In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide.
In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide.
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DOI：
10.1038/s41598-017-13735-z
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发表时间：
2017-10-31
影响因子：
4.6
通讯作者：
Wang TD
中科院分区：
文献类型：
--
作者：
Gao Z;Li G;Li X;Zhou J;Duan X;Chen J;Joshi BP;Kuick R;Khoury B;Thomas DG;Fields T;Sabel MS;Appelman HD;Zhou Q;Li H;Kozloff K;Wang TD
早期乳腺癌中ErbB2的表达可以预测大规模患者人群中肿瘤的侵袭性和临床结局。物理活检和常规病理学的准确评估可能受到肿瘤异质性的限制。我们的目标是证明实时光学切片使用近红外标记的ErbB2肽，产生肿瘤特异性对比在人体异种移植乳腺肿瘤在体内。我们使用IRDye800CW作为荧光团，验证了体外特异性肽与细胞结合的性能特征，并使用光声断层扫描研究了肿瘤中的峰值肽摄取。我们使用手持式双轴共焦荧光显微镜进行实时光学成像，该显微镜收集离轴光以减少组织散射，从而获得更大的成像深度。以亚细胞分辨率收集垂直或水平平面中的光学切片。此外，我们发现显着更大的肽结合临床前异种移植乳腺癌在体内和人类样本的浸润性导管癌，表达ErbB2离体。我们使用了一种混乱的肽来进行控制。肽生物分布显示与其他器官相比肿瘤摄取较高，以支持安全性。这种新的综合成像策略有希望可视化乳腺肿瘤中的ErbB2表达，并在手术过程中作为辅助手段，以提高诊断准确性，识别肿瘤边缘和早期癌症分期。
ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo. We used IRDye800CW as the fluorophore, validated performance characteristics for specific peptide binding to cells in vitro, and investigated peak peptide uptake in tumors using photoacoustic tomography. We performed real-time optical imaging using a handheld dual-axes confocal fluorescence endomicroscope that collects light off-axis to reduce tissue scattering for greater imaging depths. Optical sections in either the vertical or horizontal plane were collected with sub-cellular resolution. Also, we found significantly greater peptide binding to pre-clinical xenograft breast cancer in vivo and to human specimens of invasive ductal carcinoma that express ErbB2 ex vivo. We used a scrambled peptide for control. Peptide biodistribution showed high tumor uptake by comparison with other organs to support safety. This novel integrated imaging strategy is promising for visualizing ErbB2 expression in breast tumors and serve as an adjunct during surgery to improve diagnostic accuracy, identify tumor margins, and stage early cancers.
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影响因子：
3.1
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DOI：
10.1109/tpds.2017.2684158
发表时间：
2017-09-01
影响因子：
5.3
作者：
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