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一种用于动脉粥样硬化小鼠模型中动脉粥样硬化斑块PET成像的F标记腱生蛋白-C适配体的临床前评估。

Preclinical evaluation of an F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis.

作者信息

Park Jun Young, Kim Hyun Jeong, Chae Ju Ri, Cho Ye Lim, Kang Won Jun

机构信息

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.

出版信息

Biochem Biophys Res Commun. 2024 Apr 9;703:149650. doi: 10.1016/j.bbrc.2024.149650. Epub 2024 Feb 7.

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 (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.

摘要

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。

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