血管内皮生长因子结合的微泡对血管生成的超声分子成像。,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

血管内皮生长因子结合的微泡对血管生成的超声分子成像。
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-02-15 00:00:00 , DOI: 10.1021/acs.molpharmaceut.6b01033
Jianjun Wang ₁ , Bin Qin ₁ , Xucai Chen ₁ , William R. Wagner ₂ , Flordeliza S. Villanueva ₁

Affiliation

血管生成受体的成像可提供一种灵敏且临床上有用的方法，用于检测恶性肿瘤中发生的新血管形成，以及对此类肿瘤的抗血管生成疗法的反应。我们测试了以下假设：用人VEGF ₁₂₁（MB _VEGF）标记的微泡（MB）在体外和体内血管生成内皮均与激酶插入结构域受体（KDR）结合，并且这种特异性结合可以在临床超声系统上成像。在这项工作中，使用含有吸附的重组人KDR的平行板流动系统在体外评估了MB _VEGF的靶向粘附。MB _VEGF有更多的粘附当增加每个MB上的VEGF ₁₂₁的量或板上的KDR密度时，将其添加到KDR涂布的板上。MB _VEGF对KDR涂层板的粘附力随壁剪切速率的增加而降低。在bFGF刺激的大鼠提睾肌的活体显微成像中，与同型IgG结合的对照MB（MB _CTL）相比，MB _VEGF具有更大的微血管粘附性。为了确定MB _VEGF是否可用于对血管生成进行超声成像，在静脉注射MB _VEGF后对患有鳞状细胞癌的小鼠进行了超声成像。MB _VEGF在肿瘤中的超声视频强度增强明显更高（17.3±9.7 dB），而MB _CTL（3.8±4.4 dB，n = 6，p <0.05）。这项工作证明了使用MB _VEGF对血管生成标记物进行定向超声成像的可行性。这种方法提供了一种检测肿瘤血管生成的无创床旁方法，并且可以扩展到其他应用，例如在心血管疾病或癌症中对治疗性血管生成或抗血管生成疗法进行分子监测。

"点击查看英文标题和摘要"

Ultrasound Molecular Imaging of Angiogenesis Using Vascular Endothelial Growth Factor-Conjugated Microbubbles

Imaging of angiogenesis receptors could provide a sensitive and clinically useful method for detecting neovascularization such as occurs in malignant tumors, and responses to antiangiogenic therapies for such tumors. We tested the hypothesis that microbubbles (MB) tagged with human VEGF₁₂₁ (MB_VEGF) bind to the kinase insert domain receptor (KDR) in vitro and angiogenic endothelium in vivo, and that this specific binding can be imaged on a clinical ultrasound system. In this work, targeted adhesion of MB_VEGF was evaluated in vitro using a parallel plate flow system containing adsorbed recombinant human KDR. There was more adhesion of MB_VEGF to KDR-coated plates when the amount of VEGF₁₂₁ on each MB or KDR density on the plate was increased. MB_VEGF adhesion to KDR-coated plates decreased with increasing wall shear rate. On intravital microscopic imaging of bFGF-stimulated rat cremaster muscle, there was greater microvascular adhesion of MB_VEGF compared to that of isotype IgG-conjugated control MB (MB_CTL). To determine if MB_VEGF could be used to ultrasonically image angiogenesis, ultrasound imaging was performed in mice bearing squamous cell carcinoma after intravenous injection of MB_VEGF. Ultrasound videointensity enhancement in tumor was significantly higher for MB_VEGF (17.3 ± 9.7 dB) compared to MB_CTL (3.8 ± 4.4 dB, n = 6, p < 0.05). This work demonstrates the feasibility of targeted ultrasound imaging of an angiogenic marker using MB_VEGF. This approach offers a noninvasive bedside method for detecting tumor angiogenesis and could be extended to other applications such as molecular monitoring of therapeutic angiogenesis or antiangiogenic therapies in cardiovascular disease or cancer.

更新日期：2017-02-15

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南