Park Jun Young, Kim Hyun Jeong, Chae Ju Ri, Cho Ye Lim, Kang Won Jun
Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Department of Nuclear Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin, 16995, Republic of Korea.
Biochem Biophys Res Commun. 2024 Apr 9;703:149650. doi: 10.1016/j.bbrc.2024.149650. Epub 2024 Feb 7.
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 (F)-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 F-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 F-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 F-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.
腱生蛋白-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。适体是与特定靶分子高亲和力结合的单链寡核苷酸。本研究假设,在体内动脉粥样硬化斑块处的腱生蛋白-C表达可通过使用正电子发射断层扫描(PET)的腱生蛋白-C特异性适体来检测。本文报道了一种用于载脂蛋白E缺陷(ApoE)小鼠体内腱生蛋白-C表达的生物分布和PET成像的氟-18(F)标记的腱生蛋白-C适体的放射性合成。ApoE小鼠的主动脉油红O染色阳性面积比对照C57BL/6小鼠显著增加,并且在ApoE小鼠内皮下病变中积聚的泡沫细胞中检测到腱生蛋白-C表达。F标记的腱生蛋白-C适体的离体生物分布显示在ApoE小鼠的主动脉处摄取显著增加,并且主动脉的离体放射自显影显示F标记的腱生蛋白-C适体在ApoE小鼠的动脉粥样硬化病变中高度积聚,这与油红O染色检测到的动脉粥样硬化斑块位置一致。F标记的腱生蛋白-C适体的PET成像显示,ApoE小鼠主动脉中的平均标准化摄取值显著高于对照C57BL/6小鼠。这些数据突出了腱生蛋白-C适体在体内诊断动脉粥样硬化病变的潜在用途。