18F-4V for PET-CT imaging of VCAM-1 expression in atherosclerosis.
18F-4V for PET-CT imaging of VCAM-1 expression in atherosclerosis.
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DOI：
10.1016/j.jcmg.2009.04.016
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发表时间：
2009-10
影响因子：
14
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Nahrendorf, Matthias;Keliher, Edmund;Panizzi, Peter;Zhang, Hanwen;Hembrador, Sheena;Figueiredo, Jose-Luiz;Aikawa, Elena;Kelly, Kimberly;Libby, Peter;Weissleder, Ralph
迭代开发和验证18F标记的小分子VCAM-1亲和配体，并证明通过PET-CT在小鼠动脉中成像VCAM-1表达的可行性。混合PET-CT成像可以通过开发新型示踪剂（PET）同时评估动脉粥样硬化病变形态（CT）和生物学，从而促进个体患者的早期风险评估。首先用DOTA对通过VCAM-1介导的结合内化到内皮细胞中的环状、线性和寡聚体亲和肽进行衍生化，以确定其结合特征和药代动力学。然后将先导化合物进行18F标记，并在apoE−/−小鼠以及MI和心脏移植排斥模型中进行测试。四聚体肽对VCAM-1具有最高的亲和力和特异性（对可溶性VCAM-1的97%抑制）。使用18F-4V的体内PET-CT成像显示鼠动脉粥样化中的0.31±0.02 SUV（离体%IDGT 5.9±1.5）。18F-4V摄取与油红O染色的动脉粥样硬化斑块共定位，并且与通过定量RT-PCR测量的VCAM-1 mRNA水平相关（R=0.79，p=0.03）。用阿托伐他汀治疗的小鼠具有显著较低的病变摄取（p<0.05）。此外，心肌缺血和移植心脏中的18F-4V成像显示出与VCAM-1 mRNA的离体测量良好的相关性。18F-4V允许炎性动脉粥样硬化中VCAM-1的非侵入性PET-CT成像，具有量化治疗效果的动态范围，并与炎性基因表达相关。
To iteratively develope and validate an 18F labeled small molecule VCAM-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by PET-CT in murine arteries. Hybrid PET-CT imaging may allow simultaneous assessment of atherosclerotic lesion morphology (CT) and biology through the development of novel tracers (PET), thus facilitating early risk assessment in individual patients. A cyclic, a linear, and an oligomer affinity peptide, internalized into endothelial cells by VCAM-1–mediated binding, were initially derivatized with DOTA to determine their binding profiles and pharmacokinetics. The lead compound was then 18F labeled and tested in apoE−/− mice as well as models of MI and heart transplant rejection. The tetrameric peptide had the highest affinity and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). In vivo PET-CT imaging using 18F-4V showed 0.31±0.02 SUV in murine atheroma (ex vivo %IDGT 5.9±1.5). 18F-4V uptake colocalized with atherosclerotic plaques on Oil Red O staining, and correlated to mRNA levels of VCAM-1 measured by quantitative RT-PCR (R=0.79, p=0.03). Mice treated with atorvastatin had significantly lower lesional uptake (p<0.05). Furthermore, 18F-4V imaging in myocardial ischemia and in transplanted hearts showed good correlation with ex vivo measurement of VCAM-1 mRNA. 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in inflammatory atherosclerosis, has the dynamic range to quantify treatment effects and correlates with inflammatory gene expression.
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影响因子：
37.8
作者：
Aikawa, M;Sugiyama, S;Libby, P
通讯作者：
Libby, P
影响因子：
64.8
作者：
Sanz, Javier;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.
DOI：
10.1016/s0735-1097(01)01721-1
发表时间：
2002-01-16
影响因子：
24
作者：
Maekawa, Y;Anzai, T;Ogawa, S
通讯作者：
Ogawa, S
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
影响因子：
9.3
作者：
Rudd, James H. F.;Myers, Kelly S.;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.