Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence.
Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence.
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DOI：
10.1016/j.jcmg.2012.01.017
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发表时间：
2012-06
影响因子：
14
通讯作者：
Jaffer, Farouc A.
中科院分区：
文献类型：
--
作者：
Hara, Tetsuya;Bhayana, Brijesh;Thompson, Brian;Kessinger, Chase W.;Khatri, Ashok;McCarthy, Jason R.;Weissleder, Ralph;Lin, Charles P.;Tearney, Guillermo J.;Jaffer, Farouc A.
开发和验证一种新型纤维蛋白靶向成像剂，能够对深静脉血栓 (DVT) 进行高分辨率近红外荧光 (NIRF) 成像。纤维蛋白的近红外荧光（NIRF）成像可以实现体内血栓形成综合征的高灵敏度和非侵入性分子成像。纤维蛋白靶向肽与 NIR 荧光团 Cy7 缀合，称为 FTP11-Cy7。 NIRF 肽基于已完成 II 期临床磁共振成像 (MRI) 试验的纤维蛋白特异性成像剂。通过荧光反射成像 (FRI) 评估 FTP11-Cy7 与人血浆凝块的体外结合。接下来，将 FTP11-Cy7 静脉注射到局部 7.5% 氯化铁治疗诱导股骨 DVT 的小鼠体内。对患有 DVT 的小鼠（总共 n = 32 只）进行活体荧光显微镜检查 (IVFM) 和无创荧光分子断层扫描 (FMT)-计算机断层扫描 (CT)，然后进行组织学分析。体外人体凝块结合分析显示，FTP11-Cy7 的 NIRF 凝块目标与背景比 (TBR) 比游离 Cy7 高 6 倍（6.3 ± 0.34 对比 1.2 ± 0.03，p < 0.0001）。通过 IVFM 获得的 FTP11-Cy7 急性和亚急性股骨 DVT 的血栓 TBR 比不含 Cy7 的对照高 >400%。 FTP11-Cy7 与血栓的结合在体外和体内均被 100 倍过量的未标记竞争肽阻断（每种 p < 0.001）。组织学分析证实FTP11-Cy7特异性地积聚在血栓中。通过 FMT-CT 对颈静脉 DVT 中的纤维蛋白进行无创 FMT-CT 成像，结果显示与假手术颈静脉相比，血栓中存在强烈的 NIRF 信号（平均 TBR = 3.5 ± 0.7 与 1.5 ± 0.3，p < 0.05）。纤维蛋白靶向 NIRF 试剂 FTP11-Cy7 强烈且特异性地结合人类和小鼠血栓，并能够对体内急性和亚急性小鼠 DVT 进行灵敏、多模式活体和非侵入性 NIRF 分子成像检测。
To develop and validate a new fibrin targeted imaging agent that enables high-resolution near-infrared fluorescence (NIRF) imaging of deep venous thrombosis (DVT). Near-infrared fluorescence (NIRF) imaging of fibrin could enable highly sensitive and noninvasive molecular imaging of thrombosis syndromes in vivo. A fibrin-targeted peptide was conjugated to an NIR fluorophore Cy7, termed FTP11-Cy7. The NIRF peptide is based on a fibrin-specific imaging agent that has completed phase II clinical magnetic resonance imaging (MRI) trials. In vitro binding of FTP11-Cy7 to human plasma clots was assessed by fluorescence reflectance imaging (FRI). Next, FTP11-Cy7 was intravenously injected in mice with femoral DVT induced by topical 7.5% ferric chloride treatment. Intravital fluorescence microscopy (IVFM), and noninvasive fluorescence molecular tomography(FMT)-computed tomography (CT) were performed in mice (n = 32 total) with DVT, followed by histological analyses. In vitro human clot-binding analyses showed a 6-fold higher NIRF clot target-to-background ratio (TBR) of FTP11-Cy7 than free Cy7 (6.3 ± 0.34 vs. 1.2 ± 0.03, p < 0.0001). The thrombus TBR of acute and sub-acute femoral DVT with FTP11-Cy7 obtained by IVFM was >400% higher than control free Cy7. Binding of FTP11-Cy7 to thrombi was blocked by a 100-fold excess of unlabeled competitor peptide both in vitro and in vivo (p < 0.001 for each). Histological analyses confirmed that FTP11-Cy7 specifically accumulated in thrombi. Noninvasive FMT-CT imaging of fibrin in jugular DVT via FMT-CT demonstrated strong NIRF signal in thrombi compared to sham-operated jugular veins (mean TBR = 3.5 ± 0.7 vs. 1.5 ± 0.3, p < 0.05). The fibrin-targeted NIRF agent FTP11-Cy7 avidly and specifically binds human and murine thrombi, and enables sensitive, multimodal intravital and noninvasive NIRF molecular imaging detection of acute and sub-acute murine DVT in vivo.
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影响因子：
24
作者：
Jaffer, Farouc A.;Calfon, Marcella A.;Rosenthal, Amir;Mallas, Georgios;Razansky, R. Nika;Mauskapf, Adam;Weissleder, Ralph;Libby, Peter;Ntziachristos, Vasilis
通讯作者：
Ntziachristos, Vasilis
蛋白水解活性动脉粥样硬化中炎症的实时导管分子传感。
影响因子：
37.8
作者：
Jaffer FA;Vinegoni C;John MC;Aikawa E;Gold HK;Finn AV;Ntziachristos V;Libby P;Weissleder R
通讯作者：
Weissleder R
影响因子：
82.9
作者：
Ntziachristos, Vasilis;Tung, Ching-Hsuan;Weissleder, Ralph
通讯作者：
Weissleder, Ralph
DOI：
10.1161/atvbaha.108.162289
发表时间：
2008-03-01
影响因子：
8.7
作者：
Wakefield, Thomas W.;Myers, Daniel D.;Henke, Peter K.
通讯作者：
Henke, Peter K.
影响因子：
14
作者：
Miserus, Robbert-Jan J. H. M.;Herias, M. Veronica;Kooi, Marianne Eline
通讯作者：
Kooi, Marianne Eline