Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green
Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green
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DOI：
10.1073/pnas.1718917115
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发表时间：
2018-04-24
影响因子：
11.1
通讯作者：
Bruns, Oliver T.
中科院分区：
文献类型：
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作者：
Carr, Jessica A.;Franke, Daniel;Bruns, Oliver T.
荧光成像是一种体内实时分子跟踪的方法，已使许多临床技术成为可能。与传统的可见光和近红外（NIR）荧光成像相比，短波红外（SWIR; 1，000 - 2，000 nm）成像具有更高的对比度、灵敏度和穿透深度。然而，SWIR成像在临床环境中的采用受到限制，部分原因是缺乏美国食品和药物管理局（FDA）批准的在SWIR中具有峰值发射的荧光团。在这里，我们表明，市售的近红外染料，包括FDA批准的造影剂吲哚菁绿色（ICG），表现出适合在体内短波红外荧光成像的光学特性。尽管它们的发射光谱在NIR中达到峰值，但这些染料的性能优于商业SWIR荧光团，并且可以在SWIR中成像，甚至超过1，500 nm。我们显示了使用ICG在临床相关剂量下的实时荧光成像，包括活体显微镜检查、血液和淋巴管中的非侵入性成像以及肝胆清除成像，并显示与NIR荧光成像相比对比度增加。此外，我们展示了IRDye 800 CW标记的曲妥珠单抗（一种在多项临床试验中测试的NIR染料）的肿瘤靶向SWIR成像。我们的研究结果表明，高对比度的短波红外荧光成像可以实现与现有的成像方式切换传统的近红外荧光系统的检测从硅基近红外相机新兴的铟镓砷基短波红外相机。特别是使用ICG打开了将SWIR荧光成像转化为人类临床应用的可能性。事实上，我们的研究结果表明，新兴的SWIR荧光在体内造影剂应针对SWIR发射ICG在血液中的基准。
Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.