动脉粥样硬化纳米体超声分子成像:可翻译微泡靶向小鼠和人血管细胞粘附分子

Mukesh Punjabi, Lifen Xu, Amanda Ochoa-Espinosa, A. Kosareva, T. Wolff, A. Murtaja, A. Broisat, N. Devoogdt, B. Kaufmann
{"title":"动脉粥样硬化纳米体超声分子成像:可翻译微泡靶向小鼠和人血管细胞粘附分子","authors":"Mukesh Punjabi, Lifen Xu, Amanda Ochoa-Espinosa, A. Kosareva, T. Wolff, A. Murtaja, A. Broisat, N. Devoogdt, B. Kaufmann","doi":"10.1161/ATVBAHA.119.313088","DOIUrl":null,"url":null,"abstract":"OBJECTIVE\nContrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MBcAbVcam1-5) and microbubble with a control nanobody (MBVHH2E7) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MBcAbVcam1-5 and MBVHH2E7. Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×105 per microbubble. Compared with MBVHH2E7, MBcAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MBcAbVcam1-5 in early (P=0.0003 versus MBVHH2E7) and late atherosclerosis (P=0.007 versus MBVHH2E7); in wild-type mice, there were no differences between MBcAbVcam1-5 and MBVHH2E7. CEUMI in human endarterectomy specimens showed a 100% increase in signal for MBcAbVcam1-5versus MBVHH2E7 (20.6±27.7 versus 9.6±14.7, P=0.0156).\n\n\nCONCLUSIONS\nCEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.","PeriodicalId":8404,"journal":{"name":"Arteriosclerosis, Thrombosis, & Vascular Biology","volume":"54 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"30","resultStr":"{\"title\":\"Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies: Translatable Microbubble Targeting Murine and Human VCAM (Vascular Cell Adhesion Molecule) 1.\",\"authors\":\"Mukesh Punjabi, Lifen Xu, Amanda Ochoa-Espinosa, A. Kosareva, T. Wolff, A. Murtaja, A. Broisat, N. Devoogdt, B. Kaufmann\",\"doi\":\"10.1161/ATVBAHA.119.313088\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE\\nContrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MBcAbVcam1-5) and microbubble with a control nanobody (MBVHH2E7) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MBcAbVcam1-5 and MBVHH2E7. Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×105 per microbubble. Compared with MBVHH2E7, MBcAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MBcAbVcam1-5 in early (P=0.0003 versus MBVHH2E7) and late atherosclerosis (P=0.007 versus MBVHH2E7); in wild-type mice, there were no differences between MBcAbVcam1-5 and MBVHH2E7. CEUMI in human endarterectomy specimens showed a 100% increase in signal for MBcAbVcam1-5versus MBVHH2E7 (20.6±27.7 versus 9.6±14.7, P=0.0156).\\n\\n\\nCONCLUSIONS\\nCEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.\",\"PeriodicalId\":8404,\"journal\":{\"name\":\"Arteriosclerosis, Thrombosis, & Vascular Biology\",\"volume\":\"54 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"30\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arteriosclerosis, Thrombosis, & Vascular Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1161/ATVBAHA.119.313088\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arteriosclerosis, Thrombosis, & Vascular Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1161/ATVBAHA.119.313088","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 30

摘要

目的造影增强超声分子成像(CEUMI)检测血管细胞粘附分子(VCAM)-1在内皮细胞中的表达可改善动脉粥样硬化的危险分层。用于临床前研究的微泡造影剂不适合临床应用。我们的目的是利用临床可翻译的单变量免疫球蛋白(纳米体)配体来表征和验证微泡造影剂。方法与结果:制备了靶向VCAM-1纳米体的微泡(MBcAbVcam1-5)和对照纳米体的微泡(mbvh2e7),并对其进行了体外表征。利用活化的小鼠内皮细胞,研究了连续和脉动流对VCAM-1的附着效率。在体内注射MBcAbVcam1-5和MBVHH2E7后,对动脉粥样硬化双敲除小鼠和野生型小鼠进行主动脉CEUMI。人动脉内膜切除术标本的离体CEUMI在闭环循环模型中进行。纳米体配体的表面密度为3.5×105 /微泡。与MBVHH2E7相比,MBcAbVcam1-5在连续流动条件下,剪切应力增加1-8 dynes/cm2,附着增加,而在脉动流动条件下,剪切应力增加,附着增加。双敲除小鼠CEUMI在动脉粥样硬化早期(P=0.0003,与MBVHH2E7相比)和晚期(P=0.007,与MBVHH2E7相比)MBcAbVcam1-5的信号增强;在野生型小鼠中,MBcAbVcam1-5和MBVHH2E7之间没有差异。人动脉内膜切除术标本的CEUMI显示mbcabvcam1 -5的信号比mbvh2e7增加100%(20.6±27.7比9.6±14.7,P=0.0156)。结论:在小鼠动脉粥样硬化模型和人体组织中,使用含有VCAM-1靶向纳米体的临床可翻译微泡检测VCAM-1的表达是可行的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies: Translatable Microbubble Targeting Murine and Human VCAM (Vascular Cell Adhesion Molecule) 1.
OBJECTIVE Contrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MBcAbVcam1-5) and microbubble with a control nanobody (MBVHH2E7) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MBcAbVcam1-5 and MBVHH2E7. Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×105 per microbubble. Compared with MBVHH2E7, MBcAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MBcAbVcam1-5 in early (P=0.0003 versus MBVHH2E7) and late atherosclerosis (P=0.007 versus MBVHH2E7); in wild-type mice, there were no differences between MBcAbVcam1-5 and MBVHH2E7. CEUMI in human endarterectomy specimens showed a 100% increase in signal for MBcAbVcam1-5versus MBVHH2E7 (20.6±27.7 versus 9.6±14.7, P=0.0156). CONCLUSIONS CEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信