further bathochromic shift. So, the donor structure thiophene expand the SMDs
NIR-II fluorophores category (e.g. Q1, Q2, Q3 and Q4) [11]. These synthesis
strategies open a quick route for translation of NIR-II imaging technique into clinical
applications.
2.3 Application In Vivo
As a Food and Drug Administration (FDA)-approved dye, the indocyanine green
(ICG) has been widely used in NIR-I window for a long period time. Recent study
exhibits unprecedented imaging opportunities of ICG in NIR-II window with higher
resolution than that in NIR-I window, including contact-free monitoring of vital
signs, generation of microvasculature blood flow maps, real-time metabolic imaging,
and molecularly targeted imaging. For example, in 2017, small-molecule dye ICG
for the first time was reported with the enhanced the NIR-II fluorescent brightness
(tail up to 1,150 nm) via assemblies with FBS [9, 10]. Moreover, Starosolski et al.
demonstrate that ICG display a significant enhanced NIR-II (1,000–1,250 nm)
emission in plasma and low polar solvents such as ethanol. In vivo imaging results
have demonstrated that the signal-to-noise ratio values of ICG in the NIR-II window
are two times than that of in the NIR-I window [34]. So, ICG has a very good
prospect to image in clinical in NIR-II window and get the approval from FDA in the
near future. CH1055-PEG has an emission peak at 1,055 nm and with a tail
extending emission into the NIR-IIa region (1,300–1,400 nm). Compared with
ICG for NIR-I imaging, not only it enables detection of tumors in the brain at depths
up to 4 mm with a noninvasive through-skull technique [8] but offers higher
resolution in diagnosis sentinel lymph nodes (SLN) for surgical resection in real
time. Tumor-specific-targeting NIR-II fluorescent probe can also be obtained by
conjugating CH1055 with an anti-epidermal growth factor receptor (EGFR) affibody
molecule. The affibody-conjugated CH1055 allows accurate image-guided tumor
removal surgery due to the specifically targeting xenograft human squamous cell
carcinoma tumors. Importantly, pharmacokinetic studies of CH1055-PEG demonstrate rapid urinary 90% excretion via the kidneys in 24 h. Moreover, NIR-II window
molecular imaging gives a fivefold higher tumor-to-normal tissue ratio than that in
the NIR-I window, as shown in Fig. 3.
In another novel work, Feng et al. conjugate CH1055 to follicle-stimulating
hormone (FSH) to specifically image ovaries in live mice [15]. They are also able
to detect specific FSH receptor in bones. According to the expression of FSH
receptors, it could resolve earlier controversies in osteoclasts (see Fig. 4a–c). By
replacing the carboxylic acid groups of CH1055 with more negatively charged
sulfonic acid groups and using supramolecular assemblies with serum proteins,
Antaris et al. synthesize a water-soluble SMDC NIR-II dye in FBS (CH-4T-FBS).
This novel NIR-II complex fluorophores show a 110-fold fluorescence enhancement
and a fast video-rate imaging at a 50 frames per second and benefit a lot in NIR-II
window for imaging deep anatomical features (Fig. 4d–f) [10].
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S. He and Z. Cheng
NIR-II fluorophores category (e.g. Q1, Q2, Q3 and Q4) [11]. These synthesis
strategies open a quick route for translation of NIR-II imaging technique into clinical
applications.
2.3 Application In Vivo
As a Food and Drug Administration (FDA)-approved dye, the indocyanine green
(ICG) has been widely used in NIR-I window for a long period time. Recent study
exhibits unprecedented imaging opportunities of ICG in NIR-II window with higher
resolution than that in NIR-I window, including contact-free monitoring of vital
signs, generation of microvasculature blood flow maps, real-time metabolic imaging,
and molecularly targeted imaging. For example, in 2017, small-molecule dye ICG
for the first time was reported with the enhanced the NIR-II fluorescent brightness
(tail up to 1,150 nm) via assemblies with FBS [9, 10]. Moreover, Starosolski et al.
demonstrate that ICG display a significant enhanced NIR-II (1,000–1,250 nm)
emission in plasma and low polar solvents such as ethanol. In vivo imaging results
have demonstrated that the signal-to-noise ratio values of ICG in the NIR-II window
are two times than that of in the NIR-I window [34]. So, ICG has a very good
prospect to image in clinical in NIR-II window and get the approval from FDA in the
near future. CH1055-PEG has an emission peak at 1,055 nm and with a tail
extending emission into the NIR-IIa region (1,300–1,400 nm). Compared with
ICG for NIR-I imaging, not only it enables detection of tumors in the brain at depths
up to 4 mm with a noninvasive through-skull technique [8] but offers higher
resolution in diagnosis sentinel lymph nodes (SLN) for surgical resection in real
time. Tumor-specific-targeting NIR-II fluorescent probe can also be obtained by
conjugating CH1055 with an anti-epidermal growth factor receptor (EGFR) affibody
molecule. The affibody-conjugated CH1055 allows accurate image-guided tumor
removal surgery due to the specifically targeting xenograft human squamous cell
carcinoma tumors. Importantly, pharmacokinetic studies of CH1055-PEG demonstrate rapid urinary 90% excretion via the kidneys in 24 h. Moreover, NIR-II window
molecular imaging gives a fivefold higher tumor-to-normal tissue ratio than that in
the NIR-I window, as shown in Fig. 3.
In another novel work, Feng et al. conjugate CH1055 to follicle-stimulating
hormone (FSH) to specifically image ovaries in live mice [15]. They are also able
to detect specific FSH receptor in bones. According to the expression of FSH
receptors, it could resolve earlier controversies in osteoclasts (see Fig. 4a–c). By
replacing the carboxylic acid groups of CH1055 with more negatively charged
sulfonic acid groups and using supramolecular assemblies with serum proteins,
Antaris et al. synthesize a water-soluble SMDC NIR-II dye in FBS (CH-4T-FBS).
This novel NIR-II complex fluorophores show a 110-fold fluorescence enhancement
and a fast video-rate imaging at a 50 frames per second and benefit a lot in NIR-II
window for imaging deep anatomical features (Fig. 4d–f) [10].
86
S. He and Z. Cheng