Near-Infrared-II (NIR-II) Bioimaging via Off-Peak NIR-I Fluorescence Emission

Abstract

Significantly reduced photon scattering and minimal tissue autofluorescence levels in the second biological transparency window (NIR-II; 1000-1700 nm) facilitate higher resolution in vivo biological imaging compared to tradition NIR fluorophores (~700-900 nm). However, the existing palette of NIR-II fluorescent agents including semiconducting inorganic nanomaterials and recently introduced small-molecule organic dyes face significant technical and regulatory hurdles prior to clinical translation. Fortunately, recent spectroscopic characterization of NIR-I dyes (e.g., indocyanine green (ICG), IRDye800CW and IR-12N3) revealed long non-negligible emission tails reaching past 1500 nm. Repurposing the most widely used NIR dye in medicine, in addition to those in the midst of clinical trials creates an accelerated pathway for NIR-II clinical translation. This review focuses on the significant advantage of imaging past 1000 nm with NIR-I fluorophores from both a basic and clinical viewpoint. We further discuss optimizing NIR-I dyes around their NIR-II/shortwave infrared (SWIR) emission, NIR-II emission tail characteristics and prospects of NIR-II imaging with clinically available and commercially available dyes.

An IR820 Dye–Protein Complex for Second Near‐Infrared Window and Photoacoustic Imaging

“…This finding highlights the possibility of using conventional NIR‐I dyes for NIR‐II imaging . Further imaging studies using commercially available NIR‐I dyes clearly demonstrate the success of this strategy, opening an entirely new route to realize NIR‐II imaging in preclinical research and even clinical imaging . However, this research direction is currently still in its infancy, and very few NIR‐I dyes have been identified with the capability for NIR‐II imaging.…”

Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

“…The recent introduction of near‐infrared tracers, such as ICG, permits real‐time transcutaneous and intraoperative visualization of lymphatic vessels and sentinel LNs. Currently, a huge number of clinical trials have showed that ICG method can be used as a reliable and safe alternative to the radiotracer method, which reduces operating time and potentially improve localization of the sentinel LNs . However, the ICG based clinically used contrast agents suffer from severe photobleaching, poor imaging detection depth, signal contrast, and sensitivity.…”

“…Currently, a huge number of clinical trials have showed that ICG method can be used as a reliable and safe alternative to the radiotracer method, which reduces operating time and potentially improve localization of the sentinel LNs. [3][4][5][6][7] However, the ICG based clinically used contrast agents suffer from severe photobleaching, poor imaging detection depth, signal contrast, and sensitivity. Hence, current image-guided surgeries are performed under dim light or with frequent toggling of room light to avoid light interference and bleaching of dyes under repeated light exposure.…”

“…Also, NIR-II imaging offers greater tissue penetration and contrast compared to conventional imaging. [3,[8][9][10][11][12][13][14][15][16][17] Although the peak emission of donor-acceptor-donor (D-A-D) dyes and the tail emission of cyanine dyes can be both used for NIR-II imaging, [18][19][20][21] the benefit of NIR-II imaging is better realized in the NIR-IIb sub-window (>1500 nm), where light can penetrate nearly all tissues. [22] Imaging in the NIR-IIb window can minimize photon scattering and simultaneously avoid high absorbance by water, affording high resolution of mouse vasculature at depths of several millimeter in the brain or other tissues.…”

Molecular imaging with nanoparticles: the dwarf actors revisited 10 years later

“…The discussion has focused in part on the relationship between the sp 2 -bonded regions in the dot’s core and the oxygen- and nitrogen-containing groups on its surface (Zheng et al 2015; Zhu et al 2018a, b; Ray et al 2009; Zhu et al 2012a, b; Wei et al 2014; Bourlinos et al 2008a, b; Li et al 2002; Kozák et al 2016). Some authors posit two separate mechanisms of emission (Baker and Baker 2010; Sun et al 2006; Li et al 2012a, b, c; Cao et al 2012a, b; Myung et al 2003; Zheng et al 2009).…”