Abstract：
Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE-/-) mice. The aortas ApoE-/- mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE-/- mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE-/- mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE-/- mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE-/- mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo.
摘要：
生腱蛋白C是一种在冠状动脉粥样硬化斑块中强烈表达的细胞外基质糖蛋白。适体是以高亲和力与特定靶分子结合的单链寡核苷酸。这项研究假设，通过使用正电子发射断层扫描（PET）的生腱蛋白C特异性适体可以检测到体内动脉粥样硬化斑块上的生腱蛋白C表达。本文报道了氟18（18F）标记的生腱蛋白C适体的放射合成，用于载脂蛋白E缺陷（ApoE-/-）小鼠生腱蛋白C表达的生物分布和PET成像。主动脉ApoE-/-小鼠油红O染色阳性面积明显高于对照C57BL/6小鼠,在ApoE-/-小鼠内皮下病变中积累的泡沫细胞中检测到生腱蛋白C的表达。18F标记的生腱蛋白-C适体的离体生物分布显示ApoE-/-小鼠主动脉的摄取明显增加，和离体主动脉放射自显影显示18F标记的生腱蛋白C适体在ApoE-/-小鼠的动脉粥样硬化病变中的高积累，这与油红O染色检测到的动脉粥样硬化斑块的位置一致。18F标记的生腱蛋白-C适体的PET成像显示ApoE-/-小鼠的主动脉中的平均标准化摄取明显高于对照C57BL/6小鼠。这些数据强调了生腱蛋白-C适体在体内诊断动脉粥样硬化病变的潜在用途。
