cNGR: A novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo
cNGR: A novel homing sequence for CD13/APN targeted molecular imaging of murine cardiac angiogenesis in vivo
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DOI：
10.1161/01.atv.0000245807.65714.0b
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发表时间：
2006-12-01
影响因子：
8.7
通讯作者：
de Muinck, Ebo D.
中科院分区：
文献类型：
--
作者：
Buehler, Alexandra;van Zandvoort, Marc A. M. J.;de Muinck, Ebo D.
目的-以前，肽序列cNGR已被证明特异性归巢肿瘤内皮细胞上的CD13/APN（氨肽酶N）。在这里，我们调查的可行性，选择性成像的心脏血管生成cNGR-CD 13/APN system.Methods和结果-CD 13/APN诱导和cNGR归巢在小鼠心肌梗死（MI）模型进行了研究。通过实时聚合酶链反应（PCR）在MI后7天，CD13/APN的表达是10 - 20倍高，在血管生成的梗死边缘区和MI区比非MI区。在体内荧光显微镜证实特异性归巢的荧光团标记的cNGR的边界区和MI领土在4和7天后MI的局部优势为2.3，但不是在MI后1或14天。组织滞留半衰期为9.1 +/-0.3小时，而血浆中的半衰期为15.4 +/-3.4分钟。脉冲追踪实验证实了cNGR在梗死区的可逆结合。体内注射荧光标记的cNGR缀合物或抗体，并通过双光子激光扫描显微镜（TPLSM）离体研究其分布。cNGR仅与CD13/APN和血管上的内皮标记物CD31共定位。结论-在心脏血管生成中，内皮CD13/APN上调。它可以用cNGR缀合物特异性靶向。在心脏中，cNGR仅在血管生成区域结合其内皮靶。
Objective - Previously, the peptide sequence cNGR has been shown to home specifically to CD13/APN (aminopeptidase N) on tumor endothelium. Here, we investigated the feasibility of selective imaging of cardiac angiogenesis using the cNGR-CD13/APN system.Methods and Results - CD13/APN induction and cNGR homing were studied in the murine myocardial infarction (MI) model. By real-time polymerase chain reaction (PCR) at 7 days after MI, CD13/APN expression was 10- to 20-fold higher in the angiogenic infarct border zone and the MI area than in non-MI areas. In vivo fluorescence microscopy confirmed specific homing of fluorophore-tagged cNGR to the border zone and MI territory at 4 and 7 days after MI with a local advantage of 2.3, but not at 1 or 14 days after MI. Tissue residence half-life was 9.1 +/- 0.3 hours, whereas the half-life in plasma was 15.4 +/- 3.4 minutes. Pulse chase experiments confirmed reversible binding of cNGR in the infarct area. Fluorescent labeled cNGR conjugates or antibodies were injected in vivo, and their distribution was studied ex vivo by 2-photon laser scanning microscopy (TPLSM). cNGR co-localized exclusively with CD13/APN and the endothelial marker CD31 on vessels.Conclusions - In cardiac angiogenesis endothelial CD13/APN is upregulated. It can be targeted specifically with cNGR conjugates. In the heart cNGR binds its endothelial target only in angiogenic areas.