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New near-infrared dyes light up deep tissue imaging

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Science Translational Medicine  22 Feb 2017:
Vol. 9, Issue 378, eaam6065
DOI: 10.1126/scitranslmed.aam6065

Abstract

A newly synthesized class of near-infrared dyes offers strong absorption and efficient fluorescent emission for deep-tissue molecular imaging applications.

Fluorescence imaging tools can be found throughout translational research in applications ranging from small animal in vivo imaging to molecular-guided surgery. From high-resolution methods such as confocal and multiphoton microscopy to clinical toolkits including fluorescein angiography and intraoperative fluorescence imaging, fluorescence-based methods are unarguably invaluable in biomedicine. Despite their utility, there is a major limitation in the application of fluorescence tools in tissues: Light scattering from the turbid tissue environment limits the useful depth of fluorescence imaging methods. Because the severity of light scattering is reduced at longer wavelengths, a large body of work in technology development and probe design has been devoted to driving the light used for fluorescence imaging as far as possible into near-infrared wavelengths.

In an important study, Lei et al. reveal a new class of near-infrared fluorophores that has strong near-infrared absorption at 880 nm and efficient emission from 915 to more than 1000 nm. These “ECX” dyes were synthesized using a modular reaction scheme that allowed the authors to introduce various functional groups to explore the photochemical properties of the new molecular family. The authors found that all ECX dyes shared a set of highly desired features for use in biological applications: the dyes aggregated minimally; maintained their properties across solvents (low solvatochromism); were chemically stable—in particular against nucleophilic attack; and, most importantly, had low photobleaching rates (high photostability). One dye in particular, called ECXb, had a fluorescence quantum efficacy of over 13%, making it highly useful for tissue imaging applications.

The authors used their ECXb dye for microscopy on fixed HeLa cells, as well as for small animal in vivo imaging via tail vein injection of the dye into mice. The low observed cytotoxicity of the dye was noted as promising for future biomedical applications. Although longer-wavelength dyes like the ECX family will likely require new hardware and imaging tools, the ability to combine a small molecule near-infrared fluorophore with the existing libraries of chemical conjugation techniques and molecular targets will no doubt soon prove useful for deep tissue imaging applications.

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