疾病（CVD）的潜在因素。动脉粥样硬化斑块的早期检测被认为对于心血管疾病的成功预防和/或治疗及饮食干预至关重要。另一方面，当前的诊断方法只能在疾病晚期检测到问题。本研究的目的是探讨使用放射性标记的胆固醇酯类似物/乙酰化低密度脂蛋白（AcLDL）结合物作为诊断剂用于动脉粥样硬化的早期非侵入性检测以及监测药物治疗效果的潜力。
合成、放射性标记碘番酸胆固醇酯（CI），一种胆固醇酯类似物，并将其掺入AcLDL中。在新西兰白兔中诱导早期动脉粥样硬化病变。以2微居里/千克的剂量静脉注射¹²⁵I-CI/AcLDL。注射后在不同时间间隔采集血样，研究注入药物从血液中的清除情况。72小时后处死兔子，研究放射性在各个器官中的分布。取出动脉粥样硬化病变兔子和对照兔子的主动脉进行苏丹IV染色和放射自显影，以确认动脉粥样硬化病变的形成和放射性的定位。
发现注入的药物按照二室模型从血液中清除。发现动脉粥样硬化主动脉中的放射性比正常主动脉中的放射性高约8倍，这表明所提出的诊断探针被动脉粥样硬化病变选择性摄取。放射自显影和染色证实所提出探针的定位与动脉粥样硬化病变部位重叠。
结果表明将CI掺入AcLDL中导致CI在动脉粥样硬化斑块区域选择性定位。用适当放射性同位素标记的CI/AcLDL有潜力用作使用闪烁扫描技术可视化早期动脉粥样硬化病变的探针。
